Current Regulations of Dietary Supplements: DSHEA Revisited

By Felise Milan, MD, and Ronit Fallek, BA

Herbal medicine consistently has been found to be one of the most popular—if not the most popular—alternative therapies used in this country.1-4 Eisenberg et al found that the use of herbal remedies increased 380% during the earlier part of the last decade (2.5% in 1990 to 12% in 1997).2

In 1994, the estimated market for herbal medicines was $1.6 billion annual retail sales and by 1998 that figure was up to $4 billion.5 Since 2000, retail sales for herbal supplements have increasingly dropped each year with a fall of 13.9% in 2002.6 This fall has been attributed to negative media coverage and medical reports about herbs, with the greatest decrement in sales seen in kava and St. John’s wort, herbs that have received some of the most negative press.7

Current Regulation of the Herbal Industry

In 1993, the U.S. Food and Drug Administration (FDA) expressed concern about the quality and safety of vitamins, minerals, herbs, and other nutritional supplements and proposed tougher regulations governing their production and marketing. The supplement industry responded by trying to convince the public that such regulations essentially would eliminate the availability of these products from the market. In response to the flood of letters from consumers against these stricter regulations,8 Congress passed the Dietary Supplement Health and Education Act of 1994 (DSHEA), which severely restricted the FDA’s authority over these products. This federal regulation created a new category of therapeutic, non-prescription substances called "dietary supplements" (herbs, vitamins, minerals, amino acids, and other nutritional supplements) that would not be subject to premarket safety evaluations, but also could not make claims to prevent or treat disease. DSHEA allows manufacturers to make claims about a supplement’s effects on the "structure and function" of the body or on the consumer’s "well-being."9 Dietary supplements must carry the disclaimer, "These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease." Product labels may claim that a product affects common conditions associated with "natural states," such as postmenopausal hot flashes, premenstrual moodiness, and occasional constipation.

Prior to DSHEA, supplements were regulated as foods and could not be placed on the market without FDA approval. Now, manufacturers must notify FDA within 30 days after a product is released to the public and are not required to perform any post-marketing surveillance of their product. The FDA may warn the public if it feels a product may be hazardous, but can remove the product from the market only if it proves it unsafe in a court of law, or if the director of the Department of Health and Human Services (HHS) determines the supplement to be hazardous in an administrative hearing. DSHEA proposed the creation of quality control standards, known as GMPs (Good Manufacturing Practice standards), for dietary supplements, but the industry remains without these 10 years later.

Current Problems with Dietary Supplements

In response to reports of lack of standardization, adulteration, drug interactions with, and toxicity of herbal medicines, the medical community has voiced many concerns about herbal products. Standardization and quality control are challenging issues as the potency and constituents of any herbal product can be affected by a multitude of factors including: genetic variation; growing and harvesting conditions; storage and handling; processing and preparation; and which part of the plant is used (i.e., root, leaf, whole plant, seeds).10

However, several studies commissioned by consumer groups have demonstrated that herbal products sold in the United States vary widely in the concentrations of their active ingredients and that these variations are not reflected on the product label.11 Consumer Reports has published studies on ginseng8,12 that reveal variations in relevant constituents from 5% to 140% of the labeled amounts and different brands of the same herb containing up to 10 times as much as another. Several studies published in the scientific literature have found the same to be true for ephedra products.11,13 Along with variations in active constituents, there is well-documented evidence of adulteration of herbal products made in Asia.14 In a study conducted by the California Department of Health, 32% of the 260 products tested contained undeclared pharmaceuticals or heavy metals.14 In February 2002, the California Department of Health ordered a recall of the product PC-SPES (a blend of Chinese herbs used to treat prostate cancer) after tests showed that it contained warfarin and diethylstilbestrol.15

The most serious concerns have been raised about kava (an herb used for anxiety), ephedra or ma huang (a plant-derived alkaloid used commonly for weight loss and enhanced sports performance), and St. John’s wort (an herb used for mild-to-moderate depression). Kava has been associated with 25 cases of fulminant hepatitis, 11 requiring liver transplant.16 In a review of serious adverse events from ephedra reported to the FDA from June 1997 until March 1999, the authors concluded that "dietary supplements that contain ephedra alkaloids pose a serious health risk to some users."17 A RAND report published on ephedra found that ephedra and ephedrine were implicated in five deaths, five myocardial infarctions, 11 cerebrovascular accidents, four seizures, and eight psychiatric cases.18 St. John’s wort has been found to interfere with many medications metabolized by the liver including phenytoin, theophylline, protease inhibitors, warfarin, digoxin, and cyclosporin.19

Limitations of the Current Regulatory System

FDA response to reports of serious adverse effects from ephedra and kava raises questions about the ability of the federal regulatory system to adequately protect the public from unsafe dietary supplements. As mentioned previously, FDA does not have the power to prohibit the sale of dietary supplements that it considers dangerous. FDA has released warnings about ephedra and kava to which the industry has not responded. Currently, FDA is receiving comment on a proposed warning to be added to labels of all ephedra products.20 This label would say:

WARNING: Contains ephedrine alkaloids. Heart attack, stroke, seizure, and death have been reported after consumption of ephedrine alkaloids. Not for pregnant or breast-feeding women or persons under 18. Risk of injury can increase with dose or if used during strenuous exercise or with other products containing stimulants (including caffeine). Stop use and contact a doctor if side effects occur....20

Although FDA is relatively impotent in this area, the Federal Trade Commission has responded by suing several herb and supplement producers for false advertising claims.

