A-Fib and Omega-3 Fatty Acids

A recent article has suggested that omega-3 fatty acids are associated with an increased risk of atrial fibrillation, commonly termed as A-fib (1). A-fib occurs when you develop a fast and irregular heartbeat in the two upper chambers of the heart. The development of A-fib may potentially lead to clot formation if blood pools in the heart’s upper chamber. However, a far more dangerous condition is ventricular arrhythmias. These are irregular heartbeats in the heart’s lower chambers that can lead to sudden death. As the authors of the published study point out, omega-3 fatty acids seem to reduce ventricular arrhythmias (2,3).

To determine the strength of the article’s conclusion about omega-3 fatty acids increasing A-fib, I did a deep dive into the Supplemental data of the article that nobody usually reads. But, as usual, the devil is in the details. First and foremost, there were significant differences in the molecular composition of the omega-3 fatty acid products compared in the study. For example, one study used an ethyl ester product consisting of pure EPA with no DHA. The second group of studies was composed of ethyl esters with a combination of EPA and DHA, and the third group was a free fatty acid product consisting of both EPA and DHA.

In the Supplemental section, the only two studies that demonstrated a statistical significance for increased A-fib either used only the EPA ethyl ester or the free fatty acid form of EPA and DHA. It has been shown that using the EPA-only ethyl ester product reduces the levels of DHA. (4) This is important since many important resolvins (the hormones that turn off inflammation) come from DHA. Therefore, reducing DHA levels in the blood would also reduce the potential formation of DHA-based resolvins. The free fatty acids are highly prone to oxidation compared to ethyl esters, increasing oxidative stress that can increase A-fib. Removing these two studies of the five presented makes their conclusions much weaker, if not non-existent.

Another aspect is that atrial fibrillation is only a problem if the clot forms in the heart’s upper chambers. That is unlikely to occur if one is consuming high-dose omega-3 fatty acids (5). Therefore, the possibility of developing a clot even if atrial fibrillation did develop is improbable.

So, the supportable conclusion I draw from this article is that you should only use ethyl ester products that contain both EPA and DHA for optimal cardiovascular results. Do not use free fatty acid EPA and DHA products, nor use ethyl ester products consisting of only EPA and containing no DHA.



  1. Lombardi M et al. Omega-3 fatty acids supplementation and risk of atrial fibrillation: an updated meta-analysis of randomized controlled trials. Eur Heart J Cardiovasc Pharmacother 2021 doi: 10.1093/ehjcvp/pvab034.
  2. Lombardi M et al. Impact of different doses of omega-3 fatty acids on cardiovascular outcomes: a pairwise and network meta-analysis. Curr Atheroscler Rep 2020; 22:45.
  1. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Lancet 1999;354: 447–455.
  2. Braeckman RA et al. “Icosapent ethyl: Effects on plasma and red blood cell fatty acids.” Prostagl Leuko Essen Fatty Acid 2013; 89: 195-201.
  3. Tremoli E et al. Prolonged inhibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy volunteers. Am J Clin Nutr 1995; 61: 607-13.
9 replies
  1. Harjit says:

    Hello Dr. Sears
    I am highly impressed reading your RX Zone, have already started the diet, and recently ordered the fish oil.
    I have a question in regard to the consumption of fish oil. The capsules are 1000 mg in order to make it 3 grams one needs to consume 3 capsules, however, wanted to know if these capsules can be taken at 3 different times of the day or if all 3 are needed to be taken simultaniously?
    Also, my fish oil does not mention metals-free, instead, it says “Passed international norms of heavy metals by Labdoor. So is this fine to consume?

  2. Barry Sears says:

    The OmegaRx 2 capsules have 75% EPA and DHA. Thus, you need to take four capsules of OmegaRx 2 to reach an intake of three grams of EPA and DHA per day. Since the half-life of the EPA and DHA in the blood is about two days, you can take all the capsules at one time.

    I would be more concerned about the levels of PCBs in the capsules. Removal of heavy metals is easy, removal of PCBs is extremely difficult.

  3. Alan Holland says:

    Been taking Omega Rx (3-4 gr/day) for a few years and am in good health. Went through some heart issues but things have stabilized. I take a low dose of Amiodarone along with a few other prescriptions as I had a bout of ventricle tachycardia in 2020 when I also had an ablation. Ablation resolved some PVC’s but Dr. couldn’t get VT to act up during procedure so he’s not 100% sure ablation knocked out the possibility of future VT events so I take a low dosage of Amiodarone (100 mg/day) which is known to be harsh on body (including liver) at least in higher doses. Recent bloodwork showed high liver enzymes (AST/ALT 1.5x high normal) and a liver echo showed mild hepatic steatosis (fatty liver). I tend to think it’s prescription related but my GP is adamant that the fish oil could be causing the liver enzymes to be high. The only negative thing I’ve ever seen regarding Omega 3 and the liver was in a Medical News Today article suggesting long-term use of fish oil could make you vulnerable to NAFLD but this contradicts all the articles where omega 3 is supposed to reduce fatty liver. See this link for article: https://www.medicalnewstoday.com/articles/320795

    1. What’s the latest research on Omega 3 either causing NAFLD or helping/hurting you if you have NAFLD?
    2. The strength trial suggested that patients could be more susceptible to Afib if they consumed Omega 3. Thoughts?


