Op-Ed: Omega-3 Pills and Risk of Atrial Fibrillation


While preparing my presentation on omega-3s and the risk of cardiovascular disease, I reviewed in detail three recent, large randomized studies that showed no benefit of fish oil supplements on cardiovascular outcomes.

These studies confirmed several other randomized studies over the past 20 years that have shown no benefit from over-the-counter fish oil supplements. So I stuck to what I first advised on my blog in 2013: “There is no evidence that taking over-the-counter fish oil supplements or eating functional foods containing omega-3 fatty acids increases the risk of cardiovascular disease. Illnesses decreased. “

In the past, when patients were asked if there were any side effects from taking omega-3 fatty acids (OMFAs), I said, “No, but their production is devastating the marine ecosystem and you are wasting your money and driving a multi-billion dollar industry that shouldn’t be. “

However, after reviewing these recent studies in detail, I found that a health risk was identified in the treatment arms: high-dose fish oil supplements increase the risk of atrial fibrillation (AF).

This is a remarkable change from what observational studies in the field had suggested. Low blood levels of OMFAs and vitamin D have both been linked to a higher risk of atrial fibrillation. Therefore, many have advocated taking these mostly useless dietary supplements in high doses to prevent atrial fibrillation. Of course, the association does not prove causality, but generates hypotheses that should be tested according to the gold standard of medical science – the randomized controlled trial (RCT).

The VITAL Rhythm RCT, published in JAMA last month, found no effects of supplementation with OMFAs or vitamin D on the incidence of atrial fibrillation (or cancer or cardiovascular outcomes). The patients randomly assigned to OMFA supplementation received low doses of eicosapentaenoic acid and docosahexaenoic acid (460 mg EPA and 380 mg DHA daily). As the authors wrote:

“The vitamin D3 dose was designed to test the effect of high-dose supplementation on cancer and cardiovascular disease in a primary prevention population, and the EPA-DHA dose was approved by the American Heart Association for cardioprotection in individuals with high Risk recommended and was above the recommended dose from food intake for the general population. The placebo for vitamin D3 contained soybean oil and the placebo for EPA-DHA contained olive oil. “

However, two large randomized controlled trials with higher-dose formulations of OMFAs in patients with established cardiovascular disease found a significantly higher AF risk in the treatment groups.

In the REDUCE-IT study, people at high cardiovascular risk were randomly assigned 4 g / day of highly purified EPA ethyl ester (icosapentethyl, Vascepa) and showed a significantly 48% higher risk of hospitalization for AF compared to placebo (3.1 % vs = 0.004) over almost 5 years of follow-up. (Notably, the benefits of icosapent ethyl used in this study on cardiovascular outcomes have been questioned due to the use of mineral oil in the placebo arm, which I discuss at length in my OMFA talk.)

The STRENGTH study randomized patients to 4 g / day omega-3 carboxylic acid, a mixture of EPA and DHA, compared to placebo over a median follow-up period of 3.2 years and found that more atrial fibrillation developed in the active treatment arm (2nd , 2%). vs 1.3% HR 1.69, 95% CI 1.29-2.21, P <0.001). (Note that in this study using corn oil in the placebo arm, there was no evidence of any benefit from OMFAs in reducing cardiovascular outcomes.)

A third study, the OMEMI study, found no benefit in reducing cardiovascular outcomes by adding 1.8 g of OMFA (930 mg EPA and 660 mg DHA) daily versus standard corn oil placebo in patients aged 70 to 82 years of age with recent (2 to 8 weeks) acute myocardial infarction. A not significantly increased risk of atrial fibrillation was found (HR 1.84, P = 0.06).

The authors of VITAL-rhythm concluded: “Possibly the adverse effect on the risk of atrial fibrillation may be dose-dependent, and the higher doses of EPA used in these other studies could be responsible for the significant adverse effect on atrial fibrillation . “

I agree with the conclusions of an accompanying editorial by Gregory Curfman, MD:

“Taken together, the data from the 4 studies suggest, but do not prove, that there can be a dose-dependent AF risk when taking omega-3 fatty acids. At a dose of 4.0 g / d there was a statistically high significant increase in risk (almost a doubling). At a mean dose of 1.8 g / d, the increase in risk (hazard ratio 1.84) was not statistical Significance and at a standard daily dose of 840 mg / d there was no apparent increase in risk (although the data agree with an increase in risk of up to 24%) in patients who opted for omega-3 fatty acids, in particular In high doses, decide should be informed of the risk of atrial fibrillation and followed up for the possible development of this common and potentially dangerous arrhythmia. “

A 2019 report on the global OMFA over the counter supplement industry was quite enthusiastic despite the mass of scientific evidence showing no benefits for consumers. He found global sales of $ 4.1 billion and estimated $ 8.5 billion by 2025.

This thoughtless consumption (my adjective), according to the report, goes beyond pills to “functional foods” driven by a perception of health and performance enhancement:

“Omega-3 is increasingly finding use in nutritional supplements, functional foods and beverages, pharmaceuticals, baby foods, and pet foods and feeds. Dietary supplements are seen as the largest market due to fast-paced and busy lifestyles; consumers prefer to consume nutritional supplements to ensure they are theirs Get optimal levels of nutrients and omega-3 supplements are used to improve health and performance, with athletes advised to get adequate omega-3 intake for a fit and healthy body.

OMFAs are backed by a huge, powerful industry that wants to encourage the consumption of their useless products. I call it the “academic-industrial” complex that has sprung up from doctors / scientists on the fish oil industry’s payroll who in some cases own, sell, and shamelessly promote their own fish oil supplements. These doctors / scientists often publish biased analyzes of the OMFA area looking for values ​​where none are present.

Rather than promoting or benefiting from the sales of OMFAs, doctors should actively decline prescribing fish oil supplements so patients can focus on taking pills that have been shown to be safe and beneficial.

Anthony C. Pearson, MD, is a non-invasive cardiologist and professor of medicine at St. Louis University School of Medicine. He blogs about nutrition, heart tests, quackery, and other skeptical things at The Skeptical Cardiologist, which is where a version of this post first appeared.


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