An Ideal Folate: Myth or Reality?

For citation: Mikhailyukova V.A. An Ideal Folate: Myth or Reality? Doctor.Ru. 2020; 19(8): 55–60. (in Russian). DOI: 10.31550/1727-2378-2020-19-8-55-60

Objective of the Review: To assess the benefits and risks of using various doses and forms of folic acid as part of pre-conception care and during pregnancy.

Key Points: Folic acid (vitamin B9) is known to be an essential microelement, required for DNA replication and several enzyme reactions in amino acid synthesis and metabolism of vitamins. During pregnancy folate requirements rise. According to Order No. 572n of the Russian Federation Ministry of Health, dated November 1, 2012, women should receive folic acid starting in the pre-conception period at doses not exceeding 400 µg/day. A pregnant woman’s folate status is critical for the prevention of folate-associated birth defects and for the baby’s postnatal development. There is still some controversy about the advantages of different forms of folates, the safety of low and high folate doses, the duration of treatment, and the benefits of folates compared with multivitamins.

Conclusion: Currently, there is no doubt that women should receive vitamin-mineral products containing folic acid as part of their pre-conception care and during pregnancy. There is a need, however, for a formal federal protocol for pre-conception care that will guide the use of vitamin-mineral products containing various forms of folates and describe a personalized approach to micronutrient support for various categories of women, including its composition, doses, and duration.

Conflict of interest: The author declares that she does not have any conflict of interests.

V.A. Mikhailyukova — I.I. Mechnikov Northwestern State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Ministry of Health; 41 Kirochnaya St. Petersburg, Russian Federation 191015. E-mail: venera.mikhaylyukova@gmail.com


Fig. 1. Folate metabolism in the intestine [10]


Fig. 2. Synthesis, breakdown, and metabolism of different forms of tetrahydrofolate (THF) [12]


Fig. 3. Relationship between the duration of pre-conception care and the effectiveness of folates [16]


Fig. 4. Time frames for occurrence of folate-associated birth defects2 [4]


Fig. 5. Placenta-associated complications of gestation [23]


Received: 21.08.2020

Accepted: 28.09.2020


2 WHO/CDC/ICBDSR. Birth defects surveillance training: facilitator`s guide. Geneva: World Health Organization; 2015. 162 p.

