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.