A Systematic Review of Marine Omega-3 Fatty Acids for the Reduction of Neuroinflammation in Major Depressive Disorder

Shah Nawaz; Bilal Safdar; Sana Ahmed; Arooj Fatima Awan; Muhammad Uzair Mazhar; Farkhunda Naz

doi:10.61919/db8j7j66

Authors

Shah Nawaz Senior Registrar, Balochistan Institute of Psychiatry and Behavioural Sciences, Quetta, Pakistan Author
Bilal Safdar House Officer, CMH Lahore Medical and Dental College, Lahore, Pakistan Author https://orcid.org/0009-0009-1316-3371
Sana Ahmed Lecturer in Inorganic Chemistry, Department of Chemistry, Faculty of Basic Sciences, Sardar Bahadur Khan Women’s University, Quetta, Pakistan Author
Arooj Fatima Awan MBBS, MD, King Edward Medical University, Lahore, Pakistan. Muhammad Uzair Mazhar Author https://orcid.org/0009-0004-0711-0883
Muhammad Uzair Mazhar MBBS, MD, King Edward Medical University, Lahore, Pakistan. Muhammad Uzair Mazhar Author
Farkhunda Naz Senior House Officer, Al Kharj Armed Forces Hospital, Riyadh, Saudi Arabia Author

DOI:

https://doi.org/10.61919/db8j7j66

Keywords:

Major Depressive Disorder; Omega-3 Fatty Acids; Eicosapentaenoic Acid; Docosahexaenoic Acid; Inflammatory Biomarkers; Systematic Review.

Abstract

Background: Major depressive disorder is increasingly linked with immune-inflammatory dysregulation, and elevated inflammatory biomarkers may contribute to symptom persistence and treatment resistance in selected patients. Marine omega-3 fatty acids, particularly eicosapentaenoic acid and docosahexaenoic acid, have been proposed as adjunctive modulators of inflammatory pathways, but evidence remains inconsistent. Objective: This systematic review evaluated whether marine-derived omega-3 fatty acid supplementation is associated with modulation of inflammatory biomarkers in adults with major depressive disorder. Methods: A systematic review without meta-analysis was conducted using studies identified from PubMed, Scopus, Web of Science, and the Cochrane Library. Eligible studies included randomized controlled trials and observational studies involving adults with major depressive disorder receiving EPA, DHA, or combined marine omega-3 supplementation and reporting inflammatory biomarker outcomes. Risk of bias was assessed according to study design, and findings were synthesized qualitatively because of heterogeneity in interventions, comparators, and outcome reporting. Results: Eight studies comprising 525 participants were included. Five were randomized controlled trials, two were cohort studies, and one was case-control. Omega-3 supplementation showed a consistent qualitative trend toward reductions in IL-6, CRP, and TNF-α, particularly in EPA-containing interventions. However, exact biomarker values, confidence intervals, and effect sizes were incompletely reported. Conclusion: Marine omega-3 fatty acids may modestly improve inflammatory biomarker profiles in major depressive disorder, but current evidence remains suggestive rather than definitive. Larger standardized trials are required.

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