ALDH2 genotype has no effect on salivary acetaldehyde without the presence of ethanol in the systemic circulation.

BACKGROUND: Acetaldehyde associated with alcoholic beverages was recently classified as carcinogenic (Group 1) to humans based on uniform epidemiological and biochemical evidence. ALDH2 (aldehyde dehydrogenase 2) deficient alcohol consumers are exposed to high concentrations of salivary acetaldehyde and have an increased risk of upper digestive tract cancer. However, this interaction is not seen among ALDH2 deficient non-drinkers or rare drinkers, regardless of their smoking status or consumption of edibles containing ethanol or acetaldehyde. Therefore, the aim of this study was to examine the effect of the ALDH2 genotype on the exposure to locally formed acetaldehyde via the saliva without ethanol ingestion. METHODS: The ALDH2 genotypes of 17 subjects were determined by PCR-RFLP. The subjects rinsed out their mouths with 5 ml of 40 vol% alcohol for 5 seconds. Salivary ethanol and acetaldehyde levels were measured by gas chromatography. RESULTS: Acetaldehyde reached mutagenic levels rapidly and the exposure continued for up to 20 minutes. The mean salivary acetaldehyde concentrations did not differ between ALDH2 genotypes. CONCLUSIONS: For ALDH2 deficient subjects, an elevated exposure to endogenously formed acetaldehyde requires the presence of ethanol in the systemic circulation. IMPACT: Our findings provide a logical explanation for how there is an increased incidence of upper digestive tract cancers among ALDH2 deficient alcohol drinkers, but not among those ALDH2 deficient subjects who are locally exposed to acetaldehyde without bloodborne ethanol being delivered to the saliva. Thus, ALDH2 deficient alcohol drinkers provide a human model for increased local exposure to acetaldehyde derived from the salivary glands.

A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity.

The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 µM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 µmol/l, p<0.05) and without (258 vs. 89 µmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure.

Reducing carcinogenic acetaldehyde exposure in the achlorhydric stomach with cysteine.

BACKGROUND: Acetaldehyde, associated with alcohol consumption, has recently been classified as a group 1 carcinogen in humans. Achlorhydric atrophic gastritis is a well-known risk factor for gastric cancer. Achlorhydria leads to microbial colonization of the stomach. Several of these microbes are able to produce significant amounts of acetaldehyde by oxidation from alcohol. Acetaldehyde can be eliminated from saliva after alcohol intake and during smoking with a semi-essential amino acid, L-cysteine. The aim of this study was to determine whether cysteine can be used to bind acetaldehyde in the achlorhydric stomach after ethanol ingestion. METHODS: Seven volunteers with achlorhydric atrophic gastritis were given either slow-release L-cysteine or placebo capsules in a double-blinded randomized trial. Volunteers served as their own controls. A naso-gastric tube was inserted to each volunteer. The volunteers ingested placebo or 200 mg of L-cysteine capsules, and ethanol 0.3 g/kg body weight (15 vol%) was infused intragastrically through a naso-gastric tube. Five-milliliter samples of gastric contents were aspirated at 5-minute intervals. RESULTS: During the follow-up period, the mean acetaldehyde level of gastric juice was 2.6 times higher with placebo than with L-cysteine (13 vs. 4.7 µM, p < 0.05, n = 7). CONCLUSIONS: L-cysteine can be used to decrease acetaldehyde concentration in the achlorhydric stomach during alcohol exposure. Intervention studies with L-cysteine are needed on reducing acetaldehyde exposure in this important risk group for gastric cancer.

Lactulose reduces intracolonic acetaldehyde concentration and ethanol elimination rate in rats.

BACKGROUND: Normal colonic bacteria possessing alcohol dehydrogenase activity can oxidize ethanol to acetaldehyde. Acetaldehyde recently has been shown to be a local carcinogen in humans. The aim of the study was to examine the effect of lactulose feeding on fecal and cecal pH, intracolonic acetaldehyde concentration, and total ethanol elimination rate in rats. METHODS: Sixty Wistar rats were divided into four groups. Groups 2 and 4 received lactulose daily (11 g/kg body weight for 14 days). On days 7 and 14, groups 1 and 2 received ethanol (1.5 g/kg body weight) intraperitoneally, whereas groups 3 and 4 received saline. RESULTS: Fecal and cecal pH values decreased significantly after lactulose treatment compared with the controls. Lactulose feeding reduced the total ethanol elimination rate by 13.8% (257 +/- 0.008 mg/kg/hr vs. 298 +/- 0.003 mg/kg/hr, p < 0.001) and the intracecal acetaldehyde concentration by 66.2% after ethanol (49 +/- 29 microM vs. 145 +/- 47 microM, p = 0.03) compared with the controls. CONCLUSION: Lactulose feeding to rats significantly reduces ethanol elimination rate and intraluminal acetaldehyde concentration in the colon after ethanol administration. This prebiotic thus could be used as an effective agent to block the microbial production of carcinogenic acetaldehyde in the large intestine.