Vitamin D

Vitamin D
Drug class
Cholecalciferol (D3)
Class identifiers
Synonyms	Calciferols
Use	Rickets, osteoporosis, osteomalacia, vitamin D deficiency
ATC code	A11CC
Biological target	vitamin D receptor
Clinical data
Drugs.com	MedFacts Natural Products
External links
MeSH	D014807
Legal status
In Wikidata

Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions.^[1][2] In humans, the most significant compounds within this group are vitamin D₃ (cholecalciferol) and vitamin D₂ (ergocalciferol).^[2][3]

Unlike the other twelve vitamins, vitamin D is only conditionally essential - in a preindustrial society people had adequate exposure to sunlight and the vitamin was a hormone, as the primary natural source of vitamin D was the synthesis of cholecalciferol in the lower layers of the skin’s epidermis, triggered by a photochemical reaction with ultraviolet B (UV-B) radiation from sunlight or UV-B lamps. Cholecalciferol and ergocalciferol can also be obtained through diet and dietary supplements. Foods such as the flesh of fatty fish are good sources of vitamin D, though there are few other foods where it naturally appears in significant amounts.^[2][4] In the U.S. and other countries, cow's milk and plant-based milk substitutes are fortified with vitamin D₃, as are many breakfast cereals. Dietary recommendations typically assume that all of a person's vitamin D is taken by mouth, given the paucity of sunlight exposure due to urban living, cultural choices for amount of clothing worn when outdoors, and use of sunscreen because of concerns about safe levels of sunlight exposure, including risk of skin cancer.^[2][5]

Vitamin D obtained from the diet or synthesised in the skin is biologically inactive. It becomes active by two enzymatic hydroxylation steps, the first occurring in the liver and the second in the kidneys.^[3] Since most mammals can synthesise sufficient vitamin D with adequate sunlight exposure, it is technically not essential in the diet and thus not a true vitamin. Instead, it functions as a hormone; the activation of the vitamin D pro-hormone produces calcitriol, the active form. Calcitriol then exerts its effects via the vitamin D receptor, a nuclear receptor found in various tissues throughout the body.^[6]

Cholecalciferol is converted in the liver to calcifediol (also known as calcidiol or 25-hydroxycholecalciferol), while ergocalciferol is converted to ercalcidiol (25-hydroxyergocalciferol). These two vitamin D metabolites, collectively referred to as 25-hydroxyvitamin D or 25(OH)D, are measured in serum to assess a person's vitamin D status.^[7] Calcifediol is further hydroxylated by the kidneys and certain immune cells to form calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D.^[8] Calcitriol circulates in the blood as a hormone, playing a major role in regulating calcium and phosphate concentrations, as well as promoting bone health and bone remodeling.

The discovery of the vitamin in 1922 was due to effort to identify the dietary deficiency in children with rickets.^[9] Present day, government food fortification programs in some countries and recommendations to consume vitamin D supplements are intended to prevent or treat vitamin D deficiency rickets and osteomalacia. There are many other health conditions linked to vitamin D deficiency. However, the evidence for health benefits of vitamin D supplementation in individuals who are already vitamin D sufficient is unproven.^{[2][10][11][12]}