Proof: The Science of Booze

by Adam Rogers

When you bring a glass of wine to your nose and mouth, you smell the air in the headspace, and volatilized wine molecules jump onto your olfactory epithelium. You take a sip, and all those polymodal nociceptors pick up texture and temperature. You get “mouthfeel,” a subjective measure of viscosity and astringency due in large part to the presence of tannins. It’s actually the sensation of proteins getting stripped out of your saliva, and it’s received by the trigeminal nerve endings. Your taste buds pick up the sweetness and bitterness of the ethanol, plus the broad flavors of everything else. You swallow, pumping a whole new set of volatile organic compounds into your epithelium. That’s where you taste the oak of the barrel, and a whole bunch of other associative words you’ve learned to connect with wine flavors—blackberry, leather, butterscotch, grass, green apple. And the ethanol itself changes those flavors, alters your judgment on them. (Nobody’s exactly sure whether ethanol makes a red wine taste better, but from experience I’ll tell you that while nonalcoholic beer can be pretty good, “de-alcoholized” red wine tastes like existential death.)

He studies how rats and mice acquire a taste for ethanol, a chemical that wild-type mice and rats won’t have anything to do with. Bachmanov’s theory—and this is controversial—is that no one actually likes the taste of ethanol. “Well, I think so,” he says, biting a nail. So why does anyone drink it? “I think the reason is that ethanol has pleasurable effects after it’s consumed.” Bachmanov is right to be nervous. He’s suggesting, essentially, that liquor stores, wine connoisseurship, home brewing, cocktail culture, the full contents of Wine Spectator, and everything that comes out of a sommelier’s mouth other than spit is essentially designed to get us over the fact that alcohol tastes bad. This is more than Richard Quandt–scale bullshit. This is epic bullshit. Can Bachmanov prove it?

Bachmanov’s conclusion is that the postingestive effects outweigh those aversive tastes and sensations.

People have always added sugar, or sugary stuff, to make lousy booze taste better.

every drink other than vodka is really just a glass full of misdirection to get us around the fact that we hate the taste of the key ingredient.

People who teach wine-tasting classes often tell funny stories about how their students, even with training, prefer box wine in a blind test. And research shows that people say they enjoy a wine more if they know it’s more expensive. Sure, that bottle of red from the little village you found when you and your first love got lost in Tuscany on that rainy night was the best bottle of wine the world has ever made. Just don’t try the same bottle again alone, sitting in front of a Star Trek rerun.

our state of mind affects what alcohol does to us, just as alcohol affects our state of mind.

Absinthe takes a base distillate, either something neutral like vodka or a flavored spirit like brandy, and adds herbs and botanicals as flavoring. The main contributor is anise; in that respect it’s like ouzo, raki, Sambuca, and other licorice-flavored regional firewaters. But also on the list is wormwood, which contains trace amounts of a hallucinogenic compound called thujone. In the early 1900s, thujone was blamed for “absinthism,” a syndrome that turned otherwise normal people into murderous epileptic psychopaths.

in the process found that pre-ban absinthe had thujone levels of just about five parts per million, nowhere near enough to have a hallucinogenic effect. He also found that the alcohol levels hovered around a sky-high 140 proof. That goes a long way toward explaining how habitual consumption could give someone seizures and homicidal tendencies.

Some winemakers use them to eat the sharp malic acid that can sometimes result from a fermentation, thereby softening the flavor of some red wines. Usually enzymes break tyramine down before it can do any damage, but some people don’t make enough of those, and others are taking high blood pressure medication that inhibits them. For those folks, tyramine can actually cause panic attacks.

In my experience, lots of people who believe that red wine specifically gives them a headache blame sulfites, and it’s possible . . . but not likely. In small subsets of the population, sulfites can induce asthmatic responses and even headache, and as a possible mechanism, sulfites can induce the release of histamine in the body. But red wine actually contains less sulfite than white wine.

If you really want to blame a chemical for wine-induced headaches, I might point you to another choice—5-hydroxytryptamine, more generally known as serotonin. It’s a neurotransmitter used widely throughout the brain, involved in things like mood regulation. Psychiatric drugs like Prozac are selective serotonin reuptake inhibitors; they enhance the effects of serotonin in the brain. Red wine induces the release of serotonin more effectively than white wine. Like Prozac, red wine also inhibits its reuptake at synapses in the brain. It blocks serotonin from locking into receptors, specifically a subtype called 5-HT1.

