Folic acid accumulation in blood plasma and erythrocytes in women of reproductive age depending on vitamin B₉ forms and polymorphic variants of folate pathway genes

BACKGROUND: Taking the synthetic form of folic acid (vitamin B₉ or pteroylmonoglutamic acid) at a dose of 400 mcg at the pregravid stage to correct plasma homocysteine levels can reduce the risk of neural tube defects in fetuses. Furthermore, the use of the reduced form of folic acid, 5-methyltetrahydrofolate, has been shown to offer advantages over synthetic folic acid, particularly in patients with the MTHFR c.665C>T polymorphism. However, the efficacy of 5-methyltetrahydrofolate has not been confirmed in large clinical trials, which makes it important to study its effect on methionine metabolism compared to that of synthetic folic acid.

AIM: The aim of this study was to assess folic acid accumulation in blood plasma and erythrocytes in women of reproductive age depending on vitamin B₉ forms and polymorphic variants of the genes involved in the folate pathway.

METHODS: This randomized controlled open-label prospective study included 60 women of reproductive age, who were divided into two groups of 30 individuals each. In the both study groups, the participants took one of the folic acid forms — 5-methyltetrahydrofolate or pteroylmonoglutamic acid — at a dose of 400 mcg for 3 months. All women were tested for folate pathway gene polymorphisms, while measuring serum homocysteine and vitamin B₁₂ levels, as well as plasma and red blood cell folate levels before and after folate supplementation.

RESULTS: In the both study groups, we observed an increase in folic acid concentrations in erythrocytes and blood plasma. In the group of women taking 5-methyltetrahydrofolate, these parameters increased from 152.86 to 205.99 ng/ml (p < 0.05) and from 10.96 to 25.39 nmol/l (p < 0.05), respectively. In the pteroylmonoglutamic acid group, the parameters increased from 144.33 to 228.46 ng/ml (p < 0.05) and from 14.08 to 33.37 nmol/l (p < 0.05), respectively. Moreover, in the both study groups, we noted a reliable increase in folic acid concentrations regardless of the presence of genetic defects in folate cycle enzymes.

CONCLUSION: Three-month folate supplementation in women of reproductive age increases plasma and red blood cell folate levels, regardless of the form of folic acid (5-methyltetrahydrofolate or pteroylmonoglutamic acid) taken or the presence of genetic defects in folate cycle enzymes.