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					           Società Medico Chirurgica di Ferrara

                  Ferrara, 9 Aprile 2005

        Alimentazione e Nutrizione nelle
  Malattie Infiammatorie Croniche dell’Intestino



          G. ZOLI
Centro Diagnosi e Cura per le
   Malattie dell’Intestino
      Medicina Interna
 Ospedale SS. Annunziata,
         Cento (Fe)
       NUTRITIONAL TREATMENT of IBD
       Frequency of Nutritional Deficiencies
          Reported in Patients with IBD

Weight loss              65-75 %
Growth failure           15-30 %
Hypoalbuminemia          25-80 %
Anemia                   60-80 %
Iron deficiency          39-81 %
Vitamin B12 deficiency   48 %
Folic acid deficiency    35-54 %
Calcium deficiency       13 %
Magnesium deficiency     14-33 %
Potassium deficiency     6-20 %
Vitamin A deficiency     11 %
Vitamin C deficiency     +
Vitamin D deficiency     75 %
Vitamin K deficiency     +
Zinc deficiency          40-50 %
Copper deficiency        +
Vitamin E deficiency     +
Metabolic bone disease   +
                            Driscoll et al. 1978,mod.
NUTRITIONAL TREATMENT of IBD
 Pathogenesis of malnutrition in IBD
  Increased requirements
      Inflammmation
      Fever
      Steroids
      Growth
  Increased nutrient losses
      Exudation from ulcerated mucosa
      Steroids
      Interrupted entero-hepatic circulation of bile salts
  Reduced nutrient absorption
    Loss of surface area
     By pass, resection, disease
     Bacterial overgrowth
     Rapid transit
  Reduced food intake
    Post prandial pain
    Zinc deficiency
    Anorexia
    NUTRITIONAL TREATMENT of IBD
  Causes of disorders of nutritional status in
              Crohn’s Disease

                 Maldigestion Disordered Losses   Reduced
                              absorption          intake
Carboydrate          +++                           +
Fat                  +++      +         +++      ++
Protein defic.       ++        +++       +++      ++
Calcium defic.                 +++       +++      +++
Magnesium defic.               +++       ++       ++
Zinc defic.                    +++       ++       ++
Folate defic.                  +++                 ++
Vitamin B12 defic.             +++                 ++
Vitamin A defic.               +++                 ++
Vitamin D defic.               +++                 ++
Vitamin K defic.               +++                 ++
     NUTRITIONAL TREATMENT of IBD

   Causes of disorders of nutritional status in
               Ulcerative Colitis

                     Maldigestion Disordered   Losses Reduced
                                  absorption          Intake
Carbohydrate             +++                           +
Fat                       +        +           +++     ++
Protein defic.           ++        ++         +++     ++
Calcium defic.                     +++        +++     +++
Magnesium defic.                   +++        ++      ++
Zinc defic.                        +++        ++      ++
Folate defic.                      +                   ++
Vitamin B12 defic.                                     +
Iron defic.                         +          +++
          NUTRITIONAL TREATMENT of IBD


   50
                 Resting energy expenditure/Kg fat free mass
Kcal/Kg
                 in Crohn’s disease and controls
FFM
   40




   30




   20



            CD                  CD                    Controls
            G     P<0,05                    NS
   10


                              P<0,01

                                                 G. Zoli, DDS 1996
   NUTRITIONAL TREATMENT of IBD

2500   Kcal/24h
                    Energy Expenditure in Crohn’s disease


2000




                                             - 1670
1500
                  1482 -




1000               Predicted             Measured
                               P<0.003

                                              G. Zoli, DDS 1996
NUTRITIONAL TREATMENT of IBD

        •   Supportive


        • Primary


        • Maintenance


        • Growth
      NUTRITIONAL TREATMENT of IBD

Low Fiber Diet               - Strictures
                             - Symptoms?
                             - Inflammations?
                             - Complications?
High Fiber Unrefined         - Shorter hospitalization (Crohn’s Disease?)
Carbohydrate diet

Exclusion Diet               - Relapse reduction (Crohn’s Disease?)


