Editing Vitamin C (section)

== History ==
Scurvy was known to [[Hippocrates]], described in book two of his ''Prorrheticorum'' and in his ''Liber de internis affectionibus'', and cited by James Lind.<ref name="Lind-1772">{{cite book | vauthors = Lind J | title = A Treatise on the Scurvy | location = London, England | publisher = G. Pearch and W. Woodfall | date= 1772 | edition = 3rd | url = https://archive.org/details/treatiseonscurvy1772lind/page/285 | page = 285 | archive-url=https://web.archive.org/web/20160101135046/https://books.google.com/books?id=T1OT3tYmh5wC&pg=PA285&lpg=PA285 | archive-date=January 1, 2016 }}</ref> Symptoms of scurvy were also described by [[Pliny the Elder]]: (i) {{cite book | vauthors = Pliny | title = Naturalis historiae | volume = 3 | chapter = 49 }}; and (ii) Strabo, in ''Geographicorum'', book 16, cited in the 1881 International Encyclopedia of Surgery.<ref name="William Wood and Co.-1881">{{cite encyclopedia | veditors = Ashhurst J | title = The International Encyclopedia of Surgery | volume = 1 | location = New York, New York | publisher = William Wood and Co. | date = 1881 | url = https://books.google.com/books?id=mDV11NpZyNgC&pg=PA278 | page = 278 | archive-url = https://web.archive.org/web/20160505051643/https://books.google.com/books?id=mDV11NpZyNgC&pg=PA278&lpg=PA278 | archive-date=May 5, 2016}}</ref>

