Fish Oil and Atrial Fibrillation

Fish oil is the bomb - Greenland Yupik and the rise of fish oil

Fish oil first became a "hot topic" when a 1980 publication showed that Yupik in Greenland had a lower incidence of cardiovascular disease.

Their paper concluded, "The rarity of ischemic heart disease in Greenland Eskimos may partly be explained by the antithrombotic effect of the long-chained polyunsaturated fatty acids, especially eicosapentaenoic acid prevalent in diets rich in marine oils." (Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland. Am J Clin Nutr. 1980 Dec;33(12):2657-61. doi: 10.1093/ajcn/33.12.2657. PMID: 7435433).

This led to more scientific bodies looking at the evidence for fish oil, and ultimately omega 3 fatty acids, and if it did reduce the incidence of cardiovascular disease. And even 22 years after the publication of that study, the American Heart Association put out a statement that fish oil was protective against cardiovascular disease. (Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19;106(21):2747-57. doi: 10.1161/01.cir.0000038493.65177.94. Erratum in: Circulation. 2003 Jan 28;107(3):512. PMID: 12438303)

The other predictable tract this led on was the inevitable marketing of fish oils in the supplement industry trying to sell fish oil capsules, from whatever source, as a "must take" to prevent the number one killer in the United States. As with most supplements, being unregulated, they would make claims that their oil was better than others - because it came from krill, or it was vegan-based, or from cod, or pick something that sounds like it can be marketed. Some would claim their fish oil was more pure omega 3 fatty acids. Radio and television spots were secured, and when it was confirmed that the "good cholesterol" or HDL was indeed raised by omega 3 fatty acids it raised their game and intensity of marketing.

Back in the world of science, testing continued and the results that came back didn't match the conclusions.

Some papers would conclude that fish oil didn't produce a significant decrease in first time cardiac events but might help prevent secondary cardiac events (Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8. doi: 10.1016/S0140-6736(07)60527-3. Erratum in: Lancet. 2007 Jul 21;370(9583):220. PMID: 17398308).

In 2004 the Cocharane database looked at 48 randomized controlled trials and concluded that taking fish oils did not reduce mortality from cardiovascular disease. It also concluded that it didn't matter where the fish oil came from, fish or plant sources, or other sources. This, as you might imagine, throws a monkey wrench into the statement by the American Heart Association that fish oils were good for you, especially coming two years later.

Marketing moves faster than medicine, so while doctors and scientists were working to find out why there were inconsistent results, the marketing of fish oils continued to expand. Given that there was no regulation in the supplement industry, they continued to market the "benefits" of their product. By 2020 the sales of over-the-counter fish oil products became to a SIX BILLION dollar industry, (https://www.grandviewresearch.com/industry-analysis/omega-3-supplement-market).

Scientists worked at looking at the different components of dietary, or essential fatty acids. Because the literature was confusing, and the American Heart Association had a bit of salmon egg on their face, they decided to get their best and brightest to review the data and come to a conclusion. They did come to some interesting conclusions: 8 percent of the US population in 2012 had consumed fish oil capsules in the previous 30 days. When they looked at the purity of the supplement they were pleased to find that "the analytical content of EPA and DHA was for the most part reflective of the labeled amounts." They found that free fatty acids were more bioavailable than the products containing ethyl esters. But the more interesting conclusions were:

(a) people who have not had a heart attack, the supplementation with fish oils will not prevent one.

(b) people who have diabetes, and thus at a higher risk of heart attacks, also had no benefit from taking fish oils

(c) people who have a high risk of cardiovascular disease could not conclude that they would have a benefit from taking fish oils

(d) they did recommend people who had had a previous heart attack might benefit from a lower dose of fish oil but their recommendation was a class 2b - meaning the evidence is weak and the usefulness or effectiveness is not known.

(e) There was no reduction in stroke risk by taking fish oil

(f) For people who had a stroke, taking fish oil capsules did not offer protection against a second stroke

(g) For people with heart failure they concluded it was "reasonable" to take fish oil but thought further randomized control trials were needed

 This should have been a nail in the coffin for the marketing of fish oil, or fish oil frenzy, but alas, it was not. If you wish to see the full report, it is available online. (Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D; American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Epidemiology and Prevention; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation. 2017 Apr 11;135(15):e867-e884. doi: 10.1161/CIR.0000000000000482. Epub 2017 Mar 13. PMID: 28289069; PMCID: PMC6903779)

But that was just conclusions based on many other reports, so the American Heart Association enrolled over 77,000 people in their own trial to quantify the effects of omega-3 fatty acid supplementation on fatal coronary heart disease (CHD), nonfatal heart attacks, stroke, major vascular events, and all-cause mortality. The study was well designed, and it showed no benefit from taking fish oil capsules. From their own words: "This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease."

