In recent years, the safety of ephedra-containing dietary supplements has been questioned by the United States Food and Drug Administration , the National Center for Complementary and Alternative Medicine, and the medical community as a result of a high rate of serious side effects and ephedra-related deaths. In response to accumulating evidence of adverse effects and deaths related to ephedra, the FDA banned the sale of ephedra-containing supplements on April 12 2004. A suit by an ephedra manufacturer was upheld by a judge in Utah on April 14 2005. The FDA appealed this ruling, and on August 17 2006 the U.S. Court of Appeals for the Tenth Circuit upheld the FDA's ban of ephedra. The sale of ephedra-containing dietary supplements remains illegal in the United States due to evidence of adverse ephedra-related effects.
The alkaloids ephedrine and pseudoephedrine are the active constituents of the plant. Pseudoephedrine is used in decongestants. Derivatives of ephedrine are used to treat , but alternatives with reduced cardiovascular risk have replaced it for treating asthma. Ephedrine is also considered a performance-enhancing drug and is prohibited in most competitive sports. Some species in the ''Ephedra'' genus have no alkaloid content and are therefore essentially inert; however, the most commonly used species, ''E. sinica'', has a total alkaloid content of 1–3% by dry weight. Ephedrine constitutes 40–90% of the alkaloid content, with the remainder consisting of pseudoephedrine and the demethylated forms of each compound.
Effects and uses
Ephedra is both a stimulant and a thermogenic; its biological effects are due to its ephedrine and pseudoephedrine content. These compounds stimulate the brain, increase heart rate, constrict blood vessels , and expand bronchial tubes . Their thermogenic properties cause an increase in metabolism, evidenced by an increase in body heat.
In traditional Chinese herbology, ''E. sinica'' is included in many herbal formulas used to treat cold and flu such as 麻黃湯 ''ma huang tang'' or 麻杏石甘湯 ''ma xing shi gan tang'' . Ephedra is used therapeutically as a diaphoretic to help expel exterior pathogens and regulate the proper functioning of the lungs.
Ephedra is widely used by athletes, despite a lack of evidence that it enhances athletic performance. Ephedra may also be used as a precursor in the illicit manufacture of methamphetamine.
Ephedra has also been used for weight loss, sometimes in combination with aspirin and caffeine. Some studies have shown that ephedra, when taken in a regulated and supervised environment, is effective for marginal short-term weight loss , although it is unclear whether such weight loss is maintained. However, several reports have documented the large number of adverse events attributable to unregulated ephedra supplements.
Side effects of ephedra may include severe skin reactions, irritability, nervousness, dizziness, trembling, headache, insomnia, profuse perspiration, dehydration, itchy scalp and skin, vomiting, hyperthermia, , seizures, , stroke, or 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. 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.
Safety and regulatory actions in the United States
Escalating concerns regarding the safety of ephedra supplements led the FDA to ban the sale of ephedra-containing supplements in the United States in 2004. This ban was challenged by supplement manufacturers and initially overturned, but ultimately upheld. However, the FDA ban only applies to ephedra-based dietary supplements that contain ephedrine alkaloids.
Initial concerns and supplement industry response
In 1997, in response to mounting concern over 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 , stroke, or death.
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. The Ephedra Education Council also attempted to block publication of a study confirming wide discrepancies between the labeled potency of supplements and the actual amount of ephedra in the product. Senators Orrin Hatch and Tom Harkin, 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, Hatch's son was working for a firm hired to Congress and the FDA on behalf of ephedra manufacturers.
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."
Ultimately, in 2000, the FDA withdrew the proposed labeling changes and restrictions.
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.
Death of Steve Bechler
Steve Bechler, a 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. 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 Congress dropped objections to an ephedra ban and started demanding the FDA act."
In response to renewed calls for the regulation of ephedra, the FDA commissioned a large meta-analysis of ephedra's safety and efficacy by the RAND Corporation. This study found that while ephedra promoted modest short-term weight loss, there was no evidence that it was effective for long-term weight loss or performance enhancement. The use of ephedra in this study was associated with significant gastrointestinal, psychiatric, and side effects. Almost simultaneously, a study in ''Annals of Internal Medicine'' found that ephedra was 100 to 700 times more likely to cause a significant adverse reaction than other commonly used supplements such as kava or Ginkgo biloba. Subsequently, on April 12 2004, the FDA issued a final rule banning the sale of ephedra-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."
The ruling was appealed to the U.S. Court of Appeals for the Tenth Circuit in Denver, Colorado. On August 17 2006, the Appeals Court upheld the FDA's ban of ephedra, finding that the 133,000-page administrative record compiled by the FDA supported the agency's finding that ephedra posed an unreasonable risk to consumers. The U.S. National Football League banned players from using ephedra as a dietary supplement in 2001 after the death of Minnesota Vikings offensive tackle Korey Stringer; ephedra was found in Stringer's locker and lawyers for the team contend that it contributed to his death. The substance is also banned by the National Basketball Association.
Prominent cases of ephedra use
In the 1994 , the footballer tested positive for ephedrine. The Japanese motorcycle racer Noriyuki Haga tested positive for it in 2000, being disqualified from two races and banned from two more as a result. NFL Todd Sauerbrun of the Denver Broncos was suspended for the first month of the 2006 season after testing positive for ephedra.