Dietary polyunsaturated fatty acid and risk of gout: a cohort study integrating genetic predisposition and metabolomics.

Objectives: Gout is the most common inflammatory arthritis and affects quality of life. Dietary polyunsaturated fatty acids (PUFAs) have protective effects against various diseases, but its role in gout remains uncertain. Our study aims to assess the association between PUFAs intake and gout risk, the role of genetic factors, and the possible impact of metabolites.

Methods: This study included 198,033 participants who were free of gout at baseline and completed at least one reliable dietary assessment in the UK Biobank. Cox proportional hazard models were used to estimate the associations between PUFAs intake and gout risk, and the modified effects of genetic predisposition. Mediation analysis also explored the mediating role of metabolic signature in associations between specific PUFAs intake and gout.

Results: Over a median follow-up of 9.47 years, 1,708 incident cases of gout were recorded. Gout risk was significantly associated with the second quartile of linoleic acid (LA) (0.86 [0.75, 1.00]) intake and the highest quartiles of alpha-linolenic acid (ALA) (0.72 [0.62, 0.84]), total PUFA (HR: 0.84 [95% CI:0.71, 0.99]), n-6 PUFA (0.84 [0.71, 0.99]), n-3 PUFA (0.83 [0.71, 0.98]), and eicosapentaenoic acid (EPA) (0.79 [0.68, 0.91]), compared to the lowest quartiles. We observed joint effects of PUFAs intake and genetic susceptibility on gout risk. Mediation analysis showed that high-density lipoprotein (HDL) and triglycerides mediated the associations of ALA and LA with gout risk.

Conclusion: Our findings suggested the potential benefits of PUFAs in reducing gout risk, particularly vegetable sources, with HDL and triglycerides as key mediators.