Commonly Used Medicinal Herbs

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					                                                          SPECIAL ARTICLE

A Review of 12 Commonly Used
Medicinal Herbs
MaryAnn O’Hara, MD, MSt; David Kiefer, MD;
Kim Farrell, MD; Kathi Kemper, MD, MPH

              large and increasing number of patients use medicinal herbs or seek the advice of their
              physician regarding their use. More than one third of Americans use herbs for health
              purposes, yet patients (and physicians) often lack accurate information about the safety
              and efficacy of herbal remedies. Burgeoning interest in medicinal herbs has increased
scientific scrutiny of their therapeutic potential and safety, thereby providing physicians with data to
help patients make wise decisions about their use. This article provides a review of the data on 12 of
the most commonly used herbs in the United States. In addition, we provide practical information
and guidelines for the judicious use of medicinal herbs.                Arch Fam Med. 1998;7:523-536
                                     More than one third of Americans use herbs         • Your spouse has high cholesterol, your
                                     for health purposes, spending over $3.5 bil-           child has recurrent ear infections, and
                                     lion annually.1,2 Yet patients (and physi-             you have trouble relaxing after a hectic
                                     cians) often lack accurate information about           day at the clinic. Prompted by your pa-
                                     the safety and efficacy of herbal remedies.            tients’ questions, you wonder if any herbal
                                     Imagine the following are patients in your             remedies might benefit your family.
                                     primary care practice. How would you ad-                  Popular use of medicinal herbs makes
                                     vise them?                                         it necessary for physicians to become aware
                                     • Jane, who has chronic hepatitis C and            of their health benefits, risks, and uncertain-
                                        receives medicine for both hyperten-            ties so that they can educate their patients
                                        sion and schizophrenia, asks if she can         about these issues. To assist clinicians in this
                                        take milk thistle to protect her liver.         task, this article reviews existing data on the
                                     • John, who has the human immunode-                history, safety, and efficacy of 12 of the most
                                        ficiency virus, has an increasing viral         commonly used and best-studied medicinal
                                        load. He expresses fear of “medicine,”          herbs (Table 1). In addition, it summarizes
                                        but requests information about St John’s        general information about herbal therapies,
                                        wort (SJW) in hopes of “naturally” cur-         including an overview of regulatory history
                                        ing his human immunodeficiency vi-              (Table 2), important similarities and dif-
                                        rus and depression.                             ferences between medications approved by
                                     • Sam’s wife bought him valerian to help           the Food and Drug Administration (FDA)
                                        him sleep, saw palmetto for his urinary         and herbal therapies (Table 3), and the
                                        difficulties, and gingko to improve his         nature of available data about medicinal
                                        memory. He is inclined to throw the             herbs. Finally, lists of reliable introduc-
                                        herbs away but wants your opinion.              tory resources (Table 4) and guidelines
                                     • After you inform Stephanie that she is 3         for patients (Table 5) are provided.
                                        months pregnant, she asks what effects
                                        the herbs she has taken for months will             A HISTORICAL PERSPECTIVE
                                        have on her fetus (ginger for nausea,
                                        feverfew for headaches, and pen-                Plants have been used medicinally through-
                                        nyroyal to induce a period).                    out history. Through the first half of this cen-

From the Robert Wood Johnson Clinical Scholars Program, University of Washington
Health Sciences Center (Dr O’Hara), and the University of Washington Family               This article is also available on our
Medicine Network, Swedish Family Medicine Residency (Drs Kiefer and Farrell),
Seattle; and the Center for Holistic Pediatric Education and Research, The Children’s
                                                                                          Web site:
Hospital, Boston, Mass (Dr Kemper).

                                                    ARCH FAM MED/ VOL 7, NOV/DEC 1998
                                        Downloaded from on August 19, 2007
                                        ©1998 American Medical Association. All rights reserved.
  Table 1. Twelve Common Medicinal Herbs*

  Herb                               Common Uses
  Scientific Name                  (Type of Evidence/
  Part Used                        Recommendation)†                                  Safety‡§                                  Dose¶               Cost**
  Chamomile                Mild sedative (III-C)                 GRAS††                                               Tea as necessary          $0.10 per tea
    Matricaria recutita,   Mild spasmolytic (III-B)              Rare allergic reaction and contact irritation.       Compress as necessary       bag
    Chamaemelum nobile     Vulnerary (wound healing), (II.3-B)     Avoid ocular preparations
  Echinacea                URI treatment (I-B)                   No serious side effects known                        Not standardized          $0.25-$4 per
    Echinacea purpurea,    URI prevention (I-C)                  Historically misidentified and contaminated          Dried extract:              day
    Echinacea              Vulnerary (wound healing), (III-C)    Long-term use may be immunosuppressive                  300-400 mg tid
       angustifolia        Immune stimulation (III-C)                                                                 Tincture: 30-50 drops
    Leaf, stalk, root      Antimicrobial (HIV), (IV-C [D])                                                               (1 drop = 20 µL) tid
  Feverfew                 Headache prophylaxis (I-B)            5%-15% oral or GI irritation                         25-75 mg (1-3 leaves)     $0.10-$0.50
    Tanacetum                Rheumatoid arthritis (I-E)          Rebound headaches possible                              bid, standardized to     per day
       parthenium                                                Avoid in pregnancy (traditional menses inducer)         0.2% parthenolide
    Leaf                                                         May potentiate platelet inhibitors
  Garlic                     9% ↓ lipids (LDL, TG), (I-B)        GRAS, including in pregnancy, lactation, and         Fresh cloves: 0.5-1 qd    $0.04-$0.70
    Allium sativum         Mild antihypertensive (I-B)             childhood                                          Pills: 600 mg-900 mg        per day
    Cloves, root           Antiplatelet (II.1-B)                 No serious side effects known                           qd, standardized to
                           Antioxidant (I-B)                     Mild side effects: halitosis, body odor, topical        0.6%-1.3% allicin
                           Antimicrobial (bacteria, fungus, and    irritation, allergy (rare), GI upset               Powder: 0.4-1.2 g
                             viruses [HIV]), (III, IV-C [D])     May potentiate hypoglycemic and antiplatelet
                           Cancer prevention (II.3-D) and          therapy
                             treatment (III-D)
  Ginger                   Antiemetic (I-B) (mildly prophylactic GRAS, including in pregnancy, lactation, and         Capsules: 250-1000 mg     $0.12 per
    Zingiber officinale      and therapeutic against nausea         childhood                                           tid-qid                   dose
    Root                     from motion, chemotherapy,          No serious side effects known                        Tea: steep powder or
                             pregnancy, and surgery)             May inhibit platelet aggregation                       fresh herb
                                                                 GI upset (mild)
                                                                 Allergy (rare)
  Ginkgo                   Dementia: slows cognitive             No serious side effects known                        Use extract               $0.30-$1.80
    Ginkgo biloba            deterioration (I-B)                 Mild side effects: GI upset, headaches, allergic        standardized to 6%       per day
    Leaf                   Mild effects, similar to tacrine         skin reactions                                       terpenoids, 24%
                           Claudication: 50% ↑ in pain-free      May inhibit platelet aggregation                        flavonoids
                             walking distance (II.1-B)                                                                   40-80 mg bid-tid
  Ginseng                  Endurance/adaptation enhancer         GRAS                                                 Root: 1-3g qd             $0.30-$2.00
    Panax ginseng,           —Conflicting motor results (C)      High cost without proven benefit                     Pills: 100-300 mg tid,      per day
    Panax quinquefolius      —↑ Cognitive function (I-C)         Avoid use with other stimulants and in patients         extract standardized
    Root                     —Resistance to stress (III-D)          with cardiovascular disease (potential               to 7%
    (“Siberian ginseng”      —Androgenic and estrogenic             hypertensive and chronotrope)                        ginsenosides
       is not a true         (II.2-D)                            May increase digoxin levels
       ginseng)            Enhances “quality of life” (II.1-D)   Mastalgia and postmenopausal bleeding (rare)
                           Immune/endocrine stimulant (III-D) Rare fatalities attributed to contaminants

tury,manyherbswereconsideredcon-                      be considered drugs based on tradi-                         HERBS AND FDA-APPROVED
ventional medicines and as such were                  tional use alone. A would-be manu-                          MEDICATIONS: SIMILARITIES
included in medical curricula and for-                facturer must gain FDA approval; the                            AND DIFFERENCES
mularies (eg, United States Pharmaco-                 profit to be made from a patented
poeia and The National Formulary).                    product is the motivating factor. Tra-                      Patients are often unaware of im-
Twoimportantfactorsfosteredaschism                    ditional herbal therapies cannot be                         portant similarities and differences
between mainstream drugs and herbal                   patented, and therefore lack spon-                          between medicinal herbs and FDA-
therapies in the United States: the de-               sors for the costly ($230 million) and                      approved medications. For ex-
velopment of a pharmaceutical indus-                  lengthy (8-10 years)3 approval pro-                         ample, some mistakenly think of
trycapableofmass-producingpurified                    cess. By default, many medicinal                            herbs as “natural” alternatives to
chemicals, and regulatory changes by                  herbs are not legally considered drugs                      chemicals, failing to recognize that
the FDA.                                              and are not regulated as such by the                        herbs are composed of bioactive
      In 1962, thalidomide was found                  FDA. The FDA suggests but cannot                            chemicals, some of which may be
to be teratogenic and Congress passed                 require that manufacturers of herbal                        toxic (see Table 6 for a list of com-
an amendment to the Food and Drug                     therapies provide customers with sci-                       monly used herbs with toxic effects
Act to increase assurance of drug                     entific data in support of advertis-                        that probably outweigh their poten-
safety and efficacy. While successful                 ing claims. Furthermore, the FDA                            tial benefits). Also, patients are of-
in general, the amendment initiated                   must prove that an herbal product is                        ten unaware that about 25% of mod-
a regulatory dilemma regarding                        unsafe or ineffective before it can re-                     ern pharmaceutical drugs have
herbal therapies in the United States                 quire the product to be removed from                        botanical origins, such as digoxin
(Table 2). No longer can substances                   the market.                                                 from foxglove, morphine from pop-

