Vitamin C
32509
225918500
2008-07-16T00:35:18Z
130.182.30.48
/* Deficiency */
{{Mergefrom|Vitamin C and Common Cold|date=April 2008}}
{{about|the nutrient|the chemical compound|ascorbic acid}}{{other uses}}
{{drugbox |
| IUPAC_name = 2-oxo-L-threo-hexono-1,4- lactone-2,3-enediol<br />''or''<br />(''R'')-3,4-dihydroxy-5-((''S'')- 1,2-dihydroxyethyl)furan-2(5''H'')-one
| image = Kwas askorbinowy.svg
| width = 180
| image2 = L-ascorbic-acid-3D-balls.png
| width2 = 180
| CAS_number = 50-81-7
| CAS_supplemental =
| ATC_prefix = A
| ATC_suffix = 11G
| ATC_supplemental =
| PubChem = 5785
| DrugBank =
| chemical_formula =
| C=6 | H=8 | O=6
| molecular_weight = 176.14 grams per mol
| smiles =
| synonyms = <small>L</small>-ascorbate
| density =
| melting_point = 190
| melting_high = 192
| melting_notes = ''decomposes''
| boiling_point =
| boiling_notes =
| solubility =
| specific_rotation =
| sec_combustion =
| bioavailability = rapid & complete
| protein_bound = negligible
| metabolism =
| elimination_half-life = 30 minutes <!-- As it states further down in the article, vitamin-c's half-life is _30 minutes_, not 16 days, etc. -->
| excretion = renal
| licence_EU = <!-- EMEA requires brand name -->
| licence_US = <!-- FDA may use generic name -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category= A
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = general public availability
| routes_of_administration = oral
}}
{{Double image stack|right|Ascorbic acid structure.png|Dehydroascorbic acid.png|150|[[ascorbic acid]]<br />([[reducing agent|reduced form]])|[[dehydroascorbic acid]]<br />([[oxidizing agent|oxidized form]])}}
'''Vitamin C''' or ''' <small>L</small>-ascorbate''' is an [[essential nutrient]] for a large number of [[simian|higher primate]] species, a small number of other [[mammal]]ian species (notably [[guinea pig]]s and [[bat]]s), a few species of birds, and some fish.
<ref name="McCluskey1985">{{ cite journal | last = McCluskey | first = Elwood S. | authorlink = | coauthors = | year = 1985 | month = | title = Which Vertebrates Make Vitamin C? | journal = Origins | volume = 12 | issue = 2 | pages = 96–100 | doi = | url = http://www.grisda.org/origins/12096.pdf | accessdate = | quote = }}</ref>
The presence of ascorbate is required for a range of essential [[metabolism|metabolic reactions]] in all animals and plants. It is [[biosynthesis|made internally]] by almost all organisms, humans being the most well-known exception. It is widely known as the [[vitamin]] whose deficiency causes [[scurvy]] in humans.<ref name="UKFSA">{{cite web |url=http://www.eatwell.gov.uk/healthydiet/nutritionessentials/vitaminsandminerals/vitaminc/ |title=Vitamin C |accessdate=2007-02-19 |publisher=Food Standards Agency (UK) }}</ref><ref name="UMM">{{cite web |url=http://www.umm.edu/ency/article/002404.htm |title=Vitamin C |accessdate=2008-03-31 |date=January 2007 |author= |publisher=University of Maryland Medical Center }}</ref><ref name="OSU">{{cite web |url=http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC/|title=Vitamin C |accessdate=2007-03-07 |date=2006-01-31 |first=Jane, Ph.D. |last= Higdon|publisher=Oregon State University, Micronutrient Information Center}}</ref> It is also widely used as a [[food additive]].
The [[pharmacophore]] of vitamin C is the ascorbate [[ion]]. In living organisms, ascorbate is an [[antioxidant]], since it protects the body against [[oxidative stress]],<ref name="Padayatty">{{cite journal |author=Padayatty S, Katz A, Wang Y, Eck P, Kwon O, Lee J, Chen S, Corpe C, Dutta A, Dutta S, Levine M |title=Vitamin C as an antioxidant: evaluation of its role in disease prevention |url=http://www.jacn.org/cgi/reprint/22/1/18.pdf |journal=J Am Coll Nutr |volume=22 |issue=1 |pages=18–35 |year=2003 |pmid=12569111}}</ref> and is a [[cofactor]] in several vital [[enzyme|enzymatic]] reactions.<ref name="UKFSA Risk" />
The uses and the daily requirement amounts of vitamin C are matters of on-going debate. People consuming diets rich in ascorbate from natural foods, such as fruits and vegetables, are healthier and have lower mortality from a number of chronic illnesses. However, a recent meta-analysis of 68 reliable antioxidant supplementation experiments involving a total of 232,606 individuals concluded that consuming additional ascorbate from supplements may not be as beneficial as thought.<ref>{{cite journal |author=Bjelakovic G, et al |title=Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. |journal=JAMA |volume=297 |issue=8 |pages=842–57 |year=2007 |pmid=17327526 | doi = 10.1001/jama.297.8.842 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
== Biological significance ==
{{further|[[ascorbic acid]]}}
Vitamin C is purely the [[Enantiomer|<small>L</small>-enantiomer]] of ascorbate; the opposite [[Enantiomer|<small>D</small>-enantiomer]] has no physiological significance. Both forms are [[Chirality (chemistry)|mirror images]] of the same molecular structure. When <small>L</small>-ascorbate, which is a strong [[reducing agent]], carries out its [[Redox|reducing]] function, it is converted to its [[Redox|oxidized]] form, [[Dehydroascorbic acid|<small>L</small>-dehydroascorbate]].<ref name="UKFSA Risk">{{cite web |url=http://www.food.gov.uk/multimedia/pdfs/evm_c.pdf |title=Vitamin C – Risk Assessment |accessdate=2007-02-19 |publisher=UK Food Standards Agency }}</ref> <small>L</small>-dehydroascorbate can then be reduced back to the active <small>L</small>-ascorbate form in the body by [[enzyme]]s and [[glutathione]].<ref>{{cite journal |author=Meister A |title=Glutathione-ascorbic acid antioxidant system in animals |url=http://www.jbc.org/cgi/reprint/269/13/9397.pdf |journal=J Biol Chem |volume=269 |issue=13 |pages=9397–400 |year=1994 |pmid=8144521}}</ref>
<small>L</small>-ascorbate is a [[weak acid|weak]] [[sugar acids|sugar acid]] structurally related to [[glucose]] which naturally occurs either attached to a [[hydrogen ion]], forming [[ascorbic acid]], or to a [[metal|metal ion]], forming a [[mineral ascorbate]].
=== Function ===
In humans, vitamin C is a highly effective [[antioxidant]], acting to lessen [[oxidative stress]], a substrate for [[ascorbate peroxidase]],<ref name="OSU" /> as well as an enzyme [[cofactor]] for the [[biosynthesis]] of many important biochemicals. Vitamin C acts as an [[electron donor]] for eight different [[enzyme]]s:<ref>Levine M, Rumsey SC, Wang Y, Park JB, Daruwala R. Vitamin C. In Stipanuk MH (ed): "Biochemical and Physiological Aspects of Human Nutrition." Philadelphia: W B Saunders, pp 541–567, 2000.</ref>
* Three participate in [[collagen]] [[hydroxylation]].<ref>Prockop DJ, Kivirikko KI: Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem 64:403–434, 1995.</ref><ref>Peterkofsky B: Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 54:1135S–1140S, 1991.</ref><ref>Kivirikko KI, Myllyla R: Post-translational processing of procollagens. Ann N Y Acad Sci 460:187–201, 1985.</ref> These reactions add [[Hydroxide|hydroxyl groups]] to the amino acids [[proline]] or [[lysine]] in the collagen molecule (via [[prolyl hydroxylase]] and [[lysyl hydroxylase]]), thereby allowing the collagen molecule to assume its triple helix structure and making vitamin C essential to the development and maintenance of [[granulation tissue| scar tissue]], [[blood vessel]]s, and cartilage.<ref>McGee, William, M.D., M.H.A., Assistant Professor of Medicine and Surgery, Tufts University School of Medicine; [http://www.nlm.nih.gov/medlineplus/ency/article/002404.htm Medical Encyclopedia: Ascorbic acid]</ref>
* Two are necessary for synthesis of [[carnitine]].<ref name="Ascorbicacidcarnitine">{{cite journal |author=Rebouche CJ |title=Ascorbic acid and carnitine biosynthesis |url=http://www.ajcn.org/cgi/reprint/54/6/1147S.pdf |journal=Am J Clin Nutr |volume=54 |issue=6 Suppl |pages=1147S–1152S |year=1991 |pmid=1962562}}</ref><ref name="Carnitinebiosynthesis">{{cite journal |author=Dunn WA, Rettura G, Seifter E, Englard S |title=Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gamma-butyrobetaine hydroxylase. |url=http://www.jbc.org/cgi/reprint/259/17/10764.pdf|journal=J Biol Chem |volume=259 |issue=17 |pages=10764–70 |year=1984 |pmid=6432788}}</ref> Carnitine is essential for the transport of [[fatty acid]]s into [[mitochondria]] for [[Adenosine triphosphate|ATP]] generation.
