Alcohol & Health according to Andrew Huberman (Podcast Summary)

In Sloww Sunday newsletter #142, I mentioned quitting alcohol and asked if anyone had recommendations on what worked for them. I received 50+ responses, and one of the most popular recommendations was this Huberman Lab podcast on alcohol:

So, I binged the entire thing in one sitting (bad pun intended) and summarized it all below. In this summary, I focus more on the damage alcohol causes to the brain and body and less on things like curing hangovers (my goal is to cut out the middle man of alcohol completely so I don’t have to worry about hangovers anymore at all).

“If we were to get really honest with one another and ask what’s the best way to avoid a hangover, it would be to not drink in the first place … The best amount of alcohol to drink would be zero glasses/ounces per week.” — Andrew Huberman

🔒 Sloww Premium members have access to the companion post: Behind the Scenes: Why I’m Quitting Alcohol

Quick Housekeeping:

All content in “quotation marks” is from Andrew Huberman (otherwise it’s minimally paraphrased).
All content is organized into my own themes (not necessarily the video timestamps).
Emphasis has been added in bold for readability/skimmability.

Post Contents:

Alcohol & The Body
Alcohol & The Brain
Serotonin, Cortisol, Testosterone, & Estrogen
Experience & Feeling of Alcohol
Genes, Age, Tolerance, & Quitting

Alcohol & Health: What Drinking does to the Brain & Body (Andrew Huberman Podcast Summary)

Alcohol & The Body

“Alcohol is a known toxin to the cells of the body … It produces substantial stress and damage to cells.”

Alcohol processing in the body:

“When you drink alcohol, it can pass into all the cells and tissues of your body. It has no trouble just passing right into those cells … The fact that it can pass into so many organs and cells so easily is really what explains its damaging effects.”

“There are three main types of alcohol: isopropyl, methyl, and ethyl alcohol. Only the last one, ethyl alcohol or ethanol, is fit for human consumption. However, it is still toxic.”
“When you ingest ethanol, NAD (a molecule present in all our cells) and related biochemical pathways are involved in converting that ethanol into something called acetaldehyde. If you thought ethanol was bad, acetaldehyde is particularly bad. Acetaldehyde is poison. It damages and kills cells and it is indiscriminate as to which cells it damages and kills. That’s a problem, and the body deals with that problem by using another component of the NAD biochemical pathway to convert acetaldehyde into something called acetate.”
“If your body can’t do this conversion of ethanol to acetaldehyde to acetate fast enough, acetaldehyde will build up in your body and cause more damage, so it’s important that your body be able to do this conversion very quickly. The place where it does that is within the liver, and cells within the liver are very good at this conversion process, but they are cells and they are exposed to the acetaldehyde in the conversion process, and so cells within the liver really take a beating in the alcohol metabolism events.”
“The key thing to understand here is that when you ingest alcohol, you are ingesting a poison, and that poison is converted into an even worse poison in your body, and some percentage of that worse poison is converted into a form of calories that you can use to generate energy.”
“The reason why alcohol is considered ’empty calories’ is because the entire process is very metabolically costly, but there’s no real nutritive value of the calories that it creates. You can use it for immediate energy, but it can’t be stored in any kind of meaningful or beneficial way. It doesn’t provide any vitamins, it doesn’t provide any amino acids, it doesn’t provide any fatty acids—it’s truly empty calories.”
“If you’re somebody that has a sip of alcohol and you just feel horrible, it makes you feel nauseous, chances are you have gene variants that create a situation where you’re not making very much alcohol dehydrogenase. You just simply can’t metabolize alcohol so you get a rapid buildup of the toxic effects of alcohol, the acetaldehyde—you’re not converting it into those empty calories.”

Gut microbiome & bacteria:

“Alcohol kills bacteria and it is indiscriminate with respect to which bacteria it kills, so when we ingest alcohol and it goes into our gut, it kills a lot of the healthy gut microbiota.”

“In thinking about the biochemical effects of alcohol and what it’s doing to the body, what it’s doing in all cases is: it’s consumed into the gut, goes into the stomach, the liver immediately starts the conversion (ethanol to acetaldehyde to acetate), and some amount of acetaldehyde and acetate are making it into the brain by crossing the blood-brain barrier. Alcohol, because it’s water- and fat-soluble, just cruises right across this fence and into the milieu, the environment of the brain.”
“People who ingest alcohol in any amount are inducing a disruption in the gut microbiome—the trillions of little microbacteria that take residence in your gut, live inside you all the time, help support your immune system, and that literally signal by way of electrical/chemical signals to your brain to increase the release of things like serotonin and dopamine and regulate your mood generally in positive ways.”
“You’ve now got disruption of the gut microbiota. As a consequence, the lining of the gut is disrupted and you develop, at least transiently, leaky gut. That is, bacteria that exists in the gut which are bad bacteria can now pass out of the gut into the bloodstream.”