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                                            ©1998 American Medical Association. All rights reserved.
   Table 1. Twelve Common Medicinal Herbs* (cont)

   Herb                                    Common Uses
   Scientific Name                       (Type of Evidence/
   Part Used                             Recommendation)†                                   Safety‡§                                 Dose¶               Cost**
   Goldenseal                    Mask illicit drugs in urine (II.3-E)   Generally well tolerated                            Use alternate sources of $0.45-$1.25
     Hydrastis canadensis        Berberine constituent effects:         Traditional literature warns that huge                berberine, 10 mg/kg      per dose
     Root, rhizome                 Antidiarrheal in children               (unspecified) doses can cause GI upset,            per day
                                     (Escherichia coli, Giardia, and       hypertension, cardiac inotropy, seizures, and
                                     cholera), (I-B)                       respiratory failure
                                   Antiseptic, topical (III-C)          Avoid in pregnancy (uterotonic) and neonates
                                                                           (causes jaundice)
                                                                        May oppose anticoagulants
   Milk thistle                  Hepatoprotection against:              No serious side effects known                       Capsules: 140 mg           $0.44-$2.00
     Silybum marianum              —Acute hepatitis, ie, mushroom       Rare: diarrhea, allergy                                bid-tid, standardized     per day
     Fruit                            poisoning (II.3-B), drugs                                                                to 70% silymarin          (oral)
                                      (III-C)                                                                               IV silymarin in acute
                                   —Chronic active hepatitis (I-B)                                                             poisoning: 20-50
                                   —Cirrhosis (I-B, conflicting data)                                                          mg/kg per day
   St John’s wort                Mild-moderate depression (I-B)         Photosensitization is rare, usually in fair-skinned Tablets: 300 mg tid of     $0.17-$1.35
      Hypericum perforatum         (long-term use not yet studied)        people taking large doses                            extract standardized      per day
      Flower, leaf               Antimicrobial (HIV), (III-C [D])       No clinical MAO-inhibition and/or related              to 0.3% hypericin         (oral)
                                 Vulnerary (III-C)                        drug/food interactions                            Topical
                                 Neoplastic inhibition (III-D)          Avoid use with other antidepressants
   Saw palmetto                  Benign prostatic hypertrophy (B)       Unlike finasteride, not associated with ↓ libido    Tablets: 320 mg qd of      $ 0.80-$1.20
     Serenoa repens                —↑ Flow, ↓ frequency, ↓ PVR            or changes in PSA                                    extract standardized       per day
     Fruit                            (No. 7 II-1)                      No serious side effects or drug interactions           to 85%-95% fatty
                                   —Efficacy = finasteride (I)            known                                                acids and sterols
                                   —↓ Androgen and estrogen             Mild, rare effects: GI upset, headaches, diarrhea
                                      prostatic nuclear receptors (I)
                                   —5 reductase inhibition (IV)
   Valerian                      Somnogogue (sleep aid), (I-B)          GRAS                                                Capsules: 400 mg qhs       $0.06-$0.19
     Valeriana officinalis       Spasmolytic (III-C)                    Mild, rare effects: headache, palpitations,            as necessary ( 12         per dose
     Root                                                                 insomnia                                             years)
                                                                                                                            Tea: 2-3 g = 1 tsp tid
                                                                                                                            Tincture: 3-5 mL tid

   *GRAS indicates generally recognized as safe; URI, upper respiratory infection; HIV, human immunodeficiency virus; tid, three times daily; GI, gastrointestinal;
bid, twice daily; LDL, low-density lipoprotein; TG, triglycerides; qd, every day; qid, four times daily; IV, intravenous; MAO, monoamine oxidase; PVR, post–void
residual; PSA, prostate-specific antigen; qhs, every night. See text for more information and references.
   †Adapted from study reference system of the US Preventative Services Task Force (USPSTF), 1996, 2nd edition. Type of Evidence: I indicates randomized
controlled trial; II, other human study (1 = placebo-controlled trial, 2 = cohort or case-controlled study, 3 = case series); III, animal study (vs expert opinion in
USPSTF rating); IV, in vitro studies (not a category in USPSTF). Recommendation: A indicates safe and effective; B, probably safe and effective; C, probably safe,
possibly effective; D, insufficient data; and E, unsafe or ineffective.
   ‡Data are often lacking on drug interactions and effects of long-term use.
   §Content and quality of commercial products are not regulated in the United States and can vary considerably.
     Safety in pregnancy, lactation, and childhood is unknown (and use in these groups therefore not recommended) unless specifically indicated.
   ¶ Patients should use standardized preparations, which are more reliable and cost-effective.
   **Range of costs for commercial products ( brands) in typical drug store.
   ††Generally recognized as safe as a food supplement by the FDA.

pies, aspirin from willow bark, and                       age. In addition, herbs may be con-                         ably the best compendium of clini-
tamoxifen from the Pacific yew tree.4                     taminated or misidentified at any stage                     cal information about herbs in the
      Unlike the FDA-approved over-                       from harvesting through packaging.                          world, it does not disclose the sci-
the-counter and prescription medi-                                                                                    entific basis for its conclusions. Nev-
cations, medicinal herbs are not                            THE NATURE OF EVIDENCE                                    ertheless, such guidelines provide
required to demonstrate either safety                       ABOUT MEDICINAL HERBS                                     hypotheses to prompt quality human
or efficacy prior to marketing, nor are                                                                               trials, optimally with randomized,
they regulated for quality. Neverthe-                     Most research on medicinal herbs is                         double-blind, placebo-controlled
less, herbal therapies are not neces-                     conducted in areas of the world                             (RDBPC) trials. Research in the
sarily less expensive than patented                       where the use of medicinal herbs is                         United States will be bolstered by the
drugs and are rarely covered by medi-                     mainstream, particularly in Asia and                        creation of the Office of Comple-
cal insurance. In contrast to the pu-                     Europe. For the past 3 decades, the                         mentary and Alternative Medicine
rified, standardized, and potent FDA-                     German Health Authority has sys-                            within the National Institutes of
approved drugs, herbs contain an                          tematically reviewed the evidence on                        Health, Bethesda, Md.
array of chemicals, the relative con-                     about 300 herbs and formulated                                    Data about the safety and efficacy
centration of which varies consider-                      clinical guidelines. An English trans-                      ofmedicinalherbsarelimitedinanum-
ably depending on genetics, grow-                         lation of the resulting German Com-                         berofways.Insomecases,thebestdata
ing conditions, plant parts used, time                    mission E Monographs is due for                             are years old, limited to in vitro or ani-
of harvesting, preparation, and stor-                     release in 1998.5 Although argu-                            mal studies, and/or only available in

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  Table 2. Genesis of a Regulatory Dilemma: US Legislation on Herbal Remedies

