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Herbal Therapy: What a Clinician Needs to Know to Counsel Patients Effectively

  • Brent A. Bauer
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    Address reprint requests and correspondence to Brent A. Bauer, MD, Division of Area General Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905
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    From the Division of Area General Internal Medicine, Mayo Clinic, Rochester, Minn
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      The use of herbal medicine in the United States has been increasing at a steady pace over the past decade. Most recent estimates suggest that the US population spends $5 billion per year for herbal supplements alone. Herbal supplements are receiving increasing exposure through national media, in lay journals, and more recently in the scientific press. Interest in herbal medicine has been facilitated by multiple factors, including the perception that. pharmaceutical medications are expensive, overprescribed, and often dangerous. Alternatively, herbal medicine is often perceived as being “natural” and is therefore considered safe. While the growth of the herbal medicine industry in the United States can probably not continue at this accelerated pace indefinitely, there is little indication of any major slowing. Therefore, patients will continue to use herbal medications. Knowledge of these preparations (including their potential benefits and risks as well as their ability to interact with pharmaceutical medications) will enable physicians to provide a balanced and objective view to patients seeking information on herbal therapy.
      DSHEA (Dietary Supplement Health and Education Act), FDA (Food and Drug Administration), NCCAM (National Center for Complementary and Alternative Medicine), NF (National Formulary), ODS (Office of Dietary Supplements), PDR (Physicians' Desk Reference), USP (United States Pharmacopeia)
      Based on recent estimates, Americans spend $5 billion annually for herbal supplements. Physicians need to become familiar with the potential risks and benefits of these preparations, as well as their ability to interact with pharmaceutical medications, so that they can discuss these issues with their patients.

      HERBS

      By strict botanical definition, an herb is “a seed-producing annual, biennial, or perennial that does not develop persistent woody tissue but dies down at the end of a growing season.”
      Of course, patients and consumers do not adhere to this strict classic definition when inquiring about or using “herbal” products. Another definition for an herb is a “plant or plant part valued for its medicinal, savory, or aromatic qualities.”
      This broader definition is probably closer to most people's concept of herbal medicines. For example, gingko is a popular herb but is actually a tree. To avoid semantic confusion, some experts prefer the term botanical, which encompasses any plant-derived product used for a medicinal or health purpose. Others use the term phytomedicine or phytotherapeutics to denote plant-derived products used for medicinal purposes.
      Further complicating the issue is the fact that herbs are also classified as dietary supplements, as a result of the Dietary Supplement Health and Education Act of 1994 (DSHEA).
      • US Food and Drug Administration
      • Center for Food Safely and Applied Nutrition
      Any discussion of herbal therapies requires an understanding of this classification and its regulatory implications.

      DIETARY SUPPLEMENTS

      For the purposes of the DSHEA, a dietary supplement (1) is a product (other than tobacco) that is intended to supplement the diet that bears or contains 1 or more of the following ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid; (2) is intended for ingestion in pill, capsule, tablet, or liquid form; (3) is not used as a conventional food or as the sale item of a meal or diet; and (4) is labeled as a dietary supplement.2 Of note, this classification of dietary supplements is specifically separate from food or drug categories and, as such, lies outside the jurisdiction of many of the safety and regulatory rules that cover these categories.

