Graham · Journal of applied physiology (Bethesda, Md. : 1985) 1991 · Randomized double-blind crossover trial · n=7

Performance and metabolic responses to a high caffeine dose during prolonged exercise.

Cited 339 times in the scientific literature.

Level 2 - randomized trial

Randomized, double-blind crossover clinical trial.

PubMed 1778925 · doi:10.1152/jappl.1991.71.6.2292 · record verified 2026-08-29

What was done

Seven trained competitive runners (mean maximal oxygen uptake 72.6 +/- 1.5 ml/kg/min) completed four randomized, double-blind exercise trials at approximately 85% VO2max to exhaustion: two running trials and two cycling trials. Subjects ingested either placebo (9 mg/kg dextrose) or caffeine (9 mg/kg) 1 hour before exercise. Plasma catecholamines, respiratory exchange ratio, plasma free fatty acids, plasma glycerol, and urinary caffeine concentrations were measured.

What was found

Caffeine ingestion significantly increased endurance times (P < 0.05) compared to placebo during running (71.0 +/- 11.0 vs. 49.2 +/- 7.2 min) and cycling (59.3 +/- 9.9 vs. 39.2 +/- 6.5 min). Resting plasma epinephrine was higher with caffeine before running (0.44 +/- 0.08 vs. 0.22 +/- 0.02 nM) and cycling (0.45 +/- 0.06 vs. 0.31 +/- 0.06 nM). Epinephrine remained significantly elevated at 15 minutes of exercise (running: 2.51 +/- 0.33 vs. 1.23 +/- 0.13 nM; cycling: 2.53 +/- 0.32 vs. 1.24 +/- 0.24 nM) and at exhaustion. Caffeine had no effect on plasma norepinephrine, respiratory exchange ratio, or plasma free fatty acids at rest or during exercise. Plasma glycerol was elevated by caffeine before exercise, at 15 minutes, and at exhaustion during running, but only at exhaustion during cycling. Post-exercise urinary caffeine concentrations reached 8.7 +/- 1.2 micrograms/ml after running and 10.0 +/- 0.8 micrograms/ml after cycling.

Why it matters

This study shows that high-dose caffeine ingestion substantially extends high-intensity endurance capacity in trained individuals. It demonstrates that these performance gains occur alongside marked elevations in plasma epinephrine but without measurable alterations in whole-body substrate oxidation or free fatty acid availability.

Limits

The sample size was very small (n = 7) and restricted to highly trained competitive runners. The high dose tested (9 mg/kg) produced urinary caffeine concentrations approaching athletic doping thresholds and may cause adverse effects not evaluated in the abstract.

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