Scientific and Medical Research Literature

We have pulled together a wide ranging list of references relevant to the immunology and biochemistry (fatty acids) of multiple sclerosis and other related auto-immune diseases, and the health benefits of fats and fatty acids in MS. The references are compiled in order of topic and can be found by clicking on the dropdowns below. If we have missed any that you think may be important please send us the reference via our contacts page, thanks.

References

Plasma and Blood Cell Omega-6 Fatty Acids in Multiple Sclerosis

  • Gul S, Smith AD, Thompson RHS, et al. (1970) Fatty acid composition of phospholipids from platelets and erythrocytes in multiple sclerosis. J Neurol Neurosurg Psychiat 33, 506–510.
  • Thompson RHS (1975) Unsaturated fatty acids in multiple sclerosis. In Multiple Sclerosis Research, pp. 184–193 [AN Davison, JH Humphrey, AL Liversedge, WI McDonald and JS Porterfield, editors]. USA, Elsevier: North Holland.
  • Tsang WM, Belin J, Monro JA, Smith AD, Thompson RHS and Zilkha KJ (1976) Relationship between plasma and lymphocyte linoleate in multiple sclerosis. J Neurol Neurosurg Psychiatry 39, 767–771.
  • Heipertz R, Klauke W, Pilz H and Ritter G (1977) Serum fatty acids in multiple sclerosis. J. Neurology 214, 153–157.
  • Shukla VKS & Clausen J (1978) Linoleate and fatty acid patterns of serum lipids in multiple sclerosis. Acta. Neurol. Scandinav 57, 270–274.
  • Homa ST, Belin J, Smith AD, et al. (1980) Levels of linoleate and arachidonate in red blood cells of healthy individuals and patients with multiple sclerosis. J Neurol Neurosurg Psychiat 43, 106–110.
  • Homa ST, Conroy DM, Belin J, Smith AD, Monro JA & Zilkha KJ (1981) Fatty acid patterns of red blood cell phospholipids in patients with multiple sclerosis. Lancet, August 29 474.
  • Crawford M and Stevens P (1981) A study on essential fatty acids and multiple sclerosis. Prog Lipid Res 20. 255-258.
  • Neu IS (1983) Essential fatty acids in the serum and cerebrospinal fluid of multiple sclerosis patients. Acta. Neurol. Scand. 67, 151–163.
  • Yoshida M, Takase S, Itahara K and Nakanishi T (1983) Linoleate and fatty acid compositions in the serum lipids of Japanese patients with multiple sclerosis. Acta Neurol Scand 68, 362–364. 
  • Cherayil GD (1984) Sialic acid & fatty acid concentrations in lymphocytes, red cells, and plasma from patients with multiple sclerosis. J Neuro Sci. 63, 1–10.
  • Fisher M, Johnson MH, et al. (1987) Linoleic acid levels in white blood cells, platelets & serum of multiple sclerosis patients. Acta Neurol Scand 76, 241–5.
  • Navarro X and Segura R (1989) Red blood cell fatty acids in multiple sclerosis. Acta Neurol Scand 79, 32–37.
  • Holman RT, Johnson SB and Kokmen E (1989) Deficiencies of polyunsaturated fatty acids and replacement by nonessential fatty acids in plasma lipids in multiple sclerosis. Proc. Natl. Acad. Sci. USA. 86, 4720–4724
  • Hon GM, Hassan MS, van Rensburg SJ, Abel S, Marais DW, van Jaarsveld P, Smuts CM, et al (2009). Erythrocyte membrane fatty acids in patients with multiple sclerosis. Mult Scler. 2009 Jun;15(6):759-62. doi: 10.1177/1352458509103321.  
  • Dunlop, Eleanor et al (2024) Plasma levels of polyunsaturated fatty acids and multiple sclerosis susceptibility in a US case-control study. Multiple Sclerosis and Related Disorders, Volume 92, 105920
  • Chen Y, Li C, Chen K, Shang H, Association of Omega-3 and Omega-6
  • with neurodegenerative disorders: a UK biobank prospective cohort study, Parkinsonism and Related
  • Disorders, https://doi.org/10.1016/j.parkreldis.2025.108145
  • Chen Y, Li C, Chen K, Shang H, Association of Omega-3 and Omega-6
  • with neurodegenerative disorders: a UK biobank prospective cohort study, Parkinsonism and Related
  • Disorders, https://doi.org/10.1016/j.parkreldis.2025.108145
  • Chen Y, Li C, Chen K, Shang H, Association of Omega-3 and Omega-6
  • with neurodegenerative disorders: a UK biobank prospective cohort study, Parkinsonism and Related
  • Disorders, https://doi.org/10.1016/j.parkreldis.2025.108145
  • Chen Y, Li C, Chen K, Shang H, Association of Omega-3 and Omega-6
  • with neurodegenerative disorders: a UK biobank prospective cohort study, Parkinsonism and Related
  • Disorders, https://doi.org/10.1016/j.parkreldis.2025.108145
  • Chen Y, Li C, Chen K, Shang H (2025), Association of Omega-3 and Omega-6 with neurodegenerative disorders: a UK biobank prospective cohort study, Parkinsonism and Related Disorders, https://doi.org/10.1016/j.parkreldis.2025.108145

