Clinical Briefs-With Comments from John La Puma, MD, FACP
Dangers of Products Containing Ephedra
February 2001; Volume 4; 23-24
Source: Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-1838.
"Dietary supplements that contain ephedra alkaloids (sometimes called ma huang) are widely promoted and used in the United States as a means of losing weight and increasing energy. In the light of recently reported adverse events related to use of these products, the Food and Drug Administration (FDA) has proposed limits on the dose and duration of use of such supplements. The FDA requested an independent review of reports of adverse events related to the use of supplements that contained ephedra alkaloids to assess causation and to estimate the level of risk the use of these supplements poses to consumers.
"We reviewed 140 reports of adverse events related to the use of dietary supplements containing ephedra alkaloids that were submitted to the FDA between June 1, 1997, and March 31, 1999. A standardized rating system for assessing causation was applied to each adverse event.
"Thirty-one percent of cases were considered to be definitely or probably related to the use of supplements containing ephedra alkaloids, and 31 percent were deemed to be possibly related. Among the adverse events that were deemed definitely, probably, or possibly related to the use of supplements containing ephedra alkaloids, 47 percent involved cardiovascular symptoms and 18 percent involved the central nervous system. Hypertension was the single most frequent adverse effect (17 reports); followed by palpitations, tachy-
cardia, or both (13); stroke (10); and seizures (7). Ten events resulted in death, and 13 events produced permanent disability, representing 26 percent of the definite, probable, and possible cases.
"The use of dietary supplements that contain ephedra alkaloids may pose a health risk to some persons. These findings indicate the need for a better understanding of individual susceptibility to the adverse effects of such dietary supplements."
Source: Gurley BJ, et al. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm 2000;57:963-969.
The ephedra alkaloid content of 20 ephedra-containing supplements was determined by high-performance liquid chromatography. Contents of (-)-ephedrine, (+)-pseudoephedrine, (-)-methylephedrine, (-)-norephedrine, and (+)-norpseudoephedrine were measured.
Ephedra alkaloid content varied considerably among products. Total alkaloid content ranged from 0.0-18.5 mg per dosage unit. Ranges for (-)-ephedrine and (+)-pseudoephedrine were 1.1-15.3 mg and 0.2-9.5 mg, respectively. (+)-Norpseudoephedrine, a Schedule IV controlled substance, was often present. Significant lot-to-lot variations in alkaloid content were observed for four products. For one product, lot-to-lot variations in the content of (-)-ephedrine, (+)-pseudoephedrine, and (-)-methylephedrine exceeded 180%, 250%, and 1,000%, respectively. Half of the products exhibited discrepancies between the label claim for ephedra alkaloid content and actual alkaloid content in excess of 20%. One product was devoid of ephedra alkaloids.
Assays of 20 ephedra-containing dietary supplements showed that alkaloid content often differed markedly from label claims and was inconsistent between two lots of some products.
COMMENT
Manufacturers and distributors of Metabolife 356®, Dexatrim®, and other popular over-the-counter ephedra-containing agents should read these articles, because it may help them avoid liability. Clinicians should read them because it may help their patients avoid stroke, myocardial infarction, and even death—without exaggeration.
These data demonstrate what most clinicians have heard by anecdote—hypertension, stroke, seizures, and death have been attributed to ephedra-containing compounds. What’s worse is that it’s not predictable how much ephedra or a metabolite is in any one given formulation—from nothing at all to, more commonly, 1,000% of expected. Lot-to-lot variation in any supplement is disturbing, but especially so in a deadly one.
Perhaps the only disease about which it is socially acceptable to taunt the victim, obesity is as frustrating to patients as it is to doctors. Patients who want to lose weight and seek a physician’s help in so doing are among the most motivated of all patients. It takes courage to make this request of a doctor, since patients realize that doctors know little about obesity treatment and have less time than ever for the behavior modification that is needed and effective.
Yet physician encouragement does not take long at all, and is much more helpful than any over-the-counter or prescription medication. Instead of medications, ask patients to do just two things to start: First, always sit while eating, and second, never eat out of the refrigerator. These two steps help people recognize ways to identify and control portion size, and to value the flavor and quality of the food they are about to inhale.
Recommendation
There are just no two ways about it: Ephedra alkaloids not only are unpredictably quantified in over-the-counter preparations, but are dangerous. In part they’re dangerous because of the demonstrated wild variance in concentration, and in part because of their sympathomimetic effects. Insist that patients avoid them...no exceptions.
February 2001; Volume 4; 23-24
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