Recovery of gastric function in patients affected by chronic atrophic gastritis using l-cysteine (Acetium®): one year survey in comparison with a control group.: L-cysteine and Chronic Atrophic Gastritis

Recovery of gastric function in patients affected by chronic atrophic gastritis using l-cysteine (Acetium®): one year survey in comparison with a control group.

L-cysteine and Chronic Atrophic Gastritis

Authors

  • Pellegrino Crafa Department of Medicine and Surgery, University of Parma
  • Francesco Di Mario https://orcid.org/0000-0002-8189-7336
  • Simone Grillo Department of Medicine and Surgery, University of Parma; Parma - Italy
  • Stefano Landi Department of Medicine and Surgery, University of Parma
  • Marilisa Franceschi Endoscopy Unit, Department of Medicine, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy, Schio (Vi), IT
  • Kryssia Rodriguez-Castro Endoscopy Unit, Department of Medicine, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy, Schio (Vi), IT
  • Antonio Tursi Territorial Gastroenterology Service, Azienda Sanitaria Locale Barletta-Andria-Trani, Andria, Italy
  • Giovanni Brandimarte Division of Internal Medicine and Gastroenterology, Cristo Re Hospital, Rome, Italy
  • Lorella Franzoni Department of Medicine and Surgery, University of Parma

Keywords:

Pepsinogen I, Gastrin 17, Chronic atrophic Gastritis, L-cysteine, Acetaldehyde

Abstract

Background and aim: Chronic Atrophic Gastritis (CAG) is a precancerous condition for gastric cancer (GC) as single risk factor, being a consequence of a previous Helicobacter pylori (Hp) infection or based on autoimmune mechanisms. Achlorhydria plays an important role towards the formation of a class I carcinogen, acetaldehyde, after food intake. L-cysteine has been claimed to be able to bind in a covalent way acetaldehyde when administered at means.

Methods: In this study we enrolled two CAG groups of patients, one treated whit 300 mg/daily of L-cysteine for one year, the other one untreated.

We assessed gastric function lasting the one year follow-up by using non invasive surrogates, i.e. Pepsinogen I (PGI) and gastrin 17 (G17).

Results: In the group of 77 CAG on therapy we found a statistically significative increase in PGI values and a decrease in G17 levels, in comparison with unchanged values in control group.

Conclusions: L-cysteine seems able to provide a recovery in gastric function when administered in CAG patients and could be proposed as a possible therapy in such patients.

References

Correa P. Human gastric carcinogenesis: a multistep and multifactorial

process—First American Cancer Society Award Lecture on Cancer Epidemiology

and Prevention. Cancer Res 1992;52:6735-40.

Correa P. The biological model of gastric carcinogenesis. IARC Sci Publ.

;157:301–10.

de Vries AC, van Grieken NC, Looman CW,Casparie MK, de Vries E, Meijer GA, et al. Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology. 2008 Apr; 134(4): 945–52.

Agreus L, Kuipers EJ, Kupcinskas L, et al. Rationale in diagnosis and

screening of atrophic gastritis with stomach-specifc plasma biomarkers.

Scand J Gastroenterol. 2012;47:136–47.

Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia

as a premalignant lesion of gastric cancer. J Cancer Prev. 2015;20:25–40.

Walter IR, Strickland RG, Ungar B, Mackay IR. Simple atrophic gastritis and gastric carcinoma. Gut 1971; 12:906–11.

Sipponen P, Kekki M, Haapakoski J et al. Gastric cancer risk in chronic atrophic gastritis: statistical calculations of cross-sectional data. Int. J. Cancer 1985; 35: 173–7.

Valle J, Kekki M, Sipponen P et al. Long-term course of a32 year follow-up study. Scand. J. Gastroenterol. 1996; 31:546–50

Niemelä S, Karttunen T, Kerola T. Helicobacter pylori-associated gastritis. Evolution of histologic changes over10 years. Scand. J. Gastroenterol. 1995; 30: 542–9.

Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P; faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015 Sep;64(9):1353-67.

Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.

Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S and Yamakido M: Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001; 345: 829-832.

Rugge M, Savarino E, Sbaraglia M, Bricca L, Malfartheiner P. Gastritis: The clinico-pathological spectrum. Dig Liver Dis. 2021 Mar 27:S1590-8658(21)00100-6.

