The Impact of Omega-3 Fatty Acids on DNA Methylation in Midlife Woman: Epigenetic Mechanisms of Anti-Inflammatory Effects

Introduction: Midlife women experience a convergence of hormonal decline, chronic low-grade inflammation (inflammaging), and accelerated epigenetic aging, which together increase the risk of cardiometabolic, neurodegenerative, and mood disorders. Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), particularly EPA and DHA, are considered promising non-pharmacological interventions with multi-level anti-inflammatory and epigenetic effects. Methods: A narrative literature review was conducted using PubMed (MEDLINE) and Google Scholar databases for the period 2020-2025. Priority was given to human clinical trials. Results: Omega-3 supplementation induces locus-specific DNA methylation changes in peripheral blood mononuclear cells, particularly in genes regulating lipid metabolism and immune response (24,842 differentially methylated CpG sites). These epigenetic modifications occur in conjunction with direct anti-inflammatory actions, including NF-κB pathway inhibition, NLRP3 inflammasome suppression, and the production of specialized pro-resolving mediators (SPMs). Estrogen decline during menopause disrupts DNA methyltransferase (DNMT) activity and endogenous omega-3 biosynthesis (via FADS gene downregulation), creating a "critical window" for exogenous omega-3 supplementation. Conclusion: Current research supports the integration of omega-3 fatty acids into primary care as a cost-effective preventive strategy. However, randomized controlled trials specifically targeting epigenetic outcomes in menopausal women remain limited.