AAFP 2006 - Evidence-Based Complementary and Alternative Medicine (CAM): What Should Physicians Know?

Désirée Lie, MD, MSEd

Disclosures

December 11, 2006

Editorial Collaboration

Medscape &

Introduction

The herbal and dietary supplement industry is currently booming, with annual sales of over $20 billion in the United States.[1] Being well informed and current about patient use of complementary and alternative medicine (CAM) has become part of daily practice as more patients obtain and use over-the-counter dietary supplements and herbal products, based on Internet and other marketing sources. Questions of safety and efficacy are important to address as is awareness of potentially harmful drug-dietary supplement interactions, only some of which find their way into the popular media. At the 2006 American Academy of Family Practitioners (AAFP) Annual Scientific Assembly, Robert A. Bonakdar, MD, FAAFP, Director of Pain Management at Scripps Center for Integrative Medicine, La Jolla, California, addressed the major questions facing physicians as their patients disclose their CAM use.[2] Mary Elizabeth Roth, MD, FACPE, President of the Pennsylvania Academy of Family Physicians Foundation, Allentown, Pennsylvania, focused on natural therapies and options other than hormonal replacement therapy, currently available for menopausal symptoms, including evidence for their safety and efficacy.[3]

Herbal and Dietary Supplements: An Evidence-Based Update

Dr. Bonakdar offered double continuing medical education (CME) credit to his audience along with a dynamic, evidence-based presentation on current issues most often addressed by patients and physicians. He reviewed patterns of dietary supplement use, safety, regulation, efficacy, potential adverse effects and drug interactions based on known prevalence of use in the United States. After prayer, dietary supplements are the most commonly used type of CAM[4] and use is higher in those who[4,5]:

  • Are female (ratio of 2:1 compared with males);

  • Have achieved a higher education level;

  • Demonstrate active coping behaviors; and

  • Are healthy or have chronic health conditions.

Patients are more likely to receive CAM information from friends, family, the popular media and the Internet than from their physicians.[6,7] In a recent poll[7]:

  • 68% of Americans believed that dietary supplements were regulated by the government;

  • 55% believed that manufacturers could not make claims of product efficacy without scientific evidence; and

  • 59% believed that dietary supplements were FDA-approved.

Several sources suggest that patients underreport dietary supplement use to physicians[8,9,10] because the physician "did not ask," "would not understand," or "would disapprove."[11] Disclosure rates do increase when physicians ask about usage.[12]

The top herbals used in 2004 were:

  • Garlic;

  • Echinacea;

  • Saw palmetto;

  • Gingko;

  • Soy;

  • Cranberry;

  • Ginseng;

  • Black cohosh;

  • St. John's wort; and

  • Milk thistle.

Patients undergoing surgery are at particularly increased risk for bleeding complications if use of herbals or dietary supplements is not elicited by the provider.[13,14] Commonly used dietary supplements associated with blood thinning include garlic, ginseng, and gingko. Each of these agents should be discontinued at least 2 weeks before surgery.[15]

Other agents of concern around the time of surgery, because they may interact with the sedative effects of anesthesia or with liver metabolism of drugs, include echinacea, kava, valerian, and St. John's wort.

Dr. Bonakdar recommended several up-to-date and reliable sources for physicians seeking more information on drug-herb interactions. (See Resources section at the end of this article.)

Regulation of Dietary Supplements

Dietary supplement regulation is currently dictated by the Dietary Supplement Health and Education Act (DSHEA) of 1994, which allows initial marketing without proof of safety, efficacy, bioavailability or standardization.[16] A recent proposal, yet to be legislated, suggests setting Good Manufacturing Practices (GMP) for manufacturing, packaging, and holding of dietary supplements, and Qualified Health Claims have been proposed by the FDA.[17] There is also a suggestion for mandatory reporting of botanical drugs such as cascara sagrada (sacred bark; bitter bark), psyllium, and senna.[18]

Within the dietary supplement industry, self-regulation occurs to a limited degree. Consumer Lab, for example, is an independent organization that offers random third-party shelf testing of branded dietary supplements, with a seal of approval offered to products passing their testing. The National Sanitation Foundation is involved in field testing and the Dietary Supplement Verification Program works with the FDA and manufacturers to set standards. The FDA now provides a hotline for reporting any illness or injury specifically associated with a dietary supplement: 1-800-FDA-1088. Unlawful sales of dietary supplements on the Internet should be reported to the FDA and the Federal Trade Commission (FTC). (See Resources section.)

Despite the lack of regulation (or perhaps because of it), control is sorely needed due to dose variability, adulteration, mislabeling, inadequate labeling, and inconsistent reporting of adverse effects. Examples given by Dr. Bonakdar included:

  • Adulteration of the Chinese herbal Liqiang with glyburide in 2005;[19]

  • Controversies about the potential hepatotoxicity of both black cohosh[20,21] and kava;[22,23] and

  • The ban on ephedra by the FDA in 2004, now partially reversed to include only doses over 10 mg.[24]

There now is also a long list of products available with claims similar to ephedra, including bitter orange, Hoodia gordonii, and guarana seed.

In an overview of the most commonly used dietary supplements, Dr. Bonakdar summarized the recent evidence as follows:

  • Glucosamine and chondroitin for knee osteoarthritis: A recent Cochrane review[25] provided evidence of efficacy for glucosamine compared with placebo, with 2 trials showing better efficacy than nonsteroidal anti-inflammatory drugs (NSAIDs); the benefit of chondroitin is less certain. To date, glucosamine sulfate (rather than hydrochloride) at a dose of 1500 mg daily has been shown to be a more effective product than chondroitin.

