Omega-3 and cardiovascular health: what is new knowledge?
The reputation of Omega 3 as an ally of heart health has its roots in studies conducted now 50 years ago, when the reduced incidence of cardiovascular problems in the Inuit people who inhabited Greenland found its justification in a diet rich in these very fats. Since then, research on the subject has multiplied; those on the effects of Omega 3 naturally present in food have been joined by those on the benefits of taking supplements that provide higher or lower doses, and today there are even Omega 3-based drugs used in the context of cardiovascular prevention.
In clinical practice, such drugs are used in the control of blood triglyceride levels, which is also the main use that is made of Omega 3 supplements of marine origin (EPA - eicosapentaenoic acid - and DHA - docosahexaenoic acid). In the case of supplementation, this use is supported by two health claims approved by the European Food Safety Authority (EFSA):
- "DHA helps maintain normal blood triglyceride levels."
- "DHA and EPA help maintain normal blood triglyceride levels."
Alongside these, other EFSA-authorized claims support the usefulness of adequate Omega 3 intake for cardiovascular health:
- "DHA and EPA contribute to normal heart function."
- "DHA and EPA help maintain normal blood pressure."
- "ALA [alpha-linolenic acid, the precursor to EPA and DHA, ed.] helps maintain blood cholesterol concentrations in the normal range."
Effectiveness under the magnifying glass
Relatively recently, the debate on the efficacy of Omega 3-based treatments for the reduction of Major Adverse Cardiovascular Events (MACE) has been enlivened by the publication of the results of two randomized, placebo-controlled, double-blind trials conducted in large groups of individuals at high cardiovascular risk undergoing statin therapy: the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), which found that the treatment was effective; and the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial (STRENGTH), which found that, in contrast, Omega 3 intake did not produce significant effects in terms of reducing MACE.
This discrepancy in results could depend on the different formulation of the supplements used (in the case of REDUCE-IT, EPA in the form of ethyl ester; in the case of STRENGTH, EPA and DHA in the form of carboxylic acids). Nor can it be ruled out that it was the nature of the control (mineral oil in the former case, corn oil in the latter) that led to the observed differences.
And, to be fair, even the STRENGTH results do not totally argue against the hypothesis of the benefits of Omega 3 in terms of cardiovascular risk reduction: an analysis of the Asian subpopulation (corresponding to 10 percent of the sample) shows favorable effects despite the fact that the study was stopped earlier than expected. What's more, participants from the Asian and Pacific area also achieved greater risk reduction in REDUCE-IT; although the small sample size does not allow the finding to be considered statistically significant, it seems clear that individual confounding factors such as ethnicity should also be taken into account.
Other, new, perspectives
Alongside this long-running debate, reflections from new perspectives are also being ignited. In particular, in an article published in Nutrients in December 2024, a group of experts from the Catholic University of the Sacred Heart and the Agostino Gemelli University Hospital in Rome considered the effect of Omega 3 on erythrocyte membrane fluidity.
The latter is a possible cardiovascular risk factor. Any membrane malfunction may have undesirable consequences in terms of atherosclerosis; the same benefits that emerged from REDUCE-IT could depend on improvements in erythrocyte membrane fluidity due to EPA incorporation. Indeed, it seems that only this Omega 3 (and not DHA) improves this parameter, and this would also justify the differences between the REDUCE-IT and STRENGTH results.
Atrial fibrillation risk
Finally, it is worth reflecting on what has emerged about the association between taking Omega 3 supplements and the risk of atrial fibrillation. In an information note agreed with European regulatory authorities, the Italian Medicines Agency (AIFA) informed healthcare professionals of the need to discontinue treatment with Omega 3 ethyl ester-based medicines if symptoms of this condition appear.
For many, this warning has been an opportunity to foment debate about the usefulness and safety of Omega 3 products, generalizing it. However, important details emerge from reading the note:
- the increased risk is dose-dependent and is higher at dosages (4 g/day) higher than those normally used by those taking Omega 3 supplements (250 mg/day to promote heart function, 2 g/day to control triglycerides, and 3 g/day to control blood pressure);
- the increased risk concerns "patients with established cardiovascular disease or cardiovascular risk factors."
- increased risk has been found from taking Omega 3 in the form of ethyl esters; many of the high-quality supplements on the market today provide Omega 3 in other forms (triglycerides, re-esterified triglycerides or phospholipids).
Cardiovascular health allies with specific benefits
The conclusion that can be reached with the information available today is that Omega 3s are allies of cardiovascular health with pleiotrophic effects on the cardiovascular system. These effects take the form of benefits that may depend specifically on factors involving both the form in which they are taken and the individual characteristics of those taking them (such as ethnicity or resting heart rate).
The wide availability of scientific evidence, collected over decades, makes it possible and compels a non-superficial assessment of the possible cardiovascular health benefits of taking Omega 3 supplements. Their main use is undoubtedly the control of blood triglyceride levels, the benefits of which are supported by studies such as REDUCE-IT and can be maximized by taking into account the peculiarities of individual clinical cases - peculiarities that should also be considered when assessing any risks associated with treatment. Dosage optimization and selection of the most suitable formulations can further contribute to the efficacy and safety of supplementation.
Find out all the latest research on the benefits of Omega 3 for cardiovascular health by reading the Omegor Blog!
Bibliographical references
Aifa. Information Note November 8, 2023
Capece U, Gugliandolo S, Morciano C, Avolio A, Splendore A, Di Giuseppe G, Ciccarelli G, Soldovieri L, Brunetti M, Mezza T, Pontecorvi A, Giaccari A, Cinti F. Erythrocyte Membrane Fluidity and Omega-3 Fatty Acid Intake: Current Outlook and Perspectives for a Novel, Nutritionally Modifiable Cardiovascular Risk Factor. Nutrients. 2024 Dec 14;16(24):4318. doi: 10.3390/nu16244318
European Commission. Food and Feed Information Portal Database. Last viewed 14/01/25
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
Kim JY, Kong SYJ, Jung E, Cho YS. Omega-3 Fatty Acids as Potential Predictors of Sudden Cardiac Death and Cardiovascular Mortality: A Systematic Review and Meta-Analysis. J Clin Med. 2024 Dec 25;14(1):26. doi: 10.3390/jcm14010026
Zhang W, Gan D, Huo S, Chen P. Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches. Front Nutr. 2024 Dec 19;11:1490953. doi: 10.3389/fnut.2024.1490953
