Comparative Studies in Niacin Metabolism. The Fate of Niacin in Man, Rat, Dog, Pig, Rabbit, Guinea Pig, Goat, Sheep and Calf

Abstract

Metabolism studies were conducted in 9 mammalian species (man, dog, rat, pig, calf, sheep, goat, guinea pig and rabbit) on normal diets and after the ingestion of nicotinamide, N¹-methylnicotinamide and the 6-pyridone of the latter. In a group of 10 healthy human subjects on a normal diet, from 3.6 to 12.0 mg of the 6-pyridone were excreted in 24 hours, with an average of 8.6 mg. The ingestion of large amounts of nicotinamide by two male subjects for a period of 5 days resulted in the excretion of 35 to 45% of the dose as 6-pyridone and 30 to 40% as N¹-methylnicotinamide; thus, 82 to 89% of ingested nicotinamide could be accounted for in the urine as niacin, N¹-methylnicotinamide, and the 6-pyridone. Only 30 to 40% of an oral dose of N¹-methylnicotinamide was recovered in the urine of these two subjects as 6-pyridone and N¹-methylnicotinamide. Parenteral administration of N¹-methylnicotinamide led to a recovery of 91% in the urine as N¹-methylnicotinamide plus the 6-pyridone. Ingested doses of the 6-pyridone were almost completely excreted unchanged. In the rat, only 3 to 5% of an oral dose of nicotinamide or of N¹-methylnicotinamide is excreted as the 6-pyridone. This animal excretes unchanged 80 to 90% of a dose of the 6-pyridone. N¹-methylnicotinamide accounts for 40 to 50% of an oral or intraperitoneal dose of N¹-methylnicotinamide or nicotinamide in this species. In the dog, in which N¹-methylnicotinamide accounts for almost all of the ingested niacin at saturation, no 6-pyridone could be detected in the urine after the administration of nicotinamide and only small amounts after doses of N¹-methylnicotinamide. The 6-pyridone, when given orally to dogs, was largely recovered in the urine. In the urine of the pig, N¹-methylnicotinamide accounted for 7% and 6-pyridone for 10% of an oral dose of nicotinamide. Almost half of the dose of 6-pyridone administered to the pig was not recovered in the urine. The rabbit excreted less than 4% of a total dose of nicotinamide as N¹-methylnicotinamide and the 6-pyridone. However, in response to an oral dose of N¹-methylnicotinamide, 17% appeared in the urine as N¹-methylnicotinamide and 25% as 6-pyridone. This indicates that N¹-methylnicotinamide is not a normal metabolite of niacin in this species. No appreciable amounts of 6-pyridone are “destroyed” by the rabbit when given orally. Relatively small amounts of 6-pyridone and N¹-methylnicotinamide are found in the urine of the guinea pig, sheep, calf, and goat, normally and after large doses of nicotinamide and N¹-methylnicotinamide. From 42 to 89% of an oral dose of the 6-pyridone could not be recovered in the urine of these species. Only 4 to 16% of an oral dose of N¹-methylnicotinamide could be accounted for in the urine of these herbivora. Apparently, in man, dog, rat and pig (and possibly other omnivora and carnivora?) excesses of niacin are largely disposed of by methylating processes. On the other hand, in the herbivora (rabbit, guinea pig and the polygastric species) niacin is probably disposed of by pathways other than those involving methylation.