Array ( [0] => {{Short description|Vitamin D3, a chemical compound}} [1] => {{Use dmy dates|date=October 2022}} [2] => {{Infobox drug [3] => | INN = Colecalciferol [4] => | image = Cholecalciferol.svg [5] => | width = [6] => | alt = [7] => | image2 = Cholecalciferol-vitamin-D3-from-xtal-3D-sticks.png [8] => | width2 = [9] => | alt2 = [10] => | caption = [11] => [12] => [13] => | pronounce = {{IPAc-en|ˌ|k|oʊ|l|ə|k|æ|l|ˈ|s|ɪ|f|ə|r|ɒ|l}} [14] => | tradename = [15] => | Drugs.com = {{Drugs.com|ppa|cholecalciferol}} [16] => | MedlinePlus = [17] => | DailyMedID = Cholecalciferol [18] => | pregnancy_AU = [19] => | pregnancy_AU_comment = [20] => | pregnancy_category= [21] => | routes_of_administration = [[By mouth]], [[intramuscular injection|intramuscular]] [22] => | class = [23] => | ATC_prefix = A11 [24] => | ATC_suffix = CC05 [25] => | ATC_supplemental = [26] => [27] => | legal_AU = [28] => | legal_AU_comment = [29] => | legal_CA = Rx-only [30] => | legal_CA_comment = {{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=[[Health Canada]] | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024}}{{cite web | title=Regulatory Decision Summary for Vitamin D3 Oral Solution | website=[[Health Canada]] | date=5 February 2021 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS00793 | access-date=25 March 2024}} [31] => | legal_DE = [32] => | legal_DE_comment = [33] => | legal_NZ = [34] => | legal_NZ_comment = [35] => | legal_UK = [36] => | legal_UK_comment = [37] => | legal_US = OTC [38] => | legal_US_comment = [39] => | legal_UN = [40] => | legal_UN_comment = [41] => | legal_status = [42] => [43] => [44] => | bioavailability = [45] => | protein_bound = [46] => | metabolism = [47] => | metabolites = [48] => | onset = [49] => | elimination_half-life = [50] => | duration_of_action = [51] => | excretion = [52] => [53] => [54] => | CAS_number = 67-97-0 [55] => | CAS_supplemental = [56] => | PubChem = 5280795 [57] => | PubChemSubstance = [58] => | IUPHAR_ligand = [59] => | DrugBank = DB00169 [60] => | ChemSpiderID = 4444353 [61] => | UNII = 1C6V77QF41 [62] => | KEGG = C05443 [63] => | ChEBI = 28940 [64] => | ChEMBL = 1042 [65] => | NIAID_ChemDB = [66] => | synonyms = vitamin D3, calciol, activated 7-dehydrocholesterol [67] => [68] => [69] => | IUPAC_name = (3''S'',5''Z'',7''E'')-9,10-secocholesta-5,7,10(19)-trien-3-ol [70] => | C=27|H=44|O=1 [71] => | SMILES = O[C@@H]1CC(\C(=C)CC1)=C\C=C2/CCC[C@]3([C@H]2CC[C@@H]3[C@H](C)CCCC(C)C)C [72] => | StdInChI = 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 [73] => | StdInChI_Ref = {{stdinchicite|changed|chemspider}} [74] => | StdInChIKey = QYSXJUFSXHHAJI-YRZJJWOYSA-N [75] => | density = [76] => | density_notes = [77] => | melting_point = 83 to 86 [78] => | melting_high = [79] => | melting_notes = [80] => | boiling_point = 496.4 [81] => | boiling_notes = [82] => | solubility = Practically insoluble in water, freely soluble in ethanol, methanol and some other organic solvents. Slightly soluble in vegetable oils. [83] => | sol_units = [84] => | specific_rotation = [85] => }} [86] => [87] => '''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]].{{cite book | vauthors = Coulston AM, Boushey C, Ferruzzi M |title=Nutrition in the Prevention and Treatment of Disease |date=2013 |publisher=Academic Press |isbn=9780123918840 |page=818 |url=https://books.google.com/books?id=pmapb3rvzpYC&pg=PA818 |access-date=29 December 2016 |archive-url=https://web.archive.org/web/20161230000458/https://books.google.ca/books?id=pmapb3rvzpYC&pg=PA818 |archive-date=30 December 2016 |url-status=live }} [88] => [89] => [90] => Cholecalciferol is made in the skin following [[Ultraviolet#Subtypes|UVB light]] exposure.{{cite journal | vauthors = Norman AW | title = From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health | journal = The American Journal of Clinical Nutrition | volume = 88 | issue = 2 | pages = 491S–499S | date = August 2008 | pmid = 18689389 | doi = 10.1093/ajcn/88.2.491S | doi-access = free }} It 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.{{cite web|title=Cholecalciferol (Professional Patient Advice) - Drugs.com|url=https://www.drugs.com/ppa/cholecalciferol.html|website=www.drugs.com|access-date=29 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161230002705/https://www.drugs.com/ppa/cholecalciferol.html|archive-date=30 December 2016}} It is found in food such as some [[fish]], beef liver, eggs, and cheese.