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.

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

We analyzed two independent subgroups of Atherosclerosis Risk in Communities (ARIC) study participants (n₁=1,594, n₂= 1,776) 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 December 31, 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) out of 359 metabolites were associated with PHDI score. During a median follow-up of 24 years for CVD and 29 years for mortality 1,352 incident CVD cases and 2,088 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 HR = 0.89, 95% 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 US adults, 29 metabolites were associated with PHDI score. Four of these metabolites were associated with incident CVD or all-cause mortality, highlighting potential mechanisms of the health impacts of the EAT-Lancet diet.