Acetaldehyde, Alcohol & Cancer

Acetaldehyde, a pungent, colorless liquid, is a primary metabolic product of ethanol on its route to becoming acetic acid. As a food additive it is generally regarded as safe (GRAS) and is widely used. However, recent evidence suggests that its GRAS status should be re-evaluated, and the classification of acetaldehyde as a carcinogen should be upgraded.

Acetaldehyde is produce by the enzyme alcohol dehydrogenase, which occurs primarily in the liver but also to a small extent in the retina. Generally, the bigger the person, the bigger the liver, and the quicker the alcohol is metabolized and removed from circulation. Acetaldehyde is one of the chemical agents responsible for a hangover, although there are also numerous complicated and interrelated contributions from the physiological changes that occur as the body responds to unnaturally high ethanol levels and the mild narcosis, acid imbalance, and dehydration it induces.

Alcohol dehydrogenase is present in our bodies because we need to metabolize the alcohol produced in small amounts by the normal digestion and breakdown of carbohydrates, and in large amounts by the bacteria in our intestines.

Some substances (notably other alcohols) compete with ethanol for alcohol hydrogenase. These alcohols are present in fusel oil, a byproduct of fermentation, and hence are present in some distilled spirits. The metabolism of wine and spirits is therefore slower than that of vodka, which is largely free from everything except ethanol and water.

Acetaldehyde is also a product of the action of Saccharomyces cerevisiae, a yeast which is allowed to develop on fino and amontillado sherries and imparts to them their nutty flavor. It also contributes to the odor of ripe fruits.

Acetaldehyde and Breast Cancer

Increasing evidence suggests that acetaldehyde, the first and genotoxic metabolite of ethanol, mediates the carcinogenicity of alcoholic beverages. Epidemiological studies consistently indicate that alcoholic beverages are an independent risk factor for female breast cancer. Although the mechanism underlying this effect remains unknown, the predominant hypothesis implicates mutagenesis via the ethanol metabolite acetaldehyde, whose impact on the carcinogenesis of several types of cancer has been shown in both experimental models and molecular studies.2



Acetaldehyde and Oral Cancer

Acetaldehyde is the first product of alcohol (ethanol) metabolism. Ethanol is metabolized to acetaldehyde by both mucosal and microbial enzymes. Many microbes produce acetaldehyde from ethanol, but their capacity to eliminate acetaldehyde is low, which leads to the accumulation of acetaldehyde in saliva during an alcohol challenge. Acetaldehyde is the most abundant carcinogen in tobacco smoke, and it readily dissolves into saliva during smoking. Fermented food and many alcoholic beverages can also contain significant amounts of acetaldehyde. Thus acetaldehyde, derived from mucosal or microbial oxidation of ethanol, tobacco smoke, and/or diet, appears to act as a cumulative carcinogen in the upper digestive tract of humans.5

Ethanol is also contained in a number of ready-to-use mouthwashes typically between 5 and 27% vol. An increased risk of oral cancer has been identified for users of such mouthwashes. A twice-daily use of alcohol-containing mouthwashes leads to a systemic acetaldehyde exposure which has been found significantly above normal levels and corresponding to concentrations normally found after alcoholic beverage consumption.3

Acetaldehyde and Esophagus Cancer

Several lines of evidence indicate that acetaldehyde, the first product of alcohol metabolism, plays a very important role in alcohol-related carcinogenesis, particularly in the esophagus.4

References

  1. Molecules. P.W. Atkins
  2. Interaction of the Effects of Alcohol Drinking and Polymorphisms in Alcohol-Metabolizing Enzymes on the Risk of Female Breast Cancer in Japan.Kawase T, Matsuo K, Hiraki A, Suzuki T, Watanabe M, Iwata H, Tanaka H, Tajima K. In: J Epidemiol. 2009 Aug 8.
  3. Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer.Lachenmeier DW, Gumbel-Mako S, Sohnius EM, Keck-Wilhelm A, Kratz E, Mildau G. In: Int J Cancer. 2009 Aug 1;125(3):730-5.
  4. Acetaldehyde stimulates FANCD2 monoubiquitination, H2AX phosphorylation, and BRCA1 phosphorylation in human cells in vitro: implications for alcohol-related carcinogenesis.Marietta C, Thompson LH, Lamerdin JE, Brooks PJ. In: Mutat Res. 2009 May 12;664(1-2):77-83. Epub 2009 Apr 5
  5. Acetaldehyde as a common denominator and cumulative carcinogen in digestive tract cancers.Salaspuro M. In: Scand J Gastroenterol. 2009 Apr 24:1-15.