{{cite web|title=Office of Dietary Supplements - Vitamin D|url=https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/|website=ods.od.nih.gov|access-date=30 December 2016|date=11 February 2016|url-status=live|archive-url=https://web.archive.org/web/20161231073744/https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/|archive-date=31 December 2016}}{{cite book | collaboration = Institute of Medicine (US); Committee to Review Dietary Reference Intakes for Vitamin D and Calcium | vauthors = Ross AC, Taylor CL, Yaktine AL, Del Valle HB |title=Dietary Reference Intakes for Calcium and Vitamin D |date=2011 | publisher = National Academies Press |doi=10.17226/13050 |pmid=21796828 |isbn=978-0-309-16394-1 | s2cid = 58721779 |url=https://www.ncbi.nlm.nih.gov/books/NBK56070/pdf/Bookshelf_NBK56070.pdf}} Plants, cow milk, fruit juice, yogurt, and margarine also may have cholecalciferol added to them in some countries, including the United States. [91] => [92] => [93] => Cholecalciferol can be taken as an oral dietary supplement to prevent [[vitamin D deficiency]] or as a medication to treat associated diseases, including [[rickets]].{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|pages=703–704|edition=69}}{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization }} It is also used for [[familial hypophosphatemia]], [[hypoparathyroidism]] that is causing [[low blood calcium]], and [[Fanconi syndrome]].{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=231}} Vitamin-D supplements may not be effective in people with severe [[kidney disease]].{{cite web|title=Aviticol 1 000 IU Capsules - Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/31838|website=www.medicines.org.uk|access-date=29 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161230085711/https://www.medicines.org.uk/emc/medicine/31838|archive-date=30 December 2016}} Excessive doses in humans can result in vomiting, constipation, weakness, and confusion. Other risks include [[kidney stones]]. Doses greater than 40,000{{nbsp}}[[International unit|IU]] (1,000{{nbsp}}μg) per day are generally required before [[high blood calcium]] occurs.{{cite journal |vauthors=Vieth R |title=Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety |journal=The American Journal of Clinical Nutrition |volume=69 |issue=5 |pages=842–56 |date=May 1999 |pmid=10232622 |url=http://www.ajcn.org/content/69/5/842.full.pdf |doi=10.1093/ajcn/69.5.842|doi-access=free }} Normal doses, 800–2000 IU per day, are safe in [[pregnancy]]. [94] => [95] => [96] => Cholecalciferol was first described in 1936.{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=451 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA451|language=en|access-date=29 December 2016|archive-url=https://web.archive.org/web/20161230085612/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA451|archive-date=30 December 2016|url-status=live}} It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }} In 2021, it was the 65th most commonly prescribed medication in the United States, with more than 10{{nbsp}}million prescriptions.{{cite web | title = The Top 300 of 2021 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 14 January 2024}}{{cite web | title = Cholecalciferol - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Cholecalciferol | access-date = 14 January 2024}} Cholecalciferol is available as a [[generic medication]] and [[over the counter]].{{cite conference | vauthors = Rizor SE, Arjo WM, Bulkin S, Nolte DL |title=Efficacy of Cholecalciferol Baits for Pocket Gopher Control and Possible Effects on Non-Target Rodents in Pacific Northwest Forests |url=https://naldc.nal.usda.gov/download/39036/PDF |conference=Vertebrate Pest Conference (2006) |publisher=USDA |quote=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. |access-date=27 August 2019 |archive-url=https://web.archive.org/web/20120914083512/http://naldc.nal.usda.gov/download/39036/PDF |archive-date=14 September 2012 |url-status=live }} [97] => [98] => ==Medical uses== [99] => Cholecalciferol appears to stimulate the body's [[interferon type I]] signaling system that protects against bacteria and viruses, unlike [[Vitamin D2|vitamin D2]].