* The remaining three have the following functions:
** [[dopamine beta hydroxylase]] participates in the biosynthesis of [[norepinephrine]] from [[dopamine]].<ref>Levine M, Dhariwal KR, Washko P, Welch R, Wang YH, Cantilena CC, Yu R: Ascorbic acid and reaction kinetics in situ: a new approach to vitamin requirements. J Nutr Sci Vitaminol (Tokyo) Spec No:169–172, 1992.</ref><ref>Kaufman S: Dopamine-beta-hydroxylase. J Psychiatr Res 11: 303–316, 1974.</ref>
** another enzyme adds [[amide]] groups to [[peptide hormone]]s, greatly increasing their stability.<ref>Eipper BA, Milgram SL, Husten EJ, Yun HY, Mains RE: Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains. Protein Sci 2:489–497, 1993.</ref><ref>Eipper BA, Stoffers DA, Mains RE: The biosynthesis of neuropeptides: peptide alpha-amidation. Annu Rev Neurosci 15:57–85, 1992.</ref>
** one modulates [[tyrosine]] metabolism.<ref>{{cite journal |author=Englard S, Seifter S |title=The biochemical functions of ascorbic acid |journal=Annu. Rev. Nutr. |volume=6 |issue= |pages=365–406 |year=1986 |pmid=3015170 |doi=10.1146/annurev.nu.06.070186.002053}}</ref><ref>Lindblad B, Lindstedt G, Lindstedt S: The mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate. J Am Chem Soc 92:7446–7449, 1970.</ref>
[[Biological tissue]]s that accumulate over 100 times the level in blood plasma of vitamin C are the [[adrenal gland]]s, [[pituitary]], [[thymus]], [[corpus luteum]], and [[retina]].<ref>[http://www.nature.com/nm/journal/v8/n5/full/nm0502-445.html New view at C] Matthias A. Hediger , ''Nature Medicine'' 8, 445 - 446 (2002)
doi:10.1038/nm0502-445</ref>
Those with 10 to 50 times the concentration present in blood plasma include the [[brain]], [[spleen]], [[lung]], [[testicle]], [[lymph nodes]], [[liver]], [[thyroid]], [[small intestine|small intestinal]] [[mucous membrane|mucosa]], [[leukocytes]], [[pancreas]], [[kidney]] and [[salivary glands]].
=== Biosynthesis ===
[[Image:Ascorbic-acid-3D-vdW.png|thumb|200px|left|Model of a vitamin C [[molecule]]. Black is [[carbon]], red is [[oxygen]], and white is [[hydrogen]]]]
The vast majority of animals and plants are able to synthesize their own vitamin C, through a sequence of four [[enzyme]]-driven steps, which convert [[glucose]] to vitamin C.<ref name="UKFSA Risk" /> The glucose needed to produce ascorbate in the liver (in [[mammals]] and [[perching birds]]) is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process.<ref>{{cite journal |author=Bánhegyi G, Mándl J |title=The hepatic glycogenoreticular system |journal=Pathol Oncol Res |volume=7 |issue=2 |pages=107–10 |year=2001 |pmid=11458272}}</ref> In [[reptiles]] and [[birds]] the biosynthesis is carried out in the [[kidney]]s.
Among the animals that have lost the ability to synthesise vitamin C are [[simian]]s (specifically the suborder [[haplorrhini]]), [[guinea pig]]s, a number of species of [[passerine]] birds (but not all of them), and in apparently many major families of bats and perhaps all of them. Humans have no enzymatic capability to manufacture vitamin C. The cause of this phenomenon is that the last enzyme in the synthesis process, [[L-gulonolactone oxidase|<small>L</small>-gulonolactone oxidase]], cannot be made by the listed animals because the gene for this enzyme, [[Pseudogene]] ΨGULO, is defective.<ref>{{cite book | title = Ascorbic Acid: Subcellular Biochemistry | author = Harris, J. Robin | publisher = Springer | isbn = 0306451484 | year = 1996 | pages = p. 35}}</ref> The [[mutation]] has not been lethal because vitamin C is abundant in their food sources. It has been found that species with this mutation (including humans) have adapted a vitamin C recycling mechanism to compensate.<ref>{{cite journal |title=How Humans Make Up For An 'Inborn' Vitamin C Deficiency |url=http://www.sciencedaily.com/releases/2008/03/080320120726.htm }}</ref>
<!-- sorry, but the idea that vitamin C synthesis is defective mostly in fruit eating species, does not survive scrutiny. Birds which lack it are not notably fructivores, and ALL bats, not just fruit-eaters, lack it.-->
Most [[simian]]s consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans.<ref>Milton, K. (1999) "Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?" Nutrition. 1999 Jun;15(6):488-98.</ref> This discrepancy constitutes the basis of the controversy on current recommended dietary allowances.
It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the evolutionary loss of the ability to break down [[uric acid]]. Uric acid and ascorbate are both strong [[reducing agent]]s. This has led to the suggestion that in higher primates, uric acid has taken over some of the functions of ascorbate.<ref>{{cite journal |author=Proctor P |title=Similar functions of uric acid and ascorbate in man? |journal=Nature |volume=228 |issue=5274 |pages=868 |year=1970 |pmid=5477017|doi=10.1038/228868a0}}</ref> Ascorbic acid can be [[oxidised]] (broken down) in the human body by the enzyme [[ascorbic acid oxidase]].
An adult [[goat]], a typical example of a vitamin C-producing animal, will manufacture more than 13,000 mg of vitamin C per day in normal health and the biosynthesis will increase "many fold under stress".<ref>{{cite web |url=http://www.seanet.com/~alexs/ascorbate/197x/stone-i-orthomol_psych-1979-v8-n2-p58.htm |title=Eight Decades of Scurvy. The Case History of a Misleading Dietary Hypothesis |accessdate=2007-04-06 |last=Stone |first=Irwin |authorlink=Irwin Stone |coauthors= |date=July 16, 1978 |year= |month= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=''Biochemical research in the 1950’s showed that the lesion in scurvy is the absence of the enzyme, L-Gulonolactone oxidase (GLO) in the human liver (Burns, 1959). This enzyme is the last enzyme in a series of four which converts blood sugar, glucose, into ascorbate in the mammalian liver. This liver metabolite, ascorbate, is produced in an unstressed goat for instance, at the rate of about 13,000 mg per day per 150 pounds body weight (Chatterjee, 1973). A mammalian feedback mechanism increases this daily ascorbate production many fold under stress (Subramanian et al., 1973)}}</ref> Trauma or injury has also been demonstrated to use up large quantities of vitamin C in humans.<ref>{{cite journal| author = C. Long, et al. | title = Ascorbic acid dynamics in the seriously ill and injured. | journal = Journal of Surgical Research | volume = 109 | issue = 2 | pages= 144–148| doi = 10.1016/S0022-4804(02)00083-5 | year = 2003}}</ref>
Some [[microorganism]]s such as the yeast ''[[Saccharomyces cerevisiae]]'' have been shown to be able to synthesize vitamin C from [[Monosaccharide|simple sugars]].<ref name="yeastAA">{{cite web |url=http://www.scri.sari.ac.uk/publications/annualreports/02Indiv/20Ascorb.pdf |title=Ascorbic acid biosynthesis in higher plants and micro-organisms |accessdate=2007-02-20||author=R.D. Hancock & R. Viola |publisher=Scottish Crop Research Institute}} </ref><ref>{{cite journal|author=Hancock RD, Galpin JR, Viola R.|title=Biosynthesis of <small>L</small>-ascorbic acid (vitamin C) by Saccharomyces cerevisiae |accessdate=2007-02-19 |journal=FEMS Microbiol Lett.|volume=186|issue=2|pages=245–50|url=http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T2W-405SX5F-M-3&_cdi=4929&_user=308069&_orig=search&_coverDate=05%2F05%2F2000&_sk=998139997&view=c&wchp=dGLbVzb-zSkzS&md5=d38569a901eecfe57b39eafa00a1d738&ie=/sdarticle.pdf|pmid=10802179}}</ref>
=== Deficiency ===
[[Scurvy]] is an [[avitaminosis]] resulting from lack of vitamin C, since without this vitamin, the synthesised [[collagen]] is too unstable to perform its function. Scurvy leads to the formation of liver spots on the skin, spongy gums, and bleeding from all [[mucous membrane]]s. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, [[suppuration|suppurating wounds]] and loss of [[teeth]] and, eventually, death. The human body can store only a certain amount of vitamin C,<ref>{{cite web |url=http://www.nlm.nih.gov/medlineplus/ency/article/002404.htm |title=Vitamin C |accessdate=2007-03-09 |date=[[2007-01-02]] |first=William |last =McGee |publisher=National Institutes of Health }}</ref> and so the body soon depletes itself if fresh supplies are not consumed.
It has been shown that smokers who have diets poor in vitamin C are at a higher risk of lung-borne diseases than those smokers who have higher concentrations of Vitamin C in the blood. <ref>{{cite web |url=http://news.bbc.co.uk/2/hi/health/901196.stm|title=The influence of smoking on vitamin C status in adults|accessdate=2007-12-12 |date=[[2000-31-09]]|publisher=BBC news and Cambridge University}}</ref>
== History of human understanding ==
[[Image:James lind.jpg|right|thumb|[[James Lind]], a British Royal Navy surgeon who, in 1747, identified that a quality in fruit prevented the disease of scurvy in what was the first [[scientific method|recorded controlled experiment]].]]
