Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes
One hundred and one competitive male athletes rode a 10-km cycling time trial after 0, 2 or 4 mg/kg caffeine, and were genotyped for the -163A > C polymorphism of CYP1A2, which affects caffeine metabolism. Overall, 4 mg/kg made riders 3% faster than placebo, but with a significant caffeine-gene interaction.
AA carriers improved by 4.8% at 2 mg/kg and 6.8% at 4 mg/kg; AC carriers showed no effect; CC carriers were 13.7% slower at 4 mg/kg. The authors conclude that CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for endurance performance.
Participants
n=101 competitive male athletes, age 25 ± 4 yr.
Protocol
10-km cycling time trial under three conditions: 0, 2 or 4 mg of caffeine per kg body mass.
Split-plot randomised, double-blinded, placebo-controlled design.
DNA from saliva, genotyped for CYP1A2 -163A > C (rs762551).
Key Results
Overall: 4 mg/kg decreased cycling time by 3% vs placebo (17.6 ± 0.1 vs 18.1 ± 0.1 min, mean ± SEM, P = 0.01).
Caffeine-gene interaction: significant (P < 0.0001).
AA genotype: -4.8% at 2 mg/kg (17.0 ± 0.3 vs 17.8 ± 0.4 min, P = 0.0005); -6.8% at 4 mg/kg (16.6 ± 0.3 vs 17.8 ± 0.4 min, P < 0.0001).
AC genotype: no effects.
CC genotype: 4 mg/kg increased cycling time by 13.7% vs placebo (20.8 ± 0.8 vs 18.3 ± 0.5 min, P = 0.04).
Practical Application
"Why does caffeine do nothing for me?" In 101 competitive male athletes in a randomised, placebo-controlled 10-km cycling time trial, caffeine helped only those with the CYP1A2 AA genotype (4.8% faster at 2 mg/kg, 6.8% at 4 mg/kg); AC carriers saw no effect and CC carriers were 13.7% slower at 4 mg/kg. Genotype is one real reason for non-response.
Not from this paper; the base's own practice: test caffeine against no caffeine on two matched hard sessions before relying on it in a race — that works whether or not the genotype is known. The base's CYP1A2 phenotyping note is REF-446; standard dosing is REF-350.
Inference, not tested here: a CC carrier who wants caffeine should try the low end (2 mg/kg) in training rather than 4 mg/kg; the trial found no CC benefit at either dose shown in the abstract.
Limitations
Men only; one 10-km cycling time trial.
Genotype subgroup sizes are not given in the abstract; the CC group is the smallest genotype in most populations (not from this paper), so its estimate is the least precise (P = 0.04).
Values are mean ± SEM, which look tighter than SD.
Written from the abstract and record metadata only (full text not read).
How this entry was checked and changed
Why this level
RCT, n=101; the genotype subgroups are smaller and their sizes are not in the abstract