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Polyunsaturated Fatty Acid Supplementation in Multiple Sclerosis Management: A Scoping Review.

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Τίτλος: Polyunsaturated Fatty Acid Supplementation in Multiple Sclerosis Management: A Scoping Review.
Συγγραφείς: Oliveira R; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, MedTech, Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal., Lopes CM; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, MedTech, Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal., Silva C; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal., Guerra RS; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal.; LAETA-Associate Laboratory for Energy, Transports and Aerospace, INEGI-Institute of Science and Innovation in Mechanical and Industrial Engineering, 4200-465 Porto, Portugal.
Πηγή: Nutrients [Nutrients] 2026 Sep 05; Vol. 18 (17). Date of Electronic Publication: 2026 Sep 05.
Τύπος έκδοσης: Journal Article; Scoping Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI Publishing
Ιατρικοί όροι (MeSH): Fatty Acids, Unsaturated*/administration & dosage , Multiple Sclerosis*/drug therapy , Dietary Supplements*, Fatty Acids, Omega-3/administration & dosage ; Fatty Acids, Omega-6/administration & dosage ; Humans
Περίληψη: Polyunsaturated fatty acids (PUFA) have long been investigated as potential adjunctive therapies for multiple sclerosis because of their immunomodulatory, anti-inflammatory, and neuroprotective properties. However, the available evidence remains heterogeneous and has not been comprehensively mapped. This scoping review aimed to characterize the evidence on PUFA supplementation, identify research trends and knowledge gaps, and contextualize findings from primary studies alongside systematic reviews. This scoping review followed the Joanna Briggs Institute methodology and the PRISMA-ScR guidelines. MEDLINE (via PubMed), Scopus, Web of Science, ScienceDirect, Cochrane CENTRAL, ClinicalTrials.gov, WHO ICTRP, and EU CTR/EudraCT were searched up to June 2026. Eligible evidence included randomized and non-randomized intervention studies, longitudinal cohort studies, systematic reviews, and clinical trial registry records evaluating omega-3, omega-6, or combined PUFA supplementation in persons with multiple sclerosis. Data were descriptively charted and narratively synthesized. Thirty reports representing 24 independent evidence sources (18 primary studies and 6 systematic reviews) were included. Research evolved from early omega-6 interventions, which demonstrated biological activity but limited clinical benefit, to omega-3 supplementation, where mechanistic evidence expanded despite inconsistent clinical outcomes. More recent studies investigated combined PUFA formulations, reporting the most promising findings for relapse-related outcomes and inflammatory biomarkers, while evidence remains limited by a small number of studies and heterogeneous interventions. Systematic reviews consistently interpreted the evidence more cautiously than individual primary studies. PUFA research in multiple sclerosis has progressed from exploratory studies to more sophisticated intervention strategies integrating clinical and mechanistic outcomes. Although PUFAs show biological activity and favorable safety profiles, consistent evidence of clinically meaningful disease modification remains limited. This evidence map highlights methodological advances, persistent heterogeneity, and priorities for future well-designed randomized controlled trials.
