Exploring the Preventive Effects of Omega-3 Polyunsaturated Fatty Acids Supplementation on Global Cognition: A Systematic Review and Meta-Analysis of Cognitively Unimpaired Older Adults
Abstract
1. Introduction
2. Materials and Methods
2.1. Literature Search and Study Selection
2.2. Data Analysis and Risk of Bias
3. Results
3.1. Characteristics of the Included Studies
3.2. Qualitative Synthesis of n-3 FA Supplementation in Global Cognition
3.3. Quantitative Synthesis of n-3 FA Supplementation in Global Cognition
3.4. Risk of Bias
4. Discussion
Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DHA | Docosahexaenoic acid |
EPA | Eicosapentaenoic acid |
n-3 FA | Omega-3 polyunsaturated fatty acids |
RCT | Randomized controlled trials |
ALA | Alpha-linolenic acid |
PUFA | Polyunsaturated fatty acids |
References
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First Author, Year | Study Design | Sample Size | Duration (Weeks) | Mean Age | Baseline Cognition Score | Intervention | Additional Supplements | Global Cognition Test | Results |
---|---|---|---|---|---|---|---|---|---|
Ogawa, 2023 [13] | Parallel | 60 (30; 30) | 12 | 71.9; 72.1 | 28.8; 29.3 * | Flaxseed Oil a | - | MMSE, MoCA | n.s. |
Hashimoto, 2022 [14] | Parallel | 31 (17; 14) | 52 | 67.0; 68.9 | 28.8;28.8 * | Perilla frutescens seed oil (PO) a | Cordifolia leaf powder (CL) | MMSE, MoCA | PO+CL |
Ichinose, 2021 [15] | Parallel | 53 (26; 27) | 52 | 69.1; 69.1 | 29.3; 29.4 * | Enriched milk b,c | - | MMSE, MoCA | DHA+EPA |
Dangour, 2010 [16] | Parallel | 866 (433; 433) | 104 | 74.7; 74.6 | 29.0; 29.0 * | Capsules b,c | - | Composite score | n.s. |
Giudici, 2022 [17] | Parallel | 362 (180; 182) | 52 | 78.4; 78.2 | 28.1; 28.1 * | Nutritional blend b,c | Multi vitamins and others || | Composite score | n.s. |
Kuszewski, 2020 [18] | Parallel | 126 (32; 31; 32) | 16 | 65.8; 66.1; 65.8 | 92.5; 93.1; 91.8 § | Fish oil b,c | Curcumin | ACE-III | n.s. |
Hashimoto, 2022 [19] | Parallel | 44 (23; 21) | 52 | 68.7; 70.2 | 28.3; 28.7 * | Perilla seed oil a | Ponkan powder | MMSE, MoCA | n.s. |
Kühn, 2022 [20] | Parallel | 57 (31; 26) | 12 | 71.8; 73.6 | 93.4; 91.1 **** | Canned pilchards (CP) and fish spread (FP) a,b,c | - | CASI | CP+FP |
Power, 2022 [21] | Parallel | 50 (28; 22) | 104 | 69.0; 69.8 | 27.5; 27.0 ¶ | Fish oil b,c | Carotenoids and vitamin E | MoCA, RBANS | n.s. |
Kang, 2022 [22] | Parallel | 2923 (1440; 1483) 515 (251, 264) | 146 and 104 | 71.9; 71.8) (67.1; 67.1) | (33.9; 33.9) ** (94.5; 95.2) ‡ | Capsules b,c | Vitamin D3 | Composite score, MMSE, TICS | n.s. |
Bischoff-Ferrari, 2020 [30] | Factorial | 2157 (1073; 1084) | 156 | 74.7; 75.2 | 28.5; 28.5 * | Marine algae b,c | Vitamin D3, physical exercise (PE) | MoCA | n.s. |
