Your body relies on two main enzymes to break down alcohol: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). These enzymes work in sequence, first converting ethanol into a toxic intermediate called acetaldehyde, then converting acetaldehyde into harmless acetate. Most of this process happens in the liver, and it runs at a relatively fixed pace of about 20 mg/dL of blood alcohol per hour for the average adult.
Step One: ADH Converts Alcohol to Acetaldehyde
The first enzyme to act on alcohol is alcohol dehydrogenase, or ADH. Found primarily in liver and stomach cells, ADH strips hydrogen atoms from ethanol molecules and produces acetaldehyde. This is a straightforward chemical reaction: ethanol goes in, acetaldehyde comes out. ADH uses a zinc atom in its active site to position the ethanol molecule precisely for this conversion.
ADH doesn’t just work in the liver. A version of this enzyme also operates in the stomach lining, where it begins breaking down alcohol before it even reaches the bloodstream. This “first-pass metabolism” in the stomach can meaningfully reduce how much intact alcohol enters your circulation. However, the amount of stomach ADH varies from person to person, which partly explains why two people drinking the same amount can end up with very different blood alcohol levels.
Step Two: ALDH Clears the Toxic Byproduct
Acetaldehyde, the product of that first reaction, is significantly more toxic than alcohol itself. It damages DNA, triggers inflammation, and causes the nausea and headache many people associate with hangovers. Your body needs to clear it quickly, and that’s where the second enzyme steps in: aldehyde dehydrogenase, or ALDH.
Two forms of ALDH handle the bulk of this work. ALDH1 operates in the general fluid inside cells, while ALDH2 works inside the mitochondria, the energy-producing compartments of each cell. Of the two, ALDH2 is by far the more important for keeping acetaldehyde levels extremely low. It converts acetaldehyde into acetate, a harmless compound your body can use for energy or simply excrete. When this enzyme works well, acetaldehyde barely accumulates at all.
Alternative Pathways for Heavy Drinking
ADH and ALDH handle the vast majority of alcohol metabolism, but your body has backup systems that become more active under certain conditions. The most significant is a liver enzyme called CYP2E1, which is part of a broader system sometimes called the microsomal ethanol oxidizing system (MEOS). In moderate drinkers, CYP2E1 plays a minor role. But it’s inducible, meaning chronic or heavy alcohol exposure ramps up its production. In heavy drinkers, CYP2E1 can account for roughly 20% of alcohol metabolism.
CYP2E1 also responds to other substances. Nicotine, for instance, increases CYP2E1 activity in the brain and liver, which is one reason smoking and drinking interact in complex ways. Unlike ADH, CYP2E1 generates harmful byproducts called free radicals during the process of breaking down ethanol, which contributes to the liver damage seen in chronic heavy drinkers.
A third enzyme, catalase, plays a smaller but interesting role, particularly in the brain. Catalase uses hydrogen peroxide as a co-substrate to convert ethanol into acetaldehyde. In the brain specifically, the catalase system is the primary pathway for local alcohol metabolism. Research in rodents has shown that the acetaldehyde produced this way in the brain influences some of alcohol’s behavioral effects, including the drive to keep drinking.
Why Some People Process Alcohol Faster
The average person clears alcohol from their blood at about 20 mg/dL per hour. But individual variation is substantial. In emergency department measurements, the standard deviation was nearly 7 mg/dL per hour, meaning a sizable minority of people clear alcohol at rates well above or below that average. Several factors drive this variation.
Genetics is the biggest one. Some people carry ADH variants that are unusually fast at converting ethanol to acetaldehyde. Others carry ALDH variants that are unusually slow at clearing acetaldehyde. Both situations elevate acetaldehyde levels, but they produce different experiences and long-term risks.
Body composition and biological sex also matter. Women have less gastric ADH activity than men, resulting in less first-pass metabolism in the stomach. One study found that the gender difference was most pronounced at higher alcohol concentrations. At a 40% alcohol concentration (like spirits), women had noticeably less stomach metabolism than men. At a 5% concentration (like beer), the difference nearly disappeared. This reduced first-pass metabolism is one of the main reasons women typically reach higher blood alcohol levels than men after the same number of drinks, even after adjusting for body weight.
The ALDH2 Variant and Alcohol Flushing
About 540 million people of East Asian descent carry a genetic variant called ALDH2*2, which produces a much less effective version of the ALDH2 enzyme. This single mutation affects roughly 8% of the world’s population and is the most common cause of “alcohol flush reaction,” the facial redness, rapid heartbeat, headache, and nausea that some people experience after even small amounts of alcohol.
When ALDH2 doesn’t work properly, acetaldehyde accumulates in the blood instead of being quickly converted to acetate. In a Japanese cohort, nearly 43% of participants with ALDH2 deficiency experienced flushing symptoms including palpitations, muscle weakness, and nausea. This buildup isn’t just uncomfortable. Acetaldehyde is a known carcinogen. East Asians who carry the ALDH2*2 variant and drink regularly face a significantly higher risk of esophageal, head and neck, and lung cancers compared to people with fully functional ALDH2.
The protective effect of this variant is that many carriers find drinking unpleasant enough that they drink less or not at all. But for those who drink despite the flushing, the long-term health consequences are more severe than they would be for someone whose ALDH2 enzyme works at full capacity. ALDH2 deficiency has also been linked to higher rates of cardiovascular disease and, in people with certain rare genetic conditions, accelerated bone marrow failure.
How Acetaldehyde Drives Hangover Symptoms
Much of what people experience as a hangover traces back to acetaldehyde. When you drink faster than your ALDH enzymes can clear this intermediate compound, acetaldehyde temporarily accumulates. It irritates tissues, triggers inflammatory responses, and produces the characteristic cluster of headache, nausea, and general malaise. People with less efficient ALDH2 feel these effects sooner and more intensely, but anyone who drinks enough will eventually overwhelm their acetaldehyde clearance capacity.
Because the rate-limiting step in alcohol metabolism is largely enzymatic and fixed, there’s no reliable way to speed the process up. Your liver works through its queue at roughly one standard drink per hour. Coffee, cold showers, and exercise don’t change the enzymatic math. The only variable you truly control is how much and how fast you drink relative to your body’s fixed processing speed.