Dose-Response Effect of Oral Caffeine Use on Aerobic Exercise Performance: A Systematic Review and Meta-Analysis

Background/Objective: Caffeine has demonstrated ergogenic effects across various doses (2-9 mg·kg^-1). However, aerobic responses to caffeine vary substantially, with time-trial performance ranging from ~-3% to +16%. Given that higher doses may increase adverse effects without clear additional benefits, this review examined the effects of low (≤3 mg·kg^-1), moderate (4-6 mg·kg^-1), and high (>6 mg·kg^-1) caffeine doses on time-trial performance. Methods: A systematic review and meta-analysis of randomized, placebo-controlled trials was conducted using PubMed, Embase, and Virtual Health Library databases. Eligible studies included healthy adults (18-59 years) acutely ingesting oral anhydrous caffeine before aerobic time-trial tests, with performance outcomes measured exclusively as time-to-completion variables. Data were pooled using standardized mean differences (SMDs) and 95% confidence intervals under random-effects models, and risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Forty-eight studies (689 participants) met the inclusion criteria. Both low and moderate caffeine doses significantly reduced time-trial completion time relative to placebo. Low doses produced a standardized mean difference of -0.27 (95% CI: -0.44 to -0.11; p = 0.001), whereas moderate doses resulted in an SMD of -0.52 (95% CI: -0.77 to -0.28; p < 0.0001). No studies evaluating high caffeine doses (>6 mg·kg^-1) and reporting time-to-completion outcomes met the inclusion criteria. Subgroup analyses demonstrated similar ergogenic effects in both trained and highly trained individuals consuming moderate caffeine doses. Conclusions: This is the first meta-analysis specifically focused on aerobic time-trial performance to suggest that pre-exercise ingestion of low caffeine doses (1.3-3 mg·kg^-1) may enhance endurance performance by reducing time-trial completion time. Notably, the use of moderate caffeine doses (4-6 mg·kg^-1) appears to produce a more consistent ergogenic effect.