===Scurvy at sea===
[[File:Wiki Loves Cocktails at WikiCon 2016, 2017 (1Y7A1464).jpg|thumb|left|alt=Limes, lemons and oranges identified as preventing scurvy|Limes, lemons and oranges were among foods identified early as preventing or treating scurvy on long sailing voyages.]]
In the 1497 expedition of [[Vasco da Gama]], the curative effects of citrus fruit were known.<ref name="pmid11581484">{{cite journal | vauthors = Rajakumar K | title = Infantile scurvy: a historical perspective | journal = Pediatrics | volume = 108 | issue = 4 | pages = E76 | date = October 2001 | pmid = 11581484 | doi = 10.1542/peds.108.4.e76 | url = http://pediatrics.aappublications.org/content/108/4/e76.full | archive-url = https://web.archive.org/web/20150904021206/http://pediatrics.aappublications.org/content/108/4/e76.full | archive-date=September 4, 2015 | quote = As they sailed farther up the east coast of Africa, they met local traders, who traded them fresh oranges. Within six days of eating the oranges, da Gama's crew recovered fully | citeseerx = 10.1.1.566.5857 }}</ref> In the 1500s, Portuguese sailors put in to the island of [[Saint Helena]] to avail themselves of planted vegetable gardens and wild-growing fruit trees.<ref name="Livermore-2004">{{cite journal | vauthors = Livermore H | title = Santa Helena, a forgotten Portuguese discovery | journal = Estudos Em Homenagem a Luis Antonio de Oliveira Ramos | trans-journal = Studies in Homage to Luis Antonio de Oliveira Ramos. | date = 2004 | pages = 623–631 | url = http://ler.letras.up.pt/uploads/ficheiros/4999.pdf | archive-url= https://web.archive.org/web/20110529065201/http://ler.letras.up.pt/uploads/ficheiros/4999.pdf | archive-date = May 29, 2011 | quote = On returning, Lopes' ship had left him on St Helena, where with admirable sagacity and industry he planted vegetables and nurseries with which passing ships were marvelously sustained. [...] There were 'wild groves' of oranges, lemons and other fruits that ripened all the year round, large pomegranates and figs. }}</ref> Authorities occasionally recommended plant food to prevent scurvy during long sea voyages. [[John Woodall]], the first surgeon to the British [[East India Company]], recommended the preventive and curative use of [[lemon]] juice in his 1617 book, ''The Surgeon's Mate''.<ref name="Woodall-1617">{{cite book | vauthors = Woodall J | title = The Surgion's Mate | location = London, England | publisher = Edward Griffin | date = 1617 | page = 89 | url = https://archive.org/stream/surgionsmateortr00wood#page/89/mode/1up | archive-url = https://web.archive.org/web/20160411083503/https://archive.org/stream/surgionsmateortr00wood | archive-date=April 11, 2016 | quote = Succus Limonum, or juice of Lemons ... [is] the most precious help that ever was discovered against the Scurvy[;] to be drunk at all times; ... }}</ref> In 1734, the [[Netherlands|Dutch]] writer [[Johann Bachstrom]] gave the firm opinion, "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens."<ref name="Armstrong-1858">{{cite journal | vauthors = Armstrong A |journal=British and Foreign Medico-chirurgical Review: Or, Quarterly Journal of Practical Medicine and Surgery |title=Observation on naval hygiene and scurvy, more particularly as the later appeared during the Polar voyage |volume=22 |pages=295–305 |year=1858 |url =https://books.google.com/books?id=7VJYAAAAMAAJ&pg=PA295 }}</ref><!--https://books.google.com/books?id=azXx4cbrMZMC&pg=PA74 would also work out--><ref name="Bachstrom-1734">{{cite book | vauthors = Bachstrom JF | title = Observationes circa scorbutum | trans-title = Observations on scurvy | language = Latin | location = Leiden (Lugdunum Batavorum), Netherlands | publisher = Conrad Wishof | date = 1734 | page = 16 | url = https://books.google.com/books?id=bj8_AAAAcAAJ&pg=PA16 | archive-url = https://web.archive.org/web/20160101135046/https://books.google.com/books?id=bj8_AAAAcAAJ&pg=PA16 | archive-date = January 1, 2016 | quote = ... sed ex nostra causa optime explicatur, que est absentia, carentia & abstinentia a vegetabilibus recentibus, ... ( ... but [this misfortune] is explained very well by our [supposed] cause, which is the absence of, lack of, and abstinence from fresh vegetables, ... }}</ref> Scurvy had long been a principal killer of sailors during the long sea voyages.<ref name="url_BBC_Captain_Cook_Scurvy">{{cite web |url=https://www.bbc.co.uk/history/british/empire_seapower/captaincook_scurvy_01.shtml |title=Captain Cook and the scourge of scurvy |publisher=BBC |work=British History in depth | vauthors = Lamb J |date=February 17, 2011 |url-status=live |archive-url=https://web.archive.org/web/20110221073823/http://www.bbc.co.uk/history/british/empire_seapower/captaincook_scurvy_01.shtml |archive-date=February 21, 2011 }}</ref> According to Jonathan Lamb, "In 1499, Vasco da Gama lost 116 of his crew of 170; In 1520, Magellan lost 208 out of 230;&nbsp;... all mainly to scurvy."<ref name="Lamb-2001">{{cite book | vauthors = Lamb J |title=Preserving the self in the south seas, 1680–1840 |publisher=University of Chicago Press |year=2001 |page=117 |isbn=978-0-226-46849-5 |url=https://books.google.com/books?id=hSoj1DR4ZSMC |url-status=live |archive-url=https://web.archive.org/web/20160430065803/https://books.google.com/books?id=hSoj1DR4ZSMC&pg=&dq |archive-date=April 30, 2016 }}</ref>

[[File:James Lind by Chalmers.jpg|thumb|upright|[[James Lind]], a British Royal Navy surgeon who, in 1747, identified that a quality in fruit prevented scurvy in one of the first recorded [[Scientific control#Controlled experiments|controlled experiments]]<ref name="Baron2009">{{cite journal | vauthors = Baron JH | title = Sailors' scurvy before and after James Lind--a reassessment | journal = Nutrition Reviews | volume = 67 | issue = 6 | pages = 315–32 | date = June 2009 | pmid = 19519673 | doi = 10.1111/j.1753-4887.2009.00205.x | s2cid = 20435128 }}</ref>]]

