Identification of serum metabolites associated with the EAT-Lancet planetary health diet, and their mediating role in weight status and weight changes in adults

Abstract Purpose Better adherence to a healthy and sustainable diet has been associated with a lower body weight, but the underlying metabolic mechanisms remain unclear. We examined whether serum metabolites mediate this association. Methods We used data from three Finnish population-based health examination studies ( n = 9225, 54% of women, mean age of 54 years). Diet quality was assessed with a dietary score based on the Planetary Health Diet (PHD) adapted to Finnish food culture. Weight, height, waist circumference (WC), and body mass index were measured at baseline and follow-up, and their percentual changes over seven years were calculated. Serum metabolites ( n = 158) were quantified using a high-throughput nuclear magnetic resonance (NMR) spectroscopy metabolomics platform (Nightingale Health Plc). The role of individual metabolites in the diet-anthropometry associations by sex were assessed by mediation analyses using multivariable linear regression. Analyses were replicated in an independent dataset of three additional Finnish studies ( n = 10242). Results Mediation analyses indicated that seven metabolites partly mediated diet-WC association in both men and women: short-chain fatty acid acetate (7.6/3.1%, respectively), degree of fatty acid unsaturation (26.0/23.1%), and several fatty acid-to-total fatty acid ratios (polyunsaturated (35.6/46.5%), docosahexaenoic (5.5/9.6%), omega-3 (4.0/9.8%), linoleic (31.4/49.9%), and saturated fatty acids (12.1/13.0%). Conclusion The association between higher PHD adherence and a smaller WC was partly explained by several serum metabolites likely reflecting higher fiber intake and better fat quality of the PHD. These findings suggest that healthy and sustainable diets may contribute to weight management through favourable metabolic profiles.