The health benefits of fish oil, particularly omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have been studied for decades. The key discoveries regarding the beneficial effects of n-3 LC-PUFAs include anti-inflammation, lowering blood lipid levels, anti-thrombotic effects, and possibly anti-arrhythmia (Mason, Libby, and Bhatt 2020). The market size of fish oil supplements expands rapidly in recent years and is estimated to reach USD 4.5 billion by 2027 (REPORTS AND DATA 2020). In many European nations, omega-3-acid ethyl esters have been prescribed to patients to reduce blood lipid levels for at least a decade and they also obtained US FDA approval in 2004 (Bays et al. 2008). However, not all news is encouraging. The findings of anti-arrhythmia effects of fish oil are mixed, with some trials demonstrating beneficial outcomes (Fig 1) and others finding no significant effects (Mozaffarian and Wu 2011; Reiffel and McDonald 2006).
The results of REDUCE-IT clinical trial published in 2019 promised a bright future for cardiovascular risk reduction using omega-3 fatty acids (Bhatt et al. 2019). In AHA 2020 late-breaking science session: “Fish Oil, Fancy Drugs, and Frustrations in Lipid Management”, Drs. A Michael Lincoff, Are Annesoenn Kalstad and Alberico Catapano presented compelling evidence on surprising neutral effects with omega-3 carboxylic acids supplement in two clinical trials. These controversial results provide an interesting argument on whether or not to take fish oil supplements for cardiovascular health protection.
Dr. Lincoff presented recent results about the effects of high-dose omega-3 fatty acids from the STRENGTH clinical trial (Nicholls et al. 2020). Despite moderate improvements in the blood lipid levels, patients with omega-3 supplementation have significantly increased risks of atrial fibrillation. The net outcome of omega-3 fatty acid supplementation is not beneficial. One of the possible explanations for this controversial result is using corn oil as a control condition instead of mineral oil–the control treatment in REDUCE-IT trial. Mineral oil treatment caused adverse effects, and corn oil had neutral effects on patients. Dr. Kalstad shared results from another clinical trial which showed similar findings (the OMEMI clinical trial) (Kalstad et al., n.d.). The overall effects of omega-3 fatty acids were neutral with an increased risk of atrial fibrillation. To bring together what we have learned, a summary was presented by Dr. Catapano to further evaluated the STRENGTH and OMEMI clinical trials. He thoughtfully discussed the discrepancies in REDUCE-IT, STRENGTH, and OMEMI trials, and provided several explanations such as the biochemical nature of DHA and EPA, different control conditions, and treatment dosage discrepancies.
Regardless of the discrepancies between STRENGTH and OMEMI trials, one thing is common, the increased risk of atrial fibrillation. So, if you are elderly with high cardiovascular risk, please think twice and monitor your response closely when taking fish oil as a dietary supplement. The frustrating results from STRENGTH and OMEMI trials don’t necessarily negate the beneficial effects in other aspects of the physiological benefits of fish oil (Fig 1) (Mozaffarian and Wu 2011). More research studies are needed in the future to better understand the effects and mechanisms of fish oil supplementation.
REPORTS AND DATA. 2020. Omega-3 Market To Reach USD 4.50 Billion By 2027 | CAGR: 7.2% | Reports And Data. Aug 10. https://www.prnewswire.com/news-releases/omega-3-market-to-reach-usd-4-50-billion-by-2027–cagr-7-2–reports-and-data-301109147.html.
Bays, Harold E., Ann P. Tighe, Richard Sadovsky, and Michael H. Davidson. 2008. “Prescription Omega-3 Fatty Acids and Their Lipid Effects: Physiologic Mechanisms of Action and Clinical Implications.” Expert Review of Cardiovascular Therapy. https://doi.org/10.1586/14779072.6.3.391.
Bhatt, Deepak L., P. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Steven B. Ketchum, Ralph T. Doyle, et al. 2019. “Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia.” New England Journal of Medicine. https://doi.org/10.1056/nejmoa1812792.
Kalstad, Are Annesønn, Peder Langeland Myhre, Kristian Laake, Sjur Hansen Tveit, Erik Berg Schmidt, Pal Smith, Dennis Winston Trygve Nilsen, et al. n.d. “Effects of N-3 Fatty Acid Supplements in Elderly Patients after Myocardial Infarction: A Randomized Controlled Trial.” Circulation 0 (0). https://doi.org/10.1161/CIRCULATIONAHA.120.052209.
Mason, R. Preston, Peter Libby, and Deepak L. Bhatt. 2020. “Emerging Mechanisms of Cardiovascular Protection for the Omega-3 Fatty Acid Eicosapentaenoic Acid.” Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.119.313286.
Mozaffarian, Dariush, and Jason H.Y. Wu. 2011. “Omega-3 Fatty Acids and Cardiovascular Disease: Effects on Risk Factors, Molecular Pathways, and Clinical Events.” Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2011.06.063.
Nicholls, Stephen J, A Michael Lincoff, Michelle Garcia, Dianna Bash, Christie M Ballantyne, Philip J Barter, Michael H Davidson, et al. 2020. “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, November. https://doi.org/10.1001/jama.2020.22258.
Reiffel, James A., and Arline McDonald. 2006. “Antiarrhythmic Effects of Omega-3 Fatty Acids.” American Journal of Cardiology. https://doi.org/10.1016/j.amjcard.2005.12.027.
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