Ephedra is a medicinal preparation from the plant Ephedra sinica. Several additional species belonging to the genus Ephedra have traditionally been used for a variety of medicinal purposes, and are a possible candidate for the soma plant of Indo-Iranian religion., from Encyclopædia Iranica. Accessed March 15, 2007. It has been used in traditional Chinese medicine, in which it is referred to as Ma Huang, for more than 2,000 years. Native Americans and Mormon pioneers drank a tea brewed from other Ephedra species, called "Mormon tea" and "Indian tea".

Dietary supplements containing ephedra alkaloids are unsafe, with reports of serious side effects and ephedra-related deaths. In response to accumulating evidence of adverse effects and deaths related to ephedra, the U.S. Food and Drug Administration (FDA) banned the sale of supplements containing ephedrine alkaloids in 2004. The ban was challenged in court by ephedra manufacturers, but ultimately upheld in 2006 by the U.S. Court of Appeals for the Tenth Circuit. Ephedra extracts not containing ephedrine have not been banned by the FDA and are still sold legally.

Biochemistry and effects

A wide variety of alkaloid and non-alkaloid compounds have been identified in various species of Ephedra. Of the six ephedrine-type ingredients found in ephedra (at concentrations of 0.02-3.4%), the most common are ephedrine and pseudoephedrine, which are the sources of its stimulant and thermogenic effects. These compounds stimulate the brain, increase heart rate, constrict blood vessels (increasing blood pressure), and expand bronchial tubes (making breathing easier). Their thermogenic properties cause an increase in metabolism, as evidenced by an increase in body heat.

Ephedra is widely used by athletes as a performance-enhancing drug, despite a lack of evidence that it improves athletic performance. Ephedra may also be used as a precursor in the illicit manufacture of methamphetamine.

Ephedra has been used as a weight-loss aid, sometimes in combination with aspirin and caffeine. Some studies in regulated and supervised environments have shown that ephedra is effective for marginal short-term weight loss (0.9 kg/month more than the placebo), although it was untested whether such weight loss is maintained. However, several reports have documented a number of adverse events attributable to unregulated ephedra supplements.

Adverse effects of ephedra consumption may include severe skin reactions, irritability, nervousness, dizziness, trembling, headache, insomnia, profuse perspiration, dehydration, itchy scalp and skin, vomiting, and hyperthermia. More serious potential side effects include irregular heartbeat, seizures, heart attack, stroke, and death.

Purity and dosage

There are no formal requirements for standardization or quality control of dietary supplements in the United States, and the dosage of effective ingredients in supplements may vary widely from brand to brand or batch to batch."Swallowing Ephedra" , by Sharon Brownlee. Published online at Salon.com on June 7, 2000. Accessed 8 February 2007.Dietary Supplements: Background Information . From the Office of Dietary Supplements at the National Institutes of Health. Accessed 7 February 2007.Herbal Rx: the promise and pitfalls. Consumer Reports, 1999, pp 44–48. Studies of ephedra supplements have found significant discrepancies between the labeled dose and the actual amount of ephedra in the product. Significant variation in ephedrine alkaloid levels, by as much as 10-fold, was seen even from lot to lot within the same brand.

Regulation in the United States

Escalating concerns regarding the safety of ephedra supplements led the FDA to ban the sale of supplements containing ephedrine alkaloids (specifically ephedrine, pseudoephedrine, norephedrine, and methylephedrine) in the United States in 2004. This ban was challenged by supplement manufacturers and initially overturned, but ultimately upheld.

Initial concerns and industry response

In 1997, in response to mounting concern over the serious side effects of ephedra, the FDA proposed a ban on products containing 8 mg or more of ephedrine alkaloids and stricter labeling of low-dose ephedra supplements. The FDA also proposed that ephedra labels be required to disclose the health risks of ephedra, such as heart attack, stroke, and death."Dietary Supplements Containing Ephedrine Alkaloids; Proposed Rule" , from the Federal Register, June 4, 1997. Accessed 7 February 2007.

In response, the supplement industry created a public relations group, the Ephedra Education Council, to oppose the changes, and commissioned a scientific review by a private consulting firm, which reported that Ephedra was safe."Dangerous supplements: Still at large", from Consumer Reports magazine. Published May 2004, accessed 7 February 2007. The Ephedra Education Council also attempted to block the publication of a study confirming wide discrepancies between the labeled potency of supplements and the actual amount of ephedra in the product.

Metabolife, makers of the best-selling brand of ephedra supplement, had received over 14,000 complaints of adverse events associated with its product. These reports were not initially provided to the FDA.Criminal investigation sought for diet supplement seller, published in USA Today on August 15, 2002. Accessed April 10, 2007. Co-founder of Metabolife, Michael Ellis, was sentenced in 2008 to six months in federal prison for his failure to report adverse effects from his company's products to the FDA.Metabolife Founder Sentenced For Lying To FDA Senators Orrin Hatch (R. Utah) and Tom Harkin (D. Iowa), authors of the Dietary Supplements Health and Education Act, questioned the scientific basis for the FDA's proposed labeling changes and suggested that the number of problems reported were insufficient to warrant regulatory action. At the time, Senator Hatch's son was working for a firm hired to lobby Congress and the FDA on behalf of ephedra manufacturers."Senator, His Son Get Boosts From Makers of Ephedra" , published in the Los Angeles Times on March 5, 2003. Purchase required to view full text. Accessed 7 February 2007.