In short: different drinks affect different people differently at different times—even holding ethanol constant. The problem isn’t that this fact is a surprise. The problem is that these observations don’t quite square with a molecular or neurocircuitry approach. Other drugs of abuse have fairly clear modes of action and predictable behavioral outcomes. But not booze. It doesn’t have either.

Drunken Comportment: A Social Explanation, is essentially an ethnological study, rounding up observations on alcohol use patterns from cultures all over the world.

MacAndrew and Edgerton hypothesized that alcohol’s effects existed only, as they put it, within limits drawn by cultural norms. It was only in “confused cultures” like the United States, where alcohol was sometimes prohibited and sometimes lionized, that ethanol-induced behavior became dangerous. MacAndrew and Edgerton walk right up to the line—while never crossing it—of suggesting that ethanol doesn’t have any intrinsic effects at all. “Even if, say, the brain physiologists were fully to accomplish their task of explicating the effects of alcohol on the human brain in the most minute and final detail,” they wrote, “we would remain no better informed concerning the relationship between this now fully explicated state of affairs, and the purportedly resultant changes in man’s comportment than we are today.”

My hypothesis has been similar. Alcohol affects are based on situation and underlying mood. Sometimes external events once buzzed.

Subsequent population-scale research has shown that one thing ethanol does, as distinct from any other drug of abuse, is increase levels of violence. It’s true that the markets for illicit drugs can be violent, but except for some stimulants (like methamphetamine), alcohol is the only drug that has the intrinsic ability to make people violent—across cultures and genders.

“You get the olfactory cues. You watch me mix the drink. Voilà, that’s an effective placebo. Any feelings they report, any behaviors they engage in, are a function not of alcohol’s pharmacological effects but of expectancy.”

People with positive expectancies for how their drinking will turn out—they’ll be more outgoing, have better sex, whatever—tend to get those better outcomes. The converse is true, too. If you expect to become more aggressive or do things you’ll regret, you’re more likely to get that less fun evening. Which set of expectancies you subscribe to seems to depend on early-life modeling, what you’ve seen in the media and what kinds of behaviors you recognize and remember in your own parents, if they drank.

a Mississippi state senator, asked in 1958 how he felt about whisky: If, when you say whiskey, you mean the devil’s brew, the poison scourge, the bloody monster that defiles innocence, yea, literally takes the bread from the mouths of little children; if you mean the evil drink that topples the Christian man and woman from the pinnacles of righteous, gracious living into the bottomless pit of degredation and despair, shame and helplessness and hopelessness, then certainly I am against it with all my power. But if, when you say whiskey, you mean the oil of conversation, the philosophic wine, the stuff that is consumed when good fellows get together, that puts a song in their hearts and laughter on their lips and the warm glow of contentment in their eyes; if you mean Christmas cheer; if you mean the stimulating drink that puts the spring in the old gentleman’s step on a frosty morning; if you mean the drink that enables a man to magnify his joy, and his happiness and to forget, if only for a little while, life’s great tragedies and heartbreaks and sorrows, if you mean that drink, the sale of which pours into our treasuries untold millions of dollars, which are used to provide tender care for our little children, our blind, our deaf, our dumb, our pitiful aged and infirm, to build highways, hospitals, and schools, then certainly I am in favor of it. This is my stand. I will not retreat from it; I will not compromise.

You, my friend, have a hangover. Scientists have a more inscrutable name for it: veisalgia, from the Greek word for “pain,” algia, and kveis, a Norwegian word meaning “uneasiness following debauchery.” That sounds about right.

and—here is the amazing part—“what causes hangover? Nobody really knows,” says epidemiologist Jonathan Howland. “And what can you do about it? Nobody knows.” It wasn’t even until the last decade that researchers agreed on a basic definition of a hangover, much less started thinking carefully about how to treat it.

