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Natural Ways to Increase Calcitriol and Activate The Vitamin D Receptor Gene – Oct 2017

 Selfhacked

 Download a poor PDF of the online version from VitaminDWiki

CONTENTS

[(R) = online reference]
Active Vitamin D vs Vitamin D3
The Benefits of Vitamin D3
Other Benefits of the Vitamin D Receptor

  • The most popular benefits for vitamin D3 is it’s role in bone health.
  • Low blood levels of vitamin D3 are associated with lower bone density (R). Clinical trials have shown that Calcitriol is helpful for people with lower bone density (R).
  • VDR activation induces the expression of liver and intestinal phase I detox enzymes (e.g., CYP2C9 and 3A4) that play major roles in metabolizing drugs and toxins (R).
  • The Vitamin D Receptor is important for hair growth and loss of VDR is associated with hair loss in experimental animals (R).
  • The VDR regulates intestinal transport of calcium, Iron and other minerals (R).
  • Since many infections block the Vitamin D Receptor, our body can’t fight them off well. Researches are using a combination of Calcitriol (active D) and antibiotics with good effects in many conditions. It’s a good idea to gradually eliminate pathogens over several years to minimize immune reactions. (R)
  • Calcitriol/VDR increases dopamine by increasing the enzyme that’s the rate limiting step for dopamine production (tyrosine hydroxylase) (R).
  • Calcitriol/VDR increases tyrosine hydroxylase in the hypothalamus (R), adrenal glands (R), substantia nigra (R) and likely other areas. This means that it increases productions of dopamine, adrenaline and noradrenaline. Although having more neurotransmitters is a good thing, Tyrosine hydroxylase also increases oxidative stress, so it doesn’t provide a free lunch. (R)
  • Calcitriol increases GAD67 and therefore increases GABA (R).
  • Calcitriol increases glial derived neurotrophic factor (GDNF) (in vitro), which protects dopamine neurons. (R)
  • Researchers hypothesize that inadequate levels of circulating vitamin D could lead to dysfunction in the substantia nigra, an area of the brain in which the characteristic dopaminergic degeneration occurs in parkinsonian disorders (R).
  • A high prevalence of vitamin D deficiency has been reported in Parkinson’s patients and Parkinson’s has been associated with decreased bone mineral density (R).
  • Active D has different effects in cancer. In breast cancer cells, estrogen (and aromatase) production decreased, while Testosterone/androgens increased (both GOOD). In adrenal cancer cells, it decreased DHT (GOOD). In prostate cancer cells, the production of testosterone and DHT increased (BAD). (R)
  • High levels of the enzyme that breaks down active D is found in lung cancer (R) and breast cancer (R). This would suggest that increasing its levels are good for breast and lung cancer.
  • Active vitamin D increases prolactin production (R).
  • Technical: 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate kidney calcium and phosphate reabsorption (R).

Natural Ways to Increase Calcitrol and Vitamin D Receptor Gene Expression

  • Exercise (R)- increases calcitriol, but not aerobic exercise (R).
  • RXR (and retinol) is needed to produce proteins with the VDR (R). 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 (R) and PTH -related peptide (R),
  • SIRT1 -potentiates VDR (R, R2) – acetylation of VDR lessens 1,25D/VDR signaling. SIRT1 increased the ability of VDR to associate with RXR.
  • PGC-1a (R) – potentiates VDR. It is a coactivator of the VDR, but it still needs 1,25D3.
  • Dopamine (R)
  • Bile – specifically Lithocholic acid or LCA (R),
  • 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 facilitates disposal from the cell via the ABC efflux transporter (R).
  • Omega-3: DHA, EPA (R), – Fish oil/DHA
  • Omega-6: Linolenic acid, Arachidonic acid (R),
  • Curcumin (R) – 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 (R) – Potentiates VDR by: (1) potentiating 1,25D binding to VDR; (2) activating RXR; (3) stimulating SIRT1.
  • Forskolin (R), – increases 1,25D3 from 25D3 in-vitro.
  • Gamma Tocotrienol (R)- Tocotrienols or Tocopherols (IHERB)
  • Vitamin E/alpha-tocopherol (R)- doesn’t compete with calcitriol for the VDR.
  • Dexamethasone (R) – 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 1,25D binding to the VDR or nuclear VDR levels. IFN-γ impairs VDR-RXR binding to VDRE through a Stat1-mediated mechanism) (R),
  • Estradiol increases VDR expression (R, R2) and calcitriol levels (R).
  • Phytoestrogens (R),
  • Testosterone (R),
  • Prostaglandins (R),
  • Bisphosphonates (R),
  • DHA, EPA, linoleic acid and arachidonic acid are all 10,000X less capable than 1,25 D3 at activating the VDR (R).
  • Curcumin is 1,000X less capable than 1,25 D3 in inducing VDR gene expression (R).
  • Curcumin and bile have similar binding ability to the VDR and similar levels of gene expression (R).
  • Curcumin, Bile, DHA, EPA, Arachidonic acid all compete with 1,25 D3 for binding. Dexamethasone and alpha-tocopherol don’t compete (R).
  • A natural question to pose would be that if these are competitive binders and have 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 (R).
  • Excess Bile/LCA given to rats caused the same effect that 1,25D3 would cause (in particular calcium transport activation) (R).
  • Kidney glandular might contain some 1,25 vitamin D.

