Lower-dose omega-3 supplements were not associated with a statistically significant increase in atrial fibrillation in a large analysis of randomized trials, while a modest increase appeared among people with cardiovascular disease taking higher doses.
The findings help clarify years of conflicting research about whether omega-3 supplements may contribute to the irregular heart rhythm. However, the industry-supported analysis does not prove that lower doses carry no risk, and it should not be interpreted as a blanket endorsement of fish oil supplements.
The meta-analysis included 35 randomized clinical trials involving 114,592 participants. It was published in Circulation: Arrhythmia and Electrophysiology.
The project received support from the Global Organization for EPA and DHA Omega-3s, an industry group. The organization had no reported role in the study design, conduct, analysis, interpretation or publication decisions. Several authors also reported financial ties related to omega-3 products or testing.
Researchers examined whether the relationship between omega-3 treatment and atrial fibrillation differed according to dose and participants’ underlying cardiovascular risk.
Atrial fibrillation, often called AFib, is an irregular heart rhythm that can raise the risk of stroke and other cardiovascular complications.
Among people at high cardiovascular risk who received more than 1,500 milligrams of EPA and DHA per day, omega-3 treatment was associated with a 48% increase in the relative odds of developing atrial fibrillation.
The absolute difference was considerably smaller. Atrial fibrillation occurred in about 0.8 percentage points more participants in the higher-dose omega-3 groups than in the comparison groups.
That distinction matters because relative risk can make an effect sound larger than the actual difference experienced across a study population.
The analysis did not find a statistically significant increase among participants taking 1,500 milligrams or less per day, including those with elevated cardiovascular risk.
“Our findings show that the relationship between omega-3s and atrial fibrillation is much more nuanced than previous headlines suggested,” said William S. Harris, president of the Fatty Acid Research Institute and senior author of 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.”
The finding is reassuring, but “not statistically significant” does not mean researchers proved that lower doses have no effect. The estimates at lower doses still leaned slightly toward increased risk, but the differences could not be reliably distinguished from chance.
The analysis also cannot identify an exact point at which risk begins. Researchers divided doses at 1,500 milligrams per day to compare lower and higher intake, but that should not be viewed as a strict safety threshold.
A person taking 1,400 milligrams should not assume the dose is risk-free, just as someone taking 1,600 milligrams should not assume atrial fibrillation is likely.
The study’s broader evidence base is one of its strengths. Earlier analyses often focused on a small number of large cardiovascular trials. The new review included 35 trials, including 15 with previously unpublished atrial fibrillation data and studies in which no cases occurred.
Including unpublished findings and zero-event trials can reduce the risk that the overall picture is distorted by studies with more dramatic results.
The analysis also separated participants by cardiovascular risk. That distinction matters because someone taking a standard supplement for general wellness may differ considerably from a patient receiving prescription-strength treatment for high triglycerides or established cardiovascular disease.
Lower-dose omega-3 supplements commonly provide several hundred milligrams to around 1,500 milligrams of EPA and DHA daily. Prescription products may provide 2 to 4 grams per day.
Those categories are not interchangeable. Prescription omega-3 therapy is used for specific medical reasons and should be evaluated according to the particular product, dose and patient.
The findings also do not show that eating fish and taking concentrated omega-3 products have identical effects. The analysis examined randomized trials of omega-3 treatment, not ordinary dietary patterns.
Eating fish provides protein and other nutrients along with omega-3 fatty acids, while supplements and prescription products deliver concentrated doses in different formulations.
The press release argued that cardiovascular benefits from high-dose omega-3 treatment may outweigh the small increase in atrial fibrillation risk. That balance is not the same for every patient or product.
Some trials of high-dose purified EPA have reported fewer heart attacks, strokes and other cardiovascular events. Other omega-3 formulations have not consistently produced the same benefits.
The decision to use high-dose omega-3 therapy should therefore depend on why it was prescribed, the patient’s cardiovascular risk and any history of atrial fibrillation or other rhythm disorders.
“The decision to take or discontinue omega-3 supplements should be a discussion between a patient and his/her healthcare provider,” Harris said.
People should not stop a prescribed omega-3 medication based on the study without speaking with a clinician. Those taking over-the-counter supplements may also want to review the label carefully because products vary widely in the amount of EPA and DHA they contain.
The front of a bottle may list the total amount of fish oil rather than the actual dose of EPA and DHA. Those numbers are not always the same.
The findings offer a more detailed picture than claims that omega-3 supplements either broadly cause atrial fibrillation or are entirely free of heart rhythm concerns.
For most adults taking lower doses, the analysis did not detect a clear increase in risk. For people with cardiovascular disease receiving higher doses, it found a modest rise that should be considered alongside the potential benefits of treatment.
The project was supported in part by the Global Organization for EPA and DHA Omega-3s, which reported no role in the research design, conduct, analysis, interpretation, manuscript preparation or publication decision. Nada Abuknesha received a 2023 research award from the organization supporting participation in omega-3 clinical trial database research. James O’Keefe is chief medical officer of CardioTabs, a company that sells omega-3 products. William Harris owns stock in OmegaQuant Analytics, which provides blood fatty acid testing. Yun Qian receives support from the National Heart, Lung, and Blood Institute.