High-Dose Omega-3s Tied to Higher Risk for Atrial Fibrillation

Taking high-doses of marine omega-3 fatty acids, more than 1 gram daily, may raise the risk for atrial fibrillation (AF), according to a meta-analysis of relevant research. 

However, the risk of developing AF appears to be “relatively small” for those taking 1 gram or less of fish oil per day, Christine Albert, MD, chair of the  Department of Cardiology at the Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told theheart.org | Medscape Cardiology. 

The study was published online October 6 in the journal Circulation.

It’s estimated that 7.8% of US adults — almost 19 million in all — take fish oil supplements, often unbeknownst to their healthcare provider, the researchers note. Yet, the literature on the effects of omega-3 fatty acid supplementation on cardiovascular outcomes are mixed.

“Some, but not all,” large-scale randomized controlled trials investigating the effects of marine omega-3 fatty acid supplements on cardiovascular outcomes have reported increased risks for AF. The potential reasons for differing findings may be dose related, the authors note in their paper.

The goal of this meta-analysis was to “bring clarity, answers, and actionable information” to doctors and patients, said Albert. The results suggest, however, that there may not be a “straightforward answer” to whether fish oil is good or bad for AF. Instead, the answer may depend on the dose, she added.

Pooled Data

After screening 4049 articles and abstracts, the researchers included in their analysis 7 large-scale randomized controlled trials reporting cardiovascular outcomes of marine omega-3 fatty acids.

The trials reported results for AF, either as prespecified outcome, adverse event, or a reason for hospitalization. Each had a minimum of 500 patients and a median follow-up of at least 1 year. 

Trials examining the effects of omega-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were excluded.

The seven trials enrolled a total of 81,210 patients (mean age, 65 years; 39% women); 72.6% of participants were enrolled in clinical trials testing ≤1 gram of marine omega-3 fatty acids per day and 27.4% were enrolled in clinical trials testing >1 gram of the supplement per day. The weighted average follow-up was 4.9 years.

Overall, use of omega-3 fatty acids was associated with a 25% increased risk for AF (hazard ratio [HR] 1.25; 95% CI, 1.07 – 1.46; P = .013).

In analyses stratified by dose, the risk for AF was “significantly more pronounced” in trials testing high doses of marine omega-3 fatty acid supplements (>1 gram per day: HR, 1.49; 95% CI, 1.04 – 2.15; P = .042) compared with those testing lower doses (≤1 gram per day: HR, 1.12; 95% CI, 1.03 – 1.22; P = .024; P for interaction < .001).

In meta-regression, the HR for AF increased per 1 gram increase in daily omega-3 fatty acid dose (HR. 1.11; 95% CI, 1.06 – 1.15; P = .001).

Risk–Benefit Balance

“This meta-analysis adds new evidence regarding the risk of AF in patients taking marine omega-3 fatty acid supplements,” write Albert and colleagues.

“Since the benefit of omega-3 fatty acids also appears to be dose dependent, the associated risk of AF should be balanced against the benefit on atherosclerotic cardiovascular outcomes,” they suggest.

They caution that the meta-analysis pooled aggregate-level trial data, not individual patient data. Therefore, subgroup analyses by age or other patient level characteristics were not possible.

The risk of developing AF increases with advancing age and is more common in men than in women. Additional risk factors include elevated blood pressure, coronary artery disease, heart failure, heart valve defects, obesity, and diabetes.

The authors say the potential risk of developing AF with high doses of omega-3 fatty acid supplements should be discussed with patients and they should know the signs and symptoms of the condition.

The study had no specific funding. Albert has received grants from St. Jude Medical, Abbott, and Roche Diagnostics.

Circulation. Published online October 6, 2021. Abstract

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