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Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during Exercise¹

Department of Internal Medicine and the Howard Hughes Medical Institute (G.I.S.), Yale University School of Medicine, New Haven, Connecticut 06510; and Physiological Performance and Operational Medicine Department, Naval Research Center (K.E.S., W.K.P., H.W.G.), San Diego, California 92186

Address all correspondence and requests for reprints to: Gerald I. Shulman, M.D., Ph.D., Howard Hughes Medical Institute, Yale University School of Medicine, 254C BCMM, 295 Congress Avenue, P.O. Box 9812, New Haven, Connecticut 06510. E-mail: gerald.shulman{at}yale.edu

To examine the effect of caffeine ingestion on muscle glycogen utilization and the neuroendocrine axis during exercise, we studied 20 muscle glycogen-loaded subjects who were given placebo or caffeine (6 mg/kg) in a double blinded fashion 90 min before cycling for 2 h at 65% of their maximal oxygen consumption. Exercise-induced glycogen depletion in the thigh muscle was noninvasively measured by means of ¹³C nuclear magnetic resonance spectroscopy (NMR) spectroscopy, and plasma concentrations of substrates and neuroendocrine hormones, including ß-endorphins, were also assessed. Muscle glycogen content was increased 140% above normal values on the caffeine trial day (P < 0.001). After cycling for 2 h, caffeine ingestion was associated with a greater increase in plasma lactate (caffeine: +1.0 ± 0.2 mmol/L; placebo, +0.1 ± 0.2 mmol/L; P < 0.005), epinephrine (caffeine, +223 ± 82 pg/mL; placebo, +56 ± 26 pg/mL; P < 0.05), and cortisol (caffeine, +12 ± 3 mg/mL; placebo, +2 ± 2 mg/mL; P < 0.001) levels. However, plasma free fatty acid concentrations increased (caffeine, +814 ± 133 mmol/L; placebo, +785 ± 85 mmol/L; P = NS), and muscle glycogen content decreased (caffeine, -57 ± 6 mmol/L muscle; placebo, -53 ± 5 mmol/L muscle; P = NS) to the same extent in both groups. At the same time, plasma ß-endorphin levels almost doubled (from 30 ± 5 to 53 ± 13 pg/mL; P < 0.05) in the caffeine-treated group, whereas no change occurred in the placebo group. We conclude that caffeine ingestion 90 min before prolonged exercise does not exert a muscle glycogen-sparing effect in athletes with high muscle glycogen content. However, these data suggest that caffeine lowers the threshold for exercise-induced ß-endorphin and cortisol release, which may contribute to the reported benefits of caffeine on exercise endurance.

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