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Herbal 'Health' Products: What Family

Physicians Need to Know
THERESE ZINK, M.D., M.P.H.,
University of Cincinnati College of Medicine, Cincinnati, Ohio
JODI CHAFFIN, R.PH.,
HealthPartners, Minneapolis-St. Paul, Minnesota
Patients who self-medicate with herbs for preventive and therapeutic purposes may assume that
these products are safe because they are "natural," but some products cause adverse effects or
have the potential to interact with prescription medications. The United States lacks a regulatory
system for herbal products. Although only limited research on herbs has been published, St
John's wort shows promise as a treatment for depression. Ginkgo biloba extract is possibly
effective for cerebrovascular insufficiency and dementia. Feverfew is used extensively in Canada
for migraine prophylaxis but needs more rigorous study. Ephedrine has been regulated by many
states because its misuse has been associated with several deaths. Echinacea is being tried as
an agent for immune stimulation, and garlic is under study for cholesterol-lowering properties, but
both require more study. Physicians should educate themselves and their patients about the
efficacy and adverse interactions of herbal agents and the limitations of our present knowledge of
them.

A significant minority of American adults self-medicate with herbal preparations for

preventive or therapeutic purposes. Sales of herbal products in the United States have
increased sharply in recent years, according to industry reports. An estimated $2 billion
was spent in health food stores in 1996 for herbs in bulk, as well as capsules, tablets,
extracts and teas.1 A 1995 telephone survey of 136 customers who purchased supplements
at two health food stores in Milwaukee during a 15-day period found that the respondents
were taking a total of 805 supplements, an average of 5.9 supplements per person. Of this
group, 85 percent reportedly had a regular physician.2
Patients may believe that herbal products are inherently safe simply because they are
"natural." Yet herbs contain hundreds of components, some of which can cause ill effects
directly, while others can interact adversely with pharmaceutical agents. Such issues are
not addressed in a systematic way in this country because the United States lacks a
regulatory system for herbal products that are marketed as "foods" or "dietary
supplements." They are not regulated under federal drug laws; safety and effectiveness do
not have to be demonstrated before these products are marketed. No legal standards are

applied to their harvesting, processing or packaging, so the possibilities of poor quality,

adulteration, contamination and varying strengths must be kept in mind when evaluating
them.
Herbs are available in a myriad of forms and dosages, but some standardized products are
beginning to appear. An herbal extract is considered standardized when a guaranteed
level of a certain constituent or group of constituents from the herb is present in the final
product. This level is usually expressed as a percentage of the weight of the extract. For
example, standardized extracts of St. John's wort use one of the plant's constituents,
hypericin, as the reference, with the concentration ranging from 0.13 to 0.3 percent.
This article discusses some of the popular herbs that our patients may be taking and
reviews what is in the literature about their effectiveness, dosages, side effects, toxicities
and possible drug interactions (Table 1). While some research studies have been
published, most of them are in languages other than English.

TABLE 1
Popular Herbal Products
Herb

Use

Echinacea

Immune
stimulation

Feverfew

Dosage

No well-controlled
studies define
dosing
Traditional dosing:
Maximum daily
dosage in adults: 6
to 9 mL of
expressed fresh
juice, or 1.5 to 7.5
mL of tincture or 2
to 5 g of dried root
Migraine headache 125 mg daily of
prophylaxis
standardized
extract
(standardized to
0.2% parthenolide)

Garlic

Atherosclerosis

Ginkgo
biloba

Mild to moderate
cerebral

Comments
Human and animal studies:
increases phagocytosis,
lymphocytic activity, cellular
respiration and activity against
tumor cells; no bactericidal and
bacteriostatic properties;
probably should not be taken for
more than 8 successive weeks;
no documented side effects,
drug interactions or toxicity

Inhibits prostaglandin production;

serotonin antagonist; not
recommended in pregnancy;
induces menstruation; caution
with anticoagulants; no
documented problems
No well-controlled Inhibits platelet function;
studes define
increases serum insulin levels
dosing
and improves glycogen storage;
Traditional dosing:4 concerns about increased
to 12 mg of allicin, postoperative bleeding
or 0.4 to 12 g of
dried powder or 2 to
5 g of fresh bulb
daily
120 to 160 mg daily Complaints of transient
of standardized
headache; no documented

