What Alcohol Does to Your Body, Brain & Health | Huberman Lab Podcast

Video: https://www.youtube.com/watch?v=DkS1pkKpILY

Low to Moderate Alcohol Consumption

12-24 drinks per week is clearly bad for the brain. Is 1-2 drinks a day bad for your brain? Yes.

30k people were studied and it was found that 1-2 drinks/day leads to thinning of neocortex and other regions of the brain.

Alcohol metabolism

Alcohol is water and fat soluble so it can pass into all cells and tissues of the body. This contributes to its damaging effects. Most alcohols are fatal. Ethyl alcohol is merely toxic.

Alcohol is first converted into acetaldehyde, then it's turned into acetate. Conversion is metabolically expensive. These calories therefore cannot be stored, hence the empty calorie designation.

Alcohol      Acetaldehyde       Acetate ion 

                                         (-) 
  H H   H         H                H   O   
  | |  /          |                |  /
H-C-C-O    ->   H-C-C=O    ->    H-C-C=O
  | |             |                |   
  H H             H                H

Acetaldehyde, the most poisonous along the pathway is the compound responsible for the feeling of being inebriated. Both it and the final product acetate cross the blood-brain barrier.

General timestamp: https://youtu.be/DkS1pkKpILY?t=1426

Acetaldehyde doesn't bind to any particular receptors but it goes everywhere with a slight affinity for some areas of the brain.
Acetaldehyde suppresses activity in the pre-frontal cortex. This leads to a louder voice, more gesticulation, sitting down and standing up, and dancing!
The areas responsible for flexible behavior shut down, so habitual and impulsive behavior tends to increase. Frequent use causes changes in the areas that control habitual/impulsive behavior so the effect carries on past the hangover. This has been shown in increases the number of synapses in areas responsible for habitual/impulsive behaviors. After 2-6 months these neural circuits have been seen to recover.
Acetaldehyde also affects memory formation and storage.

Chronic users and people with a genetic predisposition tend to experience a longer-lasting increase in energy and mood.

Food

Eating before you drink slows the absorption of alcohol if what was eaten includes carbs, fats, and proteins but if you're drunk and you eat, then that won't help with what's already been absorbed.

Neurotransmitter effects

Serotonin is a neuromodulator. It modifies the activity of neural circuits.

Serotonin levels can't really explain depression. It's not as much about the serotonin level but about the changes in circuitry it causes to enable people to feel elevated mood, feelings of well-being, and self-image.

Acetaldehyde acts as a toxin which first makes serotonin synapses hyperactive. By the 4th-5th drink there's no chance of getting the elevated feeling back.

Some with a genetic predisposition or chronic drinkers actually feel more alert and better at the 4th and 5th drink.

When blacking out, the hippocampus is completely shut off and the person will have no recollection despite being awake and alert at the time. There's no test available to determine if you are susceptible to getting blackout drunk.

There's an important phenomenon with something called the hypothalamic-pituitary-adrenal (HPA) axis. This axis defines changes in the relationship between the hypothalamus, the pituitary gland, and the adrenal glands. This axis maintains a balance between what you perceive as stressful or not. The hypothalamus again responsible for modulating anger, temperature, appetite, and thirst.

General timestamp: https://youtu.be/DkS1pkKpILY?t=2403

Chronic users have increased cortisol release even when they are not drinking. So they feel more stress and anxiety at other times.

The result is then:

Increased stress when not drinking.
Diminished mood and feelings of well-being when not drinking.
Changes in neural circuitry that require increased consumption to get back to the baseline of stress modulation and mood that was established before ever drinking in the first place.

Genetic predisposition, behavioral, and environmental

Genetics pay a part in our serotonin receptors, GABA receptors, and HPA-axis but other conditions that can predispose us to alcoholism include environmental factors, trauma, and peer-pressure.

Genetics can lead to low levels of alcohol dehydrogenase is the enzyme that converts ethanol to acetaldehyde. https://www.snpedia.com/index.php/Rs671 says they also shouldn't smoke because acetaldehyde is generated by that activity as well.

Regardless of genetics early use in life (before 15-16) leads to greater risk of alcoholism.

Gut-liver-brain axis

The gut, which runs from throat to end of intestine, communicates with brain and also with the liver. Meanwhile the liver is also communicating with brain at chemical and neural level.

Alcohol disrupts the microbiome in the gut by killing a lot of the healthy gut microbiota.

The NAD (nicotinamide adenine dinucleotide) pathway is pro-inflammatory, releasing inflammatory cytokines. What this means is that alcohol causes the gut to become leaky. This is an example of how 1+1 can equal 4 in a bad way. This leakiness allows bad bacteria to enter the bloodstream with the net effect of disrupting circuits that control alcohol intake, thereby causing increased consumption. Bad bacteria also causes inflammation throughout brain and body.

Related: The inflammatome which is the total array of genes and proteins that control inflammation.

To replenish the gut microbiome you can have 2-4 servings of low-sugar fermented foods per day. This is things like kimchi, sauerkraut, low sugar varieties of yogurt, and cheese.

Hangover

Related: Check out the episode called Master Stress.

After even one drink sleep is not the same. The architecture of sleep is disrupted becoming like pseudo-sleep, trance-like, waking often.

Headaches in hangover are caused by vasoconstriction which is a reaction to the vasodilation that alcohol causes.

What about consuming more alcohol while hungover? "Hair of the dog" simply delays a worse hangover.

Do cold showers help? This is worth exploring. He has an episode on deliberate cold exposure. Increasing epinephrine (aka adrenaline) can accelerate the clearance of alcohol from brain and bloodstream. One risk is that alcohol lowers core body temperature and disrupts the medial pre-optic area which may lead to hypothermia. If you can spike adrenaline, like from a cold shower, it can help clear alcohol. 1-3 minutes.

Every drink should come with two drinks of water plus electrolytes. Alcohol is a diuretic so body excretes water along with sodium, magnesium, potassium. Related is vasopressin (hormone responsible for water retention and release).

Does the types of alcohol affect hangover? Lore says high sugar content but that's not the case.

least hangover ------------------------------------------------- most hangover
diluted ethanol in OJ -> Beer -> Vodka -> Gin -> Whiskey -> Red Wine -> Brandy

Conjuners (nitrites) main effect is to disrupt gut microbiome.

So drink 2 glasses of water per alcoholic drink, with elecrolytes, fermented foods (or cheese), and take a quick cold shower.

Tolerance

Tolerance is caused mainly by changes in brain due to toxicity.

People with higher tolerance experience negative effects on dopamine levels for longer.

Cancer-risk

Increased risk of breast cancer due to DNA methylation. 4-13% in for every 10g of alcohol consumed per day. That's like one drink in the US.

PD1 pathway upregulated. Downregulation of anti-inflammatory molecules.

From a cancer perspective, 1 beer a day is like smoking 10 cigarettes a day. (Clip)

How to reduce risk for cancer:

Take folate and B-vitamins (B12 esp)
Support the gut microbiome as mentioned above.

Hormones

Alcohol increased conversion of testosterone to estrogen which is called aromatization. This can lead to increase in estrogen-related cancers, gynecomastia, and altered T-to-E ratios.