Reduction in cardiovascular risk was greatest for eicosapentaenoic acid (EPA) alone rather than combination of EPA and another omega-3 fatty acid.
For decades, there has been great interest in whether omega-3 fatty acids can lower rates of cardiovascular events. In 2018, results from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) were published in the New England Journal of Medicine and showed that a high dose of a purified ethyl ester of eicosapentaenoic acid (EPA) in patients at elevated cardiac risk significantly reduced cardiovascular events. Results from the trial led to the US Food and Drug Administration, Health Canada, and European Medicines Agency approval of the prescription drug icosapent ethyl for reducing cardiovascular risk in patients with elevated triglycerides, as well as updates to worldwide guidelines. But prior and subsequent studies of omega-3 fatty acid supplements that combine EPA and docosahexaenoic acid (DHA) have had mixed results.
EPA Outperforms Combination Supplements
Investigators from Brigham and Women’s Hospital and elsewhere conducted a systematic review and meta-analysis of 38 randomized controlled trials of omega-3 fatty acids. Overall, they found that omega-3 fatty acids improved cardiovascular outcomes. Results, now published in eClinical Medicine, showed a significantly greater reduction in cardiovascular risk in studies of EPA alone rather than EPA+DHA supplements.
“REDUCE-IT has ushered in a new era in cardiovascular prevention,” said senior author Deepak L. Bhatt, MD, MPH, the executive director of Interventional Cardiovascular Programs at the Brigham and lead investigator of the REDUCE-IT trial. “REDUCE-IT was the largest and most rigorous contemporary trial of EPA, but there have been other ones as well. Now, we can see that the totality of evidence supports a robust and consistent benefit of EPA.”
Bhatt and colleagues performed a meta-analysis of 38 randomized clinical trials of omega-3 fatty acids, including trials of EPA monotherapy and EPA+DHA therapy. In total, these trials included more than 149,000 participants. They evaluated key cardiovascular outcomes, including cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation. Overall, omega-3 fatty acids reduced cardiovascular mortality and improved cardiovascular outcomes. The trials of EPA showed higher relative reductions in cardiovascular outcomes compared to those of EPA+DHA.
Biological Differences Between EPA and DHA
The researchers note that there are crucial biological differences between EPA and DHA — while both are considered omega-3 fatty acids, they have different chemical properties that influence their stability and strength of the effect that they can have on cholesterol molecules and cell membranes. No trials to date have studied the effects of DHA alone on cardiovascular outcomes.
“This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically prescription EPA,” said Bhatt. “It should encourage investigators to explore further the cardiovascular effects of EPA across different clinical settings.”
Reference: “Effect of Omega-3 Fatty Acids on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis” by Safi U. Khan, Ahmad N. Lone, Muhammad Shahzeb Khan, Salim S. Virani, Roger S. Blumenthal, Khurram Nasir, Michael Miller, Erin D. Michos, Christie M. Ballantyne, William E. Boden and Deepak L. Bhatt, 8 July 2021, eClinical Medicine.
DOI: 10.1016/j.eclinm.2021.100997
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for the work Bhatt did as the trial chair and as the international principal investigator. The present analysis was unfunded.
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5 Comments
Why would the researchers celebrate prescription EPA and downplay EPA supplements? I take a high-quality, pure fish oil and blood tests confirmed that my serum EPA rose significantly. So, why exactly do I need a prescription and pay a pharmaceutical company?
I agree
Christopher, only a “drug” can treat disease according to the FDA. It’s ridiculous. What is rickets? Treated with vitamin C. It’s greed. But sushi dinner places will sell anything and tell you it contains what he “say” it contains but it may not be the correct amount and could be contaminated with other things, even dangerous things, so I see some purpos in making sure something is regulated as well. There is greed by drug companies and also greed by supplement companies that funny really know what is truly in their products because they don’t have them tested etc.
Since the FDA does not regulate supplements the argument against them is the process of extracting pure EPA is costly and now regulated by the FDA for only one brand name: Vascepa, which happens to be manufactured by the entity that funded this study: Amarin. Therefore the only approved FDA prescibable ‘med’ will cost on the average $1000-1400 per month, since hardly any insurance covers it and the generic version cannot be acquired. Go figure!
Omega-3 is a successful medicine to cardiovascular diseases.Regular neutrine is to be added.The causal root of the disease must be prevented.Other riskful diseases are to be cured to regain health.