What Inhibits The Vitamin D Receptor (VDR) or Calcitriol

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

Pathogens That Inhibit The Vitamin D Receptor
High Levels of Calcitriol Indicate Inflammatory/Autoimmune Disease
Calcitriol/Active Vitamin D on Self Decode
Figuring Out Calcitriol Levels From Vitamin D3
VDR Snps

  • You need to order your 23andme to find out what your genotype is.
  • If you want to interpret your genes, you can use SelfDecode, the best SNP analyzer around.
  • The program has a bunch of SNPs in the VDR Gene.
  • RS11574143 (VDR) CC
  • RS1540339 (VDR) CC
  • RS1544410 (VDR) CT
  • RS2107301 (VDR) GG
  • RS2228570 (VDR) AG
  • RS2238136 (VDR) CC
  • RS2239182 (VDR) CC
  • RS2239185 (VDR) AA
  • RS2239186 (VDR) AA
  • RS3782905 (VDR) CG
  • RS3819545 (VDR) AA
  • RS4516035 (VDR) TT
  • RS7041 (VDR) AC
  • RS731236 (VDR) AG
  • RS757343 (VDR) CT
  • RS7975232 (VDR) AA

See also VitaminDWiki

Vitamin D Receptor category has the following

525 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

See also: 48 studies in the Resveratrol category

It appears that 30% of the population have a poor VDR (40% of the Obese )
Several diseases protect themselves by deactivating the Vitamin D receptor. Example: Breast Cancer
- - - - - - - -
The Vitamin D Receptor is associated with many health problems

Health problems include: Autoimmune (19 studies), Breast Cancer (23 studies), Colon Cancer (13 studies), Cardiovascular (23 studies), Cognition (16 studies), Diabetes (24 studies), Hypertension (9 studies), Infant (22 studies), Lupus (6 studies), Metabolic Syndrome (4 studies), Mortality (4 studies), Multiple Sclerosis (14 studies), Obesity (17 studies), Pregnancy (24 studies), Rheumatoid Arthritis (10 studies), TB (8 studies), VIRUS (36 studies),   Click here for details
Some health problems, such as Breast Cancer, Diabetes, and COVID protect themselves by reducing VDR activation

55 health problems associated with poor VDR


A poor VDR is associated with the risk of 55 health problems  click here for details
The risk of 48 diseases at least double with poor VDR as of Jan 2023  click here for details
Some health problem, such as Breast Cancer reduce the VDR

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


How to increase VDR activation


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 Receptor
13) Sulfroaphane and perhaps sulfurVitamin D Receptor
14) Butyrate especially gutVitamin D Receptor
15) BerberineVitamin 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


Increased risk of diseases if poor VDR

Increased risk associated with a poor Vitamin D Receptor
   Note: Some diseases reduce VDR activation
those with a * are known to decrease activation

Risk
increase
Health Problem
50Lyme Disease *
28Leprosy - another says 3X
15Chronic Heart Failure
15Temporary hair loss
14.7Childhood solid cancers
14Hand, Foot, and Mouth disease
13Sepsis
12COVID Death
11Metabolic Syndrome
9.6Chronic Periodontitis
   and smoke
8Juvenile Rheumatoid Arthritis
8.0Preterm birth
7.6Crohn's disease
7.5Respiratory Tract Infections
7.0Lung Cancer
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 3.7
4.6Breast Cancer * 16.9 X another study
4.3Severe COVID in kids
4.1Vitiligo
4Liver Cirhosis
4Polycystic ovary syndrome
3.8Lupus
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
9X in women
3Parkinson’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
2.3Cardio
2.3Autism
2.2Juvenile idiopathic arthritis
2.1Adolescent idiopathic scoliosis in Asians
2Obesity
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
1.5Gout
1.5Pertussis
1.5Obesity
1.4Graves Disease
1.4 Rheumatoid arthritis
1.3Hypertension
1.3Childhood asthma see also 5X
1.3Psoriasis in Caucasians
1.3Tuberculosis

Created by admin. Last Modification: Thursday December 24, 2020 01:48:04 GMT-0000 by admin. (Version 5)