How Alcohol Causes Anxiety

It’s well-known that excessive drinking of alcohol can lead to next-day anxiety. That anxiety can in turn lead to the desire to drink more alcohol to ease it, leading to a cycle of excess alcohol and addiction. A study I read on this leads to speculate on how alcohol causes anxiety.

Binge drinking increases bacterial components in the bloodstream

The study is Acute Binge Drinking Increases Serum Endotoxin and Bacterial DNA Levels in Healthy Individuals.

Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to men, women had higher blood alcohol and circulating endotoxin levels. In addition, alcohol binge caused a prolonged increase in acute phase protein levels in the systemic circulation. The biological significance of the in vivo endotoxin elevation was underscored by increased levels of inflammatory cytokines, TNFα and IL-6, and chemokine, MCP-1, measured in total blood after in vitro lipopolysaccharide stimulation. Our findings indicate that even a single alcohol binge results in increased serum endotoxin levels likely due to translocation of gut bacterial products and disturbs innate immune responses that can contribute to the deleterious effects of binge drinking.

The contents of the gut are not intended to be placed into the circulation. Normally, so-called tight junctions in the lining of the intestines keep bacterial contents inside the gut and out of the circulation, but binge drinking opens up the tight junctions and allows leakage of contents into the circulation.

In the study, healthy volunteers ingested “2 ml vodka 40% v/v ethanol/kg body weight in a total volume of 300 ml orange/strawberry juice”. Using myself as an example, at 73 kg body weight, that would be 146 ml, or (146/750) about 1/5 of a bottle of liquor, or about 5 ounces. That comes to just over 3 drinks which, while it was ingested at one sitting, isn’t really all that much.

Blood alcohol went to a maximum of about 85 mg/dl, or just over the legal driving limit (which used to be 100 mg/dl). Again, not all that high. The chart below shows how levels of bacterial DNA climbed, by about 60%. Levels of bacterial lipopolysaccharide (LPS), which is a seriously toxic product that consists of parts of the bacterial cell wall, rose to a similar degree.




These bacterial components that get into the bloodstream wreak havoc, increasing levels of inflammation and contributing to liver damage.

The connection between bacterial LPS and anxiety

In animal models, “Lipopolysaccharide (LPS), a component of gram-negative bacteria, is widely used to systematically stimulate the immune system and generate profound physiological and behavioural changes, also known as ‘sickness behaviour’ (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness).”

Inject a rat with LPS, and acts sick and displays signs of anxiety.

In healthy human volunteers, “LPS was found to produce increases in the concentrations of cytokines and CSs [corticosteroids], as well as inducing mild fever, anorexia, anxiety, depressed mood and memory impairment. The levels of anxiety, depression and cognitive impairment were positively correlated with the levels of circulating cytokines, a finding supporting yet again the involvement of cytokines in the mediation of the emotional and cognitive responses to illness.”

In humans, LPS produces depression and anxiety.

If binge-drinking alcohol produces increases in LPS in the blood, then that’s probably the cause of day-after, alcohol-induced anxiety.

And of course anxiety and depression go together. Binge-drinking could cause depression.

The authors of the first paper observe, “Mutant mice lacking genes related to immune function exhibit decreased alcohol consumption indicating immune signaling promotes alcohol consumption. Thus, it is tempting to speculate that LPS increase in the systemic circulation after an acute alcohol binge could promote the desire for alcohol consumption.”

In other words, the immune reaction to binge-drinking stimulates the need for more alcohol, leading to addiction.


To my mind, the fact that binge-drinking as few as 3.5 drinks promotes leaky gut and increases in LPS in the blood stream provides a clear mechanism as to why alcohol leads to anxiety. It’s completely related to well-founded observations in biological psychiatry that bacterial LPS is elevated in people with depression and anxiety, and that fixing leaky gut can help overcome these conditions. Same in chronic fatigue syndrome.

And yes, leaky gut is real.

PS: I devoted a chapter to the vagaries of drinking alcohol in my new book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

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Leave a Comment:

anonymous says June 8, 2017

Does this point to any supplements to help deal with the endotoxins in the blood?

Montgomery says June 9, 2017

That “leaky gut” phenomenon seems to be a central threat to health and well-being, even mental health, and by extension of increasing systemic inflammation, effectively shortening life span.

Therefore I think gut health should be much more looked into;
for example,

certain widely-used ingredients for food processing, common emulsifiers (for example methyl cellulose), seem to interact with the gut microbiome of some (individuals have different compositions of the gut microbiome) and change it in a way to cause a leaky gut.
It is noteworthy that those emulsifiers themselves are non-toxic – they only cause serious problems after interacting with the gut microbiome.
Such food additives are, of course, thoroughly tested before they are legalized, but there were never any test requirements that looked at the interactions with the gut microbiome – for good reasons, because that seemed too difficult, given the fact that it is very different in composition among people.

So we get the effect that some people are not harmed by foods containing such ingredients,
while other people get sick, weak and more stupid from them and effectively are aging at an accelerated rate.

Rob H says June 9, 2017

Great article Dennis, it really does appear that encouraging a healthy gut biome can protect against almost every condition. Maybe a future post on prebiotics/ soluble fibre/ resistant starch? Moreover, the gut is directly connected to the mouth biome, and for example alcohol containing mouthwashes have been shown to wreak havoc on the oral biome and even lead to oesophagal cancer..

On a related note, I read a new article in the BMJ today about how “abstinence may be better than even one drink a day”: I quote: “Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.” and “we found no support for a protective effect of light consumption on brain structure”. I’ll still have my glass of red wine with my weekly (rare) steak – but otherwise will be trying to cut out the booze. I cut it out over lent, and would recommend a similar period of enforced abstinence to anyone – you can clearly see how much better you feel without it.. Although life would be too dull without the occasional glass or 2!!

David The Good says June 9, 2017

I’ve noticed that going without alcohol gives me a better sense of balance the next day, which I found surprising. If I have a few drinks one night, the next day I’m not as limber on my feet. An interesting side effect. Took me a while to figure out what was going on. And we’re not talking “binge” levels. Just a cocktail before bed. Without alcohol, I feel better as well. Much like cutting out sugar.

    Bill says June 9, 2017

    It’s a long while since I drank anything other than a glass of red wine; a shiraz or a malbec for example.
    But I notice in recent years, that if I drink even 2 glasses in the evening, I have brain fog and headache the following morning. For the past 6 months I have drunk alcohol even more rarely : only on special events like a birthday etc. as part of my own weight loss campaign – alcohol is metabolised to sugar in the gut. And I am not missing it..

    I am 69. I still enjoy a glass when I drink one but binging is not on my radar.

Nick Westgate says July 10, 2017

The prevailing hypothesis about receptor changes can’t be ignored though, as it applies to alcohol and benzos. E.g. “Long-term exposure to ethanol affects the baseline of neuronal excitability.”

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