Sugar- and Artificially Sweetened Beverages, Proteomic Signatures, and Risk of Liver Outcomes: A Prospective Cohort Study in the UK Biobank

Objectives: To evaluate the association of sweetened beverages and their plasma proteomic signatures with the risk of adverse liver outcomes. Methods: We used data from the UK Biobank with 173,840 participants (40-69 years). Sugar- and artificially sweetened beverage intake were assessed by multiple 24-hour dietary recalls. Liver outcomes were ascertained using data from the in-hospital records, cancer registry, and death registry, including a full spectrum of liver disease and mortality. We used elastic net regression to calculate the proteomic score (Olink platform) related to sweetened beverage intake and Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for sweetened beverage intake or proteomic signatures and liver outcomes adjusting for multiple confounding factors. Results: After a median follow-up of 8.9 years, we documented 1112 NAFLD, 954 cirrhosis, 204 liver cancer, 548 severe liver diseases (SLD), and 60 chronic liver disease (CLD) deaths. One serving increment of sugar-sweetened beverage daily was positively associated with risk of NAFLD (HR [95% CI]: 1.10 [1.02-1.19]), cirrhosis (1.21 [1.12-1.32]), SLD (1.18 [1.06-1.31]), and CLD mortality (1.37 [1.06-1.78]), but nonsignificant association with liver cancer. Artificially sweetened beverage intake was positively associated with risk of NAFLD (1.15 [1.07-1.23]), SLD (1.14 [1.02-1.26]), and CLD deaths (1.41 [1.13-1.75]). The proteomic score of sugar-sweetened beverages (96 proteins) and artificially sweetened beverages (105 proteins) showed stronger positive associations with the risk of NAFLD, liver cirrhosis, and SLD (all Ptrend< 0.05) with HRs for one-unit standard deviation increase ranging from 1.57 for cirrhosis to 2.34 for SLD. Conclusions: In this prospective cohort, sugar- and artificially sweetened beverages intake and their proteomic signatures are associated with a spectrum of liver diseases indicating the potential importance of reducing sweetened beverage intake to improve liver health. Funding Sources: Xuehong Zhang is supported by NIH/NCI R21 CA238651, R21 CA252962, R37 CA262299, U01 CA259208, U01 CA272452, American Cancer Society (RSG NEC-130476, PASD-22-1003396).