    • Barry Sears says:

      Only at EPA and DHA levels greater than 3.4 grams per day is any impact seen on NAFLD. The key to reducing fatty acid build-up in the liver is activating AMPK,, the master regulator of metabolism. Omega-3 fatty acids represent only one way to doing so. The other dietary interventions are the calorie restriction such as the Zone diet and the intake of polyphenols such as delphinidins. When all three dietary interventions are used in combination, significant benefits can be obtained.

  4. Emilio Pou says:

    Hello Dr sears,
    I’m happy to see you finally decided to address this topic but I find your conclusion very narrow focused and dismissive of the other 3 studies.
    I have been taking 1 tbsp of your Rx2 oil for the last 6 years. I’m a healthy man over 65 and all of the sudden I developed AFib and my cardiologist told me the oil could have been the cause and asked me to stop taking it immediately.
    There are other studies coming up frequently on this topic and by reputable cardiologist and published in JAMA , Lancet and others reputable publishers. I believe it would be more productive if you reviewed some other of these reports and not dismiss their conclusion so quickly w/o providing solid reasoning.
    undoubtedly they have found a link otherwise none of these articles would have been published.

    I understand you have a business interest in the fish oil which I believe is more of a reason for you to look into this more deeply understanding that these studies and conclusions involve many medical professionals including reputable nationally known cardiologists.
    You did not address that it was also mentioned that the doses had to be higher than 1 gram to have A fib increased risk and you recommend 2.5 grams daily and your new formula includes over 6 grams per serving size.
    I believe due to this new information your company needs to delete from their fish oil advertising the part that says its “GOOD FOR YOUR HEART HEALTH” until this discrepancy is resolved once and for all! As it stand now this claim is not really all true and may misinform others to take the oil for their heart health and even in larger doses thinking more is better.
    Please give this some serious consideration.
    Thank you. I will be looking for your comments.

    • Barry Sears says:

      Omega-3 fatty acid ethyl ester products containing 3 grams of EPA and DHA have GRAS (Generally Recognized As Safe) status by the FDA. ESFA (the European equivalent of the FDA) has higher limits (5 grams of EPA and DHA per day) as safe for consumption.

      I don’t believe I was dismissive about the studies; I was only pointing out methodical flaws in their analysis and the different types of preparations used in those studies that might explain the differences in the results.

      I refer you to a recent paper in the American Journal of Clinical Nutrition indicating increased longevity with a higher level of omega-3 fatty acids in the blood (Am J Clin Nutr 2021;114:1447–1454). Based on the results of that large multi-year study, I may have to change the statement you refer to “Good For Your Longevity.”

      • Barry Sears says:

        I forgot to add an even larger study in Nature on the reduction of all-cause mortality, cancer, CHD, and other chronic conditions (Nat Commun. 2021 Apr 22;12(1):2329. doi: 10.1038/s41467-021-22370-2.)

      • Emilio Pou says:

        Dr Sears
        thank you for your kind reply. I do not disagree with anything you say in your answer! The issue is not FDA approval or Overall mortality, or the quality of the studies. The issue is does omega 3 fatty acids in doses higher than 1 gram are conducive to causing A fib in the person taking this dose or higher.
        Based on the answer to this, if positive, you would not only have to modify the “good for your heart” claim but also your recommended dose to take or put a clear warning on your liquid fish oil bottle of the danger of AFib in doses higher than 1 gram.

  5. Barry Sears says:

    The underlying cause of NAFLD is a disrupted metabolism leading to lipid accumulation and eventual fibrosis in the liver. This strongly suggests that inhibition of AMPK activity is at the central core of the condition. However, high-dose omega-3 fatty acids (>3.4 grams per day) positively affect NAFLD. The most likely reason is that at that dose, sufficient resolvin formation can activate AMPK, which would reduce the lipotoxic fat build-up in the liver (https://doi.org/10.1002/art.40896). But you probably need a multi-factorial dietary approach for maximum AMPK activation to resolve existing fibrosis. This would include increased polyphenol consumption (delphinidins being the best) and calorie restriction as additional nutritional interventions.

    The Strength trial used free acids instead of ethyl esters of omega-3 fatty acids. Free acids are highly prone to oxidation and thus increasing inflammation. This is why nearly all human clinical studies with omega-3 fatty acids use the ethyl ester form. As I point out in my blog, the risk of a-fib is increased clot formation, yet omega-3 fatty acids reduce clot formation. Furthermore, higher blood levels of EPA and DHA are strongly associated with decreased CHD mortality and greater longevity.


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