Nicotinamide Methylation in Patients with Cirrhosis

Methylation reactions play an important role in the transformation of endogenous and exogenous substances. Up to 85% of all transmethylation reactions occur in the liver. Several studies have shown that these metabolic processes are greatly influenced by the presence of hepatic diseases. We investigated the methylation of nicotinamide in 16 control subjects and in 29 patients with cirrhosis (19 Child A, 10 Child B). The basal serum value of N-methyl-nicotinamide was measured in all subjects. In seven controls and in nine patients with cirrhosis (5 Child A and 4 Child B), the serum levels and urinary excretion (5 and 24 h) of N-methyl-nicotinamide were also evaluated after oral administration of nicotinamide (1.5 mg/kg body weight). The basal serum levels of N-methyl-nicotinamide were significantly (p < 0.05) higher in patients with cirrhosis (Child A: median 34 ng/ml, 16th percentile 24, 84th percentile 61; Child B median 45, 16th percentile 34, 84th percentile 81) than in controls (median 22, 16th percentile 13, 85th percentile 28). After the nicotinamide load the urinary excretion and the time course of serum N-methyl-nicotinamide in cirrhosis were also higher (p < 0.05) than in controls (24 h urinary excretion = 66.2 mg +/- 5 S.D. in cirrhosis; 47.2 +/- 10.3 in controls) (area under the serum concentration versus time curve = 68 micrograms.ml-1.min-1 +/- 22 S.D. in cirrhosis; 32 +/- 15 in controls). In conclusion, our results show that cirrhosis does not impair the efficiency of nicotinamide methylation.