  Year               Act/Agency                              Purpose/Details                         Effects on the Status of Herbal Therapies
  1906       Food and Drug Act               Outlawed misbranding and adulteration              Therapeutic herbs continue to be included in the
                                                                                                   National Formulary and the United States
  1938       Federal Food, Drug and          Required safety testing prior to marketing after   Most traditional remedies with history of safe use
               Cosmetic Act                    new elixir killed 105 people                        are grandfathered in under law
  1962       (Kefauver-Harris) Drug          Required proof of safety and efficacy to be        Most herbs not patentable and therefore
               Amendments                      marketed as a drug                                  Lacked sponsor for costly approval process
                                             Considered only evidence presented to expert          Never considered for approval, irrespective of
                                               panels, primarily by companies interested in           efficacy or safety
                                               marketing a patentable (therefore profitable)       Reassigned status to “foods or food
                                               drug                                                   supplements”
                                                                                                   No longer legally considered medications
                                                                                                   No longer regulated by Food and Drug
                                                                                                      Administration (FDA)
                                                                                                   Subject to confiscation if labeled like a drug, eg,
                                                                                                      with traditional indications, doses, or cautions
   ...       FDA GRAS List                   FDA maintains a list of substances generally       Includes about 250 herbs based on their use as food
                                                recognized as safe (GRAS)                          additives (eg, garlic and ginger)
  1993       FDA Commissioner David          Proposed removing herbal products from the         More protest letters sent to Congress than about any
               Kessler, MD                      market given booming market despite                issue since the Vietnam war, fueled by a
                                                unproven safety or efficacy                        multimillion-dollar industry campaign
  1994       Dietary Supplement Health       Shifted burden of proof to FDA (eg, that claims    Ineffective assurance of safety, efficacy, or quality
               and Education Act                are misleading or an herb is unsafe)            Confusing guidelines about labeling:
                                             Altered restriction on labeling                       May state: effect on “structure or function of the
                                                                                                      body” or “mechanism” or “describe general
                                                                                                      well-being from consumption of the nutrient”
                                                                                                   May not state: false or misleading claims, or that
                                                                                                      the product can treat or prevent any specific
                                                                                                   May be accompanied by: balanced,
                                                                                                      nonpromotional literature
  1997       Federal Commission on           Recommended manufacturers provide                  Anticipate little effect, as lacks enforcement
               Dietary Supplements             science-based evidence about product to             capability

journalsoutsidetheUnitedStates.Some                            CHAMOMILE                               clusive results. A recent RDBPC
clinically important types of informa-                        Matricaria recutita                      trial found no difference between
tion are particularly sparse in the lit-                                                               chamomile and placebo in prevent-
erature, such as the results of negative           Common name: German chamo-                          ing mucositis in 164 patients
trials, drug interactions, effects in spe-            mile                                             receiving fluorouracil, half of
cialpopulations(eg,childrenandpreg-                Chamaemelum nobile (English or                      whom used chamomile 3 times
nantorlactatingwomen),andtoxicre-                     Roman chamomile)                                 daily for 14 days).6 However, the
actions. In some cases, good evidence              Common uses: Sedative, spasmo-                      study was possibly too short to
about short-term side effects comes                   lytic, anti-inflammatory, vulner-                detect a difference, as mucositis is
from well-controlled human trials.                    ary (wound healing)                              largely a result of immunosuppres-
However,informationabouttheeffects                 Investigational uses: Antioxidant                   sion, and therefore takes weeks to
oflong-termuseisusuallybasedoncase                 Side effects: Allergy (rare)                        develop. In another randomized,
reports rather than prospective stud-                    Chamomile is a daisylike,                     placebo-controlled trial, radiation-
ies.Asnotedearlier,traditionalusehas               apple-scented flower that has been                  induced skin reactions were less
revealedserioustoxiceffectsassociated              used medicinally for thousands of                   frequent and appeared later in
with some common medicinal herbs                   years. Anglo-Saxons believed it was                 chamomile-treated areas, but the
(see Table 6). On the other hand, the              1 of the 9 sacred herbs given to hu-                differences were not statistically
FDA categorizes about 250 herbs as                 mans by the god Woden. In con-                      significant.7
“generally recognized as safe” (GRAS)              temporary Germany, it is consid-                          Animal studies support cham-
for consumption based on long-term                 ered a cure-all. Chamomile is                       omile’s traditional use as a vulner-
and/orwidespreadtraditionalusewith-                cultivated worldwide for use as a                   ary anti-inflammatory, spasmo-
out significant side effects. This article         sedative, spasmolytic, anti-inflam-                 lytic, and anxiolytic agent. The
reviews several herbs on the FDA                   matory, and vulnerary (wound-                       flavonoid component apigenin
GRASlist,includingchamomile,garlic,                healing) agent. Few human studies                   exhibits dose-dependent, revers-
ginger,ginseng,andvalerian.Evidence                have evaluated these traditional uses.              ible inhibition of irritant-induced
about the safety and efficacy of these                   Only chamomile’s vulnerary                    skin inflammation8 and protects
and 7 other commonly used medici-                  effects have been studied in a con-                 against gastric ulcers induced by
nal herbs are reviewed below.                      trolled human trial, with incon-                    medications, stress, and alcohol.9

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  Table 3. Herbs and Food and Drug Administration (FDA)–Approved Drugs: Similarities and Differences

  Factor                        Legal Medications (FDA-Approved)                                           Herbal Therapies
  Mechanism             Biochemical                                           Biochemical
  Origins               25% Plant origin                                      Raw plants
  Efficacy              Evidence required, but not always based on            Proof not required
                          well-controlled trials
  Safety                Must be well studied, within acceptable limits, and   Evidence of safety not required and often unavailable
                          detailed on drug label or insert                    Burden of proof with FDA to show herbal therapies unsafe
  Dose                  Established, usually by dose-response studies         Some guidelines exist, usually based on historical precedent or tradition,
                                                                                occasionally based on dose-response in clinical trials
                                                                              Standardized products are preferential and available for some herbs (eg,
                                                                                garlic, ginkgo, St-John’s-wort, saw palmetto, and valerian)
                                                                              Not necessarily standardized by content of active ingredients, which are often
  Pharmacokinetics      Usually well characterized                            Rarely known
  Potency               Standardized                                          Varies with genetics, growing conditions, time harvested, plant part used,
                                                                                preparation, and storage
  Proof of purity       Required                                              Varies greatly
                                                                              High potential for contamination; history of case reports
  Identification        Some confusion possible with coexistence of           Problematic, beginning with misidentification of plants at harvesting
                          generic and multiple trade names                    Products should be labeled with and chosen by scientific name (genus
                                                                                species, eg, Echinacea purpurea is the most used and studied Echinacea
                                                                                species—many of its common names are shared by other plants)
  Quality control       Required                                              Not required
                                                                              Improving with self-regulation by herb industry
  Cost                  Wide range                                            Highly variable
                        Elevated for patented drugs                           Extracts are the most concentrated and cost effective
  Insurance coverage    Often                                                 Rarely

                                                                                                             should not be taken in conjunction
  Table 4. Introductory References                                                                           with other sedatives, such as ben-
                                                                                                             zodiazapines or alcohol.
    Blumenthal M, Gruenwald J, Hall T, Riggins C, Rister R. German Commission E Monographs:
       Medicinal Plants for Human Use. Austin, Tex: American Botanical Council; 1998. English
       translation in press.                                                                                    Echinacea purpurea, Echinacea
    Duke JA, Emmanus PA. The Green Pharmacy. Emmaus, Pa: Trondal Press; 1997.                                 angustifolia, and Echinacea pallida
    Murray M. The Healing Power of Herbs. 2nd ed. Rocklin, Calif: Prima Publishing; 1995.
    Tyler VE. Herbs of Choice: The Therapeutic Use of Phytomedicinals. Binghamton, NY:
       Pharmaceutical Products Press; 1994.                                                                  Common name: Purple cone-
  Journals                                                                                                      flower
    American Botanical Council, Austin, Tex. HerbalGram                                                      Common uses: Prevention and treat-
    Facts and Comparisons, St Louis, Mo. Lawrence Rev Nat Prod                                                  ment of colds, wound healing
    The American Botanical Council:
                                                                                                             Investigational use: Anticancer
    The Phytochemical Database:                                              Side effects: Possible suppression of
                                                                                                                immunity with habitual use
                                                                                                                   Echinacea is a purple cone-
                                                                                                             flower native to North America.
Apigenin also binds the same                          remain to be definitively proven in                    Plains Indians valued this member
receptors as benzodiazapines; it                      human trials, its beneficial effects                   of the daisy (Asteraceae) family for
exerts anxiolytic and mild seda-                      seen in animals and its good safety                    its medicinal properties and intro-
tive effects in mice10 and relaxes                    record in widespread traditional                       duced it to European settlers. By the
intestinal spasms.11 In vitro, the                    use by humans make it an accept-                       1920s, this acclaimed anti-infec-
essential oil acts as an antioxi-                     able home remedy for soothing                          tious and vulnerary agent was listed
dant12 and kills some skin patho-                     mild skin irritation, intestinal                       in the National Formulary and out-
gens (some Staphylococcus and                         cramps, or agitated nerves. In the                     sold all other products of one ma-
Candida species).13                                   United States, it is commonly con-                     jor pharmaceutical company. Its
     Chamomile is considered safe                     sumed as a tea or applied as a com-                    popularity dwindled after the ad-
by the FDA, with no known                             press. Patients with severe allergies                  vent of antibiotics, only to experi-
adverse effects in pregnancy, lacta-                  to ragweed should be warned                            ence a resurgence in recent years. It
tion, or childhood. It caused no                      about possible cross-reactivity to                     is the most popular herb in the
adverse reactions in the human tri-                   chamomile and other members of                         United States, generating more than
als discussed earlier. While chamo-                   the aster family (eg, echinacea,                       $300 million in sales annually. 1
mile’s therapeutic effects and safety                 feverfew, and milk thistle). It                        Three of the 9 species of Echinacea

