Dietary intervention in multiple sclerosis carries potential therapeutic implications. While studies utilizing animal models of multiple sclerosis (MS) have demonstrated intriguing findings, well-designed clinical trials are few in number.
Objective:
The objective of this study is to review the animal model and clinical literature regarding dietary factors in experimental autoimmune encephalitis (EAE) and MS.
Methods:
This manuscript provides a comprehensive review of current animal model and clinical knowledge related to dietary factors in MS.
Results:
While there is currently little data for any specific diet in MS, there is growing evidence that certain dietary factors may influence the disease.
Conclusions:
Definitive information regarding dietary factors as a modifiable risk factor in MS will require larger randomized clinical trials.
DavidLAMauriceCFCarmodyRN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature2014; 505(7484): 559–563.
2.
OpazoMCOrtega-RochaEMCoronado-ArrazolaI, et al. Intestinal microbiota influences non-intestinal related autoimmune diseases. Front Microbiol2018; 9: 432.
3.
RothhammerVMascanfroniIDBunseL, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med2016; 22(6): 586–597.
4.
RiccioP.The molecular basis of nutritional intervention in multiple sclerosis: A narrative review. Complement Ther Med2011; 19(4): 228–237.
5.
van HorssenJWitteMESchreibeltG, et al. Radical changes in multiple sclerosis pathogenesis. Biochim Biophys Acta2011; 1812(2): 141–150.
6.
YoonHKlevenAPaulsenA, et al. Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system. Biochim Biophys Acta2016; 1862(4): 545–555.
7.
MastronardiFGMinWWangH, et al. Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-beta plus vitamin B12: Treatment to modify notch-1/sonic hedgehog balance. J Immunol2004; 172(10): 6418–6426.
8.
BererKMuesMKoutrolosM, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature2011; 479(7374): 538–541.
9.
LeeYKMenezesJSUmesakiY, et al. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A2011; 108(Suppl. 1): 4615–4622.
10.
BererKGerdesLACekanaviciuteE, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A2017; 114(40): 10719–10724.
11.
Ochoa-RepárazJMielcarzDWHaque-BegumS, et al. Induction of a regulatory B cell population in experimental allergic encephalomyelitis by alteration of the gut commensal microflora. Gut Microbes2010; 1(2): 103–108.
12.
StanisavljevicSCepicABojicS, et al. Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats. Sci Rep2019; 9(1): 918.
13.
StanisavljevicSDinicMJevticB, et al. Gut microbiota confers resistance of albino oxford rats to the induction of experimental autoimmune encephalomyelitis. Front Immunol2018; 9: 942.
14.
HeBHoangTKTianX, et al. Lactobacillus reuteri reduces the severity of experimental autoimmune encephalomyelitis in mice by modulating gut microbiota. Front Immunol2019; 10: 385.
15.
Lavasani DzhambazovBNouriMFakF, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS ONE2010; 5(2): e9009.
16.
TakataKKinoshitaMOkunoT, et al. The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells. PLoS ONE2011; 6(11): e27644.
17.
RezendeRMOliveiraRPMedeirosSR, et al. Hsp65-producing lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells. J Autoimmun2013; 40: 45–57.
18.
Ochoa-ReparazJMielcarzDWWangY, et al. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol2010; 3(5): 487–495.
19.
TimmermansSBogieJVanmierloT, et al. High fat diet exacerbates neuroinflammation in an animal model of multiple sclerosis by activation of the renin angiotensin system. J Neuroimmune Pharmacol2014; 9(2): 209–217.
20.
DupreeJLFeinsteinDL.Influence of diet on axonal damage in the EAE mouse model of multiple sclerosis. J Neuroimmunol2018; 322: 9–14.
21.
AhnJJRevelobXWinerDA, et al. Diet-induced obesity enhances the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol2014; 275(1–2): 133.
22.
HaghikiaAJörgSDuschaA, et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity2015; 43(4): 817–829.
23.
HarbigeLSLaywardLMorris-DownesMM, et al. The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-beta1) up-regulation and increased prostaglandin E2 (PGE2) production. Clin Exp Immunol2000; 122(3): 445–452.
24.
HarbigeLSYeatmanNAmorS, et al. Prevention of experimental autoimmune encephalomyelitis in Lewis rats by a novel fungal source of γ-linolenic acid. Br J Nutr1995; 74(5): 701–715.
25.
