Resveratrol treats Multiple Sclerosis and other autoimmune diseases – many studies

Resveratrol, Vitamin D and Omega-3 should synergistically treat Multiple Sclerosis
A few recent Vitamin D and MS studies

• Multiple Sclerosis treated when use high doses of vitamin D – meta-analysis May 2018
• Multiple Sclerosis 32 percent less likely among those with more than 32 ng of vitamin D – Dec 2019
• Multiple Sclerosis and Omega-3 – eight studies as of Aug 2019
• Multiple Sclerosis Society continues to fund Vitamin D research -Oct 2018
• Sugary drinks associated with 5X worse Multiple Sclerosis (reduces vitamin D levels)– March 2019

Dr. Coimbra Protocol for MS - High dose Vitamin D, Omega-3, Magnesium, etc

• Vitamin D has treated Multiple Sclerosis and autoimmune diseases for 16 years – Coimbra April 2018
• Multiple Sclerosis - Coimbra Protocol (high-dose Vitamin D) - by one of the 120 doctors of 20,000 patients - Dec 2018
• Successful high dose vitamin D (Coimbra Protocol) should be evaluated – June 2019

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Resveratrol improves health (Vitamin D receptor, etc.) - many studies

Has the following

• The Vitamin D Receptor can restrict how much of the Vitamin D in the blood actually gets to cells
• Resveratrol is one of 14+ ways to negate the Vitamin D Receptor restrictions
• Resveratrol is produced by several plants in response to injury or, when the plant is under attack by pathogens such as bacteria or fungi
• Benefits of Resveratrol, like Vitamin D, appear to be increased when used with other things
  • Quercetin and Curcumin in the case of Resveratrol

18 articles in both of the categories Resveratrol and Vitamin D Receptor

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VitaminDWiki - Vitamin D Receptor activation can be increased in many ways

Resveratrol,  Omega-3,  Magnesium,  Zinc,   Quercetin,   non-daily Vit D,  Curcumin,   Berberine,  intense exercise, Butyrate   Sulforaphane   Ginger,   Essential oils, etc  Note: The founder of VitaminDWiki uses 10 of the 16 known VDR activators

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Resveratrol (50 mg/kg) blocked blood-brain barrier of mice from getting MS (EAE) – Nov 2016

Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice.
J Neurophysiol. 2016 Nov 1;116(5):2173-2179. doi: 10.1152/jn.00510.2016
Wang D1, Li SP1, Fu JS1, Zhang S2, Bai L1, Guo L3.



The mouse autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), is primarily characterized as dysfunction of the blood-brain barrier (BBB). Resveratrol exhibits anti-inflammatory, antioxidative, and neuroprotective activities. We investigated the beneficial effects of resveratrol in protecting the integrity of the BBB in EAE mice and observed improved clinical outcome in the EAE mice after resveratrol treatment. Evans blue (EB) extravasation was used to detect the disruption of BBB. Western blot were used to detected the tight junction proteins and adhesion molecules zonula occludens-1 (ZO-1), occludin, ICAM-1, and VCAM-1. Inflammatory factors inducible nitric oxide synthase (iNOS), IL-1β, and arginase 1 were evaluated by quantitative RT-PCR (qPCR) and IL-10 by ELISA. NADPH oxidase (NOX) levels were evaluated by qPCR, and its activity was analyzed by lucigenin-derived chemiluminescence. Resveratrol at doses of 25 and 50 mg/kg produced a dose-dependent decrease in EAE paralysis and EB leakage, ameliorated EAE-induced loss of tight junction proteins ZO-1, occludin, and claudin-5, as well as repressed the EAE-induced increase in adhesion proteins ICAM-1 and VCAM-1. In addition, resveratrol suppressed the EAE-induced overexpression of proinflammatory transcripts iNOS and IL-1β and upregulated the expression of anti-inflammatory transcripts arginase 1 and IL-10 cytokine in the brain. Furthermore, resveratrol downregulated the overexpressed NOX2 and NOX4 in the brain and suppressed NADPH activity. Resveratrol ameliorates the clinical severity of MS through maintaining the BBB integrity in EAE mice.
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Resveratrol (250 mg/kg) Promotes Remyelination in mice MS (EAE) – 2017

Resveratrol Promotes Remyelination in Cuprizone Model of Multiple Sclerosis: Biochemical and Histological Study.
Mol Neurobiol. 2017 Jul;54(5):3219-3229. doi: 10.1007/s12035-016-9891-5
Ghaiad HR1, Nooh MM2, El-Sawalhi MM2, Shaheen AA2.

