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{{Cleanup|reason=Text copied and pasted from sourced. Also too much detail and too technical. | date = May 2020}} '''Vitamin C''', also known as '''ascorbic acid''', is a water-soluble vitamin found particularly in citrus fruits and green vegetables. It is essential for [[collagen]], [[catecholamine]], and [[carnitine]] biosynthesis.<ref>{{Cite journal | last =Michels | first=Alexander J. | last2 = Hagen | first2=Tory M. | last3 = Frei | first3 = Balz| date = 2013 | title = Human Genetic Variation Influences Vitamin C Homeostasis by Altering Vitamin C Transport and Antioxidant Enzyme Function|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357493/|journal=Annual review of nutrition|volume=33|pages=45β70|doi=10.1146/annurev-nutr-071812-161246|issn=0199-9885|pmc=4357493|pmid=23642198}}</ref> One of its roles is as an antioxidant, that is, it helps to protect cells from damage by oxidative stress and also improves mitochondrial function. Another role is as a cofactor for several enzymes.<ref>{{Cite book | url =https://www.worldcat.org/oclc/55641398 | title = Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids : a report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. | date = 2000 | publisher=National Academy Press | last =National Research Council | authorlink = | last2 = Institute of Medicine | authorlink2 = Institute of Medicine |isbn=0309597196|location=Washington, D.C.|oclc=55641398}}</ref> After absorption, Vitamin C is present throughout the whole body. Large cross-sectional population studies confirm that vitamin C deficiency is common in humans, affecting 5%β10% of adults in the industrialized world. Moreover, significant associations between poor vitamin C status and increased morbidity and mortality have consistently been observed. However, the absorption, distribution and elimination kinetics of vitamin C ''in vivo'' are highly complex, due to dose-dependent non-linearity, and the specific regulatory mechanisms are not fully understood.<ref name="lindblad2013" /> In addition, the optimal daily intake as well as the typical total body pool of vitamin C during health and disease remain unknown.<ref name="ginter1979" /><ref name="ginter1980" /><ref name="ginter1982" /><ref name="lykkesfeldt2019" /> There are also discrepancies in global vitamin C recommendations, and the various national authorities recommend the minimum amount of vitamin C, however, this is likely not meeting the health needs of various subpopulations. For example, smokers and people with obesity have higher requirements than the general population, and national authorities should reassess their dietary recommendations.<ref name="carr2020" /> [[File:Nutrients-05-02860-g001.jpg|right|300x300px]] ==Biology== Vitamin C is found in the whole body, even skin tissue.<ref name="padayatty2016" /><ref name="pullar2017" /> High levels of vitamin C are found in the [[eyes]], [[pituitary]], [[adrenal gland]], [[pancreas]], [[liver]], [[spleen]] and [[brain]]. Vitamin C is also found in relative high levels in the [[bone marrow]], [[muscles]] and [[skin]].<ref name="pullar2017" /><ref name="snodgrass">{{Cite journal | title = Vitamin neurotoxicity|url=https://www.ncbi.nlm.nih.gov/pubmed/1463588| last=Snodgrass | first = S. Robert | journal=Molecular Neurobiology | publisher=Springer Science and Business Media LLC | volume=6 | issue=1 | date = 1992 | issn=0893-7648 | doi=10.1007/bf02935566 | pages=41β73|pmid = 1463588| via=}}</ref> Bone marrow is probably also involved in the vitamin C homeostasis process.<ref name="padayatty2016" /><ref name="seftel1966" /><ref name="aghajanian2015" /> [[File:VitCinskinPullar2017.jpg|right|300x300px]] The adrenal gland can inject vitamin C into the blood.<ref name="padayatty2016" /> Too much sun exposure may deplete the Vitamin C stores in the skin tissue.<ref name="pullar2017" /> == 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> == Supplementation == Several studies indicates the recovery from Vitamin C depletion will require several months of treatment. <ref name="padayatty2016" /> == Notable studies == * 2014, Mitochondrial dysfunction and chronic disease: treatment with natural supplements<ref>{{Cite journal | last =Nicolson | first=Garth L. | author-link = Garth Nicolson| date = 2014 | title = Mitochondrial dysfunction and chronic disease: treatment with natural supplements|url=https://www.ncbi.nlm.nih.gov/pubmed/24473982|journal=Alternative Therapies in Health and Medicine|volume=20 |issue =Suppl 1|pages=18β25|issn=1078-6791|pmid=24473982|quote=|via=}}</ref> [https://www.researchgate.net/publication/259960416_Mitochondrial_Dysfunction_and_Chronic_Disease_Treatment_With_Natural_Supplements (Full text)] ==See also== *[[Hypovitaminosis C]] *[[Collagen]] *[[Mast cell activation syndrome]] *[[Vitamin]] *[[Irritable bowel syndrome]] *[[Osteoporosis]] *[[Diet]] ==Learn more== *[http://lpi.oregonstate.edu/mic/vitamins/vitamin-C Linus Pauling Institute Micronutrient Information Center - Vitamin C] ==References== <references> <ref name="ginter1979">{{Citation| issue = 33| pages = 104-141| last = Ginter | first = Emil| title = Chronic marginal vitamin C deficiency: biochemistry and pathophysiology.