Breath Acetaldehyde Levels Research Articles

Protective effects of Alda-1, an ALDH2 activator, on alcohol-derived DNA damage in the esophagus of human ALDH2*2 (Glu504Lys) knock-in mice.

Alcohol consumption is the key risk factor for the development of esophageal squamous cell carcinoma (ESCC), and acetaldehyde, a metabolite of alcohol, is an alcohol-derived major carcinogen that causes DNA damage. Aldehyde dehydrogenase2 (ALDH2) is an enzyme that detoxifies acetaldehyde, and its activity is reduced by ALDH2 gene polymorphism. Reduction in ALDH2 activity increases blood, salivary and breath acetaldehyde levels after alcohol intake, and it is deeply associated with the development of ESCC. Heavy alcohol consumption in individuals with ALDH2 gene polymorphism significantly elevates the risk of ESCC; however, effective prevention has not been established yet. In this study, we investigated the protective effects of Alda-1, a small molecule ALDH2 activator, on alcohol-mediated esophageal DNA damage. Here, we generated novel genetically engineered knock-in mice that express the human ALDH2*1 (wild-type allele) or ALDH2*2 gene (mutant allele). Those mice were crossed, and human ALDH2*1/*1, ALDH2*1/*2 and ALDH2*2/*2 knock-in mice were established. They were given 10% ethanol for 7 days in the presence or absence of Alda-1, and we measured the levels of esophageal DNA damage, represented by DNA adduct (N2-ethylidene-2′-deoxyguanosine). Alda-1 significantly increased hepatic ALDH2 activity both in human ALDH2*1/*2 and/or ALDH2*2/*2 knock-in mice and reduced esophageal DNA damage levels after alcohol drinking. Conversely, cyanamide, an ALDH2-inhibitor, significantly exacerbated esophageal DNA adduct level in C57BL/6N mice induced by alcohol drinking. These results indicate the protective effects of ALDH2 activation by Alda-1 on esophageal DNA damage levels in individuals with ALDH2 gene polymorphism, providing a new insight into acetaldehyde-mediated esophageal carcinogenesis and prevention.

Establishment of a Quick and Highly Accurate Breath Test for ALDH2 Genotyping.

Objectives:Acetaldehyde, the first metabolite of ethanol, is a definite carcinogen for the esophagus, head, and neck; and aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that catalyzes the metabolism of acetaldehyde. The ALDH2 genotype exists as ALDH2*1/*1 (active ALDH2), ALDH2*1/*2 (heterozygous inactive ALDH2), and ALDH2*2/*2 (homozygous inactive ALDH2). Many epidemiological studies have reported that ALDH2*2 carriers are at high risk for esophageal or head and neck squamous cell carcinomas by habitual drinking. Therefore, identification of ALDH2*2 carriers would be helpful for the prevention of those cancers, but there have been no methods suitable for mass screening to identify these individuals.Methods:One hundred and eleven healthy volunteers (ALDH2*1/*1 carriers: 53; ALDH2*1/*2 carriers: 48; and ALDH2*2/*2 carriers: 10) were recruited. Breath samples were collected after drinking 100 ml of 0.5% ethanol using specially designed gas bags, and breath ethanol and acetaldehyde levels were measured by semiconductor gas chromatography.Results:The median (range) breath acetaldehyde levels at 1 min after alcohol ingestion were 96.1 (18.1–399.0) parts per billion (p.p.b.) for the ALDH2*1/*1 genotype, 333.5 (78.4–1218.4) p.p.b. for the ALDH2*1/*2 genotype, and 537.1 (213.2–1353.8) p.p.b. for the ALDH2*2/*2 genotype. The breath acetaldehyde levels in ALDH2*2 carriers were significantly higher than for the ALDH2*1/*1 genotype. Notably, the ratio of breath acetaldehyde level-to-breath ethanol level could identify carriers of the ALDH2*2 allele very accurately (whole accuracy; 96.4%).Conclusions:Our novel breath test is a useful tool for identifying ALDH2*2 carriers, who are at high risk for esophageal and head and neck cancers.

Acetaldehyde/ethanol breath test for identifying people at high risk of upper aerodigestive tract cancer.

