DSHEA: Implications for the Pharmacy
By Gerry Gianutsos, PhD, JD
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.
Pharmacists and consumers alike are familiar with this statement, found on the labels of dietary supplements marketed in the United States. However, pharmacists need to recognize the significance of this disclaimer, particularly how it impacts product selection and the use of dietary supplements.
Not Evaluated by the FDA
The first part of the statement describes one of the major differences between the regulation of dietary supplements and pharmaceutical drugs. Under the Food, Drug, and Cosmetic (FDC) Act of 1938, the Food and Drug Administration (FDA) regulates the marketing and sale of drugs, foods, and supplements. Simply stated, this act, and its later amendments, set up a rigorous, lengthy, and costly procedure for the premarket testing of drugs to ensure that they are both safe and effective. Food additive manufacturers are also required to de-monstrate safety before the FDA will permit them into the marketplace. However, when the FDA attempted to regulate dietary supplements using the same criteria, their efforts were challenged. Since dietary supplements do not fit neatly into the drug or food additive categories, courts often sided with dietary supplement manufacturers. An early response to the FDA’s efforts to regulate supplements, the Proxmire Amendment of 1976 prohibited the FDA from setting maximum limits on vitamin and mineral contents in foods and from classifying a vitamin or mineral as a drug solely because the potency exceeded the amount deemed nutritionally sound.
Dietary Supplement Health and Education Act
To address the issues raised by the proliferation of supplement products, Congress passed the Dietary Supplement Health and Education Act (DSHEA) in 1994.1 This act broadened the definition of dietary supplements beyond vitamins, minerals, and amino acids to include herbs and botanicals. DSHEA also defined the limits of the FDA’s regulatory authority of dietary supplements.
As a result of these changes, dietary supplement manufacturers are not required to prove that a product is safe and effective; a manufacturer only needs to give the FDA notice of its intent to market a product. This is similar to the exemption for homeopathic remedies that has been in effect since 1938. Only claims on product labels are reviewed or restricted by the FDA. Thus, unlike pharmaceutical drugs, marketing of dietary supplements is not subjected to an independent or governmental review. This, of course, does not mean that herbal remedies are inherently unsafe or ineffective. It does mean, however, that safety and efficacy have not been independently verified, and pharmacists should consult objective sources of information when counseling patients or making recommendation regarding use of dietary supplements. (See Table 1 for information about DSHEA.)
| Table 1-Recommendations for the pharmacist | |||||
| • Be familiar with product labeling and know how to properly evaluate product claims. | |||||
| • Know that promotional literature may contain claims, but must be physically separated from product displays in retail locations. | |||||
| • Be familiar with information sources on product quality and standards in order to help patients choose products wisely. | |||||
| • Recognize the consumer who relies on misleading information and be able to educate that consumer. | |||||
| • Be familiar with state regulations on particular supplements. | |||||
As required by DSHEA, the Office of Dietary Supplements of the National Institutes of Health provides fact sheets and a database of bibliographic information on its website (http://dietary-supplements.info.nih.gov). Product literature and other written information are available in most pharmacies where supplements are sold. However, DSHEA exempts such publications from FDA review even though they may contain therapeutic information. These publications cannot accompany the product (i.e., they must be displayed separately from the product) or be part of an integrated plan to promote the product.
Pharmacists also should be familiar with the process by which the FDA responds when there are concerns about post-marketing adverse events caused by a dietary supplement. Under DSHEA, the FDA is obligated to demonstrate that a product is unsafe before it can take an enforcement action to remove it from commerce. This is unlike the situation with pharmaceutical drugs where the manufacturer has the burden of demonstrating safety.
With expanded use and misuse of supplements, there is an increased incidence of reported adverse effects. Examples include g-butyrolactone (GBL) and its metabolite, g-hydroxybutyrate (GHB), marketed as sleep aid and bodybuilding supplements, and ephedrine, most often marketed inappropriately as a stimulant and weight reduction product. GHB is reported to induce seizures2 while ephedrine has been associated with at least 15 deaths.3 The FDA has issued warnings about these products, but pharmacists also need to be aware of possible sales restrictions on products since individual states can regulate the sale of supplements under state law. For example, Texas and Ohio restrict sales of ephedrine. State Boards of Pharmacy will be able to supply this information.
