Omega-3 fatty acids supplementation and risk of atrial fibrillation. An updated meta-analysis of randomized controlled trials

Omega-3 fatty acid (O3FA) supplementation is widely used to lower cardiovascular risk, especially in patients with elevated triglycerides. However, this updated meta-analysis of randomized controlled trials (RCTs) raises safety concerns, revealing a significant association between O3FA use and increased risk of atrial fibrillation (AF). The analysis included five RCTs and used a Poisson regression model with random effects to compare AF incidence between O3FA-treated and placebo groups. Results showed that O3FA supplementation was linked with a 37% increased risk of AF (IRR 1.37; 95% CI 1.22–1.54), a finding consistent even when including the VITAL Rhythm trial in sensitivity analysis. Despite prior evidence supporting O3FA’s cardiovascular benefits—particularly in the REDUCE-IT trial—recent studies such as STRENGTH and others reported no benefit or even neutral effects. Notably, AF risk appeared elevated regardless of O3FA dose or formulation. The biological mechanisms behind this pro-arrhythmic effect remain unclear, though previous data hinted at both anti- and pro-arrhythmic properties. The study concludes that clinicians should consider the potential AF risk when prescribing O3FA, particularly in high-risk patients, and emphasizes the need for further mechanistic studies and targeted trials.