UnodaKDoiYNakajimaH, et al. Eicasapentaenoic acid (EPA) induces peroxisome proliferator-activated receptors and ameliorates experimental autoimmune encephalomyelitis. J Neuroimmunol2013; 256(1–2): 7–12.
26.
ManceraPWappenhansBCordobillaB, et al. Natural docosahexaenoic acid in the triglyceride form attenuates in vitro microglial activation and ameliorates autoimmune encephalomyelitis in mice. Nutrients2017; 9(7): e681.
27.
CondeCEscribanoBMLuqueE, et al. The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat. Nutr Neurosci2020; 23(1): 37–48.
28.
PlemelJRJuzwikCABensonCA, et al. Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review. Mult Scler2015; 21(12): 1485–1495.
29.
SpainRPowersKMurchisonC, et al. Lipoic acid in secondary progressive MS: A randomized controlled pilot trial. Neurol Neuroimmunol Neuroinflamm2017; 4(5): e374.
30.
WilckNMatusMGKearneySM, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature2017; 551(7682): 585–589.
31.
MizunoMNotoDKagaN, et al. The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models. PLoS ONE2017; 12(2): e0173032.
32.
ChoiIYPiccioLChildressP, et al. A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep2016; 15(10): 2136–2146.
33.
CignarellaFCantoniCGhezziL, et al. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab2018; 27(6): 1222–1235.
34.
SpachKMNasholdFEDittelBN, et al. IL-10 signaling is essential for 1,25-Dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol2006; 177(9): 6030–6037.
35.
RumahKRLindenJFischettiVA, et al. Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease. PLoS ONE2013; 8(10): e76359.
36.
JangiSGandhiRCoxLM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun2016; 7: 12015.
37.
MiyakeSKimSSudaW, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS ONE2015; 10(9): e0137429.
38.
ChenJChiaNKalariKR, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep2016; 6: 28484.
39.
TremlettHFadroshDWFaruqiAA, et al. Gut microbiota in early pediatric multiple sclerosis: A case−control study. Eur J Neurol2016; 23(8): 1308–1321.
40.
TremlettHFadroshDWFaruqiAA, et al. Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. BMC Neurol2016; 16(1): 182.
41.
CantarelBLWaubantEChehoudC, et al. Gut microbiota in multiple sclerosis: Possible influence of immunomodulators. J Investig Med2015; 63(5): 729–734.
42.
FarrokhiVNematiRNicholsFC, et al. Bacterial lipodipeptide, Lipid 654, is a microbiome-associated biomarker for multiple sclerosis. Clin Transl Immunology2013; 2(11): e8.
43.
TremlettHFadroshDWFaruqiAA, et al. Gut microbiota composition and relapse risk in pediatric MS: A pilot study. J Neurol Sci2016; 363: 153–157.
44.
Katz-SandIZhuYNtranosA, et al. Disease-modifying therapies alter gut microbial composition in MS. Neurol Neuroimmunol Neuroinflamm2018; 6(1): e517.
45.
TankouSKRegevKHealyBC, et al. A probiotic modulates the microbiome and immunity in multiple sclerosis. Ann Neurol2018; 83(6): 1147–1161.
46.
KouchakiETamtajiORSalamiM, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr2017; 36(5): 1245–1249.
47.
SintzelMBRamettaMRederAT.Vitamin D and multiple sclerosis: A comprehensive review. Neurol Ther2018; 7(1): 59–85.
48.
FitzgeraldKCTyryTSalterA, et al. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology2018; 90(1): e1–e11.
49.
HadgkissEJJelinekGAWeilandTJ, et al. The association of diet with quality of life, disability, and relapse rate in an international sample of people with multiple sclerosis. Nutr Neurosci2015; 18(3): 125–136.
50.
MarckCHDe LiveraAMWeilandTJ, et al. Pain in people with multiple sclerosis: Associations with modifiable lifestyle factors, fatigue, depression, anxiety, and mental health quality of life. Front Neurol2017; 8: 461.
51.
TetteyPSimpsonSTaylorB, et al. An adverse lipid profile and increased levels of adiposity significantly predict clinical course after a first demyelinating event. J Neurol Neurosurg Psychiatry2017; 88(5): 395–401.
52.
ChiuSWilliamsPTKraussRM.Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidemia: a randomized controlled trial. PLoS ONE2017; 12(2): e0170664.
53.
AzarySSchreinerTGravesJ, et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry2018; 89(1): 28–33.
54.
HoareSLithanderFvan der MeiI, et al. Higher intake of omega-3 polyunsaturated fatty acids is associated with a decreased risk of a first clinical diagnosis of central nervous system demyelination: Results from the Ausimmune study. Mult Scler2016; 22(7): 884–892.