St. John's
wort

insufficiency;
extract
favorable for PMS (standardized to
and vertigo
24% flavone
glycosides and 6%
terpene lactones)
Dementia
120 mg daily of
standardized
extract, as above
Mild to moderate 300 mg three times
depression
daily or 450 mg
twice daily of
standardized
extract
(standardized to
0.13 to 0.30%
hypericin)
Maximum in
studies: 1,000 mg
daily

severe side effects (one case

report of spontaneous subdural
hematoma in a healthy adult);
caution with concurrent use of
aspirin and NSAIDs

Inhibits uptake of
neurotransmitters serotonin,
norepinephrine and dopamine,
and binds to GABA receptors in
vitro; MAOI activity in vitro, not in
vivo; no major side effects--minor
complaints of dry mouth,
dizziness, constipation and
confusion; photosensitivity with
high dosages (600 mg three
times daily of 0.24 to 0.32%
hypericin); uterotonic in animals
in pregnancy; no known drug
interactions, but because of
neurotransmitter activity,
exercise caution if used with
other antidepressants

PMS=premenstrual syndrome; NSAIDs=nonsteroidal anti-inflammatory drugs;

GABA=gamma-aminobutyric acid; MAOI=monoamine oxidase inhibitor.

St. John's Wort

St. John's wort (Hypericum perforatum) has been used as a folk medicine for numerous
indications, including depression, bladder problems and dermatologic conditions. It is
licensed in Germany for use in the treatment of anxiety, sleep disorders and depression.3
Its mechanism of action in vivo is unknown, but in vitro, it inhibits the uptake of the
neurotransmitters serotonin, norepinephrine and dopamine and binds to gammaaminobutyric acid (GABA) receptors. Whether it crosses the blood-brain barrier is
unknown.4 Continued research is needed to identify the constituents most responsible for
the agent's activity so that preparations can be optimally standardized.
Most of the research on St. John's wort has taken place in Germany, where reports of
more than 37 randomized trials have been published. Two meta-analyses have been
published, one in a botanical journal5 and one in a medical journal.3 Both analyses led to
the conclusion that St. John's wort is significantly superior to placebo and comparably
effective to standard antidepressants (maprotiline, imipramine and amitriptyline) in the
treatment of mild to moderately severe depression and produces fewer side effects.
However, researchers concluded that although the data are promising, there is not yet
sufficient evidence for St. John's wort to be accepted as an effective antidepressant
preparation. No studies published to date compare St. John's wort with selective serotonin

reuptake inhibitors (SSRIs), but the U.S. National Institutes of Health has recently funded
such a study. Dose standardization, studies in severely depressed patients and long-term
studies to assess the risk of relapse and the emergence of late side effects are also needed.
St. John's wort is in the early stages of U.S. clinical trials as an antiviral agent.
The daily dosage used in clinical trials for depression has varied from 300 to 1,000 mg of
the standardized extract in tablet or capsule form. The standardized extract has ranged
from 0.13 to 0.30 percent of hypericin. (St. John's wort is also available as a tea or a
tincture.)
Study subjects have complained of dry mouth, dizziness, confusion, constipation and
other gastrointestinal symptoms.4 Photosensitivity has been demonstrated in a controlled
clinical trial with high dosages of hypericin.6 There have been some reports of
monoamine oxidase-inhibiting activity in vitro but not in vivo.6 Studies in animals have
shown slight uterotonic effects, raising concern about use in pregnancy.6 No drug
interactions have been documented in humans, but St. John's wort probably should not be
used in combination with other antidepressants because of its potential neurotransmitter
activity.7,8

Ginkgo Biloba
Ginkgo biloba health products are extracted from the world's oldest living tree. The seeds
and leaves are used in traditional Chinese medicines. A concentrated standardized extract
of Ginkgo biloba (GBE), with 24 percent flavone glycosides and 6 percent terpene
lactones, has been studied to assess its value in increasing peripheral blood flow and
dilating capillary vessels in patients with intermittent claudication and cerebrovascular
insufficiency. A review of 40 European controlled trials of GBE, eight of them judged to
be of good quality, concluded that GBE is effective for mild to moderate symptoms of
cerebral insufficiency and is promising for use in patients with intermittent claudication.9
GBE has compared favorably with placebo in the treatment of premenstrual syndrome
and vertigo.10 Several studies have examined GBE for antioxidant and cholesterollowering properties.10 One study11 showed that GBE stabilized or modestly improved the
cognitive performance and social functioning of
demented patients for the study period of six to 12
months.
Ginkgo biloba was found to
stabilize or modestly improve
The dosage of GBE used in clinical trials for
cognitive performance and
cerebrovascular insufficiency was 120 to 160 mg
social functioning in patients
daily; treatment for four to six weeks was required with dementia during a study
before positive effects were noticed.9 The dosage
period of six to 12 months.
given for treatment of dementia was 120 mg daily in
one study,11 but dosages as high as 240 mg a day
have been reported in German studies.12
Transient headache has been documented as a side effect.9 A case report13 describes
spontaneous bilateral subdural hematoma in a 33-year-old healthy woman who presented

