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Vitamin D Receptor - activation and deactivation- self-hacked June 2019

First 3 sections clipped from Vitamin D Receptor Gene: Activation, Calcitriol, Benefits

Natural Ways to Increase Calcitrol and VDR

  • Exercise 38 – increases calcitriol, but not aerobic exercise 39.
  • RXR (and retinol) is needed to produce proteins with the VDR. 1,25D3 binds to the VDR, which then combines with RXR to activate gene expression. (Not all VDR dependent genes need RXR.)
  • Parathyroid hormone (PTH) – increases Calcitriol/1,25 D3 40 and PTH-related peptide 41,
  • SIRT1 – potentiates VDR 42, 43 – acetylation of VDR lessens 1,25D/VDR signaling. SIRT1 increased the ability of VDR to associate with RXR.
  • PGC-1a 44 – potentiates VDR. It is a coactivator of the VDR, but it still needs 1,25D3.
  • Dopamine 45
  • Bile specifically Lithocholic acid orLCA 46, The VDR evolved from its ancient role as a detoxification nuclear receptor. LCA is produced from the gut bacteria (metabolizing liver-derived chenodeoxycholic acid). LCA travels to the colon, where the VDR binds to LCA or 1,25 D and activates the CYP3A4 and SULT2A genes facilitate disposal from the cell via the ABC efflux transporter 47.
  • Omega-3: DHA, EPA 47, – Fish oil/DHA
  • Omega-6: γ-Linolenic acid, Arachidonic acid 47,
  • Curcumin 1 – Curcumin is more active than LCA/Bile in driving VDR-mediated transcription and that it binds to VDR with approximately the same affinity as LCA.
  • Resveratrol 42 – Potentiates VDR by: (1) potentiating 1,25D binding to VDR; (2) activating RXR; (3) stimulating SIRT1
  • Forskolin 40 – increases 1,25D3 from 25D3 in-vitro
  • Gamma Tocotrienol 47 – Tocotrienols or Tocopherols (IHERB)
  • Vitamin E/alpha-tocopherol 47 – doesn’t compete with calcitriol for the VDR.
  • Dexamethasone 47 – doesn’t compete with 1,25
  • Interferon-gamma – IFN-γ treatment inhibited 1,25D3 induction of 24-hydroxylase, the enzyme that breaks down 1,25 D3. This means 1,25D3 increased. (Technical: IFNy did not change the base level activity of the promoter, or change 1,25 D binding to the VDR or nuclear VDR levels. IFN-γ impairs VDR-RXR binding to VDRE through a Stat1-mediated mechanism) 48.
  • Estradiol increases VDR expression 49, 50 and calcitriol levels 51.
  • Phytoestrogens 52
  • Testosterone 53
  • Prostaglandins
  • Bisphosphonates

DHA, EPA, linoleic acid and arachidonic acid are all 10,000X less capable than 1,25 D3 at activating the VDR 47.

Curcumin is 1,000X less capable than 1,25 D3 in inducing VDR gene expression 47.

Curcumin and bile have a similar binding ability to the VDR and similar levels of gene expression 47.

Curcumin, Bile, DHA, EPA, Arachidonic acid all compete with 1,25 D3 for binding. Dexamethasone and alpha-tocopherol don’t compete 47.

A natural question to pose would be that if these are competitive binders and have a much lower binding capacity for the VDR, are they of use? The answer seems to be yes.

High concentrations of PUFAs could occur in select cells or tissues and exert bioactivity 47.

Excess Bile/LCA given to rats caused the same effect that 1,25D3 would cause (in particular calcium transport activation) 47.Kidney glandular might contain some 1,25 vitamin D.

What Inhibits The Vitamin D Receptor (VDR) or Calcitriol

  • Caffeine decreases VDR production 54
  • Cortisol/Glucocorticoids decreases VDR production 25
  • Prolactin 55
  • Thyroid hormones repress VDR activation 56
  • TGF-beta reduces the activation of VDR/RXR combination, which results in VDR-mediated gene expression 57
  • TNF 58 (inhibits osteocalcin interaction with VDR, but not osteopontin)
  • Corticosteroids decrease calcitriol 59
  • Phosphatonin, Ketoconazole, Heparin, and Thiazides decrease calcitriol 59
  • Ubiquitin 60autophagy stops this

Pathogens That Inhibit The Vitamin D Receptor

Many pathogens inhibit some aspect of the vitamin D system – either the VDR, the ability of molecules to bind to it or the ability of VDR to cause gene expression. These are some examples, but I’m sure I haven’t covered all of them known to the body of science.

