VITAMIN D3

VITAMIN D3

Vitamin D3 (cholecalciferol) is a steroid hormone produced in the skin when exposed to ultraviolet light or obtained from dietary sources. 
The active form of Vitamin D3, 1,25-dihydroxycholecalciferol (calcitriol) plays an important role in maintaining blood calcium and phosphorus levels and mineralization of bone. 
The activated form of Vitamin D3 binds to vitamin D receptors and modulates gene expression. 
This leads to an increase in serum calcium concentrations by increasing intestinal absorption of phosphorus and calcium, promoting distal renal tubular reabsorption of calcium and increasing osteoclastic resorption.

CAS: 67-97-0
European Community (EC) Number: 200-673-2

Molecular Formula: C27H44O
Molecular Weight: 384.6 g/mol

IUPAC Name: (1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol

Chemical Classes: Biological Agents -> Vitamins and Derivatives

Vitamin D3, CAS # 67-97-0, also known as cholecalciferol, is a steroid hormone produced in the skin or obtained from dietary sources. 
Vitamin D3 is an essential mediator of bone calcium metabolism.

Vitamin D3 is used as an essential mediator of intestinal calcium absorption and bone calcium metabolism. 
Vitamin D3 is also used as a therapeutic vitamin. 
Further, Vitamin D3 is used as a nutritional supplement and to fortify foods. 
In addition to this, Vitamin D3 is used as pharmaceutical drug and used in the treatment of respiratory diseases involving chronic inflammation such as asthma.

Vitamin D3 is one of five forms of vitamin D. 
Vitamin D3 is an inactive steroid molecule with one ring open (secosteroid). 
Vitamin D3 is converted to bioactive calcitriol by successive hydroxylations in the liver and kidney.

General Description
• Vitamin D3 is a steroid hormone generated in the skin when the 7-dehydrocholesterol interacts with ultraviolet irradiation. 
Vitamin D3 can also be found in several types of food for daily intake.
• Vitamin D3 binds to vitamin D receptors, thus modulating gene expression

Applications
• Vitamin D3 presents in vitro antiproliferative and antimetastatic activities on breast, colon, and prostate cancer cells

Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement.

Vitamin D3 is made in the skin following UVB light exposure.
Vitamin D3 is converted in the liver to calcifediol (25-hydroxyvitamin D) which is then converted in the kidney to calcitriol (1,25-dihydroxyvitamin D).
One of its actions is to increase calcium uptake by the intestines.
Vitamin D3 is found in food such as some fish, beef liver, eggs, and cheese.
Plants, cow milk, fruit juice, yogurt, and margarine also may have Vitamin D3 added to them in some countries, including the United States.

Vitamin D3 can be taken as an oral dietary supplement to prevent vitamin D deficiency or as a medication to treat associated diseases, including rickets.
Vitamin D3 is also used for familial hypophosphatemia, hypoparathyroidism that is causing low blood calcium, and Fanconi syndrome.

Vitamin D3 was first described in 1936.
Vitamin D3 is on the World Health Organization's List of Essential Medicines.
In 2020, Vitamin D3 was the 60th most commonly prescribed medication in the United States, with more than 11 million prescriptions.
Vitamin D3 is available as a generic medication and over the counter.

Vitamin D3 is a steroid hormone produced in the skin when exposed to ultraviolet light or obtained from dietary sources. 
The active form of Vitamin D3, 1,25-dihydroxycholecalciferol (calcitriol) plays an important role in maintaining blood calcium and phosphorus levels and mineralization of bone. 
The activated form of cholecalciferol binds to vitamin D receptors and modulates gene expression. 
This leads to an increase in serum calcium concentrations by increasing intestinal absorption of phosphorus and calcium, promoting distal renal tubular reabsorption of calcium and increasing osteoclastic resorption.

