Preclinical safety assessments of nicotinamide riboside hydrogen malate

Nicotinamide riboside (NR) is an analog of vitamin B3, which is naturally present in trace amounts in selected foods. Several B3 analogs are known precursors in the synthesis of nicotinamide adenine dinucleotide, including nicotinic acid (niacin) and nicotinamide (niacinamide). The safety of nicotinamide riboside hydrogen malate (NRHM), a salt of NR, was assessed in a bacterial reverse mutagenesis assay (Ames), in vitro micronucleus assay in human peripheral lymphocytes, a 14-day acute toxicology test (Sprague-Dawley rats), and a 90-day sub-chronic toxicology study in Sprague-Dawley rats. Based on the results of the 14-day study, the 90-day sub-chronic study was conducted comparing oral NRHM at 1000, 1500, and 3000 mg/kg/day with a vehicle control. No genotoxicity was observed. There were no mortalities or clinical observations attributed to the NRHM test substance administration over the course of the study. The no-observed-adverse effect level for NRHM was determined to be 3000 mg/kg bw/day in the female rats but 2000 mg/kg bw/day in the male rats due to a significantly lower body weight in males at the high dose. The results of this study imply that NRHM can be manufactured at a high level of purity, is not genotoxic, and is well-tolerated in in Sprague-Dawley rats.