Ephedra

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Ephedra

What Kind of Drug Is It?

Ephedra plants are yellow cone-bearing bushes that grow in desert areas. The Chinese herbal remedy ma huang (ma-HWANG) is made from the twigs of the ephedra bush. It has been used to treat asthma (AZ-muh), a lung disorder, for thousands of years. Asthma is a disease that involves swelling and congestion in the lungs, which makes it difficult to breathe.

Ephedra is a natural source of ephedrine, just as coffee beans are a natural source of caffeine. For nearly a decade prior to its ban by the U.S. government in 2004, ephedra was associated with very serious side effects, including strokes, heart attacks, and even death in some users.

Overview

The Chinese herbal remedy ephedra, also called ma huang, has generated a whirlwind of debate since the mid-1990s, when some of its users became seriously ill. Reports of adverse events, or negative side effects, related to ephedra use raised considerable concern among physicians and legislators. Until it was banned by the U.S. Food and Drug Administration (FDA) in 2004, ephedra was most often taken by young and middle-aged adults for weight loss, increased energy, and bodybuilding. Chinese herbalists argue that ephedra should not be used for these purposes.

The earliest known use of ephedra was in ancient China, where it was used as an herbal remedy to treat a variety of ailments. In the 1920s, Dr. K. K. Chen studied ephedra and isolated its active ingredient—ephedrine. An active ingredient is the chemical or substance in a compound known or believed to have a therapeutic, or healing, effect.

Official Drug Name: Ephedra (ih-FEH-druh) Ephedra sinica, ephedrine (ih-FEH-drinn), ephedrine alkaloids

Also Known As: Ma huang, mahuang, Mormon tea

Drug Classifications: Not scheduled; dietary supplement

Ephedrine alkaloids act as powerful stimulants on the heart, causing an increase in heart rate and a rise in blood pressure. (Stimulants are substances that increase the activity of a living organism or one of its parts.) Ephedrine also helps dilate, or open up, the breathing passages in the lungs.

Soon after the discovery of ephedrine alkaloids, physicians in the United States began prescribing ephedra as a decongestant for stuffy noses. It was also used as a bronchodilator—a drug that relaxes

breathing muscles, allowing air to flow more easily through the tubes that lead to the lungs.

Serious side effects associated with ephedra include high blood pressure, irregular heart rate, seizures, heart attacks, and strokes. Extensive research and analysis have linked the use of this herbal stimulant to 155 deaths. One tragedy involved a healthy sixteen-year-old high school student from Lincoln, Illinois. In September of 2002, Lincoln Community High School football player Sean Riggins died of heat stroke after taking a strength-boosting ephedra supplement he had purchased at a gas station. As of early 2005, the controversy surrounding ephedra—and its ban—raged on.

Bulking Up and Slimming Down

Before ephedra was banned by the FDA in 2004, products containing the herb were used primarily for weight reduction. Health food stores, supermarkets, drugstores, convenience stores, and even gas stations sold products containing ephedrine alkaloids. These included products with names such as Easy Trim, Diet Max, Xtreme Lean, Metabolife 356, Xenadrine RFA-1, Ultimate Orange, Yellow Jacket, Quick Shot, Stacker 2, and Ripped Fuel. The products' labels promised they would fight fat, build lean muscle mass, curb the appetite, boost energy, and help users lose weight.

Under the U.S. Dietary Supplement Health and Education Act (DSHEA), which was passed in 1994, herbs are treated as foods rather than drugs. The act allowed dozens of brands of supplements containing ephedrine alkaloids to flood the market without being tested for safety. As a rule, herbal supplements do not have to undergo the extensive testing required for over-the-counter (OTC) medications and prescription drugs. In fact, it is up to the FDA to show that an herbal supplement is unsafe. As Snigdha Prakash explained in a National Public Radio (NPR) story on ephedra, "the FDA must prove that problems associated with ephedra supplements are caused by them."

As far back as April of 1996, the FDA issued a consumer warning about ephedra. The government agency noted that ephedra may have been connected with a dozen deaths and several hundred complaints of adverse reactions. From that point on, the reports of complications linked to ephedra use kept climbing. In an article published in the Virginian Pilot in 2000, Dr. Neal L. Benowitz of the University of California at San Francisco noted that heart attacks, strokes, seizures, and deaths were occurring in "otherwise healthy young people" who had taken the herbal stimulant. He and fellow researcher Dr. Christine Haller concluded: "Dietary supplements that contain ephedra alkaloids pose a serious health risk to some users."

