Nicotinamide riboside

Nicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+. Nicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+. While the molecular weight of nicotinamide riboside is 255.25 g/mol, that of its chloride salt is 290.70 g/mol. As such, 100 mg of nicotinamide riboside chloride provides 88 mg of nicotinamide riboside. Nicotinamide riboside (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+. In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase, which led several research 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 (nicotinic acid mononucleotide). When NAD+ synthase (glutamine-hydrolysing) was deleted from yeast cells, NR permitted yeast cells to grow. Thus, these Dartmouth College investigators proceeded to clone yeast and human nicotinamide riboside kinases and demonstrate the conversion of NR to NMN by nicotinamide riboside kinases in vitro and in vivo. They also demonstrated that NR is a natural product found in cow's milk. Although it is a form of vitamin B3, NR exhibits unique properties that distinguish it from the other B3 vitamins—niacin and nicotinamide. In a head-to-head experiment conducted on mice, each of these vitamins exhibited unique effects on the hepatic NAD+ metabolome with unique kinetics, and with NR as the form of B3 that produced the greatest increase in NAD+ at a single timepoint. Different biosynthetic pathways are responsible for converting the different B3 vitamins into NAD+. The enzyme nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of the two-step pathway converting nicotinamide to NAD+. Two nicotinamide riboside kinases (NRK1 and NRK2) convert NR to NAD+ via a pathway that does not require Nampt. Animal studies have demonstrated that these enzymes respond differently to age and stress. In a mouse model of dilated cardiomyopathy, NRK2 mRNA expression increased, while Nampt mRNA expression decreased. A similar increase in NRK1 and NRK2 expression has been observed in injured central and peripheral neurons. Niacin is known for its tendency to cause an uncomfortable flushing of the skin. This flushing is triggered by the activation of the GPR109A G-protein coupled receptor. NR does not activate this receptor, and has not been shown to cause flushing in humans—even at doses as high as 2,000 mg/day.