What Actually Happens When You Drink

This is not a temperance leaflet

Let me be honest from the start: I enjoy a dram. A good single malt — particularly the peaty, medicinal, TCP-flavoured Islay whiskies like Lagavulin — is one of the genuine pleasures in my life. That combination of peat smoke, iodine and sea salt, the warmth spreading down your chest, the ritual of it. There is something in that experience that goes beyond the pharmacology of ethanol. It is sensory, cultural, emotional, and yes — dopaminergic. The brain likes it. I like it. I'm not pretending otherwise.

Which is exactly why I'm qualified to write this piece. The worst alcohol advice comes from two places: people who've never enjoyed a drink telling you not to, and people who drink too much telling you it's fine. I sit somewhere in the middle, where most of my clients sit, and where most of you reading this sit. You drink occasionally or moderately, you suspect it's not doing you any favours, but you're not about to give it up entirely — and you shouldn't have to, provided you understand what's actually happening.

What follows is the clinical reality. What your liver does. What your gut does. What your blood sugar does. What your brain does. And what you can do — practically, specifically — to make informed choices rather than guilty ones.

What your liver actually does with alcohol

Every drink you take follows the same metabolic path, regardless of whether it arrives in a crystal tumbler of Lagavulin or a tin of cheap lager. Ethanol enters your bloodstream through the stomach and small intestine — faster on an empty stomach, slower with food — and heads straight to the liver, where the real work begins.

The liver processes alcohol in two enzymatic steps. First, the enzyme alcohol dehydrogenase (ADH) converts ethanol into acetaldehyde — a compound roughly 10 to 30 times more toxic than the alcohol itself. This is the molecule responsible for facial flushing, headaches, nausea, and that dreadful morning-after feeling. Your body wants it gone as quickly as possible.

The second step uses aldehyde dehydrogenase (ALDH2) to convert acetaldehyde into acetate, which is relatively harmless and eventually broken down into carbon dioxide and water. The speed at which these two steps happen — and crucially, the balance between them — determines how well you tolerate alcohol and how much damage it does.

The enzyme adaptation problem

Here's where it gets clinically interesting. If you drink regularly, your liver upregulates ADH and the cytochrome P450 system (specifically CYP2E1) to process alcohol more efficiently. This is what most people call "building a tolerance." You can drink more without feeling drunk. This sounds like a good thing. It is not.

Increased CYP2E1 activity generates more reactive oxygen species — free radicals that damage liver cells. Your liver is simultaneously getting faster at processing alcohol and accumulating more oxidative damage in the process. Tolerance is not resilience. It is your liver running a hotter engine with no oil change.

Conversely, if you drink infrequently, your CYP2E1 levels are lower, your ADH activity is lower, and you process alcohol more slowly. You feel two glasses of wine more intensely. But you're generating less oxidative damage per drink. The occasional drinker who gets tipsy quickly is often metabolically healthier than the regular drinker who "handles it well."

The genetic lottery: why your friend can drink more than you

Roger Williams, in his landmark book Biochemical Individuality, made the case over sixty years ago that individual variation in enzyme activity, nutrient requirements, and metabolic capacity is far wider than medicine acknowledges. Nowhere is this more visible than in alcohol metabolism.

Variants in the ADH1B and ALDH2 genes create dramatically different alcohol experiences. The ALDH2*2 variant — common in East Asian populations but present globally — produces a slower version of the enzyme that clears acetaldehyde. The result: rapid facial flushing, nausea, and tachycardia even from small amounts of alcohol. This is not an "allergy." It is a genetic bottleneck in phase two clearance.

But it goes further than the well-known "Asian flush" variants. Within any Scottish family — and I see this in my own clinical practice — you'll find one sibling who can drink whisky all evening and appear fine at breakfast, and another who's wrecked after two glasses of wine. Williams was right: intrafamilial variation in alcohol tolerance is enormous, and it's largely enzymatic.