The Ephedra Education Council, a group backed and supported by the herbal products industry and supplement manufacturers, has always insisted that ephedra is completely safe when taken as directed. They blame adverse reactions to ephedra on: 1) improper dosing; 2) preexisting health problems among users; and 3) the combined effects of caffeine or other drugs taken along with the herbal supplement.

Tragedy on the Ball Field

On February 16, 2003, the ephedra controversy became front-page news when twenty-three-year-old Steve Bechler, a pitcher with the Baltimore Orioles, collapsed during a preseason workout in Florida. He died the next day.

Bechler was trying to lose about ten pounds that he had put on between seasons. He had not eaten regular meals for several days and was reportedly taking a weight-loss supplement that contained ephedra and caffeine. By speeding up body processes, ephedra and ephedrine alkaloids create more heat within the body. The substances also act to constrict, or narrow, the blood vessels, making it harder for the body to release the pent-up heat through the skin in the form of sweat. In addition, experts note that the energy-enhancing effect of ephedra may prompt users to exercise longer and harder than they normally would or should.

Aside from being overweight, Bechler had other health problems, including an enlarged heart, higher blood pressure than he should have had, and trouble with his liver. On the day of his fatal spring training workout, he is said to have taken three ephedra-containing supplement pills—one pill more than the recommended dosage. Bechler later collapsed on the field from severe heat stroke. His organs simply stopped working. According to a New York Times article by George Vecsey, "conditions in Florida on Sunday were 81 degrees" with "74 percent humidity, far below the danger level" for heat stroke. Still, Bechler's body temperature rose to 108.4 degrees Fahrenheit before his death.

In March of 2003, reports from the medical examiner in Broward County, Florida, stated that ephedra "played a significant role" in Bechler's death. This tragedy followed earlier reports of ephedra-related fatalities among young athletes. One and a half years earlier, twenty-two-year-old Northwestern University cornerback Rashidi Wheeler died during a workout. The cause of death was listed as an asthma attack, but Wheeler had been taking a powdered performance-enhancing dietary supplement containing ephedra and caffeine. The company that manufactured the supplement had discontinued the product and all other ephedra supplements shortly before Wheeler died.

Athletic Associations Take Action

In September 2001, just one month after Wheeler's death, the National Football League (NFL) joined the National Collegiate Athletic Association (NCAA) and the International Olympic Committee (IOC) in banning its players from using ephedrine. The ephedrine ban allows for the random testing of NFL players for ephedrine use.

Drugs and Baseball

The controversy surrounding the death of Steve Bechler in 2003 prompted Major League Baseball (MLB) to take a good look at its drug-testing policy. Ephedra and ephedrine alkaloids had already been banned in minor league baseball, as well as by the International Olympic Committee (IOC), the National Collegiate Athletic Association (NCAA), and the National Football League (NFL). Suspected steroid use among professional baseball players had sparked arguments about the prevalence of drugs in the league as well. "Both ownership and the players have been widely criticized for not facing up to the use of legal muscle-building drugs that gave new muscles to Mark McGwire and many other sluggers," noted George Vecsey in the New York Times.

Mounting Evidence of Health Risks

Authorities in Canada were equally concerned about the safety of ephedra. Health Canada, the agency that regulates Canadian health care, requested a voluntary recall of products containing ephedra or ephedrine in 2002. The agency's Web site posted an advisory stating: "A risk assessment concluded that these products pose a serious risk to health." Health Canada received sixty reports of adverse events and a report of one death related to ephedra use. The agency noted that it would "continue to monitor reports of adverse events" and "take further action if necessary."

By January of 2003, 7-Eleven stores announced that they would stop selling ephedra-containing products such as Metabolife. The General Nutrition Centers (GNC) retail chain followed suit in May. Meanwhile, the makers of Metabolife announced the release of a new formula of their supplement—one that did not contain ephedra. At the time, Metabolife International, the San Diego-based maker of Metabolife, was being investigated by the U.S. government following claims that the company had lied about the safety of its ephedra product.

