Vitamin D3 (cholecalciferol)

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Vitamin D3 is manufactured from cholesterol, a sterol. It is made by the action of UVB sunlight as it strikes the cholesterol found in the epidermis and on bare skin.

Although initially a vitamin, it is converted by the liver to 25-OHD3 (calcidiol). This is then converted by the kidneys and other tissues to 1,25-OH2D3 (calcitriol), a potent steroid hormone. The skin has been found to have the ability to convert vitamin D into 1,25-OH2D3 (calcitriol).

Vitamin D was finally isolated in 1937.

Research published in late 2009, found a lack of vitamin D3 reduces the benefits of progesterone.

Vitamin D regulates gene expression, has a positive fundamental effect on cell differentiation and growth, with anti-oxidative and autoimmune anti-inflammatory mechanisms. It positively effects the nervous system by stimulating neurotrophic factors, quenching oxidative hyperactivity and regulating autoimmune responses.

It is one of the oldest hormones, probably predating them all, except for progesterone. It's believed vitamin D is about 750 million years old. As opposed to the 2 plus billion years suggested for progesterone.

This is a short list below showing some of the actions of vitamin D3. All of which also apply to progesterone. It...

  • induces the anti-inflammatory Th2 response
  • inhibits the Th1 inflammatory response
  • suppresses inflammatory cytokines such as TNF-a, IL2 and IL6
  • increases anti-inflammatory cytokines like IL-10
  • inhibits mast cell secretions
  • inhibits the oestrogen induced increase in dendritic spine density
  • increases the expression of brain-derived neurotrophic factor (BDNF)
  • positively affects neurologic functioning
  • prevents neurodegeneration and enhance myelin repair
  • positively affects motorneuron disease
  • reduces damage in traumatic brain injury
  • reduces hypertension
  • regulates bone metabolism
  • prevents lipid peroxidation
  • is essential for pregnancy
  • positively affects the skin and hair
  • increases the concentrations of glutathione, the cells master antioxidant
  • increases levels of superoxide dismutase, a powerful antioxidant
  • inhibits mitosis, causing cell differentiation and apoptosis
  • down-regulates the expression of glucocorticoids
  • modulates fibroblast proliferation and collagen synthesis

Reduced levels of vitamin D3, and progesterone, are found in all the following diseases or disorders, and therefore constitutes an increased risk factor for...

  • asthma and respiratory problems
  • depression
  • early ageing
  • cancer
  • epilepsy
  • heart disease
  • migraines/headaches
  • polycystic ovaries
  • miscarriage
  • fibroids
  • peripheral neuropathy
  • myopathy
  • autoimmune diseases, such as MS, lupus, Sjogren's syndrome, arthritis etc
  • SAD (seasonal affective disorder)
  • Alzheimer's disease

There seems some uncertainty about what constitutes an adequate level. The NHS in the UK stating 20ng/ml (50nmol/L) is adequate. The FDA have set their adequate level at 30ng/ml (75nmol/L). Whereas vitamin D3 specialists are arguing for a minimum of 50ng/ml (125nmol/L), some suggesting a range of 70-100ng/ml (175-250nmol/L).

This study highlights the controversy...

"Laboratory professionals are often confronted with challenges related to vitamin D testing, including controversy over optimal and target vitamin D concentrations, variable reference ranges across marketed assays and reference laboratories, lack of standardization of vitamin D assays, and misordering of 1,25- dihydroxyvitamin D testing."

A study conducted in tropical Hawaii found despite adequate sun exposure, 51% of participants had vitamin D3 levels below the cut point of 30ng/ml.

Another study, conducted in subtropical Queensland, Australia, found inadequate levels amongst 23.4% of the sample, with levels equal to or less than 20ng/ml (50 nmol/L). While 8% of the sample had levels equal or less than 15.2ng/ml (38 nmol/L). If the cut point had been at 30ng/ml (75nmol/L) the percentage would have been much higher.

Studies in rural communities have found levels ranging from 23.2ng/ml (58nmol/L) to 68.4ng/ml (171nmol/L), giving a median of 46ng/ml (115nmol/L). A later study done by the same group found much the same thing.