The first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the [[Royal Navy]], [[James Lind]]. 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 one of the world's first controlled experiments.<ref name="Baron2009" /> The results showed that citrus fruits prevented the disease. Lind published his work in 1753 in his ''Treatise on the Scurvy''.<ref name="lind_james">{{cite book | vauthors = Lind J |title=A treatise of the scurvy |publisher=A. Millar |location=London |year=1753 }} In the 1757 edition of his work, Lind discusses his experiment starting on {{cite web |title=A treatise of the scurvy | url = https://archive.org/stream/treatiseonscurvy00lind#page/149/mode/1up | page = 149 | archive-url = https://web.archive.org/web/20160320155753/https://archive.org/stream/treatiseonscurvy00lind | archive-date=March 20, 2016 }}</ref>

Fresh fruit was expensive to keep on board, whereas boiling it down to juice allowed easy storage, but destroyed the vitamin (especially if it was boiled in copper kettles).<ref name="Oxford" /> It was 1796 before the British navy adopted [[lemon]] juice as standard issue at sea. In 1845, ships in the West Indies were provided with [[Lime (fruit)|lime]] juice instead, and in 1860 lime juice was used throughout the Royal Navy, giving rise to the American use of the nickname [[Glossary of names for the British|"limey"]] for the British.<ref name="Baron2009" /> [[James Cook|Captain James Cook]] had previously demonstrated the advantages of carrying [[Sauerkraut|"Sour krout"]] on board by taking his crew on a 1772–75 Pacific Ocean voyage without losing any of his men to scurvy.<ref name="isbn0-14-043647-2">{{cite book |vauthors=Beaglehole JH, Cook JD, Edwards PR |title=The journals of Captain Cook |publisher=Penguin |location=Harmondsworth [Eng.] |year=1999 |isbn=978-0-14-043647-1 |url=https://archive.org/details/journalsofcaptai00jame }}</ref> For his report on his methods the British Royal Society awarded him the Copley Medal in 1776.<ref name="The Royal Society-2015">{{cite web |url=https://royalsociety.org/grants-schemes-awards/awards/copley-medal/ |title=Copley Medal, past winners |date= |website=The Royal Society |access-date=January 1, 2024 |archive-date=September 6, 2015 |archive-url=https://web.archive.org/web/20150906190948/https://royalsociety.org/grants-schemes-awards/awards/copley-medal/ |url-status=live }}</ref>

The name ''antiscorbutic'' was used in the eighteenth and nineteenth centuries for foods known to prevent scurvy. These foods included lemons, limes, oranges, sauerkraut, cabbage, [[malt]], and [[portable soup]].<ref name="isbn1-74114-200-8">{{cite book |vauthors=Reeve J, Stevens DA |title=Navy and the nation: the influence of the navy on modern Australia |publisher=Allen & Unwin Academic |year=2006 |page=74 |isbn=978-1-74114-200-6 |chapter-url=https://books.google.com/books?id=BGs6__kbqKIC&pg=PA74 |chapter=Cook's Voyages 1768–1780 }}</ref> In 1928, the Canadian Arctic anthropologist [[Vilhjalmur Stefansson]] showed that the [[Inuit]] avoided scurvy on a diet largely of raw meat. Later studies on traditional food diets of the [[Yukon]] [[First Nations in Canada|First Nations]], [[Dene]], [[Inuit]], and [[Métis#Métis people in Canada|Métis]] of Northern Canada showed that their daily intake of vitamin C averaged between 52 and 62&nbsp;mg/day.<ref name="pmid15173410">{{cite journal | vauthors = Kuhnlein HV, Receveur O, Soueida R, Egeland GM | title = Arctic indigenous peoples experience the nutrition transition with changing dietary patterns and obesity | journal = The Journal of Nutrition | volume = 134 | issue = 6 | pages = 1447–53 | date = June 2004 | pmid = 15173410 | doi = 10.1093/jn/134.6.1447| df = mdy-all | doi-access = free | title-link = doi }}</ref>

