ULTRA-PROCESSED FOOD CONSUMPTION AND RISK OF GALLSTONE DISEASE: ANALYSIS OF THREE PROSPECTIVE COHORTS

Majority of dietary intake in US adults comes from ultra-processed foods (UPFs), which have been linked to several adverse health outcomes. Gallstone disease is highly prevalent and constitutes a significant burden to the US health system but remains understudied. This study aims to investigate the association between UPF consumption and incident gallstone disease risk. In this analysis, 44,149 males in the Health Professionals' Follow-up Study (HPFS: 1986–2022), 71,145 females in the Nurses' Health Study (NHS: 1986–2021) & 90,932 females in the Nurses' Health Study II (NHS II: 1991–2021) were prospectively followed. Dietary intake was quadrennially assessed with semi-quantitative food frequency questionnaires and used to identify UPFs. The primary outcome was defined as cholecystectomy. Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Baseline median age was 54y in HPFS, 53y in NHS and 36y in NHS II. We identified 32,374 incident gallstone disease cases over 5,077,059 person-years. Participants in the highest UPF quintile had a higher incidence of gallstone disease compared to those in the lowest quintile (aHR: 1.29, 95% CI: 1.24–1.36, p<0.001). The incremental risk of incident gallstone disease was 2.8% per daily serving (95% CI: 2.4%–3.2%, p<0.001). This risk was driven by sugar-sweetened beverages and artificially-sweetened beverages on UPF subgroup-analyses. The proportion of risk mediated by obesity was 12.8% (95% CI: 7.7%–20.5%, p <0.001) in HPFS, 14.3% (95% CI: 10.4%–19.4%, p<0.001) in NHS and 39.4% (95% CI: 31.2%–48.1%, p<0.001) in NHS II. The partial population attributable risk was estimated at 15.9% (95% CI: 13.4%–18.3%). UPF consumption is associated with a higher risk of gallstone disease, particularly consumption of sugar-sweetened beverages and artificially-sweetened beverages. A substantial proportion of this risk is potentially mediated by obesity in younger females.