Do Fish Oil Supplements Reduce A-Fib?

Since we debated DiNicolantonio and O’Keefe about the use of fish oil supplements (FOS) to reduce cardiovascular diseases in Missouri Medicine,^1,2 new data have emerged regarding a potential side-effect of FOS—atrial fibrillation (AF). Recently, Gencer et al. published a meta-analysis of seven randomized, placebo-controlled clinical trials of FOS that reported AF as an endpoint.³ This well-conducted meta-analysis revealed a statistically significant increase in AF in subjects receiving FOS, with the greatest risk associated with high-dose therapy (i.e. 4 g daily). However, the AF data were not adjudicated (i.e. rigorously confirmed) in four of the trials included in the analysis. Furthermore, AF was a secondary, tertiary, or exploratory endpoint in all but one of the trials, and bias attributable to informative censoring may have over-estimated effects of FOS on AF.⁴ Thus far, the only FOS study that included AF as a primary endpoint was the VITAL Rhythm Study,⁵ a large, randomized, placebo-controlled clinical trial which showed that daily treatment with eicosapentaenoic acid (EPA) 460 mg and docosahexaenoic acid (DHA) 380 mg had no significant effect on incident AF among adults aged ≥50 years during a median follow-up of >5 years. However, VITAL Rhythm did not exclude the possibility that high-dose FOS increases AF risk.

What are reasonable conclusions that can be drawn from currently available data regarding FOS and the risk of AF, and how should the data guide everyday practice? First, it is clear that FOS do not reduce AF, as had been postulated from epidemiologic data.⁶ Secondly, the statistically significant, dose-dependent association of AF with FOS revealed in Gencer’s meta-analysis is cause for significant concern, as prescription of high-dose EPA is increasing based on results of the REDUCE-IT trial.⁷ Third, when discussing initiation of FOS with patients, clinicians should make them aware of the possible connection between high-dose FOS and AF (particularly patients with risk factors for developing AF), and clinicians should be on the lookout for AF in patients taking FOS. Nevertheless, clinicians can also inform patients that, when using primary endpoints from clinical trials as the main guide, as should be the case, there are currently no definitive data implicating FOS as facilitators of AF, nor are there data suggesting that FOS increase the risk of stroke, the most significant complication of AF. Lastly, clinical trials involving high-dose FOS and AF as a primary endpoint are needed to shed more light on this important issue.