Antioxidants, enzyme induction, and chronic pancreatitis: a reappraisal following studies in patients on anticonvulsants

Abstract

Our published dietary and pharmakokinetic studies in 15 patients with idiopathic chronic pancreatitis and 15 age- and sex-matched controls suggested that a combination of subnormal antioxidant intakes and chronic induction of the cytochromes P450 facilitates the pancreatic problem. We have now attempted to determine the relative importance of these two factors by studying a group of 15 institutionalized patients with epilepsy (EP), but without abdominal pain, who were on long-term treatment with anticonvulsant inducers of cytochromes P450 so that their clearance of theophylline (which reflects cytochromes P450 activities, and thereby provides an index of antioxidant demand) was as high as in the patients with chronic pancreatitis (CP) (mean +/- s.d., 123 +/- 59 ml/kg/h versus 120 +/- 62 respectively), and significantly higher than in controls (74 +/- 16 ml/kg/h, P less than 0.02). Canonical variate analysis of the drug kinetic and dietary data provided two functions with which to separate the three groups. The first function, heavily weighted on selenium, separated the controls from the other two groups whose values were lower; the second function, equally weighted on methionine and vitamin C, separated the EP group from the CP group whose values were generally lower. The results suggest that enzyme induction per se is not the critical factor in the development of CP. Instead, suboptimal availability of antioxidants in the face of increased demand--in particular of those substances that protect cells against non-biological free radicals--may be the key consideration, a deduction reinforced by observations in patients with epilepsy who went on to develop chronic pancreatitis.