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Calcifediol, also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D (abbreviated 25(OH)D),[1] is a prehormone that is produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) by the enzyme cholecalciferol 25-hydroxylase. Physicians worldwide measure this metabolite to determine a patient's vitamin D status.[2][3] At a typical daily intake of vitamin D3, its full conversion to calcifediol takes approximately 7 days.[4]
Calcifediol is then converted in the kidneys (by the enzyme 25(OH)D-1α-hydroxylase) into calcitriol (1,25-(OH)2D3), a secosteroid hormone that is the active form of vitamin D. It can also be converted into 24-hydroxycalcidiol in the kidneys via 24-hydroxylation.[5][6]
Contents
1Blood test
1.1Clinical significance
2Interactive pathway map
3History
4See also
5References
Blood test
In medicine, a 25-hydroxy vitamin D (calcifediol) blood test is used to determine how much vitamin D is in the body.[7] The blood concentration of calcifediol is considered the best indicator of vitamin D status.[2]
This test can be used to diagnose vitamin D deficiency, and it is indicated in patients with high risk for vitamin D deficiency and when the results of the test would be used as supporting evidence for beginning aggressive therapies.[8] Patients with osteoporosis, chronic kidney disease, malabsorption, obesity, and some other infections may be high risk and thus have greater indication for this test.[8] Although vitamin D deficiency is common in some populations including those living at higher latitudes or with limited sun exposure, the 25(OH)D test is not indicated for entire populations.[8] Physicians may advise low risk patients to take over-the-counter vitamin D in place of having screening.[8]
It is the most sensitive measure,[9] though experts have called for improved standardization and reproducibility across different laboratories.[2] According to MedlinePlus, the normal range of calcifediol is 30.0 to 74.0 ng/mL.[7] The normal range varies widely depending on several factors, including age and geographic location. A broad reference range of 20–150 nmol/L (8-60 ng/mL) has also been suggested,[10] while other studies have defined levels below 80 nmol/L (32 ng/mL) as indicative of vitamin D deficiency.[11]
US labs generally report 25(OH)D levels as ng/mL. Other countries often use nmol/L. Multiply ng/mL by 2.5 to convert to nmol/L.
Clinical significance
Increasing calcifediol levels are associated with increasing fractional absorption of calcium from the gut up to levels of 80 nmol/L (32 ng/mL).[2] Urinary calcium excretion balances intestinal calcium absorption and does not increase with calcifediol levels up to ~400 nmol/L (160 ng/mL).[12]
A study by Cedric F. Garland and Frank C. Garland of the University of California, San Diego analyzed the blood from 25,000 volunteers from Washington County, Maryland, finding that those with the highest levels of calcifediol had a risk of colon cancer that was one-fifth of typical rates.[13]
However, randomized controlled trials failed to find a significant correlation between low-dosage (400iu/day) vitamin D supplementation and the risk of colon cancer.[14]
A population study in Copenhagen, Denmark, found a correlation between both low and high serum levels and increased mortality, with a level of 50–60 nmol/L being associated with the lowest mortality.
The study did not show causation.[15][16]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway (view / edit)]]
Vitamin D Synthesis Pathway (view / edit)
^The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".
History
Research in the laboratory of Hector DeLuca identified 25(OH)D in the 1968 and showed that the liver was necessary for its formation.[17] The enzyme responsible for this, cholecalciferol 25-hydroxylase, was isolated by Michael F. Holick in 1972.[18]
See also
Hypervitaminosis D
Hypovitaminosis D
Vitamin D
Health effects of Vitamin D
References
^"Nomenclature of Vitamin D. Recommendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN)" reproduced at the Queen Mary, University of London website. Retrieved 21 March 2010.
^ abcdHeaney, Robert P (Dec 2004). "Functional indices of vitamin D status and ramifications of vitamin D deficiency". American Journal of Clinical Nutrition. 80 (6): 1706S–9S. doi:10.1093/ajcn/80.6.1706S. PMID 15585791.
^Theodoratou, E; Tzoulaki, I; Zgaga, L; Ioannidis, JP (1 April 2014). "Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials". BMJ (Clinical Research Ed.). 348: g2035. doi:10.1136/bmj.g2035. PMC 3972415. PMID 24690624.
^Heaney, RP; Armas, LA; Shary, JR; Bell, NH; Binkley, N; Hollis, BW (June 2008). "25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions". The American Journal of Clinical Nutrition. 87 (6): 1738–42. doi:10.1093/ajcn/87.6.1738. PMID 18541563.
