How Alcohol Is Metabolized: The ADH Pathway, Acetaldehyde, and Why Calories Count

Your liver is doing a lot of work on your behalf every time you drink. Understanding the chemistry explains why alcohol behaves so differently from other calorie sources, why some people flush red, and why the calorie count on a beer bottle undersells the metabolic picture.

The Two Enzymes

Alcohol metabolism runs through two enzymes in sequence.

Alcohol dehydrogenase (ADH) is the first responder. It’s found in the stomach lining and in liver cells. ADH oxidizes ethanol (alcohol) into acetaldehyde. This reaction is the body’s main first-pass attempt to dismantle the alcohol before it circulates widely.

Then aldehyde dehydrogenase (ALDH) takes over. It converts acetaldehyde into acetate (acetic acid, the same compound in vinegar). Acetate enters the bloodstream, gets picked up by peripheral tissues, and is oxidized to water and carbon dioxide for energy.

The chain is: ethanol (ADH) acetaldehyde (ALDH) acetate energy.

The problem is the middle step. Acetaldehyde is not benign.

Why Acetaldehyde Matters

Acetaldehyde is a reactive organic compound that binds to proteins, DNA, and membrane structures. The International Agency for Research on Cancer classifies acetaldehyde as a Group 1 carcinogen, meaning there is sufficient evidence that it causes cancer in humans (IARC Monographs, 2012).

This carcinogenicity is central to alcohol’s association with cancers of the mouth, throat, esophagus, liver, and breast. The acetaldehyde produced during alcohol metabolism, and acetaldehyde produced by oral bacteria from alcohol, creates adducts with DNA that can initiate tumor formation.

Think of it like a reactive industrial solvent running through biological machinery. Most of it gets cleared quickly by ALDH. But the window of exposure matters, and anything that slows ALDH activity extends that window.

The ALDH2 Genetic Variant

About 35-40% of people with East Asian ancestry carry an ALDH2*2 variant that severely reduces ALDH activity (Edenberg, 2007, Alcohol Research and Health). When they drink, acetaldehyde accumulates faster than their diminished ALDH can clear it.

The symptoms are immediate: flushing of the face, neck, and chest, nausea, rapid heartbeat, and headache. This is the alcohol flush reaction, sometimes called the Asian glow. It’s not alcohol sensitivity in a casual sense. It’s acetaldehyde toxicity.

The carcinogenic consequence is serious. People with the ALDH2*2 variant who continue to drink regularly have substantially elevated risk of esophageal cancer, estimated at 6-10 times higher than non-carriers who drink the same amount. The flush reaction is a biological warning system, and ignoring it carries real risk.

Flushing while drinking is worth mentioning to a doctor.

How Alcohol Calories Work

Ethanol contains 7 kilocalories per gram, more than carbohydrates (4 kcal/g) or protein (4 kcal/g), less than fat (9 kcal/g). These are real metabolic calories that count toward daily energy intake.

But the processing path is unusual (Cederbaum, 2012, Clinics in Liver Disease).

When you drink, acetate production ramps up. Peripheral tissues preferentially oxidize acetate for fuel. While acetate is being burned, fat oxidation drops. You’re temporarily running on alcohol-derived energy, which means fat that would have been burned sits in storage instead.

This isn’t the same as alcohol converting to body fat, which is biochemically inefficient and doesn’t happen in significant amounts. The weight effect from alcohol comes from the total caloric surplus combined with appetite effects. Research by Yeomans (2010, Physiology and Behavior) shows alcohol specifically increases appetite for energy-dense foods and weakens satiety signaling, so people tend to eat more after drinking.

The calories in a standard drink are real. One beer (12 oz, 5%) delivers about 150 kcal. A glass of wine (5 oz, 12%) delivers about 120 kcal. A shot of 80-proof spirits (1.5 oz) delivers about 96 kcal. None of these account for the appetite stimulation that often follows.

The MEOS: High-Dose and Chronic Drinking

At low to moderate doses, ADH and ALDH handle most of the work. But at high blood alcohol concentrations, a second pathway activates.

The microsomal ethanol-oxidizing system (MEOS), driven primarily by the CYP2E1 enzyme, contributes an estimated 20-25% of alcohol metabolism in people who drink heavily or chronically. This pathway is inducible: heavy drinking upregulates CYP2E1 expression, making the liver more efficient at metabolizing alcohol over time. This is part of why chronic drinkers develop tolerance.

MEOS generates reactive oxygen species during alcohol oxidation, more than the ADH pathway does. This oxidative burden on liver cells is one mechanism linking heavy drinking to alcoholic liver disease.

First-Pass Metabolism and Sex Differences

Not all ethanol makes it to the liver. Some is metabolized in the stomach lining by gastric ADH before absorption.

Women have lower gastric ADH activity than men on average, which means more ethanol reaches the bloodstream per drink consumed. This is one biochemical contributor to sex differences in alcohol tolerance and liver disease susceptibility, though body water distribution (women have less) also plays a role.

This article is for educational purposes only. It’s not medical advice. Talk to your doctor or a registered dietitian before making significant changes to your diet.