      CURRENT REGULATORY STATUS OF HERBS IN THE UNITED STATES

      The current regulatory status of herbs is directed by the DSHEA. In the late 1980s and early 1990s, concern was growing regarding the safety of the herbs and other supplements that Americans were consuming in ever-increasing amounts. The eosinophilia-myalgia syndrome (which resulted from tainted preparations of l-tryptophan) was a particularly notable incident of harm arising from these products. Thus, in the early 1990S, the Food and Drug Administration (FDA) set forth a proposal to increase the regulatory oversight of this type of product. However, herbal manufacturers and many consumers viewed this as the first step toward eliminating access to dietary supplements. An unusually effective campaign flooded mem bers of Congress with pleas to preserve access to and availability of herbs and other supplements. Congress responded by passing the OSHEA, an act that in many respects had the opposite effect of the FDA proposal. Rather than creating more stringent controls for the quality and safety of herbs, the DSHEA granted some unique exemptions and privileges to the class of agents known as dietary supplements.
      The DSHEA created a new and broader definition for dietary supplements that includes vitamins, minerals, herbs, botanicals, amino acids, and “other dietary substances for human use to supplement the diet.” The act specifically states that, unlike pharmaceutical preparations, dietary supplements can be marketed without proven safety or efficacy. Thus, it is the responsibility of the FDA to ensure safety. Rather than requiring manufacturers to perform extensive tests to prove safety or efficacy, the DSHEA basically means that the FDA must demonstrate that a supplement is unsafe. Thus, the FDA can restrict the sale of an herbal product only if well-documented health problems have occurred.
      Furthermore, for the first time, the DSHEA allowed herbal preparations to have suggested dosages on the label. Before the DSHEA, herbal preparations could not suggest a dosage without the risk of being classified as a drug and being subjected to the tighter regulatory oversight that is associated with drugs.
      The DSHEA prevents manufacturers from making specific medical claims (ie, saw palmetto reduces the frequency of urination). However, the act allows descriptions of the herb's effect on “structure or function” of the body. Thus, a claim that saw palmetto promotes healthy prostate functioning is acceptable. The distinction between medical claims and structure or function claims is often a fine line, and many manufacturers have tested the limits of this restriction. Recently, claims made by herbal manufacturers have come under greater scrutiny, and some penalties have been levied against manufacturers whose claims were deemed medical. Interestingly, the DSHEA mandates that the following disclaimer be present on each product label, “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.” However, much like warnings on cigarette packages, this disclaimer seems to be relatively unnoticed by most consumers. A common misperception is that, because the herb is in a sealed plastic container on a shelf next to other products, such as overthe-counter drugs that are FDA approved, herbs must also be FDA approved.
      In this regulatory environment, US herbs should be viewed as a “buyer beware” situation. With limited regulatory oversight, herbs in the United States have no guarantee on quality, batch-to–batch variability, or even identity of products being sold. There are well-documented cases of inaccurate labeling, intentional substitution, etc, which truly create a caveat emptor situation.

      PURITY OF HERBS

      The DSHEA gives the FDA authority to establish good manufacturing practice regulations regarding the preparation, packaging, and storage of dietary supplements under conditions that would ensure their safety. Some manufacturing groups have begun implementing voluntary standards and policing efforts. At this time, however, there is still no formal regulatory oversight to ensure that all dietary supplement manufacturers adhere to good manufacturing practices.

      UNITED STATES PHARMACOPEIA DESIGNATION

      The United States Pharmacopeia (USP) is a not-forprofit private organization that sets the standards man ufacturers must fulfill to sell their drugs in the United States. The USP has also established standards for botanical and nonbotanical dietary supplements. Dietary supplements may carry the USP symbol if they comply with the appropriate standards and if the supplement has an FDA-approved or USP-accepted use. Thus, consumers who purchase a product that carries the USP symbol are ensured that the supplement fulfills USP standards for identity, strength, quality, purity, packaging, and labeling.
      Since most herbal products are sold as dietary supplements (and hence do not have FDA-approved uses), most will not qualify for a USP designation. However, a substance that does not have FDA approval or a USP-accepted use but has been used extensively with no documented adverse safety risks may carry the National Formulary (NF) symbol. Thus, an herbal product that carries the NF designation fulfills the quality standards set by the USP but does not carry FDA or USP endorsement regarding its intended use.

