The aim was to describe the discovery of niacin, biotin, and pantothenic acid. By the 1920s, it became apparent that ‘water-soluble B’ (vitamin B) is not a single substance. In particular, fresh yeast could prevent both beriberi and pellagra, but the ‘antipolyneuritis factor’ in yeast is thermolabile, while the antipellagra factor is heat stable, suggesting that there are at least two water-soluble vitamins. Various terms were proposed for these water-soluble factors, but vitamins B1 and B2 were most widely used to refer to the thermolabile and heat-stable factors, respectively. Although vitamin B1 proved to be a single chemical substance (thiamin), vitamin B2 was ultimately found to be a complex of several chemically unrelated heat-stable factors, including niacin, biotin, and pantothenic acid. Recognition that niacin is a vitamin in the early 20th century resulted from efforts to understand and treat a widespread human disease – pellagra. American epidemiologist and US Public Health Service officer Joseph Goldberger (1874–1929) had been instrumental to elucidating the nutritional basis for pellagra. Goldberger conducted a classic series of observational and experimental studies in humans, combined with an extensive series of experiments with an animal model of the condition (black tongue in dogs). In contrast, recognition that biotin and pantothenic acid are vitamins occurred somewhat later as a result of efforts to understand microbial growth factors. The metabolic roles in humans of these latter substances were ultimately elucidated by human experiments using particular toxins and by studies of rare inborn errors of metabolism. Symptomatic nutritional deficiencies of biotin and pantothenic acid were, and continue to be, rare.

1.
Lanska DJ: Historical aspects of the major neurological vitamin deficiency disorders: the water-soluble B vitamins. Handb Clin Neurol 2010;95:445–476.
2.
Lanska DJ: Stages in the recognition of epidemic pellagra in the United States: 1865–1960. Neurology 1996;47:829–834.
3.
Etheridge WE: The Butterfly Caste: A Social History of Pellagra in the South. Westport, Greenwood, 1972.
4.
Marie A: Pellagra (An authorized abridged version of Lombroso C. Trattato profilattico e clinico della pellagra. Turin, 1892. Translated into English and edited by Lavinder CH and Babcock JW). Columbia, The State Co., 1910.
5.
Goldberger J: The etiology of pellagra: the significance of certain epidemiological observations with respect thereto. Public Health Rep 1914;29:1683–1686.
6.
Kraut AM: Goldberger’s War: The Life and Work of a Public Health Crusader. New York, Hill and Wang, 2003.
7.
Parsons RP: Trail to Light: A Biography of Joseph Goldberger. Indianapolis, The Bobbs-Merrill Co., 1943.
8.
Terris M: Goldberger on Pellagra. Baton Rouge, Louisiana State University Press, 1964.
9.
Elvehjem CA, Madden RJ, Strong FM, Woolley DW: Relation of nicotinic aid and nicotinic acid amide to canine black tongue. J Am Chem Soc 1937;59:1767–1768.
10.
Elvehjem CA, Madden RJ, Strong FM, Woolley DW: The isolation and identification of the anti-black tongue factor. J Biol Chem 1938;123:137–149.
11.
Fouts PJ, Helmer OM, Lepkovsky S, Jukes TH: Treatment of human pellagra with nicotinic acid. Proc Soc Exp Biol Med 1937;37:405–407.
12.
Spies TD: The response of pellagrins to nicotinic acid. Lancet 1938;i:252.
13.
Spies TD, Cooper C, Blackenhorn MA: The use of nicotinic acid in the treatment of pellagra. JAMA 1938;110:622–627.
14.
Spies RD, Aring CD, Gelperin J, Bean WB: The mental symptoms of pellagra: their relief with nicotinic acid. Am J Med Sci 1938;196:461–475.
15.
Vilter RW, Mueller JF, Bean WB: The therapeutic effect of tryptophan in human pellagra. J Lab Clin Med 1949;34:409–413.
16.
Goldsmith GA: Experimental niacin deficiency. J Am Diet Assn 1956;32:312–316.
17.
Goldsmith GA: Niacin-tryptophan relationships in man and niacin requirement. Am J Clin Nutr 1958;6:479–486.
18.
Goldsmith GA, Miller ON, Unglaub WG: Efficiency of tryptophan as a niacin precursor in man. J Nutr 1961;73:172–176.
