Ephedra is a medicinal preparation from the plantEphedra sinica.[1][a] Several additional species belonging to the genusEphedra have traditionally been used for a variety of medicinal purposes, and are a possible candidate for thesoma plant ofIndo-Iranian religion.[3] It has been used intraditional Chinese medicine, in which it is referred to as Ma Huang, for more than 2,000 years.[4][5]Native Americans andMormon pioneers drank a tea brewed from otherEphedra species, called "Mormon tea" and "Indian tea".
Dietary supplements containing ephedra alkaloids are unsafe, with reports of serious side effects and ephedra-related deaths.[6][7][8][9] In response to accumulating evidence of adverse effects and deaths related to ephedra, theU.S. Food and Drug Administration (FDA) banned the sale of supplements containing ephedrine alkaloids in 2004.[10] The ban was challenged in court by ephedra manufacturers, but ultimately upheld in 2006 by theU.S. Court of Appeals for the Tenth Circuit.[11] Ephedra extracts not containing ephedrine have not been banned by the FDA and are still sold legally.[12]
A wide variety ofalkaloid and non-alkaloid compounds have been identified in various species ofEphedra. Of the six ephedrine-type ingredients found in ephedra (at concentrations of 0.02-3.4%), the most common areephedrine andpseudoephedrine,[13] which are the sources of itsstimulant andthermogenic effects.[4] These compounds stimulate the brain, increaseheart rate, constrict blood vessels (increasingblood 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 aperformance-enhancing drug,[14] despite a lack of evidence that it improves athletic performance.[15][16] Ephedra may also be used as a precursor in the illicit manufacture ofmethamphetamine.[17]
Ephedra has been used as a weight-loss aid, sometimes in combination withaspirin andcaffeine. 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.[18] However, several reports have documented a number ofadverse events attributable to unregulated ephedra supplements.[19]
Adverse effects of ephedra consumption may include severe skin reactions, irritability, nervousness, dizziness, trembling,headache,insomnia, profuse perspiration,dehydration, itchy scalp and skin, vomiting, andhyperthermia. More serious potential side effects includeirregular heartbeat,seizures,heart attack,stroke, anddeath.[20]
There are no formal requirements forstandardization orquality 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.[21][22][23] 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.[24][25]
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.
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 asheart attack,stroke, and death.[26]
In response, thesupplement industry created apublic 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.[27] 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.[21]
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.[27][28] 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.[29] SenatorsOrrin Hatch (R. Utah) andTom 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 tolobby Congress and the FDA on behalf of ephedra manufacturers.[30]
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.[31]Business Week reported that efforts to regulate ephedra and other potentially harmful supplements had been "beaten down by deep-pocketed industry lobbying."[32]
In 2000, the FDA withdrew the proposed labeling changes and restrictions.[33]
A review of ephedra-related adverse reactions, published in theNew England Journal of Medicine in 2000, found a number of cases ofsudden cardiac death or severe disability resulting from ephedra use, many of which occurred in young adults using ephedra in the labeled dosages.[6] Subsequently, in response to pressure from theconsumer advocacy groupPublic Citizen,[32] Metabolife was compelled by theDepartment of Justice in 2002 to turn over reports of over 15,000 ephedra-related adverse events, ranging frominsomnia to death, which the company had previously withheld from the FDA.[27][34] Use of ephedra was considered to have possibly contributed to the death ofMinnesota Vikingsoffensive linemanKorey Stringer fromheatstroke in 2001.[35]
Steve Bechler, apitcher for theBaltimore Orioles, died of complications from heatstroke following aspring training workout on February 17, 2003. Themedical examiner found that ephedra toxicity played a "significant role" in Bechler's sudden death.[36] Following Bechler's death, the FDA re-opened its efforts to regulate ephedra use. According to Bruce Silverglade, legal director for theCenter 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."[27]
SenatorOrrin 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."[30]
In response to renewed calls for the regulation of ephedra, theU.S. Department of Health and Human Services commissioned a largemeta-analysis of ephedra's safety and efficacy by theRAND 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, andautonomic side effects.[37] Almost simultaneously, a study inAnnals 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 askava orGinkgo biloba.[7]
