Alcohol and the gut: what happens even at small amounts

Friday evening, two glasses of wine, nothing special. On Saturday morning the head is more or less in order, but the belly is not. First that pulling feeling, then three trips to the toilet, then half a day with the sense that something inside is rumbling. Not a hangover in the classic meaning. More like a gut that is letting you know.

Many people know this pattern and tell nobody about it. Because it seems small. Because two glasses of wine are not something you raise in a consultation. And because the answer you expect anyway is: well, drink less then.

I find that answer useless. Not because it is wrong, but because it answers no question. The question that is actually being asked is a different one. It goes: what exactly is happening down there? And there are answers to that, measurable ones, with numbers, with time courses and with clear limits on what we know.

This text is not a call for abstinence and not an all clear. It is a set of directions. We walk alcohol station by station through the digestive tract, from the mouth to the large intestine, and at each station we look at what the data give and where they stop.

A word about the headline, so that no false impression arises: most of what follows was measured cleanly at larger drinking amounts. For small everyday amounts the measurements are thin, and no threshold can be derived from them. Wherever a number applies only to a lot of alcohol, I say so.

The route alcohol takes: mouth, oesophagus, stomach, small intestine, liver

Almost everything you have heard about alcohol breakdown is about the liver. That is understandable, because that is where the largest part of the work happens. It is also the reason why the most interesting part of the story is rarely told. Because before a single molecule reaches the liver, it has passed four other stations. And at each of them something happens.

Station one: the mouth

The mouth is not a corridor, it is an inhabited space. Bacteria and yeasts live there, and some of them can metabolise ethanol. What arises from that is acetaldehyde, and it arises directly on the mucosa. We will come back to this, because it is the point that almost no popular guide mentions.

Station two: the oesophagus

The oesophagus is a transport route, not an organ of absorption. It still takes something, because it has to withstand the contact without owning the protective mucus layer of the stomach. The lower sphincter will come up shortly, when heartburn is the topic. That is also where a popular explanation starts to wobble.

Station three: the stomach, the first customs post

Here is the point I find most exciting. The gastric mucosa has an enzyme of its own, alcohol dehydrogenase. It breaks down part of the ethanol before it even reaches the blood. The technical term is first pass metabolism. Put into a picture: the stomach is a customs post where part of the cargo is cleared before the rest enters the country.

And this customs post is not staffed equally well in everybody.

Station four: the small intestine, where most of it arrives

By far the largest part of the uptake happens in the upper small intestine. The surface there is huge, the mucosa is thin, and it goes fast. From this follows an everyday observation many people know: on an empty stomach alcohol arrives faster. The reason is not that it would act differently, but that the gatekeeper at the stomach outlet lets it through earlier. If there is food in the stomach, the alcohol stays longer at the customs post.

Station five: the liver and the way back

The main breakdown runs in the liver, via alcohol dehydrogenase to acetaldehyde and further via aldehyde dehydrogenase to acetate. I deliberately keep the liver short here, because it is a topic of its own and already has an article of its own on this blog. For alcohol related liver disease there are separate guidelines from the ACG and EASL societies, both are listed in the sources. If the liver part interests you in more detail, you can read on here:
Liver and detoxification, factually framed and Fructose, sugar and liver metabolism.

Only one connection matters for this article: the liver gets a large part of its blood from the gut. Whatever passes the barrier in the gut lands with the liver first. This axis between gut and liver is the thread that holds the next sections together.

And now you know why the same bottle of wine takes two completely different courses in two people at the same table. Not because one of them is more robust, but because five stations are staffed differently.

Acetaldehyde: the substance this is actually about

If you take a single term away from this article, take this one. Ethanol itself is chemically rather sluggish. It dissolves fats, it makes you tired, it lowers inhibition. But it does not attack cells particularly aggressively.

Its first breakdown product very much does. Acetaldehyde is reactive. It binds to proteins and to DNA. And it does not only arise where we expect it.

I like to use a picture for this. Imagine alcohol as a guest walking through your house. The guest himself leaves little behind. But behind him walks a workman who briefly sets to work on every wall. The workman is the acetaldehyde. And the interesting question is not how many guests arrive, but where exactly the workman does his work.

A large part does not arise in the liver at all

This is the point where the specialist literature and popular health writing are furthest apart. In guide articles, acetaldehyde barely appears at all. In research, almost everything has turned on it for thirty years, and with a clear finding: a considerable part of the acetaldehyde your mucosa is exposed to is not formed by the liver but by microorganisms directly on site.

That this is not about the form of the drink but simply about the contact of ethanol with colonised mucosa is shown by a study that at first glance leads away from the topic.

And the same principle in the large intestine

The large intestine is the most densely colonised place in your body. If oral bacteria can make acetaldehyde from ethanol, the thought that colonic bacteria do the same is close at hand. That is exactly what is assumed, and in an animal model it has been shown.

Why this is of interest at all is shown by a look into the cell.

And now you know why the specialist world talks so persistently about a substance you will find nowhere in the supermarket. It arises along the way.