^Bender, David A.; Mayes, Peter A (2006). "Micronutrients: Vitamins & Minerals". In Victor W. Rodwell; Murray, Robert F.; Harper, Harold W.; Granner, Darryl K.; Mayes, Peter A. (eds.). Harper's Illustrated Biochemistry. New York: Lange/McGraw-Hill. pp. 492–3. ISBN 978-0-07-146197-9.CS1 maint: Uses editors parameter (link) Retrieved December 10, 2008 through Google Book Search.
^Institute of Medicine (1997). "Vitamin D". Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, D.C: National Academy Press. p. 254. doi:10.17226/5776. ISBN 978-0-309-06403-3. PMID 23115811.
^ ab"25-hydroxy vitamin D test: Medline Plus". Retrieved 21 March 2010.
^ abcdAmerican Society for Clinical Pathology, "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, American Society for Clinical Pathology, retrieved August 1, 2013, which cites
Sattar, N.; Welsh, P.; Panarelli, M.; Forouhi, N. G. (2012). "Increasing requests for vitamin D measurement: Costly, confusing, and without credibility". The Lancet. 379 (9811): 95–96. doi:10.1016/S0140-6736(11)61816-3. PMID 22243814.
Bilinski, K. L.; Boyages, S. C. (2012). "The rising cost of vitamin D testing in Australia: Time to establish guidelines for testing". The Medical Journal of Australia. 197 (2): 90. doi:10.5694/mja12.10561. PMID 22794049.
Lu, Chuanyi M. (May 2012). "Pathology consultation on vitamin D testing: Clinical indications for 25(OH) vitamin D measurement [Letter to the editor]". American Journal of Clinical Pathology. American Society for Clinical Pathology (137): 831–832., which cites
Arya, S. C.; Agarwal, N. (2012). "Pathology Consultation on Vitamin D Testing: Clinical Indications for 25(OH) Vitamin D Measurement". American Journal of Clinical Pathology. 137 (5): 832. doi:10.1309/AJCP2GP0GHKQRCOE. PMID 22523224.
Holick, M. F.; Binkley, N. C.; Bischoff-Ferrari, H. A.; Gordon, C. M.; Hanley, D. A.; Heaney, R. P.; Murad, M. H.; Weaver, C. M. (2011). "Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline". Journal of Clinical Endocrinology & Metabolism. 96 (7): 1911–1930. doi:10.1210/jc.2011-0385. PMID 21646368.
^Institute of Medicine (1997), p. 259
^Bender, David A. (2003). "Vitamin D". Nutritional biochemistry of the vitamins. Cambridge: Cambridge University Press. ISBN 978-0-521-80388-5. Retrieved December 10, 2008 through Google Book Search.
^Hollis BW (February 2005). "Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D". J Nutr. 135 (2): 317–22. doi:10.1093/jn/135.2.317. PMID 15671234.
^Kimball; et al. (2004). "Safety of vitamin D3 in adults with multiple sclerosis". J Clin Endocrinol Metab. 86 (3): 645–51. doi:10.1093/ajcn/86.3.645. PMID 17823429.
^Maugh II, Thomas H. "Frank C. Garland dies at 60; epidemiologist helped show importance of vitamin D: Garland and his brother Cedric were the first to demonstrate that vitamin D deficiencies play a role in cancer and other diseases.", Los Angeles Times, August 31, 2010. Accessed September 4, 2010.
^Wactawski-Wende, J; Kotchen, JM, Women's Health Initiative Investigators (Mar 9, 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.
^"Too much vitamin D can be as unhealthy as too little" (Press release). University of Copenhagen. May 29, 2012. Retrieved 2015-05-27.
^Durup, D.; Jørgensen, H. L.; Christensen, J.; Schwarz, P.; Heegaard, A. M.; Lind, B. (May 9, 2012). "A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice: The CopD Study". The Journal of Clinical Endocrinology & Metabolism. Endocrine Society. 97 (8): 2644–2652. doi:10.1210/jc.2012-1176. PMID 22573406.
^Ponchon, G; Kennan, AL; DeLuca, HF (November 1969). ""Activation" of vitamin D by the liver". The Journal of Clinical Investigation. 48 (11): 2032–7. doi:10.1172/JCI106168. PMC 297455. PMID 4310770.
