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A comprehensive new meta-analysis involving over 114,000 participants has challenged the prevailing notion that omega-3 fatty acid supplements universally increase the risk of atrial fibrillation (AF). Published in the journal 'Circulation: Arrhythmia and Electrophysiology', the research conducted by the Fatty Acid Research Institute (FARI) indicates that any modest increase in AF risk is predominantly confined to high-dose omega-3 therapies administered to patients already at elevated cardiovascular risk.
Dr. William S. Harris, President of FARI and senior author of the study, emphasized the nuanced nature of the findings. 'Our findings show that the relationship between omega-3s and atrial fibrillation is much more nuanced than previous headlines suggested,' he stated. '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.'
Previous meta-analyses had raised concerns, with some suggesting that omega-3 supplements could increase AF risk, including one report indicating a 25% increased risk with consumption. However, the FARI researchers pointed out that these earlier reports typically included no more than eight randomized trials, often focusing on cardiovascular outcomes and neglecting a significant body of eligible trials where AF data, though available, remained unpublished.
The researchers highlighted 'emerging evidence' that has begun to question these earlier conclusions. As an example, a 2023 biomarker-based meta-analysis of 17 prospective cohorts revealed an inverse association between higher circulating levels of marine omega-3 fatty acids and incident AF, suggesting a potential protective effect from low to intermediate doses that produce such blood levels.
With over 3,900 Randomized Controlled Trials (RCTs) on omega-3 fatty acids published over the past four decades, the FARI team identified a substantial opportunity to re-examine the omega-3/AF relationship using a broader evidence base. Their goal 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.' Crucially, they integrated both published and previously underutilized data sources, including trial registries and unpublished datasets, to mitigate selective reporting bias and ensure that trials reporting no AF events were included.
The analysis, which encompassed 35 RCTs and 114,592 participants, stratified results by cardiovascular disease (CVD) risk and omega-3 dose. It found that low-dose omega-3 supplementation (defined as less than 1,500 mg/day of EPA+DHA) was not linked to an increased risk of AF, even among individuals with elevated cardiovascular risk. This approach, which also included 15 trials with previously unpublished AF data and studies reporting zero AF events, offered a more clinically meaningful interpretation of the evidence.
The study also reiterated that prior research on high-dose EPA had demonstrated significant reductions in heart attacks, stroke, and other major cardiovascular events. These substantial benefits, the analysis concluded, 'substantially outweigh the small increase in atrial fibrillation risk' observed in specific high-dose scenarios.
Dr. Harris advised that 'The decision to take or discontinue omega-3 supplements should be a discussion between a patient and his/her healthcare provider.' He added that the study provides 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, Medical Director of Cardiac Rehabilitation and Preventive Cardiology at the Ochsner Heart and Vascular Institute, who was not involved in the study, corroborated its strength. He noted 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.'
Dr. Lavie also underscored the importance of patient and clinician reassurance, stating, 'This information should be very reassuring to patients and many clinicians who have been told that omega-3 increases AF.' While acknowledging that 'doses above 2,000 mg per day certainly seem to increase the risk of AF,' he stressed that 'this needs to be balanced against the marked benefits that omega-3 has in meta-analyses and large RCTs.' Source: Circulation: Arrhythmia and Electrophysiology