These issues also demonstrate the critical need for post-marketing surveillance to monitor the incidence of adverse effects. Pharmacists are in a unique position to provide valuable information protective of public health, since they will often be the first to recognize adverse events associated with dietary supplement use. Health professionals can report adverse events to the FDA’s Special Nutritionals Adverse Event Monitoring System (http://vm.cfsan.fda.gov/~dms/aems.html) or the MedWatch program (http://www.fda.gov/medwatch/report).
Product Claims
The second part of the familiar disclaimer refers to the claims a dietary supplement manufacturer may make regarding a product.4 A substance that is intended for use to diagnose, cure, mitigate, treat, or prevent a disease falls under the FDA definition of a drug and would be subjected to the normal regulatory standards required for drug approval. Consequently, dietary supplement health claims are essentially limited to: (1) a benefit related to a classical nutritional deficiency; (2) a claim that the product can promote general well-being, or (3) a "structure-function" claim. The subtle distinction between a structure-function claim made for a dietary supplement and a disease claim made for a drug may easily confuse the consumer. For example, a claim that a product "promotes cardiovascular function" or "maintains a healthy circulatory system" (both related to physiologic functioning) would be permissible on a supplement label. A claim that a product "prevents atherosclerosis" (related to a disease) would not be permissible. The average consumer, however, may have difficulty discriminating between these distinctions and might conclude that the product will prevent heart disease, which is often the very intent of the manufacturer. Pharmacists should be able to correctly evaluate label claims in order to counsel consumers appropriately. (To test your knowledge of product labeling claims, see below.) Many consumers fail to notify their physicians that they are taking herbal or supplement products and some may self-medicate to avoid conventional therapy. In these instances, it is especially important to recognize consumers who rely on misleading information.
A manufacturer can use a structure-function claim without prior FDA approval, but the claim must be based on the manufacturer’s review and interpretation of the scientific literature. The FDA’s ability to regulate claims made by dietary supplement manufacturers continues to evolve and has been at least partially eroded by a recent legal challenge (Pearson v. Shalala, 164 F3d 650 [D.C. Cir. 1999]).
Recent Developments
In January 2000, the FDA issued new rules for claims on dietary supplements in an effort to clarify the distinction between disease and structure-function claims.5 The rule prohibits both express claims ("prevents osteoporosis") and implied disease claims ("prevents bone fragility in postmenopausal women"). It also prohibits claims made through product name (e.g., "CardioCure"); the use of pictures or symbols on the label (e.g., EKG tracings); or product formulation statements (e.g., contains aspirin). Claims for common, minor symptoms associated with life stages of aging (e.g., absentmindedness), menopause (e.g., hot flashes), and adolescence (e.g., noncystic acne) are permitted, but not claims for serious conditions such as osteoporosis. Pregnancy was originally included as a life stage, but the FDA has since advised that no claims for symptoms associated with pregnancy should be made until a further ruling is completed.6
Quality and GMPs
In evaluating the validity of any research on the use of supplements, pharmacists also need to be aware of the effects of different product formulations. For example, a product that may be used as a tea in folk medicine, may be available commercially only as a capsule containing the ground leaf; components, and therefore results, may not be identical. Conversely, there may be evidence that a particular active principle may exert pharmacological activity, but the dose available in a crude commercial preparation may be inappropriate for optimal therapeutic activity.