with headache and no history of head trauma or concurrent use of aspirin or nonsteroidal
anti-inflammatory drugs (NSAIDs). She had taken 120 mg of GBE per day for two years.
The use of GBE has not been associated with other severe side effects to date. The whole
plant, seeds and pulp are occasionally associated with severe allergic reactions.10
The only published report of drug interaction with GBE involved a 70-year-old man who
had been taking aspirin for three years following coronary artery bypass surgery. He
developed a hyphema one week after he began taking GBE.14 Patients taking aspirin
should exercise caution when adding GBE therapy.14,15

Feverfew
Feverfew leaf has a long history as a folk medicine for fever, headache and arthritis. A
standardized extract is available. Canada's Health Protection Branch allows the marketing
of feverfew as a nonprescription drug for the prevention of migraine headache.16
Feverfew appears to be an inhibitor of prostaglandin synthesis and a serotonin
antagonist.17 In a large randomized, double-blind, placebo-controlled crossover trial,18
patients treated with feverfew experienced a significant decrease in headache incidence.
In another study,19 patients who were switched to placebo after taking feverfew developed
headaches, sleep disturbances, myalgias and arthralgias, a condition referred to as "postfeverfew syndrome." Feverfew has shown no apparent benefit when compared with
placebo in the treatment of rheumatoid arthritis.20
The daily dosage in studies for migraine headache prevention was 125 mg of a
standardized extract containing no less than 0.2 percent of parthenolide. Feverfew has a
short shelf life.16 No studies of long-term use or chronic toxicity have been published.
Interactions with anticoagulants have not been documented but may be clinically
important because aqueous extracts of feverfew show in vitro inhibition of platelet
aggregation.17 Feverfew should not be used by pregnant women, because menstruation
may be induced.17

Ephedrine
Ephedrine, an isolated active constituent of the herb ma huang (ephedra), is marketed as
an herbal product. Ma huang has been used in China for thousands of years as a treatment
for respiratory conditions. Ephedrine has been sold over the counter in the United States
since the 1930s for the treatment of asthma, in products such as Primatene. In the past 20
years, it has been promoted in health food stores as a "natural" herbal stimulant and
weight loss product. Side effects of ephedrine include insomnia, motor disturbances, high
blood pressure, glaucoma, impaired cerebral circulation, urinary disturbances and
hyperglycemia.7,8 Reports of widespread misuse and several deaths related to ephedrinecontaining products have led some states to impose a ban on their sale, except by
pharmacists.21 In June, 1997, the U.S. Food and Drug Administration (FDA) issued
proposed regulations that would limit the amount of ephedrine in dietary supplements.22

A combination of ephedrine and St. John's wort has been marketed as "herbal fen-phen,"
a nonprescription approach to weight loss, but no published scientific studies support its
use. Pseudoephedrine, another active constituent of ma huang, has little adverse cardiac
effect and is sold as a nasal decongestant in Sudafed and other such products.

Echinacea
Echinacea is used extensively in Germany and elsewhere to promote wound healing and
stimulate the immune system. Numerous studies of its effects have been reported, but few
are of good quality.23 Both human and animal studies show increases in phagocytosis,
lymphocyte activity, cellular respiratory activity and activity against tumor cells, but
direct bactericidal or bacteriostatic properties have not been demonstrated.23 In a doubleblind German study, flu-like symptoms were significantly reduced in persons who took
echinacea compared with those who took placebo. The benefit was evident within three
to four days.24 In another double-blind study,23 patients taking echinacea had 36 percent
fewer respiratory infections, a shorter duration of illness and less severe symptoms
compared with subjects taking placebo. Researchers at Bastyr University, a naturopathic
institution in Bothwell, Washington, are studying the effect of echinacea on the frequency
and severity of respiratory tract infections.
A German Commission E monograph, a consensus statement of expert opinions,
recommends that use of echinacea should not exceed a period of eight successive weeks
and that the agent should not be prescribed for progressive systemic diseases such as
acquired immunodeficiency syndrome, tuberculosis, collagen vascular diseases and
multiple sclerosis.25
Echinacea is administered intravenously, orally and topically in Germany. No wellcontrolled studies have evaluated the appropriate formulation or the dosages that are
available on the market. Herbal publications typically state that the maximum adult daily
dosage is 6 to 9 mL of expressed, fresh juice, 1.5 to 7.5 mL of tincture (preferred because
not all the constituents are water soluble) or 2 to 5 g of dried root.7 No reports on side
effects, drug interactions or toxicity have been published.

