Nicotinamide Riboside (NR) has gained significant attention as a potent precursor to Nicotinamide Adenine Dinucleotide (NAD+), a crucial coenzyme in cellular metabolism. NAD+ plays a fundamental role in various biological processes, including energy production, DNA repair, and gene expression regulation.

However, NAD+ levels naturally decline with age, contributing to the physiological decline associated with aging and the onset of age-related diseases.

NR, a form of vitamin B3, contributes to the biosynthesis of NAD+ through a salvage pathway that is distinct from the pathways utilizing other NAD+ precursors such as Nicotinamide (NAM) and Nicotinic Acid (NA). Once ingested, NR is converted into Nicotinamide Mononucleotide (NMN) by the action of the enzyme nicotinamide ribose kinase (NRK). Subsequently, NMN is converted to NAD+ through the activity of NMN adenylyltransferases (NMNATs).

This conversion process is particularly efficient because NR bypasses a feedback inhibition mechanism that typically limits the rate of NAD+ synthesis from NAM, the most common NAD+ precursor. NR does not require the use of NAMPT, an enzyme that catalyzes the rate-limiting step in NAD+ synthesis from NAM and is subject to regulation by cellular NAD+ levels. Therefore, NR supplementation can effectively increase cellular and tissue levels of NAD+ without the corresponding feedback inhibition that can accompany increased NAM levels.

Research has shown that increasing NAD+ levels through NR supplementation can improve mitochondrial function, enhance energy metabolism, and potentially delay the physiological changes associated with aging. For example, studies have demonstrated that NR enhances the function of sirtuins, a family of NAD+-dependent deacetylases that play key roles in cellular stress resistance, metabolic regulation, and longevity.

The therapeutic potential of NR extends beyond aging, as increasing NAD+ levels has been shown to benefit several models of disease, including cardiovascular diseases, neurodegenerative disorders, and metabolic conditions like obesity and diabetes.

NR represents a promising intervention for boosting NAD+ levels, supporting cellular health, and potentially mitigating the effects of aging and disease. The mechanism by which NR enhances NAD+ synthesis, combined with its ability to circumvent feedback inhibition, positions it as a superior supplement for maintaining optimal health and longevity.

References:

• Bieganowski, P., & Brenner, C. (2004). Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell, 117(4), 495-502.
• Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., ... & Auwerx, J. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metabolism, 15(6), 838-847.
• Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S. (2011). Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism, 14(4), 528-536.