Preeclampsia, a complex disorder unique to pregnancy, is characterized by high blood pressure and proteinuria, typically emerging after the 20th week of gestation. It poses significant risks to both the mother and the fetus. While the exact etiology remains elusive, it is believed to involve genetic, immunological, and endothelial dysfunction factors.

MTHFR and Its Role in Preeclampsia

Methylenetetrahydrofolate Reductase (MTHFR) is a pivotal enzyme in folate metabolism, converting synthetic folate derivatives into absorbable 6S-5-methyltetrahydrofolate. The C677T polymorphism in the MTHFR gene, which involves the substitution of cytosine (C) with thymine (T) at the 677th nucleotide, can diminish enzyme activity. This reduction can impede the conversion of 6S-5-methyltetrahydrofolate, affecting homocysteine metabolism and potentially increasing the risk of cardiovascular diseases. In China, approximately 78.4% of the population is affected by MTHFR 677 folate metabolism disorders.

Recent research indicates that the MTHFR C677T polymorphism may be linked to the development of preeclampsia.

MTHFR Polymorphism and Preeclampsia: A Global Perspective

A 2013 meta-analysis, synthesizing data from 51 case-control studies and encompassing diverse ethnic groups including Caucasians, Latin Americans, East Asians, South Asians, and Africans, investigated the link between the MTHFR C677T polymorphism and preeclampsia risk. The study involved 6,403 patients and 11,346 controls.

Findings revealed a significant association between the MTHFR C677T polymorphism and preeclampsia risk in the general population, particularly among Caucasians and East Asians, with no significant link observed in Latin American, South Asian, and African populations.

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Naturalization Folate and Preeclampsia Prevention

In contrast to synthetic folic acid, Naturalization Folate (active folate, 6S-5-methyltetrahydrofolate, 5-MTHF) can be directly absorbed, bypassing the limitations of MTHFR enzyme activity. This enhancement in folate levels and reduction in homocysteine (HCY) can aid in preeclampsia prevention. A clinical controlled study conducted in Italy from 2009 to 2013 demonstrated that pregnant women supplemented with 5-MTHF experienced significantly lower rates of recurrent preeclampsia, severe preeclampsia, and preterm preeclampsia.

Conclusion

Preeclampsia is a grave pregnancy complication with a multifactorial pathogenesis. The C677T polymorphism of the MTHFR gene is associated with an increased risk of preeclampsia, especially in certain ethnic groups. Naturalization folate (5-MTHF), as an active form of folate, can circumvent the constraints of the MTHFR enzyme and be directly utilized by the body, offering a potential preventative measure against preeclampsia. For pregnant women at risk, supplementation with natural folate may be an effective strategy.

References:

1. Wang XM, Wu HY, Qiu XJ. Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T Polymorphism and Risk of Preeclampsia: An Updated Meta-analysis Based on 51 Studies. Archives of Medical Research 44 (2013) 159-168.

2. Saccone G, Sarno L, Roman A, Donadono V, Maruotti GM, Martinelli P. 5-Methyl-tetrahydrofolate in prevention of recurrent preeclampsia. J Matern Fetal Neonatal Med. 2015; DOI: 10.3109/14767058.2015.1023189.

3. Lian Zenlin, Liu Kang, Gu Jinhua, Cheng Yongzhi, et al. Biological characteristics and applications of folate and 5-methyltetrahydrofolate. Food Additives in China, Issue 2, 2022.

4. Lamers Y, Prinz-Langenohl R, Braumswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006;84:156-161.