“The Role Of Omega-3 Fatty Acids In Cardiovascular Health: A Review.”

Abstract

This review aims to provide a comprehensive evaluation of the role of omega-3, omega-6, and omega-9 fatty acids in the prevention and management of cardiovascular diseases (CVDs). Specifically, the objective is to analyze the underlying mechanisms of action and critically evaluate the available clinical evidence, addressing current controversies regarding efficacy and safety, particularly concerning different formulations and dosages.

Materials and methods: This review is based on an extensive analysis of current scientific literature, including epidemiological studies and randomized controlled trials (RCTs). Key large-scale contemporary trials such as REDUCE-IT, STRENGTH, OMEMI, VITAL, and ASCEND were critically analyzed to assess the impact of marine omega-3 polyunsaturated fatty acids (PUFAs), particularly Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA), on cardiovascular outcomes. The scope also encompassed the chemical characterization, natural sources, and metabolic pathways of these lipids.

Results: Omega-3 PUFAs exert multifaceted effects, most consistently reducing serum triglyceride levels through inhibition of hepatic lipogenesis6. EPA and DHA possess potent anti-inflammatory properties, acting as precursors to specialized pro-resolving mediators (SPMs), and exhibit antithrombotic and hypotensive effects. Clinical efficacy is highly dose- and formulation-dependent8. High-dose purified EPA (4 g/day) demonstrated significant risk reduction in major cardiovascular events in statin-treated high-risk patients (secondary prevention). Conversely, mixed EPA/DHA formulations often yielded inconsistent results. A significant safety signal emerged, linking high-dose omega-3 supplementation (doses >1 g/day) to a dose-dependent increased risk of incident atrial fibrillation (AF).

Conclusion: Omega-3 fatty acids remain a cornerstone in managing severe hypertriglyceridemia and reducing residual CVD risk in specific high-risk patients with atherogenic dyslipidemia. For the general population, a "food-first" approach is recommended13. High-dose purified EPA represents a distinct and effective pharmacological intervention in secondary prevention, acting beyond simple lipid lowering through plaque stabilization and anti-inflammatory pathways14. Further research is required to fully elucidate the pathophysiological mechanism linking high-dose omega-3s to AF and to establish optimal dosing strategies based on the "Omega-3 Index".