The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review
Abstract
:1. Introduction
2. Nutritional Lifestyle as Risk Factor or Complementary Treatment for Patients with Multiple Sclerosis
2.1. Food-Derived Factors
2.2. Diets
2.2.1. Low-Carbohydrate Diets
2.2.2. Gluten-Free Diet (GFD)
2.2.3. Mediterranean Diet (MD)
2.2.4. Low-Fat Diet: Swank and McDougall Diets
2.2.5. Fasting-Mimicking Diets (FMD)
2.2.6. Western Diets (WD)
3. Clinical Impact of Exercise in Patients with Multiple Sclerosis
3.1. Biological and Radiological Modifications Induced by Physical Activity in EAE/MS
3.1.1. Pre-Clinical Studies
3.1.2. Clinical Studies
3.2. Recommendations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Food-Derived Factor | Molecular Mechanism Proposed | Benefits on PwMS | References |
---|---|---|---|
PUFAs | EPA improves EAE by reducing IFN-γ and IL-17 production, specifically in CNS lesions infiltrated by CD4 T cells, and it enhances PPARs. DHA reduces the expression of transcription factors in DCs for Th1 and Th17 differentiation as well as the mortality in mice with EAE | Omega-3 improve the metabolic profile, EDSS score, and reduces inflammatory markers such as MMP-9, TNF α, IL-1β, and IL-6 | [14,15,16,17] |
Food-Derived Factor | Molecular Mechanism Proposed | Benefits on PwMS | References |
---|---|---|---|
Luteolin | Suppress the migration of PMBCs in animal model and prevent disease relapses by influencing the monocytic GTPase activity. | Reduction of EAE severity with protective effect on chronic EAE. Dose-dependent anti-inflammatory effect by reducing IL-1β, TNF-α, and MMP-9. The therapy with IFN-β has a summation effect with that of luteolin. | [19,20] |
Baicalin | Reduces oxidative stress in myelin-producing cells through the Nrf2/HO-1 signaling pathway Reduces CNS inflammation by suppressing IL-17, IFN-γ, GM-CSF, IL1-β, IL-6, IL-1, and IL-23 | Improvement in the clinical score. Stopping baicalin results in recurrence of symptoms 7–8 days after the treatment. | [21,22] |
Curcumin | Improves EAE through inhibition of the STAT3-phosphorylation and reduction of IL-12 production from microglial cells In PMBCs, suppressed IFN-γ and increased IFN-β Reduced production of MMP-9 in human astrocytes. | A dose of 80 mg daily for six months in pwRRMS reduced pro-inflammatory pathways compared to control without improving EDSS score. It might potentially reduce BBB permeability ameliorating MS clinical manifestation. | [23,24,25,26,27] |
Resveratrol | In EAE, decreases the production of pro-inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-2, IL-9, IL-12, and IL-17), induces T regulatory cells, and decreases in a dose-depended manner the BBB disruption by reducing the loss of TJ components (e.g., claudin-5, occludin). Contrasts EAE development through suppression of the miRNA-124/SK1 pathway. Neuroprotection during optic neuritis in an EAE model by reducing axonal loss. | Although 150 mg daily resveratrol supplementation in association with vitamin D in pwMS showed a reduction in serum levels of MMP-9, it did not demonstrate an improvement in signs and symptoms | [28,29,30,31,32,33] |
Epigallocatechin gallate | Modulates GABAergic pathway. Improves EAE severity by reducing Th1 and Th17 cells. | It reduces IL-6, improving anxiety and depression. More in men than women, it improves the energy metabolism during exercise without any clinical and radiological effects | [34,35,36,37,38] |
Cocoa | Increases cerebral blood flow. Antioxidant properties alleviate lipid peroxidation and axon damage | Mild reduction in fatigue and fatigability | [39] |
Caffeine | In EAE after immunization with 10–30 mg/kg daily, caffeine reduces inflammatory cells in the spinal cord and neurological as well as IFN-γ production and disease severity. | An estimated amount of 250 to 300 mg caffeine intake (2–3 cups) improves fatigue and mental capacity, especially in patients with an EDSS higher than 0 but lower than 4 | [40,41,42] |
