The topic of this first issue -- herbal remedies -- was suggested by members of the Oklahoma Physicians Research/Resource Network (OKPRN). Alternative medicine has attracted a great deal of attention and was the subject of several articles in the November 1998 journals published by the American Medical Association (JAMA, Arch Int Med, Arch Peds Adoles Med, Arch Gen Psychiatry). Dr. Mary K. Lawler, OSU Extension Service, is guest editor. Last summer, Dr. Lawler served as advisor to Kerry Balentine, a second year medical student participating in OAFP’s Future Physicians of Oklahoma (FPO) Summer Research Track. They investigated alternative therapy use by patients in family practice settings. In that study, Dr. Lawler and Ms. Balentine identified the 10 most common herbal remedies used by patients in those practices. In this issue, we provide information about those 10 products including the usages, mechanisms of action, dosages where known, some drug interactions and the evidence available about the effectiveness of herbal products. We also include editorials from two Oklahoma physicians, Dale Petersen, MD, and Paul Preslar, DO, who share their opinions and practice regarding herbal remedies.

Laine McCarthy, MLIS, Editor-in-Chief

Mary K. Lawler, RN, Ph.D. and Kerry Balentine, MS II

Studies of patients in family practice settings have reported use of herbal remedies as high as 50 percent. A recent article in the Journal of the American Medical Association reported that 15 million Americans spent $21 billion on alternative therapies in 1997 alone. Herbal therapy is often used in conjunction with over-the-counter and prescription medications; interactions between medications and herbal products can occur.

Herbal products are not regulated by the FDA. There is no guarantee that the product purchased contains the promised herb or that the contents are free from unknown additives or other adulterants. Toxic ingredients such as pesticides, undeclared drugs, heavy metals and prescription drugs have all been found in herbal remedies. The words ìstandardized,î USP (United States Pharmacopoeia) or True Label Program on the label offer some assurance that the product has met some preparation guidelines.

Nearly 600 botanicals available on the U.S. Physicians should be routinely asking their patients about herbal products they may be taking and be prepared to openly discuss the pros and cons of herbal products with their patients but reliable information about herbal remedies can be difficult to find; most books on the subject are neither complete nor evidence-based.

In this issue, we describe the ten herbal remedies most commonly taken by patients in family practice setting in Oklahoma as identified by our survey. Where possible, we have cited relevant research and literature.

[Editor's Note: Much of the clinical evidence reported here is equivocal, antithetical and controversial. Ambiguities are most evident in the contraindications, interactions, side effects and dosing. The German E Commission Monographs, a compendium of

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Primary Use: To relieve symptoms of menopause, PMS.

Mechanism of Action:

Triterpene and flavonoid constituents bind to and presumably stimulate estrogen receptors.

Clinical Evidence:

A 1998 review of several German studies concluded that remifemin (the extract) is effective in reducing menopausal symptoms, and stimulating vaginal mucosa.

Contraindications and Side-Effects:

• Not to be taken by lactating women and women who cannot take birth control pills.
• Stimulates uterus; should not be taken by pregnant women.
• Can cause dizziness, nausea, vision problems, vomiting, hypotension.

Herb-Drug Interactions:

• Herb contains tannin which inhibits iron absorption.
• Concomitant use with estrogen replacement theoretically may cause nausea, bloating, hypotension, breast tenderness, migraine, edema. Best to avoid simultaneous estrogen use although no incidents of estrogen excess have been reported.

Dosage Recommended:

Cost: $10/60 capsules; 1 mg/capsule

Primary Use: To relieve symptoms of cold and flu.

Mechanism of Action:

Clinical Evidence:

A meta-analysis of German in vitro studies found Echinacea possesses immunostimulating properties useful in treating and preventing colds and flu. An RCT of 302 healthy volunteers given E. purpurea, E. angustifolia or placebo for 12 weeks found no prophylactic effect for either extract, possibly due in part to small sample size. There is no clinical evidence supporting bactericidal or bacteriostatic claims in vivo.

