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The Vitamin D Receptor has many really important functions. People mistakenly believe that to get Vitamin D related benefits, they need to supplement with Vitamin D3. Often, vitamin D3 isn’t enough. If you’re interested in a supplement that provides a full package approach to superior cognitive function and health, we recommend Qualia, which contains a bioactive form of Vitamin D and many other great brain-boosting ingredients.  Use the coupon code ‘selfhacked’ and get 10% off a 1-time order or 15% off of a recurring order.

Active Vitamin D vs Vitamin D3


We think of vitamin D3 as causing a bunch of health effects, but vitamin D3 is mainly just the beginning of the process that leads to its health benefits.

Vitamin D3 needs to convert to Calcitriol, the active form.

Then, Calcitriol needs to attach to a specific receptor – the Vitamin D Receptor or VDR.  Some infections or toxins block these receptors. If this happens, you won’t get the health effects of Calcitriol or vitamin D3.

After Calcitriol binds to the VDR, for many bodily functions, this complex then needs to go to the nucleus and bind to another protein such as RXR.

After that, there are cell-specific responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D [R].

In some cases, various steps can be left out.  For example, in skin cells, the Vitamin D Receptor can have effects without Calcitriol to increase hair growth (via Wnt) [R].

The Benefits of Vitamin D3

The active Vitamin D (calcitriol) has many benefits…

Vitamin D protects against:

Vitamin D is particularly good for Th1 and Th17 dominant people.

Vitamin D’s Anti-Inflammatory Role


Vitamin D mainly lowers the “adaptive” immune system.

Vitamin D also boosts the immune system:

Vitamin D mainly stimulates the “innate” immune system.

  • Crucial for T Cell Activation. In this sense, it’s an immune booster [R]
  • Increase CD8+ T  Cells, which is important in controlling viral infections.
  • Increases Natural Killer T Cells [R] – good for preventing an autoimmune disease, but bad for asthma.
  • Increases NK cells [R] ( are associated with…)
  • Releases Antimicrobials in response to an infection such as cathelocidin and beta-defensin 4 [R].

Other Benefits of the Vitamin D Receptor

The most popular benefits for vitamin D3 is its 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 the 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.  Researchers 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.  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 [RR] – 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 facilitate disposal from the cell via the ABC efflux transporter [R].
  • Omega-3: DHA, EPA [R], – Fish oil/DHA
  • Omega-6: γ-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 1,25 D 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, R] and calcitriol levels [R].
  • Phytoestrogens [R],
  • Testosterone [R],
  • Prostaglandins,
  • Bisphosphonates,

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 a 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 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 [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


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.”[R] Antibiotics don’t work well [R].
  • H. pylori (responsible for stomach ulcers). 50% of the global population has this. Produces “Sulfonolipid ligand capnine.”[R].
  • Lyme/Borrelia – Live Borrelia reduces VDR by 50 times (in monocytes) and  “dead” Borrelia reduces it by 8 times [R] – This could explain why people develop autoimmune conditions after Lyme infection.
  • Tuberculosis – Reduces VDR 3.3-fold [R]
  • “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 [R].
  • Mycobacterium leprase – produces mir-21 to target multiple genes associated with the VDR [R]
  • Epstein-Barr virus (EBV) – Decreases VDR by a factor of about five [R] EBV also blocks the ability of VDR to produce products [R]
  • HIV – binds to the VDR [R] and inhibits conversion to active D [R].
  • 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 [R].
  • Hepatitis C virus – Inhibits CYP24A1, the enzyme responsible for breaking down excess 1,25-D [R]

Screenshot 2015-01-14 15.57.25

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.

High Levels of Calcitriol Indicate Inflammatory/Autoimmune Disease

As bacterial products compromise the activity of the VDR, the receptor is prevented from expressing an enzyme (CYP24) that breaks the calcitriol/1,25-D down into its inactive metabolites.  This allows 1,25-D levels to rise without a feedback system to keep them in check, resulting in the elevated levels of the hormone [R].

Studies show a strong association between these autoimmune conditions and levels of 1,25-D greater than 110 pmol/L (46 pg/mL [R]), even though there were no apparent cases of high blood calcium.  38 of the 100 people in a group of people with autoimmune conditions had over 160 pmol/L (66.6 pg/mL [R]) [R].

I see clients with chronic inflammation often have active vitamin D levels between 50-80 pg/mL.

However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that blood levels of vitamin D3 or 25-D are a sensitive measure of the autoimmune disease state [R].

Acquired hormone resistance has also been recognized with insulin, thyroid, steroid, and GHRH and elevated levels of hormones are seen in some autoimmune conditions [R].

Calcitriol/Active Vitamin D in SelfDecode

Figuring Out Calcitriol Levels Of Vitamin D3

Common blood tests measure a variety of markers that indicate how much active vitamin D you have.

The following indicate higher calcitriol:

  • Higher Parathyroid hormones
  • Higher blood calcium and phosphorous [R]
  • Higher albumin [R]
  • Higher creatinine [R]
  • Lower alkaline phosphatase [R]

Since at least some of these (maybe all) require the vitamin D receptor, checking Calcitriol Active/Vitamin D (1,25 Hydroxy) blood levels in combination with the other tests might indicate the degree of VDR resistance.


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.

  1. RS11574143 (VDR) CC
  2. RS1540339 (VDR) CC
  3. RS1544410 (VDR) CT
  4. RS2107301 (VDR) GG
  5. RS2228570 (VDR) AG
  6. RS2238136 (VDR) CC
  7. RS2239182 (VDR) CC
  8. RS2239185 (VDR) AA
  9. RS2239186 (VDR) AA
  10. RS3782905 (VDR) CG
  11. RS3819545 (VDR) AA
  12. RS4516035 (VDR) TT
  13. RS7041 (VDR) AC
  14. RS731236 (VDR) AG
  15. RS757343 (VDR) CT
  16. RS7975232 (VDR) AA

CYP24A1 breaks down the active form of vitamin D (Calcitriol).  Check out the CYP24A1 gene that breaks down calcitriol.

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  • Karen

    This article seems like a very comprehensive and extensive list of the regulation of the vitamin D receptor. Especially the list about pathogens interfering with VDR expression was interesting ot me. However, when looking up the original references, there was no evidence about the interference with VDR. (e.g. it does not appear in the Cytomegalovirus transcriptome analysis linked, it is not regulated by HCV in the paper linked, it does not appear in the Borrelia study linked).
    Did I miss something? Or are the wrong references given?

  • Duane

    Linolenic acid is an omega-3, not an omega-6. Might wanna correct the copy above.

  • carol close

    Emu oil also reduces eczema, and other inflammatory skin conditions.

  • carol close

    I for to mention that the benefits of emu oil on inflammation, cholesterol, diabetes, arthritis are from topical application; however, emu in inflammatory bowel diseases is from emu oil in an oral dose.

  • carol close


    Vitamin D is responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc. Immune function begins in the stomach. Vitamin D makes progesterone effective. Progesterone works synergistically with Vitamin D in the central nervous system and also synergistically with Vitamin A in immune function. Vitamin D increases stomach absorption of calcium, iron, magnesium, phosphate and zinc. “Progesterone and vitamin D hormone for treatment of traumatic brain injury in the aged.” Vitamin D and progesterone together promote better functional outcomes than either treatment independently. “Vitamin D and the Immune System.” “Vitamin D supplementation and regulatory T cells in apparently healthy subjects: vitamin D treatment for autoimmune diseases?” Vitamin D increases regulatory T cells. The regulatory T cells (Tregs), formerly known as suppressor T cells, are a subpopulation of T cells which modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease “1α,25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically inhibit the differentiation and expansion of Th17 cells.” Vitamin D3 synergizes with retinoic acid (an active vitamin A metabolite). “Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential.”

    BLUE LIGHT IN SUNLIGHT ACTIVATES IMMUNE CELLS-WHY VITAMIN D SUPPLEMENTATION IS NOT AS EFFECTIVE AS SUNLIGHT. “Some Benefits of Sunlight May Be Independent of Vitamin D.” The study suggests that blue light specifically, within the visible light spectrum, may directly activate key immune cells and increase their motility. The researchers studied both human and mouse T lymphocytes after exposure to blue light. They found that the blue light triggered the synthesis of hydrogen peroxide, which in turn activated key signaling pathways that led to increased movement and motility of the T cells. This is a process that can take place naturally. When T cells are stimulated by infection or the presence of a foreign invader, they will release hydrogen peroxide, and this will mobilize other T cells and other immune cells to mount an immune response. So it seems very biologically plausible that blue light could be having this effect, which can be replicated by exposing the T cells directly to hydrogen peroxide. Why is this of particular interest? Blue light is known to reach the dermis, the second layer of the skin, and the dermis has a very high concentration of T lymphocytes. In fact, it’s been estimated that there are twice as many T lymphocytes in the dermis as circulating in the bloodstream. When mobilized, these T lymphocytes can travel through the dermis and into the bloodstream. This suggests that there may, indeed, be a separate pathway through which sunlight exposure (specifically blue light exposure) may affect immune function.

  • carol close


    Forget the hype about the anti-aging/longevity benefits of reservatrol in a glass of red wine. The alcohol in that daily glass of red wine seriously ages your body. Take your resveratrol in a capsule instead because alcohol, a diuretic, thins your skin from dehydration from reduced aldosterone and increases cortisol, a catabolic hormone that breaks down tissues which also increases MMPs also involved in breaking down tissue, including collagen. Alcohol removes cholesterol/triglycerides from adipose tissue and sends triglycerides to your liver which makes fatty liver disease. Alcohol by removing cholesterol from skin in effect shuts down your whole body’s hormone factory because skin and adipose tissue need cholesterol to make pregnenolone, the mother of all hormones. Pregnenolone is used to make Vitamin D and progesterone, and progesterone inhibits mTOR which activates stem cells in your body to renew your body’s cells. Natural real progesterone inhibits mTOR; however, synthetic progesterone does not inhibit mTOR. Natural real progesterone is also another neurosteroid benefiting the brain. Alcohol can interfere with your body’s ability to absorb and activate vitamin D which vitamin D also manufactures your hormones in your mitochondria. Vitamin D and progesterone function better together than with independent treatment. The beneficial effects of wine on cardiovascular risk are primarily due to the alcohol with benefits in raising good cholesterol, meanwhile red wine thins your blood over white wine due to polyphenols. A better alternative to alcohol to raise good cholesterol is olive oil. The type of heart-healthy fat found in olives and olive oil can increase your HDL and lower the inflammatory impact of LDL cholesterol on your body. Horny Goat Weed restores triglycerides, lipids, fatty acids and amino acids to younger levels. Ashwagandha reduces cortisol, reduces MMPs, and activates p53 tumor suppressor proteins to prevent skin cancer and other cancers. Natural progesterone increases aldosterone, lowers cortisol, reduces MMPs and activates p53 tumor suppressor proteins in preventing skin and other cancers, and strengthens skin and connective tissue. Use emu oil for skin which has a similar fatty acid content as human skin and is known for anti-inflammatory effects in skin and also orally in Crohn’s and other inflammatory bowel diseases, chemo therapy induced bone loss, rheumatoid arthritis, reducing high cholesterol, and also has anti-diabetic activity. “Effects of alcohol on blood pressure and production of vascular aldosterone and corticosterone.” Aldosterone affects the body’s ability to regulate blood pressure. Alcohol decreases aldosterone and increases corticosterone increasing stress (cortisol is catabolic and tears down your body.) The aldosterone hormone also causes the bloodstream to re-absorb water with sodium to increase blood volume. Alcohol is a diuretic and dehydrates skin and your whole body because of reduced aldosterone. “Matrix Metalloproteinases in Skin.” Benefits, but also excessive breakdown in connective tissue, including collagen and skin. “Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin” “Activity of MMP-2, MMP-8 and MMP-9 in serum as a marker of progression of alcoholic liver disease in people from Lublin Region, eastern Poland.” Alcohol increases MMP activity. “Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis.” (So adipose tissue loses ability to make hormones because alcohol takes cholesterol away from skin and transports cholesterol to the liver instead.) “mTOR signaling plays a critical role in the defects observed in muscle derived stem/progenitor cells isolated from a murine model of accelerated aging.” Inhibiting mTOR improves defective, aged stem cells which stem cells renew the body. (Natural real progesterone inhibits mTOR.) “Anti-tumor effects of progesterone in human glioblastoma multiforme; Role of P13k/Akt/mTOR signaling.” Real progesterone inhibits mTOR.
    http://www.ncbi/nlm/ “Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin 9mTOR) in endometrial cells.” Synthetic progesterone does not inhibit mTOR, so pharmaceutical companies are trying to find other drugs to add to synthetic progesterone that can make synthetic progesterone act like natural real progesterone because natural real progesterone is not patentable. Progesterone is one of many neurosteroids that benefit the brain. “Does Alcohol Inhibit Vitamin D Uptake? | Healthy Eating | SF Gate Alcohol inhibits Vitamin D uptake. “Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease”. The alcohol in red wine actually improves HDL levels. “Effects of moderate consumption of red wine on platelet aggregation and haemostatic variables in healthy volunteers.” “Red and white wine differently affect collagen-induced platelet aggregation.” The polyphenols in red wine thin your blood, with no effect of white wine. “HDL- Foods to increase good cholesterol.” Olive oil increases good cholesterol. Metabonomic characterization of aging and investigation on the anti-aging effects of total flavones of Epimedium. (Epimedium/Icariin/Horny Goat Weed restores lipids, fatty acids and amino acids to younger levels.) “A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in “Does Alcohol Inhibit Vitamin D Uptake? | Healthy Eating | SF Gate Alcohol inhibits Vitamin D uptake. “Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease”. The alcohol in red wine actually improves HDL levels. “Effects of moderate consumption of red wine on platelet aggregation and haemostatic variables in healthy volunteers.”
    adults.” Ashwadandha reduces cortisol and stress. “Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action.” Ashwagandha activates p53 tumor suppressor protein and downregulates MMP’s, prevents skin cancer and other cancers. “Effect of progesterone on aldosterone secretion in rats.” Progesterone increases aldosterone and decreases cortisol. “Progesterone Exposure Prevents Matrix Metalloproteinase-3 (MMP-3) Stimulation by Interleukin-1α in Human Endometrial Stromal Cells.” “Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study.” Progesterone strengthens skin. “Composition of Emu oil- fatty acids from Emu and Human Skin.” They are almost identical to each other in fatty acids. “Antagonism of croton oil inflammation by topical emu oil in CD-1 mice.” “Review of emu products for complementary and alterative medicine.”