In 1999, the FDA modified its rules for supplement packaging. A supplement facts panel is now required to appear on all product labeling and includes: the product name, quantity, serving size, and total weight of each ingredient; directions for use; a list of other ingredients; and the identity of any plant part from which a botanical ingredient is derived. Unfortunately, the label does not always reflect the contents of the package, so pharmacists who counsel on the use of supplements must consider quality control.7 For example, a recent analysis of marketed ginseng products showed a tenfold variation in the amount of active ingredient among different brands that were labeled to contain the same amount; some brands contained no active ingredient at all.8 Similar problems have been observed with other products.7 Variability and lack of standardization can lead to significant under- or over-dosing.
In a recent study of Asian medicines available in California retail stores, almost 15% of the products examined had significant concerns, including the presence of adulterants, high levels of lead, and the presence of drugs not noted on the label.8 Clearly, it is important for pharmacists to rely on reputable manufacturers.
The United States Pharmacopeia (USP) is developing standards for selected products; manufacturers who follow these standards are permitted to use USP or NF (National Formulary) on the label (more information can be found at http://www.usp.org).
The Institute for Nutraceutical Advancement Methods Validation Program is an industry-sponsored international project designed to select, validate, and publish scientific methods for use in analyzing raw botanical materials (http://www.nutraceuticalinstitute.com). Other potential sources of information on product quality include the Consumer Lab, an independent laboratory that tests dietary supplement quality and posts the results on their website, http://www.consumerlab.com (four product categories have been tested so far; more are forthcoming), and the Dietary Supplement Quality Initiative (http://www.dsqi.org).
If these sources do not provide information on a particular product that a patient is interested in using, a pharmacist may request a certificate of analysis from a manufacturer that indicates product ingredients and any known impurities. Pharmacists may also want to request proof that the product is not adulterated with pesticides, herbicides, heavy metals, or other harmful contaminants. Reputable manufacturers will be willing to supply such information.
DSHEA also gave the FDA authority to establish good manufacturing practices (GMPs) for dietary supplements. These regulations establish minimum requirements for methods and facilities used in the manufacture, processing, and packaging of dietary supplements and permits the FDA to inspect facilities for compliance. The FDA has been reviewing these proposed GMPs for several years, but has yet to issue new regulations.
DSHEA continues to evolve; the FDA recently announced a comprehensive 10-year strategy for achieving effective regulation of supplement products that includes issues of safety, labeling enforcement activities, and outreach. The strategy is available on the FDA website.9
Conclusion
DSHEA has ushered in a new era of consumer autonomy in selecting medicinal products. Along with this increase in consumer choice, there are concerns about product safety, efficacy, and purity. The pharmacist who recognizes both the benefits and shortcomings of DSHEA will be in a unique position to provide appropriate recommendations and advice to the public.
Dr. Gianutsos is an Associate Professor of Pharmacology at the University of Connecticut School of Pharmacy in Storrs, CT.
References
1. Kurtzweil P. An FDA guide to dietary supplements. FDA Consumer 1998;32:28-35.
2. Dyer JE. Gammahydroxybutyrate—a health food product producing coma and seizures. Am J Emergency Med 1991;9:321-324.
3. Stewart TL. Getting high with a little help from the feds: Federal regulation of herbal stimulants. J Pharmacy Law 1997;6:101-115.
4. McNamara SH. So you want to market a food and to make health related claims. Food Drug Law J 1998;53:421-436.
5. U.S. Food and Drug Administration. "FDA finalizes rules for claims on dietary supplements." Available at: http://vm.dfsan.fda.gov/~lrd/tpdsclm.html. Accessed April 18, 2000.
6. U.S. Food and Drug Administration. "FDA statement concerning structure/function rule and pregnancy claims." Available at: http://vm.cfsan.fda.gov/~lrd/hhssupp3.html. Accessed April 18, 2000.
7. Angell M, Kassirer JP. Alternative medicine—the risks of untested and unregulated remedies. New Engl J Med 1998;339:839-841.
8. Ko RJ. Adulterants in Asian patent medicines. New Engl J Med 1998;339:847-849.
9. U.S. Food and Drug Administration. "Dietary supplement strategy (ten year plan)." Available at: http://vm.dfsan.fda.gov/~dms/ds-strat.html. Accessed April 18, 2000.
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