They came to one overwhelming conclusion: pretty much everything anyone has ever told you about the causes of hangover is wrong. Or as Howland would have it, probably more accurately: unproven. Dehydration? It makes sense, sure. Alcohol suppresses the antidiuretic hormone vasopressin, which ordinarily keeps you from peeing too much. Plus, if you’re drinking booze, you’re probably not drinking water. But in terms of hangovers, levels of electrolytes don’t differ too much from baseline controls—and when they do, they don’t correlate with hangover severity. So yes, drinking booze dehydrates you. But that doesn’t cause the hangover. Plus, drink a glass of water. Now you’re hydrated. Did your hangover go away? How about acetaldehyde, that toxic byproduct of ethanol breakdown in the body? It’s another good guess; a lot of the symptoms of acetaldehyde toxicity overlap with hangover. Unfortunately hangover symptoms are at their worst when acetaldehyde levels are low—and again, those levels don’t correlate with severity. You can probably cross it off the list, though to be fair acetaldehyde is tough to study because it tends to evaporate before you can get a good reading. Blood sugar has some intuitive power behind it. Dehydration causes glucose levels in the blood to drop, and the body compensates by creating other sources of energy. Free fatty acids, ketones, and lactic acid all build up, making the blood more acidic in general. That’s called metabolic acidosis, and it, too, has ...

The myth about sugary drinks, though, does get us to the admonitions against drinks with high levels of congeners. Vodka, you might have heard, is supposed to give you less of a hangover than red wine or whisky. There might be some truth to this one. Few researchers have studied the relative toxicities and effects of things like acetone, tannins, or furfural, the congeners that make brown liquor taste like brown liquor. Indeed, one study—dicey, I should say, since it was only presented at a conference and not published—ranked different types of booze in order of hangover severity: brandy, red wine, rum, whisky, white wine, gin, with vodka coming in last.

If we’re looking for congeners to blame, we might set our sights on methanol. Levels aren’t high in anything you buy in the store, because the stuff can kill you, but it’s present at nontoxic levels in almost every alcoholic beverage. The enzyme alcohol dehydrogenase breaks it down rapidly in the body, but where ADH turns ethanol into acetaldehyde, it turns methanol into formaldehyde. These molecules are toxic and very unpleasant. The science here isn’t clear, because some studies dismiss the effects of methanol and its metabolites, but one piece of evidence is suggestive: the relative efficacy of the “hair of the dog”—drinking more booze. Ethanol might help with a hangover because it stops the body from breaking down methanol.

That’s ADH making formaldehyde, which is bad, but doesn’t last long. The problem is, it turns into formic acid—ant venom. Formic acid or formate, a product of the acid, inhibits the action of an enzyme called cytochrome oxidase, which is vital to a cell’s ability to use oxygen. Under normal conditions, the eyes, specifically the optic nerve, use a huge amount of oxygen—that’s why a couple of the first signs of suffocation are tunnel vision and the loss of the ability to see color. So with a big enough dose of methanol, the eyes go first. And in fact people killed by methanol show a characteristic pattern of lesions on the optic nerve and in the brain.

The thing is, alcohol dehydrogenase would much rather stick to ethanol than methanol—one way doctors treat methanol toxicity is to administer a lot of booze. The enzyme goes to work on the ethanol, so the methanol doesn’t turn into formaldehyde,

Nowadays, not many cocktails are socially acceptable at breakfast. The Mimosa and the Greyhound, champagne with orange or grapefruit juice, work, as do the members of the Bloody Mary family, spicy tomato juice with a base spirit. (Try it with tequila—it’s called a Bloody Maria, and it actually tastes good, as opposed to the Bloody Mary, which is just a ruined glass of tomato juice.)

The best theory going today about what really causes hangovers is that they are an inflammatory response, like what happens when we get an infection. Hangovers are accompanied by elevated levels of molecules called cytokines, molecules used as communications signals by the immune system.

dihydromyricetin as an over-the-counter supplement. It’s called BluCetin.

another compound with proven effect on hangover symptoms, extract of the skin of the prickly pear cactus, Opuntia ficus indica. Mexican restaurants sell the paddles of this plant as nopales, and they’re delicious with eggs. The plant also seems to induce the body to produce heat shock proteins, protective molecules that repair cellular damage. People who make a lot of them naturally tend to be less affected by altitude sickness, for example—a

The anti-inflammatory Clotam, the vitamin B6 analogue pyritinol, Ayurvedic herbal compound Liv.52, and Opuntia ficus indica extract are the only four medicines or supplements that actual clinical trials have shown to be at all effective in treating hangovers. Add dihydromyricetin to the list—the thing Olsen isolated—even though it hasn’t had rigorous human trials.

Proof was my attempt to enrich memories with facts, to start with what happens and add the why of the thing.