Omega-3 Polyunsaturated Fatty Acid Formulations in Cardiovascular Prevention: Balancing Clinical Efficacy, Safety,...

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are critical modulators of cardiovascular physiology, acting through anti-inflammatory signaling, membrane remodeling, and transcriptional regulation. Despite strong biological plausibility, clinical evidence remains heterogeneous. This narrative review evaluates the complexities of ω-3 supplementation, moving beyond standardized dosing to discuss the emerging role of biomarker-based assessments. While traditional low-dose mixed formulations often failed to show significant benefits, high-dose purified EPA (icosapent ethyl, 4 g/day) has demonstrated a substantial reduction in residual cardiovascular risk in specific populations. However, this clinical success is accompanied by a modest but consistent increase in atrial fibrillation risk at pharmacological doses, suggesting a need for better risk stratification. We highlight that therapeutic efficacy is closely tied to bioavailability-driven by chemical form and dietary context. In this setting, objective metrics such as the ω-3 Index or EPA/arachidonic acid (AA) ratio are discussed as validated biomarkers of ω-3 status that, although not yet incorporated into clinical guidelines as routine treatment targets, may help account for inter-individual variability. Furthermore, we address the environmental burden of marine-derived oils, considering microalgae-based alternatives as sustainable solutions. Ultimately, this review advocates for a more nuanced approach that integrates clinical evidence, the potential of biomarker monitoring, and global environmental responsibility.