Alcohol Detoxification

After alcohol is consumed, it is absorbed mainly from the small intestine into the bloodstream and then to the liver, where it is exposed to enzymes and metabolised.

Genetics

Alcohol is detoxified in two steps or phases.

The first phase is the conversion of ethanol (alcohol) by ADH genes to acetaldehyde – which is much more toxic than ethanol. If your alcohol intake is high and your ADH gene capacity is exceeded, the CYP2E1 gene takes over to metabolise ethanol to acetaldehyde. However, CYP2E1 activity is associated with more reactive oxygen species (ROS) production and protein and DNA damage.

In phase 2, acetaldehyde is metabolised by ALDH to the inert metabolite acetic acid. This may in turn be converted to acetyl-CoA and enter the Krebs cycle.

Essentially, we don't want phase 1 to be too fast (and create excess acetaldehyde), but we do want phase 2 to work efficiently and as fast as possible (to effectively remove acetaldehyde).

Indeed, faster metabolism of ethanol to acetaldehyde and/ or slower metabolism of acetaldehyde to acetic acid can significantly raise acetaldehyde levels, which, in turn, can stimulate histamine release. Acetaldehyde is also found in indoor air, tobacco smoke, and as a product of Candida overgrowth.

Acetaldehyde toxicity can cause unpleasant symptoms such as facial flushing, urticaria, dermatitis, rhinitis and asthma-like reactions (bronchoconstriction), nausea, tachycardia, headaches, more severe hangovers, and protein and DNA damage.

Genetic polymorphisms on the ADH, ALDH and CYP2E1 genes can significantly impact your capacity to detoxify alcohol, resulting in more extreme symptoms.

For example, some SNPs on ADH1B (Alcohol Dehydrogenase 1B Beta Polypeptide) can lead to significantly increased enzyme activity and a higher rate of conversion of ethanol to acetaldehyde, which can worsen toxicity symptoms (but may be protective against alcoholism).

There are two primary SNPs on the ADH1B gene. One SNP is common in Asian populations but much less prevalent in European and African populations. It can result in up to 100 times faster metabolism of ethanol to acetaldehyde! The other SNP is much rarer, with a frequency of less than 1% in all populations. These SNPs can be supported by replenishing cofactors NAD+ (vitamin B3) and zinc, which the detoxification process may deplete.

Additionally, there are two main SNPs that impact another member of the alcohol dehydrogenase family – the ADH1C gene (Alcohol Dehydrogenase 1C Gamma Polypeptide). The wild allele is the most detrimental, increasing the rate of alcohol conversion to acetaldehyde by up to 70%. Consequently, it is shown in red in our pathway diagram. It is also the most common genotype in Asian populations.

Along with ADH1B and ADH1C, CYP2E1 is one of the most important enzymes for alcohol metabolism – accountable for up to 10% of ethanol oxidation in the liver. In the absence of ADH cofactors (i.e. due to chronic drinking), oxidation of ethanol to aldehyde by CYP2E1 produces more ROS. Variants on the CYP2E1 gene are associated with up-regulated enzyme activity, which may increase the risk of oxidative damage. Isothiocyanates, found in foods such as radish, Brussels sprouts, watercress, mustard and wasabi, have been found to help reduce CYP2E1 activity.

Finally, in the second phase, polymorphisms on ALDH2 (Aldehyde Dehydrogenase 2 Family (mitochondrial)) can result in an inactive ALDH enzyme and a high risk of acetaldehyde toxicity after consumption of alcohol or smoking. Side effects (again – facial flushing, urticaria, dermatitis, rhinitis, asthma like reactions, and more severe hangovers linked to histamine release) may deter carriers from drinking, reducing their risk of alcoholism and alcohol-related diseases.

However those with ALDH2 SNPs who do drink or smoke have an increased risk of oesophageal cancer. Approximately 50% of East Asians lack the mitochondrial form of ALDH2, which could partly explain a higher frequency of acute alcohol intoxication among Asians. This pathway can be supported by limiting alcohol consumption and increasing cofactors – vitamins B2 and B3, magnesium, molybdenum and zinc.

Lifecode Gx® Reports

Our Detoxification Report shows how your genes impact alcohol detoxification.

The Detoxification Report not only looks at genes for alcohol detoxification, but also many other genes involved in other areas of metabolism – such as mould, pesticides, NSAIDs, paracetamol, medications, environmental pollutants, smoke, and other toxins.