Dr. Ray Woosley has finally won the battle he has been fighting for more than a decade: He helped prod the Food & Drug Administration to ban the controversial dietary supplement ephedra. But Woosley, vice-president for health sciences at the University of Arizona, is hardly celebrating. In the face of growing concern, the $4 billion herbal supplement industry has been flooding the shelves of health-food stores with ephedra-free products that purport to boost athletic performance and weight loss. Trouble is, says Woosley, "it is very likely that the substitutes for ephedra are going to be just as toxic." And without a change in the law, it would take many years for the FDA to amass enough evidence to take each one of them off the market if problems arise, just as with ephedra.
Ephedra was banned because the active ingredient in ephedra supplements, ephedrine, causes blood pressure and heart rate to rise. Chemically similar to amphetamines, or "speed," ephedrine is used in products that have been linked to heart attacks, strokes, and deaths. Those effects are even more pronounced when combined with caffeine, yet many so-called natural dietary supplements that include ephedrine also contain the stimulant. That's one reason why over-the-counter drugs, regulated separately by the FDA, cannot combine the two.
The new products, such as Diet Fuel Ephedra Free from Twinlab Corp., Metabolife International Inc.'s Ultra, and Cytodone Technologies' Xenadrine EFX, typically substitute an herb called bitter orange. But bitter orange contains synephrine, a chemical kissing cousin of ephedrine that produces some of the same effects. Already, there are reports of adverse reactions to the new ephedra-free products, says pharmaceutical sciences professor Bill J. Gurley at the University of Arkansas. The ephedra ban is "like putting your finger in the dike when the river is overflowing," says Dr. Marvin M. Lipman, chief medical adviser for Consumers Union.
Industry representatives concede that bitter orange can raise blood pressure and heart rates, yet insist it is safe. "We have reviewed all available publications," says Metabolife spokesperson Jan Strode. "None indicate any significant side effects in normal individuals." Twinlab and Cytodyne did not return calls.
NO DATA, NO ACTION. How did we get into this mess? Blame Congress for a 1994 dietary supplement law. Makers don't have to show that a product works or that it's safe. They don't even have to report problems to the FDA, as drugmakers must. To order a product off the market, the agency must prove that it poses "imminent harm" -- a standard met only by a sudden, dramatic rise in injuries or deaths -- or "unreasonable risk." To make its case, the FDA must rely largely on doctors' or consumers' voluntary reports. But under 1% of problems are reported, and those reports are often vague.
That's why it took years for the FDA to build its case against ephedra. It had been trying to regulate the products since the mid-1990s, only to be undercut by Congress and the courts for lacking sufficient evidence. Now, the FDA has reports of more than 16,000 adverse events, including at least 155 deaths. And lab results show that ephedra can cause heartbeat changes associated with higher risk of heart attacks. Even so, there's no guarantee that the agency will win an expected court challenge, though a loss might ultimately give it more authority. "If the judge says we don't have enough evidence, it's pretty clear the FDA is out of the game and Congress has to change the law," says one top official.
With the potential threat of harm from ephedra-free products, leaving the law unchanged is too great a risk. But unless the FDA can argue that the synephrine in bitter orange is chemically close enough to ephedrine to be covered by the coming ban, the agency will find it tough to restrict. "A lot of people will die waiting to get it off the market," Woolsey says. If that happens, the ephedra ban would be little more than a hollow victory.
By John Carey