Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications
Brain Commun. 2022 Jun 30;4(4):fcac171. doi: 10.1093/braincomms/fcac171. eCollection 2022.
Manon Galoppin 1, Saniya Kari 2, Sasha Soldati 3, Arindam Pal 3, Manon Rival 1, Britta Engelhardt 3, Anne Astier 2, Eric Thouvenot 1
Vitamin D dose response chart (for low doses)
Vitamin D deficiency has been associated with the risk of multiple sclerosis, disease activity and progression. Results from in vitro experiments, animal models and analysis of human samples from randomized controlled trials provide comprehensive data illustrating the pleiotropic actions of Vitamin D on the immune system. They globally result in immunomodulation by decreasing differentiation of effector T and B cells while promoting regulatory subsets. Vitamin D also modulates innate immune cells such as macrophages, monocytes and dendritic cells, and acts at the level of the blood-brain barrier reducing immune cell trafficking. Vitamin D exerts additional activity within the central nervous system reducing microglial and astrocytic activation. The immunomodulatory role of Vitamin D detected in animal models of multiple sclerosis has suggested its potential therapeutic use for treating multiple sclerosis. In this review, we focus on recent published data describing the biological effects of Vitamin D in animal models of multiple sclerosis on immune cells, blood-brain barrier function, activation of glial cells and its potential neuroprotective effects. Based on the current knowledge, we also discuss optimization of therapeutic interventions with Vitamin D in patients with multiple sclerosis, as well as new technologies allowing in-depth analysis of immune cell regulations by vitamin D.
VitD therapy in multiple sclerosis patients (clipped from PDF)
Despite all previous data about the potential immunological regulation and neuroprotective effects of VitD in multiple sclerosis models and multiple sclerosis patients, controversial results have been obtained from clinical trials evaluating VitD supplementation in multiple sclerosis patients. Kimball et al. evaluated tolerance and safety of escalating doses of active VitD ranging from 28 000 to 280 000 IU/week in an open-label study including 12 RRMS patients over a total of 28 weeks.172 Despite final mean serum concentrations of 25(OH)D of 386 ± 157 nmol/l, they did not observe any severe adverse events (SAEs) on this very small cohort. Since then, several SAEs (e.g. severe gastric symptoms, pseudobrain tumour and seizures, tonic-clonic seizures, severe hypercalcemia) were observed at extremely high doses (100 000 IU/day for 1-36 months), suggesting that excessive supplementation with VitD can be dangerous despite a plateau concentration close to 400 nmol/l and that treatment duration might play a role in VitD toxicity.268 Moreover, little is known about the immunological effects of very high levels of circulating VitD. In animal models, the higher VitD dose, the higher immunomodulatory effect is generally observed,
although excessive VitD treatment achieving serum levels over 250 nmol/L resulted in pro-inflammatory effects through lymphocyte activation and demyelination and myeloid infiltration into the brain, in addition to perturbations of phosphocalcic homeostasis.269
Since the original study by Mahon et al. in 2003, we identified more than 20 published case-control studies and double-blind RCTs aiming at evaluating the potential clinical and radiological benefits of VitD supplementation in multiple sclerosis patients.47,81-94,171,173,270-276 Some of these were recently reviewed and showed limited improvement in multiple sclerosis clinical and/or MRI features including fatigue, expanded disability status scale, relapses, T2-lesions, non-evidence of disease activity (NEDA-3) and in retinal nerve fibre layer thickness.21,277 These trials also evaluated safety of VitD supplementation at more physiological dosages (<15 000 IU/day) and did not observe a significant increase of AEs or SAEs in VitD-treated groups compared with placebo groups (CHOLINE,275 SOLAR171). Importantly, phosphocalcic homeostasis seemed respected at this level of supplementation, as no cases of calciuria and hypercalcemia were observed (SOLAR).
The safety range of VitD levels has been defined by an expert consensus in 2010 as of 30-100 ng/ml (equivalent to 75-250 nmol/l), considering that in healthy subjects who have spent prolonged periods in a sunny environment, measured 25(OH)D concentrations rarely exceed 100 ng/ml.278 In populations with light skin frequently exposed to the sunlight, the upper limit of circulating VitD levels is located between 75 and 150 nmol/l, providing an optimal range to reach after VitD supplementation, as defined by experts of bone and calcium homeostasis in order to prevent osteoporosis and fractures.279 However, so far, there are no recommendations for multiple sclerosis patients on potential VitD supplementation to achieve optimal levels for immune modulation and clinical effect.
