Pharmacokinetics of (6S)-5-Methyltetrahydrofolate dicholine salt compared to folic acid: a randomized double-blind single dose cross-over study.
Level 2 - randomized trial
Randomized, double-blind, crossover trial in humans.
PubMed 41059007 · doi:10.29219/fnr.v69.12633
What was done
Researchers assessed the physicochemical properties (solubility, conductivity, melting point) of (6S)-5-Methyltetrahydrofolate dicholine salt ((6S)-5-MethylTHF-2Chol). They then compared its single-dose oral pharmacokinetics against equimolar folic acid in a randomized, double-blind, crossover trial.
What was found
The dicholine salt showed high solubility (650 mg/mL in water; 40 mg/mL under acidic conditions). In the pharmacokinetic evaluation, the incremental area under the curve (iAUC 0-8h) was significantly higher after (6S)-5-MethylTHF-2Chol administration compared to folic acid: 1.64-fold higher for total folate (P < 0.0001) and 2.56-fold higher for (6S)-5-MethylTHF (P < 0.0001).
Why it matters
This indicates that (6S)-5-MethylTHF-2Chol achieves greater short-term systemic folate exposure than traditional folic acid, supporting its application as a folate source in dietary supplements and nutraceuticals.
Limits
The abstract does not report the sample size, subject characteristics, specific dose amounts, or washout duration. The study only evaluated single-dose acute pharmacokinetics over 8 hours, leaving long-term safety and functional efficacy unassessed.
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