Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde : results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis

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Hellström , P M , Hendolin , P , Kaihovaara , P , Kronberg , L , Meierjohann , A , Millerhovf , A , Paloheimo , L , Sundelin , H , Syrjanen , K , Webb , D-L & Salaspuro , M 2017 , ' Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde : results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis ' Scandinavian Journal of Gastroenterology , vol. 52 , no. 2 , pp. 230-237 . DOI: 10.1080/00365521.2016.1249403

Title: Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde : results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis
Author: Hellström, Per M.; Hendolin, Panu; Kaihovaara, Pertti; Kronberg, Leif; Meierjohann, Axel; Millerhovf, Anders; Paloheimo, Lea; Sundelin, Heidi; Syrjanen, Kari; Webb, Dominic-Luc; Salaspuro, Mikko
Contributor: University of Helsinki, Clinicum
Date: 2017
Number of pages: 8
Belongs to series: Scandinavian Journal of Gastroenterology
ISSN: 0036-5521
URI: http://hdl.handle.net/10138/232746
Abstract: Introduction: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Methods: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Results: Administration of L-cysteine increased MTCA (p <.0004) and decreased gastric acetaldehyde concentrations by 68% (p <.0001). The peak L-cysteine level was 7552 +/- 2687 mu mol/L at 40 min and peak MTCA level 196 +/- 98 mu mol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. Conclusions: After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.
Subject: Alcohol
carcinogenesis
ethanol
prophylaxis
stomach
ALCOHOL-DEHYDROGENASE ACTIVITY
ALDEHYDE DEHYDROGENASE-2
STOMACH-CANCER
SALIVARY ACETALDEHYDE
GENETIC POLYMORPHISMS
ETHANOL-CONSUMPTION
RISK
DRINKING
PYLORI
ALDH2
3121 Internal medicine
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