Caffeine as an Ergogenic Aid: Meta-Analyses on Endurance, Strength, and Power

Mechanism: how caffeine affects muscles and the nervous system

Caffeine is a competitive antagonist of adenosine receptors (primarily A1 and A2A). Adenosine is an inhibitory neurotransmitter whose levels accumulate as fatigue builds. By blocking its receptors, caffeine reduces the subjective perception of effort and perceived fatigue without reducing the actual mechanical load on the muscle.

Peripherally, caffeine increases calcium release from the sarcoplasmic reticulum, enhancing cross-bridge activation in muscle fibers and thereby increasing force output at the same level of neuromuscular activation. Caffeine also stimulates catecholamine release (adrenaline and noradrenaline), enhancing fatty acid mobilization — which is primarily relevant for aerobic exercise.

Endurance: what randomized studies show

Wang Z., Qiu B., Gao J., Del Coso J. analyzed 21 randomized trials with a combined sample of 254 participants (runners of varying fitness levels), published in Nutrients (2022). Dose range: 3–9 mg/kg.

Running endurance results:

• Time to exhaustion: g = 0.392 (95% CI 0.214–0.571; moderate effect), mean improvement +16.97%
• Time-trial performance (time to cover a fixed distance): g = −0.101 (small effect, statistically significant)
• The effect was significant for both recreational (g = 0.469) and trained runners (g = 0.344)

Practical interpretation: in running tasks to failure, caffeine substantially increases work duration; in time-trial formats (how long a fixed distance takes), the effect is smaller but reproducible.

Strength and power: data from the umbrella meta-analysis

Taghizadeh Bilondi H. et al. (Heliyon, 2024) conducted an umbrella meta-analysis — a meta-analysis of meta-analyses — synthesizing the highest-level evidence on caffeine and muscular function. Article e35025 in Volume 10, Issue 15.

Overall estimates:

• Muscular strength: SMD = 0.18 (95% CI 0.14–0.21; p < 0.001)
• Muscular endurance (repetitions to failure): SMD = 0.30 (95% CI 0.21–0.38; p < 0.001)

A parallel meta-analysis by Xiao X. et al. (Frontiers in Nutrition, 2025) focused on speed-strength characteristics during resistance training: 12 RCTs, a combined 230 participants (aged 20–29 years).

Power results:

• Mean movement velocity: SMD = 0.42 (95% CI 0.19–0.65; I² = 85%)
• Mean power output: SMD = 0.21 (95% CI 0.12–0.30; I² = 14%)

The high heterogeneity for velocity (I² = 85%) reflects differences in dose, timing, and participant characteristics. Power output (I² = 14%) is substantially more consistent across studies.

What is the optimal dose and does habitual intake matter

Most studies used doses of 3–6 mg/kg body weight. For a 75 kg person that is 225–450 mg of caffeine — roughly 2–4 standard cups of filter coffee or one pre-workout supplement. The optimal pre-exercise timing is 45–60 minutes: this is the time required to reach peak plasma concentration.

A key moderator of the effect is habitual caffeine intake. The analysis by Xiao et al. (2025) showed: participants with low habitual intake (less than 3 mg/kg/day) had a greater velocity gain — SMD = 0.87 (95% CI 0.72–1.02) vs. SMD = 0.21 in moderate and high consumers. This is consistent with the mechanism: tolerance to caffeine develops rapidly through upregulation of adenosine receptor density.

Limitations, side effects, and tolerance

Despite a good safety profile at moderate doses, caffeine has clinically relevant limitations:

• Sleep disruption. The half-life of caffeine in adults is 3–7 hours. Intake after 2:00–3:00 PM significantly reduces nighttime sleep quality. For most athletes this is the key constraint on using caffeine for evening training sessions.
• Tachycardia and anxiety. At doses above 6 mg/kg, heart rate increases and anxiety or tremor may occur — particularly in sensitive individuals and when combined with other stimulants.
• Tolerance. Regular daily intake reduces effectiveness. Rest days without caffeine or a week-long washout period before competition may restore sensitivity — evidence for this strategy is preliminary.
• Individual variability. Some individuals are "fast metabolizers" (CYP1A2 gene variant): caffeine is cleared more rapidly and its effect is shorter-lived. Others — "slow metabolizers" — are more prone to side effects.