Sex-Specific Dietary Inflammation and Metabolic Syndrome: A Cross-Cultural Population-Attributable Gradient Across Three Nations
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Objective
To test whether higher dietary inflammatory potential (Dietary Inflammatory Index, DII) is associated with metabolic syndrome (MetS) in a sex-specific manner across three nations.
Methods
We harmonised individual-participant data from 56,475 adults (US NHANES 2017-2018; Korean KNHANES 2015-2021; Mexican ENSANUT 2018-2019). Sex-stratified logistic regression estimated DII-MetS associations. Two-sample Mendelian randomization (MR) used CRP genetic instruments. Population-attributable fractions (PAFs) quantified cross-country consistency.
Results
A female-specific DII-MetS association was observed (pooled OR=1.15 per DII unit, 95% CI 1.04-1.27; Q5-vs-Q1 OR=1.56; sex interaction FDR q<0.001), consistent across all three countries. Male associations were null (OR=0.99). CRP-based MR was directionally concordant but inconclusive (primary 84-SNP OR=1.03, P=0.31; overlap-prone 56-SNP OR=1.19). PAFs were positive (US 23.4%, Korea 3.9%, Mexico 1.8%).
Conclusions
A pro-inflammatory diet shows a robust female-specific MetS association across three nations. These observational findings, if confirmed prospectively, may support sex-targeted anti-inflammatory dietary guidance.
