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==History== The name "riboflavin" comes from "[[ribose]]" (the sugar whose [[reduction (chemistry)|reduced]] form, [[ribitol]], forms part of its structure) and "[[Flavin group|flavin]]", the ring-moiety that imparts the yellow color to the oxidized molecule (from Latin ''flavus'', "yellow").<ref name=PKIN2020B2 /> The reduced form, which occurs in metabolism along with the oxidized form, appears as orange-yellow needles or crystals.<ref name=pubchem/> The earliest reported identification, predating any concept of vitamins as essential nutrients, was by Alexander Wynter Blyth. In 1879, Blyth isolated a water-soluble component of cows' milk whey, which he named "lactochrome", that [[fluorescence|fluoresced]] yellow-green when exposed to light.<ref name="anm"/> In the early 1900s, several research laboratories were investigating constituents of foods, essential to maintain growth in rats. These constituents were initially divided into fat-soluble "vitamine" A and water-soluble "vitamine" B. (The "e" was dropped in 1920.<ref name=Rosenfeld>{{cite journal | vauthors = Rosenfeld L | title = Vitamine—vitamin. The early years of discovery | journal = Clinical Chemistry | volume = 43 | issue = 4 | pages = 680–685 | date =1997 | pmid = 9105273 | doi = 10.1093/clinchem/43.4.680 | doi-access = free }}</ref>) Vitamin B was further thought to have two components, a heat-labile substance called B<sub>1</sub> and a heat-stable substance called B<sub>2</sub>.<ref name="anm">{{cite journal | vauthors = Northrop-Clewes CA, Thurnham DI | title = The discovery and characterization of riboflavin | journal = Annals of Nutrition & Metabolism | volume = 61 | issue = 3 | pages = 224–30 | year = 2012 | pmid = 23183293 | doi = 10.1159/000343111 | s2cid = 7331172 }}</ref> Vitamin B<sub>2</sub> was tentatively identified to be the factor necessary for preventing [[pellagra]], but that was later confirmed to be due to [[Niacin (nutrient)|niacin]] (vitamin B<sub>3</sub>) deficiency. The confusion was due to the fact that riboflavin (B<sub>2</sub>) deficiency causes [[stomatitis]] symptoms similar to those seen in pellagra, but without the widespread peripheral skin lesions. For this reason, early in the history of identifying riboflavin deficiency in humans the condition was sometimes called "pellagra sine pellagra" (pellagra without pellagra).<ref>{{Cite journal | doi = 10.2307/4583104 |volume = 54 |issue = 48 |pages = 2121–31 | vauthors = Sebrell WH, Butler RE |title = Riboflavin Deficiency in Man (Ariboflavinosis) |journal = Public Health Reports |date = 1939 |jstor = 4583104}}</ref> In 1935, [[Paul Gyorgy]], in collaboration with chemist [[Richard Kuhn]] and physician T. Wagner-Jauregg, reported that rats kept on a B<sub>2</sub>-free diet were unable to gain weight.<ref>{{cite journal | vauthors = György P | title = Investigations on the vitamin B(2) complex: The differentiation of lactoflavin and the "rat antipellagra" factor | journal = The Biochemical Journal | volume = 29 | issue = 3 | pages = 741–759 | date = March 1935 | pmid = 16745720 | pmc = 1266542 | doi = 10.1042/bj0290741 }}</ref> Isolation of B<sub>2</sub> from yeast revealed the presence of a bright yellow-green fluorescent product that restored normal growth when fed to rats. The growth restored was directly proportional to the intensity of the fluorescence. This observation enabled the researchers to develop a rapid chemical bioassay in 1933, and then isolate the factor from egg white, calling it ovoflavin.<ref name=anm/> The same group then isolated the a similar preparation from whey and called it lactoflavin. In 1934, Kuhn's group identified the chemical structure of these flavins as identical, settled on "riboflavin" as a name, and were also able to synthesize the vitamin.<ref name=anm/> Circa 1937, riboflavin was also referred to as "Vitamin G".<ref>{{cite journal |vauthors=Levine H, Remington RE |title=The Vitamin G Content of Some Foods |journal=J Nutr |volume=13 |issue=5 |pages=525–42 |date=May 1937 |doi=10.1093/jn/13.5.525 |url=https://doi.org/10.1093/jn/13.5.525 |access-date=5 October 2021 |archive-date=20 March 2024 |archive-url=https://web.archive.org/web/20240320024336/https://www.sciencedirect.com/science/article/abs/pii/S0022316623128598?via%3Dihub |url-status=live }}</ref> In 1938, Richard Kuhn was awarded the [[Nobel Prize in Chemistry]] for his work on vitamins, which had included B<sub>2</sub> and B<sub>6</sub>.<ref>{{cite web|url=https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1938/index.html|title=The Nobel Prize in Chemistry 1938|access-date=5 July 2018|website=Nobelprize.org|archive-date=8 July 2018|archive-url=https://web.archive.org/web/20180708045113/https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1938/index.html|url-status=live}}</ref> In 1939, it was confirmed that riboflavin is essential for human health through a clinical trial conducted by William H. Sebrell and Roy E. Butler. Women fed a diet low in riboflavin developed stomatitis and other signs of deficiency, which were reversed when treated with synthetic riboflavin. The symptoms returned when the supplements were stopped.<ref name=anm/>
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