Two interesting findings came out of the studies. One that vitamin D levels do not drop with age, and in fact increase. One 65 year old having a level of 70ng/ml (175nmol/L). And that pregnant women had high levels. One pregnant woman in fact had a level of 105ng/ml (262.5nmol/L), 5ng/ml higher than a level many regard as toxic!

Is it any wonder people living at high latitudes have an increased risk of disease. Africa might be beset with a vast number of parasitic diseases like malaria, dengue, sleeping sickness, elephantiasis and bilharzia, but it's rare to find heart disease, cancer, diabetes, stroke and the autoimmune diseases in rural communities. All of which are reaching epidemic proportions in higher latitudes.

Is the answer for humans to migrate back to their origins and live again semi-naked in tropical regions? Or to take supplements to raise vitamin D levels. Supplements are the cheaper option. Although there is mounting evidence that the sun plays a greater role in health than merely forming vitamin D on our skins. The more time that can be spent in the sun the better.

Diet of course plays a huge role in the emergence of western diseases, now taking hold of urban communities in Africa with the introduction of nutrient deficient processed foods. But the immediate environment plays a bigger role in low vitamin D levels. Full clothing when in the sun, and working or studying indoors. The few studies of Muslin women are showing very low levels of vitamin D too.

The people most affected by a lack of vitamin D are those with the darkest skin living in higher latitudes. Skin type is critical to vitamin D production, the darker the skin the more time in the sun is required to produce it.

A 2010 study published in America found 90% of the darker skinned people, and three quarters of the white population had levels below 30ng/ml.

Altitude also plays a role, the higher it is, the greater the amount of UV rays. The highest UV intensity is found on the top of Mount Kilimanjaro, with an altitude of 5,895 m, situated at latitude 03S, almost on the equator. Sunburn can be severe at high altitudes and low latitudes.

Animals, including humans make vitamin D3, plants and fungi make vitamin D2. Why do living things make and need it? According to research done by Holick et al in the 1980's... 

"...the UV absorption spectrum for provitamin D, previtamin D, and vitamin D completely overlap the UV absorption spectra for DNA, RNA, and proteins, it is possible that the provitamin D evolved as a natural sunscreen to protect the UV sensitive macromolecules from solar ultraviolet radiation damage."

Professor Holick discovered the conversion of vitamin D to calcidiol and thence to calcitriol.

Vitamin D deficiency is now a worldwide problem, but it wasn't until the Industrial Revolution that this began. Working in factories, living under darkened smog filled skies, the sun rarely reached the earth. Rickets began manifesting in the late 1600's, by the end of the 1900's an estimated 90% of children had it. This lead to young women unable to give birth due to a deformed pelvis, so the first Cesarean was performed.

Many studies are coming out to show that it's on the rise again. One study in America finding 74% to 95% of pregnant black women and 46% to 62% of pregnant white women were vitamin D insufficient. A 2010 study in Qatar found 23.9% of children had rickets, and came from a family history of vitamin D deficiency and diabetes.

Two studies done in Southampton, UK found 20% of children had rickets, while mothers had insufficient levels. The lead author said "He was astonished by the results, which, he said, were "very reminiscent of 17th Century England".

Latitude is inversely related to age at menarche, i.e. the higher the latitude the younger the girls begin their periods. But early menarche is also a risk factor for cardiometabolic disease and cancer. A 2011 study found that vitamin D deficiency is associated with earlier menarche.

The age of menarche is falling. In Europe the average age was seventeen prior to 1830. In the USA the average age in 2000 was about 12.6 years for white girls, 12.1 for black girls and 12.2 for Mexican American girls.

But what of the other problems that have increased since pre-industrial times, insulin resistance, cardiovascular disease, hypertension, infections, cancer, stroke, behavioural disorders, autoimmune diseases, asthma, autism, Alzheimer's, polycystic ovaries and more. Epidemiological evidence points to a lack of vitamin D in every case. Many other studies support this.

