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Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes


Medicine & Science in Sports & Exercise: August 2018 - Volume 50 - Issue 8 - p 1570–1578
doi: 10.1249/MSS.0000000000001596

Purpose Many studies have examined the effect of caffeine on exercise performance, but findings have not always been consistent. The objective of this study was to determine whether variation in the CYP1A2 gene, which affects caffeine metabolism, modifies the ergogenic effects of caffeine in a 10-km cycling time trial.

Methods Competitive male athletes (n = 101; age = 25 ± 4 yr) completed the time trial under three conditions: 0, 2, or 4 mg of caffeine per kilogram body mass, using a split-plot randomized, double-blinded, placebo-controlled design. DNA was isolated from saliva and genotyped for the −163A > C polymorphism in the CYP1A2 gene (rs762551).

Results Overall, 4 mg·kg−1 caffeine decreased cycling time by 3% (mean ± SEM) versus placebo (17.6 ± 0.1 vs 18.1 ± 0.1 min, P = 0.01). However, a significant (P <0.0001) caffeine–gene interaction was observed. Among those with the AA genotype, cycling time decreased by 4.8% at 2 mg·kg−1 (17.0 ± 0.3 vs 17.8 ± 0.4 min, P = 0.0005) and by 6.8% at 4 mg·kg−1 (16.6 ± 0.3 vs 17.8 ± 0.4 min, P < 0.0001). In those with the CC genotype, 4 mg·kg−1 increased cycling time by 13.7% versus placebo (20.8 ± 0.8 vs 18.3 ± 0.5 min, P = 0.04). No effects were observed among those with the AC genotype.

Conclusion Our findings show that both 2 and 4 mg·kg−1 caffeine improve 10-km cycling time, but only in those with the AA genotype. Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg·kg−1 in those with the CC genotype. CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance.

1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, CANADA;

2Department of Statistical Sciences, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, CANADA; and

3Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, CANADA

Address for correspondence: Ahmed El-Sohemy, Ph.D., Department of Nutritional Sciences, University of Toronto, 150 College Street, Room 350 Toronto, ON M5S 3E2, Canada; E-mail:

Submitted for publication December 2017.

Accepted for publication February 2018.

© 2018 American College of Sports Medicine