Omega-6 Fatty Acid Clinical Trials and Supplementation in Multiple Sclerosis

  • Millar JHD, Zilkha KJ, Langman MJS, Payling-Wright H, et al. (1973) Double-blind trial of linoleate supplementation of the diet in multiple sclerosis. Br Med J 1, 765–768.
  • Bates D, Fawcett PRW, Shaw DA and Weightman D (1978) Polyunsaturated fatty acids in the treatment of acute remitting multiple sclerosis. Br Med J. 2, 1390–1391.
  • Field EJ and Joyce G (1983) Multiple sclerosis: effect of gamma-linolenate administration upon membranes and the need for extended clinical trials of unsaturated fatty acids. Eur. Neurol. 22, 78–83.
  • Dworkin RH, Bates D, Millar JHD, et al. (1984) Linoleic acid and multiple sclerosis: a reanalysis of three double blind trials. Neurology 34, 1441–1445.
  • Harbige L S, Crawford M A, Jones J, Preece A W and Forti A (1986) Dietary intervention studies on the phosphoglyceride fatty acids and electrophoretic mobility of erythrocytes in multiple sclerosis. Prog. Lipid. Res. 25. 243-248.
  • Fitzgerald G, Harbige LS, Forti A, Crawford MA (1987) The effect of nutritional counselling on diet and plasma EFA status in multiple sclerosis patients over 3 years. Hum Nutr Appl Nutr. 1987 Oct;41(5):297-310. PMID: 3692896.
  • Harbige, L S and Sharief M (2007) Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis, Br J Nutr. 98 Suppl. 1, 46-53.
  • Mehta LR, Dworkin RH, Schwid SR (2009) Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis. Nat Clin Pract Neurol. Feb;5(2):82-92.
  • Pantzaris MC, Loukaides GN, Ntzani EE, et al. (2013) A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial. BMJ Open 2013;3:e002170. doi:10.1136/bmjopen-2012-002170
  • Rezapour-Firouzi S, Arefhosseini S, et al (2015) Alteration of delta-6-desaturase (FADS2), secretory phospholipase-A2 (sPLA2) enzymes by hot-nature diet with co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients. Complementary Therapies in Medicine, Volume 23, Issue 5, 652-657.
  • Majdinasab N, Namjoyan F, Taghizadeh M, Saki H (2018) The effect of evening primrose oil on fatigue and quality of life in patients with multiple sclerosis. Neuropsychiatr Dis Treat. 2018 Jun 12;14:1505-1512. doi: 10.2147/NDT.S149403.

