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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. 3. 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. 4. 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. 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.
AuthorsFrank F Willems, Godfried H J Boers, Henk J Blom, Wim R M Aengevaeren, Freek W A Verheugt
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 141 Issue 5 Pg. 825-30 (Mar 2004) ISSN: 0007-1188 [Print] England
PMID14769778 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Tetrahydrofolates
  • Folic Acid
  • 5-methyltetrahydrofolate
Topics
  • Aged
  • Biological Availability
  • Coronary Artery Disease (metabolism)
  • Cross-Over Studies
  • Female
  • Folic Acid (blood, pharmacokinetics)
  • Humans
  • Male
  • Middle Aged
  • Tetrahydrofolates (blood, pharmacokinetics)

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