The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native peoples living in marginal areas incorporated this into their medicinal lore. For example, spruce needles were used in temperate zones in infusions, or the leaves from species of drought-resistant trees in desert areas. In 1536, the French explorer [[Jacques Cartier]], exploring the [[Saint Lawrence River|St. Lawrence River]], used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the [[Thuja|arbor vitae]] tree to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams.<ref>{{cite web |url=http://www3.sympatico.ca/goweezer/canada/z00cartier3.htm |title=Jacques Cartier's Second Voyage - 1535 - Winter & Scurvy |accessdate=2007-02-25 }}</ref><ref>{{cite journal |pmid=12422875 |title=Jacques Cartier witnesses a treatment for scurvy |date=June 2002 |author=Martini E. |journal=Vesalius}}</ref>
Throughout history, the benefit of plant food to survive long sea voyages has been occasionally recommended by authorities. [[John Woodall]], the first appointed surgeon to the [[British East India Company]], recommended the preventive and curative use of [[lemon]] juice in his book "The Surgeon's Mate", in 1617. The [[Netherlands|Dutch]] writer, [[Johann Bachstrom]], in 1734, gave the firm opinion that ''"scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease."''
While the earliest documented case of scurvy was described by [[Hippocrates]] around the year 400 BC, the first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the British [[Royal Navy]], [[James Lind]]. Scurvy was common among those with poor access to fresh fruit and vegetables, such as remote, isolated [[sailor]]s and [[soldier]]s. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon per day, in addition to normal rations, while others continued on [[cider]], [[vinegar]], [[sulfuric acid]] or [[seawater]], along with their normal rations. In the [[history of science]] this is considered to be the first occurrence of a controlled experiment comparing results on two populations of a factor applied to one group only with all other factors the same. The results conclusively showed that citrus fruits prevented the disease. Lind published his work in 1753 in his ''[[Treatise on the Scurvy]]''.
[[Image:Ambersweet oranges.jpg|left|thumb|[[Citrus|Citrus fruits]] were one of the first sources of vitamin C available to ship's surgeons.]]
Lind's work was slow to be noticed, partly because he gave conflicting evidence within the book, and partly because the British admiralty saw care for the well-being of crews as a sign of weakness. In addition, fresh fruit was very expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles<ref name="Oxford"/>). Ship captains assumed wrongly that Lind's suggestions didn't work because those juices failed to cure scurvy.
It was 1795 before the British navy adopted lemons or [[Lime (fruit)|lime]] as standard issue at sea. Limes were more popular as they could be found in British West Indian Colonies, unlike lemons which weren't found in [[Dominion|British Dominions]], and were therefore more expensive. This practice led to the American use of the nickname [[Alternative words for British|"limey"]] to refer to the British. [[James Cook|Captain James Cook]] had previously demonstrated and proven the principle of the advantages of carrying [[Sauerkraut|"Sour krout"]] on board, by taking his crews to the [[Hawaiian Islands]] and beyond without losing any of his men to scurvy<ref>{{cite book |last=Cook |first=James |authorlink=James Cook |coauthors=Philip Edwards |title=The Journals of Captain Cook |pages=38 |year=1999 |publisher=Penguin Books |location= |isbn=0140436472}}</ref>. For this otherwise unheard of feat, the British Admiralty awarded him a medal.
The name "antiscorbutic" was used in the eighteenth and nineteenth centuries as general term for those foods known to prevent scurvy, even though there was no understanding of the reason for this. These foods included but were not limited to: lemons, limes, and oranges; sauerkraut, cabbage, malt, and [[portable soup]].
In 1907, [[Axel Holst]] and [[Theodor Frølich]], two [[Norway|Norwegian]] physicians studying [[beriberi]] contracted aboard ship's crews in the Norwegian Fishing Fleet, wanted a small test mammal to substitute for the [[pigeon]]s they used. They fed [[guinea pig]]s their test diet, which had earlier produced beriberi in their pigeons, and were surprised when scurvy resulted instead. Until that time scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease.
=== Discovery of ascorbic acid ===
[[Image:GyorgyiNIH.jpg|thumb|220px|right|Albert Szent-Györgyi, pictured here in 1948, was awarded the 1937 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Medicine]] for the discovery of vitamin C]]
In 1912, the [[Polish-American]] biochemist [[Casimir Funk]], while researching deficiency diseases, developed the concept of [[vitamins]] to refer to the non-mineral micro-nutrients which are essential to health. The name is a [[portmanteau]] of "vital", due to the vital role they play biochemically, and "amines" because Funk thought that all these materials were chemical [[amine]]s. One of the "vitamines" was thought to be the anti-scorbutic factor, long thought to be a component of most fresh plant material.
In 1928 the Arctic anthropologist [[Vilhjalmur Stefansson]] attempted to prove his theory of how the [[Eskimo]]s are able to avoid scurvy with almost no plant food in their diet, despite the disease striking European Arctic explorers living on similar high-meat diets. Stefansson theorised that the natives get their vitamin C from fresh meat that is minimally cooked. Starting in February 1928, for one year he and a colleague lived on an exclusively minimally-cooked meat diet while under medical supervision; they remained healthy. (Later studies done after vitamin C could be quantified in mostly-raw traditional food diets of the Yukon, Inuit, and Métís of the Northern Canada, showed that their daily intake of vitamin C averaged between 52 and 62 mg/day, an amount approximately the [[dietary reference intake]] (DRI), even at times of the year when little plant-based food were eaten.)<ref> [http://jn.nutrition.org/cgi/content/full/134/6/1447 Accessed Feb.3 2008]: this is the full text for J. Nutr. 134:1447-1453, June 2004</ref>
From 1928 to 1933, the [[Hungary|Hungarian]] research team of [[Joseph L Svirbely]] and [[Albert Szent-Györgyi]] and, independently, the [[United States|American]] [[Charles Glen King]], first isolated the anti-scorbutic factor, calling it "ascorbic acid" for its vitamin activity. Ascorbic acid turned out ''not'' to be an amine, or even to contain any nitrogen. For their accomplishment, Szent-Györgyi was awarded the 1937 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Medicine]].<ref>{{cite web |url=http://www.pitt.edu/history/1932.html |title=Pitt History - 1932: Charles Glen King |accessdate=2007-02-21 |quote=In recognition of this medical breakthrough, some scientists believe that King deserved a Nobel Prize. |publisher=[[University of Pittsburgh]] }}</ref>
Between 1933 and 1934, the British chemists Sir [[Walter Norman Haworth]] and Sir [[Edmund Hirst]] and, independently, the Polish chemist [[Tadeus Reichstein]], succeeded in synthesizing the vitamin, making it the first to be artificially produced. This made possible the cheap mass-production of what was by then known as vitamin C. Only Haworth was awarded the 1937 [[Nobel Prize in Chemistry]] for this work, but the "Reichstein process" retained Reichstein's name.
In 1934 [[Hoffmann–La Roche]] became the first pharmaceutical company to mass-produce synthetic vitamin C, under the brand name of [[Redoxon]].
In 1957 the American [[J.J. Burns]] showed that the reason some mammals were susceptible to scurvy was the inability of their [[liver]] to produce the active [[enzyme]] [[L-gulonolactone oxidase|<small>L</small>-gulonolactone oxidase]], which is the last of the chain of four enzymes which synthesize vitamin C.<ref>Burns, J. J., and Evans, C., J. Biol. Chem., 200, 125 (1953).</ref><ref>Burns, J. J., Peyser, P., and Maltz, A., Science, 124, 1148 (1956).</ref> American biochemist [[Irwin Stone]] was the first to exploit vitamin C for its food preservative properties. He later developed the theory that humans possess a mutated form of the <small>L</small>-gulonolactone oxidase coding gene.
== Daily requirements ==
The [[North America]]n [[Dietary Reference Intake]] recommends 90 [[orders of magnitude (mass)|milligram]]s per day and no more than 2 grams per day (2000 milligrams per day).<ref name="US RDA">{{cite web |url=http://www.iom.edu/Object.File/Master/7/296/webtablevitamins.pdf |title=US Recommended Dietary Allowance (RDA) |accessdate=2007-02-19 |date= |author= |publisher= }}</ref> Other related species sharing the same inability to produce vitamin C and requiring [[exogenous]] vitamin C consume 20 to 80 times this reference intake.<ref name="Primates"/><ref name="paulingevolution">{{cite journal |title=Evolution and the need for ascorbic acid |accessdate=2007-03-06 |url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=283405&blobtype=pdf |journal=Proc Natl Acad Sci U S A |volume=67 |issue=4 |pages=1643–8 |first=Linus |last=Pauling |authorlink= Linus Pauling |pmid=5275366 |doi=10.1073/pnas.67.4.1643 |year=1970 }}</ref> There is continuing debate within the orthodox scientific community over the best dose schedule (the amount and frequency of intake) of vitamin C for maintaining optimal health in humans.<ref name="PR Newswire">{{cite web |url=http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/07-06-2004/0002204911 |title=Linus Pauling Vindicated; Researchers Claim RDA For Vitamin C is Flawed |accessdate=2007-02-20 |date=[[6 July]], [[2004]] |publisher=PR Newswire }}</ref> It is generally agreed that a balanced diet without supplementation contains enough vitamin C to prevent scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more.<ref name="US RDA" />
High doses (thousands of milligrams) may result in [[diarrhea]] in healthy adults. Proponents of alternative medicine (specifically [[orthomolecular medicine]])<ref name="Cathcart">{{cite web |url=http://www.orthomed.com/titrate.htm |title=Vitamin C, Titrating To Bowel Tolerance, [[Anascorbemia]], and Acute Induced Scurvy |accessdate=2007-02-22 |date=1994 |first=Robert |last= Cathcart |authorlink=Robert Cathcart |publisher=Orthomed }}</ref> claim the onset of [[diarrhea]] to be an indication of where the body’s true vitamin C requirement lies, though this has yet to be clinically verified.
