[5][6] It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome.

[5][10] Drinking alcohol in addition to consuming calcium cyanamide can cause permanent or long-lasting intolerance (nitrolime disease),[11][12] contributing (in conjunction with other substances) to the accumulation of harmful acetaldehyde in the body by inhibiting the acetaldehyde dehydrogenase enzyme.

[13][5][6] Common signs and symptoms of alcohol intolerance include nasal congestion, skin flushing (redness), headaches, low blood pressure, nausea, and vomiting.

[1][2] Individuals that have the ALDH2*2 allele, a variant that has a mutation when compared to the wild-type ALDH2 isozyme, are known to have higher blood acetaldehyde levels.

[22] Epigenetic factors, which are heritable changes in gene expression that do not involve alterations to the DNA sequence, can play a significant role in the deficiency of aldehyde dehydrogenase 2 (ALDH2), a key enzyme in metabolizing alcohol.

[24] Lower methylation at these sites reduces ALDH2 production, intensifying alcohol intolerance symptoms like facial flushing, headaches, and rapid heartbeat.

[25] For individuals with ALDH2 deficiencies, these epigenetic changes can worsen the body’s ability to break down acetaldehyde, resulting in more frequent or severe symptoms over time.

[25] In addition to DNA methylation, other epigenetic mechanisms, such as histone modifications (chemical changes to the proteins that help package DNA) and non-coding RNAs (RNA molecules that regulate gene expression without encoding proteins), also influence ALDH2 regulation.

[24] These factors can alter chromatin structure, the organization of DNA and proteins within the nucleus, reducing gene accessibility and decreasing enzyme production.

[24] Combined with genetic predispositions, these epigenetic factors play a significant role in alcohol intolerance, as they contribute to inefficient alcohol metabolism and a buildup of acetaldehyde, resulting in the discomfort and adverse reactions experienced by affected individuals.

Various genetic and environmental factors exist that can lead to an increased risk for developing alcohol intolerance.

Individuals with two copies of the ALDH2*2 allele are known to have high blood acetaldehyde levels and experience “hangover” symptoms such as heart palpitations for longer durations, even with low alcohol consumption.

[34] The increased accumulation of acetaldehyde in affected individuals due to deficient aldehyde dehydrogenase enzymes often leads to the characteristic symptom of having flushed skin.