Alcohol & the Body
The documented biology of ethanol — what happens after swallowing, why it affects the brain, and why individual responses vary enormously.
This page documents the pharmacology and toxicology of ethanol from named official scientific sources. It is not medical advice. It does not constitute guidance on safe consumption levels for any individual. Individual responses to alcohol vary significantly and depend on body weight, sex, food intake, medication, genetic factors, and health status. Always consult a qualified medical professional for personal health questions. If you are concerned about your relationship with alcohol, please speak with a qualified healthcare professional. International helpline resources: WHO Alcohol Information.
Ethanol (C₂H₅OH, also written as C₂H₆O) is a psychoactive substance classified as a central nervous system depressant. Upon ingestion, ethanol is absorbed from the gastrointestinal tract into the bloodstream, distributed throughout total body water, and metabolised primarily in the liver by two sequential enzyme reactions: (1) oxidation of ethanol to acetaldehyde by alcohol dehydrogenase (ADH), and (2) oxidation of acetaldehyde to acetic acid by aldehyde dehydrogenase (ALDH, specifically the ALDH2 isoform in the primary pathway). Blood Alcohol Concentration (BAC) is the standard measure of ethanol in the bloodstream, expressed as grams of ethanol per 100 millilitres of blood (g/100mL or g/dL) or as a percentage by mass. The Widmark formula (1932) provides a pharmacokinetic model for estimating peak BAC from the amount of ethanol consumed, body weight, sex-specific distribution constant, and metabolic elimination rate. Source: Casarett and Doull's Toxicology, 10th edition; WHO Global Status Report on Alcohol and Health 2018.
What ethanol is and how the body processes it
Ethanol is a small, water- and fat-soluble molecule. Because it dissolves readily in water, it distributes throughout all water-containing tissues in the body — blood, brain, muscle, organs. Because it also dissolves in fat, it crosses the blood-brain barrier quickly. This combination of properties explains why ethanol affects the brain rapidly and affects mood, coordination, and judgement long before it has been metabolised.
The liver metabolises approximately 90% of all ethanol consumed. The primary pathway: ethanol → acetaldehyde (toxic intermediate) → acetic acid (relatively harmless) → CO₂ + water (eliminated). The limiting factor in this process is the enzyme ALDH2 — which converts the toxic acetaldehyde to harmless acetic acid. ALDH2 works at a relatively constant rate regardless of how much ethanol is consumed — approximately 7–10 grams of pure alcohol per hour in a typical adult.
When ethanol is consumed faster than ALDH2 can clear the acetaldehyde, acetaldehyde accumulates in the blood and tissues. Acetaldehyde is responsible for the flushing, nausea, racing heartbeat, and headache associated with alcohol excess — and with the "Asian flush" reaction experienced by people with a deficient ALDH2 enzyme.
Why different people experience alcohol very differently
The most significant documented source of variation in alcohol metabolism is genetic: the ALDH2*2 allele, carried by approximately 36% of East Asian populations (documented in pharmacogenomics literature), produces a deficient ALDH2 enzyme that is approximately 200 times less effective at metabolising acetaldehyde than the wild-type enzyme. Carriers of ALDH2*2 accumulate acetaldehyde rapidly when drinking — causing facial flushing, nausea, and palpitations at low ethanol doses. This genetic variant is the most common cause of the "Asian flush" reaction and is protective against heavy alcohol consumption (because drinking feels uncomfortable) but increases cancer risk from acetaldehyde if alcohol is consumed despite these symptoms.
Body weight, sex, food intake, and hydration state also affect how ethanol is distributed and how fast BAC rises. Female bodies have proportionally less total body water than male bodies of the same weight (due to higher average fat percentage) — meaning ethanol distributes into a smaller water volume and produces higher BAC per gram consumed. This is reflected in sex-specific constants in the Widmark BAC formula.
The Widmark formula — BAC calculation
The Widmark formula (1932, Erik M.P. Widmark, Swedish chemist) is the pharmacokinetic model used internationally for estimating peak Blood Alcohol Concentration from known ethanol intake. It is used in legal contexts (drunk driving cases), medical contexts, and forensic toxicology globally.