Garlic
Garlic has been used in a variety of ways in folk medicine for centuries. It has recently
attracted attention for its reputed ability to slow the process of atherosclerosis. The
scientific literature is contradictory. Two sets of reviewers concluded that no evidence
existed to recommend it as an effective lipid-lowering agent.26,27 Results of a metaanalysis28 led to the conclusion that although the quality of the controlled trials was
limited, the equivalent of one-half clove of fresh garlic daily could significantly reduce
total cholesterol levels. Garlic has also been studied for possible antineoplastic activity.29
Other studies suggest a mild, short-term antihypertensive effect.30 Garlic has also been
shown to increase serum insulin levels and improve glycogen storage.29 Garlic oil inhibits
platelet function.28 No published studies have evaluated the effect of garlic and its extracts
in diabetic patients or in patients treated with anticoagulants.29

The manner of consumption is important because stomach acidity inactivates allinase, the
enzyme-releasing allicin considered by most authorities to be the primary active agent
and a precursor to others. Allicin is absorbed quickly in the mouth. Thus, for maximum
effectiveness, garlic must be well masticated before swallowing or ingested in the form of
enteric-coated tablets containing carefully dried garlic powder that will be absorbed
rapidly in the small intestine. Other formulations, such as garlic oil, are less reliably
absorbed.31,32
No well-controlled studies define proper dosing. Garlic is used extensively for culinary
purposes with no known ill effects, but the safety of long-term use of concentrated
extracts is unclear.29 Some case reports indicate that nondietary or excessive intake of
garlic may increase the risk of postoperative bleeding.33

Herbal Product Safety

The FDA becomes involved in safety issues for herbal products only after they are on the
market and complaints are filed. Prescription and over-the-counter drugs are different;
they go through a premarket approval process for safety.16 The safety issues that are
beginning to be addressed are good manufacturing practices, labeling and postmarketing
surveillance. Some herbal remedies have been found to contain lead, arsenic and other
heavy metals, as well as pharmaceutical agents such as steroids and benzodiazepines.33 In
February 1997, the FDA published proposed regulations for good manufacturing
practices for dietary supplements, a category that contains herbal products.34
Under current law, only substances that are legally considered to be drugs can have
labeling on the product package that includes approved uses, dosages, possible side
effects, toxicity and contraindications. Since herbs are not classified as drugs, the package
labels of herbal products give little guidance to the consumer. The report of the federal
Commission on Dietary Supplement Labels, published in 1997,35 recommends further
research and consideration of other regulatory options, including a system of approval for
herbal products when requested by the industry. The report gives no indication as to when
appropriate labeling for self-medicating with herbal products can be expected.35
Postmarketing surveillance for adverse reactions to herbal supplements has been limited.
The Commission on Dietary Supplement Labels has recommended that the herb industry
and the FDA work together to improve the agency's tracking system for adverse effects.35
Physicians are encouraged to report individual cases of apparent drug and herb
interactions or suspected herb side effects to FDA MED WATCH at this telephone
number: 800-FDA-1088.
Concern has been expressed that the uncontrolled promotion of herbal products may
present hazards to persons who consume them. Some readers may recall events relating
to laetrile, a component of apricot pits that was promoted as an alternative cancer therapy.
Laetrile was eventually proved to be toxic (it contains cyanide) and was shown to be
ineffective in the treatment of cancer. Herbs can enhance or block the effects of
conventional drugs. Examples include the ability of ginkgo to potentiate aspirin or that of

TABLE 2
Herbal Education Resources
for Physicians
licorice to counteract antihypertensive
medications.36