References: Prostaglandins Leukot Essent Fatty Acids. 2009 Feb-Mar;80(2-3):131-6. (PMID: 19171471)
Curr Opin Clin Nutr Metab Care. 2019 Mar;22(2):116-123. (PMID: 30550388)
Br Med J. 1977 Oct 8;2(6092):932-3. (PMID: 334337)
Afr J Tradit Complement Altern Med. 2013 Oct 03;10(6):519-27. (PMID: 24311880)
Br Med J. 1978 Nov 18;2(6149):1390-1. (PMID: 363236)
BMJ Neurol Open. 2022 Nov 4;4(2):e000334. (PMID: 36353267)
Complement Ther Med. 2013 Oct;21(5):473-80. (PMID: 24050582)
Cochrane Database Syst Rev. 2020 May 19;5:CD004192. (PMID: 32428983)
Nat Clin Pract Neurol. 2009 Feb;5(2):82-92. (PMID: 19194388)
Eur Neurol. 1983;22(1):78-83. (PMID: 6301844)
Arch Neurol. 2012 Aug;69(8):1044-51. (PMID: 22507886)
J Clin Neurol. 2023 May;19(3):217-229. (PMID: 37151139)
Arthritis Res Ther. 2022 May 7;24(1):100. (PMID: 35526074)
Oxid Med Cell Longev. 2013;2013:709493. (PMID: 23861993)
Adv Nutr. 2017 May 15;8(3):463-472. (PMID: 28507011)
Mult Scler. 2017 Apr;23(4):513-524. (PMID: 28151074)
Nutrients. 2025 Oct 30;17(21):. (PMID: 41228487)
Eur Neurol. 1978;17(2):67-76. (PMID: 631143)
Curr J Neurol. 2022 Jan 5;21(1):52-63. (PMID: 38011464)
Lancet. 2008 Oct 25;372(9648):1502-17. (PMID: 18970977)
Acta Neurol Scand Suppl. 2012;(195):70-5. (PMID: 23278660)
J Neurol Neurosurg Psychiatry. 1989 Jan;52(1):18-22. (PMID: 2540285)
Autoimmun Rev. 2024 Nov;23(11):103651. (PMID: 39357585)
Am J Neurodegener Dis. 2016 Jun 01;5(2):145-51. (PMID: 27335704)
Complement Ther Med. 2015 Oct;23(5):652-7. (PMID: 26365444)
Mol Nutr Food Res. 2025 May;69(10):e202400752. (PMID: 40159804)
Nat Rev Neurol. 2012 Dec;8(12):678-89. (PMID: 23026980)
J Comp Eff Res. 2021 Apr;10(6):495-507. (PMID: 33620251)
Lancet Reg Health Eur. 2024 Aug 22;44:100977. (PMID: 39444703)
Prog Lipid Res. 2025 Jan;97:101318. (PMID: 39736417)
Nutrients. 2021 Oct 19;13(10):. (PMID: 34684661)
N Engl J Med. 1952 May 8;246(19):721-8. (PMID: 14929306)
Ann Intern Med. 2018 Oct 2;169(7):467-473. (PMID: 30178033)
Nutr Neurosci. 2021 Jul;24(7):569-579. (PMID: 31462182)
BMJ Open. 2013 Apr 17;3(4):. (PMID: 23599375)
Clin Neurol Neurosurg. 2017 Dec;163:173-178. (PMID: 29126030)
Foods. 2024 Dec 27;14(1):. (PMID: 39796335)
CNS Neurol Disord Drug Targets. 2019;18(7):523-529. (PMID: 31096898)
Immunotherapy. 2026 Apr-Apr;18(5-6):365-375. (PMID: 42200313)
Food Sci Nutr. 2025 Sep 01;13(9):e70884. (PMID: 40905016)
Cell Mol Neurobiol. 2025 Mar 17;45(1):25. (PMID: 40097862)
Avicenna J Phytomed. 2026;16(1):122-129. (PMID: 41647455)
J Neuroimmunol. 1995 Feb;56(2):143-53. (PMID: 7860710)
Medicines (Basel). 2019 Sep 12;6(3):. (PMID: 31547410)
Nutr Hosp. 2018 Jan 12;35(1):162-168. (PMID: 29565165)
Campbell Syst Rev. 2022 Mar 27;18(2):e1230. (PMID: 36911350)
Complement Ther Med. 2014 Dec;22(6):986-93. (PMID: 25453518)
Lancet. 2024 Jan 13;403(10422):183-202. (PMID: 37949093)
Mult Scler. 2008 Sep;14(8):1113-9. (PMID: 18632773)
PLoS One. 2016 Jan 22;11(1):e0147195. (PMID: 26799942)
Contributed Indexing: Keywords: fish oil; multiple sclerosis; omega-3; omega-6; polyunsaturated fatty acids; scoping review; supplementation
Substance Nomenclature: 0 (Fatty Acids, Omega-3)
0 (Fatty Acids, Omega-6)
0 (Fatty Acids, Unsaturated)
Entry Date(s): Date Created: 20260915 Date Completed: 20260915 Latest Revision: 20260922
Update Code: 20260922
PubMed Central ID: PMC13567611
DOI: 10.3390/nu18172915
PMID: 42739087
Βάση Δεδομένων: MEDLINE
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  Data: <searchLink fieldCode="AU" term="%22Oliveira+R%22">Oliveira R</searchLink>; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, MedTech, Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.<br /><searchLink fieldCode="AU" term="%22Lopes+CM%22">Lopes CM</searchLink>; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, MedTech, Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.<br /><searchLink fieldCode="AU" term="%22Silva+C%22">Silva C</searchLink>; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal.<br /><searchLink fieldCode="AU" term="%22Guerra+RS%22">Guerra RS</searchLink>; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal.; RISE-Health, Fernando Pessoa Teaching and Culture Foundation, Fernando Pessoa University, 4200-150 Porto, Portugal.; LAETA-Associate Laboratory for Energy, Transports and Aerospace, INEGI-Institute of Science and Innovation in Mechanical and Industrial Engineering, 4200-465 Porto, Portugal.
