Balancing NAD deficits with nicotinamide riboside: therapeutic possibilities and limitations.

Alterations in cellular nicotinamide adenine dinucleotide (NAD) levels have been observed in multiple lifestyle and age-related medical conditions. This has led to the hypothesis that dietary supplementation with NAD precursors, or vitamin B3s, could exert health benefits. Among the different molecules that can act as NAD precursors, Nicotinamide Riboside (NR) has gained most attention due to its success in alleviating and treating disease conditions at the pre-clinical level. However, the clinical outcomes for NR supplementation strategies have not yet met the expectations generated in mouse models. In this review we aim to provide a comprehensive view on NAD biology, what causes NAD deficits and the journey of NR from its discovery to its clinical development. We also discuss what are the current limitations in NR-based therapies and potential ways to overcome them. Overall, this review will not only provide tools to understand NAD biology and assess its changes in disease situations, but also to decide which NAD precursor could have the best therapeutic potential.