Comprehensive safety assessment of novel dicholine folate vitamin.

Novel vitamin salt forms can offer formulation advantages while retaining the biological activity of the parent compound. This safety assessment evaluates dicholine (6S)-5-methyltetrahydrofolate (dicholine L-5-MTHF), a reduced folate source designed to deliver biologically active L-5-MTHF with improved water solubility and stability relative to existing reduced folate salts. As L-5-MTHF salts dissociate to yield L-5-MTHF and their respective counterions, the safety of dicholine L-5-MTHF was assessed using a weight-of-evidence approach that integrates published data for existing L-5-MTHF salts together with information on choline exposure. A standard in vitro genotoxicity battery conducted with dicholine L-5-MTHF, including bacterial reverse mutation, chromosome aberration, and mammalian micronucleus assays, was negative and consistent with the broader genotoxicity profile of other reduced folate sources. In addition, subchronic oral toxicity studies in rats with calcium and sodium L-5-MTHF salts identified no adverse effects at the highest doses tested, and human clinical studies with L-5-MTHF salts support tolerability, including at intakes above the adult UL established for folic acid. Collectively, these data support the safety of dicholine L-5-MTHF at the proposed use level.