Total Parenteral Nutrition   - Bowel rest
                             - Induce remission (Crohn’s Disease?)
                             - Improve nutritional status
                             - Before and after surgery
Liquid Diet                  - As for total parenteral nutrition
                             - Less risk of complications
                             - Cheaper
  NUTRITIONAL TREATMENT of IBD

                      Diet

• There are no fixed dietary rules in chronic
  inflammatory bowel diseases

• There is no diet which works for all patients
  with chronic inflammatory bowel disaeases

• Every patient must look carefully at himself
  and his own dietary habits
    NUTRITIONAL TREATMENT of IBD

The following foods are often identified as
         the cause of symptoms


•   Wheat                 69%
                          48%
•   Milk/milk Products
                          31%
•   Yeast                 24%
•   Maize
•   Bananas,              14%
    Tomatoes,wine
    and Eggs
  NUTRITIONAL TREATMENT of IBD
Dietary recommendations during symptom-
              free periods
• Diet matched to needs ( 38-45 kcal/kilogram weight;
  high protein, vitamin-rich and mineral-rich )
• Eat everything which is well-tolerated ( if necessary,
  testing intolerance by means of diet records )
• Give preference to high fibre foods ( except in the
  presence of stenosis )
• No/little sugar
• Few white-flour products ( e-g- white bread )
• Avoid solid fats ( margarine and block fats )
• Avoid lactose in the presence of lactose intolerance
• Avoid lactalbumin in ulcerative colitis
• Eat fish regularly
  NUTRITIONAL TREATMENT of IBD
      Structure of diet after flare up

1. Tea (with sugar), white bread, gruel
2. In addition: rolls, marmelade, cooked
   vegetables ( possibly strained) / fruit
   (possibly strained) / potatoes
   (possibly matched) / rice or noodles
3. In addition: lean meat, milk, milk
   products, fish, poultry, sausages or
   cheese, perhaps MCT margarine
4. In addition: butter/margarine and
   switch to “light normal diet”
     NUTRITIONAL TREATMENT of IBD
                    (Kidney Stones)

Foods rich in oxalic acid   Foods high in calcium
  - avoid :                 - give preference to :

•   Rhubarb                 • Milk
•   Spinach
                            • Yogurt
•   Beet
                            • Milk products (quark
•   Dandelion
                              contains little calcium)
•   Walnuts/hazelnuts
                            • Cheese (especially hard
•   Cocoa (chocolate)
                              cheese, e.g. Emmentaler)
•   beetroot
      Food Allergy in Patients with Inflammatory
                   Bowel Diseases


35%                       P=0.04
30%


25%


20%


15%


10%


5%


0%

          IBD PATIENTS
           IBD Patients
                              CONTROLS
                              Controls Group




                                               G. Zoli et al., Gut 2002
NUTRITIONAL TREATMENT of IBD
        NUTRITIONAL TREATMENT of IBD
                   Diet as a Risk Factor


Crohn’s Disease

- Urban diet containing microparticles (i.e. soil and dust)
- Food additives

Ulcerative Colitis

-High intakes of mono and polyunsatured fat and vit. B6
-Food Additives

-
                               The duration of breast feeding in Crohn's disease patients and control subjects. The mean length of the breast-feeding
                                   period was significantly (P<0.01) shorter among CD patients 4.59 months) compared to controls (5.76 months)

                     140




                     120
                                                                                        -                                                                   HC




                     100
Number of subjects




                      80
                                                                                                                                                   CD
                                                                                                                                                                 Serie1
                                                                                                                                                                 Serie2



                      60




                      40




                      20




                       0
                           1                 2                 3                 4                  5               6                 7                 8