{{Cite web | vauthors = Haridy R |date= 28 February 2022 |title=One type of vitamin D found to boost immune system, another may hinder it |url=https://newatlas.com/health-wellbeing/differences-between-vitamin-d2-d3-immune-system-supplements/ |access-date=7 April 2022 |website=New Atlas |language=en-US}} [100] => [101] => ===Vitamin D deficiency=== [102] => {{Main|Vitamin D deficiency}} [103] => Cholecalciferol is a form of vitamin D which is naturally synthesized in skin and functions as a pro-hormone, being converted to [[calcitriol]]. This is important for maintaining calcium levels and promoting bone health and development. As a medication, cholecalciferol may be taken as a dietary supplement to prevent or to treat vitamin D deficiency. One gram is 40,000,000 (40x106) [[International unit|IU]], equivalently 1 IU is 0.025 μg or 25 ng. Dietary reference intake values for vitamin D ([[ergocalciferol]] which is D2 and/or cholecalciferol which is D3) have been established and recommendations vary depending on the country: [104] => *In the US: 15 μg/d (600 IU per day) for all individuals (males, females, pregnant/lactating women) between the ages of 1 and 70 years old, inclusive. For all individuals older than 70 years, 20 μg/d (800 IU per day) is recommended.[http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/DRI-Values.aspx DRIs for Calcium and Vitamin D] {{webarchive|url=https://web.archive.org/web/20101224064915/http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/DRI-Values.aspx |date=24 December 2010 }} [105] => *In the EU: 15 μg/d (600 IU per day) for all people older than 1 year and 10 μg/d (400 IU per day) for infants aged 7–11 months, assuming minimal cutaneous vitamin D synthesis.{{cite web | url=https://www.efsa.europa.eu/en/efsajournal/pub/4547 | title=Dietary reference values for vitamin D | EFSA | date=28 October 2016 }} [106] => *In the UK: a ‘Safe Intake’ (SI) of 8.5-10 μg/day (30-400 IU per day) for infants < 1 year (including exclusively breastfed infants) and a SI of 10 μg/day (400 IU per day) for children aged 1 to <4 years; for all other population groups aged 4 years and more (including pregnant/lactating women) a Reference Nutrient Intake (RNI) of 10 μg/day (400 IU per day).{{Cite web|url=https://www.efsa.europa.eu/sites/default/files/documents/news/explanatory_note_EFSA_SACN_vitaminD.pdf|title=Joint explanatory note by the European Food Safety Authority and the UK Scientific Advisory Committee on Nutrition regarding dietary reference values for vitamin D}} [107] => [108] => Low levels of vitamin D 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, obese, having darker skin, or wearing clothes that cover most of the skin.{{cite journal | vauthors = Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, El-Hajj Fuleihan G, Josse RG, Lips P, Morales-Torres J | title = Global vitamin D status and determinants of hypovitaminosis D | journal = Osteoporos Int | volume = 20 | issue = 11 | pages = 1807–20 | date = November 2009 | pmid = 19543765 | doi = 10.1007/s00198-009-0954-6 | s2cid = 52858668 | url = https://research.vumc.nl/en/publications/4861a0b5-49a4-47e2-bbb4-dda46208c058}}{{cite web |url=http://www.nhs.uk/Conditions/vitamins-minerals/Pages/Vitamin-D.aspx |title=Vitamins and minerals – Vitamin D |website=[[National Health Service (England)|National Health Service]] |date=3 August 2020 |access-date=15 November 2020}} Supplements are recommended for these groups of people. [109] => [110] => The [[Institute of Medicine]] in 2010 recommended a maximum uptake of vitamin D of 4,000 IU/day, 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.{{cite journal | vauthors = Vieth R | title = Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety | journal = The American Journal of Clinical Nutrition | volume = 69 | issue = 5 | pages = 842–56 | date = May 1999 | pmid = 10232622 | doi = 10.1093/ajcn/69.5.842 | doi-access = free }} 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.{{cite journal | vauthors = van Groningen L, Opdenoordt S, van Sorge A, Telting D, Giesen A, de Boer H | title = Cholecalciferol loading dose guideline for vitamin D-deficient adults | journal = European Journal of Endocrinology | volume = 162 | issue = 4 | pages = 805–11 | date = April 2010 | pmid = 20139241 | doi = 10.1530/EJE-09-0932 | doi-access = free }} [111] => [112] => There are conflicting reports concerning the relative effectiveness of cholecalciferol (D3) versus [[ergocalciferol]] (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.