Pharmacokinetic study on the utilisation of 5‐methyltetrahydrofolate and folic acid in patients with coronary artery disease

Abstract

1 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). 2 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. 5 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. 6 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.

Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability

“…T polymorphism negatively affects the folate and homocysteine response [39]. However, in a pharmacokinetic study, no significant difference in pharmacokinetic parameters was found between patients with TT genotype and patients with CC genotype [40]. Likewise, in the present study, no significant difference was observed in the pharmacokinetic parameters of subjects having CC and CT genotypes of MTHFR.…”

5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

“…In a recent study comparing a single daily oral dose of 5 mg folic acid versus 5 mg of 5-MTHF, the peak concentration of 5-MTHF was nearly sevenfold higher than folic acid [30]. The authors also detected high levels of the non-natural isomer 6[R] 5-MTHF that lasted over a prolonged period of time; however, the significance of this isomer is not known.…”

“…The pharmacokinetic profile of 5-MTHF results in a higher bioavailability of folic acid irrespective of the patient’s genotype [30]. In a recent study comparing a single daily oral dose of 5 mg folic acid versus 5 mg of 5-MTHF, the peak concentration of 5-MTHF was nearly sevenfold higher than folic acid [30].…”

Prevention of NTDs - Proposal of a New Concept

“…However, the [6R]-isomer of the racemic mixture is presumed to be biologically inactive and therefore without nutritional significance. In addition, adverse effects of the [6R]-isomer on storage are under discussion (Mader et al, 1995;Willems et al, 2004). Thus, interventional trials with the racemic mixture of 5-MTHF as conducted by Fohr et al (2002), Litynski et al (2002), and Willems et al (2004) are not considered in this chapter.…”