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Vitamin C
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== In human disease == Vitamin C is important in [[mast cell activation disorder]] for its role in the breakdown of [[histamine]] and as a [[mast cell]] stabilizer. Vitamin C is also a co-factor in [[collagen]] synthesis, making it a potentially important nutrient in [[Ehlers-Danlos syndrome]] and other [[connective tissue]] disorders.<ref>{{Cite journal | last =Mantle | first = D. | last2 = Wilkins | first2 = R.M. | last3 = Preedy | first3 = V. | date = 2005-01-01 | title = A novel therapeutic strategy for EhlersβDanlos syndrome based on nutritional supplements|url=http://www.sciencedirect.com/science/article/pii/S0306987704004566|journal=Medical Hypotheses|volume=64|issue=2|pages=279β283|doi=10.1016/j.mehy.2004.07.023|issn=0306-9877}}</ref><ref>{{Cite journal | last =Dembure | first = Philip P. | last2 = Janko | first2 = Anita R. | last3 = Priest | first3 = Jean H. | last4 = Elsas | first4 = Louis J. | date = 1987-07-01 | title = Ascorbate regulation of collagen biosynthesis in Ehlers-Danlos syndrome, type VI|url=http://www.sciencedirect.com/science/article/pii/0026049587901557|journal=Metabolism|volume=36|issue=7|pages=687β691|doi=10.1016/0026-0495(87)90155-7|issn=0026-0495}}</ref><ref>{{Cite journal | last =Elsas | first = Louis J. | last2 = Miller | first2 = Robert L. | last3 = Pinnell | first3 = Sheldon R. | date = 1978-03-01 | title = Inherited human collagen lysyl hydroxylase deficiency: Ascorbic acid response|url=http://www.sciencedirect.com/science/article/pii/S0022347678804235|journal=The Journal of Pediatrics|volume=92|issue=3|pages=378β384|doi=10.1016/S0022-3476(78)80423-5|issn=0022-3476}}</ref><ref>{{Cite journal | last = Kanof | first = Abram | date = 1952-02-01 | title = EHLERS-DANLOS SYNDROME: Report of a Case with Suggestion of a Possible Causal Mechanism|url=https://jamanetwork.com/journals/jamapediatrics/fullarticle/495523|journal=A.M.A. American Journal of Diseases of Children|language=en|volume=83|issue=2|pages=197β202|doi=10.1001/archpedi.1952.02040060063007|issn=0096-8994}}</ref><ref>{{Cite journal | last =Ringsdorf | first = W. M. | last2 = Cheraskin | first2=E. | date = 1982-03-01 | title = Vitamin C and human wound healing | url =http://www.sciencedirect.com/science/article/pii/003042208290295X|journal=Oral Surgery, Oral Medicine, Oral Pathology|volume=53|issue=3|pages=231β236|doi=10.1016/0030-4220(82)90295-X|issn=0030-4220}}</ref><ref>{{Cite book | url =https://books.google.com/books?hl=en&lr=&id=x-Z-cXUGlL8C&oi=fnd&pg=PR5&ots=FzzS-w8isY&sig=vY_ard7hUgYcNfbXatqmS7ltZGA#v=onepage&q&f=false | title = Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects | last =Royce | first = Peter M. | last2 = Steinmann | first2=Beat | date = 2003-04-14|publisher=John Wiley & Sons|isbn=978-0-471-46117-3|language=en}}</ref> Deficiency of vitamin C may contribute to [[osteoporosis]].<ref name="seftel1966" /><ref name="aghajanian2015" /> Vitamin C deficiency leads to altered function of [[procollagen-proline dioxygenase]] and [[lysyl hydroxylase]] enzymes. Each are essential for collagen synthesis and require Vitamin C as a cofactor.<ref>{{Cite book | last=Wu | first = Marlyn | last2 = Crane | first2 = Jonathan S. | date = 2019 | title=Biochemistry, Collagen Synthesis|url=http://www.ncbi.nlm.nih.gov/books/NBK507709/|location=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29939531}}</ref> === Mast cell activation disorder === Numerous studies have found Vitamin C to be inversely correlated with histamine and that the administration of Vitamin C reduces blood [[histamine]] levels.<ref name="clemetson1980" /><ref name="johnston1992" /><ref>{{Cite journal | last= Johnston | first = CS | last2 = Solomon | first2 = RE | last3 = Corte | first3=C | date = Dec 1996 | title = Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults|url=https://www.ncbi.nlm.nih.gov/pubmed/8951736|journal=J Am Coll Nutr.|volume=15 | issue =6 | pages = 586-591| doi=10.1080/07315724.1996.10718634|via=}}</ref> It does this potentially through several mechanisms: by inhibiting mast cell production; by increasing [[diamine oxidase]] (an [[enzyme]] that breaks down histamine); by inhibiting mast cell degranulation and the release of histamine in the first place (i.e., as a mast cell stabilizer),<ref name="Mio1999">{{Cite journal | last =Mio | first = M | date = 1999 | title=Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds|url=https://www.sciencedirect.com/science/article/pii/S0162310998000538|journal=Immunopharmacology|volume=|pages=|via=}}</ref> and by inhibiting [[histidine decarboxylase]] (the enzyme that forms histamine).<ref name="PMC4903110">{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/ | title = Pharmacological treatment options for mast cell activation disease | last =Molderings | first=Gerhard | date = 2016 | journal=Naunyn Schmiedebergs Arch Pharmacol|volume=|pages=|via=}}</ref> [[File:Nihms-754526-f0008.jpg|right|300x300px]] === Ehlers-Danlos Syndrome === A case study found improved wound healing in a patient with vascular [[Ehlers-Danlos Syndrome]] who was given high-dose (4g/day) oral vitamin C supplementation for two years.<ref>{{Cite journal | last =Ringsdorf | first = W. M. | last2 = Cheraskin | first2=E. | date = 1982-03-01 | title = Vitamin C and human wound healing | url =http://www.sciencedirect.com/science/article/pii/003042208290295X|journal=Oral Surgery, Oral Medicine, Oral Pathology|volume=53|issue=3|pages=231β236|doi=10.1016/0030-4220(82)90295-X|issn=0030-4220}}</ref> A case study of two patients with Kyphoscoliotic EDS received high-dose Vitamin C (5g/day). After one year, they had reduced bleeding time and improve wound healing, and muscle strength.<ref>{{Cite journal | last =Dembure | first = Philip P. | last2 = Janko | first2 = Anita R. | last3 = Priest | first3 = Jean H. | last4 = Elsas | first4 = Louis J. | date = 1987-07-01 | title = Ascorbate regulation of collagen biosynthesis in Ehlers-Danlos syndrome, type VI|url=http://www.sciencedirect.com/science/article/pii/0026049587901557|journal=Metabolism|volume=36|issue=7|pages=687β691|doi=10.1016/0026-0495(87)90155-7|issn=0026-0495}}</ref>
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