Poor Vitamin D Receptor increases the risk of Multiple Sclerosis in people of European descent – Feb 2024

Evidence supports a causal association between allele-specific vitamin D receptor binding and multiple sclerosis among Europeans

PNAS 121 (8) https://doi.org/10.1073/pnas.2302259121 PDF is behind a paywall
Cameron Adams, Ali Manouchehrinia, Hong L. Quach, +6, and Lisa F. Barcellos lbarcellos at berkeley.edu

There is evidence for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels and multiple sclerosis (MS), but the underlying mechanisms are unknown. We conducted a Mendelian Randomization study to estimate causal associations between vitamin D receptor (VDR) binding at a locus and MS susceptibility using genetic instrumental variables constructed from variants previously associated with allele-specific VDR-binding (VDR-binding variant; VDR-BV) and serum 25(OH)D. Two VDR-BV (rs2881514; rs2531804) were independently associated with MS and rs2881514 demonstrated significant interaction with 25(OH)D, providing evidence for a causal association between rs2881514 and MS. Our results demonstrate that genetic variation in individual VDR binding sites contributes to MS and are relevant to other autoimmune diseases for which a role for vitamin D has been implicated.

Abstract
Although evidence exists for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels, and multiple sclerosis (MS), the role of variation in vitamin D receptor (VDR) binding in MS is unknown. Here, we leveraged previously identified variants associated with allele imbalance in VDR binding (VDR-binding variant; VDR-BV) in ChIP-exo data from calcitriol-stimulated lymphoblastoid cell lines and 25(OH)D serum levels from genome-wide association studies to construct genetic instrumental variables (GIVs). GIVs are composed of one or more genetic variants that serve as proxies for exposures of interest. Here, GIVs for both VDR-BVs and 25(OH)D were used in a two-sample Mendelian Randomization study to investigate the relationship between VDR binding at a locus, 25(OH)D serum levels, and MS risk. Data for 13,598 MS cases and 38,887 controls of European ancestry from Kaiser Permanente Northern California, Swedish MS studies, and the UK Biobank were included. We estimated the association between each VDR-BV GIV and MS. Significant interaction between a VDR-BV GIV and a GIV for serum 25OH(D) was evidence for a causal association between VDR-BVs and MS unbiased by pleiotropy. We observed evidence for associations between two VDR-BVs (rs2881514, rs2531804) and MS after correction for multiple tests. There was evidence of interaction between rs2881514 and a 25(OH)D GIV, providing evidence of a causal association between rs2881514 and MS. This study is the first to demonstrate evidence that variation in VDR binding at a locus contributes to MS risk. Our results are relevant to other autoimmune diseases in which vitamin D plays a role.

Vitamin D Life - 12 studies in both categories MS and VDR

This list is automatically updated

Vitamin D Life – 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
  
  
  There is less of an effect recently - air conditioning now allows people to stay indoors

  
  
  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: Increasing levels of Vitamin D is associated with lower MS risk, as well as lower risk of many other diseases

  
• 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

Vitamin D Life – 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

• 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

Vitamin D Life – Vitamin D Receptor is associated in over 58 autoimmune studies

Vitamin D Life - The risk of 50+ diseases at least double with poor Vitamin D Receptor

Vitamin D Life - 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 Vitamin D Life uses 10 of the 16 known VDR activators

How does the incidence of multiple sclerosis vary with race?

Large Language Model conclusion to question:
The incidence of MS varies significantly by race and ethnicity, with whites of European ancestry historically being the most affected. However, recent studies have shown an increasing incidence among African Americans and unique disease characteristics and progression in African Americans and Hispanics:
full response by Perplexity Feb 2024