{{cite journal | vauthors = Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, Chope G, Hyppönen E, Berry J, Vieth R, Lanham-New S | display-authors = 6 | title = Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis | journal = The American Journal of Clinical Nutrition | volume = 95 | issue = 6 | pages = 1357–64 | date = June 2012 | pmid = 22552031 | pmc = 3349454 | doi = 10.3945/ajcn.111.031070 }} [113] => [114] => A much less common use of cholecalciferol therapy in [[rickets]] utilizes a single large dose and has been called ''stoss'' therapy.{{cite journal | vauthors = Shah BR, Finberg L | title = Single-day therapy for nutritional vitamin D-deficiency rickets: a preferred method | journal = The Journal of Pediatrics | volume = 125 | issue = 3 | pages = 487–90 | date = September 1994 | pmid = 8071764 | doi = 10.1016/S0022-3476(05)83303-7 }}{{cite journal | vauthors = Chatterjee D, Swamy MK, Gupta V, Sharma V, Sharma A, Chatterjee K | title = Safety and Efficacy of Stosstherapy in Nutritional Rickets | journal = Journal of Clinical Research in Pediatric Endocrinology | volume = 9 | issue = 1 | pages = 63–69 | date = March 2017 | pmid = 27550890 | pmc = 5363167 | doi = 10.4274/jcrpe.3557 }}{{cite journal | vauthors = Bothra M, Gupta N, Jain V | title = Effect of intramuscular cholecalciferol megadose in children with nutritional rickets | journal = Journal of Pediatric Endocrinology & Metabolism | volume = 29 | issue = 6 | pages = 687–92 | date = June 2016 | pmid = 26913455 | doi = 10.1515/jpem-2015-0031 | s2cid = 40611968 }} Treatment is given either orally or by [[intramuscular injection]] of 300,000 IU (7,500 μg) to 500,000 IU (12,500 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. [115] => [116] => Low circulating vitamin D levels have been associated with lower total [[testosterone]] levels in males. Vitamin D supplementation could potentially improve [[total testosterone concentration]], although more research is needed.{{cite journal | vauthors = Chen C, Zhai H, Cheng J, Weng P, Chen Y, Li Q, Wang C, Xia F, Wang N, Lu Y | display-authors = 6 | title = Causal Link Between Vitamin D and Total Testosterone in Men: A Mendelian Randomization Analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 104 | issue = 8 | pages = 3148–3156 | date = August 2019 | pmid = 30896763 | doi = 10.1210/jc.2018-01874 | s2cid = 84841517 | doi-access = free }} [117] => [118] => ===Other diseases=== [119] => A meta-analysis of 2007 concluded that daily intake of 1000 to 2000 IU per day of vitamin D3 could reduce the incidence of colorectal cancer with minimal risk.{{cite journal | vauthors = Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MF | display-authors = 6 | title = Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis | journal = American Journal of Preventive Medicine | volume = 32 | issue = 3 | pages = 210–6 | date = March 2007 | pmid = 17296473 | doi = 10.1016/j.amepre.2006.11.004 | type = Meta-Analysis }} 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.{{cite journal | vauthors = Yang K, Kurihara N, Fan K, Newmark H, Rigas B, Bancroft L, Corner G, Livote E, Lesser M, Edelmann W, Velcich A, Lipkin M, Augenlicht L | display-authors = 6 | title = Dietary induction of colonic tumors in a mouse model of sporadic colon cancer | journal = Cancer Research | volume = 68 | issue = 19 | pages = 7803–10 | date = October 2008 | pmid = 18829535 | doi = 10.1158/0008-5472.CAN-08-1209 | doi-access = free }} In humans, with 400 IU daily, there was no effect of cholecalciferol supplements on the risk of colorectal cancer.{{cite journal | vauthors = 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 | display-authors = 6 | title = Calcium plus vitamin D supplementation and the risk of colorectal cancer | journal = The New England Journal of Medicine | volume = 354 | issue = 7 | pages = 684–96 | date = February 2006 | pmid = 16481636 | doi = 10.1056/NEJMoa055222 | s2cid = 20826870 | url = http://www.escholarship.org/uc/item/43r416nc | doi-access = free }} [120] => [121] => Supplements are not recommended for prevention of cancer as any effects of cholecalciferol are very small.