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					Integrative Gastroenterology
                   Weil Integrative Medicine Library

                 Published and Forthcoming Volumes

                            series editor

                          andrew weil, md


Donald I. Abrams and Andrew Weil: Integrative Oncology
Timothy Culbert and Karen Olness: Integrative Pediatrics
Gerard E. Mullin: Integrative Gastroenterology
Victoria Maizes and Tieraona Low Dog: Integrative Women’s Health
Randy Horwitz and Daniel Muller: Integrative Rheumatology
Daniel A. Monti and Bernard Beitman: Integrative Psychiatry
Stephen Devries and James Dalen: Integrative Cardiology
Integrative Gastroenterology

                     edited by
            Gerard E. Mullin, MD
             Associate Professor, Medicine
      Johns Hopkins University School of Medicine
              The Johns Hopkins Hospital
                    Baltimore, MD




                 1
                                               1
                     Published in the United States of America by Oxford University Press, Inc.,
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                               ____________________________________________
                                Library of Congress Cataloging-in-Publication Data

                            Integrative gastroenterology/[edited by] Gerard E. Mullin.
                                    p.; cm.—(Weil integrative medicine library)
                                  Includes bibliographical references and index.
                                     ISBN-13: 978-0-19-537110-9 (alk. paper)
                                        ISBN-10: 0-19-537110-0 (alk. paper)
                1. Gastrointestinal system—Diseases. 2. Integrative medicine. I. Mullin, Gerard E.
                                    II. Series: Weil integrative medicine library.
              [DNLM: 1. Gastrointestinal Diseases—therapy. 2. Complementary Therapies—methods.
                                                 WI 140 I605 2010]
                                                   RC817.I47 2010
                                                    616.3’3—dc22
                                                                                            2009023877
                                                 978-0-19537110-9
                             ____________________________________________

                                               1 3 5 7 9 10 8 6 4 2

                                           Typeset in Minion Pro Regular
                                             Printed on acid-free paper
                                       Printed in the United States of America

This material is not intended to be, and should not be considered, a substitute for medical or other professional advice.
Treatment for the conditions described in this material is highly dependent on the individual circumstances. And,
while this material is designed to offer accurate information with respect to the subject matter covered and to be
current as of the time it was written, research and knowledge about medical and health issues is constantly evolving
and dose schedules for medications are being revised continually, with new side effects recognized and accounted
for regularly. Readers must therefore always check the product information and clinical procedures with the most
up-to-date published product information and data sheets provided by the manufacturers and the most recent codes
of conduct and safety regulation. The publisher and the authors make no representations or warranties to readers,
express or implied, as to the accuracy or completeness of this material. Without limiting the foregoing, the publisher
and the authors make no representations or warranties as to the accuracy or efficacy of the drug dosages mentioned
in the material. The authors and the publisher do not accept, and expressly disclaim, any responsibility for any
liability, loss or risk that may be claimed or incurred as a consequence of the use and/or application of any of the
contents of this material.
To the more than 70 million Americans who are known to suffer from
digestive disorders.
To my loved ones for their unwavering support over the years.
To the many who mentored me throughout my career.
To Andrew Weil MD for selecting me to edit this textbook.
And the beloved memory of my parents.
This page intentionally left blank
                              FOREWORD




A
         few years ago, a leading gastroenterologist in Tucson asked me to
         meet with him. Over dinner, he expressed the hope that integrative
         medicine (IM) might have something to offer him. He was frustrated,
he said, because, “ninety percent of the patients I see have problems that my
training does not enable me to solve.”
    At that time, the Arizona Center for Integrative Medicine was offering a
comprehensive IM fellowship in distributed learning format to physicians and
nurse practitioners. We were training family medicine doctors, internists, and
surgeons, but had not yet had a GI specialist apply. That disappointed me,
because I knew that integrative medicine could greatly enrich the field of gas-
troenterology, increasing its efficacy and reducing the frustration expressed by
my colleague in Tucson and shared by many others.
    One of the core curricular areas of IM is mind/body medicine. It covers the
theory and evidence base for interactions between mental/emotional states
and physiology, as well as therapies that take advantage of those interactions.
Steven Gurgevich, PhD, a clinical psychologist on the faculty of the American
Society of Clinical Hypnosis, helped design the mind/body medicine module.
He has said, “Patients with gastrointestinal problems should be seen by hypno-
therapists before they go to gastroenterologists,” and over the years, I have
referred many patients with GI complaints to him and other mind/body prac-
titioners, with good outcomes. His reasoning is that the organs of the GI
system, along with the skin, have the greatest amount of innervation of any
organs and, as a result, are the most frequent sites of expression of stress-
related disorders. Michael Gershon, MD, chairman of the Department of

                                                                             vii
viii FOREWORD


Anatomy and Cell Biology at Columbia University Medical Center, in an excel-
lent book on enteric neurology, refers to the gut as the “second brain.”
   Many common GI disorders arise from disturbed function of the gut—in
particular, an imbalance between its intrinsic motility and extrinsic control by
the autonomic nervous system (often caused by stress-related overactivity of
the sympathetic nerves). Without harmonious coordination, gut motility is
abnormal and digestion impaired. In late stages of these disorders, we can
visualize or otherwise detect pathological changes, but early on they present as
functional complaints. Patients seek relief of GI symptoms; there are few or no
measurable correlates of the symptoms.
   “Functional disorder” is a loaded term in conventional medicine. Often it is
used to dismiss complaints of patients without visible pathology; at worst, it is
used as a synonym for “imagined disease.” Patients are easily angered by sug-
gestions that their GI problems are all in the mind. Practitioners must be able
to help them understand the underlying somatopsychic mechanism that
accounts for their very real symptoms.
   Traditional Chinese medicine (TCM) classifies diseases as “visible” or
“invisible” and postulates that all visible disease is preceded by an invisible
stage, in which “energy” (chi) circulation through the body is disturbed. TCM
practitioners believe that if invisible disease goes untreated (by acupuncture,
herbal therapy, dietary adjustment, etc.), it will eventually produce pathologi-
cal changes in the physical structure of the body. Therefore, TCM prioritizes
the diagnosis and treatment of what conventional Western medicine often dis-
misses as functional disorders. Doctors here tend to minimize the significance
of these problems, in part because they find it frustrating to manage them.
Their training does not enable them to do so.
   Because dietary habits and other lifestyle factors can both trigger and aggra-
vate this class of GI disorders, it is not sufficient to send patients to stress-
management training or hypnotherapy. Physicians must also give them specific
recommendations about foods, beverages, physical activity, rest and sleep, and
more. And they should know when the pharmaceutical drugs now so widely
prescribed for GI problems are really indicated, and for how long patients
should be on them. Proton-pump inhibitors for GERD and steroids for inflam-
matory bowel disease may be useful for short-term suppression of symptoms,
but over time the benefit-to-risk ratio changes significantly and unfavorably,
and data on the risks are accumulating.
   Practitioners of integrative medicine are fully trained to diagnose and treat
invisible and functional disease before it damages tissues and organs and
requires drastic, costly intervention. They work from the premise that the body
can heal itself if given a chance, that mind/body interactions are real and often
very relevant to issues of health and illness, that all aspects of lifestyle must be
                                                                   FOREWORD      ix


considered in evaluating patients, and that the doctor/patient relationship is a
key factor in the outcome of treatment. In addition, they are familiar with a
wide range of therapeutic options other than drugs. In recommending thera-
pies not commonly included in mainstream practice, they pay attention to the
evidence that supports them, always working from the principle that the
greater the potential of a treatment to cause harm, the stricter the standards of
evidence for efficacy it must be held to.
    A major initiative of the Arizona Center for Integrative Medicine is
“Integrative Medicine in Residency” (IMR). We have developed a 200-hour,
comprehensive curriculum in IM, much of it taught online, that is currently a
required component of eight residency programs around the United States.
This is a pilot phase of IMR; the center’s long-range goal is to have this com-
prehensive curriculum become a required, accredited part of all residency
training, including that of specialists and subspecialists. Then all physicians
(and surgeons), including gastroenterologists, will know the basics of nutri-
tional medicine, botanical medicine, mind/body medicine, lifestyle influences
on health, the indications for and strengths and weaknesses of other systems
(like Chinese and Ayurvedic medicine) and of complementary and alternative
therapies.
    I am certain that the resulting transformation of medicine is a prerequisite
for building a functional, cost-effective health care system, one that empha-
sizes disease prevention and health promotion and that uses costly, technol-
ogy-based interventions (including pharmaceutical drugs) only when they are
really indicated, managing common forms of illness with simpler, less expen-
sive interventions. It is my hope that this series of volumes from Oxford
University Press will help achieve these goals.
    I have looked forward to the publication of Integrative Gastroenterology
with great anticipation. Not only does it give all clinicians an overview of the
subject and specific guidance about the integrative management of common
GI problems, it has the potential to hasten the day when integrative gastroen-
terology will be a vital field of research and practice. The editor, Gerard Mullin,
MD, has done a commendable job of assembling expert contributors and
informative articles. I have learned much from working with him on the proj-
ect, and I hope the information in these pages will lessen the frustration of
practitioners faced with GI problems that conventional education and training
does not enable them to solve.
                                                                Andrew Weil, MD
                                                                Series Editor
                                                                Tucson, Arizona
                                                                May, 2009
This page intentionally left blank
                               CONTENTS




   Contributors                                                     xv

1. Why Integrative Gastroenterology?                                  
   Gerard E. Mullin
2. The American Digestive Disease Epidemic                           
   Gerard E. Mullin
3. An Overview of Digestive, Sensing, and
   Immune Functions of the Gut                                      
   Patrick J. Hanaway, Laura K. Turnbull, and Gerard E. Mullin
4. The Intestinal Microbiota in Health and Disease: Bystanders,
   Guardians, or Villains?                                          
   Fergus Shanahan
5. Alternative Laboratory Testing for Gastrointestinal Disease       
   David M. Brady, J. Alexander Bralley, Richard S. Lord,
   and Gerard E. Mullin
6. New Molecular Techniques Revolutionize Understanding
   of the Influence of Gut Microbiota on Health and Disease         
   J. Alexander Bralley
7. Principles of Integrative Gastroenterology: Systemic Signs
   of Underlying Digestive Dysfunction and Disease                   
   Laura K. Turnbull, Gerard E. Mullin, and Leonard B. Weinstock
8. The Skin and the Gastrointestinal Tract                           
   Andrew G. Franks, Jr.
9. Premenstrual and Menstrual Exacerbation of IBS: An Integrative
   Medicine Analysis of the Bi-Directional Connection
   between Female Hormones and Gut Health                           
   Joel M. Evans


                                                                     xi
xii   CONTENTS


10. Fibromyalgia and Gastrointestinal Disorders                 
      David M. Brady and Michael J. Schneider
11. Acupuncture for Digestive System                            
      Sanghoon Lee and Ta-Ya Lee
12. Ayurveda and Digestive Health                               
      David Simon and Valencia Porter
13. Osteopathic Medicine                                        
      Diane Clawson
14. Gastroenterology and an Integrative Chiropractic Approach   
      Loren Marks and David M. Durkin
15. Energy Medicine and Gastrointestinal Disorders              
      Ann Marie Chiasson
16. Guided Imagery and Gastroenterology                         
      Martin L. Rossman
17. Hypnosis and Gastrointestinal Disorders                     
      Anastasia Rowland-Seymour
18. Homeopathy Origins and Therapeutic Principles               
      Savely Yurkovsky
19. Massage for Digestive Health                                
      Stephanie Porcaro and Gerard E. Mullin
20. Mindfulness Based Stress Reduction
    for Health and Diseases                                     
      Padmini D. Ranasinghe
21. Naturopathic Medicine and Digestion                         
      Joseph Pizzorno
22. Taiji, Qigong, and Digestive Health                         
      Yang Yang and Bob Schlagal
23. Digestive Health and Reiki Energy                           
      Beth Nolan
24. Self-Care Journaling for Digestive Health                   
      Danna M. Park
25. Spirituality                                                
      Frederic C. Craigie, Jr.
26. What Patients Want from Their Doctors                       
      Donna Jackson Nakazawa
                                                               CONTENTS xiii


27. The Value of Support Groups                                         
    Pearl L. Lewis and Gerard E. Mullin, with a foreword
    by Bernie Siegel
28. Overview of Visceral Manipulation for the
    Integrative Gastroenterologist                                      
    Jean-Pierre Barral and Gail Wetzler
29. Probiotics in the Prevention and Treatment of
    Gastrointestinal Disease                                            
    Gerald Friedman
30. The Role of Nutritional Genomics and Functional Medicine
    in the Management of Crohn’s Disease                                
    Sheila G. Dean and Kathie M. Swift
31. Functional Foods for Digestive Health and Disease                   
    Elizabeth Lipski
32. The Role of Herbal Medicine in Integrative
    Gastroenterology                                                    
    Tieraona Low Dog
33. Brief Review of Mind–Body Medicine in
    Gastroenterology Practice                                           
    Miranda A.L. van Tilburg, Stephan R. Weinland,
    and Olafur S. Palsson
34. Mind–Body Medicine in Digestive Disease                             
    Douglas A. Drossman and William E. Whitehead
35. Yoga and Digestive Health                                           
    Sajida Chaudry and Beth Nolan
36. Integrative Approaches to Abdominal Pain                            
    Robert A. Bonakdar and Emily G. Singh
37. Over-the-Counter Remedies for Digestive Health:
    Potion or Poison?                                                   
    Jerry Hickey and Gerard E. Mullin
38. Systemic Interactions Between Dental and
    Gastroenterological Diseases                                        
    Philip E. Memoli
39. Upper Gastrointestinal Disorders: Dyspepsia, Heartburn,
    Peptic Ulcer Disease, and Helicobacter pylori                       
    Anil Minocha
xiv   CONTENTS


40. Celiac Disease                                                        
      S. Devi Rampertab and Peter H.R. Green
41. Food Reactions and Their Implications in the
    Irritable Bowel Syndrome                                              
      Trent W. Nichols, Gerard E. Mullin, and Laura K. Turnbull
42. An Evidence-Based Review of Complementary and
    Integrative Approaches for Irritable Bowel Syndrome                   
      Octavia Pickett-Blakely, Ashwini S. Davison, and Gerard E. Mullin
43. Nutrition Strategies for the Treatment of IBS and the
    Prevention of Digestive Complaints                                    
      Ashley Koff
44. Alternative Approaches to the Patient with
    Inflammatory Bowel Disease                                            
      Leo Galland, Katarzyna Kines, and Gerard E. Mullin
45. Obesity                                                               
      Lawrence J. Cheskin and Katrina Seidman
46. Nutrition and Colorectal Health                                       
      Mitra Rangarajan and Gerard E. Mullin
47. Liver Disease                                                         
      Matthew Cave, Naeem Aslam, Christopher Kulisek,
      Luis S. Marsano, and Craig J. McClain
48. Integrative Approaches to Diseases of the
    Pancreas and Gallbladder                                              
      Vinay Chandrasekhara and Anthony N. Kalloo
49. An Integrative Approach to Gender-Specific
    Digestive Health Issues                                               
      Laura K. Turnbull, Gerard E. Mullin, and Sharon Dudley-Brown
50. Gastrointestinal Disorders and Eating Disorders                       
      Carolyn Coker Ross
51. Ethical Issues in Integrative Gastroenterology                        
      Julie Stone
52. There Is No Alternative to Evidence                                   
      Ronald L. Koretz


      Index                                                               653
                            CONTRIBUTORS




Naeem Aslam, MD                            J. Alexander Bralley, PhD
Fellow, Department of Medicine             Chief Executive Officer
Division of Gastroenterology and           Metametrix Clinical Laboratory
  Hepatology                               Duluth, GA
University of Louisville School of
  Medicine                                 Matthew Cave, MD
Louisville, KY                             Assistant Professor of Medicine
                                           Division of Gastroenterology/
Jean-Pierre Barral, DO                       Hepatology
Director of the Department of              Department of Medicine
  Osteopathic Manipulation                 University of Louisville
University of Paris, School of Medicine    Louisville, KY
Paris, France
                                           Vinay Chandrasekhara, MD
Robert Alan Bonakdar, MD, FAAFP
                                           Clinical Fellow
Director of Pain Management
                                           Division of Gastroenterology &
Scripps Center for Integrative
                                             Hepatology
  Medicine
                                           Johns Hopkins University School of
Assistant Clinical Professor
                                             Medicine
Department of Family and
                                           Baltimore, MD
  Preventative Medicine (Voluntary)
University of California, San Diego,
                                           Sajida Chaudry, MD, MPH
  School of Medicine
                                           Family Medicine and Preventive
San Diego, CA
                                             Medicine
David M. Brady, ND, DC, CCN,               Johns Hopkins Community Physicians
DACBN                                      Odenton, MD
Vice Provost, Health Sciences Division
Director, Human Nutrition Institute
Associate Professor of Clinical Sciences
University of Bridgeport
Bridgeport, CT

                                                                                xv
xvi   CONTRIBUTORS


Ann Marie Chiasson, MD,                Ashwini S. Davison, MD
MPH, CCFP                              Senior Resident
Clinical Assistant Professor of        Department of Internal Medicine
  Medicine                             Johns Hopkins Hospital
Arizona Center for Integrative         Baltimore, MD
  Medicine
University of Arizona                  Sheila G. Dean, DSc, RD, LD,
Tucson, AZ                             CCN, CDE
                                       Integrative Nutrition Solutions
Lawrence J. Cheskin, MD, FACP          Adjunct Professor of Nutrition
Associate Professor of Health,           Science
   Behavior & Society                  University of Tampa
Joint Appointment in Medicine          Palm Harbor, FL
   (Gastroenterology)
Director, Johns Hopkins Weight         Douglas A. Drossman, MD
   Management Center                   Professor of Medicine and
Johns Hopkins Bloomberg School of        Psychiatry
   Public Health                       Co-Director, UNC Center for
Johns Hopkins University School of       Functional GI and Motility
   Medicine                              Disorders
Baltimore, MD                          Division of
                                         Gastroenterology and Hepatology,
Diane Clawson, DO                        Department of Medicine
Attending Physician                    University of North Carolina at Chapel
Department of Psychiatry                 Hill
Department of Pediatrics               Chapel Hill, NC
University of New Mexico
Albuquerque, NM                        Sharon Dudley-Brown, PhD,
                                       FNP–BC
Frederic C. Craigie, Jr., PhD          Co-Director, Gastroenterology &
Psychologist/Faculty, Maine-             Hepatology Nurse Practitioner
  Dartmouth Family Medicine              Fellowship Program
  Residency                            Johns Hopkins Hospital
Associate Professor of Community and   Assistant Professor
  Family Medicine                      Johns Hopkins University Schools of
Dartmouth Medical School                 Medicine & Nursing
Visiting Associate Professor           Baltimore, MD
Arizona Center for Integrative
  Medicine                             David Durkin, DC
University of Arizona School of        Chiropractor
  Medicine                             Durkin Chiropractic Center
Augusta, Maine                         Gastonia, NC
                                                          CONTRIBUTORS       xvii


Joel M. Evans, MD                       Jerry Hickey, RPh
Assistant Clinical Professor            Scientific Director
Department of Obstetrics, Gynecology,   InVite Health, Inc.
  and Women’s Health                    New York, NY
Albert Einstein College of Medicine
Bronx, NY                               Anthony N. Kalloo, MD
                                        The Moses and Helen Golden Paulson
Andrew G. Franks, Jr., MD, FACP           Professor of Gastroenterology
Clinical Professor of Dermatology and   Chief, Division of Gastroenterology
  Medicine (Rheumatology)                 and Hepatology
Director, Skin Lupus, and Connective    Johns Hopkins Hospital
  Tissue Disease                        Baltimore, MD
New York University School of
  Medicine                              Katarzyna Kines, MS, MA, LDN,
New York, NY                            CNS, CN
                                        Holistic Nutrition Naturally, LLC
Gerald Friedman, MD, PhD, MS,           Contractual Practitioner with
FACP, MACG                              Johns Hopkins Integrative Medicine
Clinical Professor of Medicine            and Digestive Center
Department of Medicine, Division of     Green Spring Station,
  Gastroenterology                        Lutherville, MD
The Mount Sinai School of Medicine
New York, NY                            Ashley Koff, RD
                                        Founder, AshleyKoffApproved.com
Leo Galland, MD
Director                                Ronald L. Koretz, MD
Foundation for Integrated Medicine      Emeritus Professor of Clinical
New York, NY                              Medicine
                                        David Geffen–UCLA School of
Peter H.R. Green, MD                      Medicine
Professor of Clinical Medicine          Department of Medicine
Celiac Disease Center                   Olive View–UCLA Medical Center
Columbia University College of          Sylmar, CA
  Physicians and Surgeons
New York, NY                            Christopher Kulisek, MD
                                        Resident, Department
Patrick Hanaway, MD                       of Medicine
Chief Medical Officer                   University of Louisville School of
Genova Diagnostics                        Medicine
Asheville, NC                           Louisville, KY
xviii CONTRIBUTORS


Sanghoon Lee, OMD, PhD, DiplAc, LAc    Tieraona Low Dog, MD
Associate Professor of Acupuncture &   Director of the Fellowship
  Moxibustion                          Arizona Center for Integrative
College of Oriental Medicine             Medicine
WHO Collaborating Centre for           Clinical Associate Professor
  Traditional Medicine                 Department of Medicine
East–West Medical Research Institute   University of Arizona
Kyung Hee University                   Tucson, AZ
Seoul, South Korea
                                       Dan Lukaczer, ND
Ta-Ya Lee, MSN, CRNP, MAc, LAc,        Associate Director of Medical
MBA, MPH                                 Education
Johns Hopkins Community Physicians     Institute for Functional Medicine
Wyman Park Internal Medicine           Gig Harbor, WA
Canton Crossing Integrative Medicine
Baltimore, MD                          Loren Marks, DC, DACBN
                                       Diplomate American Clinical Board
Pearl L. Lewis                           of Nutrition
Founder, Maryland Chapter Crohn’s      Integrative Assessment Technique,
   and Colitis Foundation                Founder
Founder, Maryland Patient Advocacy     200 W 57 St. Ste 1010 NY
   Group
Maryland Renal Advocate                Luis S. Marsano, MD
National Kidney Foundation of          Professor of Medicine
   Maryland                            Jewish Hospital Distinguished
National Kidney Foundation               Professor of Hepatology
   Malignancy Advisory Board           Division of GI/Hepatology
Author, Access to Care for Special     University of Louisville School of
   Needs Populations (19 states)         Medicine
Ellicott City, MD                      Louisville, KY

Liz Lipski, PhD, CCN                   Craig J. McClain, MD
Director of Doctoral Studies           Professor, Departments of
Hawthorn University                      Medicine and Pharmacology &
Founder of Innovative Healing            Toxicology
Founder of Access to Health Experts    Associate Vice President for
Asheville, NC                            Translational Research
                                       Distinguished University Scholar
Richard S. Lord, PhD                   University of Louisville School of
Chief Science Officer                    Medicine
Metametrix Institute                   Louisville, KY
Duluth, GA
                                                       CONTRIBUTORS      xix


Philip E. Memoli, DMD,               Danna Park, MD, FAAP
FAGD, CNC                            Medical Director
Founder, Institute of Systemic       Integrative Healthcare Department
  Medicine and Dentistry             Mission Hospital
Attending, Overlook Hospital         Asheville, NC
Summit, NJ
and                                  Octavia Pickett-Blakely, MD
Private Practice                     Post Doctoral Fellow
Berkeley Heights, NJ                 Division of Gastroenterology
                                     Johns Hopkins School of Medicine
Anil Minocha, MD                     Baltimore, MD
Professor of Medicine
                                     Joseph Pizzorno, ND
LSU Health Sciences Center
                                     Editor-in-Chief, Integrative Medicine,
Chief of Gastroenterology
                                       A Clinician’s Journal
VA Medical Center
                                     Co-Author, Textbook of Natural Medicine
Shreveport, LA
                                     President Emeritus, Bastyr University
                                     Seattle, WA
Donna Jackson Nakazawa
Author and Lecturer                  Stephanie Porcaro, LMT
The Autoimmune Epidemic              Massage By Stephanie
www.autoimmuneepidemic.com           Baltimore, MD

Trent W. Nichols, Jr., MD            Valencia Porter, MD, MPH
Center for Digestive Disorders and   Director of Women’s Health
  Nutrition                          The Chopra Center for Wellbeing
Hanover, PA                          Carlsbad, CA

Beth Nolan, LMT                      S. Devi Rampertab, MD
Massage Therapist                    Assistant Professor of Medicine
Life Support Wellness Center         Division of Gastroenterology
Butler, NJ                           Penn State College of Medicine
                                     Hershey Medical Center
Olafur S. Palsson, PsyD              Hershey, PA
Associate Professor of Medicine
Division of Gastroenterology and     Padmini D. Ranasinghe, MD, MPH
  Hepatology                         Assistant Professor of Medicine
Department of Medicine               Division of General Internal Medicine
University of North Carolina at      Johns Hopkins University School of
  Chapel Hill                          Medicine
Chapel Hill, NC                      Baltimore, MD
xx   CONTRIBUTORS


Mitra Rangarajan, MSN, ANP-BC,           Michael J. Schneider, DC, PhD
MPH, CDE, MS, RD                         Visiting Assistant Professor
Nurse Practitioner, Advanced             School of Health & Rehabilitation
  Therapeutic Endoscopy & GI                Sciences
  Motility                               University of Pittsburgh
Division of Gastroenterology &           Pittsburgh, PA
  Hepatology
Johns Hopkins University School of       Katrina B. Seidman, MS, RD, LDN
  Medicine                               Registered Dietician
Baltimore, MD                            Johns Hopkins Weight Management
                                           Center
Carolyn Coker Ross, MD, MPH              Department of Health, Behavior and
Clinical Assistant Professor of            Society
  Medicine                               Johns Hopkins Bloomberg School of
University of Arizona, Tucson, AZ          Public Health
Eating Disorder, Addiction Medicine      Baltimore, MD
  and Integrative Medicine
  Consultant                             Fergus Shanahan, MD
Denver, CO                               Professor and Chair, Department of
                                           Medicine
Martin L. Rossman, MD                    Director, Alimentary Pharmabiotic
Clinical Instructor                        Centre
Department of Family and                 Cork University Hospital and
  Community Medicine                       University College Cork
University of California San Francisco   National University of Ireland
  Medical School
San Francisco, CA                        David Simon, MD
                                         Medical Director, Co-Founder
Anastasia Rowland-Seymour, MD            The Chopra Center for
Assistant Professor of Medicine            Wellbeing
Division of General Medicine             Carlsbad, CA
Department of Internal Medicine
Johns Hopkins University School of       Emily G. Singh, MD
  Medicine                               Division of Gastroenterology
Baltimore, MD                            Scripps Clinic Carmel Valley
                                         San Diego, CA
Bob Schlagal, PhD
Professor                                Julie Stone, MA, LLB
Department of Language, Reading, &       Visiting Professor, Peninsula Medical
  Exceptionalities                         School
Appalachian State University             Universities of Exeter and Plymouth
Boone, NC                                United Kingdom
                                                           CONTRIBUTORS        xxi


Kathie Madonna Swift, MS, RD             Gail Wetzler, PT, EDO, BI–D
Director, Food As Medicine               Director of Physical Therapy
Center for Mind Body Medicine            Center for Alternative Medicine
Washington DC                            University of California, Irvine
and                                      and
Lead Nutritionist                        Director of Curriculum and Program
Kripalu Center for Yoga and Health         Development
Stockbridge, MA                          Barral Institute
                                         and
Laura K. Turnbull, BA, RNc               Owner of Wetzler Integrative Physical
Johns Hopkins University School of         Therapy Center
  Nursing                                Newport Beach, CA
Baltimore, MD
                                         William E. Whitehead, PhD
Miranda A.L. van Tilburg, PhD            Professor of Medicine and Adjunct
Assistant Professor of Medicine            Professor of Obstetrics and
University of North Carolina School of     Gynecology
  Medicine                               Co-Director of the Center for
Department of Gastroenterology and         Functional GI and Motility
  Hepatology                               Disorders
UNC Center for Functional GI and         University of North Carolina at Chapel
  Motility Disorders                       Hill
Chapel Hill, NC                          Chapel Hill, NC

Stephan R. Weinland, PhD                 Yang Yang, PhD
Assistant Professor of Medicine          Adjunct Faculty
University of North Carolina at          Department of Kinesiology and
  Chapel Hill                              Community Health
Center for Functional GI and Motility    University of Illinois at Urbana-
  Disorders                                Champaign
Chapel Hill, NC                          and
                                         Director
Leonard B. Weinstock, MD                 Center for Taiji and Qigong Studies
Associate Professor of Clinical          New York, NY
   Medicine and Surgery
Washington University School of          Savely Yurkovsky, MD
   Medicine                              Private Practice
Director, Specialists in                 Chappaqua, NY
   Gastroenterology, LLC
St. Louis, MO
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Integrative Gastroenterology
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                                 1
    Why Integrative Gastroenterology?
                       GERARD E. MULLIN




                           key concepts

■   Digestive diseases encompass more than 40 acute and chronic
    conditions of the gastrointestinal tract, ranging from common
    digestive disorders to serious, life-threatening diseases.
■   More than 70 million Americans are afflicted with diseases of
    the digestive system.
■   Digestive diseases are the second leading cause of disability
    due to illness in the United States, with more than 2 million
    Americans impaired to some degree.
■   The annual economic impact on the U.S. economy is more than
    $141 billion.
■   Westernized diet and lifestyles are the major cases of the
    digestive disease epidemic.
■   Many of the most common digestive diseases in the United
    States are also common in Canada and Europe, but are uncom-
    mon in Asia and Africa, suggesting that these diseases are pre-
    ventable through dietary and lifestyle modifications.
■   The escalating prevalence of obesity, anxiety, depression, stress,
    fast food consumption, and food-borne illnesses, is contribut-
    ing to the digestive disease epidemic.
■   Adoption of an integrative model by physicians would achieve
    more effective prevention and treatment of digestive disease.
                                  ■




                                                                         3
                                Introduction



A
          s gastroenterologists, internists, primary-care practitioners, nurse
          practitioners, or alternative providers, we need to realize that over
          50% of patients with digestive disorders incorporate complementary
and alternative medicine (CAM) into their treatment regimen. Studies have
shown that approximately 72% of patients who utilize alternative strategies are
reluctant to disclose this to their providers for fear of being stigmatized.
    Since our patients seek our guidance and expertise in overseeing their
healthcare, it is time for us to realize that consumer demand has driven the
present dynamic of patients paying out of pocket to achieve improved health
and well-being by “integrating” alternative strategies into their lives.
    There is a body of experiential and evidence-based literature to support the
utilization of these “alternative” strategies in digestive healthcare. Thus, the
ongoing utilization of alternative strategies by the public, the evidence sup-
porting its use, and the expanding groups of practitioners achieving improved
health outcomes, led Dr. Andrew Weil to commission me to synthesize a com-
prehensive how-to guide for advising digestive disease patients, aimed at the
everyday practitioner.
    Integrative medicine is a rapidly growing and highly credible field that seeks
to integrate the best of Western scientific medicine with a broader understand-
ing of the nature of illness, healing and wellness.
    Dr. Andrew Weil defines integrative medicine as a “healing-oriented medi-
cine that takes account of the whole person (body, mind and spirit), including all
aspects of lifestyle. It emphasizes the therapeutic relationship and makes use of all
appropriate therapies, both conventional and alternative.”


   The Principles of Integrative Medicine by Dr. Andrew Weil:
   • A partnership between patient and practitioner in the healing process
   • Appropriate use of conventional and alternative methods to facilitate
     the body’s innate healing response
   • Consideration of all factors that influence health, wellness, and disease,
     including mind, spirit, and community, as well as body
   • A philosophy that neither rejects conventional medicine nor accepts alter-
     native therapies uncritically
   • Recognition that good medicine should be based in good science, be
     inquiry driven, and be open to new paradigms
   • Use of natural, effective, less invasive interventions whenever possible
                                              Why Integrative Gastroenterology? 5



  • Use of the broader concepts of promotion of health and the prevention of
    illness, as well as the treatment of disease
  • Training of practitioners to be models of health and healing, committed to
    the process of self-exploration and self-development.



  Integrative medicine aims to transform healthcare by moving the boundar-
  ies of the existing field of medicine to include the wisdom inherent in
  healing the “whole person”—mind, body and spirit.




                 The Digestive Disease Epidemic

Digestive disease is known to affect more than 70 million Americans today.
An estimated 70% of Americans have either digestive disease or digestive
symptoms over their lifetime. Countless others have migraines, arthritis, fibro-
myalgia, chronic fatigue, depression, neurological disease, osteoporosis, skin
disorders, menstrual irregularities, premenstrual syndrome (PMS), and other
conditions that are related to undiagnosed core digestive discord.
   This emerging epidemic of digestive disease is a social disease that results
from a breakdown in the infrastructure of society as we promote stress, meals
on the run from fast-food vendors, unhealthy norms in food choices, and
exposure to carcinogens and xenobiotics, while producing record rates of
mental disorders, social isolation, obesity, and inactivity, which all adversely
affect the gut.
   The end result is a nation in which one in three individuals have a digestive
disorder, 63 million either have or show signs of autoimmune disease, and
125 million overall have a chronic disease. This is no accident!


             Roots of Integrative Gastroenterology

  “A person whose basic emotional and physical tendencies are in balance,
  Whose digestive power is balanced,
  Whose bodily tissues, elimination functions and activities are in balance,
  And whose mind, senses and souls are filled with vitality,
  That person is said to be healthy.”

     Sushruta Samhita, 2000 B.C.
6 INTEGRATIVE GASTROENTEROLOGY




                            AYURVEDIC MEDICINE

The human digestive system is our inside track to balanced health and
vitality. This principle has been the fundamental basis of health and healing for
centuries in Eastern civilization, which comprises most of the world’s popula-
tion today. Sushruta Samhita is one of the founders of modern Ayurdevic
medicine, which is used by healers worldwide to prevent disease and promote
health. The driving principle of Ayurveda (translated as the wisdom and
science of life) is that disease is the absence of vibrant health, which begins in a
breakdown of the spirit, and evolves in definable stages beginning with
improper digestion. According to Sushruta Samhita, the Ayurvedic secret to a
long, happy, and vital life is predicated upon balanced energetic, metabolic,
and protective forces; strong digestion; optimal cellular, tissue and organ func-
tion; efficient elimination; and clear senses, joyful mind, and transpersonal
connection. For more about Ayurveda and digestive health, see Chapter 12.


                      TRADITIONAL CHINESE MEDICINE

Traditional Chinese medicine (TCM) was the first formalized system of health
and healing in modern civilization. In Eastern philosophy, all life occurs within
a circle of nature, with all things in this matrix interconnected and mutually
dependent upon each other. Human beings represent a microcosm of nature
and are the juncture between heaven and earth. In TCM, health and vitality
are predicated upon spiritual connection, balanced living, a vegetable-based
diet, proper digestion, and peace of mind. The flow of energy, or chi, is the
essence of health and well-being. A blockage in the flow of chi through energy
channels called meridians is the beginning of illness, and loss of adaptability is
the beginning of disease.
    In TCM, the foods we eat are not merely nutrients but are vehicles of energy
to be dispersed to our body in either a healthy or unhealthy manner, as deter-
mined by the outcome of digestion. When the digestive fire is too weak or too
strong, the resultant energy imbalances create disharmony and illness. In
TCM, chi is centered around the digestive tract in a ball of energy called the
don tien. This virtual force field of energy circling our digestive tract is essen-
tial to health and well-being.
    Ayurveda and TCM principles guide the care of billions who are among
the world’s healthiest people. These well-proven models of healthy living
share in common sound mind, peace, wholeness and harmony, a healthy
                                               Why Integrative Gastroenterology? 7


vegetarian-based diet, spiritual connection, and herbs for early symptoms of
illness. In both systems, individuals are the sum of their diet and lifestyle
choices. Proper digestion of a healthy diet is the key to a life filled with vibrant
health and free of disease.


                              WESTERN MEDICINE



   “Let food be thy medicine and let medicine be thy food.”
   “Leave your drugs in the chemist’s pot if you can heal the patient
   with food.”
   “Above all else, do no harm.”
                                                    —Hippocrates, 450 B.C.

The Western model of healthcare has been traced to Hippocrates, who is con-
sidered to be the father of medicine. As physicians, we recite the Hippocratic
Oath at our medical school graduation. What I remember most, while reciting
a moving self-proclamation of service to mankind by facilitating healing, is
Hippocrates, as well as Sushruta Samhita and the early emperors of China,
who believed that physicians are healers of the body, mind, and spirit. Th e job
of the physician was to provide proper instruction of diet in the prevention
and treatment of illness. Hippocrates also strongly believed that the body,
mind, and spirit were inseparable in health and disease.

   “As man thinketh in his head, so shall his life be made.”
                                                      —Hippocrates, 1450 B.C.


        Western Philosophy: The Doctor as Mechanic

In the seventeenth century, Rene Descartes and Sir Isaac Newton introduced
the principle of “reductionism,” whereby human beings were viewed as the sum
of their parts, and the matters of the “spirit” were left to religious organizations.
This unfortunate sustained separation of “church and state” excommunicated
the very soul of Western medicine, the doctor–patient relationship. People were
merely the sum of body parts and molecules. The Cartesian principle of medi-
cine forever transformed the delivery of care to its present-day assembly line of
10-minute office visits, whereby the doctor writes a prescription and barely has
time to lay eyes upon his or her patients. Rene Descartes began what managed
care has finished—the near extinction of the physician as a healer.
8   INTEGRATIVE GASTROENTEROLOGY


   Western medicine is a very sophisticated and advanced form of health-
care for acute illness, emergencies, curable malignancies, sustaining chronic
disease, and surgical miracles. When it comes to optimizing health and pre-
venting disease, our results are inferior compared to every country in the
industrialized world. For example, the United States is 41st in longevity among
industrialized countries—dead last! Despite our poor results, Western-trained
physicians still consider the long-standing and highly successful Eastern heal-
ing arts to be archaic and quackery, and proudly view our modern system of
care to be far superior.
   As a profession, we perpetuate this reductionist approach more than ever
before. Doctors in training are now taught that our health is merely the result
of the genes that we inherited from our parents, and that health is all prepro-
grammed and predetermined. This view excludes the possibility that health
also reflects the accumulation of the choices that we make and the circum-
stances around us.
   The reality is that our health and well-being are the result of how our envi-
ronment interacts with our genes. How we were parented, whether we were
breastfed, how we connect to spirit, ourselves, and others, what we eat, how we
process our food and emotions, and whether our lives are balanced or toxic, all
have profound influences on health. Our genes can either become our protec-
tors and partners for wellness, or target practice for pollutants and toxins in
producing illness and disease. We do make choices every day that influence
the expression of our genes.


          Table 1.1. Comparison of Conventional, Western-Based Medicine
                            versus Integrative Medicine
Aspects of care           Conventional                 Integrative

Focus                     Disease detection            Disease prevention

Orientation               Doctor-centered              Patient-centered

Treatment                 Drugs only                   All inclusive

Healing                   Drugs only                   Self-healing

Empathy                   Variable                     Loving

Office visits             Rushed, inattentive,         Open mind, open heart,
                          prescription-oriented        healing

Doctor–Patient            Doctor-centered              Partnership
Relationship

Satisfaction              Low                          High
                                             Why Integrative Gastroenterology? 9


   Nutritional genomics is an evolving field, started by Nobel Laureate
Dr. Linus Pauling and championed by his protégée, Dr. Jeffrey Bland. There has
been an explosion of research showing how nutrients derived from food
directly influence genetic expression and cellular function. There is more to
health and wellness than just the genes that we inherit from our parents.


                The Doctor–Patient Relationship:
               Returning to the Roots of Medicine

Digestive disease specialists are fighting to stay afloat financially by severely
limiting their allotment of time to perform procedures and see patients for
office visits. In the end, patients are being treated as though they are on an
assembly line, rather than being present in the nurturing environment of a
doctor’s office. Likewise, physicians are speeding through patient care encoun-
ters like a “rat race,” constantly fighting an uphill battle.
   As a measure of the modern doctor–patient relationship that has evolved in
the era of Westernized managed care, a study was conducted to determine
doctors’ empathy for patients. Previous work suggests that exploration and
validation of patients’ concerns is associated with greater patient trust, lower
healthcare costs, improved counseling, and more guideline-concordant care.
   The study by Dr. Ronald Epstein and colleagues included 4,800 patient sur-
veys concerning doctor visits, and 100 covertly recorded visits by actors posing
as patients. The results showed that only 15% of the doctors voiced empathy. In
the study, published in the Journal of General Internal Medicine, the research-
ers analyzed the patient surveys and actor visits and characterized the responses
by type, frequency, pattern, and communication style, and correlated them
with patient satisfaction ratings. Empathy was associated with higher patient
ratings of interpersonal care.

   “The best physicians are empathic. They show neither sympathy nor dis-
   dain. Empathy does not develop as naturally as sympathy or disdain. We
   must nurture this emotion, allowing it to blossom. True empathy greatly
   helps the doctor–patient relationship.”
                                                  —Robert M. Centor, 2005

   A key element to Dr. Weil’s vision of integrative medicine is for the practi-
tioner to return to the roots of medicine by fostering partnerships with patients.
We know that the stronger the doctor–patient relationship, the more powerful
the healing response. This is called the placebo response by researchers, but is
underutilized in today’s version of “hit and run” medicine. The restoration of
10    INTEGRATIVE GASTROENTEROLOGY


faith and trust in the treating practitioner by the patient is an essential element
to healing.
    At Johns Hopkins, the first physician-in-charge was Sir William Osler
(1849–1919), who was the father of modern medicine. In his writings and
teachings, Sir William Osler emphasized humanity, compassion, observing
and listening to patients with an open mind and heart, and to minimize the
use of pharmaceutical medications. Following are some excerpts from many of
his famous quotations.

     “Observe, record, tabulate, and communicate. Use your five senses. Learn
     to see, learn to hear, learn to feel, learn to smell, and know that by practice
     alone you can become expert.”
     “It is much more important to know what sort of a patient has a disease
     than what sort of a disease a patient has.”
     “The good physician treats the disease; the great physician treats the patient
     who has the disease.”
     “Teach young physicians to care more particularly for the individual patient
     than for the special features of the disease.”
                                                   —Sir William Osler (1849–1919)


     The integrative practitioner should strive to:
     • Humanize healthcare: Combine old-fashioned caring with superb medical
       care
     • Prevent disease and promote health
     • Listen to and communicate effectively with patients and their families in
       order to form partnerships
     • Appreciate and bridge cultural differences, so that care plans are under-
       stood by their patients
     • Share decision making with patients and their families as partners
     • Emphasize the necessity of a team approach in caring for each patient
     • Integrate the best medical knowledge into healthcare that is accessible,
       patient friendly, and high quality
     • Act as an advocate for patients and the health needs of society
     • Act as a steadfast guide and source of support to patients, no matter where
       they choose to seek specialty care
     • Raise awareness that book-smart doctors can lack emotional intelligence,
       and appreciate how a disease affects a patient’s daily life




  Sir William Osler followed in the footsteps of the ancient Greek physician,
Hippocrates (460–377 B.C.). These quotations by Hippocrates reflect his
                                               Why Integrative Gastroenterology? 11


philosophy of the body’s natural healing force and the importance of proper
nutrition and exercise to good health. There is also a message to young physi-
cians to guide the patient’s healing, that it is better to do nothing than to harm
the patient.

   “Everyone has a doctor in him or her; we just have to help it in its work.
   The natural healing force within each one of us is the greatest force in
   getting well.”
   “To do nothing is sometimes a good remedy.”
   “Walking is man’s best medicine.”
   “If we could give every individual the right amount of nourishment and
   exercise, not too little and not too much, we would have found the safest
   way to health.”
                                                             —Hippocrates


                                  Conclusions

Digestive diseases are responsible for a major economic burden in the United
States and worldwide. Preventive care, education about the influence of diet
and lifestyle on digestive disease development and treatment, and research
support, all lag behind in meeting the need to correct the economic burden
and to provide future generations of scientists in the digestive sciences. Given
the American digestive disease epidemic, there is a need for governments to
readdress this shortcoming and to review its methods of support, as well as for
physicians to adopt an integrative approach to the prevention and treatment of
digestive disease.

   “The doctor of the future will give no medicine, but will interest her or his
   patients in the care of the human frame, in a proper diet, and in the cause
   and prevention of disease.”
                               —Thomas A. Edison, U.S. inventor (1847–1931)


                                       NOTES

 I. The term iatrogenic is defined as “induced in a patient by a physician’s activity,
    manner, or therapy. Used especially to pertain to a complication of treatment.”
II. Sources: Vital Statistics of the United States—1970, National Center for Health
    Statistics, Table 1-26, “Deaths from 281 Selected Causes, by Age, Race, and Sex:
    United States, 1970”; death certificates from 31 states, reported in “Mortality of
    Dentists, 1968 to 1972,” Bureau of Economic Research and Statistics, Journal of the
12 INTEGRATIVE GASTROENTEROLOGY


   American Dental Association, January 1975, pp. 195ff; death reports collected by the
   American Medical Association, reported in “Suicide by Psychiatrists: A Study of
   Medical Specialists Among 18,730 Physician Deaths During a Five-Year Period,
   1967–72,” Rich et al., Journal of Clinical Psychiatry, August 1980, pp. 261ff.;
   Vital Statistics of the United States—1990, National Center for Health Statistics,
   Table 1-27, “Deaths from 282 Selected Causes, by 5-Year Age Groups, Race, and
   Sex: United States—1990”; National Occupational Mortality Surveillance data-
   base, reported in “Mortality Rates and Causes Among U.S. Physicians,” Frank
   et al., American Journal of Preventive Medicine, Vol. 19, No. 3, 2000.
                                      2
   The American Digestive Disease Epidemic
                            GERARD E. MULLIN




                                key concepts

     ■   Digestive diseases are highly prevalent in the United States.
     ■   The age-adjusted increase in the prevalence of digestive diseases
         between 1998 and 2004 was 35%.
     ■   The International Foundation of Functional Gastrointestinal
         Disorders (IFFGD) has projected that the prevalence in America
         today for gastroesophageal reflux disease (GERD) is 30 to
         60 million, and for irritable bowel syndrome (IBS), 30 to
         45 million.
     ■   The annual cost of digestive diseases was estimated to be
         $142 billion annually in 2004.
     ■   Proton pump inhibitors (PPIs) have dominated the pharma-
         ceutical market since 2000. Prescriptions for PPIs collectively
         represent 50.7 percent of total number of prescriptions and
         77.3 percent of total cost in 2004.
                                       ■




            Digestive Disease: The Cold, Hard Facts



I
     n 2002, the American Gastroenterology Association (AGA) became the
     first physician-based organization to address the growing burden of diges-
     tive disease on the nation’s healthcare resources. Led by Dr. Robert S.
Sandler, the AGA published a special report that outlined the prevalence and
economic burden of digestive disease in the United States as of 1998, with finan-
cial projections to the year 2000 (Sandler, Everhart, Donowitz et al., 2002).

                                                                               13
14     INTEGRATIVE GASTROENTEROLOGY


   Due to the changes in perceived disease prevalence, and the rising cost of
technology, the AGA and the National Institutes of Digestive Diseases, Diabetes
and Kidney Diseases (NIDDK) partnered to update the burden of digestive
disorders to the U.S. economy, so that effective resources can be allocated and
directed to disease prevention (Everhart & Ruhl, 2009a, 2009b, 2009c).
   In Sandler’s 2002 report, the estimated direct costs for 17 of the most
common digestive diseases in 1998 dollars was $85.5 billion for all direct costs,
with estimated indirect costs of $22.8 billion, for a total of $108.8 billion.
   Dr. Everhardt and colleagues reported that in 2004, the total direct cost of
digestive disease in the U.S. was $97.8 billion, with estimated indirect costs of
$44 billion, for a total of $141.8 billion. The distribution of costs according to
disease classification in 2004 is shown in Table 2.2.
   From 1998, the prevalence of Irritable Bowel Syndrome (IBS) has risen to
affect from 30 to 45 million individuals (10%–15% of the U.S. population),
according to the International Foundation for Functional Gastrointestinal
Disorders (IFFGD).1


               THE PREVALENCE OF DIGESTIVE DISEASE IN AMERICA

The NIDDK of the National Institutes of Health (NIH) is a government agency
that has collected data from a variety of sources to estimate the burden of
digestive disease.2 The overall prevalence of digestive diseases was reported by
the NIH in 1996 to be 60 to 70 million.

      U.S. Government statistics of digestive disease prevalence were updated in
      a special report on February 02, 2009.(Everhart & Ruhl, 2009a,b,c)



   There are numerous studies that analyze the burden of digestive disease in
the United States. The past decade has seen a rapid expansion of individuals
who suffer from chronic digestive symptoms. The prevalence of digestive dis-
ease in America has reached epidemic proportions. Based on the latest avail-
able evidence, we collected and summarized data on the prevalence of digestive
disease in Tables 2.1 and 2.2. The resulting burden to the U.S economy is shown
in Tables 2.3 and 2.4. Since prescription medications represent a great part
of this financial burden, the costliest medications to consumers are listed in
Table 2.4.

1
    (www.aboutgerd.org)
2
    (http://digestive.niddk.nih.gov/statistics/statistics.htm)
                                               The American Digestive Disease Epidemic 15


             Table 2.1. The Burden of Digestive Diseases in America in 2008
Digestive disease        Prevalence               Prevalence         Year   Reference
                         (% U.S. population)      (U.S. population
                                                  in millions)

Abdominal wall hernia 1.66                          4,968,809        1990   NIDDK

Cancer of digestive      0.9                          255,640        2004   American Cancer
system                                                                      Society

Colonic adenomas         30% above age 50          24,980,000        2006   Levine & Ahnen
                                                                            (2006); Terhaar
                                                                            et al. (2009)

Celiac disease**         1.0                        3,000,000        2007   Green (2006)

Clostridium difficle     1.0                        3,000,000        2007   Ricciardi,
colitis                                                                     Rothenberger,
                                                                            Madoff, & Baxter
                                                                            (2007)

Chronic liver disease/   0.15                         451,710        2007   NIDDK,
cirrhosis                                                                   population-
                                                                            adjusted

Constipation             1.0                        3,100,000        1996   Adams,
                                                                            Hendershot, &
                                                                            Marano (1999)

Diverticulosis           20                        60,200,000        1969   Hughes (1969)

Diverticular disease     0.9–2.2                    2,500,000–       1996   NIDDK, Duggan
(complicated)            4.0                        6,000,000        2006   (2006)
                                                   12,040,000

Gallstones               11–22                     30,000,000–       1999   NIDDK
                                                   60,000,000

Gastritis; non-ulcer     1.4                       37,000,000        1996   Adams,
dyspepsia                                                                   Hendershot, &
                                                                            Marano (1999)

GERD                     30–42                     90,000,000–       2007   Singh et al.
                                                  127,000,000               (2007); http://
                                                                            www.aboutgerd.
                                                                            org

Helicobacter pylori      20–52                     60,000,000–       2002   NEJM. 2003;
infection                                            157,000                347:1175–1186

                                                                                   (Continued)
16    INTEGRATIVE GASTROENTEROLOGY


                                    Table 2.1. (Continued)
Digestive Disease         Prevalence             Prevalence         Year    Reference
                          (% U.S. Population)    (U.S. Population
                                                 in Millions)

Hemorrhoids               3.2–4.4                  8,500,000        1996    Adams,
                                                                            Hendershot &
                                                                            Marano (1999)

Infectious diarrhea       36.4–44.8              135,000,000        1980–   NIDDK
                                                                    1998

IBD                       0.33–0.47                1,000,000–       2007    www.ccfa.org
                                                   1,400,000

IBS                       10–15                  30–45,000,000 2007         http://www.
                                                                            aboutibs.org/

Lactose intolerance       10–16.7%               30–50,000,000 1994         Rusynyk & Still
                                                                            (2001)

Non-alcoholic fatty       22–33%                  66,250,788–       2003    Angulo (2007);
liver disease (NAFLD)                             99,376,182                Suzuki & Diehl
                                                                            (2005)

Pancreatitis              0.05%                      160,000        1995    Everhart (1995)

Peptic ulcer disease      4.90%                   14,500,000        2003    NIDDK

Viral hepatitis

Hepatitis A               31%                     93,500,000        1998–   NIDDK,
                                                                    1994    NHANES (2005)

Hepatitis B               0.05–5%                  1,500,000–       1998–   NIDDK,
                                                  15,057,000        2004    McQuillan et al.
                                                                            (1999)

Hepatitis C               1.36–1.8%                4,100,000–       2007    NIDDK,
                                                   5,420,000                Armstrong et al.
                                                                            (2006)

Hepatitis D               unknown                unknown;           1990    NIDDK
                                                 75,000 new
                                                 cases

* US Population was 301,139,947 as of July 2007.
**Only 3% of people with disease are diagnosed, according to Peter HR Green Available at http://
www.ncbi.nlm.nih.gov/pubmed/17593160/pubmed?term=%22Green%20PH%22%5BAuthor%
5D”Green PH Comment on: HYPERLINK “/pubmed/17355413”Am J Gastroenterol. 2007 Jul;
102(7):1454–60
                                              The American Digestive Disease Epidemic 17


           Table 2.2. The Prevalence and Costs of Digestive Disease in the
                           United States from 1985 to 2004
Diseases                     1985           1998             2004            1985         2004
                          prevalence     prevalence       prevalence         cost          cost
                                                                          ($millions)   ($millions)

Abdominal hernias         4,741,000       4,500,000        4,968,809     2,760           6,078

Constipation              4,458,000       3,100,000        3,100,000       360           1,712

Diverticula               1,900,000       2,500,000      60,200,000      1,550           4,041

Enteric                    8,300,00    135,000,000      135,000,000      4,990           7,300
infections*

Enteritis                 5,700,000      75,000,000      75,000,000        820           1,119
(noninfectious)*

Gastritis–                2,793,000       3,700,000        3,700,000     1,130           1,269
dyspepsia,****

Gallstones                  956,000      20,500,000      30,000,000–     4,710           6,169
                                                         60,000,000

GERD**                      546,000      53,000,000      90,000,000–     1,100          12,639
                                                        127,000,000

GI malignancy               258,000         227,700          255,560     6,080          24,148

Hemorrhoids              10,360,000       8,500,000        8,500,000       830             873

IBD                       2,308,000       1,081,200        1,000,000–      820           2,166
                                                           1,400,000

IBS                       1,379,000       2,100,000      30,000,000–       400           1,007
                                                         45,000,000

Liver disease               552,000      21,950,000     108,825,788–     3,250          13,095
(chronic)**                                             119,928,182

Peptic ulcer*             4,491,000      14,500,000      14,500,000      2,520           3,118

All Digestive            62,000,000      60,000,000– ??????????          56,140         141,826
Disease                                  70,000,000
(Chronic)****

* 2008 data based upon NIH/NIDDK statistics from 1996.
** GERD was not included in the 1985 report as a distinct entity, but rather incorporated as
“GERD and related esophageal diseases.”
*** Chronic Liver Disease includes NAFLD and chronic viral hepatitis (B,C,D).
**** Helicobacter pylori infection was not listed for 1985, and was not included for enteric infec-
tions or gastritis.
**** Prevalence according to NIH/NIDDK; summation by hand shows the true number of diges-
tive disease diagnoses in 1998 to be 345,658,900.
18   INTEGRATIVE GASTROENTEROLOGY


             Table 2.3. NIH Research Expenditures by Disease in FY 2000
Research                                                      $$$

Diseases                                                      (in millions)

Chronic Liver Disease and Cirrhosis                           218.6

Liver Cancer                                                  46.2

Ulcerative Colitis and Crohn’s Disease                        27.0

Pancreatic Cancer                                             20

Gallbladder Disease                                           14.5

Chronic Hepatitis C                                           66.5

Irritable Bowel Syndrome                                      8.2

Peptic Ulcer Disease                                          12.1

Foodborne Illness                                             57.5

Colorectal Cancer                                             205.2

Reprinted with permission from Everhart JE, Ruhl CE. Gastroenterology 2009;136(2):376–386.


               Table 2.4. All Digestive Diseases: Costliest Prescriptions
Drug                         Prescription    Prescription %           Retail Cost    Cost
                               number

Lansoprazole                20,898,993       15.5%                 $3,104,963,208   25.2%

Esomerprazole               19,458,470       14.3                   2,845,565,944   23.1

Pantoprazole                11,716,033         8.6                  1,408,222,944   11.4

Raberprazole                 8,019,431         5.9                  1,135,819,908    9.2

Omeprazole                   8,582,644         6.3                  1,038,622,087    8.4

Mesalamine                   2,448,971         1.8                    468,426,719    3.8

Ranitidine                  13,171,338         9.7                    319,418,374    2.6

Tegaserod                    1,618,699         1.2                    238,030,688    1.9

Ribavirin                      221,035         0.2                    229,351,616    1.9

Peginterferon alfa-2a          131,001         0.1                    191,754,177    1.6

Other                       49,378,593       36.4                   1,351,443,116   11.0

TOTAL                      135,735,478      100.0%             $12,331,718,182      100.0%

Reprinted with permission from Everhart JE, Ruhl CE. Gastroenterology 2009;136(4):
1134–1144.
                                             The American Digestive Disease Epidemic 19


   The U.S. Congress has been relying on NIH/NIDDK figures in allocating
funding initiatives. Thus, the NIH/NIDDK database for the economic impact
of digestive disease was updated in 2009in order to properly advocate for and
allocate government funding. However, an up to date reviewof the prevalence
of digestive disease was not reported. Since individuals can carry more than
one digestive disease diagnosis, it may be difficult to know with certainty the
actual prevalence.


         DIGESTIVE DISEASE AFFLICTS EVERY AMERICAN HOUSEHOLD

Based upon the data in Table 2.1, there were enough digestive disorders in
2007 for each of 301,139,947 Americans to carry at least 2–3 diagnoses each!
For example, in one study, 48% of patients diagnosed with IBS had concomi-
tant GERD.(Nastaskin, Mehdikhani, Conklin, Park, & Pimentel, 2006).
Likewise, many inflammatory bowel disease IBD patients have IBS diagnosed
as well. In other words, many patients suffer from more than one digestive
disorder at a time. This is not surprising, since our Westernized diet and sed-
entary lifestyles have led to many of these digestive illnesses.


    DIGESTIVE DISEASE: A GROWING EPIDEMIC IN OUR WESTERN WORLD

An epidemic3 is a classification of a disease that appears as new cases in a given
human population, during a given period, at a rate that substantially exceeds
what is “expected” based on recent experience. In 1996 the prevalence of diges-
tive diseases was estimated to affect 60 to 70 million Americans. Digestive
diseases are a silent epidemic, and the incredible number of Americans
with functional digestive disorders may be an underestimate of the true U.S.
prevalence.

      In Olmsted County, Minnesota, the reported prevalence of functional gas-
      trointestinal disease (e.g., IBS, abdominal pain) was shown to be 42.3% in a
      recent study by the Mayo Clinic. (Halder et al., 2007)



   A study by Halder and colleagues showed that two-thirds of studied patients
with functional gastrointestinal disorders had chronic symptoms 10 years after


3
    (from Greek epi- upon + demos people).
20    INTEGRATIVE GASTROENTEROLOGY


the onset of disease. This study out of the Mayo Clinic was the longest and
most comprehensive, population-based, follow-up study of functional gastro-
intestinal disorder (FGID) patients, and the only long-term U.S. study.
Dyspepsia (abdominal discomfort as a separate and additional diagnostic
entity) has been recently reported to be present in 11.5% to 14.7% of the popu-
lation (El-Serag & Talley, 2004).


                   LOSING THE DIGESTIVE DISEASE BATTLE

There is no doubt that enormous economic resources are being consumed by
the burden of digestive disease. Despite the losing battle being fought by many
physicians, government funding is funding is inadequately allocated to combat
diseases that are affecting easily over 60 million Americans today. In 2000,
NIH research expenditures for digestive disease research reached a record
$676 million.

     The NIH spent more than 72.5% of its digestive disease budget for just two
     groups of conditions—liver disease ($285 million) and colorectal cancer
     ($205.2 million).



   Certainly, colorectal cancer and liver diseases are worthy causes toward
which to devote available resources. However, there are more than 40 other
known digestive disease conditions that constitute the vast majority of diges-
tive disease prevalence in America, and that deserve proportionate allocation
of resources.
   Despite concerted efforts by the NIH to control the spread of digestive dis-
ease, its prevalence is rapidly rising. For example, celiac disease is now reported
to affect 3 million Americans and is silent in 97% of those who have the dis-
ease, according to Dr. Peter Green in his book, Celiac Disease: A Hidden
Epidemic (Green, 2006). The detection rate can be increased 43-fold just by
instituting proper screening of all patients who have suggestive symptoms.
   Other emerging silent epidemics include non-alcoholic fatty liver disease
and hepatitis C (Angulo, 2007). Non-alcoholic fatty liver disease (NAFLD) has
been estimated to affect from 22% to 33% of Americans and is closely linked to
obesity and insulin resistance as the major factors for its rapid emergence
(Angulo, 2007; Suzuki & Diehl, 2005). The hepatitis C virus is known to infect
4.1 million Americans and 200 million people worldwide, resulting from per-
son-to-person transmission (Armstrong et al., 2006). Due to the epidemic
proportion of hepatitis C in the United States, a special website was established
                                              The American Digestive Disease Epidemic 21


to educate the public and warn about its dangers.4 Both diseases are silent
killers.
   To demonstrate the magnitude of the economic impact of constipation
today, a report published in 2007 analyzed the healthcare resource utilization
of Medicaid patients in California. Dr. Gurkirpral Singh and colleagues from
Stanford University showed that 105,130 patients of the state’s 10 million ben-
eficiaries (1.05%) consumed $18.9 million to treat constipation in a 15-month
period of time. The total economic impact of constipation on the U.S. econ-
omy was estimated to be $54.4 billion in 2007 (Singh et al., 2007).

      The total economic impact to the United States economy would be
      $9.9 billion just to treat constipation for 18.2% of the population on Medicaid
      assistance.



   The Singh et al. study was funded by the Novartis Pharmaceuticals
Corporation of East Hanover, New Jersey. Although the report appears credi-
ble and highlights the magnitude of the problem of constipation in the United
States, there is a self-serving interest for Novartis to fund this study. By show-
ing that constipation produces an untoward economic burden on the U.S.
economy, Novartis can make a strong argument to the FDA to reverse its ban
on Zelnorm (touted as a magic bullet for constipation).
   In order to calculate the true total costs of digestive disease in 2007, the
actual prevalence of disease would need to be known, along with the actual
costs of prescription medications, hospitalizations, procedures, office visits,
and mortality, as well as indirect costs of lost wages and productivity.
   In 2002, an intensive effort by the American Gastroenterology Association
estimated the burden of digestive diseases on the U.S. economy (Sandler RS,
2002). Since 1998, the Consumer Price Index (CPI) has risen approximately
4% per year and the economic impact of digestive diseases today must be in
excess of 40% higher when compared to 1998 statistics, totaling $141.7 billion
((Everhardt JE. 2008).
   In 2008, the economic burden of digestive disease appears to be much
greater than reported in 1998. (Everhardt JE. 2008)We know from the IFFGD
that the prevalence of the irritable bowel syndrome has risen two to three
times since 1998.5 In 2003, the estimated annual direct costs for irritable bowel
syndrome rose to $1.35 billion, having an estimated impact to the U.S. economy
upward of $30 billion annually, excluding prescription and over-the-counter

4
    (http://www.epidemic.org/theFacts/theEpidemic/
5
    (http://www.aboutgerd.org/site/learning-center/congressional-testimony/2007)
22    INTEGRATIVE GASTROENTEROLOGY


medications (Leong et al., 2003; Inadomi, Fennerty & Bjorkman, 2003; Hulisz,
2004).

     IBS is second only to hypertension in healthcare costs in the United States
     annually. (Cash, Sullivan, & Barghout, 2005)



    Pancreatitis, an uncommon disorder, causes more than 200,000 hospital-
izations and costs between $3.6 to $6.0 billion annually (Draganov & Toskes,
2002). The American Digestive Disease Epidemic (ADDE) is wreaking havoc
in the lives of many, and is costing government and industry billions of dollars
annually.
    The most common and costly digestive conditions can be either prevented
(e.g. colorectal cancer) or treated (e.g. NAFLD, GERD) with diet, lifestyle mod-
ifications, improved self-care, and a more integrative approach to healthcare.


                                 CELIAC DISEASE

Celiac disease is the most common genetic disease in Europe. About 1 in
250 people in Italy and about 1 in 300 people in Ireland have celiac disease.
It is rarely diagnosed in African, Chinese, and Japanese people. The prevalence
of celiac disease in the United States is similar to that of Europe. This is
one example of how our North American and European gene pool renders
susceptibility to a diet-induced digestive disorder. : In other words, a combina-
tion of genetic susceptibility and environment (Western lifestyle) produce the
disease.
    Celiac disease, by itself, is of epidemic proportions, but only 3% of affected
individuals have been diagnosed due to the silent nature of this disease. For
example, neuropathy, diabetes, bone disease, anemia and other systemic con-
ditions are caused by celiac disease, but physicians who are unaware of their
association fail to connect the dots. As a consequence, physicians are under-
utilizing available blood tests to screen for celiac disease due to their lack of
recognition of its systemic occult manifestations.


      DIVERTICULAR DISEASE: A WORLDWIDE OR WESTERN DISEASE?

“Westernized” nations such as the United States have prevalence rates of diver-
ticular disease from 5% to 45%, depending on the method of diagnosis and age
of the population. The prevalence of diverticular disease has increased from
                                      The American Digestive Disease Epidemic 23


5%–10% eighty years ago, to 35%–50% in an autopsy series published in 1969
(Hughes, 1969); there are no recent population-based studies. The prevalence
of diverticular disease is age-dependent, increasing from less than 5% at age
40, to 30% by age 60, to 65% by age 85. The overall prevalence of diverticular
disease in America is estimated to be 20% of the population. The hospital
admission rate and surgical rate for diverticular disease has been reported to
have increased by 16% for males and by 12%–14% for females in England from
1990–2000 (Kang et al., 2003).
   Diverticulosis is another example of a disease that has a prevalence in
Europe slightly lower, but not significantly different, than in the United States.
The relatively high prevalence in Europe is related to Westernization of the
European diet. Diverticulosis is rare in Africa and Asia (except in Japan, which
has been rapidly become Westernized) and in cultures that consume a high-
fiber diet (Delvaux, 2003).

   Diverticular disease is a Western condition due to a poor, low-fiber diet in
   our fast-food culture.



   In contrast to the high prevalence in Western societies, the frequency of
diverticulosis in Iran was recently reported to be 1.6% in people above the age
of 20, 2.4% in people above the age of 50, and 1.2% in people between the ages
of 20 and 50 (Dabestani, Aliabadi, Shah-Rookh, & Borhanmanesh, 1981). The
prevalence of diverticula in an aging Western population is relatively high,
compared with the low prevalence in developing countries where a high-
vegetable diet is consumed, because a diet low in plant products is a precipi-
tous factor in the pressure changes needed to produce diverticula. This is the
most generally discussed cause of diverticular disease, and provides the basis
for much of the advice given to reduce the prevalence of diverticular disease,
as well as to manage established disease. Clearly, our unhealthy “Westernized”
diets and lifestyles produce these stark differences in digestive diseases in the
United States versus other, non-Western civilizations.


                            COLORECTAL CANCER

Colorectal cancer is another condition in which Western diets high in satu-
rated fat and red meat and low in fiber, compounded by sedentary lifestyles
and high obesity rates, portend toward a greater susceptibility.
   Colorectal cancer is the most common cancer of the digestive organs,
accounting for more than 60% of all digestive organ cancers and 25% of all
24   INTEGRATIVE GASTROENTEROLOGY


cancer mortality in the United States (Boyle & Ferlay, 2005). In 2004, more
than 660,000 Europeans were living with a diagnosis of colon cancer.
   Colorectal cancer is the second most common cancer in Europe and the
United States. Like diverticular disease, colon cancer is rare in Africa and Asia
(except Japan). In both conditions, a high-fiber diet appears to be protective. A
high-fat diet is a risk factor for the development and recurrence of colorectal
cancer (Rennert, 2007).
   The seven Western behavioral risk factors that are associated with an
increased risk for colorectal cancer are: smoking; low physical activity; low fruit
and vegetable intake; high caloric intake from fat; obesity; high alcohol intake;
and low intake of multivitamins (Coups, Manne, Meropol, & Weinberg, 2007).


                      INFLAMMATORY BOWEL DISEASE

The highest incidence rates and prevalence for ulcerative colitis and Crohn’s
disease (inflammatory bowel disease) are reported in North America and
northern Europe. The lowest incidence rates are reported in South America,
Southeast Asia, Africa (with the exception of South Africa) and Australia.
Aside from differences in sanitation, the dietary association between excessive
consumption of carbohydrates, and polyunsaturated fats such as corn oil and
margarine, correlate with the development of inflammatory bowel disease
(Riordan, Ruxton, & Hunter, 1998; Geerling et al., 2000).


                             GALLSTONE DISEASE

Gallstones are found more commonly in Europe (15.7% prevalence overall)
and the UnitedStates, (13.2%), than in Africa (5%–10%) and Asia (3.1%–6.1%).
The prevalence of gallstones in Europe is higher for northern countries (e.g.,
Norway, 19.7%; Germany, 21.7%) when compared to Chianciano (5.9%) and
Bari (0.1%), Italy. This is believed to be related to the higher intake of saturated
fat in the diet versus the Mediterranean-based diet of the Italian people (Kratzer
et al., 1998; Kratzer, Mason, & Kachele, 1999).


                        IRRITABLE BOWEL SYNDROME

As for IBS, in the United States, Europe, and Canada, the prevalence is 10%–15%
with a female to male ratio of 2:1. IBS is less common in Asia and underdevel-
oped countries, and males and females have equivalent disease prevalence.
                                     The American Digestive Disease Epidemic 25


In China, the history of functional GI disorders (FGID) may be traced back
more than 2,500 years, but it was not until 1987 that more attention began to
be paid to FGID, especially IBS (Si, Chen, Sun & Dai, 2004). A 1996 random-
ized sampling study (2,486 subjects randomly chosen from urban, suburban,
and rural areas of the United States) showed a point prevalence of IBS of 7.01%
(7% of the population at any given time presented with IBS symptoms
(Drossman DA et al., 1996) The point prevalence of IBS in the United States
doubled to tripled in 2004 when compared to 1998. Figure 2.1 shows the world-
wide prevalence of IBS (Gwee, 2005).


              GASTROESOPHAGEAL REFLUX DISEASE (GERD)

GERD is common in the United States, Canada, and Europe, and is uncom-
mon in Asia (except Japan) and underdeveloped regions of the world (Wang,
Luo, Dong, Gong, & Tong, 2004).Like other diseases we have discussed, diet
and lifestyle play a role in disease pathogenesis. The prevalence of GERD and
obesity in Japan has approximated that in the United States in recent years,
unlike the rest of Asia, possibly due to the Westernization of their society. For
example, since the first McDonald’s fast food restaurant opened in Japan on
May 1, 1971, there have been 104 franchises opened, which correlate with the
growth of obesity and GERD.


                      Western-Based Digestive Diseases

  Celiac Disease                        Gallstone Disease
  Diverticular Disease                  Irritable Bowel Syndrome
  Colorectal Cancer                     Gastroesophageal Reflux Disease
  Inflammatory Bowel Disease




                               Conclusions

Despite our affluence and economic world leadership, the United States con-
tinues to struggle with suboptimal pay for performance in healthcare out-
comes, infant mortality, and life expectancy. America and Western societies
continue to be sedentary, obese, consume a nutrition-poor Western-based
diet, and rely solely upon pharmaceutical agents to prevent and treat disease—
thus, digestive disease prevalence continues to soar. An emerging digestive
26   INTEGRATIVE GASTROENTEROLOGY


disease epidemic is damaging the physical and economic health of the United
States. Lessons should be learned from the low prevalence of digestive disease
in countries that adopt more nutritious diets and active lifestyles, and are less
avid consumers of pharmaceutical drugs. The remainder of this book is
devoted to helping those who have a digestive condition to restore their health,
and to those who want to prevent alimentary tract disease and enjoy optimum
health.
                                 3
An Overview of Digestive, Sensing, and
    Immune Functions of the Gut
        PATRICK J. HANAWAY, LAURA K. TURNBULL ,
                 AND GERARD E. MULLIN




                            key concepts

■   The gastrointestinal tract is a “tube within a tube” that performs
    a myriad of functions for each individual.
■   We ingest 30–40 tons of nutrients as food in our lifetime. The
    ability of the gut to properly digest, absorb, and extract the
    nutrients we need determines which of the essential macro-
    nutrients and micronutrients are available for our cells to func-
    tion properly.
■   The gut is our principal interface with our environment, acting
    as the barrier and the sorter of information in the form of food
    and organisms.
■   The concept of “oral tolerance” is the education of our immune
    system by exposure to phytonutrients and organisms (primarily
    bacteria) within the gut that arise after we are born.
■   The bacteria, yeast, viruses, and parasites that coexist within our
    gastrointestinal tract are known as the commensal flora, or gut
    microflora.
■   We are born with the keys (known as toll-like receptors and pat-
    tern-recognition receptors) to relate directly to, learn from, and
    integrate the messages from our environment (food and flora)
    directly into our beings via our immune systems.
■   The enteric nervous system, or “second brain,” has more neu-
    rotransmitters in the gastrointestinal tract than in the entire
    brain.
                                   ■



                                                                          27
                                Introduction



T
        his chapter moves beyond the descriptive view of gut function, and
        serves to illustrate the systems approach to understanding the interre-
        lationship of major gut functions. The evaluation of fundamental pro-
cesses helps us to understand when, how, and if there is an imbalance within
the gut, as well as how to bring it back into balance (i.e., treat it!). Thus, we
have organized the chapter according to the five elements of traditional Chinese
medicine, the very roots of integrative gastroenterology:

   • the process of digestion and absorption (EARTH/nurturance)
   • the selective barrier function that defines our relationship to the
     “outside” world (WOOD/structure)
   • the commensal microflora of the gut with which we are interdepen-
     dent (METAL/interrelationship to the web of life)
   • the physiologic inflammation that is necessary to activate and main-
     tain the immune surveillance system (FIRE/connection)
   • the enteric nervous system, which communicates with the rest of the
     body—based upon all of the above inputs. (WATER/balance).


                       THE GASTROINTESTINAL TRACT

The gastrointestinal tract, the tube within a tube, connects us to our environ-
ment through a dynamic interface that is larger than a doubles tennis court.
Over the course of our lifetimes, we will ingest 30–40 tons of macronutrients,
micronutrients, chemicals, and toxins, providing the building blocks for every-
thing human. Disturbances in our functional ability to make the most of these
nutrients have ramifications on every aspect of our being, and imbalance in
the gastrointestinal system has implications that extend far beyond gastroin-
testinal symptoms. Thus, in nearly every clinical interaction, the clinician must
be vigilant to gastrointestinal dysfunction.
   Classically, the role of digestion and absorption are considered the principal
functions of the gastrointestinal epithelium. The quality of discernment that
traditional Chinese medicine (TCM) attributes to the “small intestine official”
is manifested through its ability to “separate the wheat from the chaff ” (Jarrett,
1999), but is also seen in the intertwined relationship of the innate and
adaptive immune system within the gastrointestinal system. The role of
diet and nutrients in the balance of the commensal flora, the role of digestion
and absorption in providing proper macronutrients and micronutrients,
            An Overview of Digestive, Sensing, and Immune Functions of the Gut 29


the appropriate physiologic inflammation, the development of “oral tolerance,”
the production of neurochemicals within the “second brain,” and the appro-
priate excretion of waste, are the functions that must remain within balance to
foster health and well-being.
   Dysfunction within the gastrointestinal system manifests in typical diges-
tive diseases such as: gastroesophageal reflux “disease” (GERD), irritable bowel
syndrome (IBS), inflammatory bowel disease (IBD; Sansonetti, 2004), non-
alcoholic steatohepatitis (NASH; Angulo, 2002), and even colorectal cancer
(CRC; McGarr, Ridlon, & Hylemon, 2005). It is also necessary for us to
recognize that gastrointestinal dysfunction can manifest as imbalanced immu-
nologic function, thus creating both atopic illness (Brandtzaeg, 2002), includ-
ing allergy and asthma, and autoimmune dysfunction (Rook et al., 2004),
including rheumatoid arthritis, Type I Diabetes Mellitus, and Hashimoto’s
thyroiditis.


   Other diseases of immune dysregulation and gastrointestinal dysfunction
   now include the autism spectrum disorders.


    The evolution of these diseases begins long before the presentation of symp-
toms; thus, the opportunity for prevention and early intervention can have
tremendous impact on the burden of suffering and disease.
    Dietary approaches provide the most effective means of returning balance
to dysfunction within the gastrointestinal system, and there are many oppor-
tunities to bring these tools to patients. However, the profound dietary changes
that man has adopted over the past 10,000 years, and that have accelerated
over the past 100 years, have created a discord between the nutritional input
that our genetic structure has evolved to maximize, and what we are choosing
to ingest (Cordain et al., 2005). This discordance creates a much more complex
array of clinical opportunities for supporting the whole being to regain bal-
ance and optimal function.
    Diagnostic considerations include, first and foremost, an extensive health
history with an exploration of the patient’s dietary inputs, as well as his or her
utilization of antibiotics, laxatives, fiber, herbs, etc. In addition, one must elicit
the current pattern of bowel movements including frequency, history, abdom-
inal pain, gas, bloating, duration, and relationship of bowel elimination to
meals. It is amazing how many patients consider their altered bowel move-
ments to be normal. Western medicine does not have a defined norm of bowel
movement frequency, while other forms of healing such as Ayurveda and TCM
(see figure 3.1 A) view the regular functioning of the gastrointestinal tract to be
a critical barometer of health and well-being, with one well-formed bowel
movement per day to be the norm (Svoboda & Lade, 1988). Other diagnostic
30    INTEGRATIVE GASTROENTEROLOGY


considerations include the evaluation of stool to gather information on param-
eters of digestion, absorption, inflammation, infection, intestinal permeability,
and altered gut flora (known as dysbiosis).
   Let us look more closely at the specific functional imbalances faced by clini-
cians, as we examine how they manifest in pathophysiology and how they can
be rebalanced to optimize health.


                        Digestion and Absorption

                                    DIGESTION

As simple as it seems, basic evaluation of digestion and absorption are often
not part of the initial evaluation of gastrointestinal function in patients
with IBS.


     Factors that have a negative impact on digestion of food include: inadequate
     mastication, hypochlorhydria, pancreatic insufficiency, bile insufficiency,
     and villous atrophy. Mastication is a simple clinical point to make with
     patients and is often overlooked (see Chapter 38 by Dr. Memoli).




                 IATROGENIC HYPOCHLORHYDRIA AND GERD

The plethora of advertisements claiming we have too much stomach acid
appears to limit the clinical relevance of hypochlorhydria when, in fact, there
is no evidence to support this assertion. In actuality, the symptoms associated
with gastroesphageal reflux are more likely attributed to our current diets and
lifestyle (i.e., obesity), leading to laxity of the gastroesophageal (GE) junction
and causing excessive reflux of gastric enzymes, acid, and bile. Measures to
block the production of gastric acid do not address the root cause of the
pathologies and core imbalances that produce the symptoms of heartburn—
mainly, disordered gut motility and impaired lower esophageal sphincter pres-
sure from structural derangements (i.e., hiatal hernia). By overlooking these
structural anomalies and, instead, emphasizing pharmaceuticals to reduce
stomach acid, we induce a state of hypochlorydria, making patients more sus-
ceptible to vitamin and mineral deficiencies, as well as alterations in the normal
microbial flora. A more integrative approach to heartburn that addresses these
core imbalances is addressed by Dr. Minocha in Chapter 39.
            An Overview of Digestive, Sensing, and Immune Functions of the Gut 31



  Consequences of suppressing gastric acid production include: vitamin defi-
  ciency (folate, B12), mineral deficiencies (calcium, magnesium, zinc, iron,
  chromium, manganese, and copper), altered bowel flora, dysbiosis, and
  small bowel bacterial overgrowth.




       IATROGENIC HYPOCHLORHYDRIA AND SMALL INTESTINAL
                 BACTERIAL OVERGROWTH (SIBO)

In addition to the important nutrient absorption implications, the role of low
stomach acid in IBS is particularly notable in small intestinal bacterial over-
growth (SIBO). Pimentel, Chow, and Lin (2000) demonstrated that 78% of
IBS patients tested were positive for SIBO, a condition in which coliform and
anaerobic bacteria from the large intestine produce deleterious effects within
the delicate environment of the small intestine.
   The common assay to evaluate for SIBO utilizes the fermentation of
sugars, such as lactulose, which stimulates gas production (hydrogen and
methane) measurable with a simple breath test. Total gases reflect the quantity
of coliform and anaerobic bacteria present in the small intestine. Treatment
commonly includes the use of broad-spectrum antibiotics for 7–10 days to
eliminate the overgrowth. Pimentel, Chow, and Lin (2000) reported that
48% of patients no longer met the Rome II criteria for IBS when treated with
rifaximin. Although antibiotics are the mainstay treatment of conventional
medicine, other herbal preparations containing berberine, along with essential
oils, will have a similar bacteriocidal effect (see Chapter 7). Lactobacillus
acidophilus and Lactobacillus casei help minimize the side effects of antibiot-
ics, and independently decrease the hydrogen gas production (Gaon et al.,
2002).
   While antimicrobial agents are important to eliminate excessive and dis-
placed colonic flora, it is also necessary to address the underlying root
causes of SIBO, including antacids, proton pump inhibitors, antihistamines,
slowed transit time, maldigestion, lactose intolerance, and excess simple carbo-
hydrates (see Chapter 7).



                        PANCREATIC INSUFFICIENCY

Pancreatic insufficiency is a common dysfunction that can be evaluated non-
invasively. Beyond symptoms of maldigestion (belching, bloating, flatus),
32 INTEGRATIVE GASTROENTEROLOGY


there are relationships between decreased pancreatic function, osteoporosis
(Moran et al., 1997), and diabetes (Hardt et al., 2000). Evaluation of pancreatic
function can utilize pancreatic enzymes, such as chymotrypsin and elastase, or
indirect markers, such as fecal fat. Elastase is the most sensitive marker of
pancreatic insufficiency because, unlike chymotrypsin, it is not subject to bac-
terial degradation as it flows through the gastrointestinal tract. Treatment is
simple, with pancreatic enzyme supplementation being a safe and effective
therapeutic intervention to improve digestive function.



                                 ABSORPTION

A fundamental source of malabsorption is maldigestion, as evidenced by the
example of SIBO. Maldigestion of fermentable starches (i.e., legumes) can
cause an overgrowth of bacteria, which injures the gut integrity and results in
a subsequent decrease in absorptive capacity. In addition to its critical role in
oral tolerance and immune activation, the intestinal mucosa absorbs nutrients
while acting as a barrier to toxins and macromolecules.



                             Barrier Function

The ability of the body to be able to discern between friend and foe highlights
the critical importance of the single-cell-layer gastrointestinal mucosa. This
physical barrier, as large as a high school basketball court, provides the princi-
pal interface through which the body communicates with its environment. In
addition to this single-cell layer, the gut microflora provide an additional bar-
rier by competing with pathogens and producing a mucopolysaccharide
matrix, known as the biofilm.
   Alterations in barrier function through intestinal permeability [a.k.a.
“leaky gut”], changes in the microflora, and alterations in the biofilm layer can
lead to immune upregulation. Permeability changes in the gut mucosa can
have profound effects on anatomic and immunologic barriers to disease
(Figure 3.2) (Baumgart & Dignass, 2002). Intestinal permeability can lead to
increased inflammatory cytokine production, and a propagation of inflamma-
tion within the intestine (Clayburgh, Shen, & Turner, 2004). In fact, there is a
great deal of evidence linking increased intestinal permeability with multior-
gan system failure, systemic disease and immune dysfunction (DeMeo et al.,
2002).
               An Overview of Digestive, Sensing, and Immune Functions of the Gut 33




 ALTERED BARRIER FUNCTION: INCREASED INTESTINAL PERMEABILITY

A central theme of this book is that a number of conditions (stress, toxins,
inflammation, infection, poor diet, etc.) can alter the barrier function and
increase intestinal permeability, thus creating a “leaky gut” (see Chapter 7).
Animal models demonstrate that stress significantly increases intestinal per-
meability (Baumgart & Dignass, 2002), particularly in the cases of trauma and
sepsis (Wells, Hess, & Erlandsen, 2004).
   This process of intestinal permeability is not a disease entity unto itself, but
rather a dysfunction that can increase the overall toxic and antigenic burden.
When the paracellular junctions are altered, there is an increased antigen pre-
sentation to the immune system (Figure 3.3, Table 3.1). Alessio Fasano, one of
the world’s leading researchers on celiac disease, proposes that intestinal per-
meability is also a necessary precursor for many autoimmune diseases, and
these processes can be prevented by reestablishing intestinal barrier function
(Fasano & Shea-Donohue, 2005).
   With autoimmune disease, the presentation of an environmental antigen to
the gastrointestinal mucosal immune system first requires that the antigen
pass from the intestinal lumen into the submucosal layer, then on to the mes-
enteric lymph nodes and the Peyer’s patches. Immune activation occurs if and
when there is a genetic predisposition to respond aberrantly (overactively) to
the environmental antigen (Clemente et al., 2003). For example, those patients
who are DQ2 and DQ8 positive will have the genetic basis for gliadin’s activa-
tion of the inflammatory cytokine pathways. This pathophysiologic process is
predicated upon the incompletely digested molecule traversing the intestinal
barrier to initiate this sequence of events.



                 Table 3.1. Diagnoses of Altered Intestinal Permeability
Intestinal permeability test interpretation

Mannitol                          Lactulose         Suspect

Normal/High                       High              Increased Permeability

Low                               Low               Malabsorption

Low                               High              Increased Permeability &
                                                    Malabsorption
34   INTEGRATIVE GASTROENTEROLOGY


   Increased permeation of intestinal luminal antigens into the portal circula-
tion leads to an increase in the inflammatory and metabolic stress on the liver.
Removal of the initial conditions is necessary to reverse this increase in intes-
tinal permeability. L-glutamine and zinc carnosine have been demonstrated to
be important in supporting the healthy growth of enterocytes and microvilli
(Zhou et al., 2003). Probiotics have also been shown to reverse increased intes-
tinal permeability in infants, over and above their anti-inflammatory effects
(Isolauri, Kirjavainen, & Salminen, 2002).


       MALABSORPTION: DECREASED INTESTINAL PERMEABILITY

Absorption of nutrients is impaired when there is chronic inflammation of the
small intestine, which injures the villi. The absorption of dipeptides, monosac-
charides, and long-chain fatty acids is dependent upon the available surface
area of small intestine. Since microvilli increase the absorptive area of the
small intestine by a log-order of magnitude, minimal assaults have a tremen-
dous impact upon vitamin and nutrient absorption. Conditions that may pro-
duce substantial inflammation and injury to the small intestine include, but
are not limited to, Crohn’s disease, celiac disease, and infections. However, iat-
rogenic injury from medications such as nonsteroidal anti-inflammatories is
an overlooked but common cause.


                                   GUT FLORA

The makeup of the community of organisms that comprise the microflora of
the gut is principally established during the first one to two years of life, and is
maintained throughout our lives. The composition of the gut flora is indicative
of our environmental exposures prenatally, intrapartum, and throughout
infancy. Factors that influence the succession of gut flora from that time for-
ward include type of delivery (Penders et al., 2006), feeding habits (Harmsen
et al., 2000), gestational age, hospitalization (Björkstén, 2004), and infant anti-
biotic use (Teitelbaum & Walker, 2002). At birth, the digestive tract is sterile
but begins to be colonized within the first few days of life. During the subse-
quent two years of life, the GI tract becomes home to 100 trillion commensal
bacteria, fed by milk and other foods. These simple foods that stimulate the
growth and maintenance of bowel flora are known as prebiotics.
    Cordain describes the dietary patterns most common today, and compares
them with the characteristics of ancestral diets Cordain et al., 2005).There
are significant alterations in glycemic load, fiber content, essential fatty acid
            An Overview of Digestive, Sensing, and Immune Functions of the Gut 35


composition, pH balance and macronutrient/micronutrient composition. All
of these factors have tremendous effects on the balance of the commensal flora
within the gastrointestinal tract.

   Because nearly 70% of the immune system is localized to the digestive tract,
   a state of controlled physiologic inflammation, along with environmental
   contact with commensal bacteria, is essential for proper development of the
   immune system.



   New evidence is evolving that the persistent interactions between host and
bacteria taking place in the gut may constantly reshape the immune system
(Guarner & Magdelena, 2005). Clinicians see the profound effects of altered
commensal flora in the nearly 20% of the population who are affected by the
functional GI disorder, irritable bowel syndrome (IBS) (Drossman, Camilleri,
& Whitehead, 1997). It is also becoming clear that the immune dysregulation
of Crohn’s disease and ulcerative colitis (IBD) is profoundly influenced by the
role of gut flora (Shanahan, 2004).
   Immune balance is maintained as gastrointestinal microflora compete with
pathogens to prevent inflammation and intestinal permeability. In addition, met-
abolic processes facilitate the proper breakdown of foods, thus minimizing gas-
trointestinal inflammation. Finally, these bacteria help to stimulate growth and
epithelial cell differentiation. These processes together provide the importance of
gastrointestinal microflora in preventing and treating intestinal permeability.


                                   BIOFILMS

In addition to the role of individual organisms within the gastrointestinal
microflora in promoting homeostasis and decreasing intestinal permeability,
there is an additional interest in the collective action of these bacteria working
together to form unique ecological niches, the biofilm layer. This 30-micron-
thick layer of “pond scum” acts to protect the intestinal lining, metabolize food
remnants (especially carbohydrates), and may communicate with the immune
system. In fact, it is postulated that the short-chain fatty acid (SCFA) synthesis
that provides energy to the gut epithelium may also be involved in the “cross-
talk” that influences the development of humoral and cell-mediated portions
of the mucosal immune system. When an inflammatory process is present
within the gut, the 30-micron-thick biofilm layer decreases in thickness, and
there is a concomitant increase in intestinal permeability (Swidsinski et al.,
2007).
36   INTEGRATIVE GASTROENTEROLOGY


   The bacteria growing in these biofilm structures often behave differently
from their nonadherent counterparts, with changes in the nature and efficiency
of their metabolism (Macfarlane & Macfarlane, 2006). Once the bacteria in
the gut achieve a certain concentration, they begin to communicate across
species, which changes the fundamental expression and action of the DNA
from that of an individual cell to that of a multicelled organism. This phenom-
enon is known as quorum-sensing, a truly holistic phenomenon in which the
“whole is greater than the sum of the parts” (Sifri, 2008).


                             GUT IMMUNOLOGY

The process of oral tolerance is analogous with the view of traditional Chinese
medicine (TCM) regarding the “small intestine meridian.” Note that the chan-
nels of “chi” are not limited to physical properties; thus, the “sorter” (as this
meridian is also known) is involved in “separating the wheat from the chaff ”
through digestion and absorption, but it is also involved in the process of
teaching the immune system to determine self from nonself via oral tolerance,
as well as all other “sorting” functions throughout body, mind, and spirit. This
phenomenon relates, deeper still, to the concept of sorting through informa-
tion for decision making in which we have a “gut feeling,” and learning to trust
that quality of “sorting”—even when it may not make sense.
   Through the process of evolution, the body has developed a number of
methods to identify microbes and modulate the adaptive immune system,
based upon the proper timing and presence of the bacterial stimuli. The body
responds differentially to bacterial stimuli, and responds to a variety of struc-
tural components on each bacterium. The innate immune response stimulates
the adaptive immune system and influences the nature of the adaptive response
(Figure 3.4; see Abbas & Lichtman, 2003). The process of “oral tolerance” is an
important example of this. (Brandtzaeg, 2002).
   Oral tolerance is mediated by regulatory T cells (Treg), which have anti-
inflammatory capabilities. Precursor T cells are transformed into Treg cells
when antigen-presenting dendritic cells (DCs) of the gut have not been exposed
to inflammation. Precursor T cells are transformed into Teffector cells (TH1 or
TH2) when the DCs are mature (i.e., activated by inflammatory signals)
(McGuirk & Mills, 2002). However, gut flora (like Lactobacillus) can down-
regulate DC maturation, thus preventing the activation of Teffector cells (Figure
3.5; see Christensen, Frøkiaer, & Pestka, 2002).
   The gut flora trains the innate immune system to begin to recognize “self.”
There are molecules of recognition—pattern recognition receptors (PRR),
            An Overview of Digestive, Sensing, and Immune Functions of the Gut 37


toll-like receptors (TLR), and pathogen-associated molecular patterns
(PAMP)—that facilitate the mucosal immune system’s awareness of the bacte-
rial environment, and determine its release of stimulating or suppressive
cytokines (see figure 3.6). The epithelial mucosa is equipped with PRRs
that recognize bacterial DNA from commensal bacteria and effectively modu-
late immune function (Jijon et al., 2004). Pathogenic bacteria will upregulate
the adaptive immune system (via IL-12) within the Peyer’s patches and the
mesenteric lymph nodes, inducing NF-kB activation of the inflammatory
cascade Figure 3.7). Conversely, the normal gut microflora promotes immune
modulation (via IL-10) and has anti-inflammatory properties (Figure 3.8
and 3.9).
   Disruption of gut flora disrupts oral tolerance by driving the T effector
responses in the gut toward a TH1 proinflammatory response. Correction of
gut flora improves oral tolerance. Thus, the immune system is dynamically
educated by the presence of bacteria at the interface of the intestinal epithe-
lium. The gut flora interacts with our innate immunity, and influences the
adaptive immune response, in an important dialogue between the immune
system and the environment. Commensal bacteria are also able to modulate
expression of host genes involved in important intestinal functions, including
nutrient absorption, mucosal stimulation, xenobiotic metabolism, and intesti-
nal maturation (Hooper et al., 2001).
   Different bacteria induce different immunologic responses. Nonpathogenic
bacteria also elicit different cytokine responses from epithelial cells, inducing
differential effects on the gut-associated lymphoid tissue GALT and the adap-
tive immune system (Borruel et al., 2002).Because of this dynamic interplay
between the gut flora and the GALT, the immunologic response system can be
modified, based upon dietary change (in the form of prebiotics) and beneficial
bacteria (in the form of probiotics).
   Hooper and Gordon (2001) have highlighted the effects of imbalance within
this complex ecosystem. Their work has expanded our understanding of
the metabolic effects of the microflora by highlighting the metabolic effects
that altered gut flora can have on the development (and treatment!) of obesity.
The increasing prevalence of allergy and atopy are associated with alterations
of intestinal colonization, and decreased tolerance to common food proteins
and inhaled allergens. Treatment with probiotics has helped to shift these
symptoms back to normal (Kallomaki et al., 2003). Overall, we see that these
critical environmental interactions highlight immunologic dysregulation
arising from the combination of varied bacterial species (commensal and
pathogenic), altered adaptive immune system activation, and multiple anti-
genic stimuli.
38 INTEGRATIVE GASTROENTEROLOGY




                       Enteric Nervous System

                FACTORS INVOLVED IN GUT HOMEOSTASIS

Gastrointestinal homeostasis requires a dynamic balance of the “five elements”
of gastrointestinal function (digestion/absorption, intestinal barrier, enteric
commensal flora, enteric nervous system, mucosal immunity; see Figure 3.1).
Under the guidance of the central nervous system (CNS), the enteric nervous
system regulates digestive functions (i.e., digestion, motility) and is crucial to
our overall health and well-being.
   In order to achieve homeostasis, the enteric and central nervous systems
communicate via bidirectional signaling. Our ability to adapt to psychological
and physical stressors depends upon an optimal functioning of this signaling
pathway. In the face of emotional stress, a sympathetic dominant state of ner-
vous system operation diminishes blood flow and motility to the gut, leading
to severe impairments in digestive function (Schwetz, Bradesi, & Mayer, 2004).
Thus, when there are interferences in Enteric nervous system – central ner-
vous system ENS–CNS coordination in functional bowel disorders such as
IBS, consequent disordered modulation of gastrointestinal motility, visceral
pain thresholds, barrier defenses, mucosal immune responses, and nutrient
processing occur (see Chapter 33).



                         ROLE OF GUT MICROBIOTA

It has been long thought that disordered regulation of serotonin production
played a central role in the pathogenesis of IBS (Sikander, Ranam, & Prasad,
2009). However, emerging evidence suggests that the crosstalk between the
enteric nervous system (ENS) and the central nervous system (CNS) is influ-
enced by the interplay between by-products of the gut microbiota and the
enteric nerve terminals (ENTs), through the enterochromaffin cells (ECs; see
Rhee, Pothoulakis, & Mayer, 2009). Thus, the enteric microbiota can directly
influence the relationship between the ENS and the CNS (Figure 3.10 .). Rhee
and colleagues have recently reviewed 85 articles that, in totality, suggest that
the enteric microbiota maintain gut homeostasis by regulating motility,
immune responses, and processing of nutrients (2009).
           An Overview of Digestive, Sensing, and Immune Functions of the Gut 39




            UNIDIRECTIONAL SIGNALING (BRAIN              ENTERIC)

Altered brain states, such as psychological stress, can modulate the biomass
and composition of the enteric microbiota (Bailey, Lubach, & Coe, 2004).
Furthermore, the enteric bacterial environment may be directly linked to the
increased motility caused by stress states (resulting in shedding of the organ-
isms). The emotional motor system (EMS) of the brain causes changes in the
flora in two ways (either alone or in combination) (Holstege, Bandler, & Saper,
1996):

  • Directly via host enteric microbiota signaling
  • Indirectly via changes in the floral environment

   As to which populations of the enteric flora are most influenced by the
EMS, reports suggest that the bacteria in biofilms that adhere to the epithe-
lium are actually less vulnerable than luminal populations to the changes in
motility and luminal contents. As a consequence, bacteria in biofilms are more
involved in bidirectional signaling than luminal populations (Macfarlane &
Dillon, 2007).


       CNS-Related Changes in the Gut Environment

                         PARASYMPATHETIC TONE

In the state of parasympathetic tone, the vagus nerve of the CNS establishes
the rhythmic propagation of gastrointestinal (GI) motility to ensure its “house-
keeper” function. Thus, GI motility affects the delivery of nutrients to enteric
flora, alters the pH of the luminal environment in both healthy and diseased
states, and protects the proximal gut against the buildup of the colonic type of
enteric flora (i.e., SIBO; see Van Felius et al., 2007).


            SYMPATHETIC NERVOUS SYSTEM, ENTERIC FLORA
                    AND MUCOSAL IMMUNITY

The aforementioned biofilm is the part of the enteric flora that is adherent to
the gut epithelium. Or, These bacteria influence mucosal immunity and enteric
nerves differently than luminal microbes. The intestinal mucus layer is
40   INTEGRATIVE GASTROENTEROLOGY


the habitat for the biofilm. In a sympathetic dominant state, unregulated
stimulation of the autonomic nervous system (ANS), or insufficient regulation
by the parasympathetic nervous system, impairs proper mucus secretion, thus
affecting the biofilm (Cooke, 2000). As shown in Figure 3.11 XXX., the sym-
pathetic nervous system can moderate the mucosal immune system’s response
to luminal bacteria via degranulation of mast cells, whose by-products
(i.e., corticotropin-releasing factor; CRF) increase intestinal permeability,
thus allowing even more nonselective antigen presentation to gut macrophages
driving the process in a feed-forward manner. Under stress conditions,
intestinal barrier function is weakened by a number of different mechanisms
other than local release of CRF, and is reviewed elsewhere (Demaude et al.,
2006).


            BIDIRECTIONAL SIGNALING (BRAIN                ENTERIC)

Enteric microbes can affect intestinal motility, which can either assist (espe-
cially Bifidobacterium bifidum & Lactobacillus acidophilus, to promote motil-
ity) or harm (Escherichia inhibits motility) the host (Mazmanian, Round, &
Kasper, 2008). Since the by-products of bacteria within the intestines can
influence gut motility by stimulating the enteric nervous system, dysbiosis
can, therefore, alter gut motility in the host—which, in turn, affects the bal-
ance of enteric microbes.
   Another key concept that is central to this discussion is that there is an
ongoing dialogue between the enteric flora and the intestinal epithelium, as
well as crosstalk between different luminal bacterial species themselves (a.k.a.,
interkingdom signaling; see Figure 3.12 (Hughes & Sperandio, 2008). For exam-
ple, enteric bacteria can cause the release of norepinephrine into the intestinal
lumen, along with an increased expression of adrenergic receptors on the gut
epithelium, to influence fluid and electrolyte secretion and local immune func-
tion (Valet et al., 1993).
   As mentioned previously, quorum sensing (Lowery, Dickerson, & Janda,
2008) is a type of decision-making process used by decentralized groups to
coordinate behavior. Many species of bacteria use quorum sensing to coordi-
nate their gene expression according to the local density of their population. It
is used by bacteria to regulate gene expression by responding to signals from
both other bacteria and the host. The signals received by the bacteria (from the
host and other bacteria) regulate physiological processes within the bacteria,
including pathogenicity, metabolite production, and bacterial motility.
Therefore, through interkingdom signaling and quorum sensing, the host’s
nervous system can influence microbial behavior (Hughes & Sperandio, 2008).
            An Overview of Digestive, Sensing, and Immune Functions of the Gut 41


While this has been demonstrated in pathogenic bacteria, it is likely that it is
also the case in commensal flora.

  Microbial signals can interact with afferent nerve terminals when there is
  compromised intestinal integrity (as in leaky gut, stress, or inflammation).
  As intestinal permeability increases, bacterial by-products and inflamma-
  tory mediators are able to directly access nerve endings in the mucosa.




                   Neuroendocrine Immune Signaling

The signals released from bacteria interact with receptors on both other bacte-
ria and on host cells, which influence the nervous system via endocrine,
immune, and neural signaling mechanisms. The effects on gastrointestinal
function of signals released by enteric microbes are widely studied, but the
systemic consequences are less well known (Walsh & Mayer, 1993).
   Enterochromaffin cells (EC cells) produce mediators (i.e., serotonin) that
serve as signal transducers to translate bidirectional signals from the enteric
microbes to the nerve terminals. EC cells have access to the microbes on the
luminal side, and both afferent and efferent nerve terminals on the lamina
propria, making them ideal for bidirectional signaling. Enterochromaffin cells
secrete signaling-gut-derived peptides such as serotonin, CRF, cholecystoki-
nin and somatostatin, in response to factors elaborated by gut microbes
(Figure 3.12; see Wheatcroft et al., 2005).
   EC cells can affect gut motility via elaboration of the main neurotransmitter
of the gut, serotonin, whose production is impaired in IBS (Sikander, Ranam,
& Prasad, 2009). Furthermore, the state of the luminal environment is trans-
mitted to the CNS by the vagus nerve, the nerve terminals of which are near
EC cells. Thus, signaling from EC cells to the afferent terminals of the vagus
nerve could directly connect chemical signaling within the lumen to supra-
spinal networks.


