Gene variants can reduce Vitamin D response by 1.7X (14,000 IU daily, Multiple Sclerosis) – Dec 2021

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Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis

PLoS ONE 16(12): e0261097. https://doi.org/10.1371/journal. pone.0261097
Mimpen M, Rolf L, Poelmans G, van den Ouweland J, Hupperts R, Damoiseaux J, etal.

Low Response: Vitamin D Binding Protein

High Response: CYP27B1
  Note : very few people with MS seem to have the G/G form

A poor 25-hydroxyvitamin D (25(OH)D) status is a much replicated risk factor for developing multiple sclerosis (MS), and several vitamin D-associated single nucleotide polymorphisms (SNPs) have been associated with a higher risk of MS. However, studies on the benefit of vitamin D supplementation in MS show inconclusive results. Here, we explore whether vitamin D-associated SNPs and MS risk alleles confound serological response to vitamin D supplementation.

Methods
34 participants from the SOLARIUM study consented to genotyping, of which 26 had vitamin D data available. The SOLARIUM study randomised relapsing-remitting MS patients to placebo or 14,000 IU vitamin D3 for 48 weeks. Participants were categorised as either ‘carriers’ or ‘non-carriers’ of the risk allele for 4 SNPs: two related to D binding protein (DBP) and associated with lower 25(OH)D levels (rs4588 and rs7041), and two related to vitamin D metabolism enzymes CYP27B1 and CYP24A1 and associated with a higher risk of MS (rs12368653; rs2248359, respectively). 25(OH)D levels were determined at baseline and after 48 weeks.

Results
The DBP-related SNPs showed no difference in 25(OH)D status at baseline, but carriers of the rs7041 risk allele showed lower 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 224.2 vs. 332.0 nmol/L, p = 0.013). For CYP related SNPs, neither showed a difference at baseline, but carriers of the rs12368653 risk allele showed higher 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 304.1 vs. 152.0 nmol/L, p = 0.014).

Discussion
Vitamin D-related SNPs affect the serological response to high-dose vitamin D supplementation. The effects on more common doses of vitamin D, as well as the clinical consequence of this altered response, need to be investigated further.
 Download the PDF from VitaminDWiki

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VitaminDWiki - Genetics category

332 articles in the Genetics category

see also

• Vitamin D Receptor has 513 items
• Vitamin D Binding Protein = GC has 176 items
• CYP27B1 has 60 items
• CYP24A1 in title of 34+ items
• CYP2R1 25+ items
• Calcidiol has 46 items
• Calcitriol has 56 items
• Topical Vitamin D
• Nanoemulsion Vitamin D may be a substantially better form
• 1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
• CYP3A4 (7 as of Dec 2022)
• Getting Vitamin D into your body
• 

Vitamin D blood test misses a lot

• Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
• Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
• A Vitamin D test in cells rather than blood was feasible (2017 personal communication)   Commercially available 2019
  • However, test results would vary in each tissue due to multiple genes
• Good clues that Vitamin D is being restricted from getting to the cells
  1) A vitamin D-related health problem runs in the family

    especially if it is one of 51+ diseases related to Vitamin D Receptor

+2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase) +3) DNA and VDR tests - 120 to 200 dollars $100 to $250 +4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)

   Genes are good, have enough Magnesium, etc.

+4) Back Pain

   probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc

• The founder of VitaminDWiki took action with clues #3&4

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VitaminDWiki - CYP27B1 category

The CYP27B1 gene activates Vitamin D in the Kidney,    Skin,    Lungs,    Brain,   Eyes   Breasts   etc.
Poor CYP27B1 is assocated with COVID, Miscarriage,   Lupus,   Alz, Parkinson, MSA,   Rickets

CYtochrome P450 family 27 subfamily B member 1    = 25-Hydroxyvitamin D3 1-alpha-hydroxylase

• 60 items in CYP27B1 category
• 332 articles in the Genetics
• 513 articles in Vitamin D Receptor
• 176 articles in Vitamin D Binding Protein
• CYP27B1 and other genes are less activated in seniors
• CYP27B causes many health problems – March 2020
• Every Parkinson’s brain had a poor CYP27B1 gene

What can be done if have a poor CYP27B1

• Larger doses of Vitamin D
• More Bio-available: Gut-friendly form, Topical form, taken with fatty meal, taken with evening meal
• Additional sources: UV
• Increase Vitamin D metabolism: additional Magnesium, Omega-3
  • All cytochrome P450 enzymes require Mg++ as a cofactor
• Increase the amount of Vitamin D in the blood that gets to cells: increase activation of VDR
  • See: Reasons for low response to vitamin D

Vitamin D blood test misses CYP27B1 and other genes

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VitaminDWiki - Vitamin D Binding Protein category listing has 176 items

Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,

• GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
• The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
• The actual D getting to the cells is a function of measured D and all 4 genes
• There is >2X increase in 8+ health problems if have poor VDBP (GC)
• It appears that VDBP only blocks oral vitamin D,
  • but NOT Vitamin D from sun, UV, topical or inhaled (tissue activated)
  • A clue: - Vitamin D from UV is 2X better for MS than oral Vitamin D

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VitaminDWiki - Vitamin D Binding Protein increases risk of some health problems

Increased Risk	Health Problem
11 X	Preeclampsia
6.5X	T1D in SA Blacks
6 X	Food Allergy
5 X	PTSD
4 X, 5X	Kidney Cancer
4 X	Poor Response to Oral Vitamin D
3 X	Ear infection
2.8 X	MS
2 X	Colorectal Cancer
2 X	Prostate Cancer -in those with dark skins
1.3 X	Infertility

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VitaminDWiki - Some diseases reduce vitamin D getting to blood or cells

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