This study aimed to investigate the associations between carbohydrate intake and gout risk, along with interactions between genetic susceptibility and carbohydrates, and the mediating roles of biomarkers. We included 187,387 participants who were free of gout at baseline and completed at least one dietary assessment in the UK Biobank. Cox proportional hazard models were used to estimate the associations between carbohydrate intake and gout risk. Over a median follow-up of 11.69 years, 2548 incident cases of gout were recorded. Total carbohydrate intake was associated with a reduced gout risk (Q4 vs. Q1: HR 0.67, 95% CI 0.60-0.74), as were total sugars (0.89, 0.80-0.99), non-free sugars (0.70, 0.63-0.78), total starch (0.70, 0.63-0.78), refined grain starch (0.85, 0.76-0.95), wholegrain starch (0.73, 0.65-0.82), and fiber (0.72, 0.64-0.80), whereas free sugars (1.15, 1.04-1.28) were associated with an increased risk. Significant additive interactions were found between total carbohydrates and genetic risk, as well as between total starch and genetic risk. Serum urate was identified as a significant mediator in all associations between carbohydrate intake (total, different types, and sources) and gout risk. In conclusion, total carbohydrate and different types and sources of carbohydrate (excluding free sugars) intake were associated with a reduced risk of gout.
Keywords: biomarkers; cohort study; dietary carbohydrates; genetic risk; gout; mediation analysis.