Effects of N-acetyl- l-cysteine in patients with chronic atrophic gastritis and nonulcer dyspepsia: a phase III pilot study

Abstract

Several studies have suggested that oxidative damage may contribute to gastritis. This damage is counteracted by various scavengers including glutathione (GSH), which may help defend the gastric mucosa. N-acetyl- l-cysteine (NAC), a GSH precursor, could thus be of therapeutic interest. This multiple-dose, double-masked, randomized, parallel-group, phase III pilot study was designed to assess the effects of NAC in 18 patients undergoing upper gastrointestinal endoscopy for dyspepsia who had endoscopically and histologically confirmed chronic atrophic gastritis but no peptic ulcer. Patients were randomly allocated to one of three treatment groups (NAC 1 g/d at bedtime, 1 g two times a day [2 g/d], or 2 g two times a day [4 g/d]) for 4 weeks. After treatment, patients underwent a second endoscopy. During both endoscopies, multiple biopsies were taken for histologic examination (based on a semiquantitative score according to the Sydney system). Reduced/oxidized glutathione (GSH/GSSG) and malondialdehyde (MDA) were also measured (using high-performance liquid chromatography and fluorometric assay). At recruitment, 6 patients tested negative and 12 tested positive for Helicobacter pylori. Serologic findings and symptoms (semiquantitatively scored) were collected at the beginning and end of the trial. After treatment, 13 (72%) of 18 patients showed improvement on endoscopy, irrespective of NAC dose, and 5 (28%) showed no change. Histologically, polymorph infiltration was significantly reduced in patients who received 2 g of NAC. The 5-point total symptom score was lower, but not significantly so, in patients who received the other doses. Because of a high variability, no significant change in GSH and MDA was found. No difference was observed between H pylori-positive and -negative patients. No relevant changes were detected in laboratory findings, and the most common adverse events were constipation, abdominal pain, and flatulence. Our findings suggest that in patients with gastritis and nonulcer dyspepsia, NAC is fairly well tolerated and apparently leads to endoscopic, symptomatic, and to some extent histologic improvement, unrelated to changes in mucosal GSH levels.