Data from four randomized clinical trials suggest that there is a dose-related risk of atrial fibrillation (AF) with omega-3 fatty acid intake.

The most recent study to evaluate the association, the VITAL-RHYTHM Study, showed that the use of a low dose of omega-3 fatty acids or a vitamin D supplement did not significantly affect the risk of developing incident-related atrial fibrillation.

The study, first reported at last year’s American Heart Association meeting, was published online today in the Journal of the American Medical Association.

However, along with three other randomized clinical trials, these results suggest a possible dose-dependent effect of omega-3 fatty acids on AF risk, according to an accompanying “Editor’s Note”.

In the message from JAMA’s assistant editor, Dr. Gregory Curfman, it is noted that four randomized clinical trials have provided data on the risk of AF with omega-3 fatty acid intake over the past two years.

In the studies STRENGTH and REDUCE-IT, in which both examined high doses (4 g / day) of omega-3 fatty acids in patients with (or at high risk of) heart disease, there was a statistically highly significant increase in the risk for AF in the omega-3 groups versus control in both studies.

In the OMEMI study in elderly patients with a recent myocardial infarction, a mean dose of (1.8 g / day) omega-3 fatty acids also showed an increase in AF risk (hazard ratio 1.84), but it was not significant. And now the VITAL-RHYTHM study shows no significant effect of a low dose (840 mg / day) of omega-3 fatty acids on the risk of developing AF in a primary prevention population.

“Patients who choose to consume omega-3s, especially in high doses, should be informed about their risk of AF and evaluated for the possible development of this common and potentially dangerous arrhythmia,” concludes Curfman.

The authors of the VITAL-RHYTHM study, led by Dr. Christine M. Albert, MPH, Cedars-Sinai Medical Center, Los Angeles, California, explain that the study was conducted after observational studies showed that people with low blood omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA ) and vitamin D3 are at higher risk for AF, but the data on dietary or supplemental intake of these nutrients on AF risk were mixed.

“To the best of our knowledge, this study is the first randomized, placebo-controlled study to prospectively test the effects of an intervention on the AF incident. It is the only study to find sufficient alternative upstream preventive agents for AF in a sufficiently large population long period of time to test the plausible benefits and risks, “they write.

The VITAL-RHYTHM study was an additional study that was embedded in the vitamin D and omega-3 study (VITAL). A 2 x 2 factor design was used to assess daily supplementation with 2000 IU vitamin D3 and / or 840 mg marine omega. 3 fatty acids (460 mg EPA and 380 mg DHA) for the primary prevention of cardiovascular disease and cancer in 25,871 men and women aged 50 and over in the USA.

The results showed that over a median of 5.3 years of treatment and follow-up, the primary endpoint of incident-related atrial fibrillation occurred in 3.6% of the study population. For the omega-3 portion of the study, 3.7% of patients taking EPA / DHA experienced AF events versus 3.4% of the placebo group, giving a nonsignificant hazard ratio of 1.09 (P. = 0.19).

When comparing vitamin D3 and placebo, the results were very similar, with AF events occurring in 3.7% versus 3.4% of participants, giving a hazard ratio of 1.09, which again was not significant (P = 0.19). There was no evidence of an interaction between the two study agents.

“Overall, these results do not support the use of additional EPA-DHA or vitamin D3 for the primary prevention of atrial fibrillation and provide assurance of the lack of a major risk for AF incidence associated with these commonly used supplements at these doses,” conclude the authors .

The REDUCE-IT and STRENGTH studies found that a significant increase in atrial fibrillation was observed at much higher doses of omega-3 fatty acids. The EPA used in these other studies could be responsible for the significant adverse effect on AF. “

The researchers say this is the only randomized study to their knowledge that assesses the effect of vitamin D3 supplementation on AF risk. The results suggest a zero effect. They add that subgroup analyzes in patients with vitamin D levels considered deficient (<20 ng / ml) suggested no benefit; However, the ability to determine a benefit in this much smaller subset of the population has been limited.

They point out that while there were no significant differences in incident AF for omega-3 fatty acids or vitamin D across the study population, an increased risk of incident AF associated with randomized treatment was observed in selected subgroups .

For omega-3 fatty acids, the risk of AF was slightly increased in taller people, and for vitamin D3, an increase in the risk of AF was seen in younger people and participants who drank less alcohol.

“Although the hazard rates and interaction tests were significant, the P-values ‚Äč‚Äčassociated with these subgroup analyzes were not adjusted for multiple comparisons. Therefore, these results should be interpreted with caution and viewed as hypothesizing,” they warn.

The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Albert reported receiving grants from St. Jude Medical, Abbott, and Roche Diagnostics. Curfman does not report any relevant information.

JAMA. Published online March 16, 2021. Executive summary, editor’s note

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