FDA Consumer magazine
May-June 2003
Table of Contents

Public Health Officials Caution Against Ephedra Use

By Michelle Meadows

The death of Baltimore Orioles pitcher Steve Bechler in February 2003 brought renewed attention to the dangers of using the herb ephedra. Bechler died from multiple organ failure due to heat stroke, and a dietary supplement containing ephedra was a contributing factor, according to Joshua Perper, M.D., chief medical examiner in Broward County, Fla.

Soon after Bechler's death at age 23, minor league baseball banned ephedra, joining other sports organizations that had already banned its use--the National Football League, the National Collegiate Athletic Association, and the International Olympic Committee.

Health officials recently cautioned American consumers against using ephedra-containing products, especially if strenuous exercise is involved, or in combination with other stimulants such as caffeine. Because ephedra is an adrenaline-like stimulant, it can have potentially dangerous effects on the nervous system and heart.

A naturally occurring substance derived from ma huang, a Chinese herbal medicine, ephedra has been promoted to help people lose weight, enhance athletic performance, and increase energy. Its principal active ingredient is a chemical called ephedrine.

Because ephedra is an herb, it is considered a dietary supplement regulated under the Dietary Supplement Health and Education Act of 1994. Under that law, the FDA does not review dietary supplements for safety and effectiveness before they are marketed. Rather, the law allows the FDA to prohibit sale of a dietary supplement only if it "presents a significant or unreasonable risk of injury."

Synthetic ephedrine, however, is regulated as a drug. Ephedrine-containing products taken orally can be sold over-the-counter (OTC) without premarket approval as long as they conform to the final monograph for OTC drug products used for temporary relief of asthma symptoms. Final monographs cover the formulation, use, and labeling of OTC drug products. Prescription medicines with ephedrine for uses other than those covered by the monograph require premarket review for safety and effectiveness.

Synthetic ephedrine can be found in OTC and prescription drugs taken orally for temporary relief of shortness of breath, chest tightness, and wheezing due to bronchial asthma. Synthetic ephedrine can also be used as a topical nasal decongestant (nose drops, sprays, or jelly) for temporary relief of nasal congestion due to colds, hay fever, sinusitis, or other upper respiratory allergies. As a regulated drug product, synthetic ephedrine has mandatory warnings and labeling for short-term use. It also isn't allowed to be used in combination with caffeine or other stimulants that could interact with it. The controlled availability of synthetic ephedrine drug products under FDA regulation has not been reported to be associated with the same level of severe adverse events that have been reported with dietary supplements containing ephedra.

Still, Barbara Michal, a paralegal in San Bernardino, Calif., says she's extremely concerned about the OTC availability of ma huang, ephedra, and ephedrine, whether in herbal form in dietary supplements or as synthetic ephedrine in drugs. She founded a nonprofit group called Halt Ephedrine Abuse Today (HEAT) after her son Kristopher died in 1997, at age 24, of sudden cardiac arrest due to an accidental ephedrine overdose.

"I got a frantic call from Kristopher's wife, Nicole, saying that he collapsed," says Michal. "All the paramedics could tell me was that he was down for 10 minutes and that they were working on him," she says. "I drove for three hours to get there--knowing without really knowing that my son was dead."

Michal says Kristopher was using one of two over-the-counter products containing synthetic ephedrine at different times: maximum strength Efedrin and Mini Two Way Action, formerly called Mini Thins. "The products are labeled as asthma aids, but I've known people who bought them from gas stations, truck stops, convenience stores and liquor stores, and used them as stimulants," Michal says. "Kristopher took them for a pick-me-up and, like many people, had no idea of the risks. For one thing, if he wasn't drinking Mountain Dew, he was drinking coffee. I have since learned that caffeine makes ephedrine even more dangerous." Both beverages contain caffeine.

HHS Announces New Actions

In February 2003, researchers at the RAND Corporation released results of a federally sponsored study that examined available information on products containing the herb ephedra and the drug ephedrine. The study included a review of more than 1,500 adverse event reports related to ephedra that were voluntarily reported to the FDA, and 125 such reports related to products containing synthetic ephedrine.

The researchers concluded that ephedra is associated with risks of side effects such as heart palpitations, psychiatric and upper gastrointestinal effects, and symptoms of hyperactivity such as tremor and insomnia, especially when taken with other stimulants.

RAND's review of some 15,000 additional reports submitted by Metabolife International in the summer of 2002 revealed two deaths, four heart attacks, nine strokes, one seizure, and five psychiatric cases involving ephedra, in which no other contributing factors were identified. RAND called such cases "sentinel events" because they may indicate a safety problem, but don't prove that ephedra caused the adverse event. The review also found some evidence of ephedra's modest effect on short-term weight loss and scant evidence of its effect on performance enhancement in certain physical activities.

In February 2003, the Department of Health and Human Services and the FDA announced a series of actions designed to protect Americans from potentially serious risks of dietary supplements containing ephedra. These include:

Seeking rapid public comment on the new information on health risks associated with dietary supplements containing ephedrine alkaloids. This will establish an up-to-date public record to support new restrictions on products containing ephedrine alkaloids.
Seeking rapid public comment on whether currently available information and medical literature present a "significant or unreasonable risk of illness or injury" from dietary supplements containing ephedra. In seeking comment, the FDA reopened a 1997 proposed rule titled "Dietary Supplements Containing Ephedrine Alkaloids." That rule would have required a warning statement for these products, as well as restrictions on dosage. The FDA withdrew parts of this 1997 proposed rule because of concerns expressed by the General Accounting Office about the information used to establish dose limits.
Seeking public comment on a mandatory warning label on any ephedra products that continue to be marketed. The proposed warning label warns about the risks of serious adverse events, including heart attack, seizure, stroke, and death, and further cautions that the risk can increase with dose, with strenuous exercise, and when used with other stimulants, such as caffeine. The proposed label specifies those who should never use these products, such as women who are pregnant or breast-feeding. It also lists other conditions, such as diabetes and the use of certain medications, that rule out the use of products containing ephedra.
Taking actions against ephedra products making unsubstantiated claims about sports performance enhancement. The FDA has sent more than two dozen warning letters to firms marketing dietary supplements that contain ephedrine alkaloids. The letters explain that any claims products make on the structure and function of the human body must be truthful and not misleading. The agency letters also warn companies that they must not make claims about their products' ability to treat or cure a disease or condition, such as obesity. Under the Federal Food, Drug, and Cosmetic Act, dietary supplements with disease claims are considered unapproved new drugs and therefore subject to prompt regulatory actions, including injunctions against firms and seizures of their products.

The FDA continues to work closely with the Federal Trade Commission to ensure that makers of dietary supplements containing ma huang or ephedra don't make false and misleading claims.

Commissioner of Food and Drugs Mark B. McClellan, M.D., Ph.D., says the steps announced show the FDA's commitment to taking the most effective actions possible under current law. "The standard for regulating the safety of dietary supplements is largely untested," McClellan says, "but we are committed to finding the right public health solution."

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