{| class="wikitable" align="right"
|-
! align="center" colspan="2" | United States vitamin C recommendations<ref name="US RDA" />
|-
| [[Recommended Dietary Allowance]] (adult male)
| 90 [[milligram|mg]] per day
|-
| Recommended Dietary Allowance (adult female)
| 75 [[milligram|mg]] per day
|-
| Tolerable Upper Intake Level (adult male)
| 2,000 [[milligram|mg]] per day
|-
| Tolerable Upper Intake Level (adult female)
| 2,000 [[milligram|mg]] per day
|-
|}
=== Government recommended intakes ===
Recommendations for vitamin C intake have been set by various national agencies:
*40 milligrams per day: the United Kingdom's [[Food Standards Agency]]<ref name=" UKFSA" />
*45 milligrams per day: the [[World Health Organization]]<ref>{{cite web |url=http://whqlibdoc.who.int/publications/2004/9241546123_chap7.pdf |title=Vitamin and mineral requirements in human nutrition, 2nd edition |accessdate=2007-02-20 |date=2004 |publisher=World Health Organization }}</ref>
*60 mg/day: Health Canada 2007 [http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/mono_vitamin_c_e.html]
*60–95 milligrams per day: United States' [[United States National Academy of Sciences|National Academy of Sciences]]<ref name="US RDA "/>
The United States defined [[Dietary Reference Intake|Tolerable Upper Intake Level]] for a 25-year-old male is 2,000 milligrams per day.
=== Alternative recommendations on intakes ===
Some independent researchers have calculated the amount needed for an adult human to achieve similar blood serum levels as vitamin C synthesising mammals as follows:
*400 milligrams per day: the [[Linus Pauling Institute]].<ref>{{cite web |url=http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC/index.html#lpi_recommend|title=Linus Pauling Institute Recommendations |accessdate=2007-04-11 |last=Higdon |first=Jane |authorlink= |coauthors= |date= |year= |month= |format= |work= |publisher=Oregon State University |pages= |language= |archiveurl= |archivedate= |quote= }}</ref>
*500 milligrams per 12 hours: Professor [[Roc Ordman]], from research into biological [[Radical (chemistry)|free radicals]].<ref>{{cite web |url=http://www.beloit.edu/~nutritio/vitCdose.htm |title=The Scientific Basis Of The Vitamin C Dosage Of Nutrition Investigator |accessdate=2007-02-22 |author=Roc Ordman |publisher=Beloit College }}</ref>
*3,000 milligrams per day ''(or up to 300,000 mg during illness)'': the [[Vitamin C Foundation]].<ref>{{cite web | url=http://www.vitamincfoundation.org/vitcrda.htm | title=Vitamin C Foundation's RDA | accessdate=2007-02-12}}</ref>
*6,000–12,000 milligrams per day: [[Thomas E. Levy]], Colorado Integrative Medical Centre.<ref>{{cite book |last=Levy |first=Thomas E. |authorlink=Thomas E. Levy |coauthors= |title=Vitamin C Infectious Diseases, & Toxins |year=2002 |publisher=Xlibris |location= |isbn=1401069630}} Chapter 5 - Vitamin C optidosing. </ref>
*6,000–18,000 milligrams per day: [[Linus Pauling]]'s personal use.<ref name="Pauling book">{{cite book |first=Linus |last=Pauling |authorlink= Linus Pauling|title=How to Live Longer and Feel Better |year=1986 |publisher=W. H. Freeman and Company |isbn=0-380-70289-4 }}</ref>
== Vitamin C high dose arguments==
{{main|Vitamin C megadosage|Megavitamin therapy|Orthomolecular medicine}}
There is a strong advocacy movement for large doses of vitamin C based on some [[in vitro]] and [[retrospective]] studies <ref>{{cite journal|author=Douglas RM, Hemilä H|date=2005|title= Vitamin C for Preventing and Treating the Common Cold|journal=PLoS Medicine|volume= 2|issue=6|pages=e168|doi=10.1371/journal.pmed.0020168}}</ref>, though large, randomized clinical trials are still lacking. Many pro-vitamin C organizations promote usage levels well beyond the current [[Dietary Reference Intake]]. The movement is led by scientists and doctors such as Robert Cathcart, [[Ewan Cameron (Vitamin C)|Ewan Cameron]], [[Steve Hickey]], [[Irwin Stone]] and the twice [[Nobel Prize]] laureate [[Linus Pauling]] and Dr [[Matthias Rath]]. Pauling's 1986 book ''How to Live Longer and Feel Better'' was a bestseller and advocated taking many grams per day orally. There is some scientific literature critical of governmental agency dose recommendations.<ref name="PR Newswire"/><ref>{{cite journal |author = Forman, Robert |year=1981 |title=Medical Resistance To Innovation |journal=Medical Hypotheses |volume=7 |issue=8 |pages=1009–1017 |url=http://www.seanet.com/~alexs/ascorbate/198x/forman-r-med_hypotheses-1981-v7-n8-p1009.htm |accessdate=2007-02-23 | doi = 10.1016/0306-9877(81)90096-7 <!--Retrieved from CrossRef by DOI bot-->}}</ref> The [[biological halflife]] for vitamin C is fairly short, about 30 minutes in blood plasma, a fact which high dose advocates say that mainstream researchers have failed to take into account. Researchers at the [[National Institutes of Health]] decided upon the current RDA based upon tests conducted 12 hours (24 half lives) after consumption. Mainstream medicine remains skeptical of these claims.
=== Genetic rationales for high doses===
Four gene products are necessary to manufacture vitamin C from glucose. The loss of activity of the gene for the last step, [[L-gulonolactone oxidase|Pseudogene ΨGULO]] (GLO) the terminal enzyme responsible for manufacture of vitamin C, has occurred separately in the history of several species. The loss of this enzyme activity is responsible of inability of [[guinea pig]]s to synthesize vitamin C enzymatically, but this event happened independently of the loss in the [[haplorrhini]] suborder of primates, including humans. The remains of this non-functional gene with many mutations, is however still present in the genome of the guinea pigs and in primates, including humans.<ref> J Biol. Chem. 1992 PMID 1400507</ref><ref> Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis. Biochim Biophys Acta. 1999 PMID 10572964</ref> GLO activity has also been lost in all major families of bats, regardless of diet.<ref> A trace of GLO was detected in only 1 of 34 bat species tested, across the range of 6 families of bats tested: See Jenness, R., E. Birney, and K. Ayaz. 1980. Variation of L-gulonolactone oxidase activity in placental mammals. Comparative Biochemistry and Physiology 67B:195-204. Earlier reports of only fruit bats being deficient were based on smaller samples. </ref> In addition, the function of GLO appears to have been lost several times, and possibly re-acquired, in several lines of [[passerine]] birds, where ability to make vitamin C varies from species to species. <ref> Can passerines synthesize vitamin C? Carlos Martinez del Rio. The Auk, July, 1997. [http://findarticles.com/p/articles/mi_qa3793/is_199707/ai_n8765385] </ref>
Loss of GLO activity in the [[primate]] order supposedly occurred about 63 million years ago, at about the time it split into the suborders [[haplorrhini]] (which lost the enzyme activity) and the more primitive [[strepsirrhini]] (which retained it). The haplorrhini ("simple nosed") primates, which cannot make vitamin C enzymatically, include the tarsiers and the simians (apes, monkeys and humans). The suborder strepsirrhini (bent or wet-nosed [[prosimians]]) which are still able to make vitamin C enzymatically, include [[loris]]es, [[galago]]s, [[potto]]s, and to some extent, [[lemur]]s. <ref> Am J Phys Anthropol. 1987 May;73(1):65-70. Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of Tarsius. Pollock JI, Mullin RJ. PMID 3113259 </ref>
Stone<ref>{{cite book |first=Irwin |last= Stone |title=The Healing Factor: Vitamin C Against Disease |year=1972 |publisher=Grosset and Dunlap |url=http://www.vitamincfoundation.org/stone/ |isbn=0-448-11693-6 }}</ref> and Pauling<ref name="paulingevolution">{{cite journal |title=Evolution and the need for ascorbic acid |journal=Proc Natl Acad Sci U S A |volume=67 |issue=4 |pages=1643–8 |first=Linus |last=Pauling |authorlink= Linus Pauling |pmid=5275366 |doi=10.1073/pnas.67.4.1643 |year=1970 }}</ref> calculated, based on the diet of our primate cousins<ref name="Primates">{{cite journal |author=Milton K |title=Micronutrient intakes of wild primates: are humans different? |journal=Comp Biochem Physiol A Mol Integr Physiol |volume=136 |issue=1 |pages=47–59 |year=2003 |pmid=14527629| url=http://nature.berkeley.edu/miltonlab/pdfs/kmilton_micronutrient.pdf | doi = 10.1016/S1095-6433(03)00084-9 <!--Retrieved from CrossRef by DOI bot-->}}</ref> (similar to what our [[common descent|common descendants]] are likely to have consumed when the gene mutated), that the optimum daily requirement of vitamin C is around 2,300 milligrams for a human requiring 2,500 [[calorie|kcal]] a day.
