Vitamin D occurs in two related forms:

a. Cholecalciferol (vit. D3): It is produced in the skin from 7-dehydrocholesterol by the action of ultraviolet light from the sun rays.

b. Ergocalciferol (vit. D2 calciferol): It is obtained from vegetable source. It is the form which is used in commercial vitamin formulations and in dairy products.

Vitamin D3 is a prohormone and is not biologically active. It is first hydroxylated in the endoplasmic reticulum of liver to form to active calcifediol (25 (OH) D3).

This metabolite is then cs-hydroxylated by the mitochondrial P-450 in the kidney to the major active metabolite calcitriol (1,25 (OH)2 D3). This step is modulated by parathyroid hormone.

Vitamin D3 and its metabolites circulate in plasma after tightly binding with alf a-globulin. Excess vitamin is stored in fat and adipose tissues.

Actions of Vitamin D on Target Tissues

  1. Calcitriol stimulates calcium and phosphorus absorption from intestine.

2. Calcitriol has antirachitic effect due to its ability to increase osteoblast mediated activation of osteoclasts. It also promotes differentiation of osteoclast precursors which is facilitated by parathyroid hormone.

3. Both calcitriol and calcifediol increase reabsorption of calcium ions and phosphorus from proximal tubules. However, this action is weaker and less marked compared to PTH.

4. Vitamin D regulates secretion of PTH.

5. Vitamin D has some immunoregulatory properties because it enhances lymphokine production.

The net effect of vitamin D3 is to raise both serum calcium and phosphorus levels. Their high levels reduce the rate of production of calcitriol by the kidney.

Calcitriol itself inhibits PTH secretion. Thus there are negative feedback loops which control secretion of calcitriol and PTH.

Preparations of Vitamin D

• Cholecalciferol (1 pg vitamin D3 = 40 U of vitamin D): Daily requirement to prevent the deficiency symptoms is 200—400 fIJI day.

• Ergocalciferol (calciferol, vitamin D2) is derived from yeast and fungal sterol.

• Calcitriol (active vitamin D2) is available for oral as well as parenteral use.

• Alfa calcidol (1-ct-hydroxy cholecalciferol) and dihydrotachysterol are synthetic prodrugs which are rapidly hydroxylated to calcitriol in liver. These are used to treat renal rickets, vitamin dependent rickets and hypoparathyroidism.

• Calcipotriol (calcipotriene), doxercalciferol (1-ct-hydroxy-D2) and paricalcitol are calcitriol analogues. Their clearance is faster because they are poorly bound with alfaglobulin. So there is less risk of causing hypercalcaemia and hypercalciuria.

Therefore, they are useful in other conditions like psoriasis and secondary hyperthyroidism with chronic renal disease.

Vitamin D Deficiency

• In children, it causes rickets due to deficient calcification of osteoid tissue. So there occurs bony deformities like bow legs, enlarged skull, spinal curvature, chest deformities and hepatosplenomegaly.

• In adults, osteomalacia occurs due to decalcification and demineralization of bones. It is characterized by bone tenderness with pain and loss of bone density.

Hypervitaminosis D

Hypervitaminosis D develops after chronic administration of more than 15,000 lU/day of vitamin D3. So there occurs increased plasma calcium levels and its ectopic deposition in blood vessels, parenchymal organs and soft tissues.

It is characterized by weakness, fatigue, vomiting, diarrhoea, polyuria, renal stones, and hypertension and growth retardation (in children).

Treatment consists of stopping vitamin intake and keeping the patient on low calcium diet. However, recovery may not be complete and may take longer time.

Drug Interactions of Vitamin D

• Liquid paraffin reduces Vitamin D absorption

• Phenytoin and phenobarbitone on prolonged use enhance metabolism of vitamin D by enzyme induction