Safety of stabilized, orally absorbable, reduced nicotinamide adenine dinucleotide (NADH): a 26-week oral tablet administration of ENADA/NADH for chronic toxicity study in rats.

The safety of the stabilized, orally absorbable form of reduced nicotinamide adenine dinucleotide (NADH), known under the brand name ENADA, was investigated over a period of 26 weeks. Eighty healthy rats (40 males and 40 females) were divided into two groups. One tablet ENADA/NADH 5 mg per day was administered orally to one group while identical-looking white tablets not containing NADH (placebo) were given to the other group. The following parameters were statistically analyzed: body weight, body weight gain, food consumption, hematology, clinical chemistry, organ weight and organ histology. Clinical signs and mortality were recorded. There were no deaths associated with the study drug and no treatment-releated clinical signs. No differences in body weight between the placebo and the ENADA-treated males were observed. In the second half of the treatment period (weeks 13-26) females treated with NADH gained significantly (p < 0.05) more body weight than the controls. Food consumption in the treated males was similar to that in controls. From approximately week 15, the treated females consumed up to 10% more food than the controls. No differences were observed between the control and the treated groups in terms of hematology or clinical chemistry parameters. There was no apparent treatment-related effect on urine analysis parameters or on either the absolute or the relative organ weight. Furthermore, no macroscopic evidence of specific target organ toxicity associated with the test drug was observed. Histological findings in the treated rats were generally similar to those in control rats. A daily dose of 5 mg in a rat corresponds to a dose of 175 mg per day in a 70-kg human. This is 175 times the recommended daily dosage of 1 ENADA tablet per day. Hence ENADA/NADH 5 mg tablets can be generally regarded as safe.