  1. Pustotina O.A. Achievements and risks of folate use during and not in pregnancy. Medical Council. 2015; 9: 92–9. (in Russian). DOI: 10.21518/2079-701X-2015-9-92-99
  2. De-Regil L.M., Peña-Rosas J.P., Fernández-Gaxiola A.C. et al. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst. Rev. 2015; 12: CD007950. DOI: 10.1002/14651858.CD007950.pub3
  3. Radzinsky V.E., Pustotina O.A., Verizhnikova E.V. et al. Preconception care: a clinical protocol. M.: Publishing House of Status Praesens; 2016. 80 p. (in Russian)
  4. Gromova O.A., Serov V.N., Torshin I.Yu. et al. A role of folic acid-containing vitamin-mineral complexes in prophylaxis of congenital heart diseases and neural tube defects. Effective Pharmacotherapy. Obstetrics and Gynecology. 2015; 4(36): 4–15. (in Russian)
  5. Gromova O.A., Torshin I.Yu., Ailamazyan E.K. et al. The use of folic acid in obstetric practice. UNESCO education programs. M.: 2009. 57 p. (in Russian)
  6. Gromova O.A., Torshin I.Yu., Tetruashvili N.K. et al. New trends in nutritional support of pregnancy. Obstetrics and Gynecology. 2018; 1: 21–8. (in Russian). DOI: 10.18565/aig.2018.1.21-28
  7. Mamedova E.I. Pros and cons of folic acid fortification of foods. International Student Bulletin. 2016; 4–3. URL: https://www.eduherald.ru/ru/article/view?id=16210 (Accessed August 15, 2020). (in Russian)
  8. Cantarella C.D., Ragusa D., Giammanco M. et al. Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature. Genes Nutr. 2017; 12: 14. DOI: 10.1186/s12263-017-0560-8
  9. Muggli E.E., Halliday J.L. Folic acid and risk of twinning: a systematic review of the recent literature, July 1994 to July 2006. Med. J. Aust. 2007; 186(5): 243–8.
  10. Pietrzik K., Bailey L., Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin. Pharmacok. 2010; 49(8): 535–48. DOI: 10.2165/11532990-000000000-00000
  11. Snitsarenko E.N., Yakovets S.M. The clinical aspects of hyperhomocysteinema. Medical and Biological Problems of Life Activity. 2016; 2(16): 12–20. (in Russian)
  12. Kareva E.N., Zorina L.A., Sudnitsyna M.V. Tetrahydrofolate: role in periconceptional supplementation and prenatal care. Obstetrics and Gynecology: News, Opinions, Training. 2019; 7(2): 59–63. (in Russian). DOI: 10.24411/2303-9698-2019-12007
  13. Castaño E., Piñuñuri R., Hirsch S. et al. Folate and pregnancy, current concepts: it is required folic acid supplementation? Rev. Chil. Pediatr. 2017; 88(2): 199–206. DOI: 10.4067/S0370-41062017000200001
  14. Blom H.J., Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J. Inherit. Metab. Dis. 2011; 34(1): 75–81. DOI: 10.1007/s10545-010-9177-4
  15. Clarke R., Bennett D. Folate and prevention of neural tube defects. BMJ. 2014; 349: g4810. DOI: 10.1136/bmj.g4810
  16. Gromova O.A., Torshin I.Yu., Rudakov K.V. The clinical and molecular pharmacology of folic acid. Folates for pregnant women: dotted i's and crossed t's. Clinical Pharmacology and Pharmacoeconomics. 2010; 3(1): 38–9. (in Russian)
  17. Gromova O.A., Limanova O.A., Torshin I.Yu. et al. The dose-dependence of the protective effects of folic acid in pre-conception care and during pregnancy and lactation. Russian Medical Journal. 2014; 22(1): 27–34. (in Russian)
  18. Khoshnood B., Loane M., de Walle H. et al. Long term trends in prevalence of neural tube defects in Europe: population based study. BMJ. 2015; 351: h5949. DOI: 10.1136/bmj.h5949
  19. Tkachenko L.V., Khomich E.A. Characteristics of pregravidpreparation in women with non-developing pregnancy in anamnesis. Medical Alphabet. 2016; 3(27): 14–19. (in Russian)
  20. Bitsadze V.O., Samburova N.V., Makatsariya N.A. et al. Folate deficiency in obstetrics and the problem of its correction. Obstetrics, Gynecology and Reproduction. 2016; 10(1): 38–48. (in Russian). DOI: 10.17749/2313-7347.2015.10.1.038-048
  21. Wen S.W., Chen X.K., Rodger M. et al. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am. J. Obstet. Gynecol. 2008; 198(1): 45.e1–7. DOI: 10.1016/j.ajog.2007.06.067
  22. Yang J., Xie R.H., Krewski D. et al. Exposure to trimethoprim/sulfamethoxazole but not other FDA category C and D anti-infectives is associated with increased risks of preterm birth and low birth weight. Int. J. Infect. Dis. 2011; 15(5): e336–41. DOI: 10.1016/j.ijid.2011.01.007
  23. Kuznetsova I.V. Role of preconception endothelial dysfunction in development of obstetric complications. Medical Alphabet. 2019; 1(1): 53–8. (in Russian). DOI: 10.33667/2078-5631-2019-1-1(376)-53-58
  24. Shikh E.V., Makhova A.A. Benefits of folate status correction using metafolin-contained vitamin-mineral complex. Difficult Patient. 2013; 11(8–9): 26–31. (in Russian)


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