When an enzyme is slow: ALDH2 and the red face

You may know someone who turns red after half a glass of wine. Not pleasantly tipsy, but properly red in the face, with a pounding heart, sometimes with nausea. In many circles of friends this counts as a funny quirk. It is in fact something else.

The breakdown runs in two steps. Ethanol becomes acetaldehyde, acetaldehyde becomes acetate. Aldehyde dehydrogenase 2, ALDH2 for short, is responsible for the second step. There is a widespread genetic variant in which this enzyme works considerably more slowly. Then the intermediate builds up. The vessels widen, the face turns red, the pulse rises.

Put differently: the workman from the picture above stays in the house longer, because nobody shows him out.

The first two numbers come from a paper on the worldwide distribution of the variant and not from a single measurement in patients: Chen CH et al. EBioMedicine. 2020;55:102753. PMID: 32403082 · DOI: 10.1016/j.ebiom.2020.102753. They are orders of magnitude and not precision values. On the third point: that the risk of oesophageal cancer can be clearly raised in carriers who drink regularly is described in the paper by Brooks and colleagues cited above. I deliberately leave out a figure for it, because the numbers in the literature diverge widely and I cannot name a single robust source for one.

Because here two things separate that otherwise belong inseparably together. In people with this variant the amount of alcohol is the same, but the acetaldehyde exposure is higher. And exactly the risk that should rise with acetaldehyde is raised in the available investigations as well. That is a strong argument that the intermediate could be a driving factor and not merely an accompanying finding.

The genetics behind this, meaning why enzyme variants occur with different frequencies in different populations and what that means for nutrition and metabolism, is set out in detail in an article of its own:
Genetics, metabolism and ancestry.

And now you know why a red face at the first glass carries more information than any table of drinking amounts.

The gut barrier: what becomes permeable and for how long

Between your gut contents and your blood lies a single layer of cells. One cell thick. Over an area that, depending on the calculation, covers several dozen square metres. It is held together by protein connections between the cells, the so called tight junctions.

For this picture I do not like the wall, because a wall is meant to be tight. The gut is not meant to be tight, it is meant to select. I find the grout between tiles a better fit. The tiles are the cells, the grout holds everything together and regulates what gets through. If the grout becomes softer, other things come through than intended.

As for the concept behind it, meaning zonulin, measurement methods and the question of how robust the whole term is, there is an article of its own:
Leaky gut, intestinal permeability and zonulin.

Here only one question matters: what does alcohol do to it? And that one is unusually well studied, because it has been approached with three different methods.

Up to this point you could say: fine, that concerns people with an alcohol use disorder. That is true as well. Which is exactly why the third study is the most interesting one, because it has nothing to do with alcohol use disorder.

Why the grout becomes softer

The mechanistic thread closes here with the previous section. A symposium report from the American health institutes describes how this hangs together: alcohol can favour the growth of gram negative bacteria in the gut, through which more endotoxin can accumulate. And acetaldehyde, which is formed both by these bacteria and by the intestinal cells themselves, can alter the proteins of the cell connections through an increased tyrosine phosphorylation. In addition, alcohol induced nitric oxide can attack the cell scaffold.

With that, acetaldehyde is not only the candidate for the cancer question. It is at the same time the substance that can let the grout become softer.

And now you know why the belly sometimes still speaks up on Sunday when the head has long been clear again.

The microbiome: what changes, and in whom

If you search online for alcohol and gut flora, you very quickly find the sentence that alcohol damages the gut flora. As a headline that is not wrong. As a statement about you it is too coarse.

Because the two most important papers on this topic both say the same additional thing, and this addition drops out of almost every summary: it is a subgroup. Not everyone.

And the small intestine?

The small intestine is meant to be comparatively sparsely colonised. If too many bacteria sit there, this is called a bacterial overgrowth, SIBO for short. What that is, how it is investigated and how it is treated is covered completely in an article of its own:
SIBO: bacterial overgrowth in the small intestine.

Here only the connection with alcohol is of interest, and it is remarkable, but more weakly documented than everything mentioned so far.

What does not follow from this: a stool test to survey your own flora after the weekend. Why these tests say less than their reports promise is covered under Stool testing and dysbiosis diagnostics.

And now you know why the blanket statement about the gut flora is of little use to you and the question about your own reaction is of a great deal of use.

The symptoms many people really do know

Now to the part that searching is mostly about. Not endotoxin and not phyla, but the pulling in the upper abdomen, the burning behind the breastbone and the trip to the toilet on Saturday morning.

Six symptom pictures, each of them short, with what the data give.

First: reflux and heartburn

Here many studies point in the same direction. A meta-analysis pooled 29 studies and worked through the association between alcohol consumption and reflux disease.

The usual explanation for this goes: alcohol lets the lower sphincter of the oesophagus go slack. That sounds convincing. It is simply not consistently documented.

What else plays a role in heartburn, from the question about the amount of acid to the handling of acid blockers, is here: Understanding heartburn and acid blockers. One note that matters to me: acid blockers are never stopped, reduced or started on your own. That belongs in the hands of the treating practice.

Second: gastric mucosa and gastritis

That alcohol attacks the gastric mucosa is not merely suspected in humans, it is documented endoscopically.