The established RDA has been criticized by Pauling to be one that will prevent [[acute (medical)|acute]] [[scurvy]], and is not necessarily the dosage for optimal health.<ref name="Pauling book" />
== Therapeutic uses ==
{{main|Vitamin C megadosage|Megavitamin therapy|Orthomolecular medicine}}
Since its discovery vitamin C has been considered by some enthusiastic proponents a "[[panacea (medicine)|universal panacea]]", although this led to suspicions by others of it being over-hyped.<ref>{{cite web |url=http://ethesis.helsinki.fi/julkaisut/laa/kansa/vk/hemila/dovitami.pdf |title=Do vitamins C and E affect respiratory infections? |accessdate=2007-02-21 |date=January 2006 |author=Hemilä, Harri |publisher=[[University of Helsinki]] | format = PDF}}</ref> Other proponents of high dose vitamin C consider that if it is given "in the right form, with the proper technique, in frequent enough doses, in high enough doses, along with certain additional agents and for a long enough period of time,"<ref>{{cite book | last = Levy | first= Thomas E. | authorlink = Thomas E. Levy | title = Curing the Incurable: Vitamin C, Infectious Diseases, and Toxins | edition = | publisher = Livon Books | year = 2002 | id = ISBN 1-4010-6963-0 | pages = p. 36}}</ref> it can prevent and, in many cases, cure, a wide range of common and/or lethal diseases, notably the [[common cold]] and [[heart disease]],<ref>Rath MW, Pauling LC. {{US patent|5278189}} Prevention and treatment of occlusive cardiovascular disease with ascorbate and substances that inhibit the binding of lipoprotein(a). USPTO. 11 Jan 1994.</ref> although the NIH considers there to be "fair scientific evidence against this use."<ref>{{cite web | title = Vitamin C (Ascorbic acid) | work = MedLine Plus | publisher = National Institute of Health | date = [[2006-08-01]] | url = http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-vitaminc.html | accessdate = 2007-08-03 }}</ref> Some proponents issued controversial statements involving it being a cure for [[AIDS]],<ref>{{cite web |url=http://allafrica.com/stories/200605220885.html |title=Nigeria: Vitamin C Can Suppress HIV/Aids Virus |accessdate=2006-06-16 |date=[[2006-05-22]] |author= |publisher=allAfrica.com }}</ref> [[H5N1|bird flu]], and [[SARS]].<ref>{{cite journal |author=Hemilä H |title=Vitamin C and SARS coronavirus |journal=J Antimicrob Chemother |volume=52 |issue=6 |pages=1049–50 |year=2003 |pmid=14613951 |doi= 10.1093/jac/dkh002}}</ref><ref>{{cite news | url = http://www.guardian.co.uk/aids/story/0,7369,1483821,00.html |title=Discredited doctor's 'cure' for Aids ignites life-and-death struggle in South Africa | accessdate=2007-02-21 |date=[[2005-05-14]] |author= Boseley, Sarah | publisher = [[The Guardian]] }}</ref><ref>{{cite web |url=http://www4.dr-rath-foundation.org/THE_FOUNDATION/openletter_20060407.htm |title=Open letter from Dr. Matthias Rath MD to German Chancellor Merkel |accessdate=2007-02-21 |date=2005 |author=Rath, Matthias |publisher=Dr. Rath Health Foundation }}</ref>
Probably the most controversial issue, the putative role of ascorbate in the management of AIDS, is still unresolved, more than 16 years after a study published in the [[Proceedings of National Academy of Sciences]] (USA) showing that non toxic doses of ascorbate suppress [[HIV]] replication ''in vitro''.<ref>{{cite journal |author=Harakeh S, Jariwalla R, Pauling L |title=Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells |journal=Proc Natl Acad Sci U S A |volume=87 |issue=18 |pages=7245–9 |year=1990 |pmid=1698293 | doi = 10.1073/pnas.87.18.7245 <!--Retrieved from CrossRef by DOI bot-->}}</ref> Other studies expanded on those results, but still, no large scale trials have yet been conducted.<ref>{{cite journal |author=Harakeh S, Jariwalla R |title=Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells |journal=Am J Clin Nutr |volume=54 |issue=6 Suppl |pages=1231S–1235S |year=1991 |pmid=1720598}}</ref><ref>{{cite journal |author=Harakeh S, Jariwalla R |title=NF-kappa B-independent suppression of HIV expression by ascorbic acid |journal=AIDS Res Hum Retroviruses |volume=13 |issue=3 |pages=235–9 |year=1997 |pmid=9115810}}</ref><ref>{{cite journal |author=Harakeh S, Jariwalla R |title=Ascorbate effect on cytokine stimulation of HIV production |journal=Nutrition |volume=11 |issue=5 Suppl |pages=684–7 |year= |pmid=8748252}}</ref>
In an animal model of lead intoxication, vitamin C demonstrated "protective effects" on lead-induced nerve and muscle abnormalities<ref name="pmid12818354">{{cite journal |author=Hasan MY, Alshuaib WB, Singh S, Fahim MA |title=Effects of ascorbic acid on lead induced alterations of synaptic transmission and contractile features in murine dorsiflexor muscle |journal=Life Sci. |volume=73 |issue=8 |pages=1017–25 |year=2003 |pmid=12818354 | doi = 10.1016/S0024-3205(03)00374-6 <!--Retrieved from CrossRef by DOI bot-->}}</ref> In smokers, blood lead levels declined by an average of 81% when supplemented with 1000 mg of vitamin C, while 200 mg were ineffective, suggesting that vitamin C [[Dietary supplement|supplement]]s may be an "economical and convenient" approach to reduce lead levels in the blood.<ref>{{cite journal |author=Dawson E, Evans D, Harris W, Teter M, McGanity W |title=The effect of ascorbic acid supplementation on the blood lead levels of smokers |journal=J Am Coll Nutr |volume=18 |issue=2 |pages=166–70 |year=1999 |pmid=10204833}}</ref> The [[Journal of the American Medical Association]] published a study which concluded, based on an analysis of blood lead levels in the subjects of the Third ''National Health and Nutrition Examination Survey'', that the independent, inverse relationship between lead levels and vitamin C in the blood, if causal, would "have public health implications for control of lead toxicity".<ref name="pmid10386552">{{cite journal |author=Simon JA, Hudes ES |title=Relationship of ascorbic acid to blood lead levels |journal=JAMA |volume=281 |issue=24 |pages=2289–93 |year=1999 |pmid=10386552 | doi = 10.1001/jama.281.24.2289 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
Vitamin C has limited popularity as a treatment for [[autism spectrum]] symptoms. A 1993 study of 18 children with ASD found some symptoms reduced after treatment with vitamin C,<ref name="pmid8255984">{{cite journal |author=Dolske MC, Spollen J, McKay S, Lancashire E, Tolbert L |title=A preliminary trial of ascorbic acid as supplemental therapy for autism |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry |volume=17 |issue=5 |pages=765–74 |year=1993 |pmid=8255984 | doi = 10.1016/0278-5846(93)90058-Z <!--Retrieved from CrossRef by DOI bot-->}}</ref> but these results have not been replicated.<ref>{{cite journal |journal= Ment Retard Dev Disabil Res Rev |year= 2005 |volume= 11 |issue= 2 |pages= 131–42 |title= Novel treatments for autistic spectrum disorders |author= Levy SE, Hyman SL |doi= 10.1002/mrdd.20062 |pmid= 15977319}}</ref> Small clinical trials have found that vitamin C might improve the [[sperm count]], sperm motility, and sperm morphology in infertile men<ref>{{cite journal |author=Akmal M, Qadri J, Al-Waili N, Thangal S, Haq A, Saloom K |title=Improvement in human semen quality after oral supplementation of vitamin C |journal=J Med Food |volume=9 |issue=3 |pages=440–2 |year=2006 |pmid=17004914 | doi = 10.1089/jmf.2006.9.440 <!--Retrieved from CrossRef by DOI bot-->}}</ref>, or improve immune function related to the prevention and treatment of [[Senescence-associated diseases|age-associated diseases]].<ref>{{cite journal |author=de la Fuente M, Ferrández M, Burgos M, Soler A, Prieto A, Miquel J |title=Immune function in aged women is improved by ingestion of vitamins C and E |journal=Can J Physiol Pharmacol |volume=76 |issue=4 |pages=373–80 |year=1998 |pmid=9795745 |doi=10.1139/cjpp-76-4-373}}</ref> However, to date, no large clinical trials have verified these findings.
A preliminary study published in the Annals of Surgery found that the early administration of antioxidant supplementation using α-tocopherol and ascorbic acid reduces the incidence of organ failure and shortens ICU length of stay in this cohort of critically ill surgical patients.<ref>{{cite journal |author=Nathens A, Neff M, Jurkovich G, Klotz P, Farver K, Ruzinski J, Radella F, Garcia I, Maier R |title=Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients |journal=Ann Surg |volume=236 |issue=6 |pages=814–22 |year=2002 |pmid=12454520 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1422648 | doi = 10.1097/00000658-200212000-00014 <!--Retrieved from CrossRef by DOI bot-->}}</ref> More research on this topic is pending.
Dehydroascorbic acid, the main form of oxidized Vitamin C in the body, was shown to reduce neurological deficits and mortality following [[stroke]], due to its ability to cross the blood-brain barrier, while "the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood-brain barrier".<ref name="ascorBBB">
{{cite journal |author=Huang J, Agus DB, Winfree CJ, Kiss S, Mack WJ, McTaggart RA, Choudhri TF, Kim LJ, Mocco J, Pinsky DJ, Fox WD, Israel RJ, Boyd TA, Golde DW, Connolly ES Jr. |title=Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke |doi= 10.1073/pnas.171325998 |journal=Proceedings of the National Academy of Sciences |volume=98 |issue=20 |pages=11720–11724 |year=2001 |pmid=11573006}}</ref> In this study published by the [[Proceedings of the National Academy of Sciences]] in 2001, the authors concluded that such "a pharmacological strategy to increase cerebral levels of ascorbate in stroke has tremendous potential to represent the timely translation of basic research into a relevant therapy for thromboembolic stroke in humans". No such "relevant therapies" are available yet and no clinical trials have been planned.
