Meta-Analysis Raises Questions Around Risk of Atrial Fibrillation Associated with Omega-3 Supplements

A meta-analysis and systematic review of 7 RCTs suggests consuming more than 1 gram of marine omega-3 fatty acid supplements per day could increase a patient's risk of atrial fibrillation.

A systematic review and meta-analysis from Cedars-Sinai Medical Center is raising the alarm on the potential increase in risk of atrial fibrillation (AF) among patients consuming omega-3 supplements.

With interest and use of both pharmaceutical- and consumer-grade omega-3 supplements at an all-time high, results of the study, which indicated patients consuming more than 1 gram of omega-3 fatty acids per day had a 49% increase in risk of AF, provide valuable insight for clinicians.

“Our goal was to bring clarity, answers and actionable information to the broader medical field and to patients,” said Christine Albert, MD, MPH, a professor of Cardiology and chair of the Department of Cardiology in the Smidt Heart Institute, in a statement from Cedars-Sinai. “In this instance, the results suggest that there may not be a straightforward answer to, ‘Is fish oil good or bad for atrial fibrillation?’ but instead, the answer may depend on the dose.”

With recent clinical trials producing results suggesting use of marine omega-3 fatty acid supplements could increase risk of AF, Albert and a team of colleagues conducted the current study to provide further clarity on the potential for arrhythmias associated with these agents. To do so, investigators designed a systematic review and meta-analysis with the intent of assessing this potential for increased risk using data obtained from the MEDLINE and Embase databases as well as a meta-analysis of randomized clinical trials published in 2019.

For inclusion in the analysis, randomized clinical trials needed to report results for AF, either as pre-specified outcome, adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year. For the purpose of analysis, investigators meta-analyzed HRs for reported AF outcomes within each trial using random-effects model with Knapp-Hartung adjustment and potential dose-response relationships were assessed with a meta-regression model.

In total, 4059 records were screening for inclusion. Of these, 7 were considered eligible for inclusion, including 5 that were previously included in the 2019 meta-analysis. A total of 81,210 patients were identified from the 7 trials, including 58,939 enrolled in trials testing low dose marina omega-3 fatty acids and 22,271 examining high doses of omega-3 fatty acids. The overall study cohort had a mean age of 65 years, 39% were female, and the average weighted follow-up was 4.9 years. Of note, low dose marine omega-3 fatty acids was considered 1 gram or less per day and high dose was considered more than 1 gram per day.

Results of the meta-analysis indicated use of marine omega-3 fatty acid supplements was associated with an increased risk of atrial fibrillation (HR, 1.25 [95% CI, 1.07-1.46]; P=.013). When stratifying by dose, results indicated those receiving a high dose (HR, 1.49 [9545CI, 1.04-2.15]; P=.042) appeared to be at a greater risk of AF than those receiving a low dose (HR, 1.12 [95% CI, 1.03-1.22]; P=.024) when compared to those not receiving marine omega-3 fatty acid supplements (P for interaction <.001). In meta-regression, results indicated the risk of AF increased 11% for every 1 gram increase of omega-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; P=.001).

“For patients, the risk of developing atrial fibrillation appears to be relatively small for those taking one gram or less of fish oil per day,” said Albert. “Taking more than one gram of fish oil per day is something you should only do following your doctors’ advice.”

This study, “Effect of Long-Term Marine Omega-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis,” was published in Circulation.