Multiple sclerosis (MS) is a demyelinating neurodegenerative disease, representing a major cause of neurological disability in young adults. Resveratrol is a stilbenoid polyphenol, known to pass blood brain barrier and exhibit antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. Cuprizone model of MS is particularly beneficial in studying demyelination/remyelination. Our study examined the potential neuroprotective and pro-remyelination effects of resveratrol in cuprizone-intoxicated C57Bl/6 mice. Mice were fed with chow containing 0.7 % cuprizone for 7 days, followed by 3 weeks on 0.2 % cuprizone diet. Resveratrol (250 mg/kg/day, p.o.) was given for 3 weeks starting from the second week. At the end of the experiment, animals were tested on rotarod to evaluate changes in balance and motor coordination. Mice were then sacrificed to measure the brain content of glutathione, lipid peroxidation products, adenosine triphosphate, and phospho-inhibitory subunit of nuclear factor κB-α. The activities of cytochrome oxidase and superoxide dismutase were also assessed. The gene expression of myelin basic protein, 2',3'-cyclic nucleotide 3' phosphodiesterase, oligodendrocyte transcription factor-1 (Olig1), NF-κB p65 subunit, and tumor necrosis factor-α was also estimated. Luxol fast blue/periodic acid-Schiff stained brain sections were blindly scored to assess the myelin status. Resveratrol effectively enhanced motor coordination and balance, reversed cuprizone-induced demyelination, improved mitochondrial function, alleviated oxidative stress, and inhibited NF-κB signaling. Interestingly, resveratrol increased Olig1 expression that is positively correlated to active remyelination. The present study may be the first to indicate a pro-remyelinative effect for resveratrol which might represent a potential additive benefit in treating MS.

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MS supplements 2018 (resveratrol not in abstract)

Use of Vitamins and Dietary Supplements by Patients With Multiple Sclerosis: A Review.
JAMA Neurol. 2018 Aug 1;75(8):1013-1021. doi: 10.1001/jamaneurol.2018.0611.
Evans E1, Piccio L1, Cross AH1.

IMPORTANCE:
Surveys of patients with multiple sclerosis report that most are interested in modifying their diet and using supplements to potentially reduce the severity and symptoms of the disease. This review provides an updated overview of the current state of evidence for the role that vitamins and dietary supplements play in multiple sclerosis and its animal models, with an emphasis on recent studies, and addresses biological plausibility and safety issues.

OBSERVATIONS:
Several vitamins and dietary supplements have been recently explored both in animal models and by patients with multiple sclerosis. Most human trials have been small or nonblinded, limiting their generalizability. Biotin and vitamin D are currently being tested in large randomized clinical trials. Smaller trials are ongoing or planned for other supplements such as lipoic acid and probiotics. The results of these studies may help guide clinical recommendations.

CONCLUSIONS AND RELEVANCE:
At the present time, the only vitamin with sufficient evidence to support routine supplementation for patients with multiple sclerosis is vitamin D. Vitamin deficiencies should be avoided. It is important for clinicians to know which supplements their patients are taking and to educate patients on any known efficacy data, along with any potential medication interactions and adverse effects of individual supplements. Given that dietary supplements and vitamins are not subject to the same regulatory oversight as prescription pharmaceuticals in the United States, it is recommended that vitamins and supplements be purchased from reputable manufacturers with the United States Pharmacopeia designation.

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Resveratrol protects mice from MS (EAE) - 2012

Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis
Front. Neurol., 24 May 2012 | https://doi.org/10.3389/fneur.2012.00084
Zoe Fonseca-Kelly†, Mayssa Nassrallah†, Jorge Uribe, Reas S. Khan, Kimberly Dine, Mahasweta Dutt and Kenneth S. Shindler*
Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Scheie Eye Institute, Philadelphia, PA, USA

Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for MS.
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Resveratrol made EAE MS WORSE in mice - 2013

Resveratrol Exacerbates Both Autoimmune and Viral Models of Multiple Sclerosis
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44 Google Scholar citations of this study as of Dec 2019
   More recent studies appear to not agree
The effect of emerging nutraceutical interventions for clinical and biological outcomes in multiple sclerosis: a systematic review - 2019
Neuroprotective natural products against experimental autoimmune encephalomyelitis: A review - 20119
The role of flavonoids in autoimmune diseases: therapeutic updates = 2019
Use of vitamins and dietary supplements by patients with multiple sclerosis: a review - 2018 JAMA
Antiviral activity of resveratrol against human and animal viruses - 2015 Free PDF
“Disease modifying nutricals” for multiple sclerosis - 2015

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MS supplements pilot study resveratrol did not help (only used 150 mg) – March 2018

Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study.
Exp Biol Med (Maywood). 2016 Mar;241(6):620-35. doi: 10.1177/1535370215618462
Riccio P1, Rossano R2, Larocca M2, Trotta V2, Mennella I3, Vitaglione P3, Ettorre M4, Graverini A5, De Santis A5, Di Monte E6, Coniglio MG6.

The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status.
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