Article date: March 2004
By: Frank F Willems, Godfried H J Boers, Henk J Blom, Wim R M Aengevaeren, Freek W A Verheugt in Volume 141, Issue 5, pages 825-830
Methylenetetrahydrofolate reductase (MTHFR) is a regulating enzyme in folate‐dependant homocysteine remethylation, because it catalyses the reduction of 5,10 methylenetetrahydrofolate to 5‐methyltetrahydrofolate (5‐MTHF).
Subjects homozygous for the 677C → T mutation in the MTHFR enzyme suffer from an increased cardiovascular risk. It can be speculated that the direct administration of 5‐MTHF instead of folic acid can facilitate the remethylation of homocysteine in methionine.
The aim of this study was to determine the pharmacokinetic properties of orally administered 6[R,S] 5‐MTHF versus folic acid in cardiovascular patients with homozygosity for 677C → T MTHFR.
This is an open‐controlled, two‐way, two‐period randomised crossover study. Patients received a single oral dose of either 5 mg folic acid or 5 mg 5‐MTHF in each period. The concentrations of the 6[S] 5‐MTHF and 6[R] 5‐MTHF diastereoisomers were determined in venous blood samples.
All pharmacokinetic parameters demonstrate that the bioavailability of 5‐MTHF is higher compared to folic acid. The peak concentration of both isomers following the administration of 6[R,S] 5‐MTHF is almost seven times higher compared to folic acid, irrespective of the patient's genotype. However, at 1 week after the administration of a single dosage 6[R,S] 5‐MTHF, we detected 6[R] 5‐MTHF following the administration of folic acid, indicating storage of this isomer in the body.
Our results demonstrate that oral 5‐MTHF has a different pharmacokinetic profile with a higher bioavailability compared to folic acid, irrespective of the patient's genotype. Detrimental effects of the storage of high levels of the non‐natural isomer 6[R] 5‐MTHF cannot be excluded.
Methylenetetrahydrofolate reductase (MTHFR) is a regulating enzyme in folate‐dependant homocysteine remethylation, because it catalyses the reduction of 5,10 methylenetetrahydrofolate to 5‐methyltetrahydrofolate (5‐MTHF).
Subjects homozygous for the 677C → T mutation in the MTHFR enzyme suffer from an increased cardiovascular risk. It can be speculated that the direct administration of 5‐MTHF instead of folic acid can facilitate the remethylation of homocysteine in methionine.
The aim of this study was to determine the pharmacokinetic properties of orally administered 6[R,S] 5‐MTHF versus folic acid in cardiovascular patients with homozygosity for 677C → T MTHFR.
This is an open‐controlled, two‐way, two‐period randomised crossover study. Patients received a single oral dose of either 5 mg folic acid or 5 mg 5‐MTHF in each period. The concentrations of the 6[S] 5‐MTHF and 6[R] 5‐MTHF diastereoisomers were determined in venous blood samples.
All pharmacokinetic parameters demonstrate that the bioavailability of 5‐MTHF is higher compared to folic acid. The peak concentration of both isomers following the administration of 6[R,S] 5‐MTHF is almost seven times higher compared to folic acid, irrespective of the patient's genotype. However, at 1 week after the administration of a single dosage 6[R,S] 5‐MTHF, we detected 6[R] 5‐MTHF following the administration of folic acid, indicating storage of this isomer in the body.
Our results demonstrate that oral 5‐MTHF has a different pharmacokinetic profile with a higher bioavailability compared to folic acid, irrespective of the patient's genotype. Detrimental effects of the storage of high levels of the non‐natural isomer 6[R] 5‐MTHF cannot be excluded.
British Journal of Pharmacology (2004) 141, 825–830. doi:10.1038/sj.bjp.0705446
DOI: 10.1038/sj.bjp.0705446
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