Vitamin D is fundamental to cellular health, the vitamin D receptor is found in every cell. It directly or indirectly regulates up to 2,000 genes.

Vitamin D is made on the skin and in the epidermis, which comprises 90-95% keratinocytes. Embedded within the keratinocytes are melanocytes, containing melanin. Melanin gives skin it's colour, but it is the ultimate sunscreen, as it absorbs the entire UV and visible light range protecting it from sun damage. The greater the exposure to sun, the more melanin will be produced leading to the skin becoming darker, or producing a tan.

Keratinocytes have ample vitamin D receptors, and are capable of converting vitamin D into 1,25 (OH)2D3 or calcitriol, the active metabolite. Calcitriol in turn regulates epidermal proliferation and differentiation. Topical application has been found effective against psoriasis, a hyper-proliferative state of keratinocytes. Keratinocytes also have ample progesterone receptor sites.

Although the skin makes vitamin D from UVB rays, it also suffers from UVB and UVA damage. This can cause a significant increase in free radicals. In particular UV radiation caused a rapid and significant increase in hydrogen peroxide levels. Free radicals damage DNA, cause inflammation, death of skin cells, skin ageing and skin cancer. Vitamin D has a photo protective effect, reversing the above effects. It's a powerful anti-inflammatory and antioxidant too, as is progesterone.

UV light causes photo ageing by inducing matrix metalloproteinases (MMPs). These enzymes break down skin connective tissue, causing a pathological reaction such as inflammation and tissue degeneration when in excess. Excess oestrogen also stimulates MMPs, it accelerates the ageing of collagen too. Vitamin D and progesterone are natural inhibitors of MMPs.

1,25-OH2D3 (calcitriol) stimulates the production of cathelicidin and -defensin in kerotinacytes, antimicrobial peptides that protect the skin against bacterial attack. Cathelicidin also promotes wound healing, tissue repair and heals inflammation.

One study says... 

"Humans with deficient cathelicidin production... are prone to infections of epithelial surfaces such as the skin and mucosal membranes. Therefore, anti-microbial peptides such as cathelicidin constitute an integral part of the innate immune response to a variety of infections especially at barrier sites."

Another study says... 

"A cutaneous barrier defends the body against invading pathogenic microorganisms due to both innate and adaptive immunity. Among these microbicidal agents......defensins and cathelicidins directly or indirectly kill a wide range of bacteria, fungi, and viruses.....these peptides not only act as endogenous antibiotics but also display additional roles, such as regulation of inflammatory and immune responses, chemoattracting immune or inflammatory cells to wound or infection/inflammation sites, acceleration of angiogenesis, promotion of wound healing, and reepithelization, and binding and neutralizing of lipopolysaccharides."

Sebocytes have been identified as 1,25(OH)2D3-responsive target cells. Sebocytes are highly specialised, sebum-producing epithelial cells. Sebum forms an integral part of the epidermal barrier and the immune system of the skin. Lauric acid, an extract of coconut oil, dramatically enhances the expression of human beta-defensin in skin sebocytes.

Sebum synthesis is regulated by hormones, in particular the androgens. Excess androgen production leads to excessive sebum production, as seen in acne. Progesterone inhibits the secretion of androgens by increasing sex hormone binding globulin. It also inhibits 5-alpha reductase, the enzyme that converts testosterone into DHT, implicated in acne.

Inflammatory skin diseases can benefit from topical applications of vitamin D and progesterone, together with lauric acid. This has bactericidal properties and acts as a natural antibiotic against Propionibacterium acnes which causes inflammatory acne.

As vitamin D is made naturally in the skin, and is then transported from the epidermal layer down into the blood vessels, topically applied vitamin D is also transported into the blood stream. It does raise blood levels of vitamin D.

Because keratinocytes have the ability to convert vitamin D3 into calcitriol, supplying additional vitamin D to the skin should increase the calcitriol content without harm. Calcitriol is a potent hormone, people given it to take can develop resistance.

One 2012 study found people with low levels of vitamin D had lower average skin moisture. They state further that... 

"Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D(3)."

