Omega-3 fatty acids as modulators of anti-inflammatory gene expression
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Date
2025
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UMT, Lahore
Abstract
Chronic inflammation is a key initiator of numerous pathological states, such as autoimmune diseases, neurodegeneration, and metabolic syndromes. Over the past decade, the function of omega-3 polyunsaturated fatty acids (PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the regulation of inflammatory processes has gained prominence. Though their anti-inflammatory properties at the level of the body have been extensively characterized, research data focus on their capacity to modulate inflammation through mechanisms of gene expression. This meta-analysis examines the modulatory role of omega-3 fatty acidsi.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—on anti inflammatory gene expression in clinical and pre-clinical models. This research integrates results from 14 peer-reviewed clinical trials and animal studies that appeared between 2004 and 2024. Standardized mean differences, odds ratios, and correlation coefficients were analysed with Comprehensive Meta-Analysis (CMA) software, providing a multifaceted statistical analysis. The review adhered to PRISMA standards to identify and critically appraise 35 peer-reviewed papers. Extraction of data was on study design, dosage, duration, inflammatory markers, gene expression signatures, and molecular pathways affected. The findings showed a reproducible pattern of omega-3 fatty acids downregulating central pro-inflammatory genes, TNF-α, IL-1β, and IL-6, and upregulating anti-inflammatory mediators like IL10 and TGF-β. Mechanistically, these actions were largely regulated by NF-κB inhibition, PPARγ activation, and a boost to the AMPK/SIRT1 pathway. Epigenetic effects, such as changes in DNA methylation and histone modification, were also noted in some studies. The funnel plot showed slight heterogeneity but no publication bias. Omega-3 fatty acids have an impressive and biologically important ability to regulate anti-inflammatory gene expression. This evidence underlines their application not only as dietary supplements, but also as therapeutic agents in anti inflammatory strategies aimed at the genomic level. Additional randomized controlled studies are warranted. Future studies should also investigate epigenetic pathways to increase knowledge about omega-3s' long-lasting effects on gene regulation.