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

Abstract

Summary 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 ϩ 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 ϩ or NADH (5 mol/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), N 1 -methylnicotinamide (MNA), N 1 -methyl-2-pyridone-5-carboxamide (2-Py), and N 1 -methyl-4-pyridone-3-carboxamide (4-Py), was unchanged from day 0 to day 4. Intraperitoneal injection of Nam, NAD ϩ and NADH produced significant increases in urinary excretion of Nam and its metabolites. Similar results were obtained when Nam and NAD ϩ 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.

Pharmacokinetic aspects of reduced nicotinamide adenin dinucleotide (NADH) in rats

“…Our results assessing the absorption in the everted gut sac amend the experiments of Kimura and co-workers (31), who showed that NADH administered orally will be decomposed in the acidic pH of the stomach. With our in vitro experiments using the established model of the everted gut sac we could confirm an enteral absorption of the intact NADH molecule.…”

“…On the other hand the results indicated that oral administration was ineffective. This is confirmed by Kimura and co-workers (31) showing that oral administered NADH did not change NADH metabolite concentrations in rats. The authors suggest that NADH may be converted in the acidic milieu of the stomach or may not be absorbed in the gastrointestinal system.…”

“…The authors suggest that NADH may be converted in the acidic milieu of the stomach or may not be absorbed in the gastrointestinal system. They could demonstrate that NADH was converted into an unknown compound after a short time of incubation under acidic conditions (31). However, whether or not NADH is absorbed in the intestinal tract remained still unknown.…”

Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes

“…To determine nutritional and therapeutic benefits due to maintenance of NAD + levels in tissues, organs, and cells, supplementation with either NAD + and its reduced form NADH or its precursors represents a potential therapeutic strategy to slow down the aging process and/or improve the management of age-related degenerative disease. Oral supplementation with NAD + and NADH has not shown any significant elevation in plasma or tissue levels of NAD + , potentially due to inefficient metabolism of NAD + through the gut, thus leading to poor bioavailability (177). In addition, oral NADH may not be oxidized to NAD + in the body, may not be efficiently absorbed by the gastrointestinal system, or may be converted to a product before absorption that cannot yield NAM (34,35).…”

Antioxidant metabolism induced by quinic acid. increased urinary excretion of tryptophan and nicotinamide

“…Even when samples were included in the analysis after 4 months of follow-up after no Aqua Bimini, the tryptophan and nicotinamide levels in urine remained elevated (Table 1). Tryptophan and nicotinamide in urine are wellknown strong indicators of the status of these nutrients in the rest of the body (McCreanor and Bender, 1986;Shibata, 1989;Shibata and Matsuo, 1990;Shibata and Toda, 1997;Kimura et al, 2006), and so it was concluded that quinic acid supplementation not only increased the synthesis of hippuric acid in the GI tract but also tryptophan and nicotinamide.…”