                                                                            Breast-feeding period (months)
NUTRITIONAL TREATMENT of IBD
            LIQUID DIETS
(elemental, semielemental, polymeric)

      AS PRIMARY THERAPY
NUTRITIONAL TREATMENT of IBD
      MECHANISMS OF LIQUID DIETS
- Bowel rest

- Reduced antigenic load

- Nutritional effect

- Provision of trophic aminoacids

- Modification of gut flora

- Modification of intestinal permeability

- Modification of fecal pH
                             Corticosteroid    Liquid diet
                             more effective   more effective

       Lochs 1991
    Malchow 1984
Gonzalez-Hulx 1993
      Gorard 1993
       Lindor 1992
    O'Morain 1980
    Seidman 1993
    Seidman 1991


   Log Odds ratio (95% CI)
                                                                   10
                                              Griffiths A. M. et al. Gastroenterology 1995
   Liquids Diet vs Steroids


        Messori et al.1996: steroids better
relative risk of treatment failure (RTF): 0.35 ↓ in Steroids



        Zachos et al. 2001: steroids better
          odds ratio: 0.30 favouring Steroids
               Permeability index
6                                                Before
              P < 0,01                           After
5

4

3
                                    P < 0,01
2

1

0
    Oral elemental diet         Steroids

                            Zoli G. et al. Alim. Pharm. Ther. 199
                      Follow up
      % of patients

100

80

60
                      Oral elemental diet
40
                      Steroids
20

 0
     0            3        6           9           12
         Months
                               Zoli G. et al. Alim. Pharm. Ther. 1997
   NUTRITIONAL TREATMENT of IBD


            79%       27%     63%




A: Patients who achieved remission,
B: Patients who did not achieve remission
PEN 1: MUFA DIET
PEN 2: PUFA DIET
                                            Gassull MA, Gut, 2002
  Factors contributing to treatment failure
Feed
• Palatability
• Osmolality
• Transient side effects: headache, nausea, dizziness, diarrhoea

Patient
• Level of motivation
• Inability to cope with length of time without solid food
• Social inconvenience
• Stricturing disease or bulky inflammatory mass requiring surgery

Hospital
• Human resources issue (dietitians)
• Lack of support
• Lack of robust protocols
• Physician scepticism


                                       J. Goh, C.A. O’Morain, Aliment Pharmacol Ther, 2003
        NUTRITIONAL TREATMENT of IBD

 LIQUID DIETS, IN CROHN’S DISEASE, SHOULD BE CONSIDERED IN:


- Incomplete small bowel obstruction

- Severe painful perianal disease

- Steroid resistancy in active disease

- Borderline intestinal failure

- Children with active disease or growth failure
        NUTRITIONAL TREATMENT of IBD

            FUTURE PERSPECTIVES

- Oral glutamine
- n-3 fatty acids (fish oil)

- Short chain fatty acids
- Plantago ovata

- Transforming growth factor-β-2
- Hydrothermally processed cereals
- Antioxidants
                Potential use

Prevention of increased intestinal permeability
and villous atrophy in TPN and bowel rest

Reduction of increased intestinal permeability in
Crohn's disease

Prevention of toxic agents mucosal damage (e.g.
chemio-radio theraphies)
                Permeability Index

10              Before
9               After
8
7
     P < 0,01
6
5
4
3
2
1
0
                         Zoli et al. 1996
                  Antioxidant variables Crohn’s disease (CD)
                    Active CD                                                         Controls           P value
                                      P value   Inactive CD           P value
                     (n=12)                                                            (n=70)

  Vitamin A
                   1.80 (1.33-2.48)    0.23     2.25 (1.80-2.83)        0.11        2.40 (2.00-3.00)       0.03
   (umol/l)

Beta Carotene                                                           0.003
                   1.04 (0.71-1.54)    0.017    1.74 (1.28-2.45)                    2.24 (1.80-2.86)      0.000
   (umol/l)

