Nicotinamide riboside

Nicotinamide riboside

Names
Other names 1-(β-D-Ribofuranosyl)nicotinamide; N-Ribosylnicotinamide
Identifiers
CAS Number	1341-23-7
ChEBI	CHEBI:15927
PubChem	439924
Properties
Chemical formula	C11H15N2O5+
Molar mass	255.25 g/mol
Vapor pressure	{{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Nicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B₃ that functions as a precursor to nicotinamide adenine dinucleotide or NAD+. NR has been a recent focus of life extension research after David Sinclair published a study in 2013 showing NAD+ levels decrease with age in mice.

Discovery

Bacterial NAD precursor

NR was first described in 1944 as a growth factor, termed Factor V, for Haemophilus influenza, a bacterium that lives in and depends on blood. Factor V, purified from blood was shown to exist in three forms: NAD+, NMN and NR. NR was the compound that led to the most rapid growth of this bacterium. Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.

Eukaryotic NAD precursor vitamin

In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase, which led several groups to probe yeast NAD+ metabolism for genes and enzymes that might regulate lifespan. Biosynthesis of NAD+ in yeast was thought to flow exclusively through NAMN.

Surprisingly, when NAD+ synthase (glutamine-hydrolysing) was deleted from yeast cells, NR permitted yeast cells to grow. Thus, these investigators proceeded to clone yeast and human nicotinamide riboside kinases and demonstrate the conversion of NR to NMN by these enzymes in vitro and in vivo. They also demonstrated that NR is a natural product, the so-called hidden vitamin found in cow's milk.

Potential applications in human health

High dose nicotinic acid is used as an agent that elevates high-density lipoprotein cholesterol, lowers low-density lipoprotein cholesterol and lower free fatty acids through a mechanism that is not completely understood. It was suggested that nicotinamide riboside might possess such an activity by elevating NAD in the cells responsible for reverse cholesterol transport. An experiment with mice on high fat diet appears to support the potential of treatment or prevention of dyslipidemia with nicotinamide riboside.

The discovery that the Wallerian degeneration slow gene encodes a protein fusion with NMN adenylyltransferase 1 indicated that increased NAD+ precursor supplementation might oppose neurodegenerative processes. NR blocks degeneration of surgically severed dorsal root ganglion neurons ex vivo and protects against noise-induced hearing loss in living mice.

Nicotinamide riboside prevents muscle, neural and menalocyte stem cell senescence. Increased muscular regeneration in mice has been observed after treatment with nicotinamide riboside, leading to speculation that it might improve regeneration of organs such as the liver, kidney, and heart.

Commercialization

ChromaDex acquired intellectual property on uses and synthesis of NR from Dartmouth College, Cornell University, and Washington University and began distributing NR as Niagen in 2013. ChromaDex completed a clinical study on nicotinamide riboside in 2015, demonstrating that it can increase the co-enzyme NAD+, and began a clinical trial in March 2016 to examine the benefits if taken daily for eight consecutive weeks.

See also

• Nicotinamide mononucleotide

Further reading

• NIH researchers find potential target for reducing obesity-related inflammation
• Beyond Resveratrol: The Anti-Aging NAD Fad
• Mechanism of Nicotinamide Riboside as an Aid to Weight Loss
• Increasing NAD+ availability in skeletal muscle to augment energy metabolism
• NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice