NAD+ Precursors in Human Health and Disease: Current Status and Future Prospects.

Significance: Nicotinamide adenine dinucleotide (NAD+) acts as a cofactor in many important biological processes. The administration of NAD+ precursors increases the intracellular NAD+ pool and has beneficial effects on physiological changes and diseases associated with aging in various organisms, including rodents and humans. Recent Advances: Evidence from preclinical studies demonstrating the beneficial effects of NAD+ precursors has rapidly increased in the last decade. The results of these studies have prompted the development of clinical trials using NAD+ precursors, particularly nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). In addition, in vivo studies of NAD+ metabolism have rapidly progressed. Critical Issues: Several studies have demonstrated that the oral administration of NAD+ precursors, such as NR and NMN, is safe and significantly increases NAD+ levels in humans. However, the efficacy of these NAD+ precursors is lower than expected from the results of preclinical studies. In addition, the identification of the contribution of the host-gut microbiota interactions to NR and NMN metabolism has added to the complexity of NAD+ metabolism. Future Directions: Further studies are required to determine the efficacy of NAD+ precursors in humans. Further in vivo studies of NAD+ metabolism are required to optimize the effects of NAD+ supplementation. There is also a need for methods of delivering NAD+ precursors to target organs or tissues to increase the outcomes of clinical trials. Antioxid. Redox Signal. 39, 1133-1149.