=== Discovery ===
{{Further|Vitamin#History}}

Vitamin C was discovered in 1912, isolated in 1928 and synthesized in 1933, making it the first vitamin to be synthesized.<ref name=Squires>{{cite book |vauthors=Squires VR |title=The role of food, agriculture, forestry and fisheries in human nutrition - Volume IV |date=2011 |publisher=EOLSS Publications |isbn=978-1-84826-195-2 |page=121 |url=https://books.google.com/books?id=VJWoCwAAQBAJ&pg=PA121 |access-date=September 17, 2017 |archive-date=January 11, 2023 |archive-url=https://web.archive.org/web/20230111085247/https://books.google.com/books?id=VJWoCwAAQBAJ&pg=PA121 |url-status=live }}</ref> Shortly thereafter [[Tadeus Reichstein]] succeeded in synthesizing the vitamin in bulk by what is now called the [[Reichstein process]].<ref name="pmid356548">{{cite book | vauthors = Stacey M, Manners DJ | title = Advances in carbohydrate chemistry and biochemistry | chapter = Edmund Langley Hirst | volume = 35 | pages = 1–29 | year = 1978 | pmid = 356548 | doi = 10.1016/S0065-2318(08)60217-6 | isbn = 978-0-12-007235-4 }}</ref> This made possible the inexpensive mass-production of vitamin C. In 1934, [[Hoffmann–La Roche]] bought the Reichstein process patent, trademarked synthetic vitamin C under the brand name [[Redoxon]], and began to market it as a dietary supplement.<ref name=Roche1934>{{cite web|url=http://www.trademarkia.com/redoxon-71350953.html|title=Redoxon trademark information by Hoffman-la Roche, Inc. (1934)|access-date=December 25, 2017|archive-date=November 16, 2018|archive-url=https://web.archive.org/web/20181116044212/https://www.trademarkia.com/redoxon-71350953.html|url-status=live}}</ref><ref name="Wang-2016">{{cite book | chapter-url = https://books.google.com/books?id=WgamCgAAQBAJ&pg=PA161 | chapter = Industrial fermentation of Vitamin C | vauthors = Wang W, Xu H | year = 2016 | page = 161 | title = Industrial biotechnology of vitamins, biopigments, and antioxidants | veditors = Vandamme EJ, Revuelta JI | publisher = Wiley-VCH Verlag GmbH & Co. KGaA. | isbn = 978-3-527-33734-7 }}</ref>

In 1907, a laboratory animal model which would help to identify the antiscorbutic factor was [[Serendipity|serendipitously]] discovered by the Norwegian physicians [[Axel Holst]] and [[Theodor Frølich]], who when studying shipboard [[beriberi]], fed [[guinea pig]]s their test diet of grains and flour and were surprised when scurvy resulted instead of beriberi. Unknown at that time, this species did not make its own vitamin C (being a [[caviomorph]]), whereas mice and rats do.<ref name="pmid12555613">{{cite journal | vauthors = Norum KR, Grav HJ | title = [Axel Holst and Theodor Frolich--pioneers in the combat of scurvy] | language = no | journal = Tidsskrift for den Norske Laegeforening | volume = 122 | issue = 17 | pages = 1686–7 | date = June 2002 | pmid = 12555613 }}</ref> In 1912, the [[Poland|Polish]] biochemist [[Casimir Funk]] developed the concept of [[vitamin]]s. One of these was thought to be the anti-scorbutic factor. In 1928, this was referred to as "water-soluble C", although its chemical structure had not been determined.<ref name="pmid9105273">{{cite journal | vauthors = Rosenfeld L | title = Vitamine--vitamin. The early years of discovery | journal = Clinical Chemistry | volume = 43 | issue = 4 | pages = 680–5 | date = April 1997 | doi = 10.1093/clinchem/43.4.680 | pmid = 9105273 | doi-access = free | title-link = doi }}</ref>

[[File:Albert Szent-Györgyi.jpg|thumb|right|upright|[[Albert Szent-Györgyi]], pictured here in 1948, was awarded the 1937 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Medicine]] "for his discoveries in connection with the biological combustion processes, with special reference to vitamin{{nbsp}}C and the catalysis of fumaric acid".<ref name="pmid19239412"/>|alt=Albert Szent-Györgyi was awarded the Nobel Prize in Medicine in part for his research on vitamin C]]

