Neuro problems (AD, PD, MSA) associated with poor vitamin D genes (CYP27A1, CYP27B1) – Sept 2022

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Role of cytochrome P450 for vitamin D metabolisms in patients with neurodegenerative disorders

Clinical Parkinsonism & Related Disorders Volume 7, 2022, 100162 https://doi.org/10.1016/j.prdoa.2022.100162
AsakoKakimotoabHiromuOguraaMidoriSuenagacTakayasuMishimaaShinsukeFujiokaaShinjiOumaaYoichiMatsunagaa YoshioTsuboia

Highlights

• Low serum concentrations of CYP27A1 in AD, PD and MSA patients.
• Low serum concentrations of CYP27B1 in MSA patients.
• Serum P450 concentrations affect VD metabolites in neurodegenerative disorders.

Introduction
We previously reported lower serum 25-hydroxyvitamin D concentrations in patients with Alzheimer’s disease (AD), Parkinson’s disease (PD) and Multiple system atrophy (MSA) compared to healthy controls (HC), whereas 1,25-di-hydroxyvitamin D levels were solely lower in MSA patients. We investigate serum concentrations of P450 involved in Vitamin D(VD) hydroxylation to clarify the responsible hydroxylase for the low serum concentrations of VD metabolites.

Methods
A total of 79 individuals were enrolled including 20 HC, 20 AD, 19 PD and 20 MSA patients. The serum concentrations of P450 involved in VD hydroxylation were assayed by ELISA. The data were analyzed by the nonparametric Kruskal-Wallis test between groups.

Results
Though CYP2R1 and CYP27A1 mediate 25-hydroxylation for VD, CYP2R1 is the main hydroxylase, and CYP27A1 is also involved in VD synthesis. CYP2R1 concentrations showed no differences among groups, while lower CYP27A1 concentrations were found in PD (p < 0.05) and MSA (p < 0.005) compared to HC and differences between AD and MSA (p < 0.05), however no differences between PD and MSA. CYP27B1 is the main 1α-hydroxylase for 25-hydroxyvitamin D and showed differences between HC and PD (p < 0.05), between HC and MSA (p < 0.005) and between PD and MSA (p = 0.055). CYP24A1, which inactivate 1,25-di-hydroxyvitamin D, showed no differences among groups.

Conclusions
CYP27A1 might affect VD synthesis and cause low 25-hydroxyvitamin D levels in AD, PD and MSA patients. Low 1,25-di-hydroxyvitamin D levels in MSA patients might be caused by impaired feedback mediated by CYP27B1.
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VitaminDWik - CYP27B1 category contains

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

• 63 items in CYP27B1 category
• 343 articles in the Genetics
• 530 articles in Vitamin D Receptor
• 178 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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Genetics category listing contains the following

343 articles in the Genetics category

see also

• Vitamin D Receptor has 530 items
• Vitamin D Binding Protein = GC has 178 items
• CYP27B1 has 63 items
• CYP24A1 in title of 39+ items
• CYP2R1 25+ items
• Calcidiol has 48 items
• Calcitriol has 62 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 - 100 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.
  5) 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&5

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VitaminDWiki - 9 studies in both categories Cognition and Genetics

This list is automatically updated

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Wonder why this study did not consider the Vitamin D Receptor (which limites Vitamin D getting to cells)

VitaminDWiki - 16 studies in both categories Cognition and Vitamin D Receptor

This list is automatically updated

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VitaminDWiki - Overview Alzheimer's-Cognition and Vitamin D contains

• FACT: Cognitive decline is 19X more likely if low vitamin D
• FACT: Dementia is associated with low vitamin D levels.
• FACT: Alzheimer’s Dementia 2.3X more likely in elderly if low vitamin D – Dec 2022
• FACT: Dementia is associated with low vitamin D - many studies
• FACT: Alzheimer's Disease is 4X less likely if high vitamin D
• FACT: Every single risk factor listed for Alzheimer's Disease is also a risk factor for low vitamin D levels
• FACT: Elderly cognition gets worse as the elderly vitamin D levels get even lower (while in senior homes)
• OBSERVATION: Reports of increased vitamin D levels result in improved cognition
• OBSERVATION: Alzheimer’s patients 3X more likely to have a malfunctioning vitamin D receptor gene – 2012
• OBSERVATION: Alzheimer's Disease has been seen to halt when vitamin D was added.
• OBSERVATION: Alzheimer’s is associated with all 7 of the genes which restrict vitamin D
• OBSERVATION: 39 vitamin D and Alz. or Cognition intervention trials as of Sept 2018
• OBSERVATION: 2 Meta-analysis in 2012 agreed that Alzheimer's Disease. associated with low vitamin D
• OBSERVATION: 50X increase in Alzheimer's while decrease in vitamin D
• OBSERVATION: Vitamin D reduces Alzheimer’s disease in 11 ways
• OBSERVATION: Alzheimer’s cognition improved by 4,000 IU of vitamin D
• OBSERVATION: Plaque removed in mice by equiv. of 14,000 IU daily
• OBSERVATION: DDT (which decreases Vit D) increases risk of Alzheimer's by up to 3.8X
• OBSERVATION: 2% of people have 2 copies of the poor gene reference: Alz Org
• OBSERVATION: Genes do not change rapidly enough to account for the huge increase in incidence
• OBSERVATION: End of Alzheimer's videos, transcripts and many studies protocol has been very successful
  • It adjusts Vitamin D, B-12, Iron, Omega-3, food, etc, and can now be done at home.
• FACT: Vitamin D is extremely low cost and has very very few side effects
• CONCLUSION: Everyone concerned about cognitive decline or Alzheimer's Disease should take vitamin D
• PREDICTION MET: By 2024 Omega-3 and high dose Vitamin D will be found to reverse Alzheimer's in humans
  There are 13+ Alzheimer’s meta-analyses in VitaminDWiki
  There are 97+ Alzheimer’s studies in VitaminDWiki
  Dementia is associated with low vitamin D - many studies 50+ studies
  16+ studies in both categories Cognitive and Omega-3

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VitaminDWiki - Overview Parkinson's and Vitamin D contains

• Vitamin D associated with Parkinson’s Disease in 55 studies, more studies needed- March 2022
• Parkinson's category has 117 studies
• Parkinson’s Disease and Vitamin D – review of 52 studies – May 2022
• Parkinson patients: 60 % taking Vitamin D – Dec 2019
• Low Vitamin D increases Parkinson's by 3X– July 2010 "only" a 30 year test, need more study
• Parkinson's disease prevented by Vitamin D, but small doses do not treat it - Aug 2023
• 10 clinical trials for PD with vitamin D intervention as of June 2023
• Parkinson’s Disease Summer School – alternative therapies included 60-80 ng of Vitamin D – Sept 2019
• Associated with PD are: Meta-analyses (12 ), Cognition (24 studies), Multiple Sclerosis (18 studies), VIRUS (4 studies), Omega-3 (3 studies), Vitamin D Receptor (11 studies)
• Note by the Founder of VitaminDWiki: I have twice recommended lots of Vitamin D to treat PD. Both got much better, but one had his doctor him cut back to just 2,000 IU. All of his recovery got reversed. With lots of vitamin D he could sing and bike, but now he can barely talk or walk