Multiple Sclerosis is associated with low vitamin D via 24 paths – Nov 2024

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Association between 25(OH) vitamin D and multiple sclerosis: cohort, shared genetics, and Causality

Nutr J. 2024 Nov 30;23(1):151. doi: 10.1186/s12937-024-01059-4.
Xing-Hao Yu # 1 2 3 4 5, Hui-Min Lu # 6, Jun Li 1 2 7, Ming-Zhu Su 1 8, Xiao-Min Li 9 10 11, Yi Jin 12 13 14

Background: Multiple Sclerosis (MS), an autoimmune disorder causing demyelination and neurological damage, has been linked to 25-hydroxyvitamin D (25OHD) levels, suggesting its role in immune response and MS onset. This study used GWAS datasets to investigate genetic associations between 25OHD and MS.

Methods: We utilized a large-scale prospective cohort to evaluate serum 25OHD levels and MS risk. Linkage Disequilibrium Score Regression (LDSC) assessed genetic correlations between 25OHD levels and MS. Cross-trait genome-wide pleiotropy analysis revealed shared genetic loci. MAGMA analysis identified pleiotropic genes, enriched tissues, and gene sets. Stratified LDSC estimated tissue-specific and cell-specific heritability enrichment, and multi-trait co-localization analysis identified shared immune cell subsets. Bidirectional Mendelian Randomization (MR) assessed the causal association between 25OHD and MS risk.

Results: The observational study found a nonlinear relationship between 25OHD levels and MS risk, with the lowest quartile showing significant risk elevation. Our findings revealed shared genetic structure between 25OHD levels and MS, suggesting a common biological pathway involving immune function and CNS integrity.

We found 24 independent loci shared between 25OHD levels and MS risk, enriched in brain tissues and involved in pathways like LDL, HDL, and TG metabolism. Four loci (6p24.3, 6p22.2, 12q14.1, and 19p13.2) had strong co-localization evidence, with mapped genes as potential drug targets. Bidirectional MR analysis supported a causal effect of 25OHD levels on MS risk, suggesting 25OHD supplementation could modulate MS risk.

Conclusion: This study reveals the complex relationship between 25OHD levels and MS, indicating that higher levels are not always advantageous and recommending moderation in supplementation. We identified SMARCA4 as a potential therapeutic target and detailed key pathways influencing this interaction.
 Download the PDF from VitaminDWiki

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VitaminDWiki - 14 studies in both categories Multiple Sclerosis and the Vitamin D Receptor

This list is automatically updated

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Wonder how the study missed the very important Vitamin D Receptor gene

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VitaminDWiki - CYP24A1 enzyme and Vitamin D - many studies

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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

• 22 studies in Genetics - genes can restrict Vitamin D getting to the blood and to the cells
• 14 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