EAT‐Lancet Diet, Plasma Metabolites, and Risk of Peripheral Artery Disease: A Prospective Cohort Study

BACKGROUND: The Planetary Health Diet Index, developed by the EAT-Lancet Commission, promotes sustainable and healthy eating, yet its association with peripheral artery disease (PAD) remains underexplored. Furthermore, the metabolic mechanisms potentially linking this dietary pattern to PAD warrant deeper investigation. METHODS: In 192 166 UKB (UK Biobank) participants with 24-hour dietary recall, Cox proportional hazards models were used to evaluate the association between the EAT-Lancet diet index and PAD. In a subcohort (n=93 961), diet-related metabolites were identified via elastic net regression to construct a metabolic signature, which was analyzed for its association with PAD risk and potential mediating role. RESULTS: Over a median follow-up of 10.55 years, 1579 PAD events occurred. Higher adherence to the EAT-Lancet diet was associated with a lower PAD risk (hazard ratio [HR], 0.74 [95% CI, 0.62-0.87]), consistent across subgroups and sensitivity analyses. Sixty metabolites formed the diet-related metabolic signature, inversely associated with PAD (HR, 0.66 [95% CI, 0.50-0.88]) and mediating 12.9% (95% CI, 4.6%-28.5%) of the diet's protective effect, with mediating metabolites mainly enriched in the fatty acids subclass. CONCLUSIONS: Greater adherence to the EAT-Lancet diet is associated with a lower risk of PAD, with its metabolic signature potentially mediating this relationship, underscoring the importance of dietary interventions and metabolic monitoring for PAD prevention.