Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies

Abstract

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Fig. 1. Adjusted hazard ratios (HR, 95% CI) for total mortality for circulating eicosapentaenoic (EPA) plus docosahexaenoic acid (DHA) in the 17 contributing studies of the Fatty Acids and Outcomes Research Consortium.

Study-specific estimates for HRs (dark squares) are shown per interquartile range (comparing the midpoint of the top to the bottom quintiles) their sizes indicate study weights (column 3). The horizontal line through each HR is 95% CI. Compartments included erythrocyte phospholipids, plasma phospholipids, cholesteryl esters, and total plasma. All HRs are adjusted for age, sex, race, field center, body-mass index, education, occupation, marital status, smoking, physical activity, alcohol intake, prevalent diabetes, hypertension, and dyslipidemia, self-reported general health, and the sum of circulating n-6 PUFA (linoleic plus arachidonic acids). See Table 1 footnote for abbreviations of cohorts.

Fig. 2. Associations of circulating long-chain n-3 PUFA levels with all-cause mortality: nonlinear dose-response meta-analysis in the Fatty Acids and Outcomes Research Consortium. Hazard ratios and cohort-specific quantiles are presented in the vertical and horizontal axis, respectively.

The best estimates and their confidence intervals are presented as black lines and gray-shaded areas, respectively. The 10th percentile was selected as a reference level and the x-axis depicts 5th to 95th percentiles. Potential nonlinearity was identified for EPA (p = 0.0004) but not for the others (p > 0.05). All HRs are adjusted for age, sex, race, field center, body-mass index, education, occupation, marital status, smoking, physical activity, alcohol intake, prevalent diabetes, hypertension, and dyslipidemia, self-reported general health, and the sum of circulating n-6 PUFA (linoleic plus arachidonic acids).