Metabolic effects of nicotinamide administration in rats

Male rats fed a 12% casein diet without choline were injected i.p. daily for 2 or 5 weeks with either saline or 6, 20 or 60 mg of nicotinamide (NAM) per 100 g body weight. Weight gain, food intake and gain/food were lower for the NAM-treated groups compared to the controls. Urinary excretion of the major metabolite, N1-methylnicotinamide (NMN) increased with increasing dose of NAM. NAM administration did not alter the activity of hepatic nicotinamide methyltransferase. Excretion of another metabolite, N1-methyl-2-pyridone-5-carboxamide (2-PYR) was low and showed minimal changes in response to NAM administration. NAM administration did not affect urinary creatinine excretion. Livers of the NAM-injected groups were hypertrophied, and the total lipid content was increased. Kidney hypertrophy was also noted. Plasma and liver choline levels were decreased in response to NAM administration. We conclude that chronic NAM administration resulted in a methyl-group deficiency state due to the greatly increased need for methylation of NAM.