Cholecalciferol | |
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(3β,5Z,7E)-9,10-secocholesta-
5,7,10(19)-trien-3-ol |
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Other names
vitamin D3, activated 7-dehydrocholesterol.
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Identifiers | |
CAS number | 67-97-0 = |
ChemSpider | 9058792 |
UNII | 1C6V77QF41 |
EC number | 200-673-2 |
ChEMBL | CHEMBL1042 |
O[C@@H]1CC(\C(=C)CC1)=C\C=C2/CCC[C@]3(C2CC[C@@H]3[C@H](C)CCCC(C)C)C
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InChI=1S/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18-24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23-13-/t21-,24+,25-,26?,27-/m1/s1
Key: QYSXJUFSXHHAJI-QWSSABAFSA-N InChI=1/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18-24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23-13-/t21-,24+,25-,26?,27-/m1/s1 Key: QYSXJUFSXHHAJI-QWSSABAFBD |
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Properties | |
Molecular formula | C27H44O |
Molar mass | 384.64 g/mol |
Appearance | White, needle-like crystals |
Melting point |
83–86 °C |
(what is this?) (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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Infobox references |
Cholecalciferol is a form of vitamin D, also called vitamin D3 or calciol.[1][2]
It is structurally similar to steroids such as testosterone, cholesterol, and cortisol (though vitamin D3 itself is a secosteroid).
Contents |
Forms
Vitamin D3 has several forms:
- Cholecalciferol, (sometimes called calciol) is an inactive, unhydroxylated form of vitamin D3)
- Calcifediol (also called calcidiol, hydroxycholecalciferol, or 25-hydroxyvitamin D3, and abbreviated 25(OH)D) is one of the forms measured in the blood to assess vitamin D status[3]
- Calcitriol (also called 1,25-dihydroxyvitamin D3) is the active form of D3.
Metabolism
7-Dehydrocholesterol is the precursor of vitamin D3 and forms cholecalciferol only after being exposed to solar UV radiation and also indoor sun tanning machines.
Cholecalciferol is then hydroxylated in the liver to become calcifediol (25-hydroxyvitamin D3).
Next, calcifediol is again hydroxylated, this time in the kidney, and becomes calcitriol (1,25-dihydroxyvitamin D3). Calcitriol is the most active hormone form of 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).
As food fortification
Although cholecalciferol can be synthesized in the skin (see Metabolism), it is also a form of vitamin D added to fortify foods. Cholecalciferol is produced industrially by the irradiation of 7-dehydrocholesterol extracted from lanolin found in sheep's wool. In foods where animal products are not desired, an alternative compound is ergocalciferol (also known as vitamin D2) derived from the fungal sterol ergosterol.
Dose
One gram of pure vitamin D3 is 40 000 000 (40x106) IU, where one IU is equivalent to 0.025 μg. Recommendations are: 5 micrograms (200 IU or International Units) daily for all individuals (males, female, pregnant/lactating women) under the age of 50 years-old. For all individuals from 50-70 years-old, 10 micrograms daily (400 IU) is recommended. For those who are over 70 years-old, 15 micrograms daily (600 IU) is suggested. Some authors have questioned whether the current recommended adequate levels are sufficient to meet physiological needs, particularly for individuals deprived of regular sun exposure. The upper limit (UL) for vitamin D has been recommended as 2,000 IU daily due to toxicities that can occur when taken in higher doses."[4] 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, Latin American, 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 toxicity had consistently occurred when doses of 40,000 IU daily were taken,[5] and that there was a single case of toxicity above 10,000 IU daily; this case of toxicity occurred under circumstances which have led other researchers to dispute it as a credible case to consider when making vitamin D intake recommendations.[5] The Institute of Medicine did not find evidence of toxicity between 4,000 IU and 10,000 IU, so the 4,000 IU number is more of an estimate than a number based on evidence of toxicity above 4,000 IU. [6] 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.[7]
Also, there is a therapy for rickets utilizing a single dose, called stoss therapy in Europe - taking from 300 000 IU (7500 μg) to 500 000 IU (12 500 μg), as a single dose, or two to four divided doses.[8]
The 25-hydroxy vitamin D (calcifediol) blood test is used to determine how much vitamin D is in the body. The normal range of calcifediol is 30.0 to 74.0 ng/mL.[3]
"Vitamin D 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."[4]
There are conflicting reports concerning the absorption of cholecalciferol (D3) versus ergocalciferol (D2), with some studies suggesting less efficacy of D2,[9] and others showing no difference.[10] At present, D2 and D3 doses are frequently considered interchangeable, but more research is needed to clarify this.
