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

  • Arne Astrup
    Correspondence
    Address reprint requests to Arne Astrup, MD, Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, 25 Rolighedsvej, DK-1958 Frederiksberg, Copenhagen, Denmark.
    Affiliations
    Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.

    Institute of Medical Physiology C, University of Copenhagen, Copenhagen, Denmark.

    the Department of Clinical Research, The DAK-Laboratory A/S, Copenhagen, Denmark.
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  • Søren Toubro
    Affiliations
    Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.

    Institute of Medical Physiology C, University of Copenhagen, Copenhagen, Denmark.

    the Department of Clinical Research, The DAK-Laboratory A/S, Copenhagen, Denmark.
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  • Stephen Cannon
    Affiliations
    Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.

    Institute of Medical Physiology C, University of Copenhagen, Copenhagen, Denmark.

    the Department of Clinical Research, The DAK-Laboratory A/S, Copenhagen, Denmark.
    Search for articles by this author
  • Pia Hein
    Affiliations
    Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.

    Institute of Medical Physiology C, University of Copenhagen, Copenhagen, Denmark.

    the Department of Clinical Research, The DAK-Laboratory A/S, Copenhagen, Denmark.
    Search for articles by this author
  • Joop Madsen
    Affiliations
    Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.

    Institute of Medical Physiology C, University of Copenhagen, Copenhagen, Denmark.

    the Department of Clinical Research, The DAK-Laboratory A/S, Copenhagen, Denmark.
    Search for articles by this author
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      Abstract

      Animal and human studies have suggested a thermogenic synergism between ephedrine (E), a β-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, Math Eq, Math Eq, and Math Eq, measured by indirect calorimetry in six healthy, lean subjects. The thermogenic effect after E + C Math Eq 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 < .01), which exceeded the predicted additive effect fivefold to sevenfold. Diastolic blood pressure was not increased by E + C Math Eq, whereas the other two combinations increased it by approximately 4 mm Hg more than placebo. E + C Math Eq and Math Eq increased heart rate more than placebo, while E + C Math Eq 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. The combination of E + C Math Eq has a favorable thermogenic effect (Math Eq), with no marked effect on mean blood pressure and heart rate. This combination may be useful in the treatment of obesity.
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