Omega-3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials
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Abstract
A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of anti-inflammatory mediators, cell membrane fluidity, intracellular signaling, and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represents a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.
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The protective effects exerted by n-3 LCPUFAs are likely to be modulated by patient-related factors, some of which may have a significant genetic component and may be unmodifiable, and may be unpredictable via routine clinical and biochemical evaluation.
“Avallone and colleagues [90] stated that the protective effects exerted by n-3 LCPUFAs are likely to be modulated by patient-related factors, some of which may have a significant genetic component and may, therefore, be unmodifiable, and furthermore, may be unpredictable via routine clinical and biochemical evaluation.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [90]
Inconsistent results are not unusual in clinical research between observational and randomized studies, particularly when investigating treatments with dietary supplements or integrators.
“The authors highlighted that inconsistent results are not unusual in clinical research between observational and randomized studies, particularly when investigating treatments with dietary supplements or integrators.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [90]
n-3 LCPUFA supplementation may be a valuable and biologically plausible tool in the management of neurodegenerative diseases.
“Therefore, Avallone and colleagues [90] concluded n-3 LCPUFA supplementation may indeed be a valuable and biologically plausible tool in the management of neurodegenerative diseases.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [90]
A recent systematic review reported an inconsistency between evidence from prospective observational studies and randomized trials on the effects of n-3 LCPUFA supplementation on cognitive function in patients with Parkinson's disease or Alzheimer's disease.
“A recent systematic review on the effects of n-3 LCPUFA supplementation on cognitive function in patients with PD or AD also reported an inconsistency between the evidence from prospective observational studies and randomized trials, and the authors suggested some potential reasons for the inconsistency [90].”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [90]
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Obesity and aging: Molecular mechanisms and therapeutic approaches
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Patel, A., Desai, S. S., Mane, V. K., Enman, J., Rova, U., Christakopoulos, P., & Μάτσακας, Λ. (2022) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2022.01.006 · Cited by 152 · see citing works
Van Dael, P. (2021) · Nutrition Research and Practice · doi:10.4162/nrp.2021.15.2.137 · Cited by 138 · see citing works
DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases
Kousparou, C. A., Fyrilla, M., Stephanou, A., & Patrikios, I. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310717 · Cited by 123 · see citing works
Ferreira, I., Falcato, F., Bandarra, N., & Rauter, A. P. (2022) · Molecules · doi:10.3390/molecules27051677 · Cited by 120 · see citing works
ESPEN guideline on nutrition and hydration in dementia – Update 2024
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Microalgal biorefineries: a systematic review of technological trade-offs and innovation pathways
Geng, Y., Shaukat, A., Azhar, W., Raza, Q.-U.-A., Tahir, A., Abideen, M. Z. U., Zia, M. A. B., Bashir, M. A., & Rehim, A. (2025) · Biotechnology for Biofuels and Bioproducts · doi:10.1186/s13068-025-02694-7 · Cited by 96 · see citing works
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Neurodegenerative Pathways in Alzheimer’s Disease: A Review
Ramachandran, A. K., Das, S., Joseph, A., Shenoy, G. G., Alex, A. T., & Mudgal, J. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200807130637 · Cited by 94 · see citing works
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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside
Ma, Y., Li, X., Yu, J., & Wang, Y. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00404-1 · Cited by 87 · see citing works
Chiu, H., Venkatakrishnan, K., & Wang, C. (2020) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2020.03.008 · Cited by 86 · see citing works
Early life adversity as a risk factor for cognitive impairment and Alzheimer’s disease
