While preparing my presentation on omega-3s and the risk of cardiovascular disease, I reviewed three recent large randomized studies that showed no benefit of fish oil supplements for cardiovascular outcomes.
These studies confirmed several other randomized studies over the past 20 years that showed no benefit from over-the-counter fish oil supplements. So I stuck to what I first recommended on my blog in 2013: “There is no evidence that taking over-the-counter fish oil supplements or eating functional foods that are omega-3 fatty acid supplements pose a risk for cardiovascular diseases decreased. “
In the past, if patients have asked if there are any side effects from taking omega-3 fatty acids (OMFAs) I would say, “No, but their production has hit the marine ecosystem and you are wasting your money and driving a multi-billion 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 the observational studies in this area. Low levels of OMFA in the blood and vitamin D have both been linked to a higher risk of atrial fibrillation. Hence, many have advocated taking these mostly useless 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 medicine – the randomized controlled trial (RCT).
The VITAL Rhythm RCT, published last month in JAMA, found no effect of supplementation with OMFAs or vitamin D on the incidence of atrial fibrillation (or cancer or cardiovascular outcomes). The patients randomized 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 CVD in a primary prevention population. The EPA-DHA dose was recommended by the American Heart Association for cardioprotection in high-risk individuals and was higher than the dose recommended by the American Heart Association for cardioprotection in high-risk individuals 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 OMFA formulations in patients with established cardiovascular disease found a significantly higher risk of AF in the treatment groups.
The REDUCE-IT study randomized people at high cardiovascular risk to 4 g / d highly purified EPA ethyl ester (icosapent ethyl, Vascepa) and showed a significantly 48% higher risk of hospitalization for AF compared to placebo (3.1% compared to 2 , 1%; P. = 0.004) for almost 5 years of follow-up. (Notably, the benefits of icosapent ethyl used in this study for CV results have been questioned due to the use of mineral oil in the placebo arm, which I will discuss in detail in my OMFA talk.)
In the STRENGTH study, patients were randomized to 4 g / d omega-3 carboxylic acid, a mixture of EPA and DHA, compared to placebo over a median of 3.2 years of follow-up and were found to be active Treatment arm developed more AF (2.2%) vs 1.3%; HR 1.69, 95% CI 1.29-2.21, P <0.001). (Notably, in this study that used corn oil in the placebo arm, there was no evidence of any benefit from OMFAs in reducing CV scores.)
A third study, the OMEMI study, found no benefit in reducing CV results by adding 1.8 g of OMFA (930 mg EPA and 660 mg DHA) daily versus corn oil placebo as the standard of care in elderly patients from 70 to 82 years of age with recent (2-8 weeks) acute myocardial infarction. A non-significantly increased risk of AF incidents was found (HR 1.84, P = 0.06).
The VITAL Rhythm authors concluded, “Possibly the adverse effect on AF risk is dose-dependent, and the higher EPA dosages used in these other studies could be responsible for the significant adverse effect on AF.”
I agree with the conclusions of an accompanying editorial by Gregory Curfman, MD:
“Taken together, the data from the 4 studies indicate, but do not prove, that there is a dose-dependent AF risk with the ingestion of omega-3 fatty acids. A dose of 4.0 g / d was a statistically high value before a significant one Increase in risk (nearly doubling): at an intermediate dose of 1.8 g / d, the increase in risk (hazard ratio, 1.84) did not reach statistical significance, and at a standard daily dose of 840 mg / d it was None apparent increase in risk (although data were consistent with an increase in risk of up to 24%). Patients who choose to take omega-3s, especially in high doses, should be informed about the risk of AF and be 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 vast amount of scientific evidence that showed no consumer benefit. He had worldwide sales of $ 4.1 billion and estimated at $ 8.5 billion by 2025.
This senseless consumption (my adjective), according to the report, goes beyond pills into “functional foods”, driven by the 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 the fast-paced and busy lifestyle. Consumers prefer to consume nutritional supplements to ensure they are at their optimal level Preserved percentage of nutrients and omega-3 supplements are used to improve health and performance, with athletes advised to get enough omega-3 fatty acids for a healthy and healthy body. “
OMFAs are backed by a huge, powerful industry that seeks to encourage the consumption of their useless products. I call it the “academic-industrial” complex that comes from doctors / scientists who are on the payroll of the fish oil industry and in some cases own, sell and shamelessly promote their own fish oil supplements. These doctors / scientists often publish biased analyzes of the OMFA field looking for values where there are none.
Instead of promoting or benefiting from the sales of OMFAs, doctors should actively prescribe 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, quacks, and other things that deserve skepticism at The Skeptical Cardiologist, which first appeared in a version of this post.