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

Scand J Med Sci Sports. 2026 Feb;36(2):e70214. doi: 10.1111/sms.70214.

Abstract

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.

Keywords: caffeine metabolism; ergogenic aid; muscular performance; resistance training; sex differences.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Caffeine* / administration & dosage
  • Caffeine* / pharmacology
  • Cross-Over Studies
  • Cytochrome P-450 CYP1A2* / genetics
  • Double-Blind Method
  • Female
  • Genotype
  • Humans
  • Male
  • Muscle Strength* / drug effects
  • Performance-Enhancing Substances* / administration & dosage
  • Performance-Enhancing Substances* / pharmacology
  • Physical Endurance* / drug effects
  • Physical Endurance* / genetics
  • Resistance Training
  • Young Adult

Substances

  • Caffeine
  • Cytochrome P-450 CYP1A2
  • CYP1A2 protein, human
  • Performance-Enhancing Substances