Cancer risk:

“The more alcohol people drink, the greater their increase of cancer (in particular breast cancer).”

“Because of the toxicity of acetaldehyde and the related pathways, it can alter DNA methylation (gene expression). That can mean many things in different tissues, but it is associated with a significant increase in cancer risk.”
“Cancer, the growth of tumors, is a dysregulation in cell cycles.”
“Alcohol increases tumor growth, and it decreases the sorts of molecules that suppress and combat tumor growth.”

Alcohol & The Brain

“Alcohol is indiscriminate in terms of which brain areas it goes to.”

Neurodegeneration & neocortex:

“If people are ingesting alcohol chronically, even if it’s not every night, there are well-recognized changes in neural circuits, there are well-recognized changes in neurochemistry within the brain, and there are well-recognized changes in the brain-to-body stress system.”

Brain-to-body stress system changes generally point in three directions:

Increased stress when people are not drinking.
Diminished mood and feelings of well-being when people are not drinking.
Changes in the neural circuitry that cause people to want to drink even more in order to get just back to baseline or the place that they were in terms of their stress modulation and in terms of their feelings of mood before they ever started drinking in the first place.

Heavy drinking:

“To make it very clear, drinking a lot (3-4 drinks per night, every night of the week) is clearly bad for the brain.”
“For many years, it’s been known that high levels of alcohol consumption (12-24 drinks per week or more) is certainly causing neurodegeneration, in particular of the neocortex—the outer layers of the brain that house associative memories, that house our ability to think and plan, that house our ability to regulate our more primitive drives according to context, etc.”

Low-to-moderate drinking:

“Not just heavy alcohol consumption, but also light to moderate alcohol consumption of any type, does reduce the cortical thickness of the brain. In fact, it actually scales with the amount of alcohol that people drink, and this has been well-documented in a number of different studies. One of the more striking ones actually shows that there’s almost a dose-dependent increase in shrinkage of gray matter volume and in these white matter tracts, these axons/wires, that connect different neurons as a function of how much alcohol people drink.”
“Even for people that were drinking low-to-moderate amounts of alcohol (1-2 drinks per day) there was evidence of thinning of the neocortex (loss of neurons in the neocortex) and other brain regions.”
“If you’re consuming even just 7 glasses of wine across the week, it’s likely that there is going to be some degeneration of your brain in response to that alcohol intake.”

Habitual & impulsive behavior:

“Rarely do we hear about the changes in neural circuits from just one or two nights of regular drinking.”

After 1-2 drinks:

“One of the first things that happens is, at least after the first drink or second drink, there’s a slight suppression in the activity of neurons in the prefrontal cortex. This is an area of your neocortex that’s involved in thinking and planning and, perhaps above all, in suppression of impulsive behavior.”
“When people drink, the prefrontal cortex and top-down inhibition is diminished. Habitual behavior and impulsive behavior start to increase. Now, what’s interesting is this is true in the short term, so after people have one or two (maybe three or four drinks), but it’s also true that the more often that people drink, there are changes in the very circuits that underlie habitual and impulsive behavior.”

Affects beyond drinking:

“For the person that drinks every Thursday or Friday night or goes out only on Saturdays (but every Saturday), there’s evidence that there are changes in the neural circuits of the brain that control habitual behavior and impulsive behavior, and they are modified and strengthened in ways that make those people more habitual and more impulsive outside the times in which they are drinking, and when they drink, impulsive and habitual behavior tends to increase even further.”
“Chronic drinking doesn’t necessarily mean every day and every night. It could be the person that simply drinks every Thursday or every Friday or just once a week has three or four drinks or maybe even a few more. That person is going to experience a decrease in this top-down inhibition, so an increase in impulsivity and habitual behavior, because the brake on those behaviors has been removed while they’re drinking, but also changes in the very neural circuits that allow habitual and impulsive behavior to occur more readily even when they’re not drinking.”

Reversing the damage:

“Fortunately, it is reversible. In animals or humans that undertake a period of abstinence of anywhere from two to six months, these neural circuits return to normal except in cases where people have been chronically drinking large volumes of alcohol for many, many years. And in those cases, while there is some recovery of brain circuitry after people get sober (meaning completely sober, they stop drinking entirely), there is evidence of long-lasting impact of heavy alcohol usage throughout the lifespan.”

Serotonin, Cortisol, Testosterone, & Estrogen

“There are long-term plastic changes, meaning changes in neural circuitry and hormone circuitry … Making people less resilient to stress, higher levels of baseline stress, and lower mood overall.”

