|Jmol-3D images||Image 1|
|Molar mass||384.64 g/mol|
|Appearance||White, needle-like crystals|
| (what is: / ?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Vitamin D3 has several forms:
- Cholecalciferol (sometimes called calciol) is an inactive, unhydroxylated form of vitamin D3).
- Calcifediol (also called calcidiol, hydroxycholecalciferol, 25-hydroxyvitamin D3, etc. and abbreviated 25(OH)D) is one of the forms measured in the blood to assess vitamin D status.
- Calcitriol (also called 1,25-dihydroxyvitamin D3) is the active form of D3.
7-Dehydrocholesterol is the precursor of vitamin D3. Within the epidermal layer of skin, 7-Dehydrocholesterol undergoes an electrocyclic reaction as a result of UVB radiation, resulting in the opening of the vitamin precursor B-ring through a conrotatory pathway. Following this, the previtamin D3 undergoes a [1,7] antarafacial sigmatropic rearrangement  and therein finally isomerizes to form vitamin D3.
Regulation of metabolism
- Cholecalciferol is synthesized in the skin from 7-dehydrocholesterol under the action of ultraviolet B light. It reaches an equilibrium after several minutes depending on several factors including conditions of sunlight (latitude, season, cloud cover, altitude), age of skin, and color of skin.
- Hydroxylation in the endoplasmic reticulum of liver hepatocytes of cholecalciferol to calcifediol (25-hydroxycholecalciferol) by 25-hydroxylase is loosely regulated, if at all, and blood levels of this molecule largely reflect the amount of vitamin D3 produced in the skin or the vitamin D2 or D3 ingested.
- Hydroxylation in the kidneys of calcifediol 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).
Cholecalciferol is produced industrially for use in vitamin supplements and to fortify foods by the ultraviolet irradiation of 7-dehydrocholesterol extracted from lanolin found in sheep's wool. Paraphrasing a more detailed explanation, 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 stored in the skin of animals. The 7-dehydrocholesterol is then irradiated with ultra violet light. Some unwanted isomers are formed during irradiation. These are removed by various techniques, leaving a resin which melts at about room temperature and usually has a potency of 25,000,000 to 30,000,000 International Units per gram.
One gram is 40,000,000 (40x106) IU, equivalently 1 IU is 0.025 µg.
Recommendations vary depending on the country. In the US they are: 15 µg/d (600 IU per day) for all individuals (males, female, pregnant/lactating women) under the age of 70 years-old. For all individuals older than 70 years, 20 µg/d (800 IU per day) is recommended. (Recommendations in Europe: 5 µg/d, in France: 25 µg) A growing body of researchers question whether the current recommended adequate levels are sufficient to meet physiological needs, particularly for individuals deprived of regular sun exposure or those at higher risk such as those with higher melanin content in the skin (i.e., those whose ancestors are African, Middle Eastern, Latin American, Mediterranean or Asian), the obese, and those who live far from the equator. The upper limit (UL) for vitamin D has been recommended as 4,000 IU daily. The 4,000-IU cut-off was determined by the Institute of Medicine in 2010 after reviewing the then-current medical literature, finding that the dose for lowest observed adverse effect level is 40,000 IU daily for at least 12 weeks, and that there was a single case of toxicity above 10,000 IU after more than 7 years of daily intake; this case of toxicity occurred in circumstances that have led other researchers to dispute it as a credible case to consider when making vitamin D intake recommendations. The Institute of Medicine did not find evidence of toxicity between 4,000 IU and 10,000 IU, so the 4,000-IU figure is more of an estimate than a number based on evidence of toxicity above 4,000 IU. Patients with severe vitamin D deficiency will require treatment with a loading dose; its magnitude can be calculated based on the actual serum 25-hydroxy-vitamin D level and body weight.
Also, there is a therapy for rickets utilizing a single dose, called stoss therapy in Europe, taking from 300,000 IU (7,500 µg) to 500,000 IU (12,500 µg = 1.25 mg), in a single dose, or in two to four divided doses.