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                                                                                                                  In animal studies, echinacea af-
  Table 5. Medicinal Herbs: Patient Information Sheet                                                      fects several aspects of the immune
                                                                                                           system; components of echinacea in-
  • Plants have been used throughout history to improve health.                                            crease the number of circulating white
  • Many modern medicines came from plants. Examples include aspirin (from willow bark),
    morphine (from poppies), and digoxin (from foxglove). Scientists are still discovering valuable
                                                                                                           blood cells,18 enhance phagocyto-
    medicines in ancient plants; eg, tamoxifen, which is used to treat breast cancer (from Pacific yew     sis,19 stimulate cytokine production,
    trees).                                                                                                and trigger the alternate comple-
  • Herbs used for health purposes are drugs. They are chemicals that can affect the human body in         ment pathway.20 In vitro, echinacea
    helpful or harmful ways.                                                                               displays direct bacteriostatic and an-
  • Plant products are not necessarily safe. Hemlock, for example, was used to kill Socrates. Some
    commonly used herbal therapies are also unsafe.
                                                                                                           tiviral activity and stimulates the
  • Traditional herbal therapies are not necessarily effective. Only trials in humans comparing the        production of cytokines (interferon,
    herbal product with a placebo (inert substance) can determine its effectiveness, appropriate           tumor necrosis factor, interleukin 1,
    dose, and safety.                                                                                      and interleukin 6).3,15 Based on its
  • Individual reports of benefit from any drug, including herbs, are not reliable evidence. This is       stimulation of cytokine production,
    because some people will feel better when treated with a medicine they believe will work, whether
    it does or not.
                                                                                                           echinacea is being investigated as a
  • Science is not opposed to nature, but rather is a tool to help distinguish natural products that are   possible antineoplastic agent in pre-
    safe and effective from those that are not.                                                            liminary human trials.21
  • Unlike medications approved by the Federal Drug Administration, herbal products                               Topical echinacea exhibits mul-
    1. Are not required to prove claims about their safety or effectiveness.                               tiple vulnerary mechanisms, includ-
    2. Are not regulated to ensure quality control.                                                        ing the anti-infective activity noted
    3. Vary tremendously in concentration of active ingredients and other chemicals.
  • If you decide to use herbs for health purposes, the following recommendations can help
                                                                                                           above, stimulation of fibroblasts, and
    maximize the potential benefits and minimize the potential risks:                                      inhibition of inflammation (metabo-
    1. Discuss any drugs you use, including herbal remedies, with your doctor.                             lism of arachidonate to prostaglan-
    2. If you experience side effects, stop taking the herb and notify your doctor.                        dins).22 In rodents, echinacea also
    3. Avoid preparations containing more than one herb.                                                   decreases inflammation, protects
    4. Be wary of commercial clalms about herbs; seek unbiased and scientifically based sources of         against radiation-induced skin dam-
        information. Ask your doctor or pharmacist for suggested sources.
    5. Preferentially use products that are standardized to contain a specific amount of active
                                                                                                           age, and hastens wound healing.23
        ingredients. Such formulations are generally more reliable, effective, and economical.                    Availableevidenceonechinacea’s
    6. Select herbal products carefully. In general, the highest quality products come from Europe or      therapeuticpotentialisincomplete,but
        large companies in the United States with national reputations to protect. Only buy brands that    does suggest a possible supportive role
        list the following information on the package: the herb’s common and scientific name, the          in treating infections and wounds.
        name and address of the manufacturer, a batch and lot number, an expiration date, dosing
        guidelines, potential side effects, and details of how quality is ensured.                         However, well-designed clinical trials
                                                                                                           are needed to substantiate echinacea’s
are used medicinally: E purpurea, E                      upper respiratory tract infections. In            confirmsafety.Despitethefactthatthe
angustifolia, and E pallida. Echina-                     one, echinacea extract demon-                     dosage has not been standardized and
cea purpurea is the most commonly                        strated a statistically significant               that preparations are frequently adul-
used and extensively studied.                            decrease in symptoms and dura-                    terated,noserioussideeffectshavebeen
      In Germany, where most stud-                       tion of “flulike” illness (n = 180).15            reported in more than 2.5 million pre-
ies have been conducted, echinacea                       The effects were dose dependent;                  scriptions per year in Germany and
is approved by the Federal Health                        benefits were noted beginning on day              morethanacenturyofuseintheUnited
Agency as supportive therapy for up-                     3 or 4 in patients taking 180 drops               States.24 Toxicitystudiesfoundnomu-
per respiratory tract infections, uro-                   (1 drop = 20 µL) of extract daily,                tagenicityintissueculture,andnoclini-
genital infections, and wounds.5 In                      whereas volunteers taking 90 drops                cal or histologic side effects in rats
the United States, echinacea is usu-                     per day showed no benefit. In the sec-            treated with huge doses of echinacea
ally marketed alone or in combina-                       ond RDBPC trial with 108 volun-                   (5 g/kg intravenously and acutely or 8
tion with other herbs as a purported                     teers who had a history of recurrent              g/kgperdayorallyfor1month).24 Ger-
immune booster, particularly for the                     URIs, prophylactic echinacea extract              manguidelinesdiscourageuseofechi-
prevention or treatment of colds. Al-                    was associated with less frequent                 nacea in place of antibiotics or for
though 26 published controlled tri-                      (14% relative risk reduction) and less            morethan8weeks(onestudysuggests
als have evaluated echinacea’s thera-                    severe recurrences.16,17 In some stud-            that long-term use may suppress im-
peutic effects, none is of sufficient                    ies, immunocompromised patients                   munity).5
methodologic quality to be conclu-                       seemed to benefit the most.14 While
sive.14 For example, in addition to                      provocative, interpretation of the                          FEVERFEW
sharing the flaws of the best studies                    results is limited in both of the                       Tanacetum parthenium
discussed later, most other controlled                   RDBPC trials by inadequate use or
trials use formulations of echinacea                     description of the following: diag-               Common use: Migraine prophylactic
combined with other herbs. Treat-                        nostic criteria, randomization pro-               Investigational use: Antiarthritic
ment assignment is neither random                        cess, treatment interventions, meth-              Side effects: Oral ulcers, rebound
nor blind in most studies.14                             ods for assessing outcome, assurance                headaches, allergic reaction (rare)
      Only 2 RDBPC trials have                           of blinding, detail of results, and                     Feverfew is a daisylike peren-
evaluated E purpurea’s effect on                         quality statistical analysis.14                   nial found commonly in gardens and

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  Table 6. Common, Potentially Toxic Herbs*

  Herb (Scientific Name)                                         Purported Use                                         Possible Toxic Reaction
  Arnica (Arnica montana)                        Anti-inflammatory, analgesic, antiseptic            Ingestion associated with gastrointestinal and muscle
                                                                                                     Safe topically, excepting rare allergic reactions
  Belladonna (Atropa belladonna),                Relaxant, antiulcer                                 Central nervous system and respiratory depression;
    “deadly nightshade”                                                                                anticholinergic
  Chaparral (Larrea tridentata)                  Anticancer                                          Hepatotoxic, tumor trophic
  Coltsfoot (Tussilago farfara),                 Antitussive, salve                                  Carcinogenic, hepatotoxic, genotoxic
    “cough wort”                                                                                     Cardiopulmonary stimulant
  Comfrey (Symphytum)                            Healing (wounds, ulcers, cancer)                    Carcinogenic, hepatotoxic, genotoxic
                                                                                                     Excreted in breastmilk
  Ephedra (Ma-huang) (Ephedra sinica)            Anorectic, stimulant, bronchodilator                Potent, highly variable -1 and receptor stimulation
                                                                                                     Associated with hypertensive strokes, palpitations, and
                                                                                                        nerve damage
                                                                                                     Fatalities reported
  European mistletoe (Viscum album)              Antihypertensive, antitumor                         Central nervous system and cardiac toxic reaction
                                                                                                     Gastrointestinal bleeding
  Germander (Teucrium chamaedrys)                Anorectic                                           Hepatotoxic
  Licorice (Glycyrrhiza glabra)                  Expectorant, antiulcer                              High or prolonged doses cause pseudoaldosteronism (saline
                                                                                                       retention and potassium depletion)
  Life root (Senecio aureus)                     Emetic                                              Hepatotoxic, carcinogenic
                                                 Ease labor
  Pennyroyal (Hedoma pulegioides),               Menstrual disorders, insect repellent               Hepatotoxic
    “squawmint,” “mosquito plant”                                                                    Neurotoxic
                                                                                                     Teratogenic (acetylcysteine is antidote)
  Pokeroot (Phytolacca)                          Tonic, anticancer, anti-inflammatory                Gastrointestinal, neurologic, and hematologic toxic reaction
                                                                                                     May be fatal in children
  Sassafras (Sassafras albidum)                  Stimulant, tonic, antispasmodic,                    Carcinogenic
  Indian snakeroot (Rauvofilia serpentina)       ...                                                 Neurotoxic reaction (sedation, depression)
  Tea tree oil (Malaleuca alternifolia)          Antiseptic, salve                                   Central nervous system toxic reaction if ingested
                                                                                                     Local irritation
  Yohimbe (Pausinystalia yohimbe)                Impotence                                           Cardiovascular stimulant, neurotoxic, emetic