Contraindications and Side-Effects:

• Little is known about toxicity and side-effects; no chronic or acute toxicity has been documented.
• Patients with systemic and autoimmune disorders or accerlating infection (MS, RA, SLE, HIV) should not use this herb.⁶
• Potential severe allergic reactions in those with atopy.
• Do not take if allergic to daisies.

Herb-Drug Interactions:

Dosage Recommendation:

1-3 380 mg capsules 3 x daily with water at meals. Use for 5 days, stop for 2, repeat cycle for 15 days. Do not use for longer than 6-8 weeks because of lack of clinical data on long-term use and potential for reduced effectiveness.⁴ German guidelines discourage taking for >8 weeks. Prolonged use may suppress immunity.⁷

Cost: $5-$26/100 caps, 250-500 mg capsules

Primary Use: To prevent migraines

Mechanism of Action:

Clinical Evidence:

Herb-Drug Interaction:

Dosage Recommended:

Cost: $8.50/60 caps; 80 mg/capsule

Primary Uses: To reduce total cholesterol and triglyceride levels and increase HDL; to lower blood pressure.

Mechanism of Action: Some components have been found to be antibacterial and/or antimycotic; others inhibit platelet aggregation and enhance fibrinolysis. Mechanism of these actions and the purported lipid-lowering activity are unclear.

Clinical Evidence: 1994 meta-analysis of 5 controlled trials reported garlic effective in reducing triglycerides and total cholesterol. A more recent RCT of a commercial garlic oil preparation showed no effect on cholesterol synthesis or absorption and could not be recommended in the treatment of hypercholesterolemia. Another recent RCT of garlic powder tablets (Kwai) 900 mg/d for 12 weeks found no difference from placebo. However, an RCT in 41 moderately hypercholesterolemic men reported a modest reduction in both LDLs and diastolic blood pressure in response to an aged garlic extract.

Contraindications and Side Effects:

Dosage necessary to achieve physiological effects can produce diarrhea, flatulence, anti-platelet activity, dermatitis, anorexia and vomiting, hypotension, inhibition of iodine uptake.

Herb-Drug Interactions:

Dosage Recommendations:

• Usual dose 300 mg 2-3 times/day standardized as above (equivalent to 3 g or 1 fresh clove daily).
• Heat and acid destroy active ingredients; enteric-coated products show best results. No research-based clinical information available on long-term use.

Cost: (not standardized) $5-$8/100 caps; 150-580 mg/cap

Mechanism of Action:

Clinical Evidence:

Contraindications and Side-Effects:

Herb-Drug Interactions:

Dosage Recommendations:

Cost: $7-$20/60-100 cap bottle, 40-60 mg capsules.

Primary Use: To relieve stress and related ailments.

Mechanism of Action:

Principles believed to be responsible are triterpenoid saponins, called ginsenosides by Japanese and panaxosides by Russian scientists;¹⁵ contains at least 18 triterpenoid saponins, oligoglycosides that may act at different levels within the hypothalamic-pituitary-ovarian axis.

Clinical Evidence: Purported benefits include relief from effects of stress, aging, physical and mental fatigue. Little convincing scientific data exists substantiating the purported benefits. Clinical trials supporting its use were flawed and inconclusive. An RCT of healthy males found no evidence ginseng is an ergogenic aid to improve aerobic exercise. An Italian RCT, however, showed improved muscular oxygen utilization in subjects taking ginseng.

Contraindications and Side-effects:

Herb-Drug Interaction:

Cost: $12-$16/100 caps; 100-110 mg/capsule

Primary Use: To relieve mild anxiety.

Mechanism of Action:

Clinical Evidence:

RCT of 101 patients diagnosed with non-psychotic generalized anxiety disorder by DSMIIIR criteria found significant reduction of anxiety after 25-weeks; subjects received 1 90-110 mg capsule of dry extract 3 times/day. (Each capsule was standardized to 70 mg kava-lactones.) Subjects experienced no significant side effects or withdrawal symptoms. Before recommending kava, care should be taken to distinguish anxiety disorder from other disease states such as hyperthyroidism, panic disorder, and endogenous depression.