  In unhealthy people where there is increased intestinal permeability,
  microbe signaling is able to directly access the nerve terminals, which may
  be a port of entry for the microbes to interact with the CNS (brain). However,
  in healthy individuals with an intact intestinal barrier, the mechanism by
  which this microbe–brain communication occurs is principally governed by
  EC cells.
42   INTEGRATIVE GASTROENTEROLOGY




                                Conclusions

Proper balance of form and function are required for the human system to be
in homeostasis. Nowhere in the body is this more true than in the principal
interface we have with our environment—taking in food, digesting and absorb-
ing, defending ourselves from invaders, stimulating the development of our
immune system, communicating the “status quo” throughout the body, and
living in “right relationship” with the gastrointestinal microflora. Each of these
functional components will produce pathophysiologic changes when they
are not in balance. The diagnostic and therapeutic approach of integrative
(or functional) gastroenterology is to observe the patient through these
lenses, rather than the final symptom complex referred to as ICD-9 diagnoses.
The functional approach focuses on returning the system to balance, rather
than elimination of symptoms, and offers tools that help with gastrointestinal
disease but also help with many diseases throughout the body that have their
origins within the gastrointestinal tract.
                                  4
 The Intestinal Microbiota in Health and
Disease: Bystanders, Guardians or Villains?
                        FERGUS SHANAHAN




                             key concepts

 ■   A resurgence of interest in the gut microbiota, enabled by
     advances in nonculture-based molecular techniques, has shown
     the importance of host–microbe interactions in gastrointestinal
     maturation and homeostasis.
 ■   The microbiota is a health asset, but occasionally a contributor
     to the pathogenesis of gastrointestinal disease and to certain
     extra-intestinal disorders.
 ■   Elements of a modern lifestyle, such as urbanization, domestic
     hygiene, antibiotic usage, and family size, represent proxy mark-
     ers of environmental influence on the composition of coloniz-
     ing microbiota in early life.
 ■   Comparative studies of germ-free and colonized animals pre-
     dict the existence of microbial-derived signals which can be
     mined for bioactives or novel drug discovery.
 ■   Host–microbe interactions in the gut are bidirectional.
                                    ■




                            Introduction



T
     here is an ongoing resurgence of interest in the alimentary microbiota
     (flora). For basic scientists, this is being driven, in part, by improve-
     ments in technology, particularly molecular approaches for studying


                                                                           43
44 INTEGRATIVE GASTROENTEROLOGY


the microbiota. For clinicians, the discovery that Helicobacter pylori causes
peptic ulcer disease is a continual reminder of the possibility that other chronic
diseases may have a microbial basis. Indeed, the most important lesson of that
discovery is that the solution to some diseases may never be found if research
remains focused on the host, without due attention to the host–environment
interface. Furthermore, the contribution of the microbiota to gastrointestinal
maturation and maintenance of mucosal homeostasis has stimulated the
exploration of host–microbe interactions.



                  Composition of the Microbiota

The complexity and quantity of microbes in the alimentary tract is greatest at
the orifices. The oral cavity harbors a relatively large and diverse bacterial
population, whereas gastric acid restricts bacterial numbers to fewer than
103 colony-forming units (CFU)/ml of gastric contents. Along the small intes-
tine, bacterial density increases distally with a sharp gradient across the ileoce-
cal valve, with approximately 108 bacteria per gram of ileal contents and up to
1012 per gram of colonic contents, which comprises more than 1,000 different
bacterial species (O’Hara & Shanahan, 2006; Turnbaugh et al., 2007). There is
also a gradient in the composition of bacteria from mucosa to lumen. Almost
all of the culturable bacteria in the ileum and the colon are obligate anaerobes,
but the ratios of anaerobes to aerobes are lower at mucosal surfaces. In addi-
tion, culture-independent molecular techniques have shown that mucosa-
associated bacteria differ from those recovered from feces (Zoetendal et al.,
2002).
    In the proximal small bowel, the resident bacteria are predominantly gram-
positive facultative bacteria, although enterobacteria and Bacteroides also may
be present. Peristalsis is the principal factor restricting bacterial numbers in
the small bowel.




   In the distal small bowel, the composition of the flora resembles that of the
   colon, with a preponderance of Gram-negative anaerobes. The most promi-
   nently represented genera in the distal bowel include Bacteroides,
   Clostridium, Lactobacillus, Fusobacterium, Bifidobacterium, Eubacterium,
   Peptococcus, and Escherichia.
                                The Intestinal Microbiota in Health and Disease 45




Environmental and Lifestyle Modifiers of the Microbiota

Molecular profiling has shown that the microbiota is distinct in different
people. Studies of twins suggest that the individuality of the human microbiota
may be determined, in part, by host genetics (Zoetendal et al., 2001), but envi-
ronmental variables including diet, sanitation and other lifestyle factors appear
to have profound effects, particularly on early intestinal colonization
(Sonnenburg, Angenent, & Gordon, 2004). Indeed, many of the elements of a
modern lifestyle such as domestic hygiene, antibiotic usage, urbanization, and
family size are proxy markers of microbial exposure during the early stages of
life (Bernstein & Shanahan, 2008).

  Although the numbers and composition of the microbiota are relatively
  stable after infant weaning, the metabolic activity of the microbiota is con-
  tinually subject to dietary and other lifestyle variables.




           Techniques for Studying the Microbiota

Most enteric bacteria cannot be cultured, because of a lack of selective growth
media (Marchesi & Shanahan, 2007). Furthermore, because most of the indig-
enous bacteria are obligate anaerobes, there are logistical difficulties sampling
the gut ecosystem. Therefore, molecular strategies have been devised to study
bacterial nucleic acid extracted from feces or mucosal biopsy samples (Vaughan
et al., 2000). The small ribosomal subunit RNA (16S rRNA in bacteria) con-
tains highly conserved regions of base sequences that reflect an absence of
evolutionary change, and that are interspersed with hypervariable regions that
contain mutational changes reflecting the evolutionary divergence of different
species. Sequencing of 16S rRNA permits identification and phylogenetic clas-
sification of intestinal bacteria. For rapid profiling, 16S rRNA can be amplified
by polymerase chain reaction (PCR) and a profile of the mixture of hypervari-
able RNA fragments is achieved by variations in migration distance upon
denaturing gradient gel electrophoresis. This reflects the diversity of 16S “spe-
cies” in the sample.
    Other molecular techniques for identification of specific bacterial species
are now possible because their genomic sequence has become available.
Strategies include fluorescence in situ hybridization (FISH), flow cytometry
46 INTEGRATIVE GASTROENTEROLOGY


(FISH-FLOW), and bacterial DNA microarrays. In addition, metagenomic
techniques, which involve sequencing genes from mixed microbial popula-
tions, will address many of the unresolved questions about the microbiota in
health and disease.


  Genetic information within the microbiota (microbiome) exceeds that of
  the host genome by approximately a hundredfold, but the combination of
  metagenomics with bioinformatics, biochemistry, and traditional bioassays,
  is yielding important insights into the metabolic capacity of the human gut
  microbiota. (Turnbaugh et al., 2007)




                         Life without Bacteria

From comparative studies of germ-free and colonized animals, one can deduce
that the intestinal microbiota must be a source of positive and negative regula-
tory signals for the development and function of the intestine. Life without
bacteria is associated with reduced digestive enzyme activity and epithelial
turnover, rudimentary lymphoid tissue, reduced mucosal cellularity and vas-
cularity, and impaired motility, whereas enterochromaffin cell mass is increased
(Midtvedt, 1999).
   The molecular signals that permit maturation of the gut upon colonization
with the microbiota are currently being explored (Hooper et al., 2001).
Remarkably, colonization with only a single bacterial strain, Bacteroides
thetaiotaomicron, has illustrated the impact of bacteria-derived signaling on
the expression of host genes controlling mucosal barrier function, nutrient
absorption, angiogenesis, and development of the enteric nervous system.


  A diversity of incoming bacterial signals includes: secreted chemoattrac-
  tants, such as the formylated peptide, fMet-Leu-Phe (fLMP); cell wall constit-
  uents, such as lipopolysaccharide (LPS); and peptidoglycans, flagellin, and
  bacterial nucleic acids (e.g., CpG DNA). Detection of bacterial stimuli by the
  host, and discrimination of pathogens from commensals, are mediated, in
  part, by pattern recognition receptors, such as toll-like receptors (TLRs), that
  are present on epithelial and immune (dendritic) cells. Continual signaling
  by microbial ligands engaging TLRs is required not only for optimal mucosal
  and immune development, but also for mucosal homeostasis and responses
  to injury (Rakoff-Nahoum et al., 2004; Madara, 2004).
                               The Intestinal Microbiota in Health and Disease 47




                Transduction of Bacterial Signals

The enteric mucosa is well adapted to sampling the intraluminal microbial
community, with its large surface area (approximately 400 m2) and only a sin-
gle-cell layer separating the internal milieu from the lumen. The surface
enterocytes serve an immunosensory role by producing chemokines in
response to microbial danger signals, thereby alerting the host immune
response to breaches in the mucosal barrier (Artis, 2008). Direct sampling of
the lumen across the epithelium is mediated by mucosal dendritic cell pro-
cesses that extend into the lumen between the surface enterocytes, and by
M cells, which transport particulate antigens and intact microbes to under-
lying lymphoid follicles (Rescigno et al., 2001).
   After uptake, antigenic material, including intact microbes, is transported
by dendritic cells to the mesenteric lymph node (Macpherson & Uhr, 2004).
There, local immune responses are generated, and the mesenteric lymph node
acts as a gatekeeper by preventing systemic entry by commensal bacteria. The
discriminatory function of dendritic cells, depending on whether they are
exposed to commensals or pathogens, is facilitated by their plasticity and
versatility of responses, and by their tissue-specific specialization within the
intestine.
   Transduction of bacterial signals into host immune responses after engage-
ment of TLRs proceeds along several molecular pathways. The transcription
factor, nuclear factor-κB (NF-κB), is the molecular switch for immune
responses and is a pivotal regulator of epithelial responses to invasive patho-
gens. Nonpathogenic bacteria attenuate inflammatory responses by several
mechanisms, including delaying the degradation of IκB, which is counterreg-
ulatory to NF-κB (Neish et al., 2000), and enhancing the nuclear export of the
transcriptionally active subunit (RelA) of NF-κB in a peroxisome proliferator–
activated receptor-γ (PPAR-γ)-dependent manner (Kelly et al., 2004).


        Host–Microbe Communication is Reciprocal

As with many other examples of interkingdom signaling (Hughes & Sperandio,
2008), host–microbe interactions in the gut are bidirectional. The apparent
influence of host genetics on the composition of the commensal microbiota is
supported by evidence for modulation by the immune system on the micro-
biota. Mucosal immune defects in different species have been associated
with aberrant expansion of certain commensal organisms (Ryu et al., 2008;
48 INTEGRATIVE GASTROENTEROLOGY


Suzuki et al., 2004). In addition, the transcription factor T-bet, which regulates
immune development and function, has been shown to have an unexpected
influence on commensal populations within the murine intestine. Deletion of
T-bet appeared to lead to the emergence of a “colitogenic” microbiota with the
capacity to transfer colitis (Garrett et al., 2007).


              The Microbiota is a Health Asset and
               Occasional Contributor to Disease

The distinction between a commensal and a pathogen is often one of context.
For example, the indigenous microbiota is generally a health asset, but becomes
a liability in the setting of bacterial overgrowth syndromes, including C.
difficile overgrowth after antibiotics. In other contexts, depending on the
genetic susceptibility of the host, some but not all components of the micro-
biota may become contributors to the pathogenesis of disease, such as inflam-
matory bowel disease (Sartor, 2008). While a comprehensive review of the
microbiota in different diseases is beyond the scope of this chapter, microbial
alterations linked with inflammatory bowel disease have attracted particular
interest. These include a reduction in fecal lactobacilli and bifidobacteria
(Murch, 2001), increased adherent-invasive E. coli (AIEC; see Rhodes, 2007),
increased detection of Mycobacterium avium subspec paratuberculosis (MAP;
see Feller et al., 2007) and reduced bacterial diversity by metagenomic analysis
(Peterson et al., 2008). The latter includes reductions in the anti-inflammatory
commensal, Faecalibacterium prausnitzii (Sokol et al., 2008). Whether specific
microbiota can be correlated with individual variations in the immune response
is unclear, but there is evidence that this may be so (Ivanov et al., 2008).


     The Gut Microbiota and Extraintestinal Disorders

In addition to its role in gut health, the microbiota has become an important
consideration in the context of a variety of other disorders beyond the gut. For
example, the impact of the microbiota on immune maturation is not limited to
gut-associated lymphoid tissue; peripheral lymphoid structures are also influ-
enced (Mazmanian et al., 2005). As discussed later, the microbiota has been
shown to be an environmental regulator of fat storage, and appears to influ-
ence the risk of developing obesity and metabolic syndrome (DiBaise et al.,
2008). More recent work suggests that microbiota not only influences fat
quantity but also fat quality, in terms of bioactive fatty acid composition in
adipose and hepatic tissue (Wall et al., 2009).
                               The Intestinal Microbiota in Health and Disease 49


   In addition, the composition of the gut microbiota has been shown to
modify the pathogenesis of T-cell mediated destruction of pancreatic islets in
murine diabetes. The interaction between the microbiota and the host innate
immune system appears to be a critical epigenetic modifying factor, although
the relationship between the microbiota and risk of developing diabetes is
complex (Wen et al., 2008).


              Metabolic Activity of the Microbiota

The collective metabolic activity of the enteric microbiota is tantamount to
that of a hidden organ (O’Hara & Shanahan, 2006). Coevolution with this
inner biomass has several benefits for the host. In addition to the production
of regulatory signals for mucosal homeostasis, the microbiota contributes
metabolic properties not possessed by the host. These include biotransforma-
tion of bile acids, degradation of oxalate, breakdown of otherwise indigestible
dietary components, such as plant polysaccharides, and production of short-
chain fatty acids—a major energy source for colonic epithelium—from fer-
mentable carbohydrates. Other activities include synthesis of biotin, folate,
and vitamin K. Bacterial enzymes, such as azoreductase, have been exploited
therapeutically to convert prodrugs, such as sulfasalazine, to active drug
metabolites, such as aminosalicylate. Other examples of bacterial action on
drug bioavailability include the metabolism of L-dopa to dopamine, and deg-
radation of digoxin.


  In some instances, the metabolic changes induced by the enteric microbiota
  may not beneficial to the host. For example, bacteria may promote the pro-
  duction of carcinogens from dietary procarcinogens, although they probably
  also degrade some carcinogens (Rafter, 2003).



    As alluded to earlier, the regulatory effect of the enteric microbiota on fat
storage represents a compelling example of the impact of bacterial metabolism
on the host (Backhed et al., 2004). Germ-free animals require a higher caloric
intake to sustain a body weight similar to that of colonized animals. Thus, the
microbiota of the colonized host confers a nutritional benefit. Furthermore,
intestinal bacteria promote fat storage by enhancing the bioavailability of
dietary monosaccharides for absorption, and also by suppressing epithelial-
derived, fasting-induced adipocyte factor (FIAF), which in turn releases
lipoprotein lipase activity and promotes uptake of fatty acids into adipose
tissue. Thus, the composition and activity of the intestinal microbiota should
50    INTEGRATIVE GASTROENTEROLOGY


be considered as a variable influenced by Western diets that may influence
susceptibility to obesity.
   Gas production is another familiar outcome of bacterial metabolic activity.
Of the five gases—N2, O2, CO2, H2, CH4—that comprise 99% of flatus, the latter
three are produced by the enteric bacteria, and bacteria are the sole source of
hydrogen and methane in the intestine. Hydrogen production by bacterial
action on carbohydrates and, to lesser extent, on protein, normally occurs in
the colon. The small bowel also becomes a site of H2 production when bacte-
rial overgrowth occurs. Bacterial methanogens occur in the colon and pro-
duce methane from H2 and CO2, with detectable excretion in approximately
30% of humans (Levitt & Engel, 1975; Levitt, 1980).

     While the principal gases produced are odorless, bacterial metabolism
     also generates various trace and odiferous gases in flatus, such as hydrogen
     disulfide (Moore, Jessup, & Osborne, 1987; Suarez, Springfield, & Levitt, 1998).
     Qualitative and quantitative variability in gas production with diet illus-
     trates the fluctuations in bacterial metabolic activity, despite the composi-
     tional stability of the microbiota in adulthood.




      Mining the Microbiota for Novel Drug Discoveries

Several predictions can be made regarding the identity of microbial-derived
chemical signals suitable for mining, based on what is already known of
the influence of the microbiota on host physiology and pathophysiology (see
Table 4.1). Translation of these signaling molecules into bioactives or novel
drugs is an exciting prospect for the future (Shanahan & Kiely, 2007).

              Table 4.1. Examples of Opportunities to Mine the Microbiota
                                for Novel Therapeutics
Observation              Opportunity                 Translation           Reference

Microbe–microbe        Isolation of novel            Application of        Rea et al.
communication ensures antibiotics (bacteriocins)     lacticin to treatment (2007)
stability of bacterial                               of pathogens such as
numbers in the gut                                   C. difficile

Commensals and           Bacterial components or     Evidence base for     Grangette
probiotics have          metabolites for use as      this remains to be    et al. (2005)
anti-inflammatory        anti-inflammatory drugs     explored and          Obermeie
effects on the host      (e.g., lipoteichoic acid,   exploited             et al. (2003)
                         CpG DNA)
                                        The Intestinal Microbiota in Health and Disease 51


                                  Table 4.1. (Continued)
Observation               Opportunity                  Translation           Reference

Gut microbiota is         Isolation of bacterial-      Use of cell wall   Mazmanian
required for immune       derived molecules as         polysaccharides as et al. (2005,
maturation                immunomodulatory             immunomodulatory 2008)
                          drugs                        drugs in IBD

Metabolic signals from    Manipulation of the          Use of food-grade     Backhed
the microbiota            microbiota may alter         organisms to modify   et al. (2004)
influence fat storage     bioavailability of dietary   composition of the    Wall et al.
and composition           calories                     microbiota            (2009)

Some but not all          Some components of the       An intriguing         Rousseaux
commensals or             microbiota may be            observation that      et al. (2007)
probiotics are            suitable for mining for      awaits confirmation
beneficial in irritable   analgesic activities         and exploitation
bowel syndrome




                                     Conclusions

The contribution of the microbiota to mucosal homeostasis is such that it is
has become essential to study intestinal pathophysiology in the context of the
resident bacteria. Lifestyle and environmental influences on the microbiota,
and on the developing immune system, may underpin the changing epidemi-
ology of several chronic inflammatory disorders. The molecular basis of
microbial-induced gastrointestinal and immune development is beginning to
unfold, and may be “mined” for novel therapeutics in the future.
                                           5
            Alternative Laboratory Testing for
                 Gastrointestinal Disease1
               DAVID M. BRADY, J. ALEXANDER BRALLEY ,
               RICHARD S. LORD , AND GERARD E. MULLIN




                                                      1
                                    key concepts

      ■   Gastric acid analysis is an important test to consider in patients
          with recurrent gastrointestinal infections and small intestinal
          bacterial overgrowth (SIBO).
      ■   Fecal elastase is a reliable noninvasive stool test for pancreatic
          insufficiency.
      ■   Intestinal hyperpermeability indicates ongoing injury to the
          intestinal epithelium, and is diagnosed using the lactulose-
          mannitol test—a simple, noninvasive and inexpensive test.
      ■   Lactulose breath hydrogen and methane testing can be used to
          detect abnormal fermentation in the upper digestive tract,
          indicative of small intestinal bacterial overgrowth.
      ■   Microbial analysis of stools using PCR technology may provide
          valuable information about the colonic flora and guide treat-
          ment of digestive conditions.
                                            ■




                                   Introduction



H
           ealthcare practitioners who manage digestive disorders are often-
           times challenged by the limited testing that is available without refer-
           ring to specialists who perform invasive procedures. The principal

1
 Excerpted and adapted from Richard S. Lord and J. Alexander Bralley (Eds), Chapter 7,
Gastrointestinal Function in Laboratory Evaluations for Integrative and Functional Medicine.
Metametrix Institute (2008).

52
                          Alternative Laboratory Testing for Gastrointestinal Disease 53


difficulty is that direct sampling of intestinal contents is impractical for non-
gastroenterologists. Analysis of specimens such as peripheral blood, urine,
and feces may give results that indirectly reflect difficulties with digestion and
absorption. Due to the critical role of the gastrointestinal tract in nutrient
supply, even partial answers can be of great value. Invasive procedures for
observation or luminal specimen retrieval can be highly informative when
performed in conjunction with noninvasive testing. This chapter will deal
mainly with noninvasive laboratory evaluations of gastrointestinal function, as
summarized in Table 5.1.

   Table 5.1. Summary of Laboratory Evaluations for Gastrointestinal Function
GI Aspect     Function        Testing          Abnormal      Intervention

                              Heidelberg         pH          – Mucosal building
                              capsule                          protocol
                              Direct pH                      – Betaine HCI
                              readings                       – Free-form amino acids
              Gastric acid,                                    (see Chapter 4, “Amino
Stomach                     Indirect           Multiple
              Pepsin                                           Acids”)
                            indicators         trace
                                                             – B-vitamins
                                               elements or
                                                             – Trace elements
                                               amino acids
                                                               (see Chapter 3, “Nutrient
                                                               and Toxic Elements”)

              Protease        Fecal              Activity    Pancreatic replacement
                              chymotrypsin                   enzymes (proteolytic,
                                                             lipolytic and amylytic) and
                              PABA index         Index
Pancreas                                                     essential fatty acids
              Lipase          Plasma fatty       PUFA
                              acids

                              Fecal fats         Fat

Liver/        Bile acid       Fecal fatty        Fatty acids Ox bile, choleretic herbs
Gallbladder   secretion       acids                          (milk thistle) and essential
                                                             fatty acids

                              Schilling test      Urinary    B12 by injection or ≥ 1,000
                                               B12           μg/d sublingual

Small         Absorption      Lactulose-         Urinary     Mucosal restoration
intestine                     Mannitol         mannitol
                              challenge

                              Fasting plasma Multiple low    Essential amino acid
                              amino acids    values          mixtures

                                                                              (Continued)
54   INTEGRATIVE GASTROENTEROLOGY


                              Table 5.1. (Continued)
GI Aspect   Function      Testing           Abnormal      Intervention

                          Food-specific     Multiple      Food elimination/Rotation
                          IgG               elevations    diets

            Water                             Butyrate    Increase dietary fiber
            resorption, Fecal butyrate
Colon                                         Isobutyrate Butyrate enemas
            Microbial   or other SCFA
            containment

Immune      Glycocalyx    Serum, urinary    Food-         Eliminate offending
barrier     antigen       or fecal IgA   specific IgA     antigens
            binding
                                              Total IgE   Immune-support nutrients
            Allergy-
                                                          such as Glycerrhiza
            antigen
                          Serum IgE                       glabra (licorice) root or
            elimination
                                                          l-glutamine 3,000–6,000
                                                          mg daily

                                            Many + foods Eliminate + foods by group
            Regulate                                     (Rotation Diet) Add
            nutrient     Serum IgG                       free-form amino acids and
            admission                                    glutamine Zinc 50–100
Physical
            and restrict                                 mg/d, Bs 100–200 mg/d
barrier
            toxicant and
                         Lactulose-           Urinary     Eliminate + foods
            microbial
                         Mannitol           Lactulose
            access
                         challenge
                                              Mannitol    Mucosal restoration

            Normal:       Urinary             Bacterial   Herbal or pharmaceutical
            nutrient      metabolic         markers       antibioitics (e.g., berberine
            delivery      markers                         alkaloids, etc.)

                                              Protozoal   Prebiotics and probiotics
                                            markers       with antiprotozoals
                          Hydrogen-
                                              Yeast       Restrict simple sugars with
                          Methane
Microbial                                   markers       antifungals
                          breath test
populations Pathogen:
                                               Expired    Herbal or pharmaceutical
            toxin                           gases         bacteriostatic agents
            production
                          Stool microbial     Growth      Specific antibiotics
                          DNA
                          quantititation
                          or culture &
                          sensitivity
                      Alternative Laboratory Testing for Gastrointestinal Disease 55




                                The Stomach

Standard medical treatments focusing on the gastrointestinal tract most often
involve treating digestive symptoms by using proton pump inhibitors, which
are among the most frequently prescribed medications with a myriad of poten-
tial adverse effects (see Chapter 37 by Hickey and Mullin).
    Stomach acid secretion is a principal line of defense against infection of the
gastrointestinal (GI) tract (Giannella, Broitman, & Zamcheck, 1972). The criti-
cal function of low pH in the stomach is required to set up mineral absorption.
High levels of ammonia, produced by bacterial action on amino acids, are even
more directly associated with inadequate hydrochloric acid. The loss of bacte-
ricidal action and the failure to digest protein due to low stomach acid simul-
taneously leads to higher bacterial populations and greater availability of
unassimilated amino acids for bacterial conversion.


   Simultaneous low levels of iron, zinc, copper, and manganese in serum,
   erythrocytes, or hair, is often due to gastric acid inadequacy, especially when
   intake of trace elements is normal.



   The proteolytic enzyme activity and low pH in normal gastric secretions
kill most of the bacteria and parasites that contaminate food. Chronic
hypochlorhydria, whether induced by habitual use of antacids or due to gastric
disorders, increases the risk of infection and intestinal microbial overgrowth
(Neal et al., 1996).


                          HEIDELBERG CAPSULE TEST

The Heidelberg capsule test is considered to accurately assess stomach acid,
though it is time-consuming for the patient, taking up to 90 minutes to com-
plete (Wright, 1979). This type of test can give definitive answers about the
adequacy of gastric acid secretion. The test uses a tiny plastic encapsulated pH
probe that is swallowed by the patient. The capsule, small enough to safely pass
the circuitous course of the GI tract, contains a miniature radio transmitter
that continuously measures gastrointestinal pH and transmits the data to a
waistband antenna connected to a bedside receiver. The pH readings are
recorded for a permanent record. The capsule can either be tied to a thin string
for retrieval, or swallowed untethered. The latter approach allows additional
56 INTEGRATIVE GASTROENTEROLOGY


measurements of upper intestinal pH to be gathered. After swallowing the
capsule, pH readings typically start around 7.0, and then drop toward 1.0 as the
capsule settles toward the stomach bottom. The patient then drinks a challenge
solution consisting of concentrated sodium bicarbonate (baking soda), which
has strong buffering capacity. Within half a minute, the pH will normally rise
to approximately 7. If acid secretion is normal, the pH will fall again, returning
to between 1.0 and 2.0 within 20 minutes. The challenge solution is given again
and repeated up to four times, as long as the pH response time is less than
20 minutes. Hypochlorhydria is indicated for a patient requiring more than
20 minutes to re-acidify. With achlorhydria, the patient’s stomach secretes
little acid and the pH will not fall below 4.0, even on the first challenge (Wright,
1979). Experienced technologists must administer this test, because of factors
such as the timing of bicarbonate solutions that are critical for accurate, repro-
ducible results.


                           ENDOSCOPIC SAMPLING

An alternative method to sample stomach acid is to measure gastric pH aspi-
rates during endoscopic procedures, or noninvasively by using a Smartpill
analysis. The SmartPill GI Monitoring System is a new, in-office method for
assessing gastric motility. The wireless SmartPill capsule collects pH, pressure,
and temperature data from throughout the entire gastrointestinal tract (http://
www.smartpill.com).


                   The Pancreas and Gallbladder

Pancreaticobiliary fluid composition can be highly variable. The pancreas con-
tributes to digestion by secreting alkaline bicarbonate and a variety of diges-
tive enzymes. Secretion of pancreatic fluid is controlled in part by vagus nerve
stimulation. A more important regulatory mechanism of pancreatic secretion
is the control exerted by the hormones secretin and cholecystokinin (CCK).
Both are synthesized in the duodenum (upper small intestine) and secreted in
response to the presence of acidified chyme in the small intestine. Additionally,
CCK stimulates the contraction of the gallbladder, causing the release of bile
into the duodenum. Secretin stimulates the flow of bicarbonate-rich pancre-
atic fluid that serves to raise the pH of normal chyme from below 4 to above 7,
allowing trypsin and other pancreatic digestive enzymes to reach their maxi-
mal activities.
                      Alternative Laboratory Testing for Gastrointestinal Disease 57




                        FECAL CHYMOTRYPSIN TEST

The fecal chymotrypsin test is a useful noninvasive test to determine chronic
pancreatic insufficiency (Henry & Steinberg, 1993). False positive results of up
to 10% have been reported in normal individuals. Greater reliability for diagnos-
ing chronic pancreatitis can be obtained by performing the fecal chymotrypsin
test in combination with the bentiromide (N-benzoyl-L-tyrosyl-p-amino-
benzoic acid) test (Kataoka et al., 1997). The bentiromide test measures the
amount of p-aminobenzoic acid (PABA) appearing in urine following an oral
bentiromide loading, indicating successful chymotrypsin cleavage at the
tyrosyl peptide bond. PABA excretion rates are lower in patients with compro-
mised pancreatic function than in healthy control subjects (Gagee et al.,
1992).


                        FECAL PANCREATIC ELASTASE

A newer alternative or companion test to the fecal chymotrypsin assay is fecal
pancreatic elastase. Human pancreatic elastase, a member of the acidic elastase
family, was first detected by Sziegoleit as a new endoprotease and sterol-bind-
ing protein present in both human pancreatic secretions and feces (Chey, 1999;
David-Henriau et al., 2005; Domínguez-Muñoz et al., 1995; Stein et al., 1996;
Sziegoleit, 1984; Sziegoleit et al., 1989; Sziegoleit & Linder, 1991). Elastase,
unlike chymotrypsin, has been found to remain unaffected during intestinal
transit, and to be stable in stool samples for up to a week at room temperature
(Chey, 1999; Sziegoleit et al., 1989; Sziegoleit & Linder, 1991). Elastase cannot
be detected in bovine or porcine pancreatic enzyme preparations. Therefore,
unlike chymotrypsin, it is not affected by oral pancreatic enzyme replacement
therapy (Chey, 1999; see Figure 5.1).


                                   FECAL FAT

Steatorrhea, defined as the presence of excess fat in the stool, is established by
fat-balance studies (Kalivianakis et al., 2000). Normal fecal excretion of fat is
less than 6 g/d. However, this test does not distinguish between fat maldiges-
tion and fat malabsorption. Instead, tests for fecal triglycerides and long-chain
free fatty acids can help differentiate between the two disorders.
58 INTEGRATIVE GASTROENTEROLOGY




                                 FECAL FIBERS

Microscopic inspection of stool can reveal the presence of meat and vegetable
fibers. The increase in the amount of these fibers that occurs with impaired
digestion is an indirect indicator of hypochlorhydria or insufficient output of
pancreatic enzymes (Lankisch, 1982; Moore et al., 1971).


                             Small Intestine

                     INTESTINAL HYPERPERMEABILITY

Patients with intestinal hyperpermeability have more than the normal 2%
“leakiness” to large molecules. Degradation of the physical barrier often is due
to exposure to toxic substances within the intestinal lumen that can damage
the “tight junctions” between intestinal epithelial cells, leading to an increase
in passive paracellular absorption (Fink, 1990; Galland, 1996).Common causes
of intestinal hyperpermeability are ethanol consumption (Anonymous, 1985),
nonsteroidal anti-inflammatory drugs (NSAIDs), and viral, bacterial, yeast,
and protozoan infection (Batt et al., 1992; Riordan et al., 1997; Pignata et al.,
1990; Serrander, Magnusson, & Sundqvist, 1984). Also, elevated levels of reac-
tive oxygen species coming from a variety of sources, such as bile, food, cyto-
toxic drugs (Lifschitz & Mahoney, 1989), or inflammatory cells (Grisham et al.,
1990; Sundstrom et al., 1998), can increase paracellular permeability.
   Intestinal hyperpermeability is found in all chronic inflammatory bowel
diseases, where it may play an etiologic role, or it may be a secondary conse-
quence due to the vicious cycle involving immune activation, hepatic dysfunc-
tion, and pancreatic insufficiency (Galland, 1995). The role of intestinal
hyperpermeability in many diseases is often missed. The availability of nonin-
vasive and affordable methods for measuring intestinal hyperpermeability
makes it possible for clinicians to diagnose this condition in their patients, and
to objectively assess the efficacy of treatment.


 LACTULOSE-MANNITOL INTESTINAL PERMEABILITY CHALLENGE TEST

The lactulose-mannitol protocol was developed to measure intestinal hyper-
permeability for a wide range of conditions (Andre, 1986), including food sen-
sitivities (Ventura et al., 2006), pancreatitis (Nagpal et al., 2006), Crohn’s
                      Alternative Laboratory Testing for Gastrointestinal Disease 59


              Table 5.2. The Four “R” Program for Intestinal Health
“R”              Object          Amplification

Remove           Microbial       Use bacteriostatic or mycostatic agents of sufficient
                 overgrowth      strength to reduce excessive growth rates

Replace          Digestive       Support insufficient digestive secretory factors with
                 factors         oral replacements

Reinoculate      Favorable       Employ oral dosing of viable organisms known to
                 microbes        help control toxin-producing specie

Repair           Tissue and      Support the growth of healthy intestinal mucosal
                 immune          cells, goblet cells and immune cell responses with
                 integrity       key nutrients



disease (D’Inca et al., 2006), and cirrhosis (Table 5.2). Lactulose-mannitol is a
challenge test in which patients with suspected hyperpermeability ingest the
metabolically inert sugars lactulose and mannitol. Mannitol, a monosaccha-
ride, is passively absorbed through the intestinal mucosa. In contrast, lactu-
lose, a disaccharide, is normally not absorbed unless the mucosal barrier is
compromised. Since these sugars are not metabolized, any absorbed sugar is
fully excreted in the urine within 6 hours. The urine is collected, and concen-
trations of the two sugars are measured. Percent absorptions are calculated
using the following formula:
   % compound absorption = compound concentration (mg/ml)
                           × urine volume (mL) × 100

          Lactulose-Mannitol Testing Protocol
           • Swallow a solution of 5 g mannitol and 5 g lactulose
           • Collect urine for 6 hours
           • Assay for total lactulose and mannitol
               Calculate recoveriess
               < 14% Mannitol = Carbohydrate malabsorption
                               e
               > 1% Lactulose = Disaccharide hyperpermeability


   In the healthy intestine, the mean absorption of mannitol is 14% of the
administered dose, whereas the mean absorption of lactulose is less than 1%.
The normal ratio of lactulose-mannitol recovered in urine is < 0.03. An ele-
vated ratio indicates intestinal hyperpermeability. It is best to have the patient
perform the lactulose-mannitol test twice—first in the fasting state, then again
60 INTEGRATIVE GASTROENTEROLOGY


after ingestion of a test meal (Andre et al., 1987). The lactulose-mannitol ratio
was found to be an accurate predictor of relapse when measured in patients
with Crohn’s disease who were clinically in remission (Wyatt et al., 1993).
Recent intake of high carbohydrate meals and prolonged administration of the
challenge solutions diminish responses to this test.


                        Mucosal Inflammation

                    GLUTEN SENSITIVE ENTEROPATHIES

Inherited factors make some individuals sensitive to a protein called gliadin,
present in some cereal grains. Gliadin is a part of the total protein, or gluten,
in the grains. When undigested gluten reaches the small intestine, gliadin
peptides activate autoimmune reactions in susceptible individuals. As many as
one in 133 Americans with no previous symptoms or family history of celiac
disease may be affected (Fasano et al., 2003).
   For more information on celiac disease, including testing, see Chapter 40.


            POLYMORPHONUCLEAR NEUTROPHIL DISORDERS

Human lactoferrin (Lf), an iron-binding glycoprotein secreted by mucosal
membranes, is a major granular component of polymorphonuclear neutro-
phils. When these cells respond to inflammatory signals, lactoferrin is released
as part of the defense mechanism. Fecal Lf is a marker of intestinal inflamma-
tion in which leukocytes infiltrate the mucosa, increasing the release of neu-
trophil lactoferrin. Fecal Lf has been extensively used to differentiate
inflammatory bowel disease from irritable bowel syndrome (IBS) and non-
inflammatory bacterial infections, and it is useful for monitoring IBD treat-
ment efficacy (D’Inca et al., 2006; Logsdon &, Mecsas, 2006; Larsen et al.,
2004; Buderus et al., 2004; Kane et al., 2003; Bard et al., 2003; Greenberg et al.,
2002; Vaishnavi, Bhasin, & Singh, 2000; Saitoh et al., 2000).
   Various other neutrophil-derived proteins, such as calprotectin (Cal), poly-
morphonuclear neutrophil-elastase (PMN-e), α1-antitrypsin, and lysozyme
(Lys) have been shown to be reliable indicators of intestinal inflammation,
and can aid in the differentiation of organic intestinal disorders (i.e., inflam-
matory bowel diseases (IBD), ulcerative colitis (UC), Crohn’s disease, infec-
tious gastroenteritis, etc.) from functional intestinal disorders (i.e., IBS; see
Larsen et al., 2004; Buderus et al., 2004; Kane et al., 2003; Bard et al., 2003;
Gaya et al., 2005; Gearry et al., 2005; Langhorst et al., 2005; Liu et al., 2005;
                      Alternative Laboratory Testing for Gastrointestinal Disease 61


Lundberg et al., 2005; Silberer et al., 2005; Tibble & Bjarnason, 2001; van der
Sluys Veer A et al., 1999).Fecal levels of these proteins rapidly increase with the
influx of leukocytes into the intestinal lumen during inflammation. Among
the neutrophil-derived proteins in feces, PMN-e, Cal and Lf represent the
most accurate markers of disease activity and severity in patients with ulcer-
ative colitis, with lysozyme being somewhat less useful (Langhorst et al., 2005;
Liu et al., 2005).


                              Secretory IgA Test

Secretory IgA status may be evaluated by measurement of salivary or fecal
secretory immunoglobulin A (sIgA) levels (Nagao et al., 1995). Salivary sIgA is
a predictor of the release of sIgA at intestinal surfaces (Externest et al., 2000).
A compromised immune barrier can lead to elevated serum IgA. Fecal sIgA
correlates with salivary sIgA, and both may be predictors of partial mucosal
sIgA deficiency as defined by serum IgA > 0.05 g/l (Nagao et al., 1994).
   Many studies on the effects of extreme physical and/or emotional stress in
test populations, such as military personnel in basic training and competitive
endurance athletes, have demonstrated that levels of sIgA become depressed
following such levels of stress, whereas cortisol levels increase (Brenner et al.,
2000; Filaire, Bonis, & Lac, 2004; Gomez-Merino et al., 2003; McDowell et al.,
1992; Nieman et al., 2002). Stress plays an important role in the compromise of
the gastrointestinal mucosal immune response and the development of pan-
allergy to foods and, potentially, the development of autoimmune phenomena
via antigen–antibody complex cross-reactivity and molecular mimicry.
Combining salivary sIgA with evaluation of cortisol and 5-dehydroepiandro-
sterone (DHEA) may be beneficial in the overall assessment of the stress
response and the management of gut hyperpermeability, food allergy, inflam-
matory arthritides, immunogenic thyroiditis, autoimmunity, and other chronic
diseases (Ansaldi et al., 2003; Gladman, 1991; Marker-Hermann & Schwab,
2000; Martinez-Gonzalez et al., 1994; Mielants, 1990; Petru et al., 1987; Pishak,
1999; Stebbings et al., 2002; Takuno, Sakata, & Miura, 1990; Tiwana et al., 1998;
Tomer & Davies, 1993).


                Microbial Population Assessment

The intestinal flora is a complex ecosystem consisting of over 400 bacterial
species that greatly outnumber the total number of cells making up the entire
human body (Finegold, Attebery, & Sutter, 1974). These metabolically active
62    INTEGRATIVE GASTROENTEROLOGY


bacteria reside close to the absorptive mucosal surface, and are capable of a
remarkable repertoire of transforming chemical reactions. Any orally taken
compound, or a compound entering the intestine through the biliary tract
or by secretion directly into the lumen, is a potential substrate for bacterial
transformation.

     Anaerobic bacteria are the predominant microorganisms in the human GI
     tract, outnumbering aerobes by a factor of 10,000 to 1.



    In health, the upper GI tract is sparsely populated with microorganisms.
The vast majority of bacteria washed along with saliva from the oral cavity are
destroyed in the stomach by gastric juice. The small intestine constitutes a
zone of transition between the sparsely populated stomach and the luxuriant
bacterial flora of the colon. In the distal ileum, the concentrations of bacteria
increase to 106–107 colony-forming units per milliliter (Fuller & Perdigón,
2003). Here, Gram-negative bacteria outnumber the Gram-positive species.
Beyond the ileocecal valve, the bacterial concentration increases steeply.
Colonic bacteria number between 1011 and 1012 colony-forming units per mil-
liliter of fecal material. Multiple dramatic shifts in populations of species occur
between the ileocecal valve and the rectum. By the time they are passed from
the body in stools, the large majority of the bacteria are no longer viable.


               OPPORTUNISTIC OVERGROWTH AND DISEASE

Overgrowth of any one of the more than 400 microbial species in the healthy
human gut can produce adverse clinical effects. Excessive colonization of the
gut by undesirable microorganisms alters the metabolic or immunologic status
of the host (Van Eldere et al., 1988; Rogers et al., 2006).When this state leads to
disease or dysfunction, it has been termed dysbiosis to distinguish it from the
correct balance denoted as orthobiosis (Galland & Barrie, 1993). The line
between benign opportunistic overgrowth and infectious diseases is difficult
to define because apparently benign, small numbers of colony-forming units
may be detected for pathogens such as enterohemorrhagic Escherichia coli.


                            THE TRANSITIONAL GUT

The microbial mass increases from levels around 1 × 105 to counts as high as 1 × 1011
in the region roughly encompassing the mid-ileum to the transverse colon.
                     Alternative Laboratory Testing for Gastrointestinal Disease 63


This 6-orders-of-magnitude increase represents a fantastically high rate of new
cell formation, with associated intense metabolic activity where metabolic
products are formed. Thus, it is from this mid- or transitional gut that most of
the microbial products found in breath or urine are chiefly derived.


                   Breath Hydrogen and Methane Test

This test offers reasonable sensitivity, and it is very convenient to administer,
although it will sometimes give false negative results. For greater predictive
value, it is best to also obtain a baseline breath sample from the patient before
consumption of the challenge solution. The fasting patient drinks a challenge
dose of lactulose (10 g) or glucose (75 g) solution. Breath samples should
be collected every 15 minutes for up to 3 hours. If bacteria exist in the small
intestine, they will ferment the sugar and release hydrogen and methane,
which can be detected in the breath. The typical fasting breath sample contains
less than 10 ppm hydrogen or methane; levels higher than 20 ppm indicate a
high probability of bacterial overgrowth. Following a lactulose or glucose chal-
lenge, a two-phase response may be seen. The first rise in breath hydrogen
generally occurs within 30 to 60 minutes, when lactulose contacts the small
intestine—the rise may be delayed beyond 60 minutes in those having gastro-
paresis and small intestinal transit. A second, more pronounced rise occurs
about 2–3 hours later, when the sugar enters the large intestine. A rapid and
prolonged first-phase response is frequently due to small intestine bacterial
overgrowth (Rhodes, Middleton, & Jewell, 1979). Interpretation of results is
complicated by the large number of false positive findings, as compared with
results obtained from bacterial cultures of intestinal lumen aspirates (Corazza
et al., 1990; Riordan et al., 1996).Combining the findings of elevated fasting
breath hydrogen (> 20 ppm), and raising the limit for the post-lactulose chal-
lenge increase in breath hydrogen and methane to greater than 20 ppm, will
reduce the chance of false positive responses (Hamilton, 1992).


            URINARY MARKERS OF BACTERIAL OVERGROWTH

                               Urinary Indican

Bacteria in the upper bowel produce the enzymes that catalyze the conversion
of tryptophan to indole (Figure 5.2). Absorbed indole is converted in the liver
to indoxyl, which is then sulfated to allow urinary excretion as indoxyl sulfate
(indican).
64 INTEGRATIVE GASTROENTEROLOGY


   Oral, unabsorbed antibiotics reduce indican excretion. Indican excretion is
also reduced when the gut is populated with strains of Lactobacillus at levels
above 105 organisms/g (Tohyama et al., 1981). Probiotics have been shown to
decrease indican levels (Yoshida & Hirayama, 1984).
   The urine indican test may be performed after oral loading of 5 g trypto-
phan (Smith, 1982). Reference limits may also be set from data taken under
nonloading conditions. Tryptophan loading, which can be monitored by mea-
suring periodic levels of urinary indican, results in neuropsychiatric manifes-
tations due to products of intestinal bacterial conversion of the amino acid
(Yoshida & Hirayama, 1984). When elevations of phenol and p-cresol are
included with that of indican as criteria of abnormal bacterial colonization of
the small intestine, the number of false positives is reduced (Aarbakke &
Schjonsby, 1976).


                      Urinary Phenolic Compounds

Dietary polyphenolics are the principal substrates from which products of
transitional gut bacterial metabolism are formed. In addition to the use of
polyphenol compounds, intestinal bacteria that contain l-amino acid decar-
boxylase enzymes degrade tyrosine to tyramine. The tyramine is then deami-
nated and oxidized to p-hydroxyphenylacetate. This product is excreted
unchanged and unconjugated in urine. It was used to identify small bowel
disease and bacterial overgrowth syndromes in 360 randomly selected,
acutely ill infants and children. In this study, no false negative and only 2%
false positive results were found (Chalmers, Valman, & Liberman, 1979).
Treatment with metronidazole or mepacrine has been shown to eliminate
the p-hydroxyphenylacetic aciduria. Although p-hydroxyphenylacetate
can be produced in the liver, abnormally high levels in urine are of bacterial
origin.


                             Urinary D-Lactate

Another product of bacterial fermentation of sugar is d-lactic acid. d-lactic
acidosis is usually a complication of short-bowel syndrome, or of jejunoileal
bypass surgery (colonic bacteria being the source of acidosis). Elevated
d-lactic acid can be found in cases of overpopulation of the small intestine
with L. acidophilus, as a result of low endogenous stomach acid production or
the chronic use of acid-reducing medications accompanied by ingestion of
large quantities of dietary carbohydrate (Uribarri, Oh, & Carroll, 1998).
                      Alternative Laboratory Testing for Gastrointestinal Disease 65




               URINARY MARKERS OF YEAST OVERGROWTH

                                 D-Arabinitol

d-Arabinitol (DA) is a metabolite of most pathogenic Candida species, in vitro
as well as in vivo. DA is a five-carbon sugar alcohol that can be assayed by
enzymatic analysis. Immunocompromised patients with invasive candidiasis
have elevated d-arabinitol/creatinine ratios in urine. Positive DA results have
been obtained several days to weeks before positive blood cultures, and the
normalization of DA levels has been correlated with therapeutic response in
both humans and animals (Roboz, 1994; Christensson, Sigmundsdottir, &
Larsson, 1999).
   Measuring serum DA allows prompt diagnosis of invasive candidiasis
(Christensson, Sigmundsdottir, & Larsson, 1999; Tokunaga et al., 1992).


             The Colon: Assessing Microbes in Stool

The population of the microbiota of the human GI tract is widely diverse and
complex, with a high population density. All major groups of microorganisms
are represented. Although they are predominately bacteria, a variety of proto-
zoa are also present. In the colon there are over 1011 bacterial cells per gram,
and over 400 different species. These bacterial cells outnumber host cells by at
least a factor of 10 (Rowland, 1995). This microbial population has important
influences on host physiological, nutritional, and immunological processes. In
fact, this biomass should more rightly be considered a rapidly adapting, renew-
able organ, with considerable metabolic activity and significant influence on
human health. Consequently, there is renewed and growing interest in identi-
fying the types and activities of these gut microbes (Mackie, Sghir, & Gaskins,
1999).
   The normal, healthy balance in microbiota provides colonization resistance
to pathogens. Since anaerobes comprise over 95% of these organisms, their
analysis is of prime importance. Gut microbes might also stimulate immune
responses to prevent conditions such as intestinal dysbiosis. Intestinal dys-
biosis may be defined as a state of disordered microbial ecology that causes
disease (Tamboli et al., 2004). Specifically, the concept of dysbiosis rests on the
assumption that patterns of intestinal flora— specifically, overgrowth of some
microorganisms found commonly in intestinal flora—have an impact on
human health. Symptoms and conditions thought to be caused or complicated
66   INTEGRATIVE GASTROENTEROLOGY


by dysbiosis include inflammatory bowel diseases, inflammatory or auto-
immune disorders, food allergy, atopic eczema, unexplained fatigue, arthritis,
mental/emotional disorders in children and adults, malnutrition, and breast
and colon cancer (Galland & Barrie, 1993; Hawrelak & Myers, 2004).


          DIFFICULTIES IN ASSESSING INTESTINAL MICROBIOTA

Most studies of microbiota in the GI tract have used fecal samples. These do
not necessarily represent the populations along the entire GI tract from stom-
ach to rectum. Conditions and species can alter greatly along this tract, and
generally run from lower to higher population densities. The stomach and
proximal small intestine, with highly acid conditions and rapid flow, contain
103 to 105 bacteria per gram or milliliter of content. These are predominated by
acid-tolerant lactobacilli and streptococci bacteria. The distal small intestine
to the ileocecal valve usually reaches to 108 bacteria per gram or milliliter of
content. The large intestine generates the highest growth, due to longer
residence time, and ranges from 1010 to 1011 bacteria per gram or milliliter of
content. This region generates a low redox potential, and high amount of
short-chain fatty acids.
   Not only does the microbiota content change throughout the length of the
GI tract, but there are also different microenvironments where these organ-
isms can grow. At least four microhabitats exist: the intestinal lumen, the
unstirred mucus layer that covers the epithelium, the deeper mucus layer in
the crypts between villi, and the glycocalyx of the epithelial cells (Savage, 1977).
Given this diverse ecological community, the question arises as to how to
sample the various environments to identify populations of microbes, and
ultimately understand the host–microbe interactions. This problem is an
extremely difficult one, since any intervention to obtain a sample potentially
disrupts the population. Fecal sampling has been used for years in microbiota
assessment. But it should be understood that this sample most appropriately
represents organisms growing in the lumen of the colon. In addition, > 98% of
fecal bacteria will not grow in oxygen (Savage, 1977). Therefore, standard cul-
ture techniques miss the majority of organisms present.


      CONVENTIONAL TECHNIQUES VERSUS NEW TECHNOLOGIES

                          Conventional Techniques

Conventional bacteriological methods such as microscopy, culture, and
identification are used for the analysis and/or quantification of the intestinal
                     Alternative Laboratory Testing for Gastrointestinal Disease 67


microbiota (O’Sullivan, 1999; Tannock, 1999; Finegold & Rolfe, 1983).
Limitations of conventional methods are their low sensitivities (Dutta et al.,
2001), their inability to detect noncultivatable bacteria and unknown species,
their time-consuming aspects, and their low levels of reproducibility due to
the multitude of species to be identified and quantified. In addition, the large
differences in growth rates and growth requirements of the different species
present in the human gut indicate that quantification by culture is bound to be
inaccurate. To overcome the problems of culture, techniques based on 16S
ribosomal DNA (rDNA) genes were developed (Amann, Ludwig, & Schleifer,
1995; Wilson & Blitchington, 1996).These include fluorescent in situ hybridiza-
tion (Franks et al., 1998; Jansen et al., 2000; Langendijk et al., 1995; Muyzer &
Smalla, 1998; Welling et al., 1997), denaturing gradient gel electrophoresis
(Suau et al., 1999; Simpson et al., 1999), and temperature gradient gel electro-
phoresis (Zoetendal, Akkermans, & De Vos, 1998). These techniques have high
sensitivities, but they are laborious and technically demanding.
   Another problematic issue with present stool analysis procedures is that of
transport. Since analysis is culture dependent, sample collection must be done
using nutrient broth containers to maintain microbial viability. This allows
continued growth of species during transport and until the sample is actually
plated out for culture. This growth allows for a significant change in the bal-
ance of microbes present, since some species will more actively grow at the
expense of others, especially in the presence of oxygen.


                             New Technologies

DNA analysis eliminates this problem by placing the specimen in vials which
contain a fixative for transport. This technique will be discussed in more detail
in the next Chapter.


      Microbial Metabolic Markers from Stool Testing

                         FECAL β-GLUCURONIDASE

Bacterial β-glucuronidase is an enzyme that can effectively reverse detoxifica-
tion that has taken place in the liver during the Phase II conjugation reactions.
Bacterial flora may express large amounts of glycosidase enzyme activity, the
principal glycosidase being β-glucuronidase. A report showing high levels of
β-glucuronidase calls attention to the need to restore beneficial bacterial pop-
ulations, and to the potential for greater enterohepatic circulation that can
affect metabolites such as estrogen.
68   INTEGRATIVE GASTROENTEROLOGY


   Glycosides are compounds containing a nonsugar molecule (aglycone)
attached to a sugar derivative, such as glucuronic acid, by α- or β-glycoside
linkage. Glycosides enter the GI tract through dietary intake, or from the liver
through bile secretions. Most dietary glycosides, predominately flavonoids,
come from vegetables and fruits. Glycosides coming from the liver include
toxic compounds that are inactivated by β-glucuronide formation and sub-
sequently secreted into the bowel by way of the bile. The intestinal flora can
hydrolyze the β-glucuronide bond, leading to release of the toxic compound,
which may be carcinogenic.


                                     FECAL pH

The colonic microbial mass converts food components into organic acids and
amines according to the nature of the substrate passing into the colon, and the
type of organisms that predominate. A high rate of organic acid production
gives acidic stools, whereas low acid formation with increased amines results
in higher pH of stool. One of the most important colonic health practices is
regular intake of high-fiber foods, so that beneficial organisms in the colon
receive substrate for the production of favorable products such as butyric acid.
Direct measurement of fecal pH provides an overall indicator of acid and base
balance.
   Abnormally acidic or alkaline pH of the stool may be an indicator of poor
digestive health. There is increasing evidence that fecal pH can serve as a
marker for colon cancer (Malhotra, 1982; Kashtan et al., 1990; Walker, Walker,
& Walker, 1986; Newmark & Lupton, 1990).High fecal pH, however, is only
indirectly associated with the development of colon cancer and, therefore, is a
secondary, rather than a primary, measure of cancer risk (Kashtan et al., 1990).
High stool pH appears to correlate with low levels of short-chain fatty acids
(especially butyric acid; see (Zoran et al., 1997; Segal et al., 1995; Phillips et al.,
1995; Folino, McIntyre, & Young, 1995). Alkalinity and low butyric acid levels
in the stool appear to signal inadequate intake or digestion of fiber and, pos-
sibly, low levels of beneficial colonic flora.
   Various patterns of simultaneous elevation of multiple bacterial and proto-
zoal by-products in urine are found in putrefactive dysbiosis that is also char-
acterized by lowered ratio of Bifidobacteria to Bacteroides, the major genera of
the anaerobic organisms. Fecal pH may be elevated, and β-glucuronidase
increases. This scenario has been linked to increased occurrence of colon and
breast cancer (possibly due to deconjugation of estrogen-glucuronide com-
plexes) and hepatic encephalopathy (Rowland, 1995).
                     Alternative Laboratory Testing for Gastrointestinal Disease 69




                FECAL SHORT-CHAIN FATTY ACIDS (SCFAs)

Frequently, disorders of the GI tract are associated with intestinal malabsorp-
tion. Many tests are useful in the diagnosis of GI disorders but do not effec-
tively differentiate abnormalities of absorption (mucosal function) from
digestion (pancreatic function). The fecal short-chain fatty acid test can be
helpful in making a differential diagnosis. Short-chain fatty acids (SCFAs) are
formed from bacterial fermentation of dietary carbohydrates and amino acids
that escape absorption in the small bowel. An alteration in the proportion of
various SCFAs, which stay constant in healthy colons, signifies an impaired
state of colonic health (Hoverstad, 1988).
   Short-chain fatty acids are well absorbed by the colon, and are a significant
source of energy for colonic cells. High acetic acid and low butyric acid in
relation to total SCFAs in the feces are found in patients with large bowel
adenomas and cancer (Latella & Caprilli, 1991). The fecal content of n-butyrate—
formed by the bacterial fermentation of fiber—is particularly critical for
colonic health, since it is such an important source of energy for the epithelial
cells of the colon (McCullough et al., 1998). Research suggests that inadequate
amounts of colonic n-butyrate could be a primary factor in the etiology of
inflammatory bowel disease, ulcerative colitis, and colon cancer (Royall,
Wolever, & Jeejeebhoy, 1990).
   The SCFA products of bacterial fermentation (or putrefaction), isobutyric,
valeric and isovaleric acids, come principally from undigested protein
(Rasmussen, Holtug, & Mortensen, 1988; Zarling & Ruchim, 1987).These
SCFAs are normally present at low concentrations in the healthy colon.
However, maldigestion of protein due to pancreatic enzyme insufficiency can
result in excess protein entering the colon. In these cases, fecal isobutyric
acid, valeric acid, and isovaleric acid will be elevated. Their presence is more
likely due to a pancreatic dysfunction, rather than an inadequacy of mucosal
absorption.


                               FECAPENTAENES

Fecapentaenes are polyunsaturated ether lipids that are derived from human
intestinal bacterial plasmalogens that have similar ether linkages (Van Tassell
et al., 1989). Fecapentaenes cause DNA damage and mutations in human cells
(Plummer et al., 1986; Gupta et al., 1984), and they are found in human feces,
70   INTEGRATIVE GASTROENTEROLOGY


where they are thought to play a role in the initiation of colorectal cancer
(Schiffman et al., 1989; Kingston, Van Tassell, & Wilkins, 1990).The structures
of highly mutagenic fecapentaenes have been elucidated (Hirai et al., 1985),
and methods for quantification of eight specific fecapentaenes in human
feces have been published (de Kok, ten Hoor, & Kleinjans, 1991; Kivits et al.,
1990; Kleinjans et al., 1989). Some researchers have proposed that the widely
varying ratios of two principal fecapentaenes can be traced to individual
differences in intestinal flora (Baptista et al., 1984). Bacteroides have been
identified as the source of fecapentaenes in a human autopsy study (Schiffman
et al., 1988). With the advent of more broad species identification using 16S
DNA identification techniques, there is potential for identifying more closely
the organisms in the general population with a capacity for fecapentaene
production.


                               Conclusions

Evaluation of gastrointestinal function includes detection of inadequate phys-
ical and immune barrier functions, and measures of the digestion and absorp-
tion of food. Pathogenic overgrowth of intestinal microbes in the upper
gastrointestinal tract can be detected by measuring their unique products in
urine. The patterns reflect the type of organisms that are present within broad
categories of bacteria, protozoa, or yeast. The information allows discrimina-
tion between putrefactive dysbiosis in the colon versus fermentative dysbiosis
in the small intestine, or combinations of both. The number of compounds
involved, and the degree of elevations found, change in direct proportion to
the severity of pathogenic overgrowth and loss of mucosal integrity. Stool pro-
filing yields markers of digestive function and results in direct observation of
microbial populations and can suggest specific antimicrobial therapies when
necessary.
                                     6
    New Molecular Techniques Revolutionize
     Understanding of the Influence of Gut
       Microbiota on Health and Disease
                         J. ALEXANDER BRALLEY




                                key concepts

     ■   The human GI tract contains a diverse and complex ecosystem
         of microbiota that can exert significant influence on health.
     ■   New molecular techniques now allow exploration of this
         ecosystem.
     ■   Molecular techniques solve many of the problems of traditional
         culture-based microbiology.
     ■   Molecular techniques significantly improve sensitivity and spec-
         ificity in parasitology and bacteriology of fecal samples.
     ■   Molecular techniques allow for better understanding of micro-
         biota balance, which enhances treatment options and improves
         outcomes.
                                       ■




                              Introduction



B
        acteria in the human gastrointestinal tract increase in concentration
        from stomach to rectum. There are up to 1012 organisms per gram of
        fecal material, of which approximately 95% are anaerobic. The gut
microbiota cell population outnumbers the host cells by a factor of 10. In fact,
the gut microbiota may be looked upon as a metabolically and physiologically
adaptable, rapidly renewable organ of the body, whose function is as critical to
human health as any other vital organ.

                                                                              71
72 INTEGRATIVE GASTROENTEROLOGY


   While bacteria predominate, protozoa are commonly found. It has been
estimated that more than 400 different bacterial species are present (Macfarlane
&. Macfarlane, 2004). This diverse population of bacteria can have a signifi-
cant impact upon the host environment and health of the individual. Intestinal
microbiota have been associated with the pathogenesis and pathophysiology
of many diseases, including atopic dermatitis and allergies (Bjorksten et al.,
2001; Penders, Stobberingh,van den Brandt, & Thijs, 2007; Penders et al.,
2007), chronic inflammatory bowel diseases (Kleessen et al., 2002; Farrell &.
LaMont, 2002; Linskens et al., 2001; Roediger & Macfarlane, 2002), ankylosing
spondylitis (Blankenberg-Sprenkels et al., 1998; Tiwana et al., 1998; Stebbings
et al., 2002), and rheumatoid arthritis (Wilson et al., 1998; Eerola et al., 1994;
Peltonen et al., 1994). The positive clinical results of using probiotics (Isolauri,
2001) and prebiotics (Macfarlane, Steed, & Macfarlane, 2008) to control symp-
toms and improve health underline the critical role intestinal bacteria play in
immune defense and general health.
   While the general makeup of the colonic bacteria population is similar in
humans, there can be vast differences in the inter-individual balance on the
genus and species levels. Ecological factors such as age, disease, diet, and anti-
biotic use can adversely affect this balance. Those factors that encourage eco-
logical species diversity support structural stability and metabolic homeostasis
in the population. Increased diversity has been associated with improved
health, while decreased diversity has been linked to reduced ability to resist
pathogens and inflammatory bowel diseases. (Bartosch et al., 2004; Ott,
Musfeldt, Wenderoth et al., 2004)
   The introduction of molecular techniques to assess this microbial popula-
tion has revealed much about its structure and function. This vastly improves
our ability to design therapies that manipulate gut ecology to optimize health.
Molecular techniques provide various clinical benefits: an accurate measure of
microbiota diversity; insight into genes for drug resistance; more sensitive
parasite detection; identification of species subtypes relating to potential
pathogenicity; and information regarding microbial balance that influences
energy metabolism, insulin resistance, and obesity. This chapter will briefly
review the molecular techniques used to identify and measure gut microbial
population, and the clinical benefits that result from this quantum leap over
culture techniques.


                                 Techniques

The major advantage of molecular techniques is that they can quantitatively mea-
sure the entire range of microbiota present in the human gastrointestinal tract.
        New Molecular Techniques Revolutionize Understanding of the Influence   73


Traditional culture methods cannot grow the vast majority of species present
(Eckburg et al., 2005), as only 10% to 20% of bacteria in a habitat are able to be
cultured (Wilson & Blitchington, 1996; Nadkarni et al., 2002; Suau et al., 1999).
Those that are cultured are usually quantified using relative abundance scores
such as +1 to +4 (Dutta et al., 2001; Tannock, 1999). In addition, the large dif-
ferences in growth rates, growth requirements, and the interdependence of the
different species present in the human gut make quantification by culture an
inaccurate reflection of the population. To overcome the problems of culture,
genomic techniques for bacterial identification have been developed (Wilson
& Blitchington, 1996; Welling et al., 1997; Furrie, 2006).
   The circular bacterial genome possesses multiple copies of a gene that codes
for the RNA contained in a ribosome. This ribosomal RNA gene or rDNA
gene is made up of several regions referred to by their relative molecular
weights. These 16s, 5s and 23s segments are separated by internal transcribed
spacer (ITS) regions (Figure 6.1). The rDNA genes have regions that are highly
conserved, and are exactly the same in all bacterial species. Other regions are
variable, and unique codon sequences for any bacteria can be identified. Since
these regions have now been fully sequenced for hundreds of bacteria, unique
probes can be designed that select for and identify bacteria by genus or species,
and even to the subtype level. By using unique primer sets binding to the vari-
able regions of the 16s or 23s rDNA gene regions, single bacteria or groups of
bacteria can be quantified. With the use of general primers and universal
probes, polymerase chain reaction (PCR), and hybridization array technology,
large populations of bacteria can be defined and quantified in a complex
sample such as fecal material (Figure 6.2; see Lyons, Griffen, & Leys, 2000; Ott,
Musfeldt, Ullmann, Hampe, & Schreiber, 2004).


           Specimen Integrity and Transport Issues

The extremely complex fecal microbiota ecosystem relies on anaerobic condi-
tions, pH, adequate nutrients, and temperature, for stability. Consequently, it
has been long recognized that a sample in transit can undergo significant
changes in microbial balance (Ott, Musfeldt, Timmis et al., 2004). Since tradi-
tional analysis is culture dependent, sample collection requires nutrient broth
containers to maintain microbial viability. This allows continued growth of
species during transport, and until the sample is plated out for culture. This
growth results in a significant change in the balance of microbes present,
because some species grow more actively at the expense of others. DNA analy-
sis eliminates this problem by placing the specimen in formalin or alcohol
vials for transport.
74    INTEGRATIVE GASTROENTEROLOGY


    Recent studies in our laboratory illustrate this situation. One specimen was
placed in two vials: one containing formalin, and another containing a nutrient
broth commonly used for transport. Both vials were incubated for three days at
room temperature, then DNA was extracted. The extract was incubated with
three different restriction enzymes, which cleave the DNA at specific base pair
sequences (Figure 6.3). The digestate was amplified by PCR, then placed on an
agarose gel plate and the DNA fragments were electrophoretically separated.
Since restriction enzymes cleave the DNA only at specific base pair sequences,
broths with identical populations of microbes would produce the same patterns
of banding in the electrophoretic runs. If, however, there were different amounts
and types of microbiota in the two tubes, differences would appear in the band-
ing patterns. This was clearly demonstrated in the experiment (Figure 6.4).
    Another observation from the data is the loss of banding in the nutrient
broth vial over time, indicating overgrowth of aerobes at the expense of the
anaerobic populations, and consequent loss of diversity. Opportunistic, poten-
tially pathogenic organisms also can overgrow under these conditions. This
has been seen in our laboratory. For these reasons, nutrient broth transport
vials cannot provide the specimen integrity required for accurate measure-
ment of gut microbes.


     Clinical laboratory data relying on transport of the specimen to the labora-
     tory for culture are likely erroneous and can lead to inappropriate patient
     treatment.



   Figures 6.5 through 6.7 illustrate the growth response of Bifidobacteria,
Candida species and Staphylococcus aureaus in one subject over three days.
These results indicate that clinical laboratory data relying on transport of the
specimen to the laboratory for culture are likely erroneous, and can lead to
inappropriate patient treatment. Candida species overgrowth is particularly
notable. As these data indicate, Candida proliferates in nutrient broth trans-
port media. This overgrowth in transport has likely fueled the common belief
held by many practitioners, of the deleterious health effects of Candida albi-
cans overgrowth in the gut. This may have resulted in inappropriate prescrip-
tion of antifungal agents.


                          Drug Resistance Genes

All antibiotic resistance strategies that bacteria develop are encoded in one
or more genes. Drug resistance genes are readily shared among and across
        New Molecular Techniques Revolutionize Understanding of the Influence 75


species and genera, and even among distantly related bacteria. These genes
confer resistance to different classes of drugs, and their sequences are known.
Using PCR techniques, they can be readily detected in large populations like
those found in fecal material. When considering treatment of a patient for a
pathogen, it is important for the clinician to know if a drug resistance gene is
present.
   If a pathogen is detected in stool, an analysis of the presence of antibiotic
resistance genes and drug sensitivities can be performed. If the pathogen is
found to be sensitive to two antibiotics, for example, but a gene that is resistant
to one of the drugs is present in the sample (a very possible scenario), it is
imperative that this drug not be used to treat the patient. Otherwise, even
though the pathogen is killed, the other organisms that have the gene confer-
ring resistance to the drug would thrive relative to other microbes present.
This sets up a potentially dangerous situation where antibiotic resistance is
maintained in the population, because that gene can be readily spread to other
organisms in the individual and the environment (Bergeron & Ouellette, 1998;
Martineau, Picard, Grenier et al., 2000; Martineau, Picard, Lansac et al.,
2000). Knowledge of the presence of antibiotic resistance genes in fecal speci-
mens represents a significant advance in patient treatment and maintenance of
health.


                                Parasitology

Parasitology is another field of microbiology to benefit greatly from molecular
technologies. Parasite infections are a major cause of nonviral diarrhea, even
in developed countries. Classically, parasites have been identified by micros-
copy and enzyme immunoassays (Verweij et al., 2004). In recent studies,
molecular techniques have proven to be more sensitive and specific than clas-
sic laboratory methods (Verweij et al; Ghosh et al., 2000; Morgan et al., 1998).
Because Giardia cysts are shed sporadically, and the number may vary from
day to day, laboratories have adopted multiple stool collections to help increase
identification rates for all parasite examinations (Ghosh et al.). Even with the
advent of antigen detection systems, there has long been uncertainty in diag-
nosis when no ova or parasites are found. Due to the nearly 100% sensitivity
and specificity of DNA analysis, combined with the need for very low amounts
of genomic DNA (as low as 2.5 cells per gram (Ghosh et al.), the previously
long specimen collection process, laborious and technically challenging
microscopy, and resulting delays in reporting have been alleviated. With PCR
technology, only one fecal sample is needed for near 100% sensitivity and
specificity in parasitology examinations.
76    INTEGRATIVE GASTROENTEROLOGY


   Blastocystis hominis subtypes have been associated with relative pathoge-
nicity in humans (Hussein et al., 2008). Differentiation among pathogenic
subtype populations in humans cannot be done using culture based tech-
niques, and is a unique contribution only possible through PCR technology.


                Gut Microbiota Influences on Insulin
                      Resistance and Obesity

Two predominant bacterial groups in the human GI tract are Bacteroidetes
and Firmicutes. These gut microbiota significantly affect energy harvest from
the diet, and energy storage in the host. Firmicutes bacteria, which include
Bacillus, Clostridia, and Lactobacillus species, are very efficient at metabolizing
plant polysaccharides into monosaccharides and short-chain fatty acids. These
can then be absorbed by the gut and converted to more complex lipids in the
liver. In addition, this group secretes a compound that results in increased
activity of lipoprotein lipase in adipocytes, resulting in enhanced storage of
these lipids. The Bacteroidetes group, which includes Bacteroides and Provetella
species, are not as efficient in this function. While excess caloric intake is a
significant factor in obesity, gut populations of microbiota that force an effi-
cient extraction and storage of energy may play a significant role in this grow-
ing health problem.

     The ability to assess the balance of “fat bugs” in humans may prove to be an
     important advance in understanding and treating diabetes and obesity.



   Recent studies have demonstrated another aspect of this intriguing story.
Manipulation of the gut microbiota in mice significantly alters their glucose/
insulin response (Membrez et al., 2008). The balance of bacterial populations
can actually increase levels of a bacterial lipopolysaccharide endotoxin that
dysregulates the inflammatory tone, and triggers body weight gain and diabe-
tes in mice (Cani et al., 2007). These studies demonstrate the possibility in
humans that modulation of gut microbiota can ameliorate glucose tolerance
by altering the expression of hepatic and intestinal genes involved in inflam-
mation and metabolism, and change the hormonal, inflammatory, and
metabolic status of the host. The ability to recognize this aspect of microbiota
effects in human health has only become available through the use of molecular
techniques.
        New Molecular Techniques Revolutionize Understanding of the Influence   77


   Ongoing studies are exploring the relationship between gut microbiota
and metabolic diseases. The use of specific diets and prebiotic and probiotic
therapies may significantly alter microbial balances that affect fat storage.
The ability to assess the balance of these “fat bugs” in humans may prove
to be an important advance in understanding and treating diabetes and
obesity.


                Ecosystem Diversity and Dysbiosis

Biodiversity in the gut microbiota ecosystem can now be elucidated by molec-
ular techniques. Since traditional clinical microbiological aerobic culture pro-
cedures were only able to evaluate less than 5% of organisms present, clinicians
were unable to truly assess diversity, or a “dysbiosis” condition commonly
associated with ill health (Hawrelak & Myers, 2004). The term dysbiosis was
coined to describe an imbalance in the gut microbiota caused by parasitic
infection, antibiotic use, or other factors. This dysbiotic condition can contrib-
ute to the development of many chronic degenerative diseases.
    By using molecular techniques, one can examine the major fecal anaerobic
genera in comparison to aerobic and fungal organisms, providing a much
clearer picture of the diversity and potential dysbiotic structure of the ecosys-
tem. By quantifying all of the major groups of microbiota and potential para-
sites present in the gut, the concept of dysbiosis can now be much better
defined in terms of ecosystem diversity. This concept will be useful for clini-
cians as they assess how the gut microbiota influence disease processes, and
how they might intervene.
    For example, lack of diversity has been associated with inflammatory bowel
diseases (Ott, Musfeldt, Wenderoth et al., 2004). Probiotics and prebiotics
influence diversity and, therefore, may significantly impact these diseases
(Steed, Macfarlane, & Macfarlane, 2008). Recent research is showing that
specific groups of bacteria can be preferentially stimulated to grow relative
to other populations. Individually tailored prebiotic compounds may poten-
tially be designed to selectively enhance bowel function through improved
microbiota diversity (Macfarlane &. Macfarlane, 2004; Macfarlane, Steed, &
Macfarlane, 2008; Macfarlane, & Cummings, 1999; Macfarlane, Furrie, &
Macfarlane, 2004; Macfarlane et al., 2005). Evaluating the microbiota diversity
balance using molecular techniques, and designing customized prebiotic and
probiotic regimens, will be a powerful new tool for the clinician in battling
inflammatory bowel diseases and other gut-related disorders.
78 INTEGRATIVE GASTROENTEROLOGY


                       Table 6.1. Advantages of PCR vs. Culture

• Single specimen collection vs. several
• Copies a single DNA sequence of a cell over a billion times within 1 to 2 hours,
  allowing sensitive quantitation
• Detects parasites with as few as 5 cells per/g vs. 25,000 cells per/g for microscopic
  techniques
  • 5,000 times more sensitive
• Ability to ID anaerobes (majority of bacteria—95%)
• No growth in transport vs. significant growth in transport
• Requires only 5 to 10 bacterial cells for ID vs. 1,000 to 5,000 for culture




                                    Conclusions

Molecular techniques using DNA to identify bacterial genus and species
are revolutionizing the understanding of how gut microbiota influence
human health. Clinical laboratory tests that use these techniques can provide
the clinician with practical new interventions targeted to the individual gut
ecosystem.
                                 7
Principles of Integrative Gastroenterology:
  Systemic Signs of Underlying Digestive
         Dysfunction and Disease
          LAURA K. TURNBULL, GERARD E. MULLIN ,
              AND LEONARD B. WEINSTOCK




                            key concepts

 ■   Many idiopathic syndromes overlap, and are caused by under-
     lying gut dysfunction.
 ■   Acute and chronic GI infections trigger chronic systemic diseases
     by several mechanisms, including small intestinal bacterial over-
     growth (SIBO), inflammation, and autoimmune phenomena.
 ■   SIBO underlies many poorly understood syndromes, including
     irritable bowel syndrome (IBS), restless legs syndrome (RLS),
     fibromyalgia syndrome (FMS), rosacea, and interstitial cystitis
     (IC).
 ■   Increased intestinal permeability and inflammation are compli-
     cations of SIBO.
 ■   Increased intestinal permeability may explain food allergies,
     and the increased involvement of diseases with eosinophils and
     mast cells (e.g., asthma).
 ■   SIBO treatment is effective treatment for IBS and SIBO-related
     syndromes.
                                   ■




                                                                         79
                               Introduction



G
          astrointestinal (GI) dysfunction is defined as abnormal metabolic
          function, motility, structure, infection, or inflammation, and there
          are many systemic symptoms and signs (extraintestinal manifesta-
tions) that may be an expression of such dysfunction. Classic examples of
extraintestinal manifestations include the fever and joint pain that occur
during a flare of Crohn’s disease, as well as various skin, eye, and hepatobiliary
diseases associated with inflammatory bowel disease (IBD). While these
examples are correlated with overt GI illness, the underlying cause of many
extraintestinal manifestations can also be attributed to underlying systemic
inflammation resulting from asymptomatic gut dysfunction—primarily, intes-
tinal permeability. Two predominant causes of this breach in the integrity of
the intestines are small intestinal bacterial overgrowth, and postinfectious
enteric illness. Throughout this chapter, we will primarily explore the conse-
quences of SIBO and its relationship to systemic conditions. The prevalence of
these disorders, and a review of integrative modalities to their treatment, will
be discussed.


   Common Extraintestinal Manifestations of GI Dysfunction




                Increased Intestinal Permeability

There are many barriers and defensive mechanisms by which the intestinal
tract mucosa can be exposed to antigens, bacteria, and chemicals, yet still be
selective about what is absorbed and secreted. This protection requires an
intact immunological and microanatomical defense system—a process in
which healthy commensal bacteria play a role. Therefore, bacterial over-
growth and enteric infections are two major insults to the gut that result in
increased permeability, as is shown in Figure 7.1.


   Genetics, Inflammation and Intestinal Permeability

Altered genetic background or phenotype may result in GI dysfunction in sev-
eral ways. First, specific HLA genome subtypes are found in celiac disease, and
                                     Principles of Integrative Gastroenterology 81


result in predisposition for the disease. Furthermore, a variety of genetic mark-
ers have been found in Crohn’s disease patients, as discussed in Chapters 30 and
44 Lastly, in both celiac disease and Crohn’s disease, a genetically determined
increased intestinal permeability may be a harbinger of clinical disease. Based
on the phenotypic genetic makeup, the impact of various stimuli, including
inflammation and dysbiosis, can lead to a variety of diseases or syndromes.
   Inflammation and infection of the intestinal lining can lead to increased
intestinal permeability, by damaging the tight junctions of mucosal cells. The
net effects are the stimulation of the inflammatory network, and activation of
lymphocytes and mast cells locally and systemically. This stimulation results in
the release of various cytokines, which can lead to an increase of corticotro-
pin-releasing hormone, which can in turn affect the central nervous system
(CNS), the hypothalamic-pituitary-adrenal (HPA) axis, and the peripheral
nervous system. Additionally, translocation of bacteria or the lipopolysaccha-
rides (outer covering of Gram-negative bacteria) into a damaged mucosal
lining can alter the HPA axis.
   The complex dynamics of the emotional motor system (EMS), and the
interplay of stress, cytokines, cortisol, neurological, and neuroendocrine
responses, are shown in Figure 7.2.



            Infections Triggering Digestive Disease
                     and Systemic Illness

GI and respiratory viral infections (enterovirus and adenovirus) can trigger a
number of gastrointestinal disorders (e.g. celiac disease, Crohn’s disease, IBS)
and systemic diseases. There are several good studies that have determined
the risk of developing postinfectious irritable bowel syndrome (Pi-IBS).
This risk ranges between 7%–34% after a bacterial infection (see Table 7.1).
Likewise, an existing GI condition can be worsened by a subsequent viral
infection. For example, altered immune mechanisms triggered by an abnor-
mal gene in Crohn’s disease can be a setup for an infection such as intramu-
cosal E. coli, which may exacerbate the disease process (Darfeuille-Michaud,
2002). Histological studies have shown differences in adherence and invasion
of bacteria into intestinal mucosa of patients with Crohn’s disease, and this
may also be based on altered immunity (Swindsinski et al., 2002).
   The phenomenon of postenteric infections causing systemic diseases and
syndromes is a critical concept because, of the approximately 76 million epi-
sodes of food poisoning per year in the United States, many of the diseases
and syndromes that are linked to food poisoning are poorly documented
82   INTEGRATIVE GASTROENTEROLOGY


                    Table 7.1. Incidence of Postinfectious IBS
Author                  Follow-Up   Number with acute     % of patients with acute
                        period(s)        diarrhea        diarrhea who developed IBS

Marshall 2005            2-3 yr           1137                      34

Mearin 2005              1 yr              271                      10

Okhuysen 2004            6 mo               60                      10

Neal 1997 & 2003         6 mo              357                       7
                         6yr               192                       7

Thornley 2000            6 mo               93                       9

Gwee 1999                3 mo              100                      22

McKendrick 1994          1 yr               38                      31




(Sobel et al., 2002). The well-publicized tainted food products in the past few
years have included beef, cheese, lettuce, peanut butter, spinach, sprouts, toma-
toes, and a variety of canned food (Currie et al., 2007; Dechet et al., 2006).
Hundreds of thousands of pounds of beef have been recalled because of
concerns about E. coli and salmonella. Data from the Centers for Disease
Control (CDC) show that foodborne illnesses cause 325,000 hospitalizations
and 5,000 deaths per year. However, the subsequent manifestations are not as
well publicized.
   The effects of acute food poisoning can be severe and long-lasting. Of those
infected with E. coli O517:H7, 10% develop hemolytic uremic syndrome, which
can cause kidney failure and pancreatitis (Garg et al., 2003). After recovery,
25% of these patients will develop chronic renal disease and diabetes (Oakes,
Kirkhamm, Nelson, & Siegler, 2008). The incidence of diabetes was determined
from a review of 1,139 children from 13 studies (1966–1998, aged 0.2–16 years),
and ranged from 0%–15%, with a pooled incidence of 3.2% (Suri et al., 2005).
   Other systemic illnesses that can result from acute food poisoning include
reactive arthritis, which can start 6 months or longer after a bout of Salmonella,
Shigella and Yersinia. Eye inflammation and urethritis are part of the classic
triad of Reiter’s syndrome. One of the most severe postenteric complications,
usually acquired from infected poultry, is camphylobacter-associated Guillain-
Barré syndrome (Zilbauer, Dorrell, Wren, & Bajaj-Elliott, 2008). Antibodies
against camphylobacter create an autoimmune syndrome with ascending
paralysis. Subsequent gastrointestinal dysmotilities have been reported, as well
(Nakazawa, 2008).
                                     Principles of Integrative Gastroenterology 83




          SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO)

The colon is accustomed to having trillions of coliform bacteria, but complica-
tions arise when the coliform count grows in the small intestine.


  There are several natural protective mechanisms that keep the small bowel
  bacteria at low colony counts, including the presence of stomach acid,
  gastrointestinal motility, digestive enzymes, mucosal immunity, and the
  integrity of the ileocecal valve.


  To minimize bacterial counts in the small intestine (SI), one has to:

  • maintain physiologic gastric acid production to reduce swallowed
    bacteria;
  • control the ingestion and have proper digestion of starches (i.e.,
    legumes) to limit the nutrition necessary for bacterial growth;
  • retain normal small bowel motility (as driven by the migrating
    motor complex in the fasting state) to sweep the bacteria toward the
    colon; and
  • preserve an intact ileocecal valve to act as a physical barrier (between
    the SI and colon) to prevent the reflux of stool/bacterial contents from
    the large intestine.

   These natural defenses are shown in Figure 7.3.
   SIBO is defined as a disruption or increase of the normal small bowel bacte-
rial population that can result in gas, bloating, flatulence, altered bowel func-
tion, and/or malabsorption of nutrients. Bloating, diarrhea, and nutrient
deficiencies are induced by excess intraluminal small intestinal bacteria, which
results from: (1) fermentation of nutrients producing gas, and (2) bile salt
deconjugation by bacteria, leading to fat malabsorption and subsequent steat-
orrhea and secretory effects, causing diarrhea. Deconjugation of the hydro-
philic components decreases absorption from the loss of the water-soluble
state, which is involved in fat absorption. The change in bacteria and the effect
of undigested starches are shown in Figure 7.4.
   With chronicity, weakness and weight loss from villous atrophy, and/or
malabsorption secondary to the effects of bile salt deconjugation, will become
evident. Advanced cases may have peripheral edema from hypoalbuminemia
84 INTEGRATIVE GASTROENTEROLOGY


and pallor from anemia (B12 deficiency, chronic disease, and in some cases
iron deficiency, for which achlorhydria is the most common explanation). In
advanced stages, cachexia and other changes of vitamin and nutrient defi-
ciency may become evident.
    Chronic asymptomatic SIBO can result in systemic inflammation (Lin,
2004). Circulating levels of cytokines, such as TNF-α and proinflammatory
interleukins, are elevated in SIBO (Dinan et al., 2006). Recent evidence indi-
cates that low-grade SIBO may present with virtually no GI symptoms, but
may affect the body in profound ways because of the systemic inflammation it
causes. This may explain many syndromes and symptoms associated with
chronic fatigue syndrome, rheumatoid arthritis, fibromyalgia, interstitial cys-
titis, restless legs syndrome, and rosacea (Table 7.3). SIBO may also explain
other syndromes due to the presence of systemic low-grade inflammation and
increased intestinal permeability.


                              CAUSES OF SIBO

SIBO occurs when the normal protective mechanisms that maintain bacterial
balance are interrupted. The most common causes of SIBO are poor motility
of the small intestine, allowing for overgrowth of coliform-type bacteria; pan-
creatitis, which allows for undigested nutrients to enhance bacterial growth;
and gastroparesis.


                 GASTROINTESTINAL MOTILITY AND SIBO

Neuromuscular disorders of the esophageal body, lower esophageal sphincter,
stomach, and small intestine, are important in the pathophysiology of many
GI and systemic disorders. Functional disorders such as IBS, GERD, and non-
ulcer dyspepsia are in part caused by disordered gastrointestinal motility.
When small intestinal motility is disturbed, and the ability to “sweep” patho-
genic organisms away from the upper gastrointestinal tract is impaired, the
risk of SIBO is increased. There is a growing prevalence of SIBO in IBS patients
and, as the SIBO resolves the IBS, symptoms improve.
    Other gastrointestinal motility disorders that can contribute to SIBO are
small intestinal pseudo obstruction, scleroderma, and postsurgical states. The
latter is among the most well known causes of SIBO, and is due to the decreased
motility and achlorhydria after certain gastrointestinal surgical procedures
                                          Principles of Integrative Gastroenterology 85


including, but not limited to, gastric bypass surgery and Whipple’s type surgi-
cal procedures. Additionally, gastrointestinal motility disorders, or lack of
adequate production of gastric acid with subsequent ingestion of live bacteria,
has been commonly recognized as contributing to SIBO (Lewis et al., 2001;
Parlesak et al., 2003; Lipski, Kelly, Malhotra, & Mountford, 1992). Other classic
examples of SIBO include pancreatic insufficiency, and abnormal small intes-
tinal mucosal disorders, including celiac disease and Crohn’s disease, as shown
in Table 7.2. Finally, many systemic diseases and conditions can also cause
SIBO—see Tables 7.2 and 7.3 and 7.4.



                           Table 7.2. Common Causes of SIBO
Scleroderma                                      Achlorhydria

Small intestinal pseudo-obstruction              Diabetes

Pancreatic insufficiency                         Radiation enteritis

Jejunal diverticulosis                           Immunodeficiency: CLL, IgA deficiency,
                                                 T-cell deficiency

Post-surgical anatomy: Billroth, Blind-loop,     Celiac and Crohn’s diseases
ICV resection, J–pouch




                         Table 7.3. Lesser Known Causes of SIBO
Chronic renal failure                            Rheumatoid arthritis

Cirrhosis                                        Irritable bowel syndrome

Chemotherapy                                     Fibromyalgia

Acromegaly                                       Interstitial cystitis

Hypothyroidism                                   Restless legs syndrome

Chronic fatigue syndrome                         Rosacea




   SIBO has been reported in as many as 84% of patients meeting diagnostic
   criteria for IBS. Other studies confirm a relationship of SIBO to IBS, as shown
   in Table 7.4.
86   INTEGRATIVE GASTROENTEROLOGY


 Table 7.4. Prevalence of Small Intestinal Bacterial Overgrowth in IBS Patients as
          Determined by a Positive Breath Test for Bacterial Overgrowth
Author                    Substrate          #               Prevalence
                                             Subjects        (%)

McCallum, 2005            Glucose            143             38.5

Lupascu, 2005             Glucose             65             30.7

Nucera, 2005              Lactulose           98             65

Walters, 2005             Lactulose           39             10

Noddin, 2005              Lactulose           20             10

Nucera, 2004              Lactulose          200             75

Pimentel, 2000–3          Lactulose          313             57, 76, 84

Weinstock, 2006           Lactulose          254             63




                INTESTINAL GAS AND THE DIAGNOSIS OF SIBO

The obvious consequence of bacterial fermentation is the production of gas.
The variety of gases that develop in the gut expand its diameter, causing
abdominal bloating, distention, and discomfort from the triggering of stretch
receptors (see Figure 7.5). This bloating is most often caused by excess hydro-
gen production from bacterial fermentation (King, Elia, & Hunter, 1998).
Simple lactose maldigestion is well known to cause hydrogen and lactic acid
production, with subsequent bloating and diarrhea. Diagnostic tests for SIBO
are either direct invasive studies with bacterial cultures via nasal jejunal tubes,
or indirect techniques using breath testing with either glucose or lactulose
(Koshini, Dai, Lescano, & Pimentel, 2008). Hydrogen breath testing in par-
ticular is useful in identifying patients with IBS who are affected by SIBO, but
other exhaled gases may have diagnostic benefit, as well (Koshini, Sun-Chuan,
Lezcano, & Pimentel, 2007).
    Specific characteristics of each gas pose their own hazard. The production
of hydrogen sulfide can cause increased nociception, as found in IBS and idio-
pathic constipation (IC). Excess hydrogen and methane result predominantly
in bloating (as seen in IBS), while excess methane also results in altered motil-
ity, manifested primarily as constipation.
    Early studies of the association of methane production and altered
motility looked at orocecal and whole gut transit, and found that each was
significantly delayed if methane excretion occurred early on in the lactulose
                                     Principles of Integrative Gastroenterology 87


breath test (LBT). As a result, abnormal methane production was shown to be
strongly associated with constipation-predominant IBS (Pimentel et al., 2003).
Methane was detected in 50 (17%) of 296 patients with IBS, compared with 2
(3%) of 78 patients with IBD (P < .01). Subsequently, a study of 87 patients
showed that, of the 20 that had methane production, severity of constipation
was double that of non-methane-producing IBS subjects (Chatterjee et al.,
2007). A correlation was found between the degree of methane production on
the breath test and the severity of constipation. Infusion of methane into the
small intestine has shown that gut transit can be reduced by up to 70%
(Pimentel et al., 2006). Thus, methane as a by-product of fermentation can
itself slow intestinal transit.


      THERAPY FOR SMALL INTESTINAL BACTERIAL OVERGROWTH

The basis for SIBO treatment is the understanding that most cases of SIBO are
caused by poor motility of the small intestine, which then allows for bacterial
overgrowth and subsequent damage to the intestinal lining. Antibiotic treat-
ment is the mainstay of treatment, and requires a broad-spectrum antibiotic to
be effective. Treatment with quinolones, amoxicillin, tetracycline, and met-
ronidazole, is somewhat effective, but can cause bacterial resistance and anti-
biotic-associated diarrhea.


                      RIFAXIMIN THERAPY FOR SIBO

Rifaximin offers a unique profile for SIBO, with its broad-spectrum activity,
non-absorbable moiety, bile solvency (thus increasing activity in the small
intestine), and low likelihood of long-term resistance (Su, Aberra, &
Lichtenstein, 2006). It has been shown to be effective in patients with SIBO,
IBS with SIBO, and scleroderma (Lauritano et al., 2005; Pimentel, Park,
Mirocha, Kane, & Kong, 2006; Parodi et al., 2008). The efficacy of Rifaximin in
the treatment of SIBO, IBS, and functional bowel syndrome has been evalu-
ated in several studies, as summarized in Table 7.5 (Di Stefano, Malservisi,
Veneto, Ferrieri, & Corazza, 2000).
   Nucera et al. (2005) looked at a large group of patients who were treated
with weekly courses of combination antibiotics every month for 4 months.
There was a significant improvement in the breath tests using lactulose, lactose
and fructose. Laurentino et al. (2005) showed that increasing the dose of rifax-
imin from 800 mg/day/week to 1,200 mg/day/week resulted in double the
improvement in reversing the breath test. The UCLA group has subsequently
88   INTEGRATIVE GASTROENTEROLOGY


                   Table 7.5. Rifaximin Therapy for IBS-SIBO
Author      Yr    Patients           Type            Efficacy

Nucera      ‘04   IBS-SIBO (n=200)   Open label; Rfx 87-100% effective in
                                     + paramomycin treating SI BO by reversing
                                                     3 sugar BT’s

Lauritano   ‘05   IBS-SIBO (n=90)    Dose-ranging    Dose response with Rfx

Lupascu     ‘05   IBS-SIBO (n=80)    Abx             1 wk of Rfx vs. metro/
                                     comparison;     levoquin 12/20 vs. 14/20 H2
                                     open label      BT normalized

Pimentel    ‘05   IBS-SIBO (n=87)    R/DB/PC         Statistical sig. vs. placebo;
                                                     duration of response over
                                                     2 months for 10-day Rx

Sharara     ‘06   IBS (n=70)         R/DB/PC         Statistically sig. vs. placebo

Sharara     ‘06   Fx-SIBO (n=54)     R/DB/PC         Numerically diff. vs.
                                                     placebo

Weinstock   ‘06   IBS-SIBO (n=254)   Observational   60% mod-greatly improved

Weinstock   ‘06   Fx-SIBO (n=85)     Observational   63% mod-greatly improved




reported that reversing the breath test is critical in symptom resolution
(Pimentel, Chow, & Lin, 2003).
   Pimentel, Park, Murocha et al.’s 2006 study showed that a 10-day course of
1,200 mg/day of rifaximin resulted in 10 weeks of improvement of IBS symp-
toms. Patients experienced a 36% mean improvement from baseline in the
severity of IBS symptoms at 10 weeks post-treatment, compared with a mean
improvement of 21% among 44 patients who received placebo (P = .02). The
dose of rifaximin in Sharara et al.’s study (2006) was 800 mg/day for 10 days;
global symptomatic response was achieved in 41% of 37 patients, compared
with 6 (18%) of 33 patients who received placebo (P = .04). After 10 days post-
treatment, 10 (27%) of 37 patients in the rifaximin group maintained their
symptomatic response, compared with 3 (9%) of 33 patients in the placebo
group (p=0.05).
   In an open-label, observational study, a 10-day course of rifaximin 1,200
mg/day, as part of a comprehensive treatment regimen including tegaserod
and probiotic therapy, improved IBS symptoms in 60% of 81 patients
(Weinstock et al., 2006;110:A1123). Our own experience shows that effective
                                    Principles of Integrative Gastroenterology 89


antibiotic therapy, (LBW) along with high doses of Coenzyme Q10, reduces
the severity of fatigue in IBS patients with SIBO.
   Studies have also been done comparing the effectiveness of other antibiotics
used in the treatment of SIBO compared to Rifaximin. A retrospective chart
review of 98 patients with IBS who received antibiotic therapy (Yang J, Lee HR,
Low K et al., 2008) showed that 58 (69%) of 84 patients who received at least
one course of rifaximin experienced clinical response, compared with 9 (38%)
of 24 patients who received neomycin (p<0.01) and 27 (44%) of 61 patients
who received other antibiotics (e.g. amoxicillin clavulanate and doxycycline;
P < .01).


     COMBINATION PROMOTILITY ANTIBIOTIC THERAPY FOR SIBO

Given that disturbances in gastrointestinal motility are key to the development
of SIBO (via impaired “sweeping” of bacteria in the upper digestive tract),
treatment with promotility agents are paramount to the therapy of this condi-
tion. In the past, long-term tegaserod (a serotonin agonist) was given in an
attempt to improve the Phase III abnormality of the migrating motor complex
found in patients with IBS who have SIBO (Spiller et al., 2000). A review of
IBS-SIBO patients who were treated with antibiotics and then were given tega-
serod (no longer available in the United States) versus low-dose erythromycin
(50mg dose acts as a stimulant to the migrating motor complex) showed that
tegaserod decreased recurrence of IBS-SIBO symptoms at a rate twice that of
erythromycin, and four times that of no medication after rifaximin alone
(Yang J, Lee HR, Low K et al., 2008). The problems with erythromycin include
the potential for abdominal cramps, interference with birth control pills, and
other drug interactions including an increased risk of muscle damage when
used concurrently with statin medications.
    Low-dose naltrexone may be used as an alternative to erythromycin. This
anti-opioid can stimulate the intestine, and some emerging data suggests that
it has anti-inflammatory properties, which might help repair the intestinal
lining. The problems with naltrexone include general CNS stimulation (poten-
tial for jittery feelings, insomnia, and unusual dreams). It is contraindicated
for people who take chronic opioids.
    The following are possible alternative treatments for SIBO:

  • Probiotics can reduce inflammation and improve permeability prob-
    lems (Spiller, 2005; Resta-Lenert & Barrett, 2006; Ait-Belgnaoui et al.,
    2006). Specifically, bifidobacteria-based probiotics may repair small
90 INTEGRATIVE GASTROENTEROLOGY


    intestinal permeability and immune defects characteristic of SIBO,
    IBS, and postinfectious IBS (Spiller et al., 2000; Dunlap, Hebden, &
    Campbell, 2006; Plaza, 2001).
  • Zinc can theoretically help reverse defects in small intestinal perme-
    ability (Spiller, Jenkins, Thornley et al., 2000). Experimental evidence
    shows that zinc supplementation improves intestinal permeability in
    toxin-induced colitis (Sturniolo, Fries, Mazzon et al., YEAR). Zinc
    carnosine (ZnC) stimulated migration and proliferation of cells in
    vitro, in a dose-dependent manner, and decreased gastric and small-
    intestinal injury (50% reduction in villous shortening at 40 mg/ml;
    both p<0.01; see Mahmood et al., 2007). In volunteers, indomethacin
    caused a threefold increase in gut permeability in the control arm,
    while no significant increase in permeability was seen when ZnC was
    co-administered.
  • Medical foods containing glutamine or aloe (either individually or in
    combination) are used by many practitioners to facilitate intestinal
    permeability resolution after therapy of SIBO.
  • Antimicrobial herbal preparations have been used by the author
    (G. Mullin) to resolve SIBO that is refractory to rifaximin and triple
    antibiotics (clindamycin, neomycin, metronidazole. Examples of
    products used by the author with success include:

    ° Dysbiocide (Biotics Research Laboratories)
    ° FC Cidal (Biotics Research Laboratories)
    ° ADP (Biotics Research Laboratories)
  • The role of diet therapy during the treatment of SIBO cannot be
    emphasized enough. Individuals need to be counseled to avoid fruc-
    tose, fructans, and poorly digestible starches, such as beans (see
    Appendix A).
  • Since immune GI dysfunction plays a role in IBS, there are additional
    alternative approaches to SIBO treatment, including:

    ° Probiotics administered post-treatment, once SIBO is resolved
    ° Elimination diet to avoid allergens that can trigger immune and
      inflammatory responses
    ° Avoiding food products (i.e., indigestible starches) that can fer-
      ment in the small intestine and facilitate the growth of the gut
      microbiota
    ° Hypnotherapy to downregulate the stress response on the immune
      system and the gut lining
                                     Principles of Integrative Gastroenterology 91


     ° Acupuncture to facilitate GI motility via resetting the migrating
       motor complex to sweep intestinal bacteria in an antegrade
       manner
     ° Immune enhancers such as:
         Arabinogalactans (raises mucosal sIgA levels)
         Saccharomyces boulardii (raises mucosal sIgA levels)
         IgG2000 (raises mucosal sIgA levels)
         Colostrum (rich in preformed antibodies)
     ° Behavioral therapy to attenuate the stress response, reset pain
       thresholds, and lower neuroendocrine and inflammatory
       markers.



   Systemic Consequences of SIBO-Induced Gut Injury

                      CHRONIC FATIGUE SYNDROME

Chronic fatigue syndrome (CFS) is an idiopathic complex illness character-
ized by heightened reactive oxygen metabolites, along with mitochondrial
defects that lead to aberrant fatty acid and energy metabolism. Research also
indicates that CFS patients are under increased oxidative stress, have a Type 2
helper-cell-dominant cytokine profile, frequently report allergies, have altered
essential fatty acid (EFA) status, and may have malabsorption of certain micro-
nutrients (Logan, Venket Rao, & Irani, 2003). Gastrointestinal links to chronic
fatigue syndrome include marked alterations in microbial flora, including low-
ered levels of bifidobacteria, and SIBO Lactic acid bacteria (LAB) found in
probiotics have the potential to influence the immune system in CFS patients
by supporting T-helper-cell-1-driven cellular immunity, and may decrease
allergies.
   Systemic inflammation induced by SIBO could be responsible for altera-
tions in the hypothalamic pituitary adrenal axis, causing the fatigue found in
the irritable bowel syndrome. Interestingly, IBS has also been associated with
CFS and SIBO independently (Figure 7.2; see Cleare, Miell, Heap et al., 2001;
Gaab, Rohleder, Heitz et al., 2005; Hamilton, Gallagher, Thomas, & White,
2009). Preliminary data by Pimentel et al. (2000) showed that SIBO was
common in CFS (77% of 31 patients), and there was improvement in tender
points and depression (but not in fatigue scores) when antibiotics improved
SIBO.
92   INTEGRATIVE GASTROENTEROLOGY




                      RESTLESS LEGS SYNDROME (RLS)

The prevalence of RLS is estimated at 10% of the general population, and it
results in sleep disorders and a poor quality of life (Allen, Walters, Montplaisir
et al., 2005) from the compelling urge to move the legs at night, often with
discomfort. RLS is a central nervous system disorder that is either idiopathic
(primary) or secondary to a number of conditions, including GI dysfunction.
Possible mechanisms of action in RLS include iron deficiency, inflammation,
and/or SIBO.
    In virtually all forms of RLS (primary, familial, and secondary), there is
central nervous system iron deficiency (Berger, Von Eckardstein, Trenkwalder
et al., 2002; Allen, 2004). Additionally, RLS patients often have varying degrees
of asymptomatic peripheral iron deficiency (Aul, Davis, & Rodnitzky, 1998;
Rama, Aul, Davis, & Rodnitzky, 1998). A chronic inflammatory state caused by
SIBO (Lin, 2004) could be related to RLS by affecting hepcidin production
directly (Kemna, Pickkers, Nemeth et al., 2005) and indirectly (Liu Z, Li, &
Neu, 2005), decreasing peripheral and central nervous system iron uptake and
transportation (Earley, Connor, Beard et al., 2000; Clardy, Earley, Allen et al.,
2006). There is limited recognition that iron deficiency is an integral part of
the pathophysiology of RLS. The growing understanding of iron metabolism
and the role of SIBO and systemic inflammation in RLS is exciting. The role
for modulation of dysbiosis will be determined with double-blind, placebo-
controlled studies, which are in progress.


     THEORY FOR SIBO CAUSING RLS AND CENTRAL IRON DEFICIENCY

Factors that are associated with secondary RLS include elderly status, diabetes,
end-stage renal disease, fibromyalgia, rheumatoid arthritis, and Parkinson’s
syndrome. Furthermore, all of these conditions have also been associated
with SIBO. Secondary RLS has also been associated with gastrointestinal
conditions, such as gastric resection, chronic liver disease, IBS associated
with SIBO, celiac disease, and Crohn’s disease (Banerji & Hurwitz, 1970;
Franco, Ashwathnarayan, Deshpandee et al., 2008; Weinstock, Fern, &
Duntley, 2008; Weinstock, Bosworth, Scherl et al., 2008). Patients with
scleroderma also have a reported increased incidence of RLS, although in this
single study the patients did not have symptoms of end-stage SIBO (Prado,
Allen, Trevisani et al., 2002).
                                        Principles of Integrative Gastroenterology 93




                       TREATMENT OF SECONDARY RLS

Medical trials for RLS have been recently reviewed extensively, and are sum-
marized in Table 7.6 (Trenkwalker, Hening, Montagna et al., 2008). Magnesium,
folic acid, and exercise are frequently used in practice, but are considered to be
investigational. The efficacy of oral iron is also considered investigational;
however, its efficacy appears to depend on the iron status of subjects.
Intravenous iron is likely efficacious for the treatment of RLS secondary to
end-stage renal disease, but investigational in RLS subjects with normal renal
function (Earley, Heckler, & Allen, 2005).
   Most physicians who treat RLS feel that the first approach after iron treat-
ment is to initiate dopamine agonists (Comella, 2002). Ropinirole is margin-
ally better than placebo augmentation, and a wide array of side effects of
dopamine agonists have led to interest in finding therapeutic alternatives
(García-Borreguero, Allen, Kohnen et al., 2007).


