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

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.

Characterization of folic acid, 5-methyltetrahydrofolate and synthetic folinic acid in the high-affinity folate transporters: impact on pregnancy and development

“…How this may translate to more common variations in folate metabolism enzymes will require either humanized animal or cellular models carrying these genetics variations or head-to-head folate comparisons in human populations, averaged and sub-analyzed based on more common variations. For example, MTHFR variations are associated with differences in serum folate and homocysteine, but both 5MTHF and FA improve this outcome in women challenged with infertility [ 48 ] . While hints at differences can be found in the literature, such as increased fertility with 5MTHF and vitamin B12 compared to that with FA alone in women undergoing assisted reproduction [ 49 ] , additional studies are needed to obtain definitive conclusion.…”

Anaemia and Comorbidities in Pregnant Women Routinely Supplemented With Haematinics – A Cross-Sectional Study at the Awutu Municipality of Ghana

“…Supplementation with micronutrients, such as iron (60 mg) and folic acid (400 μg) daily, is widely recommended to avert the incidence of anaemia in pregnancy as well as improve both maternal and birth outcomes (Maina -Gathigi et al, 2013). Also, supplementation with multivitamins comprising folic acid and vitamin D is recommended to minimize the risk of developing neural tube defects (NTD) in pregnancy (Kuroda et al,2021). Iron and folic acid play key roles in bone marrow proliferation as well as red blood cells and haemoglobin biosynthesis.…”

Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk

“…Two functional single nucleotide polymorphisms (SNPs) in MTHFR were identified: the MTHFR rs1801133 (C677T) polymorphism (a C to T transition at nucleotide 677 at exon 4, resulting in an alanine-to-valine conversion in protein) and MTFHR rs1801131 (A1298C) polymorphism (a A to C transition at nucleotide 1298 at exon ten, causing a glutamate-to-alanine change in protein) [19,20] . Both of the 2 polymorphisms were reported to be associated with a lower MTHFR activity, [21–28] and the reduced enzymatic activity can promote or inhibit the occurrence of HCC by affecting DNA methylation and synthesis, which indicated these 2 polymorphisms could be associated with HCC risk.…”

“…protein). [19,20] Both of the 2 polymorphisms were reported to be associated with a lower MTHFR activity, [21][22][23][24][25][26][27][28] and the reduced enzymatic activity can promote or inhibit the occurrence of HCC by affecting DNA methylation and synthesis, which indicated these 2 polymorphisms could be associated with HCC risk.…”