In addition to the activities of the Ephedra Education Council, Metabolife spent more than $4 million between 1998 and 2000 lobbying against state regulation of ephedra in Texas. Business Week reported that efforts to regulate ephedra and other potentially harmful supplements had been "beaten down by deep-pocketed industry lobbying.""Diet Pills and Pols: A Dangerous Mix" , by Arlene Weintraub and John Carey. Published in Business Week on September 2, 2002. Accessed March 31, 2007.

In 2000, the FDA withdrew the proposed labeling changes and restrictions."Dietary Supplements Containing Ephedrine Alkaloids; Withdrawal in Part" , from the Federal Register, April 3, 2000. Accessed 7 February 2007.

Additional evidence and deaths

A review of ephedra-related adverse reactions, published in the New England Journal of Medicine in 2000, found a number of cases of sudden cardiac death or severe disability resulting from ephedra use, many of which occurred in young adults using ephedra in the labeled dosages. Subsequently, in response to pressure from the consumer advocacy group Public Citizen, Metabolife was compelled by the Department of Justice in 2002 to turn over reports of over 15,000 ephedra-related adverse events, ranging from insomnia to death, which the company had previously withheld from the FDA."The Secret of Ephedra's Questionable Success". A report on "All Things Considered", National Public Radio, November 22, 2002. Accessed 7 February 2007. Use of ephedra was considered to have possibly contributed to the death of Minnesota Vikings offensive lineman Korey Stringer from heatstroke in 2001.Vikings: Stringer's use of ephedra contributed to death, published online by Sports Illustrated on February 25, 2003. Accessed March 15, 2007.

Steve Bechler, a pitcher for the Baltimore Orioles, died of complications from heatstroke following a spring training workout on February 17, 2003. The medical examiner found that ephedra toxicity played a "significant role" in Bechler's sudden death."Medical examiner: Ephedra a factor in Bechler death", from USA Today, published March 13, 2003. Accessed 7 February 2007. Following Bechler's death, the FDA re-opened its efforts to regulate ephedra use. According to Bruce Silverglade, legal director for the Center for Science in the Public Interest, "All of a sudden [after Bechler's death] Congress dropped objections to an ephedra ban and started demanding that the FDA act."

Senator Orrin Hatch (R. Utah), who in 1999 had helped block the FDA's attempts to regulate ephedra, said in March 2003 that "...it has been obvious to even the most casual observer that problems exist", and called FDA action to regulate ephedra "long overdue."

Ephedrine supplement ban

In response to renewed calls for the regulation of ephedra, the U.S. Department of Health and Human Services commissioned a large meta-analysis of ephedra's safety and efficacy by the RAND Corporation. This study found that ephedra promoted modest short-term weight loss, but there was insufficient data to determine whether it was effective for long-term weight loss or performance enhancement. The use of ephedrine alkaloids in this study was associated with significant gastrointestinal, psychiatric, and autonomic side effects. Almost simultaneously, a study in Annals of Internal Medicine found that ephedrine alkaloids were 100 to 700 times more likely to cause a significant adverse reaction than other commonly used supplements such as kava or Ginkgo biloba.

On December 30, 2003, the FDA issued a press release recommending that consumers stop buying and using products containing ephedrine alkaloids, and indicating its intention to ban the sale of ephedrine alkaloid-containing supplements."FDA Announces Plans to Prohibit Sales of Dietary Supplements Containing Ephedra": Press release from the FDA website, issued December 30, 2003, accessed 7 February 2007. Subsequently, on April 12, 2004, the FDA issued a final rule banning the sale of ephedrine alkaloid-containing dietary supplements. Tommy Thompson, the Secretary of Health and Human Services, stated that "...These products pose unacceptable health risks, and any consumers who are still using them should stop immediately." Products containing ephedra extract remain legal to this day.

Legal challenges

Nutraceutical Corporation, a supplement manufacturer based in Park City, Utah, challenged the legality of the FDA's ban of Ephedra alkaloids as exceeding the authority given to the agency by the Dietary Health Supplements and Education Act. Nutraceutical Corporation stated that while they did not intend to restart marketing ephedra, they were concerned about the scope of the FDA's regulatory action. Judge Tena Campbell of Utah's Federal District Court ruled that the FDA had not proven that low doses of ephedra alkaloids were unsafe, although she also noted that studies to address the safety of low-dose ephedra would be unethical. Nevertheless, her ruling overturned the ban on the sale of ephedra alkaloids in the state of Utah, and called into question whether the ban could be enforced anywhere in the United States."Judge's Decision Lifts Ban On Sale of Ephedra in Utah", from The New York Times, published April 15, 2005. Accessed 7 February 2007.