Comparison of Metabolic Fates of Nicotinamide, NAD<sup>+</sup> and NADH Administered Orally and Intraperitoneally; Characterization of Oral NADH

Since NADH has been implicated in medication for some symptoms and as a possible supplement for health, we characterized the metabolic fate of NADH orally given to mice by comparing with those of nicotinamide (Nam), NAD+ and NADH intraperitoneally or orally administered. Mice were individually housed in metabolic cages, and divided into two sets of four groups. Within each set, one group was intraperitoneally or orally administered saline and the other three groups received intraperitoneal or oral administration of a pharmacological dose of Nam, NAD+ or NADH (5 micromol/mouse). Twenty-four hour urine samples for the day before and days 1 to 4 after administration were collected and analyzed for Nam and its metabolites. When mice were administered saline alone, urinary excretion of Nam and its metabolites, such as nicotinamide N-oxide (Nam N-oxide), N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py), and N1-methyl-4-pyridone-3-carboxamide (4-Py), was unchanged from day 0 to day 4. Intraperitoneal injection of Nam, NAD+ and NADH produced significant increases in urinary excretion of Nam and its metabolites. Similar results were obtained when Nam and NAD+ were given orally. On the other hand, oral administration of NADH did not bring about an increase in urinary excretion of Nam and its metabolites, suggesting that NADH in digestive organs has been decomposed to a compound(s) that cannot yield Nam. In fact, incubation of NADH at acidic pH to mimic the stomach resulted in rapid conversion of NADH to an unknown compound. Better understanding of the fate of oral NADH is needed for its therapeutic and supplemental use.