on September 15, 2025
History
NR was first identified as a naturally occurring nutrient in milk in 2004, when researchers discovered its role as a NAD+ precursor in humans. This discovery laid the foundation for subsequent research on NR metabolism and its potential use in dietary supplementation.
Chemical Structure
Nicotinamide riboside is a pyridine-nucleoside derivative of nicotinamide. It consists of a nicotinamide moiety bound to a ribose sugar. NR is one of several NAD+ precursors, along with nicotinamide and nicotinamide mononucleotide (NMN), which is an intermediate in the NAD+ biosynthesis pathway.
Dietary Sources
NR occurs naturally in milk, yeast, and certain vegetables. Concentrations in typical diets are low, so NR is also supplied in supplement form as nicotinamide riboside chloride, providing a standardized dose.
Role in the Body
NR contributes to the cellular pool of NAD+, an essential coenzyme in numerous metabolic reactions. NAD+ functions in redox reactions, transferring electrons in cellular respiration, and also serves as a substrate for enzymes such as sirtuins and poly(ADP-ribose) polymerases (PARPs). These enzymes participate in energy metabolism and maintenance of genomic integrity.
In cells, NR is phosphorylated by nicotinamide riboside kinases to form NMN, which is then converted to NAD+ through the NAD+ salvage pathway. This highlights the metabolic link between NR and NMN and the multiple pathways through which NAD+ levels are maintained.
Absorption and Bioavailability
The bioavailability of NR refers to the extent and rate at which NR is absorbed and becomes available in the bloodstream for conversion to NAD+. Studies in humans have shown that NR is orally bioavailable:
- Intestinal Absorption: NR is absorbed primarily in the small intestine. Enzymes such as nicotinamide riboside kinases phosphorylate NR to NMN, which then enters the NAD+ biosynthesis pathway.
- Blood Levels: Oral NR supplementation increases NAD+ and related metabolites in whole blood and peripheral blood mononuclear cells (PBMCs). These increases are measurable within hours of ingestion and can be sustained with repeated dosing.
- Tissue Distribution: Animal and human studies suggest that NAD+ derived from NR is distributed to multiple tissues, including skeletal muscle and liver. While precise tissue distribution in humans is still being investigated, NR is considered effective at raising systemic NAD+ levels.
- Comparison with Other Precursors: NR differs from nicotinamide and nicotinic acid in absorption and conversion efficiency. NR bypasses some intermediate steps in the NAD+ salvage pathway, potentially leading to more direct NAD+ production in certain tissues. Its metabolic link to NMN illustrates how multiple pathways converge to maintain NAD+ levels.
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.
- Yoshino, J., et al. (2017). NAD+ intermediates: The biology and therapeutic potential of nicotinamide riboside. Cell Metabolism, 27(3), 529–547.
- Damgaard, M. V., et al. (2023). What is really known about the effects of nicotinamide riboside supplementation in humans? Science Advances, 9(2), eadi4862.
- Martens, C. R., et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9(1), 1286.
- Nanga, R. P. R., et al. (2024). Acute nicotinamide riboside supplementation increases cerebral NAD+ levels in healthy human volunteers. Magnetic Resonance in Medicine, 92(1), 1–9.