Experimental Properties

Physical Description: Vitamin d3 appears as fine colorless crystals. 
Water insoluble.
Color / Form: Fine needles from dilute acetone
Colorless crystals
Odor: ODORLESS
Melting Point: 183 to 185 °F
Solubility: Insoluble
Sol in the usual org solvents; slightly sol in vegetable oils

Vitamin D3, present in food, is absorbed via the intestinal lymphatics where the vitamin exists in the chylomicron fraction. 
Approximately half of absorbed vitamin D in chylomicrons is transferred to VBP in blood. 
VBP is the principle chaperone protein that facilitates uptake of vitamin D by the liver while albumin also plays a minor role in transporting vitamin D to the liver for further metabolic conversion. 
Circulating serum concentration of vitamin D3 or vitamin D2 is not clinically relevant as they are converted rapidly to their 25-hydroxylated metabolite in the liver. 
The negative feedback of 25(OH)D on the activity of CYP2R1 and is not influenced by plasma calcium and phosphorus concentrations 

Vitamin D3 is the naturally occurring vitamin D that is produced in the skin. 
Vitamin D2 comes from the UV irradiation of fungal and plant sterol ergosterol. 
Both vitamin D2 and vitamin D3 are considered to be equally biologically potent in humans. 
Once vitamin D3 is made in the skin or vitamin D2 and vitamin D3 (vitamin D without a subscript represents either vitamin D2 or vitamin D3) are ingested from the diet, the vitamin D is transported on the vitamin D binding protein and interacts with megalin to provide vitamin D to hepatocytes. 
In hepatocytes, mitochondrial and microsomal vitamin D-25-hydroxylases metabolize vitamin D to 25.

Cholecalciferol (vitamin D3) is used as a dietary supplement when the amount of vitamin D in the diet is not enough. 
People most at risk for vitamin D deficiency are older adults, breastfed infants, people with dark skin, obese people, and those with limited sun exposure, or gastrointestinal disease (GI; affecting the stomach or intestines) such as Crohn's disease or celiac disease. 
Cholecalciferol (vitamin D3) is also used along with calcium to prevent and treat bone diseases such as rickets (softening and weakening of bones in children caused by lack of vitamin D), osteomalacia (softening and weakening of bones in adults caused by lack of vitamin D), and osteoporosis (a condition in which the bones become thin and weak and break easily). 
Cholecalciferol (vitamin D3) is in a class of medications called vitamin D analogs. 
Vitamin D3 is needed by the body for healthy bones, muscles, nerves, and to support the immune system. 
Vitamin D3 works by helping the body to use more of the calcium found in foods or supplements.

Vitamin D (ergocalciferol-D2, cholecalciferol-D3, alfacalcidol) is a fat-soluble vitamin that helps your body absorb calcium and phosphorus. 
Having the right amount of vitamin D, calcium, and phosphorus is important for building and keeping strong bones. 
Vitamin D is used to treat and prevent bone disorders (such as rickets, osteomalacia).
Vitamin D is made by the body when skin is exposed to sunlight. 
Sunscreen, protective clothing, limited exposure to sunlight, dark skin, and age may prevent getting enough vitamin D from the sun.
Vitamin D with calcium is used to treat or prevent bone loss (osteoporosis). 
Vitamin D is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia). 
It may be used in kidney disease to keep calcium levels normal and allow normal bone growth. 
Vitamin D drops (or other supplements) are given to breast-fed infants because breast milk usually has low levels of vitamin D.

Cholecalciferol, also known as vitamin D3, is a secosteroid produced by the skin and can also be present in certain foods such as dairy products, eggs, and fish. 
Its primary function is to maintain normal calcium and phosphate levels in the serum. 
During winter and in areas with minimal sun exposure, dietary supplementation is necessary for optimal musculoskeletal health.

The labeled indication for cholecalciferol is dietary supplementation. 
The off-label indications for cholecalciferol include hypothyroidism, prevention of osteoporosis, and Vitamin D insufficiency/ deficiency in both healthy patients or those with chronic kidney disease (CKD).

Aside from its known role in bone mineral metabolism, various studies have found a link between Vitamin D3 supplementation and favorable prognoses of different diseases such as hypertension, type 1 and 2 diabetes, cardiovascular disease, cancer, rheumatoid arthritis (RA), polycystic ovarian syndrome (POS), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and various dermatologic diseases.

Sources/Uses
An essential mediator of intestinal calcium absorption and bone calcium metabolism; 
High concentrations found in fish liver oils; 
Used as a therapeutic vitamin; 
Active product registrations in the US for use as a rodenticide; 
Used as a nutritional supplement;
Permitted for use as an inert ingredient in non-food pesticide products.

For the treatment of vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. 
Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis.

Mechanism of Action
Vitamin D3 gets generated in the skin upon sun exposure. 
Light energy is absorbed in the skin via 7-dehydrocholesterol, where the ultraviolet B (UVB) converts 7-dehydrocholesterol to cholecalciferol, an inactive vitamin D molecule.

