THE IMPACT OF OMEGA-3 SUPPLEMENTS ON THE COGNITIVE FUNCTION IN ALZHEIMER’S PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Authors

  • Aiman Abdullah Sanosi University of Jeddah, Jeddah, Saudi Arabia. Author

DOI:

https://doi.org/10.71000/3gy36k38

Keywords:

Cognitive functions, memory, Alzheimer’s disease, eicosapentaenoic acid, docosahexaenoic acid, Alzheimer Disease, Cognition Disorders, Omega-3 Fatty Acids, Randomized Controlled Trials

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to severe cognitive decline, especially in the aging population. With limited therapeutic options to reverse disease progression, nutritional interventions such as omega-3 fatty acid supplementation have been investigated for their neuroprotective potential. However, clinical findings remain inconsistent, prompting the need for a systematic synthesis of current evidence to determine the efficacy of omega-3 in improving cognitive function in AD patients.

Objective: To evaluate the impact of omega-3 supplementation on cognitive outcomes in patients with Alzheimer’s disease through a systematic review and meta-analysis.

Methods: A comprehensive literature search was conducted across PubMed, ScienceDirect, Scopus, The Cochrane Library, and Google Scholar for relevant studies published until March 2025. Eligible studies included randomized controlled trials assessing the effects of omega-3 supplements in AD patients, with outcomes measured by MMSE and ADAS-Cog. Two independent reviewers performed data extraction and quality assessment. The Cochrane RoB 2.0 tool was used to assess the methodological quality. Meta-analyses were conducted using RevMan 5.4 software under a random-effects model. Publication bias was evaluated using funnel plots. The certainty of evidence was graded using the GRADE framework.

Results: Seventeen studies met the inclusion criteria. The pooled effect size for MMSE scores was 0.10 (90% CI, -0.02 to 0.21; p=0.16; I²=0%), while for ADAS-Cog scores it was 0.24 (90% CI, -0.45 to 0.94; p=0.56; I²=0%). The pooled odds ratio for adverse events was 0.95 (90% CI, 0.80–1.14; p=0.67; I²=0%), indicating no significant safety concerns. No publication bias was identified, but several studies exhibited methodological limitations, leading to moderate certainty of evidence.

Conclusion: Omega-3 supplementation did not significantly improve cognitive function in AD patients. Its role may be better suited as part of a broader multimodal therapeutic strategy.

Author Biography

  • Aiman Abdullah Sanosi, University of Jeddah, Jeddah, Saudi Arabia.

    Assistant professor/consultant neurology, Department of Medicine, University of Jeddah, Jeddah, Saudi Arabia.

References

Breijyeh Z, Karaman R. Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Mol. 2020;25(24):5789.

Kamatham PT, Shukla R, Khatri DK, Vora LK. Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier. Age Res Rev. 2024; 101:102481.

DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegeneration. 2019;14(1):32.

Porsteinsson AP, Isaacson RS, Knox S, Sabbagh MN, Rubino I. Diagnosis of Early Alzheimer’s Disease: Clinical Practice in 2021. J Prev Alzheimers Dis. 2021;8(3):371-86.

Li X, Feng X, Sun X, Hou N, Han F, Liu Y. Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2019. Frontiers in aging neuroscience. 2022; 14:937486.

Zhang N, Chai S, Wang J. Assessing and projecting the global impacts of Alzheimer's disease. Frontiers in public health. 2024; 12:1453489.

Skaria AP. The economic and societal burden of Alzheimer disease: managed care considerations. The American journal of managed care. 2022;28(10 Suppl): S188-s96.

Koca E, Taşkapilioğlu Ö, Bakar M. Caregiver Burden in Different Stages of Alzheimer's Disease. Noro psikiyatri arsivi. 2017;54(1):82-6.

Passeri E, Elkhoury K, Morsink M, Broersen K, Linder M, Tamayol A, et al. Alzheimer's Disease: Treatment Strategies and Their Limitations. International journal of molecular sciences. 2022;23(22).

Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A. Omega-3 fatty acids for the treatment of dementia. The Cochrane database of systematic reviews. 2016;4(4): Cd009002.

Cutuli D. Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging. Current neuropharmacology. 2017;15(4):534-42.

Wen J, Satyanarayanan SK, Li A, Yan L, Zhao Z, Yuan Q, et al. Unraveling the impact of Omega-3 polyunsaturated fatty acids on blood-brain barrier (BBB) integrity and glymphatic function. Brain Behavior Immun. 2024; 115:335-55.