In contrast to the lack of definitive action taken at the federal level, many U.S. states and counties have passed legislation banning the sale of any product containing ephedra. Other nations have a more closely regulated herbal industry. Kava has been banned in Australia, Canada, Switzerland, England, France, and Germany.16 In response to reports of adulterated imported Chinese herbal products, the Japanese Ministry of Health recalled several products and now are requiring that chemical analyses be done on all Chinese herbs imported into Japan.21

As a result of the reports of adverse effects and adulterated products, both the medical community and federal agencies are calling for increased regulation of dietary supplements. Members of the medical community have identified the current state of dietary supplement regulation as posing a serious threat to public health, and proposed new legislative action that would entail the restoration of jurisdiction to government agencies to monitor and regulate dietary supplements both pre- and postmarketing, and more strict legislation and accountability for supplement manufacturers.21,22 These specific recommendations include: GMPs modeled after those for drugs; premarket product testing; mandatory postmarketing surveillance, adverse event reporting, and registration with the FDA of every company producing dietary supplements; non-misleading advertisements; clear and accurate labeling with both botanical and common plant names, adverse effect information, and potential herb-drug interactions.21,22

Current Proposals on Supplement Regulation

A decade after DSHEA was passed, several additional legislative actions have been proposed and are pending. In March 2003, FDA submitted a new proposal to the Federal Register for industry-wide dietary supplement GMPs and labeling requirements. Both industry and non-industry factions are concerned that FDA’s proposed GMP guidelines inappropriately align dietary supplements with pharmaceutical drugs, as opposed to foods, leading to overly stringent manufacturing and surveillance requirements. FDA currently is accepting comments on the proposal and soon will finalize the guidelines.

Another current controversy over dietary supplement regulation surrounds the proposed Dietary Supplement Safety Act of 2003 (DSSA),23 introduced by Sen. Dick Durbin (D-IL) in the Senate in March 2003, and which adopts many of the medical community’s recommendations. This bill would mandate dietary supplement manufacturers and distributors to register with and receive pre-marketing approval from FDA; to conduct post-marketing surveillance; and to investigate, monitor, and report on serious adverse effects to the HHS. It authorizes the HHS secretary to discontinue the marketing of a product if its investigation finds it to be unsafe; prohibits the introduction of unapproved stimulants; and shifts the burden of proof of dietary supplement risk from the FDA to the manufacturers. The dietary supplement industry is resisting these legislative efforts, perceiving them as excessive and restrictive.

Another bill, the DSHEA Full Implementation and Enforcement Act of 2003 (DFIEA), introduced by Sen. Tom Harkin (D-IA) and Sen. Orrin Hatch (R-UT) (the authors of DSHEA), proposes to uphold DSHEA and to increase FDA’s budget to implement DSHEA from $9.7 million in 2003 to $65 million by 2008.24 The senators maintain that the current problems in product safety have resulted not from a problem with DSHEA, but from FDA’s failure to enforce the bill, due primarily to a lack of funds.

As they did in 1993, industry factions are encouraging consumers to write to Congress in protest of DSSA and in support of DFIEA, under the premises that increased regulation will severely restrict the public’s access to products.

However, a recent survey on views of dietary supplement regulation indicates that a majority of Americans favor increased governmental regulation, provided that this would not deny consumer access to products that have been tested for safety. Eighty-one percent of respondents supported premarketing approval by FDA for new supplements; 80% supported FDA’s authority to remove products from the market when proven unsafe; and a majority of respondents supported increased governmental regulation to ensure that products are unadulterated, accurately advertised, and contain standardized doses.25

Conclusion

Many patients are using herbs and dietary supplements. The data tell us that these products vary significantly in their quality and safety. The scientific literature reflects the concern of the medical community at large that the current regulatory environment does not adequately protect patients from potential harm. Significant changes are needed to increase the regulatory power and action of the federal government over the dietary supplement industry. The public seems to agree. It will be important for us to follow these developments, as they are likely to have a significant impact on our patients’ safety and health.

Ms. Fallek is Research Assistant, Montefiore Medical Center, Bronx, NY. Dr. Milan, Associate Professor of Clinical Medicine Albert Einstein College of Medicine Montefiore Medical Center Bronx, NY, is on the Editorial Advisory Board for Alternative Therapies in Women’s Health.

References

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