Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during Exercise1
Didier Laurent,
Kevin E. Schneider,
William K. Prusaczyk,
Carole Franklin,
Suzanne M. Vogel,
Martin Krssak,
Kitt Falk Petersen2,
Harold W. Goforth and
Gerald I. Shulman3
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
utilizationand the neuroendocrine axis during exercise, we studied 20
muscleglycogen-loaded subjects who were given placebo or caffeine(6
mg/kg) in a double blinded fashion 90 min before cyclingfor 2 h
at 65% of their maximal oxygen consumption. Exercise-inducedglycogen
depletion in the thigh muscle was noninvasively measuredby means of
13C nuclear magnetic resonance spectroscopy (NMR)
spectroscopy,and plasma concentrations of substrates and
neuroendocrine hormones,including ß-endorphins, were also assessed.
Muscle glycogencontent was increased 140% above normal values on the
caffeinetrial day (P < 0.001). After cycling for
2 h, caffeine ingestionwas 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-treatedgroup, whereas no change occurred in the placebo
group. We concludethat caffeine ingestion 90 min before prolonged
exercise doesnot exert a muscle glycogen-sparing effect in athletes
withhigh muscle glycogen content. However, these data suggest that
caffeinelowers the threshold for exercise-induced ß-endorphinand
cortisol release, which may contribute to the reported benefitsof
caffeine on exercise endurance.
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