PLACEBO-CONTROLLED TRIALS OF ANTIOXIDANT THERAPY INCLUDING S-ADENOSYLMETHIONINE IN PATIENTS WITH RECURRENT NONGALLSTONE PANCREATITIS

Having shown in a 20-week placebo-controlled double-blind crossover tr ial that 'global' antioxidant supplementation - including selenium, be ta-carotene, vitamin C (ascorbic acid), vitamin E (tocopherol) and met hionine - curbs symptoms while correcting oxidative stress in patients with recurrent nongallstone pancreatitis, we have investigated throug h two further trials the relative importance of methionine versus that of the other antioxidants in effecting this good outcome. 30 consecut ive patients were entered into the second study in which therapeutic i ntervention involved only the active metabolite of methionine, S-adeno sylmethionine (SAMe), 2.4g per day in divided doses, Blood analysis sh owed that subnormal baseline levels of selenium, beta-carotene and vit amins E and C were unchanged throughout and that drug treatment result ed in supranormal levels of SAMe in plasma. SAMe proved to be ineffect ive clinically as judged by attack rate and background pain, as well a s biochemically as gauged by the percentages of oxidatively altered vi tamin C and linoleic acid. The coadministration of selenium and beta-c arotene with SAMe was tested in the third study. This was abandoned wh en 3 patients had a clearcut attack of pancreatitis while on subsequen t 'open' treatment. Analysis of clinical and biochemical information f rom 14 patients who had completed the 20-week trial confirmed the inef ficacy of the combination, although active treatment normalised serum selenium and beta-carotene concentrations while SAMe levels were again pushed into the supranormal range. The results show that SAMe on its own, or with additional selenium and beta-carotene, is ineffective in patients with recurrent nongallstone pancreatitis. By a process of eli mination with reference to biochemical measurements during the 3 trial s, and considering experimental evidence of the importance of methioni ne for pancreatic integrity, we cautiously suggest that an effective a ntioxidant prescription should include SAMe (or methionine) as well as vitamin C, with additional compounds as indicated by blood measuremen ts.