Dietary ω-3 fatty acids and the incidence of atrial fibrillation in the Million Veteran Program

Abstract: Although recent large randomized clinical trials have reported an increased risk of atrial fibrillation (AF) with marine ω-3 fatty acid supplements, it is unclear whether dietary marine ω-3 fatty acids assessed through food frequency questionnaires are associated with AF risk. We sought to test the hypothesis that dietary eicosapentaenoic acid/docosahexaenoic acid/docosapentaecnoic acid (EPA/DHA/DPA) is associated with a higher risk of AF in a large prospective cohort of US Veterans. We analyzed data from Million Veteran Program participants who completed self-reported food frequency questionnaires. We used multivariable Cox regression to estimate the HRs of AF across quintiles of ω-3 fatty acid consumption and a cubic spline analysis to assess the dose–response relations between ω-3 fatty acids and AF. Of the 301,294 veterans studied, the median intake of ω-3 fatty acids (EPA/DHA/DPA) was 219 mg/d (IQR: 144–575), and the mean age was 64.9 y (SD: 12.0); 91% were men, and 84% were White. Consumption of EPA/DHA/DPA exhibited a nonlinear inverse relation with incident AF characterized by an initial decline to 11% at 750 mg/d of marine ω-3 fatty acid intake followed by a plateau. Contrary to our hypothesis, dietary EPA/DHA/DPA was not associated with a higher risk of AF but was inversely related to AF risk in a nonlinear manner.