Omega-6 Fatty Acids in Rheumatoid Arthritis:  Blood Fatty Acids and Clinical Trials

  • Belch JJ, Ansell D, Madhok R, O'Dowd A, Sturrock RD (1988) Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double-blind placebo-controlled study. Ann Rheum Dis.47(2):96-104. doi: 10.1136/ard.47.2.96. PMID: 2833184; PMCID: PMC1003460.
  • Jantti J, Nikkari T,  et al (1989) Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids. Annals of the Rheumatic Diseases, 48, 124-127.
  • M. Brzeski, Madhok R, Capell H (1991) Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs. British Journal of Rheumatology. 30 5 370–372. 
  • Leventhal LJ, Boyce EG, Zurier RB, (1993) Treatment of rheumatoid arthritis with gamma-linolenic acid, Ann Intern Med. 1993 Nov 1;119(9):867-73.
  • Watson J, Byars ML, McGill P, Kelman AW (1993). Cytokine and prostaglandin production by monocytes of volunteers and rheumatoid arthritis patients treated with dietary supplements of blackcurrant seed oil. Br J Rheumatol. 32(12):1055-8. doi: 10.1093/rheumatology/32.12.1055. 
  • Leventhal LJ, Boyce EG, Zurier RB (1994) Treatment of rheumatoid arthritis with black-currant seed oil. Br J Rheumatol. 1994 Sep;33(9):847-52. 
  • Haugen M, Kjeldsen-Kragh J, Bjerve K, et al (1994) Changes in plasma phospholipid fatty acids and their relationship to disease activity in rheumatoid arthritis patients treated with a vegetarian diet. British Journal of Nutrition. 12, 555-566.
  • Rothman D, DeLuca P, Zurier RB (1995) Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum.; 25(2):87-96. doi: 10.1016/s0049-0172(95)80021-2. PMID: 8578315.
  • Rothman D, DeLuca P, Zurier RB (1995) Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum.; 25(2):87-96. doi: 10.1016/s0049-0172(95)80021-2. PMID: 8578315.
  • Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE, White BM, Laposata M (1996) gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. 1996 Nov;39(11):1808-17. doi: 10.1002/art.1780391106. PMID: 8912502.
  • Harbige LS (2003) Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Lipids. 38(4):323-41. doi: 10.1007/s11745-003-1067-z. PMID: 12848277.
  • Cameron M, Gagnier JJ, Chrubasik S (2011) Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 16; (2): CD002948. doi: 10.1002/14651858.CD002948.pub2. 
  • Reed GW, Leung K, Rossetti RG, Vanbuskirk S, Sharp JT, Zurier RB (2014) Treatment of rheumatoid arthritis with marine and botanical oils: an 18-month, randomized, and double-blind trial. Evid Based Complement Alternat Med. 2014;2014:857456. doi: 10.1155/2014/857456. Epub 2014 Mar 19. PMID: 24803948; PMCID: PMC3977504.
  • Sergeant S, Rahbar E, Chilton FH (2016) Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes. Eur J Pharmacol. 5;785:77-86. doi: 10.1016/j.ejphar.2016.04.020. 
  • Veselinovic M, Vasiljevic D, Vucic V et al (2017) Clinical Benefits of n-3 PUFA and ɤ-Linolenic Acid in Patients with Rheumatoid Arthritis. Nutrients. 2017 Mar 25;9(4):325. doi: 10.3390/nu9040325. PMID: 28346333; PMCID: PMC5409664.
  • de Pablo P, Romaguera D, Fisk H, Calder C et al. (2018) High erythrocyte levels of the n-6 polyunsaturated fatty acid linoleic acid are associated with lower risk of subsequent rheumatoid arthritis in a southern European nested case–control study. Ann Rheum Dis 2018;0:1–7. doi:10.1136/annrheumdis-2017-212274 1 d
  • Sigaux J, Mathieu S, Nguyen Y, Sanchez P, Letarouilly JG, Soubrier M, Czernichow S, Flipo RM, Sellam J, Daïen C (2022). Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease activity in inflammatory rheumatic diseases: a systematic literature review and meta-analysis. Arthritis Res Ther. 2022 May 7;24(1):100. doi: 10.1186/s13075-022-02781-2. 
  • Sigaux J, Bellicha A, Buscail C, Julia C, Flipo RM, Cantagrel A, Laporte F, Beal C, et al (2022) Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort. Nutrients. 2022 Jul 19;14(14):2947. doi: 10.3390/nu14142947. PMID: 35889904; PMCID: PMC9322967.
  • Hajiaghayi M, Dolati-Somarin AH, Gholizadeh F, et al (2024) The efficacy of evening primrose in rheumatoid arthritis: a systematic review. Res J Pharmacogn. 11(2):71–9.

