NAD Boosters: from Bench to Bedside

Nicotinamide adenine dinucleotide (NAD) is a molecule critical to the metabolism of living cells. It serves to transport electrons within the mitochondria, where ATP, the cell’s fundamental energy source, is produced.

Decline in NAD levels is a hallmark of ageing, and this has been linked to a variety of ageing diseases. There has been increasing interest in boosting NAD levels to promote health and longevity. Supplementation with NAD precursors showed promising results in rodents, but benefits have unfortunately not translated to humans as well as had been hoped. However, it is argued here that longer clinical trials with higher dosages might be needed to properly study the effects of NAD precursors.

The conceptual evolution of nicotinamide adenine dinucleotide (NAD⁺) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to a new wave of scientific interest in NAD⁺. NAD⁺ levels decline during ageing, and alterations in NAD⁺ homeostasis can be found in virtually all age-related diseases, including neurodegeneration, diabetes and cancer. In preclinical settings, various strategies to increase NAD⁺ levels have shown beneficial effects, thus starting a competitive race to discover marketable NAD⁺ boosters to improve healthspan and lifespan. Here, we review the basics of NAD⁺ biochemistry and metabolism, and its roles in health and disease, and we discuss current challenges and the future translational potential of NAD⁺ research.

Katsyuba, E., Romani, M., Hofer, D. and Auwerx, J.
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020). NAD+ homeostasis in health and disease. Nature Metabolism, 2(1), 9-31. doi: 10.1038/s42255-019-0161-5