At the end of 2003—six years after the safety of the herbal supplement was first called into question by the U.S. government—the administration of President George W. Bush took steps to ban ephedra. This decision was based on an in-depth investigation of the situation by RAND, a nonprofit research institute. An expert panel of researchers from RAND was hired by the government to analyze the data surrounding the ephedra controversy. The group examined the results of 20 clinical trials and 284 case reports of adverse events. RAND researchers admitted that they did not have much data to work with but stated they were able to compile "enough evidence to reach fairly confident conclusions." The results of the study were released in March of 2003. Highlights include findings that:

Ephedrine-containing supplements increased the average weight loss of dieters in the short term by 0.4 to 2.2 pounds per month
The athletic benefit from supplements containing ephedrine and caffeine was limited to a "20-30 percent increase in short-term performance" only
"There may be a causal relationship between taking the substances and suffering rare serious adverse events. Catastrophic effects of ephedra, including death, cannot be ruled out."

Research from the University of California at San Francisco supports these findings. Dr. Stephen Bent and his colleagues set out to compare the health risks of ephedra with the dangers of other herbal products. The results of their study were published in the Annals of Internal Medicine in March of 2003. The researchers found that even though ephedra products amounted

to less than 1 percent of herbal supplement sales in the United States, more than 64 percent of all adverse reactions to herbal supplements were linked to their use. Bent and his colleagues concluded: "Ephedra use is associated with a greatly increased risk for adverse reactions compared with other herbs, and its use should be restricted."

FDA Bans Ephedra in 2004

In February of 2004, the FDA prohibited the sale of ephedra supplements. The agency issued a consumer advisory that stated, in part: "After a careful review of the available evidence about the risks and benefits of ephedra in supplements, the FDA found that these supplements present an unreasonable risk of illness or injury to consumers." The ban went into effect on April 12, 2004. During the weeks leading up to that date, diehard users were "reportedly stocking up" on their favorite ephedra supplements, commented Mary Duenwald in the New York Times. In some cases, users bought a large enough supply to last one to two years.

With ephedra gone from the shelves, dieters and athletes began looking for a product to take its place. "Critics … remained concerned because so little was known about the other herbal ingredients being used as substitutes," reported Christopher Drew and Ford Fessenden in the New York Times. One such substance is an ephedrine-like stimulant called synephrine (sih-NEH-frinn), also known as the bitter Seville orange (Citrus aurantium) or simply bitter orange. The substance is supposed to be safer than ephedra but has not undergone studies to prove that claim. According to the New York Daily News, bitter orange "has been linked to seven deaths."

Back in the News in 2005

The Utah-based supplement company Nutraceutical International was the first in the industry to be successful in challenging the FDA's ban on ephedra. In the spring of 2005, federal judge Tena Campbell ruled in favor of Nutraceutical, saying the FDA had failed to prove that the company's product "posed a significant health risk," wrote Penni Crabtree. The judge's ruling applies only to so-called "low-dose" supplements such as the one produced by Nutraceutical. A "low dose" supplement contains 10 or fewer milligrams of ephedrine alkaloids per daily dose.

The Utah ruling made it hard to predict the future legal status of ephedra. Under Judge Campbell's order, the FDA cannot stop Nutraceutical from selling its ephedra supplement. In addition, the FDA must determine what constitutes a "safe level" of ephedrine.

Metabolife Lawsuits

In June of 2004, just two months after ephedra supplement products were banned in the United States, Metabolife International lost a major court case that centered on the health risks connected with its product Metabolife 356. Rhea McAllister, a thirty-five-year-old Texas woman who took Metabolife 356 for about a month, suffered a stroke in 2002. She was trying to lose some weight and thought the product would help her burn off a few pounds. A jury awarded her $7.46 million in damages. The award would have been larger if McAllister had not been found partly to blame for the extent of the damage. "Jurors found McAllister 30 percent liable for failing to tell her doctors she was using Metabolife when she first complained of symptoms," noted Beth Gallaspy in an article for the Beaumont Enterprise.

