Vitamin D
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From Wikipedia, the free encyclopedia
For other uses, see Vitamin D (disambiguation).
This article is about the family of D-"vitamins". For individual forms,
see ergocalciferol, cholecalciferol, vitamin D4, vitamin D5, and calcitriol.
Vitamin D
Drug class
Cholecalciferol (D3)
Class identifiers
Synonyms Calciferols
Use Rickets, osteoporosis, 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, and for many other biological
effects.[1][2][3] In humans, the most important compounds in this group are vitamin
D3 (cholecalciferol) and vitamin D2 (ergocalciferol).[2][3][4]
The major natural source of vitamin D is synthesis of cholecalciferol in the lower layers
of the epidermisof the skin, through a photochemical reaction with Ultraviolet B (UV-B)
radiation from sun exposure or UV-B lamps.[1] Cholecalciferol and ergocalciferol can be
ingested from the diet and supplements.[1][2]Only a few foods, such as the flesh of fatty
fish, naturally contain significant amounts of vitamin D.[2][5]In the U.S. and other countries,
cow's milk and plant-derived milk substitutes are fortified with vitamin D, as are many
breakfast cereals.[1] Mushrooms exposed to ultraviolet light contribute useful amounts of
vitamin D2.[2] [6]Dietary recommendations typically assume that all of a person's vitamin D
is taken by mouth, because sun exposure in the population is variable and
recommendations about the amount of sun exposure that is safe are uncertain in view
of the skin cancer risk.[2]
Vitamin D from the diet, or from skin synthesis, is biologically inactive. It is activated by
two protein enzyme hydroxylation steps, the first in the liver and the second in the
kidneys.[1][4] Because vitamin D can be synthesized in adequate amounts by most
mammals if they get enough sunlight, it is not essential and therefore is technically not
a vitamin.[3] Instead it can be considered a hormone, with activation of the vitamin D pro-
hormone resulting in the active form, calcitriol, which then produces effects via a nuclear
receptor in multiple locations.[3]
Cholecalciferol is converted in the liver to calcifediol (25-
hydroxycholecalciferol); ergocalciferol is converted to 25-hydroxyergocalciferol.[1] These
two vitamin D metabolites (called 25-hydroxyvitamin D or 25(OH)D) are measured in
serum to determine a person's vitamin D status.[7][8] Calcifediol is further hydroxylated by
the kidneys and some of the immune system cells to form calcitriol (1,25-
dihydroxycholecalciferol), the biologically active form of vitamin D.[9][10] Calcitriol circulates
as a hormone in the blood, having a major role regulating the concentration
of calcium and phosphate, and promoting the healthy growth and remodeling of bone.
[1]
Calcitriol also has other effects, including some on cell growth, neuromuscular and
immune functions, and reduction of inflammation.[2]
Vitamin D has a significant role in calcium homeostasis and metabolism.[1] Its discovery
was due to effort to find the dietary substance lacking in children with rickets (the
childhood form of osteomalacia).[11] Vitamin D supplements are given to treat or to
prevent osteomalacia and rickets.[1] The evidence for other health effects of vitamin D
supplementation in vitamin D–replete individuals is inconsistent.[2] The effect of vitamin D
supplementation on mortality is not clear, with one meta-analysis finding a small
decrease in mortality in elderly people.[12] Except for the prevention of rickets and
osteomalacia in high-risk groups, any benefit of vitamin D supplements to
musculoskeletal or general health may be small.[13][14][15]
Types
Name Chemical composition Structure
Mixture of molecular compounds of ergocalciferol with lumisterol,
Vitamin D1
1:1
Vitamin D2 ergocalciferol (made from ergosterol)
cholecalciferol
Vitamin D3
(made from 7-dehydrocholesterol in the skin).
Vitamin D4 22-dihydroergocalciferol
sitocalciferol
Vitamin D5
(made from 7-dehydrositosterol)
Several forms (vitamers) of vitamin D exist.[1] The two major forms are vitamin D2 or
ergocalciferol, and vitamin D3 or cholecalciferol.[1] Vitamin D without a subscript refers to
either D2 or D3, or both, and is known collectively as calciferol.[citation needed]
Vitamin D2 was chemically characterized in 1931. In 1935, the chemical structure of
vitamin D3 was defined and shown to result from the ultraviolet irradiation of 7-
dehydrocholesterol. A chemical nomenclature for vitamin D forms was recommended in
1981,[16] but alternative names remain in common use.[4]
Chemically, the various forms of vitamin D are secosteroids, that is, steroids in which
one of the bonds in the steroid rings is broken.[17] The structural difference between
vitamin D2and vitamin D3 is in the side chain, which contains a double bond, between
carbons 22 and 23, and a methyl group on carbon 24 in vitamin D2.[4] Many vitamin D
analogues have been synthesized.[4]
Biology
Calcium regulation in the human body. The [18]
role of active vitamin D (1,25-dihydroxyvitamin D, calcitriol) is shown in orange.
The active vitamin D metabolite calcitriol mediates its biological effects by binding to
the vitamin D receptor(VDR), which is principally located in the nuclei of target cells.[1]
[17]
The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that
modulates the gene expression of transport proteins (such as TRPV6and calbindin),
which are involved in calcium absorption in the intestine.[19] The vitamin D receptor
belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, and
VDRs are expressed by cells in most organs, including the brain, heart, skin, gonads,
prostate and breast.
VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the
maintenance of calcium and phosphorus levels in the blood (with the assistance
of parathyroid hormone and calcitonin) and to the maintenance of bone content.[1][20]
One of the most important roles of vitamin D is to maintain skeletal calcium balance by
promoting calcium absorption in the intestines, promoting bone resorption by
increasing osteoclast number, maintaining calcium and phosphate levels for bone
formation, and allowing proper functioning of parathyroid hormone to maintain serum
calcium levels.[1] Vitamin D deficiency can result in lower bone mineral density and an
increased risk of reduced bone density (osteoporosis) or bone fracture because a lack
of vitamin D alters mineral metabolism in the body.[1][21] Thus, vitamin D is also critical
for bone remodeling through its role as a potent stimulator of bone resorption.[21]
The VDR regulates cell proliferation and differentiation. Vitamin D also affects the
immune system, and VDRs are expressed in several white blood cells,
including monocytes and activated T and B cells.[22] In vitro, vitamin D increases
expression of the tyrosine hydroxylase gene in adrenal medullary cells, and affects the
synthesis of neurotrophic factors, nitric oxide synthase, and glutathione.[23]
Vitamin D receptor expression decreases with age.[1]
Deficiency
Main article: Vitamin D deficiency
A diet with insufficient vitamin D in conjunction with inadequate sun exposure causes
vitamin D deficiency, which is defined as a blood 25(OH)D level
