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

Published online by Cambridge University Press:  09 March 2007

Isabelle Leclercq ,
Yves Horsmans ,
Jean-Pierre Desager ,
Stanislas Pauwels  and
André P. Geubel
Isabelle Leclercq
Affiliation:
Gastroenterology Unit, Université Catholique de Louvain, Brussels, Belgium
Yves Horsmans*
Affiliation:
Gastroenterology Unit, Université Catholique de Louvain, Brussels, Belgium
Jean-Pierre Desager
Affiliation:
Gastroenterology Unit, Université Catholique de Louvain, Brussels, Belgium
Stanislas Pauwels
Affiliation:
Gastroenterology Unit, Université Catholique de Louvain, Brussels, Belgium
André P. Geubel
Affiliation:
Gastroenterology Unit, Université Catholique de Louvain, Brussels, Belgium
*
*Corresponding author: Dr Y. Horsmans, fax +32 2764 8272, email [email protected]
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Abstract

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Dietary habits are often considered as a pathogenic factor for fatty liver. The impact of dietary intake and steatosis on drug metabolism remains poorly investigated. Our aim was to assess the effect of dietary intake on in vivo cytochrome P450 (CYP) activities in eleven patients with abnormal liver function tests potentially due to fatty liver and associated with a high-sugar 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 months restriction of dietary sugar intake. Features at inclusion were an increased BMI (30·3 (sd 3·2) kg/m2), high hepatic volume (1·96 (sd 0·48) litres), hyperechogenic liver parenchyma, elevated liver enzyme activities (alanine aminotransferase (EC 2.6.1.2) 58·6 (sd 17·4) IU/l with alanine aminotransferase : aspartate aminotransferase (EC 2.6.1.1) ratio > 1), together with a normal ABT value (0·68 (sd 0·21) % specific activity of administered dose of [14C]aminopyrine in breath after 1 h) and a high CYP2E1 activity (CZ AUC 20·3 (sd 7·1) μg/ml per h). A dietary sugar restriction was prescribed. On the basis of repeated interviews by the same dietitian, unaware of any clinical and biochemical data, six patients remained compliant to the diet and exhibited reductions in BMI (P < 0·001), serum alanine aminotransferase (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 of liver hyperechogenicity at ultrasound. In contrast, the five non-compliant patients did not show any significant change in any of these variables. In conclusion, CYP2E1 activity is induced in patients with perturbations of liver function tests potentially due to fatty liver. In these patients, effective dietary sugar restriction is associated with a reduction in liver volume, a reduction in CYP2E1 activity and an increased aminopyrine metabolism rate.

Keywords

Cytochrome P450AminopyrineChlorzoxazoneLiver
Type
Research Article
Information
British Journal of Nutrition , Volume 82 , Issue 4 , October 1999 , pp. 257 - 262
Copyright
Copyright © The Nutrition Society 1999

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