Date: Feb 23, 2004
For the first time, the Food and Drug Administration (FDA) has issued a final regulation concluding that a dietary supplement is "adulterated" under the Federal Food, Drug, and Cosmetic Act (FDC Act), effectively prohibiting its sale. 69 Fed. Reg. 6788 (Feb. 11, 2004). This regulation, which is effective on April 12, 2004, applies to dietary supplements containing ephedrine alkaloids (a large family of pharmacological compounds called "sympathomimetics" that are commonly derived from various Ephedra plant species). These products have been marketed with claims for weight loss, enhanced athletic performance, and increased energy (among others).
This action followed a consumer alert that FDA issued on December 30, 2003, urging the public to stop using these types of dietary supplements and stating the Agency's intent to issue the regulation. Although ephedra-based dietary supplements have been controversial for many years, it is only now that FDA has sought use its authority to prohibit the sale of dietary supplements containing particular ingredients.
Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), which amended the FDC Act, a dietary supplement is deemed "adulterated" if it presents a "significant or unreasonable risk of illness or injury" under the conditions of use recommended or suggested in labeling, or if no conditions of use are suggested or recommended in labeling, under ordinary conditions of use. FDC Act § 402(f)(1)(A). An "adulterated" dietary supplement may not be marketed. Under the statute, FDA bears the burden of proving that the "significant or unreasonable risk" standard has been met.
In the rule, FDA evaluated whether dietary supplements containing ephedrine alkaloids present an "unreasonable" risk to health under their conditions of use and did not consider whether the "significant" risk criterion was satisfied. After an analysis of the legal meaning of the criterion, FDA concluded that the assessment of an "unreasonable risk" represents a relative weighing of a product's known and reasonably likely risks against its known and reasonably likely benefits. The Agency concluded that its burden of proof for "unreasonable risk" is satisfied when a product's risks outweigh its benefits in view of the product's use. Under FDA's interpretation of this standard, there is no requirement that there be proof that the product in question has actually caused harm to particular individuals. Rather, FDA asserted that there only needs to be sufficient evidence to support the existence of sufficient risk.
In assessing whether ephedrine alkaloids present an "unreasonable risk," FDA considered three primary sources of evidence: (1) the scientifically established pharmacology of ephedrine alkaloids; (2) peer-reviewed scientific literature on the effects of ephedrine alkaloids; and (3) the adverse events (including published case reports) reported to have occurred following consumption of dietary supplements containing ephedrine alkaloids. Overall, the Agency reported that multiple studies demonstrate that dietary supplements containing ephedrine alkaloids can raise blood pressure and increase heart rate. The potential consequences from these effects can include stroke, heart attack, and death (from increased blood pressure) and increased morbidity and mortality (from worsened heart failure).
In reviewing the benefits of these products, FDA found that the best clinical evidence for a benefit is for weight loss. Even there, however, FDA found the evidence supported only modest short-term weight loss which, in the Agency's view, was insufficient to positively affect cardiovascular risk factors or health conditions associated with being overweight or obese. Even if long-term weight loss could be achieved with the use of dietary supplements containing ephedrine alkaloids, FDA felt that the risks posed by long term use generally could not be adequately mitigated except through physician supervision. In the Agency's view, other possible benefits (such as enhanced athletic performance, enhanced energy, or a feeling of alertness) lacked scientific support and/or provided only temporary benefits that were considered "trivial" compared to the risks presented.
FDA reviewed the seriousness of the risks and the quality and persuasiveness of the evidence to support the presence of those risks. The risks were then weighed against the importance of the benefits and the quality and persuasiveness of the evidence to support the existence of those benefits. FDA gave more weight to benefits that improve health outcomes (especially in the long term) than to benefits that are temporary or rely on subjective measures (such as feeling or looking better).
After this analysis, FDA concluded that dietary supplements containing ephedrine alkaloids do not provide a benefit that outweighs the risks. Furthermore, the Agency evaluated other possible regulatory measures (such as warning statements on labels) but found they would not adequately mitigate the risk.
Despite the care that FDA took in developing the supporting rationale, there is no assurance that the rule would be upheld if it were challenged. Nevertheless, three dietary supplement industry trade associations have announced that they believe FDA has "presented a balanced rationale" and do not intend to challenge the regulation in court. While there has been speculation that FDA will now attempt to use its § 402(f)(1)(A) authority against other dietary supplements, it does not appear likely that this approach will become a common practice. The Agency has invested many years and substantial resources addressing ephedrine alkaloids and, absent similarly important health risks presented by other products, it is not likely to repeat this exercise any time soon.
For further information about this issue or FDA's regulation of dietary supplements generally, please contact Frederick A. Stearns at 202-434-4288 or via e-mail at email@example.com.