EAT-Lancet Diet-Associated Serum Metabolites Are Linked to Cardiovascular Disease and Mortality

Higher adherence to the EAT-Lancet diet is associated with lower risk of cardiovascular disease (CVD) and all-cause mortality. Metabolomic profiling can identify biomarkers underlying these associations.

We aimed to investigate metabolomic markers of the EAT-Lancet diet and risk of CVD and all-cause mortality.

We analyzed 2 independent subgroups of Atherosclerosis Risk in Communities study participants (n₁ = 1594, n₂ = 1776) with serum metabolomic data at visit 1 (1987-1989). Adherence to the EAT-Lancet diet was assessed using the Planetary Health Diet Index (PHDI), calculated from a 66-item food frequency questionnaire. Multivariable linear regression models were used to identify metabolites associated with the PHDI score. Cox proportional hazards regression models were used to assess the associations of each doubling in PHDI-related metabolite levels with incident CVD and all-cause mortality. Estimates were meta-analyzed across subgroups using fixed-effects regression, with follow-up through 31 December, 2022. We accounted for multiple comparisons using the Bonferroni method in the cross-sectional analysis and using the false discovery rate in the prospective analysis.

Twenty-nine (23 positively and 6 inversely) of 359 metabolites were associated with the PHDI score. During a median follow-up of 24 y for CVD and 29 y for mortality, 1352 incident CVD cases and 2088 deaths occurred. Four PHDI-related metabolites were associated with incident CVD or all-cause mortality. Glycerate was associated with lower risks of these outcomes [incident CVD hazard ratio (HR) = 0.89, 95% confidence interval (CI): 0.82, 0.96; all-cause mortality HR = 0.86, 95% CI: 0.81, 0.91]. Indolepropionate was linked to lower risk of all-cause mortality, and 1-docosahexaenoylglycerophosphocholine (22:6n3) was associated with lower risk of incident CVD. O-methylcatechol sulfate was positively associated with both outcomes.

In a community-based cohort of United States adults, 29 metabolites are associated with the PHDI score. Four of these metabolites are associated with incident CVD or all-cause mortality, highlighting potential mechanisms of the health impacts of the EAT-Lancet diet.