The effect of dietary energy and protein deficiency on drug metabolism

The influence of a diet deficient in energy or protein on hepatic oxidation (Phase I reactions) and glucuronidation (Phase II reactions) in man has been examined. Nine healthy volunteers were fed an energy deficient diet (daily energy intake 4.3 MJ; daily protein intake 0.94 g/kg) and a protein deficient diet (daily energy intake 11.4 MJ; daily protein intake 0.31 g/kg) in random order. The control energy and protein intakes were 12.0 MJ and 1.52 g/kg, respectively. Each test diet period lasted 12 days. On Day 10, antipyrine 1000 mg and metronidazole 500 mg were given and elimination in saliva was determined. The metabolism of neither drugs was changed during the two dietary interventions, nor was their clearance to metabolites. On Day 12, the metabolism of oxazepam 15 mg was studied. The energy deficient and the protein deficient diet reduced the clearance rate of oxazepam by 20.3%, and 14.1% respectively. The elimination half-life was prolonged by 17.4% after the former and by 11.4% after the latter diet. Thus, both a low energy and a low protein intake decreased the glucuronidation of oxazepam, whereas no effect was observed on the rate of oxidation, expressed as the metabolism of antipyrine and metronidazole.