This is why blanket advice about "safe limits" — 14 units per week, no more than 6 in a session — is biochemically naive. Those numbers are population averages. Your personal threshold depends on your ADH variants, your ALDH2 efficiency, your CYP2E1 activity, your glutathione status, your sulfation capacity, and your current liver burden from everything else you're processing.

Alcohol and your gut

If the liver is where alcohol gets processed, the gut is where it does some of its most underappreciated damage.

Alcohol increases intestinal permeability — the clinical term for what's commonly called "leaky gut." Ethanol disrupts the tight junction proteins that hold intestinal cells together, allowing bacterial endotoxins (lipopolysaccharides) to cross into the bloodstream. This triggers a systemic inflammatory response. One heavy drinking session can measurably increase intestinal permeability for 24 to 48 hours. Regular moderate drinking maintains a chronically elevated baseline.

Then there's the microbiome. Alcohol selectively favours certain bacterial populations over others. It tends to reduce Lactobacillus and Bifidobacterium (the species you're trying to cultivate with probiotics and fermented foods) while encouraging gram-negative bacteria that produce more endotoxin. It is, in a sense, an antimicrobial — but an indiscriminate one that kills the bacteria you want and spares the ones you don't.

Candida and alcohol: the cycle nobody mentions

Alcohol, particularly wine and beer, provides a direct sugar substrate for Candida species in the gut. If you already have a candida overgrowth — and many of the clients I see with bloating, brain fog, sugar cravings and skin issues do — alcohol feeds it directly. But the relationship is bidirectional. Candida species produce their own endogenous ethanol and acetaldehyde through fermentation. Some clients with significant gut candida overgrowth experience mild intoxication symptoms even without drinking. They wake foggy, they crave sugar, they feel worse after bread or fruit. The GI-MAP and OAT tests together can identify this pattern with precision.

If your gut is already compromised, alcohol doesn't just add to the problem — it multiplies it.

Blood sugar, insulin and the fatty liver question

Alcohol has a paradoxical relationship with blood sugar. Initially, it can lower blood glucose by inhibiting gluconeogenesis — the liver's ability to manufacture new glucose. This is why some diabetics find their blood sugar drops after a drink. It is also why drinking on an empty stomach can cause reactive hypoglycaemia — a sharp drop in blood sugar that triggers anxiety, shakiness, poor decisions, and the impulse to eat everything in the kebab shop at midnight.

But the longer-term picture is different. Regular alcohol consumption drives insulin resistance through multiple pathways: direct hepatic lipid accumulation (fat in the liver), increased visceral adiposity, and chronic low-grade inflammation. The result, in many cases, is non-alcoholic fatty liver disease (NAFLD) — which is somewhat misnamed, because alcohol and metabolic dysfunction often coexist. The term MASLD (metabolic dysfunction-associated steatotic liver disease) is now replacing NAFLD in clinical literature, precisely because the old name implied a clean separation between alcohol-related and non-alcohol-related liver fat that doesn't exist in real people.

The sulfite question — and why it matters more than you think

When people say "wine gives me headaches but spirits don't," the reflexive answer is usually "sulfites." But the reality is more interesting than that.

Sulfites (sulphur dioxide, SO₂) are added to most conventional wines as a preservative. They prevent oxidation and microbial spoilage. White wines typically contain more added sulfites than reds. But sulfites are also produced endogenously during fermentation, so no wine is truly "sulfite-free" — the label claim means no sulfites were added, not that none are present.

The clinical question is: how well do you process sulfites? This brings us to sulfation — one of the liver's Phase II detoxification pathways. Sulfation conjugates toxins with a sulfate group to make them water-soluble for excretion. It depends on adequate DHEA-S (the sulfated form of DHEA, which we measure on the DUTCH Plus test), molybdenum status, and the activity of sulfite oxidase — the enzyme that converts sulfite to sulfate.