{{cite journal | vauthors = Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C | display-authors = 6 | title = Vitamin D supplementation for prevention of mortality in adults | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD007470 | date = January 2014 | pmid = 24414552 | doi = 10.1002/14651858.cd007470.pub3 }} Although correlations exist between low levels of blood serum cholecalciferol and higher rates of various cancers, [[multiple sclerosis]], [[tuberculosis]], heart disease, and diabetes,{{cite journal | vauthors = Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF | title = The role of vitamin D in cancer prevention | journal = American Journal of Public Health | volume = 96 | issue = 2 | pages = 252–61 | date = February 2006 | pmid = 16380576 | pmc = 1470481 | doi = 10.2105/AJPH.2004.045260 }} the consensus is that supplementing levels is not beneficial.{{cite journal | vauthors = Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA | display-authors = 6 | title = The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 96 | issue = 1 | pages = 53–8 | date = January 2011 | pmid = 21118827 | pmc = 3046611 | doi = 10.1210/jc.2010-2704 | doi-access = free }} It is thought that tuberculosis may result in lower levels.{{cite journal | vauthors = Gou X, Pan L, Tang F, Gao H, Xiao D | title = The association between vitamin D status and tuberculosis in children: A meta-analysis | journal = Medicine | volume = 97 | issue = 35 | pages = e12179 | date = August 2018 | pmid = 30170465 | pmc = 6392646 | doi = 10.1097/MD.0000000000012179 }} It, however, is not entirely clear how the two are related.{{cite journal | vauthors = Keflie TS, Nölle N, Lambert C, Nohr D, Biesalski HK | title = Vitamin D deficiencies among tuberculosis patients in Africa: A systematic review | journal = Nutrition | volume = 31 | issue = 10 | pages = 1204–12 | date = October 2015 | pmid = 26333888 | doi = 10.1016/j.nut.2015.05.003 }} [122] => [123] => ==Biochemistry== [124] => === Structure === [125] => Cholecalciferol is one of the five forms of [[vitamin D]].{{DorlandsDict|two/000020436|cholecalciferol}} Cholecalciferol is a [[secosteroid]], that is, a steroid molecule with one ring open.{{cite web |url=http://vitamind.ucr.edu/about/ |title=About Vitamin D |publisher=University of California, Riverside |date=November 2011 |access-date=15 October 2017 |url-status=live |archive-url=https://web.archive.org/web/20171016014311/http://vitamind.ucr.edu/about/ |archive-date=16 October 2017 }} [126] => [127] => ===Mechanism of action=== [128] => By itself cholecalciferol is inactive. It is converted to its active form by two [[hydroxylation]]s: the first in the liver, by [[CYP2R1]] or [[CYP27A1]], to form 25-hydroxycholecalciferol ([[calcifediol]], 25-OH vitamin D3). The second hydroxylation occurs mainly in the kidney through the action of [[CYP27B1]] to convert 25-OH vitamin D3 into 1,25-dihydroxycholecalciferol ([[calcitriol]], 1,25-(OH)2vitamin D3). All these metabolites are bound in blood to the [[vitamin D-binding protein]]. The action of calcitriol is mediated by the [[vitamin D receptor]], a [[nuclear receptor]] which regulates the synthesis of hundreds of proteins and is present in virtually every cell in the body. [129] => [130] => ===Biosynthesis=== [131] => Click on icon in lower right corner to open. [132] => {{VitaminDSynthesis_WP1531|highlight=Cholecalciferol}} [133] => [134] => [[7-Dehydrocholesterol]] is the precursor of cholecalciferol. Within the epidermal layer of skin, 7-dehydrocholesterol undergoes an [[electrocyclic reaction]] as a result of [[Ultraviolet light#Subtypes|UVB light]] at [[wavelengths]] between 290 and 315 nm, with peak synthesis occurring between 295 and 300 nm.{{cite journal | vauthors = Wacker M, Holick MF | title = Sunlight and Vitamin D: A global perspective for health | journal = Dermato-Endocrinology | volume = 5 | issue = 1 | pages = 51–108 | date = January 2013 | pmid = 24494042 | pmc = 3897598 | doi = 10.4161/derm.24494 }} This results in the opening of the vitamin precursor B-ring through a [[Conrotatory and disrotatory|conrotatory]] pathway making [[previtamin D3|previtamin D3]] (pre-cholecalciferol).{{cite journal | vauthors = MacLaughlin JA, Anderson RR, Holick MF | s2cid = 23011680 | title = Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin | journal = Science | volume = 216 | issue = 4549 | pages = 1001–3 | date = May 1982 | pmid = 6281884 | doi = 10.1126/science.6281884 | bibcode = 1982Sci...216.1001M }} In a process which is independent of UV light, the pre-cholecalciferol then undergoes a [1,7] antarafacial [[Sigmatropic reaction|sigmatropic]] rearrangement {{cite journal | vauthors = Okamura WH, Elnagar HY, Ruther M, Dobreff S | title = Thermal [1,7]-sigmatropic shift of previtamin D3 to vitamin D3: synthesis and study of pentadeuterio derivatives | journal = Journal of Organic Chemistry | volume = 58 | pages = 600–610 | year = 1993 | doi = 10.1021/jo00055a011 | issue = 3 }} and therein finally isomerizes to form vitamin D3. [135] => [136] => The active UVB wavelengths are present in sunlight, and sufficient amounts of cholecalciferol can be produced with moderate exposure of the skin, depending on the strength of the sun. 