Eicosapentaenoic acid in emotional well-being and brain aging: evidence boundaries, clinical heterogeneity, and a peripheral-to-central resolution-biology framework
Abstract
Emotional well-being and brain aging are increasingly understood as overlapping outcomes shaped by inflammatory, neuroimmune, vascular, and metabolic processes. This structured critical narrative review evaluates eicosapentaenoic acid (EPA) as a mechanistically distinct omega-3 fatty acid while explicitly separating EPA-specific evidence from mixed omega-3, fish-intake, and biomarker-status evidence. Particular attention is given to EPA-derived specialized pro-resolving mediators, especially E-series resolvins, and to the hypothesis that EPA may influence brain-relevant outcomes through peripheral inflammatory resolution, endothelial signaling, blood-brain barrier function, neurovascular pathways, and the peripheral immune-brain axis. The current evidence is heterogeneous and differs substantially in directness. EPA-predominant evidence is most developed for depressive symptoms, whereas brain-aging and imaging evidence is often based on fish intake, total omega-3 exposure, or red blood cell EPA+DHA status rather than isolated EPA intervention. This review therefore interprets such evidence as hypothesis-generating rather than as proof of EPA-specific effects. Differences in EPA dose, EPA:DHA ratio, formulation, placebo choice, duration, background diet, baseline omega-3 status, baseline inflammation, clinical phenotype, concomitant treatment, and endpoint selection are examined as potential sources of heterogeneity. The review proposes a testable peripheral-to-central…
Read the paper
Related studies
- Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review
- Effects of omega-3 polyunsaturated fatty acid intake in patients with chronic kidney disease: Systematic review and meta-analysis of randomized controlled trials
- Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials
- The role of omega-3 polyunsaturated fatty acid supplementation in the management of type 2 diabetes mellitus: A narrative review
- Paucity of evidence for a relationship between long-chain omega-3 fatty acid intake and chronic obstructive pulmonary disease: a systematic review
- Omega-3 fatty acid nanocarriers: Characterization and potential applications
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.