Weight-loss compound may cause arrhytmia.

Herbal weight-loss drug Metabolife 356 can cause subtle changes in a person's heartbeat, the kind of alterations that sometimes lead to dangerous heart arrhythmias, researchers say.

Metabolife 356 is the best-selling weight-loss supplement sold in the United States, accounting for roughly half of that market and garnering nearly $7 billion in annual sales for its maker, Metabolife International of San Diego. The drug contains 18 herbal ingredients, including ephedra, an herb that has been linked to dozens of fatalities.

Because it's classified as a nutritional supplement and not a drug, Metabolife 356 hasn't had to go through the rigorous testing that pharmaceuticals must undergo to secure approval from the Food and Drug Administration, says Jeffrey Kluger of the University of Connecticut in Hartford. However, Kluger says, after he and his colleagues completed this study on the heart-beat patterns of people taking the drug, the FDA requested their data.

The researchers randomly assigned 15 healthy volunteers, average age 26, to receive either a small dose of Metabolife 356 or an inert pill. A week later, the doses were reversed. The investigators performed electrocardiograms (EKGs) on the volunteers before taking the drug or placebo and again after 1, 3, and 5 hours.

The tests showed that 8 of the 15 volunteers registered an expanded gap on their EKG readout, at a point called the QTC interval, after getting Metabolife 356. The interval represents the time between heartbeats. The longer it is, the greater the risk of arrhythmia, says coinvestigator Brian F. McBride, also at the University of Connecticut.

While the FDA has no published guidelines on what constitutes a dangerous lengthening in the QTC interval, Kluger notes that there have been numerous drugs approved by the FDA and subsequently found to increase the risk of sudden death. Scientists later determined that these drugs affected the QTC interval with much less severity than Metabolife 356 does. "These drugs have been removed from the market," Kluger says.

Next, the researchers plan to test ephedra--free versions of Metabolife to ascertain whether ephedra or some other ingredient is responsible for lengthening the QTC interval. The FDA is already investigating ephedra, which has been associated with heart attack, stroke, high blood pressure, and irregular heartbeat. N.S.