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==History== {{See|Vitamin#History}} In the 1920s, scientists believed folate deficiency and anemia were the same condition.<ref name="Lanska">{{cite book|year=2009 |series=Handbook of Clinical Neurology|volume=95|pages=445β476|doi=10.1016/S0072-9752(08)02130-1|isbn=978-0-444-52009-8|pmid=19892133|vauthors=Lanska DJ|chapter=Chapter 30 Historical aspects of the major neurological vitamin deficiency disorders: The water-soluble B vitamins |title=History of Neurology}}</ref> In 1931, researcher [[Lucy Wills]] made a key observation that led to the identification of folate as the nutrient required to prevent [[anemia]] during pregnancy. Wills demonstrated that anemia could be reversed with [[brewer's yeast]].<ref name=Pond/><ref>{{cite journal | vauthors = Wills L | title = Nutrition Classics. British Medical Journal 1:1059β64, 1931. Treatment of "pernicious anaemia of pregnancy" and "tropical anaemia" with special reference to yeast extract as a curative agent. By Lucy Wills | journal = Nutrition Reviews | volume = 36 | issue = 5 | pages = 149β51 | date = May 1978 | pmid = 355948 | doi = 10.1111/j.1753-4887.1978.tb03735.x }}</ref> In the late 1930s, folate was identified as the corrective substance in brewer's yeast. It was first isolated via extraction from [[spinach]] leaves by [[Herschel K. Mitchell]], [[Esmond E. Snell]], and [[Roger J. Williams]] in 1941.<ref>{{cite journal|year=1941|title=The concentration of "folic acid"|journal=J Am Chem Soc|volume=63|issue=8|page=2284|doi=10.1021/ja01853a512|vauthors=Mitchell HK, Snell EE, Williams RJ|bibcode=1941JAChS..63.2284M }}</ref> The term "folic" is from the Latin word {{lang|la|[[wikt:folium|folium]]}} (which means leaf) because it was found in dark-green leafy vegetables.<ref name=Chambers/> Historic names included ''[[L. casei|L. casei]]'' factor, vitamin B<sub>c</sub> after research done in chicks and vitamin M after research done in monkeys.<ref name=Welch1983/> Bob Stokstad isolated the pure crystalline form in 1943, and was able to determine its chemical structure while working at the Lederle Laboratories of the American Cyanamid Company.<ref name=Hoffbrand2001>{{cite journal | vauthors = Hoffbrand AV, Weir DG | title = The history of folic acid | journal = British Journal of Haematology | volume = 113 | issue = 3 | pages = 579β89 | date = June 2001 | pmid = 11380441 | doi = 10.1046/j.1365-2141.2001.02822.x | s2cid = 22925228 }}</ref> This historical research project, of obtaining folic acid in a pure crystalline form in 1945, was done by the team called the "folic acid boys", under the supervision and guidance of Director of Research Dr. [[Yellapragada Subbarow]], at the Lederle Lab, Pearl River, New York.<ref name="Paul2016">{{cite journal | vauthors = Paul C | title = Folic acid in pregnancy | journal = BJOG | volume = 123 | issue = 3 | page = 392 | date = February 2016 | pmid = 26810675 | doi = 10.1111/1471-0528.13602 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Angier RB, Boothe JH, Hutchings BL, Mowat JH, Semb J, Stokstad EL, Subbarow Y, Waller CW, Cosulich DB, Fahrenbach MJ, Hultquist ME, Kuh E, Northey EH, Seeger DR, Sickels JP, Smith JM | title = Synthesis of a Compound Identical with the L. Casei Factor Isolated from Liver | journal = Science | volume = 102 | issue = 2644 | pages = 227β8 | date = August 1945 | pmid = 17778509 | doi = 10.1126/science.102.2644.227 | bibcode = 1945Sci...102..227A }}</ref> This research subsequently led to the synthesis of the antifolate [[aminopterin]], which was used to treat [[childhood leukemia]] by [[Sidney Farber]] in 1948.<ref name="Hoffbrand2001"/><ref name="FarberDiamond1948">{{cite journal | vauthors = Farber S, Diamond LK | title = Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid | journal = The New England Journal of Medicine | volume = 238 | issue = 23 | pages = 787β93 | date = June 1948 | pmid = 18860765 | doi = 10.1056/NEJM194806032382301 }}</ref> In the 1950s and 1960s, scientists began to discover the biochemical mechanisms of action for folate.<ref name="Lanska" /> In 1960, researchers linked folate deficiency to risk of neural tube defects.<ref name="Lanska" /> In the late 1990s, the U.S. and Canadian governments decided that despite public education programs and the availability of folic acid supplements, there was still a challenge for women of child-bearing age to meet the daily folate recommendations, which is when those two countries implemented folate fortification programs.<ref name=Crandall1998 /> As of December 2018, 62 countries mandated food fortification with folic acid.<ref name=Map/>
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