Omega-3 Fatty Acids: From Natural Sources to Clinical Applications: An Integrative Review

Omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are essential polyunsaturated fats known for their vital roles in cardiovascular, neurological, and inflammatory health. Growing awareness of their therapeutic benefits, coupled with sustainability concerns, has intensified research into their natural sources, biosynthesis, pharmacokinetics, and clinical applications. This review provides an integrative synthesis of recent advances in omega-3 fatty acid research, encompassing their sources, bioavailability, sustainability, mechanisms of action, and clinical relevance. Plant-based oils, marine fish, krill, and microalgae remain key natural sources, while innovations such as algal oils and genetically engineered crops present sustainable alternatives. The human conversion of ALA to EPA and DHA is inherently limited due to Δ6-desaturase and elongase enzyme constraints, with efficiency affected by genetic, hormonal, and dietary factors. Bioavailability is influenced by molecular form, with triglyceride, ethyl ester, and phospholipid structures displaying varying absorption and metabolic profiles. Mechanistically, omega-3 fatty acids regulate inflammation, maintain neuronal membrane integrity, and improve vascular function, with emerging evidence suggesting potential anti-cancer effects. Collectively, these insights underscore the significant preventive and therapeutic potential of omega-3 fatty acids and highlight the need for optimizing bioavailability, advancing sustainable production, and personalizing clinical applications to support future nutrition and healthcare strategies. Keywords: Omega-3 fatty acids, Eicosapentaenoic acid, Docosahexaenoic acid , Bioavailability, Sustainable nutrient sources, Clinical nutrition