                              ANTIBIOTICS FOR RLS

Two pilot studies have evaluated the effect of rifaximin for the treatment
of RLS.
   The first prospective clinical trial of 13 IBS patients with both SIBO and RLS
reported that 77% of patients (10/13) had ≥80% long-lasting improvement of
RLS symptoms following open-label treatment with rifaximin 1,200 mg/day



             Table 7.6. Medical Therapy for Restless Legs Syndrome

          Dopaminergic agents
          Neuroleptics
          Anti-seizure medications
          Narcotics
          Benzodiazepines
          Iron
          Investigational
             Rifaximin antibiotic therapy
             Magnesium
             Acupuncture
             Botox injections
94 INTEGRATIVE GASTROENTEROLOGY


for 10 days, followed by motility and probiotic therapy (Weinstock, Fern, &
Duntley, 2008). The next study included patients with primary RLS who had a
positive lactulose breath test for SIBO. The mean baseline IRLS score was 23.1
(Weinstock, Fern, & Duntley, 2008). Open-label treatment with rifaximin
1,200 mg/day/10 days, followed by 400 mg/every other day/20 days, resulted in
a decrease in the IRLS score by 10.7 in 9 of 14 patients. Two of the five RLS
nonresponders had improvement with a second course of rifaximin when
combined with metronidazole, and a third patient improved when she was
later diagnosed with celiac disease and placed on a gluten-free diet and iron
supplementation.


                            ALTERNATIVE THERAPIES FOR RLS

The common approaches used for many conditions include herbs, vitamins
and/or minerals, acupuncture, botulinum toxin, hyperbaric therapy∗ and chela-
tion therapy∗. Small studies have suggested improvement from magnesium,
although scientific studies of magnesium in RLS have been nonsupportive
(Hornyak, Voderholzer, Hohagen et al., 1998; Bartell & Zallek, 2006; Walters,
Elin, Cohen et al., 2007). Acupuncture has been studied in 14 studies, but
only 2 were judged worthy of comment based on the design, and there is insuf-
ficient evidence to support the use of acupuncture in RLS (Cui, Wang, & Liu,
2008). Intramuscular botulinum injections have shown success in 3 patients
(Rotenberg, Canard, & Difazio, 2006). Finally, pneumatic sequential compres-
sion devices on RLS symptoms showed success in 6 of 10 patients (Eliasson &
Lettieri, 2007). Small, open-label studies with RLS are problematic, since the
placebo response is so high.


       RESTLESS LEGS SYNDROME (RLS), CELIAC, AND CROHN’S DISEASE

      • The relationship between restless legs syndrome (RLS) and celiac dis-
        ease has recently been reported (Weinstock, Bosworth, Scherl et al.,
        2008).
      • RLS was found to be a frequently associated condition in 85 celiac
        patients: the incidence was 35.5% and the prevalence was 24.7%, com-
        pared with spouse control group of 9.5%.
      • Neurologic complications have only recently been reported in Crohn’s
        disease.

∗
    Have not been reported in the literature.
                                       Principles of Integrative Gastroenterology 95


   • The incidence of RLS was 42.7% in a large number of Crohn’s disease
     patients from three academic centers and one large community prac-
     tice (Weinstock, Bosworth, Scherl et al., 2008).
   • The prevalence of RLS in Crohn’s disease was 30.2%, compared to a
     prevalence of 8.4% in the sex-matched spouse control group.


                         Interstitial Cystitis (IC)

Interstitial cystitis (also known as painful bladder syndrome) is an idiopathic
syndrome characterized by symptoms of urinary frequency, urinary urgency,
pain with bladder filling, pelvic pain, and dyspareunia. There is a significant
overlap of interstitial cystitis (IC) with food allergies, autoimmune disease,
and IBS. GI dysfunction may play a role in IC, since food triggers, mast cells,
neural crosstalk, and SIBO have been implicated in the pathophysiology.
A connection to SIBO has been proposed, and a positive therapeutic
study using SIBO open-label antibiotic therapy was reported (Lin, 2004;
Weinstock, Klutke, & Lin, 2007). The potential interactions of mast cells,
inflammatory mediators, and the peripheral nervous system are shown in
Figure 7.7.


        Possible Role of SIBO and IC Pathophysiology

                           ROLE OF FOOD ALLERGIES

Shorter et al. (2007) determined the prevalence of the effect of food substances
on painful bladder syndrome/interstitial cystitis symptoms. Of the surveyed
patients with IC, 90.2% indicated that the consumption of certain foods or
beverages caused symptom exacerbation. Patients who reported that specific
foods worsened symptoms tended to have more severe IC symptom scores.
The most frequently reported foods causing symptom exacerbations were
coffee, tea, soda, alcoholic beverages, citrus fruits and juices, artificial sweeten-
ers, and hot pepper.


     Gut Permeability, Inflammation, and Pelvic Pain

The link between chronic pelvic pain, dyspareunia, and functional digestive dis-
eases (i.e., IBS) has been long established (Vercellini, Somigliana, Viganò et al.,
2009). Since SIBO, chronic inflammation, altered HPA axis, and systemic
96    INTEGRATIVE GASTROENTEROLOGY


proinflammatory cytokines are implicated in the pathogenesis of IBS, an exper-
imental study was undertaken to investigate the mechanism of development of
pelvic pain (Rudick, Chen, Mongiu, & Klumpp, 2007). One study explored, in
an animal model of IBS, whether pelvic pain could develop remotely from the
original site of inflammation. These investigators confirmed that there is organ
crosstalk (between the intestine and vagina), as well as modulation of pain
responses by visceral inputs distinct from the inflamed site. Thus, SIBO/IBS can
manifest in other organ systems distant from the site of pathology, via the
common mucosal immune system (see Chapter 3).


                                  Rosacea

Systemic inflammation caused by GI dysfunction may be an explanation for
rosacea, which is a common idiopathic disease that presents with transient or
persistent facial erythema, telangiectasia, edema, papules, and pustules, usu-
ally confined to the central portion of the face (Buechner, 2005). In the past,
genetic, environmental, vascular and inflammatory factors, and microorgan-
isms such as skin bacteria, including Demodex folliculorum, and gastric infec-
tions with Helicobacter pylori have been considered as etiologic factors.


                   ROSACEA AND DIGESTIVE DISORDERS


     Rosacea has been associated with gastritis and hypochlorhydria; many
     people have nonspecific gastrointestinal symptoms.




                          Helicobacter pylori

The role of Helicobacter pylori has often been a subject of investigation, with
studies showing conflicting results. A small study investigated ocular rosacea,
and clinical and serological evidence of H. pylori infection showed significant
improvement of rosacea symptoms, with ocular disease responding better
than cutaneous rosacea (Daković, Vesić, Vuković et al., 2007). An older study
from Poland on the treatment of H. pylori infection, in 60 patients with rosa-
cea having erythema and flushing on the face with visible papules and pus-
tules, was compared to 60 age and gender matched patients without any skin
diseases (Szlachcic, 2002). The effect of treatment on plasma interleukin (IL-8)
and tumor necrosis factor alpha (TNF-α) was also determined after 1 week of
                                     Principles of Integrative Gastroenterology 97


omeprazole 20 mg, clarithromycin 500 mg, and metronidazole 500 mg, all
twice daily. The H. pylori prevalence in rosacea patients was about 88%, com-
pared to 65% in control patients. There was twice the incidence among rosacea
patients of a more virulent form of H. pylori (cytotoxin-associated gene A
[CagA] positive). After antibiotics, 51 out of 53 treated rosacea patients became
Hp negative. Within 2 to 4 weeks, the symptoms of rosacea disappeared in 51
patients, markedly declined in one, and remained unchanged in one other
subject. Plasma TNF-α and IL-8 were reduced significantly after the therapy in
both groups of patients (72% and 65%, respectively).



  Rosacea could be considered as one of the major extragastric symptoms of
  H. pylori infection cytotoxins and cytokines.




                                     SIBO

Italian investigators recently discovered the link between rosacea and small
intestinal bacterial overgrowth (Parodi, Paolino, Greco et al., 2008). Of 113
consecutive rosacea patients, 52 had a positive breath test (versus 3 of 60 con-
trols). After SIBO eradication by rifaximin, as determined by reversal of the
breath test, cutaneous lesions cleared in 20 of 28, and greatly improved in 6 of
28 patients, whereas patients treated with placebo remained unchanged (18/20)
or worsened (2/20) (P<0.001) (Figure 7.8).
   The patients who were given placebo were subsequently switched to rifaxi-
min. In these patients, SIBO was eradicated in 17 of 20 cases. Fifteen of these
patients had a complete resolution of rosacea. Thirteen of 16 patients with neg-
ative breath tests for SIBO remained unchanged, and this result differed from
SIBO-positive cases (P<0.001). Eradication of SIBO induced an almost com-
plete regression of their cutaneous lesions for at least 9 months.
   The authors of the study suggested that chronic systemic inflammation
causes inflammation of the skin. Figure 7.8 shows the clinical outcome in
SIBO-positive and SIBO-negative rosacea patients treated with rifaximin.


  1. Myth: Syndromes are all “in your head” and are due to “stress.”
  2. Restless legs syndrome is caused by central nervous system iron defi-
     ciency and altered dopamine interactions. Evidence is growing for the
     role of small intestinal bacterial overgrowth.
  3. The real name for “leaky gut” is increased intestinal permeability.
98    INTEGRATIVE GASTROENTEROLOGY




                                     Summary

     1. Integrity of the gut mucosa is essential for good health.
     2. Imbalance of bacteria plays a role in many disorders.
     3. A shift of colonic type bacteria into the small intestine results in inflam-
        mation as well as fermentation, with subsequent gas production.
     4. Treatment with special antibiotics, motility medicine, and probiotics
        may provide benefits to those suffering from “syndromes.”
     5. Syndromes do not exist in a vacuum. The high prevalence of these
        idiopathic conditions in the population, and the overlapping of symp-
        toms from one condition to another, suggest that a central cause could
        be a significant factor (Figure 7.9).
                                       8
      The Skin and the Gastrointestinal Tract
                          ANDREW G. FRANKS , JR.




                                  key concepts

      ■   The neutrophilic dermatoses are a spectrum encompassing
          four distinct diseases characterized by sterile neutrophilic cuta-
          neous infiltrates, and include erythema elevatum diutinum,
          pyoderma gangrenosum, Sneddon-Wilkinson syndrome, and
          Sweet’s syndrome.
      ■   Bowel stasis, which promotes bacterial overgrowth, with either
          disease or surgically induced blind loops, can cause a bowel-
          associated dermatosis-arthritis syndrome.
      ■   Acanthosis nigricans is arguably also the most well-recognized
          cutaneous sign of internal malignancy.
      ■   Peutz-Jeghers syndrome is a dominantly inherited polyposis
          syndrome, characterized by hamartomatous polyps of the gastro-
          intestinal tract, and mucocutaneous pigmentation and melanin
          spots.
                                         ■




                                Introduction



T
        he skin and the gastrointestinal tract are both covered or lined by epi-
        thelium, and both communicate with the external environment.
        Therefore, it is not surprising that diseases that primarily affect the gas-
trointestinal tract often have cutaneous manifestations as well. These cutaneous




                                                                                 99
100   INTEGRATIVE GASTROENTEROLOGY


findings frequently provide clues to the diagnosis of the underlying gastroin-
testinal disease (Gregory & Ho, 1992a, 1992b). There are a vast number of asso-
ciations, from extremely rare genetic disorders to more common illnesses,
both benign and malignant. These more common associations, which are most
likely to be encountered in clinical practice, are the focus of this review.
   Of the benign disorders, the following will be reviewed:

  •   IBD and the neutrophilic dermatoses
  •   Bowel bypass syndrome
  •   Erythema nodosum
  •   Acrodermatitis enteropathica
  •   Dermatitis herpetiformis
  •   Pancreatic panniculitis
  •   Hepatitis C
  •   Helicobacter pylori

   Of the malignancy-associated disorders, examples of the following will also
be reviewed:

  •   Glucagonoma syndrome
  •   Bazex’s syndrome
  •   Palmar-plantar hyperkeratosis
  •   Acanthosis nigricans
  •   Gardner’s syndrome
  •   Peutz-Jeghers syndrome
  •   Cowden disease



                The Neutrophilic Dermatoses and
                     Other Benign Disorders

The neutrophilic dermatoses are a spectrum encompassing four distinct
diseases characterized by sterile neutrophilic cutaneous infiltrates. The etiol-
ogy of these disorders is not well understood, but is thought to be related
to deposition of immune complexes in dermal vessels, resulting in comple-
ment fixation and leukocytoclastic vasculitis, as well as altered neutrophilic
chemotaxis. The neutrophilic dermatoses include erythema elevatum diuti-
num, pyoderma gangrenosum, Sneddon-Wilkinson syndrome and Sweet’s
syndrome.
                                        The Skin and the Gastrointestinal Tract 101




                     ERYTHEMA ELEVATUM DIUTINUM

Erythema elevatum diutinum (EED) is characterized by multiple symmetric
papules, plaques, nodules, vesicles, or bullae on the extensor surface of joints,
particularly the elbows, knees, hands, and feet. The lesions usually are initially
red to purple in color, some becoming yellowish-brown. Many patients are
asymptomatic, but pruritus, tenderness, and pain may occur. They may be
cold-induced, and also demonstrate Koebnerization. Constitutional symp-
toms may include arthralgias and fever. The course of the disease is chronic
and frequently relapsing, though it may spontaneously remit. Lesions heal
with residual atrophic patches, with loss of collagen in the dermis.
   EED has been associated with a variety of underlying autoimmune, gastro-
intestinal, and hematopoietic disorders, including Crohn’s disease (Evans et al.,
1999; Walker & Badame, 1990). Skin biopsy is not specific, and usually reveals
a dense perivascular neutrophilic infiltrate involving the superficial and mid
dermis, with leukocytoclastic vasculitis, fibrin deposition, and endothelial
swelling. An interstitial infiltrate of lymphocytes, neutrophils, eosinophils,
plasma cells, and histiocytes may be observed. Features of older lesions include
perivascular fibrosis, intracellular lipid deposition, and capillary proliferation.


                        PYODERMA GANGRENOSUM

Pyoderma gangrenosum (PG) usually begins as painful papules/pustules,
which rapidly expand into painful burrowing ulcers with undermined borders
and/or raised violaceous rims. The pretibial areas of the legs are the most
frequent site, but any location may be involved. Different clinical presentations
of PG include: ulceration with rapidly evolving purulent wound; discrete
pustules, commonly associated with inflammatory bowel disease; superficial
bullae with development of ulcerations; and vegetative erosions and super-
ficial ulcers. An oral form of the disease, known as pyostomatitis vegetans,
occurs primarily in patients with inflammatory bowel disease (Yasuda et al.,
2008). Often the lesions heal, leaving a cribriform-shaped scar. Ulcerations of
pyoderma gangrenosum may occur after trauma or any injury to the skin,
and the term pathergy is used to describe the process. PG occurs most often
in association with inflammatory bowel disease (Crowson et al., 2003), but
also with any of the connective tissue diseases, Monoclonal gammopathy of
undetermined significance (MGUS), myeloma, myelodysplastic syndrome
102 INTEGRATIVE GASTROENTEROLOGY


(MDS) leukemia and lymphoma. Culture-negative pulmonary infiltrates are
the most common extracutaneous manifestation. Histopathologic changes
vary where the biopsy is taken in relation to the lesion. Lymphocytic vasculitis
is found in the area of erythema peripheral to the central ulceration, whereas
neutrophilic infiltrates and abscess formation are identified more centrally.


                     SNEDDON-WILKINSON SYNDROME

Sneddon-Wilkinson syndrome, or subcorneal pustular dermatosis, is a recur-
rent pustular disorder that may mimic pustular psoriasis, and presents with
bilateral crops of lesions on the flanks, trunk, and proximal extremities with a
flexural tendency. The primary lesions are pea-sized sterile pustules and papu-
lovesicles, often described as half-pustular (bottom) and half-clear (top), or
“half & half blister.” Sometimes, burning, pain, and tenderness of the affected
areas of the skin may occur. Subsequently, the lesions may coalesce and form
annular polycyclic rings, which eventually crust and erode. The histopathol-
ogy reveals a subcorneal pustule filled with polymorphonuclear leukocytes,
with only occasional eosinophils, and absence of spongiosis and acantholysis.
Constitutional features may not be prominent, but generalized arthralgias and
arthritis may occur. It is frequently associated with an MGUS, particularly
IgA, less commonly IgG. Multiple myeloma and other lymphoproliferative
disorders are sometimes found, and an association with pyoderma gangreno-
sum and inflammatory bowel disease has been noted (Delaporte et al., 1992;
Garcia-Salces et al., 2008).


                             SWEET’S SYNDROME

The combination of high fever, leukocytosis, boggy, red, painful papules and
plaques with dense neutrophilic dermal infiltrates, without evidence of vascu-
litis on skin biopsy, is characteristic of Sweet’s syndrome, or acute febrile neu-
trophilic dermatosis. Soft, pea-sized papules and papulovesicles grouped
within boggy violaceous plaques are very suggestive of the diagnosis. If the
plaque is squeezed between the thumb and forefinger, a grey-yellow coloration
may be noted within the papules. Lesions tend to occur on the extremities
more so than the trunk. Sweet’s syndrome may be associated with hemato-
logical malignancy, especially acute myelogenous leukemia, as well as inflam-
matory bowel disease, particularly Crohn’s disease (Burrows, 1995; Mustafa &
Lavizzo, 2008). The initial episode is often thought to be cellulitis or erysipelas.
Patients are placed on antibiotics empirically and, as spontaneous remission
                                       The Skin and the Gastrointestinal Tract 103


occurs, this reinforces the misdiagnosis. Patients may become secondarily
infected, further causing confusion.


                       Bowel Bypass Syndrome

Bowel bypass syndrome refers to a constellation of cutaneous and arthritic
symptoms related to, but not exclusively associated with, bypass surgery.
Although this procedure is not routinely performed today, patients with its
complications are still seen by physicians. Interestingly, a similar clinicopatho-
logical syndrome has been reported in patients without surgery but with other
bowel conditions, particularly inflammatory bowel disease. Therefore, the
term bowel-associated dermatosis-arthritis syndrome has been proposed, to
include patients without bowel bypass surgery for obesity. The common risk
factor appears to be bowel stasis, which promotes bacterial overgrowth with
either disease, or surgically induced blind loops.
    The bowel bypass syndrome consists clinically of a characteristic, intermit-
tent neutrophilic dermatosis, often associated with polyarthritis, tenosynovi-
tis, malaise, and fever. Cryoglobulinemia is commonly found. The syndrome
often mimics gonococcal sepsis. Skin manifestations consist of characteristic
lesions that are erythematous macules, oval in shape, ranging from 3 mm to
10 mm in diameter. The skin lesions consist of sweeps of neutrophils, very
much like Sweet’s syndrome. The formation of vesicles become pustular, and
may appear similar to disseminated gonococcal disease. They may become
painful, and last for up to a week but remain sterile on culture.


                          Erythema Nodosum

Erythema nodosum accompanied by gastrointestinal complaints includes
inflammatory bowel disease, Behcet’s disease, bacterial gastroenteritides, pan-
creatitis, celiac disease, and Whipple’s disease (Schwartz & Nervi, 2007).
Erythema nodosum is the most common form of septal panniculitis, and the
most frequent skin manifestation associated with inflammatory bowel disease.
Since the development of erythema nodosum is closely related with a variety
of disorders and conditions, it can serve as an important early sign of systemic
disease. Aphthous stomatitis and pyoderma gangrenosum, along with ery-
thema nodosum, are the most common skin disorders related to inflammatory
bowel disease (Farhi et al., 2008). Erythema nodosum clinically presents as
multiple, bilateral, painful, non-ulcerating, subcutaneous nodules that undergo
characteristic color changes commencing with bright erythema, and ending in
104   INTEGRATIVE GASTROENTEROLOGY


bruise-like areas. It occurs most commonly on the extensor surface of the
shins, and is less common on the thighs and arms. It usually subsides in 3 to
6 weeks without scarring or atrophy, but may be chronic.


                   Acrodermatitis Enteropathica

Acrodermatitis enteropathica is most often a hereditable disease of infancy or
childhood, related to the malabsorption of zinc (Maverakis et al., 2007). Zinc
deficiency can be an acquired condition in adults as a result of inflammatory
bowel disease, or as a result of nutritional deprivation of zinc. Eczematous,
psoriasiform, and vesicular lesions have been described, most of which occur
in acral locations and, sometimes, on the face as well. The same process may be
associated in adults with niacin deficiency and the glucagonoma syndrome
(Teixeira, Nico, & Ghideti, 2008).


                      Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease asso-
ciated with a gluten-sensitive enteropathy. Gluten sensitivity usually presents as
celiac disease in infancy and childhood, and DH later in life. It is associated
with IgA antibody formation and gluten-sensitive enteropathy, but 90% if
patients have no gastrointestinal symptoms (Oxentenko & Murray, 2003). Skin
lesions are extremely itchy groups of vesicles, most often found on extensor
surfaces. There is burning, stinging, and intense pruritus. Erythematous vesicles
are symmetrical over the extensor surfaces, including elbows, knees, buttocks,
shoulders, and neck. There may be associated crusts and erosions. Patients often
complain of stinging or burning of the skin before the appearance of new lesions
(Nicolas et al., 2003). The oral mucosa is usually not involved, nor are the palms
or soles. Biopsy is required for diagnosis. Light microscopy alone is often inad-
equate, and direct immunofluorescence is usually necessary to confirm the
diagnosis. Granular IgA deposits in dermal papillae of perilesional skin,
observed by direct immunofluorescence, are diagnostic (Kárpáti, 2004).


                        Pancreatic Panniculitis

Pancreatic panniculitis is an uncommon cutaneous eruption that is associated
with disorders of the pancreas, both benign and malignant (García-Romero &
Vanaclocha, 2008). The most common disorders associated with pancreatic
                                        The Skin and the Gastrointestinal Tract 105


panniculitis are acute or chronic pancreatitis, especially the alcohol-related
types, and pancreatic carcinoma. Although the underlying pancreatic patho-
logic conditions vary, the clinical features of pancreatic panniculitis are similar
(Sagi et al., 2008.). The legs are the most commonly affected area, but the
lesions can also occur on the arms, thighs, and trunk. They begin as erythema-
tous or red-brown subcutaneous nodules, with a tendency to central soften-
ing. In the mild form, they may involute within weeks and leave an atrophic
hyperpigmented scar. If the fat necrosis is severe, individual nodules may
break down and ulcerate (Shehan & Kalaaji, 2005).


                                 Hepatitis C

Hepatitis C may be associated with a number of cutaneous disorders, but clas-
sically with mixed cryoglobulinemia (Agnello & Romain, 1996). Cryoglobulins
are abnormal immunoglobulins that form complexes and precipitate out of
serum at low temperatures, and redissolve upon warming or returning to room
temperature. Cryoglobulins are made up of monoclonal antibodies of IgM or
IgG, rarely IgA. Types II and III cryoglobulinemia (mixed cryoglobulinemia)
contain rheumatoid factors (RFs), which are usually IgM and, rarely, IgG or
IgA. These RFs form complexes with the Fc portion of polyclonal IgG. The
actual RF may be monoclonal (in Type II cryoglobulinemia) or polyclonal (in
Type III cryoglobulinemia) immunoglobulin. Types II and III cryoglobuline-
mia represent 80% of all cryoglobulins. The cryoglobulin concentration is
usually low, just above 1mg/ml. Types II and III are called mixed cryoglobuline-
mias, and are associated with chronic inflammatory states, such as systemic
lupus erythematosus (SLE), Sjögren’s syndrome, and viral infections, particu-
larly HCV (Della Rossa et al., 2001). Cutaneous vasculitis associated with
cryoglobulinemia and hypocomplementemia is not uncommon in the course
of chronic active hepatitis C infection. The triad of necrotizing vasculitis,
chronic hepatitis C infection, and cryoglobulinemia, occurs late after initial
infection with hepatitis C (La Civita et al., 1996). In these disorders, the IgG
fraction is always polyclonal, with either monoclonal (Type II) or polyclonal
(Type III) IgM (rarely IgA or IgG), and RF activity. Cutaneous findings in
cryoglobulinemia include erythematous to purpuric macules, papules and
urticarial plaques, livedo, acral necrotic infarction, hemorrhagic erosions,
painful distal ulcers, and extensive postinflammatory hyperpigmentation.
Skin biopsy most often reveals small-vessel leukocytoclastic vasculitis and, less
frequently, inflammatory or noninflammatory purpura, noninflammatory
hyaline thrombosis, and postinflammatory sequelae. HCV virus has also been
identified in vessel walls (Schott, Hartmann, & Ramadori, 2001).
106   INTEGRATIVE GASTROENTEROLOGY




                           Helicobacter pylori

There is increasing evidence for systemic effects of gastric H. pylori infection,
which may result in extragastrointestinal disorders (Rojo-García et al., 2000).
There is some evidence for a potential link of H. pylori infection and chronic
urticaria, although the data are still conflicting. Thus, the search for H. pylori
should be included in the diagnostic management of chronic urticaria. With
regard to other skin diseases such as rosacea, a higher prevalence of H. pylori
infection in rosacea patients than in healthy controls has been reported, and
may be worth evaluation (Buechner, 2005).


                Malignancy-Associated Disorders

                        GLUCAGONOMA SYNDROME

Glucagonoma syndrome is a paraneoplastic phenomenon characterized by an
islet alpha-cell pancreatic tumor, necrolytic migratory erythema on the skin,
diabetes mellitus, weight loss, anemia, stomatitis, thromboembolism, and gas-
trointestinal and neuropsychiatric disturbances. These clinical findings, in
association with hyperglucagonemia and demonstrable pancreatic tumor,
establish the diagnosis. Glucagon itself is responsible for most of the observed
signs and symptoms, and its induction of hypoaminoacidemia is thought to
lead to necrolytic migratory erythema. Liver disease, and fatty acid and zinc
deficiency states, may also contribute to the pathogenesis of the eruption in
some cases (Chastain, 2001). At diagnosis, most glucagonomas are malignant
and often metastatic (Chen et al., 2005). The diagnostic features of necrolytic
migratory erythema include a chronic migratory cutaneous eruption with
advancing borders, which often contain vesicopustules. Patients also usually
have glossitis, angular cheilitis, blepharitis, weight loss, and abnormal glucose
tolerance.


                             BAZEX’S SYNDROME

Acrokeratosis paraneoplastica (Bazex’s syndrome) is a rare paraneoplastic der-
matosis characterized by psoriasiform and erythematous plaques, typically
affecting hands, feet, nose, and earlobes. The condition almost exclusively
affects Caucasian men older than 40 years. It is usually associated with primary
                                      The Skin and the Gastrointestinal Tract 107


malignant neoplasms of the upper digestive tract, especially esophageal carci-
noma, as well as cervical lymph node metastases from an unknown primary
tumor. Other rare associations include adenocarcinoma of the stomach or
uterus, anaplastic small-cell carcinoma of the lung, Hodgkin’s lymphoma tran-
sitional-cell carcinoma of the bladder, adenocarcinoma of the colon, and
squamous cell carcinoma of the lower leg (Rao & Shenoi, 2004). In most cases,
the skin changes precede the clinical manifestation of the underlying neo-
plasm. The dermatosis can be cured only by removal of the underlying carci-
noma (Sator, Breier, & Gschnait, 2006).


                    PALMOPLANTAR KERATODERMAS

Palmoplantar keratodermas are a heterogeneous group of disorders character-
ized by diffuse, abnormal thickening of the palms and soles, with autosomal
recessive and dominant, X-linked, and acquired forms, all having been
described. Some hereditary types, as well as some acquired forms, have been
associated with pancreatic carcinoma, as well as other carcinomas (Kaur,
Sarkar, & Kanwar, 2002).


                         ACANTHOSIS NIGRICANS

Although acanthosis nigricans is a skin condition that occurs most often with
insulin resistance associated with obesity, particularly with Cushing’s syn-
drome or Type 2 diabetes, it is arguably also the most well-recognized cutane-
ous sign of internal malignancy. Acanthosis nigricans is characterized by
hyperpigmentation, velvety cutaneous thickening, and intensified skin mark-
ings, often with the development of verrucous or skin-tag-like excrescences
typically involving the intertriginous areas, but may also be found on the lips
and within the mouth (Kaminska-Winciorek et al., 2007). It has been reported
with many kinds of cancer, but the most common underlying malignancy is an
adenocarcinoma of gastrointestinal origin, usually a gastric adenocarcinoma
(Bohm, Luger, & Metze, 1999).


                          GARDNER’S SYNDROME

Gardner’s syndrome is the association of multiple colonic and rectal polyps
with sebaceous cysts and jaw osteomas (Parks, Caldemeyer, & Mirowski,
2001). The significance of this dominantly inherited condition is that the
108   INTEGRATIVE GASTROENTEROLOGY


polyps usually undergo malignant change by the fourth decade, and the
extraintestinal lesions may be apparent before those in the bowel. Therefore,
early detection of multiple jaw osteomas and/or multiple sebaceous cysts, par-
ticularly on the scalp, may lead to appropriate further investigation and treat-
ment prior to malignant transformation (Basaran & Erkan, 2008). Gardner
described the occurrence of familial adenomatous polyposis, with the extraco-
lonic manifestations of desmoids, osteomas, and epidermoid cysts in the skin
and the gastrointestinal tract. The number of polyps can range from no detect-
able polyps at colonoscopy, to more than 7,000 seen on resected specimens of
bowel. The polyposis predominantly affects the left colon (Bilkay et al., 2004).


                         PEUTZ-JEGHERS SYNDROME

Peutz-Jeghers syndrome is a dominantly inherited polyposis syndrome char-
acterized by hamartomatous polyps of the gastrointestinal tract, and mucocu-
taneous pigmentation and melanin spots. They appear as small, flat, brown or
dark blue spots with the appearance of freckles, most commonly in the perio-
ral area. They may be present on the fingers and the toes, on the hands and the
feet, and around the anus and genitalia. Of note, the lesions may fade consider-
ably after puberty (Giardiello & Trimbath, 2006). Since its description, much
debate has centered on the true malignancy risk of Peutz-Jeghers syndrome,
including malignancy within and outside the gastrointestinal tract. Although
the intestinal lesions are hamartomas, patients with Peutz-Jeghers syndrome
are generally considered to have a 15-fold increased risk of developing intesti-
nal cancer compared to that of the general population (Homan, Strazar, &
Orel, 2005). Rare tumors such as adenoma malignum of the cervix occur in
Peutz-Jeghers syndrome. Likewise, more common cancers occur at younger
ages. Children may manifest symptoms of this disease, including gastrointes-
tinal complications and malignancy (Brichard et al., 2005).


                             COWDEN SYNDROME

Cowden syndrome is an autosomal dominant disorder characterized by mul-
tiple hamartomas and a high risk of development of breast, thyroid, endome-
trial, and other cancers (Schrager et al., 1998). The classic features of the disease
include mucocutaneous papillomatous papules and trichilemmomas on the
malar area of the face (Kovich & Cohen, 2004). Most affected people develop
these characteristic lesions by their early twenties. At least one of four types
of skin lesions is present in nearly all cases. Facial papules are flesh-colored,
                                      The Skin and the Gastrointestinal Tract 109


flat-topped, dry or warty 1mm to 5mm papules around the mouth, nostrils,
and eyes. Oral lesions are numerous 1mm–3mm smooth white spots on the
gums and palate that create a cobblestone appearance known as papillomatosis
(Jornayvaz & Philippe, 2008). Acral keratoses are flesh-colored or slightly pig-
mented smooth or warty papules on the upper surface of hands and feet.
Palmoplantar keratoses are scaly spots on the palms and soles that also may
occur. Noncancerous breast and thyroid diseases are also common.


                               Conclusions

Integrative practitioners should become aware of the various systemic mani-
festations of gastrointestinal disease. Dermatological conditions can precede,
coincide, or occur after the underlying digestive disorder. Early recognition of
dermatoses that underlie digestive health problems can lead to early diagnosis
and treatment.
                                       9
      Premenstrual and Menstrual Exacerbation
      of IBS: An Integrative Medicine Analysis of
        the Bi-Directional Connection between
           Female Hormones and Gut Health
                                JOEL M. EVANS




                                  key concepts

       ■   IBS symptoms often have premenstrual and menstrual
           exacerbations.
       ■   Progesterone dominance in the second half of the menstrual
           cycle explains the observation that constipation as an IBS symp-
           tom is more frequent in reproductive-aged women than in men.
       ■   Stress is proinflammatory and known to exacerbate IBS.
       ■   The perimenstrual release of proinflammatory cytokines
           contributes to the observed increase in IBS symptoms during
           menstruation.
       ■   Healthy gut flora and overall gut health have a direct relation-
           ship to female hormonal health.
       ■   An integrative treatment plan for IBS includes normalizing hor-
           mone levels, as well as reducing stress and inflammation.
                                        ■




                                Introduction



W
              omen have long been aware of the relationship of their menstrual
              cycle to nongynecologic health complaints. However, because
              up to 75% of women experience some recurrent premenstrual

110
                                Premenstrual and Menstrual Exacerbation of IBS 111


symptoms, there has been disagreement among medical authorities on whether
to classify these nongynecologic health complaints as normal (physiologic) or
abnormal. The premenstrual symptoms germane to IBS are the changes in
bowel habits (abdominal pain, bloating, diarrhea and constipation) described
by many healthy women, as well as those diagnosed with IBS.


         Background: Menstrual Symptoms and IBS

In 1990, the medical literature began to address the connection between the
menstrual cycle and IBS symptoms, when Whitehead et al. (1990) reported an
increase in flatulence, diarrhea, and constipation during menstruation. These
findings were confirmed by Heitkemper and Jarrett (1992) two years later. In
1998, Kane, Sable and Hanauer found that a high percentage of healthy women
have a premenstrual change in many bowel symptoms, but this change is more
pronounced in women with IBS. Interestingly, the authors also found that
patients with IBS have more extraintestinal premenstrual and menstrual com-
plaints than controls. This is an important finding when discussing possible
emotional (neurochemical) factors underlying the physiologic mechanisms
for the premenstrual worsening of IBS, including changes in serotonin levels,
progesterone levels, and prostaglandin production. Women with an IBS diag-
nosis also report a fluctuation in symptoms related to their menstrual cycle
(Heitkemper & Jarrett, 2008).


                             EMOTIONAL FACTORS

Like PMS, the extent of the contribution of emotional factors to IBS has also
been the subject of debate, with some authors even describing IBS as part of
the spectrum of purely depressive disorders (Kovacs & Kovacs, 2007). In fact,
stress is well known to both exacerbate symptoms of IBS in humans, and cause
increased intestinal permeability in rodents (Gareau et al., 2008).

   Stress itself can cause increased intestinal permeability.



    However, even though stress itself increases inflammation (Miller et al.,
2002), when describing the premenstrual and menstrual exacerbations of IBS
it is most accurate to classify stress and emotions as contributing factors, rather
than the predominant factor, to the other, more significant underlying mecha-
nisms mentioned earlier. These mechanisms will now be discussed in further
112 INTEGRATIVE GASTROENTEROLOGY


detail, to better understand the basis for an integrative approach to premen-
struation- and menstruation-exacerbated IBS.


                             HORMONES AND IBS

The second half, or luteal phase, of the menstrual cycle is associated with pro-
gesterone dominance relative to estrogen, with a sharp decrease of both hor-
mones at the end of the luteal phase causing a destabilization of the endometrial
lining, ending in menstruation.


   Because progesterone is known to have the effect of decreasing gut motility
   (Gonne et al., 2006), the hormonal milieu of progesterone dominance
   explains the clinical observation that women with IBS, as opposed to men,
   frequently present with constipation as the dominant IBS complaint (IBS-C).



    It also explains why symptoms associated with increased motility occur
immediately before and during menstruation, when progesterone levels are at
their nadir. In addition, as women go through the age-related spectrum of
hormonal transition of reproductive age to menopause, the hormonal shift
that occurs first is a drop in luteal phase progesterone levels (Lipson et al.,
1992).
    The gynecologic literature is filled with research attempting to explain the
hormonal imbalances associated with premenstrual syndrome (PMS), and a
recent Cochrane literature review on the subject (Ford et al., 2006a), found
some evidence for relief with progesterone administration. This would help
support the progesterone hypothesis, which states that decreasing levels of
progesterone are responsible for the myriad symptoms associated with PMS.
However, the trials referenced in the Cochrane review differed in route of
administration, dose, and duration of treatment, as well as selection of par-
ticipants. Although still a theory at this point, the progesterone hypothesis is a
plausible explanation for the observed worsening of IBS symptoms seen in
women with PMS (Altman et al., 2006).


                          INFLAMMATION AND IBS

The final mechanism to explain menstrual exacerbation of IBS is the proin-
flammatory state associated with menses. While all clinicians are familiar with
                              Premenstrual and Menstrual Exacerbation of IBS 113


the therapeutic efficacy of antiprostaglandin medications in the treatment of
dysmenorrhea, further research (Wander et al., 2008) has shown that men-
struation is associated with a 17% increase in C-reactive protein, a biomarker
of inflammation. This shows that menstruation induces a systemic inflamma-
tory state. Additionally, there is a documented local and systemic inflamma-
tory cytokine release that is associated with both the tissue breakdown and
progesterone withdrawal that accompanies menstruation (Critchley et al.,
2001).


  The systemic increase in proinflammatory cytokines serves as a further
  explanation for the observed increase in IBS symptoms during menstrua-
  tion (O’Mahony et al., 2005).




              Gynecological Manifestations of IBS

So far, the discussion has centered on the exacerbations of IBS that accompany
the premenstrual and menstrual phases of a woman’s hormonal cycle. However,
practitioners that are active in caring for women are likely to note that their
patients suffering from endometriosis, chronic pelvic pain, and dysmenorrhea
are more likely to also have IBS symptoms or an IBS diagnosis. In fact, one out
of three women with chronic pelvic pain has IBS symptoms (Zondervan et al.,
2001).


         Anti-Inflammatory Therapeutic Options to
               Improve Gynecological Health

The common underlying pathophysiologic mechanism of inflammation is the
link between all of these conditions, and serves as the basis for using a broad
anti-inflammatory approach (supplementing with fish oil, hops, rosemary,
bromelain, turmeric, quercetin) to address both menstrual and gut symptoms
(De Giorgio & Barbara, 2008). In addition, treating the underlying abnor-
malities in the gut—for example, by avoiding foods that create an inflamma-
tory reaction, and supplementing with anti-inflammatory probiotics (such
as Lactobacillus plantarum 299v, Lactobacillus acidophilus NCFM®, and
Bifidobacterium lactis), in order to decrease gut induced inflammation—will
often dramatically decrease the severity of gynecologic symptoms.
114    INTEGRATIVE GASTROENTEROLOGY




                The Gut–Gynecological Axis of Health

All of the preceding relationships can be summarized as showing that hor-
monal changes affect gut function, both directly (progesterone mediated
effects) and indirectly (inflammation mediated effects). However, the relation-
ship between the gut and female hormonal milieus is really bidirectional. In
other words, it is not just that hormonal health affects gut health, but also that
gut health influences hormonal health. It is crucial for practitioners treating
bowel dysfunction to be aware of this bidirectionality, because by ensuring
optimal gut health in their female patients, they are not only helping them lead
more comfortable lives but also helping prevent and treat common estrogen-
related disorders (endometriosis, fibroid tumors, breast cancer).


           The Gut and Gynecological Hormonal Health

The connection between gut health and hormonal health has its basis in the
way estrogen is eliminated by the body. All of a woman’s circulating estrogen
that does not bind to an estrogen receptor in estrogen-sensitive tissue (such as
breast and endometrium) must be eliminated through the liver via the Phase I
and Phase II detoxification pathways. It is then secreted into the bile, and
dumped into the gut for elimination via stool.


      Any process that impairs Phase I or Phase II detoxification, whether genetic
      (CYP 450 polymorphisms), environmental (increased toxic burden), or nutri-
      tional (decreased micronutrient or protein intake), will decrease estrogen
      elimination.




                Nutritional Interventions to Improve
                   Gynecological and Gut Health

Phase II detoxification of estrogen involves the attachment, or conjugation, of
other compounds to enable the estrogen molecule to be excreted in the bile
and then into the gut for elimination. The most important conjugation reac-
tion for estrogen elimination is glucuronidation, whereby a glucuronide mol-
ecule is attached to estrogen to form an estrogen glucuronide. This relates to
                               Premenstrual and Menstrual Exacerbation of IBS 115


gut health, in that the most common reason for impaired glucuronidation
(and, therefore, reduced estrogen elimination) occurs when abnormal or
unhealthy gut florae are present, as they secrete an enzyme called beta-
glucuronidase. This enzyme cleaves the glucuronide molecule from the estro-
gen-glucuronide that was sent to the gut through the bile, leaving free estrogen
to be reabsorbed systemically via enterohepatic recirculation.
   Interventions that have been shown to improve glucuronidation include a
low-animal-fat diet, and supplementation with probiotics and calcium-D-glu-
carate (Walaszek et al., 1997). Thus, eliminating constipation and ensuring
regular bowel movements in patients with IBS now has a whole new level of
importance.


                                Conclusions

In summary, the physiological mechanisms described in this chapter associ-
ated with the luteal phase of the menstrual cycle, PMS, and menstruation,
explain the observed phenomenon of IBS exacerbation during those periods.
The systemic inflammation associated with chronic pelvic pain and other
gynecologic disorders explains the observation of increased in IBS in those
patients. Lastly, the connection between gut health and estrogen elimination
demonstrates the importance that gut health has in estrogen related disorders.
Therefore, a truly integrative approach to managing IBS in women, in addition
to therapies targeting the gut, addresses all of these additional factors. Helping
women with IBS assess and normalize hormone levels, reduce systemic and
gastrointestinal inflammation, ensure healthy gut flora, and identify their
stressors and resolve their interpersonal conflicts, will not only improve their
IBS but will also help decrease the symptoms and incidence of the disorders
associated with excess estrogen, allowing women to experience healthier and
happier lives. This is the true definition of a holistic approach, and is exactly
what brings joy and fulfillment to the busy lives of integrative practitioners.
                                      10
 Fibromyalgia and Gastrointestinal Disorders
            DAVID M. BRADY AND MICHAEL J. SCHNEIDER




                                  key concepts

      ■   Fibromyalgia syndrome (FMS) does not appear to be a disorder
          of peripheral tissues, including muscle, but a dysfunction within
          the central nervous system (CNS) that involves the processing
          of sensory stimuli.
      ■   Dysfunction of CNS processing of pain, and overactivity of the
          hypothalamic-pituitary-adrenal (HPA) axis and sympathetics,
          are likely the root causes of classic FMS.
      ■   5-hydroxytryptophan, a serotonin precursor, is effective in
          improving the symptoms of FMS.
      ■   Many studies have demonstrated a common association (comor-
          bidity) between IBS and FMS, ranging from 30% to more than
          80%.
      ■   Patients with FMS frequently have nonspecific bowel complaints
          similar to those with small intestinal bacterial overgrowth (SIBO).
      ■   Significant improvement in IBS symptoms has been reported
          after antibiotic treatment, including rifaximin, typically used to
          treat SIBO.
                                         ■




                                Introduction



F
       ibromyalgia syndrome (FMS) remains an elusive condition of unknown
       etiology, with a strong prevalence of overdiagnosis, in which patients
       report chronic widespread pain (allodynia or hyperalgesia) and a variety
of other complaints, including fatigue, sleep disorders, cognitive deficit, irritable

116
                                     Fibromyalgia and Gastrointestinal Disorders 117


bowel and bladder syndrome, headache, Raynaud’s syndrome, bruxism, atypi-
cal patterns of sensory dysesthesia, and other symptoms suggestive of auto-
nomic nervous system or neuroendocrine dysregulation (Fitzcharles & Boulos,
2003; Wolfe, Smythe, Yunus et al., 1990; Wolfe, 2003; Staud, Cannon, Mauderli
et al., 2003; Gracely, Petzke, Wolf, & Clauw, 2002; Jacobsen, Danneskiold-
Samsoe, & Lund, 1993; Jain, Carruthers, & van de Sande, 2003; Abeles, Pillinger,
Solitar, & Abeles, 2007). Despite the name of the condition—“fibro-my-
algia”—there are no data to support the hypothesis that FMS is a distinct path-
ological disorder of the soft tissues. More recent data tends to support the
notion that FMS is a disorder of the central nervous system (CNS) pain-
processing pathways, and not some type of primary rheumatologic disorder
(Jacobsen et al., 1993; Jain, Carruthers, & van de Sande, 2003). It has been well
established in the literature that FMS patients are predominantly female
(female to male ratio of 10–20:1), typically report nonrefreshing sleep, general
fatigue, low energy and vague gastrointestinal complaints, and experience
concomitant anxiety and depression disorders.
   In true fibromyalgia, there are physical symptoms suggestive of an under-
lying psychological disorder, mediated by overactivity of the limbic system and
hypothalamic-pituitary-adrenal (HPA) axis, causing the multiple symptoms
seen in the “classic” cases of FMS in rheumatology clinics. These classic cases
probably represent the somatic manifestations of extreme emotional stress
and/or psychological illness, yet are distinct from a true somatization disorder
in which there is no real physical illness. It is too simplistic to state that all cases
of classic FMS merely represent a somatic manifestation of clinical depression
or anxiety, because not all patients with depression or anxiety disorders experi-
ence the symptom of widespread allodynia with multiple tender points. Yet, it
has been known for almost 20 years that FMS patients often respond well (at
least in the short term) to low doses of antidepressant medications, suggesting
that there is significant overlay between mood disorders and FMS. Recent
studies are starting to implicate the role of the limbic structures (hippocampus,
amygdala, and hypothalamus) and neuroendocrine system in the production
of FMS symptoms. One study showed differences in circadian cortisol release
in FMS versus healthy controls, suggestive of overactivity of the HPA axis in
these patients (Crofford, Young, Engleberg et al., 2004). Various types of ther-
mal, mechanical, and electrical modalities have been applied to FMS and
healthy controls, and consistently the FMS group shows signs of central sensi-
tization (Desmeules, Cedraschi, Rapiti et al., 2003). PET scans and fMRI stud-
ies of the brain activity of FMS subjects versus healthy controls, while they
receive innocuous sensory stimulation, have shown that FMS patients’ limbic
structures are activated by nonpainful stimuli, which only activate the sensory
cortex in healthy controls (Gracely, Petzke, Wolf, & Clauw, 2002).
118 INTEGRATIVE GASTROENTEROLOGY


    It is not currently known exactly why certain patients with emotional ill-
nesses or mood disorders will develop the characteristic symptoms of what is
termed FMS, and why others with the same level of psychopathology do not
experience these symptoms. There could be a combination of factors, includ-
ing genetic predispositions that may, in future research, be shown to be associ-
ated with the production of FMS symptoms. A recent study of family members
and probands of FMS patients showed that reduced pressure-pain thresholds
aggregate in families, and that FMS co-aggregates with major mood disorders
in families (Arnold, Hudson, Hess et al., 2004).
    The relevance for the physician seeing these patients is the recognition that
mental health and mood disorders may be the root cause of the symptoms of
widespread pain, allodynia, sleep disorders, and cognitive deficit that could
easily be misdiagnosed as a purely physical disorder. It would seem appropri-
ate for the primary care physician to refer these patients for cognitive behav-
ioral therapy or other forms of psychological counseling, rather than for
physical therapy. A recent systematic review of the literature has shown that
cognitive behavioral therapy is an effective treatment strategy for FMS patients,
along with mild exercise and low-dose antidepressant medication (Sim &
Adams, 2002). More recent studies have supported the use of serotonin and
norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and milnacip-
ran, and alpha-2 delta ligands, such as pregabalin, in the treatment of FMS
(Arnold, 2006). This makes sense, in light of the fact that serotonin and nor-
epinephrine are the key neurotransmitters released at the synapses between
the limbic system interneurons and the brainstem nuclei that control the
descending antinociceptive system (DANS). Other studies have supported the
use of natural serotonin precursors, such as 5-hydroxytryptophan, as well as
nutraceuticals that have a calming effect on the CNS, such as phosphytidylser-
ine, in the complementary treatment of FMS (Caruso & Puttini, 1992; Caruso
et al., 1990; Manteleone P et al., 1992). However, before any diagnosis of FMS
is rendered and treatment initiated, great attention must be paid to adequate
differential diagnosis and assurance of the existence of a central pain process-
ing disorder (Schneider & Brady, 2001; Schneider, Brady, & Perle, 2006;
Dadabhoy & Clauw, 2006).


  • The diagnosis of fibromyalgia syndrome should not be used to categorize
    all patients with widespread pain and fatigue of unknown origin.
  • Many other medical conditions can be misdiagnosed as fibromyalgia syn-
    drome, including hypothyroidism, anemia, Lyme disease, dysglycemias,
    metabolic abnormalities, mitochondrial dysfunction, myofascial pain syn-
    drome and many other musculoskeletal disorders (Schneider & Brady,
    2001; Schneider, Brady, & Perle, 2006; Dadabhoy & Clauw, 2006).
                                  Fibromyalgia and Gastrointestinal Disorders 119




        Fibromyalgia and Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) affects approximately 11% to 14% of the popu-
lation. It is a condition with multiple models of pathophysiology, including
altered motility, visceral hypersensitivity, abnormal brain–gut interaction,
autonomic dysfunction, and immune activation (Lin, 2004). This chronic
functional bowel disorder, characterized by both visceral and somatic hyper-
algesia, produces effects similar to those seen with the central hypersensitivity
mechanisms in FMS (Frissora & Koch, 2005; Moshiree, Price, Robinson,
Gaible, & Verne, 2007). Many studies have demonstrated a common associa-
tion or comorbidity between IBS and FMS, ranging from 30% to more than
80% (Riedl, Schmidtmann, Stengel et al., 2008; Garcia, 2007; Cole, Rothman,
Cabral et al., 2006; Kurland, Coyle, Winkler, & Zable, 2006; Wallace &
Hallegua, 2004; Verne & Price, 2002; Whitehead, Palsson, & Jones, 2002;
Lubrano, Iovino, Tremolaterra et al., 2001; Sperber, Carmel, & Atzmon, 2000;
Sperber, Atzmon, Neumann et al., 1999; Price, Zhou, Moshiree et al., 2006).
Prevalence rates reported by Kurland et al. (2006) of IBS in FMS patients
(n=105) was 63% by Rome I and 81% by Rome II criteria, compared to the
prevalence of IBS in controls (n=62) of 15% by Rome I and 24% by Rome II
criteria (FM vs. control; p<0.001).
    Lubrano et al. (2001) reported a prevalence of FMS in approximately 20%
of IBS patients. However, since the commonly used diagnostic criteria of FMS
include IBS, the relationship of the two syndromes is difficult to analyze
(Azpiroz, Dapoigny, Pace et al., 2000). A female predominance has been
reported in both IBS and FMS. It has been suggested that the female predomi-
nance in IBS patients may result mainly from coexisting FMS (Akkus, Senol,
Ayvacioglu et al., 2004).
    Visceral hypersensitivity, measured by decreased pain thresholds to gut dis-
tension, is considered a biological marker of IBS. However, patients with IBS
also have many extraintestinal symptoms consistent with hyperalgesic states,
and they may also exhibit cutaneous hyperalgesia similar to that seen in
other chronic and global pain disorders, including FMS (Verne & Price, 2002).
This suggests not only comorbidity between IBS and FMS, but some shared
mechanisms of central nociceptive pathophysiology. It has been hypothesized
that the visceral and cutaneous hyperalgesia seen in IBS is likely to be at least
partly related to sensitization of spinal cord dorsal horn neurons and, in this
respect, may be similar to other persistent pain conditions such as FMS (Price,
Zhou, Moshiree et al., 2006). Patients with IBS and FMS show greater thermal
hypersensitivity compared to patients with IBS alone, while IBS patients
exhibit higher pain ratings to rectal distension compared to those with both
120 INTEGRATIVE GASTROENTEROLOGY


IBS and FMS. This suggests that the regions of primary and secondary hyper-
algesia are dependent on the primary complaint (Moshiree et al., 2007).
Current research appears to indicate that, although they share a common
hypersensitivity background, multiple mechanisms may modulate perceptual
somatic and visceral responses in patients with IBS and FMS (Caldarella,
Giamberardino, Sacco et al., 2006). Whitehead et al. (2002) conclude that,
“Multivariate statistical analyses suggest that these are distinct disorders, but
their strong comorbidity suggest a common feature important to their expres-
sion, which is most likely psychological.” High rates of psychiatric comorbidity
have been reported in patients with IBS and FMS. One of the psychiatric
comorbidities associated with FMS is post-traumatic stress disorder (PTSD).
However, studies have shown a lower-than-expected prevalence of PTSD
among IBS patients (Cohen, Jotkowitz, Buskila et al., 2006). Patients with
coexisting IBS and FMS have worse scores on the health-related quality of life
(HRQOL) indices than patients with either disorder alone (Sperber et al.,
1999). In summary, the underlying pathophysiological mechanisms of IBS
and FMS have much in common, and strong comorbidity certainly exists,
but they do not necessarily appear to be the same disorder. Patients who
exhibit both disorders fare worse symptomatically, and may have greater over-
all morbidity.


Fibromyalgia and Small Intestinal Bacterial Overgrowth

Patients with FMS frequently have nonspecific bowel complaints similar to
those with small intestinal bacterial overgrowth (SIBO; see Wallace & Hallegua,
2004). SIBO is a condition in which colonic aerobic and anaerobic bacteria are
overrepresented in the small intestine. There is a growing body of evidence
suggesting that SIBO may play a significant role in a wide range of gastrointes-
tinal disorders, including Crohn’s disease and IBS (Funayama, Sasaki, Naito
et al., 1999; Pimentel., Park, Mirocha, Kane, & Kong, 2006; Pimentel, Chow, &
Lin, 2003; Sharara, Aoun, Abdul-Baki et al., 2006).


  Recent studies indicate that up to 84% of patients with IBS have an abnor-
  mal lactulose breath test result, suggesting small bowel bacterial over-
  growth. (Pimentel et al., 2006)



   Pimentel et al., (2001, 2004) using lactulose hydrogen breath testing (LHBT),
reported that of 123 subjects with FMS, 96 (78%) were found to have SIBO.
(Pimentel et al, 2001; 2004). Of these 123 subjects with FMS, 87% also met the
                                  Fibromyalgia and Gastrointestinal Disorders 121


Rome I criteria for IBS. Of 25 subjects who returned for follow-up LHBT,
11 achieved complete eradication and 14 achieved incomplete eradication of
their SIBO with antibiotic therapy. Improvement in GI symptoms, including
bloating, gas, diarrhea, constipation, and abdominal pain, as well as general
symptoms of pain, fatigue, and sleeplessness, were also reported via follow-up
patient questionnaires. Better clinical results were clearly observed with com-
plete eradication. Antibiotics, such as neomycin, seem to improve symptoms
in many subjects, but effectively eliminate SIBO in only about 25% of patients,
and side effects limit their use (Pimentel et al., 2006). Rifaximin is a gut-
selective antibiotic with negligible systemic absorption (<0.4%), minimal side
effects [similar to placebo], and broad-spectrum activity in vitro against Gram-
positive and Gram-negative aerobes and anaerobes. It results in effective erad-
ication of SIBO in up to 70% of cases (Jiang & DuPont, 2005; Di Stefano,
Malservisi, Veneto, Ferrieri, & Corazza, 2000). Rifaximin also has known
activity against Clostridium difficile (Marchese, Salerno, Pesce, Debbia, &
Schito, 2000).
   Traditionally, small bowel aspirate (>105 cfu/ml) has been accepted as the
gold standard for SIBO diagnosis. However, breath testing and urinary mark-
ers, including cholyl-PABA and indican, have frequently been used due to
their convenience and noninvasive nature. However, a systematic review by
Khoshini et al. (2008) concluded that there is no well-validated test or gold
standard for the diagnosis of SIBO. A better method for accurately identifying
SIBO is needed, and quantitative bacterial polymerase chain reaction (PCR)
may serve this role for the future. According to Khoshini, the most practical
current clinical method may be a test, treat, and outcome technique.
   Animal models have suggested that SIBO results in bacterial translocation
to mesenteric lymph nodes, and can produce systemic effects possibly medi-
ated by Gram-negative endotoxins, which could explain the soft tissue hyper-
algesia seen in some subjects labeled, incorrectly or not, with FMS (Berg,
Wommack, & Deitch, 1988; Wells, Barton, Jechorek et al., 1991; Guarner,
Runyon, Young et al., 1997; Nieuwenhuijs, Verheem, van Duijvenbode-
Beumer et al., 1998; Lichtman, Keku, Clark et al., 1990; Lichtman, Sartor,
Keku et al., 1990; Riordan, Melvor, & Williams, 1998; Maier, Wiertelak,
Martin D et al., 1993; Watkins, Wiertelak, Goehler et al., 1994; Watkins,
Wiertelak, Furness et al., 1994; Wiertelak, Smith, Furness et al., 1994; Kanaan,
Saade, Haddad et al., 1996; Cahill, Dray, & Coderre, 1998; Walker, Dray, &
Perkins, 1996a, 1996b). Lin (2004) concludes that, “The gastrointestinal and
immune effects of SIBO provide a possible unifying framework for under-
standing frequent observations in IBS, including postprandial bloating and
distension, altered motility, visceral hypersensitivity, abnormal brain–gut
interaction, autonomic dysfunction and immune activation.”
122   INTEGRATIVE GASTROENTEROLOGY




                               Conclusions

Fibromyalgia syndrome (FMS) consists of dysfunction within the central ner-
vous system that involves the processing of sensory stimuli, overactivity of the
hypopituitary-adrenal (HPA) axis and sympathetics, and dysfunction of the
descending antinociceptive system, resulting in altered pain perception,
fatigue, mild depression, vague gastrointestinal complaints, and a host of other
symptoms. A strong association exists between FMS, irritable bowel syndrome
(IBS), and small intestinal bacterial overgrowth (SIBO), which may involve
some common mechanisms of pathophysiology and provide a framework for
common treatment. The gut-selective antibiotic rifaximin has been shown to
have negligible systemic absorption, minimal side effects, and results in effec-
tive eradication of SIBO in up to 70% of cases. Improvement in GI symptoms,
including bloating, gas, diarrhea, constipation, and abdominal pain, as well as
general symptoms of pain, fatigue, and sleeplessness, has been reported with
successful eradication of SIBO.
   Serotonin appears to be a key neurotransmitter involved in altered pain per-
ception and sleep disturbances observed in FMS, and may also play a critical
role in functional bowel disorders, including IBS. The use of serotonin and nor-
epinephrine reuptake inhibitors, such as duloxetine and milnacipran, and
alpha-2 delta ligands such as pregabalin, as well as the serotonin precursor
5-hydroxytryptophan, have demonstrated effectiveness in improving the symp-
toms of FMS. Oral administration of phosphatidylserine may counteract stress-
induced activation of the HPA axis, as is commonly found in FMS subjects.
Management of each of these elements of the FMS patient’s possible clinical
presentation is essential to achieve comprehensive and successful outcomes.
                                    11
          Acupuncture for Digestive System
                    SANGHOON LEE AND TA-YA LEE




                                key concepts

     ■   Acupuncture is a modality that can channel energy and blood
         flow to influence digestive function.
     ■   Acupuncture has been shown to be beneficial for a number of
         gastrointestinal motility disorders.
     ■   Stimulating PC6 point (located on the forearm) has been most
         frequently applied for nausea and vomiting.
     ■   Electro-acupuncture may increase the threshold of rectal
         sensitivity in irritable bowel syndrome patients.
     ■   Acupuncture has been shown to benefit irritable bowel syn-
         drome and inflammatory bowel disease patients; however,
         sham-controlled studies have been inconsistent and lack
         uniformity.
                                       ■




                              Introduction



A
         cupuncture (from Lat. acus, “needle,” and pungere, “to prick”) (Mayor,
         2006) is a technique of inserting and manipulating fine needles into
         specific points on the body, with the aim of relieving pain, and for
therapeutic purposes. According to traditional Chinese acupuncture theory,
these acupuncture points lie on meridians along which qi, the vital energy,
flows. There is no generally accepted anatomical or histological basis for these
concepts, and modern acupuncturists tend to view them in functional rather
than structural terms. Acupuncture originated in China and is most com-
monly associated with traditional Chinese medicine (TCM). Different types of

                                                                             123
124 INTEGRATIVE GASTROENTEROLOGY


acupuncture (Classical Chinese, Korean, Japanese, Tibetan, and Vietnamese
acupuncture) are practiced and taught throughout the world.


                         What Is Energy Flow?

Energy, or qi, flows up and down the meridians. Sometimes the energy is
blocked, deficient, excessive, or unbalanced. This throws Yin and Yang out of
balance, which in turn causes illness. Acupuncture restores the balance, thus
encouraging healing.


                              Why Needles?

Acupuncture is performed using very fine needles, which are applied to pro-
mote healing. Overall, deficiencies are tonified or reinforced, and excesses will
be dispersed or reduced. In addition to using needles, acupuncturists may also
use heat, pressure, friction, or impulses to stimulate specific acupuncture
points. Most practitioners currently use prepackaged, sterilized, one-time use,
disposable needles. Electro-acupuncture is another example of a 20th century
adaptation, a mix of ancient and modern technology.


         Which Conditions Is Acupuncture Used For?

Acupuncture is used to treat many types of conditions, the most common of
which is pain. According to the American Academy of Medical Acupuncture,
acupuncture may be considered as a complementary therapy for the condi-
tions listed here (Braverman, 2004). The conditions labeled with an asterisk
are also included in the World Health Organization (WHO) list of acupunc-
ture indications (WHO, 1979).

  •   Abdominal distention/flatulence∗
  •   Acute and chronic pain control∗
  •   Allergic sinusitis∗
  •   Anesthesia for high-risk patients or patients with previous adverse
      responses to anesthetics
  •   Anorexia
  •   Anxiety, fright, panic∗
  •   Arthritis/arthrosis∗
  •   Atypical chest pain (negative workup)
                                            Acupuncture for Digestive System 125


   • Bursitis, tendinitis, carpal tunnel syndrome∗
   • Certain functional gastrointestinal disorders (nausea and vomiting,
     esophageal spasm, hyperacidity, irritable bowel)∗
   • Cervical and lumbar spine syndromes∗
   • Constipation, diarrhea∗
   • Cough with contraindications for narcotics
   • Drug detoxification∗
   • Dysmenorrhea, pelvic pain∗
   • Frozen shoulder∗
   • Headache (migraine and tension), vertigo (Ménière’s disease),
     tinnitus ∗
   • Idiopathic palpitations, sinus tachycardia
   • In fractures, assisting in pain control and edema, and enhancing
     healing process
   • Muscle spasms, tremors, tics, contractures∗
   • Neuralgias (trigeminal, herpes zoster, post-herpetic pain, other)
   • Paresthesias∗
   • Persistent hiccups∗
   • Phantom pain
   • Plantar fasciitis∗
   • Post-traumatic and postoperative ileus∗
   • Selected dermatoses (urticaria, pruritus, eczema, psoriasis)
   • Sequelae of stroke syndrome (aphasia, hemiplegia)∗
   • Seventh nerve palsy
   • Severe hyperthermia
   • Sleep disorders (Gooneratne, 2008)
   • Sprains and contusions
   • Temporomandibular joint (TMJ) syndrome, bruxism∗
   • Urinary incontinence, retention (neurogenic, spastic, adverse drug
     effect)∗
   • Weight loss (http://www.nature.com/ijo/journal/v27/n4/pdf/08022
     54a.pdf


                  How Does Acupuncture Work?

Currently there is no concrete, identifiable way to prove if acupuncture indeed
works, and it is still difficult to standardize the quality and quantity of treat-
ments since acupuncture usually has a patient-centered individualized
approach. But, there are several theories that attempt to explain the benefits of
treatment.
126    INTEGRATIVE GASTROENTEROLOGY


           Table 11.1. The Proposed Mechanism of Action for Acupuncture
Theory                  Proposed mechanism of action

Augmentation of         By some unknown process, acupuncture raises levels of
Immunity Theory         triglycerides, specific hormones, prostaglandins, white blood
                        counts, gamma globulins, opsonins, and overall antibody levels.

Endorphin Theory        Acupuncture stimulates the secretions of endorphins in the
                        body (specifically, enkephalins).

Neurotransmitter        Certain neurotransmitter levels (such as serotonin and
Theory                  noradrenaline) are affected by acupuncture.

Circulatory Theory      Acupuncture has the effect of constricting or dilating blood
                        vessels; this may be caused by the body’s release of vasodilators
                        (such as histamine), in response to acupuncture.

Gate Control Theory     The perception of pain is controlled by a part of the nervous
                        system that regulates the impulse, which will later be
                        interpreted as pain. This part of the nervous system is called the
                        “gate.” If the gate is hit with too many impulses, it becomes
                        overwhelmed and closes, preventing some of the impulses from
                        getting through. The first gates to close would be those that are
                        the smallest. The nerve fibers that carry the impulses of pain are
                        rather small nerve fibers called “C” fibers. These are the gates
                        that close during acupuncture.



                              Safety and Risks

Because acupuncture needles penetrate the skin, many forms of acupuncture
are invasive procedures, and therefore not without risk. Injuries are rare among
patients treated by trained practitioners (Lao, Hamilton, Fu, & Berman, 2003).
In most jurisdictions, needles are required by law to be sterile, disposable, and
used only once.


                     Common, Minor Adverse Events

A survey by Ernst et al. (2003) of some 400 patients receiving more than 3,500
acupuncture treatments found that the most common adverse effects from
acupuncture were:

      • Minor bleeding after removal of the needles, seen in roughly 3%
        of patients. (Holding a cotton ball for about one minute over the
        punctured site is usually sufficient to stop the bleeding).
                                            Acupuncture for Digestive System 127


   • Hematoma, seen in about 2% of patients, which manifests as bruises.
     These usually go away after a few days.
   • Dizziness, seen in about 1% of patients. Some patients have a kind of
     needle phobia, which can produce dizziness and other symptoms of
     anxiety. Patients are usually treated lying down, in order to reduce the
     likelihood of fainting.

    The survey concluded: “Acupuncture has adverse effects, like any therapeu-
tic approach. If it is used according to established safety rules and carefully at
appropriate anatomic regions, it is a safe treatment method.”


                              Serious Injury

Other serious, but rare, risks of injury from the insertion of acupuncture nee-
dles include:

   • Nerve injury, resulting from the accidental puncture of any nerve.
   • Brain damage or stroke, which is possible with very deep needling at
     the base of the skull.
   • Pneumothorax from deep needling into the lung (Leow, 2001).
   • Kidney damage from deep needling in the low back.
   • Hemopericardium, or puncture of the protective membrane sur-
     rounding the heart, (Yekeler et al., 2006) which may occur with nee-
     dling over a sternal foramen (a hole in the breastbone that occurs as
     the result of a congenital defect.
   • Risk of terminating pregnancy with the use of certain acupuncture
     points that have been shown to stimulate the production of adreno-
     corticotropic hormone (ACTH) and oxytocin.


      Risks from Omitting Conventional Medical Care

Receiving any form of alternative medical care without also receiving conven-
tional biomedical care can be often risky, since an undiagnosed disease may go
untreated and worsen. For this reason, interdisciplinary collaboration is
strongly recommended.


                     Historical/Theoretical Basis

Acupuncture as part of TCM dates back more than 2,000 years. It originates
from China, but was influenced by surrounding Asian countries like Korea
128   INTEGRATIVE GASTROENTEROLOGY


and Japan. One of the earliest texts is the Yellow Emperor’s Classic of Internal
Medicine, which laid out the essential theoretical foundation of TCM and
acupuncture as we know it today. The text describes the fundamental theories
of TCM, including Yin/Yang, the Five Elements, Meridians, Qi, Spirit, Blood,
etiology of disease, pathologies, and diagnostic methods, as well as a basic
knowledge concerning acupuncture points and needling techniques. The
understanding of exactly how this knowledge base had come about from
ancient times is still one of the underlying mysteries surrounding the develop-
ment of TCM.


                                     Technique

Classical acupuncture is used to stimulate specific points in the body with very
fine needles (normally 0.16 mm to 0.30 mm diameter). Many types of modi-
fied applications are available, such as acupressure, electro-acupuncture, stud,
laser, magnet, etc. Traditionally, acupuncture has been applied to various gas-
trointestinal disorders, from short-term acute symptoms (e.g., abdominal dis-
comfort, indigestion) to chronic disorders such as inflammatory bowel disease.
In addition, many clinical trials and basic studies have been performed to
verify the effectiveness of acupuncture and to investigate its mechanisms.


      Table 11.2. Acupuncture Effects on Gastrointestinal Function or Disorders
                      Clinical benefits

Nausea and            • Acupuncture, electro-acupuncture and acupressure can be
vomiting                beneficial for nausea and vomiting induced by surgery,
                        chemotherapy, pregnancy, etc. (Streitberger, Ezzo et al., 2006)

Gastric secretion     • Electro-acupuncture may inhibit acid secretion. (Tougas, Yuan
                        et al., 1992; Lux, Hagel et al., 1994)

Gastric motility      • Electro-acupuncture or acupuncture either inhibits or excites
                        gastric motility. (Sato, Sato et al., 1993; Shiotani, Tatewaki et al.,
                        2004; Noguchi, 2010)

Irritable bowel       • Inconclusive. Quality of life and symptoms were improved after
syndrome                acupuncture compared to baseline, but no group difference
                        with placebo or sham. (Forbes, Jackson et al., 2005; Schneider,
                        Enck et al., 2006)

Inflammatory bowel • Acupuncture improved disease activity compared to sham;
disease              improved quality of life compared to baseline. (Joos, Brinkhaus
                     et al., 2004; Joos, Wildau et al., 2006)
                                                Acupuncture for Digestive System 129


        Table 11.3. Possible Acupuncture Mechanism for Gastroenterology

                           • Stimulating PC-6 point (located on the forearm) has
                             been most frequently applied for nausea and vomiting.
                           • Various mechanisms have been proposed:
                             neurotransmitters (endogenous opioids and serotonin),
Nausea and vomiting
                             smooth muscle of the gut, somatovisceral reflex, sensory
                             input inhibition, somatosympathetic reflex, vagal
                             modulation, and cerebellar vestibular neuromatrix.
                             (Streitberger, Ezzo et al., 2006)

                           • Electro-acupuncture may inhibit acid secretion via
                             somatic afferent–visceral reflex mechanism (Zhou and
Gastric secretion            Chey 1984)11, releasing beta-endorphin and somatostatin
                             (Jin, Zhou et al., 1996) and opioid neural pathways (Tougas,
                             Yuan et al., 1992).

                           • Acupuncture may induce gastric relaxations via
                             somatosympathetic reflex and enhancement of c-Fos cells
                             at ventrolateral medulla (Tada, Fujita et al., 2003).13
Abdominal pain
                           • Electro-acupuncture may modulate pain via central
                             opioid pathway (Gao, Wang et al., 1997; Iwa,
                             Strickland et al., 2005).

                           • Needling on the abdomen may inhibit gastric motility via
                             sympathetic and spinal reflexes, while needling on the
                             limbs may excite gastric motility via vagal and supraspinal
Gastric and duodenal
                             reflexes (Sato, Sato et al., 1993).
motility
                           • Electro-acupuncture may induce response of duodenal
                             motility similar to that of gastric motility induced by
                             acupuncture (Noguchi, Ohsawa et al., 2003).

                         • Electro-acupuncture may increase the threshold of
                           rectal sensitivity in IBS patients (Xing, Larive et al.,
                           2004).
                         • Electro-acupuncture attenuated chronic visceral
Irritable bowel syndrome
                           hypersensitivity in correlation with decrease of
                           phosphorylation of spinal cord N-methyl-D-aspartic
                           acid (NMDA) receptors in IBS rats (Tian, Wang et al.,
                           2008).




   The most frequently used acupuncture points for gastrointestinal disorders
are Zusanli point (Stomach36;ST36) of the lower limb, and Neiguan point
(Pericardium-6;PC6) of the forearm (Takahashi, 2006). It is reported that acu-
puncture is generally very safe if it is performed by a credentialed practitioner
(Lao, Hamilton, Fu, & Berman, 2003).
130    INTEGRATIVE GASTROENTEROLOGY


      Table 11.4. Contraindications and Precautions to Acupuncture Treatment
      Contraindications

                                               •   Platelet < 50,000/mm3
                                               •   Abnormal PT, PTT
      Bleeding
                                               •   Anticoagulant therapy
                                               •   Hemophilia

                                               • ANC < 500 mm (Menten K, 2008)
                                               • No needles in skin lesions
      Infection
                                               • Other severely immunosuppressed
                                                 condition

      Cardiac disorder (especially for         • Pacemaker
      electro-acupuncture)                     • Other implantable electrical device

      CNS disorder                             • Seizure

      Allergy                                  • Metal allergy
      Precautions

        •   Pregnancy
        •   Unstable vital signs
        •   Unstable diabetes
        •   Sensory disorder
        •   Needle phobia
        •   Severe fatigue
        •   Severe hunger

      (modified from Menten K. et al., 2008)




                                         Conclusions

Acupuncture is a very old, but still practical, “ancient healing art.” It has been
applied for diverse symptoms or diseases, including gastrointestinal problems.
Extensive data support that acupuncture can relieve nausea and vomiting from
various causes. Several mechanisms are suggested for how acupuncture stimu-
lation may modulate gastric secretion and motility, which can be important
for many functional problems. On the other hand, it seems promising but not
conclusive whether acupuncture can be useful to improve the quality of life
and relieve symptoms for irritable bowel syndrome and inflammatory bowel
disease patients.
    Further high quality, well designed studies are necessary to establish strong
evidence of acupuncture for gastrointestinal disorders.
                                     12
             Ayurveda and Digestive Health
                DAVID SIMON AND VALENCIA PORTER




                                 key concepts

     ■   Patients with digestive illness should be educated about eating
         with awareness in a quiet, settled environment, paying attention
         to their body’s signals.
     ■   Patients with digestive illness should become familiar with their
         mind-body connections and be educated about how diet relates
         to body constitution type.
     ■   Patients with stagnant digestion can ignite their digestive fire by
         including ginger and lemon, and by reducing foods that are dif-
         ficult to digest (i.e., ama-reducing program).
     ■   Herbs can be utilized when needed, to enhance the processes of
         digestion, assimilation, and elimination.
                                       ■




                   General Ayurvedic Principles



A
         yurveda is an ancient traditional medical system from India that
         emphasizes health as a balance of body, mind, and spirit. This balance
         can be achieved through healthy lifestyle in accordance with nature
and one’s own body-mind constitution. The preventive practices of proper
nutrition and exercise, nourishing relationships, good emotional health, and a
regular daily routine contribute to the maintenance of health, which, accord-
ing to Ayurveda, is not simply the absence of disease.
   Digestive health is a key principle in Ayurvedic practice. Acknowledging
the multitude of functions of the digestive tract—extracting nourishment,

                                                                               131
132   INTEGRATIVE GASTROENTEROLOGY


nervous system feedback and peptide messengers, and immune system inter-
actions—Ayurveda states that digestive and metabolic fire maintains one’s
span of life, vitality, and natural resistance.
   The Sanskrit term agni, which has a common root with the English word
ignite, refers to this metabolic fire, with the primary function being digestion,
absorption, assimilation, and transformation of food and sensations into
energy. When our digestive fire is strong, and metabolism is balanced, we
experience health. An imbalance of agni can manifest as a number of physical
conditions. People can have problems with either too little or too much diges-
tive fire, resulting in delicate digestion on the one hand, and heartburn or acid
indigestion on the other. In addition, when digestion is poor, internal meta-
bolic waste, called ama, may accumulate, leading to generalized symptoms
such as fatigue and body ache. According to Ayurveda, treatment of the condi-
tion is of equal importance to eliminating the cause, rebuilding the body, and
continuing support through rejuvenative practices.


              Mind-Body Interactions in Digestion

The gastrointestinal system is truly remarkable. Through it, we ingest energy
and information from the environment to create both our physical form and
the energy we need to support our activities. This may be the most convincing
expression of the Vedic understanding that the environment is our extended
body. Nature has packaged her biological energy and information in the form
of food that contains the basic substrates needed to create and replenish our
cells. Through the process of digestion, basic codes of intelligence are exchanged
between our individual and our environmental physical sheaths. Ayurveda
describes the physical body as anna maya kosha, which means “the layer made
out of food.” In its essence, the body really is the intelligence carried on our
DNA molecules, wrapped in food.
   The key to good health is the ability to fully digest the experiences presented
to us at any moment. When we are able to extract the nourishment we need
and leave the rest behind, we create balance and integrity in mind and body.
Under ideal circumstances, this beautiful and dynamic process occurs sponta-
neously. When the mind is balanced and integrated, our appetites are strong
and appropriate. The gastrointestinal system receives healthy messages from
the brain, and is able to extract the elements necessary for maintaining struc-
ture and energy.
   Eating with awareness is great practice for living with awareness.
When we are fully present while enjoying a meal, we efficiently extract the
available nutrition and spontaneously avoid consuming that which is toxic.
                                                Ayurveda and Digestive Health 133


The Body Intelligence Techniques (see text box) are cues to bring us back to
present-moment awareness.

                         Body Intelligence Techniques

   • Include all six tastes (sweet, sour, salty, pungent, bitter, astringent) at
     every meal.
   • Eat in a quiet, settled, comfortable environment.
   • Eat only when you feel hungry.
   • Do not eat when you are upset.
   • Always sit down to eat.
   • Reduce ice-cold food and beverages.
   • Eat at a comfortable pace; stay conscious of the process.
   • Reduce talking while chewing and keep to lighthearted conversations.
   • Wait until one meal is fully digested before eating the next.
   • Sip warm water with your meals to avoid diluting digestive acids.
   • Eat freshly prepared foods. Lightly sautéed or steamed foods are prefera-
     ble to raw or overcooked.
   • Do not cook with honey; use maple syrup. Honey is best as a condiment.
   • Drink milk separately from meals, preferably warm, and either alone or
     with other sweet foods.
   • Do not overeat. Leave 1/4 to 1/3 of your stomach empty to aid digestion.
   • Sit quietly for a few minutes after your meal. Focus your attention on the
     sensation in your body, then take a short walk.


   If one is having symptoms of digestive imbalance, such as heartburn, bloat-
ing, or discomfort, use attention and intention to reestablish balance. After a
quiet meditation, localize attention to the alimentary system and visualize
comfortable, smooth, effortless, balanced digestion. Eating and digesting are
such primordial processes that simply remembering how natural they are can
improve their function.
   Nature’s gifts can be used to enliven healthy digestion. Enhance digestive
power with spices that stimulate metabolic fire, such as pepper, ginger, asafet-
ida, wild celery seeds, cardamom, cayenne, and cloves. Simplify the diet when
digestion is delicate, pay attention to appetite signals, and ensure regular elim-
ination, using gentle, natural agents to restore balance when necessary.


                        Use of Ayurvedic Herbs

According to Ayurveda, three essential elements make up a healthy digestive
system: digestion, assimilation, and elimination. The mind–body practices
134   INTEGRATIVE GASTROENTEROLOGY


described help to maintain all of the processes, and particular herbs may also
be used to aid each of these processes.


      AYURVEDIC HERBS FOR ENHANCING APPETITE AND DIGESTION

Herbs to stimulate the digestive fire are generally spicy in nature, and best
taken immediately prior to or with a meal. Ginger, black pepper, cayenne, wild
celery seeds, and long pepper contain essential oils that have effects at several
levels of the digestive process.Ginger (Zingiber officinale), known in Ayurveda
as the universal remedy, has long been used in many cultures for its culinary
and medicinal properties. Classically used to treat nausea and vomiting in a
number of conditions, it stimulates the release of salivary enzymes and
enhances stomach emptying when taken orally. According to Ayurveda, ginger
works on all three phases of gastrointestinal function and, as part of an herbal
aperitif, the pungency of ginger can kick-start the digestive process. There are
no documented problems with taking ginger in normal doses; however, it
appears to have mild anti-platelet-forming effects, and thus should be used
with caution by those who are on prescribed blood thinners.
   Bitter herbs can also enhance the first stage of digestion by way of a neural
reflex. The classic bitter is gentian, which enhances stomach emptying and
stimulates the secretion of enzymes by the stomach, gallbladder, and pancreas.
Other bitter herbs that are useful in small quantities include dandelion, orange
peel, aloe vera, and chamomile.


      AYURVEDIC HERBS FOR QUIETING EXCESSIVE DIGESTIVE FIRE

Hyperacidity, heartburn, gastroesophageal reflux, and peptic ulcers are expres-
sions of an inefficient digestive fire that is imbalanced in both location and
quantity. Cooling herbs that pacify the excessive heat, and encourage a cleaner
digestive fire, can help reduce heartburn and improve digestion. These include
cumin, coriander, fennel, and licorice, as well as amalaki and shatavari. They
are generally taken after a meal, or when the symptoms of acid indigestion are
prominent.
   Shatavari (Asparagus racemosus), also known as Indian asparagus, is one of
the prime rejuvenating herbs in Ayurveda. While particularly helpful in sup-
porting the female reproductive system, it is also effective in relieving inflam-
matory conditions and in soothing irritated tissues, and has a traditional role
as a digestive aid. This herb cools off an irritated digestive system that mani-
fests as heartburn, diarrhea, or irritable bowel syndrome. In men with a history
                                                Ayurveda and Digestive Health 135


of heartburn and indigestion after meals, shatavari was found to be as effective
as metoclopramide (Dalvi, Nadkarni, & Gupta, 1990). Shatavari also has an
established history as an antidiarrheal agent, although not formally studied for
this purpose. In studies, shatavari has been demonstrated to have immune-
modulating properties (Rege & Dahanukar, 1993; Dhuley, 1997; Thatte &
Dahanukar, 1988; Rege et al., 1989). To treat digestive distress, one teaspoon in
one-half cup of warm milk is taken after each meal. It mixes well with equal
parts of amalaki and licorice for symptoms of heartburn or indigestion.
   Amalaki (Emblica officinalis), also known as Indian gooseberry, is consid-
ered the best herbal medicine for rejuvenation in Ayurveda. It is one of the
richest natural sources of antioxidant vitamins, possessing almost 20 times as
much vitamin C as orange juice. Used alone or in combination with many
other herbs, it has wide traditional uses, including the treatment of skin dis-
eases, lung conditions, diabetes, and indigestion. Amalaki is one of the three
ingredients in triphala, the most important Ayurvedic bowel tonic. Mostly
studied in the areas of cancer inhibition, lowering cholesterol, and decreasing
platelet aggregation, amalaki has also traditionally been used in the treatment
of heartburn, and a few scientific studies have supported this use (Chawla
et al., 1982). In a clinical trial on a series of 27 patients with duodenal ulcer,
and 12 with nonulcerative dyspepsia, a significant decrease in acid and pepsin
secretion, with marked symptomatic relief, was found after 3 months of using
amalaki (Varma et al., 1977). A recent study has shown that it has a role in
mucin protection and regeneration, in the healing of ulceration related to non-
steroidal anti-inflammatory drug use (Bhattacharya et al., 2007). It also has a
reputation for the treatment of liver and pancreatic conditions, and in an
animal study was shown to reduce the extent of tissue damage caused by
experimental pancreatitis (Thorat et al., 1995). Amalaki can be taken as the
traditional rejuvenative jam, Chavan Prash, one teaspoon twice daily, either
straight or mixed in juice or warm milk. Amalaki in triphala can help those
with chronic constipation, as well as those with irritable bowel syndrome.
Mixed with shatavari, fennel, and turmeric, it can be effective in reducing
hyperacidity. To improve colon function, 1 to 2 grams daily in divided doses is
recommended. Owing to its laxative qualities, amalaki should be used care-
fully in people with a tendency toward loose bowels.
   Licorice (Glycyrrhiza glabra) is another herb that has been used among
many cultures, with a number of therapeutic effects. Used cautiously and with
respect, licorice is a valuable healing plant, but at excessive levels it can cause
potentially dangerous side effects. One of its traditional uses has been in the
treatment of peptic ulcers, and animal studies have shown that licorice stimu-
lates the production of protective mucus in the stomach lining (Nadar &
Pillai, 1989). Most complications occur in people taking excessive doses of
136 INTEGRATIVE GASTROENTEROLOGY


licorice with the component glycyrrhizic acid, which causes retention of
sodium and elevated blood pressure. It is advised not to take more than 100 mg
of glycyrrhizic acid per day, which would be approximately 2.5 grams of dried
licorice root. In addition, the German Commission E recommends limiting
use to no longer than 6 weeks at a time. It is possible to obtain and use DGL
(deglycyrrhizinated licorice), which contains less than 3% glycyrrhizic acid
and is considered quite safe. For hyperacidity, take licorice 30 minutes before
a meal or 1 hour after the meal.


            AYURVEDIC HERBS FOR ENHANCING ABSORPTION

Problems with this phase of digestion result in gas, bloating, and heaviness
after a meal. People with assimilation difficulties often report that even though
they are eating healthy foods, they do not feel they are being adequately nour-
ished. Nutmeg, chamomile, peppermint, and lemon verbena are herbs tradi-
tionally used to reduce abdominal spasms and bloating. Cinnamon, cardamom,
and bay are known as the “three carminatives,” meaning that they dispel con-
gested intestinal gas. Other culinary herbs useful in reducing bloating include
basil, oregano, thyme, coriander, cumin, dill, and fennel. Ayurvedic herbs
useful in reducing gas that are not as well known in the West include wild
celery seeds (Apium graveolens) and long pepper (Piper officinarum). Cooking
beans or legumes with asafetida (Ferula asafoetida), also known as hing, can
improve digestive ability and reduce bloating and gas.


          AYURVEDIC HERBS FOR ENCOURAGING ELIMINATION

A fiber-rich diet that includes plenty of fresh fruits, vegetables, and whole
grains is the most important contributor to daily elimination. When necessary,
adding fiber in the form of psyllium or flaxseed can invigorate sluggish bowels.
A classic Ayurvedic formula called triphala consists of three fruits—amalaki,
bibhitaki (Terminalia belerica) and haritaki (Terminalia chebula). Like psyl-
lium, the fiber in triphala can help enhance elimination in people whose
bowels are slow, and normalize bowel movements in people who tend toward
loose stools. Amalaki is discussed above. Bibhitaki has a strong purgative
action, and is also an excellent rejuvenative. Recent studies have also shown
antiviral and lipid-lowering effects (Shaila et al., 1995; Xu et al., 1998). Haritaki
is called “king of medicines” in Tibet, and recent studies have shown its prom-
ise as an antioxidant, anti-diabetic, antimicrobial, and anti-cholesterol agent
(Lee et al., 2005; Gao et al., 2008; Murali et al., 2007). One animal study showed
                                                Ayurveda and Digestive Health 137


that haritaki was comparable to metoclopramide in increasing gastric empty-
ing (Tamhane et al., 1998). When taken in larger doses at night, triphala can be
helpful in relieving constipation. Triphala can also be used as a daily rejuvena-
tive formula, and prolonged use is safe and non-habit forming.
   Herbal stimulant cathartics should only be used rarely. Castor oil, cascara
sagrada, senna, and aloe are the most common plant-based laxatives that act
by stimulating the nerve fibers to the colon, and by causing the accumulation
of salts and water in the intestines. These laxatives can cause abdominal cramp-
ing, with cascara the mildest and castor the strongest. The main problem with
repeated use of these herbal stimulants is that one can become dependent on
their use to stimulate bowel movements.
   Using these tools, to restore our digestive power to its natural state of health,
supplies us with our energy and physical needs. Listening to our body–to our


                            Table 12.1. Ayurvedic Herbs

Ayurvedic Herbs for Enhancing Digestion

Ginger                                             Dandelion

Black pepper                                       Orange peel

Cayenne                                            Aloe vera

Wild celery seeds                                  Chamomile

Long pepper                                        Gentian

Ayurvedic Herbs for Reducing Excess Acidity

Amalaki                                            Cumin

Shatavari                                          Coriander

Licorice                                           Fennel

Ayurvedic Herbs for Reducing Gas and Bloating

Nutmeg                                             Basil         Wild celery seeds

Chamomile                                          Oregano       Long pepper

Peppermint                                         Thyme         Asafetida (Hing)

Lemon verbena                                      Coriander

Cinnamon                                           Cumin

Cardamom                                           Dill

Bay                                                Fennel

                                                                         (Continued)
138 INTEGRATIVE GASTROENTEROLOGY


                                Table 12.1. (Continued)

Ayurvedic Herbs for Enhancing Elimination

Triphala (Amalaki, Bibhitaki, Haritaki)

Stimulant Cathartics:

• Castor oil

• Cascara sagrada

• Senna

Aloe (latex portion)




gut–allows us to tune into our innate intelligence, which can guide us along
the path of greater well-being.


          Mind-Body Prescription for Digestive Health

    1. Follow the Body Intelligence Techniques at every meal.
    2. Follow dietary recommendations specific to your mind–body
       constitution.
    3. Pay attention to your appetite level and only eat when you are really
       hungry, stopping when you are comfortably full.
    4. Similarly, pay attention to the natural urge to defecate.
    5. Eat an occasional meal in silence.
    6. If your digestion is delicate, follow an ama-pacifying program for a
       couple of weeks.
    7. If your appetite is weak, eat a mixture of fresh grated ginger, lemon
       juice, and rock salt (1/2 tsp. fresh ginger, 1/2 tsp. lemon juice, a pinch
       of salt) to stimulate agni, one-half hour before meals.
    8. If you tend to get heartburn after meals, chew a quarter-teaspoon of
       roasted fennel seeds or a pinch of fresh coriander leaves. Cook with
       cumin and coriander, which are also cooling herbs.
    9. To decrease gas or bloating, add cinnamon, cardamom, and bay to
       your cooking.
   10. Ayurvedic herbs traditionally used to enhance appetite and diges-
       tion include sunthi (ginger), maricha (black pepper), pippali (long
       pepper) and ajwan (wild celery seeds).
                                                     Ayurveda and Digestive Health 139


   11. Ayurvedic herbs traditionally used to quiet excessive digestive fire
       include shatavari (Indian asparagus), amalaki (Indian gooseberry),
       and yasthi madhu (licorice).
   12. Ayurvedic herbs traditionally used to enhance absorption include
       jatiphala (nutmeg), haritaki (Chebulic myrobalan) and musta (nut
       grass).
   13. Celebrate eating! Don’t strain.


                           Ama-Pacifying Program

   1. Follow the Body Intelligence Techniques.
   2. Eliminate/reduce foods that increase ama—fried foods, heavy and
      oily foods, aged cheeses, meats, rich foods, and anything that is diffi-
      cult to digest.
   3. Stimulate your digestion with ginger tea.
   4. Eat warm, freshly cooked whole foods that are light and easy to
      digest, such as rice, soups, lentils, freshly steamed or lightly sautéed
      vegetables.

        Table 12.2. Dietary Recommendations for your Mind-Body Constitution
                              (adapted from Chopra, 2000)
Mind–Body type     Favor                                 Reduce/Avoid

Vata               Warm food, moderately heavy           Cold salads, raw vegetables and
                   textures                              greens
                   Added butter and fat                  Iced drinks
                   Salt, sour and sweet tastes           Dry, salty snacks (nuts are fine in
                   Sweet fruits                          small amounts)
                   Soothing and satisfying foods         Dried fruits
                   Dairy                                 Beans (except chickpeas, mung
                                                         beans, pink lentils, tofu)
                                                         Astringent and bitter tastes

Pitta              Cool or warm, but not steaming-       Excessive salt, sour or spicy tastes
                   hot foods                             (pickles, yogurt, sour cream,
                   Moderately heavy textures             cheese, processed and fast foods)
                   Bitter, sweet and astringent tastes   Red meat and seafood
                   such as salads and legumes            Fried foods
                   Less butter and added fat             Sour or unripe fruits
                   Milk, grains, vegetables              Nuts and seeds (except coconut,
                   Sweet, ripe fruits                    pumpkin seeds, sunflower seeds)

                                                                                 (Continued)
140   INTEGRATIVE GASTROENTEROLOGY


                             Table 12.2. (Continued)
Mind–Body type   Favor                             Reduce/Avoid

Kapha            Warm, light food                  Sweet, rich and salty foods
                 Dry food, cooked without much     Cold foods
                 water                             Dairy products (especially butter,
                 Raw fruits, vegetables, salads,   ice cream, cheese)
                 legumes                           Oil (small amounts of corn,
                 Pungent, bitter and astringent    almond and sunflower oils
                 tastes                            Red meat and seafood
                 Stimulating foods                 Sweet and juicy vegetables and
                                                   fruits
                               13
                Osteopathic Medicine
                        DIANE CLAWSON




                           key concepts

■   Osteopathic Medicine is not merely a combination of traditional
    Western medicine and osteopathic manipulation (DiGiovana,
    1997). It is based on a philosophy of health that considers the
    whole patient—mind, body and spirit.
■   The evaluation and treatment of the musculoskeletal system is
    used for diagnosis and treatment of systemic disease, as well as
    musculoskeletal complaints.
■   Doctors of Osteopathic Medicine (DOs) are fully licensed
    physicians, practicing all specialties of medicine. The profession
    has overcome many obstacles to achieve equal practice rights
    with their Medical Doctor (MD) counterparts.
■   The focuses for osteopathic treatment of gastointestinal disease
    are the viscerosomatic reflexes occurring with the sympathetic
    nervous system, the parasympathetic nervous system, and
    lymphatics.
■   Osteopathic treatment is most commonly used in conjunction
    with the standard of care for each particular disorder. In mild
    cases, osteopathic manipulative medicine (OMM) may be the
    only treatment needed.
                                  ■




                                                                         141
              Introduction to Osteopathic Medicine



O
          steopathic Medicine was founded in 1874 by Andrew Taylor Still,
          MD. In the 1800s, physicians were trained primarily through appren-
          ticeships, and Dr. Still was no exception. The training was frequently
inadequate, and the treatments of the day included bloodletting, mercury,
alcohol, morphine, laxatives, and purgatives. Still watched his brother become
addicted to morphine through medical treatment, and he lost three of his chil-
dren to meningitis, unable to help them with the medical practices of the time.
He became increasingly dissatisfied with allopathic medicine, and began to
develop a method of treatment that would bring health without the often
disastrous effects of the then-current practices. Still identified the musculo-
skeletal system as a key element of health, recognizing the importance of
unobstructed circulation and innervation in maintaining health. He believed
that the body has its own “pharmacy” and an innate capacity for self-healing.
He stressed prevention, healthy eating, and exercise as necessary components
of health. Osteopathic Medicine is based on a philosophy, of which there are
four basic tenets. These are:

   1.   The body functions as a whole—mind, body, and spirit.
   2.   The body is self-regulating and self-healing.
   3.   Structure and function are interrelated.
   4.   Rational treatment is based on the above principles.



   Through a combination of intense study of anatomy and philosophical
   enlightenment, “Still came to see humans as marvelous machines, created
   and sustained by laws of nature” (Ward, 1997). This became the basis for his
   new brand of medicine called “Osteopathy.”




   Today, DOs have the same practice rights as MDs, and both are seen work-
ing together in the same hospitals, the same clinics, and the same branches of
the military. This, however, was not always the case. It has been a long and
arduous process to achieve equal practice rights. The American School of
Osteopathy in Kirksville, Missouri, was the first school to open in 1892. In 1910,
the Flexner report was published and harshly condemned both osteopathic
                                                                     Osteopathic Medicine 143


and allopathic medical schools.1 As a result, all of the osteopathic schools and
122 of the MD schools were closed.
   During World War I, the first efforts to obtain federal recognition were
undertaken so that DOs could become commissioned as military officers.
Instead, the DOs were required to serve as regular soldiers, despite their med-
ical training. In 1941, the Military Appropriations Act was passed, which
allowed for recognition of DOs in the military. However, during World War II,
DOs were deferred rather than drafted. The DOs were left to care for the thou-
sands of patients left by the MDs serving in the war. This ultimately proved to
be a positive development for the DOs, by enhancing the public’s view of them
as full-service physicians. Finally, in 1966, DOs were accepted as physicians
and surgeons in the military.
   The darkest days of osteopathy occurred in 1962, when there was an effort
to abolish the DO licenses in California. There was a merger between the
California Osteopathic Association and the California Medical Association.
DOs were able to obtain an MD degree for a small fee. The degree was not
recognized outside of California, but 85% of the DOs became MDs during this
time. The proposed referendum was passed, and the licensing of DOs in
California was discontinued. In 1974, the referendum was overturned and DOs
could once again become licensed in California.


    Vermont was the first state to grant full practice rights to DOs in 1896.
    The last state to recognize DOs as fully licensed physicians was Louisiana
    in 2001.



   Today, there are 25 osteopathic schools in 31 locations, and approximately
60,000 DOs who are licensed to practice all phases of medicine in all 50 states,
the District of Columbia, and U.S. territories. In addition to a holistic philoso-
phy, DOs use structural diagnosis and manipulative treatment, along with all


1
  The Flexner Report is a book-length study of medical education in the United States and
Canada, written by the professional educator, Abraham Flexner, and published in 1910 under the
aegis of the Carnegie Foundation. Many aspects of the present-day American medical profession
stem from the Flexner Report and its aftermath.
   The report (also called Carnegie Foundation Bulletin Number Four) called on American medi-
cal schools to enact higher admission and graduation standards, and to adhere strictly to the
protocols of mainstream science in their teaching and research. Many American medical schools
fell short of the standard advocated in the report and, subsequent to its publication, nearly half of
such schools merged or were closed outright.
144 INTEGRATIVE GASTROENTEROLOGY


of the other, more traditional, forms of diagnosis and treatment, to provide
comprehensive medical care to their patients.


     With a renewed interest in osteopathic manual medicine, a mechanism has
     been instated that will allow MDs to train and become certified in OMM.
     Additional coursework is required.




Application of Osteopathic Concepts to Digestive Issues

At the core of osteopathic treatment for digestive issues is a comprehensive
knowledge and understanding of the segmental and autonomic innervation of
the gastrointestinal tract itself. There is a reflex arc between the viscera (inter-
nal organs of the body, especially of the abdomen and thorax) and the segmen-
tally related musculoskeletal region. (Table 13.1) When there is pathology or
dysfunction, the viscera and soma become linked in a cycle of afferent and
efferent impulses, which can sustain and even exacerbate the problem. With
increased and prolonged visceral input, the spinal cord region becomes facili-
tated. As a result, there are palpatory tissue changes, joint somatic dysfunction,
and tenderness to palpation in the corresponding segments on exam (Figure
13.1). The osteopathic term for this is viscerosomatic reflex. These reflexes are
also responsible for what are known as “Chapman’s Reflexes.” They are defined
as “a system of reflex points that present as predictable anterior and posterior
fascial tissue texture abnormalities assumed to be reflections of visceral dys-
function or pathology.” (Figure 13.2.)




           Table 13.1. Segmental Arrangement of the Sympathetic Chain

T6                               Esophagus

T6-T9                            Lower Esophagus and Stomach

T6-T9 (right)                    Liver and Gallbladder

T6-T9 (left)                     Spleen and Pancreas

T7-T9                            Small Intestine

T10-L1 (right)                   Ascending and Transverse Colon

T12-L2 (left)                    Descending Colon and Rectum

(Adapted from DiGiovana, 1997)
                                                         Osteopathic Medicine 145



   Facilitated segments secondary to systemic disease do not respond well to a
   type of treatment known as high-velocity, low-amplitude (“cracking” tech-
   nique associated mostly with chiropractors). If a lesion recurs repeatedly, it
   is a sign that systemic issues may be present (Kuchera & Kuchera, 1994).



   In the OMM model, the end result of these reflexes is increased sympathetic
tone, which causes vasoconstriction and alteration of the bicarbonate and
mucous buffers (Kuchera & Kuchera, 1994). The mucosal defenses against
digestive acids and enzymes are reduced, and believed to be a factor for inflam-
mation and ulceration in the upper GI system. The goal of treatment is to nor-
malize the facilitated segments, thereby normalizing the sympathetic input.
   In addition to normalizing sympathetic input, attention must also be paid
to the parasympathetic branch of the autonomic nervous system. The para-
sympathetic input is provided by the vagus nerve and the pelvic splanchnic
nerves. The right vagus nerve innervates the lesser curvature of the stomach,
liver, gallbladder, small intestine, and right half of the colon. The left vagus
supplies the greater curvature of the stomach to the duodenum. The pelvic
splanchnic nerves, which originate from cord segments S2, S3 and S4, inner-
vate the left half of the colon and the pelvis. (Figure 13.3) When there is hyper-
activity of the parasympathetic input, there are increased bowel motility and
glandular secretions often associated with diarrhea (Kuchera, 1994. Conversely,
constipation is a likely manifestation of hypoactivity (Kuchera, 1994). Irritable
bowel syndrome results when there is uncoordinated hyperactivity of both the
parasympathetic and sympathetic systems (Kuchera, 1994).
   Lastly, with dysfunction and disease, increased demands are placed upon
the lymphatic system. Lymphatic flow can be hindered by a flattened dia-
phragm (which acts as an extrinsic pump) or torsed fascia, which can greatly
reduce the body’s ability to recover from a disease process (Kuchera, 1998).
Lymphatic drainage of the abdomen is an important consideration in the treat-
ment of an ileus or inflammatory bowel disease.


                                 Conclusion

Osteopathic medicine offers a holistic philosophy and unique approach to
medical treatment. There is recognition that the musculoskeletal system,
which comprises 60% of our body mass, is interrelated with all other body
systems. Dysfunction in one system causes altered function in others.
Osteopathic manipulative treatment of gastrointestinal issues requires exten-
sive knowledge of anatomy, and an appreciation of the autonomic nervous
system and lymphatics in maintaining or achieving health.
                                   14
          Gastroenterology and an Integrative
                Chiropractic Approach
                 LOREN MARKS AND DAVID M. DURKIN




                                key concepts

      ■   A historical review of chiropractic.
      ■   Human beings are made up of a web of structural, emotional,
          and biochemical components.
      ■   The integration of these systems within us cannot be entirely
          divided by subspecialties.
      ■   The Integrative Assessment Technique [IAT] is methodologies
          for both—the chiropractic profession (and other practitioners)
          who wish to have a more comprehensive alternative approach
          bridging together the three worlds of structure, emotions, and
          biochemistry.
      ■   It is the very essence of this text to embrace and understand
          contextually where and how the alternative medicine models fit
          into the evaluation and management of gastroenterology.
      ■   The future belongs to those willing to lay new track, and not
          merely adhering to the continuance of the status quo.
                                      ■




146
                      A Brief History of Chiropractic



D
           r. D.D. Palmer1 Dr. Daniel David (D.D.) Palmer, a Canadian-born
           teacher and healer, founded chiropractic in 1895. A man with a unique
           perspective, he was very inquisitive and determined to understand
health and promote wellness by trying to work with the body’s innate life force.
Dr. Palmer, having studied anatomy and physiology in his search to become a
healer, had developed a very in-depth knowledge of these topics by the late
1800s and, as a result, had been using magnets to try to influence his patients’
life force.
    Harvey Lillard2
    One day, a janitor in Dr. Palmer’s office building named Harvey Lillard,
who had lost his hearing some seventeen years earlier, following feeling a “pop”
in his back while in a stooped position, was working near Palmer’s office when
D.D. asked the man if he could evaluate his condition. Dr. Palmer (1910) later
recounted this story in The Chiropractor’s Adjuster. Palmer noticed a protru-
sion in the janitor’s back and asked him to lie down on a bench, at which time
Dr. Palmer applied a gentle manual force to his spine, which subsequently
restored his hearing following several such treatments. With this vantage
point, Palmer continued studying the relationship of each spinal segment and
its corresponding organ, as well as evaluating the overall health of the local
townspeople and trying to relate their overall health to their spinal function.
This type of study became his passion, and ultimately was the start of our pres-
ent-day chiropractic profession.
    Dr. B.J Palmer1
    D.D.’s son, B.J. Palmer, is attributed with developing the art, science, and
philosophy of chiropractic. B.J. raised the standards of the chiropractic educa-
tional system, to its present doctoral level. He understood, as did physicians
practicing medicine, that without knowledge of such things as microbial inva-
sion and a continued growth in the sciences, health care would be limited.
However, it has been only a decade or so that chiropractors and medical physi-
cians have been communicating at a higher level, to help ensure an integrative


1
  Pictures of D.D. Palmer and B.J. Palmer originally appeared in The Subluxation Specific ∼ The
Adjustment Specific, Davenport: Palmer College of Chiropractic, 1934; Reprinted 1995. (p.2).
Available at: http://www.cafeoflifepikespeak.com/tribute_DD.htm, and http://www.cafeoflife
pikespeak.com/tribute_BJ.htm
2
  Picture of Harvey Lillard from Chiropractic History, WikipediaOnline Encyclopedia 2008,
http://en.wikipedia.org/wiki/Chiropractic_history.
148   INTEGRATIVE GASTROENTEROLOGY


healthcare model for the future. Today’s chiropractic physicians are more ded-
icated than ever to learning from and educating other healthcare providers,
and to promoting integration of all healthcare modalities to help ensure a truly
integrative medical model. An interesting point for practitioners to focus on is
that all healthcare practitioners work in their chosen field for the love of their
specialty, and for the benefits of contributing to the health and/or wellness of
their patients. If we understand this, then it is easy to overlook some small
philosophical differences, as long as the patient’s best interest is kept in focus
when delivering care.