  *Select list of herbs most likely to be used by family medicine patients. Adapted from Tyler.2,4

along roadsides. The name stems                           cently approved encapsulated                              well as the months of use needed for
from the Latin febrifugia, “fever re-                     feverfew leaves as an over-the-                           clinical efficacy.25
ducer.” The first century Greek phy-                      counter medication for migraine                                In summary, some feverfew
sician Dioscorides prescribed fever-                      prophylaxis. However, migraines                           preparations can prevent mi-
few for “all hot inflammations.” Also                     were not prevented in a subse-                            graines, with efficacy that com-
known as “featherfew,” its feathery                       quent randomized controlled trial                         pares favorably with -blockers and
leaves are used commonly to treat                         (RCT) using a different formula-                          valproic acid.31 However, side ef-
arthritis and prevent migraines.25                        tion of feverfew (0.35% = 0.5 mg of                       fects may limit the use of feverfew,
While feverfew did not reduce symp-                       parthenolide, a suspected active in-                      as 5% to 15% of users develop aph-
toms in a double-blind, placebo-                          gredient).29 This highlights the po-                      thous ulcers and/or gastrointes-
controlled (DBPC) trial among pa-                         tential variability of contents and ef-                   tinal (GI) tract irritation.25 Sudden
tients with rheumatoid arthritis,26 it                    fects of different preparations of the                    discontinuation can precipitate re-
has been shown to prevent mi-                             same herb, as well as the inad-                           bound headaches.28 Long-term safety
graines in 2 of 3 DBPC trials.                            equacy of standardizing herbs to a                        data are lacking. Feverfew should
      The largest and best DBPC trial                     single ingredient when other bioac-                       not be used during pregnancy (his-
was a crossover study in which fe-                        tive constituent(s) are not well char-                    torically it has been used to induce
verfew use was associated with a                          acterized.                                                menstrual bleeding) or in patients
70% reduction in migraine fre-                                  Laboratory evidence indicates                       with coagulation problems (fever-
quency and severity (n = 270).27 Side                     that feverfew causes vasodilation and                     few can alter platelet activity30). For
effects were less frequent than with                      reduces inflammation. Feverfew’s                          patients who want to try feverfew,
placebo. In a trial among feverfew                        constituents inhibit phagocytosis,                        expert herbalists recommend a
users, subjects randomized to re-                         platelet aggregation, and secretion of                    gradual dose increase up to 125 mg/d
ceive a placebo instead of continu-                       inflammatory mediators (arachidon-                        orally of encapsulated leaves (2-3
ing feverfew suffered a significant in-                   ic acid and serotonin).30 Feverfew is                     leaves) standardized to contain 0.2%
crease in the frequency and severity                      thought to down-regulate cerebro-                         parthenolide. However, according to
of headaches, nausea, and vomit-                          vascular response to biogenic                             a 1992 study, none of the commer-
ing (n = 20).28 Based on these tri-                       amines, consistent with its ability to                    cially available North American
als, Canadian health officials re-                        prevent but not abort headaches, as                       preparations contained even half of

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the recommended parthenolide con-             due to a decrease in low-density li-          at least 1.3% allicin (equivalent to
centration.32                                 poprotein (LDL) ± decreased tri-              approximately 3 g or 1 fresh clove
                                              glyceride levels.40-43                        daily. Finally, the quality of com-
              GARLIC                                Of the factors that contribute to       mercial preparations varies greatly,
           Allium sativum                     the discrepancies in data regarding           a problem common to many herbal
                                              garlic’s antilipidemic effects, 2 are         therapies. In an analysis of suppos-
Common uses: Antiatherosclero-                probably most important: publica-             edly standardized preparations,
   sis (lipid lowering, antithrom-            tion bias (the preferential publica-          93% were found to be so lacking in
   botic, fibrinolytic, antihyperten-         tion of trials with positive findings)        allicin that they were declared
   sive)                                      and methodologic flaws. Both fac-             expensive placebos.4
Investigational uses: Anticancer              tors tend to overestimate the effect
Side effects: Sulfuric odor, con-             of a treatment. In contrast, exclud-                       GINGER
   tact irritation (rare)                     ing patients likely to benefit most                    Zingiber officinale
      Garlic’s historic and world-            (patients with severe hyperlipid-
wide medicinal use have made it               emia or high-fat diets) might under-          Common uses: Antiemetic
one of the most extensively stud-             estimate garlic’s effect.                     Side effects: Heartburn, allergic re-
ied medicinal herbs. Nevertheless,                  Blood pressure has been                    action (rare)
the actual therapeutic benefits of            monitored in most recent studies                    Like garlic, ginger has been a
this member of the Liliaceae fam-             of garlic’s antilipidemic effects,            popular culinary and medicinal herb
ily is unclear. Louis Pasteur first           showing a decrease (systolic and/or           for thousands of years. For 2500
demonstrated garlic’s antiseptic              diastolic) in the treatment group of          years, the Chinese have used this
activity.4 Both animal studies and            some, but not all, trials. Previously,        plant as a flavoring agent and anti-
epidemiological analyses suggest              a number of placebo-controlled tri-           emetic. Ancient Greeks wrapped gin-
anticancer effects.33 Most current            als that focused on the antihyper-            ger in bread and ate it after meals as
research, popularity, and contro-             tensive effects of garlic demon-              a digestive aid. Ginger is now culti-
versy relate to garlic’s use as a             strated a modest (−5% to −7%)                 vated in Asia, Africa, and the Carib-
putative antiatherosclerotic agent            effect.44 Several small, nondefini-           bean and is used worldwide as a nau-
(via antithrombotic, antiplatelet,            tive RCTs also corroborate garlic’s           sea remedy.
antihypertensive, and especially              antiplatelet, antithrombotic, and                   The characteristic odor and fla-
antilipidemic effects).                       fibrinolytic activity found in ani-           vor of ginger root come from a vola-
      Mainstream medical interest in          mal and in vitro studies.45                   tile oil (1%-3% by weight) that is
garlic’s potential lipid-lowering ef-               Dozens of trials suggest, but           composed of shogaol and gin-
fects was stimulated by 2 meta-               have not adequately proven, that              gerols. In laboratory animals, the
analyses of RPC trials that found a           garlic can decrease the risk factors          gingerols have analgesic, sedative,
9% to 12% decrease in cholesterol             for atherosclerosis, particularly             antipyretic, antibacterial, and GI
in hyperlipidemic patients after at           hypercholesterolemia. Pending                 tract motility effects.46,47
least 1 month of treatment with 600           conclusive evidence from addi-                      Ginger reduces nausea, accord-
to 900 mg/d of garlic tablets.34,35           tional well-designed and ade-                 ing to some, but not all, controlled
However, definitive conclusions               quately powered studies, it is rea-           human trials. In an RDBPC cross-
were limited by methodologic flaws            sonable for patients to choose to             over trial of 30 women suffering
in the trials analyzed.                       take garlic given that it is safe and         from hyperemesis gravidarum, gin-
      Results of subsequent better-           generally inexpensive. Garlic is              ger (250 mg 4 times a day) signifi-
designed RPC trials have been                 considered safe by the FDA, based             cantly decreased the severity of nau-
mixed, with most (4/7) failing to find        on the lack of known serious                  sea (P=.04).48 Two RDBPCTs report
a significant change in any lipopro-          adverse outcomes despite culinary             a significant decrease in periopera-
tein component36-39 These studies ex-         and medicinal use throughout                  tive nausea and vomiting in gyne-
plicitly sought to overcome limita-           human history (including daily use            cological surgery patients who were
tions of previous trials, such as by          by pregnant or lactating women).              given 1 g of ginger before sur-
providing dietary stabilization prior         Malodorous breath and skin can be             gery.49,50 In one, ginger was as effec-
to treatment and detailing methods            diminished with enteric-coated                tive as metoclopramide in reducing
to ensure proper control processes            tablets or by consuming garlic with           the number of episodes of nausea or
and laboratory standards. How-                protein. Allergies and contact irri-          emesis. 4 4 However, in another
ever, 3 of the negative trials were           tation occur rarely. Patients who             RDBPCT, ginger was not found to
relatively small (N 28), which in             decide to use garlic medicinally              be effective in preventing nausea af-
one case yielded a marginal power             should be aware of a few caveats.             ter laparoscopic gynecologic sur-
(80%) to detect the expected 9% re-           The main purported active ingredi-            gery.51 Regarding motion sickness,
duction in cholesterol.38 Three RPC           ent, allicin, is degraded by crush-           ginger was more effective than di-
trials support the positive findings          ing, heat, and acid; thus, efficacy is        menhydrinate in one controlled
of the meta-analyses, finding a 6.1%          optimized by consuming raw                    trial,52 but was not effective in an-
to 11.5% cholesterol reduction in the         cloves or enteric-coated tablets.             other.53 Such inconsistency of re-
garlic-treated patients. Similar to pre-      The usual dose is 300 mg, taken 2             sults is found in studies of conven-
vious studies, the lipid reduction was        to 3 times per day, standardized to           tional antiemetics as well, due in part