      PATIENT INTEREST IN HERBAL MEDICINE

      There are many theories to account for the rapid increase in the use of herbal products in the United States during the past 20 years. Some cite the political and social upheaval of the 1960s and the subsequent reemphasis on “back-toearth” philosophies. Others point to a growing disenchantment with pharmaceutical medications. In the early 1900s, herbs and herbal preparations constituted a substantial portion of the pharmacopeia of the United States. Many pharmaceuticals in common use today had their origins in herbal preparations (aspirin from willow bark, digitalis from foxglove, etc). However, because of the lack of standardization and the variability of potency of preparations, safe and reproducible results were difficult to achieve. Hence, purified and standardized preparations became more prevalent, helping to initiate the growth of the pharmaceutical industry. By the mid–1900s, numerous serious illnesses were being effectively treated with pharmaceutical medications (eg, antibiotics). This led to an expectation that eventually all illnesses would be conquered with pharmaceuticals. Modem medicine, while amazingly successful in some areas, has not been particularly effective in eradicating many chronic diseases (eg, hypertension, arthritis, dementia, etc). Disenchantment with the unfulfilled promises of the pharmaceutical preparations has led many people to look for alternatives, including those within the herbal realm.
      Awareness of herbs has also been facilitated by the proliferation of home computers and the explosive growth of the Internet, which have provided ready access to information about herbs. Ordering supplies of botanical products from around the world is usually an easy process.
      The establishment of the Office of Alternative Medicine (by congressional mandate in 1992), which has now become the National Center for Complementary and Alternative Medicine (NCCAM), was in response to growing public demand for information on complementary and alternative medicine. Now, in 2000, with a budget of almost $70 million, the NCCAM is increasing patient awareness of complementary and alternative medicine in general and herbal therapy in particular. This is occurring as patients hear about large clinical trials and grants via press coverage. The NCCAM Web site is also frequently visited by consumers looking for reliable information.
      The public has recently been inundated with reports of adverse outcomes from pharmaceutical medications. Statistics are cited on the evening news and front pages of newspapers, suggesting a high rate of mortality in US hospitals due to pharmaceutical misfortunes. Adding further to the public's disillusionment with pharmaceutical medications is the perception that many are prohibitively expensive. Thus, patients seeking alternatives have been attracted to herbs and herbal preparations. Herbs are generally viewed as “natural” and therefore gentler and safer than pharmaceuticals. Promoters of herbal medicine emphasize the role of herbs in preventing disease or restoring health, often implying that traditional medicine or pharmaceutical medicines treat disease whereas herbs are often viewed as promoting health.
      Another major factor has been the move from a paternalistic form of medical practice to one in which patients often wish to be viewed as collaborators in their health care. Having access to herbs allows patients to self medicate and thereby control more of their health care decisions.