Immune Cells and Cytokines in the Pathogenesis of Multiple Sclerosis

  • Hirsch RL, Panitch HS and Johnson KP (1985) Lymphocytes from multiple sclerosis patients produce elevated levels of gamma interferon in vitro. J Clin Immunol 5, 386–389.
  • Beck J, Rondot P, Catinot L, et al. (1988) Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in MS: do cytokines trigger off exacerbations? Acta Neurol Scand 78, 318–323.
  • Brosnan CF, Selmaj K, Raine CS. (1988) Hypothesis: a role for tumor necrosis factor in immune-mediated demyelination and its relevance to multiple sclerosis, J Neuroimmunol. 1988 Apr;18(1):87-94.
  • Merrill JE, Strom SR, Ellison GW, et al. (1989) In vitro study of mediators of inflammation in multiple sclerosis. J Clin Immunol 9, 84–96.
  • Ota K, Matsui M, Milford E et al. (1990) T cell recognition of an immunodominant myelin basic epitope in multiple sclerosis. Nature 346, 183–187.
  • Sharief MK and Hentges R (1991) Association between tumour necrosis factor-alpha and disease progression in patients with multiple sclerosis. N. Engl. J. Med. 325, 467–472.
  • Kuroda Y & Shimamoto Y (1991) Human tumor necrosis factor-alpha augments experimental allergic encephalomyelitis in rats. J Neuroimmunol 34, 159–164.
  • Selmaj K, RaineCS, Farooq M, et al. (1991) Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin. J Immunol 147, 1522–9. 
  • Chou YK, Bourdette DN, Offner H, et al. (1992) Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis. J Neuroimmunol 38, 105–114.
  • Lu CZ, Jensen MA and Arnason BG (1993) Interferon gammaand interleukin-4-secreting cells in multiple sclerosis. J Neuroimmunol 46, 123–128.
  • McCarron RM, Wang L, Racke MK, et al. (1993) Cytokine regulated
    adhesion between encephalitogenic T lymphocytes and cerebrovascular endothelial cells. J Neuroimmunol 43, 23–30.
  • Imamura K, Suzumura A, Hayashi F, et al. (1993) Cytokine production by peripheral blood monocytes/macrophages in multiple sclerosis patients. Acta Neurol Scand 87, 281–285.
  • Kerlero de Rosbo N, Milo R, Lees MB, et al. (1993) Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein. J Clin Invest 92 2602-8.
  • Zhang J, Markovic-Plese S, Lacet B, et al. (1994) Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 179, 973–984.
  • Fredrikson S, Soderstrom M, Hillert J, et al. (1994) Multiple sclerosis: occurrence of myelin basic protein peptide-reactive T cells in healthy family members. Acta Neurol Scand 89, 184–189.
  • Mokhtarian F, Shi Y, Shirazian D, et al. (1994) Defective production of anti-inflammatory cytokine, TGF-beta by T cell lines of patients with active multiple sclerosis. J Immunol 152, 6003–6010.
  • Rieckmann P, Albrecht M, et al (1994) Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis. Neurology 44, 1523–1526.
  • Cannella B and Raine CS (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 37, 424–435.
  • Vartanian T, LiY, Zhao M, et al. (1995) Interferon-gamma-induced oligodendrocyte cell death: implications for the pathogenesis of multiple sclerosis. Mol Med 1, 732–743.
  • Philippe J, Debruyne J, Leroux-Roels G, et al. (1996) In vitro TNF-alpha, IL-2 and IFN-gamma production as markers of relapses in multiple sclerosis. Clin Neurol Neurosurg 98, 286–290.
  • Kerlero de Rosbo N, Hoffman M, Mendel I, et al. (1997) Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions. Eur J Immunol 27, 3059–69.