Contraindications and Side Effects:

• Mild GI distress, allergic skin rxns, sedation.
• Ataxia, somnolence, difficulty in hearing and vision.
• Consistent and heavy use can produce dizziness and yellow discoloration of hair, skin and nails.
• Do not use if pregnant, nursing, diagnosed with depression, or operating heavy machinery.

Herb-Drug Interaction:

May potentiate CNS effects of barbiturates, alcohol, antidepressants (benzodiazepines), antipsychotics. One case of coma in a patient taking kava and alprazolam was reported.

Dosage recommendations:

No clinical data available on long-term use.

Cost: $17/60 caps; 128 mg/capsule

Mechanism of Action:

Clinical Evidence:

Contraindications and Side Effects:

Herb-Drug Interactions:

Dosage Recommendation:

Cost: $12-$20/120 caps;150-900 mg/capsule

Primary uses: To relieve symptoms of benign prostatic hyperplasia (BPH); anti-inflammatory.

Mechanism of action:

Mechanism of action may include alteration of cholesterol metabolism, antiestrogenic, antiandrogenic, and anti-inflammatory effects.

Clinical evidence: Systematic review of 18 RCTs found it produced similar improvement in urinary tract symptoms and urinary flow with fewer adverse events compared to finasteride. Average study duration was 9 weeks.

Contraindications and side-effects:

• erectile dysfunction
• mild headache, nausea, and dizziness
• possible hypertension

Herb-Drug Interaction:

• No serious drug interactions have been reported but clinical trials usually exlcuded men taking diuretics, alpha blockers and anti-coagulants.

Cost: $6-$15/60 caps; 150-160 mg/capsule

Primary Use: Sedative, hypnotic anxiolytic.

Contraindications and Side-effects:

Herb-Drug Interaction:

Dosage recommended:

Cost: $8/100 caps; 530 mg/capsule

The American Botanical Council: http://www.herbalgram.org/
Alternative Medicine Alert: www.altmednet.com/
                                          www.ahcpub.com/altmed.html
Health World Online: www.healthy.net
Medscape: www.medscape.com/
Medical Matrix: www.medmatrix.org/
NN/LM Guide to Internet Discovery: Tools for Health Professionals  www.nnlm.nlm.nih.gov/tools.html
U.S. Pharmacopia: www.usp.org/did/mgraphs/botanica
Office of Dietary Supplements: dietary-supplements.info.nih.gov
Herbnet: www.herbnet.com/
Bastyr University: www.bastyr.edu/
Alternative Health News Online: www.altmedicine.com/
Herbal Reference Library: www.all-natural.com/herbindx.html
Quackwatch: www.quackwatch.com/
Natural HealthLine: www.healthvillage.com/

Acupuncture
http://wwwindex.nlm.nih.gov/pubs/cbm/acupuncture.html

Path: oam/resources/cam-ci/

The fact that this initial issue of Primary Care Exchange is dedicated to a presentation of herbal remedies says much about the direction medical care has been moving over the past decade. When I began asking patients about their intake of supplements, less than 10% were taking anything, and it was a rare individual who had tried an herbal remedy. Today a majority of my patients are taking supplements and many prefer herbal therapies.

Given the wealth of information now available via the internet, through practitioners of other disciplines, and in print, it is time for us to stop using the royal "we" when addressing questions related to herbs and other supplements. It is far better to be honest and say, "I don't know anything about that.", than to hide behind the collective, "We don't know anything about that," as though no information on the subject existed. Intelligent people are becoming aware that peer reviewed medical journals do not represent the sole (nor necessarily the best) source of knowledge regarding health and nutrition. Due to economic constraints, we are unlikely to see many double-blinded, placebo controlled, cross-over studies of herbal preparations. Still, centuries of common usage coupled with an understanding of the mechanism of action is not bad clinical evidence.