Vitamin D3 undergoes two hydroxylation processes to activate it. 
The initial hydroxylation occurs in the liver via the enzyme 25-hydroxylase and results in 25-hydroxycholecalciferol, which is used to assess the body’s reserve of vitamin D because it has a longer half-life compared to 1,25-dihydroxycholecalciferol. 
1,25-dihydroxycholecalciferol has a half-life of 15 hours, while 25-hydroxycholecalciferol has a half-life of 15 days.

The second hydroxylation occurs in the kidneys via the enzyme 1-alpha-hydroxylase, yielding 1,25- dihydroxycholecalciferol (calcitriol), the biologically active form of vitamin D. 
1,25-dihydroxycholecalciferol production in the kidneys undergoes regulation by parathyroid hormone (PTH), calcium, and phosphorus levels.

Calcitriol is a hydrophobic molecule requiring a carrier protein such as vitamin D-binding protein for transport in the bloodstream. 
Once released, calcitriol binds intracellular vitamin D receptors (VDR) that researchers discovered to not only be in the small intestines, renal tubules, and bones but also various types of cell types such as lymphocytes, pancreatic cells, keratinocytes, parathyroid, and pituitary gland cells. 
The activated VDR, in turn, induces transcription activation of certain genes and suppression of others.

Calcitriol is the main hormone controlling mineral homeostasis and bone function. 
It promotes calcium and phosphate absorption from the small intestine, increases bone mineral density by suppressing bone resorption, and increases phosphate secretion in the renal tubule.

Vitamin D3 (cholecalciferol) has a few health benefits, including helping the body absorb calcium. 
Foods such as fish, beef liver, eggs, and cheese naturally contain vitamin D3. 
Vitamin D3 can also be produced in the skin following exposure to ultraviolet (UV) radiation from the sun.

Supplement forms of vitamin D3 are also available and may be used for general health, as well as the treatment or prevention of vitamin D deficiency.

Vitamin D3 is one of two types of vitamin D. 
Vitamin D3 differs from vitamin D2 (ergocalciferol) in both its structure and sources.

Vitamin D2 and vitamin D3 are chemically similar and are both well-absorbed in the gut. Where they differ significantly is in their sources:

Vitamin D2 is naturally found in mushrooms, including shiitake, Portobello, and crimini mushrooms. 
The vitamin D content increases when these mushrooms are exposed to UV radiation.
Vitamin D3 is naturally found in animals and animal-derived products like milk. 
Vitamin D3 is also directly synthesized in the skin when it is exposed to ultraviolet B (UVB) radiation.

Aside from the fact that vitamin D3 is likely easier to consume in your day-to-day diet, unless you are a vegetarian or vegan, vitamin D3 has proven superior to vitamin D2 in two other important ways:

Vitamin D3 has better bioavailability, meaning more of the vitamin enters the bloodstream and can be used by the body
Vitamin D3 has a better half-life, meaning it stays in circulation for longer

Vitamin D3 (cholecalciferol) is an over-the-counter dietary supplement that's taken by mouth to raise vitamin D levels. 
It's for adults and children who aren't getting enough vitamin D through food or sunlight, or for people who've certain conditions that cause vitamin D deficiency, like liver or kidney problems. 
Vitamin D3 (cholecalciferol) is usually taken daily, but it's sometimes taken weekly, depending on the dose. 
Vitamin D3 (cholecalciferol) isn't known to cause any side effects if you're taking the recommended dose.

Vitamin D3 is the form of vitamin D called cholecalciferol. 
Vitamin D3 is the most widely known of the vitamin D series and is a fat soluble vitamin that is stored to some degree in the body. 
Vitamin D3 is used as a dietary supplement, for the treatment of vitamin D deficiency, or to prevent a deficiency.

Vitamin D, in general, is a secosteroid generated in the skin when 7-dehydrocholesterol located there interacts with ultraviolet irradiation - like that commonly found in sunlight. 
Both the endogenous form of vitamin D (that results from 7-dehydrocholesterol transformation), vitamin D3 (cholecalciferol), and the plant-derived form, vitamin D2 (ergocalciferol), are considered the main forms of vitamin d and are found in various types of food for daily intake. 
Structurally, ergocalciferol differs from cholecalciferol in that it possesses a double bond between C22 and C23 and has an additional methyl group at C24. Finally, ergocalciferol is pharmacologically less potent than cholecalciferol, which makes vitamin D3 the preferred agent for medical use.