In January 2007 the US [[Food and Drug Administration]] approved a Phase I toxicity trial to determine the safe dosage of intravenous vitamin C as a possible cancer treatment for "patients who have exhausted all other conventional treatment options."<ref>{{cite web |url=http://www.physorg.com/news87833644.html |title=FDA OKs vitamin C trial for cancer |accessdate=2007-04-06 |last= |first= |authorlink= |coauthors= |date=January 12, 2007 |year= |month= |format= |work= |publisher=[[Physorg.com]] |pages= |language= |archiveurl= |archivedate= |quote=Federal approval of a clinical trial on intravenous vitamin C as a cancer treatment lends credence to alternative cancer care, U.S. researchers said.}}</ref> Additional studies over several years would be needed to demonstrate whether it is effective.<ref>{{cite web |url=http://clinicaltrials.gov/ct/show/NCT00441207?order=1 |title=Study of High-Dose Intravenous (IV) Vitamin C Treatment in Patients With Solid Tumors |accessdate=2007-08-02 |last= |first= |authorlink= |coauthors= |date= |year= |month= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=The primary purpose of this study is to evaluate the safety and tolerability of vitamin C (ascorbic acid) given by injection into the vein.
The second and third purpose of conducting this study is to observe any evidence of tumor response to the vitamin C and compare the level of fatigue (weakness), pain control, ability to do things, and quality of life, before and after vitamin C is given. (Phase I)|}}</ref>
In February 2007, an uncontrolled study of 39 terminal cancer patients showed that, on subjective questionnaires, patients reported an improvement in health, cancer symptoms, and daily function after administration of high-dose intravenous vitamin C.<ref name="pmid17297243">{{cite journal |author=Yeom CH, Jung GC, Song KJ |title=Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration |journal=J. Korean Med. Sci. |volume=22 |issue=1 |pages=7–11 |year=2007 |pmid=17297243 |doi= }}</ref> The authors concluded that "''Although there is still controversy regarding anticancer effects of vitamin C, the use of vitamin C is considered a safe and effective therapy to improve the quality of life of terminal cancer patients''".
Vitamin C has been shown to lower IOP in glaucoma patients when taken in massive amounts according to the September 2007 issue of GLEAMS.
== Testing for ascorbate levels in the body ==
Simple tests use [[dichlorphenolindophenol|DCPIP]] to measure the levels of vitamin C in the [[urine]] and in [[serum]] or [[blood plasma]]. However these reflect recent dietary intake rather than the level of vitamin C in body stores.<ref name="UKFSA Risk" /> Reverse phase [[high performance liquid chromatography]] is used for determining the storage levels of vitamin C within [[lymphocyte]]s and [[Tissue (biology)|tissue]].
It has been observed that while serum or blood plasma levels follow the [[circadian rhythm]] or short term dietary changes, those within tissues themselves are more stable and give a better view of the availability of ascorbate within the organism. However, very few hospital laboratories are adequately equipped and trained to carry out such detailed analyses, and require samples to be analyzed in specialized laboratories.<ref>{{cite journal | author = Emadi-Konjin P, Verjee Z, Levin A, Adeli K | title = Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC).|url=http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TDD-4FMHSY9-2-1&_cdi=5196&_user=308069&_orig=search&_coverDate=05%2F31%2F2005&_sk=999619994&view=c&wchp=dGLzVzz-zSkWW&md5=05a80321d3767c0cdfd386ef7121a781&ie=/sdarticle.pdf
|journal = Clinical Biochemistry | volume = 38 | issue = 5 | pages = 450–6 | year = 2005 |pmid=15820776 |doi = 10.1016/j.clinbiochem.2005.01.018 }}</ref><ref>{{cite journal | author= Yamada H, Yamada K, Waki M, Umegaki K. | title= Lymphocyte and Plasma Vitamin C Levels in Type 2 Diabetic Patients With and Without Diabetes Complications | journal= Diabetes Care | year=2004 | volume=27 | issue = | pages=2491–2 | url= http://care.diabetesjournals.org/cgi/reprint/27/10/2491.pdf | format=PDF |pmid=15451922 | doi = 10.2337/diacare.27.10.2491 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
== Adverse effects ==
=== Common side-effects ===
Relatively large doses of vitamin C may cause [[indigestion]], particularly when taken on an empty stomach.
When taken in large doses, vitamin C causes [[diarrhea]] in healthy subjects. In one trial, doses up to 6 grams of ascorbic acid were given to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. With the higher doses, toxic manifestations were observed in five adults and four infants. The signs and symptoms in adults were nausea, vomiting, diarrhea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes.<ref>{{cite web |url=http://www.inchem.org/documents/jecfa/jecmono/v05je20.htm |title=Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents |accessdate=2007-04-13 |date=4 July 1973 |author= |publisher=World Health Organization }}</ref> On the other hand, Cathcart has demonstrated that sick patients, with influenza and cancer for example, do not suffer any adverse effects whatsoever until the dosage is raised to fairly high levels such as 100 grams or higher.<ref>{{cite journal |last=Cathcart |first=Robert F. III |title=Vitamin C: the nontoxic, nonrate-limited, antioxidant free radical scavenger |journal=Medical Hypotheses |volume=18 |issue=1 |year=1985 |month=September |doi=10.1016/0306-9877(85)90121-5 | pages = 61}}</ref>
=== Possible side-effects ===
As vitamin C enhances iron absorption<ref name="pmid12450906">{{cite journal | author = Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ | title = Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort | journal = Am. J. Clin. Nutr. | volume = 76 | issue = 6 | pages = 1375–84 | year = 2002 | pmid = 12450906 | url = http://www.ajcn.org/cgi/reprint/76/6/1375.pdf}}</ref>, [[iron poisoning]] can become an issue to people with rare [[iron overload disorder]]s, such as [[haemochromatosis]]. A genetic condition that results in inadequate levels of the enzyme [[glucose-6-phosphate dehydrogenase]] (G6PD), can cause sufferers to develop [[hemolytic anemia]] after ingesting specific oxidizing substances, such as very large dosages of vitamin C.<ref name="pmid11124756">{{cite journal | author = Cook JD, Reddy MB | title = Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet | journal = Am. J. Clin. Nutr. | volume = 73 | issue = 1 | pages = 93–8 | year = 2001 | pmid = 11124756 | url=http://www.ajcn.org/cgi/reprint/73/1/93.pdf}}</ref>
There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which is based on little science.<ref name=BattlingQuackery>{{cite journal |author=Goodwin JS, Tangum MR |title=Battling quackery: attitudes about micronutrient supplements in American academic medicine |journal=Arch. Intern. Med. |volume=158 |issue=20 |pages=2187–91 |year=1998 |month=November |pmid=9818798 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=9818798}}</ref>
Although some individual recent studies have found a relationship<ref name=pmid15987848>{{cite journal | author = Massey LK, Liebman M, Kynast-Gales SA | title = Ascorbate increases human oxaluria and kidney stone risk | journal = J. Nutr. | volume = 135 | issue = 7 | pages = 1673–7 | year = 2005 | pmid = 15987848 | url=http://jn.nutrition.org/cgi/reprint/135/7/1673.pdf }}</ref> there is no clear relationship between excess [[ascorbic acid]] intake and [[kidney stone]] formation. <ref name=VCreview2003>{{cite journal | author = Naidu KA | title = Vitamin C in human health and disease is still a mystery? An overview. | journal = J. Nutr. | volume = 2 | year = 2003 | pages = 7| url=http://www.nutritionj.com/content/pdf/1475-2891-2-7.pdf| pmid = 14498993 | doi = 10.1186/1475-2891-2-7 | issue = 7}}</ref>
In a study conducted on rats, during the first month of pregnancy, high doses of vitamin C may suppress the production of [[progesterone]] from the [[corpus luteum]].<ref name="pmid4467736">{{cite journal | author = Ovcharov R, Todorov S | title = [The effect of vitamin C on the estrus cycle and embryogenesis of rats] | language = Bulgarian | journal = Akusherstvo i ginekologii͡a | volume = 13 | issue = 3 | pages = 191–5 | year = 1974 | pmid = 4467736 | doi = }}</ref> Progesterone, necessary for the maintenance of a pregnancy, is produced by the corpus luteum for the first few weeks, until the placenta is developed enough to produce its own source. By blocking this function of the corpus luteum, high doses of vitamin C (1000+ mg) are theorized to induce an early miscarriage.
In a group of spontaneously aborting women at the end of the first trimester, the mean values of vitamin C were significantly higher in the aborting group. However, the authors do state: 'This could not be interpreted as an evidence of causal association.'<ref name="pmid988001">{{cite journal | author = Vobecky JS, Vobecky J, Shapcott D, Cloutier D, Lafond R, Blanchard R | title = Vitamins C and E in spontaneous abortion | journal = International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition | volume = 46 | issue = 3 | pages = 291–6 | year = 1976 | pmid = 988001 | doi = }}</ref>
However, in a previous study of 79 women with threatened, previous spontaneous, or habitual abortion, Javert and Stander (1943) had 91% success with 33 patients who received vitamin C together with bioflavinoids and vitamin K (only three abortions), whereas all of the 46 patients who did not receive the vitamins aborted. <ref>{{cite journal | author = Javert CT, Stander HJ | title = Plasma Vitamin C and Prothrombin Concentration in Pregnancy and in Threatened, Spontaneous, and Habitual Abortion | journal = Surgery, Gynecology, and Obstetrics | volume = 76 | issue = | pages = 115–122 | year = 1943 | pmid = | doi = }}</ref>
=== Chance of overdose ===
As discussed previously, vitamin C exhibits remarkably low toxicity. The [[LD50|LD<sub>50</sub>]] (the dose that will kill 50% of a population) in rats is generally accepted to be 11.9 grams per kilogram of body weight when taken orally.<ref name="Oxford">{{cite web |url=http://physchem.ox.ac.uk/MSDS/AS/ascorbic_acid.html |title=Safety (MSDS) data for ascorbic acid |accessdate= 2007-02-21 |date= [[2005-10-09]] | publisher= [[Oxford University]] }}</ref> The LD<sub>50</sub> in humans remains unknown, owing to [[medical ethics]] that preclude experiments which would put patients at risk of harm. However, as with all substances tested in this way, the LD<sub>50</sub> is taken as a guide to its toxicity in humans and no data to contradict this has been found.
