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| Pronunciation | /ˌkoʊləkælˈsɪfərɒl/ |
| Other names | vitamin D3 |
| AHFS/Drugs.com | Professional Drug Facts |
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| Routes of administration | By mouth,intramuscular |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.612 |
| Chemical and physical data | |
| Formula | C27H44O |
| Molar mass | 384.648 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 83 to 86 °C (181 to 187 °F) |
| Boiling point | 496.4 °C (925.5 °F) |
| Solubility in water | Practically insoluble in water, freely soluble in ethanol, methanol and some other organic solvents. Slightly soluble in vegetable oils. |
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Cholecalciferol, also known asvitamin D3,colecalciferol orcalciol, is a type ofvitamin D that is produced by the skin when exposed toUVB light; it is found in certain foods and can be taken as adietary supplement.[3]
Cholecalciferol is synthesised in the skin following sunlight exposure.[4] It is then converted in the liver tocalcifediol (25-hydroxycholecalciferol D), which is further converted in the kidney tocalcitriol (1,25-dihydroxycholecalciferol D).[4] One of calcitriol's most important functions is to promotecalcium uptake by the intestines.[5] Cholecalciferol is present in food such as fatty fish, beef liver, eggs, and cheese.[6][7] In some countries, cholecalciferol is also added to products like plants, cow milk, fruit juice, yogurt, and margarine.[6][7]
Cholecalciferol can be taken orally as a dietary supplement to preventvitamin D deficiency or as a medication to treat associated diseases, includingrickets.[8][9] It is also used in the management offamilial hypophosphatemia,hypoparathyroidism that is causinglow blood calcium, andFanconi syndrome.[9][10] Vitamin-D supplements may not be effective in people with severekidney disease.[11][10] Excessive doses in humans can result in vomiting, constipation, muscle weakness, and confusion.[5] Other risks includekidney stones.[11] Doses greater than40000 IU (1000 μg) per day are generally required beforehigh blood calcium occurs.[12] Normal doses,800–2000 IU per day, are safe inpregnancy.[5]
Cholecalciferol was first described in 1936.[13] It is on theWorld Health Organization's List of Essential Medicines.[14] In 2023, it was the 68th most commonly prescribed medication in the United States, with more than 9 million prescriptions.[15][16] Cholecalciferol is available as ageneric medication.[10][17][18]
Cholecalciferol (vitamin D3) appears to stimulate the body'sinterferon type I signaling system that protects against bacteria and viruses, unlikevitamin D2.[19]
Cholecalciferol is a form of vitamin D which is naturally synthesized in skin and functions as a pro-hormone, being converted tocalcitriol. This is important for maintaining calcium levels and promoting bone health and development.[4] As a medication, cholecalciferol may be taken as a dietary supplement to prevent or to treat vitamin D deficiency. One gram is40000000 (40×106)IU, equivalently1 IU is0.025 μg, or25 ng. Dietary reference intake values for vitamin D (ergocalciferol, which is D2, or cholecalciferol, which is D3), or both, have been established and recommendations vary depending on the country:
Low levels of vitamin D3 are more commonly found in individuals living in northern latitudes or with other reasons for a lack of regular sun exposure, including being housebound, frail, elderly, or obese, having darker skin, and wearing clothes that cover most of the skin.[23][24] Supplements are recommended for these groups of people.[24]
TheInstitute of Medicine in 2010 recommended a maximum uptake of vitamin D of4000 IU/d, finding that the dose for lowest observed adverse effect level is 40,000 IU daily for at least 12 weeks,[25] and that there was a single case of toxicity above10000 IU after more than seven years of daily intake; this case of toxicity occurred in circumstances that have led other researchers to dispute whether it is a credible case to consider when making vitamin D intake recommendations.[25] Patients with severe vitamin D deficiency will require treatment with aloading dose; its magnitude can be calculated based on the actual serum 25-hydroxy-vitamin D level and body weight.[26]