18 Background: Alcohol drinking increases the risk of upper aerodigestive tract cancer, and acetaldehyde (a metabolite of alcohol) is a definite carcinogen for this type of cancer. Acetaldehyde is formed mainly by the oxidation of ethanol by alcohol dehydrogenase 1B (ADH1B) and is eliminated by aldehyde dehydrogenase 2 (ALDH2) in the liver. About 50% of Asian people have the ALDH2*2 variant allele, which encodes an inactive enzyme. Those with the ALDH2*2 allele and an alcohol drinking habit are at definite risk of esophageal and head and neck cancers. Genetic testing is the most reliable method for identifying the ALDH2 genotype, but it is not practical for mass screening because of the cost and time. Therefore, we have established a simple method to identify the ALDH2 genotype by analyzing breath samples. Methods: One hundred seven consecutive healthy Japanese volunteers participated in this study. After providing informed consent, participants drank 100 ml of 0.5% ethanol in a single gulp. Breath samples were collected with originally developed simple gasbags before the alcohol was consumed, and 1, 2, and 5 minutes later. The concentrations of acetaldehyde and ethanol in the bag were measured by high-sensitivity gas chromatography. The ALDH2 and ADH1B genotypes of all participants were confirmed using blood DNA. The relationships between acetaldehyde level and genotypes were determined. Results: The frequencies of ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2 were 46.7%, 43.9%, and 9.3%, respectively. The breath acetaldehyde levels at 1 minute after alcohol ingestion were 89.2 (18.1–399.0) ppb in those with ALDH2*1/*1, 346.3 (78.4–1218.4) ppb in those with ALDH2*1/*2, and 537.1 (213.2–1353.8) ppb in those with ALDH2*2/*2. The breath acetaldehyde level was significantly higher in the ALDH2*2 carrier group regardless of the ADH1B genotype (P<0.001). Setting the cutoff for the acetaldehyde/ethanol ratio at 22.3×10–3 to include ALDH2*2 carriers yielded an accuracy for the detection of ALDH2*2 carriers of 96.3% (95% CI: 91.5–96.9%), sensitivity of 100%, and specificity of 92%. Conclusions: Our breath test may be a convenient screening tool for identifying those at high risk of upper aerodigestive tract cancer.

On-line, simultaneous quantification of ethanol, some metabolites and water vapour in breath following the ingestion of alcohol

Selected ion flow tube mass spectrometry, SIFT-MS, has been used to measure simultaneously the concentrations in exhaled breath of ethanol, acetaldehyde, ammonia, acetone and, routinely, water vapour, following the ingestion of various amounts of ethanol in 500 ml of water. These breath analyses were obtained from only single exhalations, the results being available immediately in real time. The breath ethanol reaches concentrations that are only approximately consistent with its dilution in blood and body water. For moderate ethanol doses the decay quickly exhibits first-order kinetics (a single exponential decay) whereas for relatively large ethanol doses, the initial decay of ethanol from the breath is slow, indicating saturation kinetics. For smaller doses, and following a meal, the breath ethanol increases only slightly indicating that it is largely metabolized in the stomach. We suggest that the time delay (following ethanol ingestion) before the breath ethanol begins to increase is an indicator of the gastric emptying rate. Then the rate of decay of ethanol from the breath/blood is related to its rate of metabolism subsequent to its dispersal into the body water. The much lower breath acetaldehyde levels correlate well with the ethanol levels indicating that it is mostly formed from the metabolism of the ethanol. The breath ammonia is seen to ‘dip’ following the water/alcohol drink and this is consistent with previous work in which this same phenomenon was observed following the ingestion of comparable volumes of liquid meals. The simultaneous breath acetone concentrations increase somewhat with time as is expected during the fasting state. The water vapour measurements are indicators of the precision and accuracy of the breath analyses, these being sufficient to show the differences between the breath (body) temperatures of the individuals of less than 1 °C. This study demonstrates the potential of SIFT-MS for non-invasive physiological measurement.

The role of acetaldehyde in pregnancy outcome after prenatal alcohol exposure.

It is not known why some heavy-drinking women give birth to children with alcohol-related birth defects (ARBD) whereas others do not. The objective of this study was to determine whether the frequency of elevated maternal blood acetaldehyde levels among alcoholics is in the range of ARBD among alcoholic women. MEDLINE was searched from 1980 to 2000 using the key words acetaldehyde, pharmacokinetics, and alcoholism for controlled trials reporting blood or breath acetaldehyde levels in alcoholics and nonalcoholics. Separately, using the key words fetal alcohol syndrome, epidemiology, prevalence, incidence, and frequency, articles were identified reporting ARBD incidences among the offspring of heavy drinkers. Of 23 articles reporting acetaldehyde levels in alcoholics, four met the inclusion criteria. Forty-three studies reported on the rate of ARBD in heavy drinkers, and 14 were accepted. Thirty-four percent of heavy drinkers had a child with ARBD, and 43% of chronic alcoholics had high acetaldehyde levels. The similar frequencies of high acetaldehyde levels among alcoholics and the rates of ARBD among alcoholic women provide epidemiologic support to the hypothesis that acetaldehyde may play a major role in the cause of ARBD.

