Niacin is different from other vitamins because nicotinamide is biosynthesized from tryptophan. We have studied tryptophan-nicotinamide metabolism to elucidate the physiological importance of this tryptophan-nicotinamide conversion pathway for maintenance of niacin nutritional status in rats and humans. Human studies revealed that 1 mg of nicotinamide was converted from a tryptophan intake of 67 mg, and that the conversion ratio of tryptophan to nicotinamide was enhanced from mid to late pregnancy in a time-dependent manner. Animal experiments showed that the supply of nicotinamide from tryptophan was able to maintain a sufficient niacin nutritional status without niacin intake, and that the liver, but not the kidney, played a critical role in the synthesis of nicotinamide from tryptophan. Phthalate esters dramatically increased the tryptophan-nicotinamide conversion via inhibition of aminomuconate semialdehyde decarboxylase, the key enzyme in the tryptophan-nicotinamide conversion pathway.