From 1928 to 1932, [[Albert Szent-Györgyi]] and Joseph L. Svirbely's Hungarian team, and [[Charles Glen King]]'s American team, identified the anti-scorbutic factor. Szent-Györgyi isolated hexuronic acid from animal adrenal glands, and suspected it to be the antiscorbutic factor.<ref name="pmid16744896">{{cite journal | vauthors = Svirbely JL, Szent-Györgyi A | title = The chemical nature of vitamin C | journal = The Biochemical Journal | volume = 26 | issue = 3 | pages = 865–70 | year = 1932 | pmid = 16744896 | pmc = 1260981 | doi = 10.1126/science.75.1944.357-a | bibcode = 1932Sci....75..357K }}</ref> In late 1931, Szent-Györgyi gave Svirbely the last of his adrenal-derived hexuronic acid with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this, but published the result without giving Szent-Györgyi credit for it. This led to a bitter dispute over priority.<ref name="pmid16744896" /> In 1933, [[Walter Norman Haworth]] chemically identified the vitamin as {{sm|l}}-hexuronic acid, proving this by synthesis in 1933.<ref name="pmid11963399">{{cite journal | vauthors = Juhász-Nagy S | title = [Albert Szent-Györgyi--biography of a free genius] | language = hu | journal = Orvosi Hetilap | volume = 143 | issue = 12 | pages = 611–4 | date = March 2002 | pmid = 11963399 }}</ref><ref name="pmid4589872">{{cite journal | vauthors = Kenéz J | title = [Eventful life of a scientist. 80th birthday of Nobel prize winner Albert Szent-Györgyi] | language = de | journal = Munchener Medizinische Wochenschrift | volume = 115 | issue = 51 | pages = 2324–6 | date = December 1973 | pmid = 4589872 }}</ref><ref name="pmid4612454">{{cite journal | vauthors = Szállási A | title = [2 interesting early articles by Albert Szent-Györgyi] | language = hu | journal = Orvosi Hetilap | volume = 115 | issue = 52 | pages = 3118–9 | date = December 1974 | pmid = 4612454 }}</ref><ref name="url_NLM_Profiles_Szent-Gyorgyi">{{cite web |url=http://profiles.nlm.nih.gov/WG/Views/Exhibit/narrative/szeged.html |title=The Albert Szent-Gyorgyi Papers: Szeged, 1931-1947: Vitamin C, Muscles, and WWII |work=Profiles in Science |publisher=United States National Library of Medicine |url-status=live |archive-url=https://web.archive.org/web/20090505232208/http://profiles.nlm.nih.gov/WG/Views/Exhibit/narrative/szeged.html |archive-date=May 5, 2009 }}</ref> Haworth and Szent-Györgyi proposed that L-hexuronic acid be named a-scorbic acid, and chemically {{sm|l}}-ascorbic acid, in honor of its activity against scurvy.<ref name="url_NLM_Profiles_Szent-Gyorgyi"/><ref name=Squires /> The term's etymology is from Latin, "a-" meaning away, or off from, while -scorbic is from Medieval Latin ''scorbuticus'' (pertaining to scurvy), cognate with Old Norse ''skyrbjugr'', French ''scorbut'', Dutch ''scheurbuik'' and Low German ''scharbock''.<ref name="Online Entymology Dictionary-2015">{{cite web |url=https://www.etymonline.com/word/scurvy |title=Scurvy |publisher=Online Entymology Dictionary |access-date=November 19, 2017 |archive-date=December 15, 2020 |archive-url=https://web.archive.org/web/20201215135611/https://www.etymonline.com/word/scurvy |url-status=live }}</ref> Partly for this discovery, Szent-Györgyi was awarded the 1937 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Medicine]],<ref name="pmid19239412">{{cite journal | vauthors = Zetterström R | title = Nobel Prize 1937 to Albert von Szent-Györgyi: identification of vitamin C as the anti-scorbutic factor | journal = Acta Paediatrica | volume = 98 | issue = 5 | pages = 915–19 | date = May 2009 | pmid = 19239412 | doi = 10.1111/j.1651-2227.2009.01239.x | s2cid = 11077461 }}</ref> and Haworth shared that year's [[Nobel Prize in Chemistry]].<ref name="pmid15416703">{{cite journal |vauthors=Hirst EL |title=Sir Norman Haworth |journal=Nature |volume=165 |issue=4198 |pages=587 |date=April 1950 |pmid=15416703 |doi=10.1038/165587a0 |bibcode=1950Natur.165..587H |url=}}</ref>

