Omega-3 Fatty Acids and Atrial Fibrillation (2024)

In 2019, the global market for omega-3 fatty acids reached $4.1 billion, and it is expected to double by 2025.¹ These impressive expenditures reflect the worldwide popularity of these products and the belief by many that omega-3 fatty acids are beneficial to their health. Although the health benefits of these products remain questionable, it is important for consumers who take them to understand their potential risks. In this issue of JAMA, the VITAL Rhythm Study² examined the risk of atrial fibrillation (AF), the most common cardiac arrhythmia, with intake of omega-3 fatty acids.

In the past 2 years, 4 randomized clinical trials have provided data on the risk of AF with omega-3 fatty acid intake. In the STRENGTH trial,³ 13 078 high-risk patients with cardiovascular disease were randomized to receive a high dose, 4 g/d, of a carboxylic acid formulation of omega-3 fatty acids (a combination of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or corn oil. After a median of 42 months, there was no significant difference between the 2 randomized groups in the primary composite cardiovascular end point, but there was an increase in risk of developing AF in the omega-3 fatty acids group compared with the corn oil group (2.2% vs 1.3%; hazard ratio, 1.69; 95% CI, 1.29-2.21; P < .001).

In the REDUCE-IT trial,⁴ 8179 participants were randomized to a high dose (4 g/d, as in STRENGTH) of an omega-3 fatty acid preparation consisting of purified EPA (icosapent ethyl) or mineral oil. After a median follow-up of 4.9 years, icosapent ethyl resulted in a 25% relative reduction in the primary composite cardiovascular end point compared with mineral oil. As in STRENGTH, there was a significant increase in risk of AF with omega-3 fatty acids compared with mineral oil (5.3% vs 3.9%; P = .003).

In a third clinical trial, OMEMI,⁵ 1027 older patients who had had a recent myocardial infarction were randomized to receive an intermediate dose, 1.8 g/d, of omega-3 fatty acids (a combination of EPA and DHA) or corn oil. After 2 years, there was no significant difference between the 2 groups in the primary composite cardiovascular end point, but 7.2% of the omega-3 fatty acids group vs 4.0% of the corn oil group developed AF (hazard ratio, 1.84; 95% CI, 0.98-3.45; P = .06).

In the VITAL Rhythm Study,² published in this issue of JAMA, 12 542 participants were randomized to receive a standard dose of omega-3 fatty acids, 840 mg/d (a combination of EPA and DHA) and 12 557 to receive placebo. After a median of 5.3 years, the incidence of AF was 7.2 per 1000 person-years in those taking omega-3 fatty acids vs 6.6 per 1000 person-years in those taking placebo (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19).

Considered together, the data from the 4 trials suggest, but do not prove, that there may be a dose-related risk of AF with omega-3 fatty acid intake. At a dose of 4.0 g/d, there was a highly statistically significant increase in risk (nearly a doubling). With an intermediate dose of 1.8 g/d, the increase in risk (hazard ratio, 1.84) did not achieve statistical significance, and with a standard daily dose of 840 mg/d, there was no apparent increase in risk (although the data were consistent with as much as a 24% increase in risk). Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF and followed up for the possible development of this common and potentially hazardous arrhythmia.

Corresponding Author: Gregory Curfman, MD, JAMA, 330 N Wabash Ave, 41st Floor, Chicago, IL 60611 (gregory.curfman@jamanetwork.org).

Conflict of Interest Disclosures: None reported.