Appropriate levels of vitamin D must be upheld in the body in order to maintain calcium and phosphorus levels in a healthy physiologic range to sustain a variety of metabolic functions, transcription regulation, and bone metabolism. 
However, studies are also ongoing to determine whether or not cholecalciferol may also play certain roles in cancer, autoimmune disorders, cardiovascular disease, and other medical conditions that may be associated with vitamin D deficiency.

SYNONYMS:

Vitamin D3
cholecalciferol
67-97-0
Colecalciferol
Calciol
Ricketon
Oleovitamin D3
Deparal
Arachitol
Delsterol
Trivitan
Ebivit
Vigorsan
vitamin d-3
Colecalcipherol
Colecalciferolum
Cholecalciferolum
D3-Vicotrat
D3-Vigantol
(+)-Vitamin D3
Vi-de-3-hydrosol
NEO Dohyfral D3
Provitina
Quintox
Rampage
Vitinc Dan-Dee-3
1406-16-2
Delta-D
Cholecalciferol, D3
Colecalciferolo
Vi-De3
Duphafral D3 1000
Colecalciferol D3
Vitamin D 3
Irradiated 7-dehydrocholesterol
CCRIS 6286
HSDB 820
Videkhol
7-Dehydrocholesterol, irradiated
FeraCol
CHEBI:28940
Granuvit D3
Vitamin d (cholecalciferol)
CC
EINECS 200-673-2
EPA Pesticide Chemical Code 202901
NSC 375571
NSC-375571
UNII-1C6V77QF41
VIGANTOLETTEN
Colecalciferol [INN]
9,10-Secocholesta-5,7,10(19)-trien-3-beta-ol
Vitamin d3 (as cholecalciferol)
DP-R206
1C6V77QF41
Vitamin d assay system suitability
(1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol
AK R215 COMPONENT COLECALCIFEROL
AK-R215 COMPONENT COLECALCIFEROL
9,10-Seco(5Z,7E)-5,7,10(19)-cholestatrien-3-ol
DTXSID6026294
(3beta,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-3-ol
(5Z,7E)-(3S)-9,10-secocholesta-5,7,10(19)-trien-3-ol
9,10-Secocholesta-5,7,10(19)-trien-3-ol, (3beta,5Z,7E)-
VidDe-3-hydrosol
NSC375571
DP-R206 COMPONENT VITAMIN D3
Colecalciferol (INN)
(3S,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-3-ol
Vitamin D3 10 microg/mL in Acetonitrile
(5Z,7E)-(3S)-9,10-seco-5,7,10(19)-cholestatrien-3-ol
9,10-Secocholestra-5,7,10(19)-trien-3-ol, (3beta,5Z,7E)-
FOSAMAX PLUS D COMPONENT CHOLECALCIFEROL
9,10-Secocholesta-5,7,10(19)-trien-3-ol
CHOLECALCIFEROL COMPONENT OF FOSAMAX PLUS D
Vitamin D3 (Cholecalciferol)
COLECALCIFEROL (MART.)
COLECALCIFEROL [MART.]
Micro-dee
9,10-Seco(5Z,7E)-5,7,10(19)-cholestatrien-3beta-ol
Colecalciferolo [DCIT]
9,10-Secocholesta-5(Z),7(E),10(19)-trien-3(.beta.)-ol
9,10-Secocholesta-5,7,10(19)-trien-3-ol, (3.beta.,5Z,7E)-
CHOLECALCIFEROL (EP MONOGRAPH)
CHOLECALCIFEROL [EP MONOGRAPH]
CHOLECALCIFEROL (USP MONOGRAPH)
CHOLECALCIFEROL [USP MONOGRAPH]
(1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-1-[(1R)-1,5-dimethylhexyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylene-cyclohexanol
(S,Z)-3-(2-((1R,3aS,7aR,E)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-4H-inden-4-ylidene)ethylidene)-4-methylenecyclohexan-1-ol
Cyclohexanol, 3-[(2E)-2-[(1R,3aS,7aR)-1-[(1R)-1,5-dimethylhexyl]octahydro-7a-methyl-4H-inden-4-ylidene]ethylidene]-4-methylene-, (1S,3Z)-