If your sulfation pathway is already under strain — from a high dietary load of sulfates and sulfites (dried fruits, processed meats, certain medications), from SNP variants affecting sulfite oxidase or the SULT enzyme family, or from low DHEA-S (common in chronic stress and adrenal dysfunction) — then the additional sulfite load from wine can tip you over a threshold. The headache isn't really about wine. It's about cumulative sulfite burden exceeding your clearance capacity.

This is where biodynamic and organic wines become genuinely relevant — not as a lifestyle badge, but as a practical reduction in exogenous sulfite load for people whose biochemistry handles sulfites poorly. Lower-intervention winemaking, minimal added SO₂, no synthetic pesticide residues. For someone with compromised sulfation, that's a clinically meaningful difference.

What alcohol does to your brain

Alcohol is pharmacologically unique: it's both a stimulant and a depressant, with the timing determining which you experience.

The first drink raises dopamine in the nucleus accumbens — the same reward pathway activated by food, sex, achievement, and social connection. This is the buzz. The confidence. The loosening of social anxiety. The reason people say "I'm more myself after a drink" — which is neurochemically interesting, because what's actually happening is a temporary suppression of the prefrontal cortex (the overthinking, self-monitoring part of the brain) combined with a dopamine surge that feels like reward.

But dopamine is a short-lived spike, not a sustained state. As blood alcohol rises, GABA activity increases and glutamate activity decreases — this is the depressant phase. Speech slows, coordination drops, and the emotional bandwidth narrows. Continued drinking borrows against tomorrow's neurotransmitter reserves. The anxiety you feel the morning after — sometimes called "hangxiety" — is a genuine neurochemical rebound: depleted GABA, elevated glutamate, suppressed serotonin.

For people already managing depression, anxiety, or ADHD, this rebound is particularly destabilising. The 48-hour neurochemical hangover from a heavy session can mimic or exacerbate clinical symptoms. Many clients report that their anxiety is "worse on Mondays" without connecting it to Saturday's drinking.

Alcohol and everything else: the downstream effects

Joints and muscles

Alcohol elevates uric acid — beer particularly, due to its purine content, but all alcohol to some degree via impaired renal excretion. Elevated uric acid drives gout flares obviously, but chronically elevated uric acid is also associated with systemic inflammation, endothelial dysfunction, and joint stiffness that doesn't meet the diagnostic threshold for gout but makes you feel ten years older than you are. If you wake up stiff after drinking, it's not just dehydration. It's an inflammatory load.

Migraines and headaches

Multiple mechanisms: histamine release (red wine is high in histamine), tyramine content (aged wines, beer), sulfite sensitivity as discussed above, vasodilation followed by rebound vasoconstriction, and dehydration. The specific trigger varies between individuals, which is why some people get headaches from red wine but not white, others from beer but not spirits. If you consistently get headaches from one type of alcohol and not another, that's useful diagnostic information — it points toward histamine, tyramine, or sulfites rather than ethanol itself.

Alcohol and diabetes

The relationship is genuinely complex. Small amounts of alcohol may modestly improve insulin sensitivity in the short term. Larger amounts drive insulin resistance, hepatic fat accumulation, and glycaemic instability. For someone already managing type 2 diabetes or prediabetes, alcohol adds an unpredictable variable that makes blood sugar management harder. The pragmatic clinical position: if you're working on insulin sensitivity and HOMA-IR is your primary target, alcohol is a complicating factor worth reducing — even if it's not the primary cause.

The cultural contract

In Scotland — and across much of the UK, Ireland, and northern Europe — alcohol is woven into the social fabric so deeply that not drinking requires more explanation than drinking. The office leaving do. The rugby club. The Friday night ritual. The Christmas party season that starts in November and ends in January. The funeral. The wedding. The christening. The Tuesday.