  Vitamin E
                   30.0 (25.3-33.5)    0.98     29.0 (23.8-34.0)        0.05        31.0 (27.0-38.3)       0.20
   (umol/l)

  Vitamin C
                   23.0 (16.0-50.0)    0.07     38.0 (26.8-57.0)        0.002       54.0 (40.8-70.0)      0.001
   (umol/l)

Copper (umol/l)    26.2 (21.3-38.8)    0.009    19.9 (17.1-23.7)        0.14        18.0 (15.1-25.2)      0.007



 Zinc (umol/l)     10.9 (10.3-14.4)    0.57     12.4 (10.8-13.5)        0.007       13.1 (12.2-13.9)       0.06


  Selenium
                   0.80 (0.69-0.92)    0.20     0.87 (0.76-1.02         0.000       1.00 (089-1.12)       0.000
   (umol/l)

     SOD
                   16.9 (15.0-20.2)    0.035    15.5 (13.8-17.3)         ----             NR               ----
 (U/mmol Hb)

     GPx
                   746 (658-1012)      0.45     815 (707-945)           0.002       972 (784-1163)         0.02
 (U/mmol Hb)
                                                                   B.J. Geerling et al. – Scand J Gastroenterol 1999
Plasma antioxidants in Crohn’s Patients and Controls




                             Agdhassi E., et Al., Am J Clin Nutr, 2001
Plasma Antioxidant Vitamins




                    Agdhassi E., et al., Am J Gastroenterol 2003
NUTRITIONAL TREATMENT of IBD
     Fish oil vs Olive oil
       Ulcerative Colitis
NUTRITIONAL TREATMENT of IBD
 HYDROTERMALLY PROCESSED CEREALS




                           Bjorck S, et Al., GUT 2000
NUTRITIONAL TREATMENT of IBD
 HYDROTERMALLY PROCESSED CEREALS




                          Bjorck S, et Al., GUT 2000
            Short chain fatty acid rectal irrigation for left-sided
                              ulcerative colitis


   Double-blind
      Open-label




   Stool                Rectal                Mucosal                     Life impact
frequency              bleeding              appearance
                                                             Breuer R I et al; GUT 1997
                                         Ulcerative Colitis

                             1
Probability of remission




                           0.8



                           0.6
                                                 Plantago ovata seed
                                                 Mesalamine
                                                 Plantago+Mesalamine
                           0.4


                           0.2


                       0         2   4      6               8               10             12
                                          Months     Fernandes-Banares F., et a., Am J Gastroenterol, 1999
     NUTRITIONAL TREATMENT of IBD
                        Crohn’s Disease
                               - Benefits similar to those of steroids,
- TPN                            but short lived
                               - Steroid refractory patients
                               - Growth improvement
- Liquid Diet                  - Improve nutritional status
   ( Elemental, Semielemental, Polymeric)

                                - Improve intestinal permeability ?
- Oral Glutamine ?              - Improve nutritional status ?
                                - Uneffective ?

- Fish Oil                       - Effective in preventing clinical relapse

- Antioxidants                  - Effective on flogosis ?

- Hydrotherm. proc. cereals                    AF production

- Growth factor Beta 2                         Mucosal healing
     NUTRITIONAL TREATMENT of IBD
                  Ulcerative Colitis


• TPN
                          • Unmodification of flogosis

                          • Helpfull before and after surgery

• LIQUID DIET
     (Elemental, semielemental, polimeric)

• FISH OIL          • Decreased steroid dosing?
• SHORT CHAIN FATTY ACIDS          • Effective in distal U C?

• PLANTAGO OVATA SEEDS      • Effective in maintenance
• HYDROTHERM. PROC. CEREALS           • AF production
   NUTRITIONAL TREATMENT of IBD

                   DIET


There is no such things as a “Crohn’s diet” or
“colitis diet.”


    The patient can be allowed
  to eat anything that is tolerated
NUTRITIONAL TREATMENT OF IBD

				
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