Omega-3 and Cardiovascular Health: What's New?
The reputation of Omega-3s as heart health allies dates back to studies conducted 50 years ago, when the low incidence of cardiovascular problems in Greenland's Inuit populations was attributed to their Omega-3-rich diet. Since then, research on the topic has multiplied; studies on naturally occurring Omega-3s in foods have been joined by those on supplements providing varying doses, and today there are even Omega-3-based drugs used in cardiovascular prevention.
In clinical practice, these drugs are used to control blood triglyceride levels, which is also the primary use of marine-derived Omega-3 supplements (EPA - eicosapentaenoic acid - and DHA - docosahexaenoic acid). For supplementation, this use is supported by two health claims approved by the European Food Safety Authority (EFSA):
- "DHA contributes to maintaining normal blood triglyceride levels";
- "DHA and EPA contribute to maintaining normal blood triglyceride levels".
Alongside these, other EFSA-approved claims support Omega-3s' cardiovascular benefits:
- "DHA and EPA contribute to normal cardiac function";
- "DHA and EPA contribute to maintaining normal blood pressure";
- "ALA [alpha-linolenic acid, the precursor of EPA and DHA] contributes to maintaining normal blood cholesterol concentrations".
Effectiveness Under the Microscope
Recently, debate about Omega-3s' effectiveness in reducing major adverse cardiovascular events (MACE) was fueled by two randomized, placebo-controlled, double-blind studies involving high cardiovascular risk patients on statin therapy: REDUCE-IT (showing treatment efficacy) and STRENGTH (finding no significant MACE reduction).
This discrepancy may stem from different supplement formulations (EPA ethyl esters in REDUCE-IT versus EPA/DHA carboxylic acids in STRENGTH) or different control substances (mineral oil versus corn oil).
Even STRENGTH's results aren't entirely negative: Asian subgroup analysis (10% of participants) showed favorable effects despite early study termination. Moreover, Asian/Pacific participants showed greater risk reduction in REDUCE-IT too. While small sample sizes prevent statistical significance, these findings highlight the need to consider confounding factors like ethnicity.
New Perspectives
Alongside this longstanding debate, new perspectives are emerging. A December 2024 Nutrients article by researchers from Rome's Catholic University and Gemelli Hospital examined Omega-3s' effects on erythrocyte membrane fluidity.
This fluidity represents a potential cardiovascular risk factor. Membrane dysfunction may promote atherosclerosis; REDUCE-IT's benefits might stem from EPA improving erythrocyte membrane fluidity. EPA (not DHA) appears uniquely capable of enhancing this parameter, potentially explaining REDUCE-IT and STRENGTH's differing results.
Atrial Fibrillation Risk
We must also consider Omega-3 supplements' association with atrial fibrillation risk. Italy's AIFA regulatory agency advised healthcare professionals to discontinue Omega-3 ethyl ester medications if fibrillation symptoms appear.
While this warning fueled debate about Omega-3 safety, key details emerge:
- Risk increase is dose-dependent, occurring mainly at 4g/day doses (far exceeding typical supplement doses of 250mg/day for heart health, 2g/day for triglycerides, or 3g/day for blood pressure);
- Risk concerns "patients with established cardiovascular disease or cardiovascular risk factors";
- Risk was observed specifically with ethyl ester formulations; many high-quality supplements use other forms (triglycerides, re-esterified triglycerides, or phospholipids).
Cardiovascular Health Allies with Specific Benefits
Current evidence confirms Omega-3s as cardiovascular allies with pleiotropic effects. These effects produce benefits that may depend on formulation type and individual characteristics (like ethnicity or resting heart rate).
Decades of research demand careful evaluation of Omega-3 supplements' cardiovascular benefits. Their primary use remains triglyceride control (supported by studies like REDUCE-IT), with effects maximized by considering individual clinical characteristics - which also inform risk assessment. Optimizing dosage and formulation selection can further enhance supplementation's efficacy and safety.
Discover the latest research on Omega-3s' cardiovascular benefits on Omegor's Blog!
References
AIFA. Informational 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 accessed 01/14/25
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
