Acetaldehyde - a major pathophysiologic factor in gastric carcinogenesis

Biohit Oyj Press Release 2.4.2015 at 9:30 a.m. local time (EEST)

Stomach cancer is the third leading cause of cancer death in both sexes worldwide (723,000 deaths/year, 8.8% of the total). The highest estimated mortality rates are in Eastern Asia. In a collaborative Japanese-Finnish study it was for the first time demonstrated that a genetic deficiency (ALDH2-deficiency) to eliminate acetaldehyde results in markedly increased (5.6-fold) exposure of the gastric mucosa to carcinogenic acetaldehyde after intragastric administration of alcohol.

When combined with earlier epidemiological findings, these results provide concrete evidence for the causal relationship of acetaldehyde not only with the pathogenesis of esophageal but also with gastric cancer. ALDH2-deficiency has been calculated to affect at least 540 million individuals with Eastern Asian roots. Thus, the carcinogenicity (Group 1/IARC/WHO) of acetaldehyde to humans is based on a unique human cancer model.

The highest stomach cancer risk is among ALDH2-deficient heavy drinkers whose stomach is anacidic due to atrophic gastritis. A recent meta-analysis suggests that the use of drugs suppressing gastric acid secretion is also associated with an increased risk of gastric cancer. A common pathogenetic denominator in both cases is acetaldehyde endogenously formed from alcohol. Acid free stomach is colonized with oral microbes, which together with mucosal cells produce locally acetaldehyde from alcohol. Acetaldehyde accumulates in gastric juice, because the capacity of mucosa and microbes to eliminate it is low.

Highest intragastric acetaldehyde concentrations were found in ALDH2-deficient individuals receiving a drug inhibiting gastric acid secretion. On the other hand, high gastric juice alcohol concentrations associated with high intragastric acetaldehyde levels, underlining the important role of alcoholic beverages in local acetaldehyde production. However, elevated gastric juice acetaldehyde levels were also found at low alcohol concentrations, corresponding to those of many foodstuffs and beverages produced by fermentation e.g. pickled food, soya sauces and dairy products.

The Acetium® capsule used in the study is a CE-marked product registered in many countries as a medical device (class IIa; patented and produced by Biohit Oyj, Helsinki, Finland). This classification is based on the nature of the active ingredient, L-cysteine, as a natural amino acid and the mode of the action of the formulation. Slowly from Acetium-capsule releasing L-cysteine binds acetaldehyde to a harmless compound in the stomach, where carcinogenic acetaldehyde is formed.  200mg of slow-release L-cysteine eliminated mean 60-67 % of gastric juice acetaldehyde in PPI-treated ALDH2-deficient and -active subjects, respectively and the effect lasted for two hours.

Cancer prevention is based on the identification of specific etiological factors. The exposure of the upper digestive tract to carcinogenic acetaldehyde can be decreased by many ways both at a population and individual level. Thus, the findings of the study provide entirely novel perspectives for the prevention of stomach cancer, especially among particular risk groups: those with ALDH2-deficiency, acid free stomach (atrophic gastritis), Helicobacter pylori infection, and regular use of proton pump inhibitors.

Invited comment: Professor of Internal Medicine, Gastroenterology and Alcohol Research, Helmut K. Seitz, University of Heidelberg: ‘The carcinogenicity of acetaldehyde is well established. However, this study shows for the first time its role in gastric cancer. The study demonstrates most convincingly that there is a high gastric acetaldehyde generation under certain conditions (ALDH2 deficiency, high gastric bacterial load) and there is a significant relationship between these conditions and the prevalence of stomach cancer. Thus, according to these data acetaldehyde is a major pathophysiologic factor in gastric carcinogenesis in certain individuals. Even more important, the authors demonstrate a preventive strategy by reducing gastric acetaldehyde.’

CEO Semi Korpela, Biohit Oyj: ‘Biohit Oyj has Acetium products and a way to reduce the amount of acetaldehyde (by binding it to a harmless compound). In addition to those with genetic inability to eliminate acetaldehyde, Acetium capsules are recommended as protection for those using inhibitors of gastric acid secretion (PPI-drugs), and to persons  suffering from an acid-free stomach (atrophic gastritis, identified by GastroPanel test) (see Additional Information). Acetium lozenges can be used to bind acetaldehyde into harmless compound in saliva in the mouth, which forms as a result of smoking and alcohol consumption. Biohit Oyj also has a patented method in e.g. Finland and USA, to bind acetaldehyde into harmless compound in alcoholic beverages and food products. In 2012, the European Commission's appointed group of scientific experts gave a unanimous recommendation stating that cosmetic products may contain acetaldehyde at most 5 mg/l while no acetaldehyde may be added to mouth wash. Many alcoholic beverages and foodstuffs sold in Finland exceed the maximum permitted amount for cosmetic products multiple times.’

Article in PLOS ONE database: http://dx.plos.org/10.1371/journal.pone.0120397

Attachment: Full article (pdf)

Attachment: Additional information (pdf)

Additional information: 
CEO Semi Korpela, Biohit Oyj
tel. +358 9 773 861
investor.relations@biohit.fi
www.biohithealthcare.com

Biohit in brief

Biohit Oyj is a globally operating Finnish biotechnology company. Biohit’s mission is “Innovating for Health” – we produce innovative products and services to promote research and early diagnosis. Biohit is headquartered in Helsinki, Finland, and has subsidiaries in Italy and the UK. Biohit's Series B share (BIOBV) is quoted on Nasdaq Helsinki in the Small cap/Healthcare group. www.biohithealthcare.com