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to the difficulty in measuring symp-               In 1997, the first US-based trial       fects with tacrine. While G biloba
toms such as nausea. In addition, the        corroborated ginkgo’s efficacy in the         leaves may cause mild GI tract irri-
effect of antiemetics is often subtle        treatment of dementia. In this year-          tation, no serious adverse effects
and difficult to discern unless tested       long, RDBPC, multicenter study,               have been noted in human or ani-
in a homogeneous population with             EGb 761 was found to stabilize and            mal trials, including no mutagenic-
a high prevalence of nausea.                 in some cases improve cognition and           ity or teratogenicity.64 In contrast, G
      It is reasonable for patients to       social functioning in patients with           biloba seeds can cause fatal neuro-
try ginger to treat nausea, not only         mild to moderate dementia (Alzhei-            logic and allergic reactions and are
because data supports its efficacy,          mer disease or multi-infarct demen-           not used medicinally. 64 Patients
but also because it is inexpensive,          tia).56 In another trial, healthy geri-       should use the extract studied in all
readily available, and safe. Like gar-       atric patients demonstrated better            reported clinical trials, Egb 761. The
lic, ginger is not known to cause any        cognitive function after taking               dose is 40 mg 3 times per day or 80
serious side effects, despite world-         EGb 761.57                                    mg twice per day of an extract stan-
wide culinary and medicinal use of                 EGb 761 improves perfusion              dardized to 24% flavanoid glyco-
ginger. Only 1 of the above con-             peripherally as well as centrally.            side and 6% terpenoids. Absorp-
trolled human trials noted any side          More than 15 European studies sug-            tion is unaffected by food intake. The
effect, which, ironically, was GI tract      gest a reduction of claudication              duration of benefit after discontinu-
upset. It is on the FDA’s GRAS list.         symptoms in patients treated with             ation is unknown.65
The usual adult dose is 250 milli-           EGb 761, including a 50% increase
grams (1⁄4 tsp) to 1 g of powdered           in pain-free walking distance.58 Si-                      GINSENG
root several times per day.                  multaneous benefits on central and                       Panax ginseng
                                             peripheral perfusion are demon-                 Panax quinquefolius (American
             GINKGO                          strated in a randomized, placebo-              ginseng, an endangered species)
           Ginkgo biloba                     controlled trial among 44 Hima-                   (Eleutherococcus senticosus,
                                             layan climbers.59 The 22 subjects              so-called Siberian ginseng, is not
Common uses: Intracerebral and pe-           treated with 160 mg/d of EGb 761              in the Panax [true ginseng] genus)
   ripheral vascular insufficiency (de-      developed significantly fewer cere-
   mentia and claudication)                  bral (0% vs 41.9%, P .002) and res-           Common name: Korean ginseng
Investigational uses: Mountain sick-         piratory symptoms (13.6% vs 81.8%,            Common uses: “Tonic,” perfor-
   ness                                      P .001) of mountain sickness than                mance enhancer, “adaptogen,” an-
Side effects: Gastrointestinal tract         climbers taking the placebo. EGb                 ticancer, aphrodisiac
   disturbance, headache, contact            761 also decreased vasomotor dis-             Investigational uses: All common
   dermatitis (each is rare/mild)            orders of the extremities, mea-                  uses are as of yet unproven but are
      One of the oldest surviving tree       sured by plethysmography and                     under investigation
species, G biloba has grown in China         symptom scores.                               Side effects: Tachycardia, hyper-
for more than 200 million years. For               The mechanisms of ginkgo’s                 tension
thousands of years, traditional Chi-         therapeutic effects are not fully un-               Ginseng is one of the most
nese medicine has used ginkgo to             derstood. They are attributed in part         popular and expensive herbs in the
treat brain disorders. In the past 20        to synergistic effects of its constitu-       world. As in ancient China, gin-
years, ginkgo has gained world-              ents, particularly the flavonoids, ter-       seng is still widely believed to be a
wide popularity for similar pur-             penoids, and organic acids. These act         panacea; hence, its genus name
poses, supported by evidence of its          to varying degrees as scavengers of           Panax. The common name ginseng
ability to promote perfusion and in-         free-radicals, chemicals implicated           (“man-root”) stems from a belief that
hibit oxidative damage. By 1988,             in the pathophysiology of Alzhei-             because this root is humanoid in ap-
German physicians prescribed a               mer disease.60,61 They also inhibit           pearance, it can benefit all aspects
standardized extract of ginkgo (Egb          platelet activation factor and thereby        of the human body. At least 6 mil-
761, Willmar Schwabe GmbH & Co,              reduce thrombosis, dilate arteries            lion Americans66 use the root of this
Karlsruhe, Germany) more than any            and capillaries, and block the re-            slow-growing perennial. It is con-
other medication. 4 Sales in the             lease of chemotactic and inflamma-            sidered a tonic or adaptogen that en-
United States soared to $240 mil-            tory mediators from phagocytes.               hances physical performance (in-
lion in 1997.1 In Germany, where                   Ginkgo’s antidementia effects           cluding sexual), promotes vitality,
most of the research has been con-           are similar to that of the prescrip-          and increases resistence to stress and
ducted, the federal health authori-          tion drugs donepezil and ta-                  aging. While in vitro and animal
ties have concluded that treatment           crine.62,63 While statistically signifi-      studies suggest that it has benefi-
with Egb 761 is safe and effective for       cant, such modest effects are of              cial effects on immune and endo-
peripheral and cerebral circulatory          uncertain clinical benefit. How-              crine functions, evidence of its ef-
disturbances, including claudica-            ever, ginkgo may have other advan-            fects on humans is limited and
tion and memory impairment.5 Nu-             tages, such as improvement of pe-             contradictory.
merous European clinical trials              ripheral vascular circulation and                   One reason for lack of defini-
report EGb 761’s efficacy in dimin-          tolerance of altitude. In addition,           tive data about ginseng’s health ef-
ishing symptoms of cerebrovascu-             ginkgo’s side effects are similar to          fects is the inherent difficulty of
lar insufficiency.54,55                      placebo vs potential hepatoxic ef-            quantifying intangible benefits such