That the duodenum can take something too is described by the large review from the Hohenheim group: even a single excess episode can cause erosions and small bleeds there, as well as mucosal damage in the upper jejunum.

Third: the diarrhoea the day after

This is the most frequent search on this topic, and there is a physiological explanation for it. Among other things, the large intestine has the task of recovering sodium and water from the gut contents. It is exactly this recovery that can be inhibited by alcohol. At the same time the gut can push the contents along faster, so that less time remains for the recovery anyway. In the underlying review this is described above all for larger drinking amounts and for people with an alcohol use disorder.

Two mechanisms, then, that can point in the same direction: less water back, less time for it. On top of that a local irritation of the mucosa and, depending on the amount and the person, an altered handling of bile acids can come. If bile acids arrive in the large intestine instead of being taken up beforehand, they can in turn pull water after them. For small amounts this route has not been investigated in the same way. It does explain well, though, why the symptom can appear with a delay. What lies behind this is covered under Bile, bile acids and TUDCA.

Fourth: irritable bowel syndrome

With IBS, the question is rarely whether alcohol plays a role at all. It is usually which amount in which pattern. And there is a study on exactly that with a very clever design: not a questionnaire in hindsight, but a diary on the same day.

Fifth: histamine, and why red wine of all things

Many people report tolerating red wine and beer less well than clear spirits, even though there is less alcohol in them. That sounds contradictory at first and has an obvious explanation: it is not only about the alcohol.

Alcohol can slow down diamine oxidase, meaning exactly the enzyme that breaks down ingested histamine. And red wine and beer, as fermented drinks, bring histamine with them. Two paths that can add up, while a clear distilled spirit contains no appreciable histamine.

It expressly does not follow from this that clear spirits are the more harmless choice. High proof drinks have the most intense direct contact with the mucosa, and in the saliva measurement further up it was the pure ethanol solution of all things that produced the highest acetaldehyde peaks. Less histamine does not mean less burden.

What DAO is, how a histamine intolerance is framed and where the diagnostic limits lie is covered completely here: Histamine intolerance and DAO deficiency. If mast cells are involved, MCAS and mast cell activation is worth reading in addition.

Sixth: beer brings something extra

Beer is a special case, because three things come together there. The alcohol, the carbonation and the fermentable carbohydrates from the grain. The last of these are a known factor for people who work with the FODMAP concept. What FODMAPs are and how the concept is used sensibly is covered under Using FODMAP properly.

This means a glass of beer can be a different task for a sensitive gut than a glass of white wine with the same amount of alcohol. Not because of the alcohol, but because of the freight around it.

And now you know why the question about the most tolerable drink is almost always the wrong question.

The cancer question, factually

This is the section where most texts slide either into moralising or into playing things down. I try to avoid both by writing the numbers down and naming the points of dispute.

What the classification means, and what it does not

The International Agency for Research on Cancer, an agency of the World Health Organization, has classified alcoholic beverages in Group 1. The same goes for acetaldehyde, insofar as it comes from the consumption of alcoholic beverages. The organs named as affected are: oral cavity, pharynx, larynx, oesophagus, liver, colon and rectum, and the female breast.

Source: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 100E: Personal Habits and Indoor Combustions. IARC, Lyon 2012 [agency document]. Summary of the working group: Baan R et al. Lancet Oncol. 2007;8(4):292-3. PMID: 17431955 · DOI: 10.1016/s1470-2045(07)70099-2

The size of the effect is written in other work, and that is what we look at now.

Bowel cancer in particular

Because this paragraph is about precursors, a clear sentence belongs here: the screening examination exists precisely in order to find such precursors and remove them before something else grows out of them. What awaits you there, which procedures exist and from what age there is an entitlement in Germany is covered under Bowel cancer screening and colonoscopy. Nothing in this article is an argument for leaving out or postponing a recommended screening.

And now the point of dispute: does that hold for one glass per week as well?

Here the assessments diverge, and I consider it wrong to keep quiet about that. Both sides have arguments.

And now you know why two serious sources can arrive at different recommendations without either of them being dishonest.

What changes measurably during a break

January without alcohol has a good reputation and a poor data basis, because most of the numbers circulating about it go back to a survey and not to a study. There is, however, one published investigation, and it is more precise than what stands in the newspaper articles.

The barrier is slower than the blood pressure

Now comes the part that is missing from the four week articles. The values that react quickly are not the values this article is about. Circulation and sugar metabolism move briskly. Barrier and flora take longer.

The old Lancet paper shows the same sluggishness from the other side: in some people the permeability was still increased two weeks after the last glass. And the network structure of the microbiome was still altered in the Chicago investigation even after a longer phase of abstinence.

And now you know why the question is not whether four weeks are enough, but what they are enough for.

When the drinking is no longer voluntary

This article is about the gut and not about addiction. Even so, one paragraph belongs here, because some people need it and because leaving it out would be dishonest.

Frequently asked questions

Where this topic connects to the rest of the body

Alcohol is rarely an isolated topic. It hangs on sleep, on the uptake of micronutrients, on the liver, on mood and on the role that eating and drinking play in your own life. You will find these neighbouring topics here.