About Vitamin D3

The most natural way to get vitamin D3 into the body is through the skin. The body makes vitamin D3 in its skin and safely handles all the vitamin D3 it makes. It makes vitamin D3 through exposure to sunlight with 295-300nm ultraviolet-B light in it. And the body’s skin also safely handles unlimited amounts of applied vitamin D3, such as cod liver oil (from the 1930s on), lanolin (from the 1950s on), and synthetic vitamin D3 (from the 1980s on) based mixes. The body also stores large amounts of vitamin D3 in adipose cells throughout the body. The body simply keeps the vitamin D3 it has in the skin or in adipose cells until vitamin D-binding protein from the liver is made available to pick the vitamin D3 up and carry it into circulation. Making vitamin D3 in skin or putting vitamin D3 on skin, rather than ingesting it, allows the skin to absorb the vitamin D3 into skin cells (to begin protection). Vitamin D3 is hydrophobic “water fearing”, so remains in skin. Blood has a saltwater base (what vitamin D3 fears), so the vitamin D3 doesn’t move until it is picked up and carried into and through circulation. In contrast, ingesting vitamin D3 puts it through the body’s digestive system, which results in huge losses. It passes through the digestive system unchecked, which can create dangerous surges of vitamin D3 in circulation, a condition called hypercalcemia.

Whether vitamin D3 is produced naturally in skin, or is added to skin, once attached to vitamin D-binding protein vitamin D3 is freed to move out of skin and through the body.

On passing through the liver vitamin D3 is converted to calcidiol:

an OH group (upper right) is added in the liver, which changes vitamin D3 to calcidiol (25(OH)D3)

The conversion of vitamin D3 to calcidiol is mandatory: it occurs in the liver when vitamin D3 molecules encounter the liver enzyme CYP2R1 in endoplasmic reticulum in the liver (also called “the principal vitamin D 25-hydroxylase”), or when vitamin D3 molecules encounter the liver enzyme CYP27A1 in mitochondria in the liver (also called “another vitamin D 25-hydroxylase”). Clinical note about CYP2R1: low levels of CYP2R1 activity have been found after 24-hour fasting, in obesity, in type 1 and type 2 diabetes, and in the presence of glucocorticoids. As a result, serum (circulating) calcidiol (25(OH)D3) should no longer be used as a measure of the supply of vitamin D3 in the body.

There are two important issues here, (1) for decades all the medical professionals have been relying on measurements of circulating calcidiol to tell them how much vitamin D3 is in play in the body.  Now we know that that calcidiol (25(OH)D3) measurement is often wrong. And, (2) if you are getting your vitamin D by orally ingesting vitamin D (D2 or D3) limit the amount you consume to a small amount, to 5,000 IU a day (the current FDA recommended daily allowance).  Any more may overdose you, with toxic consequences (possible hypercalcemia). It really is best to get your vitamin D through your skin. And make it vitamin D3, the animal form rather than the plant form (D2). D3 works better than D2 in the human (animal) body.

The next and final conversion of vitamin D3 is the conversion of vitamin D3 to its biologically active form, which takes place in the body mostly in the kidneys, to

an OH group (lower left, on the right side) is added in the kidneys which changes calcidiol (25(OH)D3) to calcitriol (1,25(OH)2D3)

Very little 1,25(OH)2D3 is ever seen in circulation, because it is produced only on demand and is put to work immediately by vitamin D receptors which are located throughout the body, so has little opportunity to circulate.

Active vitamin D3 (also called calcitriol or 1,25(OH)2D3)

– 1,25(OH)2D3 regulates the expression (is the controlling transcription factor) of hundreds of genes involved in skeletal and many other biological functions, particularly in immune, endocrine, and cardiovascular systems.

– 1,25(OH)2D3 regulates calcium and phosphorus homeostasis (balance) and is essential for maintenance of bone mineralization. It increases calcium and phosphorus uptake in the intestine.

– 1,25(OH)2D3 is important for normal bone development and maintenance (severe vitamin D deficiency causes rickets in children and osteomalacia in adults). Secondary hyperparathyroidism due to 1,25(OH)2D3 insufficiency increases bone breakdown and precipitates osteoporosis.

– 1,25(OH)2D3 regulates cell proliferation (cells thrive when 1,25(OH)2D3 is present) and differentiation (cells adapt when 1,25(OH)2D3 is present).

– there are reported associations between low sun exposure, poor vitamin D3 status, and increased risk of developing colorectal and breast cancer.

– there are reported inverse associations between vitamin D3 status and the susceptibility or severity of autoimmune diseases, including type 1 diabetes mellitusmultiple sclerosisrheumatoid arthritis, and systemic lupus erythematosus.

– current evidence from observational studies suggests an inverse relationship between circulating vitamin D3 concentrations and risk of type 2 diabetes mellitus. 

– randomized clinical trials are currently investigating whether vitamin D3 supplementation can limit cognitive deterioration and disease progression in subjects with neurodegenerative disease.

– vitamin D3 insufficiency in pregnant women may have several adverse effects for the mother and soon-to-be newborn. 

– observational studies have documented an association between vitamin D deficiency and increased incidence and severity of the coronavirus disease, COVID-19. 

– preliminary studies have shown that vitamin D3 supplementation offers promising improvements in the management of atopic dermatitis (eczema) and Crohn’s disease

– 1,25(OH)2D3 influences the immune system, with vitamin D receptors (VDRs) being expressed in several types of white blood cells, including monocytes and activated T and B cells.

-1,25(OH)2D3 creates calcium-binding proteins and phosphatases to break up accumulated calcium phosphate salts, and return the useful calcium and phosphate ions they are made of back to circulation.

The body is nerve, muscle, bone, all the support systems they need, and open (extracellular) space (also called ground). The body is organized for thinking (nerve) and acting (muscle and bone). Vitamin D3 uses phosphatases and calcium-binding proteins it creates to clean ground. Calcium phosphates form spontaneously from circulating calcium and phosphate ions. (1) calcium phosphates accumulate everywhere throughout the body on ground, (2) calcium phosphate accumulation is increased during fever, (3) is increased during times of metabolic imbalances, (4) is increased during pregnancy, and (5) is increased at and around sites of injury. Calcium phosphate accumulations “dirty up” ground and/or clog open spaces. As a result, the body, can’t get nutrients, especially oxygen, to cells efficiently. Clear, direct, and straight forward thinking and acting is impeded. Vague aches and pains without clear origin develop and distract away from clear thinking/acting. Cleaning ground of the calcium phosphates results in healthy bodies that better think/act.

Where there are large accumulations of calcium phosphates on ground, circulating macrophages combine and make themselves into multinucleated macrophages (Figure 4), to surround (using neoplastic, “new form” membrane), break up, dissolve, encapsulate, and transport away calcium phosphate masses, another tool the body uses to thoroughly clean ground.

Figure 4: A multinucleated macrophage looking for some calcium phosphate to consume.

WorkoutD is a method of rubbing vitamin D3 (in paste form) into your skin. Once a day rub in 100,000 IU to 200,000 IU of vitamin D3. 200,000 IU should be more vitamin D3 than you can use, no matter how active you are. It will be brought into circulation all day as vitamin D-binding protein is made available to pick the vitamin D3 up and circulate it.

WorkoutD with exercise extends open space calcium phosphate cleanup to every corner of the body. You will be working locally cleaning the extracellular (ground) spaces around cells, and working system-wide using circulating multinucleated macrophages to locate and remove calcium phosphate masses throughout your body.

J. Dalen, at WorkoutD