Huang, Z., Jordan, J. D., & Zhang, Q. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00355-z · Cited by 92 · see citing works
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Kumar, S., Goyal, L., & Singh, S. (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666211006142100 · Cited by 78 · see citing works
Toledo, A. P., Reyna‐Jeldes, M., Ortega, L., Coddou, C., & Yévenes, G. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105390 · Cited by 71 · see citing works
Khalid, W., Gill, P., Arshad, M. S., Ali, A., Ranjha, M. M. A. N., Mukhtar, S., Afzal, F., & Maqbool, Z. (2022) · International Journal of Food Properties · doi:10.1080/10942912.2022.2070642 · Cited by 70 · see citing works
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Modulatory role of dietary polyunsaturated fatty acids in Nrf2-mediated redox homeostasis
Abrescia, P., Treppiccione, L., Rossi, M., & Bergamo, P. (2020) · Progress in Lipid Research · doi:10.1016/j.plipres.2020.101066 · Cited by 64 · see citing works
Hachem, M., & Nacir, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073969 · Cited by 62 · see citing works
Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration
Sarparast, M., Dattmore, D. A., Alan, J. K., & Lee, K. S. S. (2020) · Nutrients · doi:10.3390/nu12113523 · Cited by 59 · see citing works
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Cell Death via Lipid Peroxidation and Protein Aggregation Diseases
Iuchi, K., Takai, T., & Hisatomi, H. (2021) · Biology · doi:10.3390/biology10050399 · Cited by 55 · see citing works
Dietary Antioxidants in Age-Related Macular Degeneration and Glaucoma
Dziedziak, J., Kasarełło, K., & Cudnoch‐Jędrzejewska, A. (2021) · Antioxidants · doi:10.3390/antiox10111743 · Cited by 54 · see citing works
The Role of Omega-3 and Omega-6 Polyunsaturated Fatty Acid Supplementation in Human Health
Gutierres, D., Pacheco, R., & Reis, C. P. (2025) · Foods · doi:10.3390/foods14193299 · Cited by 54 · see citing works
ω-6 and ω-3 Polyunsaturated Fatty Acids: Inflammation, Obesity and Foods of Animal Resources
Jeong, H. Y., Moon, Y. S., & Cho, K. K. (2024) · Food Science of Animal Resources · doi:10.5851/kosfa.2024.e65 · Cited by 53 · see citing works
McCarty, M. F., & Lerner, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103624 · Cited by 51 · see citing works
Borsini, A., Stangl, D., Jeffries, A. R., Pariante, C. M., & Thuret, S. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00908-0 · Cited by 50 · see citing works
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Ferreira, I., Gomes‐Bispo, A., Lourenço, H. M., Matos, J., Afonso, C. M., Cardoso, C. L., Castanheira, I. P., Motta, C., Prates, J. A. M., & Bandarra, N. M. (2020) · Biochimie · doi:10.1016/j.biochi.2020.09.022 · Cited by 44 · see citing works
Immunosenescence and inflammaging: Mechanisms and modulation through diet and lifestyle
Müller, L., & Benedetto, S. D. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1708280 · Cited by 46 · see citing works
Neurobiological findings underlying depressive behavior in Parkinson’s disease: A review
Mendonça, I. P., Duarte-Silva, E. P., Chaves-Filho, A. J. M., Andrade‐da‐Costa, B. L. D. S., & Peixoto, C. A. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106434 · Cited by 42 · see citing works
Microbiome-based therapies for Parkinson’s disease
Alam, M., Abbas, K., Mustafa, M., Usmani, N., & Habib, S. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1496616 · Cited by 46 · see citing works
Ceccarini, M. R., Ceccarelli, V., Codini, M., Fettucciari, K., Calvitti, M., Cataldi, S., Albi, E., Vecchini, A., & Beccari, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416176 · Cited by 40 · see citing works
Malau, I. A., Chang, J. P., Lin, Y., Chang, C., Chiu, W., & Su, K. (2024) · Cells · doi:10.3390/cells13211791 · Cited by 45 · see citing works
Beaulieu, J., Costa, G., Renaud, J., Moitié, A., Glémet, H., Sergi, D., & Martinoli, M. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02328-7 · Cited by 37 · see citing works
Marine Sources of DHA-Rich Phospholipids with Anti-Alzheimer Effect
Ferreira, I., Rauter, A. P., & Bandarra, N. M. (2022) · Marine Drugs · doi:10.3390/md20110662 · Cited by 36 · see citing works
Omega‐3 polyunsaturated fatty acids and Parkinson's disease: A systematic review of animal studies
Alves, B. D. S., Schimith, L. E., da Cunha, A. B., Dora, C. L., & Hort, M. A. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16154 · Cited by 33 · see citing works
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Glucosinolates and Omega-3 Fatty Acids from Mustard Seeds: Phytochemistry and Pharmacology