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, averaging 5–30 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. [137] => [138] => Cholecalciferol can be produced in skin from the light emitted by the UV lamps in [[tanning bed]]s, which produce ultraviolet primarily in the [[Ultraviolet light#Subtypes|UVA]] 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. [139] => [140] => 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. Cholecalciferol ''is'' synthesized by the body during UVB radiation exposure. [141] => [142] => The three steps in the synthesis and activation of vitamin D3 are regulated as follows: [143] => * Cholecalciferol is synthesized in the skin from 7-dehydrocholesterol under the action of ultraviolet B (UVB) light. It reaches an equilibrium after several minutes depending on the intensity of the UVB in the sunlight – determined by latitude, season, cloud cover, and altitude – and the age and degree of pigmentation of the skin. [144] => * Hydroxylation in the endoplasmic reticulum of liver [[hepatocyte]]s of cholecalciferol to calcifediol (25-hydroxycholecalciferol) by [[CYP2R1|25-hydroxylase]] is loosely regulated, if at all, and blood levels of this molecule largely reflect the amount of cholecalciferol produced in the skin combined with any vitamin D2 or D3 ingested. [145] => * Hydroxylation in the kidneys of calcifediol to calcitriol by [[25-Hydroxyvitamin D3 1-alpha-hydroxylase|1-alpha-hydroxylase]] is tightly regulated: it is stimulated by [[parathyroid hormone]] and serves as the major control point in the production of the active circulating hormone [[calcitriol]] (1,25-dihydroxyvitamin D3). [146] => [147] => ==Industrial production== [148] => Cholecalciferol is produced industrially for use in [[multivitamin|vitamin supplement]]s and [[food fortification|to fortify foods]]. As a [[pharmaceutical drug]] it is called cholecalciferol ([[United States Adopted Name|USAN]]) or colecalciferol ([[International Nonproprietary Name|INN]], [[British Approved Name|BAN]]). It is produced by the [[ultraviolet]] irradiation of [[7-dehydrocholesterol]] extracted from [[lanolin]] found in sheep's [[wool]].[http://www.agdnutrition.com/d3-story.html Vitamin D3 Story.] {{webarchive|url=https://web.archive.org/web/20120122031423/http://www.agdnutrition.com/d3-story.html |date=22 January 2012 }} Retrieved 8 April 2012. 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 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. [149] => [150] => [[File:Cholecalciferol synth.png|500px]] [151] => [152] => Cholecalciferol is also produced industrially for use in vitamin supplements from [[lichen]]s, which is suitable for vegans.{{cite web | url = http://www.vitashine-d3.com/ | title = Vitashine Vegan Vitamin D3 Supplements | access-date = 15 March 2013 | url-status = live | archive-url = https://web.archive.org/web/20130304133936/http://www.vitashine-d3.com/ | archive-date = 4 March 2013 }}{{cite journal | vauthors = Wang T, Bengtsson G, Kärnefelt I, Björn LO | title = Provitamins and vitamins D2and D3in Cladina spp. over a latitudinal gradient: possible correlation with UV levels | journal = Journal of Photochemistry and Photobiology B: Biology | volume = 62 | issue = 1–2 | pages = 118–22 | date = September 2001 | pmid = 11693362 | doi = 10.1016/s1011-1344(01)00160-9 | url = http://lup.lub.lu.se/luur/download?func=downloadFile&recordOId=133512&fileOId=624375 | archive-url = https://web.archive.org/web/20121028160041/http://lup.lub.lu.se/luur/download?func=downloadFile&recordOId=133512&fileOId=624375 | url-status = live | archive-date = 28 October 2012 }} [153] => [154] => ==Stability== [155] => Cholecalciferol is very sensitive to [[ultraviolet|UV radiation]] and will rapidly, but reversibly, break down to form supra-sterols, which can further irreversibly convert to [[ergosterol]].