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 H(2)O and 40 mg/mL in H(2)O under acidic conditions). The incremental area under the curve (iAUC(0-8h)) 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.