Basal cell carcinomas (BCCs) are the most common of all human cancers, affecting 1 million people in America. Squamous cell carcinoma (SCC), another skin cancer, is found in about 700,000 people. Hedgehog (HH) signalling underlies several human tumours, including basal cell carcinoma. Several studies are currently testing synthetic inhibitors of HH signalling against at least 8 human cancers.

Sebocyte formation is controlled by various molecular pathways, one of which is also the Hedgehog pathway.

Topical vitamin D3 blocks both proliferation and HH signalling in BCC cells in vitro and in vivo.

The study found that... 

"These results are specific for vitamin D3, because the precursor 7-dehydrocholesterol and the downstream products 25-hydroxy vitamin D3 [25(OH)D] and 1,25-dihydroxy vitamin D3 [1,25(OH)2D] are considerably less effective in reducing... cellular proliferation."

In addition to mutated HH signalling, human BCCs also have mutations in gene p53. This is commonly called the 'guardian of the genome'. Damage to p53 is caused by UV rays. A loss of this greatly accelerates BCC carcinogenesis. Interestingly, p53 controls the tanning process, a loss of p53 or mutations of it would lead to DNA damage and burning rather than tanning, and thence to cancer. Both vitamin D and progesterone activate p53.

A topical skin cream containing vitamin D, and not the usual 1,25-OH2D3 (calcitriol) would appear a safe and effective means of helping the skin heal and prevent skin cancer.

Data collected from the American NHANES studies show a marked decline in vitamin D levels from 1988-1994 compared to the 2001-2004 data. Something is causing this remarkable decline. The sun has not reduced it's output of UVB. In cities, air particulates which block the sun, have reduced since the days of the industrial revolution. Food, even natural, contains little vitamin D, so the processed food intake won't have affected levels.

Even if one supports the CO2/global warming/climate change debate, CO2 levels were 7 times higher during the Jurassic era when dinosaurs roamed the earth. The most monstrous creatures to have lived on land, and if like modern reptiles, they also needed vitamin D. Evidently CO2 didn't affect levels of vitamin D then as it won't now. The Jurassic was only 201 to 145 million years ago, vitamin D had been in existence millennia before.

So that leaves some other factor, and that's interference by man, or more specifically by dermatologists, supported by government agencies. The sun scare started about 20-25 years ago, the hysteria over skin cancer and melanoma increasing as the years passed. And yet lack of vitamin D increases the risk for cancers, including skin. People were told to cover up and apply sunscreen before going into the sun.

But one primary culprit for those living above 40 degrees latitude is the use of sunscreens. An analysis of 10 studies showed that common sunscreens block UVB, the rays that make vitamin D. But fail to block UVA, and in fact transmit large quantities of it. UVA rays penetrate far deeper into the skin, damaging DNA in the process. And therefore sunscreens which do not block UVA too, could contribute to the risk of skin cancer and melanoma in these people.

30-50% of people have a deficiency of vitamin D, particularly those living in climates with little sun, living above 35 degrees north or south of the equator during the winter, work in doors and spend little time in the sun. Or when in the sun are fully clothed and/or apply a sunscreen before going into the sun. It's most important to get the required length of time in the sun, dependant on skin type, before using a sunscreen.

Sunbathing semi-naked to the point of slight redness of the skin, or one minimal erythemal dose (MED), results in 10,000iu to 25,000iu vitamin D being produced.

After sun exposure it's also important to use an organic sunscreen to protect from UV rays damaging the skin. Most sunscreens on the market have toxic ingredients, often do little to protect the skin from UVA, and many contain carcinogens.

Vitamin D is essential for health, have a blood test done to check the level. The test should only be done for 25-hydroxyvitamin D3, also called calcidiol.

Blood levels should be 70-100ng/ml or 175-250nmol/L and not the 30ng/ml or 75nmol/L most labs and doctors regard as adequate.
The minimum daily dose should be 5000iu's per day, although the latest research indicates it should be 10,000iu's per day, see here.

For more information on vitamin D see...

For more information on progesterone see...

Reference websites

Vitamin D3 reference papers

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