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as “vitality” and “quality of life.”          should be used. Patients should be            tive than placebo and as effective as
Nevertheless, a 3-month RCT                   warned that E senticosis, marketed as         metronidazole (10 mg/kg 6 days)
showed a significant increase in sub-         “Siberian ginseng” for commercial             in treating children with giardia.77
jective “quality-of-life” scores among        reasons, contains no true ginseng.                  Berberine is thought to act in-
ginseng users (n = 625).67 Some small              Despite extensive use, adverse           traluminally, as it is poorly ab-
controlled trials report increased en-        reactions to ginseng are rare and gin-        sorbed and there is no clinical evi-
durance, whereas others do not.68 In          seng is on the FDA’s GRAS list. How-          dence for systemic anti-infective
an RDBPCT, college-aged volun-                ever, at least 1 fatality has been at-        activity.78 In vitro studies reveal pos-
teers who took 100 mg of ginseng              tributed to contamination of a                sible mechanisms of berberine’s an-
twice daily for 12 weeks experi-              ginseng product with the potent and           tidiarrheal effects. Berberine exerts
enced a statistical improvement in            unpredictable herbal stimulant ephe-          antimicrobial activity against nu-
the speed at which they were able to          dra. While clear conclusions about            merous bacteria, fungi, and proto-
perform mathematical calcula-                 the safety of ginseng cannot be               zoa.79 In addition, it blocks adhe-
tions, but did not experience im-             drawn from the uncontrolled 1979              sion of bacteria to epithelial cells,80
provement in motor function or                case series that coined the term “gin-        inhibits the intestinal secretory re-
other cognitive functions; no ad-             seng abuse syndrome,”74 ginseng can           sponse of cholera and E coli toxins,
verse effects were seen in this study.69      act as a mild stimulant and should            and normalizes mucosal histology
To our knowledge, no studies com-             probably be avoided in association            following cholera toxin damage.81
pare ginseng’s effect with that of in-        with other stimulants or in patients                Despite the antidiarrheal effi-
expensive, widely available cogni-            with cardiovascular disease. Rare en-         cacy of the chemical berberine, we do
tive stimulants such as caffeine, nor         docrinologic effects include mastal-          not recommend the use of the herb
has an RCT confirmed aphrodisiac              gia and postmenopausal bleeding,              goldenseal for this purpose, both be-
effects in humans. However, gin-              both of which cease with discon-              cause of this plant’s endangered sta-
seng was associated with a signifi-           tinuation of ginseng.75                       tus and due to the possible toxicity
cant increase in serum hormones                                                             of its other components. For ex-
(testosterone, dihydroxytestoster-                      GOLDENSEAL                          ample, traditional herbal literature
one, follitropin, and lutropin) and                   Hydrastis canadensis                  warns that large (unspecified)
in sperm numbers and motility in 46                                                         amounts of goldenseal (particularly
men with oligospermia.70 A case-              Common uses: Antidiarrheal and                the alkaloid hydrastine) can cause
control study suggests an associa-               antiseptic (berberine compo-               mucosal irritation, GI tract upset,
tion (but not necessarily a causal re-           nent)                                      uterine contractions, neonatal jaun-
lationship) between use of ginseng            Investigational uses: Antineoplas-            dice, hypertension, seizures, inotro-
and lower cancer rates (n = 1987                 tic and anti–human immunode-               pic cardiac effects, and respiratory
pairs matched for age, religion, mari-           ficiency virus (berberine compo-           failure.82 It may oppose heparin or
tal status, education, sex, occupa-              nent)                                      coumadin anticoagulation.83 Gold-
tion, and smoking status).71                         Side effects (large doses):            enseal should not be used by preg-
      In Asian cultures, ginseng is             Mucocutaneous irritation, GI tract          nant or lactating women, neonates,
commonly consumed by pregnant                 upset, cardiac and uterine contrac-           or patients with cardiovascular dis-
women and is given to newborns in             tility, vasoconstriction, central ner-        ease, epilepsy, or coagulation prob-
hopes of bolstering energy. A case-           vous system stimulation, neonatal             lems. No significant side effects have
control study of 88 pairs of women            jaundice (displaces bilirubin).               been noted in clinical or animal stud-
(matched only for age and parity)                    Cherokee Indians introduced            ies of purified berberine.
found a significantly lower rate of           this member of the buttercup fam-
pregnancy-induced hypertension,               ily to European settlers. It is used                    MILK THISTLE
but a 3-fold higher incidence of ges-         topically for eye or skin irritation,                  Silybum marianum
tational diabetes among ginseng con-          and orally for infections. A recent
sumers.72 We do not recommend                 surge in goldenseal’s popularity              Common names: “Holy Thistle,”
ginseng use for pregnant or lactat-           stems from the erroneous but wide-               “St Mary’s Thistle”
ing women or for children until               spread belief that it can mask illicit        Common uses: Hepatoprotectant,
safety and efficacy are proven in ran-        drugs in urine toxicology screens. It            antioxidant
domized controlled trials.                    is a also a popular but unproven cold         Investigational uses: Antihypergly-
      Patients who take ginseng risk          remedy. However, one of its main                 cemic
paying a high price without proven            bioactive constituents, berberine, is         Side effects: None known
benefit. Commercial preparations of           an effective antidiarrheal agent.                   For more than 2000 years, the
ginseng cost up to $20 an ounce and                  In one RCT, a single 400-mg            seeds of this prickly leafed, purple-
vary tremendously in quality. In one          dose of berberine sulfate signifi-            flowered plant have been used to
analysis of 54 available ginseng prod-        cantly reduced stool volumes and              treat liver disorders. In addition, all
ucts, 85% were determined “worth-             duration of diarrhea among pa-                parts of this Kashmir native have
less,” containing little or no gin-           tients with enterotoxigenic Esche-            been consumed historically as veg-
seng. 73 To optimize quality and              richia coli and Vibrio cholerae.76 In         etables without report of toxic ef-
chance of efficacy, only preparations         another controlled trial, berberine (5        fects. Silymarin protects against a va-
standardized to ginsenoside content           mg/kg        6 days) was more effec-          riety of hepatotoxic agents and

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processes in animal experiments.             mon dose is a 140-mg capsule, stan-           and efficacy compared with other
Evidence of its effects in humans is         dardized to 70% silymarin, 2 to 3             antidepressants.95 In response, the
provocative but preliminary.                 times a day. A high first-pass effect         Office of Complementary and
      The best human data deal with          concentrates silymarin in the liver.          Alternative Medicine of the Nat-
silymarin’s effect on cirrhosis, with        Silymarin is poorly absorbed, so con-         ional Institutes of Health and the
conflicting results from 2 RDBPC tri-        centrated products (ie, extracts) are         National Institute of Mental Health
als.84,85 In the first, the 4-year mor-      optimal.                                      recently allocated $4.3 million for
tality rate decreased by 30% in pa-                                                        the first clinical trial in the United
tients treated for 2 years with 140 mg               ST JOHN’S WORT                        States to address these issues. The
of silymarin 3 times a day. Effects                 Hypericum perforatum                   3-year multicenter trial beginning
were greatest in alcohol-related cir-                                                      in 1998 will compare SJW with
rhosis. In contrast, a recent multi-         Common use: Antidepressant                    both placebo and fluoxetine hydro-
center RDBPC trial in 200 patients           Investigational uses: Anticancer,             chloride.
with alcoholic cirrhosis found no dif-          antiviral (including human im-                   The mechanism of SJW’s anti-
ferences in progression of disease or           munodeficiency virus)                      depressant effects is only partially
mortality after 2 years of treatment         Side effects: Photosensitivity (rare,         known. Some in vitro studies dem-
with 150 mg of silymarin 3 times per            with large doses)                          onstrated monoamine oxidase inhi-
day.85 Interestingly, glycemic con-                This 5-petalled yellow flower           bition, but only at concentrations un-
trol was significantly improved (lower       grows wild in much of the world.              attainable in vivo.96 Furthermore, SJW
fasting blood glucose, glycosylated          While reduced to 1% of its original           is used extensively (66 million doses
hemoglobins, and insulin require-            population in the Pacific United              in 1994 in Germany) without restric-
ments) in a randomized, placebo-             States by ranchers who consider it            tion of tyramine-containing foods and
controlled trial of 60 patients taking       a bothersome weed, in Europe it is            without reported side effects related
silymarin for alcoholic cirrhosis.86 In      highly valued as an antidepressant.           to monoamine oxidase inhibition. Hy-
another RCT of patients with chronic         St John’s wort is by far the most com-        pericin is the putative active ingredi-
active hepatitis, 1 week of therapy          mon antidepressant used in Ger-               ent. It has a high affinity for -
with oral silymarin (240 mg/d) re-           many, where physicians prescribe it           aminobutyric acid, the stimulation of
sulted in decreased serum transami-          4 times more often as fluoxetine hy-          which is known to have antidepres-
nases and bilirubin values.87 Euro-          drochloride.94 Sales in the United            sant effects.87 Other studies indicate
pean physicians routinely treat              States increased 20-fold between              that hypericin activates dopamine re-
hepatotoxic mushroom poisoning               1995 and 1997, from $10 million to            ceptors but inhibits serotonin recep-
with intravenous silymarin (20-50            $200 million annually.1 St John’s             tor expression.97 Altered receptor
mg/kg per day), decreasing mortal-           wort has been used for thousands of           regulation is consistent with the sev-
ity rates by more than half in several       years for a myriad of conditions. It          eral-week lag between drug initia-
case series.88                               is named after St John the Baptist be-        tion and clinical efficacy, similar to
      In animal studies, silymarin           cause it blooms around his feast day          other antidepressants.
protects liver cells against a variety       (June 24) and exudes a red color                    In addition to SJW’s antidepres-
of hepatotoxins, including drugs             symbolic of his blood. Its scientific         sant effects, evidence beyond the
(acetaminophen, amitriptyline, and           name derives from the Greek hyper             scope of this article supports its his-
erythromycin),89,90 toxins (a-aman-          and eikon, “to overcome an appari-            torical anti-inflammatory, anti-
tin from deathcap mushrooms, al-             tion,” relating to ancient belief in its      infective, and vulnerary external appli-
cohol, and carbon tetrachloride),91          ability to ward off evil spirits. The         cations.96 Antineoplastic and antiviral
hemosiderin,92 viruses, and radia-           vulnerary and neurologic effects of           applications are experimental.
tion.88 Silymarin scavenges free radi-       this herb were described by Galen,                  Existing data on the therapeu-
cals, blocks toxin entry into cells by       were repeated throughout the                  tic effects of SJW are provocative.
competing for receptor sites, inhib-         Middle Ages and by early Ameri-               However, well-designed clinical tri-
its inflammation, and stimulates liver       can herbalists, and were recently             als are needed to determine long-
regeneration. As a result, it lowers         supported by many clinical trials.            term safety and therapeutic guide-
serum transaminase levels, main-                   A 1996 meta-analysis of 23              lines for use of SJW for different
tains coagulation factor produc-             randomized, controlled clinical tri-          depressive disorders. Prior to the
tion, and limits necrosis.88-91 It also      als of SJW concluded that it is sig-          availability of such information, pa-
prevents renal toxic reactions from          nificantly more effective than pla-           tients who choose to use SJW should
cisplatin.93                                 cebo in treating mild to moderate             use the regimen shown to be effec-
      Milk thistle warrants further in-      depression. 95 The 8 studies that             tive in the above clinical trials: 300
vestigation as a hepatoprotective and        compared H perforatum with low-               mg 3 times a day of an extract stan-
regenerative agent. No adverse ef-           dose tricyclics suggested equivalent          dardized to 0.3% hypericin. St John’s
fects have been reported. Diabetic           efficacy, with significantly fewer            wort is generally well tolerated, but
patients taking silymarin should             side effects. The authors noted the           can cause photosensitivity, espe-
carefully monitor their blood glu-           need for further studies to deter-            cially in fair-skinned persons tak-
cose and may require reduction in            mine optimal dosing, long-term                ing large doses. It should not be used
standard antihyperglycemic agents            side effects, efficacy in mainte-             during pregnancy (uterotonic) or
to avoid hypoglycemia.86 The com-            nance therapy, and relative safety            with other psychoactive agents.