Das, G., Tantengco, O. A. G., Tundis, R., Robles, J. A. H., Loizzo, M. R., Shin, H. S., & Patra, J. K. (2022) · Plants · doi:10.3390/plants11172290 · Cited by 31 · see citing works
A review of studies on gut microbiota and levodopa metabolism
Zhong, Z., Ye, M., & Yan, F. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1046910 · Cited by 31 · see citing works
Wojdasiewicz, P., Poniatowski, Ł. A., Turczyn, P., Frasuńska, J., Paradowska‐Gorycka, A., & Tarnacka, B. (2020) · Mediators of Inflammation · doi:10.1155/2020/3164260 · Cited by 35 · see citing works
Nanocarriers for effective nutraceutical delivery to the brain
Meenambal, R., & Bharath, M. M. S. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104851 · Cited by 29 · see citing works
Cutuli, D., Landolfo, E., Nobili, A., Bartolo, P. D., Sacchetti, S., Chirico, D., Marini, F., Pieroni, L., Ronci, M., D’Amelio, M., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00705-3 · Cited by 29 · see citing works
Bioactive Exploration in Functional Foods: Unlocking Nature's Treasures
Mittal, R. K., Mishra, R., Sharma, V., & Purohit, P. (2023) · Current Pharmaceutical Biotechnology · doi:10.2174/0113892010282580231120041659 · Cited by 29 · see citing works
Mladenović, A., Καπετάνου, Μ., Lončarević‐Vasiljković, N., Todorovic, S. T., Athanasopoulou, S., Jović, M., Prvulović, M., Taoufik, E., Matsas, R., Kanazir, S., et al. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.11.038 · Cited by 26 · see citing works
New perspectives of omega-3 fatty acids from diatoms
Tyagi, R., Rastogi, R. P., Babich, O., Awasthi, M. K., & Tiwari, A. (2023) · Systems Microbiology and Biomanufacturing · doi:10.1007/s43393-023-00202-2 · Cited by 24 · see citing works
ABCA7 Regulates Brain Fatty Acid Metabolism During LPS-Induced Acute Inflammation
Aikawa, T., Ren, Y., Holm, M., Asmann, Y. W., Alam, A., Fitzgerald, M. L., Bu, G., & Kanekiyo, T. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.647974 · Cited by 24 · see citing works
Cokdinleyen, M., Álvarez‐Rivera, G., Tejera, J. L. G., Mendiola, J. A., Valdés, A., Kara, H., Ibáñez, E., & Cifuentes, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073897 · Cited by 24 · see citing works
Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans
Saito, K., Hattori, K., Hidese, S., Sasayama, D., Miyakawa, T., Matsumura, R., Tatsumi, M., Yokota, Y., Ota, M., Hori, H., et al. (2021) · Metabolites · doi:10.3390/metabo11050268 · Cited by 24 · see citing works
Sudden unexpected death in Parkinson's disease: Insights from clinical practice
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Gao, J., Wang, L., Zhao, C., Wu, Y., Lu, Z., Gu, Y., Ba, Z., Wang, X., Wang, J., & Xu, Y. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ma0821-639rr · Cited by 18 · see citing works
Raghu, S. V., Kudva, A. K., Rao, S., Prasad, K., Mudgal, J., & Baliga, M. S. (2021) · Food & Function · doi:10.1039/d1fo02391h · Cited by 18 · see citing works
An Overview of Food Bioactive Compounds and Their Health-Promoting Features
Kamiloğlu, S., Çapanoğlu, E., & Jafari, S. M. (2022) · Food bioactive ingredients · doi:10.1007/978-3-030-96885-4_1 · Cited by 21 · see citing works
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Harlan, T. S., Gow, R. V., Kornstädt, A., Alderson, P. W., & Lustig, R. H. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1098453 · Cited by 16 · see citing works
Smoking, coffee intake, and Parkinson’s disease: Potential protective mechanisms and components
Hong, S. W., Page, R., & Truman, P. (2024) · NeuroToxicology · doi:10.1016/j.neuro.2024.12.003 · Cited by 16 · see citing works
Tu, J., Zhang, J., & Chen, G. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1522498 · Cited by 16 · see citing works
Nootropic foods in neurodegenerative diseases: mechanisms, challenges, and future
Nguyen, L. A. M., Simons, C. W., & Thomas, R. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00476-7 · Cited by 17 · see citing works
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Parkinson Symptom Severity and Use of Nutraceuticals
Mischley, L. K., Farahnik, J., Mantay, L., Punzi, J., Szampruch, K., Ferguson, T., & Fox, D. J. (2023) · Nutrients · doi:10.3390/nu15040802 · Cited by 15 · see citing works
Dietary N-6 Polyunsaturated Fatty Acid Intake and Brain Health in Middle-Aged and Elderly Adults
Gu, J., Bao, Y., Li, Y., Li, H., Deng, X., Zhang, Y., Zhu, X., & Ran, J. (2024) · Nutrients · doi:10.3390/nu16244272 · Cited by 15 · see citing works
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Parkinson’s Disease: Is there a Role for Dietary and Herbal Supplements?
