Antioxidants, enzyme induction, and chronic pancreatitis: a reappraisal following studies in patients on anticonvulsants
Uden, S.; Acheson, D.W.; Reeves, J.; Worthington, H.V.; Hunt, L.P.; Brown, S.; Braganza, J.M.
European Journal of Clinical Nutrition 42(7): 561-569
1988
ISSN/ISBN: 0954-3007 PMID: 3224602 Document Number: 308844
Published dietary and pharmacokinetic 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 P-450 facilitates the pancreatic problem. This experiment was to determine the relative importance of the 2 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 P-450 so that their clearance of theophylline (which reflects cytochromes P-450 activities, and thereby provides an index of antioxidant demand) was as high as in the patients with chronic pancreatitis (CP) (mean +or- s.d. 123 +or- 59 ml/kg h and 120 +or- 62, respectively), and significantly higher than in controls (74 +or- 16 ml/kg h). Canonical variate analysis of the drug kinetic and dietary data provided 2 functions with which to separate the 3 groups. The first function, heavily weighted on selenium, separated the controls from the other 2 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 EP who went on to develop chronic pancreatitis.