Serotonin:

“There are also dramatic changes in the activity of neurons that control the release of serotonin (a neuromodulator). It changes the activity of neural circuits and many neural circuits, in particular, those involved in mood and feelings of well-being.”

“Alcohol, when we ingest it and it’s converted into acetaldehyde, that acetaldehyde acts as a toxin at the very synapses, the connections between these serotonergic neurons and lots of other neurons.”
“In other words, when we ingest alcohol, the toxic effects of alcohol disrupt those mood circuitries, at first making them hyperactive. This is why people become really talkative, and people start to feel really good after a few sips of alcohol. As they ingest more alcohol or as that alcohol wears off, serotonin levels and the activity of those circuits really start to drop, and that’s why people feel less good. Typically what they do is go and get another drink and attempt to kind of restore that feeling of well-being and mood.”

Cortisol:

“People who drink regularly (just 1-2 drinks per night, or it could be somebody that drinks just on Fridays or just on Saturdays, or maybe just on the weekend 2-4 drinks), those people experience changes in their hypothalamic-pituitary-adrenal axis that result in more cortisol (the ‘stress hormone’) being released at baseline when they are not drinking.”

“All of those groups experience increases in cortisol release from their adrenal glands when they are not drinking, and as a consequence, they feel more stressed and more anxiety when they aren’t drinking.”

Testosterone & estrogen:

“Alcohol, in particular the toxic metabolites of alcohol, increase the conversion of testosterone to estrogen.”

“Regular ingestion of alcohol is going to increase estrogen levels whether or not you’re male or female, and it’s largely doing that through the aromatization process, by increasing the aromatase enzyme (aromatization is this process of the conversion of testosterone and other androgens to estrogens through things like aromatase enzyme).”

Experience & Feeling of Alcohol

“Most humans have been consuming alcohol in order to change their internal state, in order to feel differently than they would otherwise. That feeling of being drunk, or inebriated, or tipsy, or lightheaded is something that many humans seem to enjoy and pursue even though, typically, it leads to a feeling of being less happy, less motivated, more stressed, etc, when the alcohol wears off. That’s pretty incredible, right? I mean, we’re talking about a substance that people have been and still are highly motivated to pursue, to create and to consume, that they’ll spend money on, and that’s despite the fact that it makes them feel good and then it makes them feel lousy.”

Are you energized or sedated?

“It is the poison, the acetaldehyde itself, that leads to the effect of being inebriated or drunk … Being drunk is actually a poison-induced disruption in the way that your neural circuits work.”

Two types of people:

“When people drink, initially there’s that shutting down of the prefrontal cortical circuits, there’s a gradual shutting down of the circuits that control memory, but then people divide into these two bins. These two bins are: 1) the people who after more than a couple of drinks start to feel sedated, and 2) the people who after more than a few drinks do not start to feel sedated.”

Occasional drinkers:

“Occasional drinkers will have a briefer (less long-lasting) period of feeling good when they drink and then more quickly transition into a state in which they’re tired or they start losing motor skills, they start slurring their speech.”

Regular drinkers (or those genetically predisposed to alcoholism):

“People who have a genetic predisposition to alcohol, or people who are chronic drinkers (drinking 1-2 per night, or they’re every-other-night type drinkers, or Thursday through Sunday drinkers) those people typically experience an increase in alertness and mood when they drink.”
“For people that are regular drinkers or that have a genetic predisposition to alcoholism, when they drink they tend to feel very energized and very good for longer periods of time.”
“People who tend to feel more alert and excited every time they drink, they tend to get a real lift, they become kind of the life of the party and that lasts a long while, those people are the ones that really have to be careful about predisposition for alcoholism.”
“If you’ve noticed that you or somebody else is somebody who can drink a lot throughout the night and have increased energy and can just drink and drink and drink, and especially if there’s blackout episodes (not remembering things the next day despite being alert throughout the entire night and so on), then I would be very concerned that you might actually have a genetic variant predisposing you to alcoholism.”

Memory & blacking out:

“Alcohol has a very strong effect in suppressing the neural networks that are involved in memory formation and storage. This is why oftentimes we forget the events of a night out if we’ve been drinking.”

“Blackout drunk is when people do things (sometimes, sadly or tragically, drive home, or walk home, or hop on a bicycle and ride home, or they’ll go swimming in the ocean) because they have the energy to do them and they feel good while doing them, but they are doing them while the activity of neurons in the hippocampus, which is involved in memory formation, are completely shut off.”
“If you’ve ever been blackout drunk, and certainly if you’ve been blackout drunk more than a few times, you should be quite concerned.”

Sleep:

“The sleep that one gets after even just one glass of wine or a beer is not the same sleep that you get when you don’t have alcohol circulating in your system.”

