Adherence to the EAT-Lancet diet and its metabolic signature are associated with a lower risk of gout.

OBJECTIVE: To investigate the association of the EAT-Lancet diet and its metabolic signature with the risk of gout, taking genetic predispositions into account. METHODS: Study populations included 91,479 UK Biobank participants with concomitant information on questionnaire and molecular data. EAT-Lancet diet score was calculated using the Oxford WebQ dietary questionnaire. A metabolic signature was developed using the elastic net regression. Associations between EAT-Lancet diet score, its metabolic signature, and incidence of gout were assessed through the Cox proportional hazards models. Mediation analysis was performed to assess the mediatory effects of metabolic signature and individual metabolite. A genetic risk score (GRS) of gout was calculated and incorporated to evaluate joint associations and potential interactions between genetic susceptibility and EAT-Lancet diet score or its metabolic signature in relation to gout risk. RESULTS: During a median follow-up period of 11.61 years, 1,444 incident cases of gout were observed. Comparing the highest to lowest quartile, both the EAT-Lancet diet score (HR = 0.74, 95%CIs = 0.63-0.86) and its metabolic signature (HR = 0.40, 95%CIs = 0.32-0.50) were significantly associated with a reduced risk of gout. Joint analysis indicated that favorable metabolic profiles may attenuate the genetic predisposition to gout. Mediation analysis showed that the metabolic signature explained 39.1% (95%CIs = 24.6%-82.3%) of the EAT-Lancet diet-gout association. CONCLUSIONS: Adherence to EAT-Lancet diet and its metabolic signature are associated with a reduced risk of gout. This signature also partially mitigates the genetic susceptibility to gout.