      CONTROVERSY SURROUNDING HERBAL STUDIES

      When one considers the billions of dollars spent worldwide on various herbal medicines, it would seem reasonable to expect that a great deal of scientific literature is available to support herbal medicines. Unfortunately, rigorous scientific data are rarely available. While many herbs have been studied, frequently in European trials, the quality of the data is often suspect. Some studies have been faulted because pharmaceutical companies or herbal manufacturers have sponsored them. Many of the studies have a small number of subjects or are of brief duration. Still other studies are not available in English translation.
      When the limitations of these studies are recognized and compared to the usual studies and documentation required to bring a new pharmaceutical to the US market, physicians understandably become hesitant to embrace herbal therapies. The average cost to bring a new medication to the US market has been estimated at $350 million, reflecting the huge investment in research, regulatory hurdles, etc. However, because most herbs are not patentable, there is little incentive for a manufacturer to pursue such a rigorous scientific undertaking. Fostering research is critical since such studies would confirm the efficacy of some compounds while revealing the lack of efficacy or even toxicity of others. Once the “wheat is separated from the chaff,” identification of active ingredients in efficacious herbs might reasonably yield even safer and more purified forms. Such scientific scrutiny should help society weigh the costs and benefits of currently popular herbs, leading to more appropriate use and greater safety.
      Supporters of herbal medicine counter that such extensive studies are not needed. They point to the historical use of certain herbs over many centuries (eg, in Europe and Asia) as a good indication that herbs are not only effective but also safe. Hence, expensive evidence-based studies are viewed as unnecessary.
      Herbal detractors counter with recent reports of adverse effects of classically used preparations (eg, bleeding episodes after gingko use.
      • Matthews Jr, MJ
      Association of Ginkgo hiloba with intracerebral hemorrhage [lelter].
      • Rosenblatt M
      • Mindel J
      Spontaneous hyphema associated with ingestion of Ginkgo biloba extract [letterl.
      • Rowin J
      • Lewis SI
      Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion.
      interactions of St John's wort with prescription medications
      • Piscitelli SC
      • Burstein AH
      • Chain D
      • Alfaro RM
      • Falloon J
      Indinavir concentrations and St John's wort [letterl.
      • Johne A
      • Brockmoller J
      • Bauer S
      • Maurer A
      • Langheinrich M
      • Roots I
      Pharmacokinctic interaction of digoxin with an herbal extract from St John's wort.
      ). Acute rejection in 2 heart transplant patients due to a metabolic interaction of St John's wort and cyclosporine has been reported.
      • Ruschitzka F
      • Meier PJ
      • Turina M
      • Luscher TF
      • Noll G
      Acute heart transplant rejection due to Saint John's wort [letter].
      Herbal detractors point out that these adverse effects or interactions were not identified or discovered by simple reliance on historical use information. Scientifically rigorous placebo-controlled trials with adequate numbers of subjects followed up for extended periods are needed to ensure not only efficacy but also safety of herbal preparations.
      Thus, tension persists between herbal supporters (who believe that available information is adequate to justify use) and herbal detractors (who believe that herbal medicines should undergo the same degree of scrutiny that pharmaceutical medications currently undergo). Because it is unlikely that the herbal industry will invest substantial funds to investigate products that are already multimilliondollar sellers, the resolution to this tension will likely be the province of nationally funded studies. The NCCAM and the Office of Dietary Supplements (ODS) are currently funding such studies. Performed primarily by academic centers, this small but growing body of literature should bring scientifically valid information to the arena of herbal therapy.

      EUROPEAN PHYSICIANS' VIEW OF HERBS

      Of importance, many of the positive comments regarding the use of herbal supplements have been from the European experience. In Germany, herbal medicines are standardized, frequently prescribed by physicians, and generally covered by insurance. This standardization makes the reliability of obtaining the same amount of an active ingredient from a given preparation over time highly likely. Because of this standardization, along with greater experience over many years, European physicians have generally taken a more favorable tone regarding the use of herbs. This increased comfort with herbal preparations is also demonstrated by the much greater per capita expenditure for herbal medicine in the European countries.