Where:
A = mass of ethanol consumed (grams)
0.806 = conversion constant (specific gravity of ethanol)
BW = body weight in kilograms
r = Widmark factor (distribution coefficient)
Males: r ≈ 0.68 (documented range 0.56–0.80)
Females: r ≈ 0.55 (documented range 0.44–0.66)
β = elimination rate (typically 0.015 g/100mL/hr)
T = time elapsed since drinking started (hours)
To convert a standard drink to grams of ethanol: a 30mL shot of 40% ABV spirit contains 30 × 0.40 × 0.789 (density of ethanol) = approximately 9.5 grams of ethanol. A 150mL glass of 13% ABV wine contains approximately 15.4 grams. A 330mL beer at 5% ABV contains approximately 13 grams.
BAC legal limits — driving — by country
| Country / Region | General population BAC limit | Professional / commercial drivers | Novice / young drivers |
|---|---|---|---|
| Australia | 0.05 g/100mL | 0.02 g/100mL | 0.00 g/100mL |
| Brazil | 0.02 g/100mL (near zero) | 0.00 g/100mL | 0.00 g/100mL |
| Canada | 0.08 g/100mL (federal); provincial variations | 0.04 g/100mL | 0.00–0.04 g/100mL (varies by province) |
| European Union | 0.05 g/100mL (most states) | 0.02 g/100mL | 0.02 g/100mL (many states) |
| India | 0.03 g/100mL (30mg/100mL blood) | Same | Same |
| Japan | 0.03 g/100mL | 0.015 g/100mL | 0.00 g/100mL |
| United Kingdom | 0.08 g/100mL (England, Wales); 0.05 g/100mL (Scotland) | Same | Same |
| USA | 0.08 g/100mL (federal standard) | 0.04 g/100mL (commercial) | 0.02 g/100mL (most states) |
| Prohibition jurisdictions | 0.00 g/100mL — includes Saudi Arabia, UAE, most of Pakistan | 0.00 g/100mL | 0.00 g/100mL |
The ADH/ALDH2 pathway — enzyme biochemistry
The two-step enzymatic metabolism of ethanol is the primary hepatic pathway and accounts for approximately 90% of ethanol clearance. The remaining 10% is cleared by non-ADH pathways (microsomal ethanol oxidising system — MEOS — primarily through CYP2E1) and by direct pulmonary, renal, and dermal excretion.
Step 1: Ethanol → Acetaldehyde (ADH)
Alcohol dehydrogenase (ADH) is a zinc-containing enzyme primarily expressed in hepatocytes (liver cells). It oxidises ethanol to acetaldehyde (CH₃CHO) using NAD⁺ as a cofactor, producing NADH. The reaction: CH₃CH₂OH + NAD⁺ → CH₃CHO + NADH + H⁺. Multiple ADH isoforms (ADH1A, ADH1B, ADH1C) are expressed in human liver with different kinetic parameters. The ADH1B*2 allele — common in East Asian and some Middle Eastern populations — produces an ADH enzyme with significantly higher activity, converting ethanol to acetaldehyde faster than the common ADH1B*1 allele. Faster ADH + deficient ALDH2 = rapid acetaldehyde accumulation = pronounced flush reaction.
Step 2: Acetaldehyde → Acetic Acid (ALDH2)
Aldehyde dehydrogenase 2 (ALDH2) is the primary enzyme responsible for converting the toxic intermediate acetaldehyde to relatively harmless acetic acid (CH₃COOH), which is then converted to acetyl-CoA and enters the citric acid cycle. The reaction: CH₃CHO + NAD⁺ + H₂O → CH₃COOH + NADH + H⁺. ALDH2 is a mitochondrial enzyme with a very high affinity for acetaldehyde (low Km) — meaning it efficiently clears acetaldehyde at low concentrations. The ALDH2*2 allele (also called ALDH2 rs671) encodes a deficient enzyme with approximately 200-fold reduced activity. Heterozygous carriers (one deficient allele) have substantially reduced ALDH2 activity; homozygous carriers have near-zero activity.
ALDH2*2 — population genetics and clinical significance
The ALDH2*2 allele has a population frequency of approximately 30–36% in East Asian populations (Japanese, Korean, Chinese) and is almost absent in European and African populations — documented by the Human Genome Database and multiple population genetics studies. Its high frequency in East Asian populations is attributed by evolutionary geneticists to founder effects and genetic drift rather than to any selective advantage — the allele confers no documented benefit and significant disadvantage in environments where alcohol is consumed. Its clinical significance: carriers who drink despite the acute discomfort of acetaldehyde accumulation face substantially elevated risk of oesophageal cancer due to carcinogenic acetaldehyde exposure — documented in peer-reviewed oncology literature.