This was not the first time Metabolife International had been taken to court over Metabolife 356. "In November 2002," wrote Penni Crabtree in the San Diego Union-Tribune, "a federal jury in Alabama awarded $4.1 million in damages to four people who suffered heart attacks or strokes" after taking the product.

What Is It Made Of?

The ephedra bush grows in the desert regions of Asia, North America, and other parts of the world. Not all ephedra plants contain ephedrine alkaloids. It is the alkaloid content of the plant that gives it a medicinal effect. The Asian ephedra plant typically has the highest concentration of ephedrine alkaloids.

The chemical formula for ephedrine is C₁₀H₁₅NO, which is very similar to the structure of amphetamine or "speed," a widely abused stimulant that gives people a lot of energy. (A separate entry on amphetamines is available in this encyclopedia.) Like amphetamine, ephedrine alkaloids can have a powerfully stimulating effect on the heart. Former FDA commissioner David A. Kessler told the New York Times in 2003 that substances like ephedra are really drugs "masquerading as nutritional supplements."

How Is It Taken?

Ephedra has been sold in the form of tablets, capsules, a powder that can be combined with water to make a shake, and as a key ingredient in energy boosting bars. Asthma treatments include sprayable mists and injectable liquids containing ephedrine.

The twigs of the ma huang plant are dispensed by traditional Chinese herbalists. Tea made from the twigs is used to treat asthma, coughs, and the common cold. Herbalists caution that ephedra is a strong herb and that it should not be used for more than a week at a time.

Ephedrine starts to take effect about an hour after ingestion and, after kicking in, lasts about three to four hours. The recommended dosage of ephedrine is a maximum of 8 milligrams in 6 hours, or 32 milligrams per day. In Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy, Cynthia Kuhn and her coauthors caution that it is hard to regulate the dosage of herbal remedies because "the amount and purity of what you buy is unknown."

Are There Any Medical Reasons for Taking This Substance?

Ephedra has been used to treat a variety of ailments for thousands of years. Because it can dilate breathing tubes and ease congestion in the nasal passages, it has been used as an ingredient in some over-the-counter decongestants and cough and cold products. Until it was banned in 2004, ephedra was used in the United States mainly as a weight-loss aid, a body-building product, and a booster for improved athletic performance.

In a report on Chinese herbal medicine published in the Dallas Morning News, Esther Wu interviewed experts in the field of herbal remedies. One of these experts, Dr. Richard Tao of the Dallas College of Oriental Medicine, commented: "In the United States, the herb has been abused. Ma huang is not traditionally used for losing weight."

Usage Trends

The Knight Ridder/Tribune Business News estimated that 12 million Americans used ephedra products at the height of their popularity. Ephedra sales fell from $1.3 billion in 2002 to $510 million in 2003, according to the New York Times.

Before the ban on ephedra and ephedrine alkaloid supplements, manufacturers claimed that the products enhanced athletic performance and helped build lean muscle mass. That made ephedra supplements especially appealing to both male and female athletes. Frank Uryasz of the NCAA told Houston Chronicle reporter Janny Hu that young athletes run the greatest risk of suffering ephedra-related problems. "The age group we work with thinks they're going to live forever…. When we educate athletes about banned drugs, we say, 'Stimulant, plus exercise, plus heat and humidity, equals death."'

Government studies reveal that most drug use, including ephedrine use, begins in high school. In fact, 62 percent of student athletes in a 2001 NCAA survey reported that they had started using nutritional supplements in high school.

Effects on the Body

Ephedra supplements have amphetamine-like effects on the user. Side effects may include dizziness, headache, tiredness, shaking, nausea, and trouble sleeping. Higher dosages can cause an unusually fast heartbeat, chest pain, extremely high blood pressure, and even seizures. Health officials point out that ephedra can be dangerous even at recommended doses because the potency, or strength, of each dose varies so much from one manufacturer to another and from one batch to another. Users have been known to double or triple the recommended dosage in an attempt to lose weight faster or perform better in athletic events.

Ephedrine and Meth

The U.S. Drug Enforcement Administration (DEA) has been monitoring ephedrine powder and tablet production because these substances can be used to make methamphetamine, an illicit drug more commonly known as "meth" or "speed." Methamphetamine is highly addictive, often abused, and extremely dangerous. Illegal labs can produce about 1.5 pounds (0.68 kilograms) of meth from 2.2 pounds (1 kilogram) of ephedrine. Pseudoephedrine, a substance found in cold medicines, can be used for the same purpose.