Coati I, Fassan M, Farinati F, Graham DY, Genta RM, RuggeR.Autoimmune gastritis: Pathologist's viewpoint. World J Gastroenterol. 2015 Nov 14;21(42):12179-89.

Rugge M, Fassan M, Pizzi M, Zorzetto V, Maddalo G, Realdon S, De Bernard M, Betterle C, Cappellesso R, Pennelli G, de Boni M, Farinati F. Autoimmune gastritis: histology phenotype and OLGA staging. Aliment Pharmacol Ther 2012; 35: 1460-1466

Vannella L, Lahner E, Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal. World J Gastroenterol 2012; 18: 1279-1285

Rugge M, Sugano K, Scarpignato C, Sacchi D, Oblitas W J, Naccarato AG. Gastric cancer prevention targeted on risk assessment: Gastritis OLGA staging. Helicobacter. 2019 Apr;24(2):e12571.

Rugge M, Genta RM, Fassan M, Valentini E, Coati I, Guzzinati S, Savarino E, Zorzi M, Farinati F, Malfertheiner P. OLGA Gastritis Staging for the Prediction of Gastric Cancer Risk: A Long-term Follow-up Study of 7436 Patients. Am J Gastroenterol. 2018 Nov;113(11):1621-1628.

Fock KM. Review article: the epidemiology and prevention of gastric cancer.Aliment Pharmacol Ther. 2014; Vol. 40, 3, pp 250-260.

Hyuna Sung PhD, Jacques Ferlay MSc, ME, Rebecca L. Siegel MPH, Mathieu Laversanne MSc, Isabelle Soerjomataram MD, MSc, PhD, Ahmedin Jemal DMV, PhD, Freddie Bray BSc, MSc, PhD Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries CA: A Cancer Journal for Clinicians 2021; Vol. 71, 3, pp 209-249

Carabotti M, Lahner E, Esposito G, Sacchi MC, Severi C, Annibale B. Upper gastrointestinal symptoms in autoimmune gastritis: a cross-sectional study. Medicine (Baltimore). 2017;96:e5784.

Tosetti C, Stanghellini V, Tucci A, Poli L, Salvioli B, Biasco G, et al. Gastric emptying and dyspeptic symptoms in patients with nonautoimmune fundic atrophic gastritis. Dig Dis Sci. 2000;45:252–7.

Lahner E, Conti L., Annibale B., Corleto V.D. Current Perspectives in Atrophic Gastritis. Curr Gastroenterol Rep. 2020 Jun 15;22(8):38.

Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis: the updated Sydney system. Am J Surg Pathol. 1996; 20 (10):1161–1181.

Rugge M., Meggio A., Pennelli G., Piscioli F., Giacomelli L., De Pretis G, Graham D.Y. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007 May;56(5):631-636

Capelle L.G., de Vries A.C., Haringsma J., Ter Borg F., de Vries R.A., Bruno M.J., van Dekken H., Meijer J., van Grieken N.C.T., Kuipers E.J. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010 Jun;71(7):1150-8.

Samloff IM, Varis K, Ihamaki T, Siurala M, Rotter JI. Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology, 1982; 83 (1 Pt 2):204-9.

Sjomina O, Pavlova J, Daugule I, Janovic P, Kikuste I, Vanags A, Tolmanis I, Rudzite D, Polaka I, Kojalo I, Liepniece-Karele I, Isajevs S, Santare D, Pirags V, Pahomova J, Dzerve V, Tzivian L, Erglis A, Leja M. Pepsinogen test for the evaluation of precancerous changes in gastric mucosa: a population-based study. J Gastrointestin Liver Dis. 2018 Mar;27(1):11-17.

Germaná, B., et al. Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti-Helicobacter pylori antibodiesin the management of dyspeptic patients in primary care. Digestive and liver disease 37.7 (2005): 501-508.

Ju Yup Lee 1, Nayoung Kim 2, Hye Seung Lee 3, Jane C Oh 4, Yong Hwan Kwon 1, Yoon Jin Choi 1, Ki Chul Yoon 1, Jae Jin Hwang 1, Hyun Joo Lee 1, AeRa Lee 1, Yeonsang Jeong 1, Hyun Jin Jo 1, Hyuk Yoon 1, Cheol Min Shin 1, Young Soo Park 1, Dong Ho Lee 2 Correlations among endoscopic, histologic and serologic diagnoses for the assessment of atrophic gastritis J Cancer Prev. 2014;19(1):47-55

Venerito M, Radunz M, Reschke K, et al. Autoimmune gastritis in autoimmune thyroid disease. Aliment Pharmacol Ther 2015; 41: 686-93.

