Therapeutic potential of nicotinamide adenine dinucleotide (NAD)

Nicotinamide adenine nucleotide (NAD) is a small ubiquitous hydrophilic cofactor that participates in several aspects of cellular metabolism. As a coenzyme it has an essential role in the regulation of energetic metabolism, but it is also a cosubstrate for enzymes that regulate fundamental biological processes such as transcriptional regulation, signaling and DNA repairing among others. The fluctuation and oxidative state of NAD levels regulate the activity of these enzymes, which is translated into marked effects on cellular function. While alterations in NAD homeostasis are a common feature of different conditions and age-associated diseases, in general, increased NAD levels have been associated with beneficial health effects. Due to its therapeutic potential, the interest in this molecule has been renewed, and the regulation of NAD metabolism has become an attractive target for drug discovery. In fact, different approaches to replenish or increase NAD levels have been tested, including enhancement of biosynthesis and inhibition of NAD breakdown. Despite further research is needed, this review provides an overview and update on NAD metabolism, including the therapeutic potential of its regulation, as well as pharmacokinetics, safety, precautions and formulation challenges of NAD supplementation.