A. Jordá, M. Portolés, R. Guasch, D. Bernal and GT. Saez (1989). Effect of caffeine on urea biosynthesis and some related processes, ketone bodies, ATP and liver amino acids. Biochemical pharmacology, 38(16), 2727-32. https://doi.org/10.1016/0006-2952(89)90560-1

PubMed 2764993

[Abstract]
An increase in urea synthesis has been found in rats administered large doses of caffeine. A parallel increase in urea biosynthesis was also found in hepatocytes isolated from caffeine-treated rats, which confirms a greater capacity for urea synthesis induced by caffeine. This increase appeared only after some days of caffeine treatment; during the first days there was no increase in serum urea levels or in in vitro studies of urea synthesis in isolated hepatocytes. However, no appreciable changes were found in either cytosolic or mitochondrial redox states, or in ATP levels in in vivo and in vitro studies. A parallelism was observed between the decreased amino acid levels in caffeine-treated rats and in isolated hepatocytes incubated with different concentrations of caffeine. Several possible mechanisms to explain these findings are considered in the discussion.