^Holick, MF; Deluca, HF; Avioli, LV (1972). "Isolation and identification of 25-hydroxycholecalciferol from human plasma". Archives of Internal Medicine. 129 (1): 56–61. doi:10.1001/archinte.1972.00320010060005. PMID 4332591.
v
t
e
Vitamins (A11)
Fat soluble
A
α-Carotene
β-Carotene
Retinol#
Tretinoin
D
D2
Ergosterol
Ergocalciferol#
D3
7-Dehydrocholesterol
Previtamin D3
Cholecalciferol#
25-hydroxycholecalciferol
Calcitriol (1,25-dihydroxycholecalciferol)
Calcitroic acid
D4
Dihydroergocalciferol
D5
D analogues
Alfacalcidol
Dihydrotachysterol
Calcipotriol
Tacalcitol
Paricalcitol
E
Tocopherol
Alpha
Beta
Gamma
Delta
Tocotrienol
Alpha
Beta
Gamma
Delta
Tocofersolan
K
Naphthoquinone
Phylloquinone (K1)
Menaquinones (K2)
Menadione (K3)‡
Menadiol (K4)
Water soluble
B
B1
Thiamine#
B1 analogues
Acefurtiamine
Allithiamine
Fursultiamine
Octotiamine
Prosultiamine
Sulbutiamine
B2
Riboflavin#
B3
Niacin
Nicotinamide#
B5
Pantothenic acid
Dexpanthenol
Pantethine
B6
Pyridoxine#, Pyridoxal phosphate
Pyridoxamine
Pyritinol
B7
Biotin
B9
Folic acid
Dihydrofolic acid
Folinic acid
Levomefolic acid
B12
Adenosylcobalamin
Cyanocobalamin
Hydroxocobalamin
Methylcobalamin
Choline
C
Ascorbic acid#
Dehydroascorbic acid
Combinations
Multivitamins
#WHO-EM
‡Withdrawn from market
Clinical trials:
†Phase III
§Never to phase III
v
t
e
Vitamin D receptor modulators
VDR
Agonists: 7-Dehydrocholesterol
22-Oxacalcitriol
25-Hydroxyergocalciferol
Alfacalcidol
Calcifediol
Calciferol
Calcipotriol
Calcitriol
Cholecalciferol (vitamin D3)
Dihydrotachysterol
Doxercalciferol
EB-1089
Eldecalcitol
Ercalcidiol
Ercalcitriol
Ergocalciferol (vitamin D2)
Lithocholic acid
Paricalcitol
Tacalcitol
See also
Receptor/signaling modulators
Nuclear receptor modulators
UpToDate Contents
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Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment.
Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, Timms PM, Venton TR, Bothamley GH, Packe GE, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Mein CA, Bhaw-Rosun L, Nuamah R, Young DB, Drobniewski FA, Griffiths CJ, Martineau AR.SourceDivision of Mycobacterial Research, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom.
Proceedings of the National Academy of Sciences of the United States of America.Proc Natl Acad Sci U S A.2012 Sep 18;109(38):15449-54. Epub 2012 Sep 4.
Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effe
Epigenetic regulation of the 1,25-dihydroxyvitamin D(3) 24-hydroxylase (CYP24A1) in colon cancer cells.
Höbaus J, Fetahu IS, Khorchide M, Manhardt T, Kallay E.SourceDepartment of Pathophysiology and Allergy Research, Medical University of Vienna, Austria.
The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2012 Aug 20. [Epub ahead of print]
Calcitriol is the hormonally active form of vitamin D and has anti-proliferative and pro-apoptotic effects. Calcitriol and its precursor calcidiol (25(OH)D(3)) are degraded by the 1,25-dihydroxyvitamin D(3) 24-hydroxylase (CYP24A1). This enzyme is overexpressed in colorectal tumors, however, the mec
Chemical & pharmaceutical bulletin 44(1), 62-66, 1996-01-15
… The first synthesis of the title compound 4,a novel analog of 1α-hydroxyvitamin D (α-calcidiol) that might be therapeutically useful, is described. …
Read more about the pharmacogenomics of calcidiol on PharmGKB. ... Calcidiol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, the active form of vitamin D3. Calcitriol binds to intracellular ...
Definition of calcidiol in the Medical Dictionary. calcidiol explanation. Information about calcidiol in Free online English dictionary. What is calcidiol? Meaning of calcidiol medical term. What does calcidiol mean? calcidiol - definition ...