      RISKS ASSOCIATED WITH USING HERBAL THERAPIES

      Because many herbs are collected from various sources worldwide, the collector may or may not have specific education in discerning a beneficial plant from a similar appearing but dangerous plant. Foxglove being substituted for plantain has led to digitalis poisoning in one well documented instance.
      • Slifman NR
      • Obermeyer WR
      • Aloi BK
      • et al.
      Contamination of botanical dietary supplements by Digitalis lanata.
      There are numerous cases of intentional substitution of herbs (eg, mandrake for ginseng) with subsequent toxicity. There is also concern that some traditional medicines actually include heavy metals, such as lead,
      • Keen RW
      • Deacon AC
      • Delves HT
      • Moreton JA
      • Frost PG
      Indian herbal remedies for diabetes as a cause of lead poisoning.
      as an active ingredient (eg, ayurvedic preparations for diabetes, Mexican preparations for infant colic). Other documented cases have shown the presence of corticosteroids and anti-inflammatory drugs in “natural” preparations touted as being beneficial for rheumatoid arthritis.
      • Myerson GE
      • Myerson AS
      • Miller SB
      • Goldman JA
      • Wilson Jr, CH
      Chinese “herbal medicine” mail order syndrome-a cause of hypercortisonism (abstract 1.
      Cases of liver toxicity, especially from herbs containing pyrrolizidine alkaloids (eg, comfrey
      • Winship KA
      Toxicity of comfrey.
      ), are also described frequently in the literature. The “Chinese herb nephropathy” is a well-published phenomenon
      • Vanherweghem JL
      • Depierreux M
      • Tietemans C
      • et al.
      Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs.
      that occurred in many female patients attending a weight loss center where misidentified Chinese herbs were used. Several of these patients eventually required dialysis and renal transplantation.
      Finally, greater appreciation for the potential interactions between herbs and pharmaceutical drugs is growing.
      • Miller LG
      Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions.
      In addition to the examples cited earlier, studies have indicated that St John's wort may inhibit the bioavailability of certain antiretroviral agents. Possible interactions with anesthetic agents during surgery from central nervous system-active herbs (eg, valerian and kava) are a growing concern. Careful preoperative screening should include specific inquiry about the use of herbs or other dietary supplements. Discontinuation of supplements at least 1 week before surgery is a prudent strategy, at least until more information is available.

      LEGAL RISKS ASSOCIATED WITH HERBAL THERAPY

      Literature is evolving regarding legal risks to physicians who refer patients for alternative therapies, including herbal therapies. Referring a patient to an herbalist or naturopath may engender some risk of liability if that practitioner subsequently injures the patient. This is especially likely if the referring physician maintains some supervisory role in the care provided by the other practitioner. Even recommending a trial of an herbal product to a patient may imply some risk since the quality and purity of the substance that the patient will be purchasing may be suspect under the current regulatory status in the United States.
      With the growing number of reports in the medical literature of the high use of herbal supplements by patients (studies suggest that between 40% and 60% of patients are using dietary supplements), physicians must carefully inquire about herbal or dietary supplement use from each patient. Failure to ask may result in under recognition of toxicity of preparations that patients are using, as well as herb-herb interactions or drug-herb interactions. A discussion with patients regarding the use of herbal supplements should include a careful explanation of the current regulatory status and the possible lack of satisfactory good manufacturing practices. Most herbs have not been studied adequately in children or in pregnant women. Thus, it is prudent to counsel against use in these populations.

      REFERENCES ON SPECIFIC HERBAL THERAPIES

      Many patients and physicians have heard of the Therapeu tic Guide to Herbal Medicines: Complete German Commission E Monographs,
      This work was translated into English for the first time in late 1998. It provides a 1– to 2–page monograph on approximately 300 commonly used herbs. Each monograph contains the name of the herb, the composition of the herb, its uses, contraindications, adverse effects, interactions with other drugs, and dosage. This source has been criticized by some because it is not referenced. A more recent version, Herbal Medicine: Expanded Commission E Monographs,
      focuses in detail on approximately 100 herbs. This expanded version contains references and has generally been found to be helpful for practitioners trying to answer questions about herbal therapy.
      The PDR for Herbal Medicine
      follows the format of the familiar Physicians' Desk Reference (PDR).
      It is indexed by both the scientific and the common names of herbs, by indications, by therapeutic category, and by adverse effects. It has a drug-herb interaction guide, an herb identification guide, and herbal monographs on more than 600 medicinal herbs with common names, descriptions, actions, indications, contraindications, precautions, adverse effects, overdose, dosage, and literature citations.
      Rational Phytotherapy: A Physician's Guide to Herbal Medicine
      • Schulz V
      • Hansel R
      • Tyler VE
      is another frequently cited text. This text organizes herb information according to body system affected (eg, central nervous system, cardiovascular system, etc). Pharmacology and toxicology are addressed in detail, along with fairly exhaustive reviews of available therapeutic trials.
      Another highly regarded source of information is the Review of Natural Products.
      Information is provided in the form of detailed monographs, with excellent scientific reviews and monthly updates. A CD-ROM version is also available.
      Information on herbal therapies is easily available on the World Wide Web, with an almost infinite variety of sites. Unfortunately, many of these are of poor or suspect quality, frequently being maintained by companies selling products. However, reliable information can be obtained from the NCCAM site (nccarn.nih.gov) or from the ODS site (odp.od.nih.gov/ods/default.html). The FDA Center for Food Safety and Applied Nutrition also has a section dealing with dietary supplements (vm.cfsan.fda.gov/list.html).
      While somewhat “pro” –herb, the American Botanical Council maintains a Web site (www.herbalgram.org) that is well organized and contains many links that consumers are likely to use.