  • carol close


    Your skin is a major endocrine organ. Vitamin D activates the hypothalamus-pituitary-adrenal axis in human skin cells. First of all, estrogen, in both men and women’s skin cells, signals cholesterol to be transformed into hormones in the skin cells’ mitochondria and adipose tissue cells’ mitochondria. Vitamin D3 or 7-DHC or enzyme p450 inside the skin cells’ and adipose/fat tissue cells’ mitochondria transforms cholesterol through intracellular catalytic production into pregnenolone- the mother of all hormones. Pregnenolone transforms into progesterone or DHEA, plus pregnenolone changes into more vitamin D in a photochemical reaction from sunlight with stimulation of photons of UVB in your skin. Then progesterone transforms into cortisol. And DHEA, a neurosteroid, transforms into aldosterone, estrogen, testosterone, glucocorticoids, mineralocorticoids, and other essential hormones. Progesterone needs vitamin D to work effectively to promote better functional outcomes than either vitamin D or progesterone treatment independently. Low hormones cause high cholesterol, and hormone restorative therapy, restoring with natural (not synthetic) estrogen, testosterone, progesterone, DHEA, and pregnenolone, normalizes cholesterol levels. “Bioactive forms of vitamin D selectively stimulate the skin analog of the hypothalamus-pituitary-adrenal axis in human epidermal keratinocytes.” “2β- and 16β-hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation.” There is a direct stimulatory effects of estrogen- estradiol and estrone on pregnenolone formation which then converts to androstenedione, testosterone and DHEA. “A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin.” Vitamin D-3 or 7-DHC or p450 enzyme in mitochondria makes pregnenolone. “On the role of skin in the regulation of local and systemic steroidogenic activities.” Skin is not just a barrier of overlapping dry cells that function as a barrier to keep moisture and vital nutrients in, and damaging substances and elements out. Skin is a neuroendocrine organ endowed with steroid/secosteroidogenic activities. Skin has the ability to produce and respond to neurotransmitters, neuropeptides, hormones and neurohormones, of which expression and phenotypic activities can be modified by ultraviolet radiation, chemical and physical factors, as well as by cytokines. Cholesterol is converted to pregnenolone which is the mother of all hormones. Pregnenolone, which after exposure of UVB rays, undergoes a photochemical transformation into vitamin D. The local steroidogenic system is composed of locally expressed cytochrome P450 (or vitamin D-3 or 7-DHC) involved in local production of androgens, estrogens, gluco- and mineralo-corticosteroids from cholesterol or from steroid precursors delivered to the skin, and of their metabolism and/or inactivation. Pregnenolone circulates and goes into glands, liver, skin or genitals, then pregnenolone becomes either DHEA or progesterone. From there, these hormones can further be converted into cortisol, aldosterone, estrogen, testosterone and/or other essential hormones. “Progesterone and vitamin D hormone for treatment of traumatic brain injury in the aged.” Vitamin D and progesterone together promote better functional outcomes than either treatment independently. “Hypercholesterolemia treatment: a new hypothesis or just an accident?” Restoring normal hormone levels with natural hormones reduces high cholesterol.

  • Aaron_c

    Hi Joseph,

    First of all, thank you for the list of pathogens that inhibit VDRs (with citations!). Very helpful.

    I do have two comments regarding the item that reads: “Ubiquitin (R) – autophagy stops this.”

    First of all, ubiquitin isn’t a pathogen, it is “a small protein that is found in almost all cellular tissues in humans and other eukaryotic organisms, which helps to regulate the processes of other proteins in the body.” (

    Secondly, the article that you linked to appears to disagree with the second source it cites. The article you linked to claims: “At the receptor level, calcitriol induces ubiquitination of the VDR leading to its degradation by the ubiquitin-proteasomal pathway (38,39).” The first source details how calcitriol binding is necessary for SUG1 to degrade VDRs. So far so good, but I mention this mostly because it is important to note that it does not look at the net effect of calcitriol on VDR levels.

    The second article that was cited appears to have been misunderstood. Far from claiming that calcitriol induces ubiquitination of VDRs (which then leads to VDR degredation and fewer VDRs) the study is titled “1,25-Dihydroxyvitamin D3 INCREASES nuclear vitamin D3 receptors by BLOCKING ubiquitin/proteasome-mediated degradation in human skin.” [emphasis added] We should also note that this second, misrepresented study looks at the net effect of calcitriol on VDR levels–and found that calcitriol increases VDR levels both by increasing VDR transcription and by decreasing VDR degradation.

    1. Joseph M. Cohen

      Ubiquitin was put in the wrong section

  • RC

    Should I (a eczema patient) take vitamin D supplements if Vitamin D promotes Treg but also shift TH1 to TH2 which increase allergic response ?

  • Alexander Wolf

    What dosage do you recommend for vitamin d?

    1. Joseph M. Cohen

      Depends on many factors

      1. greg

        so what are some the factors beside blood levels

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