[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.
OBJECTIVE
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.


METHODS
Healthy females (TT, n= 16; CC, n= 8) received a single oral dose of FA (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 (AUC)], maximum concentration (C(max)) and time-to-reach-maximum (t(max)) were calculated.


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
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.
Prinz-Langenohl
R
R
Department of Nutrition and Food Sciences, Human Nutrition II, Pathophysiology, University of Bonn, Bonn, Germany. r.prinz@uni-bonn.de
Brämswig
S
S
Tobolski
O
O
Smulders
Y M
YM
Smith
D E C
DE
Finglas
P M
PM
Pietrzik
K
K
D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011110:Polymorphism, Genetic; D013763:Tetrahydrofolates / Q000493:pharmacokinetics*; D014803:Vitamin B Complex / Q000493:pharmacokinetics
D013763:Tetrahydrofolates; D014803:Vitamin B Complex; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate