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. 2025 May 9;8:100222. doi: 10.1016/j.crphar.2025.100222

Table 1.

The discovery and application of folic acid.

Date Description References
1931 Wills&Mehta found that yeast extract prevents dietary anemia in rats and named it ‘Wills’ factor’ (Wills, 1931), (Watson and Castle, 1946)
1938 Yeast and liver extracts are effective in reducing monkey vegetative cells. This factor is named vitamin M (Day et al., 1938), (Langston et al., 1938)
1941 ‘FA’ receives its name and shown to be a growth factor for Streptococcus lactis R (S. faecalis) Mitchell et al. (1941)
1945 Synthesis of FA and called pteroylglutamic acid Angier et al. (1945)
1946 Naturally occurring folate in liver is a heptaglutamate Pfiffner and Calkins (1946)
1964 folate deficiency and NTD occurrence was hypothesized Hibbard (1964)
1991 The effectiveness of FA supplementation to prevent the recurrence of NTD was determined MRC Vitamin Study Research Group (1991)
1992 Prevention by FA of a first occurrence of NTD was proven Czeizel and Dudás (1992)
1998 In the United States and Canada, mandatory fortification of enriched cereal grain products with FA was implemented Crider et al. (2011a)
1999 Reduction of the risk in NTD by 0.4 mg FA was proven by China-US Collaborative Project Berry et al. (1999)
2009 The Chinese government provides free FA for rural planned pregnant women Ren (2015)
2010 Regulations for mandatory fortification of wheat flour with FA have been in place in 53 countries Crider et al. (2011a)
2025 94 countries have mandates that require wheat flour, maize flour, and/or rice to be fortified with micronutrients Food fortification initiative (2025)