TUESDAY, Jan. 13, 2004 (HealthDayNews) -- Half the recommended dose of Metabolife 356, a dietary supplement which contains ephedra and caffeine, increased blood pressure as well as one measure of the time between heart contractions, new research shows.
Over time, increased blood pressure can increase the risk of having a heart attack while the change in heart contractions could increase the risk of developing a certain type of arrhythmia, or abnormal heart rhythm.
The findings would add fuel to the anti-ephedra fire, had the U.S. Food and Drug Administration (FDA) not already announced it was banning products containing ephedra.
According to the researchers, the FDA did, in fact, see the report before its current publication in the Jan. 14 issue of the Journal of the American Medical Association.
"[The FDA] got an advance copy in December," says senior study author C. Michael White, an associate professor of pharmacy at the University of Connecticut School of Pharmacy in Storrs. "I think it definitely did play a part in their decisions."
David Cohen, national science counsel for Metabolife, says the study is flawed for a number of reasons. For starters, the researchers did not acknowledge previous data, which showed no prolongation of the QT interval, Cohen says. Prolonged QT intervals are potentially problematic because they can lead to a dangerously irregular heartbeat called torsade de pointes. Nowhere in this study or in the clinical literature, Cohen adds, is there any record of ephedra being linked to torsade de pointes.
"It's not clear what is the clinical significance of this study," Cohen says. "At the very least, honest researchers acknowledge inconsistent data. That has been the running theme in a lot of what's been going on about ephedra. Nobody, including the FDA, wants to acknowledge all the data that's been out there for years that does not demonstrate that this is a dangerous product and this is just another piece of that."
Weight-loss supplements containing ephedra have been linked to more than 100 deaths, including that of Baltimore Orioles pitcher Steve Bechler last year. The exact physiological mechanism behind these tragedies has not been well understood.
"We have known for a very long time that stimulants like caffeine or ephedra have the potential to create arrhythmia [but] we never really understood the frequency or exactly how it was occurring," says Dr. Larry Chinitz, director of clinical cardiac electrophysiology at New York University Medical Center. "The study documents what we've always had an idea about and suggests that it may be more frequent than we suspected in the past."
Metabolife 356 contains a total of 19 ingredients, including ephedra and caffeine, and is one of the top sellers in its category. The study authors were specifically interested in the product's effect on corrected QT (QTc) interval duration and systolic blood pressure. QTc interval duration is a measure of the time intervals that occur during the electrical impulses that cause the heart to contract. Longer intervals can increase the risk of developing arrhythmia, or abnormal heart rhythms. Systolic blood pressure is the upper number on a blood pressure reading.
Fifteen young, healthy men and women were randomized to receive either the Metabolife product or a placebo. After a one-week break between sessions, the groups switched to receive the other treatment. Heart rates and blood pressure were measured right before taking the pill as well as one, three and five hours after.
Individuals taking Metabolife 356 had longer QTc intervals and higher systolic blood pressure compared with people taking the placebo. The average QTc interval for Metabolife takers was 419.5 milliseconds versus 396.1 milliseconds in the placebo group. The mean systolic blood pressure reading was 123.5 in the Metabolife group versus 118.93 in the placebo group.
Some 53 percent of participants had QTc intervals increases of at least 30 seconds while taking Metabolife 356. Thirty seconds is considered the threshold for possible concern by the European Center for Proprietary Medicinal Products. While the FDA has no similar guideline, it has removed products that induce smaller increases, say the study authors.
Which ingredient is responsible for the changes is not known, but the authors suspect ephedra is the culprit. "It has become very, very hard to find only ephedra-containing products on the U.S. market because of litigation and other things," White says. "We looked at adrenaline, which is a close cousin to ephedra, and we found that, by itself, it can also increase QTc interval, and people know that it can increase blood pressure. Since a close cousin can increase QTc, we're pretty sure that ephedra does also."
The study involved administering only half a dose (one pill versus the two recommended on the package label). "The manufacturers have contended that most of the cases of patient harm involved larger-than-average doses," White says. "We gave the equivalent of one tablet. There's the possibility that, had we given them two, the results may have been worse in terms of blood pressure or QTc interval increases."
It will be easy enough to avoid ephedra once these products are taken off the market. Whether or not to avoid caffeine is an entirely different issue. "In patients who have heart disease, this should be avoided at all costs," Chinitz says. "In the absence of heart disease, one would recommend moderation and recognize that anybody could be affected, but the risk would be smaller."