In 1957, J. J. Burns showed that some mammals are susceptible to scurvy as their [[liver]] does not produce the [[enzyme]] [[L-gulonolactone oxidase|{{sm|l}}-gulonolactone oxidase]], the last of the chain of four enzymes that synthesize vitamin C.<ref name="pmid13385237">{{cite journal | vauthors = Burns JJ, Evans C | title = The synthesis of L-ascorbic acid in the rat from D-glucuronolactone and L-gulonolactone | journal = The Journal of Biological Chemistry | volume = 223 | issue = 2 | pages = 897–905 | date = December 1956 | doi = 10.1016/S0021-9258(18)65088-4 | pmid = 13385237 | url = https://www.jbc.org/article/S0021-9258(18)65088-4/pdf | doi-access = free | title-link = doi | format = PDF | access-date = December 3, 2022 | archive-date = December 3, 2022 | archive-url = https://web.archive.org/web/20221203231846/https://www.jbc.org/article/S0021-9258(18)65088-4/pdf | url-status = live }}</ref><ref name="pmid13380431">{{cite journal | vauthors = Burns JJ, Moltz A, Peyser P | title = Missing step in guinea pigs required for the biosynthesis of L-ascorbic acid | journal = Science | volume = 124 | issue = 3232 | pages = 1148–9 | date = December 1956 | pmid = 13380431 | doi = 10.1126/science.124.3232.1148-a | bibcode = 1956Sci...124.1148B }}</ref> American biochemist [[Irwin Stone]] was the first to exploit vitamin C for its food preservative properties. He later developed the idea that humans possess a mutated form of the {{sm|l}}-gulonolactone oxidase coding gene.<ref name="pmid1672383">{{cite journal | vauthors = Henson DE, Block G, Levine M | title = Ascorbic acid: biologic functions and relation to cancer | journal = Journal of the National Cancer Institute | volume = 83 | issue = 8 | pages = 547–50 | date = April 1991 | pmid = 1672383 | doi = 10.1093/jnci/83.8.547 | url = https://zenodo.org/record/1234351 | access-date = March 18, 2020 | archive-date = December 25, 2020 | archive-url = https://web.archive.org/web/20201225062602/https://zenodo.org/record/1234351 | url-status = live | doi-access = free | title-link = doi }}</ref>
Stone introduced Linus Pauling to the theory that humans needed to consume vitamin C in quantities far higher than what was considered a recommended daily intake in order to optimize health.<ref name=IrwinStone>{{cite web |url=http://www.orthomolecular.org/history/index.shtml |title=Orthomolecular Medicine Hall of fame - Irwin Stone, Ph.D. | vauthors = Saul A |date= |website=Orthomolecular Organization |access-date=December 25, 2023 |archive-date=August 9, 2011 |archive-url=https://web.archive.org/web/20110809145751/http://www.orthomolecular.org/history/index.shtml |url-status=live }}</ref>

In 2008, researchers discovered that in humans and other primates the [[red blood cell]]s have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized {{sm|l}}-dehydroascorbic acid (DHA) back into ascorbic acid for reuse by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.<ref name="pmid18358815">{{cite journal | vauthors = Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N |s2cid = 18128118 |title = Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C |journal = Cell |volume = 132 |issue = 6 |pages = 1039–48 |date = March 2008 |pmid = 18358815 |doi = 10.1016/j.cell.2008.01.042| doi-access =  | title-link = doi }}</ref>

