Pharmacokinetics of (6S)-5-Methyltetrahydrofolate dicholine salt compared to folic acid: a randomized double-blind single dose cross-over study
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Background: (6S)-5-Methyltetrahydrofolate ((6S)-5-MethylTHF) is the physiological folate form in biological fluids. Salts of (6S)-5-MethylTHF may have advantages compared to folic acid and are increasingly used in foods and supplements. Objective and design: The present study describes the physicochemical properties of the (6S)-5-MethylTHF-2Chol salt as a source of methylfolate with respect to solubility, conductivity, and melting point. The pharmacokinetics of (6S)-5-MethylTHF-2Chol and folic acid were compared in a randomized controlled double-blind cross-over study using a single equimolar oral dose of each of the folate substances. Results: The solubility of the dicholine salt was very high (650 mg/mL in H2O and 40 mg/mL in H2O under acidic conditions). The incremental area under the curve (iAUC0-8h) was significantly higher after the administration of (6S)-5-MethylTHF-2Chol compared to folic acid ([1.64-fold, P < 0.0001] for total folate and 2.56-fold higher for (6S)-5-MethylTHF [P < 0.0001]). Discussion and conclusions: The bioavailability of (6S)-5-MethylTHF-2Chol is higher compared to folic acid. The crystalline structure of (6S)-5-MethylTHF-2Chol and its water solubility are advantageous in terms of stability in nutraceutical products and absorption in the gut. (6S)-5-MethylTHF-2Chol is the source of folate that may enable the development of new applications.
Source: Food & Nutrition Research
Authors: Christiane Schön, Antje Micka, Daniel Menzel, Manfred Wilhelm, Rima Obeid
Institutions: BioTeSys (Germany), Universitätsklinikum des Saarlandes
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,103
OpenAlex ID: W4414427005