19.
Goldsmith GA, Gibbens J, Unglaub WG, Miller ON: Studies of niacin requirement in man: III. Comparative effects of diets containing lime-treated and untreated corn in the production of experimental pellagra. Am J Clin Nutr 1956;4:151–160.
20.
Boas MA: The effect of desiccation upon the nutritive properties of egg-white. Biochem J 1927;21:712–724.
21.
Snell E: Nutrition research with lactic acid bacteria: a retrospective review. Ann Rev Nutr 1989;9:1–19.
22.
Kresge N, Simoni RD, Hill RL: The Discovery of avidin by Esmond E. Snell. J Biol Chem 2004;279:e5–e6.
23.
György P, Rose C, Eakin RE, Snell EE, Williams RJ: Egg-white injury as the result of nonabsorption or inactivation of biotin. Science 1940;93:477–478.
24.
György P, Rose C: Cure of egg-white injury in rats by the ‘toxic’ fraction (avidin) of egg white given parenterally. Science 1941;94:261–262.
25.
Sydenstricker VA, Singal SA, Briggs AP, De Vaughn NM, Isbel N: Observations on the ‘egg white injury’ in man and its cure with a biotin concentrate. JAMA 1942;118:1199–1200.
26.
Baugh CN, Malone JH, Butterworth CE: Human biotin deficiency: a case history of biotin deficiency inducted by raw egg consumption in a cirrhotic patient. Am J Clin Nutr 1968;21:173–182.
27.
du Vigneaud V, Melville DB, György P, Rose C: On the identity of vitamin H with biotin. Science 1940;92:62–63.
28.
du Vigneaud V, Hofmann K, Melville DB: On the structure of biotin. J Am Chem Soc 1942;64:188–189.
29.
Harris SA, Wolf DE, Mozingo R, Folkers K: Synthetic biotin. Science 1943;97:447–448.
30.
Gompertz D, Draffan GH, Watts JL, Hull D: Biotin-responsive beta-methylcrotonylglycinuria. Lancet 1971;2:22–24.
31.
Gompertz D, Bartlett K, Blair D, Stern CM: Child with a defect in leucine metabolism associated with beta-hydroxyisovaleric aciduria and beta-methylcrotonylglycinuria. Arch Dis Child 1973;48:975–977.
32.
Burri BJ, Sweetman L, Nyhan WL: Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency. J Clin Invest 1981;68:1491–1495.
33.
Wolf B, Grier E, Allen RJ, Goodman SI, Kien CL: Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. Clin Chim Acta 1983;131:273–281.
34.
Williams RJ, Lyman CM, Goodyear GH, Truesdail JH, Holaday D: Pantothenic acid, a growth determinant of universal biological occurrence. J Am Chem Soc 1933;55:2912–2927.
35.
Stiller ET, Harris SA, Finkelstein J, Keresztesy JC, Folkers K: Pantothenic acid. VIII. The total synthesis of pure pantothenic acid. J Am Chem Soc 1940;62:1785–1790.
36.
Lipmann F: Development of the acetylation problem: a personal account. Nobel Lecture, December 11, 1953. Nobel Lectures, Physiology or Medicine 1942–1962. Amsterdam, Elsevier Publishing Company, 1964, pp 413–437.
37.
Wakil SJ, Pugh EL, Sauer F: The mechanism of fatty acid synthesis. Proc Natl Acad Sci USA 1964;52:106–114.
38.
Gopalan C: The burning-feet syndrome. Indian Med Gaz 1946;81:22–26.
39.
Bibile SW, Lionel ND, Dunuwille R, Perera G: Pantothenol and the burning feet syndrome. Br J Nutr 1957;11:434–439.
40.
Bean WB, Hodges RE, Daum K: Pantothenic acid deficiency induced in human subjects. J Clin Invest 1955;34:1073–1084.
41.
Hodges RE, Ohlson MA, Bean WB: Pantothenic acid deficiency in man. J Clin Invest 1958;37:1642–1657.
42.
Hodges RE, Bean WB, Ohlson MA, Bleiler R: Human pantothenic acid deficiency produced by omega-methyl pantothenic acid. J Clin Invest 1959;38:1421–1425.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.