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

## TL;DR

This study finds that caffeine may worsen gut cell damage from endurance exercise, particularly in people with a specific gene variant.

## Contribution

The study is the first to show caffeine's effect on gut damage during exercise and its link to ADORA2A genotype.

## Key findings

- Caffeine increased gut cell damage markers more than placebo after exercise.
- ADORA2A genotype influenced caffeine's effect on gut damage, with TT genotype showing a larger increase.
- CYP1A2 genotype did not affect gut damage in this study.

## Abstract

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.