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workoutD

John Dalen

The following bullets are the Linus Pauling Institute’s (LPI) current (2024) summary points about vitamin D, at Vitamin D | Linus Pauling Institute | Oregon State University:

  • “Vitamin D can be synthesized in the skin upon exposure to [me: ultraviolet-B (UVB) radiation in] sunlight [me: the sun must be high in the sky for UVB to be present in sunlight at low elevations (where nearly all people live), which occurs during the mid-day hours on summer days; haze and water in open air disperse and absorb UVB radiation; skin cannot be covered over with clothing; UVB radiation does not penetrate through glass] and is then metabolized in the liver and kidney to the metabolically active form called 1α,25-dihydroxyvitamin D. Through binding to the vitamin D receptor (VDR), 1α,25-dihydroxyvitamin D can regulate the expression of hundreds of genes involved in skeletal and other biological functions [me: if vitamin D is plentiful in the body, 1α,25-dihydroxyvitamin D will regulate the expression of hundreds of genes…].
  • Vitamin D is essential for maintenance of bone mineralization through the regulation of calcium and phosphorus homeostasis. Vitamin D also exhibits many non-skeletal effects, particularly on the immune, endocrine, and cardiovascular systems.
  • Vitamin D is important for normal bone development and maintenance. Severe vitamin D deficiency causes rickets in children and osteomalacia in adults.
  • Secondary hyperparathyroidism due to vitamin D insufficiency can increase bone breakdown and precipitate osteoporosis. Randomized clinical trials indicate that supplementation with at least 800 IU/day of vitamin D may reduce the risk of falls and fractures in older individuals.
  • Vitamin D can regulate cell differentiation and growth by binding to the vitamin D receptor (VDR) found in most body cells [me: when vitamin D is plentiful, vitamin D will regulate…]. Observational studies have reported associations between low sun exposure, poor vitamin D status, and increased risk of developing colorectal and breast cancer. Randomized controlled trials are needed to evaluate whether cancer prevention may benefit from vitamin D supplementation.
  • Various observational studies have reported inverse associations between vitamin D status and the susceptibility or severity of autoimmune diseases, including type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.
  • Current evidence from observational studies suggests an inverse relationship between circulating vitamin D concentrations and risk of type 2 diabetes mellitus. It is not yet known whether correcting vitamin D deficiency in individuals with glucose intolerance can decrease the risk of progression to type 2 diabetes mellitus.
  • Randomized clinical trials are currently investigating whether vitamin D supplementation can limit cognitive deterioration and disease progression in subjects with neurodegenerative disease.
  • Vitamin D insufficiency in pregnant women may be associated with several adverse effects for the mother and newborn. Safety and benefits of vitamin D supplementation during pregnancy both need to be evaluated in clinical trials.
  • 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 D supplementation may offer promising improvements in the management of atopic dermatitis (eczema) and Crohn’s disease.”

About Vitamin D metabolism, the Linus Pauling Institute states:

“Cholecalciferol and ergocalciferol are biologically inactive precursors of vitamin D and must be converted to biologically active forms in the liver and kidneys (Figure 1). Indeed, following dietary intake or synthesis in the epidermis of skin after UVB exposure, both forms of vitamin D enter the circulation and are transported to the liver by the vitamin D-binding protein (and to a lesser extent by albumin). In hepatocytes (liver cells), vitamin D is hydroxylated to form 25-hydroxyvitamin D. Exposure to sunlight or dietary intake of vitamin D increases serum concentrations of 25-hydroxyvitamin D. 25-Hydroxyvitamin D constitutes the major circulating form of vitamin D, and the sum of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 concentrations in serum is used as an indicator of vitamin D nutritional status. The renal 25-hydroxyvitamin D3-1α-hydroxylase enzyme (also known as CYP27B1) eventually catalyzes a second hydroxylation that converts 25-hydroxyvitamin D to 1α,25-dihydroxyvitamin D (calcitriol). The production of 1α,25-dihydroxyvitamin D in the kidneys is regulated by several factors, including serum phosphorus, calcium, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and 1α,25-dihydroxyvitamin D itself. While the kidney is the main source of 1α-hydroxylase activity, extra-renal production of 1α,25-dihydroxyvitamin D has also been demonstrated in a variety of tissues, including skin, parathyroid gland, breast, colon, prostate, as well as cells of the immune system and bone cells. Most of the physiological effects of vitamin D in the body are related to the activity of 1α,25-dihydroxyvitamin D. Various forms of vitamin D are listed in Figure 1.”

