RAND Study Raises Safety Concerns About Ephedra And Ephedrine

An exhaustive review by RAND researchers of health studies involving products containing the herb ephedra or the drug ephedrine raises concern about the safety of the products, which are used by millions of American seeking to promote weight loss or enhance athletic performance.

The available evidence is sufficient to conclude that these products are related to a two- or three-fold increase in side effects such as nausea, vomiting, jitteriness, and palpitations, according to a new RAND Health study released today. Furthermore, the evidence suggests a link between these products and catastrophic events such as sudden death, heart attack or stroke.

“With regard to catastrophic events, these findings are a strong signal that there is a link between use of ephedra or ephedrine and the occurrence of death, heart attack, stroke, seizures, and serious psychiatric symptoms,” said Paul Shekelle, the RAND and Veterans Affairs physician who headed the study. “It is more likely than not that there is a relationship, although the available evidence falls short of the conventional level of scientific proof.”

The RAND study concludes that more analyses of existing data are unlikely to settle the issue and that new data are needed.

“One of the most expeditious ways to test whether there is a relationship is to conduct a 'case-control' study, where ephedra use by people who suffered death or other serious illness is compared to use by similar individuals who have not suffered the problem,” said Sally Morton, holder of the RAND Endowed Chair in Statistics and a co-author of the study.

Such a case control study was recently used to establish a link between the use of phenylpropanolamine, a drug related to ephedrine and also used for weight loss, and an increased risk of hemorrhagic stroke in women.

The RAND study was requested and funded by the U.S. Department of Health and Human Services in 2001 to examine issues related to the safety and effectiveness of products containing ephedra and synthetic ephedrine (a stimulant found in ephedra). Ephedra is an herbal supplement promoted for weight loss and athletic performance, while ephedrine is found in over-the-counter drugs used to treat stuffy nose and asthma.

The RAND study also found some evidence of benefits of ephedra and ephedrine for weight loss. Dietary supplements containing ephedra, the drug ephedrine, and ephedrine plus caffeine promoted modest short-term weight loss, averaging about two pounds per month more than among people taking a placebo. However, none of the studies reviewed followed participants for longer than six months, less than the 12 months accepted as necessary to establish a drug's value as a weight-loss aid.

Although many of the ephedra supplements and ephedrine products are taken for boosting athletic performance, researchers found no evidence that ephedra—and scant evidence that ephedrine—enhances physical performance. They found no evidence that any of the products improve long-term physical performance among athletes or the general public.

The report on ephedra and ephedrine was released today by federal officials.

The study was done by the RAND-based Southern California Evidence-Based Practice Center, which also includes researchers from the Greater Los Angeles Veterans Administration Healthcare System and Cedars-Sinai Medical Center.

RAND researchers based their findings on a detailed review of 52 clinical trials of ephedrine or herbal ephedra for weight loss or athletic performance in humans. They searched the medical literature and other sources for both published and unpublished medical trials of the substances.

Researchers also analyzed more than 1,500 “adverse event reports” related to herbal ephedra and 125 such reports related to synthetic ephedrine-containing products, which were collected by the U.S. Food and Drug Administration. Researchers discovered 70 additional adverse events in the medical literature and received a computer file of more than 18,000 adverse events from Metabolife, a maker of ephedra products.

RAND Health is the nation's largest independent health policy research organization, with a broad research portfolio that focuses on medical quality, health care costs and delivery of health care, among other topics.

The Southern California Evidence-Based Practice Center is one of 13 evidence-based practice programs nationally sponsored by the federal Agency for Healthcare Research and Quality. The center conducts systematic reviews and technology assessments of all aspects of health care.