  • P. aeruginosa (often hospital acquired). Produces “Sulfonolipid ligand capnine” 61. Antibiotics don’t work well 62.
  • H. pylori (responsible for stomach ulcers). 50% of the global population has this. Produces “Sulfonolipid ligand capnine” 61.
  • Lyme/Borrelia – Live Borrelia reduces VDR by 50 times (in monocytes) and “dead” Borrelia reduces it by 8 times 63
    • This could explain why people develop autoimmune conditions after Lyme infection.
  • Tuberculosis – Reduces VDR 3.3-fold 64
  • “Gliding” biofilm bacteria have been shown to create Capnine – Capnine (Cytophaga, Capnocytophaga, Sporocytophaga, and Flexibacter)
  • Chlamydia (trachomatis)
  • Shigella – bacteria in stool and causes intestinal problems and diarrhea. It increases Caspase-3, which is a protein which breaks apart the VDR structure and thus limits the ability of VDR to perform gene transcription 65.
  • Mycobacterium leprase – produces mir-21 to target multiple genes associated with the VDR 64.
  • Epstein-Barr virus (EBV) – Decreases VDR by a factor of about five 66 EBV also blocks the ability of VDR to produce products 67.
  • HIV – binds to the VDR 68 and inhibits conversion to active D 69.
  • Aspergillus fumigatus – In cystic fibrosis patients, the fungus A. fumigatus has been shown to secrete gliotoxin, a toxin which dose-dependently decreases VDR.
  • Cytomegalovirus – CMV decreases VDR 2.2 fold 70.
  • Hepatitis C virus – Inhibits CYP24A1, the enzyme responsible for breaking down excess 1,25-D 71

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When bacterial products block the VDR, less of the CYP24A1 is produced, which results in excess active vitamin D – as is the case in many autoimmune conditions.


See also VDR and Calcitriol in VitaminDWiki

The risk of 40 diseases at least double with poor Vitamin D Receptor as of July 2019

Vitamin D Receptor category has the following

410 studies in Vitamin D Receptor category

Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems
A poor VDR restricts Vitamin D from getting in the cells
It appears that 30% of the population have a poor VDR (40% of the Obese )

A poor VDR increases the risk of 55 health problems  click here for details
The risk of 44 diseases at least double with poor Vitamin D Receptor as of Oct 2019

VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR

Compensate for poor VDR by increasing one or more:

IncreasingIncreases
1) Vitamin D supplement
  Sun, Ultraviolet -B
Vitamin D in the blood
and thus in the cells
2) MagnesiumVitamin D in the blood
 AND in the cells
3) Omega-3 Vitamin D in the cells
4) Resveratrol Vitamin D Receptor
5) Intense exercise Vitamin D Receptor
6) Get prescription for VDR activator
   paricalcitol, maxacalcitol?
Vitamin D Receptor
7) Quercetin (flavonoid) Vitamin D Receptor
8) Zinc is in the VDRVitamin D Receptor
9) BoronVitamin D Receptor ?,
etc
10) Essential oils e.g. ginger, curcuminVitamin D Receptor
11) ProgesteroneVitamin D Receptor
12) Infrequent high concentration Vitamin D
Increases the concentration gradient
Vitamin D in the cells
13) Sulfroaphane and perhaps sulfurVitamin D Receptor

Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation. You might feel the benefit within days of adding one or more of the above

Far healthier and stronger at age 72 due to supplements Includes 6 supplements that help the VDR

If poor Vitamin D Receptor

Risk
increase
Health Problem
50Lyme Disease
28Leprosy - another says 3X
15Chronic Heart Failure
15Temporary hair loss
14Hand, Foot, and Mouth disease
13Sepsis
11Metabolic Syndrome
9.6Chronic Periodontitis
   and smoke
8Juvenile Rheumatoid Arthritis
7.6Crohn's disease
7.5Respiratory Tract Infections
5.8Low back pain in athletes
5 Respiratory Distress in preemies
5Ulcerative Colitis
5Coronary Artery Disease
5Asthma Child see also 1.3, 2.0 and 3.6
4.6Breast Cancer 16.9 X another study
4.1Vitiligo
4Polycystic ovary syndrome
3.6 Pneumonia - children
3.3 Pre-term birth
3.1 Colon Cancer survival
3 Multiple Sclerosis
3Dengue
3 Waist size
3 Ischemic Stroke
3Alzheimer’s
3Gestational Diabetes
2.9Hand, Foot, Mouth Disease
2.8Osteoporosis & COPD
2.7Gastric Cancer
2.6Lupus in children
2.5 Lumbar Disc Degeneration
2.4Lung Cancer
2.3Autism
2.2Juvenile idiopathic arthritis
2.1Adolescent idiopathic scoliosis in Asians
2Diabetic Retinopathy
2Parkinson's
2 Wheezing/Asthma see also 5X
2 Melanoma   Non-melanoma Skin Cancers
2Myopia
2Preeclampsia
1.9Uterine Fibroids
1.9Early tooth decay
1.8Diabetic nephropathy
1.8Sleep Apnea
1.6Diabetes - Type I
1.6Prostate Cancer while black
1.5 Diabetes -Type II
1.5Pertussis
1.5Obesity
1.4Graves Disease
1.4 Rheumatoid arthritis
1.3Childhood asthma see also 5X
1.3Psoriasis in Caucasians
1.3Tuberculosis
?? Rickets - Vitamin D resistant


Vitamin D Receptor and Cancers
Items in both categories Vitamin D Receptor and Cancer - Breast:

Items in both categories Vitamin D Receptor and Cancer - Colon:

Items in both categories Vitamin D Receptor and Cancer

Items in both categories Vitamin D Receptor and Cancer - other:

Items in both categories Vitamin D Receptor and Cancer - Skin:

Items in both categories Vitamin D Receptor and Cancer - Prostate:

Items in both categories Vitamin D Receptor and Cancer - Ovarian:


Calcitriol category listing has 52 items along with related searches

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Created by admin. Last Modification: Sunday July 14, 2019 21:03:21 GMT-0000 by admin. (Version 9)
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