Folate Metabolism and Its Implications in Pregnancy
Abstract
The impact of folate nutritional status on a variety of pregnancy outcomes has been acknowledged for a considerable period of time. Folate is increasingly recognized not just as a nutrient required to prevent megaloblastic anemia during pregnancy, but also as a vitamin necessary for reproductive health. Folate plays an important role in several metabolic processes including DNA synthesis and methylation. Changes in folate status can affect the stability and integrity of DNA or affect the methylation patterns of some tissues. Folate is required for cell division and cell maintenance, as it acts as a co-enzyme in the transfer and processing of carbon units and plays an important role in the synthesis of nucleotides (thymidine) that are essential for de novo construction or DNA repair. The purpose of this article is to examine the function of folic acid in human health especially in pregnancy and to evaluate the benefits, concerns, and epigenetic effects of maternal FA in light of recent discoveries that are crucial for the development of future research.
References
Binia, A., Contreras, A. V., Canizales-Quinteros, S., Alonzo, V. A., Tejero, M. E., & Silva-Zolezzi, I. (2014). Geographical and ethnic distribution of single nucleotide polymorphisms within genes of the folate/homocysteine pathway metabolism. Genes & Nutrition, 9(5), 421. https://doi.org/10.1007/s12263-014-0421-7
Chen, L., Liu, L., Hong, K., Hu, J., & Cheng, X. (2012). Three Genetic Polymorphisms of Homocysteine-Metabolizing Enzymes and Risk of Coronary Heart Disease: A Meta-Analysis Based on 23 Case–Control Studies. DNA and Cell Biology, 31(2), 238–249. https://doi.org/10.1089/dna.2011.1281
Christensen, K. E., Mikael, L. G., Leung, K.-Y., Lévesque, N., Deng, L., Wu, Q., Malysheva, O. V, et al. (2015). High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice. The American Journal of Clinical Nutrition, 101(3), 646–658. https://doi.org/10.3945/ajcn.114.086603
Czeizel, A., Dudás, I., Vereczkey, A., & Bánhidy, F. (2013). Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects. Nutrients, 5(11), 4760–4775. https://doi.org/10.3390/nu5114760
De-Regil, L. M., Peña-Rosas, J. P., Fernández-Gaxiola, A. C., & Rayco-Solon, P. (2015). Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database of Systematic Reviews, 2015(12). https://doi.org/10.1002/14651858.cd007950.pub3
Endalifer, M. L., & Diress, G. (2020). Epidemiology and determinant factors of neural tube defect: Narrative review. Surgical Neurology International, 11, 81. https://doi.org/10.25259/SNI_84_2020
Evans, S. P., Ailes, E. C., Kramer, M. R., Shumate, C. J., Reefhuis, J., Insaf, T. Z., ... & Gilboa, S. M. (2023). Neighborhood deprivation and neural tube defects. Epidemiology, 34(6), 774-785. https://doi.org/10.1097/ede.0000000000001655
Félix, T. M., Leistner, S., & Giugliani, R. (2004). Metabolic effects and the methylenetetrahydrofolate reductase ( MTHFR ) polymorphism associated with neural tube defects in southern Brazil. Birth Defects Research Part A: Clinical and Molecular Teratology, 70(7), 459–463. https://doi.org/10.1002/bdra.20011
Kancherla, V. (2023). Neural tube defects: a review of global prevalence, causes, and primary prevention. Child’s Nervous System, 39(7), 1703–1710. https://doi.org/10.1007/s00381-023-05910-7
Kondo, A., Matsuo, T., Morota, N., Kondo, A. S., Okai, I., & Fukuda, H. (2017). Neural tube defects: Risk factors and preventive measures. Congenital Anomalies, 57(5), 150–156. https://doi.org/10.1111/cga.12227
Lajin, B., Alhaj Sakur, A., Michati, R., & Alachkar, A. (2012). Association between MTHFR C677T and A1298C, and MTRR A66G polymorphisms and susceptibility to schizophrenia in a Syrian study cohort. Asian Journal of Psychiatry, 5(2), 144–149. https://doi.org/10.1016/j.ajp.2012.03.002
Liew, S.-C. (2016). Folic acid and diseases - supplement it or not? Revista da Associação Médica Brasileira, 62(1), 90–100. https://doi.org/10.1590/1806-9282.62.01.90
Ma, R., Wang, L., Jin, L., Li, Z., & Ren, A. (2017). Plasma folate levels and associated factors in women planning to become pregnant in a population with high prevalence of neural tube defects. Birth Defects Research, 109(13), 1039–1047. https://doi.org/10.1002/bdr2.1040
Meng, Q., Zhang, L., Liu, J., Li, Z., Jin, L., Zhang, Y., Wang, L., et al. (2015). Dietary folate intake levels in rural women immediately before pregnancy in Northern China. Birth Defects Research Part A: Clinical and Molecular Teratology, 103(1), 27–36. https://doi.org/10.1002/bdra.23280
Nazki, F. H., Sameer, A. S., & Ganaie, B. A. (2014). Folate: Metabolism, genes, polymorphisms and the associated diseases. Gene, 533(1), 11–20. https://doi.org/10.1016/j.gene.2013.09.063
Ohrvik, V. E., & Witthoft, C. M. (2011). Human Folate Bioavailability. Nutrients, 3(4), 475–490. https://doi.org/10.3390/nu3040475
Perez, A. B. A., D’Almeida, V., Vergani, N., de Oliveira, A. C., de Lima, F. T., & Brunoni, D. (2003). Methylenetetrahydrofolate reductase (MTHFR): incidence of mutations C677T and A1298C in Brazilian population and its correlation with plasma homocysteine levels in spina bifida. American Journal of Medical Genetics Part A, 119A(1), 20–25. https://doi.org/10.1002/ajmg.a.10059
Pertiwi, H., Nur Mahendra, M. Y., & Kamaludeen, J. (2022). Folic Acid: Sources, Chemistry, Absorption, Metabolism, Beneficial Effects on Poultry Performance and Health. Veterinary Medicine International, 2022, 1–9. https://doi.org/10.1155/2022/2163756
SACN. (2017). Update on folic acid. Scientific Advisory Committee on Nutrition.
Scaglione, F., & Panzavolta, G. (2014). Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica, 44(5), 480–488. https://doi.org/10.3109/00498254.2013.845705
Shane, B. (2008). Folate and Vitamin B Metabolism: Overview and Interaction with Riboflavin, Vitamin B, and Polymorphisms. Food and Nutrition Bulletin, 29(2_suppl1), S5–S16. https://doi.org/10.1177/15648265080292s103
Shen, Y., Gu, Y., Tang, Y., Shen, H., & Liu, C. (2024). Geographical distribution of MTHFR C677T gene polymorphisms among the reproductive-age women in Chinese Han populations: based on migration. BMC Women’s Health, 24(1), 407. https://doi.org/10.1186/s12905-024-03244-3
Subandrate, S., Athiah, M., & Safyudin. (2022). Asam Folat: Peran dalam Metabolisme dan Metode Pemeriksaan. Majalah Kedokteran Andalas, 45(1).
Talaulikar, V., & Arulkumaran, S. (2011). Folic acid in pregnancy. Obstetrics, Gynaecology & Reproductive Medicine, 21(5), 147–148. https://doi.org/10.1097/ogx.0b013e318223614c
Wang, X. W., Luo, Y. L., Wang, W., Zhang, Y., Chen, Q., & Cheng, Y. L. (2012). Association between MTHFR A1298C polymorphism and neural tube defect susceptibility: a metaanalysis. American Journal of Obstetrics and Gynecology, 206(3), 251.e1-251.e7. https://doi.org/10.1016/j.ajog.2011.12.021
World Health Organization. (2015). Serum and Red Blood Cell Folate Concentrations for Assessing Folate Status in Populations. Vitam Miner Nutr Inf Syst, 1–7.
Yafei, W., Lijun, P., Jinfeng, W., & Xiaoying, Z. (2012). Is the prevalence of MTHFR C677T polymorphism associated with ultraviolet radiation in Eurasia? Journal of Human Genetics, 57(12), 780–786. https://doi.org/10.1038/jhg.2012.113
Yang, B., Liu, Y., Li, Y., Fan, S., Zhi, X., Lu, X., Wang, D., et al. (2013). Geographical Distribution of MTHFR C677T, A1298C and MTRR A66G Gene Polymorphisms in China: Findings from 15357 Adults of Han Nationality. PLoS ONE, 8(3), e57917. https://doi.org/10.1371/journal.pone.0057917
Zheng, Y., & Cantley, L. C. (2019). Toward a better understanding of folate metabolism in health and disease. Journal of Experimental Medicine, 216(2), 253–266. https://doi.org/10.1084/jem.20181965
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