Ephedrine/Caffeine Combos Safer Than Ephedrine Alone - Researcher

Combining ephedrine alkaloids with caffeine may actually diminish the potential adverse effects of taking ephedrine alone, suggested Arne Astrup, MD/PhD, University of Copenhagen, Denmark, at a Public Health Service meeting on the safety of ephedra supplements.

FDA announced the two-day meeting, hosted by the Office of Women's Health, in the June 8 Federal Register. Throughout the event, a panel of representatives from FDA, the National Institutes of Health and the Centers for Disease Control & Prevention gathered information from various speakers (¹ (Also see "Ephedra meeting" - Pink Sheet, 12 Jun, 2000.)).

Astrup - testifying on videotape Aug. 9 - said data from his randomized, double-blind, placebo-controlled trial showed evidence that "some of the side effects of ephedrine and caffeine seen when used separately, if you use it in combination they seem to cancel out....The best example is heart rate."

Astrup maintained his study had been "distorted" the previous day by Lori Love, MD/PhD, Clinical Research & Review director at FDA's Office of Nutritional Products, Labeling & Dietary Supplements.

He said Love "mischaracterized" data on the synergistic effects of the two ingredients by stating side effects were worse when the substances were combined.

"With respect to weight loss...there was a synergistic effect between caffeine and ephedrine [but] there's no evidence of any synergies" related to side effects, Astrup asserted. He charged "there are many examples of how...our research is twisted" by Love.

Astrup also attested to the safe and effective use, since 1990, of a combination weight-loss product in Denmark. The panelists noted, however, that the product is available only by prescription. Others added caffeine and ephedrine have not previously been shown to be synergistic in preventing side effects.

In a presentation on the safety of dietary supplements containing only ephedrine, Graham Patrick, PhD, Medical College of Virginia, asserted such products, when used at appropriate doses, "are highly unlikely to cause serious adverse events."

Patrick said the "typical" supplement dose is 12 mg ephedrine alkaloids and up to 95 mg per day, compared to OTC bronchodilators, which often have a 25 mg dose and up to 150 mg/day.

"Moreover," he added, "ephedra, which contains multiple ephedrine alkaloids, may be safer than synthetic or pharmaceutical ephedrine because ephedrine itself is the most potent" alkaloid, while "it's also been suggested that the rate of absorption of ephedrine alkaloids from herbal preparations is slower."

CDC rep Rossanne Philen, MD, responded that the ephedrine in natural ephedra is more potent, meaning a smaller dose would produce a stronger effect. However, Council for Responsible Nutrition VP-Botanical Science & Regulatory Affairs John Cardellina, PhD, said some OTC products use the more powerful form of ephedrine found in supplements.

Gary Huber, MD, Texas Nutrition Institute, said a pharmaceutical ephedrine/caffeine preparation designed for one of his studies was "less efficacious than...herbal products in terms of weight loss" and had a "higher adverse risk profile." Huber is in the midst of a six-month randomized, double-blind, placebo-controlled trial on the safety and efficacy of four ephedrine alkaloid-containing supplements.

Patricia Ann Daly, MD, York Hospital (Penn.), noted she and Carol Boozer, Columbia University, have completed a study on ephedrine/caffeine combination products and weight loss and are preparing a report for publication (² (Also see "Ephedra studies" - Pink Sheet, 31 Jul, 2000.)). The trial involved 167 subjects at two centers in New York and Boston.

In the study, mildly to severely overweight subjects were given 90 mg ephedrine and 192 mg caffeine daily for six months. Subjects returned for follow-up at weeks two, three and four and then monthly. The early frequency was necessary, Daly noted, "because the cardiovascular effects of ephedra compounds are more likely to occur when [they] are first consumed."

Although the study data are still being analyzed, Daly said no one suffered "life-threatening results, such as seizure, stroke or myocardial infarction." She concluded, "given the public health...impact of an effective, safe, cheap over-the-counter treatment, government sponsorship and support for additional research is...called for."