[6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C→T polymorphism of methylenetetrahydrofolate reductase

Abstract

Background and purpose: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is responsible for the synthesis of 5-methyltetrahydrofolate (5-MTHF). The 677C→T mutation of MTHFR reduces the activity of this enzyme. The aim of this study was, first, to compare pharmacokinetic parameters of [6S]-5-MTHF and folic acid (FA) 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 FA was evaluated by measuring plasma folate derivatives. Experimental approach: Healthy females (TT, n = 16; CC, n = 8) received a single oral dose of FA (400 μg) and [6S]-5-MTHF (416 μg) 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 (AUC)], maximum concentration (C max) and time-to-reach-maximum (t max) were calculated. Key results: AUC and C max were significantly higher, and t max significantly shorter for [6S]-5-MTHF compared with FA in both genotypes. A significant difference between the genotypes was observed for t max after FA only (P < 0.05). Plasma folate consisted essentially of 5-MTHF irrespective of the folate form given. Unmetabolized FA in plasma occurs regularly following FA supplementation, but rarely with [6S]-5-MTHF. Conclusions and implications: These data suggest that [6S]-5-MTHF increases plasma folate more effectively than FA irrespective of the 677C→T mutation of the MTHFR. This natural form of folate could be an alternative to FA supplementation or fortification. © 2009 The British Pharmacological Society All rights reserved.