                      Integration or Separation

On the first look at a topic of “gastroenterology and chiropractic,” one may
wonder how chiropractic treatment can be integrated into the treatment of
gastroenterological disease or disorders. These are the type of questions that
have been asked of the chiropractic profession for over one hundred years.
However, when the nervous system is evaluated further, the possibilities and
the resulting impact of a properly functioning nervous system become more
evident for even a layperson.
   In fact, it is not uncommon for chiropractic patients to have questions about
changes with their bowel function, as well as other organs, following chiro-
practic care. How can this be? To help in the initial process of understanding
the chiropractic paradigm, a brief overview of some of the basic chiropractic
models is needed.


              The Vertebral Subluxation Complex

Vertebral Subluxation Complex (VSC) is a theoretical model of motion seg-
mental dysfunction (subluxation) that incorporates the complex interaction
of pathologic changes in nerve, muscle, ligamentous, vascular and connective
tissues (Gatterman, 1995). These aberrations of the nervous system can
result in:

   • Loss of sensory information:
         Causing inappropriate nerve responses; and
   • Altered states of function in other areas of the nervous system:
         Causing changes in body functions (Hughes & Rousso, 2004).
                   Gastroenterology and an Integrative Chiropractic Approach 149


   These changes are explained with several chiropractic models, two of which
will be our focus here to help us understand the link between musculoskeletal
changes and an overall improvement in the global health of a patient.

  • Mechanical or Mechanistic
        Abnormal changes in weight bearing, movement, or the spinal
        curves (alignment or structure).
  • Neurological or Vitalistic
        Interference in the normal physiological function of the nervous
        system, affecting every tissue, organ and system in the body.

   Chiropractic physicians are trained to locate and treat these mal-positioned
vertebrae or subluxations. Patients enter chiropractic offices daily wanting to
know how this type of physical medicine can help treat, correct, and heal
the host of symptoms that are talked about in chiropractic testimonies and
in alternative literature. Such patients need to understand that chiropractic
physicians are trained to diagnose illness, much like family physicians, but
there is a difference: Chiropractic physicians primarily treat subluxations.
Subluxations cause altered nerve function inducing a nerve impingement syn-
drome, which causes a mechanistic (alignment and structure) and a vitalistic
change (altered normal function) to the exiting nerves of the spinal cord. This
causes a potential alteration to all the areas that that specific nerve travels
(organs, tissues, and cells) throughout the entire body. Restoring normal
motion of a spinal segment can eliminate nerve impingement syndrome
and restore proper function, which helps lead to a restoration of health and
wellness.


                 The Autonomic Nervous System

   Patients need to realize that they must also exercise, eat well, and reduce
emotional stress to promote total wellness. These topics are now generally
addressed in most chiropractic offices.
   Furthermore, revolutionary changes in the chiropractic profession have
evolved through the use of computerized analysis, followed by spinal correc-
tion with some of these same computerized instruments. Such changes in
many offices have helped develop not only the traditional art of locating sub-
luxations, but have created a more scientific analysis for locating spinal hypo-
mobility and, additionally, have standardized the correction of subluxations.
150   INTEGRATIVE GASTROENTEROLOGY


Instruments such as the ProAdjusterTM from Sigma Instruments and Pro-
Solutions and the Insight Subluxation StationTM from the Chiropractic
Leadership Alliance have given the chiropractic profession an increased level
of certainty, improving the objective data to help locate and define the degree,
as well as the location of vertebral segmental dysfunction or subluxation. This,
coupled with the traditional art and science of chiropractic, yields the practic-
ing chiropractor a pool of information from which to draw upon to help rees-
tablish the normal balance (homeostasis) of the nervous system and thus the
body as a whole.
    If structural changes are not corrected, spinal or joint degeneration will
begin and symptoms may develop and/or progress. Loss of structural integrity
can cause a progression toward illness, and can even cause disease (i.e., degen-
erative disc disease, neuritis, neuropathy, gastritis, gastro-paresis, allergies,
fatigue, sleep, various sinus conditions, colds and flu (neuro-immunology)
due to the resulting nerve impingement. Structural changes are easier to iden-
tify and understand for the average patient, and for that reason is usually the
focus of education in a chiropractic office. These structural changes can even-
tually lead to the neurological changes described in the more complicated
vitalistic model of chiropractic. All types of physicians must keep in mind that
a subluxation cannot be diagnosed by decreased spinal motion (hypomobility)
alone, but must possess a neurological finding such as pain, weakness, and/or
sensory changes. However, such changes may be difficult to detect without
advanced testing like magnetic resonance imaging (MRI), electromyography
(EMG) or nerve conduction velocity (NCV) tests. This is the reason many
chiropractic physicians are now using more advanced instrumentation as dis-
cussed above, (ProAdjuster and Subluxation Station) to confirm their working
diagnoses of subluxation. Spinal hypomobility alone would be considered only
a spinal fixation, which is a precursor to subluxation but not synonymous with
it. Both conditions can be treated in chiropractic offices, but the latter is more
serious and includes mechanistic and vitalistic alterations. This is a common
error seen when evaluating physician reports and literature on the topic of
segmental dysfunction.
    An evolution of chiropractic has continued over the years and today’s chi-
ropractic practices are now more geared toward total wellness than at any
other time in the history of the profession. Due to the level of education avail-
able, the chiropractic educational standards, and the in-depth training of
today’s chiropractors, the chiropractic profession is moving toward being
trusted advisors to their patients, as opposed to treating only musculoskeletal
conditions—a “wellness advisor,” if you will, that can assist patients with health
issues including diet, sleep, nutritional supplementation, weight loss and stress
management which support healthy lifestyle behaviors. Today’s chiropractors
                     Gastroenterology and an Integrative Chiropractic Approach 151


develop relationships with many medical physicians in allied fields such as
orthopedic surgeons, physiatrists, neurologists and radiologists. Chiropractor’s
who practice via a more holistic or wellness based model, develop relation-
ships with all types of physicians and routinely refer to these doctors to sup-
port the overall wellness of there patients. More education and a greater focus
are needed in our society on the benefits of preventative medicine and well-
ness care. This is a responsibility that must be embraced by all entry-level prac-
titioners (traditional and alternative), if we are to establish a healthier society.
Embracing such standards would help decrease chronic illness and human
suffering. Promoting “wellness care” would decrease the practice of treating so
much disease at such a huge expense to our society. Such education would
allow us to help our patients understand the consequences of their lifestyle
choices, reducing illness and promoting health. Wellness is a product of
normal physiology and disease is a product of altered physiology. Often,
delayed intervention promotes disease (longstanding altered physiology),
which mandates costly allopathic intervention. If we reestablish a healthier
physiological state early on, a disease that may have occurred may be pre-
vented prior to its development, and those that do occur gain the advantage of
improved and less invasive allopathic treatment. It is the opinion of the authors
that the health of our society can best be obtained by all practitioners working
together for the benefit of patients.


                         Medicine and Disease

If we take a retrospective review of the early beginning of medicine, we find
that some of the foundational principles were based upon Pasteur’s original
doctrines, notably his view of microbes and the isolation of them as a primary
cause of disease.
   Even though we have scientifically documented the phylogenic and taxo-
nomic identification of microbial species, there remains, in many aspects of
modern medicine, too strong a practice of “isolate and eradicate” without
addressing lifestyle and dietary behaviors. This is evidenced by the over-
prescribing of antimicrobials in the United States.
   Pasteur’s successor, Beauchamp, points out that it is the terrain that has
been compromised, not the invading germs. This requires a more common
practice—to define etiologic mechanisms when patients are not in acute
states of illness. Integrative practitioners are embracing this model, and it is
the hope of these authors that we might all come to an enhanced understand-
ing of human health through the various forms and legitimate practices that
have been developed over time to address the ills of mankind.
152   INTEGRATIVE GASTROENTEROLOGY


   This text is a body of knowledge comprising an integrative approach to gas-
troenterology. It is a groundbreaking attempt to look at the various mecha-
nisms and alternative healing practices that exist, contributing to the betterment
of gastrointestinal health. The purpose of the opening of this text was to estab-
lish a template for the contextual nature of where chiropractic care and GI
disturbances meet.
   Indeed, no double-blind peer reviewed studies have been performed to
substantiate the relationship of chiropractic care to GI health, as the dynamic
nature of vitalistic changes are difficult to quantify between patients, but an
established hypothesis has been utilized over the years and has been outlined
above. Empirical knowledge—through neural segmental enervation of the
autonomic nervous system (ANS) to each organ system, diet and lifestyle, and
reflex testing—is the experiential substitute for the “evidence-based medicine
model” that exists for the doctor of chiropractic pertaining to gastroenterol-
ogy. Case studies and reviews of GI disturbances, such as childhood colic, ileo-
cecal valve disturbances, and hiatial hernias do exist in the literature. This
hardly equates to a database from which to draw. It is fair to say that the fund-
ing of research for the chiropractic profession to study the relationship of GI
health to spinal manipulative therapy (SMT) has been very difficult to achieve,
since the pharmaceutical industry’s model for health dominates the current
terrain. While not an excuse, it is a consideration that has limited the direction
of dollars allocated for non-allopathic models.
   Unquestionably, doctors of chiropractic have been treating patients since
1895, receiving feedback from patients stating that they came for low back pain
or neck pain, and since beginning care, their constipation, intestinal cramping,
or lower quadrant pain have been relieved or resolved. This empirical evidence
provides a basis, albeit far from the rigors set forth in scientific methodology,
for an evidence-based approach.
   You may ask where does this relationship originate? The nervous system,
being the supreme controller and coordinator of physiologic function in the
human body, is the template upon which chiropractic care is based. The ener-
vation of spinal nerves to the somatic structures of the body has
   A well-documented structure–function relationship. Pain and its dermato-
mal, motor, and sensory aspects are all functions of neural tissue, and the
resultant compromise that can occur when the vertebral segments encroach
the spinal cord or spinal nerve roots. A further review of the nervous system
may be helpful at this point:
   At the same time, a relationship exists of neuronal enervation of the periph-
eral nervous system (sensory-somatic and the autonomic nervous system)
that enervate the viscera, influencing their function through the sympathetic
and parasympathetic nervous system.
                    Gastroenterology and an Integrative Chiropractic Approach 153


    Sensory stimuli elicit changes in the nervous system. Segmental aberrations
(subluxations) cause a host of neural activations, from nociception at the local
tissue to autonomic responses occurring peripherally and affecting a myriad of
physiologic responses. Interestingly, all segmental dysfunction does not origi-
nate at the spinal level affecting target tissues (somatovisceral reactions).
    Many segmental disruptions (subluxations) occur as a result of visceroso-
matic responses. Aberrations in neural transmission derived from overstimu-
lation in the viscera results in autonomic nervous system (ANS) activation,
with a resultant effect at the segmental level of enervation from that respective
organ, i.e.,T9 (see Figure 14.2) and the adrenal glands. The surrounding mus-
culature can then become hypertonic and induce a biomechanical change at
that segmental level.
    We are a complex organism responding to a host of stimuli at all times, in
our attempt to adapt. Ultimately, our ability to interpret human physiology
must derive from a comprehensive review of systems that has no boundaries
set by current standards. We are a web of structural, emotional, and biochem-
ical components. The integration of these systems within us cannot be entirely
divided by subspecialties. It is true that the knowledge of each respective spe-
cialty in health care is required, due to the vast amount of data and its applica-
tion that exists today. The observed compromise is, “the isolation of information
derived from each respective specialty is applied through exclusive and narrow
parameters that are dictated by the specialty, as opposed to how the data relates
to the organism as a whole.”


           Integrative Assessment Technique (IAT) –
                 Contributing to Integration

The Integrative Assessment Technique (IAT) was created by Dr. Loren Marks
to establish an assessment methodology for the chiropractic profession, as well
as other practitioners who wish to have a more comprehensive alternative
approach bridging the three worlds of structure, emotions, and biochemistry.
This muscle response technique utilizes reflexes located on the surface of the
body that can be challenged by a doctor skilled in the art of this application, to
read these responses and derive not only a cross-referenced capacity with
known diagnostics, but also an ability to assess rapid integration of one body
system over another in an attempt to derive causation. This technique is not
intended to replace any known standards, but to enhance the role that integra-
tive care can provide, while offering natural solutions where applicable. Such
muscle testing has been extensively tested and validated by David Hawkins,
MD, PhD, following his observation of George J. Goodheart, Jr, DC, who was
154 INTEGRATIVE GASTROENTEROLOGY


utilizing such testing in his work in the 1960s. Dr. Hawkins has written several
books explaining his research, the most notable being Power Vs. Force
(Hawkins, 1995).
   Gastroenterology is a perfect example of the benefits of an integrated mech-
anism. Let’s take a patient with chronic GI complaints of gas, bloating and
bowel irregularities. The IAT model would begin with a thorough consulta-
tion, history, and review of any applicable studies that might have been previ-
ously performed, assuming the patient has seen either a primary care physician
or gastroenterologist and continues to have unresolved complaints despite
standard therapeutic intervention. The IAT model challenges the broad cate-
gories of structure, emotions, and biochemistry to identify which system is the
primarily, secondary, and tertiary driver involved in contributing to disease.
This prioritization is the key in identifying and allowing intervention from an
etiologic perspective/paradigm. No one questions the resultant effect that
patients present with, especially on an acute basis, but an example might be if
mental and emotional perpetuators are the driving force of gut disturbances in
a given case, and management from this vantage point will bring the patient to
a quicker resolve, and if this was known with reasonable certainty before a trial
of many other therapeutics, then we could accomplish improved outcomes
and lower healthcare costs. Alternatively, a patient may present with a bio-
chemical priority. Navigation through the reflexes helps to assess organ
involvement, followed by various GI metabolic functions such as HCL output,
biliary involvement, gut Ph, microbial overgrowth, or the presence of heavy
metals, etc., as a functional medicine doctor might proceed. Here, the model
allows for a unique process of reasoning, followed by diagnostic tests to con-
firm or rule out their presence.
   Chiropractic assessment of segmental dysfunction is an integral part of this
process to determine if there are spinal aberrations that are either “caused by or
the result of ” the metabolic imbalance in the gut (viscerosomatic response).
What is so interesting is that these seemingly two worlds—a bioenergetic muscle
response-testing model, and the biochemical realm of blood, urine and other
diagnostic testing to validate and cross-reference its findings— have met.
   Without a doubt, nothing can replace the quantification of some known stan-
dards such as lipid analysis, WBC, and RBC levels. It is the rapid determination
and level of integration that the IAT model purports. It seems incomprehen-
sible in our modern scientific state that a doctor can learn the standards of IAT
muscle response testing from the mapped reflexes on the surface of the skin,
and accurately assess from such parameters whether a viral, bacterial, fungal,
or parasitic infestation exists.
   Indeed, this level of accuracy is possible when one masters the fundamen-
tals of IAT combined with one’s knowledge of biochemistry, anatomy and the
                    Gastroenterology and an Integrative Chiropractic Approach 155


physiologic pathways being reviewed. The application of this model is well
suited to the gastrointestinal system, providing numerous avenues of proper
identification, from the segmental dysfunctions that arise from viscerosomatic
reactions to various states of microbial dysbiosis, inflammatory cascades,
enzymatic insufficiencies and bowel toxicities that present to clinicians daily.
   The future belongs to those willing to lay new track, and not merely adher-
ing to the continuance of the status quo. Integration between the various med-
ical practitioners will ultimately be needed to accomplish this feat and reach
new frontiers. A reality that is already becoming more common in today’s
atmosphere, with such books and literature as this. The future of integration is
bright.
                                    15
                   Energy Medicine and
                 Gastrointestinal Disorders
                          ANN MARIE CHIASSON




                                key concepts

      ■   Energy Medicine is based on the concept that there is an under-
          lying energy body within the physical body that affects health;
          energy medicine therapies are focused on shifting this energy
          body.
      ■   The National Center for Complementary and Alternative
          Medicine (NCCAM) divides the field of energy medicine into
          measurable and non-measurable energies.
      ■   Non-measurable energies are the current focus of controversy
          in energy medicine.
      ■   A Cochrane review concludes that energy medicine touch
          therapies may reduce pain and analgesic use.
      ■   There is no evidence for or against energy medicine in GI
          disorders, as there is a paucity of research in this area.
                                       ■




          Definition and Prevalence of Energy Medicine



E
        nergy Medicine is a newer term coined to refer to healing modalities
       that work with the underlying energy or vital force of the body: “In
       addition to a system of physical and chemical processes, the human
being is made up of a complex system of energy” (Hurwitz, 2001). This energy
system, called the energy body, biofield or subtle body, is housed within
the physical body, and is considered fundamental to the functioning of the

156
                               Energy Medicine and Gastrointestinal Disorders        157


physical body. Energy medicine refers to any modality that affects the under-
lying energy or vital force of the body.
    The National Center for Complementary and Alternative Medicine
(NCCAM) provides a comprehensive definition of energy medicine and the
scope of modalities included in this paradigm. The concept that human beings
are infused with a subtle form of energy has been around for 2,000 years, and
has many names, “such as Qi in traditional Chinese medicine (TCM), ki in the
Japanese Kampo system, doshas in Ayurvedic medicine, and elsewhere as
prana, etheric energy, fohat, orgone, odic force, mana, and homeopathic reso-
nance” (NCCAM, 2003). How the energy body and the physical body interact
is described differently depending on the tradition.

  Energy medicine may be a resurgence of “vitalism,” or the belief that an
  underlying vital force exists in the body and is central to health. This concept
  predates Hippocrates, who espoused that the vital force was dependent on
  balance of the four humors. More recently, Mesmer also promoted this con-
  cept and called it magnetism. When medicine shifted to organ-based sys-
  tems, with the rise of the Paris Clinics in the early 1800s, the importance of
  the body’s vital energy lost its importance in modern medicine. The resur-
  gence of energy medicine is actually an integration of prior views of health
  and healing, with conventional medicine, and may end up augmenting our
  current views of health and how we treat illness.


    Certainly, therapies that employ electromagnetic forces are used in modern
medicine. At present, the field of energy medicine deals with both measurable
and non-measurable energy fields. NCCAM recognizes two types of energy
fields, veritable and putative. The veritable energies are those that are measur-
able (through wavelengths and frequencies) and “employ mechanical vibra-
tions (such as sound) and electromagnetic forces, including visible light,
magnetism, monochromatic radiation (such as laser beams), and rays from
other parts of the electromagnetic spectrum” (NCCAM, 2003). Medical inter-
ventions that employ electromagnetic fields include magnetic resonance imag-
ing, cardiac pacemakers, radiation therapy, ultraviolet light for psoriasis and
laser keratoplasty, and more (NCCAM, 2003).
    Putative energy fields, according to NCCAM, are those that “have defied
measurement to date by reproducible methods. Therapists claim that they can
work with this subtle energy, see it with their own eyes, and use it to effect
changes in the physical body and influence health” (NCCAM, 2003). Currently,
when practitioners and research studies discuss energy medicine (EM),
they are not discussing conventional medical treatments that employ forms of
energy; most are referring to therapies that work with the putative field.
158     INTEGRATIVE GASTROENTEROLOGY


   The belief in an underlying vital force or subtle body is present in cultures
worldwide. Ninety-four cultures have a documented concept that describes
the underlying energy of the body; it is alternately characterized as spiritual
healing, EM, and includes aspects of TCM, mind–body medicine, and even
manual medicine therapies. Some nurses use EM, both in their usual work and
as a separate modality; Healing Touch was developed by a nurse, specifically
for nurses, as adjunct therapy for hospital patients.
   The definition of the scope of EM is up for debate. Since many EM practi-
tioners postulate that everything is energy, one can place much of CAM within
the EM paradigm. Table 15.1 gives a brief overview of some popular energy

 Table 15.1. Common Energy Medicine Techniques (adapted from Baggot, 1999)
Technique            Theory underlying the paradigm

Acupuncture          Inserts needles or pressure to stimulate energy flow at meridian
                     points on the body

Healing Touch        Based in the chakra system; transfers energy by laying hands
                     onto the body

Homeopathy           Uses highly diluted substances that would cause symptoms in
                     undiluted quantities to stimulate increased immunity at the level
                     of the energy body

Joh Rei              Detoxifies the energy body by sending universal energy to the
                     patient from the healers hands across a short distance

Polarity Therapy     A touch therapy that balances positive and negative energy flows
                     in the body

Qi Gong              Uses movement and laying on of hands to cultivate balanced
                     energy flow throughout the body

Reiki                Channels universal energy into the patient’s body through the
                     hands of the healer

Sound Therapy        Uses vibration through sound to affect the energy body

Tai Chi              A series of movements and postures to stimulate and increase
                     energy flow and restore balance

Therapeutic Touch    Transfers energy by placing the hands into the patient’s
                     electromagnetic field around the body

Yoga                 Philosophy, poses and breathing techniques to promote energy
                     flow and balanced energy

Zero Balancing       A gentle touch and movement therapy that balances energy at
                     the zero-point field of the body
                               Energy Medicine and Gastrointestinal Disorders   159


modalities, and the underlying conceptual framework of each modality. While
there is research on the effectiveness for some EM techniques, many of these
modalities fall into other paradigms, such as TCM and physical exercise. The
research available to date on EM therapies is primarily on therapeutic touch,
Reiki, and healing touch, and therefore will be the focus of this chapter.
   Currently, gas discharge visualization (GDV, which measures biophoton
emissions), superconducting quantum interference devices (SQUID), and
low-frequency pulsed electromagnetic field (PEMF) are being explored to
measure the electromagnetic field of the body (Di Nucci, 2005). Yet, until a
method is devised to accurately measure the body’s subtle field, the confusion
about the definition and scope of EM will likely continue. Despite the defini-
tional uncertainty, EM modalities are being used in the United States. The
2000 National Health Interview Survey study on CAM revealed that at least
1% of people in the US use Reiki or another form of EM, and this number is
growing (CDC, 2004). The percentage increases to 45% to 50% in persons with
chronic pain and chronic illness (Rao et al., 1999). Overall, women use EM
modalities more than men. Most patients used EM as an adjunct for symptom
relief rather than cure (Rao et al., 1999). As of 2002, more than 50 hospitals and
clinics in the United States provide EM as an adjunct (Di Nucci, 2005).


       Anatomy, Development of Illness, and Healing

The anatomy of the underlying energy field varies according to the tradition.
One Qi Gong system (there are multiple of forms of Qi Gong) describes one
basic energy center; the Hindu tradition introduced the chakra system, with
its 7 energy centers; and TCM describes energy flows called meridians.
Conceptually, the relationship between these anatomies can be seen as layers.
The deepest layer is the primary energy center, the next layer houses the
7 chakras and, finally, at the interface with the organs, is the meridian system.
A simple map of these layers is presented in Figure 15.1. Different EM tech-
niques work at different layers of the biofield. For example, healing touch works
at the chakra layer, while TCM works at the most superficial layer. Healers tend
to perceive the energy field of the system they have been trained in, although
some are able to perceive and work in multiple systems and layers.
    In the natural history of a disease, the energy body is postulated to be out of
balance first; then pathology develops, and finally symptoms appear. Major
cellular pathology develops months to years after a block in the natural flow of
energy, although pain, which is also considered blocked energy, can occur right
away. Factors that contribute to or cause a block include genetic or hereditary
causes, outside insults, and physical or emotional trauma. Treatment is based
160   INTEGRATIVE GASTROENTEROLOGY


on transferring energy to remove blocks and to restore the body’s normal
energy flow. Keeping the energy field clear, and the energy flowing, promotes
health and healing (University of Arizona, 2007).
   Energy medicine therapies shift or change the underlying energy field of
the body. The most common technique involves laying the hands on or over
the patient’s body. Other techniques employ vibration, light, sound, move-
ment, magnets, or direct current. Movement is extremely important, as it pro-
motes energy flow. The patient can continue to “balance” himself or herself
through movement or self-administered EM techniques, thus reducing the
frequency of visits with an EM practitioner.


            Research Evidence for Energy Medicine

While there is a paucity of well-done studies on EM, evidence is emerging. In
2003, NCCAM concluded that significant scientific evidence exists for verita-
ble EM, including studies on magnet therapy, millimeter wave therapy, sound
energy therapy, and light therapy. NCCAM also concluded that the data for
putative forms of EM are scant and of poor quality (NCCAM, 2003). While
this is true, there are studies and reviews worthy of consideration. In 2008,
Cochrane published a review of touch therapies (healing touch, Reiki, thera-
peutic touch), which concluded that touch therapies may have a modest effect
on pain relief and may decrease analgesic use. They found pain was decreased
overall by 0.85 pts (1.16–0.5,) on a scale of 1–10. However, they noted a greater
reduction in pain with more experienced practitioners (So, 2008). This review
is in agreement with most claims by the specific modalities that they decrease
pain, anxiety, and healing times.
    In the 1970s, Dr. Herbert Benson’s research demonstrated the effect of relax-
ation on the body. He documented shifts in blood pressure, heart rate, and
brain wave activity, as well as improvements in immune system, peristalsis,
and kidney function (Benson, 1976). Similar physiological changes have been
found in studies of EM treatments. For example, Wetzel demonstrated signifi-
cant increases in hemoglobin and hematocrit levels in healthy persons learning
Reiki (Miles & True, 2003), and Movaffaghi et al. (2006) demonstrated eleva-
tion of hemoglobin and hematocrit levels in healthy students treated with ther-
apeutic touch (TT); the same decrease was found in the mock TT group, and no
changes were found in the control group. Meehan (1985, 1993; Meehan et al.,
1990) performed three studies demonstrating that therapeutic touch reduces
pain after surgery and decreases the time between request for as-needed anal-
gesic dosing (p<.01). Wardell (2001) illustrated significant decreases in anxiety
and blood pressure, increased salivary IgA, increased skin temperature and
                              Energy Medicine and Gastrointestinal Disorders      161


decreased EMG during a Reiki treatment. Similar findings were demonstrated
by Manville (2008) with healing touch; he reported statistically significant
decreases in pretreatment versus post-treatment systolic and diastolic blood
pressure, heart rate, skin conductance level, EMG, and trait anxiety.


  Placebo effects, relaxation, the effects of human touch, and the healer/
  patient relationship are all potentially important factors in EM treatments.
  The effect on the autonomic nervous system during an EM session, which is
  typically an hour long, can help patients cope more effectively with their
  symptoms and illness. Notably, the patient’s breath shifts during a healing
  session to slower, deeper, abdominal breathing. While the data on the effects
  of EM on the immune system are scant, it is possible that EM treatments to
  the belly may affect the gut immune system. I have seen a decrease in
  reported symptoms with inflammatory bowel disease, although I have not
  seen a complete remission from EM alone.



   Systematic reviews of EM in various settings reveal a broad range of rigor,
and approximately half of them show benefit. Jonas (2003) reviewed 19 random-
ized controlled trials, most on therapeutic touch, and found 11 of 19 showed
statistically significant treatment effects with a mean effect size of 0.60. He
concluded that the evidence for EM modalities for relieving pain and anxiety
was “level B,” or poor to fair. Astin (2000) reported the mean effect of thera-
peutic touch was 0.63 in a systematic review of 11 TT studies. He found that
7 of 11 studies showed a positive effect on at least one outcome. When all heal-
ing trials (including prayer and distant healing) were reviewed, the mean effect
size was 0.40. The mean effect score for distant healing, which included Reiki,
was 0.38. Finally, Abbot (2000) reviewed 22 trials of EM healing. His review
concluded that of 22 trials reviewed, 10 had a significant positive outcome for
healing, 11 had no significant outcome, and 1 study was indeterminate due to
poor study design. Five out of the eight studies with a Jadad score of 5 showed
significant differences between the EM treatment group and the control group.
Further, EM has also been used for more than 20 years as an adjunct to cancer
treatment to help alleviate side effects (Stephen et al., 2007).


                 Evidence for Energy Medicine in
                     Gastrointestinal Disease

Published studies report that the prevalence of CAM use ranges from 35%
to 52% in inflammatory bowel disease patients, functional bowel disorder
162   INTEGRATIVE GASTROENTEROLOGY


patients, and gastroenterology patients (Ganguli et al., 2004; Joos et al., 2006;
Quattropani et al., 2003). However, none of these studies asked specifically
about EM modalities, such as healing touch or Reiki. There is emerging evi-
dence to support the successful use of mind–body techniques (including hyp-
notherapy), acupuncture, and relaxation training as adjunctive treatment to
standard therapy in inflammatory and functional bowel disorders (Forbes
et al., 2000; Keefer & Blanchard, 2002; Spanier, Howden, & Jones, 2003; Tan,
Hammond, & Joseph, 2005; van der Veek, Rood, & Masclee, 2007; van Tilburg
et al., 2008; Wilson et al., 2006). As already discussed in this chapter, these
paradigms can be categorized under the broad concept of EM, but are addressed
in other chapters of this book. While there is a strong possibility that EM
therapies may have a similar effect to these evidenced therapies, this needs
further research with regard to GI disorders and specific EM techniques. There
is one study worth noting for GI functional and inflammatory disorders, by
Wilkinson. He demonstrated that healing touch (HT) positively affected sIgA
levels, decreased pain, and decreased patient perception of stress. Experience
of the HT practitioner was proportional to the effect experienced (Wilkinson
et al., 2008). Further, while there is a paucity of studies with positive evidence
specifically for gastrointestinal disease and EM, it is important to note that
there are no negative studies published, either.


          Side Effects and Consideration for Referral

When properly used, EM has negligible negative effects. Practitioners report
there may be an increase in pain in long-term chronic pain patients after the
first few treatments. This is understood by the practitioners to represent the
release of blocked energies, and is expected to diminish and dissipate with
subsequent treatments.
    Patients who are seeking adjunctive therapies for their pain or related symp-
toms, with a belief, openness, or cultural alignment to EM, may be appropriate
for referral. Matching the patient’s belief system to the available modalities is
useful. Patients with longer duration of illness and more severe pain are good
candidates. EM can be a useful adjunct to their medical management, with few
side effects. If a patient does not experience positive physical or mental effects
within a few visits, it may be more appropriate for the patient to use his or her
resources on another modality. Most EM modalities have websites with certi-
fication guidelines and lists of practitioners; e.g., www.iarp.org (Reiki), www.
healingtouchinternational.org (Healing Touch), www.barbarabrennan.com,
and www.zerobalancing.com, (Zero Balancing.)
                                 Energy Medicine and Gastrointestinal Disorders          163



   When choosing a pracitioner for referral, I have a few considerations.
   I choose practitioners that do not “hex” or put down conventional medicine.
   I tend to choose practitioners that have more experience—at least 3 years,
   and preferably more than 10 years of experience. Experience is not equal
   to expertise, yet I find healers who have been doing it longer are, as a
   group, better. I try to visit the healer myself prior to referring. I often do this
   anonymously, so I can have a “standard” session to see what my patients
   will experience.




                                   Conclusion

EM techniques arise from the ancient concept of a primary vital force within
the body affecting the health of the physical body. While research is limited,
EM appears to be most helpful for increasing relaxation and decreasing pain
and anxiety. It may also have a role in increasing sIgA levels. It can facilitate a
healing relationship between practitioner and patient, which in itself is thera-
peutic. Women tend to seek out EM practitioners more than men, and EM
may be a useful adjunct for chronic functional and inflammatory gastrointes-
tinal disease.
                                     16
      Guided Imagery and Gastroenterology
                            MARTIN L. ROSSMAN




                                 key concepts

      ■   Imagery is a natural way the human nervous system stores,
          accesses, and processes information.
      ■   Guided imagery is a mind–body technique to channel informa-
          tion that may affect physiology and the way patients care for
          themselves.
      ■   Indications for guided imagery include stress-related conditions
          (e.g., anxiety), preparation for invasive procedures, chronic ill-
          ness, pain, relaxation, and symptom reduction.
      ■   Guided imagery can be learned from trained practitioners;
          this training may be supplemented by books, CDs, or audio
          downloads.
      ■   Guided imagery should be used to augment healing as an
          adjunct to conventional therapies, not as a standalone modality
          for chronic diseases.
      ■   Patients who are psychotic or who are on the verge of psychotic
          breaks, who have dissociative disorders, or who have borderline
          personality disorders or post-traumatic stress disorder, must be
          handled with care.
                                        ■




T
       he highly innervated gastrointestinal system is often a sensitive
       responder to mental and emotional influences. Most of the mind/body
       phenomena we see as clinicians are responses to stress and worry,
unintentional effects that in themselves illustrate the powerful effects of mental
imagery on GI function.



164
                                      Guided Imagery and Gastroenterology 165


    Mental imagery, which is simply thinking sensory-based thoughts, is the
natural language of the unconscious. It is the language in which we represent
our worlds to ourselves and to each other in art, poetry, music, and drama, and
it is the internal language of dreams, daydreams, memory, and future plan-
ning. The most common form of mental imagery is worry. As our minds fre-
quently return to, or are even dominated by, recurrent images and thoughts of
undesirable, fearful events, our bodies respond with physiologic stress reac-
tions. Because the GI system is a delicate network of target organs, we may
suffer GI symptoms from indigestion, nausea, reflux, diarrhea, constipation,
or abdominal pain.
    The importance of this common clinical observation is that learning to use
our imaginations in more skillful ways can help us relax, manage stress, and
relieve many GI symptoms.


  Research shows that relaxation, hypnosis, and guided imagery are the most
  effective known treatments for IBS.


   Even patients with physiologic bowel disease may suffer exacerbations in
response to stressful situations, and may find some symptom relief through
guided imagery.
   The effects of the mind on physiologic function has been described in the
West by physicians going back to the time of Hippocrates, and much earlier in
ancient treatises on Oriental medicine. In 1823, U.S. Army surgeon William
Beaumont treated a patient, Alexis St. Martin, who had been shot in the stom-
ach, leaving a nonhealing fistula into which Beaumont could see. Beaumont
observed that the lining of the stomach would turn red and dry when the patient
was angry, and pale from vasoconstriction when the patient was frightened.
   Modern research shows that when people use imagery to stimulate relax-
ation responses instead of stress responses, they can reduce or even eliminate
stress-induced GI symptoms, and reduce the amount of symptom amplifica-
tion that can occur when sympathetic and adrenergic stimulation are layered
on top of GI illness. Using guided imagery allows people to develop ways to
manage stress more effectively, so they are better able to stop using alcohol,
tobacco, or excessive eating to reduce perceived stress.



  Guided imagery has also been shown to reduce anxiety before and during
  endoscopy and colonoscopy, and has been shown to significantly reduce
  postoperative pain and complications in patients having GI surgery.
166     INTEGRATIVE GASTROENTEROLOGY




                                     WHAT IS IMAGERY?

Imagery is a natural way the human nervous system stores, accesses, and pro-
cesses information. It is the coding system in which memories, fantasies,
dreams, daydreams, and expectations are stored. It is a way of thinking with
sensory attributes. Functional MRI shows that, in the absence of competing
sensory cues, the brain and the body tend to respond to images in the same
way that they do to actual events. Imagining stressful events, or worrying,
tends to stimulate stress physiology, while imagining peaceful or comforting
settings or events tends to stimulate relaxation physiology. The applications of
guided imagery are shown in Table 16.1.



                         Table 16.1. Applications of Guided Imagery

      Relaxation training and stress reduction

      Pain relief

      Management of chronic illness and prevention of acute exacerbations

      Preparation for surgery and medical procedures

      Medication compliance and adherence issues

      Cancer treatment and life-threatening illnesses

      Terminal illnesses and end-of-life care

      Fertility, birthing, and delivery

      Grief therapy

      Post-traumatic stress disorder

      Anxiety disorders

      Depression




  Imagery has been shown in dozens of research studies to affect almost all
  major physiologic control systems of the body, including respiration, heart
  rate, blood pressure, metabolic rates in cells, gastrointestinal mobility and
  secretion, sexual function, and even immune responsiveness.
                                        Guided Imagery and Gastroenterology 167


   Imagery is also a rapid way to access emotional and symbolic information
that may affect physiology and the way the patient cares for himself or herself.
For instance, a patient may talk at length about the nature of her GI symptoms,
yet we may appreciate something more when we invite her to allow an image
to form for her symptoms. A 33-year-old patient with ulcerative colitis
described his image of his colon as “red, angry, and very irritated.” Not only
does this give us a graphic, sensory description of the symptom, it may also
lead to important psychosocial information involved in the perception of the
pain—in this case, asking him to say more about anger and irritation.


          Is Guided Imagery the Same as Hypnosis?

Guided imagery and hypnosis are closely related, and the practitioner who
uses either should be skilled in both. I think of hypnosis as the state of relaxed,
alert, attention, and imagery as the contents that most effectively create physi-
ologic effects and insight. You can’t accomplish much in hypnosis without
using imagery-based suggestion, and when people engage in guided imagery,
they spontaneously go into the relaxed state of attention that is usually termed
“hypnosis.” One advantage of using the term guided imagery is that it frees the
patient from fears, realistic or not, that many people have of hypnosis. It also
encourages people to learn how to use their minds better, rather than placing
them in the role of passive recipient.


                How Does Guided Imagery Work?

Imagining something, especially with multiple senses, tends to create an inner
experience that the brain and body react to as if the actual event were happen-
ing. A common example is sexual fantasy, which has profound influences on
physiology and behavior.
   Since the invention of the functional MRI (fMRI), we know that when
people imagine visual objects or experiences, they activate the occipital cortex,
where visual information is processed. In the same way, imagining music or
conversation activates the temporal cortex, and imagining movement activates
the premotor cortex.

   Imagery activates the parts of the cortex that process real events, and sends
   signals to the limbic and sub-limbic structures that regulate or express emo-
   tions and physiologic responses, modulating autonomic response, endo-
   crine response, circulation, digestion, rest and sleep cycles, and sexuality,
   among other functions.
168   INTEGRATIVE GASTROENTEROLOGY


   Cultivating a regular process of physiologic and mental relaxation through
relaxation techniques, meditation, self-hypnosis, or self-suggestion, allows
people to develop the skill of calming the GI system, which can have positive,
rather than negative, effects. Imagery, guided toward these ends, is often the
simplest, easiest, and least challenging approach for most people to learn.


       What Are its Applications in Gastroenterology?

Since imagery is a way of thinking, it has widespread applications in clinical
medicine, ranging from simple relaxation techniques to preparation for proce-
dures and surgery, treatment adherence, reducing convalescent time, changing
lifestyle behaviors, and finding meaning in illness.
    Guided imagery is essentially a way of working with the patient, rather
treating particular disease entities. However, it is especially effective in the
areas listed below, which are common issues with patients with GI illness:

  • Relaxation Training and Stress Reduction
         Imagery is the easiest way to teach relaxation: Simply invite some-
         one to daydream themselves to a place that is beautiful and safe,
         where they love to be. Ask them to notice what they imagine seeing,
         hearing, feeling, what the temperature is like, what time of day it is,
         and what time of year. Their immersion in the sensory cues will
         elicit a relaxation response.
  • Pain Relief
         From a safe place of relaxation (see above) invite the person to
         imagine something soothing, comforting, or healing coming to
         any areas that are uncomfortable, breathing easily and regularly
         while doing so.
  • Adapting To and Managing Chronic Illness
        In a relaxed state, invite the patient to allow an image to form that
        represents the illness. Have him describe it, its qualities and how
        he feels about it. Ask him to imagine that the image can respond in
        a way he can understand, and facilitate an imaginary dialogue,
        ultimately aiming for a way they can better coexist or “help each
        other.”
  • Preparation for Surgery and Endoscopic Procedures
         Many guided imagery CDs are available that lead people through
         relaxation and imagery, focusing on the ideal outcomes they desire.
                                             Guided Imagery and Gastroenterology 169


          This gives people a sense they are participatory rather than help-
          less, reduces anxiety, and reduces postoperative complications and
          discomfort.
   • Medication Compliance and Adherence Issues
          Asking patients to imagine medications working exactly like they’d
          want them to work encourages adherence and compliance.


   Imagery in the context of counseling or psychotherapy is especially effective
   when working with grief, post-traumatic stress disorder, anxiety disorders,
   and depression, all of which are frequently coexistent with GI illnesses.




           How Is Guided Imagery Used and Taught?

The basic self-care skills of relaxation and guided imagery can be taught easily
and inexpensively through the use of books, CDs, or audio downloads from the
sites listed in the resource section. Classes, groups, or individual instruction are
also available in many areas. The questions and techniques used in a typical
interactive guided imagery session are illustrated in Tables 16.2 and 16.3.


                    Table 16.2. A Typical Guided Imagery Session

1. Assessment (foresight):

   a. Ask what symptom, illness, or thoughts the patient would like to explore.

   b. Ask what the patient wants to get out of the session.

   c. Ask patient to narrow down the problem to a short phrase or question.

   d. Formulate a one-sentence summary of goals.

   e. Obtain patient’s consent.

2. Imagery process (insight):

   a. Relaxation:

     (1) Ask how the patient best relaxes.

     (2) Use the patient’s best method, or teach him/her one.

   b. Imagine a beautiful, safe place:

                                                                              (Continued)
170     INTEGRATIVE GASTROENTEROLOGY


                                   Table 16.2. (Continued)

        (1) “Allow yourself to imagine a comfortable and peaceful place. It might be a place
            that you have been before, or something that’s just coming into your
            imagination now. If several places come to mind, allow yourself to pick just one
            to explore now.”

        (2) Ask the patient to describe the place in regard to sensations (“What do you see,
            hear, smell, feel and taste? What makes you feel comfortable there?”).

        (3) Invite the patient to find a comfortable place to settle down.

      c. Imagery dialogue:

        (1) Invite the patient to form an image that represents the illness, symptom or
            issue.

        (2) Ask the patient to describe the image in detail. (Have him/her describe
            at least three things, such as appearance, character, and emotions of the
            image.)

        (3) Ask the patient to describe the qualities that the image portrays.

        (4) What feelings does the patient have about the image?

        (5) Invite the patient to express these feelings to the image and allow it to respond.

        (6) “Imagine that it can communicate with you in a way you can easily
            understand.”

        (7) Facilitate the imaginary conversation as needed, using “content-free” questions
            and suggestions such as:

            (a) “Do you have any questions you would like to ask the image?”

            (b) “How does it respond?”

            (c) “Ask the image what it wants from you, and let it respond.”

            (d) “What does it want you to know?”

            (e) “What does it need from you?”

            (f) “What does it have in common with you?”

            (g) “What does it have to offer you?”

            (h) Ask the image what it can tell you about the problem, so you can better
                understand.

            (i) Ask the image what it can tell you about the solution, so you can better
                understand.

            (j) Go back to the safe place, and return from the inner place.
                                                Guided Imagery and Gastroenterology 171


                                  Table 16.2. (Continued)

    d. When the image communicates, you might ask the patient how he/she feels about
       that or wants to respond, then encourage the patient to respond and let the image
       respond to that. Your role is to facilitate the dialogue, not provide the answers.

    e. If the patient appears frightened, ask whether he/she feels safe; if not, have the
       patient go back to the safe place, or ask what he/she needs to feel safe.

3. Evaluation (hindsight):

    a. Ask the patient what he/she felt was interesting or significant about the dialogue.

    b. Ask the patient whether he/she learned anything from or about the image and/or
       the symptom.

    c. Ask the patient whether the information changes his/her perspective, or how he/
       she wants to respond.

    d. Ask the patient what he/she would do next with what he/she learned.



    Table 16.3. Common Interactive Guided Imagery Suggestions and Questions

•   Allow an image to form.
•   What do you notice about it?
•   What are you aware of?
•   What are you experiencing?
•   What would you like to notice yourself having?
•   What would you like to say to it?
•   What sensations are you aware of?
•   Let me know when you are ready to move on.



   Interactive Guided Imagerysm (IGI) includes techniques that are applicable
in the course of brief medical office visits, or in longer counseling or psycho-
therapy formats. Physicians who are trained may practice it themselves, or
employ an ancillary health professional to offer longer sessions or work with
patients with more complex issues.


               Is There Any Risk in Referring a Patient
                         for Guided Imagery?

   The primary danger in using guided imagery to augment healing in medi-
cal situations is when it is used in lieu of appropriate medical diagnosis and/or
treatment. We emphasize the necessity of an accurate diagnosis, so that the
172     INTEGRATIVE GASTROENTEROLOGY


                    Table 16.4. Contraindications to Guided Imagery

•     Strong religious beliefs proscribing the use of imagery
•     Disorientation, dementia, or impaired cognition due to pharmacologic or other agents
•     Inability to hold a train of thought for at least 5 to 10 minutes
•     Potential litigation. Guided imagery may be considered a form of hypnosis, which
      affects the legal status of information obtained with its use



patient can also be made aware of the medical options for treatment. When
you refer a patient for IGI after evaluating his or her medical condition, this
risk is eliminated.
   Patients who are psychotic, or who are on the verge of psychotic breaks, who
have dissociative disorders, or who have borderline personality disorders or
post-traumatic stress disorder must be handled with care. While these diagno-
ses do not represent absolute contraindications for imagery work, they require
that health professionals who use imagery have expertise in these areas.


                                      Conclusion

Guided imagery is a method of tapping into the mind’s resources to alter phys-
iology favorably, reducing stress and improving physiology. Given the mind–
gut connection influences on many digestive conditions, guided imagery
should be considered as an adjunct to conventional therapy when stress reduc-
tion is needed. Abundant resources are available for practitioners and patients
to apply guided imagery to self-care. Caution should be exercised not to use
guided imagery in lieu of conventional therapies, or to use it in situations
where dissociative disorders, borderline personalities, psychosis, or post-
traumatic stress disorder are suspected.


                                       Resources

                 GUIDED IMAGERY SELF-CARE BOOKS AND TAPES

      The Healing Mind
      www.thehealingmind.org
      Books and home-study audio programs from Martin Rossman, MD,
        Jeanne Achterberg, PhD, Kenneth Pelletier, PhD, Rachel Remen, MD,
        Emmett Miller, MD, and more. Research reviews and professional
        community resources listed.
                                  Guided Imagery and Gastroenterology 173




            PROFESSIONAL TRAINING AND REFERRALS

Academy for Guided Imagery
www.acadgi.com
Provides professional training and certification in Interactive Guided
  Imagery,sm and referrals to certified practitioners.
                                      17
      Hypnosis and Gastrointestinal Disorders
                    ANASTASIA ROWLAND-SEYMOUR




                                  key concepts

      ■   Hypnosis has long been used to treat chronic medical illnesses.
      ■   Recent research supports the view that hypnotic suggestions
          effectively change aspects of the person’s physiological and
          neurological functions.
      ■   The possible mechanism of hypnotic effects is still unclear.
      ■   There is a large body of literature on the use of gut-directed hyp-
          notherapy suggesting that hypnosis has a role in treating refrac-
          tory irritable bowel syndrome.
      ■   A few trials suggest that hypnosis may have a role in functional
          dyspepsia, and that propose a mechanism of action.
      ■   Some preliminary data suggest a short-term effect of hypnosis
          on inflammatory markers in inflammatory bowel disease,
          although this data set has not been validated.
      ■   More rigorous trials are required to definitively say that hypno-
          sis produces long-lasting effects in gastrointestinal disorders.
      ■   Prior studies have hinted that hypnosis may actually not be
          cost-prohibitive; however, trials on its cost effectiveness need to
          be carried out.
                                         ■




174
                                Introduction

                          DEFINITION OF HYPNOSIS




T
         here is a great deal of variation in the definitions of hypnosis. According
         to the American Society of Clinical Hypnosis, the largest and most
         respected association for medical professionals using hypnosis, “hyp-
nosis is a state of inner absorption and focused concentration.” The American
Psychological Association’s definition of hypnosis notes that “[hypnosis] pro-
cedures traditionally involve suggestions to relax, though relaxation is not nec-
essary for hypnosis and a wide variety of suggestions can be used including
those to become more alert.” Many mind–body techniques aim to induce relax-
ation, and thereby upregulate the parasympathetic system, in an effort to
decrease sympathetic drive and induce the relaxation response to achieve
symptom control. Hypnosis does not require one to be relaxed; rather, it
requires one to be distracted and absorbed in one’s thoughts. Part of the hyp-
notic procedure often induces relaxation; however, the ultimate goal of hypno-
sis is focused concentration. This allows hypnosis to be used for multiple
outcomes. Hypnosis is most often used in one of three ways. The first is to
induce the imagination to take hold, correlating mental images with illness and
health; this aspect of the technique can be very similar to guided imagery.
Secondly, hypnosis allows the practitioner to give a subject direct suggestions
aimed at changing behaviors or improving health. Lastly, hypnosis can be used
to explore the psychological reasons for particular behaviors that affect health.


                   POSSIBLE MECHANISMS OF HYPNOSIS

While there is general agreement that hypnosis may have clinical effects for
some conditions, there are differences of opinion within the research and clin-
ical communities about how hypnosis works. Recent research supports the
view that hypnotic suggestions effectively change aspects of the person’s phys-
iological and neurological functions. One way of thinking about hypnosis is
that it changes the associations between occurrences and our perceptions
of them. Some describe it as “reshuffling our mental filing cabinet.” By uncou-
pling associated responses or emotions from life events, one can then interpret
new data differently and create new associations between events and
thoughts. Researchers at Penn State have been using hypnosis as a tool to better
understand the brain. They have done a number of EEG studies, looking at
176 INTEGRATIVE GASTROENTEROLOGY


pain response. One such study suggests that hypnosis can remove the emo-
tional experience of pain, while allowing the sensory sensation to remain.
Thus, one notice might notice that one was touched, but not that it hurt (Ray
et al., 2002).
   An emerging body of literature suggests that hypnosis may cause physio-
logic changes in the brain. We know from studying positron emission tomog-
raphy (PET) scans in people who have undergone hypnotic relaxation that
they experience increased regional cerebral blood flow in the anterior cingu-
late cortex, the thalamus, and the midbrain. (Rainville, Hofbauer, Bushnell,
Duncan & Price, 2002) Subjects who were experiencing increased mental
absorption, rather than relaxation, as part of their hypnotic experience, were
found to have increased regional cerebral blood flow in a distributed network
predominately ranging over the prefrontal cortices. This is very similar to the
patterns of activation that have been associated with tasks involving visual,
auditory, and somatosensory stimulation (Rainville et al., 2002; Peyron et al.,
1999).
   Hypnosis has long been studied in medical conditions and has been shown
to have wide-ranging effects. There are studies documenting its usefulness in
many illnesses, ranging from managing acute and chronic pain, decreasing
presurgical anxiety, acting as sole or adjuvant analgesia during surgical proce-
dures, promoting healing from burns, and managing nausea and vomiting,
dermatologic disorders, and gastroenterologic disorders.


     Hypnosis in Gastrointestinal Disorders Literature

Hypnosis has been studied in several gastrointestinal disorders, most notably
irritable bowel syndrome. It has also been studied in functional dyspepsia and,
most recently, in ulcerative colitis.


                       IRRITABLE BOWEL SYNDROME

A large number of trials have used gut-directed hypnotherapy in subjects with
irritable bowel syndrome (IBS). While these studies are of varying quality, the
preponderance of data suggests a positive effect of this modality in IBS. The
first published trial using hypnotherapy in IBS was a small but well-designed
placebo-controlled trial by Whorwell, Prior, and Faragher (1984). In this study,
hypnosis was compared to psychotherapy plus a placebo medication. The hyp-
nosis group was found to have fewer symptoms, including abdominal pain and
distention, than the control group (Figure 17.1).
                                           Hypnosis and Gastrointestinal Disorders 177


   The authors noted that, although the mechanism by which hypnotherapy
works is uncertain, its results might be mediated by some psychological effect
or by direct-action gut motility. The researchers favored the latter, because a
pilot study suggested that hypnosis that emphasized general relaxation did not
improve irritable bowel symptoms until sessions were directed specifically at
controlling intestinal function.
   A follow-up noted that these results were maintained for a 2-year period
post-treatment (Whorwell, Prior, & Colgan, 1987). These results have been
validated in several studies by the same group (Gonsalkorale, Houghton, &
Whorwell, 2002), as well as by several other investigators.
   It has been suggested that individual hypnotherapy is impractical for most
practice settings, given the cost and access to appropriately trained hypno-
therapists. Harvey et al. (1989) compared individual gut-directed hypnother-
apy to group sessions, with up to 8 subjects per group, in a small trial of 33
subjects. For subjects with refractory IBS who underwent individual versus
group gut-directed hypnotherapy, improvement in symptoms was compara-
ble. While the results were not as robust as those noted in the Whorwell trials,
these results were sustained for 3 months after the trial ended, without formal
intervention (Table 17.1).



         Table 17.1. Patient Characteristics and Response to Hypnotherapy
                                 No improvement       Less symptoms     Symptom free
               —
                                 (n=13)               (n=9)             (n=11)

Sex                              3M, 10F              2M, 7F            3M, 8F

Hypnotherapist A                 6                    8                 3

Hypnotherapist B                 7                    1                 8

Group Therapy                    5                    6                 6

Individual Therapy               8                    3                 5

Severe symptoms at start         4                    5                 2
(total symptom score ≥35)

Psychological Problems           5∗                   3                 0∗
(GHQ score ≥5)

Age >50 yr                       4                    2                 1

∗p<0.05 for difference between symptom-free and no-improvement groups. There were no other
significant differences between response groups.
Adapted from Harvey et al. (1989). Lancet, 1,424–425. Reprinted with permission.
178 INTEGRATIVE GASTROENTEROLOGY


  Table 17.2. 14-Day Diary Symptom Scores at Each Assessment Time in Study II∗
                                            Time 1              Time 2             Time 3

Immediate group (N=15)                  Pretreatment       Posttreatment      4 mo follow-up


  Abdominal Pain                         23.9 (2.5)         12.9 (3.2)†        12.5 (3.4)†

  Bloating                               20.3 (3.1)         15.1 (2.7)†        11.1 (3.3)†

  Proportion of hard/loose stools        0.25 (0.04)        0.10 (0.03)†       0.23 (0.05)†

  Bowel movements per day                 3.1 (0.7)          2.3 (0.5)           2.3 (0.5)

Delayed group (N=9)

  Abdominal Pain                        16.00 (1.9)         16.8 (1.2)‡        10.2 (1.8)†

  Bloating                               13.6 (2.1)        11.67 (1.7)‡          9.0 (1.48)‡

  Proportion of hard/loose stools        0.27 (0.06)        0.26 (0.06)‡         0.8 (0.03)‡

  Bowel movements per day                 2.2 (0.4)          2.1 (0.4)           1.7 (0.2)

∗ The immediate group received hypnosis treatment between time 1 and 2, whereas the Delayed
group received hypnosis between time 2 and time 3. Boxes delineate pre-versus posttreatment
contrast.
† Significantly different from pre-treatment values in this group, P < 0.05.
‡ Significantly different from Immediate Group values at the same time point P <0.05.
Reprinted with permission from Palsson O et al. (2002). Digestive Diseases and Sciences, 47(11),
2605–2614.



   In an uncontrolled prospective cohort trial, Palsson and Whitehead (2002)
noted that there was significant improvement in irritable bowel symptoms (see
Table 17.2).
   However, improvements were unrelated to the physiologic changes that
were measured. In particular, there was no change in rectal pain thresholds,
rectal smooth muscle tone and autonomic functioning, except sweat gland
reactivity (Table 17.3).
   A systematic review by Wilson et al. (2006) included 18 trials, four of which
were randomized, 2 of which were controlled and 12 of which were uncon-
trolled. These trials tended to demonstrate that hypnotherapy was effective in
managing IBS. However, the number of subjects per trial was small. The major-
ity of the studies suggested possibilities for bias, and only one of the trials
(Roberts et al., 2006) scored well with respect to internal validity.
   The subsequent Cochrane review (Webb et al., 2007) included only the
four randomized controlled trials; all other studies were discarded as method-
ologically flawed. The study designs were sufficiently varied to preclude the
                                            Hypnosis and Gastrointestinal Disorders 179


           Table 17.3. Physiological Parameters Before and After Hypnosis
                            Treatment in Study II (N = 24)
Measure                                           Pretreatment         Posttreatment       P
                                                  (mean +/-SE)         (mean +/- SE)

Skin conductance (μmhos)                           1.45 ± 0.29         1.11 ± 0.16       NS

Skin conductance stress change (μmhos)             1.41 ± 0.18         1.01 ± 0.19       0.01

Heart rate (bpm)                                   66.1 ± 1.8          67.2 ± 1.9        NS

Heart rate stress change (bpm)                      3.1 ± 1.5          4.83 ± 1.5        NS

Systolic BP (mm Hg):                             123.6 ± 2.3          121.1 ± 2.9        NS

Systolic BP stress change (mm Hg)                   5.2 ± 1.5           1.4 ± 4.8        NS

Diastolic BP (mm Hg)                               70.8 ± 2.5          70.9 ± 2.4        NS

Diastolic BP stress change (mm Hg)                  3.3 ± 1.5           3.5 ±1.0         NS

Finger skin temperature (°F)                       86.7 ± 1.7          86.9 ± 1.4        NS

Finger temperature stress change (°F)             —2.2 ± 1.0          —2.1 ± 0.4         NS

Baseline EMG (μv)                                   4.1 ± 0.6           3.5 ± 0.5        NS

Stress-related increase in EMG (μv)                 3.8 ± 1.0           3.2 ± 0.9        NS

Reprinted with permission from Palsson O et al. (2002). Digestive Diseases and Sciences, 47(11),
2605–2614.



possibility of a meta-analysis. Nonetheless, the authors did find that hypnosis
appeared to be a safe intervention and could be tried in individuals who have
failed conventional treatment for IBS. Further, they concluded that even
though there was the suggestion of a beneficial effect in the short term, this
finding has not been convincingly proven by high-quality studies. The sugges-
tion of persistent long-term benefits of hypnotherapy in IBS has been noted in
several studies; however, each of these studies is methodologically challenged.
Only one primary-care-based study measured long-term (12 months) out-
comes in a systematic method, and no benefit was found (Roberts et al.,
2006).


                               FUNCTIONAL DYSPEPSIA

More recently, hypnosis has been looked at in the setting of functional dyspep-
sia. In 2002, the same Manchester group of Whorwell et al. created a three-
arm trial designed to explore what, if any, effect hypnosis would have on
180    INTEGRATIVE GASTROENTEROLOGY


functional dyspepsia. One arm of this trial was a hypnotherapy group, another
arm was a psychotherapy plus placebo-medication group, and both were com-
pared to standard medical therapy. There was a 59% reduction in quality of life
measures, which continued to improve after treatment, reaching a 73% reduc-
tion in symptom severity at one year (Calvert et al., 2002; see Figure 17.2).
    Prior analyses have suggested that hypnotherapy was not economically fea-
sible because a standard course of treatment typically requires 12 sessions with
a single hypnotherapist. Others have observed, however, that once treated with
hypnosis, patients with IBS often require minimal further intervention. This
trial noted a statistically significant decrease in medication usage and health-
care utilization (Table 17.4).
    More recent functional studies have looked at possible mechanisms for
hypnosis’ usefulness in GI disorders. Chiarioni et al. (2006) noted in a small
trial that patients with functional dyspepsia who underwent hypnosis had a

              Table 17.4. Medication Use and Consultation Rate of Patients
                              During Long-term Follow-up
                                                     40 Week follow-up

                                     Hypnotherapy      Supportive        Medical
                                     (n = 26)          (n = 24)          (n = 29)

Number taking medication             0                 20                26

% taking medication                  0                 81.8              89.7

PPI                                  0                 6                 15

H2 antagonists                       0                 8                 8

Prokinetics                          0                 0                 0

Antacids                             0                 4                 3

Antidepressants                      0                 5                 0

None                                 26                4                 3

Total number of consultations        1 (0–2)           4 (1–10)∗         4 (0–9)∗
median (IQR)

Number of GI consultations           0 (0–0)           3.5 (0–10)∗       3 (0–9)∗
median (IQR)

NOTE. Expressed as median (interquartile range).
∗P<0.001 vs. hypnotherapy.
Reprinted with permission from Department of Medical Illustration, Withington Hospital,
Manchester, England.
Reprinted with permission from Calvert et al. (2002). Gastroenterology, 123, 1778–1785.
                                      Hypnosis and Gastrointestinal Disorders 181


shortened gastric emptying time as compared to cisapride and usual care. This
shortened gastric emptying time was also noted in the control group of normal
subjects who underwent hypnosis.


                     INFLAMMATORY BOWEL DISEASE

Hypnosis may have some effect on inflammation and immune response in a
number of diseases. There are anecdotal reports of improvement in inflamma-
tory bowel disease with the use of hypnosis. There are, however, few studies of
hypnosis in inflammatory bowel disease. In a small controlled trial by Mawdsley
et al. (2008), subjects with ulcerative colitis underwent one session of hypno-
sis. Systemic inflammatory markers were measured with interleukin-6 (IL-6)
and interleukin-13 (IL-13) serum levels, and rectal mucosal inflammation was
assessed by mucosal release of substance P, histamine, and IL-13. One session
of hypnosis reduced serum IL-6 concentrations by 53%, and reduced rectal
mucosal release of substance P by 81%, histamine by 35%, and IL-13 by 53%.
While this is data from a single time point, and in no way can it be extrapo-
lated as to whether the results would be sustained with repeated interventions,
it is interesting to note that hypnosis has a clear physiologic effect that could
explain some of the anecdotal reports of improvement with its use in inflam-
matory bowel disease.


                                Conclusion

There are significant data to support the use of clinical hypnosis in functional
gastrointestinal disorders. Although well-designed trials are few in number,
reviews suggest that hypnosis may be effective in functional disorders that are
refractory to conventional medical approaches. Similarly, while there is not
sufficient data to be conclusive, there is the suggestion of a possible improve-
ment in inflammatory bowel disease. A growing body of literature details the
neuroscience of hypnosis, and literature substantiates the organ-specific phys-
iologic changes that may account for the effects of hypnosis in GI disorders.
Clearly, further well-designed trials are needed to fully understand the effects
that hypnosis has on gastroenterologic disorders. Additionally, it would be
extremely useful to address the perceived issues of financial nonviability. Prior
studies have suggested not only that self-hypnosis pays for itself in the long
run by decreasing healthcare utilization, but also that accessibility can be
increased, while still maintaining efficacy, with group hypnotherapy. These
questions need to be answered with the help of well-designed trials.
                                     18
                   Homeopathy Origins and
                    Therapeutic Principles
                             SAVELY YURKOVSKY




                                  key concepts

      ■   Homeopathic remedies are representatives of a matter–energy
          duality phenomenon, and are the extracts of the underlying
          information content of a substance from which the remedy is
          prepared.
      ■   Therapeutic prescription of classical homeopathy is based on
          the laws of totality and complexity, which operate in humans
          both in health and disease.
      ■   For true health progress, symptoms of chronic disease, which
          are reflections of underlying etiologic agents, must not be sup-
          pressed just for the sake of palliation but must be allowed to
          manifest themselves and exit from the body according to
          Hering’s Law of Cure.
      ■   Causative homeopathy renders novel means and remedies that
          endow the body with great therapeutic potential to rid itself
          of a variety of environmental pollutants and other morbid
          agents, including carcinogens, which are ubiquitous in our daily
          environment.
      ■   The pathogenicity of these agents in chronic degenerative dis-
          eases is in accord with the accepted tenets of the science of toxi-
          cology. Both classical and causative homeopathy represent a
          strictly individualized and novel paradigm in viewing illness as
          individual disease states versus approaching these as generically
          classified diseases.
                                        ■




182
                        Classical Homeopathy

                           THE LAW OF SIMILARS




I
      n 1796, Samuel Hahnemann, of Germany, published the paper, “A New
      Principle of Healing,” which he named homeopathy (Schmidt, 1988;
      Schmidt, 1994). The name denotes “similar disease,” based on the Greek
term, homoion pathos, or the Latin term, “like cures like” (similia similibus
curentur), and is referred to as “The Law of Similars.”
    The principle itself had been known and applied through various thera-
peutics, from Egyptian alchemists to Hippocrates and Paracelsus. However,
both Hahnemann’s pharmacopeia and methodology were truly innovative.
The remedy preparation involved serial dilutions of the original, or any sub-
stance (plant, mineral, toxicological or infectious agents, etc.), along with
succussions—the parallel and repetitive mechanical impacts delivered to the
solution against the bottom of a glass bottle, even far beyond Avogadro’s
number, 6.02 × 1023. These remedies, then, would be administered to the sick
who display symptoms similar to those elicited by the same remedies, in
healthy volunteers, in the process of proving, or eliciting remedy-induced
symptoms. The picture for prescribing would include not only localized
pathology—e.g., headache, diarrhea, vomiting, etc.—but a very detailed quali-
tative analysis of these and, strangely enough, a broad range of concomitant
complaints, including mental, emotional, and general symptoms nonspecific
for disease, per se. Even more novel, the therapeutic rating of these other
symptoms—and particularly those that were considered peculiar and seem-
ingly unrelated to the main pathology; for example, ear itch, claustrophobia, or
testicular pain in a colitis case—would often prevail over the therapeutic rating
of the local disease.
    It was observed that the remedies that encompassed these other and espe-
cially peculiar symptoms yielded greater therapeutic success than those
focused on disease, per se. The rationale for the emphasis on other and pecu-
liar symptoms was that they were more reflective of the state of the body’s
defense force on the total, complex level that the remedies aimed to stimulate
in order to elicit more specific and intense response of that defense force
against any morbid factors behind an illness. This approach was deemed to be
based on the law of totality and was referred to as classical homeopathy.
    Another unique property of homoeopathy has been formulated as Hering’s
Law of Cure, summed up by Constantine Hering in the nineteenth century
(Treuherz, 2005). It is based on countless clinical observations that in any set
184   INTEGRATIVE GASTROENTEROLOGY


of pathologies, in order for true healing to take place, the pathology in the
course of the therapeutic process must move in a downward anatomical direc-
tion from head to toe, from inside out, and in reverse order of the time of onset
of pathological symptoms. The first two rules underscore a priority in protect-
ing more physiologically important organs, while the third rule implies the
process of peeling off morbid layers of disease in the corresponding chrono-
logical order of their original aggregation.
   It is of interest that the latter rule is deemed to be placebo-proof since, in the
majority of cases and only upon the return of old and often forgotten symp-
toms by patients, did the patients make their homeopaths aware of those
symptoms’ past existence.
   On the whole, neglect of Hering’s Law via mere suppression of local patho-
logical symptoms, without cure through conventional or alternative means,
has been observed to be followed by progressive disease with the passage of
time. This sequence was encountered particularly in cases with suppressed
bodily discharges, either via skin, respiratory, gastrointestinal, or urogenital
outlets. More impartial evidence for the confirmation of this tenet is based on
the successful experiences of homeopathic treatment where regression of
chronic diseases was followed by the return of the original suppressed dis-
charges, or other old symptoms. This phenomenon presupposes the existence
of some property of cellular memory in the tissues in relation to unresolved
pathogenic layers, accrued over time.
   Homeopathy also seeks to address a person’s inherited systemic weaknesses
through the prescription of certain constitutional or miasmatic remedies. It has
been observed that these were often followed by copious discharges or skin
outbreaks, as if some underlying morbid agents were indeed being released
while, in their wake, progress in health would ensue. This is the main reason
why homeopathy favors centrifugal therapeutic action versus a centripetal,
suppressive one.


                          Mechanism of Action

The main objection of critics of homeopathy is primarily based on the tenets
of chemistry, where the remedy solution, due to successive dilutions, often
exceeds Avogadro’s number and renders its composition void of the original
substance and, presumably, of therapeutic action. This argument has been
negated by data from science that is well recognized as ontologically more
fundamental than chemistry—materials science (Roy et al., 2005).
   The epistemological data considered in this context includes many perti-
nent sciences and phenomena that fall outside the scope of chemistry.
                              Homeopathy Origins and Therapeutic Principles    185


Among these are physics, quantum chemistry, quantum physics, weak quan-
tum theory, and the science of colloids and crystals. These and other authors
emphasize the difference between the structure of substance, which largely
controls its physicochemical properties, versus simply a molar composition.
Other authors cite other phenomena, including: epitaxy, pressure, nanobub-
bles and hydrogen bond networks, electromagnetic coherent forces, reduplica-
tion of original information of a solute (Roy et al., 2005; Smith, 1994; Del
Giudice et al., 1988, 1998), and even remedy information storage in the coarse
layers of a vacuum (Tiller, 1997).
   Based on this data, homeopathic remedies are deemed to be energy medi-
cines capable of not only retaining, but exponentially expanding the informa-
tion content of the original substance through the succussive cycles of their
preparation. Repetitive succussions are being singled out as playing a crucial
role in this process.


         Clinical Studies and Scientific Confirmation

Two major reviews of all clinical trials on homeopathy have confirmed the
positive biological action of homeopathic remedies (Kleijnen et al, 1991; Linde
et al., 1997).
   The more recent meta-analysis of homeopathic studies yielded a negative
report (Shang et al., 2005). However, it was deemed by its critics to be seriously
flawed(Walach et al., 2005; Bell, 2008).
   A broad review analysis of the homeopathic studies and related topics,
including those concerning gastrointestinal disorders, was published recently
(Walach et al., 2005).
   The authors, considering nonlinear action of homeopathic remedies and
other peculiar factors involved in homeopathic practice, challenge the stan-
dard clinical efficacy assessment methods as suboptimal for both conventional
pharmacology and, especially, for homeopathy.


                        Complex Homeopathy

Complex homeopathic remedies consist of a number of remedies, each with a
known affinity for certain organs or related conditions such as headaches,
diarrhea, allergies, etc. Experientially, these have been found to have some pal-
liative effect in acute ailments In chronic diseases, due to the fact that complex
homeopathy is too non-specific either in relation to true etiologic agents of
chronic diseases or to patient totality of symptoms, their effectiveness seems
marginal and of limited potential, overall.
186   INTEGRATIVE GASTROENTEROLOGY




                       Causative Homeopathy

Prescribing in causative homeopathy is based on the principle, exact treats
exact. Unlike classical homeopathy, which treats based on the totality of a
patient’s symptoms or responses as an adaptional reaction to some (usually
unknown) morbid agents, causative homeopathy uses remedies—the exact
counterparts of the morbid agents themselves—deemed to be the causative
agents of pathology. The remedies are prepared from infectious, toxicological,
radioactive, or any pathogenic agents themselves, or the patient’s own bodily
fluids, including pathological discharges or abscesses containing these agents,
and are administered with a therapeutic or prophylactic purpose.
   A rather recent striking case of homeoprophylaxis of Leptospirosis involv-
ing as many as 2.3 million people took place in Cuba and yielded a significant
reduction in morbidity and mortality in the treated population (Bracho et al.,
2010). The homeopathic vaccine was prepared out of actual circulating strains
of Leptospirosis and was administered in homeopathic dilutions far exceeding
Avogadro’s number. The study was conducted by the mainstream major medi-
cal research institute that also oversees production and administration of con-
ventional Leptospirosis and other vaccines on a national level. Besides
homeopathic vaccination showing somewhat superior protection over con-
ventional vaccination, 84% versus 78.1%, respectively, in the annual reduction
of Leptospirosis, the study authors have emphasized the advantage of homeo-
prophylaxis in costs, facility in production, availability and accessibility, par-
ticularly in the face of suddenly arising circumstances of emergency.


  Samples of Remedies and their Prescribing Keynotes
       for Common Gastrointestinal Ailments

   Constipation (Kratz, 2001)
      • Bryonia alba
      • Calcarea Carbonica
      • Lycopodium clavatum
   Diarrhea (Lilienthal, 1996)
      •   Aloe socotrina
      •   Argentum Nitricum
      •   Arsenicum Album
      •   Bryonia alba
                              Homeopathy Origins and Therapeutic Principles   187


     •   Hyoscyamus niger
     •   Oxalicum acidum
     •   Podophyllum peltatum
     •   Zincum Metallicum
  Gallbladder Disorders (Kruzel, 1988)
     •   Berberis vulgaris
     •   Calcarea carbonica
     •   Carduus marianus
     •   Chelidonium majus
  Nausea and Vomiting
     •   Cocculus Indicus
     •   Crotalus Horridus
     •   Glonoinum
     •   Ipecacuanha (Cephaëlis ipecacuanha)
     •   Kreosotum
     •   Nux Vomica (Strychnos nux vomica)
     •   Rhus Toxicodendron
     •   Tabacum (Nicotiana tabacum)
     •   Zincum metallicum


                                Summary

Since its inception, homeopathy has remained a poorly understood medical
system. The main arguments: the remedies defy accepted chemistry rules,
utilize implausible therapeutic principles based on the law of similars, treats
morbid stressors via near or identical morbid stressors, or via an approach of
totality by addressing seemingly unrelated symptoms.
   However, mounting evidence from multidisciplinary sciences over recent
decades continues to yield copious supporting data on behalf of the tenets of
homeopathy.
   Among these are laws of complexity applicable to living systems, informa-
tion and chaos theories (Bellavite & Signorini, 2002; Bell & Koithan, 2006),
the phenomena of quantum physics (Smith, 1998; Wolkowski, 1994) and cel-
lular memories (Miller, 1978; the discovery of DNA and related disease predis-
positions, and even the theory of evolution, which emphasizes adaptation of
species to stressors via exposure to the identical stressors (Darwin, 1859).
   Not surprisingly, The Law of Similars has been in extensive use in conven-
tional medicine through such practices as vaccinations, allergy desensitiza-
tion, and botulin administration in neurological diseases. Another example,
188   INTEGRATIVE GASTROENTEROLOGY


the newly emerging field of psychoneuroimmunology, has substantiated—
via experiments involving the peptide systemic network—interconnections
among multiple systems and their functions as including those of emotions
and nervous systems, as well as endocrine and immune systems (Pert, 1997).
   Modern technologies using spectral analysis obtained with the Raman laser,
infrared absorbance, and nuclear magnetic resonance (NMR), have all con-
firmed the difference in emission patterns between homeopathic remedies and
a placebo. In addition, each homeopathic remedy was found to exhibit a
unique NMR emission pattern. Furthermore, substances that were both diluted
and succussed to 30X potency, according to the full homeopathic method,
exhibited a specific band pattern in their emission spectra that was absent
when the substances were merely diluted but not succussed. (Barros et al.,
1984; Smith & Boericke, 1966; Young, 1975; Lasne et al., 1989; Smith & Boericke,
1968; Sacks, 1983; Demangeat et al., 1992).
   All this evidence does supports the scientific foundation of homeopathy
and provides a safe and at times cost-effective option to patients and practitio-
ners for a number of gastrointestinal tract ailments.
                                     19
               Massage for Digestive Health
            STEPHANIE PORCARO AND GERARD E. MULLIN




                                 key concepts

      ■   Massage can calm patients with underlying anxiety disorders.
      ■   Massage can influence gastrointestinal physiology.
      ■   There is data to support its use for patients who are constipated.
      ■   Contraindications to massage exist, and practitioners need to
          be aware of the potential risks and benefits of massage.
                                        ■




           A Brief History of the Benefits of Massage



M
            assage is one of the most ancient forms of healing. The first writings
            on massage emerged around 2000 BC. The ancient Greeks and
            Romans used massage to maintain health and promote healing. As
early as the fourteenth century, Guy deChauliac was noted to have written a
book on surgery, and bodywork was mentioned as an adjunct to surgery.
During the sixteenth century, Ambroise Pare, a French barber surgeon, was
said to have mentioned the many benefits of massage. It was Lord Francis
Bacon who observed that massage enhanced circulation. During the 1850s,
scientific massage therapy was introduced in the United States by two New
York physicians, brothers George and Charles Taylor. (Calvert, 2002)




                                                                               189
190    INTEGRATIVE GASTROENTEROLOGY




             Benefits of Massage that May Improve
                        Digestive Illness

   •   Relieves stress and promotes an overall feeling of relaxation
   •   Alleviates pain and tension
   •   Decreases inflammation
   •   Improves circulation
   •   Improves and strengthens immune system
   •   Reduces anxiety and promotes an overall feeling of well-being
   •   Increases body awareness (Takeda et al., 2008; Lee, 2006)


       Effect of Massage Therapy on Related Conditions

Aside from being very effective in relieving stress, there is evidence that mas-
sage can help with a variety of health conditions that may be linked to digestive
disorders (Lee, 2008; Chen et al., 2008; Garner et al., 2008; Piovesan et al.,
2007; Tso, 2007; Field, 2002), including:

   •   Anxiety
   •   Arthritis
   •   Chronic and acute pain
   •   Circulatory problems
   •   Depression
   •   Fibromyalgia
   •   Headaches
   •   Sleep disorders
   •   Stress


                 Massage and Digestive Disorders

There is a paucity of medical literature on the potential health benefits of mas-
sage for digestive disorders. Utilization data exists for usage of complementary
and alternative medicine (CAM) modalities; however, massage was not spe-
cifically addressed (Burgmann, Rawsthorne, & Bernstein, 2004; van Tilburg
et al., 2008). Massage therapy has been studied for its potential to promote
gastrointestinal motility and ameliorate constipation in patients with spinal
cord injury (Ayaş et al., 2006; Albers et al., 2006).
                                                Massage for Digestive Health 191


   Gastric motility has also been shown to improve in preterm neonates after
abdominal massage. Compared with preterm neonates receiving sham mas-
sage, those receiving massage therapy exhibited greater weight gain and
increased vagal tone and gastric motility during, and immediately after, treat-
ment. Gastric motility and vagal tone during massage therapy were signifi-
cantly related to weight gain.
   Postoperative motility has been shown to improve after acupressure
massage (Chen et al., 2003; Daletskaia, Ekisenina, & Lorie, 1988). Thermovi-
bromassage of the right hypochondrium area, for biliary dyskinesia, has been
reported to promote normalization of biliary system motility (Matveeva,
Kuz’menko, & Kirillova, 1997). Remission persisted for 6 to 8 months in
patients with biliary dyskinesia. Thus, massage may in part reset enteric ner-
vous system electromyographic rhythms, as suggested by human and animal
studies (Koizumi, Sato, & Terui, 1980; Liu et al., 2005). Abdominal massage to
relieve constipation is a palliative type of care that used to be a commonly
practiced therapy. Massage to promote movement of fecal wastage has been
well documented and should be considered in patients with functional consti-
pation (Di Lorenzo, Ordein, & Hyman, 1993; Culbert & Banez, 2007; Harrington
& Haskvitz, 2006; Preece, 2002; Ernst, 1999; Jeon, & Jung, 2005; Kim et al.,
2005). One study showed massage to provide a benefit for relief of symptoms
of irritable bowel syndrome (Bosseckert, 1982).


                 Massage and the Digestive Tract
                     Technique for Patients

Abdominal massage relaxes and tones the organs, muscles, and fascia of the
abdomen, while providing overall relaxation and stress relief. Abdominal mas-
sage is effective and fast. Some people feel the urge to eliminate during or just
after the massage itself, when well hydrated. In this section, we assume that
individuals are working with a partner, although most techniques described
can be performed during self-massage.
   The abdominal area is highly sensitive. Approach it with respect and posi-
tive intention. Begin with a gentle opening hold, slowly bringing your hand
down to rest in the center of your partner’s abdomen just below the navel.
Allow your partner to become comfortable with the sensation of being touched
there. Encourage deep, relaxed breathing during the massage. Open the area
with slow stretches between the floating ribs and iliac crest, reaching for the
side of the body opposite you and pulling up and toward the navel in a sweep-
ing motion. This technique addresses the obliques and transverse abdominis.
Next, effleurage the rectus abdominis in a sweeping motion, creating clockwise
192   INTEGRATIVE GASTROENTEROLOGY


circles with your hands around the center of the abdomen. Abdominal mas-
sage always proceeds in a clockwise motion, reinforcing the clockwise passage
of waste through the large intestine. Working in a counterclockwise direction
may harm the intestines and intensify existing fecal impaction.
    Now that the superficial abdominal tissue is relaxed, it is possible to per-
form intestinal massage. Please refer to the diagram (Figure 19.1) for assistance
with the anatomy. Depending on the size of the individual, and whether he or
she is constipated and remains relaxed during the session, you may actually
feel the intestines themselves. Even if you do not palpate the structures, work
in the area where they are located, with the intention of massaging them.
    Start at the upper left-hand quadrant of the abdomen just below the rib-
cage. Sink in deeply and travel with circular friction, 2 to 4 inches down the
line between the navel and the anterior superior iliac spine (the pointy part of
the front of the hip). Repeat 2 to 5 times. Next move across to the right ribcage
area and sink into the tissue, massaging across the transverse colon to the left
side. Avoid deep pressure over the fascia of the midline of the body, which you
will cross while massaging the transverse colon. Repeat 2 to 5 times. Now move
to the area between the right anterior hip and navel, and massage up the
ascending colon with circular friction. Repeat 2 to 5 times. Put the three parts
of the massage together—starting again at the ascending colon, moving to the
transverse and to the descending—in one fluid motion. Imagine your hands
pushing out the waste for elimination.
    Return back to the lower right abdomen, at the point between the navel and
the hipbone. This locates the ileocecal valve (ICV). Gently push down at this
point to feel the valve and the connection between the small and large intes-
tine. Then massage up an inch toward the left shoulder, palpating the ICV.
If this area is sore or uncomfortable, the valve flap may be stuck open. When
this occurs, waste backs up into the small intestine, causing small intestinal
bacterial overgrowth.
    Repeat the massage, starting at the ileocecal valve, continuing to use small
clockwise circles overlapping the entire pattern as before. Each circle or pass,
after that, allows the circular massage to close in around the navel. Finish
the massage by placing your hand flat over the abdomen. Turn your whole
hand—flat, and with equal pressure on the fingers and heel of the hand—in
a clockwise direction. This is calming and reinforces the direction of the
deeper work.
    There are many massage therapy modalities that focus on core work and
digestive health. For further exploration, see videos available on the Internet,
on Maya Abdominal Massage, Ayurvedic, and Tuina.
                                         Massage for Digestive Health 193




                Abdominal Massage Don’ts

• Abdominal massage should not be done if a person has inflammation
  of the uterus, bladder, ovaries, or fallopian tubes.
• Abdominal massage should not be done if a person has stones in
  the kidneys, bladder or gallbladder, or ulcers of the stomach or
  intestines.
• Abdominal massage should not be done after a heavy meal.
• The bladder should be emptied before the massage.
• Since blood pressure increases during abdominal manipulation,
  patients with hypertension should avoid abdominal massage.
• Massage should also be avoided in cases where there has been recent
  bleeding in the lungs, stomach, or the brain.
                                    20
          Mindfulness Based Stress Reduction
               for Health and Diseases
                         PADMINI D. RANASINGHE




                                 key concepts

      ■   Mindfulness-based stress reduction (MBSR) is gaining popu-
          larity as a stress reduction technique for healthy adults and ado-
          lescents, as well as for patients with various chronic conditions.
      ■   The purpose of MBSR is to allow participants to cultivate
          moment-to-moment awareness in order to facilitate reduction
          of stress and stress-related symptoms.
      ■   Physiological changes follow sustained activity, and MBSR and
          mindfulness meditation are known to produce physiological
          and anatomical changes in bodily systems over time.
      ■   MBSR triggers changes in the cardiovascular system, respiratory
          system, neurological system, endocrine and immune system.
      ■   Stress, anxiety, and depression play a role in formation and
          exacerbation of common GI diseases like IBS, IBD, PUD, GERD
          and most other chronic diseases. MBSR may be highly benefi-
          cial for patients with these conditions.
                                        ■




                  Introduction: Stress and Health



S
      tress is a complex phenomenon that occurs in humans, with multiple
      sequences of events affecting short-term to long-term health, ranging
      from endocrine to neuronal systems. Within seconds following a
stress-causing stimulus, catecholamines from the sympathetic nervous system

194
                    Mindfulness Based Stress Reduction for Health and Diseases    195


are released. Corticotropin-releasing hormone (CRH) secretes from the hypo-
thalamus, along with enhanced secretion of adrenocorticotropic hormone
(ACTH). Then gonadotropin-releasing hormone (GnRH) decreases pituitary
gonadotropins and increases secretion of prolactin and glucagon. These neuro-
humoral changes lead to various clinical reactions.
   Based on the intensity and duration of these reactions, stress can adversely
affect physical and psychological health. With the growing realization of the
role played by stress in a wide array of medical conditions, stress reduction is
now widely acknowledged to be important in the treatment and prevention of
chronic illnesses. Mindfulness-based stress reduction is receiving attention in
the medical community as an effective method for reducing stress.


                          Stress and GI Disease

Physiological changes in the gastrointestinal (GI) tract can affect mood and
psychological health, and cause physical ailments. It has been documented
that stress plays a role in the causation and exacerbation of common GI dis-
eases like IBS, IBD, PUD and GERD (Whitehead et al., 1992; Bennett et al.,
1998; Hertig et al., 2007; Maunder & Levenstein., 2008; Levenstein et al., 1999;
Davidson et al., 2007). There is a heightened response to CRH by patients with
IBS compared to healthy people (Fukudo et al., 1998). Stress reduction tech-
niques may be beneficial in treating some chronic gastrointestinal disorders.


                               What Is MBSR?

Mindfulness-based stress reduction (MBSR) methods are gaining widespread
popularity as stress reduction techniques for healthy adults and adolescents, as
well as patients with various chronic conditions. The purpose of MBSR prac-
tice is to allow participants to cultivate moment-to-moment awareness of
bodily functions in order to facilitate reduction of stress-related symptoms.
Since it was described by Kabat-Zinn in 1989, MBSR practice has been used in
various populations in multiple healthcare and non health care settings.
   As described elsewhere, conscious management of attention by selectively
focusing on breathing or other physical sensations is the foundation of any MBSR
practice. Mindfulness meditation practice, a source of inspiration for MBSR,
traces its origins to the Buddhist traditions of the East, but the practice itself can
be adopted for strictly secular use stripped of any religious or philosophical
restrictions. Due to this methodological commonality, MBSR and mindfulness
meditation will be used interchangeably in the scope of this chapter.
196   INTEGRATIVE GASTROENTEROLOGY



  Mindfulness meditation is a reflective practice followed by various Buddhist
  traditions.



   This chapter describes some of the evidence available in the literature of
the use of MBSR practices in healthy adults and populations with certain clin-
ical conditions. MBSR has been studied and shown some benefits in condi-
tions, such as chronic pain, cancer, psychiatric conditions, and some chronic
diseases.
   Physiological changes follow any sustained activity. MBSR and mindfulness
meditation are known to produce physiological and anatomical changes in
bodily systems over time, some of the changes are in the cardiovascular system,
respiratory system, neurological system, endocrine system and immune
system.


  A decrease in cardiac pre-ejection period, increase in cardiac output, and
  decrease in diastolic blood pressure (BP) were observed during mindfulness
  meditation (Ditto et al., 2006).


    Practice of long term meditation, not necessarily MBSR, has shown to pro-
duce some structural and functional changes in the brain. A small study
showed that long-term meditators had structural changes in the brain com-
pared to controls, such as increased gray matter density in lower brainstem
regions and increases in the left prefrontal cortex and right anterior insula
(Vestergaard-Poulsen et al., 2009; Lazar et al., 2005). Expert meditators who
practiced concentration meditation showed a significant activation of brain
regions associated with sustained attention as captured by functional MRI
(Brefczynski-Lewis et al., 2007). As examined by flashlight test and visual sen-
sitivity test, mindfulness meditation increased attention and changed percep-
tion at 3month follow up of 16hour/day meditation. (Brown et al., 1984).There
are also changes in immune cells, mediators, and hormones levels with MBSR
related practices.



                            MBSR in Practice

MBSR has been used in various patient populations and healthy adults to pro-
mote physical, social, and psychological health. MBSR techniques may help a
broad range of individuals to cope with clinical and nonclinical problems, and
                   Mindfulness Based Stress Reduction for Health and Diseases      197


are shown to be effective as an interventions in a variety of healthcare settings
(Praissman, 2008; Grossman, Niemann et al., 2004; Williams, Kolar et al.,
2001). In some healthcare settings MBSR technique has been taught in weekly
group sessions, usually lasting 8 to 10 weeks with video-assisted homework
assignments. Other adapted methodologies also have been used in research
settings. Group mindfulness meditation techniques have been shown to be
beneficial immediately, as well as one year after intervention, in several physi-
cal, psychological and social parameters (Reibel et al., 2001). It has been shown
that MBSR may be effectively taught by video-conferencing in patients with
chronic pain (Gardner-Nix et al., 2008).


                               HEALTHY ADULTS

Most MBSR-related studies were conducted among healthy adults. Mindfulness
meditation has been shown to play a role in cognitive flexibility, stress reduc-
tion, increased relaxation, and decreased overall psychological symptoms,
while promoting an overall sense of control in adult volunteers (Agee et al.,
2009; Moore & Malinowski, 2009; Astin, 1997). Experienced meditators
showed increasing introception awareness and heartbeat detection (Khalsa
et al., 2008).


   MBSR has been shown to improve sleep quality, improve night-time
   symptoms of insomnia and decrease pre-sleep arousal, sleep effort and dys-
   functional sleep-related cognition (Klatt et al., 2008; Winbush et al., 2007;
   Ong et al., 2008).



   MBSR related practices have demonstrated effectiveness among a wide range
of populations. While both MBSR and cognitive-based stress reduction were
effective in reducing perceived stress and depression, MBSR is more effective in
increasing mindfulness and energy, reducing pain, psychological distress and
reported medical symptoms in adults (Smith, Shelley et al., 2008; Carmody,
Reed et al., 2008). A sample drawn from the general population, as well as hos-
pital staff, who participated in an MBSR program, had a higher quit rate of
smoking in smoking cessation intervention studies (Davis et al., 2007; Michalsen
et al., 2002). Meditation has shown to lower stress and support forgiveness
among college students, and to lower distress and improve mood in medical
students (Oman et al., 2008; Rosenzweig et al., 2003). In an earlier study MBSR
also has been shown to be efficacious in decreasing stress and anxiety and
increasing empathy in medical students (Shapiro, Schwartz et al., 1998).
198   INTEGRATIVE GASTROENTEROLOGY


   Nurses who participated in a short MSBR program experienced reduced
burnout symptoms, increased general relaxation and satisfaction with life com-
pared to a wait listed control group (Mackenzie et al., 2006). It also had shown
to be beneficial to improve self-care, decrease tendencies to take on others’
negative emotions, lower burnout, and improve well-being among nurses and
nursing students (Cohen-Katz et al., 2004, 2005; Beddoe & Murphy, 2004).


                                     PAIN

MBSR techniques have been used to assist individuals with chronic pain in
different clinical conditions. Women with fibromyalgia showed a decrease in
their basal sympathetic activity, and a improve in psychological health such as
changes in depressive symptoms, anxiety and coping skills after receiving
MBSR (Grossman, Tiefenthaler-Gilmer et al., 2007; Sephton et al., 2007; Lush
et al., 2009).
   A randomized clinical trial of 30 patients with chronic musculoskeletal
pain showed that MBSR was more effective and longer lasting in mood
improvement than massage therapy (Plews-Ogan et al., 2005). In an early
study of 90 patients with chronic pain, a 10-week stress reduction and relax-
ation program was associated with improvement in present-moment pain,
negative image, mood disturbances, and other psychological symptoms like
anxiety and depression and these benefits lasted 15 months except for present
movement pain (Kabat-Zinn, Lipworth et al., 1985). In older patients with
lower back pain, MBSR has been used to increase physical function and qual-
ity of life, decrease pain, and support mood elevation, and sleep (Morone,
Greco et al., 2008; Morone, Lynch et al., 2008).


                                   CANCER

For oncology patients, MBSR is gaining recognition as a credible and benefi-
cial intervention to be incorporated in to the treatment. A review study has
shown that the patients with cancer who received MBSR training had a posi-
tive change on psychological functioning, stress reduction and increased
coping skills and well-being (Ott et al., 2006). Cancer patients who partici-
pated in an MBSR program had increased quality of life, less stress, and fewer
physical symptoms (Kieviet-Stijnen et al., 2008). Another review article found
a potential benefit for MBSR in cancer patients for sleep, mood, and reduction
in stress (Smith, Richardson et al., 2005).
   In a small study, cancer patients who underwent hematopoietic stem cell
transplant showed a statistically significant decrease in heart and respiratory
                   Mindfulness Based Stress Reduction for Health and Diseases   199


rates, and improvements in physical and psychological symptoms immediately
before and after each MBSR session suggesting potential benefits and feasibil-
ity of MBSR in hospitalized cancer patients (Bauer-Wu et al., 2008). Similarly
studies involving breast and prostate cancer patients showed that an MBSR
program was resulted in positive benefits, such as increased quality of life and
sleep, decreased stress symptoms and cortisol level, as well as immune patterns
consistent with less stress and mood disturbance, and decreased blood pres-
sure (Carlson, Speca et al., 2004, 2007; Carlson & Garland, 2005). MBSR may
also have positive effects on the quality of sleep in breast cancer patients whose
sleep disturbances were associated with stress (Shapiro, Bootzin et al., 2003).


   Studies have also shown psychological benefits for MBSR in patients diag-
   nosed with cancer.


   A randomized, controlled clinical trial showed that patients diagnosed with
breast cancer had lower depression scores, less anxiety, and less fear of recur-
rence, in addition to improved energy and physical function after MBSR
intervention (Lengacher, Johnson-Mallard et al., 2009). MBSR programs
have been shown to reduce mood disturbance and symptoms of stress, and
increase well-being and the ability to handle stress in adult patients with vari-
ous cancers (Carlson, Ursuliak et al., 2001; Speca, Carlson et al., 2000). A
meta-analysis has shown that MBSR has the potential to improve psychosocial
adjustment to the disease in cancer patients (Ledesma & Kumano 2008).
   Some other benefits of 8 weeks of MBSR in patients diagnosed with breast
cancer include an increase in serum immune markers: regained peripheral
blood mononuclear cell NK cell activity (NKCA) and IFN-gamma produc-
tion, decreased IL-4, IL-6, and IL-10 production, and decreased plasma corti-
sol levels, in addition to improved quality of life and coping (Witek-Janusek
et al., 2008). In patients with breast and prostate cancer who received MBSR
training, had decreased in pro-inflammatory immune cells and cytokines
steadily over 1 year In addition to improving symptoms stress, quality of life
and mood and they concluded that these shifts in immune parameters are
associated with the resolution of depressive symptoms (Carlson, Speca et al.,
2003).


                         PSYCHIATRIC CONDITIONS

Another major area where MBSR has been widely studied is in psychiatric
conditions like depression, anxiety, and stress.
200   INTEGRATIVE GASTROENTEROLOGY


   In one study, 28 patients with chronic recurrent depression with protracted
course and current symptoms of depression were randomized to receive mind-
fulness-based cognitive therapy or usual treatment. There was a decrease in
symptoms from severe to mild levels of depression in patients who were
assigned to the mindfulness-based cognitive therapy group (Barnhofer et al.,
2009). Mindfulness has been shown to be beneficial in relapse prevention
in patients with depression after adjusting for other variables at 12 months
follow-up (Michalak et al., 2008). Small study with 11 participants with gener-
alized anxiety disorder who received 8 week mindfulness-based cognitive
therapy showed that there was a significant reduction in anxiety, depressive
symptoms, and worry, from baseline to end of intervention (Evans, Ferrando
et al., 2008).
   Eight week MBSR practice as an intervention has been shown to decrease
perceived stress and vital exhaustion, and is strongly associated with positive
affect and quality of life and well-being in adult patients with distress from the
community and mindfulness mediated effect on stress and quality of life
(Nyklicek & Kuijpers, 2008;) Another study of 174 adults in a clinical mind-
fuleness progam has shown that 8 week MBSR had increased mindfulness,
wellbeing and decreased stress. This imporvement was singinifantly related to
the time spent on MBSR related activities and minfulness was found to be a
mediator for some outcomes. (Carmody & Baer, 2008). It also has been shown
that patients with chronic physiological and psychological stress would benefit
from an 8-week MBSR program to improve their well-being and quality of life
(Majumdar et al., 2002).
   In a study involving both cognitive behavioral therapy (CBT) and MBSR,
for patients with DSM-IV generalized social anxiety disorder receiving CBT
showed a greater improvement in social anxiety disorder related symptoms
than MBSR group, but an equally comparable improvement was recorded in
mood, disability and quality of life from both interventions. (Koszycki et al.,
2007). Three-year follow-up study of patients with anxiety has shown that
there were long-term benefits of mindfulness meditation in the treatment of
anxiety disorder (Miller et al., 1995). Kabat-Zinn et al. (1992) have shown that
MBSR with group mindfulness meditation training is beneficial in reducing
symptoms of anxiety and panic and to maintain those low levels in patient
with generalized anxiety disorder.
   It has been shown in small studies that MBSR-related techniques may also
be beneficial in treating other psychiatric conditions like obsessive-compulsive
disorder and ADHD in adults—possibly by letting go, and improving behav-
ioral and neurocognitive impairment, respectively (Hanstede et al., 2008;
Zylowska, Ackerman et al., 2008). A small study has shown that patients with
bipolar disorder who received mindfulness-based cognitive therapy did better
                  Mindfulness Based Stress Reduction for Health and Diseases   201


with anxiety symptoms specific to bipolar disorder than those who did not
receive it (Williams, Alatiq et al., 2008). There appear to be some promising
results with MBSR techniques for younger women with bulimia nervosa and
and women with sexual dysfunction (Proulx, 2008; Brotto, Basson et al.,
2008). A study of patients, 1-year after mild to moderate brain injuries, who
received MBSR showed an improvement in quality of life, cognitive affect,
domain of Beck Depression Inventory, and positive distress inventory of SCL-
90R (Bedard et al., 2003).


                         OTHER CHRONIC DISEASES

                               Type 2 Diabetes

An MBSR program for 14 patients with Type-2 diabetes has shown a positive
impact on HbA1C, blood pressure, body weight, anxiety, depression, somati-
zation, and psychological distress at 1-month after the intervention (Rosenzweig,
Reibel et al., 2007).


                            Transplant Patients

   It has been shown in an 8-week MBSR program, transplant patients have
experienced an improvement in sleep, positive mental health, anxiety score,
and overall well-being at 3months and for sleep even at 6 months after the
intervention (Kreitzer, Gross et al., 2005; Gross, Kreitzer et al., 2004).


                                Heart Disease

   Small and short duration 2 studies with 8-week MBSR practice show some
benefits in patients with heart disease. One study has shown a reduction in
anxiety score in patients with heart disease. Another study has shown a positive
trend for changes in resting levels of cortisol, physical function and, signifi-
cantly difference in pattern of breathing during exercise in women with heart
disease who received MBSR (Robert-McComb et al., 2004; Tacon et al., 2003).


                         Congestive Heart Failure

Prospective cohort study of heart failure (NYHA 11) patients who underwent
a MBSR program in addition to medications had a lower anxiety score,
202 INTEGRATIVE GASTROENTEROLOGY


less depression, and improved symptoms as measured by Kansas City
Cardiomyopathy questionnaire symptom scale and clinical scale, but there
was no treatment effect on death/rehospitalization at one year (Sullivan et al.,
2009).


                                     HIV

A single-blinded, randomized, controlled study of 48 HIV patients who
received 8-week MBSR intervention showed that CD4+ count was not
decreased from baseline compared to a control group in whom there was
reduction in CD4+ count, independent of antiretroviral therapy (Creswell
et al., 2009). Among HIV patients, natural killer cell activity and number
increased, suggesting that MBSR may play a role in improving immunity in
this population (Robinson et al., 2003).


                             Other Conditions

Thirty seven patients with psoriasis who received brief MBSR delivered by
audiotape during ultraviolet phototherapy or photochemotherapy showed an
increased rate of resolution of psoriatic lesions compared to who didn’t receive
the MBSR intervention (Kabat-Zinn, Wheeler et al., 1998).
   MBSR techniques may be used as a complementary therapy in rheumatoid
arthritis, by improving psychological distress and well-being as shown in a
randomized control study with 8-week MSBR and waitlisted control group
(Pradhan et al., 2007).
   Small Studies have shown that this technique may also be potentially ben-
eficial to improve severity and frequency of hot flushes in women and also
patients with symptoms of tinnitus. (Carmody, Crawford et al., 2006, Sadlier
et al., 2008). Currently studies are underway to further explore MBSR and
related techniques as interventions for healthy adults and populations with
various diseases.


                         HEALTHCARE UTILIZATION

There is some evidence to suggest that MBSR interventions may decrease
healthcare utilization and chronic care visits in addition to improving self-
esteem and decreasing medical and psychological symptoms, in an inner-city
English and Spanish speaking population (Roth & Stanley, 2002; Roth &
Creaser, 1997).
                  Mindfulness Based Stress Reduction for Health and Diseases   203




                                Limitations

Because of the nature of MBSR interventions and the diversity of practices that
use MBSR as a common approach, the true range of therapeutic possibilities
and limitations of MBSR are not yet clearly established. At a minimum, MBSR
may be a safe and effective technique, but requires practice to experience full
benefits. There are multiple studies looking at application of MBSR and related
techniques as an adjunctive treatment option for people with chronic diseases
and for healthy individuals, but there are some common limitations of these
studies. Most of these are small-scale studies with short-term follow-up. Only
some studies were conducted in randomized control fashion and those trials
also have used waitlisted control subjects. There are multiple limitations with
waitlisted control comparison groups. As MBSR techniques require individual
motivation and time commitment, attrition rate is also higher before and after
completion of the program. It is important to have well-conducted, large-scale,
randomized, controlled trials with long-term follow-up - to facilitate incorpo-
rating MBSR into mainstream treatment. Finally, it is apparent that MBSR
may be more attractive for people who are very motivated and committed to
these kinds of interventions, as well as to positive behavioral changes (Robinson
et al., 2003).


                                Conclusion

MBSR may be a safe and effective technique for patients to resolve certain
symptoms (anxiety, depression, fear, stress, and pain) those oftentimes incite
digestive tract and other chronic diseases. It also has been shown to improve
general wellbeing and quality of life in healthy adults and patients with certain
chronic conditions. Laboratory studies have shown an improvement in proin-
flammatory cytokine profiles, with reduction in stress-related hormones and
symptoms, as a consequence of MBSR. MBSR techniques have been studied to
some extent among healthy adults, patient with cancer, psychiatric conditions,
chronic pain and certain other conditions. It is possible most of the benefits we
see with this intervention may be explained by the fact MBSR and similar
practices help to alleviate stress and related symptoms. Although there is
paucity of data on specifically examining MBSR for symptoms of gastrointes-
tinal diseases, these techniques may be beneficial as an adjunctive treatment
for this patient population where stress plays a role in causation and exacer-
bation. Active trials are underway to examine MBSR for this population.
204   INTEGRATIVE GASTROENTEROLOGY


(Gaylord S.A. Whitehead W et al., and David Kearney) Finally although
there is a lack of studies favoring the use of MBSR in the prevention and
treatment of digestive disturbances and other chronic diseases, practitioners
may educate patients about its potential benefits, given the lack of adverse
effects.
                                    21
         Naturopathic Medicine and Digestion
                            JOSEPH PIZZORNO




                                key concepts

     ■   Naturopathic medicine prioritizes supporting the body’s innate
         healing processes.
     ■   This is primarily achieved by normalizing physiological
         function.
     ■   Digestive system dysfunction not only causes acute and chronic
         symptoms, but can contribute to, and even cause, both local and
         systemic disease.
     ■   Disorders of digestion and nutrient absorption, such as
         hypochlorhydria, pancreatic exocrine insufficiency, and exces-
         sive bowel permeability, are common.
     ■   Relatively simple interventions can have dramatic impacts on
         patients’ health.
                                       ■




                       Naturopathic Medicine



N
          aturopathic medicine is a distinct system of health-oriented medi-
          cine that stresses promotion of health, prevention of disease, support
          for the body’s own healing systems, patient education, and self-
responsibility. However, naturopathic medicine symbolizes more than simply
a healthcare system; it is a way of life. Unlike most other healthcare systems,
naturopathy is not identified with any particular therapy, but rather a way of
thinking about life, health, and disease. It is defined not by the therapies it
uses, but by the philosophical principles that guide the practitioner.

                                                                            205
206    INTEGRATIVE GASTROENTEROLOGY


    Seven concepts provide the foundation that defines naturopathic medicine,
and create a unique group of professionals practicing a form of medicine that
is fundamentally different from the disease-centric approach of conventional
medicine. Armed with a strong belief in the inherent ability of the body to
heal—if just given the chance—the profession developed these principles as a
guide to developing a curative relationship with patients.



  The seven core principles of naturopathic medicine are as follows, with
  “wellness and health promotion” emerging into the forefront of the
  scholarly discussion of naturopathic clinical theory:
  1. The healing power of nature (vis medicatrix naturae)
  2. First do no harm (primum non nocere)
  3. Find the cause (tolle causam)
  4. Treat the whole person (holism)
  5. Preventive medicine
  6. Wellness and health promotion (emerging principle)
  7. Doctor as teacher (docere)




    As an outcome of the above principles, the profession has developed spe-
cific guidelines to assist in providing patient care, beginning at the least
invasive and, as necessary, utilizing progressively more invasive procedures.
Naturopaths are not against drugs or other conventional therapies and
prescribe—or, depending on state licensure statues, refer for—drug or other
conventional treatments when necessary.



                      7 NATUROPATHIC GUIDELINES

  1. Reestablish the basis for health.
  2. Stimulate the vital force.
  3. Tonify and nourish weakened systems.
  4. Correct structural integrity.
  5. Prescribe specific substances and modalities for specific conditions
     and biochemical pathways (e.g., botanicals, nutrients, acupuncture,
     homeopathy, hydrotherapy, counseling).
  6. Prescribe pharmaceutical substances.
  7. Use radiation, chemotherapy, and surgery.
                                        Naturopathic Medicine and Digestion 207


   Because of its eclectic nature, the history of naturopathic medicine is by far
the most complex of any healing art. Naturopathic medicine traces its philo-
sophical roots to many traditional world medicines, and its body of knowledge
derives from a rich heritage of writings and practices of Western and non-
Western nature doctors since Hippocrates. Naturopathy became a formal pro-
fession in the United States after its founding by Benedict Lust, in 1896.


        A Physiological Systems Approach to Healing

While the foundation of patient care is education and counseling in diet and
lifestyle, much of naturopathic intervention centers on normalizing system
function.


  The naturopath asks basically 5 questions:
  1. What is the system supposed to be doing?
  2. What signs, symptoms, and lab tests indicate the system is
     dysfunctional?
  3. Why is the system dysfunctional?
  4. What is the least invasive way to restore function?
  5. If function cannot be restored, how can the functions be simulated?




   Dealing with the disorders of the digestive system is an excellent way to
demonstrate the applications of the principles of naturopathic medicine. The
old naturopathic adage, “disease begins in the bowel,” which sounded quaint to
new students 35 years ago, is now recognized as wise clinical insight.
   The GI system is the primary gateway by which the external environment
interacts with the body (Sult, 2006). The basic physiology of digestion and
absorption is well understood, although digestive disturbances remain unre-
solved in a significant portion of the population. Viewing digestion as a physi-
ological process, the food must be broken into its components by mechanical
homogenization and chemical breakdown, followed by absorption of the
smaller carbohydrates, lipids, proteins, vitamins, minerals, and other nutri-
ents, through a variety of passive and active processes.
   In addition to the digestion and absorption of food, the GI tract must also
defend against pathogens and toxins that we are exposed to on a continuous
basis. It has a number of protective mechanisms, including a low pH in the
stomach, coverage of the complete GI tract with a mucus layer, a diverse
array of immune cells that lie beneath this mucus layer, and the presence of
208 INTEGRATIVE GASTROENTEROLOGY


commensal microbes that abundantly colonize the GI tract (Zoetendal, Rajilic-
Stojanovic, & de Vos, 2008).
   There are many ways in which one or more of these critical processes can
break down. Rather than focus on what specific digestive disease a patient may
have, the naturopath instead focuses on restoring normal function of all diges-
tive processes.


                 Restoring Physiological Function

The largest survey of GI symptoms to date (Camilleri et al., 2005) found an
overall prevalence of at least one upper GI symptom (during the previous
3 months) of 45% those surveyed (including heartburn, early satiety, loss of
appetite and postprandial fullness). A smaller survey of Canadian adults found
a prevalence of lower GI symptoms of 5.2% (abdominal pain/bloating, consti-
pation, diarrhea) (Hunt et al., 2007). More recent studies in the United States
suggest bloating is as common as 19% to 21% among U.S. adults (Jiang et al.,
2008; Tuteja et al., 2008)

   In as many as half of the symptomatic patients seen by gastroenterologists,
   a cause (i.e., disease) is not found, and they are often given a diagnosis of
   unclear etiology, such as functional dyspepsia or irritable bowel syndrome
   (IBS). (Geeraerts & Tack, 2008)



   In reality, these symptoms indicate one or more disruptions in gastrointes-
tinal function that will usually, eventually, result in diagnosable pathology. For
example, recent research has found the prevalence of celiac disease to be much
greater than assumed, affecting up to 1% of the U.S. population. For example,
a recent report from the United Kingdom estimated that only 1 out of every
9 cases has been diagnosed (van Heel & West, 2006), and the average time of
delayed diagnosis is 4.5 to 9 years (Hopper et al., 2007). An earlier study sug-
gests that in some patients with IBS, celiac disease may be the underlying
cause, with an odds ratio (OR) of 7.0 for those with IBS (Sanders et al., 2001).
Indeed, a screening of over 13,000 individuals found that those with digestive
complaints such as constipation, diarrhea, and/or abdominal pain had a 1:56
chance of having celiac disease—a risk increase of more than twofold what was
found in the general population (Fasano et al., 2003).
   Space limitations do not allow consideration of all gastrointestinal dysfunc-
tions, such as hypochlorhydria, hyperchlorhydria, pancreatic insufficiency,
                                        Naturopathic Medicine and Digestion 209


excessive bowel permeability, imbalanced microbial flora, malabsorption,
reduced bile salt secretion, overgrowth of bacteria in the small bowel, food
intolerance/allergy, etc.


                             Hypochlorhydria

Lack of sufficient stomach acid has been associated with reduced vitamin and
mineral absorption (Hershko et al., 2005; Hirschowitz, Worthington &
Mohnen, 2008), incomplete protein digestion, and subsequent food allergy
(Untersmayr & Jensen-Jarolim, 2006, 2008), bacterial infections of the GI
tract, and a large number of chronic diseases. The incidence of hypochlorhy-
dria is controversial, ranging from 10% to 50% (Huritz et al., 1997; Rafsky &
Weingarten, 1946). Much of this is likely due to the diversity of testing meth-
odologies and age of the participants. Testing only resting pH will provide a
much lower incidence than testing the ability to acidify a standard meal or
bicarbonate challenge.


                                  DIAGNOSIS

   • Laboratory diagnosis. Heidelberg pH capsule gastric analysis,
     gastric tube, serum pepsinogen I (S-PGI) and serum gastrin-17
     (S-G-17).
   • Clinical diagnosis. High predictability factors include the H. pylori
     infection, use of antacids, H2 blockers and proton-pump inhibitors
     (PPIs), and pernicious anemia. Medium predictability factors include
     age greater than 60, acne rosacea, and rheumatoid arthritis. Lower
     predictability factors include nausea, abdominal gas, belching, consti-
     pation, chronic diarrhea, dyspepsia, weak/cracked/peeling finger-
     nails, osteoporosis, asthma, gastric ulcer, and decreased ferritin.


                                    CAUSES

Acid Secretion-Suppressing Drugs. The use of acid-suppressing drugs has
increased the incidence of problems associated with the stomach. For example,
a study of nearly 1,700 cases of C. difficile infection and acid suppression found
that the adjusted rate ratio of infection was 2.9 for the use of PPIs, and 2.0 with
H2 receptor antagonists (Dial et al., 2005). The frequency of B12 deficiency
210 INTEGRATIVE GASTROENTEROLOGY


among long-term users of PPIs was recently found to be 29%, though it is
often missed by serum cobalamin evaluation alone.10 The increasing incidence
of C. difficile infection has been proposed due to the increased use of acid sup-
pressing drugs (Dial, Delaney, Barkun, & Suissa, 2005).
   Age. The acidity of the stomach declines with age, and may contribute to
the associated nutrient deficiencies and greater infection risk. For example, the
incidence of C. difficile is higher among the elderly (Kelly & LaMont, 2008). In
a sample of nearly 250 patients aged 65 or greater, only 67% had consistent acid
secretion, while 22% had intermittent secretion and 11% were consistent
hyposecretors. This study likely underestimated the incidence of hypochlorhy-
dria, as a pH less than 3.5 was defined as acidic and no challenge testing was
done; i.e., determining if a standardized meal is acidified (Hurwitz, Brady, &
Schaal, 1997).
   H. pylori. Thirty to forty percent of the U.S. population is infected with H.
pylori, with an increasing prevalence associated with age (Chey & Wong,
2007). Data from more than 7,000 adults in the NHANES study (1988–1991)
found a seroprevalence of 16.7% for persons 20 to 29 years old, to 56.9% for
those 70 or more years old (Everhart et al., 2000). Although mostly known as
the primary cause of peptic ulcers, especially duodenal, H. pylori also causes
chronic gastritis leading to atrophy and loss of parietal cells, and thus reduced
gastric acidity. The pepsinogen I/II ratio is often used as a marker for gastric
atrophy, and correlates well with gastric pH (Kato et al., 2008).


                                 INTERVENTION

The basic clinical strategy is as follows:

   1. Stop acid secretion-inhibiting drugs if they are being used, and instead
      treat the causes of the GERD.
   2. Eradicate the H. pylori; make conditions inhospitable for its return.
   3. Stimulate regeneration of the gastric mucosa and parietal cells.
   4. If HCl production has not returned, stimulate with herbal bitters.
   5. If still no HCl production, emulate with oral supplementation.

   H. pylori. A recent study found that eradication of H. pylori was associated
with a return to normal gastric acidity (Kato et al., 2008). This is supported by
an earlier study, monitoring pepsinogens and gastrin, in 172 patients that
underwent eradication therapy; at 12–15 months the results were comparable
to those without previous infection (Ohkusa et al., 2004). The most reliable
                                         Naturopathic Medicine and Digestion 211


intervention is with triple drug therapy (two antibiotics and an H2 inhibitor);
see Chapter 39 by Minocha. Effective natural therapies include:

   • Concurrent Lactobacillus GG supplementation makes standard drug
     therapy more effective, and reduces adverse drug reactions (Armuzzi
     et al., 2001).
   • Vitamin C at 5 g/d for 4 weeks eliminates H. pylori in 30%, and long-
     term (5-year) use inhibits H. pylori growth and reverses gastric atro-
     phy as measured by pepsinogen secretion (Zhang, Wakisaka, Maeda,
     & Yamamoto, 1997; Sasazuki et al., 2003).
   • Curcuma longa has great potential, as it is both bactericidal to H.
     pylori and, in an animal model, decreases the inflammation associ-
     ated with the infection (De et al., 2009). Human research is, however,
     limited. One study concluded that since curcumin only eradicated H.
     pylori in 12% of the participants, it was not successful. However, treat-
     ment was only 7 days in duration and combined with other nutrients.
     The patients showed significant improvement in dyspeptic symptoms
     and reduction in serological signs of gastric inflammation 2 months
     after the end of the short therapy (Di Mario et al., 2007). The inhibi-
     tion of H. pylori and anti-inflammatory effects may help explain cur-
     cumin’s anti-gastric cancer effects (Cheng et al., 2001).

   Deglycyrrhizinated licorice (DGL). The flavonoids found in Glycyrrihiza
glabra impair H. pylori growth (including antibiotic-resistant strains; see Fukai
et al., 2002). It has a long history of use in the successful treatment of gastric
ulcers (Doll et al., 1962), and has been shown to stimulate regeneration of the
gastric mucosa (van Marle, Aarsen, Lind, & van Weeren-Kramer, 1981).
Glycyrrhizin is removed to allow long-term use, as it can cause pseudohyper-
aldosteronism.
   Acid secretion-suppression drugs. Rather than treat symptoms, deal
instead with the causes of GERD. While these drugs in the short run
decrease symptoms and may prevent sequelae, the long-term effects of mal-
digestion, impaired B12 absorption, etc., are serious and underappreciated (see
Chapter 37).
   Herbal bitters. Herbal bitters (sometimes known as Swedish bitters) have a
centuries-old tradition of use for digestive disorders. While they are claimed to
increase stomach acid secretion, there is actually no apparent objective
research. In fact, some constituents of bitters, such as aloe, have actually been
shown to suppress gastric acid secretion, although it does protect the gastric
mucosa (Yusuf, Agunu, & Diana, 2004).
212     INTEGRATIVE GASTROENTEROLOGY


   HCl supplementation. Oral HCl supplementation has long been used by
the CAM community to treat patients with hypochlorhydria if the efforts to
regenerate HCl production fail.


      The following are directions provided to patients for assessing HCl supple-
      mentation requirements:
      1. Begin by taking 1 HCl capsule (10 grains) at your next large meal. At every
         meal after that, of the same size, take 1 additional capsule (1 capsule at the
         next meal, 2 at the meal after that, then 3 at the next meal, and so on).
      2. Continue to increase the dose until you reach 7 capsules, or you feel a
         warmth in your stomach, whichever occurs first. A feeling of warmth in
         the stomach means that you have taken too many capsules for a meal of
         that size. Take 1 less capsule the next time. However, it is a good idea to
         try the larger dose again at another meal to make sure that it was the HCl
         that caused the warmth and not something else.
      3. After you have determined the largest dose that you can take at your
         large meals without feeling any warmth, maintain that dose at all meals
         of similar size. Take fewer capsules with smaller meals.
      4. When taking several capsules, it is best to take them throughout the meal
         rather than all at once.
      5. As your stomach begins to regain the ability to produce the amount of
         HCl needed to properly digest your food, you will notice the warm feeling
         again. This is the time to start decreasing the dose level.
      6. Every 3 days, decrease by 1 capsule per meal. If the warmth continues,
         decrease more rapidly. If maldigestion symptoms return, add capsules
         back until digestion improves again.




                    Exocrine Pancreatic Insufficiency

Inadequate pancreatic enzyme and bicarbonate secretion impairs the break-
down of food entering the small intestine, resulting in incomplete digestion
and, most consequentially, malabsorption of a variety of nutrients. Fat malab-
sorption occurs initially, and deficiencies of vitamins A, E, and K, as well as
essential fatty acids, are common. Markers of pancreatic insufficiency have
been found recently in patients with osteoporotic fractures, and the data sug-
gests that vitamin D deficiency also occurs frequently, due to poor pancreatic
output (Mann et al., 2008). While generally thought to occur as a later symp-
tom, reduced circulating levels of amino acids among patients with chronic
pancreatitis suggest that protein digestion and absorption are also impaired
(Schrader et al., 2009).
                                         Naturopathic Medicine and Digestion 213




                                  DIAGNOSIS

   • Laboratory diagnosis: Although most direct tests are generally accu-
     rate, they are usually invasive and expensive. For this reason, pancre-
     atic elastase 1 (PE1) is typically used (normal > 200 ug/g; see Naruse
     et al., 2006).
   • Clinical diagnosis. Although most clinicians use the presence of oily,
     foul-smelling and buoyant stool (due to the increased fat content) as
     an indication of pancreatic exocrine insufficiency, measurable dys-
     function can occur before these stool changes are observed. Further
     complicating the issue is that the various exocrine functions can
     become dysfunctional independently (Owyang, 2003). Other symp-
     toms, such as abdominal pain, are more likely in acute or chronic
     pancreatitis, not necessarily due to insufficiency, and gas and bloating
     are likely but not very specific.


                                    CAUSES

Chronic pancreatitis (CP): One of the most well-established causes of pan-
creatic insufficiency is chronic pancreatitis, for which alcohol use is the major
risk factor. About 70% of CP is caused by alcohol. Smoking is also a significant
risk factor, with an odds ratio of 7.8 for current smokers, and a greater risk with
an increasing cumulative amount of smoking (Lin et al., 2000).38
    Cystic fibrosis (CF): Approximately 90% of people with CF have pancre-
atic insufficiency, particularly those of Northern European descent, where a
more severe genetic mutation predominates (Rovner et al., 2007).
    Celiac disease. Chronic immunological reaction to wheat is also thought to
be a cause of exocrine pancreatic insufficiency, with at least 20% estimated to
have a deficiency (Freeman, 2007). Although the removal of gluten from the
diets of these patients improves pancreatic function in some, those with
chronic diarrhea despite gluten avoidance are more likely to have reduced
pancreatic function (Leeds et al., 2007). Recent research suggests that celiac is
seriously underdiagnosed.
    Diabetes mellitus: Diabetes mellitus is a significant cause of pancreatic
insufficiency, and although it is more common in Type 1, patients with either
type of diabetes may be affected. Overall, 27% of patients with diabetes
(n=2001) had a fecal elastase 1 < 100ug/g, a marker of severe pancreatic insuf-
ficiency, while only 58% had a level > 200ug/g (Hardt et al., 2008).
214 INTEGRATIVE GASTROENTEROLOGY


   Inflammatory bowel disease: Compared to control subjects, patients
with Crohn’s disease were found to have more than an eightfold risk for a
FE1 < 200 μg/g, and those with ulcerative colitis had nearly a 13-fold risk.


                               INTERVENTION

  1. Eliminate contributing factors.

   Although not always causative, patients should avoid alcohol and smoking,
particularly those with chronic pancreatitis. Additionally, avoidance of gluten
in those with celiac disease may improve the pancreatic insufficiency in some
cases (Carroccio et al., 1991).

  2. Pancreatic enzyme replacement.

   Complete replacement should include proteolytic enzymes, lipase, as well
as enzymes that digest carbohydrate. The supplement should be taken during
or immediately after meals for the greatest efficacy (Domínguez-Muñoz et al.,
2005).

  3. Correct related nutrient deficiencies.

   Fat soluble vitamins, (A, D, E, and K) are likely to be deficient in patients
with poor pancreatic exocrine function, along with essential fatty acids (Peretti
et al., 2005; Dodge &Turck, 2006).

  4. Potential therapies.

    Although clinical research is lacking, melatonin appears to have an impor-
tant role in pancreatic function. The concentration of melatonin in the GI tract
is 10 to 100 times higher than in the plasma, and the total amount of melatonin
is around 400 times higher than the amount of melatonin in the pineal gland
(Bubenik, 2008). Melatonin has been shown to have some protective function
for the pancreas, and to strongly stimulate pancreatic amylase secretion
(Jaworek et al., 2007).


                  INCREASED INTESTINAL PERMEABILITY

Abnormal permeability refers to a measurable increase in flux of small water-
soluble compounds across the paracellular pathway of the small intestine.
                                        Naturopathic Medicine and Digestion 215


Intracellular enterocyte and tight junction proteins regulate the rate of move-
ment and permeability through this pathway.
   The inflammation typically associated with altered permeability is not
restricted to the gut. For example, animal models of Type 1 diabetes have
shown that intestinal permeability, with resultant inflammation, plays a role in
the autoimmune destruction of pancreatic islet cells. Recent research suggests
that the same is true for Type 1 diabetes in humans. Increased lactulose perme-
ability (with normal mannitol) precedes detectable clinical onset of impaired
glucose regulation, suggesting that the small intestine participates in the
pathogenesis of the disease (Bosi et al., 2006).


  Loss of intestinal barrier function may also be associated with other autoim-
  mune diseases, such as multiple sclerosis, ankylosing spondylitis, IgA neph-
  ropathy, and nonalcoholic steatohepatitis (NASH), as well as digestive
  autoimmune processes, such as Crohn’s disease and celiac disease (Fasano
  & Shea-Donohue, 2005).




                                  DIAGNOSIS

  • Laboratory assessment is done primarily with the lactulose/mannitol
    test (see Chapter 5).


                                    CAUSES

A number of factors can alter the normal permeability, including food allergy,
food intolerance, infection, inflammatory cytokines, nutrient transporter acti-
vation, noxious environmental toxins, toxic—not infectious—bacteria, and
unknown causes. Evolving research is showing that altered intestinal permea-
bility plays a role in a number of digestive diseases, including celiac, IBD, IBS
and food allergy, and may precede the illness (Meddings, 2008).
   NSAIDs are a well-accepted cause of increased intestinal permeability in
both the short term and long term, causing significant morbidity and mortal-
ity (Bjarnason & Takeuchi, 2009). Aspirin was recently shown to increase the
susceptibility to “gut leakiness” in patients with non-alcoholic steatohepatitis
(NASH), although lactulose/mannitol was not modified by aspirin, the uri-
nary sucralose increased only in patients with NASH, suggesting a colonic
permeability increase (Farhadi, Gundlapalli, & Shaikh, 2008).
216     INTEGRATIVE GASTROENTEROLOGY




                                  INTERVENTION

The strategy to facilitate repair of the damaged intestinal mucosa entails
3 steps:

      1. Stop the damage.
      2. Reestablish a healthy microbial flora.
      3. Stimulate regeneration.

   The intestinal mucosa is damaged by allergenic foods, commonly consumed
chemicals such as alcohol, NSAIDs and some food additives, cytotoxic drugs,
and toxic microbial flora.
   Food allergy/intolerance. A recent trial found that, in subjects with adverse
reactions to food, the severity of clinical symptoms correlated with the degree
of intestinal permeability, as measured by lactulose/mannitol (Ventura,
Polimeno, & Amoruso, 2006). An immune-mediated reaction to foods can
cause increased intestinal permeability, as is well documented in celiac dis-
ease, and proper treatment results in restoration of intestinal integrity (Vilela
et al., 2008). The basic approach is to determine and eliminate the foods that
induce an immunological reaction. Unfortunately, there is no gold standard to
achieve this. The author prefers challenge testing. Once the worst allergenic
foods are eliminated, a 4-day rotation diet is recommended until proper diges-
tive function is reestablished and the intestines healed. Surprisingly, this may
take only a few weeks. However, this does not mean the allergenic foods can be
immediately reintroduced, and some patients appear to have a lifelong reac-
tion to some foods.
   Bowel microbial flora. The increased permeability caused by bacterial and
viral infections is well known. Less well appreciated is the chronic subclinical
inflammation and intestinal damage caused by commensal microbial agents
that do not cause overt infection (Tlaskalová-Hogenová, 2004).55
   Also underappreciated are the diverse roles a healthy microbial balance
plays in the maintenance of healthy digestion, as well as disease prevention.
These include the production of essential vitamins and cofactors, cidal activity
against pathogenic bacteria, enhancement of intestinal barrier function
through modulation of cytoskeletal and tight junctional protein phosphoryla-
tion, metabolism of toxins, reduction of GI inflammation, and help maintain-
ing immune homeostasis within the gut-associated lymphoid tissues (GALT;
see Ng, Hart & Kamm, 2009).
                                        Naturopathic Medicine and Digestion 217


   The clinical approach is to use low-toxicity antimicrobial agents to kill the
unwanted bacteria and to then reseed with preferred strains. This author has
seen considerable success using Hydrastis canadensis (goldenseal), which has
been shown to be active against many of the undesirable intestinal microflora
(Scazzocchio, Cometa, Tomassini, & Palmery, 2001). Many probiotics and pre-
biotics have been used to reseed the intestines.8 One of the most researched
strains is Lactobacillus rhamnosus (Hawrelak, 2006). Probiotics that support
Bifidobacteria spp. growth include fructooligosaccharides (asparagus, onion,
leek, garlic, artichoke, Jerusalem artichoke, chicory root); galactooligosaccha-
rides (cow’s milk, yogurt, human milk); xylooligosaccharides (oats); and
galactosyl lactose (human milk). Lactobacillus spp. are supported by
β-glucooligomers (oats) and raffinose (legumes, beets).
   Cabbage juice and glutamine. More than 50 years ago, daily consumption
of 1 quart of cabbage juice was found to repair gastric ulcers, which was con-
firmed radiologically (Cheney, 1949). Follow-up research unofficially dubbed
the unknown factor in cabbage juice “vitamin U” (Cheney, Waxler, & Miller,
1956). This factor was later determined to be glutamine, and subsequent
research (with a few exceptions) has clearly documented the efficacy of 500 mg
three times a day in repairing a damaged intestinal mucosal barrier (Li et al.,
2006). Several other natural agents have been shown to decrease excessive gas-
trointestinal permeability, including quercetin, glutathione, omega-3 fatty
acids, and Aloe vera (Rosella, Sinclair, & Gibson, 2000; Lash, Hagen, & Jones,
1986; Kim et al., 2005).

  • High predictability factors include IBS, Type 1 diabetes, migraine, celiac
    disease and food allergies.
  • Medium predictability factors include Type 2 diabetes, inflammatory
    bowel disease, use of ibuprofen, indomethacin, naproxen or aspirin,
    Giardia, Blastocystis hominis, Entamoeba histolytica, Candida albicans,
    atopic dermatitis, psoriasis, asthma, hypochlorhydria, abdominal bloat-
    ing, aphthous stomatitis, and chronic stress.
  • Lower probability factors include taking Vioxx or Feldene, and essential
    fatty acid deficiency.




                                Conclusion

Disorders of digestive function are surprisingly common, and often aggra-
vated by conventional drug interventions. These disorders not only cause signs
and symptoms of digestive distress, but they also cause a diverse range of
218   INTEGRATIVE GASTROENTEROLOGY


systemic diseases from chronic nutrient deficiencies, increased production and
transport of inflammatory mediators, immune complex deposition from food
allergies, and absorption of toxins from aberrant microbial flora. Restoration
of normal digestive function not only relieves symptoms, but often results in
widespread improvement in health and decreased disease burden. Finally, as
amply demonstrated in the example of vitamin D deficiency secondary to sub-
clinical pancreatic exocrine deficiency, nutrient deficiencies can occur with
digestive dysfunctions that are not clinically overt. This requires a high level of
clinical awareness of the many ways digestion become disordered.
                                    22
         Taiji, Qigong, and Digestive Health
                   YANG YANG AND BOB SCHLAGAL




                                key concepts

     ■   Research points to the value of exercise and diet in maintaining
         digestive health.
     ■   Research supports a role for stress reduction techniques in
         limiting digestive distress.
     ■   Carefully conducted studies of tai chi verify a cascade of exer-
         cise and stress reduction benefits stemming from its practice.
     ■   Focus on two core components of tai chi practice, form and
         Qigong, appears to produce the greatest health and stress reduc-
         tion benefits.
     ■   Carefully conducted scientific studies have verified many of the
         benefits of tai chi that have long been claimed by practitioners.
     ■   Tai chi’s focus on deep relaxation and gentle exercise promotes
         improved everyday physical functioning, and should assist in
         regulating the brain–gut axis.
                                       ■




                   Stress Reduction and Exercise



F
        unctional GI disorders are extremely common in the general popula-
        tion. They are not caused by the kinds of organic diseases readily
        assessed by standard diagnostic procedures (x-rays, blood tests and the
like). Instead, these diseases present themselves as abnormally functioning
digestive tracts, and are identified by process of elimination and reported symp-
toms of distress. The most common of these is the irritable bowel syndrome.

                                                                             219
220   INTEGRATIVE GASTROENTEROLOGY


   Experts estimate that 50% to 80% of those suffering from abnormal func-
tioning of the GI tract do not seek medical help and, instead, use over-the-
counter prescriptions and/or a variety of complementary and alternative
therapies (Mullin, Pickett-Blakely & Clarke, 2008).1


   The Foundation of the American Gastroenterological Association, among
   many other medical associations, makes a variety of nonmedical recom-
   mendations for maintaining GI tract health. These include recommenda-
   tions about diet, but also stress reduction and regular exercise.



    The presence or absence of stress and/or physical fitness is seen to play a
role in the onset, mitigation, or prevention of GI disorder symptoms.
    Stress is known to produce wearing effects on the immune, circulatory, and
nervous systems. By contrast, deep relaxation has been shown to produce ben-
efits in these systems (Barnes, Treiber, & Davis, 2001; Carlson, Speca, Pate, &
Faris, 2007; Jones & Heymen, 2008; Kjaer, Bertelsen, Piccini et al., 2002;
Sakakibara,Takeuchi, & Hayano, 1994; Travis & Wallace, 1999; Young & Taylor,
1998). 2,3,4,5,6,7,8. Training in some form of stress reduction tends to produce not
only benefits to these systems, but also assists in preparing individuals to
encounter stresses at a lower level of anxious arousal. This can assist in improv-
ing symptoms and in managing digestive distress (Keefer & Blanchard, 2001;
Toner, 2005).9,10


   Regular exercise is not only important for overall health, but also plays an
   important role in digestion.



   Exercise assists in regulating the rhythms of digestion and, according to the
Center for Colon and Digestive Disease, quiets the bowel: “If exercise is used
regularly and if physical fitness or conditioning develops, the bowel may tend
to relax even during non-exercise periods” (Drossman & Swantkowski,
2008a).11 Exercise can also strengthen abdominal muscles, improving their
ability to push material through the intestines.
   Addressing GI health through stress reduction and regular exercise means
addressing the “brain–gut axis” of digestive health. It has been argued that
functional GI disorders should be understood as a dysregulation of brain–gut
functioning (Drossman & Swantkowski, 2008b).12 Improved regulation of
brain–gut or mind–body connections through regular exercise and cultivated
relaxation should, therefore, play an important role in attaining GI health.
                                           Taiji, Qigong, and Digestive Health 221




                  Components of Tai Chi Practice

Tai chi (also known as t’ai chi chuan, taiji, or taijiquan) is an ancient Chinese
martial art that has long been associated with health promotion. It is practiced
in slow, even, and relaxed movements, with an emphasis on diaphragmatic
breathing and the goal of circulating energy efficiently and thoroughly through-
out the body. It also emphasizes stable, relaxed postures and dynamic balance.
Carefully conducted scientific studies have verified many of the benefits of tai
chi that have long been claimed by practitioners. These include positive effects
on blood pressure, oxygen uptake, cardiovascular fitness, bone density,
strength, balance, and agility, as well as improved immune function and
enhanced self-efficacy (Yang & Grubisich, 2008; Yang, 2005; Yang et al., under
review) To date, there appear to be no studies of tai chi exercise in relation to
GI health, though this is also one of the benefits that Chinese masters have
long believed results from this practice.

  Training the mind–body connection (by combining exercise and meditation)
  is the heart of traditional tai chi training.



    This connection is made holistically, in a variety of mutually reinforcing
ways. This is accomplished most obviously through the complementary prac-
tices of Qigong and form.
    Form consists of a choreographed sequence of movements derived from
various Chinese martial arts. These are meant to improve efficiency of move-
ment (balance, strength, and agility) and to nurture energy and stamina while
improving the mind–body connection. This is the most visible and character-
istic aspect of tai chi training.


                                   QIGONG

Qigong, however, holds an equal if not more central role. Qigong (energy cul-
tivation) is exercised through both static and dynamic methods. Static Qigong
includes standing, sitting, and lying-down meditation. Standing involves hold-
ing specific postures and relaxing into a calm, meditative state. This is one of
the ways that tai chi players cultivate the deep relaxation and strong natural
structures that are to be used while executing form practice. Although holding
a particular posture can be initially somewhat demanding, the muscles are
222 INTEGRATIVE GASTROENTEROLOGY


progressively loosened and the mind is settled on the dantian, the area that
radiates from the naval upward to the lower ribs and downward to the pelvic
floor. (The dantian is understood to be the center for cultivating and storing
energy). In this way, breathing relaxes, deepens, and becomes diaphragmatic.
It is through practice in this way that qi (internal energy) is cultivated. With
continued exercise, one can enter a state of great calm during static Qigong.
(Sitting and lying-down meditation are also central, and used to attain deep
calm and relaxation). An old saying (taiji tai he) holds that “peacefulness is a
requisite of tai chi” (Yang & Grubisich, 2008). It is also said (Qì gōng néng qū
bìng, yuán yóu zài sōng jìng) that “relaxation and tranquility/quietness are the
reasons why Qigong can heal you” (Yang & Grubisich, 2008). Lastly, it is often
said (Yào bŭ bù rú shí bŭ, shí bŭ bù rú qì bŭ, qì bŭ bù rú shén bŭ), “To improve
your health, medicine is not as good as food/nutrition; food/nutrition is not as
good as Qi(gong); Qi(gong) is not as good as spiritual nourishment” (Yang &
Grubisich, 2008). The “spiritual” component—an important facet of stress
reduction—is nurtured in tai chi during static Qigong through the use of pos-
itive and tranquil imagery.


                             DYNAMIC QIGONG

In dynamic or moving Qigong, one focuses on circulating qi, or energy,
through the body by coordinating slow, relaxed, outward movements with
movements of the dantian, using reverse breathing. In reverse breathing one
inhales slowly and gently, drawing the abdominal area (including the pelvic
floor) gently inward; in exhalation, the diaphragm relaxes and moves outward.
The purpose of reverse breathing is to gather, guide, and release the energy
cultivated through static Qigong. This pattern of breathing massages and con-
ditions the internal organs, as well as the diaphragmatic musculature. As with
static Qigong, moving Qigong is used to cultivate energies (skills) to be used
during the more complex and dynamic demands of form practice. In particu-
lar, dynamic Qigong helps to activate the movement of the dantian, from
which all movement in tai chi form must emanate. An example of such an
exercise is called “gathering qi (energy) from nature.” In this exercise, one
exhales while slowly reaching out the arms horizontally and open-handed;
while inhaling, one pulls the hands back toward the dantian, at the same time
gently closing the fists. (Illustrations of this and other important dynamic
Qigong exercises can found in Yang (2007), and an explanation of the physio-
logical effects of core tai chi/Qigong practices can be found in Yang and
Grubisich (2008).
                                            Taiji, Qigong, and Digestive Health 223




                                 TAI CHI FORM

In tai chi form, one incorporates and extends what is developed through
Qigong into a more complex arena of activity. The slow, gracefully executed
choreography of form further helps to nurture and build energy, to improve
the mind–body connection, and to train efficient body movement. Again, each
movement in the form originates in the dantian and extends from there (in
coordination with breathing) into the outer limbs. And, through the more
complex expressions of form practice, the dantian rotates in all dimensions
of movement in order to extend energy/movement in the various required
directions.


          IMPROVING BRAIN-GUT FUNCTION THROUGH TAI CHI

As stated above, tai chi has long been viewed in China as a tool for recovery
and health. It appears that the core practices of this art might play a likely role
in moderating some of the discomfort of functional GI disorders, and might
contribute to healing and promoting general GI health. The focus on deep
states of relaxation, the gentle exercise of the diaphragmatic terrain, and the
extension of these into complex actions, may allow for the reregulation of dys-
regulated brain–gut function.
   In their comprehensive review of the therapeutic benefits of tai chi, Klein
and Adams (2004) found that research confirms a variety of therapeutic
benefits of tai chi practice with respect to improved physical functioning and
quality of life.


   Tai chi leads to improvements in cardiovascular function, strength, balance,
   agility, flexibility, and kinesthetic sense, as well as pain reduction and
   enhanced immune response.




   Further, a recent article on the Mayo Clinic’s online “Stress Reduction” por-
tion of their website points to the support that scientific study has given to
many of tai chi’s ancient claims. Summarized in Table 22.1, it underscores the
depth and variety of tai chi’s health benefits, ones that reach well beyond stress
reduction alone.
224   INTEGRATIVE GASTROENTEROLOGY


              Table 22.1. Mayo Clinic Summary of Tai Chi’s Empirically
                             Supported Health Benefits

•   Reducing anxiety and depression
•   Improving balance, flexibility and muscle strength
•   Improving sleep quality
•   Lowering blood pressure
•   Improving cardiovascular fitness in older adults
•   Relieving chronic pain
•   Increasing energy, endurance and agility
•   Improving overall feelings of well-being


   We contend that relieving pain and the improved overall physical function-
ing implied across other categories would account for the potential effect of tai
chi on functional GI disorders. We also note that for all of the benefits the
research has documented, the vast majority of studies on tai chi have been
based on tai chi form practice alone. We might expect to see evidence of more
profound benefits when future tai chi research incorporates Qigong—especially
static Qigong.


                                     Conclusion

No carefully controlled scientific studies have yet examined the effect of a tra-
ditional tai chi curriculum on the mitigation of functional GI disorders.
Nonetheless, it is our experience that integrating Western medical approaches
with Eastern methods of health cultivation, like tai chi, holds significant poten-
tial for improved regulation of the brain–gut axis. This belief has been shared
by generations of tai chi practitioners based on sustained anecdotal evidence.
(Yang & Grubisich, 2008) Further, tai chi offers an approach to a variety of
health issues, has no undesirable side effects, is cost effective, and has com-
paratively low post-intervention dropout rates. (Yang et al., 2008)
                                    23
          Digestive Health and Reiki Energy
                                BETH NOLAN




                                key concepts

     ■   Reiki is an energy-based touch therapy that rebalances the
         human energy fields.
     ■   Reiki may improve digestive health by focusing on the energetic
         origins of disease and discomfort in the physical body.
     ■   Reiki has been shown to reduce stress, rebalance the autonomic
         nervous system, relieve acute and chronic pain, and ameliorate
         anxiety and depression, which may benefit patients with stress-
         related functional digestive disorders.
                                       ■




R
        eiki improves digestive health in several key ways. Despite their differ-
        ences, each of the following modalities promotes relaxation, improves
        circulation, calms the nervous system, and helps balance mind, body
and spirit, while complementing the others. In this section, we will explore
these modalities and focus on practical techniques for improved intestinal
health.
   Abdominal massage therapy techniques stimulate peristaltic contractions,
helping push waste through the intestines. In this way, massage manually
moves waste out of the body. Many yoga postures are a form of self-massage:
by doing twisting poses and compressing the torso, one indirectly massages
the intestines and digestive organs, improving blood and oxygen flow to these
areas. Finally, Reiki—an energy-based touch therapy—may improve digestive
health by focusing on the energetic origins of disease and discomfort in the
physical body. These techniques all help eliminate toxins and release chronic
patterns in muscle tissue and the energetic body.



                                                                             225
226 INTEGRATIVE GASTROENTEROLOGY




                                     Reiki

Reiki is the Japanese term for universal life energy, a visible and palpable energy
that infuses and permeates all living forms (Usui & Petter 2003; Bohm, 1980;
Zukav, 1989).
    Reiki as a healing technique is an energy-based touch therapy that allows
life force energy, or chi, to recharge, realign, and rebalance the human energy
fields (Honervogt, 1998). Similar to other touch therapies, such as therapeutic
touch and healing touch, Reiki involves the use of energy directed by the prac-
titioner’s hands to strengthen the recipient’s ability to heal. It also involves a
mind–body connection.
    Reiki is an ancient energetic healing practice believed to have originated
thousands of years ago in the Tibetan sutras, and then lost. It was rediscovered
in the 1800s by Dr. Mikao Usui, a Japanese monk (Zukav, 1989). Nurses and
others have observed that Reiki may have relaxation and stress-management
benefits, and may lessen pain and promote inner healing. However, there is
little empirical evidence to show just how it works (Miles & True, 2003; Bullock,
1997; Nield-Anderson & Ameling, 2000). Within the last 10 years, the use of
Reiki has increased among nurses, physicians, and rehabilitation therapists,
and is practiced in hospitals, hospice care, emergency departments, psychiat-
ric settings, nursing homes, operating rooms, family practice, and many other
settings (Barnett & Chambers, 1996). A review of the medical literature fails to
produce any published evidence that Reiki can benefit digestive health or dis-
ease. However, studies of its ability to reduce stress, rebalance the autonomic
nervous system, relieve acute and chronic pain, and ameliorate anxiety and
depression have been published (Shiflett, Nayak, Champa, Miles, & Agostinelli,
2002; Wardell & Engebretson, 2001; Olson, Hanson, & Michaud, 2003; Mackay,
Hansen, & McFarlane, 2004). Functional digestive disorders (IBS, non-ulcer
dyspepsia, non-cardiac chest pain, etc.) and inflammatory bowel disease are
chronic illnesses characterized by acute and chronic pain, stress-provoking
flares, frequent psychopathology, and improvement of intestinal symptoms in
response to mind–body therapies. Thus, Reiki, which has been shown to
improve these core imbalances of pain and dysfunction, is likely to benefit
patients with many digestive illnesses.
                                   24
    Self-Care Journaling for Digestive Health
                              DANNA M. PARK




                                key concepts

     ■   Journaling is a cost-effective therapy that improves immune
         system function and aids in “brain–gut axis” regulation.
     ■   Journaling may be used as an adjunctive therapeutic tool in
         treating a variety of GI conditions, including IBD, IBS, and
         functional abdominal pain.
     ■   Expression of emotions, such as fear or stress, through writing
         can lead to improvement in GI symptoms and well-being, most
         likely via neurotransmitter effects.
     ■   Journaling may be taught to patients quickly and easily in the
         office setting.
                                       ■




                    Self-Care Journaling: Theory



J
    ournaling is the process of self-exploration and expression via writing.
    Although keeping a diary is often used in gastroenterology for the elucida-
    tion of connections between foods, emotions, events, and symptoms, the
modality of journaling, also called expressive writing, may be underused.
Journaling can not only help establish and verify connections between stres-
sors/situational events and GI symptoms, it can also be a therapeutic tool in its
own right, allowing the patient to express emotions in a safe, secure, and pri-
vate environment. Although we use lay language frequently to express the




                                                                             227
228 INTEGRATIVE GASTROENTEROLOGY


mind–body connection between the gut and the brain (for example, “I knew it
was OK because I could feel it in my gut,” or “It was such a shock, I felt as if
someone had kicked me in the stomach”), there is now no doubt about the
physiologic connection between the brain and GI tract. This connection pro-
vides the theoretical evidence for using a therapy such as journaling.
    The “brain–gut axis” defines the endocrinologic links between the brain
and the GI tract. Numerous neurotransmitters and neuropeptides are involved,
including serotonin (95% of the body’s serotonin is in the GI tract, whereas 5%
is in the brain), norepinephrine, dopamine, cortisol-releasing hormone (from
both the hypothalamus and the enterochromaffin cells in the colon), inter-
feron gamma, substance P, VIP, and many others. Imbalances in these neu-
rotransmitters can lead to GI symptoms. For example, in the diarrheal form of
irritable bowel syndrome (IBS), high levels of serotonin inhibit norepineph-
rine, thereby increasing acetylcholine levels and causing increased gut motil-
ity. Conversely, a high adrenergic state with elevated levels of norepinephrine
decreases serotonin levels, inhibits acetylcholine, and decreases GI motility
and tone, consistent with the constipation form of IBS (Crowell, Schuster, &
Talley, 2000).


         Journaling: Summary of Medical Literature

The implication of psychosocial factors, emotional and physical abuse, coping
skills, and stress in relation to exacerbations of IBS and inflammatory bowel
disease (IBD) has been researched. In children with functional abdominal
pain, accommodation to the pain by responding to it as a challenge, with
determination to continue normal activities as much as possible, resulted in
positive coping mechanisms that strengthened their internal and external
coping skills Conversely, those who responded to the pain with fear were
more likely to limit their daily activities due to their pain, which propagated a
cycle of pain anticipation, focus on pain, limitation of activities, loss of psy-
chosocial developmental milestones, and eventually the likelihood of serious
anxiety and clinical depression (Walker & Jones, 2005). Patients with high
levels of prolonged stress who have inflammatory bowel disease have more
relapses in their disease (90%) as opposed to those who have lower stress levels
(relapse rate 40%; see Levenstein et al., 2000). Stress affects intestinal perme-
ability, decreasing the barrier function of the gut mucosa, which may hasten
inflammatory GI problems in patients who are susceptible, or trigger a relapse
in patients who already have such illnesses (Hollander, 2003). Literally
                                      Self-Care Journaling for Digestive Health 229


“swallowing emotions” and keeping them inside may be a trigger for IBS in
women, as in one study where women with IBS had higher rates of emotional
abuse, self-blame, and self-silencing (Ali et al., 2000).
   Expression of emotions such as fear or stress through journaling has shown
to decrease disease severity in conditions such as post-traumatic stress dis-
order (PTSD; see Davidson & Robison, 2008), rheumatoid arthritis, and
asthma (Smyth et al., 1999). Physical health benefits include improved immune
system function, indicating some kind of effect in the hypothalamus-pituitary-
adrenal axis and/or the sympathetic-adrenal-medullary axis. Improved mood
and affect, and a feeling of higher psychological well-being, may implicate
effects in neurotransmitters such as serotonin and dopamine (Baikie and
Wilhelm, 2005). Given these findings, there may be a strong role for journaling
as a component of a treatment plan for a variety of GI illnesses, especially in
functional abdominal pain, IBD, and IBS.


 Summary: Journaling Clinical Practice and Guidelines

Journaling is a simple, cost-effective adjunct to a GI treatment plan, and can be
introduced to the patient as a therapy that improves and regulates the immune
system and may help “rebalance” the brain–gut axis. Instructions to the patient
should include emphasis that their writing is for him or her alone, and does
not need to be shared with anyone unless he or she chooses to. Patients should
be counseled to find a quiet place where they will not be disturbed, and to pick
a situation that is “emotionally charged” for them, such as an upsetting or trou-
bling experience in their life. In whatever form they choose (prose, poetry,
free-form without punctuation, etc.), the patient should write continuously
about the experience for 20 minutes, expressing his or her deepest feelings
about it and about any insights he or she has had as a result of their experi-
ences. Patients are encouraged to write for 20 minutes each day, for at least
4 days (the topic they choose may be different each time), and to note any
change in their physical and/or emotional state. If helpful, this is a practice that
can be continued on a daily basis. Potential adverse effects of journaling
include emotional distress from the experience of remembering upsetting
experiences, and patients should be asked to contact their healthcare provider
if they experience such distress—the processing of emotional events may also
require mental health counseling and support. An excellent patient handout
with journaling instructions is reproduced in Table 24.1, from David Rakel’s
textbook Integrative Medicine (Second Edition; 2007).
230 INTEGRATIVE GASTROENTEROLOGY


                                Table 24.1. Patient Handout
Using journaling to aid digestive health

What Is Journaling?

Journaling is the process of writing about times in our lives that were stressful or
traumatic. It provides an avenue for the expression of thoughts and memories that may
have been internalized. These repressed emotions can often lead to a worsening of
physical symptoms. William Boyd, a pathologist at the turn of the 19th century,
described this process well; he wrote, “The sorrow that hath no vent in tears, may make
other organs weep.” Journaling is one type of therapy that can be used to aid this process.

How Does It Work?

Studies have found that if we express feelings about a time in our lives that was very
traumatic or stressful, our immune function strengthens, we become more relaxed, and
our health may improve. Writing about these processes helps us organize our thoughts
and create closure to an event that the mind has a tendency to want to suppress or hide.
This can be done in the privacy of your home and requires only pen and paper.

Does Anybody Need to Read It?

No. You can share your writings with others if you desire, but no one needs to read what
you write. The most benefit comes from writing the document, and the words can be
thrown away if you desire. In fact, some people find that burning or destroying the
document can add ceremony to the process. Letting the wind carry away the smoke can
act as a positive metaphor that helps them let go, forgive, and heal. Others prefer to keep
their writings private, so they can look back on them and see how they have grown from
the events.

Are There any Side Effects or Things I Should Be Aware Of?

Recalling stressful memories can make you feel uncomfortable for a few days. If this
were not the case, the body would not use so much energy trying to repress them.
The benefits of journaling become most apparent weeks to months after writing.

This process can bring back into mind some frightening events for which you may need
the help of a licensed counselor. Please notify your medical practitioner if you develop
feelings that would benefit from further discussion. This is often the first step toward
creating an environment that will promote healing from within.

How Is It Done?

There are many different ways to express emotions. Journaling is simple and inexpensive,
and can be done independently. It would be beneficial to keep a regular journal to write
about events that bring anger, grief, or joy. But if that is unlikely, and you just want to
deal with a specific event or see whether this technique will help your condition, follow
these steps:
                                             Self-Care Journaling for Digestive Health 231


                                  Table 24.1. (Continued)
Using journaling to aid digestive health

   1. Find a quiet place where you will not be disturbed.
   2. Using pen, pencil, or computer, write about an upsetting or troubling experience in
      your life, something that has affected you deeply and that you have not discussed at
      length with others.
   3. First describe the event in detail. Write about the situation, surroundings, and
      sensations that you remember.
   4. Then describe your deepest feelings about the event. Let go and allow your
      emotions to run freely in your writing. Describe how you felt about the event then,
      and how you feel now.
   5. Write continuously. Do not worry about grammar, spelling or sentence structure.
      If you come to a “block,” simply repeat what you have already written.
   6. Before finishing, write about what you may have learned or how you may have
      grown from the event.
   7. Write for 20 minutes for at least 4 days. You can write about different events, or
      reflect on the same one each day.
   8. If the process proves helpful, consider keeping a journal regularly.

How Can I Learn More?

An excellent resource for more information on this subject can be found in Opening Up:
The Healing Power of Expressing Emotions by James Pennebaker (Guilford Press, 1997).

There is also a comprehensive web site on the subject: www.journaltherapy.com

This article was published in Integrative Medicine, Second Edition. David Rakel, Chapter 98, page
1043. Copyright Elsevier 2007.
                                     25
                               Spirituality
                          FREDERIC C. CRAIGIE , JR.




                                 key concepts

      ■   Spirituality has to do with what is “vital and sacred” in people’s
          lives. It may or may not be expressed in religious involvement.
      ■   Spiritual care begins with the healing intention and compas-
          sionate presence of clinicians.
      ■   Spiritual care may also take the form of supportive and encour-
          aging conversations with patients about what gives their lives
          meaning and purpose, and in identifying particular spiritual
          practices that bring patients peace and comfort.
      ■   Chaplains and other spiritual care professionals help patients
          and families to address especially painful spiritual issues and
          needs.
                                        ■




S
       pirituality frames a broad and central aspect of human experience having
       to do with meaning and purpose, life force, and enlivening and sustain-
       ing relationships with spirit. (Craigie, 2010) Former Surgeon General C.
Everett Koop, for instance, has defined spirituality as “the vital center of a
person; that which is held sacred.” (Koop, 1994)
   Spirituality is not synonymous with religion. For some people, “the vital
center” and “sacredness” are expressed in the context of religious traditions
and communities; for other people, spirituality is a more personal journey, or
one that is not aligned with a particular religious faith.
   There has been lively interest in the interface of spirituality with medicine
(e.g., Levin, 2001) and with integrative medicine (Craigie, Silverman & Maizes,
2007) in recent years. The emerging literature suggests that spirituality is
important in healthcare for a variety of reasons. First, the spirituality of

232
                                                                     Spirituality 233


clinicians—variously framed as “healing presence” (McDonough-Means,
Kreitzer & Bell, 2004), “compassionate presence” (Puchalski, Lunsford, Harris,
& Miller, 2006), “intention,” (Shealy & Church, 2006), “mindfulness” (Schmidt,
2004), and even “love” (Levin, 1999)—plays a substantial role in the healing
process. A sample of family physicians, for instance, expressed the view that
their own centeredness and grounding helped them have a more peaceful
presence and be more available as instruments of healing in other people’s
lives. (Craigie & Hobbs, 1999)
    Second, the spirituality of patients is important because there are strong
epidemiological relationships between spiritual and religious beliefs and prac-
tices, and a variety of outcomes in the arenas of subjective well-being, coping,
mental health, and health. (Miller & Thoresen, 2003; Tsuang, Simpson, Koenen,
Kremen & Lyons, 2007) Spirituality promotes wholeness, energizes positive
lifestyle changes, and provides a source of strength and solace in adversity.
    Literature exploring connections between spirituality or spiritual practices
and gastroenterological disease is sparse. One may argue, however, that the
spiritual journey toward peacefulness and meaning: (a) speaks to the fre-
quently implicated relationship between stress and GI disease (Bhatia &
Tandon, 2005), and (b) may underlie some of the benefits of psychosocial
interventions in this arena, such as the effects of cognitive-behavioral therapy
on symptoms and quality of life in patients with irritable bowel syndrome.
(Lackner et al., 2007; 2008) A recent review has proposed incorporating con-
structs of mindfulness and acceptance—both of which have deep traditional
and Eastern spiritual roots—into mind–body treatment protocols for irritable
bowel syndrome. (Naliboff, Fresé & Rapgay, 2008)


             Spiritual Care in Integrative Medicine

Spiritual care begins with compassionate presence (Puchalski, 2004), and with
the ways compassion and healing intention are embodied in the clinician.
(Craigie, 2010) A family physician describes this well:

  “Before I go in a room, I stand briefly outside the door, feet flat on the floor,
  and remind myself why I want to be there for the patient I am about to see.”
                            (Interview notes from Craigie and Hobbs, 1999)

   Healthcare practitioners may pursue many approaches, such as meditation,
prayer, affirmations, and devotional or inspirational readings, to cultivate a
spirit of compassion, mindfulness, and healing intention as they move through
their days.
234 INTEGRATIVE GASTROENTEROLOGY


    Clinically, spiritual care is less defined by specific techniques than it is by
conversation with patients about what matters to them—what is “vital” and
“sacred.” (Craigie, 2010) Organizational consultant Margaret Wheatley
observes that “real change begins with the simple act of people talking about
what they care about.” (Wheatley, 2002) Providing the opportunity for patients
to talk about their hopes, their suffering, their dreams and values—wanting to
do an honest day’s work, wanting to show courage and grace to a beloved child
in facing serious illness, wanting to work their way through forgiveness and
reconciliation with an abusive parent—helps patients be affirmed, focused,
and empowered in their spiritual journeys.
    There are many ways of joining this conversation. There are a number of
templates for spiritual assessment (with subsequent conversation) in health-
care; two of the more prominent are FICA (Puchalski, 2006) and HOPE.
(Anandarajah & Hight, 2001) Both these frameworks pose four questions (e.g.,
the “I” from FICA: “What importance does faith or belief have in your life?”)
for efficiently surveying a person’s spirituality and how it relates to his or her
health and medical care. Clinicians may also utilize single-item, open-ended
conversation starters, such as “Do you have any religious or spiritual beliefs or
practices that you would like me to know about?” (Astrow, Puchalski &
Sulmasy. (2001)
    As an alternative, clinicians may also join the conversation with language of
meaning, purpose and passion: “What keeps you going? What sustains you?
Where do you find strength? What are the things that are really important to
you? What do you take pride in? What do you hope for? What helps you to be
more peaceful and centered? What do you hope the legacy of your life will be?
What are you really passionate about? When do you feel most alive?”
    As patients talk about hopes and values, and how they want to live their
lives, the “intervention” is to support and encourage them to do so: “We’ve
talked about some of the uncertainties in the future for you with stomach
cancer, and you’re saying today that it’s really important for you to have a better
relationship with your son in Minnesota. Where do you see yourself going
with that, and what would some next steps be?” Physicians and other health-
care professionals can effectively pursue many such conversations. As patients
raise more serious spiritual struggles and issues, however (“Why would the
God I have served all my adult life visit me with this terrible disease?”), referral
to spiritual care professionals such as chaplains, clergy, and spiritual directors
is often helpful.
    In terms of specific spiritual techniques, patients often take the lead when
they are asked. Patients often report particular practices like prayer or devo-
tional reading, for instance, when they are asked about where they find strength
and what helps them be more peaceful and centered. Clinicians can be aware
                                                                  Spirituality 235


of a range of practices and pursuits as they speak with patients, and may make
their own suggestions. Examples include mindfulness and meditative prac-
tices (Kabat-Zinn, 2005), rituals, ceremonies and sacraments (Hammerschlag
& Silverman, 1997), participation in religious or spiritual communities, service
or volunteer work, and creating or journeying to sacred places.


                                  Summary

Spiritual beliefs and practices are strongly associated with well-being and
health. Clinicians incorporate spirituality in healthcare by cultivating their
own centeredness, intention, and compassionate presence with patients.
Clinicians also support patients’ spiritual resources by encouraging patients to
express the values and activities that are “vital and sacred” in their lives. While
spirituality in medicine is not defined by specific techniques, there are often
particular practices, such as meditation, prayer, forgiveness, devotional read-
ing, and community gatherings that draw upon patients’ spirituality as a heal-
ing force. Chaplains and other spiritual care specialists can often be very
helpful clinical partners when patients are particularly distressed and bur-
dened by spiritual issues.
                                    26
      What Patients Want from Their Doctors
                      DONNA JACKSON NAKAZAWA




A
          fter my book, The Autoimmune Epidemic, came out, I heard from
          thousands of people from every conceivable background who suf-
          fered from a wide range of diseases. In conversations and emails, they
shared with me their experiences of illness and treatment, their hopes, disap-
pointments, and lessons gleaned. At the heart of each of their stories is the tale
of a patient’s relationship with his or her doctor and how it helped—or hin-
dered—the patient’s journey toward wellness. Their stories, along with the
experiences of patients I interviewed while researching The Autoimmune
Epidemic, and my own decade-long journey as a patient in the American med-
ical system, have taught me what American patients want—and desperately
need—from their doctors.
    Patients love to tell “doctor stories”; the good, the bad, and the unfortunate.
Often, those suffering from illness want to tell me stories about the first doctor
who really (finally) listened to them, that compassionate healer who went the
unexpected extra mile to help solve the mystery of their illness. They want to
share the tale of the practitioner who gave them a clear message of hope—a
conviction that they could be well—which became a mantra that settled some-
where in their psyche and played a part in nudging them toward recovery. But,
more often, the stories they tell me are about doctors who didn’t listen, or
didn’t seem to care, or dismissed them as malingerers; practitioners whose
obvious condescension still rankles them to this day.
    This concern with what makes a good doctor isn’t surprising when you con-
sider recent statistics that 133 million Americans suffer from a chronic disease,
be it heart disease, cancer, severe back pain, arthritis, autoimmunity, or a
plague of other challenging ailments that derail normal life. These chronically
ill patients often traipse from one healthcare professional to the next in search
of answers and relief—a process that can take years. Indeed, the average auto-
immune disease patient, of whom there are now 24 million in the United States
alone, sees four doctors over four years before receiving a proper diagnosis.
This search for a good doctor can be emotionally arduous. Recent surveys

236
                                      What Patients Want from Their Doctors 237


conducted by the American Autoimmune Related Diseases Association reveal
that 45% of patients with diagnosed autoimmune diseases were told that they
were hypochondriacs at some point in their medical care. Increasingly, patients
who feel they need more than what traditional medicine can offer go “off the
reservation,” seeking help from holistic and alternative healthcare specialists
as well.
   Whether a patient seeks the help of traditional or alternative/complimentary
practitioners (or, as a majority of patients now do, both) all “healer stories”
really contain the same key themes. If the good healthcare practitioner were a
recipe, the four integral ingredients would be these:
   1) Compassion. Patients know whether healthcare professionals have it or
they don’t. Doctors who express compassion for their patients’ pain and cir-
cumstances stand out immediately. I know a well-known transverse myelitis
and multiple sclerosis specialist at a major medical institute who, when he
diagnoses a patient, feels so deeply for them that he always hands them his cell
phone number, because he knows there will be “dark moments” where they
will have “sudden, urgent questions” that can’t wait for the next clinic visit.
And I have heard his voice crack when he talks about the loss of a young patient
he could not save. Another physician revealed the strength of his character
when, after diagnosing me with Guillain Barre Syndrome, a disease in which
the body becomes increasingly paralyzed degree by steady degree, he sat with
me in a small, white exam room at Johns Hopkins, talking with me quietly for
an hour and a half, while my mother and husband rushed to arrange admis-
sion to the hospital, collected my bags from home, and arranged for child care.
He stayed with me, he said, because he didn’t want me to wait alone after the
devastating news he’d just delivered—even though nurses were rapping on the
exam room door, and his patient waiting room was near to overflowing, and it
no doubt meant he would go home much later that night to his family than he
might like. He is a very decent man, a good man, and the numerous patients I
know who see him use those words to describe him whenever they mention
his name.
   On the other hand, there are doctors and practitioners who make it clear
that you are taking up too much or their time, or wearing their patience thin
with your illness—mentally placing you, perhaps unconsciously, somewhere
in the category of the famous Freudian hysterics (especially if you are a
woman). They don’t respect their patients. I can’t help but think of the story of
one young woman, now president of a large advocacy group for autoimmune
disease, who was in her early 30s when she began suffering from severe muscle
fatigue and disabling weakness. Her doctor, whom she’d seen eight times, was
unable to come up with a diagnosis. “We’ve given you every test known to man
but an autopsy,” he said. “Would you like one of those, too?” She was later
238   INTEGRATIVE GASTROENTEROLOGY


diagnosed with myasthenia gravis by a doctor who took time to understand
the complex portrait presented by her symptoms and lab work. I recall, in my
own health tribulations, seeing a doctor who, despite my history of severe
autoimmune issues, paralysis, and other complications, yelled at me in his
office: “Yesterday you came in here saying you were nauseated, and now today
you say you have diarrhea! Make up your mind, which one is it?”
   The next day I ended up in the emergency room and was hospitalized.
While I was there I was treated by a GI specialist who came into my hospital
room on several different occasions at the end of the day and sat down, his
briefcase on his lap, to talk to me about pursuing wellness strategies outside
the box. The hospital by that hour was growing quiet and dark, he had already
seen me earlier in the day during the requisite rounds, and his day was now
done. Yet, he had enough compassion for a mom with two young children to
take time to educate me about how to approach my GI problems more holisti-
cally—advice which, over the next two years, would lead to turning around my
GI symptoms. Of course, delivering compassion means building time into the
patient–doctor relationship to allow for that extra, meaningful exchange—a
conundrum in a healthcare climate that has shaved the average doctor’s visit
down to a mere matter of minutes. I would bet that a doctor who has been
consistently stripped of time has also been stripped of compassion.
   The question healthcare professionals need to ask themselves is this: which
type of practitioner would you prefer to see? The one who gives you their cell
number, or sits with you after a tough diagnosis, or the one who speaks to you
disrespectfully or impatiently? Granted, most practitioners fall somewhere in
between, but patients search hard and long for the former, and never forget
them when they are lucky enough to find them. Compassionate doctors emerge
as central figures when patients share their healing stories.
   2) A Deep and Growing Fund of Knowledge. Of course, compassion alone
hardly makes for a good healer. If a healthcare specialist doesn’t possess a deep
fund of knowledge—and the curiosity to constantly keep abreast in their field
to extend their acumen—all the compassion they can muster can’t make up for
what they just don’t know. One woman consulted three local doctors, several
times each, over eight months; they all missed her multiple sclerosis. She then
saw a university hospital specialist who suspected MS in the first visit, ordered
a series of tests, and diagnosed her disease that same week. “Why didn’t those
other three doctors even know enough to suspect MS?” she asks. Another
young woman described suffering from severe thirst, dizziness, fatigue, and a
20-pound weight loss over three weeks, but the doctor she was seeing dis-
missed her complaints and told her, “You just need to gain some weight. Go
have a banana split and you’ll be fine.” A few hours after that appointment, a
friend found her in a near-diabetic coma on her sofa and rushed her to the
                                        What Patients Want from Their Doctors 239


emergency room, where she was diagnosed with Type 1 diabetes. “How did he
miss it, given the state I was in?” she asks. These stories become the doctor-
who-didn’t-get-it lore that patients so often vent about with each other.
   But patients also share positive stories about practitioners who, although
they may not have ready-made answers, commit time and energy to solve their
patient’s case. One patient suffering from severe fatigue and poor appetite for
half a year told me of his relief in finding such a doctor. He had already been
to two doctors who “couldn’t find anything” (one of whom handed him anti-
depressants). A third physician confessed that he, too, was perplexed, but he
took a different approach. He put his hand on his patient’s shoulder and reas-
sured him, “I don’t know what’s causing this, but I promise you we’re going to
figure this out together.” It took several weeks and much diligence to deter-
mine that he was suffering from an uncommon parasite infection. Likewise,
another patient talks about meeting a doctor who surprised and moved her by
asking her to “start by telling me about the last time you were well.” This patient
confesses, “No one had ever asked me anything like that before.” Indeed, this
doctor’s narrative approach to obtaining her patient’s medical history was just
the first of many ways in which she showed her commitment to helping this
patient toward recovery.
   3) Open to Complementary Approaches. In a healthcare world in which
the majority of patients now use alternative medicine, it’s a given that patients
want physicians whose fund of knowledge includes being well-versed in com-
plementary medicine. Patients seek doctors who are able to offer advice on
food as medicine, safe supplements, exercise, stress management, and who are
willing to move beyond disease labels to delve into what combination of fac-
tors may lead to a patient to falling ill in the first place. But this kind of physi-
cian can be tough to find. Hundreds of patients (including many with
inflammatory bowel disease, a disease whose course is known to be influenced
by diet) have told me that the physician or specialist they see never mentions
diet or supplements to them at all. Yet, by working with a nutritionist whom
they seek out, or by researching the role of nutrition in their ailments on their
own, they are able to help turn their disease around.
   When patients find the rare physician who competently blends Western
and complementary approaches, they stick with them, and they refer other
patients to them as well. One young woman with rheumatoid arthritis told me
about her relief in finding a doctor who not only helped her sort out the
side effects among her choices of medications, he also emailed her recent
groundbreaking studies to convince her to make dietary changes that would
improve her health. Patients today take a proactive role in their own wellness
journeys—and they view allopathic physicians who rely solely on drugs as
being out of touch with the growing data that exists on how lifestyle factors
240   INTEGRATIVE GASTROENTEROLOGY


impact one’s well-being. Of course, office visits that allow time for discussions
of diet and lifestyle, as well as writing prescriptions, take longer—and patients
are choosing healthcare practitioners who have built that buffer time into their
patient schedule.
    4) A Champion of Hope. Patients seek healthcare specialists who avoid
focusing on negative outcomes and referring to diseases as “degenerative” or
“progressive,” and who, instead, offer as part of their Rx the conviction that
their patient can and will have a hopeful, positive outcome. Indeed, patients
love to tell stories about how their practitioners’ encouraging statements of
hope and healing, statements that emphasize the miracles the human body is
capable of, often become the patient’s own inner affirmation that they can and
will be well. One woman’s doctor told her, during a particularly difficult time
in her battle with cancer, “You are going to beat this and you are going to live
a totally normal life.” This doctor couldn’t know that to be true, but by saying
it with conviction, she helped her patient to believe it too, and might just have
helped to save her patient’s life. At least her patient—ten years later—believes
that her doctor’s faith helped to pull her through.
    In my own health history, this certainly has been the case. The neurologist
who sat beside me those long hours after diagnosing me with Guillain Barre
later saw me through a repeat episode of the disease. The second time Guillain
Barre strikes (and it is rare for it to strike twice) it is much more damaging. It
took me five months to learn to walk unaided again. During this time, several
other neurologists at the hospital where I was being treated made it clear that
they were dubious that I would ever regain my mobility. I asked my neurolo-
gist, “Why are they all warning me to prepare for the worst?” He shook his
head. “Don’t listen to that,” he said. “I’m your doctor and I know you. Patients
have recovered and been able to walk again after having Guillain Barre twice.
I know you. They don’t know you. And I know that if it can be done, if it is pos-
sible, then you will do it.” Could he have known, as he said these words, that his
reply would stay with me day in, day out, that long, hard summer, as I spent
hours in grueling physical therapy, first learning to walk to the door of my
bedroom, then finally—five months later—down the steps and out the door?
    Healthcare professionals who offer up compassion, a deep fund of knowl-
edge of both Western and complementary treatments, and a heartfelt prescrip-
tion for hope, facilitate better patient outcomes. But that’s not the only good
news. In my work, I also talk to and hear from numerous doctors and health-
care practitioners who tell me that when they offer this “recipe” to their
patients, their lives as healers become imbued with greater meaning, and their
own work lives are all the more joyful and rewarding.
                               27
           The Value of Support Groups
            PEARL L. LEWIS AND GERARD E. MULLIN
                with a foreword by Bernie Siegel




                            key concepts

  ■   Community support for restoring the health of ill individuals
      has been an ancient tradition in the healing arts.
  ■   Individuals with support have better outcomes for many
      illnesses.
  ■   Isolation is associated with increased all-cause mortality.
  ■   The physiologic mechanisms for group support in benefiting
      ill individuals include improved markers of stress (cortisol,
      IL-6, etc.).
  ■   Numerous support groups exist for digestive tract and liver
      diseases.
                                  ■



               Foreword by Dr. Bernie Siegel, author of
                    Love, Medicine and Miracles

Support groups are of value because “natives” (patients) under-
stand the experience of their disease—they are not tourists—
while many doctors treat the disease and not the patient’s
experience. Group members listen to each other, help each other,
and find what is right for them. Members are active and respon-
sible participants in their care. In the process, a new family is cre-
ated—one that is able to support and listen to each other,
banishing the loneliness and fear that negatively affect immune
function.



                                                                         241
242   INTEGRATIVE GASTROENTEROLOGY


   If I were a quadriplegic, I’d want another quadriplegic to talk
   to, who could give me hope and teach me practical things I could
   do, such as using a motorized wheelchair, using a telephone, and
   painting with my mouth. I’d want to hear about what is possible,
   not what is impossible. Life without hope is bleak; it is hope that
   fuels the engine of life.


                                  Overview

Illness represents an imbalance between the individual and society, and
requires participation of the patient’s family and community members to
restore balance. In many ancient traditions (e.g., Celtic, Native American
Indian), community members contribute to the healing of the sick. In Western
medicine, these traditions are often substituted with isolation and separation
of the sick from society, resulting in concomitant depression, disability, and
despair. However, groups of patients have rallied by organizing support sys-
tems that work in concert with special-interest medical societies (e.g., Crohn’s
and Colitis Foundation of America).
    The concept of group support in the healing practice of Western medicine
evolved from the success of Alcoholics Anonymous in the 1930s. Today, sup-
port group members provide each other with various types of help for a par-
ticular shared, usually burdensome, illness. The help may take the form of
providing and evaluating relevant information, relating personal experiences,
listening to and accepting others’ encounters, providing sympathetic under-
standing, and establishing social networks. A support group may also work to
inform the public or engage in advocacy.
    A variety of studies support the idea that social isolation is associated with
adverse health outcomes and that self-expression, education, and sense of
community can lower levels of stress hormones, improve quality of life, and
enhance immune function (Gordon, 2006). Key studies are summarized
below:

   1. All-Cause Mortality. Social isolation itself has been identified as an
      independent major risk factor for all causes of mortality (House,
      Landis, & Umberson, 1988). Being well integrated socially reduces all-
      cause, age-adjusted mortality by twofold—about as much as having
      low versus high serum cholesterol levels or being a nonsmoker
      (House, Landis, & Umberson, 1998).
                                                 The Value of Support Groups 243


   2. Social Support and Disease Outcome.
      a. Social Support and Depression. Depression is linked with multiple
         diseases, such as cancer, sudden death, and coronary artery disease
         CAD. Nancy Frasure-Smith has demonstrated in multiple studies
         that social support ameliorates this effect in heart patients. Social
         support does not necessarily eliminate depression, but it does
         eliminate the adverse health outcomes of depression (Frasure-
         Smith et al., 2000).
      b. Social Support and Cardiac Disease. Family and friends questioned
         149 men and women, who were set to undergo cardiac catheteriza-
         tion, about how loved and supported they felt. The number of
         blockages found on subsequent angiograms correlated positively
         with the degree of reported love and support (Seeman & Syme,
         1987).
      c. Social Support and Death Rate. Researchers surveyed 6,900 par-
         ticipants about their contact with friends and relatives, church
         membership, membership in clubs or groups, and marriage, and
         then followed them for 17 years. Those without close ties or fre-
         quent social contact had an overall death rate 3.1 times higher than
         those who did have these contacts. Both men and women in the
         low-connection category had higher rates of death from cancer.
         An analysis of breast cancer patients found that those with low
         connection had twice the death rate, regardless of race (Kaplan,
         Seeman, Cohen, Knudsen, & Guralnik, 1987).
      d. Social Support and Disease Susceptibility. In this study, 276 healthy
         volunteers were given doses of internasal rhinoviruses until they
         shed virons. The participants were also questioned about 12 types
         of relationships, such as those with their parents, children, friends,
         and social groups. Each positive relationship was scored as one
         point. Participants with fewer than 3 points developed cold symp-
         toms at a rate 4 times greater than those with higher scores.

   These studies and others indicate that social isolation, a perceived lack of
connection, is a significant risk factor for coronary artery disease (CAD),
cancer, and all-cause mortality. It is important to note that social isolation
reported in these studies is self-reported, and this risk may therefore be related
to the individual’s perception of isolation. Thus, perception likely contributes
to health outcomes, together with interpersonal connection and community
support.
244   INTEGRATIVE GASTROENTEROLOGY


  1. Connection in the Community (Egolf, Lasker, Wolf, & Potvin, 1992).
     A 50-year observational study followed the health of residents of the
     towns of Roseto, Bangor, and Nazereth, Pennsylvania. In the 1930s
     and 1940s, it was noted that the town of Roseto had a significantly
     lower rate of acute myocardial infarctions (MIs) than its neighboring
     communities, despite equal prevalence of diabetes, obesity, and high-
     fat diet in the three towns. During the follow-up in the 1970s, the rates
     of MI and overall mortality substantially increased in Roseto, but not
     the other towns. When health behaviors were analyzed, there were
     still no significant differences in the three communities as to smok-
     ing, weight, diet, diabetes, or other risk factors. What had changed,
     however, was the social structure of Roseto, whose close family ties
     and community practices (mainly religious) in the 1930s and 1940s
     began to disintegrate in the late 1960s. At the same time, the rates of
     MI and mortality began to rise. This is the longest of multiple studies
     of communities that show a clear relationship between community
     activity, social structure, and the rates of disease. It also points toward
     the role of community practice and its effect on disease prevalence.
  2. Support Group Connection as Intervention: Benefits of Support Groups.
     During the last 30 years, researchers have shown great interest in the
     phenomenon of social support, particularly in the context of health.
     Prior work has found that those with high quantity or quality of social
     networks have a decreased risk of mortality, compared with those
     who have low quantity or quality of social relationships, even after
     statistically controlling for baseline health status (Westaway, Seager,
     Rheeder, & Van Zyl, 2005). In fact, social isolation itself has been
     identified as an independent major risk factor for all-cause mortality
     (Fischer Aggarwal, Liao, & Mosca, 2008). Current research has
     focused on expanding several areas of knowledge in this field. These
     include social support influences on morbidity, mortality, and quality
     of life in chronic disease populations, understanding the mechanisms
     responsible for such associations, and understanding how we might
     apply such findings to design relevant interventions.

   In researching the topic of the value of social support in various chronic
diseases, we found that support was valuable, no matter what the disease. One
study demonstrated that: (1) socio-emotional and tangible support were the
underlying dimensions of social support; (2) socio-emotional support is an
important determinant of health and well-being; and (3) social support is
beneficial for one aspect of diabetes mellitus management, namely, blood
pressure control (Eisenberger, Taylor, Gable, Hilmert, & Lieberman, 2007).
                                              The Value of Support Groups 245


In an ethnically diverse population, emotional social support was linked to
higher high-density lipoprotein cholesterol levels, through increased physical
activity and wine intake, suggesting possible mechanisms through which
social support may reduce cardiovascular disease risk (Shepp, Chase, & Rawls,
1999).

  1. Key studies in which a psychosocial “connection” intervention altered
     disease outcomes for diseases not generally considered psychoso-
     matic diseases: Metastatic Breast Cancer (Spiegel, Bloom, Kraemer, &
     Gottheil, 1989). In this study, women with metastatic breast cancer
     attended a weekly 90-minute group support session for one year.
     Follow-up occurred over 5 years. The initial hypothesis was that group
     support would help these women adjust to their disease, as well as
     help with anxiety, depression, and other psychosocial issues. The out-
     comes supported this hypothesis. A more dramatic and surprising
     outcome was that the group-support patients lived twice as long as
     the control group (18 months versus 9 months on average). Malignant
     Melanoma (Fawzi, Fawzi, & Hyun, 1993). In this study, patients who
     had undergone local resection of malignant melanoma were placed in
     a 6-week support group. They were then followed for 5 to 6 years. No
     other intervention was used. There were 13 recurrences and 10 deaths
     in the control group, compared with 7 recurrences and 3 deaths in the
     support group, results that were statistically significant.The Ornish
     program for reversing heart disease (Ornish et al., 1983, 1990, 1998;
     Ornish, 1998). This series of studies has followed up to 477 patients.
     The intervention includes a low-fat vegetarian diet, exercise, yoga,
     and group support. These trials have had remarkable success in revers-
     ing CAD and diminishing adverse events, procedures, and cost of
     care. Individuals in groups that bond well and interact well in their
     group sessions tend to have greater improvements on subsequent
     angiograms, and fewer adverse outcomes than those in groups that
     become dysfunctional. The group model of intentional connected-
     ness is clearly one of the most powerful tools we have to combat ill-
     ness-related depression and anxiety. It is also one of the most potent
     effectors of behavioral change, as documented in chemical depen-
     dency programs. Even venting itself appears to impact the outcome of
     illness (Spiegel, 1999). The above studies (and others) show that group
     support significantly affects the clinical course of a person with an
     illness.
  2. The healing physiology of support group connection: underlying
     mechanisms.
246   INTEGRATIVE GASTROENTEROLOGY


    It is well established that a lack of social support constitutes a major risk
factor for morbidity and mortality, comparable to risk factors such as smok-
ing, obesity, and high blood pressure. Although it has been hypothesized that
social support may benefit health by reducing physiological reactivity to stres-
sors, the mechanisms underlying this process remain unclear. Cormier (2005)
reported that individuals who interacted regularly with supportive individuals
across a 10-day period showed diminished cortisol reactivity to a social stres-
sor. Moreover, greater social support and diminished cortisol responses were
associated with decreased activity in the dorsal anterior cingulate cortex
(dACC) and Brodmann’s area (BA) 8, regions previously associated with the
distress of social separation. Lastly, individual differences in dACC and BA 8
reactivity mediated the relationship between high daily social support and low
cortisol reactivity, such that supported individuals showed reduced neurocog-
nitive reactivity to social stressors, which in turn was associated with reduced
neuroendocrine stress responses. This study is the first to investigate the neural
underpinnings of the social support–health relationship, and provides evi-
dence that social support may ultimately benefit health by diminishing neural
and physiological reactivity to social stressors.
    Other mechanisms may explain the health benefits of support group con-
nection. Intentional connection (group support), interpersonal connection
(marriage, friendship, and pets), and community connection (participation in
church groups and social groups), have all been shown to decrease life stress.
Life stress is internally mediated through the release of catecholamines, corti-
sol (if chronic), and probably other neurohormonal mechanisms. Social isola-
tion is associated with elevated catecholamines and cortisol. Catecholamines
and cortisol contribute directly to disease susceptibility through the following
mechanisms: increased blood pressure, increased blood viscosity, increased
platelet adhesion, increased endovascular reactivity and endothelial inflam-
mation, increased production and release of proinflammatory cytokines. For
example, IL-6 has been found to be inversely associated with social integration
in men (Loucks et al., 2006). Social support predicted lower stimulated levels
of IL-8, IL-6, and tumor necrosis factor (TNF-α) (Marsland, Sathanoori,
Muldoon, & Manuck, 2007). Immunologic Mechanisms (Kiecolt-Glaser &
Glaser, 1993). The healing benefits of group support connections occur through
immunologic mechanisms as well. Cortisol suppresses immune function.
Group support has been shown to be effective in the treatment of autoimmune
diseases. Psychosocial factors have been shown to affect the susceptibility to,
or the progression of, autoimmune diseases, infection, and cancer. Immunologic
reactivity is altered by stress. Findings for people under stress include:
decreased NK cell activity Gamma interferon levels decreased by 90 percent,
decreased T-cell responsiveness, decreased immune responsiveness, increased
                                                 The Value of Support Groups 247


upper respiratory infections. Social connection for caregivers was correlated
directly with immune function.
   The most convincing research backing the use of support groups appears in
Current Opinion in Psychiatry (Remblin & Unchino, 2008). The researchers
postulate that the acts of giving and receiving support have unique pathways
to stress reduction: Giving is mediated by increased efficacy, leading to lower
stress, while receiving support has a direct effect on stress. Taken together,
studies such as these suggest that there is something potentially unique about
the act of giving support. It may be that people experience positive affect while
helping others, which may improve their health. Or it may be that benefits
occur in the context of a high-quality relationship in which one feels valued
and can reciprocate by providing support. In isolation, there is no hope; with-
out hope, life can be bleak. By referring your patient to a support group, and
participating with a support group yourself, you can give your patient the most
valuable of gifts—one that complements and assures compliance with your
medical treatment.


               From Where I Stand: Gerard Mullin

As a digestive healthcare practitioner, I often detect that social isolation and
disconnection from society are major influences in a patient’s illness.
Facilitating the restoration of health in digestive disease patients requires guid-
ance and support. There are dozens of national and local support foundations
to help the more than 60 to 70 million digestive disease patients become
“unstuck.” Many digestive care specialist physicians participate in these patient-
oriented support groups, in activities ranging from educational symposia to
group activities (e.g., 5K walks, etc.). Another possible opportunity for the
physician to facilitate healing is to serve as a group leader for workshops geared
toward mind–body skills. Training and certification is available through the
course taught by James S. Gordon, MD, at the Center for Mind–Body Medicine:
http://www.cmbm.org.


                 From Where I Stand: Pearl Lewis

Chronic digestive disease brings with it, besides physical symptoms, a host of
psychological and emotional issues that can have negative effects on one’s
family life, education, and progress in the work force. The path to a correct
diagnosis is often long. During this time, the patient may be told his or her
condition is either stress-related or “all in your head.” As a result, painful
248      INTEGRATIVE GASTROENTEROLOGY


symptoms such as depression, anxiety, and isolation can dash one’s hopes for
the future. In the most severe cases, income from work is replaced by Social
Security Disability; health benefits are replaced by Medicare—after a 24-month
waiting period without access to healthcare.


                    Group Support Related Specifically
                          to Digestive Disease1

Most people are familiar with the Crohn’s and Colitis Foundation of America.
This organization has existed since the 1970s and has provided education, sup-
port, and research funds for Crohn’s disease and ulcerative colitis. During the
last several decades, however, there has been a proliferation of support groups
for almost every digestive disease (refer to the list in the appendix).
    One of the newest members of the digestive healthcare team originated at a
550-bed tertiary care center in the Southeast, which created an interactive,
educational patient and family support group for people with pancreatitis. No
previous support groups for this population could be located in the United
States, even though pancreatitis may progress to include chronic pain, fre-
quent hospitalizations or emergency room visits, narcotic dependence, and
depression. The group used a partnership model as a basis for helping empower
patients and their family members to have more understanding of, adaptation
to, and participation in the treatment choices and responsibility for managing
symptoms of their chronic illness. Facilitated by a multidisciplinary team, this
is the first group of its kind in the United States and was enthusiastically
received by those who participated.
    “Abundant research supports the premise that social support facilitates
patient well-being and contributes to health and health promotion through
interpersonal interactions,” write Klytta and Wiltz (2007). “Gastroenterology
nurses are well positioned to facilitate improved outcomes in patients with
chronic hepatitis C virus by initiating interventions designed to enhance exist-
ing sources of social support or to promote new ones. Development of psycho-
social interventions, such as support groups, aimed at maintaining or fostering
social support, may improve health outcomes and promote a higher health-
related quality of life for persons living with chronic hepatitis C virus.”
    Whether one has irritable bowel syndrome, hepatitis A, B, or C, clostro-
dium difficile, gluten intolerance, celiac sprue, or an ostomy, there are support
groups for it online or located in a town nearby.


1
    See Directory of Digestive Diseases Organizations for Patients in Appendix B.
                                                The Value of Support Groups 249




                                Conclusion

Self-help groups have developed into an established pillar within the health
system. It has been shown that the patients involved benefit from such groups
in terms of both secondary and tertiary prevention. Physicians, too, can profit
from the wealth of experience gained by self-help groups. From this source,
they can obtain useful insights into patients’ problems that go well beyond
what is possible in the office setting.
    Self-help group members have been shown to differ from patients in outpa-
tient psychotherapy by expressing a more positive opinion of group work, and
higher openness to new experiences. Additionally, they discuss the topic of
self-help groups more frequently with their therapists. This may be a starting
point for promoting more self-help activities of patients in the future.
    The February 2008 issue of American Psychologist reports that more
Americans are trying to change their health behaviors through self-help than
through all other forms of professionally designed programs (Davison,
Pennebaker, Dickerson, 2000). The Internet has become a source of education
and support for almost every known disease. When diagnoses have not been
forthcoming, many people have found theirs on the Internet.
    Kathryn P. Davison, of The Human Asset in Dallas, Texas, and her col-
leagues looked at support-group participation for 20 disease categories in four
metropolitan areas (New York, Chicago, Los Angeles, and Dallas) and in
nationwide online discussion groups (Davison, Pennebaker, & Dickerson,
2000). “Support seeking was highest for diseases viewed as most stigmatizing,
including alcoholism, AIDS, breast cancer and anorexia,” they write. “Support
seeking was lowest for less embarrassing but equally devastating disorders,
such as heart disease, hypertension, migraine, ulcer, and chronic pain.”
Digestive diseases that cause diarrhea and incontinence certainly fit into this
category.
    Online support groups, which involve a relative amount of anonymity,
allow people to confide in each other without experiencing immediate social
repercussions. Yet, attendance is also high in local support groups for condi-
tions associated with embarrassment. “These groups,” according to Davison
et al., “are populated by individuals whose illnesses, either by their very nature
or as a result of treatment, have forced them to experience embarrassment and
social stigmatization. The seriousness of their conditions, the weight of their
illness’ impact, and the degree of readjustment required under the circum-
stances, set them apart from their immediate social setting and propel them
toward others who have been similarly marked.”
250 INTEGRATIVE GASTROENTEROLOGY


   An important finding of the study, say the authors, is that more than 60%
of groups describing themselves as self-help are professionally facilitated.
“Self-help and professional help are often perceived as mutually exclusive, but
the data indicate that such perceptions are misleading,” write the researchers.
“Group participants may not be resistant to professional input; rather, they
may need to speak and be heard about issues not addressed within the health-
care setting.”
   As for the effectiveness of self-help groups, the researchers say prior inves-
tigations have yielded positive results overall. The self-help movement, they
add, has tremendous therapeutic potential, especially in the current culture of
institutional healthcare, which is still far from incorporating psychological
support into healthcare delivery.
   Just as the Internet has become a lifeline for those living with myriad
chronic, life-threatening diseases, it also provides a wealth of information. The
vast majority of articles and information used here to back the use of support
groups came from MedScape. What did not come from professional sources
was derived from more than 25 years of creating and participating in support
groups. This experience has convinced me that the best healthcare puts the
patient at the center of his or her entire healthcare team. This team often
includes a primary-care physician, specialists, nutritionists, nonprofit health
agencies, support groups, and other paraprofessionals, and even the patient’s
loved ones, who all join together to create a supportive, healing family.
                                   28
   Overview of Visceral Manipulation for the
        Integrative Gastroenterologist
              JEAN-PIERRE BARRAL AND GAIL WETZLER




                                key concepts

     ■   An organ in good health has physiologic motion.
     ■   The interrelationship of structure and function among the
         internal organs is interdependent.
     ■   Mobilizing the organs increases proprioceptive communication
         in the body and enhances internal mechanisms for better health.
     ■   Research demonstrates that the beneficial effects of visceral
         manipulation are due to the return of normal organ mobility and
         pressure, rather than the return of normal anatomical position.
     ■   Current evidence suggests that during functional gastrointesti-
         nal disease, organs lose their mobility and inherent tissue
         motions. Visceral manipulation is the primary modality used to
         explore these fixations, and restore heir natural rhythm and
         motion for better function.
                                       ■




                 What Is Visceral Manipulation?



V
        isceral Manipulation (VM) is a manual therapy consisting of gentle
        yet specifically placed manual forces that encourage normal mobility,
        vascularity, tone, pressure, and inherent tissue motion of organs, their
connective tissues, and their relationship to other areas of the body where
physiologic motion has been impaired. The central premise of VM is that an
organ in good health requires physiologic motion (Barral, & Mercier, 1988).

                                                                             251
252   INTEGRATIVE GASTROENTEROLOGY


                Table 28.1. Visceral Manipulation (VM) Parameters

Visceral Manipulation is a modality concerned with the 3-dimensional dynamics of
organ biomechanics and how they relate to the body (including connective tissue
structures, vascular, nervous, and musculoskeletal systems).

Visceral Manipulation Parameters:

   • Are derived from the concept that good health is not a state, but a search for
     equilibrium.
   • Healthy organs have an axis of motion in which mobility and motility are the same.
   • Structure and function are interrelated. Movement and function are
     interdependent.
   • Movement within the organs, such as secretions, absorption, blood and lymph
     circulation, peristalsis, respiration, nutrition and immune mechanisms, creates
     physiological efficiency.




When an organ loses its mobility or its inherent tissue motion (motility), sub-
optimal physiological function of the body can develop. VM is the primary
modality used by manual therapists to explore and correct these tensions.
Once movement is restored, and communication between organs is more effi-
cient, fluid circulation and drainage are improved and irritating signals are
reduced. Overall, the body’s homeostatic mechanisms can operate more effec-
tively, thus restoring health and better function (Table 28.1.).
   Visceral mobility is tested by evaluating the sliding surfaces between one
organ and another, or between the organ and body wall or musculoskeletal
system. The study of visceral motion is now becoming more relevant to the
medical field, and increasing research is being conducted on the normal phys-
iological patterns of visceral movement (Table 28.2.). With the use of X-rays
and echograms, studies have shown that an organized and repetitive dynamic
does exist on the visceral level (Finet & Williame, 2000).
   Visceral support is provided by connective tissues that hold the viscera in a
3-dimensional, vertically oriented column, and by tension (tensegrity model)
within the body cavities (Canadas et al., 2002). Connective tissues are known
to facilitate communication between organs. This phenomenon is referred to
as mechanical dialogue (Barral, 1989).
   The interrelationship of structure and function among the internal organs is
interdependent. When a fixation within the visceral system occurs, manual
therapy treatment focuses on removing the strain on the connective tissues sur-
rounding and within the viscera. This is where mechanical strains can develop
into deformation, with an extensive loss of organ flexibility. These restrictions
alter the physical properties of connective tissues, affecting characteristics such
         Overview of Visceral Manipulation for the Integrative Gastroenterologist 253


                         TABLE 28.2. Influences of Visceral Mobility
Central nervous system           Voluntary movement of musculoskeletal system

Autonomic Nervous System         Diaphragm motion
                                 Peristalsis
                                 Reflex activity in the CNS and PNS

Articulations                    Relative position and shape of each organ,
                                 membranous sliding surfaces, orientation to blood
                                 vessels, and proximity of supportive tissues

Pressures                        Subatmospheric
                                 Tugor
                                 Gravity


as mobility, deformation, compressibility, viscoelastic compliance, elongation,
and organ secretion of fluids (Stone, 2007).
    The goal of mobilizing the organs is to facilitate their ability to move when
stimulated by central nervous system (CNS), autonomic nervous system
(ANS) or enteric nervous system (ENS) activity, and to respond to fluid
dynamics (Table 28.3; see Stone, 2007; Barral, 1989; Allison, Dhillon, Lewis
and Pounder, 1998). Further research on how manual therapy affects the ANS
is currently being conducted at the University of North Texas Health Science
Center (Osteopathic Research Center, 2008). Three major processes have been
identified as being potentially influenced by manual therapy (Barral, 1988):

   (a) repair process,
   (b) fluid flow dynamics, and
   (c) adaptation process (length; see Lederman, 2005)

                Table 28.3. The Goals of Visceral Manipulation Treatment

 1.   Restore functional mobility
 2.   Restore motility
 3.   Restore soft tissue elasticity
 4.   Restore fluid exchange
 5.   Restore pressure systems between the cavities and inside the organs
 6.   Restore physiologic function
 7.   Relieve pain
 8.   Resolve the mechanical link compensation
 9.   Restore proprioceptive communication
10.   Restore local and systemic responsiveness
11.   Restore viscerosomatic relationship
12.   Restore visceral-emotional relationship (Barral, 1988; Stone, 2007)
254 INTEGRATIVE GASTROENTEROLOGY




                                Clinical Relevance

                         INFLAMMATORY BOWEL DISEASE

It is our expert opinion that many functional digestive disorders have vascular
origins. Manual treatment of the mesenteries that house blood vessels is neces-
sary to improve functional digestive illness. Since these membranes are highly
reflexogenic, if they contain abnormal tension, vasoconstriction may result
(Barral, 1989). The literature reports that inflammatory bowel disease is associ-
ated with vasomotor instability, congestive regional lymph nodes, mucosal
ulcerations/scarring, inflammation of the intestinal wall, and abnormal tonus
and extensibility of the colon (Pounder, 1998; Hudson et al., 1992; Sankey et al.,
1993). The entire gut should be treated because it can lose elasticity easily,
create multiple adhesions, and go into more frequent spasm with ANS and
vagus nerve influences (Table 28.4.).


                           IRRITABLE BOWEL SYNDROME


     Diseases within the internal organs manifest themselves as alterations in
     the musculoskeletal system, frequently in the form of pain. (Greenman,
     1996)




   Pain, like that of irritable bowel syndrome (IBS), can be caused by edema-
tous distention of the serosa, and spreads gradually to the visceral peritoneum


       Table 28.4. Treatment Considerations for Inflammatory Bowel Disease

1.   Intestinal function depends on diaphragmatic mobility and intestinal peristalsis
2.   Hepatic and splenic flexures are suspended from the diaphragm
3.   Transverse colon is subject to diaphragm attraction
4.   Greater omentum as it links the stomach to the transverse colon and connects
     laterally on the diaphragm
5.   Dysfunctional sphincters disrupt the pressure differentials
6.   Vagus Nerve and ANS techniques for abnormal tonus and peristalsis
7.   Influence of urogenital system restrictions
8.   Colon, duodenum and jejunoileum mobility and motility
       Overview of Visceral Manipulation for the Integrative Gastroenterologist 255


and ultimately to the parietal peritoneum, causing a mechanical chain of fas-
cial pain (Steer et al., 2003). The fascial coverings of organs limit expansion
and increase internal pressure, which further compromises the neural tissue.
The pain pathways barrage the area of synapse within the cord, promoting
viscerosomatic disorders. In IBS, it is important to know how to manipulate
the colon at junctions and sharp angles (flexures), as these are areas of lesser
circulation where there can be risk of ischemia and inflammation (Steer et al.,
2003; Barral & Mercier, 1988).


                                  DYSPEPSIA

The pain associated with dyspepsia can be of muscular origin (causing a dull
pain), mucosal origin (burning pain), nervous system origin (sharp pain from
the celiac plexus), or a combination of any of these origins (Michallet, 1989).
Mechanoreceptors in the stomach, when dysfunctional, can promote an
increase or decrease of secretions (HCl) for gastric function. VM affects these
receptors by creating movement within the muscular walls of the stomach,
decreasing viscerospasm, increasing the stomach dilatation reflex, and increas-
ing the interchange of appropriate secretions. The mucosal pain can be caused
by a decrease of mobility and motility of gastric propulsion. Gastric evacua-
tion is increased when the ileum is active or externally stimulated (disinhibi-
tion of the ileal brake), which allows us to apply certain techniques to the ileum
for treatment of the stomach. (Barral, 1989)
   The specificity of a VM evaluation allows for the practitioner to locate the
point of origin for gut dysfunction. Points of origin can include an associated
organ, such as the duodenum, nerve (celiac versus vagus), supportive struc-
tures (gastrophrenic ligament versus greater omentum), or be located within
the organ itself.


                                     GERD

When reflux occurs due to a dysfunctional hiatal zone, the visceral practitio-
ner will evaluate for the dominant mechanical cause of the symptoms
(Table 28.5).
   The manual technique for gastric ptosis, or loss of elasticity in the organ
ligaments, has been checked several times with fluoroscopy. These studies
showed the pyloric antrum had moved upward by as much as 5 cm. (Dr Searge
Cohen) Manipulations of the hiatus can facilitate resolution of gastroesopha-
geal reflux disease (GERD; see Michallet, 1989). (17)
256   INTEGRATIVE GASTROENTEROLOGY


        Table 28.5. Structural Causes of GERD That Can Be Addressed by VM

•   R/O cervical or brachial plexus problems that can provoke phrenic nerve irritation
•   Diaphragmatic hypertonicity
•   Thoracic or abdominal scarring
•   Esophagus/stomach immobility
•   Fascial restrictions of surrounding tissues/organs
•   Gastrophrenic ligament and upper fundus restrictions
•   T5, T6 viscerosomatic restrictions
•   T12–L3 spinal mechanical restrictions
•   Gastric ptosis (loss of elasticity in the organ ligaments)




    Experiments
    • Alain Crobier, DO, J.P. Barral, DO. (2007–2008). Effects of manual therapy
      on the vascular system of 200 different people using the Doppler for pre-
      treatment and post-treatment evaluations.
    Dissections
    • During 1970–1974, more than 100 cadavers were dissected with Dr. Barral
      and Professor Arnaud in Grenoble, France, to better understand anatomy
      and its interrelationships.
    Video
    • Visceral Manipulation by Jean Pierre Barral, 2005, Coproduction of Eastland
      Press, Inc., and the Verlag fuer Ganzheitliche Medizin, Dr. Erich Wuehr,
      GmbH
    Website
    • www.barralinstitute.com




                                       SUMMARY

Based on the central premise that organs in good health require physiologic
motion, mobilizing the viscera can be beneficial in the treatment of internal
organ dysfunction. We have treated more than 104,000 patients with visceral
manipulation, providing us with expert evidence and real-life clinical experi-
ence. We firmly believe that manipulations should be precise, with the goal of
a whole-body response and for the achievement of homeostasis. Visceral
manipulation should be considered as part of an integrative approach to diges-
tive disorders.
                                29
Probiotics in the Prevention and Treatment
        of Gastrointestinal Disease
                         GERALD FRIEDMAN




                             key concepts

 ■   Probiotics are “live microbial feed supplements that beneficially
     affect the host animal by improving its intestinal microbial
     balance.”
 ■   Prebiotics are “non-digestible food ingredients that beneficially
     affect the host by selectively stimulating the growth and/or
     activity of one or a limited number of bacteria in the colon.”
 ■   Clinical situations where probiotics may play a role in the allevia-
     tion of disease include lactose intolerance, infantile necrotizing
     enterocolitis, antibiotic-associated diarrhea and clostridium dif-
     ficile colitis, irritable bowel syndrome, traveler’s diarrhea, ulcer-
     ative colitis, Crohn’s disease, bacterial overgrowth syndromes,
     colon carcinoma, food allergy, and gut-origin septicemia.
 ■   There are a limited number of well-regarded, randomized, pla-
     cebo-controlled, double-blind trials on the effects of probiotics
     on antibiotic-associated diarrhea, pouchitis, and irritable bowel
     syndrome. Probiotics appear to be most efficacious in the pro-
     phylaxis of disease, and as maintenance therapy.
 ■   Probiotics are derived from “normal” commensal bacteria and,
     as such, are generally safe for short-term use. Caution should be
     used with severely immune-compromised subjects, patients with
     central vein catheters, and patients with valve replacements.
 ■   Future research using single-strain or multi-strain probiotics in
     humans will provide further supporting evidence for the value
     of probiotics.
                                    ■



                                                                             257
                               Introduction



P
       robiotics have been in vogue intermittently since the turn of the cen-
       tury, when Eli Metchnikoff received the Nobel Prize for observations
       on the value of lactic acid-producing bacteria in enhancing health and
longevity (Metchnikoff, 1910). Presently, there is renewed interest in the
contributions of commensal bacteria to human health. Major advances in
defining the quality, quantity, and physiologic activity of the intestinal micro-
biota were enabled by the conversion of culture-based techniques to genetic
analysis. Now, DNA sequences can define the profiles and functions of micro-
organisms inhabiting the GI tract (Schloss & Handelsman, 2005). To better
understand the critical value of commensal microbiota, it is important to know
the nature, number, anatomic distribution, and development of these hollow-
tract bacteria.


                         Commensal Bacteria

The adult human intestinal tract contains approximately 100 trillion microbial
organisms known as microbiota (Backhed et al., 2005). These essentially
anaerobic organisms contain more than 500 species. The longitudinal distri-
bution of intestinal microorganisms increases in density, progressing from the
small bowel to the colon. In the duodenum and jejunum, aerobes and faculta-
tive anaerobes contain 103 to 105 organisms/gram luminal contents. The termi-
nal ileum contains approximately 107 to 108 organisms/gram luminal contents,
and the colon contains 1010 to 1011 organisms/gram luminal contents (Berg,
1996). The microbiota benefit the host by performing metabolic functions,
including energy-producing fermentation of malabsorbed carbohydrates, pro-
ducing short-chain fatty acids, adding to trophic action on the epithelium,
producing vitamins (B vitamins and vitamin K), and playing a pivotal role in
the development of the immune system.


             Development of Intestinal Microbiota

The initial manner of acquisition of intestinal microbiota affects the rate and
the nature of the development of the immune system. The host genotype and
birth environment are important in determining populations of intestinal
organisms (Palmer et al., 2007). Fetuses are sterile in utero. Vaginal delivery
         Probiotics in the Prevention and Treatment of Gastrointestinal Disease   259


allows infant exposure to maternal bacteria; the longer the birth process, the
greater the exposure. Infants born by Cesarean delivery acquire bacteria by
nonvaginal maternal exposure, as well as isolates transferred by nursing staff,
other infants, air, and equipment. Following birth, oral and cutaneous bacteria
from the mother are mechanically transferred to the infant by suckling, kiss-
ing, and caressing. Breastfeeding exposes the infant to bacteria, especially bifi-
dobacteria from milk ducts, nipple, and surrounding skin. Breast milk contains
antimicrobial and growth factors that stimulate the development and matura-
tion of the intestinal mucosa (Mackie, Sghir, & Gaskins, 1999). Infants born by
Cesarean section may experience a delay in the development of a full comple-
ment of commensal bacteria. Some suggest that this delay presents an oppor-
tunity for the development of certain allergic-related illnesses such as atopic
dermatitis, allergic bronchitis, and certain autoimmune diseases. After intro-
duction of solid food, by the first two years of life, the bacterial profiles of
breastfed and formula-fed infants are similar to those of adults.


    Definitions of Probiotics, Prebiotics, and Synbiotics

Probiotics are “live microbial feed supplements that beneficially affect the host
animal by improving its intestinal microbial balance” (Fuller, 1989). Prebiotics
are “non-digestible food ingredients that beneficially affect the host by selec-
tively stimulating the growth and/or activity of one or a limited number of
bacteria in the colon” (Gibson & Roberfroid, 1995). Examples of prebiotics
include fructooligosaccharides, inulin and psyllium. “Synbiotics” is the term
used when a product contains both probiotics and prebiotics.


                        How Do Probiotics Act?

