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Folates (vitamin B9) represent a large family of water-soluble B-vitamins which were first recognized by Lucy Wills in 1931 as a hematopoietic factor in yeast and liver extracts (1). In 1940, Snell et al. described a factor that is essential for the growth of Lactobacillus casei (2). This factor was isolated, characterized, and named later as folate. The term “folic acid” from Latin “folium” or “leaf” was marked by Mitchell in 1941, who extracted the substance from spinach leaves (3).

Sources of food folates in human diet are wheat germ, yeast, liver, and leafy vegetables. The main dietary folate forms are 5-methyl-THF and formyl-THF in polyglutamate forms (4). Folates enter the circulation after absorption in the small intestine. In addition to folates supplied by the diet, folates can be synthesized by the microflora of the large intestine. These folates can be absorbed in the large intestine and were believed to be insignificant for vitamin supply. The bioavailability of polyglutamates is ≈ 65 – 70% lower than that of folate monoglutamates.


The Recommended Dietary Allowance (RDA) which were set by the U.S. Institute of Medicine in 1998, represents the average daily intake that is sufficient to meet the nutrient requirements of nearly all (97 – 98%) healthy individuals in each age and gender group (5). The recommendation for food folate was based on the assumption that the bioavailability of food folates is no more than 50% of that of FA (6). In Germany, the Deutsche Gesellschaft für Ernährung (DGE) recently lowered the RDA for folate to 300 µg of dietary folate equivalents (DFE)/day for adult males and females, to 550 µg/day for pregnant women, and to 450 µg/day for lactating women (formerly: 400 µg/day for adults and 600 µg/day for pregnant and lactating women). 1 µg of DFE is defined as 0.6 µg FA (5). The upper tolerable limit (UL) for synthetic FA for adults is 1 mg/day. There is currently little, if any, evidence that high intake of natural folates can be harmful to human.



1.     Wills L. Treatment of "pernicious anaemia of pregnancy" and "tropical anaemia" with special reference to yeast extract as a curative agent. Nutrition 1931;7:323-7.
2.     Snell EE, Peterson WH. Growth Factors for Bacteria: X. Additional Factors Required by Certain Lactic Acid Bacteria. J Bacteriol 1940;39:273-85.
3.     Mitchell HK, Snell EE, Williams RJ. The concentration of "folic acid". J Am Chem Soc 1941;63:2284.
4.     Melse-Boonstra A, de Bree A, Verhoef P, Bjorke-Monsen AL, Verschuren WM. Dietary monoglutamate and polyglutamate folate are associated with plasma folate concentrations in Dutch men and women aged 20-65 years. J Nutr 2002;132:1307-12.
5.     Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. USA: Washington, DC, National Academy Press, 1998:390-422.
6.     Sauberlich HE, Kretsch MJ, Skala JH, Johnson HL, Taylor PC. Folate requirement and metabolism in nonpregnant women. Am J Clin Nutr 1987;46:1016-28.