Alternative views
There is a minority view, often associated with Trevor Marshall, which asserts that low levels of calcifediol (25-hydroxyvitamin D3) are often due to overconversion into calcitriol (1,25-dihydroxyvitamin D3, the active form of D3) because of chronic infection rather than calcifediol deficiency.[11]
Stability
Cholecalciferol is very sensitive to UV radiation and will rapidly, but reversibly, break down to form supra-sterols, which can further irreversibly convert to ergosterol.
Therapeutic application
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 prevented colon cancer development.[12] In humans, there was no effect.[13]
Poison
At high doses cholecalciferol is poisonous. 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."[14]
In New Zealand, possums have become a significant pest animal, and cholecalciferol has been used as the active ingredient in lethal gel baits for possum control. The LD50 is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added to the bait.[15][16] Kidneys and heart are target organs.[17]
See also
- Hypervitaminosis D, Vitamin D poisoning
- Ergocalciferol, vitamin D2.
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, a kidney enzyme that converts calcifediol to calcitriol.
References
- ^ "Nomenclature of Vitamin D. Recomendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN)" reproduced at the Queen Mary, University of London website. Retrieved 21 March 2010.
- ^ cholecalciferol at Dorland's Medical Dictionary
- ^ a b ""25-hydroxy vitamin D test: Medline Plus". Retrieved 21 March 2010.
- ^ a b Vitamin D: MedlinePlus Supplements with the National Academy of Sciences dosing recommendations at the Medline Plus website.
- ^ a b Vieth R (May 1999). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety". Am. J. Clin. Nutr. 69 (5): 842–56. PMID 10232622.
- ^ DRIs for Calcium and Vitamin D
- ^ van Groningen L, Opdenoordt S, van Sorge A, Telting D, Giesen A, de Boer H (April 2010). "Cholecalciferol loading dose guideline for vitamin D-deficient adults". Eur. J. Endocrinol. 162 (4): 805–11. doi:10.1530/EJE-09-0932. PMID 20139241.
- ^ 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:0.1016/S0022-3476(05)83303-7. PMID 8071764.
- ^ Armas LA, Hollis BW, Heaney RP (November 2004). "Vitamin D2 is much less effective than vitamin D3 in humans". J. Clin. Endocrinol. Metab. 89 (11): 5387–91. doi:10.1210/jc.2004-0360. PMID 15531486.
- ^ Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD (March 2008). "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D". J. Clin. Endocrinol. Metab. 93 (3): 677–81. doi:10.1210/jc.2007-2308. PMID 18089691.
- ^ "Notes from the 2008 International Congress on Autoimmunity". Bacteriality.com. http://bacteriality.com/2008/09/22/coa/. Retrieved 2010-01-23.[unreliable medical source?]
- ^ Yang, H. H.; Hu, Y.; Lee, M. P.; Hu, N.; Ng, D.; Goldstein, A. M.; Wang, C.; Taylor, P. R. (2008). Cancer Research 68: 3075. doi:10.1158/0008-5472.CAN-07-6426.
- ^ Wactawski-Wende, Jean; Kotchen, Jane Morley; Anderson, Garnet L.; Assaf, Annlouise R.; Brunner, Robert L.; O'Sullivan, Mary Jo; Margolis, Karen L.; Ockene, Judith K. et al. (2006). "Calcium plus Vitamin D Supplementation and the Risk of Colorectal Cancer". New England Journal of Medicine 354 (7): 684–96. doi:10.1056/NEJMoa055222. PMID 16481636.
- ^ "Merck Veterinary Manual - Rodenticide Poisoning: Introduction". http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/213000.htm.
- ^ Morgan, David (2006). "Field efficacy of cholecalciferol gel baits for possum (Trichosurus vulpecula) control". New Zealand Journal of Zoology 33: 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: 579–83. doi:10.1071/WR9950579.
- ^ "Kiwicare Material Safety Data Sheet". http://www.kiwicare.co.nz/index.cfm/3,80,144/no-possums-cholecalciferol-gel-bait.pdf.
External links
- 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
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