Breath acetaldehyde following ethanol consumption

Five pairs of volunteers were studied to determine the effect of drinking ethanol on breath acetaldehyde levels. On a given study day, samples of breath were obtained for measurement of acetaldehyde and ethanol from both participants at t = −1 h, t = −0.5 h, and at t = 0 to obtain baseline values. The drinkers were then given ethanol (0.3 g/kg body weight), and the controls given an equal volume of tap water. Breath samples were then taken at 0.5, 1, 1.5, 2 h, and hourly until t = 6 h. The last sample taken was at t = 23.5 h. Acetaldehyde levels in breath were quantified with a fluorigenic high-performance liquid chromatographic assay. Blood ethanol was approximated using a breath analyzer. Acetaldehyde in breath rose 50-fold at the 0.5-h, time point and returned to levels not significantly different from baseline values by 3–4 h. The mean peak blood ethanol values reached 0.055%. The t 1 2 elimination for ethanol was 1.6 h, and that for acetaldehyde was 2.25 h. Elimination of both acetaldehyde and ethanol in breath were initially 0 order. A significant correlation ( r = 0.74) was found between baseline breath acetaldehyde levels and peak acetaldehyde levels. We conclude that acetaldehyde resulting from ethanol intake rapidly partitions into breath. The correlation of baseline breath acetaldehyde values with peak values found after an ethanol challenge indicate that measurement of breath acetaldehyde may be useful in the identification of individual differences in ethanol metabolism.

Elevated endogenous breath acetaldehyde levels among abusers of alcohol and cigarettes

1. Endogenous (fasting) breath acetaldehyde levels were assessed as a discriminator between alcoholic and non-alcoholic subjects. 2. The influence of smoking as a potential confounding variable on breath acetaldehyde was determined. 3. Individuals with a history of smoking and/or drinking had higher endogenous breath acetaldehyde levels as compared to controls. 4. Mean acetaldehyde levels revealed an additive (noninteractive) pattern associated with combined abuse of these substances. 5. The similarity in acetaldehyde levels between alcoholic non-smokers and non-alcoholic smokers limits the usefulness of endogenous breath acetaldehyde for the purpose of early diagnosis of alcoholism. 6. Results support hypotheses that elevations in acetaldehyde could be a common factor in disease associated with alcohol and cigarette abuse.

Endogenous breath acetaldehyde levels among alcoholic and non-alcoholic probands: Effect of alcohol use and smoking

1. The effects of possible confounding factors on endogenous breath acetaldehyde levels were examined in alcoholic and non-alcoholic subjects. 2. Demographic characteristics, family history for alcoholism, smoking and drinking history, and breath acetaldehyde levels were assessed. 3. Differences in endogenous breath acetaldehyde levels could not be attributed to age, sex, or having a family history positive for alcoholism. 4. Individuals who smoke or abuse alcohol had higher endogenous breath acetaldehyde levels than persons who did not.

Behavioral and physiological effects of ethanol in high-risk and control children: a pilot study.

Blood and breath acetaldehyde levels were measured following ethanol ingestion (0.5 ml/kg) in 11 boys familially at risk for alcoholism and 11 age-matched controls. No significant differences were found between groups for acetaldehyde, objective, or subjective measures of intoxication. Previous reports of acetaldehyde as a marker of risk for alcoholism were not confirmed. Baseline behavioral state predicted response to alcohol. Children tended to have a subjective response in a direction opposite from the baseline mood state.

Individual differences in blood and breath acetaldehyde levels and urinary excretion of catecholamines after alcohol intake.

Sixty three male Japanese, aged 20-40 yr were evaluated as to the degree of facial flushing following a controlled dose of ethanol either as Japanese rice wine or ethanol 0.4 g kg body weight. Thirty four subjects responded with overt facial flushing. The acetaldehyde levels in blood and expired air were significantly higher in the flushing group without a change in ethanol elimination rate. Urinary excretion of Vanilmandelic acid (VMA) and 3 methyoxy-4-Hydroxyphenylglycol (MHPG) are reported.

Breath acetaldehyde levels after ethanol consumption.

Breath acetaldehyde levels in human subjects have been determined in the past by the separate collection of breath prior to analysis. Stowell et al. (1979) trapped acetaldehyde in a semicarbazide solution before enzymatic analysis while Forsander et al. (1974) used a cold water trap prior to analysis by gas chromatography. Although trapping of acetaldehyde from breath allows it to be concentrated, the disadvantages of such methods are that the recovery procedures are laborious.