| journal = World Rev Nutr Diet | date = 1979|doi=10.1159/000402551|url=https://www.ncbi.nlm.nih.gov/pubmed/392953}}</ref> <ref name="ginter1980">{{Citation| volume = 33 | issue = 3| pages = 538-539| last = Ginter | first = Emil| title = What is truly the maximum body pool size of ascorbic acid in man?| journal = Am J Clin Nutr| date = Mar 1980|doi=10.1093/ajcn/33.3.538|url=https://www.ncbi.nlm.nih.gov/pubmed/6986762}}</ref> <ref name="ginter1982">{{Citation| volume = 1 | issue = 2| pages = 66-77| last = Ginter | first = Emil| title = Optimum Intake of Vitamin C for the Human Organism| journal = Nutrition and Health| date = Apr 1982|doi=10.1177/026010608200100202|url=https://journals.sagepub.com/doi/10.1177/026010608200100202}}</ref><ref name="lindblad2013">{{Citation| issn = 2072-6643 | issue = 5| pages = 2860-2879| last = Lindblad | first = Maiken | last2 = Tveden-Nyborg | first2 = Pernille | last3 = Lykkesfeldt | first3 = Jens| title = Regulation of Vitamin C Homeostasis during Deficiency| journal = Nutrients| date = May 2013|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775232}}</ref> <ref name="lykkesfeldt2019">{{Citation| volume = 11 | issue = 10| last2 = Tveden-Nyborg | first2 = Pernille | last = Lykkesfeldt | first = Jens| title = The Pharmacokinetics of Vitamin C| journal = Nutrients| date = Oct 2019|doi=10.3390/nu11102412|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835439}}</ref> <ref name="padayatty2016">{{Citation|volume = 22 | issue = 6| pages = 463-93| last = Padayatty | first = Sebastian | last2 = Levine | first2 = Mark| title = Vitamin C: the known and the unknown and Goldilocks| journal = Oral Disease | date = June 2016 | url = https://www.ncbi.nlm.nih.gov/pubmed/26808119}}</ref> <ref name="clemetson1980">{{Citation| issn = 0022-3166| volume = 110 | issue = 4| pages = 662β668| last = Clemetson | first = C.A. | title = Histamine and ascorbic acid in human blood| journal = The Journal of Nutrition| date = April 1980 | pmid = 7365537}}</ref> <ref name="johnston1992">{{Citation| issn = 0731-5724| volume = 11 | issue = 2| pages = 172β176| last1 = Johnston | first1 = C.S. | last2 = Martin | first2 = L.J. | last3 = Cai | first3 = X.| title = Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis| journal = Journal of the American College of Nutrition| date = April 1992 | pmid = 1578094}}</ref> <ref name="seftel1966">{{Citation| volume = 1 | issue = 5488| pages = 642-644| last1 = Seftel | first1 = H| last2 = Malkin | first2 = C| last3 = Schmaman | first3 = A| last4 = Abrahams | first4 = C| last5 = Lynch | first5 = S| last6 = Charlton | first6 = S| last7 = Bothwell | first7 = T| title = Osteoporosis, Scurvy, and Siderosis in Johannesburg Bantu| journal = Br Med J|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1843929/}}</ref> <ref name="aghajanian2015">{{Citation| volume = 30 | issue = 11| pages = 1945β1955| last1 = Aghajanian | first1 = P| last2 = Hall | first2 = S. | last3 = Wongworawat | first3 = MD| last4 = Mohan | first4 = S| title = The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments| journal = J Bone Miner Res| date = 2015 |url=https://www.ncbi.nlm.nih.gov/pubmed/26358868}}</ref> <ref name="carr2020">{{Citation| volume = 30 | issue = 3| pages = 1-14| last1 = Carr | first1 = AC| last2 = Lykkesfeldt | first2 = J| title = Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives|journal = Crit Rev Food Sci Nutr| date = 2020|url=https://www.ncbi.nlm.nih.gov/pubmed/32223303 }}</ref> <ref name="pullar2017">{{Citation| volume = 9 | issue = 8| pages = 866| last1 = Pullar | first1 = JM| last2 = Carr | first2 = AC| last3 = Vissers | first3 = MCM| title = The Roles of Vitamin C in Skin Health| journal = Nutrients| date = 2017|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579659}}</ref> </references> [[Category:Potential treatments]] [[Category:Supplements]] [[Category:Vitamins]] [[Category:Nutrients]] [[Category:Depression alternative treatments]] [[Category:Depression treatments]]
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