Their full report is available if you wish to see it: Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R; Omega-3 Treatment Trialists’ Collaboration. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals. JAMA Cardiol. 2018 Mar 1;3(3):225-234. doi: 10.1001/jamacardio.2017.5205. PMID: 29387889; PMCID: PMC5885893.

Ultimately it was FISH and not fish oil that has the beneficial effect for cardiac diseases, and to this day you can see the recommendation to have fish in your diet twice a week, which is still in the American Heart Association guidelines.

The role of fish oil and atrial fibrillation

Even to this day, studies will disagree about the value of fish oil for cardiac health. For example, the studies looking at pharmaceutical-grade fish oil, came to different conclusions however there is one conclusion both studies came to: there is an increased risk of atrial fibrillation.

The one study was called REDUCE-IT (Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10. PMID: 30415628) which concluded that " Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo."

The other study was called STRENGTH which concluded "Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients." That paper can be seen in its full version (Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, Davidson MH, Kastelein JJP, Koenig W, McGuire DK, Mozaffarian D, Ridker PM, Ray KK, Katona BG, Himmelmann A, Loss LE, Rensfeldt M, Lundström T, Agrawal R, Menon V, Wolski K, Nissen SE. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020 Dec 8;324(22):2268-2280. doi: 10.1001/jama.2020.22258. PMID: 33190147; PMCID: PMC7667577)

So a meta-analysis of those studies combined with four other trials looking at omega 3 found that omega-3 supplementation led to a 30 percent increase in the risk of atrial fibrillation. (Lombardi M, Carbone S, Del Buono MG, Chiabrando JG, Vescovo GM, Camilli M, Montone RA, Vergallo R, Abbate A, Biondi-Zoccai G, Dixon DL, Crea F. Omega-3 fatty acids supplementation and risk of atrial fibrillation: an updated meta-analysis of randomized controlled trials. Eur Heart J Cardiovasc Pharmacother. 2021 Jul 23;7(4):e69-e70. doi: 10.1093/ehjcvp/pvab008. PMID: 33910233; PMCID: PMC8302253)

It is a dose-response curve, but even doses as low as 1 gram per day still increased risk of this.

The answer is never over in science because other studies show that the evidence is low, but that there might be positive outcomes from supplementation. (Khan SU, Lone AN, Khan MS, Virani SS, Blumenthal RS, Nasir K, Miller M, Michos ED, Ballantyne CM, Boden WE, Bhatt DL. Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis. EClinicalMedicine. 2021 Jul 8;38:100997. doi: 10.1016/j.eclinm.2021.100997. PMID: 34505026; PMCID: PMC8413259)

Overall?

For those who look at the science of literature, the risk of atrial fibrillation brings to the level of harm for omega-3 supplementation, but not for eating it in food. Meaning, food doesn't cause this as an issue but clearly, the supplements do. Further, it does not matter where the supplements come from.

What food sources are there for omega-3?

Mackerel is a small fatty fish, typically 100 grams (or 3.5 ounces) contains 4100 mg of omega 3 fatty acid per serving. Mackerel also has 200 % of the daily B12 requirement and 100 percent of the selenium requirement.

Salmon is perhaps my favorite. Salmon has 4123 mg per 100 grams or 3.5 ounces. Salmon will lower the risk of heart disease, as well as provide a great source of vitamin D, B, and selenium.

Herring has 946 grams per serving (100 grams or 3.5 ounces) and has 100% of your vitamin D requirement per day.

Those allergic to seafood and to crustaceans often can take mollusks (although please check with your allergists first). But oysters have 370 mg in 6 raw oysters per 100 grams or 3.5 ounces.

Sardines are also helpful with 2,200 in 100 grams or 3.5 ounces. And Anchovies have 351 mg per 100 grams (so that Cesar salad made in the original manner is going to be good for you.

For those that want a non-fish substitute Chia seeds have 5060 per ounce (28 grams) or 2 tablespoons. So 1 tablespoon, which is my typical amount in overnight oats, has 2500 mg.

Flax seeds are also good having 2350 mg per tablespoon in whole seeds.

Walnuts, 2570 mg of omega-3 per 7 walnuts or ounce.

Even soybeans, which are a healthy legume, contain 670 mg in 1/2 cup or 1443 per 100 grams. Edamame is more than a snack!

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