About Vitamin D’s mechanisms of action, the Linus Pauling Institute states:

“Most, if not all, actions of vitamin D are mediated through a nuclear transcription factor* known as the vitamin D receptor (VDR) (Figure 2). Upon entering the nucleus of a cell, 1α,25-dihydroxyvitamin D binds to the VDR and recruits another nuclear receptor known as retinoid X receptor (RXR). In the presence of 1α,25-dihydroxyvitamin D, the VDR/RXR complex binds small sequences of DNA known as vitamin D response elements (VDREs) and initiates a cascade of molecular interactions that modulate the transcription of specific genes. Thousands of VDREs have been identified throughout the genome, and VDR activation by 1α,25-dihydroxyvitamin D is thought to directly and/or indirectly regulate 100 to 1,250 genes.”

*Transcription factor: a protein that functions to initiate, enhance, or inhibit the transcription of a gene. Transcription factors can regulate the formation of a specific protein encoded by a gene.

About Vitamin D’s influence on calcium balance, the Linus Pauling Institute states:

“Maintenance of serum calcium concentrations within a narrow range is vital for normal functioning of the nervous system, as well as for bone growth and maintenance of bone density. Vitamin D is essential for the efficient utilization of calcium by the body. The parathyroid glands sense serum calcium concentrations and secrete parathyroid hormone (PTH) if calcium concentrations decrease below normal (Figure 3). Elevations in PTH stimulate the activity of the 25-hydroxyvitamin D3-1α-hydroxylase enzyme in the kidney, resulting in the increased production of 1α,25-dihydroxyvitamin D. The active vitamin D form, 1α,25-dihydroxyvitamin D, is released into the circulation and transported to target tissues. Within target cells, 1α,25-dihydroxyvitamin D binds to and induces the activation of VDR, which leads to changes in gene expression that normalize serum calcium by (1) increasing the intestinal absorption of dietary calcium, (2) increasing the reabsorption of calcium filtered by the kidneys, and (3) mobilizing calcium from bone when there is insufficient dietary calcium to maintain normal serum calcium concentrations.”

In summary points, statements about vitamin D metabolism, statements about vitamin D’s mechanisms of action, and statements about vitamin D’s influence on calcium balance, the Linus Pauling Institute states that vitamin D can regulate “the expression of hundreds of genes involved in skeletal and other biological functions,” “thousands of VDREs (vitamin D response elements) have been identified throughout the genome”, and “VDR (vitamin D receptor) activation by 1α,25-dihydroxyvitamin D is thought to directly and/or indirectly regulate 100 to 1,250 genes.”

Table 1: The functions and numbers of genes involved in producing the body’s proteins. 23.6% remained unclassified as of 2011.

function# of genes% of genome
unclassified406123.6%
transcription factors (me: vitamin D is a transcription factor*)206712.0%
transferases15128.8%
nucleic acid binding14668.5%
transporters10986.4%
receptors10766.3%
signaling molecules9615.6%
enzyme modulators8575.0%
oxidoreductases5503.2%
proteases4762.8%
hydrolases4542.6%
cytoskeletal proteins4412.6%
membrane traffic proteins3211.9%
structural proteins2801.6%
ligases2601.5%
transfer/carrier proteins2481.4%
phosphatases (me: vitamin D produces phosphatases*)2301.3%
chaperones1300.8%
defense/immunity proteins1070.6%
lyases1040.6%
isomerases940.5%
cell adhesion molecules930.5%
transmembrane receptor regulatory/ /adaptor proteins840.5%
extracellular matrix proteins720.4%
cell junction proteins670.4%
calcium-binding proteins (me: vitamin D produces calcium-binding proteins*)630.4%
storage proteins150.1%
surfactants150.1%
viral proteins70.0%

*Transcription factor: a protein that functions to initiate, enhance, or inhibit the transcription of a gene. Transcription factors can regulate the formation of a specific protein encoded by a gene.

