Caffeine ingestion and muscle metabolism during prolonged exercise in humans

We examined the effects of a high-caffeine dose on endurance performance and muscle acetyl group metabolism during prolonged exercise. Eight subjects cycled to exhaustion at approximately 80% maximal oxygen uptake (VO2max) 1 h after ingestion of 9 mg/kg body wt dextrose (Pl) or caffeine (Caf). In the Pl trial, muscle biopsies were taken at rest (1 h postingestion) and at 15 min and exhaustion during exercise. The Caf trial followed the same protocol 1 wk later, with an additional biopsy at the time corresponding to Pl exhaustion. The subjects cycled significantly longer during the Caf trial (96.2 +/- 8.8 min) than in the Pl trial (75.8 +/- 4.8 min). Net glycogenolysis during the initial 15 min of cycling was reduced in the Caf vs. Pl trial (4.7 +/- 1.5 vs. 10.6 +/- 1.3 mmol.kg dry muscle-1.min-1; P less than 0.05). Muscle citrate concentration was increased at rest with Caf (0.59 +/- 0.07 vs. 0.37 +/- 0.05 mmol/kg dry muscle; P less than 0.05) but increased to similar values in both trials during cycling. Caf elevated the acetyl-CoA/CoA-SH ratio at rest (0.316 +/- 0.046 vs. 0.201 +/- 0.023; P less than 0.05) but had no effect on the increases in muscle acetyl-CoA and acetylcarnitine during exercise. The results indicate that Caf before exercise decreased muscle glycogenolysis by approximately 55% over the first 15 min of exercise at approximately 80% VO2max. This "spared glycogen" was available late in exercise and coincided with a prolonged time to exhaustion. Increased utilization of intramuscular triacylglycerol and/or extramuscular free fatty acids after caffeine ingestion may inhibit carbohydrate use at rest and early during exercise via elevations in muscle citrate and the acetyl-CoA/CoA-SH ratio. Muscle acetyl-CoA and acetylcarnitine were maintained above resting contents even at exhaustion when muscle glycogen was depleted.