"Vitamin D2 toxicity can result from regular excess intake of this vitamin, and may lead to hypercalcemia and excess bone loss. Individuals at particular risk include those with hyperparathyroidism, kidney disease, sarcoidosis, tuberculosis, or histoplasmosis. Chronic hypercalcemia may lead to serious or even life-threatening complications, and should be managed by a physician. Early symptoms of hypercalcemia may include nausea, vomiting, and anorexia (appetite/weight loss), followed by polyuria (excess urination), polydipsia (excess thirst), weakness, fatigue, somnolence, headache, dry mouth, metallic taste, vertigo, tinnitus (ear ringing), and ataxia (unsteadiness). Kidney function may become impaired, and metastatic calcifications (calcium deposition in organs throughout the body) may occur, particularly affecting the kidneys. Treatment involves stopping the intake of vitamin D or calcium, and lowering the calcium levels under strict medical supervision, with frequent monitoring of calcium levels. Acidification of urine and corticosteroids may be necessary."
There are conflicting reports concerning the absorption of cholecalciferol (D3) versus ergocalciferol (D2), with some studies suggesting less efficacy of D2, and others showing no difference. At present, D2 and D3 doses are frequently considered interchangeable, but more research is needed to clarify this.
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 cholecaliferol per day prevented colon cancer development. In humans, with 400 IU daily, there was no effect.
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. It has been claimed that the compound is less toxic to non-target species. However, in practice it has been found that use of cholecalciferol in rodenticides represents a significant hazard to other animals, such as dogs and cats. "Cholecalciferol produces hypercalcemia, which results in systemic calcification of soft tissue, leading to renal failure, cardiac abnormalities, hypertension, CNS depression, and GI upset. Signs generally develop within 18-36 hr of ingestion and can include depression, anorexia, polyuria, and polydipsia."
In New Zealand, possums have become a significant pest animal, and cholecalciferol has been used as the active ingredient in lethal gel baits and cereal pellet baits "DECAL" for possum control. The LD50 is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added to the bait.
Kidneys and heart are target organs.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".
- Hypervitaminosis D, Vitamin D poisoning
- Ergocalciferol, vitamin D2.
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, a kidney enzyme that converts calcifediol to calcitriol.
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- Okamura, W. H., Elnagar, H. Y., Ruther, M. & S. Dobreff. (1993). "Thermal [1,7]-sigmatropic shift of previtamin D3 to vitamin D3: synthesis and study of pentadeuterio derivatives". Journal of Organic Chemistry 58 (3): 600–610. doi:10.1021/jo00055a011.
- Vitamin D3 Story. Retrieved 8 April 2012.
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- Ting Wang; Göran Bengtsson; Ingvar Kärnefelt; Lars Olof Björn (2001 Sep 1). "Provitamins and vitamins D₂ and D₃ in Cladina spp. over a latitudinal gradient: possible correlation with UV levels". J Photochem Photobiol B. (Department of Plant physiology, Lund University, Sweden). 62(1-2): 118–22. Retrieved 2013-03-15.
- DRIs for Calcium and Vitamin D
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- Shah BR, Finberg L (September 1994). "Single-day therapy for nutritional vitamin D-deficiency rickets: a preferred method". J. Pediatr. 125 (3): 487–90. doi:10.1016/S0022-3476(05)83303-7. PMID 8071764.
- Vitamin D: MedlinePlus Supplements with the National Academy of Sciences dosing recommendations at the Medline Plus website.
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- Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE (February 2006). "Calcium plus vitamin D supplementation and the risk of colorectal cancer". N. Engl. J. Med. 354 (7): 684–96. doi:10.1056/NEJMoa055222. PMID 16481636.
- "Merck Veterinary Manual - Rodenticide Poisoning: Introduction".
- Morgan D (2006). "Field efficacy of cholecalciferol gel baits for possum (Trichosurus vulpecula) control". New Zealand Journal of Zoology 33 (3): 221–8. doi:10.1080/03014223.2006.9518449.
- Jolly SE, Henderson RJ, Frampton C, Eason CT (1995). "Cholecalciferol Toxicity and Its Enhancement by Calcium Carbonate in the Common Brushtail Possum". Wildlife Research 22 (5): 579–83. doi:10.1071/WR9950579.
- "Kiwicare Material Safety Data Sheet".
- NIST Chemistry WebBook page for cholecalciferol
- University of California TV - What’s a Vitamin D Deficiency?
- University of California TV - Dose-Response of Vitamin D and a Mechanism for Cancer Prevention
- Vitamin D metabolism, sex hormones, and male reproductive function.