Sipponen, P., et al. Atrophic gastritis serum levels of amidated gastrin-17 and pepsinogen i in atrophic gastritis: an observational case-control study. Scandinavian journal of gastroenterology 37.7 (2002): 785-791.

Väänänen, H., et al. Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. European journal of gastroenterology & hepatology 15.8 (2003): 885-891.

Barchi A, Miraglia C, Violi A, et al. A non-invasive method for the diagnosis of upper GI diseases. Acta Biomed 2018;89:40–43.

Dinis-Ribeiro M, Yamaki G, Miki K, et al. Meta-analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophic gastritis screening. J Med Screen 2004; 11: 141-7.

Huang YK, Yu JC, Kang WM, et al. Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis. PLoS One 2015; 10: e0142080.

R M Zagari 1, S Rabitti 1, D C Greenwood 2, L H Eusebi 1, A Vestito 3, F Bazzoli 1 Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis Aliment Pharmacol Ther . 2017 Oct;46(7):657-667.

Yamada T, Miwa H, Fujino T, Hirai S, Yokoyama T, Sato N. Improvement of gastric atrophy after Helicobacter pylori eradication therapy. J Clin Gastroenterol 2003;36:405-410.

Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. The long‐term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta‐analysis. Helicobacter 2007;12:32-38.

Toyokawa T, Suwaki K, Miyake Y, Nakatsu M, Ando M. Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long‐term prospective cohort study. J Gastroenterol Hepatol 2010;25:544-547.

Hwang YJ, Kim N, Lee HS, et al. Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication ‐ a prospective study for up to 10 years. Aliment Pharmacol Ther 2018;47:380-390.

Di Mario F, Moussa AM, Dal Bò N, Caruana P, Pilotto A, Cavallaro LG, Cavestro GM, Iori V, Merli R, Franzé A, Rugge M. Recovery of gastric function after Helicobacter pylori eradication in subjects with body atrophic gastritis: prospective 4-year study. J Gastroenterol Hepatol. 2005 Nov;20(11):1661-6

Baan, R., Straif, K., Grosse, Y., Secretan, B., El Ghissassi, F., Bouvard, V., Cogliano, V. Carcinogenicity of alcoholic beverages. The Lancet Oncology, 2007, 8(4), 292–293.

Driver,H.E. and Swann,P.F. (1987) Alcohol and human cancer. Anticancer implications in alcohol carcinogenesis. Cancer Res., 39, 2844–2850.

Blot,W.J. (1992) Alcohol and cancer. Cancer Res., 52 (Suppl.), 2119–2123. J. Natl Cancer Inst., 69, 947–951.

Brugere,J., Guenel,P., Leclerc,A. and Rodriguez,J. (1986) Differential

effects of tobacco and alcohol in cancer of the larynx, pharynx and mouth.

Cancer, 57, 391–395.

Breslow,N.E. and Enstorm,J.E. (1974) Geographic correlations between

mortality rates, alcohol and tobacco consumption in the United States. J. Natl Cancer Inst., 53, 631–639.

Homann N., Jousimies-Somer H., Jokelainen K., Heine R.and Salaspuro M., High acetaldehyde levels in saliva after ethanol consumption:

Methodological aspects and pathogenetic implications Carcinogenesis vol.18 no.9 pp.1739–1743, 1997

Dong,Y.-J., Peng,T.-K. and Yin,S.-J. (1996) Expression and activities of

of ethanol: a gastrointestinal barrier against the systemic toxicity of class IV alcohol dehydrogenase and class III aldehyde dehydrogenase in human mouth. Alcohol, 13, 257–262.

Jauhonen,P., Baraona,E., Miyakawa,H. and Lieber,C.S. (1982) Origin of

breath acetaldehyde during ethanol oxidation. Effect of long-term cigarette

smoking. J. Lab. Clin. Med., 100, 908–916. May 19, 1997

Jokelainen,K., Heikkonen,E., Roine,R., Lehtonen,H. and Salaspuro,M.

(1996) Increased acetaldehyde production by mouthwashings of patients

with oral cavity, laryngeal or pharyngeal cancer. Alcohol. Clin. Exp. Res.,

, 1206–1210.