===History of large dose therapies===
{{Further|Vitamin C megadosage|Intravenous ascorbic acid}}
Vitamin C megadosage is a term describing the consumption or injection of vitamin C in doses comparable to or higher than the amounts produced by the livers of mammals which are able to synthesize vitamin C. An argument for this, although not the actual term, was described in 1970 in an article by [[Linus Pauling]]. Briefly, his position was that for optimal health, humans should be consuming at least 2,300&nbsp;mg/day to compensate for the inability to synthesize vitamin C. The recommendation also fell into the consumption range for gorillas&nbsp;— a non-synthesizing near-relative to humans.<ref name=pmid5275366>{{cite journal | vauthors = Pauling L | title = Evolution and the need for ascorbic acid | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 67 | issue = 4 | pages = 1643–8 | date = December 1970 | pmid = 5275366 | pmc = 283405 | doi = 10.1073/pnas.67.4.1643 | bibcode = 1970PNAS...67.1643P | doi-access = free | title-link = doi }}</ref> A second argument for high intake is that serum ascorbic acid concentrations increase as intake increases until it plateaus at about 190 to 200 micromoles per liter (μmol/L) once consumption exceeds 1,250 milligrams.<ref name=Mandl2009>{{cite journal | vauthors = Mandl J, Szarka A, Bánhegyi G | title = Vitamin C: update on physiology and pharmacology | journal = British Journal of Pharmacology | volume = 157 | issue = 7 | pages = 1097–110 | date = August 2009 | pmid = 19508394 | pmc = 2743829 | doi = 10.1111/j.1476-5381.2009.00282.x }}</ref> As noted, government recommendations are a range of 40 to 110&nbsp;mg/day and normal plasma is approximately 50&nbsp;μmol/L, so "normal" is about 25% of what can be achieved when oral consumption is in the proposed megadose range.

Pauling popularized the concept of high dose vitamin C as prevention and treatment of the common cold in 1970. A few years later he proposed that vitamin C would prevent cardiovascular disease, and that 10 grams/day, initially administered intravenously and thereafter orally, would cure late-stage cancer.<ref name="pmid1068480">{{cite journal | vauthors = Cameron E, Pauling L | title = Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 10 | pages = 3685–9 | date = October 1976 | pmid = 1068480 | pmc = 431183 | doi = 10.1073/pnas.73.10.3685| bibcode = 1976PNAS...73.3685C | doi-access = free | title-link = doi }}</ref> Mega-dosing with ascorbic acid has other champions, among them chemist [[Irwin Stone]]<ref name=IrwinStone/> and the controversial [[Matthias Rath]] and [[Patrick Holford]], who both have been accused of making unsubstantiated treatment claims for treating cancer and [[HIV]] infection.<ref name="Boseley-2008">{{cite web |url= https://www.theguardian.com/world/2008/sep/12/matthiasrath.aids2 |title=Fall of the vitamin doctor: Matthias Rath drops libel action | vauthors = Boseley S |date=September 12, 2008 |website=The Guardian |access-date=January 5, 2024 |archive-date=December 1, 2016 |archive-url=https://web.archive.org/web/20161201225117/https://www.theguardian.com/world/2008/sep/12/matthiasrath.aids2 |url-status=live }}</ref><ref name="Colquhoun-2007">{{cite news |url=https://www.theguardian.com/science/2007/aug/15/endarkenment |title=The age of endarkenment &#124; Science &#124; guardian.co.uk |newspaper=Guardian |date=August 15, 2007 |access-date=January 5, 2024 | vauthors = Colquhoun D |archive-date=March 6, 2023 |archive-url=https://web.archive.org/web/20230306023533/https://www.theguardian.com/science/2007/aug/15/endarkenment |url-status=live }}</ref> The idea that large amounts of intravenous ascorbic acid can be used to treat late-stage cancer or ameliorate the toxicity of chemotherapy is&nbsp;— some forty years after Pauling's seminal paper&nbsp;— still considered unproven and still in need of high quality research.<ref name="Barret-2014">{{cite web|url=https://www.quackwatch.org/01QuackeryRelatedTopics/pauling.html |title=The dark side of Linus Pauling's legacy| vauthors = Barret S |date=September 14, 2014|website=www.quackwatch.org|archive-url= https://web.archive.org/web/20180904155649/https://www.quackwatch.org/01QuackeryRelatedTopics/pauling.html |archive-date=September 4, 2018|access-date=December 18, 2018}}{{Unreliable source?|date=April 2024}}</ref><ref name=Wil2014>{{cite journal | vauthors = Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP | title = Review of high-dose intravenous vitamin C as an anticancer agent | journal = Asia-Pacific Journal of Clinical Oncology | volume = 10 | issue = 1 | pages = 22–37 | date = March 2014 | pmid = 24571058 | doi = 10.1111/ajco.12173 | s2cid = 206983069 | doi-access = free | title-link = doi }}</ref><ref name=Jacobs2015 />