Proinflammatory Diet, Plasma Metabolome, and the Risk of Ischemic Stroke: Evidence From the UK Biobank

Ischemic stroke (IS) imposes a substantial global burden, yet the metabolic pathways linking proinflammatory dietary patterns to its pathogenesis remain unclear.

We conducted a 3-phase prospective analysis within 502 410 participants from the UK Biobank. A total of 249 metabolites determined with high-throughput nuclear magnetic resonance spectroscopy and 168 directly metabolites were included. In phase I, sex-specific metabolic signatures were selected based on Energy-Adjusted Dietary Inflammatory Index (E-DII) with least absolute shrinkage and selection operator. In phase II and III, a Cox proportional hazards regression model was used to evaluate the associations of E-DII and selected metabolic signatures with IS risk. The joint effect of E-DII and polygenic risk score were also evaluated.

The metabolic signature, comprising 32 metabolites in women and 45 metabolites in men, were determined based on E-DII, with correlation coefficients of 0.279 and 0.296 (P<0.001). The association between E-DII and IS risk was only observed in women (hazard ratio [HR], 1.48 [95% CI, 1.16-1.89]) when comparing the participants in the highest quintile group with those in the lowest. No interaction was found between E-DII and polygenic risk score. We also found that the metabolic signature in women was positively associated with IS risk (HR, 1.59 [95% CI, 1.26-2.01]), and mediated 23.9% of this association. Among the contributing components, albumin, degree of unsaturation, and glycoprotein acetyls were identified as key factors.

We identified sex-specific metabolic signatures related to a proinflammatory diet, and confirmed their association with increased IS risk in women.