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  Data: Polyunsaturated fatty acids (PUFA) have long been investigated as potential adjunctive therapies for multiple sclerosis because of their immunomodulatory, anti-inflammatory, and neuroprotective properties. However, the available evidence remains heterogeneous and has not been comprehensively mapped. This scoping review aimed to characterize the evidence on PUFA supplementation, identify research trends and knowledge gaps, and contextualize findings from primary studies alongside systematic reviews. This scoping review followed the Joanna Briggs Institute methodology and the PRISMA-ScR guidelines. MEDLINE (via PubMed), Scopus, Web of Science, ScienceDirect, Cochrane CENTRAL, ClinicalTrials.gov, WHO ICTRP, and EU CTR/EudraCT were searched up to June 2026. Eligible evidence included randomized and non-randomized intervention studies, longitudinal cohort studies, systematic reviews, and clinical trial registry records evaluating omega-3, omega-6, or combined PUFA supplementation in persons with multiple sclerosis. Data were descriptively charted and narratively synthesized. Thirty reports representing 24 independent evidence sources (18 primary studies and 6 systematic reviews) were included. Research evolved from early omega-6 interventions, which demonstrated biological activity but limited clinical benefit, to omega-3 supplementation, where mechanistic evidence expanded despite inconsistent clinical outcomes. More recent studies investigated combined PUFA formulations, reporting the most promising findings for relapse-related outcomes and inflammatory biomarkers, while evidence remains limited by a small number of studies and heterogeneous interventions. Systematic reviews consistently interpreted the evidence more cautiously than individual primary studies. PUFA research in multiple sclerosis has progressed from exploratory studies to more sophisticated intervention strategies integrating clinical and mechanistic outcomes. Although PUFAs show biological activity and favorable safety profiles, consistent evidence of clinically meaningful disease modification remains limited. This evidence map highlights methodological advances, persistent heterogeneity, and priorities for future well-designed randomized controlled trials.