      DISCUSSIONS WITH PATIENTS ABOUT HERBAL THERAPIES

      Physicians must keep an open dialogue with patients who are taking or contemplating taking herbal medicine. Discussing the use of herbal medicine nonjudgmentally provides an opportunity for shared discussion about the risks and benefits. For patients who are planning to take herbal medicines, it has been suggested that they seek products whose labeling includes the product's scientific name, which parts of the plant are used, the name and address of the manufacturer, batch and lot numbers, and dates of manufacture and expiration. All this information does not guarantee the quality or even the identity of the parts contained therein, but it does suggest some attempt at integrity and labeling. Looking for the USP or NF symbol may also be important in finding quality products.
      Physicians must educate patients about the nature of herbs. Herbs have effects, both good and adverse, because they contain active chemical compounds and thus are not inherently more or less toxic than synthetic compounds or “chemicals.” Whether a substance is organic or inorganic, synthesized in vitro or in vivo, by plant or by a manufacturer, the laws of biochemistry and receptor modulation apply. Starting with this basic understanding may help patients more fully appreciate the concerns and reticence many physicians have in regard to herbal therapies.
      In an editorial in the Annals of Internal Medicine, Delbanco
      • Delbanco TL
      Bitter herbs: mainstream, magic, and menace [editorial).
      made several points about the approach physicians should use in dealing with patients and alternative therapies. Four are particularly germane to herbal therapy.
      • 1.
        Remain humble about our own mixture of art and science. Clearly, there are procedures we do within the confines of traditional medicine that have scant scientific backing and perhaps are used primarily on the basis of tradition.
      • 2.
        Learn more about alternative therapies so that we can have open discussions with our patients. Learning more about alternative therapies does not imply acceptance or promotion but does indicate our willingness to discuss these issues objectively with our patients.
      • 3.
        Apply our rich scientific heritage to test alternative therapies. This is being done on some levels now through the auspices of the NCCAM, the ODS, and several academic institutions.
      • 4.
        Maintain open communication with our patients.
      Clearly, this is the most important message when talking to patients who may be taking herbal supplements. Dismissing the use of such preparations or in some way implying a lack of respect for people who choose to use these medications simply forecloses the possibility of any further dialogue, the possibility for education, and the pos– sibility for preventing harm or otherwise benefiting our patients.
      Physicians and patients should increasingly be able to explore the realm of herbal therapies in collaboration. As results of studies that are currently under way become available, opportunities to share the findings with patients will increase. These educational efforts will be critical in developing a rational and safe approach to the use of herbal therapies in the United States.

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        Mayo Clinic ProceedingsVol. 80Issue 6
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          Incorrect legend: In the article by Eisenach et al entitled “Hyperhidrosis: Evolving Therapies for a Well-Established Phenomenon,” published in the May 2005 issue of the Mayo Clinic Proceedings (Mayo Clin Proc. 2005;80:657-666), the legend to Figure 1 on page 659 was incorrect. The legend should read, “A young, healthy patient with primary palmar-plantar hyperhidrosis is tested under resting conditions at room temperature. Top, Indicator powder mixture of starch, sodium carbonate, and alizarin red placed on the hyperhidrotic palms produces a color change from light orange to dark purple.
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