Under DSHEA, manufacturers are responsible for ensuring the safety of  dietary supplements they sell. FDA has received reports of adverse events associated with dietary  supplements containing ephedra, including heart attack, stroke, seizure,  psychosis, and death, that are consistent with the scientific literature. The American Medical Association and the American  Heart Association have urged FDA to ban the sale of dietary supplements  containing ephedra. Adverse Event Reports Have Led FDA to Conclude That Dietary Supplements Containing Ephedra Pose a Significant Public Health Hazard

Using the adverse event reports it has received and evidence from the  scientific literature, FDA has concluded that dietary supplements  containing ephedra pose a “significant public health hazard.” FDA and  others have received thousands of reports of adverse events among users  of dietary supplements containing ephedra, more than for any other  dietary supplement ingredient. From February  22, 1993, through July 14, 2003, FDA received 2,277 reports of adverse  events associated with dietary supplements containing ephedra, which  was 15 times more reports than it received for the next most commonly  reported herbal dietary supplement, St. John’s wort. Metabolife International Call Records Contain Reports of Adverse Events That Are Consistent with the Types of Adverse Events Reported to FDA

The types of adverse events that we identified in the Metabolife  International call records are consistent with the types of adverse events  reported to FDA and with the documented physiological effects of  ephedra. Metabolife International Call Records Contained Reports of Thousands of Adverse Events, Some of Which Were Serious, among Consumers of Metabolife 356

As we reported in March 2003, we identified 14,684 call records that  contained at least one report of an adverse event among consumers of  Metabolife 356. Within the call  records, we identified 92 reports of heart attack, stroke, seizure, and death  (see table 1). Our count of reports of these serious adverse events was  similar to that of other reviews of the Metabolife International call records,  including counts by Metabolife International and its consultants. Serious Adverse Events Were Reported among Consumers Who Used Metabolife 356 within Recommended Guidelines

Within the subset of Metabolife International call records that contained  information on how the product was used by the consumer, most of the  reported serious adverse events occurred among consumers who reported  using the product within the guidelines on the Metabolife 356 label—that  is, who reported that they did not take more of the product or take it for a  longer period than recommended. FDA Has Taken Some Actions to Oversee Dietary Supplements Containing Ephedra

As part of its oversight of dietary supplements, FDA has taken some  actions specifically focused on dietary supplements containing ephedra. FDA has issued warnings that focus on improper product labeling, issued  warnings to consumers, and issued a proposed rule in 1997 that, among  other things, would require a health warning on the label of dietary  supplements containing ephedra and prohibit a dietary supplement from  containing both ephedra and a stimulant. In the interim, FDA has taken action to regulate certain drugs that contain  ephedrine, the active ingredient in ephedra. There  currently is no similar rule prohibiting the marketing of dietary  supplements containing ephedra in combination with analgesics or  stimulants, such as caffeine. In fact, many dietary supplements  with ephedra, such as Metabolife 356, also include caffeine. The proposed  rule contains a provision that would prohibit dietary supplements from  containing both ephedra and other stimulants. On July 14, 2003, FDA reported to us that the agency is in the process of  reviewing the comments and has not reached a decision regarding further  action.
Why GAO Did This Study

Dietary supplements containing ephedra have been associated with serious health-related adverse events, including heart attacks, strokes, seizures, and deaths. The Food and Drug Administration (FDA) regulates dietary supplements under the Dietary Supplement Health and Education Act of 1994 (DSHEA). Reports of adverse events have been received by FDA and others, including Metabolife International, the manufacturer of a dietary supplement containing ephedra, Metabolife 356. Because of concerns surrounding the safety of dietary supplements containing ephedra, GAO was asked to discuss and update some of the findings from its prior work on ephedra, including its examination of Metabolife International's records of health-related calls from consumers of Metabolife 356. Specifically, GAO examined (1) FDA's analysis of the adverse event reports it received for dietary supplements containing ephedra, (2) how the adverse events reported in the health-related call records collected by Metabolife International illustrate the health risks of dietary supplements containing ephedra, and (3) FDA's actions in the oversight of dietary supplements containing ephedra.

What GAO Found

FDA has used the adverse event reports it has received to conclude that dietary supplements containing ephedra pose a significant public health hazard. Since February 1993, FDA has received 2,277 reports of adverse events associated with dietary supplements containing ephedra, 15 times more reports than it has received for the next most commonly reported herbal dietary supplement. The types of adverse events that GAO identified in the health-related call records from Metabolife International were consistent with the types of adverse events reported to FDA and with the documented physiological effects of ephedra. Although call records contained limited information for most of the reports, GAO identified 14,684 call records that had reports of at least one adverse event among consumers of Metabolife 356. GAO's count of 92 serious events--heart attacks, strokes, seizures, and deaths--was similar to that of other reviews of the call records, including counts by Metabolife International and its consultants. Many of the serious events were reported among relatively young consumers--more than one-third concerned consumers who reported an age under 30. In addition, for call records containing information on the amount of product consumed or length of product use, GAO found that most of the reported serious adverse events occurred among consumers who followed the usage guidelines on the Metabolife 356 label. As part of its oversight of dietary supplements, FDA has taken some actions specifically focused on dietary supplements containing ephedra. FDA has issued warnings that focus on improper labeling, issued warnings to consumers, and issued a proposed rule in 1997 that, among other things, would require a health warning on the label of dietary supplements containing ephedra and prohibit a dietary supplement from containing both ephedra and a stimulant. FDA subsequently banned the sale of certain classes of over-the-counter drugs containing ephedrine and related alkaloids--the active ingredient in ephedra--in combination with an analgesic or stimulant. As the 1997 proposed rule has not been finalized, there is no rule prohibiting the marketing of dietary supplements with similar ingredients, and many dietary supplements with ephedra, such as Metabolife 356, also include caffeine or other stimulants. To receive comments on new evidence, FDA recently reopened the comment period for the proposed rule, and FDA reported to GAO that the agency is in the process of reviewing comments it has received and has not reached a decision regarding further action.