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                                     ©1998 American Medical Association. All rights reserved.
         SAW PALMETTO                          inflammatory activity (inhibition of          mutagenic activity in vitro. Al-
          Serenoa repens                       cyclooxygenase and 5-lipoxygenase             though these effects have not been
                                               pathways) are thought to be impor-            reproduced in vivo even at high
Common uses: Benign prostatic hy-              tant in decreasing the edematous              doses (1350 mg/kg), valerian prob-
   pertrophy (BPH), prostatitis                component of BPH and prostatitis.4            ably should not be used by preg-
Side effects: Gastrointestinal tract                These studies support the use            nant women. Valerian should not be
   upset, headache (each is rare and           of SPE for BPH and show that its ef-          taken with other sedatives or be-
   mild)                                       ficacy is comparable to that of the           fore driving or in other situations
       Extracts from the fruit of this         5 -reductase inhibitor finasteride            when alertness is required.
short, scrubby palm have been used             with significantly fewer side ef-
historically to treat urogential prob-         fects. However, 1 antagonists are                      CONCLUSIONS
lems. Many modern clinical trials              more effective than both SPE106 and
corroborate the ability of saw pal-            finasteride.107 The usual dose of SPE         Physicians need to know about me-
metto extract (SPE) to improve the             is 160 mg twice daily of an extract           dicinal herbs because many pa-
signs and symptoms of BPH, for                 standardized to contain 85% to 95%            tients use them and are often guided
which it is a first-line treatment in          fatty acids and sterols. Side effects         by misconceptions or inaccurate in-
much of Europe.98                              are rare ( 3%) and include mild               formation. Whether or not physi-
       Seven of the 8 DBPC trials that         headaches and GI tract upset.4                cians intend to prescribe herbal
have evaluated SPE’s efficacy in treat-                                                      therapies, it is important that they
ing BPH demonstrate significant ob-                        VALERIAN                          understand the potential associ-
jective and subjective improve-                        Valeriana officinalis                 ated health consequences so that
ment in BPH symptoms in patients                                                             they can help patients make in-
taking 320 mg of SPE for 1 to 3                Common uses: Sleep-aid, anxio-                formed decisions about their use.
months.98,99 However, only 2 of these             lytic, antispasmodic                       This review aimed to familiarize cli-
trials are randomized, and their re-           Side effects: Headaches (rare), heart         nicians with available evidence on
sults conflict. In the shorter ran-               palpitations (rare), insomnia              12 commonly used herbs, as well as
domized trial, SPE is no better than              (rare)                                     to indicate areas in need of further
placebo in treating BPH (n = 70                      The malodorous root of valer-           research. Popular interest in herbal
treated for 1 month).100 In the larger,        ian, a pink-flowered perennial that           therapies is stimulating research that
randomized, multicenter trial                  grows wild in temperate areas of the          will help clarify issues such as the
(n = 176 treated for 2 months), and            Americas and Eurasia, has been a              indications, effective doses, and
in the other 6 DBPC trials, SPE sig-           popular calming and sleep-pro-                safety of common medicinal herbs.
nificantly increases urinary flow,             moting agent for centuries. Ger-                    For patients who choose to use
decreases nocturia, and decreases              man health officials have approved            herbal therapies, several guidelines
postvoid residual.101 Saw palmetto ex-         valerian for use as a mild sedative           can help them to do so most safely
tract worked as well as finasteride in         and sleep aid, based on several Eu-           and effectively (Table 5). Patients
a randomized, 6-month study of 1098            ropean clinical trials that demon-            need to understand that medicinal
men, with similar significant im-              strate these effects.                         herbs are drugs, and as such not only
provements in the International Pros-                In 2 randomized, blind, and pla-        have potential benefits, but also the
tate Symptom Score, quality of life,           cebo-controlled crossover trials              potential to interact with other drugs
and peak urinary flow rate.102 Un-             (n = 27 and n = 128), valerian (400-          and to cause toxic reactions. Pa-
like finasteride, SPE did not cause im-        450 mg before bedtime) resulted in            tients should be informed about im-
potence, decrease libido, or alter pros-       significantly improved sleep quality          portant similarities and differences
tate-specific antigen levels.                  and decreased sleep latency, with no          between FDA-approved drugs and
       A mechanism of SPE’s effect on          residual sedation in the morn-                herbal remedies, particularly that the
BPH is demonstrated in an RDBPCT               ing.108,109 In vitro, constituents of va-     herbs are not required to be proven
in which use of SPE for 3 months re-           lerian mediate the release of -               either safe or effective prior to mar-
sults in a significant decrease in pros-       aminobutyric acid110 and bind the             keting (Table 3). Given the vari-
tatic nuclear androgen and estrogen            same receptors as benzodiazepines,            able purity, potency, and quality of
receptors.103 Prostate size decreased          but with less affinity and milder clini-      herbal products, they must be se-
on serial ultrasounds in an open study         cal effects.111 Habituation or addic-         lected with care. In general, the best
of 505 men with BPH.104                        tion have not been reported.                  products are from Europe, where
       Like finasteride, SPE inhibits the            In the United States, valerian is       quality control regulations exist. In
enzyme 5 -reductase (in vitro),                approved for use in flavoring foods           the United States, large stores with
blocking the conversion of testoster-          and beverages such as root beer. No           national reputations to protect have
one to dihydroxytestosterone, a ma-            serious side effects have been re-            particular incentive to ensure qual-
jor growth stimulator of the prostate          ported. However, a small percent-             ity. Finally, patients should prefer-
gland.105 Saw palmetto extract also            age of consumers experience para-             ably use standardized products and
blocks the uptake of testosterone and          doxical stimulation, including                consult reputable sources for infor-
dihydroxytestosterone by the pros-             restlessness and palpitations, par-           mation about appropriate indica-
tate without affecting serum testos-           ticularly with long-term use.112 Some         tions, contraindications, and dos-
terone levels.105 In addition, its anti-       components display cytotoxic and              ing (see Tables 4 through 6).

                                                 ARCH FAM MED/ VOL 7, NOV/DEC 1998
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                                       ©1998 American Medical Association. All rights reserved.
Accepted for publication May 1, 1998.                              and clinical uses. HerbalGram.1994;30:33-47.                 a meta-analysis. J R Coll Physicians London.
                                                               17. Schoneberger D. Influence of the immunostimu-                1994;28:2-8.
     Thanks to the following for their
                                                                   lating effects of the pressed juice of Echinaceae      36.   Simons LA, Galaubramaniam S, von Konlgo-
thoughtful comments and assistance:                                purpureae on the duration and intensity of the               mark M, Parfitt A, Simons J, Peters W. On the
Lisa Butters, Maureen Brown, MD,                                   common cold: results of a double-blind clinical              effect of garlic on plasma lipids and lipopro-
Chris Vincent, MD, and the Swedish                                 trial. Forum Immunol. 1992;2:18-22.                          teins in mild hypercholesterolaemia. Atheroscle-
Medical Center Library staff.                                  18. Bauer V, Jurcic K, Puhlmann J, Wagner V. Im-                 rosis. 1995;113:219-225.
                                                                   munologic in vivo and in vitro examinations of         37.   Neil HAW, Silagy CA, Lancaster T, et al. Garlic
     Corresponding author: MaryAnn
                                                                   Echinacea extracts. Arzneim Forsch. 1988;38:                 powder in the treatment of moderate hyperlipi-
O’Hara, MD, Robert Wood Johnson                                    276-281.                                                     daemia: a controlled trial and meta-analysis.
Clinical Scholars Program, University                          19. Roesler J, Steinmuller C, Kiderlen A, Emmen-                 J R Coll Physicians London. 1996;30:329-334.
of Washington Health Sciences Center,                              dorffer A, Wagner H, Lohmann-Matthes M. Ap-            38.   Isaacsohn JL, Moser M, Stein EA, et al. Garlic
1959 NE Pacific, Room H-220, Box                                   plication of purified polysaccharides from cell cul-         powder and plasma lipids and lipoproteins: a mul-
                                                                   tures of the plant Echinacea purpurea to test                ticenter, randomized, placebo-controlled trial.
357183, Seattle, WA 98195 (e-mail:
                                                                   subjects mediates activation of the phagocyte sys-           Arch Intern Med. 1998;158:1189-1194.                                        tem. Int J Immunopharmacol. 1991;13:931-941.           39.   Berthold HK, Sudhop T, von Bergman K. Effect
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                                                                   Matthes M. Macrophage activation by the poly-                and cholesterol metabolism: a randomized, con-
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                                                                   ARCH FAM MED/ VOL 7, NOV/DEC 1998
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