title: Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study.
abstract: Animal and human studies have suggested a thermogenic synergism between ephedrine (E), a beta-agonist, and caffeine (C), an adenosine antagonist, which may be suitable for the treatment of obesity. To study this phenomenon, the thermogenic effect of single doses of oral placebo, E 10 mg, E 20 mg, C 100 mg, and C 200 mg were compared with the effects of three different combinations of E + C, 10 mg/200 mg, 20 mg/100 mg, and 20 mg/200 mg, measured by indirect calorimetry in six healthy, lean subjects. The thermogenic effect after E + C 20 mg/200 mg was larger than that of any of the other combinations. In this dose ratio, ephedrine and caffeine exerted a supra-additive synergism, whereas the thermogenic effects of the other two combinations were only additive. The 3-hour postintake increase in systolic blood pressure after all three combinations averaged 5 to 7 mm Hg more than placebo (P less than .01), which exceeded the predicted additive effect fivefold to sevenfold. Diastolic blood pressure was not increased by E + C 20 mg/200 mg, whereas the other two combinations increased it by approximately 4 mm Hg more than placebo. E + C 20 mg/100 mg and 20 mg/200 mg increased heart rate more than placebo, while E + C 10 mg/200 mg had no effect on heart rate. As expected, all combinations increased plasma glucose, insulin, and C-peptide from their ephedrine content. No significant effects of the combinations were found on plasma lactate, glycerol, nonesterified fatty acids (NEFA), triglyceride, potassium, or sodium.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Astrup
authors.forename: S
authors.initials: S
authors.lastname: Toubro
authors.forename: S
authors.initials: S
authors.lastname: Cannon
authors.forename: P
authors.initials: P
authors.lastname: Hein
authors.forename: J
authors.initials: J
authors.lastname: Madsen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D001833:Body Temperature Regulation / Q000187:drug effects*; D002096:C-Peptide / Q000097:blood; D002110:Caffeine / Q000494:pharmacology*; D004311:Double-Blind Method; D004357:Drug Synergism; D004573:Electrolytes / Q000097:blood; D004734:Energy Metabolism / Q000187:drug effects; D004809:Ephedrine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate; D006801:Humans; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D008055:Lipids / Q000097:blood; D008297:Male; D010919:Placebos; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004573:Electrolytes; D007328:Insulin; D007773:Lactates; D008055:Lipids; D010919:Placebos; D019344:Lactic Acid; D002110:Caffeine; D004809:Ephedrine