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  • Erica S. Zado
    Address reprint requests and correspondence: Ms Erica S. Zado, Section of Cardiac Electrophysiology, Cardiovascular Division, Hospital of the University of Pennsylvania, Founders 9, 3400 Spruce St, Philadelphia, PA 19104.
    Section of Cardiac Electrophysiology, Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
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Published:November 10, 2021DOI:
      There have been conflicting data on whether supplementation with omega 3 fatty acids increases the risk of atrial fibrillation (AF). Gencer et al (Circulation October 6, 2021;, PMID 34612056) sought to answer the question of whether the use of omega 3 fatty acid increases the risk of AF and to assess whether the dose of supplementation has an effect, through the use of meta-analysis of randomized trials. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for meta-analysis, the investigators searched databases for randomized, controlled, double-blind trials of omega 3 supplements vs placebo. The included studies needed to have at least 500 participants with a minimum follow-up of at least 1 year. From just over 4000 studies screened, 7 studies with 81,210 patients were included in this meta-analysis. Using a number of statistical techniques, these 7 trials were assessed in detail for aggregate results. Of these 7 trials, 5 trials with 58,939 patients (72.6%) studied lower dose (<1 g/d) fatty acid supplements and the other 2 with 22,271 participants (27.4%) tested >1 g/d. The mean age was 65.1 years; 39.2% were women; and the median follow-up period was 4.9 years. AF occurred in 2905 patients (3.6%) included in the meta-analysis with a pooled hazard ratio of 1.25 (95% confidence interval 1.07–1.46; P = .013). The pooled hazard ratio was higher in the high dose (>1 g/d) trials at 1.25 (95% confidence interval 1.04–2.15; P = .042) than in the low dose (<1 g/d) trials (hazard ratio 1.12; 95% confidence interval 1.03–1.22; P = .024). In meta-regression analysis, the hazard ratio for the risk of AF with every 1-g increase in omega 3 fatty acid per day was 1.11, meaning that for every gram per day increase, there is 11% increase in the risk of AF. The authors note a number of limitations including that no trial directly compared high and low dose, different doses and formulations were used among the trials, and given the methodology used, subgroup analysis based on age and other clinical characteristics was not possible. Additionally, trial participants may not be similar to real-life users of omega 3 fatty acid supplements. The authors conclude that in this meta-analysis of 7 randomized controlled trials, omega 3 fatty acid supplements were associated with an increased risk of AF and the risk was greatest at a dose of >1 g/d.
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