  • Sarchielli P, Orlacchio A, Vicinanza F, Pelliccioli GP, et al (1997) Cytokine secretion and nitric oxide production by mononuclear cells of patients with multiple sclerosis. J Neuroimmunol. 1997 Dec;80(1-2):76-86. doi: 10.1016/s0165-5728(97)00136-7. 
  • Burns J, Bartholomew B and Lobo S (1999) Isolation of myelin basic protein-specific T cells predominantly from the memory T-cell compartment in multiple sclerosis. Ann Neurol 45, 33–39.
  • Genain CP, Cannella B, Hauser SL, Raine CS. (1999), Identification of autoantibodies associated with myelin damage in multiple sclerosis, Nat Med. 1999 Feb;5(2):170-5.
  • Bertolotto A, Capobianco M, Malucchi S, et al. (1999) Transforming
    growth factor beta1 (TGFbeta1) mRNA level correlates with magnetic resonance imaging disease activity in MS patients. Neurosci Lett 263, 21–4.
  • Martino G and Hartung H-P (1999) Immunopathogenesis of multiple sclerosis: the role of T cells. Curr Opin Neurol 12, 309–321
  • Bertolotto A, Malucchi S, Capobianco M, et al. (1999) Quantitative PCR reveals increased levels of tumor necrosis factoralpha mRNA in peripheral blood mononuclear cells of multiple sclerosis patients during relapses. J Interferon Cytokine Res 19, 575–581.
  • Burns J, Bartholomew B and Lobo S (1999) Isolation of myelin basic protein-specific T cells predominantly from the memory T-cell compartment in multiple sclerosis. Ann Neurol 45, 33–39.
  • Ozenci V, Kouwenhoven M, Huang YM, Kivisäkk P, Link H (2000) Multiple sclerosis is associated with an imbalance between tumour necrosis factor-alpha (TNF-alpha)- and IL-10-secreting blood cells that is corrected by interferon-beta (IFN-beta) treatment. Clin Exp Immunol. 120(1):147-53. doi: 10.1046/j.1365-2249.2000.01175.x. 
  • Tejada-Simon MV, Hong J, Rivera VM, et al. (2001) Reactivity pattern and cytokine profile of T cells primed by myelin peptides in multiple sclerosis and healthy individuals. Eur J Immunol 31, 907–917.
  • De Stefano N, Narayanan S, Francis GS, Arnaoutelis R, Tartaglia MC, Antel JP, Matthews PM & Arnold DL (2001) Evidence of axonal damage in the early stages of multiple sclerosis and relevance to disability. Arch Neurol. 58, 65–70.
  • Hollifield RD, Harbige LS, Pham-Dinh D and Sharief M (2003) Evidence for cytokine dysregulation in multiple sclerosis: peripheral blood mononuclear cell production of pro-inflammatory and anti-inflammatory cytokines during relapse and remission. Autoimmunity 36, 133–141.
  • Bjartmar C, Wujek JR, Trapp BD (2003) Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J. Neuro. Sci. 206, 165–171. 
  • Hafler DA (2004) Multiple sclerosis. J Clin Invest. 2004 Mar;113(6):788-94. doi: 10.1172/JCI21357. PMID: 15067307; PMCID: PMC362131.
  • Van Meeteren ME, Baron W, Beermann C, Dijkstra CD & van Tol EA (2006) Polyunsaturated fatty acid supplementation stimulates differentiation of oligodendroglia cells. Dev Neurosci. 28, 196–208.
  • Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol. 15 (9): 545-58. doi: 10.1038/nri3871. 
  • Liu R, Du S, Zhao L, Jain S, Sahay K, Rizvanov A, Lezhnyova V, Khaibullin T, Martynova E, et al (2022). Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target. Front Immunol. 2022 Sep 23;13:996469. doi: 10.3389/fimmu.2022.996469. PMID: 36211343; PMCID: PMC9539795.
  • Rodríguez Murúa S, Farez MF, Quintana FJ (2022) The Immune Response in Multiple Sclerosis. Annu Rev Pathol. 24; 17:121-139. doi: 10.1146/annurev-pathol-052920-040318. Epub 2021 Oct 4. PMID: 34606377.