Carmichael, 2018 [29] | Crossover | 10 | 3.7 | 67.3 | 28.9; 29.4 * | Fish oil b,c | Others ð | MMSE | n.s. |
Andrieu, 2017 [23] | Parallel | 1525 (374; 381 380) | 156 | 75.4; 75.6; 75.1 | 28.2; 28.1; 28.1 * | Capsules b,c | Multidomain | Composite score | n.s. |
Yurko-Mauro, 2010 [24] | Parallel | 437 (219; 218) | 24 | 70.0; 70.0 | 28.3; 28.2 * | Capsules b,c,d | Others † | MMSE | n.s. |
Kamoun, 2024 [25] | Parallel | 20 (10; 10) | 6 | 66.9; 66.5 | 24.1; 24.7 ¶ | Walnuts (W) a | PE | MoCA | PE+W |
Chew, 2015 [31] | Factorial | 3024 (1521; 1503) | 261 | 72.7; 72.7 | 33.0; 33.0 ** | DHA/EPA | Lutein/ zeaxanthin | Composite score | n.s. |
Sala-Vila, 2020 [26] | Parallel | 708 (336; 321) | 104 | 69.4; 68.9 | 0.010; −0.013 *** | W a | - | Composite score | n.s. |
Valls-Pedret, 2015 [27] | Parallel | 207 (112; 95) | 214 | 66.7; 65.5 | 28.1; 28.4 * | Nuts a | Mediterranean diet (MD) | MMSE | MD+Nuts |
Arellanes, 2020 [28] | Parallel | 29 (15; 14) | 26 | 69.0; 68.5 | 27.0; 28.0 ¶ | Capsules b | - | MoCA | n.s. |
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Mulargia, R.; Ribaldi, F.; Mutel, S.; Sayin, O.; Khachvani, G.; Volpara, G.; Remoli, G.; Nencha, U.; Gianonni-Luza, S.; Cappa, S.; et al. Exploring the Preventive Effects of Omega-3 Polyunsaturated Fatty Acids Supplementation on Global Cognition: A Systematic Review and Meta-Analysis of Cognitively Unimpaired Older Adults. Clin. Transl. Neurosci. 2025, 9, 34. https://doi.org/10.3390/ctn9030034
Mulargia R, Ribaldi F, Mutel S, Sayin O, Khachvani G, Volpara G, Remoli G, Nencha U, Gianonni-Luza S, Cappa S, et al. Exploring the Preventive Effects of Omega-3 Polyunsaturated Fatty Acids Supplementation on Global Cognition: A Systematic Review and Meta-Analysis of Cognitively Unimpaired Older Adults. Clinical and Translational Neuroscience. 2025; 9(3):34. https://doi.org/10.3390/ctn9030034
Chicago/Turabian StyleMulargia, Roberta, Federica Ribaldi, Sophie Mutel, Ozge Sayin, Giorgi Khachvani, Gabriele Volpara, Giulia Remoli, Umberto Nencha, Stefano Gianonni-Luza, Stefano Cappa, and et al. 2025. "Exploring the Preventive Effects of Omega-3 Polyunsaturated Fatty Acids Supplementation on Global Cognition: A Systematic Review and Meta-Analysis of Cognitively Unimpaired Older Adults" Clinical and Translational Neuroscience 9, no. 3: 34. https://doi.org/10.3390/ctn9030034
APA StyleMulargia, R., Ribaldi, F., Mutel, S., Sayin, O., Khachvani, G., Volpara, G., Remoli, G., Nencha, U., Gianonni-Luza, S., Cappa, S., Frisoni, G. B., & Mendes, A. J. (2025). Exploring the Preventive Effects of Omega-3 Polyunsaturated Fatty Acids Supplementation on Global Cognition: A Systematic Review and Meta-Analysis of Cognitively Unimpaired Older Adults. Clinical and Translational Neuroscience, 9(3), 34. https://doi.org/10.3390/ctn9030034