Metabolic reprogramming induced by periodic dietary restriction of animal products has beneficial effects on human health

Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group of individuals who alternate between omnivory and animal product restriction (APR) for religious reasons. We find that short-term APR is associated with extensive metabolic reprogramming not detected in a control group of continuously omnivorous individuals. We identify reductions in the levels of branched-chain amino acids and of most lipid classes, driving a metabolic profile associated with decreased risk for all-cause mortality. We show that 23% of APR-associated proteins are drug targets, and highlight eight proteins displaying the greatest magnitude of change upon APR (FGF21, FOLR2, SUMF2, HAVCR1, PLA2G1B, OXT, HPGDS, SPP1). We find that APR-associated reprogramming improves metabolic health and emphasise high-value targets for pharmacological intervention.