Health Professionals

Background Risk of Seizures, Strokes, and Myocardial Infarction Compared to the Incidence of Such Events in Persons Consuming Dietary Supplements Containing Ephedrine Alkaloids

Issue: Whether the incidence of seizures, strokes, and myocardial infarctions (MIs) (i.e., heart attacks) in users of dietary supplements containing ephedrine alkaloids is higher than the background risk of such events in the general population.

Findings: FDA has failed to incorporate experience in the general population to make an assessment of background risk into its evaluation of ephedra safety and has therefore never determined whether the reports it has received are anything more than events that would have occurred even if ephedra had not been consumed. Review of the available published literature shows that seizures are a relatively common occurrence in young people, and that strokes and MIs, while not "common," are not rare -- approximately 75,000 persons under the age of 45 have strokes per year in the U.S., and approximately 22,000 to 66,000 persons under the age of 40 have heart attacks.

Expert epidemiological analysis of available data shows that the incidence of seizures, strokes, and MIs in persons consuming dietary supplements containing ephedrine alkaloids is no greater than the expected incidence in the general U.S. population. Scientific assessment of background risks confirms that dietary supplements containing ephedrine alkaloids are safe when consumed according to current national industry standards.

Methodology: Dr. Stephen Kimmel, chair of the Ephedra Education Council (EEC) Expert Panel, compared the incidence of seizures, strokes, and MIs (hereinafter "events") in users of dietary supplements containing ephedrine alkaloids to the incidence of events in the general population. Dr. Kimmel estimated the number of events in the general population by using incidence data obtained from recent studies (i.e., articles published from 1985 to present). Dr. Kimmel excluded certain studies from consideration in order to obtain the most accurate rate of events.

Dr. Kimmel estimated the number of events among ephedra users by using the number of events reported to the Food and Drug Administration's (FDA's) Center for Food Safety and Applied Nutrition (CFSAN) from June 1, 1997 to March 31, 1999. All reported events that were purportedly related to exposure to ephedrine-containing dietary supplements were included in the comparison even though there is no scientific proof that the events were caused by ephedra ingestion. Further, Dr. Kimmel included even those reports that FDA had conceded had insufficient data from which to analyze the event and in which the user abused or misused the product. Using all events in the estimate (and not eliminating from consideration those with insufficient data) provided an "upper-limit" of reported adverse events.

The true number of events among persons using ephedrine-containing products is not known. To compensate for any possibility of underreporting, Dr. Kimmel used a range of 1% - 20% of reported events in his analysis. Similarly, the actual number of persons exposed to ephedrine-containing dietary supplements is not known. Based on a survey of distributors of these products, however, Dr. Kimmel used a conservative estimate that approximately 2.8 to 11 million persons consume these products.

Numerous assumptions were made in determining the estimates of event incidences and the number of product users. Every attempt was made to overestimate the risk of events in ephedrine users.

Analysis

Seizures: Rate among Ephedra Users No Greater Than Rate among General Population

FDA received seven reports of seizures, and the age range of those who experienced the seizures is 21 to 51. The background rate of seizures in the population in this age range is 20 to 60 per 100,000. Using these estimates, Figure 1 (attached) demonstrates that the estimated risk of seizures among ephedra users is within the estimated range for background risk in the population. This analysis shows no increased risk of seizures from consuming ephedra.

Stroke: Rate among Ephedra Users No Greater Than Rate among General Population

FDA received 14 reports of stroke, and the age range of those who experienced a stroke is 18 to 64. Based on several U.S. studies, the background rate of stroke in the population in this age range is 7 to 60 per 100,000. Using these estimates, the incidence of strokes among ephedra users is within the estimated range for background risk in the population. (See Figure 2, attached.) This analysis demonstrates that there is no increased risk of stroke from consuming ephedra.

MIs: Rate among Ephedra Users No Greater Than Rate among General Population

FDA received 11 reports of MIs, and the age range of those who experienced an MI is 15 to 59. Based on two U.S. studies, the background rate of MI in the population in approximately this age range is 5 to 41 per 100,000. Using these estimates, the incidence of MI among ephedra users is within the estimated range for background risk in the population. (See Figure 3, attached.) This analysis indicates that there is no increased risk of MIs among ephedra users.

It is illogical for FDA to allege that dietary supplements containing ephedrine alkaloids are causing seizures, strokes, and MIs when the rates of those events among ephedra users are within the background rates for those events in the general population. Only if the rates of those events among ephedra users were higher than the background rates for those events would FDA have cause for concern. Furthermore, that young persons have experienced some of these events is tragic but not surprising: approximately 75,000 persons under the age of 45 have strokes per year in the U.S., and approximately 22,000 to 66,000 persons under the age of 40 have heart attacks.

Conclusion: The use of dietary supplements containing ephedrine alkaloids does not increase the risk of seizures, strokes, or heart attacks.

In a February 10, 2000 memorandum, FDA's Center for Drug Evaluation and Research (CDER) stated that "it is possible that the reported serious adverse events are reflective of coincidental background spontaneous occurrences in the population and are not necessarily causally related to [the use of dietary supplements containing ephedrine alkaloids.]" The above analysis, although in and of itself does not conclusively prove that any particular event is or is not casually related to ephedra, provides strong support for the conclusion that use of dietary supplements containing ephedrine alkaloids does not increase the risk of seizures, strokes or heart attacks.

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