“When alcohol is present in the brain and bloodstream, the architecture of sleep is disrupted. Slow-wave sleep, deep sleep, and rapid eye movement sleep, all of which are essential for getting a restorative night’s sleep, are all disrupted.”
“In fact, it’s not even sleep. It’s often considered pseudosleep, or at least that’s what it’s called in the sleep science field, because people are in kind of a low-level, hypnotic kind of trance—it’s not real sleep, there are multiple bouts of waking up, they may not even realize they’re waking up multiple times.”

Genes, Age, Tolerance, & Quitting

“It’s genes and environments. It’s not an either/or and there’s no single gene for alcoholism.”

Genes & age:

“Genes matter, but also the age in which somebody starts drinking really matters.”

Drinking at a young age:

“People who start drinking at younger ages are greatly predisposed to developing alcohol dependence regardless of your family history of alcoholism. People who start drinking younger are at great risk for developing alcoholism even if they don’t have alcoholism in their family.”
“Even people that grow up nowhere near their relatives, if they start drinking at a young age, so for instance, at 13 or younger or 14 or 15, there’s a much higher probability that they’re going to develop a long-lasting dependence on alcohol.”
“It’s very clear that drinking early in life creates a propensity for the development of alcohol use disorder later in life. And while there is a genetic component to developing alcohol use disorder, I find it very interesting that if people who have those gene variants delay their onset of drinking, well, then the probability that they’ll develop full-blown alcohol use disorder drops as well.”

Drinking at an older age:

“For people who drink only once they reach legal age of drinking (if they take their first drink at 21), the probability that they’ll go on to develop full-blown alcohol dependence or alcohol use disorder (AUD) is very low. A subset of them will because they have such a strong genetic predisposition, or maybe life circumstances create a pattern in which they become a chronic drinker.”
“Provided somebody is of drinking age, having 1-2 drinks every now and again (meaning every 3-4 weeks or once a month), is not going to cause major health concerns or major health issues for most people.”

Tolerance:

“Tolerance to alcohol is a very interesting phenomenon. It has roots mainly in the brain and in brain systems … There are more than 10 different types of tolerance: functional tolerance, chronic tolerance, rapid tolerance, metabolic tolerance, psychological tolerance, etc.”

“Tolerance refers to the reduced effects of alcohol with repeated exposure, and it is caused mainly by changes in neurotransmitter systems in the brain that are the direct consequence of the toxicity of alcohol. There’s an enormous number of chemicals that change with repeated exposure to acetaldehyde, everything from GABA to dopamine to serotonin, second messenger systems, adenosine, and on and on.”
“When people initially start drinking, there are increases in dopamine or what we call ‘dopaminergic transmission.'”
“There’s an increase in dopamine and an increase in serotonin, an increase in well-being and mood, but it’s a very short-lived increase. Very soon after, and actually triggered by that increase, is a long and slow reduction in dopamine and serotonin and related molecules in circuits. Basically what you’re getting is a blip of feel good followed by a long, slow arc of feeling not so great, which is why people will drink again and again across the night.”
“With tolerance, the duration of that long, slow reduction in dopamine and serotonin gets even longer. In other words, the negative effects of alcohol that happen after the initial feeling good, extend longer and get more robust. However, there’s also a reduction in the reinforcing properties of alcohol. There’s a shrinking of the feel good blip that happens when one first ingests alcohol … So, what you’re getting is less and less of the reinforcing properties of alcohol, the feel good stuff, and more and more of the punishment pain signal aspects of alcohol.”
“Tolerance, it seems, is a process in which people are ingesting more and more alcohol as an attempt to get that feeling of well-being back, but what they’re really getting is an extended period of punishment, of pain, and of malaise from the alcohol.”

Quitting alcohol:

“If we were to get really honest with one another and ask what’s the best way to avoid a hangover, it would be to not drink in the first place … The best amount of alcohol to drink would be zero glasses/ounces per week.”

“My understanding of what I would call ‘the center of mass’ of the literature on alcohol is that no consumption (consumption of zero ounces of alcohol) is going to be better for your health than low-to-moderate consumption of alcohol, and that low-to-moderate consumption of alcohol is going to be better for you, of course, than moderately high-to-high alcohol consumption.”
“As you try and wean yourself off alcohol, or maybe you even go cold turkey, increased anxiety and feelings of stress should be expected.”
“Some increase in stress should be expected, and it should be expected because of the increase in cortisol that occurs with even low-level consumption yet chronic alcohol consumption.”
“The increase in cortisol that leads to lower stress threshold and greater feelings of anxiety/stress is going to be present and it’s going to take some time to dissipate.”

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