Writing in the journal Circulation: Arrhythmia and Electrophysiology, researchers from the Fatty Acid Research Institute (FARI) conducted a meta-analysis of over 114,000 participants that found a modest risk of AF is limited to high-dose omega-3 therapies in high-risk patients.
“Our findings show that the relationship between omega-3s and atrial fibrillation is much more nuanced than previous headlines suggested,” said William S. Harris, PhD, president of FARI and senior author on the study. “For the vast majority of people taking nutritional doses of omega-3s, these data should provide reassurance that there is no meaningful increase in atrial fibrillation risk.”
In recent years, several meta-analyses suggested that omega-3 supplements may increase the risk of AF. However, the researchers noted that those reports included no more than eight randomized trials, focused primarily on cardiovascular outcome studies. They did not account for many eligible trials where AF data were available but unpublished, the researchers explained.
Evolving evidence
Several meta-analyses raised concerns that omega-3 fatty acid (FA) supplement could increase the risk of AF, including one study that indicated a 25% increased risk if omega-3s were consumed.
“Emerging evidence, however, has called these findings into question,” the researchers wrote. “For example, a 2023 biomarker-based meta-analysis of 17 prospective cohorts found that higher circulating levels of marine omega-3 FAs were inversely associated with incident AF, suggesting a potential protective impact of low to intermediate doses known to produce such blood levels.”
Over the last 40 years, over 3,900 RCTs were published involving omega-3 FAs. The researchers suggest there is a substantial opportunity to reexamine the omega-3/AF issue using a broader evidence base. That includes using supplementation studies where AF was not a predetermined outcome but would have been documented as an adverse event had it developed.
“The goal of this analysis was to conduct a more comprehensive review of the literature and to perform an updated meta-analysis of randomized controlled trials (RCTs) to better understand the relationship between omega-3 supplementation and AF risk,” the researchers noted. “In contrast to earlier meta-analyses, we integrated both published and underutilized data sources, including trial registries and unpublished data sets, to reduce selective reporting bias. We further ensured that trials reporting no AF events contributed to the pooled evidence base.”
Finally, they stratified results by cardiovascular disease (CVD) risk and dose to compare amounts of omega-3s typically obtained through diet or standard supplementation to that of approved pharmacological doses.
Study details
The study found that low-dose omega-3 supplementation (less than 1,500 mg/day EPA+DHA) was not associated with an increased risk of AF, even among individuals at elevated cardiovascular risk.
The new analysis included: 35 RCTs involving 114,592 participants; it incorporated 15 trials containing previously unpublished AF data; it included studies reporting zero AF events; it evaluated risk according to both omega-3 dose and underlying cardiovascular risk that the researchers claimed provided more clinically meaningful interpretation of the evidence.
Prior studies of high-dose EPA also show decreases in heart attacks, stroke and other major cardiovascular events that substantially outweigh the small increase in atrial fibrillation risk, according to the analysis.
“The decision to take or discontinue omega-3 supplements should be a discussion between a patient and his/her healthcare provider,” Harris said. “What this study does is provide clinicians with better guidance on which patients may benefit from closer monitoring when using high-dose omega-3 therapies while reassuring consumers that it is safe to consume omega-3 fatty acids from foods and dietary supplements.”
Dr. Chip Lavie, MD, medical director of cardiac rehabilitation and preventive cardiology at the Ochsner Heart and Vascular Institute in New Orleans, was not associated with the study but said that 35 RCTs of nearly 115,000 participants is extremely strong evidence that at least shows that doses under 1,500 mg per day of combined EPA and DHA do not substantially increase the risk of AF. They may not increase AF risk at all, he added.
“This information should be very reassuring to patients and many clinicians who have been told that omega-3 increases AF,” Lavie said. “On the other hand, doses above 2,000 mg per day certainly seem to increase the risk of AF, but this needs to be balanced against the marked benefits that omega-3 has in meta-analyses and large RCTs.”
Source: Circulation: Arrhythmia and Electrophysiology. doi: 10.1161/CIRCEP.125.014785. “Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals.” Authors: Nada R. Abuknesha et al.
