Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors

Coenzyme I (nicotinamide adenine dinucleotide, NAD(+)/NADH) and coenzyme II (nicotinamide adenine dinucleotide phosphate, NADP(+/)NADPH) are involved in various biological processes in mammalian cells. NAD(+) is synthesised through the de novo and salvage pathways, whereas coenzyme II cannot be synthesised de novo. NAD(+) is a precursor of coenzyme II. Although NAD(+) is synthesised in sufficient amounts under normal conditions, shortage in its supply due to over consumption and its decreased synthesis has been observed with increasing age and under certain disease conditions. Several studies have proved that in a wide range of tissues, such as liver, skin, muscle, pancreas, and fat, the level of NAD(+) decreases with age. However, in the brain tissue, the level of NADH gradually increases and that of NAD(+) decreases in aged people. The ratio of NAD(+)/NADH indicates the cellular redox state. A decrease in this ratio affects the cellular anaerobic glycolysis and oxidative phosphorylation functions, which reduces the ability of cells to produce ATP. Therefore, increasing the exogenous NAD(+) supply under certain disease conditions or in elderly people may be beneficial. Precursors of NAD(+) have been extensively explored and have been reported to effectively increase NAD(+) levels and possess a broad range of functions. In this review article, we discuss the pharmacokinetics and pharmacodynamics of NAD(+) precursors.