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  Data: Prostaglandins Leukot Essent Fatty Acids. 2009 Feb-Mar;80(2-3):131-6. (PMID: <searchLink fieldCode="PM" term="%2219171471%22">19171471)</searchLink><br />Curr Opin Clin Nutr Metab Care. 2019 Mar;22(2):116-123. (PMID: <searchLink fieldCode="PM" term="%2230550388%22">30550388)</searchLink><br />Br Med J. 1977 Oct 8;2(6092):932-3. (PMID: <searchLink fieldCode="PM" term="%22334337%22">334337)</searchLink><br />Afr J Tradit Complement Altern Med. 2013 Oct 03;10(6):519-27. (PMID: <searchLink fieldCode="PM" term="%2224311880%22">24311880)</searchLink><br />Br Med J. 1978 Nov 18;2(6149):1390-1. (PMID: <searchLink fieldCode="PM" term="%22363236%22">363236)</searchLink><br />BMJ Neurol Open. 2022 Nov 4;4(2):e000334. (PMID: <searchLink fieldCode="PM" term="%2236353267%22">36353267)</searchLink><br />Complement Ther Med. 2013 Oct;21(5):473-80. (PMID: <searchLink fieldCode="PM" term="%2224050582%22">24050582)</searchLink><br />Cochrane Database Syst Rev. 2020 May 19;5:CD004192. (PMID: <searchLink fieldCode="PM" term="%2232428983%22">32428983)</searchLink><br />Nat Clin Pract Neurol. 2009 Feb;5(2):82-92. (PMID: <searchLink fieldCode="PM" term="%2219194388%22">19194388)</searchLink><br />Eur Neurol. 1983;22(1):78-83. (PMID: <searchLink fieldCode="PM" term="%226301844%22">6301844)</searchLink><br />Arch Neurol. 2012 Aug;69(8):1044-51. (PMID: <searchLink fieldCode="PM" term="%2222507886%22">22507886)</searchLink><br />J Clin Neurol. 2023 May;19(3):217-229. (PMID: <searchLink fieldCode="PM" term="%2237151139%22">37151139)</searchLink><br />Arthritis Res Ther. 2022 May 7;24(1):100. (PMID: <searchLink fieldCode="PM" term="%2235526074%22">35526074)</searchLink><br />Oxid Med Cell Longev. 2013;2013:709493. (PMID: <searchLink fieldCode="PM" term="%2223861993%22">23861993)</searchLink><br />Adv Nutr. 2017 May 15;8(3):463-472. (PMID: <searchLink fieldCode="PM" term="%2228507011%22">28507011)</searchLink><br />Mult Scler. 2017 Apr;23(4):513-524. (PMID: <searchLink fieldCode="PM" term="%2228151074%22">28151074)</searchLink><br />Nutrients. 2025 Oct 30;17(21):. (PMID: <searchLink fieldCode="PM" term="%2241228487%22">41228487)</searchLink><br />Eur Neurol. 1978;17(2):67-76. (PMID: <searchLink fieldCode="PM" term="%22631143%22">631143)</searchLink><br />Curr J Neurol. 2022 Jan 5;21(1):52-63. (PMID: <searchLink fieldCode="PM" term="%2238011464%22">38011464)</searchLink><br />Lancet. 2008 Oct 25;372(9648):1502-17. (PMID: <searchLink fieldCode="PM" term="%2218970977%22">18970977)</searchLink><br />Acta Neurol Scand Suppl. 2012;(195):70-5. (PMID: <searchLink fieldCode="PM" term="%2223278660%22">23278660)</searchLink><br />J Neurol Neurosurg Psychiatry. 1989 Jan;52(1):18-22. (PMID: <searchLink fieldCode="PM" term="%222540285%22">2540285)</searchLink><br />Autoimmun Rev. 2024 Nov;23(11):103651. (PMID: <searchLink fieldCode="PM" term="%2239357585%22">39357585)</searchLink><br />Am J Neurodegener Dis. 2016 Jun 01;5(2):145-51. (PMID: <searchLink fieldCode="PM" term="%2227335704%22">27335704)</searchLink><br />Complement Ther Med. 2015 Oct;23(5):652-7. (PMID: <searchLink fieldCode="PM" term="%2226365444%22">26365444)</searchLink><br />Mol Nutr Food Res. 2025 May;69(10):e202400752. (PMID: <searchLink fieldCode="PM" term="%2240159804%22">40159804)</searchLink><br />Nat Rev Neurol. 