Alcohol acutely down-regulates urea synthesis in normal men

Background: Human nitrogen balance studies suggest that alcohol up-regulates urea synthesis and promotes nitrogen catabolism, whereas animal studies conversely indicate that alcohol down-regulates urea synthesis, possibly via a redox effect. This study aimed to investigate the acute effects of alcohol exposure at a plasma concentration of about 10 mmol/liter on urea synthesis in healthy volunteers and to investigate whether methylene blue alleviates the effect of alcohol. Methods: Eleven males were studied three times in a randomized sequence crossover design. They received either alanine infusion to control the rate of urea synthesis (control), alanine + alcohol, or alanine + alcohol + methylene blue. The substrate independent regulation of urea synthesis was studied by means of the functional hepatic nitrogen clearance, that is, the slope of the linear relation between blood amino nitrogen concentrations and rates of urea synthesis. Results: Alcohol reduced functional hepatic nitrogen clearance to 37% and 51% during alcohol and alcohol + methylene blue infusion, respectively (p = 0.007). Accordingly, whole body nitrogen retention was higher during alcohol infusion. Glucagon, which up-regulates urea synthesis, increased during alcohol infusion. There was no change in insulin. Blood glucose was slightly lower at the end of the experiment when alcohol was infused. Conclusion: Low-dose infusion of alcohol acutely down-regulated urea synthesis in healthy volunteers, transiently favoring nitrogen preservation. The effect seemed not to depend on hormonal changes. It remains to be explored how the present results can be reconciled with the reported nitrogen wasting of chronic alcoholics.