Opponents of ephedra claim that the product is legal methamphetamine, or speed. (An entry on methamphetamine is available in this encyclopedia.) Mental side effects of ephedrine such as euphoria, agitation, irritability, and anxiety were noted in the RAND report. Personality changes, depression, and paranoid psychosis (a severe mental disorder that can lead to a total loss of touch with reality) could not be ruled out. These types of side effects commonly occur with the use of illicit, or illegal, stimulant drugs, including amphetamines and methamphetamine.

Ephedra users also face an increased chance of seizures, heart attack, stroke, and possibly death. The use of ephedra by pregnant women and people with high blood pressure is especially risky.

Reactions with Other Drugs or Substances

Ephedra supplements typically contain caffeine. Users may already be consuming caffeine in carbonated beverages, coffee, or tea. Mixing caffeine with ephedrine increases the stimulant effects on the heart, making the user more anxious and edgy. "Ephedrine/caffeine/aspirin combinations are often 'stacked' by weight lifters, and used for weight loss," noted Kuhn prior to the substance's ban. Ephedra is especially dangerous when used in combination with over-the-counter or prescription decongestants, any other stimulants, and certain drugs used to treat depression.

Treatment for Habitual Users

Although the FDA recognizes that ephedra and ephedrine alkaloids may cause adverse health events or serious side effects, they are not considered addictive, habit-forming drugs. "Quitting abruptly is safe and does not bring on withdrawal symptoms," wrote Duenwald in the New York Times. "But people who have used the supplement to lose weight may see the pounds return."

Consequences

Healthy individuals have been known to suffer serious consequences following ephedra use. As of early 2005, ephedra was the only dietary supplement banned by the FDA. Possession and use of a banned substance can lead to trouble with the authorities. According to MSNBC.com, ephedra consumption can actually "result in a false-positive for amphetamines in urine tests." Athletes will incur a doping suspension if they test positive for ephedra.

The Law

The FDA's ban on ephedra went into effect on April 12, 2004. The ban "specifically excludes uses of the herb in traditional Asian medicine," explained Duenwald. It is aimed instead at supplements marketed for weight loss, muscle building, and enhanced athletic performance. The sale and distribution of ephedra and ephedrinecontaining supplements is against the law. It is illegal for users in the United States to obtain ephedrine supplements from countries that have not banned it. As of mid-2005, federal authorities were cracking down on Internet sites that continued to sell ephedra in the United States. It is hard to predict whether the federal ban on ephedra will remain in place.

For More Information

Books

Chang Huang, Kee. The Pharmacology of Chinese Herbs, 2nd ed. Boca Raton, FL: CRC Press, 1998.

Kuhn, Cynthia, Scott Swartzwelder, Wilkie Wilson, and others. Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy, 2nd ed. New York: W.W. Norton, 2003.

Rotblatt, M., and I. Ziment. Evidence-Based Herbal Medicine. Philadelphia: Hanley & Belfus, 2002.

Weil, Andrew, and Winifred Rosen. From Chocolate to Morphine. New York: Houghton Mifflin, 1993, rev. 2004.

Periodicals

Abramovitz, Melissa. "Ephedra: An Herbal Danger." Current Health (December, 2002): pp. 26-28.

Bent, Stephen, Thomas N. Tiedt, Michelle C. Odden, and Michael G. Shlipak. "The Relative Safety of Ephedra Compared with Other Herbal Products." Annals of Internal Medicine (March 18, 2003): pp. 468-471.

Crabtree, Penni. "Ephedra Ruling Puzzles the Industry." San Diego Union-Tribune (April 16, 2005).

Crabtree, Penni. "GNC to Remove All Ephedra Products from Its Shelves." San Diego Union-Tribune (May 3, 2003).

Crabtree, Penni. "San Diego Dietary Supplement Firm Loses Second Suit, Must Pay $7.46 Million." San Diego Union-Tribune (June 24, 2004).

Drew, Christopher, and Ford Fessenden. "Expert Panel Finds Flaws in Diet Pill Safety Study." New York Times (July 23, 2003): p. A16.

