Pooled analysis of 56,475 adults across the US, South Korea, and Mexico reveals a striking female-specific association between dietary inflammatory potential — measured by the Dietary Inflammatory Index (DII) — and metabolic syndrome (MetS). Women in the highest DII quintile faced 56% greater MetS odds versus the lowest (OR=1.56), with a pooled per-unit OR of 1.15 (95% CI 1.04–1.27) and a sex-interaction FDR q<0.001. Male associations were null (OR=0.99). CRP-based Mendelian randomization was directionally consistent but statistically inconclusive, leaving the causal mechanism unresolved.
This finding lands in a crowded but contested space: the DII has been associated with various cardiometabolic outcomes before, but robust sex-stratified, cross-national analyses at this scale are rare. The biological plausibility is real — estrogen modulates inflammatory pathways, potentially amplifying dietary inflammation's downstream metabolic effects in women — yet this remains speculative without mechanistic data. The Mendelian randomization results, bounded at OR=1.001–1.013 for the diet-attributable component, are notably weak and fail to establish causality. Population-attributable fractions varied widely (US 23.4%, Korea 3.9%, Mexico 1.8%), signaling meaningful cross-cultural heterogeneity that the pooled estimate may obscure. As an observational, cross-sectional design, reverse causation cannot be excluded. Critically, this is a preprint posted to medRxiv and has not yet undergone peer review — findings should be interpreted cautiously. If prospectively confirmed, sex-specific anti-inflammatory dietary guidance could be a pragmatic, low-cost intervention target for women's cardiometabolic health.
