Vitamin D metabolism

In the skin, sunlight and ultraviolet rays act on 7-dehydrocholesterol to form vitamin D3.

• Vitamin D2 (known as ergocalciferol) and D3 are obtained from the diet.
  • Moderate amounts of bile salts and fat are required for absorption. An alpha-globulin, vitamin D transport protein, binds to the gut- and skin-derived vitamin D3 and transports it to the liver.

Vitamin D3 has several forms:

• cholecalciferol (calciol) is an inactive, unhydroxylated form of vitamin D3
• calcidiol (25-hydroxyvitamin D3) is measured in the blood to assess vitamin D status
  • in the liver, vitamin D3 is hydroxylated at the 25' position to produce 25-hydroxycholecalciferol (calcidiol). This is then bound to another selective transport protein for transit to the kidneys.
  • most abundant form of vitamin D, but is less active than calcitriol
• calcitriol (also called 1,25-dihydroxyvitamin D3) is the active form of D3
  • produced in the kidneys through the action of 1-hydroxylase enzyme
  • Calcitriol is more potent than the other hydroxylation products in its actions on mineral physiology. Hence, by varying the activity of the 1-hydroxylase enzyme, the ratio of calcitriol to other hydroxylated products can be varied, and so the degree to which calcium and phosphate physiology is affected
    • renal hydroxylation of calcidiol to calcitriol by 1-alpha-hydroxylase is tightly regulated (stimulated by either parathyroid hormone or hypophosphatemia) and serves as the major control point in production of the most active circulating hormone calcitriol (1,25-dihydroxyvitamin D3)

The activity of the 1-hydroxylase enzyme is increased by:

• hypocalcaemia
• hypophosphataemia
• parathyroid hormone
• growth hormone

Calcidiol within the liver is the main storage form of vitamin D; it has a half life of about 14 days.

Reference

• (1) Royal Osteoporosis Society (2020). Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management.
• (2) Bilezikian JP, Formenti AM, Adler RA, Binkley N, Bouillon R, Lazaretti-Castro M, Marcocci C, Napoli N, Rizzoli R, Giustina A. Vitamin D: Dosing, levels, form, and route of administration: Does one approach fit all? Rev Endocr Metab Disord. 2021 Dec;22(4):1201-1218. doi: 10.1007/s11154-021-09693-7.