Linus Pauling claims that there is no lethal dose of vitamin C.{{Fact|date=June 2008}}
== Natural and artificial dietary sources ==
[[Image:Rosa canina hips.jpg|right|thumb|[[Rose hips]] are a particularly rich source of vitamin C]]
The richest natural sources are fruits and vegetables, and of those, the [[camu camu]] fruit and the [[Kakadu plum]] contain the highest concentration of the vitamin. It is also present in some cuts of meat, especially liver. Vitamin C is the most widely taken [[nutritional supplement]] and is available in a variety of forms, including tablets, drink mixes, crystals in capsules or naked crystals.
Vitamin C is absorbed by the intestines using a sodium-ion dependent channel. It is transported through the intestine via both glucose-sensitive and glucose-insensitive mechanisms. The presence of large quantities of sugar either in the intestines or in the blood can slow absorption.<ref>{{cite journal |author=Wilson JX |title=Regulation of vitamin C transport |journal=Annu. Rev. Nutr. |volume=25 |issue= |pages=105–25 |year=2005 |pmid=16011461| doi = 10.1146/annurev.nutr.25.050304.092647 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
=== Plant sources ===
While plants are generally a good source of vitamin C, the amount in foods of plant origin depends on: the precise variety of the plant, the soil condition, the climate in which it grew, the length of time since it was picked, the storage conditions, and the method of preparation.<ref>{{cite web |url=http://www.uk.foedevarestyrelsen.dk/Nutrition/Vitamin_mineral_content_is_stable/forside.htm |title=The vitamin and mineral content is stable |accessdate=2007-03-07 |publisher=Danish Veterinary and Food Administration }}</ref>
The following table is approximate and shows the relative abundance in different raw plant sources.<ref>{{cite web |url=http://www.nal.usda.gov/fnic/foodcomp/search/ |title=National Nutrient Database |accessdate=2007-03-07 |publisher=Nutrient Data Laboratory of the US Agricultural Research Service }}</ref><ref>{{cite web |url=http://www.healthyeatingclub.com/info/books-phds/books/foodfacts/html/data/data4i.html |title=Vitamin C Food Data Chart |accessdate=2007-03-07 |publisher=Healthy Eating Club }}</ref><ref>{{cite web |url=http://www.naturalhub.com/natural_food_guide_fruit_vitamin_c.htm |title=Natural food-Fruit Vitamin C Content |accessdate=2007-03-07 |date= |author= |publisher=The Natural Food Hub }}</ref> As some plants were analyzed fresh while others were dried (thus, artifactually increasing concentration of individual constituents like vitamin C), the data are subject to potential variation and difficulties for comparison. The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources:
<div style="float:left; padding: 1em;">
{| class="wikitable" border="1" cellpadding="2"
!Plant source
!Amount<br> (mg / 100g)
|-
|[[Kakadu plum]] || 3100
|-
|[[Camu Camu]] || 2800
|-
|[[Rose hip]] || 2000
|-
|[[Acerola]] || 1600
|-
|[[Seabuckthorn]] || 695
|-
|[[Jujube]] || 500
|-
|[[Baobab]] || 400
|-
|[[Blackcurrant]] || 200
|-
|[[Capsicum|Red pepper]] || 190
|-
|[[Parsley]] || 130
|-
|[[Guava]] || 100
|-
|[[Kiwifruit]] || 90
|-
|[[Broccoli]] || 90
|-
|[[Loganberry]] || 80
|-
|[[Redcurrant]] || 80
|-
|[[Brussels sprout]]s ||80
|-
|[[Wolfberry]] (Goji) || 73 ^
|-
|[[Lychee]] || 70
|-
|[[Cloudberry]] || 60
|-
|[[Elderberry]] || 60
|-
|[[Persimmon]] || 60
|}
^ average of 3 sources; dried
</div>
<div style="float:left; padding: 1em;">
{| class="wikitable" border="1" cellpadding="2"
!Plant source
!Amount<br> (mg / 100g)
|-
|[[Papaya]] || 60
|-
|[[Strawberry]] || 60
|-
|[[Orange (fruit)|Orange]] || 50
|-
|[[Lemon]] || 40
|-
|[[Melon]], cantaloupe || 40
|-
|[[Cauliflower]] || 40
|-
|[[Garlic]] || 31
|-
|[[Grapefruit]] || 30
|-
|[[Raspberry]] || 30
|-
|[[Tangerine]] || 30
|-
|[[Mandarin orange]] || 30
|-
|[[Passion fruit]] || 30
|-
|[[Spinach]] || 30
|-
|[[Cabbage]] raw green || 30
|-
|[[Lime (fruit)|Lime]] || 30
|-
|[[Mango]] || 28
|-
|[[Potato]] || 20
|-
|[[Melon]], honeydew || 20
|-
|[[Cranberry]] || 13
|-
|[[Tomato]] || 10
|-
|[[Blueberry]] || 10
|-
|[[Pineapple]] || 10
|}
</div>
<div clear="both" style="float:left; padding: 1em;">
{| class="wikitable" border="1" cellpadding="2"
!Plant source
!Amount<br> (mg / 100g)
|-
|[[Pawpaw]] || 10
|-
|[[Grape]] || 10
|-
|[[Apricot]] || 10
|-
|[[Plum]] || 10
|-
|[[Watermelon]] || 10
|-
|[[Banana]] || 9
|-
|[[Carrot]] || 9
|-
|[[Avocado]] || 8
|-
|[[Crabapple]] || 8
|-
|[[Cherry]] || 7
|-
|[[Peach]] || 7
|-
|[[Apple]] || 6
|-
|[[Blackberry]] || 6
|-
|[[Beetroot]] || 5
|-
|[[Pear]] || 4
|-
|[[Lettuce]] || 4
|-
|[[Cucumber]] || 3
|-
|[[Eggplant]] || 2
|-
|[[Fig]] || 2
|-
|[[Bilberry]] || 1
|-
|[[Horned melon]] || 0.5
|-
|[[Medlar]] || 0.3
|}
</div><br clear="both" />
=== Animal sources ===
[[Image:Goat.jpg|thumb|300px|Goats, like almost all animals, make their own vitamin C. An adult goat will manufacture more than 13,000 mg of vitamin C per day in normal health and levels manyfold higher when faced with stress.]]
The overwhelming majority of species of animals and plants synthesise their own vitamin C, making some, but not all, animal products, sources of dietary vitamin C.
Vitamin C is most present in the liver and least present in the muscle. Since muscle provides the majority of meat consumed in the western human diet, animal products are not a reliable source of the vitamin. Vitamin C is present in [[Breastfeeding#Benefits|mother's milk]] and, in lower amounts, in [[Milk#Nutritional benefits|raw cow's milk]], with [[pasteurized milk]] containing only trace amounts.<ref>{{cite web |url=http://www.saanendoah.com/compare.html |title= Comparing Milk: Human, Cow, Goat & Commercial Infant Formula |accessdate=2007-02-28 |date=8 January 2007 |first=Stephanie, Ph. D | last= Clark |publisher=[[Washington State University]] }}</ref> All excess Vitamin C is disposed of through the urinary system.
The following table shows the relative abundance of vitamin C in various foods of animal origin, given in milligram of vitamin C per 100 grams of food:
<div style="float:left; padding: 1em;">
{| class="wikitable" border="1" cellpadding="2"
!Food
!Amount<br> (mg / 100g)
|-
|[[Calf]] [[liver]] (raw) || 36
|-
|[[Beef]] liver (raw) || 31
|-
|[[Oyster]]s (raw) || 30
|-
|[[Cod]] [[roe]] (fried) || 26
|-
|[[Pork]] liver (raw) || 23
|-
|[[Domestic sheep|Lamb]] [[brain]] (boiled) || 17
|-
|[[Chicken]] liver (fried) || 13
|}
</div>
<div style="float:left; padding: 1em;">
{| class="wikitable" border="1" cellpadding="2"
!Food
!Amount<br> (mg / 100g)
|-
|Lamb liver (fried) || 12
|-
|Lamb [[heart]] (roast) || 11
|-
|Lamb [[tongue]] (stewed) || 6
|-
|[[Breastfeeding|Human milk]] (fresh) || 4
|-
|Goat milk (fresh) || 2
|-
|Cow milk (fresh) || 2
|}
</div><br clear="both" />
=== Food preparation ===
Vitamin C [[chemical decomposition|chemically decomposes]] under certain conditions, many of which may occur during the cooking of food. Normally, boiling water at 100°C is not hot enough to cause any significant destruction of the nutrient, which only decomposes at 190°C,
<ref name="Oxford"/> despite popular opinion. However, [[pressure cooking]], roasting, frying and [[grilling]] food is more likely to reach the [[decomposition temperature]] of vitamin C. Longer cooking times also add to this effect, as will copper food vessels, which [[catalyse]] the decomposition.<ref name="Oxford"/>
Another cause of vitamin C being lost from food is [[leaching]], where the water-soluble vitamin dissolves into the cooking water, which is later poured away and not consumed. However, vitamin C doesn't leach in all vegetables at the same rate; research shows [[broccoli]] seems to retain more than any other.<ref name=Combs>Combs GF. The Vitamins, Fundamental Aspects in Nutrition and Health. 2nd ed. San Diego, CA: Academic Press, 2001:245–272</ref> Research has also shown that fresh-cut fruits don't lose significant nutrients when stored in the refrigerator for a few days.<ref>{{cite web |url=http://www.webmd.com/content/article/123/115022.htm |title=Fresh-Cut Fruit May Keep Its Vitamins |accessdate=2007-02-25 |date=2 June 2006 |first=Miranda |last=Hitti |publisher=WebMD }}</ref>
=== Vitamin C supplements ===
[[Image:RedoxonVitaminC.jpg|thumb|right|Vitamin C is widely available in the form of tablets and powders. The [[Redoxon]] brand, launched in 1934 by [[Hoffmann-La Roche]], was the first mass-produced synthetic vitamin C.]]