Most probiotics are obtained from normal human commensal bacteria.
Predominant species include lactobacilli, bifidobacteria, E. coli and Strepto-
myces. The exception is a yeast, Saccharomyces boulardii, obtained from the
lychee plant. Experimental data gleaned from actions of single-strain and
multi-strain bacteria reveal three groups of biologic effects of probiotics. The
first includes modulation of the immune system, by increasing total and spe-
cific IgA secretion, downregulation of T-cell responsiveness, alteration of
cytokine profiles, and induction of oral tolerance. The second group includes
enhancement of intestinal barrier function by increasing mucous production,
promoting tight cellular junctions and epithelial restitution. Third, probiotics
prevent invasion of pathologic bacteria by bacteriocin production, prevent
260    INTEGRATIVE GASTROENTEROLOGY


adhesion of pathologic organisms, increase colonizing resistance, and decrease
luminal pH through the formation of organic acids (Fedorak & Madsen,
2004).


                   Clinical Applications of Probiotics

Clinical situations in which probiotics play a role in the alleviation of disease
include:

      1.   Lactose intolerance
      2.   Infantile necrotizing enterocolitis
      3.   Antibiotic-associated diarrhea and Clostridium difficile colitis
      4.   Irritable bowel syndrome
      5.   Traveler’s diarrhea
      6.   Inflammatory bowel diseases, including Crohn’s disease, ulcerative
           colitis, and pouchitis
    7.     Bacterial overgrowth syndromes
    8.     Colon carcinoma
    9.     Food allergy
   10.     Gut-origin septicemia

   A brief review of selected clinical applications follows. The review includes
a description of the clinical entity, the rationale for the use of probiotics, and
an analysis of available clinical trials supporting its use.


                             Lactose Intolerance

Lactose intolerance is a problem worldwide, its prevalence varying from 7% to
20% among Caucasians, 50% among Hispanics, 75% among Africans and
African-Americans, and more than 90% in Asian populations. Clinical symp-
toms include diarrhea, abdominal pain, and flatulence following the ingestion
of milk or milk products. The reduced amount of lactase enzyme in the glyco-
calyx of the proximal small bowel fails to hydrolyze lactose to glucose and
galactose. As a result, the poorly absorbed lactose passes into the colon where
it is metabolized by colonic microbiota, producing short-chain fatty acids
and an excess of hydrogen, methane, and carbon dioxide gases, resulting in
the symptom complex noted above. Symptoms vary based upon the dose of
lactose ingested, and the concomitant dilutional effect of the accompanying
meal. Treatment involves reducing lactose intake, using enzyme substitutes
         Probiotics in the Prevention and Treatment of Gastrointestinal Disease   261


(e.g. Lactaid tablets), or probiotics (He et al., 2008). In my personal experience,
combining a probiotic (Lactobacillus GG) and a prebiotic (fructooligosaccha-
ride) effectively ameliorates symptoms of patients with hydrogen-breath-test
proven lactose intolerance (Friedman, 2008).


                       Necrotizing Enterocolitis

Necrotizing enterocolitis is the most common gastrointestinal emergency in
neonates, particularly affecting premature infants, with an increased risk for
males and black infants. Clinically, infants present with gastrointestinal and
systemic signs including feeding intolerance, delayed gastric emptying,
abdominal tenderness and distention, occult or gross blood in the stool, leth-
argy, and respiratory distress. Treatment consists of bowel decompression,
broad-spectrum antibiotics, and careful monitoring. Up to 20% to 40% of
patients may require surgery. Probiotics reduce the risk of necrotizing entero-
colitis, reduce the risk of death, and shorten time to full feeds (Deshpande,
Rao, & Patole, 2007).


                      Irritable Bowel Syndrome

Irritable bowel syndrome is one of the most common syndromes seen by pri-
mary care physicians and gastroenterologists, with a prevalence of 10% to 15%.
It is characterized by chronic, intermittent, and recurring abdominal pain in
association with altered bowel function (diarrhea, constipation, or alternating
diarrhea and constipation) occurring longer than three to six months.
Symptoms are more common among young to middle-aged females; female to
male ratio 2:1. Etiological factors include psychologic and stress features,
altered gut motility and hypersensitivity, dysregulation of gut-based serotonin,
altered immune function, postinfectious bowel dysfunction, and bacterial
overgrowth. Predominant complaints of most patients with IBS involve “gas
syndromes,” increased flatulence, abdominal distention, and bloating.
Increased gas production is related to fermentation of malabsorbed carbohy-
drates, swallowed air, delayed small bowel and/or colonic motor function, or
altered bacterial flora. A unifying framework for understanding irritable bowel
syndrome has been offered by Dr. Henry Lin (2004), who identifies distal
small bowel bacterial overgrowth as its central feature. This model then
accounts for both intestinal and extraintestinal IBS symptoms. Further sup-
port is given to small intestine bacterial overgrowth (SIBO) in a subset of
patients with IBS (Pimentel, Chow, & Lin, 2000), and evidence exists that IBS
262 INTEGRATIVE GASTROENTEROLOGY


symptoms can be ameliorated with poorly absorbed antibiotics (Pimentel,
Chow, & Lin, 2003). Indeed, there are some physicians who use a nonabsorb-
able antibiotic (rifaximin) as therapy for IBS patients suspected of SIBO
(Pimentel et al., 2006).


      Postinfectious Irritable Bowel Syndrome (PI-IBS)

Patients experiencing infectious diarrhea may be predisposed to IBS symp-
toms. Postinfectious IBS develops in 3% to 30% of individuals following bacte-
rial or viral gastroenteritis. Major risk factors include the severity of the initial
illness, female gender, prior anxiety/depression, and other psychological fac-
tors (Spiller & Campbell, 2006). Symptoms may be sustained by immunologic
factors (Dupont, 2007). Various histologic changes include increased intra-
epithelial and lamina propria lymphocytes, as well as increased intestinal per-
meability. Cytokine profiles reveal increased expression of interleukin (IL)-1b,
a proinflammatory cytokine. Treatment and prognosis are similar to that of
other IBS patients. Special attention should be given to the elimination of
nutrients that contribute to the patient’s symptoms (reduction of lactose, sor-
bitol, fructose). Antidiarrheals for diarrhea, bulk laxatives for constipation,
low-dose anticholinergics, or selected antidepressant medications for abdomi-
nal pain or cramps should be used.


           Probiotics and Irritable Bowel Syndrome

The goal of probiotic therapy is to beneficially alter the microbial flora by ame-
liorating the symptom complex associated with IBS. More than 15 random-
ized, double-blind studies of probiotics have been published, using single or
multiple bacterial strains. These studies generally reveal methodologic design
limitations, lack of comparative standardizations, variations in dosages, lack of
dose-response curves, different durations of study, and use of small patient
numbers (Borowiec & Fedorak, 2007; Guslandi, 2007; Jonkers & Stockbrugger,
2007; Camilleri, 2006). However, it is apparent from these studies that the
symptoms in common—flatulence, bloating, distention, abdominal pain, and
altered bowel function, as measured by patient’s global assessment—are com-
pletely or partially ameliorated. Thus, in concert with Dr. Lin’s assessment
noted previously, it is this author’s belief that the commensal bacteria remain a
central focus. Probiotics can replace the diminished concentrations of lactoba-
cilli and bifidobacteria noted in IBS patients, thus counteracting the proin-
flammatory cytokines interleukin-12 (IL-12.) Abnormal colonic fermentation
        Probiotics in the Prevention and Treatment of Gastrointestinal Disease   263


(King, Elia, & Hunter, 1998) may be ameliorated, reducing the short-chain
fatty acid contractile propulsive activity. Increased deconjugation of bile acids
by lactobacilli and bifidobacteria can reduce the bile acid load, and diminish
colonic mucosal secretion, which contribute to diarrheal symptoms. Two ran-
domized controlled studies deserve mention: one with a single strain probi-
otic, and the other a multi-strain. A four-week, multicenter study with a large
number of female IBS patients used Bifidobacteria infantis compared to pla-
cebo in a dose-ranging study. Statistical improvement was demonstrated in
composite global symptom scores and bloating (Whorwell et al., 2006). This
author’s four-week, multicenter randomized placebo-controlled study used a
multi-strain probiotic (Lactobacillus acidophilus LA-5, Bifidobacterium BB-12,
Lactobacillus paracasei CRL-431 and Streptococcus thermophilus STY-31), with
diarrhea as the primary end point, and demonstrated statistical reduction of
diarrheal episodes, as well as decreased bloating (Friedman & Biancone,
2008).


                          Traveler’s Diarrhea

Interest in traveler’s diarrhea is prompted by the frequency of global vacations
and business travel. Highest risk areas (>30%) are Mexico, South and Central
America, Asia, and Africa. The most common causative bacterial organism is
enterotoxigenic E. coli (ETEC). The possible progression of this illness to
postinfectious IBS is a matter of concern. Dupont has summarized recom-
mendations for prevention and treatment.

  1. Bismuth subsalicylate, (2.1 g/day–two tablets with meals and at bed-
     time): 65% effective
  2. Levofloxacin, one 500 mg tablet once daily: 80% effective
  3. Rifaximin, one 400 mg tablet twice daily: 75% effective
  4. Probiotics, Lactobacillus GG, one capsule twice daily: 40% effective
     (Hilton et al., 1997)


             Antibiotic-Associated Diarrhea (AAD)

Antibiotic-associated diarrhea occurs in 5% to 25% of patients receiving antibi-
otics, with increased risk in the aged, immunosuppressed, and GI surgery
patients. AAD extends hospital stays by 8 to 20 days, causes higher medical care
costs, and places patients at higher risk for acquiring other nosocomial infec-
tions. Agents most likely to cause diarrhea include cephalosporins, clindamycin,
264   INTEGRATIVE GASTROENTEROLOGY


and broad-spectrum penicillins. Antibiotics alter epithelial barrier defense,
allowing insurgence of pathogens. Clostridium dificile is the most severe form
of AAD, and accounts for 15% to 25% of hospital cases. This is a toxin-mediated
illness with characteristic clinical and pathologic features (Bartlett, 2002).
Diagnosis is confirmed by assay of toxins A & B. Probiotics prevent mucosal
barrier disruption and restore normal commensal bacteria. Saccharomyces
boulardii has been effective in reducing AAD, and as adjunctive therapy for
C. difficile infection (McFarland, 2006). Mechanisms of action include inacti-
vation of toxins A & B, stimulation of host immune system, and trophic effects
on intestinal mucosa (Buts & Bernasconi, 2005). The dosage is 250 mg twice
daily for prevention, and four times daily to prevent recurrent C. difficile coli-
tis, in concert with either metronidazole or vancomycin. Lactobacillus GG
has been extensively studied as effective treatment of acute diarrhea in infants
and children, dosage being one capsule twice daily. This Gram-positive rod
has powerful adhesive properties, modulates antigen transport, augments
immune responses, and increases IgA secretion (Doron, Snydman, & Gorbach,
2005).


                   Inflammatory Bowel Diseases

Causative elements of inflammatory bowel diseases are genetic predisposition,
altered immune response, environmental factors (diet, smoking, stress), and
commensal bacteria. Commensal bacteria have been implicated in the patho-
genesis of IBD because the areas of inflammation involved have a high density
of luminal bacterial organisms, the continuity of the fecal stream is linked with
disease activity, surgical interruption of the stream results in diminished
inflammatory activity, and restoration results in renewed inflammation. These
concepts have been supported by the creation of a colitis-like disease in genet-
ically altered animals, in which colitis only occurs when microbiota are added
to the germ-free animal. Pouchitis is a nonspecific inflammation of the ileal
reservoir following ileal pouch–anal anastomosis for ulcerative colitis.
Approximately half of all pouch patients experience inflammation at some
time after the operation. There are diminished amounts of lactobacilli and bifi-
dobacteria in the pouch contents. Most patients respond to antibiotic therapy
(metronidazole or ciprofloxacin). Recurrent or refractory inflammation occurs
in 10% to 15% of patients. After suppression of the inflammation with antibiot-
ics, maintenance therapy is needed. Probiotics have been successfully used in
place of further antibiotic therapy. Probiotic treatment of pouchitis was the
first major randomized controlled trial for IBD demonstrating prophylactic
         Probiotics in the Prevention and Treatment of Gastrointestinal Disease   265


efficacy for recurrent disease (Gionchetti et al., 2000). Gionchetti et al., ran-
domized 40 patients and compared 20 patients on VSL3 (3 g twice daily; four
strains of Lactobacillus [casei, plantarum, acidophilus, and delbruckii subsp bul-
garius]; three strains of Bifidobacterium [longum, breve, and infantis]; and one
strain of Streptococcus [salivarius subsp thermophilus]) with 20 patients on pla-
cebo for nine months. In the VSL3 group three (15%) patients relapsed com-
pared with 20 (100%) in the placebo group (P=0.001). Within four months
after discontinuation of therapy, 100% of responding patients relapsed. All of
the responding patients on VSL3 showed an increase in the concentrations of
lactobacilli and bifidobacteria. Two years later, a similar study confirmed these
results (Mimura et al., 2004). Administering 6 g/day immediately after opera-
tion as a prophylactic to pouch patients for one year prevented recurrent
pouchitis in 90% of subjects, compared to 60% recurrence on placebo
(Gionchetti et al., 2003).


                             Ulcerative Colitis

Ulcerative colitis is a mucosal inflammatory disease that may affect the rectum
(proctitis), rectosigmoid (proctosigmoiditis), extend to the splenic flexure
(left-sided colitis), or involve the entire colon (pancolitis). Most human trials
have assessed the efficacy of probiotics on sustaining remission following sup-
pression by anti-inflammatory agents (steroids, immunosuppressive agents,
biologic agents, mesalamine). The reason for treating quiescent disease rather
than active colitis is related to rapid passage of the probiotic through the GI
tract secondary to diarrhea, disallowing adequate time for nidation and prolif-
eration of the probiotic. Open label studies using much larger doses of probi-
otics have shown some success. Equivalency studies, comparing remission
rates of E. coli Nissle strain 1917 with mesalamine, have been reported (Kruis
et al., 1997; Rembacken et al., 1999). These studies are interesting, but not per-
suasive. In an open label, two-center trial by Fedorak and Madsen (2004),
30 patients with mild to moderate ulcerative colitis who failed mesalamine
therapy were treated with VSL3 (1 x 1012 CFU daily) for 4 months with a remis-
sion rate of 63%. Another open label study using Saccharomyces boulardii
treated 25 mild to moderate colitis patients who failed mesalamine therapy
(Guslandi, Giollo, & Testoni, 2003). These investigators used 750 mg daily for
one month, with a response rate of 68%. In summary, the use of probiotics in
both the acute phase and maintenance of ulcerative colitis are suggestive, but
inconclusive. Large, randomized, double-blind, placebo controlled trials are
needed.
266   INTEGRATIVE GASTROENTEROLOGY




                            Crohn’s Disease

Crohn’s disease is a chronic inflammatory bowel disease that can affect any
part of the GI tract from mouth to anus, with a predominance of small bowel
and colonic involvement. Pathologically, it is transmural, affecting mucosa,
submucosa, muscularis and serosal surfaces. Crohn’s disease trials are divided
into three areas: (1) treatment of acute, active disease; (2) maintenance after
medically induced remission; and (3) maintenance after surgically induced
remission. There are no randomized, controlled trials of patients with acute,
active Crohn’s disease. In the maintenance phase of medically induced remis-
sion, a double-blind study by Malchow (1997) with 28 patients, randomized
to receive E. coli Nissle l917 compared to placebo for one year, revealed a
relapse rate of 30% in the E. coli group compared to 70% in the placebo group.
An open label maintenance study by Guslandi et al. (2003) compared
Saccharomyces boulardi 1000 mg/day + mesalamine 2 g/day with mesalamine
3 g/day for six months. The remission rate was 94% with the former and 38%
with the latter. A randomized, controlled trial of maintenance after surgical
resection by Campieri et al. (2000) treated 40 patients for one year, comparing
rifaximin l.8 g/day for 3 months followed by VSL3 for 9 months with mesala-
mine 4 g/day. Endoscopic remission was noted in 80% versus 60% of patients
on mesalamine alone. Overall, published results do not support the use of pro-
biotics in the treatment of active Crohn’s disease, or as maintenance therapy
for medical or surgically induced remission.


                              Safety Issues

The safety of the microbes traditionally used as probiotics has been confirmed
through experience. The use of non-sporing LAB in fermented foods is wide-
spread. There have been reports associating LAB and S. boulardii with clinical
infection in immunosuppressed, severely debilitated patients (Gasser, 1994;
Schlegel, Lemerle, & Geslin, 1998). Probiotics should not be used in severely
immunocompromised patients, patients with synthetic valves, or patients with
indwelling central venous catheters (Hennequin et al., 2000). Capsules should
not be broken in patients’ rooms for use in enteral tube feedings.
        Probiotics in the Prevention and Treatment of Gastrointestinal Disease   267




                                 Summary

In the past decade there has been a dramatic resurgence of interest in com-
mensal bacteria related to improved genetic analysis of intestinal microbiota.
These bacteria benefit the host by performing metabolic functions, including
energy-producing fermentation of malabsorbed carbohydrates that produce
short-chain fatty acids, adding to trophic action on the epithelium, producing
vitamins, and playing a pivotal role in the development of the immune system.
Probiotics are live microbial feed supplements that beneficially affect the host
animal by improving its intestinal microbial balance. Selected clinical studies
demonstrate that probiotics play a role in the alleviation of such illnesses as
lactose intolerance, infantile necrotizing enterocolitis, AAD and C. difficile
colitis, IBS, traveler’s diarrhea, IBD, and pouchitis. There are a limited number
of well-regarded, randomized, placebo-controlled double blind trials avail-
able. Such trials have focused on pouchitis, AAD, and IBS. Future research
using single strain and multi-strain probiotics in humans and animals will
provide further supporting evidence regarding the value of probiotics.
                                    30
       The Role of Nutritional Genomics and
      Functional Medicine in the Management
                 of Crohn’s Disease
                 SHEILA G. DEAN AND KATHIE M. SWIFT




                                 key concepts

      ■   Diet and nutritional intervention for gastrointestinal health
          may be personalized to the individual’s genetic uniqueness.
      ■   Multiple risks have been identified that can increase the risk for
          Crohn’s disease; however, research strongly supports genetic
          susceptibility and a leaky gut as predisposing factors.
      ■   Functional clinical tests to assess intestinal inflammation, such
          as fecal calprotectin, are useful diagnostic tools.
      ■   Certain nutrients such as antioxidants and polyphenols can
          provide protection of the gut mucosa, and functional foods,
          including prebiotics and probiotics, support function of the gut
          immune system.
      ■   A “4R” GI restoration program that involves removing toxic
          substances, replacing digestive factors, reinoculating with com-
          mensal bacteria, and regenerating the GI integrity, may have sig-
          nificant impact in inflammatory bowel disease, and merits
          further study.
                                        ■




268
             Introduction to Nutritional Genomics



N
          utritional genomics is an emerging field that is now defined as the
          interface between genes and nutrition. It addresses the concept of
          one’s biochemical and genetic uniqueness, and how this interaction
then gives rise to outward, physical traits known as the phenotype. While nutri-
tional genomics continues to develop, the groundwork was established over
50 years ago by pioneers such as Linus Pauling and Roger Williams. Dr. Pauling,
Nobel Prize winner for Chemistry in 1954, and Peace in 1962, was already
teaching about the importance of nutrients in modulating physiological pro-
cesses at the biomolecular level (Pauling, The Roots of Molecular Medicine).
Roger Williams is credited with developing the concept of biochemical indi-
viduality, and has been described as having “contributed to the evolution of the
understanding of the molecular origin of disease” and advanced the concept of
genotrophic disease (Williams, 1998).
   The catalyst for the development of present-day nutritional genomics has
been the Human Genome Project, a multinational undertaking that began in
1990. While there were a number of goals, the primary goal was to identify the
nucleotide sequence of the human DNA. However, the specific goals have
changed over time, since the Human Genome Project was completed in 2003,
earlier than expected. Current research is focused on identifying the total
number of genes, their chromosomal location, and their function (Human
Genome Project Information, 2007).
   Why is this important to the healthcare team? One reason may be because
the impact of the Human Genome Project has created new information that is
expected to alter the approach to risk assessment of nutritional issues. However,
in order for the digestive healthcare practitioner’s evolving role in the applica-
tion of nutritional genomics to clinical practice to occur effectively, it will
require a deepened understanding of genomics and gene–diet interactions.
(Kozma, 2003).


   Individual gene variants called SNPs (single nucleotide polymorphisms)
   result in differential response to environmental factors including diet.


    Fogg-Johnson and Kaput (2003) explain that some of the new information
of the Human Genome Project is surfacing in areas that are not totally predict-
able. Through the Human Genome Project, it has been discovered that
270 INTEGRATIVE GASTROENTEROLOGY


individual gene variations exist, and are referred to as single nucleotide poly-
morphisms (SNPs, pronounced “snips”). These SNPs result in differential
response to environmental factors, such as diet. The science of how naturally
occurring chemicals in foods alter expression of genetic information at the
molecular level, and how this affects the individual phenotype, is the essence
of what nutritional genomics scientists seek to uncover (Fogg-Johnson &
Kaput, 2003).


  An understanding of genomics and gene–diet interactions will impact the
  delivery of personalized clinical nutrition practices.



   Diet, lifestyle, and environment have significant influence on the way an
individual can metabolize specific substances based upon his or her genetic
uniqueness. These discoveries have opened the door for the future of molecu-
lar medicine, and the development of a personalized medicine that recognizes
aspects of gene–diet–environment interactions and their roles in individual
disease causation, and the design of specific intervention programs.
   The takeaway from these concepts is that one size does not fit all. Diet and
nutritional intervention must be personalized to the genetic characteristics of
the individual. Gastrointestinal health is particularly important to achieving
optimal nutrition and affords several examples of how diet and genes interface
and how the field of nutritional genomics can assist the healthcare team in
maximizing nutrition care interventions for the individual.

  The GI tract functions as a selective barrier between the internal and exter-
  nal environment and the intestinal microflora plays an active role in main-
  taining gut integrity.




                            The Healthy Gut

  Gastrointestinal health affords several examples of how nutritional genom-
  ics can maximize nutrition care intervention.




   The gastrointestinal (GI) tract is the second-largest body surface area. The
condition of this organ’s microflora is essential to optimal health. The healthy
intestinal wall is coated with hundreds of different species of microorganisms,
                     The Role of Nutritional Genomics and Functional Medicine 271


both beneficial and pathogenic bacteria, numbering in the trillions (Whitney,
Cataldo, & Rolfes, 1998). This rich protective coating of microorganisms acts
in concert with the physical barrier provided by the cells lining the intestinal
tract, and other factors, to provide the body with important filter-like protec-
tion. So, in addition to digesting, absorbing, and eliminating food substances
and nutrients, the normal GI tract functions as a critical semipermeable (selec-
tive) barrier between the internal and external environment. This prevents
toxic, antigenic, or pathogenic molecules or microorganisms from entering
the bloodstream. Ultimately, the importance of the intestinal microflora and,
more specifically, its composition, in physiological and pathophysiological
processes in the human GI tract, is becoming more evident (Jones, 2005).


                    Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a critical and chronic disorder of the
intestines. Generally, its complications can be severe, widespread, and very
painful. Crohn’s disease and ulcerative colitis (UC) are two forms of IBD.
   As researchers try to understand its long-unknown etiology, there does not
appear to be one precise cause of Crohn’s disease. However, it is clear that
Crohn’s disease is relapsing in nature, and it affects all layers of the intestines
from mouth to anus. In comparison, UC is generally limited to the large bowel
and does not necessarily affect all layers of the intestine.


                                Risk Factors

   Crohn’s disease and ulcerative colitis are two forms of inflammatory bowel
   disease (IBD) with multiple etiologies including genetic susceptibility.


   There are several risk factors (see Table 30.1) for Crohn’s disease, which
range from adult appendectomy to the use of various substances, including
nicotine (Somerville, Logan, Edmond, & Langman, 1984; Cottone, Rosselli,
Orlando, Oliva & Puleo1994; Lindberg, Jarnerot, & Huitfeldt, 1992), oral con-
traceptives, antibiotics, and nonsteroidal anti-inflammatory agents (NSAIDs).
Even second-hand smoke exposure has been shown to increase risk for devel-
oping CD (Lashner, Shaheen, Hanauer, & Kirschner, 1993; Persson et al., 1990).
Other demographic factors, such as economic, educational, geographic, and
occupational status, can increase the risk of developing CD (Sonnenberg et al.,
1991). Despite these risk factors, Ferguson (Ferguson, L., Shelling, A. N.,
272   INTEGRATIVE GASTROENTEROLOGY


                     Table 30.1. Risk Factors for Crohn’s Disease

• Genetics
• Medications: oral contraceptive agents, antibiotics, nonsteroidal
  anti-inflammatory agents (NSAIDs)
• Diet
• Stress
• Socioeconomics
• History of eczema




Browning, B. L., Huebner, C., & Petermann, I 2007) explains that “IBD is con-
sidered a genetic disease,” as approximately 20% of people with one form of
IBD have a blood relative also with IBD, and 58% of monozygotic twins share
the disease as compared to 4% of dizygotic twins (Jess et al., 2005; Halfvarson
et al., 2005). Other factors that appeared to increase disease risk were history
of eczema and consumption of a low-fiber diet (Bartel et al., 2008) Research
has demonstrated that stress can be a contributing factor in Crohn’s disease.
Crohn’s disease is characterized by increased intestinal permeability, and
extensive animal research has shown stress significantly influences intestinal
permeability (Hollander, 1999). Furthermore, psychological stress, anxiety,
depression, and altered quality of life are likely to influence further Crohn’s
disease activity following a relapse (Mittermaier et al., 2004).


            The Immune–Inflammatory Connection

The gastrointestinal tract contains trillions of bacteria that are, ideally, in
homeostasis with the host immune system (MacDonald, 2005). The gut con-
tains most of the immune cells in the body, and engages in attacking harmful
pathogens while leaving symbiotic bacteria largely unscathed (Rescigno &
Chieppa, 2005).


  Th1 & Th2 cells are important regulators of the gastrointestinal immune
  system and Th1/Th2 balance plays an important role in gut mucosal integrity.


   One theory of immune regulation involves homeostasis between T-helper 1
(Th1) proinflammatory and T-helper 2 (Th2) anti-inflammatory activity (Kidd,
2003). “Th1” and “Th2” cells are “important regulators of the class of immune
response.” (Kidd, 2003) Alterations in the host gastrointestinal flora can have a
significant influence on the Th1/Th2 balance of the gastrointestinal immune
                     The Role of Nutritional Genomics and Functional Medicine 273


system (gut-associated lymphoid tissue, or GALT; see Mazmanian et al., 2005).
Sometimes referred to as systemic versus organ-specific immune responses,
respectively, balance of Th1/Th2 cytokines produced by the mucosa-associated
lymphoreticular system (MALT) and the GALT plays a role in the stabilization
of mucosal surfaces in the gut (Neurath et al., 2002). Mullin et al. (1996) were
the first to elucidate the predominance of Th1 responses in the intestinal
mucosa of Crohn’s disease patients. These mucosal surfaces have multiple tasks
that include absorption, macromolecule transfer, and intestinal barrier and
secretory functions. Large mucosal surfaces, such as the 300 square meters
found in the human intestinal tract, are continuously exposed to millions of
potentially harmful antigens from the environment, food, and intestinal
microbes.
   The mucosal surfaces possess a unique immune system that tightly controls
the balance between responsiveness and nonresponsiveness. Loss of this
immunological recognition of “friend versus foe” in the gut can result in acti-
vation of the inflammatory process (Rescigno & Chieppa, 2005). There is
growing evidence that chronic inflammatory disorders in the mucosa, such as
IBD, are due to the dysregulation of the mucosal immune system, leading to a
Th1-dominant inflammatory reaction and impairment of the barrier function
of the gut (Neurath et al., 2002).
   The Th1–Th2 immune response paradigm hypothesizes hypotheses that,
under the influence of a variety of factors including the cytokines, interleukin
4 (IL-4) and IL-12, naive T-cells can mature into one of two phenotypes, Th1 or
Th2, that counter-regulate each other. This model illustrates that, in most cir-
cumstances, interaction between Th1 and Th2 cells is more complex than orig-
inally thought. These cell types probably represent extreme examples of a
spectrum of phenotypes, and it is possible that a cell is not committed irrevo-
cably to one phenotype (see Figure 30.1).


             Genes/Gene Variants Associated With
                  IBD—What Do We Know?

Knowing the genes and gene variants associated with IBD can be useful for the
practitioner, once it is understood what genes are involved and how their vari-
ations are related to underlying mechanisms of IBD pathogenesis. Furthermore,
evidence-based nutrition intervention can be used to modulate genetic expres-
sion, which can ultimately affect phenotypic outcome of the individual.
   While IBD appears to be of polygenic etiology, research strongly supports
the assumption that susceptibility to IBD, especially Crohn’s disease, is inher-
ited. It also indicates that IBD is not inherited as a Mendelian trait, but rather
274 INTEGRATIVE GASTROENTEROLOGY


                Table 30.2. Susceptibility Genes Associated with IBD
Name of the gene          Gene abbreviation   Gene variants                Areas genes affect
                                              (discussed in this review)

Caspase-activated         CARD15/NOD2         • Arg702Trp                  Affects bacterial
recruitment domain                            • Gly908Arg                  recognition of the
15/nucleotide                                 • 1007finsC or               intestinal wall
oligomerization                                 c.3020insC
domain 2

Autophagy-related         ATG16L1                                          Affects bacterial
16-like 1                                                                  recognition of the
                                                                           intestinal wall

Human beta defensins      HBD-2, HBD-3                                     Affects bacterial
B2, B3 and B4             and HBD-4                                        recognition of the
                                                                           intestinal wall

Major histocompatibility MHC                                               Affects immune
complex                                                                    response

Interleukin-23 receptor   IL23R                                            Affects immune
                                                                           response

Toll-like receptors       TLRs                                             Affects immune
                                                                           response

Sodium dependent          SLC22A4/            • SLC22A4 1672 C>T Affects mucosal
organic cation            SLC22A5             • SLC22A5 -207 G>C transport or
transporters              (also called                           polarity of the
                          OCTN1/                                 intestinal wall
                          OCTN2)

ATP-binding cassette      ABCB1                                            Affects mucosal
subfamily B member 1                                                       transport or
                                                                           polarity of the
                                                                           intestinal wall

Drosophila discs large    DLG5                •   DLG5 113G>A              Affects mucosal
homologue 5                                   •   P.P1371Q                 transport or
                                              •   P.G1066G                 polarity of the
                                              •   Rs2289308                intestinal wall
                                              •   DLG_e26
                                              •   P.D1507D
                      The Role of Nutritional Genomics and Functional Medicine 275


has a complex genetic basis, with many contributing genes and at least nine
susceptibility loci identified (Neurath et al., 2002; Chamaillard et al., 2006).
Table 30.2 is a classification of the susceptibility genes, their variants, and
affected areas (Hampe et al., 2001; Hugot et al., 2001; Chamaillard et al., 2006;
Schreiber et al., 2005; Ogura et al., 2001; Peltekova et al., 2004; Stoll et al., 2004;
Cho, 2006; Buning et al., 2006).


   IBD has a complex genetic basis with many contributing susceptibility genes
   and gene variants.




  This chapter is focused specifically on three IBD-associated genes that
appear to identify major susceptibility loci for Crohn’s disease: (1) CARD15/
NOD2; (2) DLG5; and (3) SLC22A4/A5 (OCTN1/OCTN2).


           Gene Variants and Their Potential Impact
                     on IBD Pathogenesis

CARD 15/NOD2. Alterations in this gene have been associated with a defective
bacterial signal that leads to NF-κB overexpression and subsequent excessive
immune response, which can lead to chronic gut inflammation in susceptible
individuals.
   DLG5. Variations in this gene seem to predispose individuals to what has
been coined “leaky gut syndrome,” thus allowing for intestinal permeability
and integrity dysfunction.
   SLC22A4/SCL22A5 (OCTN1/OCTN2). Functional polymorphisms decreas-
ing OCTN activity and/or expression have been associated with chronic
inflammation, and contribute to CD/IBD pathogenesis. Specifically, this may
be due to reduced carnitine transport function, resulting in impaired fatty acid
metabolism in the gut, and toxic bacterial metabolites generated due to reduced
ability for proper clearance of bacterial byproducts.


   CARD15/NOD2: associated with exaggerated immune response
   DLG 5: associated with increased intestinal permeability
   SLC22A4/SCL22A5 (OCTN1/OCTN2): associated with impaired fatty acid
   metabolism and reduced clearance of toxic bacterial byproducts
276    INTEGRATIVE GASTROENTEROLOGY




                   Current Medical Management

Conventional pharmacological treatment has been directed toward suppress-
ing inflammation, and antibiotics for lowering bacterial antigenic drive to the
overactive mucosal immune system. Typical drugs (see Table 30.3) used to
treat Crohn’s include aminosalicylates (such as sulfasalazine and mesalamine),
corticosteroids (such as prednisone and budesonide), immunosuppressive
agents (such as azathioprine, 6-mercaptopurine, methotrexate), and antibiot-
ics (Baumgart & Sandborn, 2007). More recently, anti-TNF-alpha monoclonal
antibodies, such as infliximab and related drugs (Remicade®, Enbrel®,
Humira®), are being prescribed, since tumor necrosis factor appears to play a
significant role in the pathogenesis of Crohn’s disease (Bamias et al., 2003;
Braegger et al., 1992). Antidepressants are typically offered for assisting with
stress management, as stress can also aggravate Crohn’s disease symptoms
(Lerebours et al., 2007).
   Unfortunately, medications used in the therapy of IBD often contribute to
the development of many nutrient deficiencies (see Table 30.4). For example,
sulfasalazine produces folate malabsorption, by competitive inhibition of the
jejunal folate conjugate enzyme (Hoffbrand et al., 1968). Corticosteroids sup-
press small intestinal calcium absorption and increase urinary calcium excre-
tion. Cholestyramine (which is sometimes used in patients who have undergone



      Table 30.3. Pharmaceuticals Used in the Management of Crohn’s Disease
Aminosalicylates                              Sulfasalazine

Corticosteroids                               mesalamine

                                              prednisone

                                              budesonide

Immunosuppressants                             azathioprine

                                              6-mercaptopurine

                                              methotrexate

Anti-TNF-alpha monoclonal antibodies          Remicade®

                                              Enbrel®

                                              Humira®
                      The Role of Nutritional Genomics and Functional Medicine 277


       Table 30.4. Drug-Induced Nutrient Deficiency and Potential Mechanisms
Drug                Nutrient depleted       Potential mechanism

Sulfasalazine       Folic acid              competitive inhibition of the jejunal folate
                                            conjugate enzyme

Corticosteroids     Calcium                 suppresses small intestinal absorption and
                                            increase urinary excretion

Cholestyramine      Fat, calcium, and       used in those who have undergone
                    fat-soluble vitamin     post-ileal resection in Crohn’s disease to
                    deficiencies            prevent diarrhea

Sulfasalazine       Water and fat-soluble   may cause nausea, vomiting, and
                    vitamins                dyspepsia

5-aminosalicylic    Water and fat-soluble
acid                vitamins

metronidazole       Water and fat-soluble
                    vitamins



post-ileal resection in Crohn’s disease to prevent diarrhea) produces fat, cal-
cium, and fat-soluble vitamin deficiencies. Sulfasalazine, 5-aminosalicylic
acid, and metronidazole may cause nausea, vomiting, and dyspepsia, which
frequently lead to decreased nutrient intake (Riley et al., 1988; Singleton et al.,
1970).


                       Nutritional Management


   Drug-induced nutrient depletion is a common side effect of commonly pre-
   scribed medications for IBD.



   Elemental diets, elimination diets, omega-3 fish oils, high-fiber, low-fiber,
high-protein, low-residue diets, and bland diets have all been used in one form
or another as part of the nutritional management of IBD, and are reviewed in
Chapter 44 (Ferguson, L., Shelling, A. N., Browning, B. L. et al., 2007; Ferguson,
L. R., Shelling, A. N., Lauren, D. et al., 2007; Han et al., 1999; O’Sullivan &
O’Morain, 2006; Hodges, 2005). However, nutritional protocols have been
inconsistent, despite growing research on IBD. Until recently, theories on
nutritional management of IBD have been somewhat disunified.
278   INTEGRATIVE GASTROENTEROLOGY




                       Functional Clinical Tests

  Genetic testing, along with functional assays, such as intestinal permeabil-
  ity, can be useful in identification and treatment of IBD.


A major task of the intestine is to form a defensive barrier to prevent absorp-
tion of damaging substances from the external environment. This protective
function of the intestinal mucosa is called permeability. Ample evidence indi-
cates that permeability is increased in most patients with Crohn’s disease, and
in 10% to 20% of their clinically healthy relatives (Secondulfo, M. de Magistris,
L., Fiandra, R., Caserta L & Belletta M 2001). The major determinant of the
rate of intestinal permeability is the opening or closure of the tight junctions
between enterocytes in the paracellular space. A combination of functional
clinical testing that includes an intestinal permeability assessment, combined
with genetic testing (e.g., screening for CARD15/NOD2, DLG5, etc.), could
prove to be a prudent way to identify those at risk of IBD.

  Increased intestinal permeability is common Crohn’s disease patients and
  10%–20% of their healthy relatives.



    Because the increase in intestinal permeability in Crohn’s disease could be
caused by the inflammation itself, or by some predisposing genetic abnormal-
ity, permeability in patients and their healthy relatives have also been studied
(Hollander, 1988) Approximately 10% to 20% of healthy relatives of patients
with Crohn’s disease also have an abnormal increase in intestinal permeability
(Hollander et al., 1986; Katz et al., 1989; May et al., 1993). These observations
link genetic abnormalities and a leaky gut, which predisposes an individual to
the development of Crohn’s disease (Hollander, 1988; Hollander, 1993). Clearly,
a genetic predisposition could not be the only abnormality; rather, the pres-
ence of specific, as yet unknown, antigens in luminal contents or infectious
agents, as well as possible abnormalities in the intestinal immune responses,
are presumed to be additional factors in the genesis of the disease. The “leaky
gut” explanation ties together the influence of luminal antigens and an abnor-
mal immune reactivity, and offers a unifying concept that explains the interac-
tion between luminal factors and the immune system (Hollander, 1994).
    Conducting a fecal calprotectin evaluation is one type of test for measuring
intestinal inflammation (Teahon, Roseth, Foster, & Bjarnason, 1997; Tibble,
Sigthorsson, & Bjarnason, 1999). Calprotectin is a calcium-binding protein
                      The Role of Nutritional Genomics and Functional Medicine 279


found in the following types of white blood cells: neutrophilic granulocytes,
monocytes, and macrophages (Teahon et al., 1997). Calprotectin resists meta-
bolic degradation and can be measured in the feces. The fecal calprotectin test
makes use of the fact that the release of calprotectin in the stool is associated
with damage to the GI mucosa, and increased inflammatory processes (Tibble
et al., 1999).


                     Nutritional Influences in IBD

Buddington and Weiher (1999) proposed that, in managing functional gastro-
intestinal disorders, the GI system should be viewed as a flow system or “river.”
The GI tract is a complex ecological system that flows from top to bottom and
requires an optimum environment, which is influenced by nourishment to
create the appropriate “ecology” within the small and large intestines.


  Fecal calprotectin is a functional measure of damage to the GI mucosa, and
  resultant inflammatory processes.



   A variety of nutrients have been found to be deficient in Crohn’s disease
patients (See Table 30.5).


            Table 30.5. Malnutrition in Individuals with Crohn’s Disease
                           (adapted from Mullin, 2009)
Deficiency                Percentage of individuals   Treatment
                         with Crohn’s disease with
                         nutrient deficiency

Negative Nitrogen                 69%                Adequate energy and protein
Balance

Vitamin B12                       48%                1000 mcg/d x 7 then Q mo

Folate                            67%                1 mg/d

Vitamin A                         11%                5,000–25,000 IU/d

Vitamin D3                        75%                5,000–25,000 IU/d

Calcium                           13%                1,000–1,200 mg/d

Potassium                         5–20%              Variable

Iron                              39%                Fe Gluconate 300 mg TID

Zinc                              50%                Zn Sulfate 200 mg daily or BID
280    INTEGRATIVE GASTROENTEROLOGY



   The GI system can be viewed as a complex ecological system that flows like a
   river and is influenced by its environment.


   Causes include:

   •   Malabsorption in the small intestine
   •   Increased nutrient need because of disease activity
   •   Low nutrient intake
   •   Nutrient loss due to chronic diarrhea or increased transit time or
       effect of medications


   Nutrient deficiencies are common in Crohn’s disease, due to:
   • Malabsorption
   • Compromised dietary intake
   • Disease activity
   • Chronic diarrhea
   • Increased nutrient losses
   • Medications



   One study examining multiple nutrient deficiencies found 85% of 279 Crohn’s
disease patients had deficiencies. Nutrients most frequently found deficient
were iron, calcium, zinc, protein, vitamin B12, and folate (Rath et al., 1998).
   It has recently been suggested that certain protective nutrients and func-
tional foods can provide protection of the gut mucosa from the CARD15/
NOD2-related Th1-dominant inflammatory reactions (Duggan et al., 2002).
The amino acids glutamine and arginine, and the essential micronutrients
vitamin A, zinc, vitamin E, and the B vitamin, pantothenic acid, are among
these protective nutrients. Evidence indicates that chronic IBD is associated
with elevated oxidative stress in the intestinal mucosa, with increased levels of
reactive oxygen species and protein carbonyls in tissues, along with other
markers of free radical injury (Lih-Brody, 1996; Ding et al., 2007). Therefore,
supplementation with antioxidants, including ascorbic acid, tocopherol, and
food flavonoids like quercetin (found in apples) and epicatechin gallate (from
green tea) may be beneficial. Shapiro et al. (2007) discuss the addition of poly-
phenols to nutritional formulas to improve the outcome of patients with IBD.
Five polyphenols in particular have shown, in animal and human studies,
(Shapiro et al., 2007; Gupta et al., 1997; Gupta et al., 2001; Gerhardt et al.,
2001; Gautam et al., 2007; Camacho-Barquero et al., 2007; Kurup et al., 2007;
Sharma et al., 2007; Holt et al., 2005; Hanai et al., 2006) to have benefit in IBD
                    The Role of Nutritional Genomics and Functional Medicine 281


by reducing inflammation associated with variations of the CARD15/NOD2
and SLC22A4/A5 genes:

  •   Boswellia
  •   Curcumin
  •   Epigallocatechin
  •   Quercetin
  •   Resveratrol

   Prebiotics and probiotics are also important substances that support proper
function of the GALT and lead to the repair phase of gastrointestinal restora-
tion (Duggan et al., 2002).

  Free radical injury, and increased oxidative stress in the intestinal mucosa,
  warrants a diet rich in antioxidants, along with concomitant nutrient
  supplementation.



  Functional medicine seeks to understand the antecedents, triggers, and
  mediators underlying dysfunction.




         Putting it all Together with the Functional
          Medicine “4RTM” GI Restoration Program

There is a growing awareness that understanding the etiology at the genetic–
molecular–environmental level may be just as important, if not more impor-
tant, than disease classification. “Functional Medicine”—an evidence-based
systems biology approach—addresses this concept of underlying etiology and
root cause solutions, and is now being encouraged by the National Institutes of
Health under the new program NIH Roadmap, a route to accelerate medical
discoveries that will improve health (OPASI, 2007). In essence, functional
medicine assessment is concerned with understanding the antecedents, trig-
gers, and mediators of dysfunction that give rise to molecular imbalances
underlying the signs and symptoms of disease (Jones, 2005).
   The following is a brief adaptation of the “4RTM GI Restoration Program”
pioneered by the Institute for Functional Medicine for the management of gut
dysfunction and chronic disease. (Jones, 2005; Liska & Lukaczar, 2001). It is a
conceptual framework within which to target therapies aimed at improving GI
function.
282 INTEGRATIVE GASTROENTEROLOGY



   The 4R GI Restoration Program is a functional medicine GPS to assist the
   practitioner in targeting therapies to improve GI function, and includes:
   • Remove (offending foods, toxins, infections, stress)
   • Replace (enzymes and other digestive factors)
   • Reinoculate (probiotics)
   • Regenerate or Repair (healing nutrients)


   1. REMOVE
         What does this patient need to have removed for healthy GI
         function?

    Remove focuses on eliminating pathogenic bacteria, viruses, fungi, para-
sites, and other environmentally derived toxic substances from the GI tract.
Dietary modification is important, since foods to which a patient is intolerant
or allergic can exacerbate GI dysfunction, and stimulate immune and inflam-
matory responses systemically. Because Crohn’s disease is characterized by
elevations in anti-Saccharomyces cerevisiae (brewer’s yeast) antibodies in up to
60% of cases (Vermeire & Rutgeerts, 2004), eliminating foods with yeast may
prove to be therapeutic. Β-glucuronidase is a marker for fecal putrefaction
associated with increased risk of the adverse effects of colonic fermentation by
bacteria. Interestingly, reduction of β-glucuronidase in the stool was a favor-
able outcome observed with rice bran supplementation, but not with wheat
bran (Gestel et al., 1994).

   2. REPLACE
         What does this patient need to have replaced to support normal GI
         function?

   Replace refers to the replenishment of enzymes and other digestive factors
lacking, or in limited supply, in an individual’s GI environment. GI enzymes
that may need to be replaced include proteases, lipases, and saccharidases nor-
mally secreted by cells of the GI tract or by the pancreas. Other digestive fac-
tors that may require replenishment include betaine hydrochloride and
intrinsic factor, normally produced by parietal cells in the stomach wall (Griffin
et al., 1989).

   Regenerate (Repair) nutrients may include:
   • L-Glutamine
   • Fish Oils (EPA/DHA)
   • Zinc carnosine
                     The Role of Nutritional Genomics and Functional Medicine 283


   3. REINOCULATE
         What does this patient need to support or reestablish a healthy
         balance of microflora?

   Reinoculate refers to the reintroduction of desirable bacteria, or probiotics,
into the intestine to reestablish microflora balance and to limit proliferation of
pathogenic bacteria, candida, and microbes associated with variation in the
CARD15/NOD2 gene. Probiotics serve a variety of functions in the GI tract:
they synthesize various vitamins, produce short-chain fatty acids necessary for
colonic cell growth and function, degrade toxins, prevent colonization by
pathogens, improve epithelial and mucosal barrier function, and alter immune
regulation via stimulation of secretory IgA or reduction in TNF-alpha (Faber,
2001; Johnston, 2001; Malin, Suomalainen, Saxelin, Isolauri. 1996; Borreul
Carol & Casellas2002, Plain & Hotz, 1993).

   4. REGENERATE (also referred to as the REPAIR phase)
         What does this patient need to support the healing of the gastric
         and mucosal layer?

   Regenerate refers to providing support for the healing and regeneration of
the GI mucosa. Part of the support for healing comes from removing insults
that continually reinjure or irritate the mucosa, and promoting healthy micro-
flora. Zinc carnosine is a chelate compound consisting of a zinc ion and
L-carnosine, a dipeptide of beta-alanine and L-histidine. Studies have demon-
strated that zinc carnosine promotes wound-healing action, has an antioxidant
effect in the GI system, and seems to have anti-Helicobacter pylori activity (Lee
et al., 2000, Mahmood et al., 2007).
   Supplementation with omega-3 fatty acid-rich oil (3.24 gm of EPA and 2.16 gm
of DHA daily) lowered the inflammatory response associated with variation of
the CARD15/NOD2 and SLC22A4/A5 genes (decreased rectal levels of leukot-
riene B4), and improved remission in patients with IBD (Belluzi et al., 1996).
   L-glutamine supplementation has also been found useful as part of a repair
and regenerate program to restore GI mucosal integrity associated with the
variation in the DLG5 gene (Souba, 1990).
   A fifth “R” has recently been added (Functional Medicine Clinical Series,
2006):

   5. RELIEVE

  Relieve addresses acute discomfort in patients while treating the underlying
conditions. Lavender oil has been used as an upper GI antispasmodic
284   INTEGRATIVE GASTROENTEROLOGY


(Blumenthal, 2003), while chamomile flower extract and peppermint leaf oil
have been studied as lower GI antispasmodics (O’Hara et al., 1998). Additionally,
Chinese licorice root, tienchi ginseng root, and astragalus root may have a role
in addressing heartburn and mild indigestion (Blumenthal, 2003.
   Promoting gastrointestinal health through this type of program may have
significant effects, not only on localized intestinal inflammatory risk, but also
on systemic inflammatory processes associated with the loss of intestinal
mucosal integrity.


  A fifth R for Relieve addresses easing the discomfort with herbs, such as lav-
  ender oil, chamomile flower extract, peppermint leaf oil, and Chinese
  herbs.




                           Future Strategies

The application of nutritional genomics can create a better understanding of
IBD pathology, and has focused attention on the interaction between genetic
factors and bacteria within the gut. Increasing scientific evidence supports the
notion that IBD results from a genetic predisposition to abnormal interaction
with an environmental stimulant—most probably, part of the normal luminal
bacterial flora—which, in turn, leads to excessive immune activation and
chronic inflammation. There are many putative bioactive molecules being
identified that can help modulate genetic expression of inflammation; how-
ever, many of these components still need to be tested further with in vivo
animal models of human disease.
   In the past decade, nutrition research has undergone a shift in focus from
epidemiology and physiology to molecular biology and genetics. This shift has
resulted in a growing realization that we cannot understand the effects of
nutrition on health and disease without determining how nutrients act at the
molecular level. Muller and Kersten (2003) pointed out that “there has been a
growing recognition that both macronutrients and micronutrients can be
potent dietary signals that influence the metabolic programming of cells and
have an important role in the control of homeostasis.” As a result, adequately
trained health professionals who possess an authentic and experienced under-
standing of the interconnectedness of the biological systems in the human
body, as well as the common underlying mechanisms that cut across many
diseases, syndromes, conditions, and organ systems, will be required to inter-
pret and communicate this information both to the public and with regulatory
officials, to responsibly develop, apply, and progress this new field.
                     The Role of Nutritional Genomics and Functional Medicine 285


    Additionally, this solid background and training will allow for far more per-
sonalized preventative care that incorporates a client-centered approach, tai-
lored to the patients’ unique needs. Nutrition-focused practitioners are at a
pivotal point in the history of their practice. Kauwell (2003) recently stated,
“Armed with the findings of the Human Genome Project and related research,
dietetics practitioners will have the potential to implement more efficient and
effective nutrition intervention strategies aimed at preventing and delaying the
progression of common chronic diseases.” Vay Liang W. Go explains in a 2005
article that “with the advent of the postgenomic era, biological and medical
research and clinical practice [have] witnessed an explosion in strategies and
goals. This eventually will revolutionize the classical practice of nutrition from
the current evidence-based medicine towards genomic-based medicine”
(Go et al., 2005). But this very explosion can be part of the barrier to realizing
the vision for healthcare professionals. Clinicians today must contend, as never
before, with a massive amount of information emerging from the scientific
literature.
    One thing that can be done now, to move this vision ahead, will be the unbi-
ased utilization of the already created and available organizational architecture
of information that moves beyond the well-established “silos” of organ system
medicine. For example, the effects of chronic inflammation on one organ
system do not necessarily stop there. The inflammatory process can operate
throughout the patient entirely, affecting multiple systems including the brain,
the immune system, and the endocrine system.
    Utilizing this type of “functional medicine” approach will allow for a more
precise and clear evaluation, formulation, and integration of all the informa-
tion at our disposal, to create a systematic and effective nutrition care plan
for our patients that can potentially alter the trajectory of their health status
forever.


                                Conclusion

The emerging field of nutritional genomics, defined as the interface between
genes and nutrition, is credited with debunking the concept that “one size fits
all” as it relates to nutritional management of chronic disease, including
inflammatory bowel disease (IBD). Crohn’s disease, a subcategory of IBD, con-
tributes to significant morbidity, particularly in industrialized nations. It is
characterized by chronic inflammation and ulceration that can occur in any
portion of the intestinal tract. A number of factors contribute to its etiopatho-
genesis, including genetic, microbial, inflammatory, immune, and permeabil-
ity abnormalities. Several susceptibility genes have been associated with IBD;
286   INTEGRATIVE GASTROENTEROLOGY


however, this review focused specifically on three IBD-associated genes that
appear to identify major susceptibility loci for Crohn’s disease: (1) CARD15/
NOD2, (2) DLG5, and (3) SLC22A4/A5 (OCTN1/OCTN2). Variations of these
genes and their potential impact on IBD pathogenesis are discussed. Nutritional
management, including the use of various functional clinical tests, nutritional
influences in IBD and a functional medicine systems biology approach referred
to as the 4R™ Gastrointestinal (GI) Restoration Program weredescribed. The
4R™ approach, “Remove, Replace, Reinoculate, Regenerate” provides a frame-
work in which to focus clinical assessment and intervention. Future strategies
including a discussion of the evolving role of the registered dietitian as a vital
clinician in the integrated healthcare team were offered.
                                    31
         Functional Foods for Digestive Health
                     and Disease
                             ELIZABETH LIPSKI




                                key concepts

     ■   Diet affects GI health: Food can be inflammatory; food can be
         healing.
     ■   The Standard American Diet (SAD) accelerates chronic disease.
     ■   Probiotics, prebiotics and fiber help restore balance in the GI
         tract.
     ■   The Elimination Diet can become a useful tool to reduce gut
         inflammation in digestive conditions.
     ■   Functional foods can facilitate and restore digestive health and
         well-being.
                                       ■




                              Introduction



F
       ood is our most intimate contact with our external environment. Each
       day we put several pounds of food into our mouth. (Amber Waves
       2005). The body must read and react to the food as friend or foe, which
is why fully two-thirds of our immune system is located in the digestive system.
Increased intestinal absorption and dysbiosis can lead to systemic illness and
symptomatology and have been well-covered previously in this text. As dis-
cussed in Chapter 30), food is information that elicits a genetic and cellular
response.



                                                                            287
288   INTEGRATIVE GASTROENTEROLOGY


   Food can be inflammatory and anti-inflammatory. In our Western culture,
much of the food that is commonly eaten is inflammatory. In a recent issue of
the Journal of the American College of Cardiology, Guiliano et al state:

   “Dietary patterns high in refined starches, sugar, and saturated and trans-
   fatty acids, poor in natural antioxidants and fiber from fruits,
   vegetables, and whole grains, and poor in omega-3 fatty acids may cause
   an activation of the innate immune system, most likely by an excessive
   production of proinflammatory cytokines associated with a reduced pro-
   duction of anti-inflammatory cytokines.”(Giugliano, Ceriello et al., 2006)

   For example, processed foods contain denatured fatty acids, which lead to a
build-up of arachidonic acid and omega-6 fatty acids and a deficit of omega-3
fatty acids. A high omega-6-to-3 ratio commonly increases production of
arachidonic acid and the resulting inflammatory PGE2 prostaglandins. For
further details, see The Omnivore’s Dilemma by Michael Pollan (2007).
   This chapter will discuss the inflammatory nature of the standard American
diet, use of elimination diets to reduce digestive and systemic inflammation,
and use of specific foods to protect the gastrointestinal system.


                  NUTRITION AND DIGESTIVE WELL-BEING

Appropriate nutrition is critical for digestive well-being. In the Surgeon
General’s Report on Nutrition and Health (Koop, 1988), diet was reported to
play an important role in 5 out of the 10 leading causes of death. Although no
digestive illness is listed in the top 10, the digestive system serves to transport
nutrients to each cell of the body. If cells cannot assimilate adequate nutrients,
virtually any illness or condition can occur. This makes the process of diges-
tion critical for overall health and well-being.
    Although there is a growing public interest in nutrition, whole foods, and food
quality, nutrition is a topic rarely discussed except peripherally in the physician’s
office. Food diaries are seldom used as part of an initial medical history, even
though they are an essential part of understanding a patient’s overall health.


        THE STANDARD AMERICAN DIET IS INFLAMMATORY AND
                       LOW IN NUTRIENTS

Dietary patterns have changed dramatically during the last decade. The cur-
rent standard American dietary pattern is high in refined starches, sugar, and
                             Functional Foods for Digestive Health and Disease    289


saturated and trans fats, poor in natural antioxidants and fiber from fruits,
vegetables, and whole grains, and poor in omega-3 fatty acids. This may lead to
(Figure 31.1):

   • activation of the innate immune system
   • excessive production of proinflammatory cytokines
   • reduced production of anti-inflammatory cytokines

    Disappearance data indicates that Americans are eating 523 calories more
each day than in 1970 (Amber Waves 2005). It’s no wonder that we are increas-
ingly obese. Our foods are mainly processed, and each time a food is processed
it loses essential nutrients. The definition of a nutrient is that it is essential for
life; chronic deficiencies lead to changes in all body systems. Americans eat
20.4 of their calories as refined grains, yet only 3.5 as whole grains. When
grains are refined, they lose 58.1 of 19 vitamins and minerals they contain (see
Appendix C). Refined sugars, such as high-fructose corn syrup and white sugar,
comprise an additional 18.6 of our caloric intake, at an average of 141 pounds
per year, or 6.2 oz. per day (United States Economic Research Service Food
Consumption, 2007). Refined vegetable oils make up another 17.6, and alco-
hol 1.4. The damaged and nutritionally depleted omega-6 fatty acids and oils
used in processed foods increase levels of arachidonic acid and inflammatory
cytokines, which help promote inflammatory gut conditions such as Crohn’s
disease. Worse, potatoes as French fries are the vegetable most commonly eaten
by toddlers over 15 months of age. In 2004, soft drinks were the third most com-
monly consumed food among American children ages 2 to 5, with cookies and
French fries ranking sixth and seventh, respectively (Demory-Luce, 2004) No
wonder rates of childhood obesity and other diseases are rapidly increasing.
    All told, the typical American eats 58 of his or her total calories as high-
sugar, highly processed, nutritionally depleted, inflammatory foods (Cordain
et al., 2005).
    The film “Supersize Me” increased public awareness about the inflamma-
tory nature of processed fast food and its overconsumption. A Swedish study
(Kechagias et al., 2008) replicated the movie’s results. An intervention group of
18 people with an average age of 26.6 were asked to eat at least two fast food
meals per day for 28 days. The goal was to double their regular caloric intake,
increase total body weight by 5 to 15, and follow a sedentary lifestyle of not
more than 5,000 steps per day. Thirteen of the subjects (72.2) had pathologi-
cal increased levels of the liver enzyme alanine aminotransferase ALT; 23 had
steatohepatitis; and 13 had fatty liver. In most subjects, these elevations
occurred during the first week. One man was dismissed in the third week due
to increased ALT of 447 (normal is 0 to 40).
290   INTEGRATIVE GASTROENTEROLOGY


   This study is relevant to the eating habits of many Americans, including
children. An estimated 26.5 of Americans eat at fast food restaurants, which
contributes one-third of their total caloric intake. Fast foods have lower levels
of vitamin A, carotenoids, vitamin C, magnesium, fruits, and vegetables
(Bowman & Vinyard, 2004). Fifteen percent of adults in the United States have
nonalcoholic fatty liver disease, and 50 of adults with diabetes or hyperlipi-
demia have hepatic steatosis (Pitt, 2007). A 2006 study at the University of San
Diego School of Medicine looked at autopsies of 742 children and teens who
had died due to accidents, homicide, or suicide. Based on their results, the
researchers estimate that 10 of children in San Diego County have steato-
hepatitis. High-fructose corn syrup and end-stage glycation products have
been implicated in steatohepatitis (Thuy et al., 2008).


                     Use of the Elimination Diet

Approximately 3 of children and 1 of adults have IgE mediated food aller-
gies. Peanut allergies alone doubled from 1997 to 2002 (Sicherer, Muñoz-
Furlong & Sampson, 2003). One person in three changes their diet to adapt for
what they consider to be food allergies, although the true incidence of such
allergies is estimated to be around 5 (Cordain et al., 2005). The majority of
the people who believe that they have food allergies likely have food hypersen-
sitivities or food intolerances instead. Seventy percent of the world’s popula-
tion is considered to be lactose intolerant, for example; others have fructose
intolerance. In addition people can have other negative reations to substances
in food such as: Food hypersensitivity reactions (IgG, IgG4, IgM, IgA), lectins,
tyramines (found in cheese, caffeine, coffee, chocolate), complement reactions,
sulfate reactions (due to impaired sulfation pathways), inability to handle phe-
nols, oxalates, food dyes, food additives, or other possible food substances.
    In my clinical experience as a nutritionist, it is common for symptomatic
patients who test negative for celiac disease to respond positively to a gluten-
free diet. Although research on gluten intolerance is nearly nonexistent, one
can hypothesize that damage from gluten-containing grains is on a continuum,
with celiac disease at the far end of the spectrum.
    When working with someone with gastrointestinal (or rheumatological,
autoimmune, or respiratory) illness, it can be useful to begin with a low-
antigen, low-inflammation diet (Sköldstam. 1986; Sköldstam & Magnusson,
1991; Kjeldsen-Kragh, Haugen et al., 1994; Kjeldsen-Kragh, Hvatum et al.,
1995). Working with a “clean slate” can clear myriad symptoms by reducing
total load, enhancing detoxification pathways, and reducing inflammatory
cytokines. It’s simple and cost-effective.
                              Functional Foods for Digestive Health and Disease   291


   Research on elimination diets has been promising, One meta-analysis
reports that the only effective dietary strategy for ulcerative colitis is the elimi-
nation diet, but this observation was based upon one study (Galandi & Allgaier,
2002) Fasting has been well-researched in rheumatoid arthritis (Muller, de
Toledo, & Resch, 2001)
   There is an increasing number of controlled studies on elevations in IgG
antibodies and the use of elimination diets for a variety of GI issues.
   Research substantiates use of IgG and IgE testing in irritable bowel, atopy,
and other digestive and systemic conditions. In a study by Atkinson, 150
patients who had IgG food antibody testing were randomized to receive either
an appropriate elimination diet or a sham diet. After 3 months, there was a 24
reduction in symptoms in the study group (Atkinson, Sheldon, Shaath, &
Whorwell, 2004). A similar study was done in China: IgG antibodies for 14
common foods were tested in 55 people with diarrhea-dominant IBS, 32 people
with constipation-dominant IBS, and 18 normal controls. Sixty-three percent of
subjects with diarrhea-dominant IBS and 43.8 of subjects with constipation-
dominant IBS had positive IgG food antibodies. Both groups had more posi-
tive food antibodies than controls. After adhering to individualized eliminated
diets for 2 months, a total of 65.7 of people reported either complete improve-
ment (31.4) or remarkable improvement (34.3; see Yang & Li, 2007). Zar,
Kumar, and Benson (2001) report that elevations of IgG antibodies in subjects
with IBS.
   Drisko et al. (2006) investigated food intolerance using Rome II criteria, in
20 patients with IBS who had failed standard care. IgG and IgE food and mold
panels, comprehensive stool analysis, and small bowel bacterial overgrowth
were assessed. Subjects filled out quality of life questionnaires and complied
with elimination diets based on IgE and IgG testing results. They were also
given probiotics. Testing was repeated at 6 months, with follow up at 12 months.
In subjects who had significant responses to the diet, 100 had baseline abnor-
malities in IgG and IgE antibody levels. There were significant improvements
in stool frequency and quality of life. At baseline, 100 of subjects had imbal-
ances in beneficial and dysbiotic flora. At 6 months, there was a trend toward
normalization of beneficial bacteria, with no change in dysbiosis. At one year,
there was continued adherence to the food rotation diet and minimal issues
with IBS.
   There is much anecdotal evidence for use of the Specific Carbohydrate Diet,
which was popularized by Elaine Gottschall Ph.D. in Breaking the Vicious
Cycle, in GI disorders, especially in Crohn’s disease. Unfortunately no con-
trolled studies have been done on the Specific Carbohydrate diet. This diet is
entirely grain-free and limits disaccharides from starchy vegetables as well.
(www.scdiet.com)
292 INTEGRATIVE GASTROENTEROLOGY


                                  Table 31. Case1 Sidebar.
Case History:

• 48-year-old male, Caucasian

• Weight: 245 lbs. Height: 6’1”

• Current Medical Diagnoses

  • IBS

  • Osteoarthritis

  • Depression

  • Hypertension

  • High cholesterol

  • Eczema

  • Obesity (BMI of 32)

  • Allergies

• Current Medications

  • Wellbutrin XL

  • Benicar HCT

  • Topical steroid ointment

  • Aspirin

  • Previously had been on Lipitor

• Primary Complaints:

  • Constant GI cramps for 2 to 3 days; sharp pains are relieved with diarrhea, which
    lasts 2 to 3 days

  • Occurs several times a month

  • Abdominal bloating

  • BM: At least three times daily

• Secondary Complaints:

  • Lower back: fairly consistent low-grade pain, with flare-ups sending pain to hips
    and legs

  • Muscle inflammation, difficult to grip without pain.

  • Constant pain in hands and feet.
                                  Functional Foods for Digestive Health and Disease           293


                                   Table 31. (Continued)
Case History:

  • Eczema

  • Allergies/stuffy nose: cats, dust, pollen, molds

  • Depression

  • Low energy level

  • Caffeine necessary to jump start

  • Legs swollen by the end of the day

• History/Family History

  • Life-long GI issues—remembers several times a year as a child recurrent abdominal
    pain (RAP) and diarrhea.

  • Asthma as a child at age 10

  • Brothers also had asthma

  • Had stomach ulcer as a child

  • No significant family history noted

• Prior Testing

  • Upper GI: negative

  • Endoscopy: negative except for hiatal hernia

  • Colonoscopy: negative

• Food Diary

  • Breakfast: fruit, cereal (oat, rice or corn), soy or rice milk, coffee, sometimes fruit juice

  • Lunch: fruit, beans & rice, or Garden burger with veggie slices and bread, mustard.

  • Dinner: beans and rice, vegetable (yams, broccoli, kale, green beans), fish, pasta,
    bread, and margarine

  • Removed meat and dairy from diet a few weeks ago. This was a drastic change

• Initial Treatment Plan:

  • IgG and IgE food sensitivity/allergy testing

     • Ask physician to run Celiac Panel (IgG, trans-glutaminase, endomysial, anti-gliaden)

  • In the meantime, begin Elimination Diet plan for 2 weeks

  • Replace potassium (99 mg), calcium (400 mg), and magnesium (200 mg) lost to
    hydrochlorothiazide.
                                                                                       (continued)
294   INTEGRATIVE GASTROENTEROLOGY


                                  Table 31. (Continued)
Case History:

• Two-Week Recheck

  • Celiac testing: negative

  • Carefully followed elimination diet, which consisted of fruits, vegetables, poultry,
    fish, rice, olive oil, salt, pepper, herbs, spices

  • Lost 8 pounds

  • No gut pain, cramping, or diarrhea

  • No hand, foot, leg or hip pain

  • Played fiddle at a concert for 3 hours

  • Depression has lifted

  • Has not started calcium, magnesium, or potassium.

  • Nasal congestion has cleared.

  • Continue with diet. Just sent blood to lab IgG/IgE.

• Four-Week Recheck

  • IgG and IgE results indicate gluten, dairy, and egg intolerance. Eliminated eggs
    from diet.

  • Experiencing continued well-being.

• Six-Week Recheck

  • More improvement without eggs in diet

  • Has lost 18 pounds

  • No arthritis

  • No IBS symptoms

  • Off Wellbutrin

  • Has good energy, not relying on caffeine

  • No improvement with eczema

  • Hyper-sensitive to gluten

  • Resistant to further testing or taking any supplements

• Three-Month Recheck

  • Continues to feel great. “I never realized I’d actually feel younger.”
                                  Functional Foods for Digestive Health and Disease    295


                                   Table 31. (Continued)
Case History:

  • Found Belgian beers without gluten

  • Lost 30 pounds

  • Energy level is high

  • No IBS/No arthritis/No depression

  • Stopped ALL Medications

  • Eczema changing slowly

  • Extreme sensitivity to gluten

  • Resistant to further testing or taking any supplements

• One-year Recheck

  • Still on the diet

  • Feeling great!

  • Off of all medications

  • Cholesterol and blood pressure improved

  • Eczema not cleared

  • Gums are healthier than ever

  • Still sensitive to gluten

  • Seems more sensitive to dairy than before

  • Hay fever and allergies are diminished

  • Resistant to further testing, nutritional supplements, or any other intervention




                                The Functional Foods

Simply stated, a functional food is a food that confers one or more specific
physiological benefits that reduce risk of disease. A food or spice may be con-
sidered to be a functional food in its natural state. Functional foods are often
manufactured foods that contain specific nutraceutical ingredients. These are
often also called “medical foods.”
296   INTEGRATIVE GASTROENTEROLOGY




                               MEDICAL FOODS

   • There are two types of medical foods that can be effective for many people,
     when working with gastrointestinal issues: those designed to upregulate
     liver detoxification, and those designed to support GI function.
   • Currently one nutraceutical manufacturer produces a product that
     is specifically designed to support gastrointestinal function. This
     product is based on a low-allergy, high-amylase rice flour, plus amino
     acids, vitamins and minerals, and gut supportive nutrients, such as
     zinc, L-glutamine, panthothenic acid, and fructooligosaccharides
     (FOS). There are no specific case studies or published clinical research
     on this product.
   • Most nutraceutical companies have a medical food product designed
     to upregulate phase I and phase II liver detoxification pathways (see
     Figure 31.3).
     • Phase I nutrients include riboflavin, niacin, pyridoxine, folic acid,
         vitamin B12, glutathione, branched-chain amino acids, flavonoids,
         and phospholipids. Nutrients included to assist with the reactive
         oxygen intermediates include carotenes, vitamins C and E, selenium,
         copper, zinc, manganese, coenzyme Q10, thiols, bioflavonoids, sily-
         marin and pycnogenol.
     • Phase II nutrients include the amino acids: glycine, taurine,
         glutamine, ornithine and arginine. Cysteine and N-acetylcysteine
         are also used as methylation cofactors.




                   PROBIOTICS AND PREBIOTICS IN FOOD

Probiotics and prebiotics are increasingly being added to foods, primarily cultured
dairy products. For an extensive review of probiotics, see Chapter 29, by Gerald
Friedman. There is a simultaneous resurgence in the popularity of probiotic-laden
fermented and cultured foods that have been used in traditional diets.



   Health Benefits of Prebiotics and Probiotics:
   • have a positive influence on immune development
   • improve colonic integrity
                            Functional Foods for Digestive Health and Disease   297



  • regulate local and systemic immune function
  • decrease incidence and duration of infections in the intestinal tract, uri-
    nary tract, vagina, and respiratory system
  • downregulate allergic response
  • improve digestion
  • regulate gut transit and stool regularity
  • increase lactose tolerance
  • improve elimination
  • prevention or regulation of diarrhea induced by antibiotics, rotovirus, and
    lactose intolerance
  • reduce concentration of cancer-promoting enzymes and/or putrefactive
    (bacterial) metabolites in the gut
  • have beneficial effects on inflammation in diseases of the gastrointestinal
    system
  • prevent or alleviate atopic disease and allergies in infants
  • beneficial effects on cholesterol, ischemic heart disease, autoimmune dis-
    ease, and oral health are less well documented
  • regulate appetite through leptin and ghrelin
  • manufacture vitamins B1, B2, B3, B5, B6, B12, and K
  • metabolic control of nutrients: glycemic control, cholesterol, amino acids

     (Hanaway 2010, Lipski 2004, Liska, 2006; de Vrese & Schrezenmeir, 2008; de
  Vrese, 2008)


   Prebiotics are insoluble fibers that selectively stimulate the growth and/or
activity of probiotics in the intestines. They are nondigestible food carbohy-
drates, and are often called resistant starch, soluble fiber, nonstarch polysac-
charides, and soluble oligosaccharides that promote the growth or activity of a
limited number of bacterial species for the benefit of host health and help
optimize microbiotica health and function (Douglas & Sanders, 2008). They
include fructans, inulin and fructooligosaccharides, arabinogalactans (larch),
and soy oligosaccharides (Plummer, Quilt, & Crockett, 2003; Liska & Bland,
2006). Prebiotics pass undigested through the stomach and small intestine
and are subsequently completely fermented in the colon by microflora,
primarily Bifidobacteria species, producing short-chain fatty acids (acetic acid,
butyric acid, and propionic acid).


  Characteristics of Prebiotics:
  • change in composition of short-chain fatty acids
  • differential stimulation of probiotic bacteria in the colon
298   INTEGRATIVE GASTROENTEROLOGY



  • promote growth of Bifidobacteria and lactobacilli
  • increased fecal weight
  • mild reduction in luminal colon pH
  • decrease in nitrogenous end-products
  • increased expression of binding proteins or active carriers associated with
    mineral absorption
  • discourage growth of clostridial species
  • normalize bowel function

     (Hanaway, 2010, Douglas & Sanders, 2008) For a list of best food sources of
  prebiotics, see Appendix X.




   Traditional populations have all had fermented foods and/or cultured dairy
products in their native diet. Koreans ate a variety of pickled vegetables.
Europeans made sauerkraut and pickles. Eskimos fermented fish by burying it
for months. Worldwide, dairy products were fermented into cheese and cul-
tured milks such as yogurt and kefir. In many cultures, grains were fermented
to create sourdough breads. Fermenting and culturing foods enhances their
digestibility, can improve nutritional content (increased B complex, decreased
mineral-binding phytates), and decrease toxicity (as in cassava or poi).
Di Cagno and colleagues (2003, 2004, 2005) have reported that traditionally
fermented sourdough bread and pasta have been well-tolerated by people with
celiac disease. Probiotics (as discussed in Chapter 4) are defined as living
microorganisms that, when consumed in adequate amounts, confer a health
symbiotic benefit to the host (Douglas & Sanders, 2008). The most well
researched bacterial species are Lactobacilli and Bifidobacteria, and a yeast
called Saccharomyces boulardii.



  Probiotic rich foods:
  • cultured dairy products (yogurt, kefir)
  • sauerkraut
  • kim chee
  • miso
  • natto
  • tempeh
  • poi
  • natural soda beverages (kvoss, ginger beer)
  • fermented grains (gruel, sourdough bread)
                             Functional Foods for Digestive Health and Disease   299




                      FIBER TO REGULATE GI FUNCTION

Prebiotics, discussed above, are one type of beneficial dietary fiber that spe-
cifically enhances digestive function. Dietary fiber refers to a group of plant
polysaccharides that are not digested or absorbed. Examples of dietary fiber
include prebiotics, cellulose, hemicelluloses, pectins, beta-glucans and gums.
    Soluble fiber dissolves and/or swells when it is added to water; some soluble
fibers can hold up to 20 times their weight in fluid.
    Insoluble fibers do not dissolve or absorb fluids. For example, oatmeal that
sits in water overnight will swell and partially dissolve; a carrot will not change.
Foods generally are composed of a blend of soluble and insoluble fibers. Most
grains and vegetables contain mainly insoluble fibers. Soluble fibers have been
shown to lower serum cholesterol levels, and add bulk to and soften stools.
Insoluble fibers are bulking agents, and help with peristalsis and bowel transit
time. Further categories of fibers include those that hold water and form a
gel-like consistency, and those that are fermentable fibers. Gel-like fibers aid in
peristalsis and increase bulk of the stools. Fibers that are fermented by
Bifidobacteria in the large intestine become short-chained fatty acids that are
the essential energy and maintenance source for colonic mucosal cells (Liska
et al., 2004; Jones, 2006; McGuire & Beerman, 2007).
    Dennis Burkitt, father of the fiber theory, believed that people in Africa
who ate traditional diets had few modern chronic diseases yet the same people
living in cities developed them. He reported that the average weight of a
Western daily bowel movement was about 3.5 oz (100 grams); people who ate
traditional diets had stools that weighed at least 1 pound daily. It is recom-
mended that we consume 20 to 35 grams of fiber daily, yet the average American
gets only about 14 to 15 grams daily. The average worldwide fiber intake is in
the 50 to 75 grams per day range.
    Fiber plays an important role in both phase I and phase II liver detoxification
pathways.(Liska et al., 2004; Jones, 2006; McGuire & Beerman, 2007) Studies in
mice show upregulation of cytochrome P450 and glucuronidation pathways.
    Foods high in dietary fiber include legumes, fruits, vegetables, nuts, seeds
and whole grains. People should increase dietary fiber gradually to prevent
flatulence and bloating.


                  Polyphenols in Digestive Health

Polyphenols are phytochemicals that are found in food substances produced
from plants. They are different from essential micronutrients in that a
300   INTEGRATIVE GASTROENTEROLOGY


                                  Table 31.1. Fiber Chart
Soluble Fiber                              Insoluble Fiber

Benefits                                   Benefits
• Lowers cholesterol levels                • Promotes peristalsis and bowel regularity
• Regulates glucose                        • Provides substrate for Bifidobacteria to
• Regulates pH balance in                    produce butyrate and other short- chain
  the intestines                             fatty acids in colon
• Binds bile acids                         • Improves IBS
• Regulates phase 1 and 2 liver            • Increases satiety
  detoxification                           • Cancer protective
                                           • May reduce risk of diverticulosis

Food Sources                               Food Sources
• Apple pulp                               • Apple skin
• Barley                                   • Beets
• Beans                                    • Bran (wheat, corn)
• Bran (oat and rice)                      • Brussels sprouts
• Carrots                                  • Carrots
• Citrus fruits                            • Cauliflower
• Flaxseed                                 • Fruit skin
• Peas                                     • Green beans
• Potatoes                                 • Green leafy vegetables
• Psyllium seeds                           • Nuts
• Oats                                     • Root vegetables
• Oranges                                  • Seeds
• Rice                                     • Turnips
• Soy                                      • Whole grains such as wheat and rye
• Strawberries




deficiency state has not been identified for them; nevertheless, these chemicals
are believed to play a biologically active role and have been shown to act as
potential immunomodulators (Clarke, Mullin et al., 2008). Polyphenols
are found in colorful foods, such as fruits, tea, coffee, and to a lesser extent,
vegetables, grains and legumes. Common polyphenols include isoflavones,
gallic acid, catechins, flavanones, flavonols, flavonoids, stilbenes, tannins and
quercetin (Manach, Williamson, Morand, Scalbert, & Rémésy 2005; alsosee
Appendix C for Polyphenols in Food chart.) On average, Americans consume
about one gram of polylphenols, phenols, and tannins daily, in ranges from
100 mg to more than 2 grams. More than 95 of these substances reach the
colon and are fermented by colonic bacteria (Parkar, Stevenson, & Skinner,
2008). Polyphenols have established antioxidant, anti-cancer, and anti-inflam-
matory effects on the digestive system and throughout the body. A growing
                            Functional Foods for Digestive Health and Disease   301


body of research indicates that they also have regulatory effects on cell
signaling pathways, and help to regulate energy metabolism and GI health.
(Stevenson & Hurst, 2007)


                            Demulcent Foods

Herbalists use the word “demulcent” to describe any substance that soothes
inflamed mucous membranes. A wide variety of foods have demulcent effects
on the digestive system, including fenugreek, flax, ghee, and oat gruel. The
following foods appear to enhance digestive function and improve overall
well-being:


                       GREEN BANANAS/PLANTAINS

It has been observed that specific varieties of “green bananas” (just barely ripe)
and plantains (bananas of the Musa species) have anti-ulcer effects. Several
studies in rats have attempted to elucidate the physiological benefits of bananas.
Green bananas have been reported to increase mucosal tolerance to stomach
acids (Rao, 1991; Best, 1984), and plantains have been reported to stimulate the
growth of gastric mucosa (Rao, 1991). Unripe bananas also contain protease
inhibitors, which may play a role in curing stomach ulcers (Rao, 1991). Other
researchers have isolated a substance called leucocyanidin, which prevents
aspirin-induced ulcers in rats.


                                BONE BROTHS

It is instinctive to bring chicken soup or beef consume to someone who is
ailing. Bone broths are alkaline and mineral rich. They have been found to
contain gelatin, free amino acids, calcium, glycinate, proline, phosphorus,
hyaluronic acid, chondroitin sulfate, magnesium, potassium, sulfate and
fluoride.
    In 1985, Dr. Erich Cohn, of the Medical Polyclinic of the University of Bonn,
recommended bone broths for catarrh, which is now known as irritable bowel
syndrome. He also recommended a concentrated calf ’s foot broth for more
serious digestive disorders. Gelatin was reported to balance both deficiencies
and excesses of hydrochloric acid.
    Traditionally, gelatin was believed to act as a demulcent, soothing the gas-
trointestinal tract. In 1908, a researcher named C. A. Herter suggested that the
302 INTEGRATIVE GASTROENTEROLOGY


gelatin in bone broths helped reduce carbohydrate fermentation due to
gastrointestinal bacterial infections, now called fermentation dysbiosis. He
stated that:

   “The use of gelatin as a foodstuff in bacterial infections of the intestinal
   tract has never received the attention it deserves. The physician is not
   infrequently confronted with a dietetic problem which consists in
   endeavoring to maintain nutrition under conditions where no combina-
   tion of the ordinary proteins with fats and carbohydrates suffices to
   maintain a fair state of nutrition. The difficulty which most frequently
   arises is that every attempt to use carbohydrate food is followed by
   fermentative disturbances of an acute or subacute nature which delay
   recovery or even favor an existing infection to the point of threatening
   life. A great desideratum, therefore, is a food which, while readily under-
   going absorption, shall furnish a supply of caloric energy and which at the
   same time shall be exempt from ordinary fermentative decomposition.
   Such a food exists in gelatin.” (Daniel, 2003)

   Bone broths are simple to prepare. The key is to use a few tablespoons of either
lemon juice or vinegar to help pull more nutrients from the alkaline bones.


   Bone Broth Recipe
   • Take the bones from poultry, beef, lamb, shellfish, or whole chicken or
     whole fish (remove meat after it has cooked for about 1 hour)
   • Cover with water and add:
   • 1 to 2 tbsp. of lemon juice or vinegar
   • 1 to 2 tsp. salt
   • ½ tsp. pepper
   • Carrots, onions, and celery
   • Parsley, sage, rosemary, thyme, and bay leaf
   • Cook between 4 and 24 hours on the stove, or in a crockpot on low
   • Remove bones and skim off fat



                                CABBAGE JUICE

There is a strong evidence-based tradition for the use of cabbage juice in people
with peptic ulcers, diabetes, cirrhosis, cancer, and arthritis (Miron, Hancianu,
Aprotosoaie, Gacea, & Stanescu, 2006). Its efficacy may be due to immuno-
modulary polysaccharide compounds found in cabbage. Cabbage juice
contains glutamine, methionine and sulforaphanes.
                            Functional Foods for Digestive Health and Disease   303


    The original research was conducted by Garnett Cheney at Stanford
University Medical School from 1949 to 1952 (Cheyney, 1949) In a study of
181 patients, Cheney reports that cabbage juice helped decrease pain and led to
improvement on X-rays. More than 80 of patients were symptom-free in
1 week, and two-thirds reported improvement within 4 days. Other studies
followed, with researchers typically recommending 1 quart of cabbage juice
daily for 7 to 10 days. Most subjects experienced relief within the first few days
(Doll & Pygot, 1954; Strehler & Hunziker, 1954, Klimov, 1961; Trusov,
Belosludtsev, Pevchikh, & Shinkareva, 1964; Dunaevskiĭ, Migunova, Rozka, &
Chibisova, 1970; Zhgun & Aloiants, 1971). More recently, sulforaphanes have
demonstrated effects against H. pylori and gastric cancers. This particular
study used sulforaphanes from broccoli and broccoli sprouts, but cabbage also
has high levels of sulforaphanes (Fahey et al., 2002).
    Dosage: 1 quart fresh, green cabbage juice daily for 7 to 10 days in divided
doses. The taste can be intense, so people will probably be more compliant if it
is diluted with other fresh vegetable juices.


                                    GINGER

Ginger is one of the most widely used culinary spices. Its best-studied active
ingredient, gingerol, has the following characteristics:

   •   Antiemetic
   •   Antitussive
   •   Bile stimulating
   •   Cancer protective
   •   Cardiotonic
   •   Hepatoprotective
   •   Hypertensive
   •   Prostaglandin suppressive
   •   Sedative

   (al Somall, Coley, Molan, & Hancock, 1994; Schulick, 1994)
   Ginger itself:

   • inhibits proinflammatory cytokines: IL-12,TNF-alpha; IL-1-beta, MCP-1,
     and RANTES
   • suppresses inducible NOS and COX-2 synthesis
   • inhibits platelet aggregation and thromboxane synthesis in vitro (Alt.
     Med.Review, 2003; Tripathi, Maier, Bruch, & Kittur, 2007)
304   INTEGRATIVE GASTROENTEROLOGY


   For the digestive system, research focus has focused mainly on ginger’s use
in reducing morning sickness of pregnancy and post-surgical nausea and
vomiting (Chaiyakunapruk, Kitikannakorn, Nathisuwan, Leeprakobboon, &
Leelasettagool, 2006). While the exact mechanism of action is unclear, ginger
seems to inhibit serotonin receptors and to have anti-emetic effects on the GI
and neurological systems, anti-spasmodic effects and carminative effects (Alt.
Med. Review, 2003; White, 2007).
   Ginger can be used fresh, dried, or as an extract. It can be added in cooking
or used as a tea, in ginger ale or ginger beer, or as crystallized ginger.


                                    HONEY

Honey has long been used worldwide for its medicinal effects on wound heal-
ing, infection, and digestive issues. Researchers in New Zealand studied 345
honey sources and found that antibacterial activity varied greatly, depending
on plant sources. Honey from manuka flowers (Leptospermum scoparium) had
the highest level of antibiotic activity. In an in vitro study, it was determined
that manuka honey had a strong inhibitory effect on H. pylori. The researchers
found that the minimum inhibitory dosage of manuka honey could be achieved
with 2.5 ml (½ tsp.) taken prior to a meal. This would be tolerable and perhaps
enjoyable for the average person, and is a low-cost, low-side-effect option to
standard therapy (al Somall et al., 1994).
   Another group looked at chemically induced ulcerative colitis in rats. They
compared honey, glucose, fructose, sucrose and maltose mixtures that were
administered orally and rectally once daily for 4 days. On the third day, a 3
acetic acid solution was used to induce colitis. Biopsies were taken on day 4.
Honey protected against acetic-acid-induced colonic damage. At dosages of
5 gram/kg there was almost 100 protection. There was no protection with any
of the other sugars used (Mahgoub, el-Medany, Hagar, & Sabah, 2002).
   Dosage: 1 tsp. daily


                                    PEPPER

Black pepper is one of the most commonly used spices. Several benefits to the
GI system are attributed to piperine, one of the active ingredients in pepper.
Piperine has been reported to stimulate pancreatic enzymes, reduce bowel
transit time, and enhance digestion (Srinivasan, 2007). It has an inhibitory
influence on drug biotransformation reactions in the liver, strongly
                           Functional Foods for Digestive Health and Disease   305


inhibiting hepatic and intestinal aryl hydrocarbon hydrolase and UDP-
glucoronyltransferase. It has also been shown in vitro to have antioxidant
effects.


                                PEPPERMINT

Peppermint oil has long been used as a flavoring and relaxes smooth
muscle in the digestive tract. Although no studies have been conducted on
peppermint-leaf tea, there is much research on the use of peppermint oil.
Enteric-coated peppermint oil has been well-researched in children and
adults for its beneficial effect on irritable bowel syndrome, non-ulcer dyspep-
sia, and colonic spasm. Two studies have found it to be of benefit in reducing
spasm during barium enema and possibly colonoscopy (Kligler & Chaudhary,
2007).


                               INDIAN SPICES

Use of spices not only makes food taste better, but simultaneously enhances
digestion. Fennel, fenugreek, cumin, cardamom, and coriander seeds are pro-
vided by Indian restaurants for this purpose. Fennel tea has been a standard of
care in Europe for colicky and fussy babies.
   A review article by Platel and Srinivasin (2004) discusses the digestive
actions of spices and herbs used in Indian cooking. They report that spices
stimulate digestive function primarily through increased bile production and
secretion. Various spices also increase production and secretion of pancreatic
lipases and amylases, and affect alkaline phosphatase.
   The same researchers report rat studies that show bowel transit time was
shortened by the ingestion of most herbs and spices. This shortening did not
affect growth rates or produce diarrhea. Shortened bowel transit time has been
associated with a decreased risk of colon cancer.


                     TURMERIC (CURCUMA LONGATA)

Turmeric, a member of the ginger family, is one of the primary anti-
inflammatory substances used in traditional Indian and Hawaiian medicine.
Much research has been done on the anti-inflammatory effects of turmeric,
and especially on one active component, curcumin.
306    INTEGRATIVE GASTROENTEROLOGY


                     Table 31.2. Digestive Stimulation from Spices
Pancreatic      Lipase activity   Significantly > activity   Stimulated > of at    Alkaline
amylases >      > up to 80%       of disaccharides:         least one disaccharase phosphatase
                                  sucrase, lactase, and     enzyme
                                  maltase. Effects most
                                  pronounced when
                                  consumed on a
                                  regular basis

• Ginger   • Curcumin             • Coriander               • Ginger              • Increased:
• Curcumin                          > nearly 300           • Ajowan              • Onion
                                  • Onion                   • Fennel              • White
                                                            • Cumin Asafetida       coriander
                                                            • Curcumin            • Decreased:
                                                            • Capsaicin (from     • Coriander
                                                              cayenne)            • Fenugreek
                                                            • Piperine (from      • Mint
                                                              black pepper)       • Mustard
                                                                                  • Asafetida

Adapted from Platel & Srinivasan, ; Indian J Med Res, , –. Review Article: Digestive
stimulant action of spices: A myth or reality?



   Turmeric has the following reported effects:

   •   inhibits inflammation
   •   antioxidant effects
   •   anti-microbial effect
   •   hepatoprotective
   •   cancer protective

   The studied mechanisms of action of curcumin include:

   •   inhibits TNF-alpha
   •   inhibits arachidonic acid production
   •   cortisone-like inhibitory action on phospholipases
   •   a potent inhibitor of transcription factor NF-kappa B
   •   antioxidant activity (Alternative Medicine Review, 2001).

   Dosage: Take either 1 finger-sized piece of fresh turmeric twice daily
or 1 tbsp. dried turmeric daily. If using fresh turmeric, place in blender with
juice or water. If using dried turmeric, mix into foods such as salad dressings,
                            Functional Foods for Digestive Health and Disease   307


grains, juice or tea. Some people enjoy simply mixing it with honey and adding
it to tea.


                              UMEBOSHI PLUMS

Umeboshi plums are a traditional condiment used throughout Japan, Korea
and China for their health benefits. The ume plum is picked unripe, dried in
the sun, then pickled in a brine of sea salt and shiso leaves. The net result is a
highly alkaline, naturally fermented pickle that is rich in enzymes and probiot-
ics. Researchers have found it to have antioxidant and antibiotic properties.
It has been used traditionally for hangovers, liver support, detoxification,
nausea, as an appetite stimulant, for skin diseases such as eczema, and for bad
breath, dysentery, typhoid, and paratyphoid (Kuleshnyk, 2008).
    Umeboshi plums can be eaten in many ways. They are used as a condiment
on vegetables or rice. The plums are very salty, but can be eaten whole from the
jar. Umeboshi vinegars are also available for use in salad dressings or on rice or
other grains. Whole plums or umeboshi paste can also be drunk as a tea.
Just let them steep in boiled water for 5 minutes, then drink. This is a very
restorative tonic.


                             WHEATGRASS JUICE

Wheatgrass has been claimed to benefit many conditions, but there has been
only one good study on the use of wheatgrass juice for digestive diseases.
Scandinavian researchers (Ben-Arye E 2002) studied 23 people with active
distal ulcerative colitis who consumed either wheatgrass juice (two-thirds of
an ounce to begin with, and increasing to 3.5 oz. daily) or placebo for one
month. There was significant improvement in overall disease activity; sigmoi-
doscopy showed improvement in 78 of people drinking wheatgrass juice,
compared to 30 of people on placebo; 33 experienced nausea, while 41
reported an increase in vitality. Other researchers have linked wheatgrass juice
to reduced need for blood transfusions in thalassemia (Marawaha, Bansal,
Kaur, & Trehan, 2004), and a pilot study reports reduced myelotoxicity in
women receiving chemotherapy for breast cancer. Wheatgrass juice can induce
nausea, perhaps by acting as a powerful cholagogue and activator of liver
detoxification, a side effect that is often too strong for many people.
   Wheatgrass can be grown in a tray in the kitchen and then juiced with
a special wheatgrass juicer. Wheatgrass juice can also be purchased at most
308   INTEGRATIVE GASTROENTEROLOGY


natural food stores. Begin with small amounts and titrate up to prevent possi-
ble nausea.


                                 Conclusion

Eating whole foods rather than packaged foods can significantly enhance GI
function. There is a growing body of research on the use of customized diets to
optimize function. When GI dysfunction occurs, it may be useful to clear the
board and begin with a modified fast or elimination diet. In clinical practice,
use of a 2- to 3-day food diary on an initial visit can be one of your most useful
diagnostic tools. Probiotics, prebiotics, fiber, and polyphenols contribute to a
well-balanced microbiota. It is the life in foods that gives us life: Think colors.
Think fresh. Think about how your ancestors ate and move toward a more
traditional diet, which will in turn move you toward optimal health.
                                 32
The Role of Herbal Medicine in Integrative
             Gastroenterology
                        TIERAONA LOW DOG

 Of the history of medicine the average person is likely to know only
 the tall tales of supposedly nonsensical treatments such as phlebotomy,
 poultices and purges… Such flippant rejection of many millennia of
 accumulated knowledge has its price, as does the rejection of traditional
 medicines from foreign cultures. Ignorance of the past has never been a
 firm foundation for the present.
                                  —Robert and Michele Root-Bernstein, Honey,
                                    Mud, Maggots and Other Medical Marvels




                             key concepts

 ■   Many functional gastrointestinal disorders are not effectively
     managed with conventional medications.
 ■   A number of botanicals show promise in the field of gastroen-
     terology, particularly when used within an integrative
     approach.
     ■ Ginger rhizome is an effective antiemetic and prokinetic.

     ■ Enteric-coated peppermint oil effectively treats irritable

        bowel syndrome.
     ■ Artichoke leaf is a reliable choleretic.

     ■ Berberine-rich plants have broad antimicrobial activity

        against numerous gut pathogens.
     ■ Turmeric is a potent anti-inflammatory in inflammatory

        bowel disease and potential chemopreventive agent in
        colorectal cancer.
     ■ Silymarin is an effective hepatic protectant against drug-

        induced damage.
 ■   Clinicians should inquire about patient use of all dietary sup-
     plements, including botanicals, and document in the medical
     chart.

                                                                               309
      ■   Report adverse events from dietary supplements to FDA
          Medwatch and/or your local poison control center.
                                        ■




      Herbal Medicine and Gastrointestinal Disorders



S
        ince specific disorders are covered in depth throughout this text, this
        chapter will explore in broad terms the physiological action of plants
        that are utilized in the treatment of gastrointestinal disorders.
Gastrointestinal complaints rank among the most frequent reasons for pri-
mary care visits in the United States. Direct costs are in excess of $85 billion
annually (Sandler et al., 2002), with an additional $20 billion in indirect costs
due to days off work (Mullin et al., 2008). Many of these complaints fall into
the category of functional gastrointestinal disorders, a group of conditions—
such as irritable bowel syndrome (IBS), GERD, chronic constipation or
diarrhea—for which no structural or biochemical cause can be found. A meta-
analysis of 53 studies published in 1996 concluded that, due to methodological
flaws, there are no proven effective therapies for the treatment of non-ulcer
dyspepsia (Veldhuyzen van Zanten et al., 1996), making many of these condi-
tions of maldigestion amenable to the use of herbal medicine. In addition,
herbal therapies are being explored for their beneficial effects in inflammatory
bowel disease (IBD), as hepatoprotectants and for their potential to reduce
gastric and colorectal cancer. While this chapter will focus on the use of botani-
cals, it should be implicitly understood that the use of these remedies must exist
within a framework that includes appropriate diagnosis and holistic treatment;
e.g., dietary recommendations, mind–body therapies, manual medicine, or
other approaches that may promote wellness and healing in the patient. For the
specific integrative management of irritable bowel syndrome, GERD, inflamma-
tory bowel disease, etc., please see the appropriate chapters within the text.


                 Introduction to Herbal Medicine

Herbal medicine, also referred to as phytotherapy or botanical medicine, is the use
of plants, plant parts, and preparations made from them for therapeutic and/or
preventive purposes. Herbal medicine gave rise to the modern sciences of botany,
pharmacy, perfumery, and chemistry. Some of our most useful and beneficial
                    The Role of Herbal Medicine in Integrative Gastroenterology 311


drugs originate from plants, including aspirin (salicylic acid derivates derived
from willow bark and meadowsweet), quinine (from cinchona bark), digoxin
(from foxglove) and morphine (from opium poppy). Through isolating the potent
actives in these plants, pharmaceutical products can be produced with a consis-
tent and uniform composition. Indeed, one primary drug discovery model has
been the identification, isolation, and production of single active compounds.
These active compounds can then be researched, patented, and sold as drugs.
    While there are drugs that are made directly from plant material, these
isolated compounds are not considered herbal medicines in the classic sense.
In the traditional practice of herbal medicine, the plants and plant parts are
themselves considered medicinally functioning wholes. They are chemically
complex mixtures, and the entire plant, or part, is considered the “active.”
Refinement of knowledge, tradition, and the preparations themselves are not
stagnant, however, and the field continues to evolve alongside our scientific
studies. Milk thistle (Silybum marianum) has been used to treat a variety of con-
ditions over the centuries. Its common name, “milk” thistle, is a reminder that
the seeds have been valued as a lactagogue, or an agent that can help stimulate
the production of breast milk. References to its use for liver and other digestive
disorders can be found over the past several hundred years. In 1830, silymarin, a
group of flavones, were isolated and extracted from the seeds. An antidote for
Amanita phalloides (deathcap mushroom) poisoning was later developed from
these compounds. From the broad to the narrow, from crude plant to highly
refined extract, the field of herbal medicine continues to grow and flourish.
    Unfortunately, there has been little financial incentive to study herbal
medicines that can be easily grown in the garden or harvested in the wild, or
to study products for which there is no type of protection for manufacturers.
Nor has there been a way for consumers to distinguish clinically tested prod-
ucts from the myriad “me-too” products in the marketplace that piggyback off
other companies’ research. And, all too often, the research that is undertaken
is focused on the use of one particular herb for one specific condition, even
though most experienced herbal practitioners individualize their prescrip-
tions based upon the unique characteristics of the patient. Herbal mixtures are
often preferred over single herbs, as they are thought to offer greater efficacy
and, to some degree, greater safety. Multi-herb formulations may have addi-
tive, or synergistic, effects and secondary herbs can be included to modify
potential side effects from the primary herb. For example, an anthraquinone-
based herbal laxative (e.g., senna, cascara sagrada) often causes intestinal
griping, which can be reduced or eliminated by adding gut antispasmodics
(e.g., fennel, ginger). Given the number of traditional medical systems that
utilize herbal formulations, the focus on single herb preparations may be a
critical shortcoming in botanical research, though monotherapy is probably
312   INTEGRATIVE GASTROENTEROLOGY


the best approach for the clinician who is just starting to use herbs in his or her
practice. Getting to know each herb in this way allows the practitioner to gain
greater familiarity and expertise with its use.


                    Quality of Botanical Products

Given the dizzying array of herbal products, it is understandable that both
consumers and healthcare professionals have difficulty navigating the supple-
ment marketplace. Consumers look down the aisle and ask, “Which product
should I take? What dose? Will it interact with my medications? Does it work?
Is it safe?” In addition to questions of efficacy and safety inherent to the plant,
there are also concerns about the quality of dietary supplements in general,
and botanical products in particular, as the media and professional literature
are filled with reports of product adulteration and contamination, as well as
variation between what is printed on the label and what is actually in the
bottle. Though not a significant problem with products manufactured in the
United States, cases of heavy metal poisoning (e.g., mercury, lead, and arse-
nic) from Chinese, Indian, Arabic, and African traditional remedies have
been reported, and testing has demonstrated that a number of these products
contain unacceptable levels of arsenic, lead, mercury, and cadmium (Cooper
et al., 2007; Obi et al., 2006; Saper et al., 2004). While many manufacturers
produce high-quality botanical products, the unscrupulous and/or incompe-
tent have, unfortunately, tarnished the industry, making it relatively difficult for
consumers or practitioners to distinguish the good companies from the bad.
    With the passage of the new good manufacturing guidelines (GMP) by the
Food and Drug Administration (FDA) in June of 2007, concerns of contami-
nation, adulteration, and poor quality will hopefully become less of an issue in
the future. The inspection of dietary supplement manufacturers by the FDA
will increase in 2009, when companies will be required to come into compli-
ance with the new guidelines. A number of companies will in all likelihood not
be able to meet the stringent requirements for supply chain management and
traceability. The burden on manufacturers, however, should actually help the
industry in the long run, as consumers will become more confident in the
products they purchase, and healthcare providers will be more comfortable
making supplement recommendations.


                                     Safety

Overall, most of the herbs in general commerce in the United States have a
relatively good safety profile when used appropriately and manufactured to
                    The Role of Herbal Medicine in Integrative Gastroenterology 313


high-quality standards. As more concentrated herbal products are introduced
into the marketplace, many of which will be taken for extended periods of
time, new questions of safety will undoubtedly arise. The chronic use of certain
herbs (e.g., comfrey, chaparral, licorice) can cause hepatic, renal, or electrolyte
abnormalities. Like any chemically active substance, whether an herb is safe or
toxic depends upon the dose, type of product, and the underlying constitution
of the patient.



   The concomitant use of botanical remedies with prescription or over-the-
   counter medications may lead to adverse interactions, especially in elders
   and those with diminished renal or hepatic function.




   A national survey noted that 16 of prescription drug users also reported
taking one or more herbals/supplements within the prior week (Kaufman
et al., 2002). It is imperative that clinicians dialogue with patients about their
use of botanical medicines and other dietary supplements, to help prevent
potentially dangerous herb–drug interactions. There are a wide variety of
herbal practices and products available in the United States, which makes gen-
eralizations difficult; however, by asking a few open-ended questions, clini-
cians should be able to assess the patient’s beliefs, cultural practices, and use of
botanical remedies:

   • When you were growing up did you, or your family, ever use any
     medicinal plants or herbal remedies to improve your health or treat
     an illness?
   • How do you use herbs or herbal remedies in your home?
   • Are you taking any herbs or herbal medicines now? If so, what are you
     trying to treat, and do you think the herbs are working?

  Document all patient responses in the medical chart and be alert for
potential adverse effects and herb–drug interactions, as well as therapeutic
benefit.



   If you suspect a possible adverse effect, report it to FDA Medwatch at www.
   fda.gov/medwatch. Another excellent resource is to contact your local poison
   control centers; the new nationwide toll-free number in the U.S. for poison
   control is 800-222-1222.
314   INTEGRATIVE GASTROENTEROLOGY




                               Herbal Actions

When examining botanicals it is useful to start with a basic understanding of
how they work. In some cases, scientific research has identified key compounds
within the plant that account for its physiological effects; in other cases, there are
multiple compounds working in harmony that account for the overall therapeu-
tic effect, making the hunt for an “active compound” futile at best. More than
2,000 years ago, anticholinergic plants such as Atropa belladonna were used to
treat painful gastrointestinal spasm, even though the tropane alkaloids atropine,
hyoscyamine, and scopolamine would not be isolated for many centuries.
Practitioners observed the physiologic action of these plants and were able to use
them effectively in their patients, even in the absence of isolating specific com-
pounds or having a detailed understanding of cellular physiology. Thus, this
section is a blending of traditional wisdom and modern science, observation and
reductionism. It is beyond the scope of this chapter to address all herbal actions;
it will focus only on those commonly considered when addressing GI disorders.