I've watched clients make extraordinary progress with their health — gut function normalised, energy restored, blood sugar stabilised — and then quietly undo a week's worth of protocol compliance over a single weekend because the social pressure to drink was stronger than their commitment to change. This is not a failure of willpower. It is a failure of environment.

Then there's the reward narrative. "Oh what a day I've had, I need a glass of wine." "I could kill for a drink." "I deserve this." The language tells you everything: alcohol positioned as compensation for suffering, as a reward for endurance. It becomes a learned stress response — the only one in many people's repertoire. The nightcap to unwind. The hot toddy that's "medicinal." These are behavioural patterns more than they are alcohol problems, and addressing them requires understanding the psychology of reward and stress management, not just the pharmacology of ethanol.

If alcohol is your only stress management tool, the issue isn't the tool — it's the toolbox. Exercise, breathwork, social connection, creative expression, sleep — these all regulate the same stress pathways without the metabolic cost. The goal is not to eliminate alcohol. It's to ensure it's one option among many, not the default.

So what does "moderation" actually mean?

Here's where most alcohol advice falls apart. "Moderation" is offered as wisdom without any attempt to define it biochemically. Fourteen units per week means nothing to your liver without knowing your ADH variant, your glutathione status, your sulfation capacity, your gut permeability, your current medication load, and your stress hormones.

What I can offer is a framework for thinking about it personally:

Frequency matters more than quantity per session. Three drinks once a week is metabolically different from one drink every night. The liver needs recovery time. Consecutive-day drinking prevents full clearance of acetaldehyde and perpetuates CYP2E1 upregulation.

Timing matters. Drinking with or after a meal — particularly one containing protein and fat — dramatically slows gastric emptying and alcohol absorption. Drinking on an empty stomach maximises the blood alcohol spike, the insulin disruption, and the gut permeability effect. If you're going to drink, eat first. This is not a hack. It's basic gastric physiology.

Context matters. Your liver doesn't process alcohol in isolation. It's simultaneously handling medications, environmental toxins, hormonal metabolites, and whatever you ate today. If you're already on paracetamol, PPIs, statins, or the oral contraceptive pill, your liver's detoxification capacity is already partially committed. Adding alcohol to an already-loaded liver is different from adding it to a rested one.

The practical support framework

If you're going to drink — and most of us are, at least occasionally — here's what the biochemistry suggests you can do to support your body before, during, and after:

Before

Eat a substantial meal containing protein and fat before you drink. This slows alcohol absorption dramatically. Cruciferous vegetables (broccoli, cauliflower, Brussels sprouts, kale) support Phase II liver detoxification via sulforaphane and indole-3-carbinol. Eggs provide cysteine, a precursor to glutathione — your liver's primary antioxidant defence.

Activated charcoal taken 30-60 minutes before drinking may bind some congeners and toxins in the GI tract before they're absorbed. The evidence is mixed but the mechanism is sound and the risk is minimal. Don't take it with medications — it'll bind those too.

During

Hydrate deliberately. Match each alcoholic drink with a glass of water. This is not about "diluting" alcohol — it's about maintaining kidney clearance and preventing the dehydration that amplifies every other symptom.

Choose lower-intervention drinks where practical. Organic, biodynamic, or low-sulfite wines reduce your exogenous chemical load. Clear spirits (gin, vodka) contain fewer congeners than darker spirits (bourbon, brandy, dark rum) — though a good Scotch is a good Scotch, and the congener difference at moderate intake is not worth losing sleep over.

After

NAC (N-acetylcysteine) supports glutathione replenishment. Take it the morning after, not before drinking — there's some evidence that NAC taken before alcohol may paradoxically increase liver toxicity by altering the metabolic pathway. 600mg the next morning is a reasonable dose.

Electrolytes — sodium, potassium, magnesium — replace what alcohol's diuretic effect depleted. This matters more than most people realise for the headache, brain fog, and fatigue of a hangover.

Exercise the next day supports detoxification through sweating, lymphatic circulation, and the upregulation of antioxidant enzyme systems. Even a 30-minute walk. Movement is medicine here.

