Despite the observed increase in atrial fibrillation with high-dose omega-3, there is no increased risk for stroke, and instead there is a decreased risk for stroke.
"You might want to be a little more attentive to AFib, but there's no increased risk for stroke. There's actually decreased risk for stroke, which would be the clinical outcome of an AFib event." (said at 1:37:07)
Large randomized controlled trials and meta-analyses confirm that omega-3 supplementation (especially at doses >1 g/day, such as high-dose icosapent ethyl in REDUCE-IT) significantly increases the risk of atrial fibrillation (AF) or AF hospitalizations. The claim that there is 'no increased risk for stroke' is supported by meta-analyses showing no overall increase in stroke risk across trials (RR ~1.04, 95% CI 0.90–1.20). However, the assertion that there is 'actually decreased risk for stroke' as a general effect is overstated: while REDUCE-IT found a reduction in stroke/ischemic endpoints among high-risk patients taking 4 g/day icosapent ethyl, systematic reviews and meta-analyses pooling all omega-3 randomized trials find no statistically significant overall reduction in stroke risk, and some subgroup analyses even suggest potential heterogeneity.
- partial: Association Between Omega-3 Fatty Acid Treatment and Atrial Fibrillation in Cardiovascular… (Cardiovascular drugs and therapy 2021)
"In meta-analysis, a significant association was noted between n-3 FA treatment and risk of AF (4.0% vs 3.3%; RR 1.24, 95% CI 1.11-1.38, p = 0.0002)... stronger association in the higher dose (n-3 FA > 1 g daily) sub-group (RR 1.51, 95% CI 1.26-1.80, p < 0.001)... There was no increase in stroke risk (RR 1.04, 95% CI 0.90-1.20)." (abstract, results)
pubmedfull study (doi) - partial: Efficacy and Safety of Omega-3 Fatty Acids in the Prevention of Cardiovascular Disease: A … (Cardiovascular drugs and therapy 2024)
"An increased risk of atrial fibrillation (RR 1.25, 95%CI 1.10 to 1.41; P = 0.000) was observed in patients in the omega-3 fatty acid group. No statistical differences were observed between the two groups in heart failure, stroke, and all-cause death." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillatio… (Journal of the American Heart Association 2023)
"Patients with prior AF or in-study AF hospitalization had consistent relative risk reductions across primary, key secondary, and stroke end points with IPE." (abstract, conclusions, passage verified)
pubmedfull study (doi)