Swanson D, Block R, Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Advances in nutrition (Bethesda, Md). 2012;3(1):1-7.

Muldoon MF, Ryan CM, Yao JK, Conklin SM, Manuck SB. Long-chain omega-3 fatty acids and optimization of cognitive performance. Military medicine. 2014;179(11 Suppl):95-105.

Kar A, Ghosh P, Patra P, Chini DS, Nath AK, Saha JK, et al. Omega-3 fatty acids mediated Cellular signaling and its regulation in Human Health. Clin Nutri Open Sci. 2023; 52:72-86.

Wei BZ, Li L, Dong CW, Tan CC, Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. The American journal of clinical nutrition. 2023;117(6):1096-109.

Wood AHR, Chappell HF, Zulyniak MA. Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer’s disease. Eur J Nutr. 2022;61(2):589-604.

Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, et al. n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood. The American journal of clinical nutrition. 2008;87(2):449-54.

Phillips MA, Childs CE, Calder PC, Rogers PJ. No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer's Disease: A Randomised Controlled Trial. International journal of molecular sciences. 2015;16(10):24600-13.

Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. Jama. 2010;304(17):1903-11.

Shah RC, Kamphuis PJ, Leurgans S, Swinkels SH, Sadowsky CH, Bongers A, et al. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease. Alzheimer's research & therapy. 2013;5(6):59.

Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf-Wagner S, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease. Journal of Alzheimer's disease: JAD. 2014;38(1):111-20.

Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimer's & dementia: the journal of the Alzheimer's Association. 2010;6(6):456-64.

Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Archives of neurology. 2006;63(10):1402-8.

Eriksdotter M, Vedin I, Falahati F, Freund-Levi Y, Hjorth E, Faxen-Irving G, et al. Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD Study. Journal of Alzheimer's disease: JAD. 2015;48(3):805-12.

Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, et al. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease: The OmegAD Study. Journal of Alzheimer's disease: JAD. 2019;69(1):189-97.

Soininen H, Solomon A, Visser PJ, Hendrix SB, Blennow K, Kivipelto M, et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial. The Lancet Neurology. 2017;16(12):965-75.

Soininen H, Solomon A, Visser PJ, Hendrix SB, Blennow K, Kivipelto M, et al. 36-month LipiDiDiet multinutrient clinical trial in prodromal Alzheimer's disease. Alzheimer's & dementia: the journal of the Alzheimer's Association. 2020;17(1):29-40.

Scheltens P, Kamphuis PJ, Verhey FR, Olde Rikkert MG, Wurtman RJ, Wilkinson D, et al. Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial. Alzheimer's & dementia: the journal of the Alzheimer's Association. 2010;6(1):1-10. e1.

Scheltens P, Twisk JW, Blesa R, Scarpini E, von Arnim CA, Bongers A, et al. Efficacy of Souvenaid in mild Alzheimer's disease: results from a randomized, controlled trial. Journal of Alzheimer's disease: JAD. 2014;31(1):225-36.

Lin PY, Cheng C, Satyanarayanan SK, Chiu LT, Chien YC, Chuu CP, et al. Omega-3 fatty acids and blood-based biomarkers in Alzheimer's disease and mild cognitive impairment: A randomized placebo-controlled trial. Brain, behavior, and immunity. 2022; 99:289-98.

Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, et al. The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Progress in neuro-psychopharmacology & biological psychiatry. 2008;32(6):1538-44.

Fiaz M, Hanif HMB, Shaheen S. The Impact of Omega-3 Fatty Acid Supplementation on Cognitive Function in the Elderly: A Randomized Controlled Trial. Insights-J Health Rehab. 2023;1(2):41-5.

Chhetri JK, de Souto Barreto P, Cantet C, Pothier K, Cesari M, Andrieu S, et al. Effects of a 3-Year Multi-Domain Intervention with or without Omega-3 Supplementation on Cognitive Functions in Older Subjects with Increased CAIDE Dementia Scores. Journal of Alzheimer's disease: JAD. 2018;64(1):71-8.

Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, et al. Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neuroscience research. 2006;56(2):159-64.

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Published

2025-06-24

How to Cite

1.
Sanosi AA. THE IMPACT OF OMEGA-3 SUPPLEMENTS ON THE COGNITIVE FUNCTION IN ALZHEIMER’S PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS. IJHR [Internet]. 2025 Jun. 24 [cited 2025 Aug. 28];3(3 (Health & Rehabilitation):760-75. Available from: https://insightsjhr.com/index.php/home/article/view/1021