Plasma omega-3 and omega-6 polyunsaturated fatty acid levels and risk for total mortality: The Mexico City Prospective Study.

Abstract

Polyunsaturated fatty acids (PUFAs), particularly omega-3 and omega-6 fatty acids, have been associated with cardiometabolic health and mortality risk. We aimed to evaluate the associations between circulating omega-3 and omega-6 PUFA levels-focusing on docosahexaenoic acid (DHA) and linoleic acid (LA)-and all-cause mortality in a large Mexican population. We analysed data from 144,900 adults aged ≥35 years, with baseline data collected between 1998 and 2004. Participants were followed up until Oct 1, 2022 for mortality. Circulating PUFAs were quantified using nuclear magnetic resonance spectroscopy in baseline plasma samples. Associations with all-cause mortality were evaluated by computing hazard ratios (HRs) and 95% confidence intervals (95% CIs) across quintiles and per interquintile range. Higher circulating omega-3 levels were consistently associated with lower all-cause mortality. Per interquintile range, HRs were 0.94 (95% CI 0.91, 0.97) for DHA, 0.83 (95% CI 0.81, 0.86) for non-DHA omega-3, and 0.88 (95% CI 0.85, 0.90) for total omega-3. Participants in the highest quintile of non-DHA omega-3 had a 20% lower hazard of mortality compared with those in the lowest quintile (HR 0.80; 95% CI 0.77, 0.83). Although LA was not associated with mortality, total omega-6 and non-LA omega-6 were inversely associated with mortality per interquintile range for the latter (HR 0.90; 95% CI 0.87, 0.92). In this large cohort, higher circulating omega-3 fatty acid levels, including DHA, were associated with lower all-cause mortality. These findings provide important evidence from an understudied population and highlight the relevance of circulating fatty acid profiles in diverse genetic and dietary contexts.