Introduction
In 1938, the pioneering vitamin-hunter Conrad Elvehjem and his coworkers put dogs on a synthetic diet supplemented with only the known B vitamins. When the dogs were near death and exhibited pellagra-like black tongue symptoms, the investigators fed the animals small-molecule fractions derived from liver. In this manner, nicotinic acid and nicotinamide, now collectively termed niacin, were identified as the “anti-black tongue factor” with essential nutritional activity (Elvehjem et al., 1938). Because niacins are the vitamin forms of nicotinamide adenine dinucleotide (NAD+), and eukaryotes also synthesize NAD+ de novo via the kynurenine pathway from tryptophan (Krehl et al. 1945, Schutz and Feigelson 1972), niacin supplementation prevents the pellagra that can occur in populations with a tryptophan-poor diet. In 1958, Jack Preiss and Philip Handler determined that nicotinic acid is phosphoribosylated to nicotinic acid mononucleotide (NaMN), which is then adenylylated to form nicotinic acid adenine dinucleotide (NaAD), which in turn is amidated to form NAD+ (Preiss and Handler 1958a, Preiss and Handler 1958b).