Preclinical safety evaluation of sodium l-methylfolate

Sodium l-methylfolate (L-5-MTHF-Na; CAS Number 151533-22-1) is a source of folate proposed to be used as an alternative source of folic acid in human food. The safety of L-5-MTHF-Na was evaluated by testing for genotoxicity, and repeated dose toxicity in guideline preclinical studies. L-5-MTHF-Na was not mutagenic in the bacterial reverse mutation assay and did not induce cytogenetic effects in an in vitro chromosome aberration test and in vitro micronucleus test. In repeated dose 14-day and 90-day oral toxicity studies, rats administered up to 1000 mg/kg bw/day of L-5-MTHF-Na via oral gavage had no adverse treatment-related effects on any endpoint: clinical observations, body weights, food consumption, ophthalmic examination, neurological battery, hematology, clinical chemistry, urinalysis, tissue weights, macroscopic and microscopic observations. There was an observation of non-adverse adaptive changes in creatine kinase levels in male and female rats in the 90-day study with no tissue weight or histopathological correlate. The lack of adverse findings observed with L-5-MTHF-Na are consistent with negative findings observed in published preclinical and clinical studies on calcium l-methylfolate (L-5-MTHF-Ca). In conclusion, L-5-MTHF-Na is shown to have an overall safe profile for its use as a dietary source of folate for nutritional purposes.