Cheese consumption and lower cholelithiasis risk a prospective UK biobank study with HDL-C mediation

Cholelithiasis affects 10-20% of adults globally, and while cheese consumption may influence risk, underlying biological pathways remain unclear. In this prospective cohort study of 399,467 UK Biobank participants without prior cholelithiasis, we examined cheese intake frequency (never to ≥1/day) via baseline food-frequency questionnaires and identified incident cholelithiasis through hospital records, primary care data, and self-reports. Multivariable COX regression and causal mediation analyses assessed risk associations and mediation by cholesterol subtypes. Over follow-up, 15,897 participants developed cholelithiasis. Higher cheese intake showed a dose-dependent inverse association, with daily consumers having 26.3% lower odds (adjusted OR = 0.737, 95% CI: 0.653-0.832) versus non-consumers. HDL-C significantly mediated this association (proportion mediated: 4.03-6.98%). Frequent cheese consumption was associated with significantly lower cholelithiasis risk, partially mediated by HDL-C, suggesting a potential dietary strategy for prevention, though residual confounding and mechanisms require further investigation.