NAD Precursors, NR and NMN

NAD+ is an essential in mitochondrial energy metabolism and supplements with this interesting compound have been associated with longevity, overall improvement in health, and attenuation of diseases, including neurodegenerative disorders.

A decrease in NAD+ in the body, notably in the liver, skin, muscle, pancreas, and fat, is a hallmark of aging, including a variety of age-related diseases, including neurodegenerative diseases, cardiovascular diseases, diabetes, and cancer.

Beneficial effects of NAD+ include repair of damaged DNA, reduced stress responses, and improved and increased energy metabolism. 

NAD+ is therefore essential to healthy longevity. NAD+ may not be well absorbed in the intestine (a special transporter is required), and there is increasing evidence indicating that NAD⁺ cannot enter cells directly – it must be converted into smaller, less charged molecules to enter cells. 

Therefore, there has been a lot of interest in the administration of NAD+ precursors that are converted to NAD+ in the body. 

The two popular NAD+ precursors available as oral supplements include nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). NAD+ can also be synthesized by nicotinamide (NAM) and nicotinic acid (NA) through different metabolic pathways, but NR and NMN are more directly converted to NAD+. When these compounds are taken orally the NAD+ content of various tissues is increased. 

NR and NMN are well absorbed in the gut, and readily pass through the “blood-brain barrier” to enter the brain, where they are converted to NAD+. 

NR is the main precursor of NAD+ in the brain. NR is the only NAD+ precursor that can prevent degeneration of the nerve “arms” called axons as well as the oxidative stress and organ damage caused by overwhelming infection.

 In general, both NR and NMN have similar beneficial health effects, which are numerous and profound. It is widely believed that these effects on healthy longevity are related to conversion of NR and NMN to NAD+, though this is unproven. 

For purposes of this series of articles on supplements, it is assumed that the benefits of NAD+ precursors such as NR and NMN are mediated via conversion to NAD+. 

Accordingly, these important health benefits will be discussed in the article on NAD+ itself.

Both NR and NMN 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

• Hara N, Yamada K, Shibata T, et al. Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. J Biol Chem 2007;282:24574-24582.
• Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA, et al. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 2003;342:1243417.
• Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab 2016;24:795-806.