Colecalciferolum [INN-Latin]
CCRIS 5813
Vitamin D3 emulsifiable
EINECS 215-797-2
MFCD00078131
DTXCID306294
UNII-9VU1KI44GP
Vitamin D3; Cholecalciferol
Devaron
(3.beta.,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-3-ol
vitaminum d3
Prestwick_63
Cholecalciferol D3
NCGC00159331-02
(1S,3Z)-3-[(2E)-2-[(1R,3AR,7AS)-7A-METHYL-1-[(2R)-6-METHYLHEPTAN-2-YL]-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-4-METHYLIDENE-CYCLOHEXAN-1-OL
Cyclohexanol, 3-((2E)-2-((1R,3aS,7aR)-1-((1R)-1,5-dimethylhexyl)octahydro-7a-methyl-4H-inden-4-ylidene)ethylidene)-4-methylene-, (1S,3Z)-
9,10-secocholesta-5,7,10-trien-3-ol
Cholecalciferol [USP:BAN:JAN:ISO]
()-Vitamin D3
Delta-D (TN)
CHOLECALCIFEROL IMPURITY A (EP IMPURITY)
Prestwick3_000429
bmse000507
UPCMLD-DP152
VITAMIN D3 [MI]
VITAMIN D3 [FCC]
SCHEMBL3126
9VU1KI44GP
CHEMBL1042
BSPBio_000418
CHOLECALCIFEROL [ISO]
CHOLECALCIFEROL [JAN]
9,10-Secocholesta-5,7,10(19)-trien-3beta-ol
Cholecalciferol; 67-97-0
Cholecalciferol (JP17/USP)
CHOLECALCIFEROL [HSDB]
CHOLECALCIFEROL [INCI]
CHOLECALCIFEROL [VANDF]
BPBio1_000460
MEGxm0_000458
COLECALCIFEROL [WHO-DD]
COLECALCIFEROL [WHO-IP]
CHOLECALCIFEROL [USP-RS]
UPCMLD-DP152:001
ACon1_001997
A11CC05
COLECALCIFEROL [EMA EPAR]
HMS2096E20
Cholecalciferol, >=98% (HPLC)
(1S,3Z)-3-((2E)-2-((1R,3AR,7AS)-7A-METHYL-1-((2R)-6-METHYLHEPTAN-2-YL)-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE)ETHYLIDENE)-4-METHYLIDENE-CYCLOHEXAN-1-OL
(3 beta,5Z,7E)-9,10-Secocholesta-5,7,10(19)-trien-3-ol
Cholecalciferol, analytical standard
BDBM50030475
CHOLECALCIFEROL [ORANGE BOOK]
LMST03020001
s4063
Cholecalciferol for system suitability
5,7-CHOLESTADIEN-3-BETAL-OL
AKOS015950641
AC-8884
CCG-268466
COLECALCIFEROLUM [WHO-IP LATIN]
CS-1179
DB00169
SMP1_000068
USEPA/OPP Pesticide Code: 202901
NCGC00091072-01
NCGC00159331-04
BS-42465
HY-15398
Cholecalciferol (D3), analytical standard
C05443
D00188
Cholecalciferol, meets USP testing specifications
9,10-Secocholesta-5,7,10(19)-trien-3?-ol
Q139347
(5E,7E)-9,10-Secocholesta-5,7,10-trien-3-ol
Q-201931
VITAMIN D ASSAY SYSTEM SUITABILITY [USP-RS]
3-beta,Z,7E-9,10-Secocholestr-5,7,10(19)-trien-3-ol
(3beta,Z,7E)-9,10-Secocholesta-5,7,10(19)-trien-3-ol
9,10-Secocholesta-5,7,10(19)-trien-3-ol, (3b,5Z,7E)-
Cholecalciferol, European Pharmacopoeia (EP) Reference Standard
Colecalciferol, British Pharmacopoeia (BP) Reference Standard
(5E,7E)-9,10-SECOCHOLESTA-5,7,10(19)-TRIEN-3beta-OL
Cholecalciferol, United States Pharmacopeia (USP) Reference Standard
(3 BETA, 5Z, 7E)-9,10-SECOCHOLESTA-5,7,10(19)-TRIEN-3-OL
Cholecalciferol for system suitability, European Pharmacopoeia (EP) Reference Standard
(1S,3Z)-3-[(2E)-2-[7a-Methyl-1-(6-methylheptan-2-yl)-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol
Cholecalciferol (Vitamin D3), Pharmaceutical Secondary Standard; Certified Reference Material