Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease.
Level 2 - randomized trial
Individual randomized crossover trial
PubMed 14769778 · doi:10.1038/sj.bjp.0705446
What was done
In an open-controlled, two-way, two-period randomized crossover pharmacokinetic study, patients with coronary artery disease and homozygosity for the MTHFR 677C->T mutation received a single oral dose of either 5 mg folic acid or 5 mg 6[R,S] 5-MTHF in each period. Venous blood samples were collected to determine the concentrations of the 6[S] 5-MTHF and 6[R] 5-MTHF diastereoisomers.
What was found
Peak concentrations of both isomers following 6[R,S] 5-MTHF administration were almost seven times higher than following folic acid administration, indicating higher bioavailability irrespective of patient genotype. At 1 week after a single dose of 6[R,S] 5-MTHF, 6[R] 5-MTHF was still detected following subsequent folic acid administration, indicating bodily storage of this unnatural isomer. Exact numerical pharmacokinetic values and patient sample size were not provided in the abstract.
Why it matters
This study demonstrates that oral 5-MTHF achieves higher peak bioavailability than folic acid in cardiovascular patients regardless of MTHFR genotype, while highlighting potential safety concerns regarding tissue accumulation of the unnatural 6[R] isomer from racemic preparations.
Limits
The abstract does not state the sample size (n) or exact pharmacokinetic parameters. The study evaluated single-dose administration rather than long-term clinical supplementation, used an open-label design, tested a racemic mixture instead of pure L-methylfolate, and did not assess clinical endpoints or homocysteine-lowering efficacy.
Cited by
- supports Methylated folate is better absorbed than standard folic acid.