Effects of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Levels Depending on Genetic Variants of Methyltetrahydrofolate Reductase in Infertile Japanese Women.

Keiji Kuroda,Takashi Horikawa,Rikikazu Sugiyama,Yoko Gekka,Koji Nakagawa,Hiroyasu Juen,Kazuki Nakao,Yuko Ojiro,Satoru Takamizawa,Azusa Moriyama

doi:10.3390/nu13041381

Abstract

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.1%), 100 (48.8%) and 33 (16.1%) had MTHFR CC, CT and TT, respectively. Serum folate and homocysteine levels in women with homozygous mutant TT were significantly lower and higher, respectively, than those in women with CC and CT. In 54 women (26.3% of all women) with a risk of NTDs, multivitamin supplementation containing folic acid and vitamin D for one month increased folate level (5.8 ± 0.9 to 19.2 ± 4.0 ng/mL, p < 0.0001) and decreased the homocysteine level (8.2 ± 3.1 to 5.8 ± 0.8 nmol/mL, p < 0.0001) to minimize the risk of NTDs in all women, regardless of MTHFR genotype. Regardless of MTHFR genotype, multivitamin supplements could control folate and homocysteine levels. Tests for folate and homocysteine levels and optimal multivitamin supplementation in women with risk of NTDs one month or more before pregnancy should be recommended to women who are planning a pregnancy.

Highlights

Neural tube defects (NTDs), such as spina bifida and anencephaly, are the most common congenital malformations in the process of neurological development, and annually, 300,000 to 400,000 infants with NTDs are born [1,2]
We examined the pregnancy outcomes in three methylenetetrahydrofolate reductase (MTHFR) genotypes as a secondanalyzed in patients with CC, CT and TT genotypes of MTHFR C677T
Regarding the distribution of MTHFR C677T, of the 205 women who participated in this study, 72 (35.1%) had wild-type CC, 100 (48.8%) had heterozygous mutant CT and

Summary

Introduction

Neural tube defects (NTDs), such as spina bifida and anencephaly, are the most common congenital malformations in the process of neurological development, and annually, 300,000 to 400,000 infants with NTDs are born [1,2]. The prevalence of spina bifida has decreased; it still has not diminished in Japan [8,9]. Folic acid is enzymatically reduced and converted to tetrahydrofolate (THF) by dihydrofolate reductase via dihydrofolate. 5-MTHF can be converted to THF again when a methyl group is passed to vitamin B12, resulting in methyl-vitamin B12. Homocysteine is catabolized to cysteine by MTHF can be converted to THF again when a methyl group is passed to vitamin B12, resulting in methyl-vitamin B12. Homocysteine is catabolized to cysteine by a vitamin B6-dependent enzyme, cystathionine β-synthase (CBS) [10]

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Conclusion