Why Did FDA Propose To Ban Most Uses Of Ephedra?
On June 4, 1997, FDA proposed severe limits on the manufacture and use of Ephedra that would have rendered these products useless for their intended purposes and that prohibited claims that these products are useful for weight loss. The main elements of FDA’s proposed rule were:
- Product potency would be limited to less than 8 mg of ephedrine alkaloids per serving, and daily intake would be limited to less than 24 mg.
- The product label would be required to include the statement “Do not use this product for more than 7 days.”
- The combination of ma huang with other stimulants, including caffeine, would be prohibited.
- Labeling claims such as weight loss and body building that encourage long-term use would be prohibited.
- For products with claims for short-term effects such as increased energy, the product label must include the warning: “Taking more than the recommended serving may result in heart attack, stroke, seizure or death.”
FDA’s proposal was based primarily on the more than 800 adverse event reports that the agency had received between 1993 and June 1997. FDA stated that it had purposefully not considered the long record of safety for the more potent over-the-counter ephedrine drug products for asthma because, according to FDA, asthmatics are less sensitive to ephedrine. However, FDA cited no scientific evidence for this assertion, and subsequent review of the medical literature has revealed no basis for rejecting this wealth of safety data. FDA also asserted that clinical studies on ephedrine for use in the treatment of obesity were also not relevant to the safety of Ephedra because obese individuals may be less sensitive to ephedrine, but again FDA cited no studies to support this theory.
In the end, careful examination of FDA’s very lengthy proposed rule showed that the proposed limits were based almost entirely on the adverse event reports, reports that FDA had historically found to be unreliable and therefore not useful for determining product risk. Therefore, the scientific validity of FDA’s proposal rose or fell depending on the quality of the adverse event reports and their relationship to Ephedra consumption.
Surprisingly, congressional inquiry into FDA’s proposed rule revealed that FDA never examined the adverse event reports on which it relied to determine if there was any relationship between the event and the consumption of Ephedra. Indeed, a number of the reports related to products that did not even contain Ephedra, but were nonetheless counted by FDA as Ephedra-related events.
As a direct result of FDA’s failure to perform even the most simple quality review of its reports, FDA’s record for the proposed rule included absurd reports such as the following:
- a report of a woman whose blood alcohol was twice the legal limit and who died of a fractured skull after driving her truck into a tree at 90 mph;
- a report of a man who shot himself;
- a report of a suicide from a gunshot wound;
- a report of a man who died of environmental hyperthermia;
- a report stating “Shot and killed store clerk”;
- a report of a woman who “got pregnant though using Norplant”; and
- reports of excessive hairiness, a 75-year old woman menstruating, a possible diagnosis of multiple sclerosis, a case of impotence and a case of constant erection.
Careful analysis of the record that FDA had compiled showed that at least 85 percent of the reports on which FDA had relied were so lacking in information essential to a scientific assessment of their relationship to the consumption of Ephedra that they were informationally worthless. Further, FDA had relied on just 13 of the reports as a basis for the proposed dose limits, even though the agency never reviewed these few reports to determine if they were causally related to the consumption of Ephedra. These immediate problems with FDA’s proposed rule led to more thorough review of the rule by Congress, a critical review by the General Accounting Office (GAO), and to the eventual and unprecedented withdrawal of the key portions of the proposed rule.
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