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 bl
inded fashion 90 min before cycling for 2 h at 65% of their maximal oxygen
consumption. Exercise-induced glycogen depletion in the thigh muscle was no
ninvasively measured by means of C-13 nuclear magnetic resonance spectrosco
py (NMR) spectroscopy, and plasma concentrations of substrates and neuroend
ocrine hormones, including beta-endorphins, were also assessed. Muscle glyc
ogen content was increased 140% above normal values on the caffeine trial d
ay (P < 0.001). After cycling for 2 h, caffeine ingestion was associated wi
th a greater increase in plasma lactate (caffeine: +1.0 +/- 0.2 mmol/L; pla
cebo, +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 f
atty acid concentrations increased (caffeine, +814 +/- 133 mmol/L; placebo,
+785 +/- 85 mmol/L; P = NS), and muscle glycogen content decreased (caffei
ne, -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 beta-endorphin le
vels almost doubled (from 30 +/- 5 to 53 +/- 13 pg/mL; P < 0.05) in the caf
feine-treated group, whereas no change occurred in the placebo group. We co
nclude that caffeine ingestion 90 min before prolonged exercise does not ex
ert a muscle glycogen-sparing effect in athletes with high muscle glycogen
content. However, these data suggest that caffeine lowers the threshold for
exercise-induced beta-endorphin and cortisol release, which may contribute
to the reported benefits of caffeine on exercise endurance.