There are conflicting reports concerning the relative effectiveness of cholecalciferol (D3) versusergocalciferol (D2), with some studies suggesting less efficacy of D2, and others showing no difference. There are differences in absorption, binding and inactivation of the two forms, with evidence usually favoring cholecalciferol in raising levels in blood, although more research is needed.[27]
A much less common use of cholecalciferol therapy inrickets utilizes a single large dose and has been calledstoss therapy.[28][29][30] Treatment is given either orally or byintramuscular injection of300000 IU (7500 μg) to500000 IU (12500 μg =12.5 mg), in a single dose, or sometimes in two to four divided doses. There are concerns about the safety of such large doses.[30]
Low circulating vitamin D levels have been associated with lower totaltestosterone levels in males. Vitamin D supplementation could potentially improve total testosterone concentration, although more research is needed.[31]
A meta-analysis of 2007 concluded that daily intake of1000 to 2000 IU/d of vitamin D3 could reduce the incidence of colorectal cancer with minimal risk.[32] Also a 2008 study published in Cancer Research has shown the addition of vitamin D3 (along with calcium) to the diet of some mice fed a regimen similar in nutritional content to a new Western diet with 1000 IU cholecalciferol per day prevented colon cancer development.[33] In humans, with400 IU daily, there was no effect of cholecalciferol supplements on the risk of colorectal cancer.[34]
Supplements are not recommended for prevention of cancer as any effects of cholecalciferol are very small.[35] Although correlations exist between low levels of blood serum cholecalciferol and higher rates of various cancers,multiple sclerosis,tuberculosis, heart disease, and diabetes,[36] the consensus is that supplementing levels is not beneficial.[37] It is thought that tuberculosis may result in lower levels.[38] It, however, is not entirely clear how the two are related.[39]
Cholecalciferol is one of the five forms ofvitamin D.[40] Cholecalciferol is asecosteroid, that is, a steroid molecule with one ring open.[41]
By itself cholecalciferol is inactive. It is converted to its active form by twohydroxylations: the first in the liver, byCYP2R1 orCYP27A1, to form 25-hydroxycholecalciferol (calcifediol, 25-OH vitamin D3). The second hydroxylation occurs mainly in the kidney through the action ofCYP27B1 to convert 25-OH vitamin D3 into 1,25-dihydroxycholecalciferol (calcitriol, 1,25-(OH)2vitamin D3). All these metabolites are bound in blood to thevitamin D-binding protein. The action of calcitriol is mediated by thevitamin D receptor, anuclear receptor which regulates the synthesis of hundreds of proteins and is present in virtually every cell in the body.[4]
Click on icon in lower right corner to open.
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
7-Dehydrocholesterol is the precursor of cholecalciferol.[4] Within the epidermal layer of skin, 7-dehydrocholesterol undergoes anelectrocyclic reaction as a result ofUVB light atwavelengths between290 and 310 nm, with peak synthesis occurring at293 nm.[42] This results in the opening of the vitamin precursor B-ring through aconrotatory pathway makingprevitamin D3 (pre-cholecalciferol).[43] In a process which is independent of UV light, the pre-cholecalciferol then undergoes a [1,7] antarafacialsigmatropic rearrangement[44] and therein finally isomerizes to form vitamin D3.
The active UVB wavelengths are little present in sunlight, and sufficient amounts of cholecalciferol can be produced with moderate exposure of the skin, depending on the strength of the sun.[42] Time of day, season, latitude, and altitude affect the strength of the sun, and pollution, cloud cover or glass all reduce the amount of UVB exposure. Exposure of face, arms and legs, averaging5–30 minutes twice per week, may be sufficient, but the darker the skin, and the weaker the sunlight, the more minutes of exposure are needed. Vitamin D overdose is impossible from UV exposure; the skin reaches an equilibrium where the vitamin degrades as fast as it is created.[42]
Cholecalciferol can be produced in skin from the light emitted by the UV lamps intanning beds, which produce ultraviolet primarily in theUVA spectrum, but typically produce 4% to 10% of the total UV emissions as UVB. Levels in blood are higher in frequent users of tanning salons.[42]
A 293 nanometer UVB light emitting diode (LED) was found to be 2.4 times more efficient in producing vitamin D3 than the sun in less than1⁄60 the time. (https://pubmed.ncbi.nlm.nih.gov/28904394/).
