Safety Spotlight: Omega-3 fatty acid supplementation can increase the risk of atrial fibrillation

Here's a quick rundown of a recent meta-analysis which explored whether EPA and DHA supplementation can increase the risk of atrial fibrillation. Currently, the answer appears to be "yes."

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Study under review: Randomized, crossover, head-tohead comparison of EPA and DHA supplementation to reduce inflammation markers in men and women: The Comparing EPA to DHA Study
Summary

The heart health benefits of omega-3 fatty acid supplementation have been recently brought into question, with two high-dose trials coming to dramatically different conclusions. On one hand, REDUCE-IT[1] found that 4 grams daily of pharmaceutical-grade EPA reduced the risk of cardiovascular events in people at high risk and with elevated triglyceride levels compared to a mineral oil placebo. On the other hand, STRENGTH[2] found that 4 grams daily of a pharmaceutical-grade mixture of roughly 2:1 EPA:DHA had no positive effect compared to a corn oil placebo. While these two landmark trials disagreed about the cardiovascular benefits of omega-3s, they did agree about one of its possible harms: that supplementation can increase the risk of atrial fibrillation.

Atrial fibrillation is a fluttering of the heart’s upper chambers due to electrical conduction problems. This can cause poor blood circulation, which can lead to blood clot formation. If the clot breaks off, it can clog the blood flow going to the brain, causing a stroke. Both REDUCE-IT and STRENGTH found a statistically significant increased atrial fibrillation risk.

A recent meta-analysis[3] pooled the evidence from REDUCE-IT, STRENGTH, and four other trials involving omega-3 supplementation to find out if other evidence also points to an increased risk of atrial fibrillation. As shown in Figure 1, it does: overall, omega-3 supplementation led to around a 30% increase in the risk of atrial fibrillation.

Figure 1: Result of the meta-analysis (with 95% confidence intervals and daily doses for each study)

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A close look at the figure also reveals hints of a dose-response effect: the risk of atrial fibrillation tends to increase for higher daily doses of omega-3 fatty acids. However, it’s notable that the data is consistent with doses as low as 1 daily gram still raising risk.

This meta-analysis only included large, landmark studies. However, another recent meta-analysis[4] that included more studies came to very similar conclusions concerning atrial fibrillation risk, with one caveat being that the certainty of the evidence was rated as low. That meta-analysis also found that omega-3 supplementation reduces the risk of many types of cardiovascular disease by a small amount, with EPA being more effective than the combination of EPA and DHA. However, the benefits became weaker, and sometimes statistically non-significant, when the STRENGTH trial was removed.

While there’s still some work to do to clear up the confusion concerning the possible cardiovascular benefits of omega-3 fatty acids, the evidence to date isn’t looking great in terms of omega-3 supplementation raising atrial fibrillation risk.