55.
ZhangSM1WillettWCHernanMA, et al. Dietary fat in relation to risk of multiple sclerosis among two large cohorts of women. Am J Epidemiol2000; 152(11): 1056–1064.
56.
BjornevikKChitnisTAscherioA, et al. Polyunsaturated fatty acids and the risk of multiple sclerosis. Mult Scler2017; 23(14): 1830–1838.
57.
GianfrancescoMAAcunaBShenL, et al. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors. Obes Res Clin Pract2014; 8(5): e435–e437.
58.
ManouchehriniaAHedstromAKAlfredssonL, et al. Association of pre-disease body mass index with multiple sclerosis prognosis. Front Neurol2018; 9: 232.
59.
TorkildsenO1WergelandSBakkeS, et al. ω-3 fatty acid treatment in multiple sclerosis (OFAMS Study): A randomized, double-blind, placebo-controlled trial. Arch Neurol2012; 69(8): 1044–1051.
60.
DworkinRHBatesDMillarJH, et al. Linoleic acid and multiple sclerosis: A reanalysis of three double-blind trials. Neurology1984; 34(11): 1441–1445.
61.
SaresellaMMendozziLRossiV, et al. Immunological and clinical effect of diet modulation of the gut microbiome in multiple sclerosis patients: A pilot study. Front Immunol2017; 8: 1391.
62.
McDonaldJGravesJWaldmanA, et al. A case-control study of dietary salt intake in pediatric-onset multiple sclerosis. Mult Scler Relat Disord2016; 6: 87–92.
63.
FarezMFFiolMPGaitanMI, et al. Sodium intake is associated with increased disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry2015; 86(1): 26–31.
64.
FitzgeraldKCMungerKLHartungHP, et al. Sodium intake and multiple sclerosis activity and progression in BENEFIT. Ann Neurol2017; 82(1): 20–29.
65.
DossiDEChavesHHeckES, et al. Effects of systolic blood pressure on brain integrity in multiple sclerosis. Front Neurol2018; 9: 487.
66.
BanwellB1Bar-OrACheungR, et al. Abnormal T-cell reactivities in childhood inflammatory demyelinating disease and type 1 diabetes. Ann Neurol2008; 63(1): 98–111.
67.
MungerKL1ChitnisTFrazierAL, et al. Dietary intake of vitamin D during adolescence and risk of multiple sclerosis. J Neurol2011; 258(3): 479–485.
68.
SwankRLGoodwinJ.Review of MS patient survival on a Swank low saturated fat diet. Nutrition2003; 19(2): 161–162.
69.
YadavVMarracciGKimE, et al. Low-fat, plant-based diet in multiple sclerosis: a randomized controlled trial. Mult Scler Relat Disord2016; 9: 80–90.
70.
LeeJEBishtBHallMJ, et al. A multimodal, nonpharmacologic intervention improves mood and cognitive function in people with multiple sclerosis. J Am Coll Nutr2017; 36(3): 150–168.
71.
IrishAKEricksonCMWahlsTL.Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: A pilot study. Degener Neurol Neuromuscul Dis2017; 7: 1–18.
72.
ThomsenHLJessenEBPassaliM.The role of gluten in multiple sclerosis: A systematic review. Mult Scler Relat Disord2019; 27: 156–163.
73.
FitzgeraldKCVizthumDHenry-BarronB, et al. Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis. Mult Scler Relat Disord2018; 23: 33–39.
74.
BrentonJNBanwellBBergqvistAGC, et al. Pilot study of a ketogenic diet in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm2019; 6(4): e565.
75.
MarrieRARudickRHorwitzR, et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology2010; 74(13): 1041–1047.
76.
Katz SandIBennEKTFabianM, et al. Randomized-controlled trial of a modified Mediterranean dietary program for multiple sclerosis: A pilot study. Mult Scler Relat Disord2019; 36: 101403.
77.
RiccioPRossanoRLaroccaM, et al. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study. Exp Biol Med2016; 241(6): 620–635.
78.
SedaghatFJessriMBehroozM, et al. Mediterranean diet adherence and risk of multiple sclerosis: A case-control study. Asia Pac J Clin Nutr2016; 25(2): 377–384.
79.
MasulloLPapasMACotugnaN, et al. Complementary and alternative medicine use and nutrient intake among individuals with multiple sclerosis in the United States. J Community Health2015; 40(1): 153–160.