{{citation needed|date=December 2012}} [156] => [157] => ==Pesticide== [158] => 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.{{cite conference |title=CHOLECALCIFEROL: A UNIQUE TOXICANT FOR RODENT CONTROL |url=https://digitalcommons.unl.edu/vpc11/22/ |conference=Proceedings of the Eleventh Vertebrate Pest Conference (1984) |publisher=University of Nebraska Lincoln |date=March 1984 |quote=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. |access-date=27 August 2019 |archive-url=https://web.archive.org/web/20190827013804/https://digitalcommons.unl.edu/vpc11/22/ |archive-date=27 August 2019 |url-status=live }} [159] => [160] => The mechanism of high dose cholecalciferol is that it can produce "[[hypercalcemia]], which results in systemic calcification of soft tissue, leading to [[kidney failure]], [[cardiac]] abnormalities, [[hypertension]], CNS depression, and GI upset. Signs generally develop within 18-36 hr of ingestion and can include depression, [[loss of appetite]], [[polyuria]], and [[polydipsia]]." High-dose cholecalciferol will tend to rapidly accumulate in [[adipose]] tissue yet release more slowly{{cite journal | vauthors = Brouwer DA, van Beek J, Ferwerda H, Brugman AM, van der Klis FR, van der Heiden HJ, Muskiet FA | title = Rat adipose tissue rapidly accumulates and slowly releases an orally-administered high vitamin D dose | journal = The British Journal of Nutrition | volume = 79 | issue = 6 | pages = 527–532 | date = June 1998 | pmid = 9771340 | doi = 10.1079/BJN19980091 | quote = 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).{{nbsp}}... We conclude that orally-administered cholecalciferol rapidly accumulates in adipose tissue and that it is very slowly released while there is energy balance. | doi-access = free }} which will tend to delay time of death for several days from the time that high-dose bait is introduced. [161] => [162] => In New Zealand, [[Common brushtail possum|possums]] have become a significant pest animal. For possum control, cholecalciferol has been used as the active ingredient in lethal baits.{{cite web | url=https://sds.rentokil-initial.com/sds/files/NZ-Rentokil-Pestoff_Decal_Possum_Bait-EN-SDS_01_CLP.pdf | title=Pestoff DECAL Possum Bait - Rentokil Initial Safety Data Sheets | access-date=10 May 2020 | archive-date=15 January 2021 | archive-url=https://web.archive.org/web/20210115134720/https://sds.rentokil-initial.com/sds/files/NZ-Rentokil-Pestoff_Decal_Possum_Bait-EN-SDS_01_CLP.pdf | url-status=dead }} The [[Median lethal dose|LD50]] is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added to the bait.{{cite journal | vauthors = Morgan D | title = Field efficacy of cholecalciferol gel baits for possum (Trichosurus vulpecula) control | journal = New Zealand Journal of Zoology | volume = 33 | issue = 3 | pages = 221–8 | year = 2006 | doi = 10.1080/03014223.2006.9518449 | s2cid = 83765759 }}{{cite journal |vauthors=Jolly SE, Henderson RJ, Frampton C, Eason CT | title = Cholecalciferol Toxicity and Its Enhancement by Calcium Carbonate in the Common Brushtail Possum | journal = Wildlife Research | volume=22 | issue=5 | pages = 579–83 | year = 1995 | doi = 10.1071/WR9950579 }} Kidneys and heart are target organs.{{cite web| url=http://www.kiwicare.co.nz/assets/Uploads/SDS/NO-Possums-Cholecalciferol-Gel-Bait2.pdf| title=Kiwicare Material Safety Data Sheet| url-status=dead| archive-url=https://web.archive.org/web/20130210101310/http://kiwicare.co.nz/assets/Uploads/SDS/NO-Possums-Cholecalciferol-Gel-Bait2.pdf| archive-date=10 February 2013}} LD50 of 4.4 mg/kg has been reported in rabbits, with lethality to almost all rabbits ingesting doses greater than 15 mg/kg.R. J. Henderson and C. T. Eason (2000), [https://www.publish.csiro.au/wr/wr99048 Acute toxicity of cholecalciferol and gliftor baits to the European rabbit, Oryctolagus cuniculus], Wildlife Research 27(3) 297-300. 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.Michael E.Peterson & Kerstin Fluegeman, [https://www.sciencedirect.com/science/article/abs/pii/S1938973613000287 Cholecalciferol (Topic Review)], Topics in Companion Animal Medicine, Volume 28, Issue 1, February 2013, Pages 24-27. [163] => [164] => Researchers have reported that the compound is less toxic to non-target species than earlier generations of anticoagulant rodenticides ([[Warfarin]] and [[Congener (chemistry)|congeners]]) or [[Bromethalin]],{{cite journal | vauthors = Kocher DK, Kaur G, Banga HS, Brar RS |title=Histopathological Changes in Vital Organs of House Rats Given Lethal Dose of Cholecalciferol (Vitamin D3) |journal=Indian Journal of Animal Research |volume=2 |issue=3 |pages=193–6 |year=2010 |doi= |issn=0367-6722 |quote=Use of cholecalciferol as a rodenticide in bait lowered the risk of secondary poisoning and minimized the toxicity of non-target species }} and that [[Relay toxicity|relay toxicosis]] (poisoning by eating a poisoned animal) has not been documented.