Duenwald, Mary. "Despite FDA Ban, Ephedra Won't Go Away." New York Times (February 17, 2004): p. F5.

Duenwald, Mary. "Slim Pickings: Looking Beyond Ephedra." New York Times (January 6, 2004): p. F1.

"Ephedra Ban Weighs Heavily on Diet Pills." Knight Ridder/Tribune Business News (April 26, 2004).

Gallaspy, Beth. "Crosby, Texas, Woman Wins $7.4 Million in Ephedra Case." Beaumont Enterprise (June 26, 2004).

Gelles, Jeff. "The Ephedra Question: To Take or Not to Take." Philadelphia Inquirer (February 24, 2003).

Harris, Gardiner, and Jay Schreiber. "Judge's Decision Lifts Ban on Sale of Ephedra in Utah." New York Times (April 15, 2005).

"Herbal Stimulant Deadly." Virginian Pilot (November 7, 2000): p. A1.

Hu, Janny. "Bringing Ephedra's Risk to Light." Houston Chronicle (February 23, 2003): p. 1.

"A Major League Loss." Time (March 3, 2003).

Manier, Jeremy, and Manya Brachear. "U.S. Moves to Ban Dietary Ephedra." Chicago Tribune (December 30, 2003).

McVicar, Nancy, and Ardy Friedberg. "Autopsy Finds 'Significant' Role for Diet Aid Ephedra in Bechler's Death." South Florida Sun-Sentinel (March 13, 2003).

O'Keefe, Michael. "Ban on Ephedra Now in Effect." New York Daily News (April 12, 2004).

Somers, Terri. "Metabolife Founder in San Diego Pleads Not Guilty in Ephedra Case." San Diego Union-Tribune (July 28, 2004).

"Two Firms Shed Ephedra Herbal Stimulant from Product Lines." Knight Ridder/Tribune Business News (January 23, 2003).

"U.S. to Prohibit Supplement Tied to Health Risks." New York Times (December 31, 2003).

Vecsey, George. "Baseball Has Failed to Confront Drugs." New York Times (February 23, 2003).

Wu, Esther. "Chinese Herb Spurs Ephedra Confusion." Dallas Morning News (January 17, 2004).

Web Sites

"Consumer Advisory: Ephedra" (April 2004). National Institutes of Health, National Center for Complementary and Alternative Medicine.http://nccam.nih.gov/health/alerts/ephedra/consumeradvisory.htm (accessed July 6, 2005).

"Ephedra and Ephedrine Alkaloids for Weight Loss and Athletic Performance." National Institutes of Health, Office of Dietary Supplements.http://ods.od.nih.gov/factsheets/ephedraandephedrine.asp (accessed July 6, 2005).

"FDA Issues Regulation Prohibiting Sale of Dietary Supplements Containing Ephedrine Alkaloids and Reiterates Its Advice That Consumers Stop Using These Products" (February 6, 2004). U.S. Food and Drug Administration, FDA News.http://www.fda.gov/bbs/topics/NEWS/2004/NEW01021.html (accessed July 7, 2005).

"Health Canada Requests Recall of Certain Products Containing Ephedra/Ephedrine" (January 9, 2002). Health Canada Online.http://www.hc-sc.gc.ca/english/protection/warnings/2002/2002_01e.htm (accessed July 7, 2005).

"Judge Strikes Down Ban on Ephedra." MSNBC.com, April 14, 2005. http://www.msnbc.msn.com/id/7504443/ (accessed July 7, 2005).

McBroom, Erica. "Ethnobotanical Leaflets: Ephedra (Ma Huang)." Southern Illinois University.http://www.siu.edu/~ebl/leaflets/ephed1.htm (accessed July 6, 2005).

Prakash, Snigdha. "The Secret of Ephedra's Questionable Success." National Public Radio, November 22, 2002. http://www.npr.org/templates/story/story.php?storyId=850679 (accessed July 6, 2005).

Shekelle, Paul G., Margaret Maglione, and Sally C. Morton. "Preponderance of Evidence: Judging What to Do about Ephedra." RAND Review.http://www.rand.org/publications/randreview/issues/spring2003/evidence.html (accessed July 6, 2005).