CYP1A2 Genotype and the Ergogenic Effect of Acute Caffeine Intake on Muscular Strength and Endurance Performance in Trained Individuals.

This study examined whether CYP1A2 (rs762551) genotype modulates the acute ergogenic effects of caffeine on muscular strength and endurance performance in resistance-trained men and women. Ninety-four resistance-trained participants (47 females, 47 males; 39 AA, 44 AC, 11 CC) completed a randomized, triple-blind, placebo-controlled, crossover trial. Participants ingested 3 mg/kg of caffeine or placebo before performing standardized bench press and back squat tests. Mean velocity was measured to assess strength performance against different loads (25%-90%) and muscular endurance during a single set performed to failure at 65% 1RM. Data were analyzed using ANCOVA with supplement, genotype, and sex as factors. Caffeine significantly improved strength and endurance performance across conditions (p < 0.01, η p 2 $$ {\eta}_p^2 $$  = 0.077-0.294). Mean velocity increased by 4%-12% in AA and 3%-9% in AC individuals, particularly at 50%-90% 1RM, whereas CC carriers showed minor changes (≤ 4%). Supplement by genotype interaction was noted only at 90% 1RM in mean velocity (p < 0.05, η p 2 $$ {\eta}_p^2 $$  = 0.094). In the muscular endurance test, mean velocity improved by 4%-6% in AA, 3%-4% in AC, and 2%-6% in CC. No sex differences or ergolytic effects were observed. Acute ingestion of 3 mg/kg caffeine enhances strength and endurance performance in resistance-trained men and women. Although CYP1A2 genotype did not alter the overall effect, benefits were greatest in AA, intermediate in AC, and minimal in CC carriers. These findings support low-dose caffeine as an effective and safe ergogenic aid in resistance training regardless of sex, with individual variability partly explained by genotype.