Abstract
Background: The individual roles of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in mitigating metabolic syndrome (MetS) have been well-documented. However, the significance of their ratio (DHA/EPA) in erythrocytes concerning MetS remains underexplored. This study evaluated the association between the DHA/EPA ratio and MetS including its separate components. Methods: This community-based prospective cohort study involved 3497 participants aged 40 to 75 years enrolled in the Guangzhou Nutrition and Health Study (GNHS) from 2008 to 2013 in China. Baseline erythrocyte fatty acids were quantified using gas chromatography. Over a 12-year follow-up, MetS status was reassessed triennially, identifying 766 new MetS cases among the 2111 participants initially free of the syndrome. The study examined both cross-sectional and prospective relationships of EPA, DHA, and the DHA/EPA ratio with both the presence and incidence of MetS alongside its individual components. Results: Multivariable cross-sectional analyses revealed that the odds ratios (ORs) and 95% confidence intervals (CIs) for MetS prevalence in quartile 4 (vs. 1) were 1.32 (1.07, 1.62) for EPA, 0.52 (0.40, 0.66) for DHA, and 0.66 (0.52, 0.83) for the DHA/EPA ratio (all P-trend < 0.05). Analogous patterns were observed for associations with hyperlipidemia, hypertension, and hyperglycemia. In the prospective analysis, higher DHA/EPA ratios and lower EPA levels were associated with reduced 12-year incidence of MetS and hyperglycemia. Hazard ratios (HRs) and 95% CIs for MetS, comparing the extreme quartiles, were 1.26 (1.02, 1.55) for EPA and 0.75 (0.60, 0.94) for the DHA/EPA ratio. Additionally, DHA was inversely associated with the incidence of hypertension. Conclusions: The study highlights a consistent inverse relationship between the DHA/EPA ratio and both the prevalence and risk of MetS. These findings underscore the potential utility of the DHA/EPA ratio as a predictive marker or therapeutic target in MetS management.