2012 Dec;8(12):678-89. (PMID: <searchLink fieldCode="PM" term="%2223026980%22">23026980)</searchLink><br />J Comp Eff Res. 2021 Apr;10(6):495-507. (PMID: <searchLink fieldCode="PM" term="%2233620251%22">33620251)</searchLink><br />Lancet Reg Health Eur. 2024 Aug 22;44:100977. (PMID: <searchLink fieldCode="PM" term="%2239444703%22">39444703)</searchLink><br />Prog Lipid Res. 2025 Jan;97:101318. (PMID: <searchLink fieldCode="PM" term="%2239736417%22">39736417)</searchLink><br />Nutrients. 2021 Oct 19;13(10):. (PMID: <searchLink fieldCode="PM" term="%2234684661%22">34684661)</searchLink><br />N Engl J Med. 1952 May 8;246(19):721-8. (PMID: <searchLink fieldCode="PM" term="%2214929306%22">14929306)</searchLink><br />Ann Intern Med. 2018 Oct 2;169(7):467-473. (PMID: <searchLink fieldCode="PM" term="%2230178033%22">30178033)</searchLink><br />Nutr Neurosci. 2021 Jul;24(7):569-579. (PMID: <searchLink fieldCode="PM" term="%2231462182%22">31462182)</searchLink><br />BMJ Open. 2013 Apr 17;3(4):. (PMID: <searchLink fieldCode="PM" term="%2223599375%22">23599375)</searchLink><br />Clin Neurol Neurosurg. 2017 Dec;163:173-178. (PMID: <searchLink fieldCode="PM" term="%2229126030%22">29126030)</searchLink><br />Foods. 2024 Dec 27;14(1):. (PMID: <searchLink fieldCode="PM" term="%2239796335%22">39796335)</searchLink><br />CNS Neurol Disord Drug Targets. 2019;18(7):523-529. (PMID: <searchLink fieldCode="PM" term="%2231096898%22">31096898)</searchLink><br />Immunotherapy. 2026 Apr-Apr;18(5-6):365-375. (PMID: <searchLink fieldCode="PM" term="%2242200313%22">42200313)</searchLink><br />Food Sci Nutr. 2025 Sep 01;13(9):e70884. (PMID: <searchLink fieldCode="PM" term="%2240905016%22">40905016)</searchLink><br />Cell Mol Neurobiol. 2025 Mar 17;45(1):25. (PMID: <searchLink fieldCode="PM" term="%2240097862%22">40097862)</searchLink><br />Avicenna J Phytomed. 2026;16(1):122-129. (PMID: <searchLink fieldCode="PM" term="%2241647455%22">41647455)</searchLink><br />J Neuroimmunol. 1995 Feb;56(2):143-53. (PMID: <searchLink fieldCode="PM" term="%227860710%22">7860710)</searchLink><br />Medicines (Basel). 2019 Sep 12;6(3):. (PMID: <searchLink fieldCode="PM" term="%2231547410%22">31547410)</searchLink><br />Nutr Hosp. 2018 Jan 12;35(1):162-168. (PMID: <searchLink fieldCode="PM" term="%2229565165%22">29565165)</searchLink><br />Campbell Syst Rev. 2022 Mar 27;18(2):e1230. (PMID: <searchLink fieldCode="PM" term="%2236911350%22">36911350)</searchLink><br />Complement Ther Med. 2014 Dec;22(6):986-93. (PMID: <searchLink fieldCode="PM" term="%2225453518%22">25453518)</searchLink><br />Lancet. 2024 Jan 13;403(10422):183-202. (PMID: <searchLink fieldCode="PM" term="%2237949093%22">37949093)</searchLink><br />Mult Scler. 2008 Sep;14(8):1113-9. (PMID: <searchLink fieldCode="PM" term="%2218632773%22">18632773)</searchLink><br />PLoS One. 2016 Jan 22;11(1):e0147195. (PMID: <searchLink fieldCode="PM" term="%2226799942%22">26799942)</searchLink>
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      – SubjectFull: Fatty Acids, Omega-3 administration & dosage
        Type: general
      – SubjectFull: Fatty Acids, Omega-6 administration & dosage
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      – TitleFull: Polyunsaturated Fatty Acid Supplementation in Multiple Sclerosis Management: A Scoping Review.
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      – BibEntity:
          Dates:
            – D: 05
              M: 09
              Text: 2026 Sep 05
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 2072-6643
          Numbering:
            – Type: volume
              Value: 18
            – Type: issue
              Value: 17
          Titles:
            – TitleFull: Nutrients
              Type: main
ResultId 1