Whether cholecalciferol and all forms of vitamin D are by definition "vitamins" can be disputed, since the definition of vitamins includes that the substance cannot be synthesized by the body and must be ingested. Cholecalciferolis synthesized by the body during UVB radiation exposure.[4]
The three steps in the synthesis and activation of vitamin D3 are regulated as follows:
Cholecalciferol is produced industrially for use invitamin supplements andto fortify foods. As apharmaceutical drug it is called cholecalciferol (USAN) or colecalciferol (INN,BAN). It is produced by theultraviolet irradiation of7-dehydrocholesterol extracted fromlanolin found in sheep'swool.[45] Cholesterol is extracted from wool grease and wool wax alcohols obtained from the cleaning of wool after shearing. The cholesterol undergoes a four-step process to make 7-dehydrocholesterol, the same compound that is produced in the skin of animals. The 7-dehydrocholesterol is then irradiated with ultraviolet light. Some unwantedisomers are formed during irradiation: these are removed by various techniques, leaving a resin which melts at about room temperature and usually has a potency of25000000 to 30000000 International Units/gram.
Cholecalciferol is also produced industrially for use in vitamin supplements fromlichens, which is suitable for vegans.[46][47]
Cholecalciferol is very sensitive toUV radiation and will rapidly, but reversibly, break down to form supra-sterols, which can further irreversibly convert toergosterol.[citation needed]
Rodents are somewhat more susceptible to high doses than other species, and cholecalciferol has been used in poison bait for the control of these pests.[48][18]
The mechanism of high dose cholecalciferol is that it can produce "hypercalcemia, which results in systemic calcification of soft tissue, leading tokidney failure,cardiac abnormalities,hypertension, CNS depression, and GI upset. Signs generally develop within18–36 h of ingestion and can include depression,loss of appetite,polyuria, andpolydipsia."[17] High-dose cholecalciferol will tend to rapidly accumulate inadipose tissue yet release more slowly[49] which will tend to delay time of death for several days from the time that high-dose bait is introduced.[48]
In New Zealand,possums have become a significant pest animal. For possum control, cholecalciferol has been used as the active ingredient in lethal baits.[50] TheLD50 is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added to the bait.[51][52] Kidneys and heart are target organs.[53] LD50 of 4.4 mg/kg has been reported in rabbits, with lethality to almost all rabbits ingesting doses greater than 15 mg/kg.[54] Toxicity has been reported across a wide range of cholecalciferol dosages, with LD50 as high as 88 mg/kg or LDLo as low as 2 mg/kg reported for dogs.[55]
Researchers have reported that the compound is less toxic to non-target species than earlier generations of anticoagulant rodenticides (Warfarin andcongeners) orBromethalin,[56] and thatrelay toxicosis (poisoning by eating a poisoned animal) has not been documented.[17] Nevertheless, the same source reports that use of cholecalciferol inrodenticides may still pose a significant hazard to other animals, such as dogs and cats, when rodenticide bait or other forms of cholecalciferol are directly ingested.[17]
Incidence of vitamin D3 toxicosis in animals is relatively less than that of anticoagulant and bromethalin toxicosis. Relay toxicosis from vitamin D3 has not been documented.
0.15% cholecalciferol bait appears to have application for pocket gopher control.' Cholecalciferol can be a single high-dose toxicant or a cumulative multiple low-dose toxicant.
{{cite journal}}: CS1 maint: overridden setting (link){{cite journal}}: CS1 maint: overridden setting (link){{cite journal}}: CS1 maint: overridden setting (link){{cite journal}}: CS1 maint: overridden setting (link){{cite journal}}: CS1 maint: overridden setting (link){{cite journal}}: CS1 maint: overridden setting (link){{cite journal}}: CS1 maint: overridden setting (link)Cholecalciferol is an acute (single-feeding) and/or chronic (multiple-feeding) rodenticide toxicant with unique activity for controlling commensal rodents including anticoagulant-resistant rats. Cholecalciferol differs from conventional acute rodenticides in that no bait shyness is associated with consumption and time to death is delayed, with first dead rodents appearing 3–4 days after treatment.
We investigated the effect of oral high-dose cholecalciferol on plasma and adipose tissue cholecalciferol and its subsequent release, and on plasma 25-hydroxyvitamin D (25(OH)D). ... We conclude that orally-administered cholecalciferol rapidly accumulates in adipose tissue and that it is very slowly released while there is energy balance.
Use of cholecalciferol as a rodenticide in bait lowered the risk of secondary poisoning and minimized the toxicity of non-target species
