What Is NAD+ and Why Is It So Important?

NAD+ stands for nicotinamide adenine dinucleotide. It is one of the most essential molecules in our bodies. It is required for energy production by the mitochondria in our cells. It is a “co-enzyme,” working with hundreds of enzymes in essential processes throughout our tissues. It plays a crucial role in maintaining and repairing damage to our DNA. Many age-related disorders are likely caused, at least in part, by a decline in NAD+ levels in our cells as we get older. In “NAD+ Part 2” we will address ways in which we may be able to maintain NAD+ stores in our bodies even as we age and hopefully stave off a variety of diseases of aging (see also, “NAD Precursors – NR and NMN.”).

The decline in NAD+ as we age is associated with metabolic disorders (obesity, type 2 diabetes), heart disease, and degenerative neurologic disease such as dementia. Along with cancer, these are the hallmarks of aging itself. 

In addition to the classic “four horsemen” of aging, we lose muscle mass with age – around 10% per decade of life after age 25 years or so. We can combat this loss of muscle through resistance training and adequate protein intake, for example. But simply increasing NAD+ levels in muscle augments mitochondrial energy production and fitness in rodents. One mechanism is that boosting NAD+ levels activates sirtuin1 (more on sirtuins in an upcoming article). Inhibition of an enzyme that breaks down NAD+ and, therefore, increase NAD+ levels, has been shown in lab and human experiments to improve muscle weakness caused by defective mitochondrial function.

High-fat diets reduce the amount of NAD+ in the body. Studies have shown that giving NAD+ boosters to mice (1) alleviates age- and diet-related weight gain and improves their exercise capacity and (2) reverses adverse effects of diabetes.

Additional studies in mice have shown that increasing NAD+ in the heart helps restore function after injury due to lack of blood, as seen in coronary artery disease.

In a mouse model of Alzheimer’s disease raising NAD+ levels in the brain decreases accumulation of pathologic proteins and improves cognitive function. It also helps protect brain cells from injury and death due to diseased arteries in the brain.

Even while further studies in humans are ongoing we might all consider ways to pump up our NAD+. In Part 2 we explore how best to do this.

Both NAD+ and its precursors are very safe and are without known, significant side effects.

Note: Although I am a physician, the content in this article is not meant to diagnose, treat, cure or prevent illness or disease in the reader – it is for educational purposes only.

References

• Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 February; 22(2): 119–141. 
• Pirinen E, Canto C, Jo YS, et al. Pharmacological inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metabol 2014;19(6):1034-41.
• Canto C, Auwerx J. Targeting sirtuin 1 to improve metabolism: All you need is NAD⁺? Pharmacol. Rev. 2012;64:166–187.
• Xing S, Hu Y, Huang X, et al. Nicotinamide phosphoribosyltransferase-related signaling pathway in early Alzheimer’s disease mouse models. Mo Med Rep 2019;20(6):5163-71.