Jokelainen,K., Roine,R.P., Va¨a¨na¨nen,H., Fa¨rkkila,M. and Salaspuro,M.

(1994) In vitro acetaldehyde formation by human colonic bacteria. Gut, 35, 1271–1274.

Jokelainen,K., Siitonen,A., Jousimies-Somer,H., Nosova,T., Heine,R. and

(1981) In vitro alcohol dehydrogenase mediated acetaldehyde production by aerobic bacteria representing the normal colonic flora in man. Alcohol. Clin. Exp. Res., 20, 967–972.

Moreno,A. and Pares,X. (1991) Purification and characterization of a

new alcohol dehydrogenase from human stomach. J. Biol. Chem., 266, 1128–1233.

Maier,H., Zo¨ller,J., Herrmann,A., Kreiss,M. and Heller,W.D. (1993) Dental

status and oral hygiene in patients with head and neck cancer. Otolaryngol. Head Neck Surg., 108, 655–661

Sprince H, Parker C M, Smith G G, Gonzales L J Protective action of ascorbic acid and sulfur compounds against acetaldehyde toxicity: implications in alcoholism and smoking Agents Actions 1975 May;5(2):164-73.

Sprince H Protective action of sulfur compounds against aldehyde toxicants of cigarette smoke Eur J Respir Dis Suppl. 1985;139:102-12.

Farinati, F.; Della Libera, G.; Cardin, R; Molari, A.; Plebani, M.; Rugge, M.; Di Mario, F.; Naccarato, R. Gastric Antioxidant, Nitrites, and Mucosal Lipoperoxidation in Chronic Gastritis and Helicobacter pylori Infection. J Clin Gastroenterol 1996 - Vol 22 - Issue 4 - p 275-281

Salaspuro V, Hietala J, Kaihovaara P, et al. Removal of acetaldehyde

from saliva by a slow-release buccal tablet of L-cysteine. Int J Cancer. 2002;97:361–364.

Salaspuro VJ, Hietala JM, Marvola ML, et al. Eliminating carcinogenic

acetaldehyde by cysteine from saliva during smoking. Cancer Epid Biomark Prev. 2006;15:146–149.

Kartal A, Hietala J, Laakso I, Kaihovaara P, Salaspuro V, Säkkinen M, Salaspuro M, Marvola M Formulation and in-vivo evaluation of L-cysteine chewing gums for binding carcinogenic acetaldehyde in the saliva during smoking. .J Pharm Pharmacol. 2007 Oct;59(10):1353-8.

Syrjänen K, Salminen J, Aresvuo U, Hendolin P, Paloheimo L, Eklund C, Salaspuro M, Suovaniemi O. Elimination of Cigarette Smoke-derived Acetaldehyde in Saliva by Slow-release L-Cysteine Lozenge Is a Potential New Method to Assist Smoking Cessation. A Randomised, Double-blind, Placebo-controlled Intervention. Anticancer Res. 2016 May;36(5):2297-306

Linderborg K, Marvola T, Marvola M, Salaspuro M, Färkkilä M, Väkeväinen S. Reducing carcinogenic acetaldehyde exposure in the achlorhydric stomach with cysteine. Alcohol Clin Exp Res. 2011 Mar;35(3):516-22.

.

Maejima R, Iijima K, Kaihovaara P, Hatta W, Koike T, Imatani A, Shimosegawa T, Salaspuro M Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration. .PLoS One. 2015 Apr 1;10(4):e0120397.

Hellström PM, Hendolin P, Kaihovaara P, Kronberg L, Meierjohann A, Millerhovf A, Paloheimo L, Sundelin H, Syrjänen K, Webb DL, Salaspuro M. 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. Scand J Gastroenterol. 2017 Feb;52(2):230-237

Downloads

Published

01-07-2022

Issue

Section

ORIGINAL ARTICLES

How to Cite

1.
Crafa P, Di Mario F, Grillo S, Landi S, Franceschi M, Rodriguez-Castro K, et al. Recovery of gastric function in patients affected by chronic atrophic gastritis using l-cysteine (Acetium®): one year survey in comparison with a control group.: L-cysteine and Chronic Atrophic Gastritis. Acta Biomed [Internet]. 2022 Jul. 1 [cited 2024 Jul. 17];93(3):e2022184. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/12812