Research Progress on the Effect of 5-Methyltetrahydrofolic Acid on Hyperhomocysteinemia in Pregnancy

  • Yuanting Zhang The Second Affiliated Hospital of Kunming Medical University
  • Wanqin Hu The Second Affiliated Hospital of Kunming Medical University
Keywords: 5-Methyltetrahydrofolin; Hyperhomocysteine; Pregnancy Complications; Pregnancy Management


As the association of hyperhomocysteinemia in pregnancy with preterm birth, abortion, preeclampsia and other pregnancy compli-cations has attracted increasing attention, 5-methyltetrahydrofolic acid has attracted much attention as a potential treatment. In this paper, the biological mechanism of 5-methyltetrahydrofolic acid, its relationship with hyperhomocysteinemia in pregnancy and clinical studies were reviewed to review the research progress of 5-methyltetrahydrofolic acid in regulating hyperhomocysteine levels in pregnancy. The purpose of this paper is to explore the role and infuence of 5-methyltetrahydrofolic acid in the management of hyperhomocysteinemia during preg-nancy.


[1] Gabbai D, Harlev A, Friger M, Steiner N, Sergienko R, Kreinin A, et al. Pregnancy outcomes among patients with recurrent preg_x005fnancy loss and uterine anatomic abnormalities. Journal of perinatal medicine. 2018; 46 (7): 728-34.

[2] Kong J. Expert Consensus on diagnosis and treatment of hyperhomocysteinemia. Electronic Journal of Tumor Metabolism and Nutrition. 2020; 7 (03): 283-8.

[3] Wei SQ. Changes of serum total homocysteine in hypertensive syndrome of pregnancy and its clinical significance. Journal of Harbin Medical University. 2001; 35 (1).

[4] Cheng S. Advances in the treatment of hyperhomocysteinemia. Advances in Physiological Sciences. 2011; 42 (5).

[5] Blom HJ, 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.

[6] Annibal A, Tharyan RG, Schonewolff MF, Tam H, Latza C, Auler MMK, et al. Regulation of the one carbon folate cycle as a shared

metabolic signature of longevity. Nat Commun. 2021; 12 (1): 3486.

[7] Wang SZ, Wang HS, Wang LZ, Li YJ. The pathogenesis of hyperhomocysteinemia and its pathophysiological significance. Chinese

Journal of Brain Diseases and Rehabilitation (electronic edition). 2019; 9 (02): 117-20.

[8] Yan H, Xiang R, Yang JC, Chi YJ. Homocysteine metabolism and diseases. Advances in Physiological Sciences. 2023; 54 (4): 290-6.

[9] Zhao A. Correlation between MTHFR gene C677T and A1298C polymorphisms and plasma homocysteine levels in recurrent abortion. China Medical Review. 2021; 18 (15).

[10] Zarfeshan FY, Kooshkaki O, Kordi TD, Anani SG. Investigation of the association between C677T polymorphism of the MTHFR

gene and plasma homocysteine level in recurrent fetal miscarriage. J Obstet Gynaecol Res. 2019; 45 (8): 1442-7.

[11] Yakub M, Moti N, Parveen S, Chaudhry B, Azam I, Iqbal MP. Polymorphisms in MTHFR, MS and CBS genes and homocysteine

levels in a Pakistani population. PLoS One. 2012; 7(3):e33222.

[12] Qin X, Li J, Cui Y, Liu Z, Zhao Z, Ge J, et al. MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering

efficacy of different doses of folic acid in hypertensive Chinese adults. Nutr J. 2012; The men.

[13] Lian ZL, Liu K, Gu JH, Cheng YZ. Biological characteristics and application of folic acid and 5-methyltetrahydrofolate. Food Additives in China. 2022; 33 (02): 230-9.

[14] Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014; 44 (5): 480-8.

[15] Patanwala I, King MJ, Barrett DA, Rose J, Jackson R, Hudson M, et al. Folic acid handling by the human gut: implications for

food fortification and supplementation. Am J Clin Nutr. 2014; 100 (2): 593-9.

[16] Kubo Y, Fukuoka H, Kawabata T, Shoji K, Mori C, Sakurai K, et al. Distribution of 5-Methyltetrahydrofolate and Folic Acid Levels in Maternal and Cord Blood Serum: Longitudinal Evaluation of Japanese Pregnant Women. Nutrients. 2020; 12 (6).

[17] Luo CC. Investigation of serum homocysteine level in normal pregnant women. Laboratory Medicine. 2014; 29 (7).

[18] Seremak-Mrozikiewicz A, Bogacz A, Bartkowiak-Wieczorek J, Wolski H, Czerny B, Gorska-Paukszta M, et al. The importance

of MTHFR, MTR, MTRR and CSE expression levels in Caucasian women with preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2015; 188:


[19] Chen DL, Xu J. Advances in research on homocysteine and pregnancy-related diseases. Preventive Medicine. 2020; 32 (02): 147-51.

[20] Yuan YD, Gong XW, Yang YH. A meta-analysis of factors associated with re-embolization in the occurrence of pulmonary thromboembolism. Chinese Journal of Medicine. 2012(34):2419-25.

[21] Lee M, No HJ, Jang SY, Kim N, Choi SH, Kim H, et al. Hereditary Thrombophilia in Korean Patients with Idiopathic Pulmonary

Embolism. Yonsei Medical Journal. 2012; 53 (3).

[22] Liu B, Liang Z, Li JP, Qin XH, Fan FF, Zhang Y, et al., editors. Comparative effect of supplementation with 5-methyltetrahydrofolate

or folic acid on reducing plasma homocysteine: a systematic review and meta-analysis. The 7th Cross-Straits and Hong Kong and Macao Nu_x0002_trition Science Conference; 2022; Qingdao, Shandong, China.

[23] Zhang CH. A meta-analysis of the relationship between maternal 5, 10-methylenetetrahydrofolate reductase gene C677T polymorphism and the susceptibility of offspring to neural tube malformation in a Chinese population. Health Research. 2018; 47 (2).

[24] Liao YP. The correlation between genetic polymorphisms of MTHFR, MTRR and MTR and the occurrence of Down syndrome.

Chinese Journal of Laser Biology. 2010; 19 (3).

[25] Hou SN. Association between folic acid gene polymorphism and high risk of Down syndrome. International Journal of Laboratory

Medicine. 2016; 37 (22).

[26] Chai O. Association between MTHFR polymorphism of methylenetetrahydrofolate reductase gene and risk of Down syndrome.

Hebei Med. 2020; 42 (6).

[27] Zhang FQ. A meta-analysis of the relationship between maternal Methylenetetrahydrofolate reductase C677T polymorphism and

offspring DS in a Chinese population. Chinese Journal of Reproductive Health. 2013; 24 (5).

[28] Henderson AM, Aleliunas RE, Loh SP, Khor GL, Harvey-Leeson S, Glier MB, et al. l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women. J Nutr. 2018; 148 (6): 885-90.

[29] Mei J. Study on therapeutic effect of active folic acid on adverse pregnancy. China Maternal and Child Health Research. 2017; 28


[30] Liang Z, Wang XF, Li SL. A clinical study on the change of homocysteine level between pregnant women and normal women.

Chinese Journal of Health Inspection. 2018; 28 (8): 979-80 + 83.

Review Article