'Ephedra-free' Dietary Supplements Pose Potential Health Risks

The research examined the effects on blood pressure and heart rateof two dietary supplements containing bitter orange extract -- asubstance that has rapidly replaced ephedra in weight-loss productssince it was banned by the FDA in 2004 because of concerns aboutserious health effects.

The study involved 10 healthy adults given single doses of oneof the two supplements or a placebo. The two supplements tested wereAdvantra Z and Xenadrine EFX. Single doses of both products increasedheart rate by an average of 11 to 16 beats per minute over baseline,the scientists found. This would be the equivalent of an 18 percentincrease if baseline rate is 80 beats per minute.

In addition, Xenadrine EFX also significantly increased bloodpressure by 7 to 12 percent (9-10 mm Hg), the researchers reported.Xenadrine EFX appears to have similar acute cardiovascular stimulantactions as banned ephedra products, according to their report.

"These findings indicate that ephedra-free dietary supplementscould have some of the same adverse health effects associated withpreviously available ephedra products, such as Metabolife 356 andRipped Fuel," said Christine Haller, MD, UCSF assistant professor ofmedicine and lead author of the paper.

The scientists call for further research on the safety andeffectiveness of bitter orange- containing supplements -- particularlyamong those most likely to take them: overweight people who may haveother health conditions.

The research is published in the September issue of The American Journal of Medicine, available September 9.

Bitter orange extract, or Citrus aurantium, is extracted fromthe dried fruit peel of bitter orange. Known in Chinese herbal medicineas Zhi shi, it is a traditional remedy for gastrointestinal ailments,the scientists said.

The predominant constituent of bitter orange is synephrine,which in pharmaceutical form is commonly used to treat low bloodpressure and nasal congestion.

Advantra Z contains only bitter orange, while one dose ofXenadrine EFX contains several other ingredients, including caffeineequivalent to the amount in 3 cups of coffee, the researchers found.The increased blood pressure from taking Xenadrine EFX is likely notdue to caffeine alone, they concluded, but potentially related to theactions or interaction of other constituents in the multi-ingredientsupplement.

The scientists call for longer term dosing studies to determinewhether the blood pressure effects of Xenadrine EFX persist withrepeated use. Until such data are available, they conclude, doctorsshould caution patients about using ephedra-free weight-loss dietarysupplements and should monitor blood pressure in those who choose touse the products.

In particular, people with hypertension, heart disease or otherpre-existing conditions that could be aggravated by the supplementsshould avoid them.

"Consumers should be aware that ephedra-free dietarysupplements have not been extensively tested for safety and the healtheffects are not well known," Haller noted.

Among other physiological measures, heart rate and bloodpressure were recorded in the study for an hour before dosing and thenat several intervals afterwards.

To rate physical symptoms, moods and emotions, questionnaireswere administered one, two and six hours six hours after taking thesupplements or placebo.

The caffeine-containing Xenadrine EFX product also increasedalertness according to responses on the questionnaire. But neitherproduct appears to have a significant effect on mood, the study found.

Co-authors on the study with Haller were Neal Benowitz, MD,professor of medicine and of clinical pharmacy at UCSF, and PeytonJacob III, PhD, a researcher in psychiatry at UCSF.

The research is funded by grants from the National Institutes of Health.