Alcohol | In EAE, male-specific disease remission induced potentially via gut microbiota modulation. | Not available | [43] |
Food-Derived Factor | Molecular Mechanism Proposed | Benefits on PwMS | References |
---|---|---|---|
Zinc | Medium dose (1.5 mg/kg) improves clinical score of EAE, suppressing T cell activation and pro-inflammatory cytokines, whereas high doses (6 mg/kg) lead to clinical worsening. | Zinc supplementation (220 mg zinc sulfate daily) is able to improve depression in MS patients without providing any benefit for movement disorders. | [44,45] |
Salt | High-sodium intake might inhibit the functions of Treg cells, promoting the shift to a Th1-like phenotype. High-salt intake induces EAE exacerbation through changes in microbiota and enhanced Th17 cells differentiation. High-salt intake might enhance corticosterone serum levels, allowing the expression of TJ molecules suppressing CNS autoimmunity. | Some authors reported that salt intake did not have a relationship with the course or brain MRI activity of MS, whereas other ones reported that high-sodium intake is associated with increased MS relapses and brain MRI activity. However, in pediatric onset MS, no associations between salt intake and pediatric onset MS risk or time to relapses were found. | [46,47,48,49,50,51,52] |
Food-Derived Factor | Molecular Mechanism Proposed | Benefits on PwMS | References |
---|---|---|---|
Vitamin D | In the EAE model, vitamin D3 suppresses Th17 and Th1 differentiation, enhancing the percentage of Treg cells. Reduces demyelination, incidence, and clinical score of EAE Increases the effectiveness of steroid therapy through mTORC1 inhibition.In EAE, high doses of vitamin D leading to hypercalcemia might promote T cells proliferation with clinical exacerbation | Vitamin D3 supplementation does not improve the depressive symptoms in MS. It enhances the response to some treatments for MS such as interferon-β | [60,61,62,63,64,65,66,67,68,69] |
Vitamin B1 | In EAE, vitamin B1 deficiency causes Th1 and Th17 spinal cord infiltration | PwMS with reduced vitamin B1 levels and depression might benefit from supplementation (potential role in fatigue severity improvement) | [70,71,72] |
Vitamin B3 | Potentiates beneficial effects on monocytes and macrophages in promoting remyelination in CNS aging | No data available | [73] |
Vitamin B7 | It promotes myelin synthesis, and it reduces axon hypoxia in MS | Some authors reported benefits in worsening EDSS score in patients with progressive MS High doses might increase the risk of relapses | [74,75,76] |
Vitamin A | Antioxidant | It might improve fatigue and depression during interferon therapy | [77] |
Vitamin E | Hippocampal remyelination, and it suppresses INF-γ production and delays EAE progression | Not available | [78,79] |
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Fanara, S.; Aprile, M.; Iacono, S.; Schirò, G.; Bianchi, A.; Brighina, F.; Dominguez, L.J.; Ragonese, P.; Salemi, G. The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review. Nutrients 2021, 13, 3774. https://doi.org/10.3390/nu13113774
Fanara S, Aprile M, Iacono S, Schirò G, Bianchi A, Brighina F, Dominguez LJ, Ragonese P, Salemi G. The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review. Nutrients. 2021; 13(11):3774. https://doi.org/10.3390/nu13113774
Chicago/Turabian StyleFanara, Salvatore, Maria Aprile, Salvatore Iacono, Giuseppe Schirò, Alessia Bianchi, Filippo Brighina, Ligia Juliana Dominguez, Paolo Ragonese, and Giuseppe Salemi. 2021. "The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review" Nutrients 13, no. 11: 3774. https://doi.org/10.3390/nu13113774
APA StyleFanara, S., Aprile, M., Iacono, S., Schirò, G., Bianchi, A., Brighina, F., Dominguez, L. J., Ragonese, P., & Salemi, G. (2021). The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review. Nutrients, 13(11), 3774. https://doi.org/10.3390/nu13113774