In order to define VitD dosing to achieve optimal VitD therapeutic range after supplementation, we analysed 24 therapeutic trials accounting for 742 treated patients and providing their final VitD levels. When plotting the time of exposure with the daily dose of VitD supplementation of the treated group, we observed that protocols were very heterogeneous with treatment duration ranging from 2 to 24 months and dosages ranging from 1000 to 20 000 UI/day (Fig. 5A). However, we observed a strong correlation between the daily dose and the final circulating VitD levels of treated patients (Spearman r = 0.803, P < 0.0001, Fig. 5B), indicating that a daily dose of VitD between 3000 and 11 000 IU for 3-24 months achieves final blood VitD levels within the 75-150 nmol/l recommended range (red dots, Fig. 5A and 
. Even at the higher doses used in the SOLAR study171 where patients received 14 000 Ul/day for 12 months, VitD levels above 200 nmol/l were obtained without occurrence of SAEs after 1 year. This potentially increases the safety of higher VitD supplementation reaching up to 250 nmol/l for short periods. However, the exact concentrations of VitD in multiple sclerosis needed to properly restore immune homeostasis over the long term remains to be determined as well as the optimal risk/benefit balance for VitD supplementation. Given the weak clinical and radiological effects of VitD treatment in short-term RCTs involving multiple sclerosis patients, further analysis of the in vivo immunological efficacy ofVitD are warranted to refine the objectives of chronic VitD supplementation in multiple sclerosis patients.
Download the PDF from VitaminDWiki
>50,000 MSers successfully treated by ~90,000 IU daily in combination with other things
VitaminDWiki - Overview MS and vitamin D contains
Clinical interventions have shown that Vitamin D can prevent, treat, and even cure Multiple Sclerosis, at a tiny fraction of the cost of the drugs now used to treat it, and without side effects.
- Fact: Low Vitamin D results in higher risk of getting MS
Increase latitude leads to decreased Vitamin D, which leads to increased risk of MS
Dark skinned people are far more likely to get MS (dark skin people typically have low vitamin D)
Elderly (who typically have low vitamin D) are more likely to get MS
Is there increased risk in people who already have diseases associated with low vitamin D - TB, for example ? ? ?
Women typically have 3X increased MS risk then men (note: women typically have 20% lower levels of vitamin D than men)
Exception: women in very sunny climates and dark-skinned women have the same MS risk as men
Obese are 60% more likely to get MS
Multiple Sclerosis 42X more likely if light brown skin and smoke (both associated with low vitamin D) – July 2020
MS recurrence is much higher in spring - the lowest time of the year for vitamin D
increase in clouds/rainfall (which reduces available Vitamin D) is associated with increased risk of MS (Scotland, Western Washington)
MS incidence has increased 70% in a decade while the incidence of vitamin D deficiency doubled
Less MS in those with outdoor occupations PDF file, not a web page - Fact: MS uses up Vitamin D
- Fact: Lower vitamin D (due to MS using up Vitamin D while fighting the disease) results in many other health problems (such as broken bones), so depleted vitamin D levels must be restored.
- Fact: Vitamin D looks so promising for preventing and treating MS that there were 25 INTERVENTION clinical trials as of Feb 2014
- Fact: Vitamin D reduced the MS relapse rate far better than Fingolimod which is now used for that purpose.
- Note: Fingolimod costs $25,000/year while vitamin D, which works better and has no side effects is 1000 times less expensive.
- Fact: 98% of the genes affected by Interferon are also affected by Vitamin D
- Note: 1 week of Interferon = $4,700, 1 week of vitamin D 10,000X lower cost
- Fact: MS Doctors in Brazil recommending 40-100 ng/mL of Vitamin D
- Fact: Many MS forums are recommending vitamin D to treat MS, with some taking 5,000 to 10,000 IU daily
Observation: Risk of going from pre-MS to MS reduced 68 percent with 7100 IU vitamin D – RCT Dec 2012- This is an observation instead of a fact - it has not yet been confirmed.
- Fact: VERY LARGE doses of vitamin D have CURED 2,000 people of MS in Brazil
- Controversy: UVB fron sunlight or UVB bulb may be BETTER than Vitamin D for reducing the risk of getting MS
- Hypothesis: In addition to Vitamin D there are many other photoproducts produced by UVB that may promote health.
Summary: lack of consensus on how much to prevent, treat, or cure MS.
