Background There is clear evidence that alcohol consumption is a risk factor for several cancers in humans. Ethanol is not carcinogenic as a molecule, but there is conclusive evidence that acetaldehyde, formed by microbial metabolism of ethanol in the upper digestive tract, acts there as a local carcinogen. Acetaldehyde is found in varying concentrations in alcoholic beverages and also in foods. This acetaldehyde could contribute to overall acetaldehyde exposure in the upper digestive tract. Consumption of calvados has been linked to an increased risk for oesophageal cancer in France. Achlorhydric gastritis is a premalignant condition, in which gastric bacterial overgrowth can lead to increased acetaldehyde concentrations in the stomach after ethanol ingestion. L-Cysteine binds to acetaldehyde and can be used to lower acetaldehyde concentrations possibly reducing acetaldehyde exposure, and the carcinogenic effects thereof. Aims The first and second aim of this thesis was to examine acetaldehyde concentrations in calvados and other alcoholic beverages, and to study the exposure to acetaldehyde after a sip of these beverages. The third aim was to develop and test a slow-release L-cysteine formulation for eliminating carcinogenic acetaldehyde in achlorhydric stomach during ethanol exposure. Methods Firstly, farm-made calvados was collected in Normandy, France. Ethanol and acetaldehyde concentrations were measured and compared to samples of commercially available alcoholic beverages. Secondly, salivary acetaldehyde concentrations were measured after small sips of alcoholic beverages. Calvados with high acetaldehyde concentration was compared to ethanol of similar concentration without acetaldehyde. Thirdly slow-release L-cysteine capsules were formulated and given to volunteers with achlorhydric gastritis prior to infusion of dilute ethanol through nasogastric intubation. Samples of gastric juice were subsequently aspirated and analysed for acetaldehyde and L-cysteine concentration. Results and conclusions We found 42% higher mean acetaldehyde concentrations in farm-made and industrially manufactured calvados when compared to other alcoholic beverages. Markedly elevated concentrations of acetaldehyde were found to be produced from ethanol in the oral cavity instantly after a small sip of alcoholic beverage, and that the exposure continued for at least 10 minutes. Acetaldehyde present in the beverage had a small, short-term increasing effect on total acetaldehyde exposure. Furthermore, we found that L-cysteine can be used to decrease acetaldehyde concentration to less than half in gastric juice after ethanol ingestion in test subjects with achlorhydric gastritis. Acetaldehyde produced microbially from ingested ethanol is probably the main source for carcinogenicity of ethanol in upper digestive tract, although acetaldehyde in beverages contributes slightly to overall acetaldehyde exposure. This could explain the increased risk for oesophageal cancer associated with consumption of hot calvados. Slow-release L-cysteine capsules can be used to reduce acetaldehyde exposure in achlorhydric stomach during ethanol consumption.
|Tila||Julkaistu - 2019|
|OKM-julkaisutyyppi||G5 Tohtorinväitöskirja (artikkeli)|
LisätietojaM1 - 79 s. + liitteet
- 3121 Yleislääketiede, sisätaudit ja muut kliiniset lääketieteet
- 3122 Syöpätaudit