                                   ANTIEMETIC

The most potent antiemetic plants are those containing the anticholinergic tro-
pane alkaloids hyoscamine, scopolamine and/or atropine. The dominant plants
in this category include belladonna (Atropa belladonna), jimson weed (Datura
stramonium) and henbane (Hyoscyamus niger). Scopolamine patches have been
widely used to reduce postoperative nausea and vomiting, as well as motion sick-
ness; however, these plants and their isolated alkaloids are associated with con-
siderable side effects and are not generally used by practicing herbalists today.
   A mild, yet effective, antiemetic is ginger (Zingiber officinale). While com-
monly referred to as “ginger root” it is actually a rhizome, or underground
stem. Ginger is a popular home remedy for dyspepsia and has been clinically
studied for hyperemesis gravidarum, motion sickness, and chemotherapy-
induced nausea and vomiting. A meta-analysis of randomized controlled trials
favored ginger over placebo for relief of nausea and vomiting in general (Ernst
& Pittler, 2000), while a review of six randomized controlled trials specifically
addressing nausea and vomiting of pregnancy found 1.0–1.5 grams/day of
dried ginger more effective than placebo (Borrelli et al., 2005a).
   The way in which ginger acts as an anti-emetic is not completely
understood. One class of antiemetics used in conventional medicine is the
5-hydroxytryptamine (5-HT) antagonists, such as ondansetron, that work
                     The Role of Herbal Medicine in Integrative Gastroenterology 315


specifically on 5-HT3. Several components of ginger; 6-gingerol, 6-shogaol
and galanolactone, have shown anti-5-HT activity with galanolactone acting
as a competitive antagonist at ileal 5-HT3 receptors (Huang et al., 1991).
Cisplatin, one of our most emetogenic chemotherapeutic agents, inhibits
gastric-emptying, which is thought to be the primary reason it causes nausea.
Both the acetone extract of ginger and ginger juice effectively reverse cisplatin-
induced delay in gastric emptying. The reversal produced by ginger acetone
extract was similar to the effect seen with ondansetron, while ginger juice at
oral doses of 2 and 4 ml/kg, was superior to the drug (Sharma & Gupta, 1998).
A study in 24 healthy human volunteers found that 1,200 mg of dried ginger
accelerated gastric emptying and stimulated antral contractions greater than
placebo (Wu et al., 2008). Note: dried rhizome is a more potent antiemetic
than fresh.



   Because of ginger’s prokinetic and antiemetic activity, it is often included in
   formulations for gastroparesis, which can present with signs and symptoms
   such as heartburn, gastroesophageal reflux, early satiety, abdominal bloat-
   ing, and nausea and/or vomiting several hours after eating a meal. The dose
   is typically one gram dried rhizome, taken 15 to 20 minutes after meals.
   Another excellent prokinetic herb is corydalis (Corydalis ambigua), a plant
   related to the opium poppy. It has been used in traditional Chinese medicine
   for centuries as a sedative and to relieve abdominal pain. The combination
   of corydalis root and pharbitis seed (Pharbitis nil. or P. purpurea) significantly
   accelerated gastric emptying, and restored delayed gastric emptying caused
   by apomorphine and cisplatin, up to almost normal levels in animal models
   (Lee, 2008).




                             ANTI-INFLAMMATORY

There are numerous botanicals with anti-inflammatory activity, and since all
orally ingested herbs pass directly through the gut, many are useful for reliev-
ing gastrointestinal irritation and inflammation. Research demonstrates that
botanicals reduce inflammation through a variety of mechanisms including
mediation of cytokine secretion, histamine release, immunoglobulin secretion,
lymphocyte proliferation, and cytotoxic activity (Plaeger, 2003). Compounds
with potent anti-inflammatory activity particularly relevant to the GI tract
include curcumin (turmeric), gingerols and shogaols (ginger), glycyrrhizin
(licorice), alpha-bisabolol and azulenes (chamomile), resveratrol (red grapes),
tea polyphenols (tea), silymarin (milk thistle), boswellic acids (boswellia) and
316 INTEGRATIVE GASTROENTEROLOGY


withanolides (ashwagandha; see Khanna et al., 2007). Green tea polyphenol
extracts (Abboud, 2008; Mazzon, Muià, & Paola, 2005) and resveratrol (Martín,
2006, 2004) attenuate intestinal injury in animal models of experimental coli-
tis. Animal data and small pilot studies in humans indicate that Boswellia ser-
rata extracts may be of some benefit in collagenous colitis, ulcerative colitis
and Crohn’s disease (Madisch, Miehlke, & Eichele, 2007, Ammon, 2006).
Ashwagandha (Withania somnifera) reduces gastric acidity and ulceration in
animal models of stress induced ulcer (Bhatnagar, Sisodia, & Bhatnagar, 2005).
The gastro-protectant effects of licorice root (Glycrrhiza glabra, G. uralensis)
have been known for centuries. Research has shown licorice to be a useful
anti-ulcer agent as effective as H2 blockers (Aly, 2005). Compounds in licorice
increase local prostaglandin levels that promote mucus secretion and cell pro-
liferation in the stomach (Baker, 1994).


  Prolonged use of licorice at doses higher than 1 gram per day can lead to
  pseudoaldosteronism. A special preparation, deglycyrrhizinated licorice
  (DGL), has had the glycyrrhizin removed and may be taken without concern.
  I find DGL to be very effective for managing GERD and for helping patients
  wean slowly off proton-pump inhibitors. The usual dosage is 760 mg,
  chewed, taken 20 minutes before meals for 4 to 6 weeks and then as
  needed.




   It is turmeric (Curcuma longa), or more often the isolated polyphenoic
compounds collectively referred to as curcumin, that is being heavily researched
these days. There are numerous Phase I and II studies evaluating the effective-
ness of curcumin alone, or in combination with other compounds, for a wide
range of conditions including colorectal cancer, pancreatic cancer, multiple
myeloma, Alzheimer’s disease, psoriasis, IBD, IBS, familial adenomatous poly-
posis (FAP), oral lichen planus, and rheumatoid arthritis (clinicaltrials.gov).
   Curcumin has a range of molecular targets that contribute to its overall
pharmacological effects, such as modulating the activation of various
transcription factors and regulating the expression of inflammatory enzymes,
cytokines, adhesion molecules and cell survival proteins. As curcumin is
poorly absorbed from the gut, much of its therapeutic benefit is concentrated
in the GI tract. Studies show that doses of 760 mg to 2.0 grams per day of cur-
cumin are beneficial for improving symptoms or preventing relapse in patients
with ulcerative colitis and Crohn’s disease (Holt, Katz, & Kirshoff, 2005; Hanai
et al., 2006). Curcumin is also a highly promising chemopreventive agent. The
combination of 480 mg of curcumin and 20 mg of quercetin taken orally three
                    The Role of Herbal Medicine in Integrative Gastroenterology 317


times a day reduced the number and size of ileal and rectal adenomas in
patients with FAP (Cruz-Correa et al., 2006).
   The average daily intake of turmeric in India is approximately 2 to 2.5 grams/
day, which corresponds to an intake of 60 to 100 mg of daily dietary curcumin
(Goel, Jhurani, & Aggarwal, 2008). Phase I clinical trials demonstrate that
curcumin is safe at doses as high as 12 grams/day (Anand, 2007). While many
practitioners recommend turmeric over the isolated or concentrated curcumi-
noids, it is important to note that the medicinal doses used in many clinical trials
would require the consumption of more than 25 grams per day of turmeric!



   When two grams of curcumin was given orally to healthy humans, serum
   curcumin levels were either very low or undetectable. Concomitant admin-
   istration of piperine, a primary alkaloid in black pepper, increased bioavail-
   ability by 2000% (Shoba et al., 1998). Interestingly, black pepper has been
   traditionally added to many herbal preparations to enhance absorption and
   increase the effectiveness of the formulation. To concentrate curcumin in
   the gut, it is best to take a non-lipid preparation without piperine on an
   empty stomach or 1 to 2 hours after eating.




                                ANTIMICROBIAL

Plants contain multiple constituents: phenols, quinones, flavones, tannins, ter-
penoids and alkaloids, with antibacterial, antiprotozoal and antiviral activity
(Cowan, 1999). Botanical antimicrobials that are safe, effective, and inexpen-
sive may have significant global health implications in areas endemic with
infectious diarrhea, and may expand our arsenal against Helicobacter pylori.
Many common spices have antimicrobial activity. Turmeric, ginger, chili, and
cumin are bactericidal to Helicobacter pylori, and turmeric reduces adhesion
of the bacterium to the stomach mucosa (O’Mahony et al., 2005). Berberine-
containing plants, such as goldenseal (Hydrastis canadensis), barberry (Berberis
vulgaris), Oregon grape root (Mahonia aquifolium) and goldthread (Coptis
sinensis), have been traditionally used to treat gastritis and infectious diarrhea.
Crude methanol extracts of goldenseal root and rhizomes are highly active
against multiple strains of H. pylori (Mahady et al., 2003). Berberine inhibits
the growth of Giardia lamblia, Entamoeba histolytica, Trichomonas vaginalis,
and Leishmania donovani (Kaneda, Tanaka, & Saw, 1990). Berberine reduces
intestinal secretion of water and electrolytes induced by cholera toxin, and
directly inhibits some V. cholera and E. coli enterotoxins, significantly reducing
smooth muscle contraction and intestinal motility (Akhter, 1979).
318 INTEGRATIVE GASTROENTEROLOGY



   I have successfully treated a number of patients with Entamoeba histolytica
   who failed multiple rounds of metronidazole with both goldenseal and
   Oregon grape root. All berberine-rich plants taste bad; better compliance will
   be achieved with encapsulated products. I generally recommend 1,000 mg of
   Oregon grape root three times daily for 14-30 days.


   Allium vegetables, particularly garlic (Allium sativum), exhibit broad anti-
microbial activity against many organisms. Louis Pasteur documented the
antibacterial activity of garlic in 1858, while Albert Schweitzer reportedly relied
upon it to treat amoebic dysentery. Modern research confirms that garlic is
active against a number of diarrhea-causing bacterium, including Salmonella
and Escherichia coli O15 (Adler, 2002). It is also active against Entamoeba
histolytica and Giardia lamblia, major sources of gastrointestinal infection
worldwide (Ankri, 1999; Harris et al., 2000).
   When the garlic clove is crushed, the odorless amino acid alliin is metabo-
lized by the enzyme alliinase, to yield allicin and other thiosulfinates that are
the source of garlic’s characteristic odor. The thiosulfinates and other second-
ary metabolites are thought to be responsible for garlic’s antimicrobial activity
(Yoshida et al., 1999). Though low heat does not appear to destroy the antimi-
crobial effects of garlic—one study found the antibacterial activity of garlic
stable at 100° C, or 212° F (Sasaki et al., 1999)—raw garlic preparations are
probably the best choice. In addition to its antimicrobial effects, there is a body
of evidence suggesting that garlic is protective to the GI mucosa. Multiple
studies confirm that aged garlic extracts prevent or reduce the gastrointestinal
toxicity that can result from administration of methotrexate (Li et al., 2008,
Horie et al., 2006, Yüncü, Eralp, & Celik, 2006), while a systematic review
found an inverse relationship between raw and cooked garlic consumption
and colorectal cancer risk (Ngo, 2007).


                               ANTISPASMODIC

Antispasmodic plants with specific affinity for the GI tract include hops
(Humulus lupulus), valerian (Valeriana officinalis; V. wallachii), wild yam
(Dioscorea villosa), bogbean (Menyanthes trifoliata), chamomile (Matricaria
recutita), and lemon balm (Melissa officinalis). Chamomile is commonly used
to alleviate minor abdominal pain in children and elders, as it is mild in action
and low in adverse effects. Animal data confirm the antispasmodic activity
of both aqueous and ethanolic extracts of chamomile, with fractions being
similar or superior to papervine, a known smooth muscle relaxant (McKay &
                    The Role of Herbal Medicine in Integrative Gastroenterology 319


Blumberg, 2006). Valerian, though primarily known as a mild sedative or
calmative, has been shown to reduce small bowel contractions in animal
studies (Gilani et al., 2005), and is often included in IBS formulations for those
with anxiety or nervousness. Wild yam was traditionally referred to as “colic”
root, a nod to its historical use in crampy intestinal pain.
   One of the most popular gut remedies for alleviating intestinal gas
and abdominal cramps is peppermint (Mentha x piperita). Peppermint oil
significantly prolongs orocecal transit time (Goerg, 2003) and directly inhibits
smooth muscle contractions by interacting with calcium channels (Hills &
Aaronson 1991). The active compounds in peppermint oil, menthol and men-
thone, are highly fat-soluble and rapidly absorbed from the proximal gut.
Thus, enteric-coated sustained release peppermint oil capsules are the ideal
formulation for IBS, particularly diarrhea dominant.
   Peppermint oil is often found in combination with caraway seed oil.
Caraway seed oil inhibits smooth muscle contraction (Al-Essa 2010) and both
peppermint and caraway oils inhibit gallbladder emptying (Goerg, 2003).
A review of four randomized clinical trials found the fixed combination of
peppermint and caraway oil to have effects of similar or greater magnitude
when compared with conventional therapies used in dyspepsia, as well as a
very good safety profile (Thompson Coon & Ernst, 2002). Interestingly, cara-
way may be protective against colon carcinogenesis (Deeptha et al., 2006), as
well as having lipid- and triglyceride-lowering effects (Lemhadri et al., 2006).


   There are a number of high-quality peppermint oil capsules in the market-
   place. The dose is 0.2 ml enteric-coated softgel capsule taken 3 times per day,
   30 minutes before meals. If this causes heartburn or anal burning, instruct
   the patient to take with food. Iberogast® is a proprietary blend of nine herbs
   (chamomile, lemon balm, caraway, peppermint, clown’s mustard (Iberis
   amara), and others) that has demonstrated beneficial effects in cases of func-
   tional dyspepsia and irritable bowel syndrome (Rosch 2006). It has a pleasant
   taste and is suitable for both children and adults, though it contains 31% alco-
   hol. It should be noted that the mixture contains small amounts of greater
   celandine (Chelidonium majus), which may induce hepatotoxicity at high
   doses. However, this blend has been used for more than 40 years in Europe
   with good postmarketing surveillance safety data, even in pediatrics.



                                      BITTERS

Bitter-tasting herbs have been used for millennia as digestive aids. The bitter
taste stimulates a sensory response in the tongue, which in turn increases the
320 INTEGRATIVE GASTROENTEROLOGY


production of gastric acid and primes the exocrine pancreas. Bitters are gener-
ally taken 20 minutes before the main meal for those who experience symp-
toms such as bloating, gas, sluggish stools, and a sense of fullness after eating.
Some of the most commonly used bitter herbs include artichoke (Cynara
scolymus), dandelion root (Taraxacum officinale), gentian (Gentiana lutea),
hops, and bitter orange peel (Citrus aurantium). Dandelion is a well-known
bitter digestant with anti-inflammatory and prebiotic activity (Schütz, 2006).
While the leaves are predominantly employed as a diuretic, the roots are used
in cases of habitual constipation, sluggish digestion, bloating after meals, and
poor appetite. Bitter orange peel is often included in small amounts in herbal
formulations as a flavoring agent, and also a mild bitter and carminative.



   Angostura bitters, a proprietary product available in the liquor section of
   most grocery stores, is a classic bitter aperitif, taken before meals to aid
   digestion. There are numerous other proprietary bitters for sale. I often
   recommend Gallexier Herbal Bitters by Floradix, as it does not contain any
   alcohol or the laxative herbs found in some blends. The small amount of
   bitter orange peel in digestive formulations is quite safe—but be aware that
   many weight-loss products contain very concentrated forms of the herb,
   standardized for high synephrine content.




                                CARMINATIVES

Carminatives are herbs that relieve bloating and intestinal gas. These plants are
often rich in volatile oils that relax the GI smooth muscle; thus, they are also
referred to as gut antispasmodics. Carminatives are usually included in herbal
laxative formulations to reduce the abdominal cramping that can occur with
both bulk-forming and stimulant laxatives. The vast majority of carminatives
fall into the spice/culinary herb category. Aniseed, cinnamon, fennel, dill, car-
away, and peppermint are classic examples. Fennel is used to relieve digestive
complaints in young children, as it is mild tasting and well tolerated. Two small
studies have shown that fennel emulsion (Alexandrovich, 2003) and fennel tea,
in combination with chamomile and lemon balm (Savino et al., 2005), improves
infantile colic. Peppermint, fennel, or anise can be made into a pleasant after-
dinner tea (tisane), or the East Indian tradition of chewing fennel seeds after
the meal is also effective for relieving bloating and gas. Herbal digestifs have a
longstanding tradition of use in Europe for improving digestion. Classic exam-
ples include Anisette and Crème de Menthe. Generally, one tablespoon is
taken alone or diluted in water after the meal.
                    The Role of Herbal Medicine in Integrative Gastroenterology 321




               CHOLERETICS/CHOLAGOGUES/DIGESTANTS

Choleretics increase the production of bile by the liver, cholagogues stimulate
the contraction and release of bile from the gallbladder, and digestant is a gen-
eral term used to describe those remedies that act on the gallbladder and exo-
crine pancreas. All three of these terms are used somewhat interchangeably in
herbal medicine. Many spices and culinary herbs fall under this category, as
gastric secretions are stimulated by their aroma and pungent taste. Ginger,
coriander, cumin, turmeric, chili, and peppercorn increase pancreatic lipase
and amylase activity (Platel & Srinivasan, 1996), as well as bile volume and bile
acid secretion, improving the digestion of dietary fats and carbohydrates
(Platel et al., 2002). Ginger, chili, and peppercorn dramatically enhance
pancreatic trypsin, enhancing the digestion of protein.
   A premiere choleretic/cholagogue is globe artichoke leaf (Cynara scolymus),
considered a specific for digestive disorders in traditional herbal medicine,
especially those accompanied by flatulence, abdominal pain, bloating, and
poor digestion of fats. Artichoke leaf is a potent choleretic and cholagogue
(Speroni, 2003) and the enhanced biliary cholesterol excretion (Saenz
Rodriguez 2002) likely contributes to its clinically documented lipid-lowering
effects. Interestingly, globe artichoke is a member of the milk thistle family and
also a source of the hepatoprotectant compound silymarin, the cold-pressed
seed oil yielding up to 85. Artichoke and yarrow are also potent choleretics.


                                 DEMULCENTS

Demulcents soothe and protect irritated tissues. These herbs are typically rich
in mucopolysaccharides that become “slimy” when they come in contact with
water. These compounds are destroyed by high alcohol content, so are best
prepared as teas. Demulcents are used to alleviate irritation of the mouth,
throat, esophagus, stomach, and bowels. Marshmallow (Althaea officinalis)
and slippery elm bark (Ulmus rubra) are classic demulcents. The British Herbal
Compendium recognizes the use of marshmallow root or leaf in cases of
duodenal ulceration, ulcerative colitis, and enteritis.
   The inner bark of slippery elm (Ulmus fulva, U. rubra) has been used as a
food and medicine for centuries, and was an official drug in the United States
Pharmacopeia from 1820 to 1936. Native Americans and early settlers made a
nutritious gruel from the inner bark, in a fashion similar to oatmeal. The
polysaccharide-rich mucilage found within the bark is an effective cough
322   INTEGRATIVE GASTROENTEROLOGY


suppressant, soothes a sore throat, and helps to heal the mucosa of the gastro-
intestinal tract. Indications listed in the British Herbal Compendium for slip-
pery elm bark include “inflammations and ulcerations of the gastrointestinal
tract, such as oesophagitis, gastritis, colitis, gastric or duodenal ulcers; diar-
rhoea” (Bradley 1992). Though there are virtually no modern studies on slip-
pery elm, the FDA has approved slippery elm as a safe nonprescription product
for demulcent use. Demulcents are usually taken at least one hour after
prescription medications to prevent interference with absorption.


   There are slippery elm lozenges, flavored and unflavored, as well as medici-
   nal teas readily available at most natural grocery stores. You can make your
   own by taking 1 tsp. of the powdered bark, adding 1 to 2 tbsp. water and
   making into a paste. Then add 2 cups boiling water. Let steep for 10 minutes.
   Pour off the liquid and add a pinch of cinnamon, nutmeg, or pumpkin pie
   spice. It’s great for soothing a sore throat, easing a cough, or relieving occa-
   sional heartburn.



                                     HEPATICS

Hepatics generally refer to herbs that have a beneficial effect upon the liver.
The prime examples include milk thistle (Silybum marianum), katuka
(Picrorrhiza kurroa), artichoke (Cynara scolymus) and phyllanthus (Phyllanthus
amarus). The most rigorous research has focused on the beneficial effects of
milk thistle. The seeds of milk thistle have been used for more than 2,000 years
as a treatment for liver and biliary disorders. Modern studies on the flavono-
lignans collectively referred to as silymarin have demonstrated hepatoprotec-
tion from various substances including alcohol, acetaminophen, and the toxins
from Amanita phalloides, or deathcap mushroom. The main effects of sily-
marin are the membrane stabilizing and antioxidant effects, which can assist
in liver cell regeneration, decrease inflammation and inhibit fibrogenesis in
the liver. These results have been established by experimental and clinical
trials. A systematic review and meta-analysis concluded that the use of sily-
marin is reasonable in Amanita phalloides poisoning, alcoholic liver disease
(as an addition to abstinence) and Child’s A cirrhosis (Saller, 2008). A recent
study using intravenous silymarin in combination with ribivarin demonstrated
rapid suppression of hepatitis C viremia (Biermer, 2009). Together, these and
other data suggest that silymarin may be used for its antiviral effects in future
clinical trials for hepatitis C.
   The flavonolignan silibinin competitively antagonizes toxins from binding to
liver cell membrane receptors in mushroom poisoning and other hepatotoxic
                     The Role of Herbal Medicine in Integrative Gastroenterology 323


exposures. Administration of silibinin up to 48 hours after mushroom inges-
tion appears to be effective for preventing severe liver damage. The dose of
silibinin: IV 20 to 50 mg/kg/d. Interestingly, while widely available in other coun-
tries, this IV form of milk thistle is not presently available in the United States. In
addition to hepatic protection, animal studies suggest that silymarin may protect
against chemotherapy-induced renal toxicity from cisplatin (Bokemeyer et al.,
1996) and adriamycin (El-Shitany 2008) and that silymarin administered prior to
radiation acts as a renal protectant (Ramadan et al., 2002).



   Milk thistle is a fantastic example of an herb that may offer a real benefit in
   today’s modern world as it can offer hepatoprotection from environmental,
   toxin- and drug-induced damage. Silymarin appears to offer both liver and
   renal protection in patients undergoing chemotherapy or radiation. It is
   reassuring that in vivo studies demonstrate that oral administration of sily-
   marin does not inhibit CYP3A4 (Fuhr 2007), however in vivo pharmacokinetic
   studies are lacking at this time for other CYP enzyme systems and intrave-
   nous administration likely has a different profile. Typical dose for silymarin
   is 420-760 mg silymarin per day, taken in three divided doses. Higher doses
   may be necessary based upon emerging evidence.



                                    LAXATIVES

Laxatives stimulate the intestines, causing the body to eliminate waste. The
primary types of plant laxatives include fiber or bulk, stimulants or cathartics,
and stool softeners. Bulk-forming laxatives are indigestible, hydrophilic
substances that absorb water, forming a bulky, emollient gel that distends the
colon and promotes peristalsis. Psyllium seed and husks are prototypical of
the category, though they often take up to four weeks for patients to notice a
significant improvement in bowel function. Encouraging patients to drink
herbal teas of ginger, fennel, or caraway can help ease the abdominal disten-
sion and gas that often accompanies initial increases in fiber intake. Flaxseed
(Linum usitatissimum) is another bulk-forming laxative, containing both
soluble and insoluble fiber, which can be used to ease constipation and may
also help reduce the risk of colon cancer when consumed regularly in the diet
(Bommareddy et al., 2006). This nutty flavored seed is also rich in alpha lino-
lenic acid, an omega 3-fatty acid, and is a good source of magnesium. Grind
flax seeds in a coffee grinder to enhance their digestibility and nutritional value.
Take 1 to 2 tbsp. two times per day to improve regularity. Each tablespoon con-
tains 2.2 grams of fiber, 1.6 grams of protein, and 1,800 mg of omega-3 fat.
324 INTEGRATIVE GASTROENTEROLOGY



   While little known in the United States, a common Ayurvedic remedy for
   constipation is Triphala, made from the dried fruits of three medicinal
   plants: Terminalia chebula, Terminalia belerica and Phyllanthus embelica.
   I have had tremendous success using it for those with constipation domi-
   nant irritable bowel syndrome, as well as elders and children with hard, dry
   stools. Take 1 to 2 grams per day for 5 to 7 days, and increase to 3 to 4 grams
   per day if needed. Triphala is not habit forming and is available in capsules
   or powders that can easily be mixed with food or in beverages.




   Many stimulant laxatives and cathartics are derived from plants rich in
bitter anthraquinone glycosides, such as cascara sagrada (Rhamnus purshi-
ana), senna (Cassia angustifolia), aloe latex (Aloe spp) and turkey rhubarb
(Rheum palmatum). The anthraquinone glycosides are metabolized slowly by
gut microflora, resulting in a period of 8 to 10 hours between ingestion and
evacuation of stool. Concerns regarding the relationship of anthraquinone
laxative use and colon cancer, or the belief that chronic use causes structural or
functional impairment of enteric nerves or intestinal smooth muscle, are
inconclusive at best (Borrelli et al., 2005b; Wald, 2003; Nusko et al., 1997). For
patients who fail to respond to bulk or osmotic laxatives, these plants represent
a reasonable alternative. Many herbalists contraindicate the use of stimulant
laxatives during pregnancy, but when bulk-forming laxatives are ineffective,
senna is considered safe (Prather, 2004).


                                  Conclusion

Herbalists consider a well-functioning GI system to be the foundation of
health. Proton pump inhibitors, antacids, and NSAIDs, while of great benefit,
are used far too often and can have devastating effects on the gut long term. In
herbal medicine, the mantra is remove, repair and restore. Remove foods and
other substances that are disruptive to the integrity of the gut (e.g., food
allergens, drugs, tobacco, etc.). Repair the gut through a wholesome diet rich
in plant fiber, appropriate use of botanicals that have anti-inflammatory and
demulcent activity, and supplements such as glutamine that nourish the
colonic tissue. Restore both motility and healthy microflora by adding fer-
mented foods, prebiotics, probiotics, dietary fiber, and by using prokinetic
agents as needed.
   When reviewing the history and contemporary research, it is clear that
herbal medicines have played, and continue to play, a significant role in treating
                    The Role of Herbal Medicine in Integrative Gastroenterology 325


disease and improving health. Given the vast number of botanicals that have
yet to be explored for their medicinal effects, it is likely that plants will con-
tinue to contribute to our understanding and management of gastrointestinal
disease. However, there remains much work to be done from “bench to bed-
side” to determine which botanicals are most efficacious and how they are best
used in clinical practice. While this text cites the clinical trials that are being
conducted on herbal medicines for various GI disorders, the research litera-
ture reflects only a very small percentage of plants that have potential benefit,
and there is definitely a need for more rigorous and creative research in
this area.
                                    33
      Brief Review of Mind–Body Medicine in
             Gastroenterology Practice
      MIRANDA A.L. VAN TILBURG, STEPHAN R. WEINLAND,
                  AND OLAFUR S. PALSSON




                                 key concepts

      ■   Mind–body medicine recognizes that illness symptoms and
          behaviors cannot be completely explained by biological pro-
          cesses alone, but only from the interaction between biological
          and psychosocial processes.
      ■   Both psychosocial and biological aspects are important targets
          for therapy.
      ■   Practicing mind–body medicine means, first and foremost, that
          physicians elicit information from the patient about his/her
          illness beliefs and expectations for treatment.
      ■   Behavioral and cognitive interventions for functional gastroin-
          testinal disorders comprise a range of therapeutic modalities
          (cognitive-behavioral therapy, hypnotherapy, biofeedback,
          guided imagery, relaxation training) that have at their core a
          therapeutic relationship and an understanding of the mind–
          body connection.
      ■   Behavioral and cognitive treatments aimed at reducing gastroin-
          testinal symptoms have proven effectiveness for the treatment of
          highly prevalent conditions like IBS and functional dyspepsia.
                                       ■




T
       he dualistic model, common in medical practice, characterizes patient
       symptoms as either of organic or functional origin, with little under-
       standing of relational aspects between the two. This view has been
propagated through medical education and persists in clinical practice and

326
               Brief Review of Mind–Body Medicine in Gastroenterology Practice 327


research. Patients are often categorized as either having “biomedical” or “psy-
chosocial” difficulties and are treated accordingly (Drossman, 1998) However,
it is increasingly recognized that this type of medicine is insufficient in treating
many bodily ailments. Mind–body medicine, on the other hand, recognizes
that illness symptoms and behaviors cannot be completely explained by bio-
logical processes alone, but only by understanding the interaction between
biological and psychosocial processes. Therefore, both biological and psycho-
social processes are addressed in medical care. The application of the mind–
body approach to medicine and gastroenterological illness has gained increased
prominence since George Engel first introduced the biopsychosocial model of
illness (Engel, 1977). Nowadays, the U. S. National Institutes of Health describes
mind–body medicine as a field that views health care providers as “catalysts
and guides” in the process of health promotion, and diseases as “opportunity
for personal growth and transformation” (NCCAM, 2008). This change in
view of medicine away from having biological focus to a more experiential one
that feels awkward to many practitioners. However, a change in name or direc-
tion does not mean that the scientific method is not applicable to studies of
mind–body relationships and treatments. Indeed, empirical validation is
critically important when considering newer treatments.
    In this chapter, we will briefly review mind–body medicine in gastroenter-
ology practice. Few areas of medicine demonstrate clearer connections between
mind and body as those seen in gastroenterology. Lay terms of experiencing
“butterflies in the stomach” in the presence of anxiety or “not having the stom-
ach” to face a situation are just some of the ways that an understanding of a
brain–gut connection is communicated (Read, 1993). Although mind–body
medicine can be and is practiced across all areas of gastroenterology, it has
gained the most acceptance for the treatment of functional gastrointestinal
disorders because of the large literature supporting its use.


                  Physician–Patient Relationship

Mind–body medicine starts in the physician’s office. Working with patients
experiencing GI difficulties in practice can be difficult when the disorders have
a “functional” presentation. Standard care for functional GI disorders by phy-
sicians and other medical professionals is aimed primarily at psychosocial
aspects, such as reassurance and advice on diet/exercise/stress, and only
secondarily at pharmacological and other biomedical approaches (Whitehead
et al., 2004). Since most patients believe in a biomedical approach to illness,
this type of treatment may not be easily accepted. Many physicians experience
difficulty in working with patients who present with increasingly complex
328   INTEGRATIVE GASTROENTEROLOGY


disorders as one moves up the care hierarchy. Mitchell and Drossman (1987)
have found that patients with irritable bowel syndrome, a typical “functional”
GI illness, make up 12 of primary care issues and up to 28 of gastroenterol-
ogy practice. Patient–physician interactions can play a significant role in the
benefit/detriment experienced by GI patients in working with clinicians.
Drossman and colleagues have extensively written on the use of effective
physician-patient communications in functional gastrointestinal disorders
(for example see (Drossman, 1997)) (Drossman, 2009) Here, we will briefly
describe some important aspects.




  Practicing mind–body medicine means, first and foremost, that physicians
  elicit information from the patient about his/her illness beliefs and expecta-
  tions for treatment. This involves understanding not only the symptoms,
  but the life context within which the symptoms developed. The patient’s
  worries and concerns must also be identified and addressed.




   A common fear often elicited from the patient is that of having an underly-
ing cancer. Quickly dismissing the concern by stating that “nothing is seri-
ously wrong” may not be reassuring to the patient, particularly if the concerns
have not been properly addressed through proper diagnostic testing. A quick
dismissal may lead the patient to believe that the physician is incompetent, or
that “it must be in my head.” When a diagnosis is made, it is helpful to explain
to the patient that the symptoms are occurring within a biopsychosocial
construct; i.e., with the integration of biological and psychosocial processes in
their illness and disease. Also, many patients have never been told what
they suffer from, and providing a positive diagnosis (e.g., of IBS) and then
explaining the physiological basis for the symptoms can be very empowering.
A physician needs to communicate that (s)he is rather confident, based on the
current findings, that the patient suffers from a functional disorder, but will
stay vigilant for changes that require future testing. This approach emphasizes
continuation of care, and understanding of the patient’s concern while limiting
ordering unnecessary tests. Furthermore, many patients feel unable to deal
with their symptoms, and therefore relinquish control of their symptoms to
the physician. With any chronic illness, no matter what the cause, self-man-
agement is a crucial aspect of medical care. Therefore, patients and physicians
should negotiate shared responsibility of care. Ideally, patients should accept a
primary role in their care, while physicians need to be available for support
and advice.
              Brief Review of Mind–Body Medicine in Gastroenterology Practice 329



   The presence of a physical or sexual abuse history in patients is often dis-
   missed or not adequately assessed in GI practice; however, an appropriate
   understanding of such a history and its effects on mind–body connections is
   critically important in patient care.




   In a study published in 1990, Drossman and colleagues reported that up to
50 of patients in a tertiary care setting have a history of physical or sexual
abuse, though only 11.4 of the physicians were aware of this history (Drossman
et al., 1990). The association between abuse and gastrointestinal symptoms has
also been found in children (Van Tilburg et al., 2010). Later work showed that
an abuse history has profound effects on health status in patients with func-
tional or structural diagnoses in terms of quality of life, health care utilization,
symptom severity, or even risk of having surgery (Drossman et al., Lesserman,
Toomey, Hu 1996) Recent literature has shown a relationship between a his-
tory of physical or sexual abuse and central upregulation of pain-reporting
centers in the brain (Drossman, 2005). For a comprehensive examination
of ways this issue can be identified and addressed during the course of the
biopsychosocial interview, readers are directed to a more comprehensive
review (Chang & Drossman, 2002).
   Standard medical care may not be sufficient for most patients. We have
found, for example, in a study of 1,665 patients with functional bowel disorders
seen in a U.S. health maintenance organization (Whitehead et al., 2004), that
only 22 of patients had a larger than 50 reduction on a global bowel symp-
tom index six months after a doctor visit for their bowel symptoms, and only
51 of patients judged their symptoms to be at least somewhat better at that
time. Similarly, Thompson et al. (1997) reported that less than half of IBS
patients in primary care are satisfied with the care they have received. This
finding is echoed by a recent study of almost 2,000 patients in an Internet
survey (Drossman. Morris, Schnek, Hu, Norton, Weinland, Dalton, Leserman.,
2008). About a third of patients pursue alternatives to regular medical care,
such as herbal medicine, massage therapy, and yoga (van Tilburg et al., 2008).




   Patients who do not respond to medical therapy and/or have comorbid psy-
   chiatric disorders may benefit from behavioral therapy such as cognitive-
   behavioral treatment, hypnosis, or biofeedback.
330   INTEGRATIVE GASTROENTEROLOGY


    Both clinical care and behavioral interventions should be integrated.
In medical communities, it is advisable to at least identify a psychologist who
is familiar with treating patients who have functional GI disorders, and who
can be closely connected with the ongoing medical care. Ideally psychologists
are part of the clinical program and are seeing patients in the same clinical set-
ting. This helps to bridge the gap between medical and psychological care, and
allows for a more unified biopsychosocial approach. There is a wealth of evi-
dence to show that behavioral treatments are effective in treating functional
gastrointestinal disorders. It must be kept in mind that these treatments
typically involve specific behavioral intervention modalities applied on top of
the behavioral and cognitive interventions (e.g., soliciting and challenging
erroneous beliefs, such as a fear of cancer) routinely provided in standard
medical care.


      Behavioral and Cognitive Therapies for Functional
                  Gastrointestinal Disorders

Behavioral and cognitive interventions for functional gastrointestinal
disorders comprise a range of therapeutic modalities that have at their core a
therapeutic relationship and understanding of the mind–body connection.
Psychologists and other licensed practitioners working in behavioral medicine
or clinical health psychology have a range of therapeutic modalities and
options that have been shown to be effective in managing GI illness (Lackner
et al., 2004). From these options, a mounting level of evidence for efficacy
has been found in utilizing cognitive-behavioral therapy (CBT), biofeedback,
hypnosis/guided imagery, and relaxation training.


                      COGNITIVE-BEHAVIOR THERAPY

CBT is a form of semi-structured psychotherapy that is usually conducted
individually as a course of 8–12 weekly treatment sessions. The therapist aims
to help patients to overcome distorted and negative thinking patterns that
amplify physical symptoms or adversely affect life functioning as well as psy-
chological well-being. Therapy tasks commonly include: increasing awareness
of the association between stressors, thoughts, and symptoms; examining and
correcting irrational beliefs; countering automatic negative thoughts; and
identifying and adopting alternative, more adaptive coping strategies to handle
challenging life situations and deal with bowel symptoms.
               Brief Review of Mind–Body Medicine in Gastroenterology Practice 331


   CBT has been most extensively used in IBS. There are several controlled
and uncontrolled trials studying its effectiveness for treating IBS. In a review
of the literature Toner (2005) concluded that there is some support for CBT in
improving symptoms associated with irritable bowel syndrome (IBS), but
many studies have important shortcomings, making it hard to draw firm
conclusions. Drossman and colleagues (2003) have completed the largest and
methodologically most rigorous trial in the history of behavioral treatments
for GI conditions—treating 431 women with functional bowel disorders, most
of whom met Rome criteria for IBS—in a randomized, placebo-controlled,
multicenter study. These investigators compared a 12-week cognitive-behavior
therapy to the same amount of education intervention. They found that cogni-
tive-behavior therapy resulted in treatment response rate that was almost twice
as high (70 versus 37) compared to the education control intervention.
   In order to increase access to CBT, low-cost self-administered treatments
are being developed as a first-line psychological intervention for IBS. Initial
results are promising. In two studies, GI symptoms were decreased as com-
pared to waitlist control, while self-administered CBT was comparable to
standard CBT (Lackner et al., 2008; Sanders, Blanchard, & Sykes, 2007).


                                BIOFEEDBACK

Biofeedback is a treatment method that uses recordings of specific physiologi-
cal parameters, such as muscle tension or intraluminal gut pressure, to provide
patients with moment-to-moment feedback of their physiological activity,
which can help them to learn to regulate physiological activity that is related to
the targeted symptoms. Patients are asked to repeatedly make attempts at
deliberate control over the targeted physiological processes while observing
the response in their body, and in that way to gradually gain control through
successive approximation.
   Biofeedback has been successfully used for chronic constipation due to
pelvic floor dyssynergia (PFD) and fecal incontinence (Heymen et al. 2007,
2009). Biofeedback for PFD is directed at teaching patients to relax their pelvic
floor muscles while simultaneously applying downward intra-abdominal
pressure to generate propulsive force (Valsalva maneuver). This is done with
the aid of visual or auditory feedback to the patients from either electromyo-
graphy sensors measuring electric activity in the external anal sphincter,
an anal canal pressure sensor device, or both of these in combination. This
training is sometimes combined with practice in defecating a water-filled
balloon.
332     INTEGRATIVE GASTROENTEROLOGY


    Biofeedback for fecal incontinence is aimed at enhancing or restoring the
key functions that maintain stool continence. Continence depends on ade-
quate rectal sensation to detect distention of the rectum, as well as on the capa-
bility to synchronously contract the external anal sphincter in response to the
reflexive inhibition of the internal anal sphincter that occurs when the rectum
fills. Three types of biofeedback to ameliorate fecal incontinence problems are:
(1) coordination training, where patients are taught to coordinate or synchro-
nize contractions of the pelvic floor muscles; (2) strength training, which trains
patients to contract the external anal sphincter to prevent leakage from the
bowel; and (3) sensory training to diminishing rectal distensions without
muscle contractions. A large research literature has accumulated over decades
on the outcomes of these two gastrointestinal biofeedback applications.
(Palsson et al., 2004, Chiarioni et al., 2008, Heymen et al., 2003, Heymen et al.,
2001).



      A 2004 systematic review of the world literature (Palsson, Heymen, &
      Whitehead, 2004) found 74 published prospective studies of biofeedback
      treatment for functional anorectal disorders, making biofeedback the most
      investigated of all behavioral treatment modalities for gastrointestinal
      disorders. A recent systematic review concludes that biofeedback helps
      about 75% of fecal incontinence and 70% of patients with PFD constipation
      (Chiarioni & Whitehead, 2008).



                       HYPNOSIS AND GUIDED IMAGERY

Hypnosis is a form of therapy that makes use of a special mental state of
narrowed focus of attention and heightened mental receptivity to suggestion
(hypnotic state), and achieves its therapeutic effects through therapeutic
suggestions and imagery given by the therapist to patients in this facilitative
state. Most of the work on hypnosis for gastrointestinal disorders has, until
recently, focused on irritable bowel syndrome. More than 20 published studies
have assessed the therapeutic utility of this mode of treatment for IBS, includ-
ing six controlled studies. Although most of the trials of hypnosis for IBS have
been small, and they have been variable in quality, recent systematic reviews
examining this entire body of literature (Gholamrezaei, Ardestani, & Emami,
2006; Whitehead, 2006; Wilson et al., 2006) have generally concluded that
hypnosis is an effective treatment for IBS, as evidenced in nearly universally
positive outcomes and high success rate. An analysis provided in the review
by Whitehead (2006) found that the median success rate of this treatment
              Brief Review of Mind–Body Medicine in Gastroenterology Practice 333


modality for IBS across all formal trials was 86, that bowel symptoms were
generally reduced by more than half after treatment, and that the therapeutic
effects commonly lasted one or more years.
    Recent randomized controlled trials have shown hypnotherapy to be equally
effective for the treatment of dyspepsia (Calvert et al., 2002), noncardiac chest
pain (Jones et al., 2006) and for functional abdominal pain in children (Vlieger
et al., 2007; Weydert et al., 2006; Van Tilburg et al).
    Hypnosis is a highly specialized form of therapy, and one of the limitations
to wide availability has been the dearth of therapists in many locations that
provide this form of treatment, as well as unfamiliarity of most therapists who
use such methods with how to apply them for treating gastrointestinal disor-
ders. However, a couple of innovations led by our research group are brighten-
ing the prospects for wide application of this treatment modality. One of these
is the development and distribution of a fully scripted hypnosis protocol for
IBS that therapists can easily follow verbatim, making it much easier to use
(Palsson, 2006). A second innovation is to develop home treatment programs
to make this treatment entirely self-administered. A pilot study (Palsson,
Whitehead, & Turner, 2003) of a home therapy version of the scripted North
Carolina Protocol, delivered via audio CDs, found that overall IBS severity was
twice as likely to show reduction of at least 50 after six months than a com-
parison group receiving standard medical care (53 versus 26 of patients).
Similarly, a controlled study by van Tilburg et al. (2009) of 30 children ages
7–15, testing a two-month home treatment of self-hypnosis, delivered on CDs,
found that children’s abdominal pain symptoms improved substantially more
after guided imagery compared to children receiving standard medical care.


                           RELAXATION TRAINING

Because functional GI symptoms are widely recognized to be associated with
heightened stress, relaxation training and meditation are sometimes applied in
their treatment to combat the physical aspects of stress. Such training can take
a variety of forms. Common techniques include progressive muscle relaxation,
autogenic training, or meditation. However, they all have in common that the
goal is to reduce sympathetic arousal (stress response) and create physiological
changes associated with physical relaxation that can have beneficial effects on
gastrointestinal symptoms. Relaxation training has often been applied as a
component of multimodal treatments, in published studies of treatment of
gastrointestinal disorders. For example, it is a common complement to cogni-
tive therapy or hypnosis treatment. However, it has been studied as the main
or sole therapeutic ingredient in four controlled studies, and found effective in
334 INTEGRATIVE GASTROENTEROLOGY


most of these trials (Shaw et al., 1991; Voirol & Hipolito, 1987; Keefer &
Blanchard, 2001) except for one, which is likely underpowered (Boyce et al.,
2003).


                                 LIMITATIONS

In spite of the numerous impressive studies discussed above, demonstrating the
advantage of cognitive and behavioral treatments over standard medical care or
other comparison groups, use of these treatments is still an exception rather
than the rule—even when patients are unresponsive to standard management.
Although standard medical care fails to give adequate relief to 4 out of every
5 patients, behavioral treatment is only offered or suggested to 10 of patients
(Whitehead et al., 2004). This disconnect can be explained by several factors.
    First, in a healthcare climate highly concerned with containing skyrocket-
ing costs, physicians and third-party gatekeepers may consider behavioral
treatments to be a luxury for functional GI problems. Physicians who take
time to develop a supportive relationship with their patients aren’t being reim-
bursed for the extra time they spend with the patient, and mental health
programs are severely underfunded. In view of long-term data in functional
dyspepsia (Calvert et al., 2002) and irritable bowel syndrome (Gonsalkorale
et al., 2003), it is almost certainly an erroneous view that behavioral treatments
are a luxury. When the cumulative benefits associated with years of reduced
medication and healthcare needs, and lessened disability following behavioral
treatments, become further documented in multiple studies, offering such
treatments to patients who are unresponsive to conventional medical care
might become a required standard of care to contain costs and maximize
positive outcomes.
    Secondly, there is an art to referral. Patients may perceive the referral as a
sign that their physician thinks they are “crazy.” Only about 30 of IBS patients
have confidence in the referral by their physician to a mental health provider
(van Tilburg et al., 2008). Lack of confidence may lead to failure to follow up
on the referral, and/or discontinuing the treatment early. An important aspect
in referral is to present these treatments in a way that is acceptable to patients.
For example, CBT can be offered as a way to learn management strategies to
better anticipate and respond effectively to episodes when they occur. In addi-
tion referral to CBT should be accompanied by reassurance that referral com-
plements the medical treatment, and does not mean the physician believes the
symptoms are “all in your head.” It is important to stress that CBT has been
found to effect IBS symptoms, independent of changes in patient’s psychologi-
cal distress (Lackner et al., 2007).
               Brief Review of Mind–Body Medicine in Gastroenterology Practice 335



   Only those patients who are open to behavioral treatments should be
   referred to a mental health provider. Otherwise, it is unlikely that the patient
   will follow up on their physician’s advice (and even if they do. it is unlikely to
   be successful), while uniformly pushing a treatment may damage the very
   important physician–patient relationship.




   Thirdly, there is an enormous shortage of qualified therapists. In a system
that prepares most mental health providers for the treatment of mental disor-
ders, very few will know how to approach behavioral treatment of medical
disorders. It is important to make sure that the patient is referred to a therapist
who understands functional gastrointestinal disorders. In many areas, no such
therapist may be around. Some centers, such as ours, have recruited and
trained our own psychologists who operate as part of a treatment team that
includes medical doctors, physician assistants, and nurses. Others have devel-
oped close relationships with therapists in the catchment area.
   The lack of availability of suitably specialized therapists, and the cost of
therapy, hinder widespread use of these treatments. Creative methods to min-
imize these hurdles could greatly increase the use of behavioral treatments.
With that aim in mind, our group at UNC-Chapel Hill has begun testing of a
home-treatment hypnosis program delivered via audio CDs and facilitated by
Internet-mediated symptom monitoring. The first pilot results have been
promising (Palsson, Whitehead, & Turner, 2003; Van Tilburg et al 2009),
although response rate is lower than in our face-to-face therapy studies.
Similarly, Lackner and colleagues in New York have reported encouraging
results from a self-administered CBT program for IBS (Lackner et al., 2008).
New treatment modalities like these offer promise for the widespread use of
behavioral treatments in FGIDs.


                                  Conclusions

Adopting a mind–body medicine approach to the care of functional gastroin-
testinal disorders is important. As no organic cause can be found to treat with
medical therapy, psychosocial aspects become an important target for therapy.
Physicians can deliver effective care when developing a good relationship
with their patients. But for many patients, additional treatment is required.
Behavioral and cognitive treatments aimed at reducing gastrointestinal symp-
toms have proven effectiveness for the treatment of highly prevalent conditions
like IBS, chronic constipation and functional dyspepsia. Adding behavioral
336 INTEGRATIVE GASTROENTEROLOGY


treatments to standard medical care can potentially reduce overall GI symp-
tom severity by more than half, provide long-lasting therapeutic benefit,
benefit treatment refractory patients, and reduce healthcare utilization sub-
stantially, while having no serious side effects. The current level of evidence
suggests it is time to start regarding behavioral treatments as serious and
responsible options in routine care for functional GI patients with moderate or
severe symptoms.
                              34
Mind-Body Medicine in Digestive Disease
 DOUGLAS A. DROSSMAN AND WILLIAM E. WHITEHEAD




                           key concepts

■   The UNC Center for Functional GI and Motility Disorders has
    a 15-year history in the biopsychosocial knowledge and care of
    patients with functional gastrointestinal and motility disorders,
    with initiatives in the area of research, patient care, training,
    and patient education:
■   The clinical program provides multidisciplinary, patient-
    centered care involving gastroenterologists, physiologists, psy-
    chologists, and physician assistants.
■   Emphasis in clinical training is placed on advanced interview
    methods and relationship building to maximize an effective
    provider–patient interaction, and on the use of newer gut-
    directed and psychopharmaceutical agents.
■   The research program is internationally recognized in the areas
    of psychosocial and psychophysiological investigation, epide-
    miology, and treatment of functional gastrointestinal and motil-
    ity disorders.
■   On-site training is provided to students, trainees, and estab-
    lished clinicians and investigators to help them gain advanced
    skills in research and patient care.
                                  ■




                                                                        337
                               Introduction



T
         he practice of gastroenterology has changed from a patient-based
         quality-of-care model to a business model with emphasis on income
         generation. This has occurred with the use of endoscopy and related
procedures, along with brief, disease-focused clinic visits. (Drossman, 2004)
Furthermore, training in the care of patients with functional gastrointestinal
disorders (FGIDs) is limited and at times deemphasized, because FGIDs are
considered “second class” (Drossman, 2005b), thus reducing motivation for
clinical practice. (Drossman, 2001) Nevertheless, people with FGIDs comprise
the largest segment of patients seen in gastroenterology practice (Russo et al.,
1999). These patients tend to believe that their care is unsatisfactory and their
needs are unmet (Drossman et al., 2008a).
   With regard to research, the greatest interest and support for federal fund-
ing is in basic and translational research; the goal is to understand the basic
mechanisms of disease, with the intent to cure and ultimately benefit the
patient. However, this research emphasis does not help patients with chronic
functional GI disorders. Furthermore, with the decreasing availability of NIH
funds, success in obtaining and sustaining research related to pathophysiolog-
ical mechanisms of the FGIDs, and the proper care of patients, has been
challenging and discouraging at best.
   In the face of these realities, the UNC Center for Functional GI and Motility
Disorders has continued to promote and successfully sustain a quality-based
model of patient care, a biopsychosocial model of research, and state- of-the-
art training in the FGIDs. The center has maintained its supremacy in provid-
ing new scientific knowledge to the field, innovative training opportunities for
physicians and investigators, and optimal service to our patients. This chapter
will review the history and philosophy of the center, and the ways in which its
goals have been accomplished.


                    Brief Overview of the Center

The UNC Center for Functional GI and Motility Disorders (www.med.unc.
edu/ibs) was established in 1994, when Dr. William Whitehead moved from
Johns Hopkins University and joined Dr. Douglas Drossman at the University
of North Carolina Division of Digestive Diseases. Prior to that, Dr. Drossman
had an active clinical practice in irritable bowel syndrome (IBS) and the
                                     Mind-Body Medicine in Digestive Disease 339


functional GI and motility disorders, as well as a biopsychosocial research pro-
gram related to clinical and psychosocial outcomes in the FGIDs. (Drossman,
1998a) Dr. Whitehead, who had established a research and biofeedback treat-
ment program for motility disorders at Johns Hopkins with Dr. Marvin
Schuster, was recruited to set up what has become a world-class motility pro-
gram at UNC. Drossman and Whitehead combined their skills and expertise
in an effort to establish a research and clinical program that was committed to
the field of functional GI and motility disorders.
   The Center’s mission (to advance the biopsychosocial understanding and
treatment of functional gastrointestinal and motility disorders through an inte-
grated approach to patient care, research, training and education) was imple-
mented through four areas of activity: (1) Patient Care – to offer state-of-the-art
evaluation and treatment for the full range of functional GI and motility dis-
orders; (2) Research – to conduct studies on the physiological and psychoso-
cial mechanisms underlying functional GI and motility disorders, their impact
on quality of life and health outcomes, and their treatment; (3) Training – to
provide multidisciplinary training and education in clinical and research skills
with an emphasis on patient-centered care and advanced research methods;
and (4) Patient Education – to provide helpful and up-to-date information
through seminars and workshops, as well as printed materials, videos, and the
Internet.


                        Structure of the Center

One of the most unique features of the new center was Drs. Drossman and
Whitehead’s shared responsibility as co-directors. This collaboration between
two senior academicians has sustained the program for more than 15 years.
Dr. Drossman coordinates the clinical activities, Dr. Whitehead established
the motility program, and both have active research programs with
independent and shared federal, foundation, and pharmaceutical support.
In addition, several new faculty and investigators have joined the center
and established their own research careers and clinical programs. The center
also has developed collaborations with dozens of investigators worldwide;
established a clinical program to implement multidisciplinary care;
recruited an administrative staff to coordinate day-to-day activities includ-
ing visiting scholars, media development, website maintenance, and the
production of teaching tools; and established data management and biom-
etry cores to provide advanced clinical and website-based research and data
analysis.
340   INTEGRATIVE GASTROENTEROLOGY




                             Clinical Program

The Functional GI and Motility Disorders Clinic is a tertiary care referral site for
patients with difficult-to-diagnose functional GI and motility disorders, who
present with challenging management issues. A team of gastroenterologists, psy-
chologists, physician assistants, gastroenterology fellows, and visitors in training
or on sabbatical, work together to provide a unique multidisciplinary approach
that integrates medical, physiological, and psychological factors in the evaluation
and treatment of patients. Emphasis is placed on a patient-centered diagnostic
interview, with the goal of establishing an effective physician–patient relationship;
state-of-the-art physiological and clinical investigations including endoscopy,
breath H2, and motility testing; and psychological assessment and pharmacological
treatments using the most advanced agents.
   The clinical program provides several therapeutic initiatives:

   1. Establishment of an Effective Physician-Patient Relationship. The
      basis for optimal treatment rests in establishing an effective physician–
      patient relationship (Drossman, 2007a). Borrowing from the work of
      George Engel (Morgan & Engel, 1969) and Karl Rogers (Rogers, 1980),
      we view the presenting symptoms in the context of the patient’s illness
      beliefs. From that point, the clinician applies his or her medical knowl-
      edge to develop an optimal negotiated treatment plan, along with provi-
      sion for continuity of care. An example of the ways in which an effective
      therapeutic relationship can be established is shown in Table 34.1.
   2. State of the Art Pharmacological Treatments. At UNC, the FGID clini-
      cians are thoroughly familiar with the full range of pharmacological treat-
      ments for the FGIDs, including the newer psychopharmacological agents
      used to treat visceral hypersensitivity and comorbid conditions. The use
      of advanced treatment approaches requires proper preparation; the
      method at the UNC Center is shown in Table 34.2. In addition, the UNC
      Center is continually involved with providing new investigative agents as
      part of Phase II and III studies, and then offering them to patients.
   3. Biofeedback. Certain FGIDs—including pelvic floor dyssynergia,
      fecal incontinence, and levator syndrome—are amenable to biofeed-
      back treatment. In fact, our clinicians and researchers have in many
      cases published the seminal literature in this area of investigation.
      The center also has a dedicated Pelvic Floor Biofeedback Clinic.
   4. Psychological Treatments. Our psychologists are skilled in the full
      range of psychological interventions, including cognitive-behavioral
      therapy, stress management, relaxation therapy, and hypnosis.
                                           Mind-Body Medicine in Digestive Disease 341


           Table 34.1. Behaviors that Affect Physician-Patient Relationship
Behavior              Facilitates                      Inhibits

Nonverbal

Clinical              Private, comfortable             Noisy, physical barriers
environment

Eye contact           Frequent                         Infrequent or constant

Body posture          Direct, open, relaxed            Body turned, arms folded

Head nodding          Helpful if well timed            Infrequent, excessive

Body proximity        Close enough to touch            Too close or too distant

Facial expression     Interest, empathy,               Preoccupation, boredom
                      understanding                    disapproval

Touching              Helpful when used to             Insincere if not appropriate or
                      communicate empathy              properly timed

Verbal

Question forms        Open-ended to generate           Rigid or stereotyped style
                      hypotheses

                      Closed-ended to test             Multiple-choice or leading
                      hypotheses                       questions (“You didn’t . . . ?”)

                      Use of patient’s words           Use of unfamiliar words

                      Fewer questions and              More
                      interruptions

Question style        Nonjudgmental                    Judgmental

                      Follows lead of patient’s        Follows preset agenda or style
                      earlier responses

                      Use a narrative thread           HPI -> PMH -> ROS -> Psych

                      Appropriate silence              Frequent interruptions

                      Appropriate reassurance          Premature or unwarranted
                                                       reassurance

                      Elicits psychosocial data in a   Ignores psychosocial data or uses
                      sensitive and skillful manner    “probes”

(Adapted from Drossman and Chang, )
342 INTEGRATIVE GASTROENTEROLOGY


     Table 34.2. Management of FGIDs with Psychopharmacological Agents

1. Choice of the agent based on:

   • The specific symptom treated

   • The side-effect profile

   • The cost of the drug

   • Previous experiences and preferences with psychotropic agents

   • Coexisting psychiatric conditions targeted

2. Initiating treatment

   • Negotiate treatment plan.

   • Consider previous drugs that worked.

   • Start with a low dose (e.g. 25 mg/day of TCA).

3. Continuing treatment:

   • Escalate dose by 25%–50% every 1–2 weeks to receive therapeutic effect with least
     possible dose.

   • Watch for side effects – Counsel that most of them disappear in 1–2 weeks. If not, try
     to continue same or lower dose from same class before switching to a different class.

   • Follow up within 1st week and then within 2–3 weeks to ensure adherence.

   • Gauge treatment benefit with improvement in coping, daily function, QOL, and
     emotional state.

   • If a poor initial response:

   • Re-address patient concerns

   • Switch to a different class

   • Consider combination therapies (eg. SSRI+TCA, pharmacological and
     psychological treatment).

   • If needed, obtain psychiatry consultation for pharmacotherapy.

   • Increase doses up to full psychiatric doses if patient can tolerate before discontinuing.

   • If there is no benefit in 6–8 weeks on higher doses, alternate strategies (e.g., adding
     psychological treatment or referral) should be sought.

   • Depending upon the response and side effects, another agent with different mechanism
     of action can be added to augment treatment efficacy and minimize side effects.

4. Stopping treatment: Continue treatment at minimum effective doses for 6–12 months.
   Long term therapy may be warranted for some patients. Gradual taper to prevent
   withdrawal symptoms.

(Adapted from Grover & Drossman, )
                                     Mind-Body Medicine in Digestive Disease 343




                           Research Program

The UNC Center has been a leader in research on the functional GI and motil-
ity disorders since its inception. Our seminal contributions to the field include
the following. (See Appendix D for details).

  • Diagnostic criteria: The center’s co-directors have made major contri-
    butions to the development and validation of reliable diagnostic crite-
    ria for the functional GI and motility disorders through their research,
    including factor analysis studies (Whitehead et al., 1990a; Whitehead
    et al., 1998a; Whitehead et al., 2003a), epidemiological surveys
    (Drossman et al., 1993), validation studies (Whitehead, 2006) and
    their leadership of the Rome Foundation. The Rome Criteria have
    been a major impetus to scientific discovery by enabling investigators
    to select more homogenous groups of patients and communicate
    replicable findings. Dr. Drossman has served as the President of the
    Rome Foundation from its inception, and Dr. Whitehead has served
    on the Board of Directors.
  • Pathophysiological mechanisms of IBS: Research by Center investiga-
    tors has established the key role of visceral hypersensitivity and motil-
    ity in the symptoms of IBS (Whitehead et al., 1990c; Dorn et al., 2007;
    Kanazawa et al., 2008b), and the CNS mechanisms that mediate
    visceral pain sensitivity. (Ringel et al., 2003a; Ringel et al., 2008)
  • Psychosocial contribution to the development of IBS: With NIH
    support, UNC Center faculty and investigators have identified and
    documented the key role played by sexual and physical abuse in the
    development of IBS. (Drossman et al., 1990; Leserman et al., 1996b)
    They have also articulated a model for understanding the ways in
    which psychosocial and biological factors interact to produce the
    symptoms of IBS and other functional GI disorders. (Drossman,
    1998b)
  • Psychological treatment of IBS: The Center has carried out the largest
    NIH-funded randomized, controlled trial of the treatment of painful
    functional bowel disorders with cognitive-behavior therapy and anti-
    depressants. (Drossman et al., 2003b) We also developed a scripted
    protocol for hypnotherapy (the “North Carolina model”) that is used
    throughout the world. In addition, we are pioneers in the investiga-
    tion of psychotropic drug treatment for IBS and the FGIDs.
344   INTEGRATIVE GASTROENTEROLOGY


  • Biofeedback treatment of pelvic floor disorders: We described
    pathophysiological mechanisms for fecal incontinence (Chiarioni
    et al., 2002a) and dyssynergic defecation (Chiarioni et al., 2005b), and
    carried out randomized, controlled trials (Chiarioni et al., 2006b;
    Heymen et al., 2007a) to show that biofeedback is the treatment of
    choice for these disorders.
  • Outcome assessment: We have developed widely used questionnaires
    for assessing symptom severity (Drossman et al., 1995; Drossman
    et al., 2000c), sexual abuse (Leserman et al., 1997a), impact on quality
    of life (Drossman et al., 2000b; Drossman et al., 2007a), and comor-
    bidity (Palsson et al., 2002).
  • Brain imaging: Center investigators have published studies, initially
    with PET and later fMRI imaging, from a hypothesis-driven perspec-
    tive, looking to understand the role of psychosocial factors and, in
    particular, sexual and physical abuse on anterior cingulate activation.
    (Ringel et al., 2008; Ringel et al., 2004; Ringel et al., 2003b; Drossman
    et al., 2003a; Drossman, 2005a) This provides a possible mechanism
    for understanding the role of stress factors on pain threshold via
    cingulate activation.
  • Pharmaceutical trials: Through our research (Whitehead et al., 2006b),
    leadership positions in the Rome Foundation (Irvine et al., 2006), and
    consultations to industry, we have shaped the guidelines for conduct-
    ing pharmaceutical trials. In addition, our broad involvement with
    current and emerging pharmaceutical agents permits the availability
    of several Phase II and III treatment trials in which our patients may
    participate.




                              RESEARCH TEAM

The center’s research program currently includes 14 faculty investigators within
the UNC Division of Gastroenterology and Hepatology (including 6 who are
principal investigators for NIH grants), plus four fellows or visiting scientists
on site. These investigators are supported by four research coordinators, three
physician assistants who participate in research, two research nurses, and
12 research assistants. We also have a large number of collaborators in other
departments and schools within UNC, and an extensive network of investiga-
tors at other institutions (see Figure 34.1).
                                     Mind-Body Medicine in Digestive Disease 345


    Center investigators have received a number of national and international
honors and awards, including: two Janssen Clinical Investigator Awards, the AGA
Fiterman Award in Clinical Research, the AGA Education Award, the AGA Mentor
Scholars Award, two FBGRG Senior Investigator Awards, an FBGRG junior inves-
tigator award, and two senior IFFGD Awards for Research Excellence. The center’s
co-directors also serve on national review panels. Dr. Drossman was on the Council
of the National Center for Complementary and Alternative Medicine, the NIDDK
Digestive Diseases Commission, and the Institute of Medicine Committee on Gulf
War and Health: Physiologic, Psychologic, and Psychosocial Effects of Deployment-
Related Stress. He chairs the program committee and the research awards commit-
tee for the IFFGD. Dr. Whitehead serves on the Data Safety and Monitoring Board
for the NIDDK Gastroparesis Research Network, and is a co-investigator on the
NICHD Pelvic Floor Disorders Network. He is a member of the NIH BMIO Review
Panel, and chairs the Rome Foundation Research Committee.
    Research support for the center has come chiefly from the NIH (approxi-
mately 60). Center investigators currently hold an R24 Mind–Body
Infrastructure grant, two RO1s, two R23s and an R21, in addition to support
they receive as co-investigators on grants by their collaborators outside the
center. This support from the NIH is supplemented by several investigator-
initiated research contracts with pharmaceutical companies for outcomes
research unrelated to drug approval (for example, estimating the impact of
FGIDs on quality of life and health economics).


                        RESEARCH INFRASTRUCTURE

Currently, the center is supported by an R24 Mind–Body Medicine infrastruc-
ture grant, which funds a number of cores that support the research of our
investigators. These cores are as follows:

   • Research Administration Core, which provides a registry of research
     participants and staff support for recruiting research subjects, assis-
     tance with the recruitment of Hispanic and other minority subjects,
     and a team of research coordinators.
   • Biometry Core, which provides consultation on experimental design
     and statistical analysis, questionnaire and data entry forms, and data
     management schemes. For selected studies, this core provides actual
     data management and data analysis.
   • Data Acquisition and Technology Applications Core, which provides
     technical support for automated data entry (scan-able questionnaires,
346   INTEGRATIVE GASTROENTEROLOGY


     Internet-based questionnaires and surveys), creation of websites for
     study management, and maintenance of a secure server, which serves
     as a reservoir for databases.
   • Education and Dissemination Core, which maintains a website to
     educate patients and healthcare providers and disseminate research
     findings, prepares posters, slides, and brochures for center investiga-
     tors, and publishes a quarterly newsletter.
   • Seed Grant Core, which provides one-year grants of $37,500 to new
     investigators to collect pilot data for grant submissions. This program
     has been highly successful, in that six of the first nine seed grant recip-
     ients have obtained independent NIH funding related to their seed
     grants (two RO1s, two R21s, one R23s, and a supplement to an R24).


                        International Activities

The center is represented nationally and internationally through a network
not only of research activities (see above) but also in leadership positions. As
noted, Dr. Drossman is President and Dr. Whitehead on the Board of Directors
of the Rome Foundation, the organizational responsible for standardization in
diagnosis in the FGIDs. Center investigators are actively involved on the advi-
sory boards of pharmaceutical companies, NIH, FDA, and the International
Foundation for Functional GI Disorders, have held leadership positions in the
Functional Brain-Gut Research Group, have served as associate editors for
Gastroenterology, and are editors or on editorial boards for Gastroenterology,
Internal Medicine, and Psychosomatic Medicine. The center is frequently high-
lighted by the media in newspapers and magazines, and several videos, radio,
and TV shows have been produced on site.


           Academic Training and Public Education

A major commitment of the center is to provide onsite training not only for
our GI fellows but for visitors from around the world. The Visiting Scholars
Program provides an opportunity for faculty, investigators, and clinicians from
other institutions to visit the center for a few days to several weeks. The Visiting
Scientists Program hosts faculty and investigators for sabbaticals and extended
stays for one to two years. In this capacity, the visitors spend enough time to
return to their home institution and establish independent research careers, or
set up their own clinical programs in the FGIDs. There are several components
to the training program:
                                     Mind-Body Medicine in Digestive Disease 347


  1. Mentored Learning. Trainees work in an individually structured
     relationship with one or more faculty mentors, who provide ongoing
     support and feedback to their work. Guidelines developed by the
     center for providing this mentored learning are available (Drossman,
     2007b). The senior investigators at the center have independently
     established research careers with NIH funding, and are able supervise
     trainees in all aspects of research, including project development,
     grant writing, ongoing project administrative support, abstract and
     manuscript preparation, and presentation skills. Clinicians are offered
     the opportunity to observe our clinical staff in the care of patients seen
     in the clinic (with patient permission). With proper credentialing,
     they are able to independently work with patients in a preceptorship
     arrangement.
  2. Training Seminars. We hold a weekly clinical case conference, where
     patients seen by the clinicians are presented and discussed among the
     entire clinical staff to provide new insights into diagnostic and thera-
     peutic approaches. In addition, the center hosts a monthly psychoso-
     cial skills seminar, with GI fellows and clinicians outside the division,
     to facilitate learning about patient care. This includes live patient
     interviews and discussions, videotaped learning sessions on the
     medical interview, role plays, and small group learning. There is also
     a monthly interdisciplinary Anorectal Motility Case Conference, in
     which gastroenterology, radiology, surgery and urogynecology staff
     discuss the diagnosis of patients with complex pelvic floor disorders
     and plan optimal treatment approaches.
  3. Public Education. The center’s education programs target patients
     and their families and friends, healthcare professionals at all levels,
     and the public at large. The center promotes increased awareness and
     understanding of the FGIDs through a biennial all-day patient sym-
     posium, printed materials, videos, and its website (www.med.unc.
     edu/ibs). Many of these programs have won national recognition,
     including the Freddy Award and the Communicator Award, and have
     been shown on TV and webcasts on major networks.


                       Concluding Comments

In the current healthcare environment that emphasizes procedures over time
spent with patients, the UNC Center has been able to sustain a patient-
centered biopsychosocial model of care that is quality based and effective.
Furthermore, with federal research emphasis on biomedical research, and
348   INTEGRATIVE GASTROENTEROLOGY


shrinking research funding, we have successfully maintained a broad and
comprehensive NIH-funded research portfolio that has helped to move the
field forward. We have also been successful in communicating our clinical and
research agenda to other healthcare providers and investigators around the
world. Hopefully this effort will ultimately help our patients with functional
GI and motility disorders.
                                    35
                 Yoga and Digestive Health
                 SAJIDA CHAUDRY AND BETH NOLAN




                                  key points

     ■   Yoga is a means to experience consciousness and harmony with
         the world.
     ■   Yoga and ayurveda are sister sciences—both believe in the
         inseparable nature of the mind, body and spirit.
     ■   Patanjali’s eight limbs of yoga include yama, niyama, asana,
         pranayama, pratyahara, dharana, dhyana and Samadhi.
     ■   Yoga poses and breathwork for digestive health enhance relax-
         ation and reduce sympathetic nervous system stimulation.
                                         ■




                               Introduction

  Evenness of the mind is called yoga.
                    —Bhagavad Gita

Yoga is believed to have two meanings, union and discipline. Yoga comes from
the Sanskrit work “yuj” which means to join together. The root is similar to the
work yoke, which also means to bond together. At its very core, yoga brings
together the individual self (jiva—our physical body) and the cosmic or uni-
versal self (atman—the entire universe) to form a single unity. Yoga is the
vehicle to achieve consciousness, to transcend the ego–personality and to
experience Unity. In this state of Unity, there is no inner conflict and complete
harmony with the world.



                                                                             349
350    INTEGRATIVE GASTROENTEROLOGY


   The practice of yoga can be dated back to the third millennium BCE.
Patanjali, the Indian sage, wrote the Yoga Sutras around 200 CE in the form of
195 organized and codified terse aphorisms. Thus, classical yoga emerged.
   Yoga and ayurveda are considered to be sister sciences—both believe in the
inseparable nature of the mind, body and spirit and both view the body as
channels of energy (nadis) that can result in disease if blocked.
   Kapha, pitta and vata imbalances affect the entire body including the gas-
trointestinal system. Balancing doshas (see ayurvedic section) is fundamental
to both yoga and ayurveda.
   Yoga is divided into eight stages, know as Patanjali’s eight limbs of yoga:

  1. Yama - universal moral commandments
  2. Niyama - self-purification by discipline
  3. Asana - posture
  4. Pranayama - rhythmic control of the breath
  5. Pratyahara - withdrawal and freedom of the mind from the senses
     and the exterior world
  6. Dharana - concentration
  7. Dhyana - meditation
  8. Samadhi - state of bliss or super-consciousness where the individual
     merges with the universal spirit

   Yoga as practiced in the West focuses mainly on asana, poses named after
animals, but really yoga intends for integration of the mind, body and spirit
through all of the above stages. The yogic path involves body and mind purifi-
cation, asana preparing the body for meditation and samadhi.


                    Yoga and Digestive Health

In terms of gastrointestinal health, yoga allows relaxation, balancing the
physiological effects of stress. Reduction in skeletal muscle tension decreases
sympathetic system stimulation and subjective tension and may improve gut
motility (Drossman, 2003). Relaxation training includes imagery, breathwork,
meditation and biofeedback—all components of yoga.
   Gastrointestinal disorders such as irritable bowel syndrome involve
enhanced motility and visceral hypersensitivity associated with brain–gut dys-
function. With its meditative approach, yoga helps with changing the relation-
ship to stress, and the actual postures bring awareness of the body with gentle
physical activity. Yoga has been compared in a small randomized, controlled
trial to standard drugs (loperamide) in diarrhea-predominant IBS. Both have
                                                      Yoga and Digestive Health 351


been shown to work at 2-month follow-up, with yoga having the additional
benefit of increased parasympathetic activity (Taneja et al., 2004). The yoga
intervention group consisted of a set of 12 asanas (e.g., Vajrasana, Shashankasana,
Ushtrasana, Marjariasana, Padhastasana, Dhanurasana, Trikonasana in two
variations, Pawanmuktasana and Paschimottanasana), along with Surya Nadi
pranayama (right-nostril breathing) two times a day for 2 months. Other
studies have looked at pranayama (yogic breathing), asanas (yoga postures)
and meditation and have concluded that yoga may be a beneficial, low-risk,
economical addition to the treatment of illnesses that can worsen gastrointes-
tinal health such as stress, anxiety and depression (Brown & Gerbarg, 2005).
   Yoga teaches us how to breathe deeply and fully. Breathing this way brings
the natural functions of the organs into balance, especially the eliminatory
organs. The diaphragm and the lungs expand and contract, thus massaging the
internal organs. In the case of weak abdominals, the digestive and eliminatory
functions are weakened as well. The diaphragm is connected to some of the
abdominal muscles via connective tissue. If the muscles are weak, a full, deep
breath is limited. Yoga postures using the complete three-part breath can
strengthen the abdominal wall and the digestive organs, supporting good
health and vitality.


   In terms of gastrointestinal health, yoga allows relaxation, balancing the
   physiological effects of stress. Reduction in skeletal muscle tension decreases
   sympathetic system stimulation and subjective tension, and may improve
   gut motility.



      Yoga Postures for Patients with Digestive Illness

   A compassionate approach to one’s body is essential. There is no benefit if
   there is pain. The goal is to find relaxation in the body and mind through
   breathing deeply and fully in the postures.



There are numerous yoga postures that address digestive health. Five will be
covered here. These five are easy and simple enough for any patient to practice.
All postures can be modified to accommodate any physical limitations by
using pillows, bolsters, and even chairs. Good advice to health practitioners is
to consider experimenting with the poses themselves, to understand them
experientially. To achieve the greatest benefit from each of these postures,
patients will need at least 10 to 15 complete yogic breaths per pose. If at any
352 INTEGRATIVE GASTROENTEROLOGY


time your patient is uncomfortable, recommend readjusting the body, or ask
your patient to take himself or herself completely out of the posture to rest.
Then ask your patient to consider returning to the posture and attempting to
challenge themselves again.
   Usually, anyone with digestive problems feels discomfort and agitation.
Starting with Viparta Karani (legs up the wall) calms the nervous system and
the mind, bringing focus to the breath deep in the lower abdomen. The height
of the bolster supporting the hips will vary according to the severity of the
discomfort. In the case of irritable bowel syndrome (IBS), it is best to use a
folded blanket—about an inch high—so as not to over-stretch the abdominal
walls and intestines, which would cause more irritation. The idea is to bring
calmness to the intestines and to one’s breathing. Due to its supportive nature,
this posture can be recommended with a hold for 10 to 15 minutes.
   Once your patient has been in Viparta Karani, and his or her body, mind,
and breath are calmer, a forward bend series will help massage and encourage
the elimination process. Patients can assume the Dandasana (staff pose) by
engaging their muscles and breathing the full three-part breath. This posture
can tone the abdominal organs, lift sagging abdominal walls, improve digestion,
and reduce heartburn and gas.
   The Janu Sirasana (head to knee pose) has the ability to massage the ascend-
ing colon when the right leg is extended out first, and the descending colon
when the left leg is extended. This posture can be recommended with a strap
to create a more vigorous massage, or with a chair or bolster. This supports the
head and arms for a more restorative effect. After your patient has completed
this pose on both sides, ask them to return to Dandasana and to prepare for
Paschimottanasana (full forward bend).
   As in the last posture, this position can be very active and engaging for
patients by using their hands or strap to fully work the posture, and by bolster-
ing their head and upper body with pillows and or a chair. The key to any of
these variations is to ask patients to keep the full three-part breath, expanding
and contracting to massage the organs from the inside out. After this pose, ask
patients to return to Dandasana with 3–5 breaths, and roll down to their backs,
resting in Savasana (relaxation or corpse pose). If there is any lower back pain
or discomfort, ask patients to bend their knees and bring them toward the
chest. Patients can gently roll around to relieve any discomfort, and then return
to Savasana. If there is still discomfort, then patients may rest with a pillow
under their knees, or keep their knees bent and feet flat on the floor. Encourage
focus on the three-part breath.
   Resting between postures or a series of postures allows your patient’s body
to integrate and feel the benefits as they rest. Marichyasana (spinal twist) is a
great benefit to the body as a whole. By twisting the spine, they are affecting
                                                      Yoga and Digestive Health 353


the nervous system, which increases energy levels and massages the organs
under the rib cage. This improves the functions of the liver, spleen, pancreas,
kidneys, and intestines. Spinal twist also has the ability to realign the spine,
allowing the nerve impulses to flow and respond more efficiently. Spinal twists
should be done with caution. Avoid recommending them if the patient has
diarrhea, dysentery, insomnia, or migraines. Variations of spinal twist can be
recommended; these are done while lying down, practicing knee-down twist
or the traditional twist with one leg bent and the other extended, or by twisting
with crossed legs.


      Advasana (Reversed Corpse or Relaxation Pose)

The next series of postures start in Advasana—the opposite of Savasana—lying
flat on the stomach. Ask your patient to turn his or her head to one side or the
other to get an even stretch in the neck while breathing the three-part breath.
This allows the stomach and/or diaphragm to expand and press into the floor
with each breath. Allow the exhalation to relax the patient into the floor. To
deepen the massage of the digestive tract, place hands or fists under the stom-
ach and continue breathing. Recommend that the patient always be gentle,
never causing pain or discomfort. A compassionate approach to one’s body is
essential. There is no benefit if there is pain. The goal is to find relaxation in the
body and mind through breathing deeply and fully.
                                        36
    Integrative Approaches to Abdominal Pain
              ROBERT A. BONAKDAR AND EMILY G. SINGH




                                    key concepts

      ■   Patients with chronic abdominal pain deserve a biopsychosocial
          approach (Figure 36.1) to their condition, including a thorough
          evaluation of organic causes as well as focus on psychological
          state, family dynamics, and coping strategies.
      ■   Use of standardized tools (Irritable Bowel Syndrome Symptom
          Severity Score, Brief Pain Inventory) is encouraged to enhance
          global understanding and monitoring.
      ■   The most common cause of abdominal pain, especially recur-
          rent pain in children, is irritable bowel syndrome (IBS).
      ■   In addition to currently approved medications, an evidence-
          guided approach should be utilized to recommend or consider
          the following treatments on an individual basis:
          ■ Mind–Body Therapies

             ■ Reassurance and education

             ■ Cognitive-behavioral therapy (CBT) for IBS, number

                 needed to treat (NNT) of 21
             ■ Biofeedback, especially for pain associated with pelvic

                 floor dyssynergia (PFD)/functional constipation
             ■ Hypnosis, especially gut-directed hypnotherapy, trial in

                 patients who fail standard medical therapy,
          ■ Biologically Based Therapies

             ■ Dietary counseling by a qualified practitioner for optimiz-

                 ing dietary intake
             ■ Peppermint oil for IBS, NNT of 2.5

             ■ Probiotics for IBS, NNT of 8.9




1
  Number Needed to Treat (NNT): Defines the number of subjects needed to be treated to have
a successful outcome versus control treatment.

354
             ■ Fiber for IBS, NNT of 11
         ■  Alternate Medical Systems/Energy-Based Treatments
            ■ Acupuncture for IBS, trial in patients who fail standard

               medical therapy
            ■ Herbal medicine and dietary interventions from a tradi-

               tional Chinese medicine, Tibetan Ayurvedic, or natur-
               opathic perspective for IBS
            ■ Transcutaneous electrical nerve stimulation (TENS) used on

               acupoints for IBS or pain related for functional dyspepsia
     ■   In some cases, a formally structured multidisciplinary program
         may need to be initiated for optimal management.
                                       ■




                               INTRODUCTION




A
         bdominal pain, especially of a chronic, functional nature, can be a
         complex, difficult-to-treat condition requiring global assessment and
         individualized care options. As described below, the most common
cause of abdominal pain, especially in children, is irritable bowel syndrome
(IBS). Unfortunately, as noted in most the recent meta-analysis of available
drug treatments in the setting of IBS currently, options are not optimal, with
global assessment and treatment required:

  “The evidence for efficacy of drug therapies for IBS is weak. Although there
  is evidence of benefit for antispasmodic drugs for abdominal pain and
  global assessment of symptoms, it is unclear whether anti-spasmodic sub-
  groups are individually effective. There is no clear evidence of benefit for
  antidepressants or bulking agents. The physician should be aware that
  global assessment is a construct containing various dimensions. For each
  individual, these will have a different weighting and treatment should be
  aimed at the most debilitating symptom.” (Quartero et al., 2005)

   In this setting, it is not surprising that many patients consider the use of
non-pharmacological (NP) and complementary and alternative medicine
(CAM) for pain and symptom management. Chapter 37 will provide an over-
view of these treatment options including prevalence, patient rationale for uti-
lization, and clinical efficacy. Most importantly, as many of these choices are
356   INTEGRATIVE GASTROENTEROLOGY


accessed without the input of a clinician, the chapter aims to provide guidance
regarding the discussion and coordination of care for these treatments.


                            OVERVIEW AND IMPACT

Chronic abdominal pain is defined as pain that has been symptomatic for three
months or more. In addition, pain may be categorized as organic or functional
(absence of anatomic abnormality, inflammation, or tissue damage). Various
diagnoses fit into the category of functional gastrointestinal disorders, as noted
Table 36.1 (Guthrie & Thompson, 2002). In some cases, a diagnosis may fit into
more than one category. For example, IBS, which will be the main discussion
point in this chapter, is typically defined as a functional bowel disorder. However,
more recent evidence demonstrates potential inflammatory and infectious eti-
ologies that may explain at least a portion of IBS cases (Alonso & Santos, 2009).
   IBS appears to be one of the most common causes of chronic or recurrent
abdominal pain. Irritable bowel syndrome affects 10 to 15 of the North
American population, and thus is comparable in incidence to other chronic
conditions such as asthma, coronary heart disease, diabetes, hypertension, and
migraine (Cash, Sullivan, & Barghout, 2005; American College of
Gastroenterology, 2002). Even though IBS accounts for nearly 3 of general
practitioner consultations, only a quarter of those with IBS actually seek
medical treatment for their symptoms (Thompson et al., 2000; Drossman &
Thompson, 1992). Thus, on average, an IBS sufferer has symptoms for 10 years
before diagnosis (International Foundation for Functional Gastrointestinal
Disorders, 2002). For many reasons, IBS has the ability to create a substantial
financial and quality-of-life burden on the patient and society (American


         Table 36.1. Categories for Functional Gastrointestinal Disorders

• Functional dyspepsia
• Ulcer-like dyspepsia
• Dysmotility-like dyspepsia
• Unspecified dyspepsia
• Functional diarrhea
• Functional constipation
• Irritable bowel syndrome
• Functional abdominal bloating
• Unspecified functional bowel disorder
• Functional abdominal pain syndrome
• Unspecified functional abdominal pain

(Reprinted with permission from Guthrie &Thompson (2002) BMJ, 325(7366), 701–703).
                                    Integrative Approaches to Abdominal Pain 357


Gastroenterological Association, 2004; Frank et al., 2002). Estimates place
combined direct and indirect costs of IBS at nearly $30 billion a year (Cash,
Sullivan, & Barghout, 2005). Because of the significant use of healthcare
resources, and indirect costs including absenteeism and loss of productivity,
the estimated cost of IBS appears to be greater than that of conditions includ-
ing asthma or migraine, and comparable with hypertension and congestive
heart failure. Additionally, chronic abdominal pain is well recognized to have
detrimental effects on quality of life, which may be more difficult to delineate
(Cash, Sullivan, & Barghout, 2005; Hahn et al., 1999).


                  OVERVIEW OF INTEGRATIVE OPTIONS *

Non-pharmacological and CAM treatments include a vast array of choices for
the abdominal pain patient. The definitions of these treatments vary and are
constantly being updated. Non-pharmacological treatments are typically
defined as options that are not prescription medications. However, several
options that have been nonprescription options in the past, such as omega-3
oils and B vitamins, are now available in formulations requiring a prescription.
In addition, several options, such as S-adenosyl methionine (SAMe), which
are nonprescription in the United States, may require prescriptions outside the
United States. Similarly, CAM was previously defined as treatments not
included in medical school training. Currently, more than 60 of the nation’s
allopathic medical schools are providing some level of instruction on CAM
(Wetzel, Eisenberg, & Kaptchuk, 1998). More recently, CAM has been defined
by the National Institutes of Health Center for Complementary and Alternative
Medicine (NCCAM) as treatments or medical systems that are not typically
incorporated in conventional treatment recommendations. This definition has
evolved to include integrative medicine, which is the practice of incorporating
selected evidence-based CAM options into mainstream practice. The NCCAM
system classifies CAM into categories that are helpful for discussion. Currently,
there is no consensus and large overlap in the use of these terms. For this chap-
ter, the non-pharmacological and CAM treatments reviewed will be referred
to collectively as NP/CAM options. An overview of NP/CAM options catego-
rized under NCCAM headings is noted in Table 36.2.


                       PREVALENCE OF NP/CAM USE *

NP/CAM use is quite common, especially in those suffering from pain. CAM
usage was reported in approximately one-third of the United States population
358    INTEGRATIVE GASTROENTEROLOGY


      Table 36.2. Overview of Non-pharmacological and Complementary and
                      Alternative Medicine (CAM) Treatments
Category Overview              Examples

1. Alternative Medical         Traditional Chinese Medicine
Systems                        Ayurveda
Systems of care based on       Naturopathy
unifying health paradigms,     Homeopathy
which may incorporate
individual treatments
including those noted in the
categories below.

2. Mind–Body                   Biofeedback                         Hypnosis
Interventions                  Meditation                          Visualization
Diverse techniques that        Yoga                                Guided imagery
utilized cognitive,            Exercise, various                   Cognitive-
behavioral, and movement       Tai chi/qi gong                     behavioral
therapies in order to modify   Creative therapies                  therapies
and increase awareness         (art, music or dance)               Group support
between mental and             Relaxation                          Autogenic training
physiological functioning                                          Spirituality

3. Biologically Based          Dietary modification (dietary elimination, fasting, or
Therapies                      specific dietary regimen)
Therapies that modify          Dietary Supplements: Herbal supplements (white willow
nutrient intake, either        bark)
through dietary intervention   Non-herbal supplements (glucosamine), vitamins
or supplementation             (vitamin D), minerals (selenium)

4. Manipulative and            Chiropractic manipulation
Body-Based Methods             Osteopathic manipulation
Techniques that utilize        Manual and massage therapy
manipulation, movement,
and/or stretching of one or
more parts of the body

5. Energy Therapies            Acupuncture
(biofield therapies)           Qi gong
Techniques that involve the    Healing Touch
application of human or        Therapeutic touch
nonhuman energy fields

Adapted from What Is CAM? http://nccam.nih.gov/health/whatiscam/
                                     Integrative Approaches to Abdominal Pain 359


in 1990, and increased to 42 by 1997. At that point, this represented 628 million
office visits and $27 million spent on CAM services, which far exceeded total
out-of-pocket expenditure and office visits (328 million) for conventional pri-
mary care providers in the same year. A follow-up analysis demonstrated that
approximately one-third of the visits to CAM providers were for the treatment
of pain (Wolsko et al., 2003).


   A more recent analysis of CAM use by the NIH found that a majority of the
   top 10 reasons for CAM use were related to pain complaints, with abdominal
   pain in the top 10 in 2002 and top 15 in 2007. (Barnes et al., 2002; Barnes,
   Bloom, & Nahin, 2007).



                    PREDICTORS AND PATTERNS OF USE *

Several surveys have demonstrated that approximately half or more of IBS
sufferers use CAM. In one survey of 413 GI clinic patients (61 IBS, 22 func-
tional dyspepsia [FD], 17 gastroesophageal reflux disorder [GERD]), a total
of 181 users of CAM were identified, or 44 of the group. The use of CAM was
most frequent for IBS (51 IBS, 36 FD, 27 GERD). The most frequently
utilized treatments were herbal medicines.



   Predictors of CAM use were diagnosis with IBS, history of abdominal surgery,
   emergency room visits, disabilities and prescription of benzodiazepines and
   3 or more medical visits for gastrointestinal tract disorders within the previ-
   ous year. (Carmona-Sánchez & Tostado-Fernández, 2005).



   In another survey examining the acceptability of various—mostly NP/
CAM—treatments for IBS, Harris and Roberts (2008) found a number of rea-
sons for non-use, including dislike or disbelief in the treatment modality, as
well as insufficient knowledge. The proportion of patients finding various
treatments for IBS acceptable is noted in Table 36.3.
   In a multicenter pediatric survey, Vlieger et al. (2008) compared CAM use
in patients with functional and organic gastrointestinal diseases. The overall
prevalence of CAM use was 37.6 and, as expected, use was higher in patients
with functional disorders than organic disorders (25.3 versus 17.2).
Predictors of CAM use included less than satisfactory or adverse effects of
conventionally prescribed medications, school absenteeism, and age 11 years
360   INTEGRATIVE GASTROENTEROLOGY


                    Table 36.3. Proportion of Patients Finding
                     Various Treatments for IBS Acceptable

                  Tablets 83.9%

                  Diet change 81.6%

                  Yoga 76.6%

                  Stomach cream 67.6%

                  Homeopathy 64.8%

                  Heat pad 63.7%

                  Hypnotherapy 63.7%

                  Acupuncture 59.0%

                  Suppository 57.4%

                 (adapted from Harris and Roberts, 2008)




or below. Interestingly, 93 of the parents considered it important for pediatri-
cians to be involved in CAM research, and 51 of were willing to participate in
CAM research trials.
   Those who utilize CAM for IBS may share characteristics with the general
CAM user, which may be important for the clinician to keep in mind. Namely,
CAM users are more likely to be women with higher levels of education and
income. Those using CAM have health values, beliefs, and coping systems that
are also quite important to keep in mind. Those who are involved in “active
coping behaviors,” which includes physical activity and particular diets, tend
to view CAM use in a similar manner (Astin, 1998). Additionally, patients with
a more “holistic outlook” wish to utilize complementary methods that take
their viewpoint into consideration (Furnham & Bhagrath, 1993).
   There has been speculation that CAM use signals dissatisfaction with
conventional care. One survey found that rheumatology patients with more
medical skepticism had a higher likelihood of utilizing a CAM provider. This
finding was especially true for abdominal pain patients (Callahan et al., 2008).
However, the more likely scenario is that of CAM as an adjunct to conven-
tional care. In fact, dissatisfaction with conventional care did not predict use of
CAM in a previous survey, and less than 5 of CAM users did so in isolation
from conventional care. Most CAM users state that their motivation for CAM
use is that it provides them more control over their health care, and up to 80
report benefit from its use a previous survey (Astin, 1998).
                                    Integrative Approaches to Abdominal Pain 361



   CAM users have been noted to have more frequent relationships with a pri-
   mary care physician, have regular physician follow-up, and good compliance
   with recommended preventative health behaviors such as regular mam-
   mography. Thus, what may be termed “medical skepticism” may in fact be
   an active coping behavior attempting to identify and incorporate poten-
   tially helpful treatments. As discussed below, the coordination of these
   efforts by a medical provider is quite important to help maximize treatment
   utility. (Astin et al., 2000).




                      Approach to the Patient*

Regardless of their experience or particular beliefs about CAM, clinicians have
an ethical obligation to discuss treatment alternatives with their abdominal
pain patients. This is quite pertinent in the abdominal pain population that has
an especially high use of NP/CAM. In this setting, it is especially important to
have an open, nonjudgmental discussion about all treatments being consid-
ered or utilized, in order to provide full and optimal coordination of care.
Unfortunately, the interaction between patients and clinicians regarding CAM
use is often suboptimal. This situation is linked to several factors noted below,
including the patient’s and clinician’s CAM knowledge base, level of discus-
sion, and management strategies such as charting and follow-up. Several strat-
egies and pertinent resources are reviewed to help optimize the approach to
the abdominal pain patient.


                             KNOWLEDGE BASE*

The knowledge base of the average clinician and consumer regarding NP/
CAM, including popular areas such as dietary supplements, is suboptimal.
Physician surveys have found that physicians may have an insufficient general
understanding of commonly utilized supplements, as well as their safety, regu-
lation, and interaction profiles (Ashar, Rice, & Sisson, 2007; Kemper, Gardiner,
Gobble, & Woods, 2006). Similarly, consumers and patients tend to have mis-
conceptions regarding product claims and efficacy. As pointed out by a previ-
ous Harris Poll, the majority of consumers believe that the government ensures
a higher level of safety and regulation than actually exists (Harris Interactive,
2002). These misconceptions, as well as biased or anecdotal information found
on some health websites and advertising, may create a scenario of decreased
362   INTEGRATIVE GASTROENTEROLOGY


perceived need for clinician guidance regarding CAM (Washington, Fanciullo,
Sorensen, & Baird, 2008).


                                 Discussion*

The level of discussion regarding NP/CAM that occurs in the average pain
consultation can be quite minimal. This is exemplified by the example of an
editorial from the journal Pain, entitled “Food and Pain: Should we be more
interested in what our patients eat?” The average pain clinician does not spend
significant time discussing diet in general, or as an intervention. The reasons
for this may include lack of training and resources and more comfort prescrib-
ing other interventions, including medication (Bell, 2007; Smith, 2004). The
level of discussion regarding CAM, specifically, may be even more deficient.


  Surveys have found that in approximately 70% of encounters there was no
  discussion of CAM use, and that neither the patient nor clinician introduced
  the topic. More concerning is the fact that if a patient is hospitalized by a
  specialist, CAM use is not identified up to 88% of the time. It is important
  to understand why patients may not discuss CAM use. (Wold et al., 2007;
  Azaz-Livshits et al., 2002).




   Surveys indicate that factors including anticipation of a negative clinician
response, as well as belief that the clinician will not provide useful informa-
tion, motivated non-discussion (Adler et al., 1999). However, most important
may be clinician inquiry, because patients demonstrate a willingness to dis-
close supplement use, but only if asked by a clinician (Hansrud et al., 1999).
Unfortunately, a recent survey of physicians found that few felt comfortable
discussing CAM with their patients. One of the major reasons for this lack of
comfort was related to a need for improved knowledge base regarding CAM
(84 of responders). It is theorized that with improved education and knowl-
edge base about CAM, physicians may be more willing to discuss and counsel
patients (Corbin-Winslow et al., 2002).


                          INVOLVING THE FAMILY

To most successfully understand and treat abdominal pain, it is imperative to
view the condition and coping strategies as linked to a complex matrix of
                                      Integrative Approaches to Abdominal Pain 363


potentially medical, as well as personal, family and community factors. Thus,
when evaluating a patient with abdominal pain, a thorough biopsychosocial
history of the patient and family is essential. Family pain histories are also
quite important, as the frequency, severity, and level of catastrophizing of chil-
dren with pain has been associated with degree of pain in the family (Schanberg
et al., 2001).


                    PATIENT AND CLINICIAN EDUCATION

A number of resources are available to clinicians interested in better under-
standing NP/CAM as a means of improving patient communication and
treatment options. These resources include print and online information on
evidence-based use of NP/CAM, as well as continuing medical education
courses available to clinicians. The H.E.R.B.A.L. Mnemonic is offered in Table
36.4 as a clinical tool for aiding clinicians when discussing and managing CAM
use, especially dietary supplements.


                                  Regulation*

The regulation of NP/CAM varies widely based on the therapy described, the
training of practitioners, and state laws. For example, acupuncture provided
by a licensed acupuncturist (LAc) or physician acupuncturist may have vastly
differing regulation as set forth by the state board, traditional Chinese medi-
cine, medical board, or department of consumer affairs. In addition, the level
of training, oversight, and continuing education for acupuncture varies widely
by state, and the referring clinician should help guide patients in finding qual-
ified and experienced CAM practitioners whenever possible. Verification of



                     Table 36.4. The H.E.R.B.A.L. Mnemonic©

                Hear the patient out with respect

                Educate the patient

                Record

                Be aware of potential interaction and side effects

                Agree to discuss and follow-up

                Learn
364   INTEGRATIVE GASTROENTEROLOGY


licensure can be obtained by contacting the state’s medical board, department
of consumer affairs, or therapy-specific national certification organizations, as
listed in Table 36.5.
    Dietary supplements are regulated according to the Dietary Supplement
Health and Education Act (DSHEA) of 1994. Regulation differs from prescrip-
tion medication, which must proceed through multiphase trials to gain
approval from the FDA. Supplements (with established ingredients) are not
strictly required to have safety, efficacy, or bioavailability data prior to market-
ing. The FDA must utilize adverse drug reports and product analysis to moni-
tor products in the marketplace (FDA, 2002, 2003). Two more recent regulatory
measures, The Dietary Supplement and Non-Prescription Drug Consumer
Protection Act (S. 3546), which mandates the reporting of serious adverse
events to the FDA, and Good Manufacturing Practices (GMPs) for dietary




      Table 36.5. Regulatory and Practitioner Resources for Behavioral and
                   Complementary and Alternative Medicine
Organization / Agency                                       Website

Federation of State Medical Boards                          http://www.fsmb.org/m_
                                                            pub.html

American Academy of Medical Acupuncture                     http://www.
                                                            medicalacupuncture.org

The National Certification Commission for Acupuncture       http://www.nccaom.org/
and Oriental Medicine

American Psychological Association                          http://www.apa.org/

American Society of Clinical Hypnosis                       http://www.asch.net

The Center for Mind–Body Medicine                           http://www.cmbm.org

The Biofeedback Certification Institute of America          www.bcia.org/

American Dietetic Association                               www.eatright.org

American Chiropractic Association’s                         http://www.acatoday.org

The National Certification Board for Therapeutic Massage    http://www.ncbtmb.com
and Bodywork

Association for Applied Psychophysiology and Biofeedback.   www.aapb.org

American Association of Naturopathic Medicine               www.naturopathic.org

Association of Accredited Naturopathic Colleges             www.aanmc.org
                                       Integrative Approaches to Abdominal Pain 365


supplements, which began incorporation in August 2007, should be helpful in
ensuring better-regulated supplements (FDA, 2007).
    In addition to the above governmental measures, several agencies offer
testing and monitoring services that allow manufacturers to demonstrate their
adherence to regulatory standards. Those that pass inspection may carry an
independent “Seal of Approval” on their label and advertising. Several of the
government and independent agencies currently involved in oversight are
listed in Table 36.6. Clinicians should become familiar with well-regulated and
well-researched brands for the supplements that are most likely to be discussed
with patients.


             Interventions—Evidence-Guided Care

Abdominal pain patients encounter, consider, and incorporate a large number
of interventions for their condition and comorbidities. Understanding the
motivation for, benefit from, and integrative potential for these treatments on




                   Table 36.6. Governmental and Independent
                               Regulatory Agencies
Agency                                                     Website

GOVERNMENTAL

Food and Drug Administration (FDA) Medwatch                www.fda.gov/medwatch
Program for collecting adverse reactions to prescription
and OTC medications, as well as dietary supplements

Federal Trade Commission (FTC) site for submitting         www.ftc.gov/ftc/complaint.
complaints on false or misleading advertising              htm

American Association of Poison Control Centers for         www.poison.org or
reporting and management of adverse effects                (800)222-1222

INDEPENDENT LABS PROVIDING SUPPLEMENT TESTING

The Consumerlab Product Review                             www.Consumerlab.com

Dietary Supplement Verification Program (DSVP) through www.uspverified.org
the United States Pharmacopeia (USP)

National Sanitation Foundation(NSF)                        www.NSF.ORG/consumer/
                                                           dietary_supplements
366   INTEGRATIVE GASTROENTEROLOGY


an individual basis is essential in helping to frame an effective multidisciplinary
treatment plan. Unfortunately, the research base in this area is quite heteroge-
neous and at times difficult to interpret. As an example, several meta-analyses
of integrative options in the setting of abdominal pain, especially IBS, have
been inconclusive. This includes meta-analyses of acupuncture and hypnosis,
and all dietary interventions for treatment of IBS (Webb, Kukuruzovic, Catto-
Smith, & Sawyer, 2007; Lim et al., 2006; Huertas-Ceballos, Logan, Bennett, &
Macarthur, 2009). Additionally, studies appear to be confounded by the high
rate of placebo effect in CAM trials of IBS (Dorn et al., 2007).
    While awaiting more definitive evidence-based guidelines in this area, the
clinician needs to provide evidence-guided care. In the setting of abdominal
pain, because of the varied number of interventions and methodologies, the
provider must often strive for evidence-guided care to find a successful com-
promise between available clinical evidence, patient preference, and clinical
experience. In this paradigm, the clinician must review the available evidence
to determine the safety and efficacy of various interventions. This is especially
true of interventions that may be provided and initiated with varied method-
ologies, dosages, and directives. A prime example of this is hypnosis for IBS/
abdominal pain, which is covered in more detail below.
    If a clinician were to follow the conclusion of a recent meta-analysis in this
area when encountering a pain patient interested in trying this intervention,
his or her response might be to avoid this intervention. However, when more
closely examined in the setting of hypnosis, or any NP/CAM, if there are no
positive trials and/or the treatment demonstrated significant potential for
harm, then the directive should be one of avoidance. However, if the treatment
is of minimal harm and has the potential of benefit (such as hypnosis), or has
positive evidence that demands a more focused detail of the intervention, the
treatment may be recommended. This recommendation requires attention to
specific protocols for modalities, and specific dosage and brand for supple-
ments, along with appropriate monitoring and follow-up reassessment after a
trial period.
    An example of this in the setting of hypnosis would be a specific gut-directed
hypnotherapy in patients with IBS whose predominant symptom was abdom-
inal pain. This specific, cost-effective modality was able to significantly decrease
physical symptoms and in six of the eight health-related quality-of-life domains
measured (emotional, mental health, sleep, physical function, energy, and
social role). These gains were most significant in female patients with abdomi-
nal pain as their predominant symptom (Smith, 2006). In this example,
through sifting of available trials, a positive protocol can be found that may be
worth discussing and incorporating by a trained professional.
                                   Integrative Approaches to Abdominal Pain 367




                          TREATMENT OVERVIEW

                                Acupuncture

Acupuncture typically involves the therapeutic insertion of fine needles at
selected body points based on a traditional or neuroanatomical basis.

  Acupuncture is often utilized in the setting of abdominal pain because it is
  believed to be helpful for pain management, based on specific and nonspe-
  cific local, neurochemical, and cortical modulation. (Pariente et al., 2005;
  Sprott, Franke, Kluge, & Hein, 1998).