*Phosphatase: an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. With respect to calcium phosphates, phosphatases cleave the phosphate ions out of calcium phosphates and return them (typically) to circulation.

*Calcium-binding protein: proteins that participate in calcium cell signaling pathways by binding to Ca2+, the calcium ion that plays an important role in many cellular processes. With respect to calcium phosphates, calcium-binding proteins bind to the calcium ions (Ca2+) in calcium phosphates and (typically) put them back to work immediately in the cells the calcium-binding proteins are working out of.

Nine years later, at year 2020, only around 8% remained unclassified (see Human genome – Wikipedia). At year 2022 the human genome had been completely sequenced, although it will be many years before it is completely understood.

WorkoutD: the body is made of cells, the basic structural and functional unit of all forms of life.  About cells the LPI (Linus Pauling Institute) states “vitamin D can regulate cell differentiation and cell growth (proliferation) by binding to the vitamin D receptor found in most body cells.” WorkoutD‘s position with regard to cell differentiation and cell growth is this: (1) as reported by the LPI, research indicates that vitamin D can control cell differentiation and cell growth; (2) since nearly all of us have been proven to be moderately to severely vitamin D deficient, when we make vitamin D plentiful in our bodies, vitamin D will come to control (a portion?) (much of?) the cell differentiation and cell growth in our bodies; and (3) doing this will improve our health and well-being. Doing this may even greatly improve our health and well-being.

WorkoutD: within the body cells are organized into nerve, muscle, bone, and support mechanisms/systems to support the nerve, muscle, and bone. Vitamin D uses the phosphatases and calcium-binding proteins it produces to clean and clear open (extracellular) space of the calcium phosphates that form and accumulate there. Those calcium phosphates form spontaneously from steadily circulating calcium and phosphate ions. WorkoutD‘s position with regard to how the body is organized is this: the body is organized for thinking (nerve) and acting (muscle and bone); (1) calcium phosphates accumulate everywhere throughout the body; (2) calcium phosphate accumulation is increased during fever; (3) calcium phosphate accumulation is increased during times of metabolic imbalances; (4) calcium phosphate accumulation is increased during pregnancy; and (5) calcium phosphate accumulation is increased at and around sites of injury. Cleaning and clearing open (extracellular) space of calcium phosphates is essential to maintaining healthy bodies that act (muscle and bone) when told to act (nerve).

WorkoutD: it also may be that vitamin D uses some calcium-binding proteins to re-split Ca2 molecules (neutral and no longer useful) to Ca++ ions (active and useful). WorkoutD asserts that maintaining plenty of vitamin D in circulation may actually reduce the number of Ca2 molecules (neutral and no longer useful) in circulation (not proven).

WorkoutD: where there are large accumulations of calcium phosphates in open space, circulating macrophages combine and make themselves into multinucleated macrophages (Figure 4), to surround (using neoplastic or “new form” membrane), break up, dissolve, encapsulate, and transport away calcium phosphate masses throughout the body, another tool the body uses to thoroughly clean and clear open space areas in the body.

Figure 4: A multinucleated macrophage looking for some calcium phosphate to consume. Multinucleated macrophages that consume calcium phosphate are also called osteoclasts (“bone splitters”).

WorkoutD is a method of applying a large amount of vitamin D powder directly to the skin to make vitamin D plentiful in the body. The powder is manufactured by Provitas, at www.Provitas.com (thank-you, Provitas). Once or twice a day apply a gram (100,000 IU, a heaping quarter (¼) teaspoon) of the vitamin D powder directly to your skin. Rub it in until it begins to dissolve into your skin. It will thoroughly dissolve into your skin very soon (but to ensure you don’t wash any away, apply the vitamin D powder after you shower each day). This is workoutD. The body stores all leftover vitamin D in adipocytes (fat cells)) for rainy days (days when you don’t apply vitamin D to your skin).

WorkoutD is also an exercise method to extend open space calcium phosphate cleanup to every corner of the body. After you apply vitamin D powder, stretch and flex your muscles on your frame. Stretch and expand your frame. Walk. Run. Lift weights. Play. Be active. You will be helping multinucleated macrophages locate calcium phosphate masses throughout your body. Phosphatases and calcium-binding protein work locally w/cells, multinucleated macrophages work system-wide, w/circulation. This is also workoutD.

WorkoutD is