Probiotics and fermented foods help restore the microbial populations that alcohol suppresses. Not a miracle cure, but part of the recovery ecology.

What about the type of drink?

I'll be direct: I don't think there's good evidence that whisky is meaningfully healthier than vodka, or red wine meaningfully healthier than gin, at equivalent ethanol doses. The "red wine is good for your heart" narrative was built on observational data that's been substantially challenged. The polyphenols in red wine (resveratrol, quercetin) are present in quantities too small to have therapeutic effects at any reasonable drinking level. You'd need to drink absurd volumes of wine to achieve the resveratrol doses used in research studies, and the alcohol damage would vastly outweigh any polyphenol benefit.

What does differ between drinks is the non-alcohol load: congeners, histamine, sulfites, purines, gluten fragments, sugar content. Beer is high in purines (uric acid), histamine, and carries gluten fragments. Conventional wine carries sulfites and histamine. Sweet wines and cocktails carry significant sugar. Cheap spirits may contain more congeners from poor distillation. But at the level of the ethanol molecule itself — which does the majority of the metabolic work — your liver doesn't distinguish between a £200 bottle of Barolo and a can of Tennent's.

Hormesis: the small-dose paradox

There is a legitimate scientific concept here. Hormesis — the principle that small doses of a stressor or toxin can stimulate beneficial adaptive responses. We see it with exercise (mechanical stress builds muscle), with phytochemicals (plant defence compounds that trigger our antioxidant systems), and with cold exposure. Can alcohol in very small doses function hormetically?

Perhaps. The epidemiological data on very light drinking (1-2 drinks per week, not per day) and cardiovascular outcomes remains genuinely mixed. But the mechanistic evidence for hormetic benefit from alcohol specifically is weak compared to, say, the hormetic effects of sulforaphane from broccoli or the polyphenols from olive oil. My clinical position: if you enjoy an occasional drink in the context of an otherwise well-supported body, the pleasure and social connection probably contribute more to your overall wellbeing than the marginal biochemical cost detracts from it. That is a different statement from "alcohol is good for you."

A word on low-alcohol and alcohol-free alternatives

The market for no-alcohol and low-alcohol drinks has exploded. Some are genuinely well-made. Some are marketing vehicles for functional ingredients — Impossibrew, for example, adds ashwagandha to their alcohol-free beer, which is interesting as a concept but shouldn't be confused with a clinical intervention. The adaptogenic dose in a beer is not the dose used in research.

If you enjoy them and they help you reduce your alcohol intake, they serve a purpose. But they're lifestyle products, not health products. A sugar-laden alcohol-free cocktail is not biochemically superior to a glass of clean wine with dinner. Read the labels. Some "healthy alternatives" contain more sugar per serving than the drinks they replace.

The summary — in the spirit of test, don't guess

Alcohol is a toxin. It's also a source of genuine pleasure, cultural connection, and in small doses, possibly hormetic benefit. These things are not contradictory. Life is not binary.

What matters is your biochemistry, not population averages. Your ADH and ALDH2 genetics. Your glutathione status. Your sulfation capacity. Your gut integrity. Your liver's current workload. Your stress hormones. Your blood sugar regulation. All of this is measurable, and all of it informs what "moderate" actually means for you.

If you're curious about where you stand — if your GGT is creeping up, if your hangovers are getting worse, if you suspect your gut isn't coping the way it used to, if you're waking stiff and foggy after what used to be a manageable evening — those are signals worth investigating. Not guessing. Testing.

The goal is not abstinence. The goal is informed autonomy. Know what your body does with alcohol, support it properly, and make choices from knowledge rather than guilt.

And if your choice tonight is a wee dram of something peaty with a splash of water, I'll not be the one to judge you. I might well be doing the same.

Stephen Duncan BSc (Hons) MSc FDN-P · Edinburgh · May 2026