On December 30, 2003, the FDA issued apress 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.[38] Subsequently, on April 12, 2004, the FDA issued a final rule banning the sale of ephedrine alkaloid-containing dietary supplements.Tommy Thompson, theSecretary of Health and Human Services, stated that "...These products pose unacceptable health risks, and any consumers who are still using them should stop immediately."[10] Products containing ephedra extract remain legal to this day.[12]
Nutraceutical Corporation, a supplement manufacturer based inPark 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'sFederal 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 beunethical. 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.[39]
The ruling was appealed to theU.S. Court of Appeals for the Tenth Circuit inDenver, Colorado. On August 17, 2006, the Appeals Court upheld the FDA's ban on Ephedra alkaloids, finding that the 133,000-page administrative record compiled by the FDA supported the agency's finding that ephedra alkaloids posed an unreasonable risk to consumers.[11] Nutraceutical Corp. filed a petition for awrit of certiorari seeking a rehearing on the ban of ephedra alkaloids; however, on May 14, 2007 theUnited States Supreme Court declined to hear this petition. The sale of ephedra alkaloid-containing dietary supplements remains illegal in the United States.[9] Sales of products containing ephedra extract not containing ephedrine remain legal.[12]
Ephedrine is listed as abanned substance by both theInternational Olympic Committee and theWorld Anti-Doping Agency.[40] TheNational Football League banned players from using ephedra as a dietary supplement in 2001 after the death ofMinnesota Vikingsoffensive tackleKorey Stringer; ephedra was found in Stringer's locker and lawyers for the team contended that it contributed to his death.[35][41] The substance is also banned by theNational Basketball Association.[39] It was also banned byMajor League Baseball after the 2003 death ofSteve Bechler. Nonetheless, ephedra remains widely used by athletes; a 2006 survey of collegiate hockey players found that nearly half had used ephedra believing it enhanced their athletic performance.[14]
In the 1994FIFA World Cup, theArgentine footballerDiego Armando Maradona tested positive for ephedrine.[42] The Japanesemotorcycle racerNoriyuki Haga tested positive for ephedrine in 2000, being disqualified from two races and banned from two more as a result.[43] NFLpunterTodd Sauerbrun of theDenver Broncos was suspended for the first month of the 2006 season after testing positive for ephedrine.[41]
Throughout the many hymns, prayers, and philosophy found in theVedas (written around 1500 BC), a mysterious plant is mentioned often and with great reverence. This plant alternates from a holy substance to an actual personified god and is considered a teacher, doctor, medicine, a bringer of insight, and a vector of inspiration.[44] The deity version of Soma was associated with medicinal herbs and the moon and was considered a bringer of health and prosperity.[45] The plant was an essential aspect of Vedic religion to alter one’s mind, enabling communion with the divine. The ritual drinking of Soma is also mentioned in the ancient Zoroastrian text, the Avesta,[44] where the rituals and importance of the plant are very similar to those in Vedic culture but are instead called by the namehaoma.[44] It is unknown why, but eventually in both the Vedic and Zoroastrian cultures a substitute substance was used in these religious ceremonies and over time the definitive identity of Soma-Haoma has been lost.[citation needed] There is much debate over which species of plant are the sacred plant of the Vedic and Zoroastrian faiths.
The Rigveda is one of the four oldest and most sacred collections of stories in Hinduism. In the Rigveda soma is a drink consumed by two of the main gods;Agni andIndra. In the texts, the drink helped the gods in battle by strengthening them physically.[46] Because of this, soma was given and consumed by warriors before wartime or a battle. The drink was supposed to give the warriors strength and luck in the upcoming conflict.[47] Immortality is also a quality associated with soma due to it being a drink of the divine. At religious ceremonies the drink was consumed to give consumers longevity in life. At birth the drink was also given to the babies for these same reasons.[47]
In Zoroastrianism, the drink is called haoma and has similar uses. Just like inHinduism, the drink was related to immortality and long life. Haoma was the first thing newborns drank. This assured the child would be healthy and live a long life.[47] The drink was also administered to people close to death to revive them back into good health.[47]
The physical appearance of Ephedra is also a reason it is believed to be the soma plant. According to the Vedic textRigveda, the plant comprising soma is shaped like an arrow. Ephedra sinica is agymnosperm that forms stalks with buds on the end. It is easy to see how this shape could be described as an arrow.[47] Another text refers to soma as a twig, which is much like Ephedra sinica when it is dried out.[44]