Clinical Briefs: Ephedra and Adverse Events
With Comments from John La Puma, MD, FACP
Source: Samenuk D, et al. Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc 2002;77:12-16.
To evaluate possible cardiovascular toxic effects associated with use of dietary supplements containing ma huang, an herbal source of ephedrine, these authors reviewed the comprehensive database Adverse Reaction Monitoring System of the Food and Drug Administration (FDA), which included clinical records, investigative reports, and autopsy reports related to ma huang use. The main outcome measurements were stroke, myocardial infarction, and sudden death. From 1995 to 1997, 926 cases of possible ma huang toxicity were reported to the FDA. In 37 patients (23 women, 14 men, mean age ± SD: 43 ± 13 years), use of ma huang was temporally related to stroke (16), myocardial infarction (10), or sudden death (11). Autopsies performed in seven of the 11 patients who experienced sudden death showed a normal heart in one, coronary atherosclerosis in three, and cardiomyopathies in three. In 36 of the 37 patients, use of ma huang was reported to be within the manufacturers’ dosing guidelines. Analysis of the 37 patients indicates the following findings: 1) ma huang use is temporally related to stroke, myocardial infarction, and sudden death; 2) underlying heart or vascular disease is not a prerequisite for ma huang-related adverse events; and 3) the cardiovascular toxic effects associated with ma huang were not limited to massive doses. Although the pathogenesis of the cardiac toxic effects of ma huang remains incompletely defined, available observational and circumstantial evidence indicates that use of the substance may be associated with serious medical complications.
This objective analysis of FDA data shows that in those patients in the FDA database through 1997, 36 of 37 had temporally related vascular events. These data have been disputed by a paid consultant to the Ephedra Education Council, who found other reasons for sudden death and for the cardiovascular events reports in 20 of the 22 fatal cases.
Fewer than 10%, and some believe that less than 1%, of adverse reactions to dietary supplements are reported to the FDA. So, these data, even if associated with other possibilities, and even though they are simply adverse event reports, need to be more carefully researched.
Is there a safe dose of ephedra? The industry recommends no more than 100 mg/d. The FDA tried unsuccessfully to limit what manufacturers could recommend to a dose of 24 mg/d for seven consecutive days. Many manufacturers recommend much more than this.
Give patients an alternative to ephedra just by raising the question. From pre-contemplation to contemplation is a big step, and can be a quantitative one: "I’m concerned about the effect your weight has on your risk factors for heart disease. Your risk is X% in 10 years. Have you thought about trying to lose weight?"