A study of plasma folate under the influence of [6S]-5-MTHF in women with 677C→T polymorphism of mthfr with different types of inheritance

R. Prinz-Langenohl, S. Brämswig, O. Tobolski


Background and purpose: 5,10-Methylenetetrahydrofolate reductase is responsible for the synthesis of 5-methyltetrahydrofolate (5-MTHF). The 677C→T mutation of 5,10-Methylenetetrahydrofolate reductase reduces the activity of this enzyme. The aim of this study was, first, to compare pharmacokinetic parameters of [6S]-5-MTHF and folic acid in women with the homozygous (TT) and wild-type (CC) 677C→T mutation, and second, to explore genotype differences. The metabolism of [6S]-5-MTHF and folic acid was evaluated by measuring plasma folate derivatives.

Experimental approach: Healthy females (TT, n = 16; CC, n = 8) received a single oral dose of folic acid (400 microg) and [6S]-5-MTHF (416 microg) in a randomized crossover design.

Plasma folate was measured up to 8 h after supplementation. Concentration-time-profile (area under the curve of the plasma folate concentration vs. time), maximum concentration (Cmax) and time-to-reach-maximum (tmax) were calculated.

Key results: Area under the curve of the plasma folate concentration vs. time and Cmax were significantly higher, and tmax significantly shorter for [6S]-5-MTHF compared with folic acid in both genotypes. A significant difference between the genotypes was observed for tmax after folic acid only (p < 0.05). Plasma folate consisted essentially of 5-MTHF irrespective of the folate form given. Unmetabolized folic acid in plasma occurs regularly following folic acid supplementation, but rarely with [6S]-5-MTHF.

Conclusions and implications: These data suggest that [6S]-5-MTHF increases plasma folate more effectively than folic acid irrespective of the 677C→T mutation of the 5,10-Methylenetetrahydrofolate reductase. This natural form of folate could be an alternative to folic acid supplementation or fortification.


5,10-Methylenetetrahydrofolate reductase; 5-methyltetrahydrofolate; folic acid; genotype

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DOI: https://doi.org/10.18370/2309-4117.2017.35.62-66


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ISSN 2411-1295 (Online), ISSN 2309-4117 (Print)