   From a mechanistic standpoint, acupuncture appears to increase solid
gastric emptying and improve dyspeptic symptoms in patients with functional
dyspepsia (Xu et al., 2006). There also appears to be improvement in heart rate
response, consistent with an increased parasympathetic tone, with acupunc-
ture that is not seen with placebo acupuncture. The increase in parasympa-
thetic tone also correlates with positively with improvement in abdominal
pain (Schneider, Weiland, & Enck, 2007).
   The potential for benefit in the setting of abdominal pain is difficult to
answer from a research perspective largely based on the poor methodology
and varied application of acupuncture in trials (Berman, Swyers, & Ezzo,
2000). The most recent Cochrane review of trials meeting inclusion criteria
found that the evidence was inconclusive (Lim et al., 2006). A more recent
trial found that quality of life related to IBS improved significantly whether
real or sham acupuncture was utilized. This led the authors to conclude that
the benefit in quality of life with acupuncture may be related to unspecific
effects (Schneider, Streitberger, & Joos, 2007).
   This demonstrates the difficulty in studying acupuncture in the setting of
IBS, as far as the placebo response. In one estimate, based on differences
between real and placebo acupuncture, a study would need 566 patients to
potentially prove benefit beyond placebo. This number is far beyond what is
typically seen in trials of IBS (Schneider, Enck, Streitberger et al., 2006).
   The dichotomy between mechanistic/observation trials and clinic trials
may be related to inappropriate study design. A more appropriate design
may be similar to that seen in headache trials. This condition has also been
demonstrated to have a nonspecific needle effect that is similar to sham acu-
puncture and superior to usual care (Vickers et al., 2004). Several trials have
368   INTEGRATIVE GASTROENTEROLOGY


demonstrated this phenomenon, and proceeded to not focus on the difference
between real/sham but instead on any acupuncture and usual care in prag-
matic design. These trials have shown benefit in severity of headache and
related measures, which has correlated to a positive economic impact
(Wonderling, Vickers, Grieve, & McCarney, 2004).
   Considering the economic impact of IBS ($30 billion/year), which exceeds
that of common conditions such as migraine, future trials of acupuncture
should focus on a pragmatic design approach. This design looks not only at
differences between needle interventions, but whether acupuncture can have a
meaningful impact compared to usual care on IBS symptoms, quality of life,
and related costs (absenteeism, office visits, and medication). One such trial
has explored this potential design (Reynolds, Bland, & MacPherson, 2008)
and found that a pragmatic, randomized, intention-to-treat controlled trial
compared 10 sessions of acupuncture plus usual primary care, with usual pri-
mary care alone. At three months, the patients receiving acupuncture in this
trial had a significant 138-point improvement on the IBS Symptom Severity
Score (scored 0–500). The authors estimate that a sample size of 108 patients
per arm would be required for a fully powered study. The authors conclude,
“A pragmatic trial design will not be able to distinguish between acupuncture
specific effects and placebo effects; however, it is the design of choice to deter-
mine cost effectiveness.”
   In summary, as a recent systematic review noted, “. . . it must be discussed
on what terms patients benefit when this harmless and obviously powerful
therapy with regard to [quality of life] is demystified by further placebo-
controlled trials” (Schneider, Streitberger, & Joos 2007). For clinicians advis-
ing patients regarding acupuncture while awaiting more definite evidence
from pragmatic or placebo-controlled trials, it is wise to assess the global
impact of the conditions and benefit from usual care. For those patients with
refractory symptomology and reduced quality of life, it appears prudent to
utilize a short trial of 8 to 10 treatments by a qualified practitioner to assess
benefit. It is also advised that a standardized questionnaire, such as the IBS
Symptom Severity Score, be utilized in conjunction with monitoring of medi-
cation use, productivity, and other lifestyle measures to pragmatically view the
potential benefit of acupuncture in this setting.


                             PHYSICAL THERAPIES

Modalities and physical therapies include a wide range of therapies that are
practitioner based and/or patient guided. The most common of these therapies
utilized in abdominal pain/IBS are various electrostimulation or transcutaneous
                                   Integrative Approaches to Abdominal Pain 369


electrical nerve stimulation (TENS) techniques. These therapies are based on
several potential areas of benefit, which may correct areas of abnormality seen
in abdominal pain/IBS, including muscular tension, autonomic hypersensitiv-
ity, altered skin temperature, and dysfunctional motility (McAllister, McGrath,
& Fielding, 1990).



                           Electrical Stimulation

Various types of transcutaneous electrical nerve stimulation (TENS) devices
have been utilized in the setting of abdominal pain. One trial found that TENS
at acupuncture points appears to improve dyspeptic symptoms and increases
high-frequency heart rate variability in patients with functional dyspepsia (Liu
et al., 2008). A pilot study also evaluated acupoint TENS in patients with diar-
rhea-predominant irritable bowel syndrome (IBS-D), constipation-predomi-
nant irritable bowel syndrome (IBS-C), functional constipation (FC) and
healthy controls. IBS-D patients had significantly lower rectal sensory thresh-
olds of the first sensation of stool, urgency of defecation, and pain than IBS-C
or FC patients or healthy controls (P < 0.05). After 2 months of acupoint TENS
treatment in IBS-D patients, there was significant improvement in rectal sen-
sory thresholds, stool times, and the intensity of abdominal pain (Xiao & Liu,
2004). Electrostimulation may be considered based on preliminary data in the
setting of refractory symptoms, especially diarrhea-predominant irritable
bowel syndrome (IBS-D).



                       Mind–Body Therapies (MBT)

Mind–body Therapies (MBTs) are diverse techniques that utilize cognitive,
behavioral, and movement therapies to modify and increase awareness between
mental and physiological functioning. These therapies can be as simple as one-
time directed educational efforts, and as elaborate as long-term behavioral and
psychological interventions. Several MBTs utilized in the setting of abdominal
pain/IBS are reviewed below. Overall, the recent Cochrane review concluded
that “psychological interventions may be slightly superior to usual care or
waiting list control conditions at the end of treatment,” although few long-
term follow-up results were available for review (Zijdenbos et al., 2009).
Specifically, for improvement in abdominal pain, the standardized mean dif-
ference (SMD) at 2 and 3 months were 0.54 and 0.26 compared to usual care,
and the SMD versus placebo at 3 months was 0.31.
370   INTEGRATIVE GASTROENTEROLOGY


reassurance Several articles have noted poor patient understanding of
their condition, as well as catastrophizing, as factors related to increased symp-
tom severity in IBS (Lackner, Quigley, & Blanchard, 2004). One trial attempted
to determine the benefit of a single session of reassurance in self-perception of
impairment in patients with IBS. In 55 patients seen for initial consultation, a
questionnaire was provided to assess factors related to healthcare seeking.
These included pain/discomfort, 78; cancer fear, 11; daily function impair-
ment, 33; symptom related to stressfulness, 60; and none, 2. Afterwards,
patients were provided with an explanation of the disease and reassurance,
with readministration of the questionnaire. The authors found that one-time
reassurance acutely decreased self-perception of daily function impairment
(P=.003) and was independent of the subjects’ educational level (Schmulson,
Ortiz-Garrido, Hinojosa, & Arcila, 2006).

cognitive-behavioral therapies (cbt) Cognitive-behavioral ther-
apies enable patients to better understand how various beliefs, thoughts, and
perceptions can affect their condition. Techniques such as restructuring, pri-
oritization, and goal-setting are utilized to repattern behavior. Mechanistically,
PET scanning in conjunction with CBT training has demonstrated reduction
in limbic activity (Lackner et al., 2006). In the setting of CBT clinical trials,
meta-analysis of 17 trials found an odds ratio of 12.0 in creating a >50 reduc-
tion in GI symptoms. Overall, the NNT to provide benefit versus controls was
2 (Lackner et al., 2004). This intervention should be freely recommended,
especially in patients who exhibit psychological sequelae as a means of better
approaching their condition or other therapies.

hypnosis Hypnosis has been defined in various ways, but typically involves,
“the use of aroused, attentive, focused concentration and relative suspension
of peripheral awareness to create opportunities for suggestion” (Astin, Shapiro,
Eisenberg, & Forys, 2003). The overall evidence for hypnosis in the setting of
IBS is inconclusive, as noted by a recent Cochrane meta-analysis (Webb,
Kukuruzovic, Catto-Smith, & Sawyer, 2007). However, for short-term benefit
in the setting of abdominal pain and IBS symptoms, the authors noted that
hypnotherapy was superior to waiting list control or usual medical manage-
ment in patients who fail standard medical therapy. As mentioned above, the
most-studied regimen is known as gut-directed hypnotherapy, which has
demonstrated significant benefit in the majority of clinical trials (Wald &
Rakel, 2008). Unfortunately, incorporation has not been universal because
trials have suffered from methodological weaknesses and treatment requires
a 6 to 12 week commitment. Alternatives to the treatment have been investi-
gated, including a self-hypnosis audio recording, which provided similar (52)
                                   Integrative Approaches to Abdominal Pain 371


improvement to gut-directed hypnotherapy (Forbes, MacAuley, & Chiotakakou-
Faliakou, 2000). At this point, hypnosis may be considered as a likely effective
mind–body therapy in the motivated or refractory pain/IBS patient.

biofeedback Biofeedback utilizes various techniques or sensors to
increase mind-body awareness and identify areas of potential modification
such as muscle tension (sEMG) or autonomic tone (peripheral temperature,
heart rate variability [HRV], galvanic skin response). Because of the autonomic
dysfunction described in IBS, biofeedback training affords a potential treat-
ment for active nervous system retraining. Trials in this area have used various
biofeedback techniques in a number of GI conditions including IBS, fecal
incontinence, and pelvic floor dyssynergia (PFD)/functional constipation,
which is often associated with anorectal pain. The most robust evidence for
pain management appears to be in the area of PFD, in which a review of
38 trials found that the overall average probability of successful treatment
outcome for patients treated with biofeedback was 62.4 (Palsson, Heymen, &
Whitehead, 2004).

guided imagery Guided imagery encompasses various techniques,
which combine “the use of inner images and symbols (self-guided or interac-
tive) with therapies to induce a specific psychobiologic state (e.g., immune
enhancement, relaxation, conflict resolution)” (Astin, Shapiro, Eisenberg, &
Forys, 2003). In a preliminary trial of 22 children (aged 5 to 18 years), guided
imagery with progressive muscle relaxation (GI +PMR) was compared to
breathing exercises, as provided in 4 weekly sessions with a therapist. At base-
line, the children who received guided imagery had more days of pain during
the preceding month (23 versus 14 days). Children who learned guided imag-
ery with progressive muscle relaxation had significantly greater decrease in the
number of days with pain and days with missed activities, at one and two
months. At 2-month follow-up, more children who had learned guided imag-
ery had 4 or fewer days of pain each month, with no missed activities. Although
a small trial, the ability to reduce days of pain from greater than 20 to fewer
than 5, with a relatively short-term, benign intervention, deserves consider-
ation while awaiting additional trials (Weydert et al., 2006).


                       Biologically Based Therapies

A number of trials have attempted to investigate the use of dietary interven-
tion for IBS-related symptoms including pain. These are subdivided in the
following sections.
372   INTEGRATIVE GASTROENTEROLOGY


fiber Fiber supplementation studies for IBS symptoms vary based on types
(soluble vs. insoluble), formulation (food based, dietary supplement) and
amount recommended. Overall, fiber has been compared with placebo or a
low-fiber diet in 6 studies with a total of 591 subjects (Quigley et al., 2008).
Fiber improved symptoms in 48 of subjects versus 43 in the placebo or low
fiber groups. The NNT with fiber for clinical success is 11, although the range
was large a large range (5 to 100) based on varied methodology.
   Bran fiber has specifically been compared with placebo or a low-fiber diet
in 5 studies with a total of 221 subjects. A summary of all trials demonstrates
no statistically significant improvement in IBS symptoms with use of bran
fiber. Psyllium (ispaghula husk) has specifically been compared with placebo
in 6 studies with a total of 321 patients. Psyllium improved symptoms in 48
of subjects versus 36 in the placebo group. Overall, the number needed to
treat with ispaghula to prevent one patient having persistent symptoms was 6,
although the range was large (3–50) based on varied methodology. Lastly, guar
gum (5 g/day) has been compared to wheat bran (30g/day) in one IBS. Although
both treatments improved symptoms related to abdominal pain and bowel
habits, guar gum was better tolerated and preferred by patients (Parisi et al.,
2002).

probiotics Probiotics are broadly defined as beneficial microbes taken to
improve health. Because IBS has been linked to microflora alteration, the use
of probiotics has been discussed as a helpful treatment. The mechanism of
benefit, in addition to reducing the population of symptom-causing micro-
flora, may also include the anti-inflammatory and opioid-releasing ability of
some strains. In a study of bifidobacteria, 8 different strains were analyzed
for their effects on in vitro models of non-inflamed and inflamed intestinal
epithelium. The results demonstrated that although none of the bifidobacteria
induced nuclear factor κB (NF-κB) activation, six of the eight bifidobacteria
tested inhibited lipopolysaccharide- (LPS-) induced NF-κB activation in a
dose- and strain-dependent manner. This response was accompanied in
specific strains by a dose-dependent reduction of interleukin 8 (IL-8) secretion
and by decreased mRNA levels for inflammatory markers including IL-8,
TNF-α, cyclooxygenase 2 (Cox-2) and intercellular adhesion molecule 1
(ICAM-1). The authors stated that certain bifidobacteria may be of benefit in
the setting of chronic intestinal inflammation (Riedel et al., 2006).
   A number of clinical trials have attempted to test various probiotic strains
in the setting of IBS pain and symptom management. In a meta-analysis of 20
such trials, McFarland and Dublin (2008) compared 23 probiotic treatment
arms in 1,404 subjects. In this analysis, probiotic use was associated with
improvement in global IBS symptoms compared to placebo (relative risk
                                    Integrative Approaches to Abdominal Pain 373


RR=0.77, 95 confidence interval [95 CI; 0.62–0.94]). Specifically, probiotics
were associated with decreased abdominal pain compared to placebo (RR =
0.78 [0.69–0.88]). The number needed to treat (NNT) for reducing abdominal
pain was 8.9. Considering that this is a relatively benign intervention, a trial
should be considered in the appropriate setting. Several limitations are
present, however, in the use of probiotics for abdominal pain associated with
IBS. Namely, numerous strains at various doses have been studied, as noted in
Table 36.7. In the setting, the clinician should be aware of various formulations,
as noted below, and may need to attempt various brands before finding one
potentially helpful.

peppermint The use of peppermint extract for IBS-related symptoms has
been studied in four placebo-controlled trials. These trials, which enrolled 392
patients, were reviewed by Ford et al (2008). While 65 of patients receiving
placebo had persistent symptoms, this dropped to 26 of patients randomized
to peppermint oil. The NNT with peppermint oil to prevent one patient having
persistent symptoms was 2.5 (2.0 to 3.0). A review of these trials is noted in
Table 36.8.

other dietary interventions A number of herbal medicines have
demonstrated benefit versus placebo in IBS trials, including Chinese herbal
formulas, STW 5, STW 5-II and Tongxie Yaofang, Tibetan herbal formula
Padma Lax, and certain Ayurvedic formulas (Liu, Yang, Liu, Wei, & Grimsgaard,
2006). Other dietary interventions, including incorporating food antibody
testing and dietary supplements such as l-glutamine, zinc, and cromolyn
sodium, have been mentioned in the setting of IBS (Wald & Rakel, 2008).
Although individualized cases may benefit from the incorporation of various
interventions, the evidence for generalized benefit is either lacking or conflict-
ing. Clinicians should openly discuss these options to ascertain the potential
benefit of a particular intervention.


              Conclusion and Coordination of Care

Abdominal pain is a complex disorder that involves both central and periph-
eral sensitization, causing pain amplification and multisystem dysfunction,
creating significant autonomic, functional, and psychological sequelae. It is
quite important to take a biopsychosocial approach to this condition, as single
modality approaches are rarely curative or of long-term benefit. A model of a
biopsychosocial approach is noted in Figure 36.1. Because of the sometimes
disparate presentation of patients with abdominal pain/IBS it is imperative to
                                      Table 36.7. Relief of Abdominal Pain in 11 Probiotic/Placebo Treatment Arms
Reference           Probiotic                                          Improvement in abdominal pain   Definition of secondary outcome1

                                                                Probiotic n/n (%)    Placebo n/n (%)

Gade(46)            Strept faccalis                             25/32 (78)           10/22(45)         Absence or presence of symptom

Nobaek(48)          L. plantarum                                9/25 (36)            5/27 (18)         Decrease ≥ 1.5 on VAS symptom scale

O’Sullivan(49)      L. rhamnosus GG                             9/19 (47)            12/19 (63)        Symptom improved

Niedzielin(50)      Lacto plantarum                             20/20 (100)          11/20 (55)        Absence or symptoms

Bausserman(52)      Liicto rhamnosus GG                         11/25 (44)           10/25 (40)        Decrease of ≥ 1 point symptom score

Kajander(54)        L. rhamnosus GG + L. rham. LC705 +          27/41 (66)           17/40 (43)        Symptoms alleviated
                    Bifid. brene Bb99 +Prop. freudenreichii

Whorwell(35)        Bifido. infantis (106 dose)                 32/74 (43)           39/76 (52)        Adequate relief of symptoms

Whorwell(35)        Bifido. infantis (108 dose)                 42/72 (59)           39/76 (52)        Adequate relief of symptoms

Whorwell(35)        Bifido. infantis (1010 dose)                28/71(39)            39/76 (52)        Adequate relief of symptoms

Enck(59)            E. coli + Strept faccalis                   108/149 (72)         66/148 (45)       ≥ 50% decrease in symptom score

Gawronska(60)       Lacto rhamnosus GG                          6/18 (33)            1/19 (5)          Absence of pain
1
  All secondary outcomes are defined based on patient report.
Reprinted with permission from Lynne V. McFarland.
                   Table 36.8. Peppermint for IBS: Characteristics of randomized controlled trials of peppermint oil versus
                                                    placebo in irritable bowel syndrome
Study            Country       Setting       Diagnostic        Criteria to define symptom            Sample   Dose of peppermint   Duration of   Jadad
                                             criteria for      improvement after therapy            size     oil                  therapy       score
                                             irritable bowel
                                             syndrome

Lech 1988w29     Denmark       Secondary     Clinical       Patient reported improvement in         47       200 mg three times 4 weeks         3
                               care          diagnosis and global symptoms                                   daily
                                             investigations

Liu 1997w30      Taiwan        Secondary     Clinical       Patient reported improvement in         110      187 mg three or      1 month       4
                               care          diagnosis and abdominal pain                                    four times daily
                                             investigations

Capanni          Italy         Secondary     Rome II           Improvement in global                178      2 capsules three     3 months      5
2005w32                        care                            symptoms assessed by validated                times daily
                                                               questionnaire

Cappello         Italy         Secondary     Rome II and ≥50% improvement from                      57       225 mg twice daily 4 weeks         5
2007w31                        care          investigations baseline in overall irritable bowel
                                                            syndrome symptom score using
                                                            questionnaire data

Reprinted with permission from Ford AC et al. BMJ. 2008 Nov 13;337:a2313. doi: 10.1136/bmj.a2313.
376 INTEGRATIVE GASTROENTEROLOGY


individualize care. In addition, because of several factors, including high levels
of treatment failure, potential sensitivity to pharmacological interventions,
and preference for specific treatment options, it is imperative for clinicians to
be aware of NP/CAM options and to actively engage patients in discussion and
coordination of these therapies when appropriate. Several resource tables and
figures are provided to enable initial and ongoing discussion and management
of NP/CAM options in abdominal pain.
   Several of the therapies reviewed in this chapter can provide safe, effective
avenues of treatment for abdominal pain and its comorbidities. In many cases,
the clinician is essential in helping abdominal pain patients to practically
incorporate the various NP/CAM options available, to come up with a suc-
cessful integrative management plan. If properly coordinated, there is evidence
that an integrative/multidisciplinary approach, which typically involves both
biological and MBT, may be more effective than monotherapy in creating a
more satisfied abdominal pain patient with self-management skills. In the
future, we look forward to additional research that helps to understand the
synergy of NP/CAM therapies with conventional pharmacological care.




   *Portions of this chapter are excerpted with permission from
Non-pharmacological, Complementary & Alternative (CAM) Treatments for
Fibromyalgia, McCarberg W and Clauw D, eds., Fibromyalgia, Informa
Healthcare USA, Inc., New York, 2009.
                              37
Over-the-Counter Remedies for Digestive
       Health: Potion or Poison?
           JERRY HICKEY AND GERARD E. MULLIN




                           key concepts

■   More than 50 million American adults experience frequent
    heartburn.
■   Proton-pump inhibitors (PPIs) are the third-bestselling class of
    medications in the United States.
■   Omeprazole is the only PPI that inhibits CYP2C19 while increas-
    ing the expression of CYP1A2.
■   Proven complications of PPI therapy include:
    ■ Bacterial colonization

    ■ C. difficle infection

    ■ Interstitial nephritis

    ■ Small bowel bacterial overgrowth

    ■ Community-acquired pneumonia

    ■ Hip fracture

    ■ Nutrient malabsorption (calcium [O’Connell et al., 2005],

       magnesium, iron, vitamin B12)
■   H2 receptor antagonists (H2RAs) are weaker than PPIs but can
    suppress 24-hour gastric acid secretion by about 70.
■   Cimetidine:
    ■ interacts with various Phase 1 detoxification enzymes includ-

       ing CYP1A2, CYP2C9, and CYP2D6
    ■ can cause a broad array of CNS symptoms

    ■ can include galactorrhea in women, and gynecomastia,

       reduced sperm count, and impotence in men (Hoogerwerf
       WA, Pasricha PJ, 2006 1) For all H2 Receptor Antagonists
       (H2RAs), thrombocytopenia and other blood dyscrasias
       have also been reported.Nutrient depletions are similar to
       the PPIs.

                                                                       377
    ■   Stimulant Laxatives:
        ■ induce low-grade inflammation and enhance gastrointesti-

           nal motility
        ■ long-term use of irritant laxatives may lead to colonic pathol-

           ogy, “cathartic colon”
        ■ mineral oil side effects include leakage of oil, greasy stools;

           rarely, if aspirated, it can cause lipid pneumonitis.
    ■   Mineral Oil:
        ■ side effects include leakage of oil, greasy stools

        ■ rarely, if aspirated, it can cause lipid pneumonitis

        ■ can interfere with the absorption of minerals and all fatty

           soluble nutrients.
                                      ■




                                 Outline

●   Proton Pump Inhibitors
•   Issues concerning OTC drugs for gastrointestinal indications:
•   Side effects
•   Toxicity
•   Complications of PPIs
•   Drug interactions
•   Nutrient depletions
●   H2 Receptor Antagonists (H2RAs)
•   Issues concerning OTC drugs for gastrointestinal indications:
•   Side effects
•   Toxicity
•   Drug interactions
•   Nutrient depletions
●   Antacids
•   Issues concerning OTC drugs for gastrointestinal indications:
•   Side effects
•   Toxicity
•   Drug interactions
•   Nutrient depletions
             Over-the-Counter Remedies for Digestive Health: Potion or Poison? 379


  ●   Laxatives
  •   Issues concerning OTC drugs for gastrointestinal indications:
  •   Side effects
  •   Toxicity
  •   Drug interactions
  •   Nutrient depletions


                Proton Pump Inhibitors for GERD

                     TREATING FREQUENT HEARTBURN

Frequent heartburn is defined as symptoms occurring two or more days per
week. More than 50 million American adults experience frequent heartburn.
In the United States, 25 million adults experience heartburn daily. Heartburn
affects quality of life, disrupting sleep and interfering with work and social
activities (National Heartburn Alliance, 2003; Oliveria et al., 1999; Revicki
et al., 1998). Heartburn is slightly more common in women; the mean age of
reporting symptoms is 45 to 50 years of age. In rare cases it can lead to esopha-
geal adenocarcinoma (Cappell, 2005). Access to OTC medications has been
reported to improve patient adherence to a treatment regimen.


        PROTON PUMP INHIBITORS FOR FREQUENT HEARTBURN

Increasingly, the more powerful proton pump inhibitors are replacing
Histamine-2 (H2) antagonists in clinical practice. Omeprazole is the first
proton pump inhibitor available without a prescription.
   Omeprazole is available as Prilosec OTC Delayed-Release Tablets 20 mg.

  • Prilosec OTC is the first proton pump inhibitor (PPI) to be available
    over-the-counter for frequent heartburn treatment.
  • Prilosec OTC is for people with frequent heartburn (two or more days
    per week).
  • One pill a day of Prilosec OTC works to relieve heartburn for up to
    24 hours as part of a 14-day course of therapy.*
  • Directly shuts down many active proton pumps over time that make
    acid, but purported to leave enough acid for digestion, with one pill
    a day.
380    INTEGRATIVE GASTROENTEROLOGY




                                  Side Effects

The most common side effects are:

   •   Nausea
   •   Abdominal pain
   •   Constipation
   •   Flatulence
   •   Diarrhea

   However, mild myopathy, arthralgias, headaches and skin rashes have also
been reported. Chronic use of omeprazole may lead to hypergastrinemia in 5
to 10 of chronic users. Discontinuation of omeprazole after chronic use in
patients with hypergastrinemia may cause a rebound hypersecretion of gastric
acid (Freston, 1994).


                            Complications of PPIs

the top ten list
    1) PPIs can lead to twofold increased rates of Clostridium difficile
        colitis
Gastric acid provides a natural protective barrier to orally ingested pathogens.
The significance of this association is accentuated by the emergence of a hyper-
virulent strain of C. difficile that is highly transmissible, causes severe colitis
that sometimes requires colectomy, and has a fatality rate as high as 20. This
disease is more commonly a complication of outpatient antibiotic usage, which
is being overprescribed at record levels (Dial et al., 2005b). Development of
drug resistance and alteration of the intestinal flora are felt to predispose to
digestive disease. PPIs are a major contributor to nosocomial Clostridium dif-
ficile infection (Howell MD et al., 2010).

   2) Bacterial colonization with resistant microbes in the intensive care
      unit (ICU) setting.
Many investigations have reported the overuse and misuse of PPIs by physi-
cians hospital-wide and in the intensive care unit (ICU) setting (Eid SM et al,
2010). Our own surveys demonstrate misperceptions, misuse, and overuse of
PPIs by resident and attending physicians. Our findings led to restricted usage,
              Over-the-Counter Remedies for Digestive Health: Potion or Poison? 381


to reduce inappropriate use and to diminish the risk from nosocomial
infection in the intensive care setting (White, Storch & Mullin, 2003; Mian
et al., 2003).

   3) PPIs are associated with an increased risk of community-acquired
      pneumonia.
PPIs increase the risk of bacterial infections by reducing the bactericidal
activity of immune cells (Zedtwitz-Liebenstein et al., 2002). A study using a
database of 500,000 records reported in JAMA found that current use of PPIs
was associated with an increased risk of community-acquired pneumonia
(CAP).

   4) Drug-induced acute interstitial nephritis.
PPIs are one of the most frequent causes of drug-induced acute interstitial
nephritis (in some cases leading to renal failure), which is a trade secret, since
most gastroenterologists are unaware of this potential toxic effect (Geevasinga
et al., 2006).

   5) Possible cardiovascular events.
In 2007, Astra Zeneca provided the FDA data from two small ongoing
studies showing that individuals taking the “purple pill” were at an increased
risk for cardiovascular events, such as myocardial infarction and congestive
heart failure. The agency did not issue a safety warning at that time. On
August 7, 2007, the FDA made an unprecedented “early communication” to
dismiss the adverse events as age-related and preexisting conditions. iiIn
early 2009, some proton pump inhibitors were reported by Canadian
researchers to reduce or eliminate the antiplatelet benefits of clopidogrel
(Plavix) and increase the risk of a second heart attack (Juurlink et al., 2009).
In a six-year population-based study of heart attack patients published in the
Canadian Medical Association Journal, current use of three proton pump
inhibitors was associated with a 27 increase in the risk of another heart
attack.




   Explain to interested patients that clopidogrel (Plavix) is prescribed after a
   heart attack for secondary prevention. Note that this study found that
   taking the drug along with some proton pump inhibitors increases the risk
   of recurrence.
382   INTEGRATIVE GASTROENTEROLOGY


   The finding came as the FDA began a review of the so-called “clopidogrel
resistance phenomenon,” in which between 5 and 15 of patients do not
respond to the drug at all. Sanchez-Munoz-Torrerro et al (2010) subsequently
reported that in patients with established arterial disease, concomitant use of
PPIs and clopidogrel was associated with a nearly doubling of the incidence of
subsequent myocardial infarction or ischemic stroke. The story of the interac-
tion between clopidogrel and PPIs and their potential increase risk to patients
with underlying coronary artery disease is unfolding.

   6) Bacterial overgrowth of the stomach and proximal small intestine.
A concern for physicians and their patients about PPI usage is that chronic
acid inhibition may lead to bacterial overgrowth of the stomach and proximal
small intestine. In GERD patients who are being treated with PPIs, there is an
increased load of intragastric bacteria compared with those in whom PPI ther-
apy has been discontinued (Gregor, 2004). Furthermore, a study that used a
well-defined database consisting of about 500,000 patient medical records
showed that acid-suppressive drugs such as PPIs are associated with an
increased risk of community acquired pneumonia (CAP) (Laheij et al., 2004).
Bacterial overgrowth may not only become a source of pneumonia from colo-
nization, but it appears to become a susceptibility factor for a subtype of IBS
that requires antibiotics to improve symptoms (Pimentel & Lezcano, 2007,
Lombardo et al., 2010).

   7) Pneumonia in the elderly: increased risk and worse prognosis.
PPIs may be particularly risky for the elderly. Pneumonia is a major source of
mortality in the elderly, immunocompromised patients, individuals with
asthma or chronic obstructive lung disease, and children. Due to the age-
related reduction of gastric acid after 60 years, and partially due to a decreased
immune response, elderly patients are likely to experience severe infection
(Dial et al., 2005a). This study demonstrated a dose-response effect, as the
relative risk of pneumonia was greatest for those taking more than one daily
dose of a PPI. To avoid excessive pneumonia in the elderly, the study’s authors
recommended that the elderly, “immunocompromised patients, those with
asthma or chronic obstructive lung disease, and children should be treated
with acid-suppressive drugs only when needed and with the lowest possible
dose.”

   8) Hip fracture.
Most recently, and of particular concern, long-term PPI use appears to
predispose to the development of hip fracture (adjusted odds ratio 2.6; see
Yang et al., 2006). Millions of individuals have been using these medications
             Over-the-Counter Remedies for Digestive Health: Potion or Poison? 383


on a continuous or long-term basis. Given that the elderly have reduced
omeprazole clearance, caution should be exercised toward this complication,
and bone density scanning may become necessary for early detection of
osteoporosis from PPIs.

   9) PPIs cause malabsorption of calcium, iron, and vitamin B12 from
      lowering gastric acidity
Significant deficiency in gastric acid, called “hypochlorhydria,” is already
prevalent among the elderly population without adding PPIs to the mix
(Malfertheiner et al., 2007). The elderly appear to have decreased PPI clear-
ance from their bloodstream, and may be more likely to have more profound
hypochlorhydria at baseline (without any PPI usage), due to a higher preva-
lence of Helicobacter pylori infection, which itself causes hypochlorhydria (Lai
& Sung, 2007). PPIs result in calcium malabsorption, since gastric acid is
required for solubilization prior to absorption (Recker, 1985). In fact, limited
animal and human studies have shown that PPI therapy may decrease insolu-
ble calcium absorption or bone density (O’Connell et al., 2005; Camilleri et al.,
2007).

   10) Bacterial gastroenteritis.
   Gastric acid is a defense mechanism against gastrointestinal infections
caused by ingested bacteria. Studies have suggested that the use of acid-
suppressing drugs may increase the risk of gastroenteritis (GE).
   Current use of PPIs was found by scientists in Madrid, Spain, to be associ-
ated with an increased risk of bacterial GE compared with nonuse, regardless
of the treatment duration (Garcia Rodriguez, Ruigomez, & Panes, 2007). In
contrast, no association with gastroenteritis was observed with histamine
receptor-2 antagonists (H2RA), which are weak stomach acid blockers.
Doubling the PPI dose further increased the risk of developing bacterial GE.
The effect of PPI use did not vary significantly with regard to treatment
indication.
   The increased risk associated with PPI use was similar for both omepra-
zole and lansoprazole, whereas neither of the H2RAs, cimetidine nor raniti-
dine, showed any increased risk. Campylobacter (n = 4124) and Salmonella
(n = 1885) were the two species most frequently responsible for GE episodes
in the case group (n = 6414). The case-control group consisted of 50,000
non-PPI users. When analyzed separately, both species reproduced the
increased risk associated with PPI use and not H2RA therapy. Conclusions:
This study strongly suggests that gastric acid suppression induced by PPIs,
but not H2RA, is associated with an increased risk of Campylobacter and
Salmonella GE.
384   INTEGRATIVE GASTROENTEROLOGY



                                      Fact
  Omeprazole therapy significantly decreased calcium absorption in elderly
  women. (O’Connell et al., 2005).




   Proton-pump inhibitors (PPIs) are among the most commonly prescribed
drugs, and a large number of patients use these on a daily basis as maintenance
therapy for gastroesophageal reflux disease.



                                Fact about PPIs

  Despite the widespread use of PPIs in GERD, the prevalence of pre-neoplastic
  complications of GERD (Barrett’s esophagus) and esophageal adenocarci-
  noma are on the rise in the United States.




   Although they are considered safe by the FDA and approved for long-term
use, a number of concerns continue to be raised. Because of their strong
acid-suppressive effect, PPIs lead to increased secretion and plasma levels of
the hormone gastrin, which may support the development of neoplasia at high
sustained levels.
   Two studies (Yang et al., 2007; Robertson et al., 2007) published in the jour-
nal Gastroenterology (United Kingdom, Denmark) found that long-term PPI
therapy (> 5 years) at regular doses was not associated with a significantly
increased risk of colorectal cancer (CRC). However, the study by Yang et al.,
found a strong association between recent (<1 year) PPI therapy and the risk of
CRC (OR, 2.6; 95 CI, 2.3–2.9; P < .001). The increased risk in Yang’s study
was observed exclusively with recent short-term use (within the preceding
12 months).
   Jan Tack and John M. Carethers wrote a commentary about these articles in
the September 2007 issue of Gastroenterology. Their closing comment on the
articles stated:

  “Both studies found that long-term PPI therapy was not associated with a
  significantly increased risk of CRC. These reassuring findings are important
  from a public health point of view for patients taking PPIs as well as for
             Over-the-Counter Remedies for Digestive Health: Potion or Poison? 385


  gastroenterologists prescribing PPIs. However, as PPI use increases over
  time, continued monitoring of the effect of PPI therapy on the risk of CRC
  over longer follow-up times seems warranted.”


                             Drug Interactions

Omeprazole has a number of drug interactions because it is metabolized by
various cytochrome-p 450 enzymes. Omeprazole is the only PPI that inhibits
CYP2C19, therefore decreasing the rate of excretion of disulfiram, phenytoin,
and other drugs. Omeprazole increases the expression of CYP1A2, thereby
increasing the rate of excretion of imipramine, some antipsychotic drugs,
tacrine, and theophylline. Additionally, omeprazole interacts with warfarin,
diazepam, and cyclosporine (Relling MV & Giacomini KM, 2006).
   Nutrient Depletion
   Calcium. Researchers at the University of Pennsylvania School of Medicine
report that chronic use of proton pump inhibitors, especially at higher doses,
increases the risk of hip fracture. Hypochlorhydria interfered with the absorp-
tion of calcium (Yang, Lewis, Epstein, & Metz, 2006).
   Magnesium. There have been reports of severe magnesium depletion in
users of omeprazole. Researchers from the University of Auckland found that
omeprazole inhibited the absorption of magnesium, and this effect could be
partially corrected by supplementing with high-dose oral magnesium (Cundy
& Dissanayake, 2008). Other nutrients: omeprazole inhibits the absorption of
zinc (Ozutemiz et al., 2002), vitamin B12, vitamin B1, folic acid, and iron,
sodium, and beta-carotene (Vagnini & Fox, 2005). Although PPIs are consid-
ered by many to be devoid of adverse effects, nutrient depletions can be severe.
Recently, there was a case of omeprazole-induced hyponatremic delirium
accompanied with rhabdomyolysis in an emergency department patient. After
cessation of omeprazole and emergency treatment, the patient recovered com-
pletely (Bebarta & King, 2008).

nutrients depleted by ppis:
  •   Calcium
  •   Magnesium
  •   Zinc
  •   Vitamin B12
  •   Vitamin B1
  •   Folic acid
  •   Iron
386   INTEGRATIVE GASTROENTEROLOGY


  • Sodium
  • Beta-carotene


                  H2 RECEPTOR ANTAGONISTS (H2RAS)

H2-receptor antagonists competitively inhibit the binding of histamine at
receptor sites on parietal cells, decreasing the production of acid. Although
weaker than PPIs, H2RAs can suppress 24-hour gastric acid secretion by about
70 (PPIs; 80-95) (Hoogerwerf WA, Pasricha PJ, 2006-1). These drugs are
approved for treating uncomplicated GERD, but are increasingly being
replaced by PPIs in clinical practice.
   H2-receptor antagonists available without a prescription include:

  •   Cimetidine (Tagamet HB)
  •   Famotidine (Pepcid AC)
  •   Nizatidine (Axid AR)
  •   Ranitidine (Zantac 75)


                                Side Effects

The side effects of H2-receptor antagonists are considered to be minor, but
include:

  •   Diarrhea
  •   Headaches
  •   Drowsiness
  •   Fatigue
  •   Muscular pain
  •   Constipation

   There are less common but more serious side effects that affect the CNS,
including delirium, confusion, hallucinations, and slurred speech, which can
occur in elderly subjects. Cimetidine, in particular, affects sex steroid hor-
mones if used long term and, typically, at higher dosages. The drug influences
estrogen metabolism in women and testosterone binding in men. The result
can include galactorrhea in women, and gynecomastia, reduced sperm
count, and impotence in men (Hoogerwerf WA, Pasricha PJ, 2006-2).
Thrombocytopenia and other blood dyscrasias have also been reported
(Freston, 1982). Increased incidence of community-acquired pneumonia has
been linked to the use of famotidine (Hauben, Horn. Reich, & Younus, 2007).
             Over-the-Counter Remedies for Digestive Health: Potion or Poison? 387




                             Drug Interactions

Cimetidine interacts with various phase 1 detoxification enzymes, including
CYP1A2, CYP2C9 and CYP2D6. Ranitidine also interacts with hepatic CYPs
but with only 10 of the affinity seen with cimetidine. Famotidine and nizati-
dine have very little influence on these enzymes (Pharmacotherapy, 2006).
Therefore, any drug metabolized by these CYPs will have an interaction with
cimetidine and a possible interaction with ranitidine.


                            Nutrient Depletions

Calcium is reportedly depleted at least to some extent by H2-receptor antago-
nists (Vagnini & Fox, 2005).
    Iron: Gastric acid secretion is required to facilitate iron absorption.
Malabsorption of dietary iron may result from inhibition of acid secretion by
the H2-receptor antagonists. H2-receptor antagonists are considered to be effi-
cient chelators of Fe2+. This probably lacks clinical importance during the short
term; however, long-term use of these drugs could contribute to the occurrence
of iron-deficiency anemia. Such impairment of nonheme iron absorption could
be amplified for individuals concurrently using antacids on a regular basis in
conjunction with H2-receptor antagonists (Aymard et al., 1988).
    Zinc: Reduced gastric acid secretion can exert both direct and indirect
effects on the absorption of zinc that parallel its impairment of iron absorp-
tion. In a study involving healthy adults, 300 mg/day of ranitidine for 3 days
significantly reduced gastric acid and zinc absorption (Sturniolo et al., 1991).
    Vitamin B12: H2-receptor antagonists decrease acid secretion by the gastric
parietal cells. Gastric acid and pepsin produced by these cells are required for
the cleavage of vitamin B12 from dietary sources. H2-receptor antagonists pre-
vent dietary B12 from being freed from its protein binder during digestion.
Studies have demonstrated a significant reduction in food-bound vitamin B12
absorption secondary to decreased acid secretion in patients taking H2-receptor
antagonists. This probably lacks clinical importance during the short term;
however, long-term use could contribute to the occurrence of vitamin B12-
deficiency anemia. Such impairment of vitamin B12 absorption could be ampli-
fied for individuals taking antacids on a regular basis along with ranitidine
(;Aymard et al., 1988; Force & Nahata, 1992).
    Other nutrients: H2-receptor antagonists have also been reported to inter-
fere with the absorption of copper, folic acid, and vitamins B1 and D (Vagnini
& Fox, 2005; Gaby et al., 1999).
388    INTEGRATIVE GASTROENTEROLOGY



                               Pharmacist’s Corner

   I have been recommending deglycyrrhizinated licorice (DGL) to clients with
   GERD for more than a decade with little or no untoward effects, although I
   have had a few complaints regarding taste. Licorice contains a chemical
   known as glycyrrhizic acid, which is responsible for many of its reported side
   effects, including those associated with electrolyte disturbances. The DGL
   form of licorice has the glycyrrhizic acid component removed, and therefore
   is considered safer to use (Medline Plus; Petry & Hadley, 2001).
       DGL is used for heartburn (PDR Health) and has a number of beneficial
   effects in patients with GERD. It enhances mucus secretion and accelerates
   healing of digestive tissue (van Marle, Aarsen, Lind, & van Weeren-Kramer,
   1981; Das, Das, Gulati, & Singh, 1989).



                                   ANTACIDS

Antacids have largely been replaced by more effective and convenient drugs.
Nevertheless, they continue to be used by patients for a variety of indications
(Hoogerwerf WA, Pasricha PJ, 2006-3).
   Antacids are used to relieve heartburn, acid indigestion, and stomach upset.
They may be used to treat these symptoms in patients with peptic ulcer, gastritis,
esophagitis, hiatal hernia, or too much acid in the stomach (gastric hyperacid-
ity). They combine with stomach acid and neutralize it. Aluminum hydroxide,
magnesium hydroxide, and calcium carbonate are common ingredients in
antacids.Simethicone is added to a number of antacids. Simethicone is a
surfactant that breaks up gas bubbles. It also may reduce foaming, and may
hence aid esophageal reflux (Hoogerwerf WA, Pasricha PJ, 2006-3).
   Side effects from aluminum hydroxide and magnesium hydroxide are not
common, but may include:

   •   Diarrhea
   •   Constipation
   •   Loss of appetite
   •   Unusual tiredness
   •   Muscle weakness

   Side effects of calcium carbonate are rare and mild:

   • Belching
   • Abdominal distention
             Over-the-Counter Remedies for Digestive Health: Potion or Poison? 389


   • Flatulence
   • Rebound acid secretion


                               Drug Interactions

Because they alter gastric acidity and urine pH, antacids can inhibit the absorp-
tion of some drugs including thyroid hormones, allopurinol, and imidazole
antifungal agents. Aluminum and magnesium, antacids are notorious for their
ability to chelate other drugs present in the GI tract, forming insoluble com-
plexes that are not absorbed (Hoogerwerf WA, Pasricha PJ, 2006-3).


                              Nutrient Depletions

Because they alter gastric acidity and have an affinity to chelate, antacids can
inhibit the absorption of many nutrients. There is evidence that antacids
decrease the levels of vitamins A and D and folic acid, as well as binding with
calcium, chromium, iron, magnesium, phosphorus, and zinc (Vagnini & Fox,
2005; Gaby et al., 1999).


                                   LAXATIVES

Johns Hopkins Medicine Health Alerts defines constipation as a common but
typically benign condition characterized by infrequent bowel movements and
difficulty passing stool. The eleventh edition of Goodman & Gilman cites a few
interesting studies: by questionnaire, 25 of the U.S. population, more com-
monly women and the elderly, complain of constipation. A survey of bowel
habits in the United States showed that 18 of respondents used laxatives at
least once a month but nearly one-third of these users did not have constipation
(Pashricha PJ, 2006).
    In the bowel, water accounts for at least 70 of stool weight, and fluid
largely determines its volume and consistency. The digestive tract has to extract
fluid, minerals, and nutrients from food to supply the body for its needs, and
leave behind sufficient fluid for regular expulsion of waste matter via defeca-
tion. Normally, 8 or 9 liters of water enter the small intestine daily from exog-
enous and endogenous sources. Pressure differentials due to the flow of ions
cause absorption of water from the small intestines, leaving only about 1 to
1.5 liters of water to cross into the large intestine. The colon extracts most of the
remaining fluid, leaving about 100 ml daily for the feces (Pashricha PJ 2006).
390    INTEGRATIVE GASTROENTEROLOGY


So, fluid intake is important for avoiding constipation. Fiber intake is also
important. Unfortunately, many Americans do not respond well to their phy-
sicians’ advice for consuming more fruits and vegetables, but many do respond
to using fiber supplements A variety of fiber products are available on the
market, including psyllium, wheat, and methylcellulose. Fiber also protects
against colon diverticulosis, carcinoma of the large bowel and stomach, Type 2
diabetes, metabolic syndrome, and cardiovascular disease (Trepel, 2004).


                    Medication for Constipation

            NONSPECIFIC STIMULANT OR IRRITANT LAXATIVES

Stimulant laxatives have direct effects on enterocytes, neurons, and GI smooth
muscle. These agents trigger low-grade inflammation in the bowels, inducing
the accumulation of fluid and electrolytes and increasing intestinal motility.
Stimulant laxatives include bisacodyl, and the herbs senna and castor oil.
   Bisacodyl is a common ingredient in OTC laxative products. The gastroin-
testinal tract is in a constant state of contraction, absorption and secretion.
Bisacodyl works to inhibit net fluid absorption and secretion by augmenting
intestinal permeability (Farack & Nell, 1984). It also increases motility. Food
can decrease the absorption of bisacodyl. Laxatives with bisacodyl include
Carter’s Little Pills, Correctol, Dulcolax, Feen-a-Mint and PMS-Bisacodyl.
   Castor oil is an age-old remedy. It is derived from the bean of the castor
plant. Castor oil is a brisk cathartic, and as little as 4 ml if taken on an empty
stomach can produce a laxative effect within just 1 to 3 hours. The cathartic
dosage for an adult ranges from 15 to 60 ml. The products Neoloid and Purge
contain castor oil (Pashricha PJ, 2006).
   Senna is obtained from the dried leaflets of pods of Cassia acutifolia or
Cassia angustifolia. Senna is found in Senokot and Ex-Lax.
   Side effects of stimulant laxatives include:

   •   Upset stomach
   •   Stomach cramps
   •   Diarrhea
   •   Possible dehydration
   •   Stomach and intestinal irritation
   •   Faintness
   •   Irritation or burning in the rectum (from suppositories)
   •   Senna commonly causes yellow-brown urine; this is harmless
   •   Long-term use of irritant laxatives may lead to colonic pathology
             Over-the-Counter Remedies for Digestive Health: Potion or Poison? 391




                              Drug Interactions

Irritant laxatives can deplete potassium possibly increasing the toxicity of
digoxin. Bisacodyl can decrease the effectiveness of warfarin.


                             Nutrient Depletions

Irritant laxatives deplete calcium, potassium and sodium (Gaby et al., 1999;
Vagnini & Fox, 2005).


                          STOOL-WETTING AGENTS

Stool-wetting agents include docusate and mineral oil.
    Docusate is a surfactant. It lowers the surface tension of the stool, allowing
fatty soluble and water soluble components to mix and making the stool softer,
permitting easier defecation. Dioctyl sodium sulfosuccinate is found in Colace,
DSS, and Doxinate, and dioctyl calcium sulfosuccinate is in Surfak. Docusate
is only marginally helpful in many cases of constipation.
    Mineral oil is a mixture of hydrocarbons obtained from petrolatum, which
in turn is obtained from petroleum. These fatty hydrocarbons penetrate and
soften the stool, easing passage. Mineral oil side effects include leakage of oil
and greasy stools. Rarely, if aspirated, it can cause lipid pneumonitis.
    Depletions: Mineral oil can interfere with the absorption of minerals and
all fatty soluble nutrients. These include beta-carotene, vitamins A, D, E, and K,
calcium, phosphorus, and potassium (Vagnini & Fox, 2005; Gaby et al., 1999).
    Osmotic laxatives include magnesium citrate, magnesium sulfate, magne-
sium hydroxide, and sodium phosphate. They create an osmotic effect, bring-
ing water to the stool stimulating peristalsis and evacuation. These drugs are
fairly well tolerated.
                                  38
  Systemic Interactions Between Dental and
        Gastroenterological Diseases
                            PHILIP E. MEMOLI




                               key concepts

      ■   GI conditions producing soft tissue oral lesions:
          ■ Crohn’s Disease

          ■ Behcet’s Disease

          ■ Celiac Disease

      ■   The dental-systemic management of generalized immunodys-
          function:
          ■ Infections and Antigens from Marginal Periodontitis

          ■ Infections and Antigens from Apical Periodontitis

          ■ Antigenic Potential of Dental Biomaterials

          ■ Clinical Nutritional Considerations

      ■   GI disturbances producing hard tissue oral lesions:
          ■ Gastroesophageal Reflux

          ■   I Conditions Producing Halitosis
          ■ Bulimia Nervosa

      ■   The dental-systemic management of GI-induced hard tissue
          lesions:
          ■ Prevention, Treatment and Monitor Model

          ■ Management of the Aggressive, Pathological Complex Lesion


                                     ■




392
       GI Diseases Producing Soft Tissue Oral Lesions

                              CROHN’S DISEASE




I
     nflammatory bowel disease (IBD) consists primarily of Crohn’s disease
     and ulcerative colitis. Crohn’s disease is characterized as a panenteric
     inflammatory condition, while ulcerative colitis is, by definition, generally
limited to the colon. The etiology is unknown although the mechanism of acute
episodes is believed to be of an unknown antigenic origin that stimulates the
immune cells of the intestinal mucosa to produce the pro-inflammatory cytok-
ines TNF-α, IL-1b and IL-6, resulting in enteric inflammation (Griffiths, 1999).
   The oral lesions may precede GI lesions in up to 30 of cases where both
oral and gastroenterological pathology are evident (Lisciandrano et al., 1996).
A wide range of nonspecific oral lesions has been reported, ranging from a
“cobblestone” appearance of the mucosa, to aphthous-like ulcerative lesions, to
deep granulomatous ulcers. Perioral symptoms may occur, and include angu-
lar cheilosis and lip fissures. Other symptoms may include gingival bleeding,
gingival hyperplasia and metallic dysgeusia.
   Pyostomatitis vegetans, an oral finding, appears to be a marker for IBD and
precedes GI symptoms (Ficarra et al., 1993). The lesions appear as yellow-white
pustules with a characteristic “snail-track” appearance, speckled over an ery-
thematous palatal and vestibular mucosa. Oral management is rarely required
except in the event pustules rupture and ulcerate (Neville et al., 2002). The
lesions of pyostomatitis vegetans will, as stated, precede GI symptoms, and
generally follow the pattern of appearing with GI exacerbations and regressing
with GI remissions. One study found that healing of pyostomatitis vegetan
lesions occurred when oral zinc was supplemented, a mineral frequently lost
when chronic diarrhea is present. The conclusion was that oral lesions may, in
specified cases, be a result of malnutrition caused by nutrient excretion (Ficarra
et al., 1993).


                              BEHCET’S DISEASE

The syndrome, first described by Hulusi Behcet in 1937, compromised a com-
bination chronic ocular inflammation with oral, genital, and anal ulcerations.
The mechanism appears also to be immunodysregulatory and either primary
or secondary to specific triggers, which may include streptococci, viruses,
heavy metals, and pesticides.
394   INTEGRATIVE GASTROENTEROLOGY


   The oral lesions appear similar to aphthous ulcers; that is, a diffuse ery-
thematous mucosa with an irregular bordered ulceration, but differ in number
and location. Whereas aphthae may number from one to five, Behcet’s patients
will frequently have six or more lesions. Further, lesions differ in location;
Behcet’s syndrome lesions usually appear on the soft palate and oropharynx,
whereas aphthae are most commonly found on the ventral surface of the tongue,
followed by the mucobuccal fold and floor of the mouth. The soft palate and
keratinized gingiva are rarely involved, but may form as extensions from adja-
cent areas. Oral involvement is present at least once in 99 of patients, and is
the first manifestation in 25 to 75 of those cases (Krause et al., 1999).


                               CELIAC DISEASE

Primary immunodysfunction, it is hypothesized, may be associated with
specific histocompatibility antigen (HLA) types in the subgroups of patients
with aphthous and aphthous-type ulcerative lesions in the oral cavity. Crohn’s
disease and Behcet’s disease have been associated with HLA subgroups, which
demonstrate aphthous-like lesions. Celiac disease has been associated with
similar HLA subgroups and hence, has the potential to also demonstrate
aphthous-like lesions.


 Systemic Dental Management of Immunodysfunction

The oral cavity, structurally, functionally, and immunologically, represents the
“gateway” to the gastrointestinal system. As such, there are factors of immuno-
logical importance such as nutrition, flora, pathogens, and antigens of either
bacterial or dental biomaterial origin, which must be considered in the
interdisciplinary management of immunodysfunction. Dentate status can also
affect nutritional status, and may indirectly compromise immune function.
Further, the oral tissues possess the unique tendency to serve as a marker for
nutrient deficiency which, in turn, is conducive when monitoring nutrient
status, immunologic status, and malabsorption.
    Dentate status refers to the number of natural teeth and the ability of
patients to properly chew or masticate their food. Poor dentate status, by
contrast, refers to a condition in which there are insufficient teeth for mastica-
tion, resulting in the delivery of unchewed food into the stomach with the
potential for maldigestion and malabsorption. Studies have found the chewing
efficiency of people with full dentures to be 20 of those with a full dentition
(Kapur & Soman, 1964). Various studies have consistently demonstrated that
        Systemic Interactions Between Dental and Gastroenterological Diseases 395


poor dentate status results in food choices higher in carbohydrates, choles-
terol, and saturated fats, with fewer vegetables and nutrient-dense foods
(Joshipura. Willet, & Douglass, 1996). In cases of weight loss associated with
protein-calorie malnutrition among the elderly, poor dentate status is often a
causative factor (Sullivan et al., 1993). Poor oral health, and edentulousness
in particular, has been found to be associated with various gastrointestinal
disorders (Brodeur et al., 1993).
   Certain GI diseases, such as Crohn’s, Behcet’s, and celiac disease, appear, as
previously indicated, to exhibit an etiopathological basis in immunodysfunc-
tion and, if one is susceptible, to produce aphthous-like lesions in the oral
cavity. The immunodysfunction may be primary, which may involve one of
several specific histocompatibility antigens (HLA) types, such as HLA-B12,
B51 and CW7. Secondary immunodysfunction, at least for the oral aphthae,
has a highly variable etiology, which contains numerous population subsets
including nutritional deficiencies, infectious agents, allergies, stress, trauma,
genetic predisposition, and hematologic and hormonal influences. Infectious
agents may range from streptococci to viruses such as herpes simplex, cyto-
megalovirus, adenovirus, and varicella zoster virus (Neville et al., 2002).
   Antigens and infections, with the potential to elicit an immune dysfunction
response in susceptible individuals, are present in the oral cavity. These include
pathogens and their antigens from marginal and apical periodontal infections,
as well as antigens from implanted dental biomaterials. In those gastroentero-
logical cases mediated by immunodysfunction and exhibiting moderate–
severe and severe–fulminant exacerbation, the treating physician must
consider ruling out dental contribution as a predisposing secondary factor.


  Infections and Antigens from Marginal Periodontitis

Systemic implantation from periodontal disease is perhaps one of the most
researched subjects in current dental studies. Mattila and colleagues discov-
ered an epidemiological relationship between gum infections, myocardial
infarction, ischemia and atherosclerosis (Mattila et al., 1989). The DeStefano
study, the result of a 14-year follow-up of 9,760 individuals, further demon-
strated the relationship of oral focal infections, strokes, and coronary artery
disease (DeStefano et al., 1993). Relationships have thus far been demonstrated
in the following areas, with other areas still under study:

   • Myocardial infarction (Genco, 1998; Mattila et al., 1989)
   • Coronary artery disease (Xu et al., 1991, 1993; Mattila et al., 1993, 1995;
     Syrjänen, 1990)
396   INTEGRATIVE GASTROENTEROLOGY


   • Diabetes (Genco et al., 1998; Grossi et al., 1997, 1998; Loe, 1993)
   • Respiratory infections and complications (Scannapicco et al., 1996,
     1998; Donowitz & Manell, 1990; Fiddian-Green & Baker, 1991)
   • Obstetric complications such as preterm birth and low birth weights
     (Dasanayake, 1998; Loe & Silness, 1963; Offenbacher et al., 1996, 1998,
     1998)

   The periodontal flora comprise as many as 300 to 500 species, serotypes,
and ribotypes of bacteria, all of which are considered nonpathogenic (Loesche,
1994, 1997; Kilian, 1982; Paige, 1998). When a patient has decreased immune
function, virulence factors present in the oral flora may now initiate chronic
inflammatory periodontal disease (CIPD). CIPD represents an opportunistic
or endogenous infection, and efforts to control the systemic focal activity of
such infections must be based in proper immune system nutrition, function,
and regulation. Once the pathogens predominate, a complex biofilm can evade
the immune system and function to gain access to systemic circulation
(Socransy & Haffajee, 2002).
   There are three metastatic mechanisms by which microorganisms, bacterial
antigens, and local cytokines from the oral tissue gain access to circulation to
produce systemic and secondary site effects, such as in the gastrointestinal
system (Van Velzen et al., 1984). Metastatic infection is the result of bactere-
mia, which, although transient, may find susceptible tissue. Those bacteria
that have evolved or acquired mechanisms for cellular adherence and coloni-
zation have been demonstrated to cause such conditions as infective endo-
carditis, acute bacterial myocarditis, brain abscess, prosthetic joint infections,
and others (Rams & Slots, 1992). Metastatic injury, another mechanism, may
occur from microbial toxins such as exotoxins and endotoxins (Van Velzen
et al., 1984). Gram-negative bacteria are constantly shedding endotoxins or
lipopolysaccharides (LPS) which, in circulation, produce systemic effects.
Even when Gram-negative bacteria are killed by antimicrobials, large amounts
of LPS are released that continue to exert immunological reactions, such as
pyrexia and malaise. Finally, metastatic inflammation is another mechanism
whereby soluble antigen may react with a specific antibody, giving rise to
immune complex formation (Van Velzen et al., 1984; Van Dyke et al., 1986;
Rams & Slots, 1992).
   The risk of metastasis from the oral cavity must be considered in those
conditions possibly involving an immunodysfunction mechanism. Regarding
metastatic inflammation, it is believed this mechanism can cause immunologi-
cal injury and promote secondary inflammation in inflammatory bowel disease
(IBD; see Walker, 1975). Although circulating immune complexes have been
found in IBD, their etiology is still unknown (Jewell & Machennan, 1973).
        Systemic Interactions Between Dental and Gastroenterological Diseases 397


    Among the various systemic manifestations of IBD are its oral symptoms,
particularly ulcerations, and moderate to advanced involvement of periodon-
tal disease. The oral flora of those with IBD was studied and was found to be
remarkably different from those without IBS; see Van Dyke, 1986). Whereas
typical oral florae consist of aerobic, Gram-positive cocci and rods, the IBD
patients demonstrated motile, anaerobic, Gram-negative rods found to be
consistent with the Wolinella species. Further, the altered florae were similar in
all IBD patients with and without periodontal disease, although those subjects
with CIPD simply showed higher gingival sulcus bacterial levels. Regarding
host resistance, the patients afflicted with IBD and CIPD were found to possess
a serum-mediated neutrophil chemotaxis defect (Van Dyke, 1986). A similar
defect is found in localized juvenile periodontitis, although this form of CIPD
is not particular to IBD patients.
    The goal of an interdisciplinary and integrated periodontal treatment plan for
those with immunodysfunction follows the traditional prevention–monitor–
treatment paradigm. CIPD patients with immune dysfunction do not respond
well to conventional therapy such as root planing and periodontal surgery.
Nonetheless, proper oral hygiene and a proper maintenance period to monitor
signs of exacerbations are necessary to minimize disease activity. Further,
inflammatory gingivitis and periodontitis must be closely controlled to mini-
mize the risk of metastasis and the potential for secondary complications.
Also, nutritional therapy should be instituted to determine whether the patient
presents with nutrient deficiencies, has conditional nutrient requirements, or
has any offending food sensitivities or allergies.


    Infections and Antigens from Apical Periodontitis

Another potential source of bacterial infection and antigens may reside in apical
periodontitis (AP) or endodontal (root canal) lesions; that is, infections of tooth
origin at the tip or “apex” of the root. AP is a condition characterized as an acute
or chronic condition, existing in the untreated or pre-root-canal-treated tooth.
Some researchers are questioning the persistence of AP in apparently healed
and asymptomatic root-canal-treated teeth, and the potential for bacterial
pathogens and antigens to gain access to systemic circulation. AP was studied
in epidemiological studies in which those with chronic dental infections dem-
onstrated associations between acute myocardial infarction (Mattila et al.,
1989) and coronary atherosclerosis (Mattila et al., 1993). AP infections may
possess 200 species of predominately anaerobic, Gram-negative rods, of which
proximity to circulation can facilitate metastasis and systemic dissemination
(Tronstad, 1992). A study isolated Gram-positive anaerobic bacteria from
398   INTEGRATIVE GASTROENTEROLOGY


patients undergoing treatment of AP and concluded, based on biochemical
and antibiotic sensitivity testing, that recovered microorganisms from the
bloodstream originated from the teeth undergoing endodontic therapy
(Debilian, 1995). The primary cause of AP is untreated dental caries, which
infect the pulpal cavity of the tooth resulting in apical extension into the
surrounding bone to produce a lesion. Treatment options include tooth extrac-
tion or endodontic therapy, the former being the current treatment of choice.
    The goal of endodontic or root canal therapy is to sterilize the tooth and, by
the use of bacterial sampling, to verify sterility before completion of the root
canal. However, due to the inability to reach secondary canals and the dentinal
microtubules, the assumption these teeth are sterile and not capable of focal
infections is currently being questioned (Wu et al., 2006). Post-treatment AP,
a condition characterized as an asymptomatic tooth with radiographic healing
after root canal therapy, may, in fact, still present as a chronic infection capable
of activating immune cells. (Wu et al., 2006) Further, post-treatment AP may
be associated with 50 to 90 of root-canal-treated teeth (De Moor et al.,
2000; Kirevang et al., 2001; Dugas et al., 2003) and may serve as a physiological
attempt to prevent metastasis of bacteria and toxic metabolic byproducts into
systemic circulation. (Wu et al., 2006)
    The standard of care in the determination of healing of the AP lesion is the
absence of a radiographic translucency, as an indication that no osseous lesion
is present. However, several researchers have repeatedly documented the pres-
ence of post-treatment AP despite radiographic evidence to the contrary.
(Bender & Selzer, 1961; Bender, 1982; van der Stelt, 1985; Huumonen & Orstavik,
2002) Some have found that a lesion up to 8 mm may be present without any
trace of radiographic evidence (Ricucci & Bergenholtz, 2003).
    The treatment of AP has recently been redefined as the elimination of
post-treatment AP at both the radiographic and the histologic level. (Orstavik
& Pitt Ford, 1998; Friedman, 2002; Trope, 2003) The causes of post-treatment
AP are well documented and are, for the most part, not treatable with
current endodontics. Apical microsurgery, recently perfected by microscopy
(Rubenstein & Kim, 1999; Nari et al., 2005), removes the causative infected
apical portion of the root and surrounding bone, resulting in clinical removal
of the post-treatment AP lesion. The early reported successes of apical micro-
surgery are promising; 97 of lesions greater than 10 mm were completely
healed within one year after surgery. (Rubenstein & Kim, 1999) It is a concern,
particularly in patients presenting with immunodysfunction, to rule out apical
periodontitis and chronic inflammatory periodontal disease as sources of
longstanding, low-grade infections capable of activating immune cells, which
may then cause secondary immunologic injury to other normal cells and
infiltrate the gut. (Ridker et al., 1997, 2001)
        Systemic Interactions Between Dental and Gastroenterological Diseases 399




          Antigenic Potential of Dental Biomaterials

Another area of metastatic concern may involve dental restorative and implant
materials, or biomaterials proper. All materials are reactive, and all biological
interfaces are receptive; hence, there is no such phenomenon as a nonreactive
or universal biocompatible material. When biomaterials are placed in the oral
cavity, they undergo corrosion, degradation, separation and absorption
(Clifford, 1990; Wataha, 2003). Once absorbed, each individual’s immune
system will independently react or not react to determine if the test material is
compatible for the person. Sensitized biomaterial antigens, unlike environmental
antigens, when placed into the mouth present the possibility of chronic (24 hours
a day, 365 days a year) exposure. There are very few government or industry
standards for biocompatibility testing and, until recently, such testing was not per-
formed routinely (Wataha, 2003). Recently, toxicological research in Europe has
generated intense interest in dental biomaterial compatibility (Ahlqwist et al., 1998;
Richardson, 1999; Berlin et al., 1999; Lindh et al., 2001; Siblerud, 1990; Lindqvist
et al., 1996; Lichtenberg, 1993; 1997; Halbach, 1998) and protocols are currently
being developed to ensure a new level of safety can be achieved (Wahaha, 2003).
    Adverse reactions from sensitized dental materials include toxicity, inflam-
mation, allergenicity, and mutagenicity (Wataha, 2003). Allergenicity in the
oral cavity may occur by nickel, palladium or acrylic, which may result in
contact dermatitis (Wataha, 2003). Thirty-eight percent of women demon-
strate nickel allergies, whereas up to 3 of men may be affected (Hindsen et al.,
1999). Nickel is utilized in adult crowns, pediatric stainless steel crowns, par-
tial denture frameworks, and orthodontic brackets and wires (Wataha, 2003).
Metal ions such as mercury (Hg2+) and palladium (Pd2+), components of
restorative materials and crowns, both deplete glutathione levels in monocytes
at subtoxic concentrations. Hydroxyethylmethacrylate (HEMA), a component
of dental bonding systems, has also been demonstrated to reduce TNF-α secre-
tion by monocytes at subtoxic levels (Wataha, 2003). Bonded composites and
sealants contain bisphenol-A (BPA), an estrogenic substance, although the
physiological impact is unknown (Wataha, 2003). Titanium, a component of
implants, can negatively impact the immune system by causing hypersensitiv-
ity (Stejskal et al., 1999; Ahlgren et al., 2002; Ahnlinde et al., 2000). Further,
titanium has been found to corrode in the body, particularly when exposed to
fluoride. (Strietzel et al., 1998; Reclaro et al., 1998) IL-1 and complement were
also found to be upregulated by titanium implants. (Perala et al., 1991) Nickel,
copper, beryllium, some components of root canal sealers, and dental resins
have demonstrated mutagenic potential (Wataha, 2003). The carcinogenicity
400   INTEGRATIVE GASTROENTEROLOGY


of arsenic, hexavalent chromium (Cr6+) and nickel (Ni2+) has been established,
whereas antimony and cobalt may be human carcinogens (Hayes, 2005).
Clinical biomaterials can corrode to produce systemic and remote site concen-
trations sufficient to predict that an adverse reaction could occur, particularly
with immune responses, metal overload, and accumulation conditions (Black,
1984). Epidemiological studies on a large scale are necessary to assess the
systemic effects of biomaterials, whether oral, knee, or hip (Black, 1984).
Further, the release of metals in the mouth is of sufficient quantity to elicit an
immunological reaction in sensitive individuals (Lindh et al., 2002).
   The management of a biomaterial-sensitized individual must focus on
prevention and monitoring. The mechanism of toxicity, both individual and
quantal, must be considered in relation to what these biomaterials can exert on
the whole individual in terms of exposure, toxicokinetics, toxicodynamics,
and toxic interactions. Treatment, if necessary, must consider the immuno-
logical record of the patient. All known allergens and mutagens, regardless of
amount, concentration, or bioavailability, should not be implanted or placed
in the oral cavity. If a sensitive or allergic material must be placed for lack of a
biocompatible equivalent, steps should be taken, if possible, to desensitize the
individual. A dental and orthopedic material reactivity screening test is now
available to screen individuals for potential sensitization (Clifford Consulting
and Research). There are at least 89 known reactive groups in more than 6,000
dental materials, and these can be analyzed to determine IgG or IgM sensitiv-
ity (Clifford, 1990). A positive or adverse immunological reaction would
preclude the use of any material containing a proven reactant to that patient.
Such precautions would prevent the corrosion of dental reactive products and
the consequent release of chemical compoundsand haptens, and diminishsys-
temic and gastroenterological adverse events.


               Clinical Nutritional Considerations

The oral tissues, by virtue of a high mucosal cellular turnover rate, high sali-
vary production, and high alveolar bone growth rate, are an excellent indicator
of nutritional health due to a high nutrient demand, and may be the first
visible body tissue to reflect nutritional status (DePaola et al., 1999). The rela-
tionship between nutrition and disease is illustrated in Figure 38.1, which
exemplifies the multifactorial causative interactions that, if homeostatic mech-
anisms break down, will give rise to tissue disturbances (Memoli., 2007). It is
interesting to note the role of the gastrointestinal system in this algorithm as
being the centerpiece of the interactions between nutrients, metabolism,
immune system, and exposure.
        Systemic Interactions Between Dental and Gastroenterological Diseases 401


   Diseases of malabsorption, ranging from maldigestion, to mucosal
dysfunction, to luminal dysfunction may, as a result of nutrient deficiency,
produce a sign or symptom in the oral cavity. Malabsorption most commonly
presents with GI symptoms such as a watery diarrhea to a steatorrhea. Non-
gastrointestinal symptoms, however, are not uncommon and may produce
other malabsorption-related conditions such as (Kelly, 1999):

  •   Fatigue, malaise
  •   Muscle weakness, tetany, cramps
  •   Bone pain, pathologic fractures
  •   Poor wound healing
  •   Paresthesia, numbness

  Further, it is not uncommon for non-gastrointestinal diseases to have an
underlying malabsorption syndrome resulting in systemic manifestation
(Kelly, 1999):

  • Rheumatological (Raynaud’s) and arthralgias may suggest inflamma-
    tory bowel disease, scleroderma, or Whipple’s disease.
  • Vascular disease of an extensive nature may indicate mesenteric isch-
    emia.
  • Endocrinopathies such as hyperthyroidism, hyperparathyroidism,
    and diabetes mellitus can result in malabsorption.

   The treating gastroenterologist who suspects malabsorption in a particular
patient can survey the oral cavity, where systemic nutrient deficiency may first
appear. Likewise, the treating dentist can apprise his or her colleague of any
changes in the oral tissues that indicate malabsorption or a change in gastro-
enterological status. The following list highlights such oral manifestations
(adapted from DePaola et al., 1999).


      Oral Signs and Symptoms of Nutrient Deficiency

                                  MINERALS

  Iron: burning tongue, angular cheilosis, dysphagia; non-oral: pale blue
     sclera, pagophagia (ice eating)
  Calcium: tooth mobility, osteomalacia, osteoporosis, excessive bone
     resorption and bone fragility
  Magnesium: alveolar bone fragility, gingival hypertrophy
402   INTEGRATIVE GASTROENTEROLOGY


  Zinc: increased susceptibility to caries during tooth formation, increased
    susceptibility to infections and candidiasis, loss of taste and smell
    acuity
  Copper: decreased alveolar bone trabeculation, decreased tissue vascularity


                                 Vitamins

  Vitamin A: impaired healing, mucosal desquamation, xerostomia (dry
     mouth), leukoplakia, gingival inflammation
  B-Complex: angular cheilosis, leukoplakia, burning tongue
  Folic Acid: angular cheilosis, stomatitis, mucositis, aphthous-like ulcers,
     sore or burning mouth
  Cobalamin: angular cheilosis, sore burning mouth, xerostomia, epithe-
     lial dysplasia, paresthesia, delayed wound healing, halitosis, tooth
     mobility; non-oral: yellow sclera (note: compare to iron deficiency)
  Vitamin C: susceptibility to infection, blood vessel fragility, increased
     risk of gingivitis and periodontitis, delayed healing
  Vitamin D: incomplete tooth and alveolar bone calcification, osteomal-
     acia, osteoporosis
  Vitamin K: risk of hemorrhage, candidiasis


       GI Disturbances Producing Hard Tissue Lesions

                   GASTROESOPHAGEAL REFLUX (GERD)

GERD can be considered a major health concern for two overriding reasons.
First, it is a common condition that affects up to an estimated 20 to 25 of
the American population. Second, it may predispose one to esophageal cancer,
which, over the last 25 years, has outdistanced all other malignancies by a 350
increase in incidence (Glenn, 2001). Regarding the symptomatic population
reporting the condition, one-half of those report weekly dysfunction whereas
one-quarter suffer daily symptomology. Recent studies (Vial M et al., 2010)
have revealed male gender, obesity and GERD (in the form of heartburn) as
high risk factors for the development of esophageal adenocarcinoma.
   Reflux of stomach acids in the oral cavity generally results in erosion of
tooth structure. Loss of enamel after tooth formation can occur from dental
caries, trauma, attrition, abrasion, amelogenesis imperfecta and dentinogene-
sis imperfecta, and erosion (Neville et al., 2002). Erosive-type lesions are
characterized by a chemical or electrochemical breakdown of tooth structure.
         Systemic Interactions Between Dental and Gastroenterological Diseases 403


The treating dentist, with proper history and examination, can rule out all
other etiology and further determine whether the lesions are of an exogenous
or endogenous nature (Dawson, 2007). Exogenous factors include prolonged
oral exposure to many foods or drinks below the critical pH 5.5 necessary to
induce tooth demineralization (Grippo et al., 2004). Acidic substances causing
erosive-type lesions include chronic use of chewable vitamin C tablets, cola
“swishers,” fruit “mullers” and exposure to industrial acids (Abrahamsen, 1992).
Further, alcoholics undergoing disulfiram (Antabuse) therapy may suffer ero-
sion as a result. Endogenous factors occur primarily from GERD or bulimia
nervosa, and are primarily diagnosed by the treating gastroenterologist.
   The clinical lesion associated with GERD occurs at the lingual (inside) sur-
face of the posterior molars (Dawson, 2007). Severity is dependent upon the
degree of the condition and the oral health care measures taken by the patient.
Dentists detecting such lesions should refer the patient to a gastroenterologist,
and follow preventive dental management protocols.


                 GI Conditions Producing Halitosis

Halitosis, that is, oral malodor, may affect up to 30 of the population and is
most commonly associated with poor oral hygiene in combination with food
debris accumulation (Porter & Scully, 2006). Oral microorganisms produce
odiferous toxins such as volatile sulfides, diamines, and short-chain fatty acids,
which have been determined to cause the disorder. Ten percent of halitosis
cases have been determined to be systemic in origin, of which certain gastro-
enterological disorders may be etiologic (Hughes & McNab, 2008). The dif-
ferential diagnosis between oral and systemic halitosis is based upon exhalation;
a systemic condition is suspected when nasal exhalation produces the same
malodor as oral exhalation. Another common etiology is respiratory, in the
form of a sinus infection or nasal obstruction; however, this form is usually
transient and occurs in the morning upon wakening as morning halitosis. GI
disorders that may produce systemic halitosis include (Porter & Scully, 2006):

   •   Gastroesophageal reflux
   •   Pharyngoesophageal diverticulum
   •   Pyloric stenosis
   •   Duodenal obstruction
   •   Hepatic failure (fetor hepaticus)

   Helicobacter pylori infection has also been implicated in subjective changes
in oral odor. (Hoshi et al., 2002) A finding of chronic, nontransient halitosis
404   INTEGRATIVE GASTROENTEROLOGY


with no apparent oral etiology would therefore warrant a gastroenterological
assessment. GERD-associated halitosis, as with GERD proper, possesses oral
lesions and likewise requires interdisciplinary management.


                            Bulimia Nervosa

Eating disorders, such as anorexia nervosa and bulimia nervosa, represent
deviations in behavior that can result in esophageal irritation and dental ero-
sion lesions. Bulimia is common in young adult women concerned with body
shape and weight. The condition features binge eating followed by self-induced
vomiting, the frequency of which determines the severity of the disorder. No
symptoms may be present until frequency produces dental erosive lesions and
calluses of the knuckles (Huse & Lucas, 1999).
   The bulimia-associated dental lesion is caused by the acidic purge, which
consists of stomach acids in the pH 1 range, well below the critical pH 5.5
levels to induce enamel demineralization. The lesion proper is characterized
as erosive on site-specific tooth surfaces; the palatal (inside) surface of the
maxillary (upper) anterior teeth and the occlusal (biting) surfaces of the pos-
terior teeth. The symptoms attending the lesions range from an asymptomatic
dentition to tooth hypersensitivity, which may involve thermal or contact
sensitivity and, in some cases, involve sensitivity to normal mastication.
Hypersensitivity may further be indicative of chronicity and serve as a marker
for cessation of purging and, hence, for recovery of the disorder. Further,
parotid gland enlargement and sensitivity to palpation is another indication,
as the parotids become symptomatic between two and six days after vomiting
(DePaola et al., 1999).
   In the case of severe bulimia, an oral lesion characterized as a “complex”
lesion may be seen primarily as an erosive lesion from the bulimia, and sec-
ondarily as a result of toothbrush attrition. Once erosion penetrates the enamel
and exposes the underlying dentin, demineralization now proceeds sevenfold.
Many of these patients, being concerned with their appearance, are equally
obsessed with their dental cosmetic image and oral hygiene. In an effort to
cleanse their mouth of vomitus and its taste, copious amounts of abrasive-
containing toothpastes are employed in aggressive brushing patterns, which
together produce an attrition lesion on a previously compromised erosive
lesion. The result is severe pathological loss of tooth structure and gum tissue
which, in some cases, cannot be corrected with restorative dentistry. I have
seen cases where complex lesions have so debilitated the dentition as to require
prosthetic rehabilitation with full dentures in young women.
        Systemic Interactions Between Dental and Gastroenterological Diseases 405




    Dental Systemic Management of GI-Induced Hard
                     Tissue Lesion

When hard tissue lesions are present, the role of the dentist becomes one of
interdisciplinary intervention with the treating gastroenterologist. The process
of dental management for GERD and bulimia follows a prescribed prevention,
monitoring, and treatment paradigm. Preventive measures are employed to
minimize tooth loss during exposure. Monitoring occurs in the form of dental
prophylaxis and communication of the dentist with the treating gastroenter-
ologist. Treatment results when irreversible tooth loss occurs, which must be
restored before the general dentition becomes compromised.
    In regard to GERD, preventive procedures must be tailored to the type of
secretions that enter the oral cavity. While acid reflux from gastric acids is the
dominant form of heartburn, an alkaline reflux from pancreatic secretions in
the duodenum may also occur. Further, patients on antacids, proton-pump
inhibitors (e.g., Prilosec) and histamine 2 receptor antagonists (Tagamet) may,
in theory, produce a neutral reflux. Therefore, it is important for the treating
dentist to measure pH to determine whether the reflux is acidic, alkaline, or
neutral, and thereupon determine treatment. If the reflux is acidic in nature
and enters the oral cavity, I will recommend an alkaline rinse for one minute.
The patient will be instructed to mix one teaspoon of baking soda with four
ounces of water and rinse for a full minute. If the reflux continues, the rinse
should be repeated every hour. In severe cases, with nocturnal reflux associ-
ated with lower esophageal sphincter incompetence, a mouth guard can be
employed with a slight alkaline solution to maintain a buffered environment
around the teeth, particularly in those cases in which xerostomia (dry mouth)
is a secondary factor. For those patients exhibiting an alkaline reflux, I instruct
them to squeeze 10 to 20 drops from a fresh organic lemon in a four-ounce
glass of water and to rinse for a full minute. Again, if the reflux continues, rinse
continuously. Further, if there is a nocturnal component, employ a mouth
guard.
    The monitoring component should first determine whether oral lesions are
of a GERD-associated endogenous component or exogenous in nature. For
those diagnosed with a history of GERD, monitoring protocols are meant to
ensure that preventive measures are stabilizing the oral component. For undi-
agnosed cases, a history and inquiry into the patient’s dietary habits, and the
result of the oral examination of the lesions, should determine the nature of
the lesions. For cases of an exogenous nature, preventive behavioral changes
406 INTEGRATIVE GASTROENTEROLOGY


can easily retard the progress of such lesions. Progressive endogenous lesions
likewise indicate further treatment measures.
   The treatment of GERD-associated oral lesions would primarily involve
composite bonding to restore lost tooth structure. Monitoring of these restora-
tions on a regular basis is essential to guard against microleakage of the bond-
ing interface and decalcification around the margins. Either of those defects
would result in the destruction of more tooth structure and the need to
perform more extensive dental restorations.
   The dental preventive management of bulimia nervosa must also be tai-
lored to the frequency of the reflux and the compliancy of the patient. General
oral hygiene measures should include brushing only once per day, particularly
in the morning. After a reflux episode, the patient should be instructed to
avoid brushing altogether, especially with abrasive toothpastes. A mouth guard
should be constructed, preferably for the patient to insert before vomiting. If
the patient is not compliant with this procedure, the alkaline rinse previously
described should be performed to cleanse the teeth, periodontium, and mucosa
of acid residues. After rinsing, an alkaline paste of simply water and baking
soda should be placed inside the mouth guard and worn for a minimum of
thirty minutes.


                  PREVENTIVE MEASURES WITH BULIMIA

  • Brush only once per day with nonabrasive toothpaste (do not use
    baking soda or whitening formulations). Note: one may rinse but not
    brush with baking soda.
  • Insert mouth guard before vomiting (if possible).
  • After vomiting, do not brush; instead, rinse or apply alkaline paste
    (baking soda and water) inside the mouth guard and wear for a mini-
    mum of 30 minutes.

   It is of particular importance to guard against the creation of the aggres-
sive, pathological complex lesion; therefore, a monitoring system at a fre-
quency suitable to prevent tooth destruction must be instituted. During the
periodic dental examination, an acid exposure and lesion assessment must
accompany the dental prophylaxis. Acid exposure must still be analyzed in
terms of exogenous and endogenous exposure. Exogenous acids must be
ruled out, and if the patient presents with such lesions she must be coun-
seled to reduce such habits. Severe endogenous exposure must be commu-
nicated to the treating gastroenterologist in order for an interdisciplinary
approach to treat recurrences. Lesion analysis should include charting,
        Systemic Interactions Between Dental and Gastroenterological Diseases 407


measurement, and symptomology, in order to further determine frequency
and recurrences.
   The treatment of the complex lesion must consider potential dental impli-
cations, such as the loss of lower facial skeletal height and pathological tooth
destruction. A bonded hybrid composite restoration is primarily utilized to
treat the early erosive lesions. Again, these restorations must be monitored for
caries, microleakage, and decalcification. If the patient is noncompliant with
preventative and monitoring measures, there is an increased risk of developing
severe complex lesions. In general, as the teeth erode, there is a compensatory
eruption of tooth and bone in order to maintain facial height. However, if the
erosive lesions occur more rapidly than biological compensation, lower face
height may be lost, resulting in cosmetic disfigurement. Prosthetic efforts such
as restoring posterior teeth and maintaining proper anterior guidance can
prevent edge-to-edge attrition, which can further result in accelerated tooth
destruction. If such efforts cannot be performed, prosthetic rehabilitation
in the form of implant-retained dentures may be necessary to reestablish
function, comfort, and esthetics. (Neville et al., 2002).
   With the knowledge of the possibility of a bulimic or anorexic patient devel-
oping a pathological complex erosive lesion that could potentially destroy a
patient’s dentition, it behooves both gastroenterologist and dentist to coordi-
nate a preventive interdisciplinary treatment plan.
                                   39
          Upper Gastrointestinal Disorders:
          Dyspepsia, Heartburn, Peptic Ulcer
           Disease, and Helicobacter pylori
                              ANIL MINOCHA




                                key concepts

      ■   Most complementary therapies are based on clinical-symptom
          complexes. There is a paucity of studies employing precise,
          modern day diagnostic criteria.
      ■   Therapies based on Chinese medicine (e.g., multi-herbal
          formulation Iberogast also known as STW 5 and acupuncture)
          are effective in functional dyspepsia.
      ■   The addition of probiotics to standard antibiotic treatment
          increases Helicobacter pylori eradication while reducing the
          therapy-associated side effects. On the other hand, vitamin C
          and E supplements may reduce the efficacy of H. pylori eradica-
          tion therapy.
      ■   Use of psychological interventions can improve outcome in
          functional GI disorders.
      ■   Lifestyle modifications like cessation of smoking and drinking
          may help ameliorate dyspeptic symptoms. The role of diet
          in management of upper gastrointestinal disorders is patient-
          specific.
                                       ■




408
                                Introduction



U
          pper gastrointestinal illness, whether induced by ulcers, gastritis,
          dysmotility, or H. pylori, is a common problem that affects hundreds
          of millions of people worldwide. However, patients are more inter-
ested in relief and less interested in what may be causing the problem. Whether
the diagnosis is ulcer or gastritis based on modern medicine, or a disharmony
of the body systems of Vata, Pita, or Kapha as in Ayurveda, the patient’s goal
remains the same. Many patients just use over-the-counter medications, but
complementary and alternative treatments are gaining in popularity. A smaller
number of people actually see a doctor.


                          Historical Perspective

Until the late eighteenth and early nineteenth centuries, most symptoms of possi-
ble gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) were
lumped into the category of dyspepsia or indigestion. Treatments varied depend-
ing upon the culture or civilization. Some of these treatments have stood the test of
time and are still preferred over modern medicine by millions of people.
   The ancient descriptions of the use of powdered coral, chalk, and seashells
for relief of dyspepsia provide clues to the occurrence of this problem long
before the modern descriptions of GERD and PUD. Hunter in 1784 advocated
the use of milk as a natural antacid.
   Illogical approaches, such as the use of antimony, arsenic, and mercury, as
well as application of leeches to the abdomen, were in vogue in the eighteenth
century. In 1876, Leube advocated the use of bowel rest on top of implausible
interventions like alcohol and glucose rectal enemas.
   Other treatments used in the past include synthetic resins, cabbage, pectin,
pituitary extract, insulin, and histamine.
   Surgeons like Billroth made the first advance in modern treatment by
performing surgery for PUD in the 1880s. H. pylori was rediscovered by
Warren and Marshall in the 1980s, which earned them the Nobel prize.


                             CAM Treatments

Most diagnoses made by practitioners of complementary and alternative med-
icine (CAM) are based on symptoms and follow the holistic treatment pattern.
410   INTEGRATIVE GASTROENTEROLOGY


The diagnosis is mostly clinical, and centers on dyspepsia or some equivalent.
Similar patients may receive different treatment plans, however, based on vari-
ety of other factors (e.g., based on body constitution in Ayurveda).
    In this chapter, we will review the human data wherever available; in addi-
tion, we will discuss the laboratory investigations supporting or refuting the
biological plausibility of treatment effect. Since there is overlap in herbal ther-
apies, we will review them as one category regardless of the system of medicine
from which they are derived. The depth and breadth of discussion of any par-
ticular therapy in this chapter are related more to the extent of peer-reviewed
literature on the subject than to the popularity of the treatment.


                            Herbal Therapies

An herbal medicinal product is defined as any medicinal product containing
as active ingredients only plants, parts of plants or plant materials, or combi-
nations thereof, whether in the crude or processed state. Herbal therapies may
be administered individually or as combinations of herbs.


                   PEPPERMINT OIL (MENTHA PIPERITA L)

Peppermint oil has been used for dyspepsia and spasms/colic in various cul-
tures for centuries. It may be used singly or in combination with other herbs.
The clinical efficacy of the combinations (except for caraway) will be discussed
in the subsection about herbal combinations.


                            The Science Behind It

In addition to relaxing pylorus, peppermint oil enhances the early phase of
gastric emptying (Inamori et al., 2007), thus affecting gastroduodenal motility.
Others have shown that the effect of peppermint oil and caraway on gastric
emptying is similar to that of the drug, cisapride; however, there were no dif-
ferences as compared to placebo (Goerg & Spilker, 2003). Caraway (Carum
carvi) is frequently added to peppermint, and is also known to cause inhibi-
tion of smooth muscle relaxation.
   Peppermint oil and caraway act locally in the stomach and duodenum to
produce smooth-muscle relaxation (Micklefield, Jung, Greving, & May, 2003).
The principal effect of intraluminal peppermint oil on the gastrointestinal tract
(Bell, 2004) is a dose-related antispasmodic action on the smooth musculature
                                            Upper Gastrointestinal Disorders 411


due to the interference of menthol with the movement of calcium across the
cell membrane (Grigoleit, 2005). A randomized, double-blind, double-dummy,
controlled trial showed that peppermint oil reduces gastric spasm during
upper endoscopy (Hiki Kurosaka, & Tatsutomi, 2003). An instillation of 20 ml
of 1.6% peppermint oil solution in the duodenum during ERCP results in duo-
denal relaxation (Yamamoto et al., 2006). Peppermint has choleretic and anti-
foaming effects and attenuates postinflammatory visceral hyperalgesia in rats
(Adam et al., 2006).
   Peppermint inhibits the in vitro proliferation of various bacteria, including
H. pylori, in a dose-dependent manner (Imai et al., 2001). Interestingly, these
antibacterial activities were almost the same against antibiotic-resistant and
antibiotic-sensitive strains of H. pylori.
   Peppermint aromatherapy has major effects on decreasing pain and
depression levels, suggesting another possible mechanism for peppermint in
dyspepsia i.e., analgesia (Kim, Nam & Paik 2005)
   Peppermint oil inhibits daytime sleepiness, and this invigorating effect may
favorably affect psychological disturbances associated with various upper
gastrointestinal disorders (Norrish & Dwyer, 2005).


                                Clinical Data

Peppermint oil improves abdominal symptoms in patients with abdominal
pain and irritable bowel syndrome. May and colleagues conducted studies of
the efficacy and tolerability of a combination of peppermint oil and caraway oil
versus placebo in patients with functional dyspepsia. They found the active
treatment was superior with respect to pain intensity, sensation of pressure
and heaviness plus fullness, as well as the investigators’ rating of global
improvement (May, Köhler, & Schneider, 2000; May, Kuntz, Kieser, & Köhler,
1996). A multicenter, reference-controlled, double-blind equivalence study
using a peppermint/caraway oil preparation or cisapride found them to be
equivalent for treatment of functional dyspepsia (Madisch et al., 1999). The
efficacy of peppermint oil and caraway oil in patients with functional dyspep-
sia is unaffected by H. pylori (May, Funk, & Schneider, 2003). The beneficial
effects of a peppermint/caraway oil combination in functional dyspepsia are
similar whether the drug is taken in an enteric-coated capsule or as an enteric
soluble formula (Freise & Kohler, 1999).
    Patients with GERD have long been warned to avoid peppermint oil.
However, this recommendation appears to be based predominantly on theo-
retical grounds and lacks good scientific data to support it. This recommenda-
tion also flies in the face of centuries-old use of peppermint after meals, with
412 INTEGRATIVE GASTROENTEROLOGY


perceived beneficial effects against indigestion. The administration of pepper-
mint oil eliminates chest pain, as well as simultaneous esophageal contrac-
tions, in patients with diffuse esophageal spasm (Pimentel et al., 2001).
   Aromatherapy effectively reduces the perceived severity of postoperative
nausea. However, aromatherapy with peppermint is no better than saline pla-
cebo in relieving postoperative nausea, suggesting that beneficial effects may
be related more to controlled breathing patterns than to the actual aroma
inhaled (Anderson & Gross, 2004). Side effects of peppermint oil include
allergic contact dermatitis.


                                    LICORICE

Licorice is widely used in the medicinal and the confectionery sectors.
However, the ingestion of licorice, and/or its active metabolites, can lead to an
acquired form of apparent mineralocorticoid excess syndrome manifested by
sodium retention, potassium loss and suppression of the renin-angiotensin-
aldosterone system, leading to increased blood pressure and edema. Compared
to licorice, deglycyrrhizinated licorice (DGL) does not significantly affect
blood pressure and salt retention, and some practitioners have advocated
its use.


                            The Science Behind It

Numerous studies have documented the gastroprotective effects of licorice.
Cimetidine and DGL combined provide greater protection than either drug
alone against aspirin-induced gastric mucosal damage in rats (Bennet et al.,
1980). Most studies that show beneficial effects have used licorice as part of an
herbal combination product.


                                 Clinical Trials

Clinical trials using DGL in peptic ulcer disease have yielded conflicting results.
Turpie et al. (1969) conducted a randomized, placebo-controlled clinical trial of
DGL in gastric ulcers. They found a reduction in ulcer size in patients on DGL
versus the placebo (78% vs. 34%). In addition, the ulcer completely resolved in
44% of patients in the treatment group, compared to 6% in the placebo group.
Other researchers have reported similar results (Doll & Hill, 1962; Doll, Hill, &
Hutton, 1965; Engqvist, von Feilitzen, Pyk, & Reichard, 1973). Some studies,
                                           Upper Gastrointestinal Disorders 413


however, have failed to confirm these gastroprotective findings (Bardhan,
Cumberland, Dixon, & Holdsworth, 1978; Feldman & Gilat, 1971). DGL does
not appear to have prophylactic effects against recurrence of healed gastric
ulcer (Hollanders et al., 1978).


                          TURMERIC (CURCUMA)

                           The Science Behind It

Turmeric increases bile formation and secretion and promotes gallbladder
contraction in addition to having antispasmodic activity. It protects against
gastric ulcers by blocking H2 type histamine receptors (Kim, 2005).It also
increases the gastric wall mucus and restores the nonprotein sulfhydryl content
in glandular stomachs (Rafatullah, Tariq, & Al-Yahya, 1990).
   Phenolic fractions of Curcuma amada are potent inhibitors of proton potas-
sium ATPase activity, as well as H. pylori growth (Siddaraju & Dharmesh,
2007).


                               Clinical Trials

One study found that turmeric (Curcuma longa Linn 600 mg x 5/d x 4 weeks)
resulted in healing of 48% of cases of peptic ulcer. Seventy-six percent of
patients did not have ulcers at the end of 12 weeks (Prucksunand et al., 2001).
A controlled clinical trial found liquid antacid and Curcuma longa Linn to be
equivalent in the treatment of gastric ulcers (Kositchaiwat, Kositchaiwat, &
Havanondha, 1993). Another randomized, placebo-controlled study compar-
ing curcuma with an herbal formulation is described in the section on herbal
combinations (Thamlikitkul et al., 1989).


                               CHILI POWDER

                           The Science Behind It

A chili-rich diet decreases capsaicin-stimulated gastrin secretion from human
antral glands (Ericson, Nur, Petersson, & Kechagias, 2008). Intragastric perfu-
sion of aqueous spice extracts of red pepper increases acid secretion in anes-
thetized albino rats (Vasudevan, Vembar, Veeraraghavan, & Haranath, 2000).
Both black and red pepper may induce epigastric pain by removing the
414 INTEGRATIVE GASTROENTEROLOGY


stomach’s hydrophobic lining and activating intramucosal pain receptors
(Lichtenberger et al., 1998).


                              Human Studies

Capsaicin administered as 20g of chili orally protects against aspirin-induced
gastroduodenal injury in healthy human subjects (Yeoh et al., 1995). Endoscopy
showed that the median gastric injury score after chili was 1.5 compared to 4 in
the control group (P < 0.05). On the other hand, capsaicin enhances noxious
postprandial heartburn, presumably by direct effects on sensory neurons
(Rodriguez-Stanley et al., 2000).



  While chili pepper may cause symptoms in susceptible subjects in the short
  term, over the long term it relieves functional dyspepsia by capsaicin-
  induced desensitization of the selective nociceptive C fibers.



   Epidemiologic surveys in Singapore have shown that gastric ulcers are three
times more common in people of Chinese descent than in those of Malaysian
and Indian descent, who tend to consume more chili peppers (Satyanarayana,
2006). Among Chinese patients, the median amount of chili use per month
was much lower in those with ulcers than in the controls (Kang et al., 1995).
   Bortolotti et al. (2000) examined the effect of red pepper (2.5g/d) on the
treatment of functional dyspepsia (n=30) in a double-blind, placebo-controlled
trial. The overall symptom score, as well as the epigastric pain, fullness, and
nausea scores, improved significantly in the red pepper group compared to the
placebo.


                                  AMALAKI

Amalaki is an Ayurvedic herbal remedy derived from pericarp of the dried
fruit of Emblica officinalis.
   Chawla et al. (1982) compared the treatment of dyspepsia using Amalaki or
gel antacids for 4 weeks. Patients (n=38) included those with peptic ulcer
(n=10) and non-ulcer dyspepsia (n=28). Compared to the baseline, symptoms
improved in both treatment groups. Side effects during Amalaki treatment
included diarrhea and vomiting in some patients.
                                              Upper Gastrointestinal Disorders 415




                  BANANA POWDER (PLANTAIN BANANA)

                             The Science Behind It

The natural flavonoid present in unripe plantain banana pulp protects the gastric
mucosa from aspirin-induced erosions (Lewis, Fields, & Shaw, 1999). Plantain
banana powder strengthens mucosal resistance and promotes the healing of
ulcers via its action on gastric mucosal shedding (Mukhopadhyaya et al., 1987).


                                Clinical Studies

Treatment with banana powder (8 capsules per day for 8 weeks) results in
marked improvement (partial or complete relief) of patients with non-ulcer
dyspepsia compared to controls (Arora & Sharma, 1990).


                                     MASTIC

Mastic is a concrete resinous exudate obtained from the stem of the tree
Pistacia lentiscus.


                             The Science Behind It

It reduces the intensity of experimentally induced gastric mucosal damage asso-
ciated with decrease of free acidity (Al-Said, Ageel, Parmar, & Tariq, 1986). Mastic
gum kills H. pylori (Huwez, Thirlwell, & Cockayne, 1998), although the effect
is modest (Al-Said et al., 1986). Monotherapy with mastic does not eradicate
H. pylori infection in mice (Loughlin, Ala’Aldeen, & Jenks, 2003).


                                Clinical Studies

A double-blind, placebo-controlled trial of mastic (1g/d for two weeks) for the
treatment of duodenal ulcer demonstrated endoscopically proven healing in
70% patients on mastic compared to 22% patients on placebo (Al-Habbal,
Al-Habbal, & Huwez, 1984).
416   INTEGRATIVE GASTROENTEROLOGY




                                   BRAHMI

Fresh juice from the whole plant of Bocapa monniera Wettst, commonly known
as Brahmi, is used in Ayurveda for dyspepsia. Brahmi promotes mucosal
defenses via enhanced mucin secretion and mucosal glycoprotein, and decreased
cell shedding in experimental models of ulcer (Rao, Sairam, & Goel, 2000).


                  ASPARAGUS RACEMOSUS (SHATAVARI)

Asparagus racemosus (Shatavari) is used in Ayurveda for dyspepsia and as a
galactogogue. It reduces gastric emptying time in normal healthy volunteers.
Asparagus racemosus has an inhibitory effect on the release of gastric hydro-
chloric acid, and its protection against indomethacin-induced gastric mucosal
damage in animals is comparable to that of ranitidine (Bhatnagar, Sisodia, &
Bhatnagar, 2005).


            ASHWAGANDHA (WITHANIA SOMNIFERA DUNAL)

W. somnifera shows potent inhibitory activity towards the complement system,
mitogen induced lymphocyte proliferation, and delayed-type hypersensitivity
reaction. This Ayurvedic remedy, also known as ashwagandha, is effective in
the treatment of stress-induced ulceration in animals and its efficacy is compa-
rable to that of ranitidine (Bhatnagar et al., 2005).


               GREATER CELANDINE (CHELIDONIUM MAJUS)

Greater celandine or tetterwort is derived from the celandine plant, which is a
member of the poppy family. Its roots, herb, and juice are used for medicinal
purposes. It is reputed to have calming effects and is widely used for intestinal
spasms.


                            The Science Behind It

Celandine contains about 20 biologically active alkaloids, which have anti-
spasmolytic action on smooth muscles and also stimulate bile flow.
                                               Upper Gastrointestinal Disorders 417




                                Clinical Studies

Ritter and colleagues studied the effect of a standardized celandine extract in a
placebo-controlled, double-blind trial of 60 patients with functional dyspepsia
over a 6-week period (Ritter et al., 1993). Patients in the treatment group reported
fewer gastrointestinal symptoms compared to those on placebo (27% vs. 60%).


                          ARTICHOKE LEAF EXTRACT

Holtmann et al. (2003) studied the efficacy of artichoke leaf extract (2 x 320 mg
plant extract 3 times a day for 6 weeks) in the treatment of patients with functional
dyspepsia in a double-blind, randomized placebo-controlled trial. The artichoke
leaf extract demonstrated superior efficacy in alleviating symptoms and improved
the disease-specific quality of life in patients with functional dyspepsia.


                                  GINGER ROOT

Ginger root has been studied for postoperative nausea and morning sickness,
as well as chemotherapy-induced nausea. The results are promising (Ernst &
Pittler, 2000).


                             The Science Behind It

Ginger accelerates gastric emptying and stimulates antral contractions in
healthy volunteers (Wu et al., 2008). These effects could potentially be benefi-
cial in symptomatic patient groups.


                                   TERMINALIA

Terminalia arjuna is a deciduous tree, the bark of which is used in herbal med-
icine. Terminalia is widely used in Ayurveda to regulate blood pressure and
promote cardiovascular health. It suppresses the release of nitric oxide and
superoxide from macrophages, and also inhibits aggregation of platelets.
Terminalia has antioxidant actions and may reduce oxidative stress and inhibit
anaerobic metabolism. It ameliorates severe cellular damage and pathological
418   INTEGRATIVE GASTROENTEROLOGY


changes caused by H. pylori lipopolysaccharide (Devi, Kist, Vani, & Devi,
2008). Terminalia arjuna has protective effects on diclofenac sodium-induced
gastric ulcer in experimental rats. Terminalia chebula is commonly advocated
in Ayurveda to improve gastrointestinal motility. It has been shown to
reduce gastric emptying time in rats (Tamhane, Thorat, Rege, & Dahanukar,
1997).


                               TANGWEIKANG

Tangweikang is a Chinese herbal preparation used in diabetes. It improves
glucose and lipid metabolism and regulates microcirculation. It hastens gastric
emptying in diabetic gastroparesis (Jiang, Zhang, & Bai, 2007).


                         Herbal Combinations

Both functional and organic disorders have multiple underlying pathogenic
mechanisms. The use of herbal combinations has the potential to affect a dis-
ease process at multiple levels in its pathogenesis.


                                     STW 5

STW 5 is a fixed combination of nine herbs: bitter candytuft plant (aka
clown’s mustard), German chamomile flower, peppermint leaves, caraway
fruit, licorice, lemon balm leaves, celandine, angelica root and rhizome, and
milk thistle.


                            The Science Behind It

STW 5 modulates the amplitude and frequency of slow waves in circular
smooth muscle of the mouse small intestine (Storr et al., 2004). It also lowers
gastric acidity and inhibits secondary hyperacidity (Khayyal et al., 2006). In
addition, STW 5 lowers serum gastrin levels in rats, an effect that runs parallel
to its ability to lower gastric acid production (Khayyal et al., 2006).
STW 5-induced stimulation of gastric relaxation and antral motility may con-
tribute to its effects on functional dyspepsia (Pilichiewicz et al., 2007).
                                             Upper Gastrointestinal Disorders 419




                          Clinical Studies of STW 5

Multiple studies have documented the efficacy of STW 5 and STW 5-II in the
treatment of functional dyspepsia (Madisch et al., 2004). A multicenter, dou-
ble-blind, placebo-controlled study on the effects of STW 5 in 315 patients with
functional dyspepsia for 8 weeks reported a significant improvement in the
Gastrointestinal Symptom Score of patients taking STW 5 compared to pla-
cebo, irrespective of H. pylori status (von Arnim, Peitz, Vinson, Gundermann,
& Malfertheiner, 2007).
   A double-blind, double-dummy study demonstrated that the effects of
STW 5 and STW 5-II administered for 4 weeks are equivalent to those of cisap-
ride for the treatment of patients with functional dyspepsia of dysmotility type
(Rösch et al., 2002).
   A retrolective multicenter epidemiological cohort study with parallel groups
found STW 5 to be superior to metoclopramide in patients with functional
dyspepsia (Raedsch et al., 2007). Significantly more patients were symptom-
free after STW 5 treatment (71.6% vs. 62.8% p = 0.012). The median duration
of inability to work (1 vs. 3 days) was significantly different in favor of STW 5,
and more physicians assessed STW 5 as effective (71.6% vs. 63.1% p<0.01) and
very well tolerated (90% vs. 70.6% p<0.001).
   Meta-analysis of double-blind, randomized, clinical trials on the efficacy of
STW 5 in patients with functional dyspepsia has demonstrated a clear, highly
significant overall therapeutic effect (Gundermann, Godehardt, & Ulbrich,
2003; Melzer et al., 2004). Tolerability of the drug was excellent (Gundermann
et al., 2003). A recent review came to simil