What is Vitamin D and what does it do in the body?

Vitamin D, also known as the “sunshine vitamin”, is a very unique vitamin in that it also acts as a hormone in the body. Previtamin D3 is synthesized in the skin from 7-dehydrocholesterol by ultraviolet light. Previtamin D3 is then converted into D3 (cholecalciferol) by the lower layers of the skin. This D3 is then transported to the adipose tissue for storage or to the liver for activation.

 

 

 

The cytochrome P450 enzymes then change the D3 or D2 (ergocalciferol) into 25-hydroxyvitamin D3. Finally, the kidneys convert 25-hydroxyvitamin D3 through the CYP27B1 enzyme into the active form of 1α,25-dihydroxyvitamin D. It has also been shown that a variety of tissues, including skin, parathyroid gland, breast, colon, prostate, as well as cells of the immune system and bone cells can produce 1α,25-dihydroxyvitamin D. 

Once this active form is made, it enters cells to perform actions in the body.  Upon entering the nucleus of a cell, 1α,25-dihydroxyvitamin D binds to the VDR and recruits another nuclear receptor: 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. We have identified thousands of VDREs throughout the genome, and VDR activation by 1α,25-dihydroxyvitamin D is thought to directly and/or indirectly regulate around 100 to 1,250 genes. 

 

 

 

One action that vitamin D exerts in the body is calcium balance. When the parathyroid gland senses that calcium levels are lower than normal, it secretes parathyroid hormone (PTH), which triggers the kidneys to produce 1α,25-dihydroxyvitamin D. This active form of vitamin D is released into circulation and enters target cells where it binds to and activates VDR, which leads to changes in gene expression that normalizes serum calcium by increasing the absorption of calcium in the intestine, increasing the reabsorption of calcium in the kidneys, and takes calcium from the bones if there isn’t sufficient dietary calcium to normalize serum levels. 

Vitamin D also regulates phosphorus balance, which is very closely related to calcium balance. 1α,25-dihydroxyvitamin D increases the absorption of phosphorus in the intestines by stimulating the expression of a sodium-phosphate cotransporter in the small intestine. PTH increases urinary excretion of phosphorus by reducing reabsorption in the kidney, but it is unknown if 1α,25-dihydroxyvitamin D can directly regulate phosphorus transport in the kidneys. 

 

 

 

Vitamin D also regulates cell differentiation, which is essential for the specialization of cells as well as the prevention of uncontrolled proliferation that can lead to cancer. 1α,25-dihydroxyvitamin D, inhibits proliferation and stimulates the differentiation of cells by binding to the VDR in cells. 

Vitamin D also modulates the immune system through the VDR. In specific circumstances, monocytes, macrophages, and T cells can express the 25-hydroxyvitamin D3-1α-hydroxylase enzyme and produce 1α,25-dihydroxyvitamin D, which acts locally to regulate the immune response. Studies have shown that 1α,25-dihydroxyvitamin D has a variety of effects on immune system function, including enhancing innate immunity and inhibiting the development of autoimmunity. On the other hand, Vitamin D deficiency may compromise the integrity of the immune system and lead to inappropriate immune responses such as autoimmune disorders. 

Vitamin D also plays a role in insulin secretion. The VDR is also expressed in the insulin-secreting cells of the pancreas; animal studies have shown that 1α,25-dihydroxyvitamin D plays a role in insulin secretion under conditions of increased insulin demand. Conversely, insufficient vitamin D status may have an adverse effect on insulin secretion and glucose tolerance in type 2 diabetes mellitus. 

 

 

 

Vitamin D may also play a role in blood pressure regulation. The renin-angiotensin system is a system that helps regulate blood pressure by constricting blood vessels and increasing sodium and water retention when the system is activated. In mice studies, it was shown that 1α,25-dihydroxyvitamin D decreases the expression of the gene encoding renin through its interaction with the VDR. Since faulty activation of the renin-angiotensin system can contribute to the development of hypertension, adequate vitamin D status may be important for decreasing the risk of hypertension. 

Vitamin D is also essential for the health of the intestinal lining. Studies have shown that Vitamin D boosts intestinal mucosal immunity, preserves tight junctions, and supports the function of the colonic epithelium. On the other hand, deficient vitamin D enhances gut permeability, colon mucosa bacterial infiltration, and translocation of intestinal pathogens in the gut leading to inflammation and metabolic endotoxemia. 

Vitamin D is essential for the health of the microbiome and thus related to brain health due to the gut-brain axis. VDR are present in the gut; Vitamin D deficiency has been linked to dysbiosis, which is associated with poor mental health and cognitive function. 

Vitamin D is also directly related to brain health. It has been shown to decrease memory impairment by enhancing cholinergic (the use of acetylcholine) activity activity and reducing the expression of inflammatory factors. Vitamin D is integral for neurological health because of its neuro protective effects and its influence on neurotrophic factors and neurotransmitter synthesis. 

 

What are some causes of Vitamin D deficiency?

There are many factors that can put people at risk for vitamin D deficiency. Seasonal changes, geographic location, pollution, and clouds all affect the strength of UVB rays that are needed to synthesize vitamin D. Not spending enough time outside and/or covering up from the sun with clothing and sunscreen can also block the synthesis of vitamin D in the skin and bring a need for increased oral intake. Exclusively breastfed infants are at risk for deficiency due to the low amount of Vitamin D in breast milk especially if they have darker skin and don’t have much sun exposure; it is recommended that the infant supplement vitamin D or the mother supplement to increase vitamin D intake through breast milk. 

People with darker skin synthesize less vitamin D. Older people also do not synthesize as much vitamin D in the skin and often spend less time in the sunlight. Chronic kidney disease affects vitamin D status because recall from above, the kidneys help convert vitamin D to its active form: 1α,25-dihydroxyvitamin D. Fat malabsorption syndromes can also decrease absorption of vitamin D because it is a fat-soluble vitamin. People with inflammatory bowel disease have been shown to be at a higher risk of vitamin D deficiency. 

Obesity can also lead to vitamin D deficiency because vitamin D is stored in fat tissue and thus not as much is available for use in the body. Finally, magnesium deficiency can put someone at risk for vitamin D deficiency because magnesium is needed for the metabolism steps of vitamin D into its active form. 

 

 

 

Vitamin D deficiency can put someone at risk for bone health problems including osteoporosis. As discussed above, vitamin D is needed for calcium regulation. Insufficient vitamin D leads to inefficient calcium absorption, so the body must rely on parathyroid hormone, which mobilizes calcium from the bones and can lead to issues with bone health. 

Severe vitamin D deficiency in infants and children can lead to rickets, which is the inability of the bones to properly calcify leading to bowed weight bearing limbs, delayed closure of soft spots on the skull, and a deformed rib cage. In adults, severe vitamin D deficiency is known as osteomalacia where bone mineral is progressively lost leading to bone pain, softening bones, and increased risk of osteoporosis. Vitamin D deficiency also causes muscle weakness and pain in children and adults. 

To continue reading, see Vitamin D (Part 2).