Family physicians should be aware of several factors when evaluating or recommending herbal products. First, herbs encompass a very wide spectrum. Traditional Chinese herbalists separate herbs into various categories. Some herbs are considered "superior" herbs. These are substances that support basic functions within the body and are safe for long-term consumption. Other herbs are classified as "inferior" herbs, not because they are less active or less effective, but because they have a greater potential for producing harmful or unwanted effects and are recommended only for short term use to correct specific imbalances in the body.

Second, herbs generally work more effectively in combination. This is in stark contrast to the standard medical paradigm which suggests that it is better to treat with a single drug whenever possible. Traditional Chinese herbalists commonly use a dozen or more herbs in a single remedy.

Third, herbal products sold in the United States are largely unregulated. The consumer must seek out products from manufacturers with high internal quality control standards. Professionals who recommend herbals must be aware of the quality of those products. A wise practitioner will not risk endorsing an herbal formulation that contains no activity or, worse still, is laced with contaminants. Some companies have been found to extract hypericum from St. John's wort, then sell the extract to one source and the residual "St. John's wort" to another. High lead or mercury levels have been discovered in other preparations.

Finally, a physician should recognize the limits of his or her knowledge. Reading a brief overview such as this does not make one an expert in herbal medicine. Texts, such as the recent translation of the German Commission E documents, courses, and journals are available to provide more detailed information to those interested in incorporating herbal remedies into their practices.

Dale H. Peterson, M.D.

Private Practice

Edmond, Oklahoma

As an osteopathic physician, I was trained, and whole-heartedly believe, that the balance of the mind, body, and soul make a healthy person. I have been opened-minded in the use of acupuncture, chiropractic, and other alternative medicine options. In my practice with the Central Oklahoma Medical Group (COMG), I have received many inquiries from patients regarding "herbal remedies." My standard response has been, "I have enough trouble keeping up with the FDA-approved medications, where I know their drug interactions have at least been tested for 5-10 years before being released."

As pointed out by Drs. Angell and Kassirer, in a recent article in the New England Journal of Medicine, what most sets alternative medicine apart from ordinary medicine is that it has not been scientifically tested and its advocates largely deny the need for testing. They rely on anecdotes and theories (usually published in books and magazines for the general public), considered sufficient in themselves as support for therapeutic claims.

Until the 20th century, most remedies were botanicals, found through trial and error to be helpful. But therapeutic successes with botanicals came at great human cost.

No longer must we rely on trial and error or anecdotes. We now demand reliable evidence before drugs are permitted to be marketed. However, in 1994, in response to the lobbying efforts of the multibillion-dollar "dietary supplement" industry, Congress exempted these products from FDA regulation. (Homeopathic remedies have been exempted since 1938.) Since then, these products have flooded the market, subject only to the scruples of their manufacturers. The FDA can intervene only after a product has been shown to be harmful.

Most patients do not understand that the bioavailability, stability, and purity of herbal mixtures can influence the safety and efficacy of these products. The bottomline, caveat emptor -- buyer beware! My advice...save your money, maintain a healthy eating and exercise program, see your family physician and follow their advice.

Paul Louis Preslar, DO, MBA

American Board of Family Practice

American Osteopathic Board of Family Physicians

Central Oklahoma Medical Group

Dept. of Family & Preventive Medicine

The University of Oklahoma Health Sciences Center

900 NE 10th Street

Oklahoma City, Oklahoma 73104-5499

(405) 271-4224

The University of Oklahoma Health Sciences Center is an equal opportunity institution.

This publication, printed by Printing Services in Norman and is issued by the Board of Regents of the University of Oklahoma as authorized by 70 Okl. State 1981 §3305(o). 1,200 copies have been prepared and distributed at a cost of $490. Copies will be deposited with the University of Oklahoma Health Sciences Center Library. (January 1999)