Plasma 3-methylbutanal in man and its relationship to hepatic encephalopathy.

3-Methylbutanal is a volatile aldehyde which in the rat is derived, at least in part, from colonic bacterial breakdown of leucine. It has been proposed as a toxin of importance in the pathogenesis of hepatic encephalopathy in man. A rapid, reliable and highly reproducible method for estimating 3-methylbutanal in plasma is described using a gas-chromatograph with a head space-sampler. The mean plasma 3-methylbutanal concentration in non-fasting patients with hepatic encephalopathy, 0.244 mumol/litre (range 0-1.30) was not significantly different from the mean value in controls, 0.116 mumol/litre (0-0.349). Oral leucine feeding resulted in significant increases in plasma 3-methylbutanal concentrations in both control subjects and patients with cirrhosis. Peak leucine and 3-methylbutanal values occurred at approximately the same time and usually within 120 min of leucine ingestion. Pre-treatment with neomycin had no effect on the results of leucine feeding. No changes occurred in the clinical condition or psychometric performance of patients with cirrhosis fed leucine despite increases in plasma 3-methylbutanal of up to 700% over basal values. In man plasma 3-methylbutanal, at least in part, derives from ingested leucine independently of the action of colonic bacteria. The role of this compound in the pathogenesis of hepatic encephalopathy in man needs further exploration.