- How much Vitamin D to prevent many diseases - such as MS
- How much Vitamin D is needed to treat MS? There is currently no agreement
The recommendations range from 40 to 100 ng - which can result of a dose ranging from 3,000 to 20,000 IU/day - How Vitamin D is needed to Cure MS?: It appears that 20,000-140,000 IU daily may be needed to CURE the disease
You must be under the supervision of a doctor who knows what to watch for in your individual situation.
High doses of Vitamin D cannot be used as a monotherapy.
You will need to adjust the cofactors: Typically increasing Magnesium and Vitamin K2, and reducing Calcium intake.
Your doctor will monitor these and might increase your intake of Vitamins B2, C, as well as Omega-3899 - Epstein-Barr virus increases risk of Multiple Sclerosis by 32X - Jan 2022
- Multiple Sclerosis treated by Vitamin D, recommends investigating high dose Coimbra - Oct 2021
- Multiple Sclerosis patients had fewer COVID-19 problems (Note: many MSers take Vitamin D) – April 30, 2021
- Vitamin D Resistance hypothesis confirmed by Coimbra high-dose vitamin D protocol – April 2021
- Multiple Sclerosis relapses cut in half by 100,000 IU of Vitamin D every 2 weeks– RCT 2019
VitaminDWiki - Multiple Sclerosis and (lots of) Vitamin D - book by patient on Coimbra protocol - Feb 2016 contains protocol
Vitamin D Protocol used by Dr. Coimbra for Multiple Sclerosis etc.
Snips as of April 2016 http://www.vitamindprotocol.com/dr.-coimbra-s-ms-protocol.html
- 1,000 IU's vitamin D per kilogram as a first approximation
(apparently increased/decreased depending of resulting vitamin D blood level) - Vitamin B2, magnesium glycinate, boron, chromium picolinate, Omega 3 DHA, Zinc, Methylcobalamin form of B12, Choline, etc.
- Lack of B12 may affect 10%–15% of the general population and may be the most prevalent genetic risk factor for several human diseases
- Discontinue eating or drinking dairy products or calcium enriched foods or beverages, also no Ca supplements
- Drink as least 2.5 liters [85 ounces] of fluids, preferably water
- Required Tests: Vitamin D, Parathyroid, Blood calcium, urinary calcium
VitaminDWiki - Multiple Sclerosis 32 percent less likely among those with more than 32 ng of vitamin D – Dec 2019
- Overview MS and vitamin D
- An opportunity - use Vitamin D to treat Multiple Sclerosis (has been used for 14 years) - Feb 2022
- Multiple Sclerosis treated when use high doses of vitamin D – meta-analysis May 2018
- Multiple Sclerosis: 10 percent fewer relapses for each 10 ng higher level of vitamin D – Meta-analysis April 2020
- Multiple Sclerosis: number needed to treat with vitamin D may be as low as 1.3 – Meta-analysis Oct 2013
- Multiple Sclerosis more likely if poor vitamin D genes - 22nd study – Aug 2017
- Multiple Sclerosis relapses cut in half by 100,000 IU of Vitamin D every 2 weeks– RCT 2019
UV and Sunshine reduces MS risk
- Multiple Sclerosis 2X more likely if low winter UV – June 2018
- Multiple Sclerosis half as likely if get plenty of sunshine (not a news item) – March 2018
Other things also help
- Multiple Sclerosis treated by 50,000 IU Vitamin D bi-weekly plus Omega-3 – RCT July 2018
- Multiple Sclerosis 40 percent less likely if consume tinned fish (Vitamin D and Omega-3) – Sept 2019
- Resveratrol treats Multiple Sclerosis and other autoimmune diseases – many studies
- Not a single case of multiple sclerosis in 15,000,000 people (plant-based diets)
High Dose Vitamin D and cofactors
- Coimbra protocol using high-dose Vitamin D is safe – April 2022
- The use of high dose Vitamin D (Coimbra Protocol) for multiple sclerosis in Germany – 2019
- Comparing High-dose vitamin D therapies MS and other health problems
Number of MS studies which are also in other categories
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22 studies in Genetics - genes can restrict Vitamin D getting to the blood and to the cells 12 studies in Vitamin D Receptor - gene which restricts D from getting to the cells 7 studies in Vitamin D Binding Protein - gene which restricts D from getting to the cells 21 studies in Ultraviolet light - may be even better than Vitamin D in preventing and treating MS 9 studies in Omega-3 - which helps Vitamin D prevent and treat MS Printer Friendly Follow this page for updates2849 visitors, last modified 11 Jul, 2022,