Caffeine exacerbates exercise‐induced gut cell damage and is influenced by ADORA2A genotype but not CYP1A2 genotype: A preliminary study

Endurance exercise may be associated with acute damage to intestinal epithelial cells. The effect of caffeine supplementation, and whether this is influenced by common genetic polymorphisms (ADORA2A: rs5751876 and CYP1A2: rs762551), is not currently known. Participants ( n = 18 men and women) ingested caffeine (3 mg/kg body mass) or placebo 45 min before cycling (20 min at 70% maximal oxygen uptake followed by a 15‐min performance time‐trial). Plasma intestinal fatty acid binding protein (iFABP) was measured pre‐supplementation, pre‐ and post‐exercise. Four‐way mixed ANOVAs revealed significant main effects of treatment, time, and treatment × time interaction ( p < 0.05). Post hoc tests revealed a post‐exercise increase in plasma [iFABP], which was greater with caffeine; and a trial × ADORA2A genotype interaction p = 0.021, with further post hoc analysis revealing a significant post‐exercise increase only in ADORA2A TT (“high sensitivity”) participants in the caffeine trial (increase ~109%, p = 0.027, vs. 48% increase p > 0.05 for “low sensitivity” participants). There were no other main effects or interactions (all p > 0.05). Acute damage to gut cells caused by endurance exercise may be exacerbated by caffeine, especially in sensitive individuals. The potential implications of this for gastrointestinal responses to exercise warrant further examination.