  • St. John's wort is best used, if indicated, for mild-to-moderate depression[26] and has both serotonergic and dopaminergic effects. Use should be avoided with products with synergistic effects. If efficacious, effects should be seen within 3 weeks and side effects within 2 weeks. St. John's wort should not be used concomitantly with cytochrome P450-inducing liver enzyme drugs and should be discontinued before surgery.

  • Gingko has bleeding side effects and, although touted for memory improvement, has only shown minor-to-moderate benefit for cognitive impairment associated with dementia progression.[27] There is currently no head-to-head trial comparing it with Alzheimer's disease medications. Use should be discontinued before surgery.

  • Plant sterols and stanols are used for hyperlipidemia with a 10% reduction in LDL cholesterol.[28] They have additive effects with statins[29] and should not be used in combination.

  • Fish oils have anti-inflammatory, antiplatelet and antithrombotic effects;[30] 2-3 g daily reduces LDL cholesterol and triglycerides,[31] with reduction in sudden death[32] and myocardial infarct shown in one trial; a benefit for cancer prevention, however, has not been shown.

Principles recommended by Dr. Bonakdar to physicians for using and selecting dietary supplements and for advising patients are listed as follows[33]:

  1. Seek evidence of laboratory testing on the bottle.

  2. Choose herbals or dietary supplements that have been on the market for a long period without reported serious adverse effects.

  3. Find products with good clinical trials demonstrating efficacy.

  4. Use single-agent products rather than those with multiple agents.

  5. Examine the evidence for efficacy and safety using available evidence-based sources.

In office practice, document the type, brand name, and dosage used by patients so that drug-herb interactions can be anticipated when prescribing drugs.

Natural Therapies for Menopausal and Perimenopausal Symptoms

Vasomotor symptoms (hot flashes) affect 85% of women in perimenopause and menopause;[34] currently, only one third of women wish to use hormone replacement therapy for menopausal symptoms due to concerns about the findings of the Women's Health Initiative.[35] The North American Menopause Society (NAMS) practice guidelines recommend lifestyle change including diet, exercise, smoking cessation, and stress management as the first line of treatment for such symptoms, followed by nonpharmacologic and then pharmacologic therapies.[35] The use of nonhormonal therapies for the treatment of menopause was recently reviewed.[36,37] Position statements on the treatment of menopause-related symptoms have been offered by NAMS, American College of Obstetricians and Gynecologists (ACOG), and the Agency for Healthcare Research and Quality (AHRQ).[35,38,39]

Among the natural products on the market, Dr. Roth discussed the following[3]:

  • Unopposed transdermal progesterone as reviewed in 2005 by Wren with the conclusion that the evidence was currently anecdotal and not based on sound scientific research.[41] ACOG's Report on the Use of Botanicals for Menopause Symptoms[42] and NAMS[36] both agreed that scientific data for the safety and efficacy of progesterone creams was lacking and neither recommended this therapy.

  • The use of compounded bioidentical estrogen therapies such as estriol only and combinations of estradiol, estriol, and estrone is discouraged by ACOG because of lack of rigorous clinical testing for safety and efficacy; concerns about potency, purity, and quality of products; and the failure of many products in quality tests.[43]

  • Phytoestrogens comprise mainly plant products including isoflavones (found in soy bean products), lignans (found in whole grains, flaxseed, and vegetable oils) and coumestans (found in red clover, sunflower seeds, and sprouts). ACOG concluded that soy and isoflavones may be helpful for short-term (less than 2 years) use to control vasomotor symptoms. Given the possibility that these compounds may interact with estrogen, these agents should not be considered free of potential harm in women with estrogen-dependent cancers.[42] NAMS adds that the use of soy and isoflavones may improve lipoprotein profile and reduce cardiovascular risk.[44] Evidence for the beneficial effects of phytoestrogens is increasing, but further studies are needed.[45]

  • Testosterone therapy has not been recommended for the treatment of menopausal symptoms due to concerns about cardiovascular safety and breast cancer risk,[46] despite a conclusion of a Cochrane review that adding testosterone to hormone therapy improved sexual function in postmenopausal women.[47]

  • Red clover and Chinese ginseng are dietary supplements for which evidence is currently still lacking. Efficacy and safety concerns have been voiced by ConsumerLab.com as has some question about the quality and purity of supplements on the market.[48,49]

  • Black cohosh: NAMS has recommended that treatment with black cohosh is "likely to do no harm and may provide relief of hot flashes"; at the same time, NAMS discourages use of dong quai, evening primrose oil, ginseng, licorice, Chinese herb mixtures, acupuncture, and magnetic therapy[44]

Dr. Roth concluded with the following recommendations for physicians from ACOG[42]:

  1. Elicit history of use of herbals and dietary supplements from patients and document this in their charts.

  2. "Natural" ingredients are not an assurance of safety or efficacy.

  3. Be alert to potential drug-herb interactions.

  4. Use only recommended doses of botanicals and dietary supplements.

  5. The placebo effect ranges from 10% to 30% and a positive effect does not necessarily indicate efficacy for conventional or alternative treatments.

Resources Herb and Supplement Information, and Drug-Herb Interactions Regulation of Dietary Supplements

www.consumerlab.com
www.nsf.org
www.uspverified.org

FDA Hotline to report adverse effects associated with any dietary supplement: 1-800-FDA-1088 or online at http://www.fda.gov/medwatch/report/hcp.htm

Report unlawful Internet sales to both the FDA at http://www.fda.gov/oc/buyonline/buyonlineform.htm and the FTC at http://www.ftc.gov/

References
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