Vitamin C is the most widely taken dietary supplement.<ref> [http://www.thedietchannel.com/Vitamin-C.htm The Diet Channel] Vitamin C might be the most widely known and most popular vitamin purchased as a supplement.</ref> It is available in many forms including [[caplets]], tablets, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, and crystalline powder. Timed release versions are available, as are formulations containing [[bioflavonoids]] such as quercetin, hesperidin and rutin. Tablet and capsule sizes range from 25 mg to 1500 mg. Vitamin C (as ascorbic acid) crystals are typically available in bottles containing 300 g to 1 kg of powder (a teaspoon of vitamin C crystals equals 5,000 mg).
=== Artificial modes of synthesis ===
Vitamin C is produced from [[glucose]] by two main routes. The [[Tadeusz Reichstein|Reichstein process]], developed in the 1930s, uses a single pre-fermentation followed by a purely chemical route. The modern two-step [[Fermentation (biochemistry)|fermentation]] process, originally developed in [[China]] in the 1960s, uses additional fermentation to replace part of the later chemical stages. Both processes yield approximately 60% vitamin C from the glucose feed.<ref>{{cite web |url=http://www.competition-commission.org.uk/rep_pub/reports/2001/fulltext/456a4.2.pdf |title=The production of vitamin C |accessdate=2007-02-20 |date=2001 |publisher=Competition Commission }}</ref>
Research is underway at the [[Scottish Crop Research Institute]] in the interest of creating a strain of yeast that can synthesise vitamin C in a single fermentation step from [[galactose]], a technology expected to reduce manufacturing costs considerably.<ref name="yeastAA" />
World production of synthesised vitamin C is currently estimated at approximately 110,000 tonnes annually.
Main producers have been [[BASF]]/[[Takeda Chemical Industries|Takeda]], [[DSM (company)|DSM]], [[Merck KGaA|Merck]] and the China Pharmaceutical Group Ltd. of the [[People's Republic of China]]. China is slowly becoming the major world supplier as its prices undercut those of the US and European manufacturers.<ref>{{cite web |url=http://www.nutraingredients.com/news/ng.asp?n=63349-dsm-vitamin-c |title=DSM makes last stand against Chinese vitamin C |accessdate=2007-02-20 |date=[[2005-10-20]] |first=Dominique |last=Patton |publisher=nutraingredients }}</ref> By 2008 only the DSM plant in Scotland remained operational outside the strong price competition from China. <ref>[http://www.nutraingredients.com/news/ng.asp?n=86166-dsm-carbon-foot-printing-quali-c DSM vitamin plant gains green thumbs-up] Shane Starling,Decision News Media SAS , 26-Jun-2008. Accessed July 2008</ref> The world price of Vitamin C rose sharply in 2008 partly as a result of rises in basic food prices but also in anticipation of a stoppage of the two Chinese plants , situated at [[Shijiazhuang]] near [[Beijing]], as part of a general shutdown of polluting industry in China over the period of the [[2008 Summer Olympics|Olympic games]].<ref>[http://www.flex-news-food.com/pages/17441/China/Vitamin/vitamin-distruptions-production-china-maintain-firm-market.html Vitamin C: Distruptions to Production in China to Maintain Firm Market] FLEXNEWS, 30/06/2008, Accessed July 2008</ref>
== See also ==
*[[C. Alan B. Clemetson]]
*[[Evolution of Vitamin C]]
*[[Vitamin C and Common Cold]]
== References ==
{{Reflist|2}}
== Further reading ==
{{portal|Food}}{{portal|Health}}
;Journals
* {{cite journal |author=Dolske, M.C., et al. |title=A preliminary trial of ascorbic acid as supplemental therapy for autism |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry |volume=17 |issue=5 |pages=765–74 |year=1993 |pmid=8255984| doi = 10.1016/0278-5846(93)90058-Z <!--Retrieved from CrossRef by DOI bot-->}}
* {{cite journal |author=Green VA, Pituch KA, Itchon J, Choi A, O'Reilly M, Sigafoos J |title=Internet survey of treatments used by parents of children with autism |journal=Research in developmental disabilities |volume=27 |issue=1 |pages=70–84 |year=2006 |pmid=15919178 |doi=10.1016/j.ridd.2004.12.002}}
;Books
*{{cite book |last=Pauling |first=Linus |authorlink=Linus Pauling |coauthors= |title=Vitamin C and the Common Cold |year=1970 |publisher=W. H. Freeman & Company |location= |isbn=071670160X}}
*{{cite book |last=Pauling |first=Linus |authorlink=Linus Pauling |coauthors= |title=Vitamin C, the Common Cold, and the Flu'' |year=1976 |publisher=W H Freeman & Co |location= |isbn=0716703610}}
*{{cite book |last=Cameron |first=Ewan |authorlink=Ewan Cameron (Vitamin C)|Ewan Cameron |coauthors=[[Linus Pauling]], |title=Cancer and Vitamin C |year=1979|publisher=Pauling Institute of Science and Medicine|location= |isbn=0393500004}}
*{{cite book |last=Kent |first=Saul |authorlink=Saul Kent |coauthors= |title=Life Extension Revolution|year=1980 |publisher=Morrow |location= |isbn= }}
*{{cite book |last=Pearson |first=Durk |authorlink=Durk Pearson|coauthors=Sandy Shaw|title=[[Life Extension: A Practical Scientific Approach]] |year=1982 |publisher=Warner Books |location= |isbn=0446387355 }} see Part IV, Chapter 7: Vitamin C
*{{cite book |last=Pauling |first=Linus |authorlink=Linus Pauling |coauthors= |title=How to Live Longer and Feel Better|year=1986 |publisher= Oregon State University press "20th Anniversary Edition"|location= |isbn=0380702894}}
*{{cite book |last=Pelton |first=Ross |authorlink= |coauthors= |title=Mind Food and Smart Pills: How to Increase Your Intelligence and Prevent Brain Aging |year=1986 |publisher=T & R Pub |location= |isbn=0936809000 }} see Chapter 3: Vitamin C, The Champion Free Radical Scavenger
*{{cite book |last=Clemetson |first=C.A.B |authorlink= |coauthors= |title=Vitamin C |year=1989 |publisher=CRC Press |location=Boca Raton, Florida |isbn=0-8493-4841-2 }} Monograph - Volumes I, II, III.
*{{cite book |last=Levy |first=Thomas E. |authorlink=Thomas E. Levy |coauthors= |title=Vitamin C Infectious Diseases, & Toxins |year=2002 |publisher=Xlibris |location= |isbn=1401069630}}
== External links ==
* {{pauling|id=vitamins/vitaminC|title=Vitamin C|author=Jane Higdon}}
* [http://www.seanet.com/~alexs/ascorbate/ AscorbateWeb] — a collection of twentieth century medical & scientific literature on vitamin C in the treatment and prevention of human disease at seanet.com
* [http://autism.healingthresholds.com/therapy/vitamin-c Healing Thresholds — Research on Vitamin C in the treatment of autism.] at healingthresholds.com
* {{US patent|5278189}} — "Prevention and treatment of occlusive [[cardiovascular disease]] with ascorbate and substances that inhibit the binding of lipoprotein (a)", Inventors: Matthias W. Rath and Linus C. Pauling
* [http://www.eatwell.gov.uk/healthydiet/nutritionessentials/vitaminsandminerals/vitaminc/ vitamin C] at [[Food Standards Agency|United Kingdom Food Standards Agency]]
* {{cite journal |author=Naidu KA |title=Vitamin C in human health and disease is still a mystery? An overview |journal=Nutrition journal |volume=2 |issue= |pages=7 |year=2003 |pmid=14498993 |doi=10.1186/1475-2891-2-7 |url=http://www.nutritionj.com/content/2/1/7}}
* [http://www.acu-cell.com/vitc.html Vitamin C Requirements: Optimal Health Benefits vs Overdose] — a moderate dose advocacy site
* [http://www.doctoryourself.com/vitciv.html For Doctors: Preparation of Vitamin C IV's] — by Andrew W. Saul, PhD. at doctoryourself.com
* [http://www.orthomed.com/bird.htm Information regarding treatment of the Bird Flu with massive doses of ascorbate.] — by Robert Cathcart, M.D. at orthomed.com
{{Vitamin}}
[[Category:Food antioxidants]]
[[Category:Dietary antioxidants]]
[[Category:Organic acids]]
[[Category:Orthomolecular medicine]]
[[Category:Oxygen heterocycles]]
[[Category:Sugar acids]]
[[Category:Vitamins|C]]
[[Category:Coenzymes]]
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