Dietary restriction of energy and sugar results in a reduction in human cytochrome P450 2E1 activity

Dietary habits are often considered as a pathogenic factor for fatty liver. The impact of dietary intake and steatosis on drug metabolism remains poor ly investigated. Our aim was to assess the effect of dietary intake on in v ivo cytochrome P450 (CYP) activities in eleven patients with abnormal liver function tests potentially due to fatty liver and associated with a high-s ugar diet. Liver function tests, liver volume, aminopyrine breath test (ABT ) and chlorzoxazone (CZ) pharmacokinetics (area under the curve, AUC) which are known to reflect CYP2E1 activity were evaluated before and after 2 mon ths restriction of dietary sugar intake. Features at inclusion were an incr eased BMI (30.3 (SD 3.2) kg/m(2)), high hepatic volume (1.96 (SD 0.48) litr es), hyperechogenic liver parenchyma, elevated liver enzyme activities (ala nine aminotransferase (EC 2.6.1.2) 58.6 (SD 17.4) IU/l with alanine aminotr ansferase: aspartate aminotransferase (EC 2.6.1.1) ratio > 1), together wit h a normal ABT value (0.68 (SD 0.21) % specific activity of administered do se of [C-14]aminopyrine in breath after 1 h) and a high CYP2E1 activity (CZ AUC 20.3 (SD 7.1) mu g/ml per h). A dietary sugar restriction was prescrib ed. On the basis of repeated interviews by the same dietitian, unaware of a ny clinical and biochemical data, six patients remained compliant to the di et and exhibited reductions in BMI (P < 0.001), serum alanine aminotransfer ase (P = 0.008), liver volume (P = 0.002) and CYP2E1 activity (P = 0.007), a significant increase in ABT (P < 0.001) together with the disappearance o f liver hyperechogenicity at ultrasound. In contrast, the five non-complian t patients did not show any significant change in any of these variables. I n conclusion, CYP2E1 activity is induced in patients with perturbations of liver function tests potentially due to fatty liver. In these patients, eff ective dietary sugar restriction is associated with a reduction in liver vo lume, a reduction in CYP2E1 activity and an increased aminopyrine metabolis m rate.