Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study

Metabolism. 1991 Mar;40(3):323-9. doi: 10.1016/0026-0495(91)90117-f.


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)

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Blood Pressure
  • Body Temperature Regulation / drug effects*
  • C-Peptide / blood
  • Caffeine / pharmacology*
  • Double-Blind Method
  • Drug Synergism
  • Electrolytes / blood
  • Energy Metabolism / drug effects
  • Ephedrine / pharmacology*
  • Female
  • Heart Rate
  • Humans
  • Insulin / blood
  • Lactates / analysis
  • Lactic Acid
  • Lipids / blood
  • Male
  • Placebos
  • Reference Values


  • Blood Glucose
  • C-Peptide
  • Electrolytes
  • Insulin
  • Lactates
  • Lipids
  • Placebos
  • Lactic Acid
  • Caffeine
  • Ephedrine