Fish oil supplements increase atrial fibrillation risk in healthy individuals: a population-based cohort study and Mendelian randomization analysis

Abstract

Abstract Background There is a paucity of information on the risk of atrial fibrillation (AF) in healthy individuals taking fish oil supplements. Purpose We aimed to investigate the epidemiologic and causal relationships between fish oil supplement intake and the long-term risk of AF. Methods From the population-based UK Biobank, we selected healthy individuals without a history of AF, other cardiac arrhythmias, or cardiovascular diseases, who were not taking lipid-lowering medications or dietary supplements other than fish oil. The 10-year risk of AF in Fish-Oil-Users vs. Non-Users was evaluated in the total population and propensity-score matched cohort. The causal relationship between n-3 polyunsaturated fatty acids (PUFA) and AF was evaluated using a two-sample summary-level Mendelian randomization analysis with fixed effects robust inverse-variance weighted method, using genetic instruments from previous studies genome-wide association studies for n-3 PUFA levels and AF, respectively. Results A total of 338,199 participants (aged 55.2±8.1, 44.3% men) were analysed. Of these, 35.0% (n=118,300) was taking fish oil supplements. The 10-year risk of AF was significantly higher in the Fish-Oil-Users than in the Non-Users (3.83% vs. 2.91%, adjusted hazard ratio [HR] 1.05, 95% CI [1.01–1.10], P=0.023). The result was consistent in the propensity-score matched cohort (propensity-score matched HR 1.06, 95% CI [1.00–1.12], P=0.043). The increased risk of AF by fish oil supplement was prominent in low-risk participants with healthy lifestyles. Among n-3 PUFA, the docosapentaenoic acid (DPA) showed significant causal estimates for the increased risk of AF (odds ratio [OR] 1.15, 95% CI [1.08–1.22], P<0.001), while higher eicosapentaenoic acid (EPA) levels caused a decrease of AF risk (OR 0.85, 95% CI [0.80–0.90], P<0.001). Conclusion Fish oil supplement intake significantly increased the long-term risk of AF in a healthy population. The causal effect of fish oil intake on the risk of AF may depend on the specific types of n-3 PUFA. Funding Acknowledgement Type of funding sources: None.