Onaolapo, O. J., Odeniyi, A. O., & Onaolapo, A. Y. (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666210218082954 · Cited by 15 · see citing works
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Crime and Nourishment: A Narrative Review Examining Ultra-Processed Foods, Brain, and Behavior
Prescott, S. L., Logan, A. C., LaFata, E. M., Naik, A., Nelson, D. H., Robinson, M. B., & Soble, L. (2024) · Dietetics · doi:10.3390/dietetics3030025 · Cited by 14 · see citing works
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The Interplay of Sports and Nutrition in Neurological Health and Recovery
Clemente‐Suárez, V. J., Redondo-Flórez, L., Beltrán-Velasco, A. I., Belinchón-deMiguel, P., Ramos‐Campo, D. J., Curiel-Regueros, A., Martín-Rodríguez, A., & Tornero-Aguilera, J. F. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13072065 · Cited by 13 · see citing works
Salahuddin, M., Abdel‐Wareth, A. A. A., Rashwan, A. K., Hiramatsu, K., Fulzele, S., & Lohakare, J. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.105096 · Cited by 11 · see citing works
da Silva, E. K. A., & Rial, R. C. (2024) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2024.106819 · Cited by 11 · see citing works
Oils’ Impact on Comprehensive Fatty Acid Analysis and Their Metabolites in Rats
Stawarska, A., Jelińska, M., Czaja, J., Pacześniak, E., & Bobrowska‐Korczak, B. (2020) · Nutrients · doi:10.3390/nu12051232 · Cited by 11 · see citing works
Tiwari, S., Yang, J., Morisseau, C. H. P., Durbin-Johnson, B. P., Hammock, B. D., & Gomes, A. V. (2021) · Scientific Reports · doi:10.1038/s41598-021-86284-1 · Cited by 11 · see citing works
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Techaniyom, P., Korsirikoon, C., Rungruang, T., Pakaprot, N., Prombutara, P., Mukda, S., Kettawan, A., & Kettawan, A. (2024) · Food Science & Nutrition · doi:10.1002/fsn3.4265 · Cited by 10 · see citing works
Mitrović, N., Adžić, M., Kontić, M. Z., Dragić, M., Petrović, S., Paunović, M., Vučić, V., & Grković, I. (2024) · Cells · doi:10.3390/cells13141184 · Cited by 10 · see citing works
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- Authors
- Avallone, R., Vitale, G., & Bertolotti, M.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Avallone, Rossella
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2019-08-30
- Volume
- 20
- Issue
- 17
- Pages
- 4256
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC6747747
- OpenAlex
- W2963446643
- Cited by
- 218
- References
- 83
- Citations by year
- 2026: 14 · 2025: 43 · 2024: 35 · 2023: 29 · 2022: 37 · 2021: 31 · 2020: 28 · 2019: 1
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondazione Cassa di Risparmio di Modena (2018.0334)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- omega-3 fatty acids, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, dietary supplementation, polyunsaturated fatty acids, anti-inflammatory mediators, cell membrane fluidity, intracellular signaling, gene expression, disease prevention
- MeSH terms
- Clinical Trials as Topic, Humans, Fatty Acids, Omega-3, Neurodegenerative Diseases, Observational Studies as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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