Risks of Ephedra Usage in Spotlight

The deaths this year of three football players who may have been taking nutritional supplements containing ephedra compounds has everyone from professional athletes to teenage dieters to weekend gym rats wondering what they’ve been putting into their bodies--and at what risk.

Doctors cannot say for sure whether the supplements contributed to the deaths of Rashidi Wheeler of Northwestern University, Devaughn Darling of Florida State, or Curtis Jones, an indoor league player. But industry analysts say that ephedra-based products are helping fuel a growing sports nutrition and supplement market in which millions of people are taking strong stimulants to lose weight or to get “amped” for a workout.

Going by names such as Metabolift, Stacker 3 and Hydroxycut, the products typically contain a cocktail of ingredients that include caffeine, aspirin and one or more ephedra compounds, such as ephedrine, derived from the reedy ma huang shrub native to China. According to Dr. George Ricuarte, a neurologist at Johns Hopkins University in Baltimore who studies the activity of amphetamines, ephedra extracts quickly activate the sympathetic “fight or flight” nervous system, opening bronchial airways, increasing blood pressure and heart rate, releasing adrenaline and putting the body into a state of full alert. Although many athletes equate this wired sensation with better performance, some researchers are doubtful.

“As far as I know, there’s no good data showing the ephedrine by itself measurably improves speed, strength or overall performance,” said Rick Kreider, director of the exercise and sports nutrition lab at the University of Memphis. “We tell our athletes that it’s not a performance enhancer and not to take it.”

In scores of studies, researchers have given people preparations of around 25 milligrams of ephedra stimulants, usually mixed with about 200 milligrams of caffeine, said Conrad Earnest, a supplement specialist at Cooper Institute for Aerobics Research in Dallas. This 25-200 combination is considered a “therapeutic” dose, he says, and it’s roughly the recommended dose listed on many product labels. “You get heightened awareness, slight increases in heart rate and blood pressure, and that’s about it,” he said. “We see very few, if any, adverse effects in the studies.”

Supplements Not Tested by FDA

Outside the laboratory, it’s a different story, doctors say. Millions of Americans, young and old, are taking ephedra supplements in wildly varying doses. And because nutritional supplements are not regulated as drugs, they’re not tested for safety by the Food and Drug Administration. Nor do regulators carefully verify the amounts of ingredients listed on the label. “You really don’t know what you’re getting in these products, or how much,” said Bill Gurley, a pharmaceutical researcher at the University of Arkansas who has analyzed about 150 dietary and sports supplements.

Many consumers taking these products are not even aware they’re ingesting ephedra at all, because it travels under several names-- ma huang , for instance, or sida cordifolia--and gets lost in a list of exotica. “That’s another problem,” Gurley said. “There’s a whole botanical milieu of other stimulants in there which interact with the ephedrine and caffeine,” which probably amplify their effect.

For these reasons, many doctors now believe there is no ephedra preparation that is safe for everyone. The products’ amphetamine-like punch, they say, hits a small percentage of apparently healthy people very hard, putting them at increased risk of heart palpitations, stroke, and cardiac arrest. “They could be people who have a weak blood vessel in the brain, for instance, or a weak heart valve, or they’re susceptible to arrhythmia. We just don’t know,” said Dr. Neal Benowitz, a professor of medicine at UC San Francisco who has studied products with ephedrine. “And there’s no test I know of to tell us who the vulnerable people are.”

Major Risks Not Revealed in Smaller Studies

The incidence of such problems is impossible to quantify, researchers say, because major risks have not shown up in scores of mostly smaller studies of ephedra done so far. But warning signs have been there for years. Between June 1, 1997, and March 31, 1999, for instance, the FDA received 140 complaints of adverse reactions to ephedra-based supplements. Benowitz investigated each of the cases and determined that 43 of the incidents were very likely attributable to the supplements. The most common problems were elevated blood pressure, heart palpitations and rapid heartbeat, which struck 18 people. But the cases also included four strokes, two heart attacks, one seizure--and three deaths. The victims ranged in age from 18 to 45 years old, Benowitz said, and most of them reported taking only moderate doses of the extracts, from 18 to 36 milligrams.

Many users of ephedra-based supplements take a whole lot more than that, further compounding the risks. “Athletes in particular often assume that if a little is good, more is better,” said Earnest, who has worked in the supplement industry. “And your body adapts, like it does to coffee. You take it for a week or two weeks, and suddenly you find you need more to get the same sensation.”

Earnest said he knows of bike racers who take 10 times the recommended dose of these products to get up for a race. Before the race has even begun, he said, the bicyclists’ heart rates have sometimes reached 150 beats per minute, and “they’re ready to explode.”

Add 100 degrees of summer heat, a heavy quilt of humidity--plus the exercise--and you put an enormous strain on the heart, doctors agree. As the heart beats frantically, the body sweats, losing water, which lowers blood volume, which can in turn further increase blood pressure, cardiologists said. “The body is already releasing adrenaline, and the sympathetic nervous system is highly stimulated,” said Ricuarte, “and you’re combining this with the product, which is doing the same things. It’s excessive stimulation. In vulnerable individuals, it’s a recipe for big problems.”

Industry executives have long argued that ephedra has a good safety record: Millions of people use the supplements each year, and there were only 140 complaints to the FDA between June 1997 and March 1999. But the FDA does not require supplement makers to report consumer complaints, and industry critics believe there are thousands of side-effects caused by the products that the FDA never hears about.

According to Gurley, several surveys now show that consumers are less likely to attribute headaches, nausea, dizziness or other symptoms to supplements than to prescription drugs they’re taking. “Even when people are having some strange reaction or symptoms,” he said, “they don’t think of the supplements. They think the supplements are somehow ‘natural’ and wouldn’t cause problems.”

The FDA took action against drugs containing ephedrine compounds in the early 1980s. But because ephedra supplements are not regulated as drugs, the FDA has limited power to act. “The important thing to know,” Gurley said, “is that these are active drug entities, whether they’re called drugs or not.”

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Effect on the Body

Ephedra compounds are derived from the ma huang shrub native to China. Even small doses of these extracts noticeably stimulate the central nervous system, researchers say, and heighten alertness. But documenting potential adverse effects and who’s at risk has been difficult.

Effects:

Researchers consider 25 milligrams to be the recommended, “therapeutic” dose, usually given with about 200 milligrams of caffeine. One dose usually produces:

* Heart rate quickens.

* Bronchial airways open, making more oxygen available.

* Blood vessels constrict, increasing blood pressure.

Potential Dangers:

Some people react more strongly to ephedra compounds than others. In a recent study of adverse events reported to the FDA, researchers found that a variety of problems were definitely or probably due to the supplements. They included:

* Hypertension

* Palpitations, and/or rapid heart rate

* Arrhythmia

* Cardiac arrest, or sudden death

* Stroke

Source: New England Journal of Medicine, Dec. 21, 2000

* Sampling of popular products containing ephedra extracts:

Metabolife

Ripped Fuel

Diet Fuel

Stacker 3

NaturalTRIM

Hydroxycut

Xenadrine RFA-1

Metab-O-Lite

Metabolift

Up Your Gas

Truckers Luv It

Yellow Jackets

* Label ingredients indicating ephedra compounds:

Ephedra

Ma huang

Ephedrine

Ephedra sinica

Sida cordifolia

Epitonin

Pseudoephedrine

Methyl ephedrine

* Ingredients that contain other stimulants, such as caffeine:

Guarana

Kola nut

Yerba mate

Citrus aurantium

DMAE

*

Source: University of Arkansas College of Pharmacy