Drugs Alias Dietary Supplements

Dietary supplements encompass a wide spectrum of products, including vitamins and minerals, herbal products and botanical agents, and extracts from organs or glands.¹ Herbal products and other botanical agents are among the most popular dietary supplements. These diverse products are used by millions of people in the United States and account for billions of dollars in sales each year.² As with other dietary supplements, herbal products are readily available and widely promoted, usually with unsubstantiated claims of benefit and seldom with any mention of potential harms.³ New findings reported in this issue of THE JOURNAL illustrate the inappropriate claims for some commonly used herbal products, provide new information on the mechanisms of herb-drug interactions, and underscore the need for more effective regulation of dietary supplements.

The study by Morris and Avorn⁴ provides evidence for the easily accessible and widespread potentially misleading claims made by vendors of herbal products on the Internet. The authors used 5 frequently used search engines to search the Internet for the 8 most commonly used herbal supplements: ginkgo biloba, St John's wort, echinacea, ginseng, garlic, saw palmetto, kava kava, and valerian root. Among the 443 studied Web sites, 338 (76%) were retail, ie, either selling a product or directly linked to a vendor. Eighty-one percent of retail Web sites made 1 or more health claims, and of these 55% claimed to prevent, diagnose, treat, or cure diseases. Furthermore, only 48% of sites (139/292) with a health claim included the disclaimers specifically required by federal law.

Herbal products and other dietary supplements are regulated by the US Food and Drug Administration (FDA) but under different regulations than those governing prescription medications and over-the-counter drugs.⁵ In 1994 the Dietary Supplement Health and Education Act established that dietary supplements are not drugs and substantially altered the role of the FDA in regulating these products.⁵ Under the act's provisions, manufacturers of dietary supplements, unlike manufacturers of pharmaceuticals, are not required to provide evidence of safety or efficacy prior to marketing. Also, except for supplements that contain "a new dietary ingredient," dietary supplements are not required to have FDA approval or even be registered with the FDA before they are produced and marketed. Once a dietary supplement is marketed, the onus is on the FDA to demonstrate that the product is unsafe before it can take regulatory action, amounting to a postmarketing regulatory system.^{1 ,6}

While the FDA primarily regulates labeling of dietary supplements, the Federal Trade Commission (FTC) has primary responsibility for claims in advertising, including print and broadcast advertisements, infomercials, catalogs, direct marketing materials, and marketing on the Internet.⁷ The FTC "truth in advertising" law essentially involves 2 elements: "advertising must be truthful and not misleading; and, before disseminating an ad, advertisers must have adequate substantiation for all objective product claims."⁷ The combination of a postmarketing regulatory system by the FDA and the dual regulatory bodies (FDA and FTC) responsible for truthful advertising provide the chaotic environment that breeds a real danger to the public.

The study by Morris and Avorn⁴ demonstrates that "disease claims" by makers of dietary supplements are frequently made on the Internet, despite the FDA ruling that these are not permitted. These findings show that the more than 280 advisory letters sent by the FTC in July 2002 to retailers warning that their Web site claims must be supported by scientific evidence⁸ cover a small portion of possible infractions. It would be interesting to know how many of those advisory letters resulted in elimination of unsubstantiated claims. Yet, even if all were successful, it hardly solved the problems one year later, suggesting that the current system of regulation of advertising for dietary supplements has not been working. However, several recent enforcement actions by the FTC against direct marketers of dietary supplements have targeted deceptive efficacy, safety, and "no side effects" claims. The FTC required these companies to stop making false and deceptive advertising claims, to include warnings about health risks of their products, and to pay fines as "consumer redress."⁹

In another report in this issue of THE JOURNAL, Markowitz and associates¹⁰ present an elegant pharmacokinetic study showing that ingestion of St John's wort for 14 days significantly induced the activity of cytochrome P450 (CYP)3A4, an enzyme that participates in the metabolism of many prescription drugs and over-the-counter medications.¹¹ The authors note that this finding suggests that regular use of St John's wort may result in diminished clinical effectiveness or the need for increased dosage for half of all marketed drugs.¹⁰

The study by Markowitz et al adds to the growing literature on the biological actions and adverse effects of other dietary supplements such as ephedra,¹² yohimbine,¹³ and saw palmetto.¹⁴ In addition, Palmer et al¹⁵ studied telephone calls made to 11 poison control centers in the United States in 1998. They documented events such as myocardial infarction, liver failure, bleeding, seizures, and death associated with ingestion of dietary supplements. Their findings provide further evidence that a postmarketing system of regulation by the FDA is not effective in preventing such risks to the public.

Because many dietary supplements have or promote biological activity, they must be considered active drugs and regulated as such. It makes no sense to have a double standard, and we are not alone in our concern about this issue. Marcus and Grollman¹⁶ pointed out the problems of lack of standardization, adulteration of botanical preparations, interactions between herbs and drugs, and lack of reporting of adverse events that are not being handled appropriately by the current regulatory mechanism. Wollschlager¹⁷ has argued that the Dietary Supplement Health and Education Act already provides a mechanism for regulation and enforcement and that the problem lies with appropriate funding and resources to enforce existing regulations.

We recognize that insufficient funding and resources are a great part of the problem. However, having 2 mechanisms, one to handle dietary supplements and another to handle drugs (as many if not most dietary supplements are or claim to be), is not a cost-effective answer. We also know that requiring the same responsibilities for regulation of dietary supplements as for drugs would add substantially to the workload of the FDA, which is barely managing to regulate drug companies now.¹⁸ However, double standard regulation is simply wrong. The US public deserves to have the funding and resources allocated for their protection.