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

Background: Although recent large randomized clinical trials have reported an increased risk of atrial fibrillation (AF) with marine co-3 fatty acid supplements, it is unclear whether dietary marine co-3 fatty acids assessed through food frequency questionnaires are associated with AF risk.Objectives: 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.Methods: We analyzed data from Million Veteran Program participants who completed self-reported food frequency questionnaires. We used multi variable Cox regression to estimate the HRs of AF across quintiles of ?-3 fatty acid consumption and a cubic spline analysis to assess the dose-response relations between ?-3 fatty acids and AF.Results: Of the 301,294 veterans studied, the median intake of co-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 ?-3 fatty acid intake followed by a plateau.Conclusions: 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.