Omega-3 fatty acids (fish oil) supplementation reduces the occurrence of cardiovascular disease (CVD) and CVD-related mortality in patients at high-risk of CVD and in patients with elevated plasma triglyceride level. Yet, some studies have found an increased risk of atrial fibrillation (AF). AF is the most common sustained cardiac arrhythmia worldwide. It is associated with high morbidity and mortality rates and significant public health burden. Previous studies of the effect of omega-3 fatty acids on AF occurrence have reported contradictory results.
This review evaluated the effect of omega-3 fatty acids on the risk of AF. The results suggest that omega-3 fatty acids supplementation is associated with increased AF risk, particularly in trials that used high doses. Therefore, several factors should be considered before prescribing omega-3 fatty acids, including their dose, type, and formulation (fish, dietary fish oil supplements, and purified fatty acids), as well as patient-related factors and atrial mechanical milieu. Because the benefits of omega-3 fatty acids are dose-dependent, the associated AF risk should be balanced against the benefit for CVD. Patients who take omega-3 fatty acids, particularly at high doses, should be informed of the risk of AF and followed up for the possible development of this common and potentially hazardous arrhythmia.
Another recent review included 54,799 participants from 17 cohorts. A total of 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively.
The authors concluded that in vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.
Faced with contradictory results based on non-RCT evidence, we clearly need an RCT. Luckily such a trial has recently been published. It was an ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017.
Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed). The primary outcome was incident AF confirmed by medical record review.
Among the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39).
The authors concluded that among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF.
So, does the regular supplementation with omega-3 fatty acids increase the risk of atrial fibrillation? The evidence is not entirely clear but, on balance, I conclude that the risk is low or even non-existent.