N-3 Fatty Acids (EPA and DHA) and Cardiovascular Health - Updated Review of Mechanisms and Clinical Outcomes

PURPOSE OF REVIEW: We synthesize the latest evidence (published 2020 to 2025) on the role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in cardiovascular health, emphasizing biological mechanisms and key findings from observational studies and clinical trials related to cardiovascular disease (CVD) risk and outcomes. RECENT FINDINGS: EPA and DHA modulate lipid metabolism, inflammation, platelet and endothelial function, the gut-heart axis, ion channels and autonomic function via vagal tone, supporting cardiovascular health. While individual RCTs have produced variable results, updated cohort data and recent meta-analyses consistently link higher intake or circulating levels of EPA and DHA to reduced risk of cardiovascular events. However, evidence from RCTs indicates that high-dose supplementation may be associated with an increase in atrial fibrillation (AF) risk. Evidence supports a role for EPA and DHA in CVD prevention and treatment, with effects influenced by dose, formulation, and individual variability. Moderate intake appears safe and protective, while high dose EPA may offer added benefits in high-risk individuals but also might increase AF risk.