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.
BACKGROUND
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 μmol/L at 40 min and peak MTCA level 196 ± 98 μmol/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.
a Department of Medical Sciences, Gastroenterology and Hepatology Unit , Uppsala University Hospital, Uppsala University , Uppsala , Sweden.
Per M
PM
Hellström
b Clinical Sciences , Biohit Oyj , Helsinki , Finland.
Panu
P
Hendolin
b Clinical Sciences , Biohit Oyj , Helsinki , Finland.|c Research Unit on Acetaldehyde and Cancer, University of Helsinki , Helsinki , Finland.
Pertti
P
Kaihovaara
d Laboratory of Organic Chemistry , Johan Gadolin Process Chemistry Centre, Åbo Akademi University , Turku , Finland.
Leif
L
Kronberg
d Laboratory of Organic Chemistry , Johan Gadolin Process Chemistry Centre, Åbo Akademi University , Turku , Finland.
Axel
A
Meierjohann
e Clinical Trial Consultants , Uppsala University Hospital , Uppsala , Sweden.
Anders
A
Millerhovf
b Clinical Sciences , Biohit Oyj , Helsinki , Finland.
Lea
L
Paloheimo
d Laboratory of Organic Chemistry , Johan Gadolin Process Chemistry Centre, Åbo Akademi University , Turku , Finland.
Heidi
H
Sundelin
b Clinical Sciences , Biohit Oyj , Helsinki , Finland.
Kari
K
Syrjänen
a Department of Medical Sciences, Gastroenterology and Hepatology Unit , Uppsala University Hospital, Uppsala University , Uppsala , Sweden.
Dominic-Luc
DL
Webb
c Research Unit on Acetaldehyde and Cancer, University of Helsinki , Helsinki , Finland.
Mikko
M
Salaspuro
D000079:Acetaldehyde / Q000032:analysis*; D000328:Adult; D002243:Carbolines / Q000032:analysis / Q000378:metabolism*; D063646:Carcinogenesis / Q000187:drug effects; D018592:Cross-Over Studies; D003545:Cysteine / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005750:Gastric Juice / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D005757:Gastritis, Atrophic / Q000378:metabolism* / Q000382:microbiology; D016998:Helicobacter / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D013274:Stomach Neoplasms / Q000378:metabolism; D013548:Sweden
D002243:Carbolines; D003692:Delayed-Action Preparations; D005755:Gastrins; D000431:Ethanol; C038114:1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid; C013550:gastrin 17; D000079:Acetaldehyde; D003545:Cysteine
Alcohol; carcinogenesis; ethanol; prophylaxis; stomach