Omega-3 and Risk of atrial fibrillation: Vagally-mediated double-edged sword

Studies regarding effects of omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on risk of atrial fibrillation (AF) have reported discordant results. The aim of this review is to clarify effects of marine omega-3 intake on risk of AF.

A PubMed search was performed using terms: atrial fibrillation, omega-3, EPA, DHA, vagal tone. We summarized findings from randomized clinical trials (RCTs), epidemiology studies, and meta-analyses evaluating effects/associations of DHA + EPA on risk of AF. Also, vagal tone was explored as a mediator between omega-3 and risk of AF.

Meta-analyses of 8 RCTs and 17 prospective cohort studies comprised of 83,112 and 54,799 individuals, respectively, investigated the link between omega-3 intake and incident AF. The RCTs reported that treatment with DHA and/or EPA was associated with a 24 % increased relative risk of AF (absolute risk 4.0 % vs 3.3 %; relative risk [RR] 1.24, 95 % confidence interval [CI] 1.11-1.38, p = 0.0002). This was dose-dependent; DHA + EPA doses of ∼1000 mg/d increased AF risk ∼12 %, whereas 1800 to 4000 mg/d increased AF risk by ∼50 %. In contrast, observational studies focused on DHA + EPA blood levels or dietary intake have generally reported that higher omega-3 levels/consumption are associated with lower AF risk. Maximal AF risk reduction. (12 %) occurred at ∼650 mg/d of dietary DHA + EPA. Other studies have indicated that omega-3 fatty acids can dose-dependently increase vagal tone, which could explain the biphasic relationship between DHA + EPA and AF risk. Experimental studies show that low-level vagal stimulation decreases risk of AF, whereas high-level vagal stimulation increases risk of AF.

Higher consumption of dietary omega-3 is associated with decreased AF risk. In contrast, pharmaceutical dosing of omega-3 increases AF in a dose-dependent manner, which may be mediated by vagal tone.