Caffeine increases time to fatigue by maintaining force and not by altering firing rates during submaximal isometric contractions.

Caffeine increases time to fatigue [limit of endurance (T(lim))] during submaximal isometric contractions without altering whole muscle activation or neuromuscular junction transmission. We used 10 male volunteers in a randomized, double-blind, repeated-measures experiment to examine single motor unit firing rates during intermittent submaximal contractions and to determine whether administering caffeine increased T(lim) by maintaining higher firing rates. On 2 separate days, subjects performed intermittent 50% maximal voluntary contractions of the quadriceps to T(lim), 1 h after ingesting a caffeine (6 mg/kg) or placebo capsule. Average motor unit firing rates recorded with tungsten microelectrodes were constant for the duration of contractions. Caffeine increased average T(lim) by 20.5 +/- 8.1% (P < 0.05) compared with placebo conditions. This increase was due to seven subjects, termed responders, who increased T(lim) significantly. Two other subjects showed no response, and a third had a shorter T(lim). Neither the increased T(lim) nor the responders' performance could be explained by alterations in firing rates or other neuromuscular variables. However, the amplitude of the evoked twitch and its maximal instantaneous rate of relaxation did not decline to the same degree in the caffeine trial of the responders; this resulted in values 20 and 30% higher at the time point matching the end of the placebo trial (P < 0.05). The amplitude of the evoked twitch and the maximal instantaneous rate of relaxation were linearly correlated (caffeine r = 0.72, placebo r = 0.80, both P < 0.001), suggesting that the increase in T(lim) may be partially explained by caffeine's effects on calcium reuptake and twitch force.