Learning About Herbal Agents

Physicians are encouraged to become
acquainted with the herbal products their
patients are consuming so they can give
guidance about how patients' choices may
affect their health or current therapeutic
regimens. Reviewing the current medical
literature will provide limited information on
herbs. Other useful resources are listed in
Table 2.
The German monographs mentioned in Table
2 were published between 1978 and 1994 by a
division of the German Federal Health
Authority, which is equivalent to the FDA.
The monographs contain therapeutic
information on herbs, including
pharmacologic properties, pharmacokinetics,
toxicology, uses and contraindications. Their
content is based on traditional information
about herbs as well as laboratory data, clinical
studies, testimonials and physician input. No
plan to update these monographs has been
announced, although they are to be published
in book form (and in English) by the American
Botanical Council.

How to Talk with Patients

Review of Natural Products*

Facts and Comparisons, 111 West Port
Plaza,
Suite 400, St. Louis, MO 63146-3098;
Telephone: 314-878-2515
Herbal medicine chart
Document no. 1390901
Pharmacist's Letter and Prescriber's
Letter
Telephone: 209-472-2240; fax: 209-4722249
German Commission E monographs
American Botanical Council,
P.O. Box 144345, Austin, Texas 787144345;
Telephone: 512-926-4900
Web site: http://www.herbalgram.org
Schulz V, Hansel R, Tyler VE. Rational
phytotherapy:
a physician's guide to herbal medicine.
3d ed.
New York: Springer, 1998.
McGuffin M, Hobbs C, Upton R,
Goldberg A, eds.
American Herbal Products Association's
botanical safety handbook. Boca Raton,
Fla.: CRC Press, 1997.

*--Monograph updated on a monthly basis.

--Published by both the Pharmacist's Letter
and the Prescriber's Letter.

--To be published in book form in English

An effective strategy for talking with patients
translations in 1998.
about herbal products must take into
consideration the fact that these products are
widely marketed, and many patients are taking --The American Botanical Council is a
nonprofit research and educational
them. Their reasons for doing so vary and
association.
include belief in a product's efficacy based on
advertising, advice from friends or personal
experience. Other reasons include dissatisfaction with the conventional health care
system and a desire to be in control of their own life and health.

While there is some objective evidence for the value of some herbal products in some
conditions, this evidence is typically tentative and incomplete. Information about toxicity
and adverse interactions is similarly fragmentary.

Because the subject of medicinal herbs is complex, achieving scientific clarity and
sorting through the advertising hyperbole will be a slow and arduous process.
Physicians often talk with patients about controversial subjects, so discussing the merits
and drawbacks of herbs does not require new skills. Inquiring about the use of herbs,
vitamins and other remedies should be a part of normal history taking, along with
questions about smoking, alcohol use, exercise and other health promotion topics. Good
communication requires openness to patient choices relating to unconventional remedies
as the physician works toward shared decision making and "relationship-centered" care.37
Withholding judgment on the value of an unfamiliar remedy may be a wise course. As
experts in conventional medicine and pharmaceuticals, physicians should discuss with
each patient the treatments that are known to be effective for the condition. Patients
should receive information about the potential for drug and herbal interactions. Simply
telling patients to stop using a product if no clear risk is known can be harmful to the
physician/patient relationship. Continuing the relationship while monitoring the patient's
progress with an herbal product provides a mutual learning opportunity.
The authors thank Joyce Generali, Pharm.D., for assistance with this article.

The Authors
THERESE ZINK, M.D., M.P.H.,
is currently an assistant professor of family medicine at the University of Cincinnati
College of Medicine. Dr. Zink graduated from Ohio State University College of
Medicine, Columbus. She completed a family practice residency at Regions Family
Medicine Program, St. Paul, Minn. She obtained a master's degree in public health
administration from the University of Minnesota School of Public Health, Minneapolis.
JODI CHAFFIN, R.PH.,
is the resource pharmacist on herbs and dietary supplements for HealthPartners in
Minneapolis-St. Paul. A graduate of the University of Minnesota College of Pharmacy,
Minneapolis, she has developed continuing medical education material for physicians,
nurses and pharmacists on the use of herbal products. She also writes information
handouts on herbal medicines and teaches herbal classes for patients.
Address correspondence to Therese Zink, M.D., M.P.H., Department of Family Medicine,
University of Cincinnati, P.O. Box 670582, Cincinnati, OH 45267. Reprints are not available from
the authors.

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