{{cite web |url= https://www.merckvetmanual.com/toxicology/rodenticide-poisoning/cholecalciferol |title=Merck Veterinary Manual - Rodenticide Poisoning: Introduction | vauthors = Khan SA, Schell MM |date=November 2014 |access-date=10 October 2021 |quote=''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.'' }} Nevertheless, the same source reports that use of cholecalciferol in [[rodenticide]]s 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. [165] => [166] => == See also == [167] => * [[Hypervitaminosis D]], Vitamin D poisoning [168] => * [[Ergocalciferol]], vitamin D2 [169] => * [[25-Hydroxyvitamin D 1-alpha-hydroxylase]], a kidney [[enzyme]] that converts calcifediol to calcitriol [170] => [171] => == References == [172] => {{Reflist}} [173] => [174] => == External links == [175] => * [https://webbook.nist.gov/cgi/cbook.cgi?ID=C67970 NIST Chemistry WebBook page for cholecalciferol] [176] => * [https://rep.bioscientifica.com/view/journals/rep/144/2/135.xml Vitamin D metabolism, sex hormones, and male reproductive function.] [177] => [178] => {{Vitamins}} [179] => {{Sterols}} [180] => {{Terpenoids}} [181] => {{Vitamin D receptor modulators}} [182] => {{portal bar|Food|Medicine}} [183] => [184] => [[Category:Cyclopentanes]] [185] => [[Category:CYP2D6 inhibitors]] [186] => [[Category:Polyenes]] [187] => [[Category:Rodenticides]] [188] => [[Category:Secosteroids]] [189] => [[Category:Vitamers]] [190] => [[Category:Vitamin D]] [191] => [[Category:World Health Organization essential medicines]] [192] => [[Category:Wikipedia medicine articles ready to translate]] [193] => [[Category:Vinylidene compounds]] [] => )
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Cholecalciferol

Cholecalciferol, also known as vitamin D3, is a type of vitamin D that is essential for the human body. This Wikipedia page provides a comprehensive overview of cholecalciferol, including its chemical structure, sources, synthesis, biological functions, and health implications.

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This Wikipedia page provides a comprehensive overview of cholecalciferol, including its chemical structure, sources, synthesis, biological functions, and health implications. The page explains that cholecalciferol is primarily obtained through exposure to sunlight, as our skin converts a precursor molecule into its active form in the presence of UVB rays. Additionally, cholecalciferol can be obtained from certain animal-based foods, such as fatty fish and egg yolks, as well as from dietary supplements. The article delves into the biochemical aspects of cholecalciferol, detailing its conversion into the active metabolite calcitriol, which plays a critical role in regulating calcium and phosphate levels, promoting bone mineralization, and modulating immune system functions. It also discusses various physiological processes influenced by cholecalciferol, such as calcium homeostasis, muscle strength, and overall immune health. Moreover, the Wikipedia page explains the significance of cholecalciferol in preventing and treating various health conditions, including rickets, osteoporosis, and certain autoimmune disorders. It highlights the role of vitamin D supplementation in addressing deficiencies, especially in individuals with limited sun exposure or certain medical conditions. The page also provides information on controversies and debates surrounding optimal dosage recommendations, potential toxicity risks of excessive cholecalciferol intake, and the ongoing research to better understand its role in overall health and disease prevention. Overall, the Wikipedia page on cholecalciferol serves as a comprehensive resource for understanding the importance, functions, sources, and implications of this essential vitamin D compound in human physiology and health.

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