When the human body processes alcohol, it relies on a system of enzymes to break down the substance into less harmful components. However, for some individuals, this natural detoxification pathway is impaired, leading to a condition known as alcohol dehydrogenase deficiency. This deficiency means the body struggles to efficiently process alcohol, resulting in various physical reactions and potential health concerns. Understanding this condition involves examining the body’s normal alcohol breakdown process and how genetic variations can alter it.
Understanding Alcohol Metabolism
The primary site for alcohol metabolism in the human body is the liver, though some breakdown also occurs in other tissues. The initial step in this process involves an enzyme called alcohol dehydrogenase (ADH), which converts ethanol, the alcohol found in beverages, into a toxic compound known as acetaldehyde. This oxidation reaction requires nicotinamide adenine dinucleotide (NAD+) as a cofactor, which is converted to its reduced form, NADH, during the process.
Following this initial conversion, acetaldehyde must be quickly processed due to its harmful nature. Another enzyme, aldehyde dehydrogenase (ALDH), primarily ALDH2 located in the mitochondria, rapidly oxidizes acetaldehyde into acetate. Acetate is a non-toxic substance that can then be broken down into carbon dioxide, fatty acids, and water by peripheral tissues. While ADH and ALDH are the main players, other enzyme systems, such as the microsomal ethanol oxidizing system (MEOS) involving cytochrome P450 (CYP2E1), also contribute to a smaller fraction of alcohol metabolism.
What is Alcohol Dehydrogenase Deficiency?
Alcohol dehydrogenase deficiency describes a genetic variation that affects the body’s ability to process alcohol effectively, often due to altered activity of the enzymes involved in alcohol metabolism. This condition is not an allergy but rather an inherited metabolic disorder. The deficiency primarily stems from genetic variations in the genes that encode alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes.
Specifically, variants of the ALDH2 gene, such as ALDH2\2, lead to an enzyme that is less active or inactive. This significantly impairs the conversion of acetaldehyde to acetate, causing acetaldehyde to accumulate in the bloodstream and tissues. Additionally, some individuals may have variants of ADH enzymes, like ADH1B\2, which can lead to a more rapid initial conversion of alcohol to acetaldehyde.
The prevalence of these genetic variants varies across populations, with the ALDH2\2 allele found almost exclusively in individuals of East Asian descent, including Chinese, Japanese, and Koreans. Approximately one-third of Han Chinese individuals, for example, possess at least one ALDH2\2 allele. The ADH1B\2 allele is also highly prevalent among Asians, with the exception of individuals of Indian descent. This genetic predisposition explains why alcohol dehydrogenase deficiency and its associated symptoms are more commonly observed in these populations.
Recognizing the Symptoms
Individuals with alcohol dehydrogenase deficiency experience unpleasant physical symptoms shortly after consuming alcohol. The primary symptom is facial flushing, often referred to as the “alcohol flush reaction” or “Asian flush.” This involves reddening of the face, neck, and chest.
These symptoms occur because of the buildup of acetaldehyde, the toxic byproduct of alcohol metabolism. The accumulation of acetaldehyde causes blood vessels to dilate, leading to the visible flushing. Other common symptoms include nausea, vomiting, a rapid heart rate, headaches, dizziness, a stuffy nose, and diarrhea are frequently reported.
Health Implications and Living with the Deficiency
Living with alcohol dehydrogenase deficiency means the body struggles to properly metabolize alcohol, which can have long-term health implications if alcohol consumption is not managed. The accumulation of acetaldehyde is a known carcinogen, meaning it can increase the risk of certain cancers. Individuals with low ALDH2 activity have an elevated risk for cancers of the upper aerodigestive tract, including esophageal, oropharyngeal, and laryngeal cancers. Some studies indicate a relative risk of 11.0 for oropharyngeal and laryngeal cancer and 12.5 for esophageal cancer in affected individuals.
The risk for esophageal cancer, specifically squamous cell carcinoma, is notably higher, with some individuals experiencing a 50-fold increased risk of developing a second tumor in the esophagus. Liver damage, including alcoholic liver disease, is another concern. The increased acetaldehyde burden can contribute to oxidative stress and cellular damage within the liver. Beyond these specific risks, general long-term alcohol consumption can lead to conditions such as chronic pancreatitis, hypertension, and various other cancers, even in individuals without this specific deficiency.
Given these health risks, the effective strategy for individuals with alcohol dehydrogenase deficiency is to avoid alcohol consumption entirely or practice strict moderation. The unpleasant symptoms often serve as a natural deterrent, leading many individuals with this deficiency to consume less alcohol than those without it. Consulting with a healthcare provider can provide personalized guidance and help individuals understand their specific health implications.