Abstract
Coffee’s health effects are well studied, but its relationship with gastrointestinal diseases (GIDs) remains unclear, particularly with the frequent use of sweeteners. A prospective cohort of 147,263 participants without pre-existing GIDs was analyzed. Coffee intake, assessed via a 24-h dietary recall, was categorized as unsweetened, naturally sweetened, or artificially sweetened. Incident GIDs were identified through medical records. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Genetic predisposition was assessed using polygenic risk scores (PRS), with subgroup and sensitivity analyses conducted for robustness. Over a 12.6-year median follow-up, 29,118 incident GIDs occurred. Unsweetened coffee showed a dose-dependent, U-shaped association with lower GID risk (P-non-linear < 0.001), with the lowest risk at 2-4 cups/day (HR: 0.84, 95% CI: 0.81-0.88). Naturally sweetened coffee had limited benefits, while artificial sweeteners showed inconsistent associations. Protective effects were observed for GERD, gastritis/duodenitis, and biliary diseases. Unsweetened coffee mitigated genetic GID risk, with significant additive interactions for diverticulosis and cirrhosis. Findings were robust across subgroup and sensitivity analyses. Unsweetened coffee consumption is associated with a lower GID risk, supporting its inclusion in dietary recommendations. Further studies are needed to clarify underlying mechanisms and validate findings in diverse populations.