What Alcohol Does to Your Body, Brain & Health

The episode opens by describing alcohol as one of the most commonly consumed substances on the planet, taken by humans and by non-human animals for recreation, for medicinal reasons and for other purposes. The host lays out a broad plan: alcohol's effects on cells, organs and organ systems in the brain and body; what being inebriated does to thinking and behavior, and how; and a question the host calls one of the most common, namely whether low to moderate drinking is better for health than drinking nothing at all.

Later sections are promised on binge drinking, on hangovers (including steps taken before or during drinking, which the host calls "inoculatory," and steps taken once a hangover has set in), on genetic differences related to alcohol and alcoholism, and on drinking in young people, which the host says is especially harmful for reasons most listeners will find surprising. The stated goal is to help listeners decide between zero alcohol and small to moderate amounts, with "small to moderate" to be defined precisely, and to point people with clearly harmful drinking toward routes and resources for stopping.

It is not about judging alcohol intake or lack of alcohol intake.

The host returns to this neutral stance later, saying the aim is not to "demonize alcohol in any way," and accepts that some people who drink moderately feel fine the next morning. The stated purpose is to explain what alcohol is, how it produces its effects, and what those effects are even for people who drink only one or two nights a week, a few drinks across a weekend, or all of their alcohol on one night a week or a month.

Before the main material, the host takes up a frequent question: whether low to moderate drinking, roughly one or two drinks a day, harms the brain, and in particular whether it causes neurons to degenerate. The question comes up because heavy drinking has long been known to cause neurodegeneration. The host defines heavy drinking as 12 to 24 drinks per week or more, or three or four drinks every night. The damage falls particularly on the neocortex, the outer layers of the brain involved in associative memory, thinking and planning, and in regulating more primitive drives according to context.

The study cited is titled "Associations Between Alcohol Consumption and Gray and White Matter Volumes in the UK Biobank." The host explains that gray matter consists of neuronal cell bodies, which hold the cells' genomes, and white matter consists of the connecting fibers, or axons. White matter is called white because it is wrapped in myelin, a fatty tissue that lets nerve cells communicate quickly. The study examined both tissue types in more than 35,000 generally healthy middle-aged and older adults in the United Kingdom who drank varying amounts of alcohol.

According to the host, the study found that even people drinking one or two drinks per day showed evidence of thinning of the neocortex, meaning loss of neurons there and in other brain regions. The host says this is not meant to alarm anyone. The host presents the data as important because they address the long-standing question of whether chronic intake can disrupt the brain even when that intake is very low. The study's own title describes associations, and the population was limited to generally healthy middle-aged and older UK adults.

Much of this section turns on how the word "chronic" is defined. The host points out that many people hear "chronic" and think of five or ten drinks a night, or of drinking every night. In this study the relevant group averaged one or two drinks per night, and that average could come from one drink per night, from seven drinks on a Friday, or from 14 drinks over a weekend. The host suggests many people drink around seven to 14 drinks per week and concludes that "even just seven glasses of wine across the week" likely produces some brain degeneration. The host adds that measures which may protect against some of this neuronal loss will be covered later in the episode.

The host notes that humans have consumed alcohol for thousands of years. Archaeological evidence from Mesopotamia shows wine vessels from 5,000 years ago. On distillation, the host corrects a common online claim: the Irish were not the first to distill alcohol. The host says the Chinese were, in the 1st century.

Alcohol has been used for several purposes. Some cultures used it for nutrition and still regard its calories as useful, a view the host challenges later by calling them empty calories. It has been used as medicine because it kills bacteria. The host warns that the same property means it also kills beneficial gut bacteria, which can lead to problems such as leaky gut syndrome, and says ways of dealing with this will come later. Alcohol is also used to clean surfaces and to make up reagents in the host's laboratory.

Still, the host argues that most people drink to change their internal state. Many people, though not all, enjoy and seek out feeling drunk, tipsy or lightheaded, even though the host says it typically leaves them less happy, less motivated and more stressed once it wears off. The host finds it striking that people stay so motivated to make, buy and consume a substance that first makes them feel good and then makes them feel lousy.

The basic explanation starts with solubility. Because alcohol is both water soluble and fat soluble, it passes directly into the cells and tissues of the body. The host contrasts this with many drugs that bind to receptors on the cell surface, described as "little parking spots," and then set off cascades of downstream effects. Alcohol acts directly on cells. The host says this ease of entry into so many organs and cells explains much of its damage.

Of the three main types of alcohol (isopropyl, methyl and ethyl), only ethyl alcohol, or ethanol, is fit for human consumption. The host stresses that ethanol is nonetheless toxic and causes substantial stress and damage to cells. Because it is toxic, the body has to convert it into something else.

That conversion involves NAD, a molecule present in all cells from birth to death. The host mentions that NAD levels tend to decline over the lifespan and that it is popular in longevity discussions, where some propose that raising NAD could extend lifespan. The host flags that idea as still controversial, or at least still under investigation. In alcohol metabolism, NAD and related pathways convert ethanol into acetaldehyde.

Acetaldehyde is poison. It will kill cells.

The host says acetaldehyde damages and kills cells indiscriminately. The body then uses another part of the NAD pathway to convert it into acetate, which can be used as fuel. Speaking more technically, the host identifies the NAD to NADH ratio as the rate-limiting step of ethanol metabolism. In practice, if the conversion is too slow, acetaldehyde accumulates and does more damage.

The conversion happens mainly in the liver. Liver cells are good at it, but because they are exposed to acetaldehyde during the process, they "really take a beating." The host's summary: drinking alcohol means ingesting a poison that the body converts into a worse poison, part of which is then turned into calories that can be used to produce energy (ATP).

This is the basis for calling alcohol calories empty. The host says the process is metabolically costly, and the resulting calories can be used for immediate energy but cannot be stored in any meaningful or beneficial way. They provide no vitamins, amino acids or fatty acids. The host contrasts this with sugar, which is sometimes also called empty calories but is described as a far better fuel source than alcohol or acetate.

The host then makes a claim that frames the rest of the discussion: being drunk is caused by the toxic intermediate, acetaldehyde, rather than by ethanol in some benign form. In the host's words, "being drunk is actually a poison-induced disruption in the way that your neural circuits work." This leads to the question of which neural circuits, brain areas and body areas are involved in feeling drunk.

The host describes a pattern said to be little known. Regular drinkers and people with a genetic predisposition to alcoholism tend to feel very energized and good for long stretches when they drink. Using the episode's broad definition of chronic, regular drinkers include people who have one or two drinks a night, drink every other night, or drink Thursday through Sunday. Occasional drinkers, by contrast, have a shorter period of feeling good and move more quickly into tiredness, loss of motor skills and slurred speech.

The host separates this from tolerance, which is promised for later. The claim is that the shape and timing of alcohol's effects reliably indicate who is predisposed to alcoholism or drinks regularly. People who consistently become more alert and excited, "the life of the party," for a long time are the ones who most need to be careful about predisposition and about how much they drink, even if they are not "full-blown alcoholics." The host adds that inexperienced drinkers face different risks, mainly impaired motor function and judgment.

The host traces the route alcohol takes. It enters the gut and stomach, and the liver immediately begins converting ethanol to acetaldehyde and acetate. Some acetaldehyde and acetate reach the brain. The blood-brain barrier blocks most substances, but alcohol, being water and fat soluble, "just cruises right across this fence." Inside, it reaches the brain's two main cell types, neurons and the glial cells that sit between them.