Did Delay of Ephedra Ban Cause Unnecessary Deaths?

The Food and Drug Administration (FDA) is banning sale of dietary supplements containing ephedrine alkaloids (ephedra). The agency is also urging consumers to stop using ephedra products immediately.

Health and Human Services Secretary Tommy Thompson issued a consumer alert on the safety of dietary supplements containing ephedra and has notified manufacturers of its intent to publish a final rule on dietary supplements containing ephedrine alkaloids. The rule will state that dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury.

The rule would have the effect of banning the sale of dietary supplements containing ephedrine alkaloids when it becomes effective, 60 days following publication. Sixty-two firms that market dietary supplements containing ephedra and ephedrine alkaloids received the letter from the FDA alerting them of the final rule.

Thompson said the final rule “will formalize its conclusions that dietary supplements containing ephedrine alkaloids present unreasonable risks to those who take them for any reason.”

Ephedra, also called Ma huang, is a naturally occurring substance derived from botanicals. Its principal active ingredient is ephedrine, which when chemically synthesized is regulated as a drug. In recent years ephedra products have been extensively promoted for use to aid weight loss, enhance sports performance, and increase energy. The supplement has also been linked to a variety of adverse events, including psychiatric complications.

This year the RAND Corporation’s Southern California Evidence-Based Practice Center issued the report “Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects.” The report provided evidence that ephedra is associated with major health risks—including psychiatric effects—and found only limited evidence of health benefits resulting from its use.

The RAND Corporation’s review of some 16,000 adverse-event reports revealed two deaths, four heart attacks, nine strokes, one seizure, and five psychiatric cases involving ephedra in which the records appeared thorough and no other contributing factors were identified.

In addition, three cases of psychosis related to use of ephedra-containing herbal supplements were reported in the July 2003 Southern Medical Journal.

Study authors Ruth Walton, M.D., and Gail H. Manos, M.D., of the department of psychiatry at Portsmouth Naval Medical Center in Portsmouth, Va., observed, “Toxicity may occur at only two or three times the maximum therapeutic dose of 150 mg/d. Most reports have focused on medical complications such as stroke, seizure, hepatic toxicity, or even death” (Psychiatric News, November 21, 2003).

In 1997 the FDA first proposed a rule on dietary supplements containing ephedra including requiring a warning statement on these products. The agency modified this proposed rule in 2000, and a year ago the agency announced a series of comprehensive actions designed to protect Americans from the potentially serious risks of dietary supplements containing ephedra.

At least one critic charged the FDA’s action comes too late.

Sidney Wolfe, M.D., director of Public Citizen’s Health Research Group, claimed that the FDA knew of more than 155 deaths of ephedra users and said the agency had waited more than two years after Public Citizen first petitioned the agency to ban the supplement.

The delay “shows the dangerous cowardice of FDA Commissioner Mark McClellan and HHS Secretary Tommy Thompson,” Wolfe said. “All the scientific evidence and legal authority to ban ephedra was in place at the time of our petition, which we filed in September 2001. One reason major manufacturers have stopped selling ephedra is that the companies have become uninsurable because of massive losses in product liability cases. When we filed our petition, there were reports of 81 ephedra-related deaths. Now, after that number has nearly doubled and very little ephedra is being manufactured, the FDA finally announces a ban.

“This is an inexcusable dereliction of responsibility by an agency that has acted more like an ephedra sales extension agency than the public health agency it is supposed to be,” Wolfe said.

More information on the FDA’s actions related to ephedra can be found online at www.fda.gov/ola/2003/dietarysupplements1028.html. ▪