Hangover Cures
From The New Yorker :
A few months ago, while watching Instagram stories, I came across a provocative advertisement. A man with scruffy brown hair said, “What if I told you alcohol is not actually bad for you?” He explained that our livers convert alcohol into acetaldehyde, a toxic molecule that he described as a main cause of hangovers. His brief chemistry lesson, which used glass beakers filled with colorful liquids as props, was accompanied by a link to a product: a supplement that promised to neutralize acetaldehyde more quickly than my body could on its own. Eliminating acetaldehyde, the ad claimed, would help conquer hangovers. One reviewer of the supplement said that she’d drunk more than five glasses of wine and felt fine the next day.
I usually have a strong aversion to the science-y veneer of supplement marketing, yet I stuck with the ad to the end. I like drinking; I learned about fine wine while working in restaurants, and I still enjoy pairing a carefully selected bottle with dinner. My favorite cocktail, the Perfect Manhattan, is basically all booze: rye whiskey, sweet vermouth, and dry vermouth, plus bitters and a brandied cherry. But as I entered my thirties, hangovers became more menacing—I began limiting my drinks and gulping well-timed waters—and I grew concerned about the health effects of drinking. Somehow, I’d never heard of acetaldehyde.
After I watched the ad, more purported hangover remedies flooded my Instagram feed. I scrolled through them with detached curiosity, occasionally clicking on a link, and this, of course, unleashed even more ads. There were many different products, with various ingredients, but they all seemed to tell the same story—that they could vanquish hangovers by counteracting acetaldehyde. Some, with peppy names like Cheers, Drinking Buddies, and No Days Wasted, highlighted dihydromyricetin, more commonly known as DHM, a flavonoid, derived from East Asian plants, which had been tested in mice. One company, ZBiotics, touts a bacteria modified to produce an enzyme that breaks acetaldehyde down. Another was marketing an amino acid that also purportedly processed acetaldehyde. The ads made it sound like a sort of morning-after pill for drinking had just been discovered. Could it really be so simple?
Scientists have known about acetaldehyde for decades, and it’s widely agreed that the compound—a known carcinogen—can make us feel sick. As Howard Edenberg, a molecular biologist and geneticist at the Indiana University School of Medicine, explained to me, when we drink alcohol a group of enzymes called alcohol dehydrogenases, or ADHs, convert it into acetaldehyde. But, under normal circumstances, the metabolic journey of alcohol doesn’t end there. A family of enzymes called aldehyde dehydrogenases, or ALDHs, soon turn it into a harmless molecule called acetate.
Sometimes our body’s machinery for processing alcohol falters in instructive ways. In the nineties, Edenberg helped identify genetic differences linked to overactive ADH enzymes, which would cause people to turn alcohol into acetaldehyde more quickly. Another genetic variation reduces the effectiveness of ALDHs, meaning that the toxic acetaldehyde sticks around for longer than it should. People with this genetic variant often experience facial flushing (sometimes called “Asian glow” because it’s common among people of East Asian descent), or have a very hard time clearing out the acetaldehyde at all, leading to nausea after only small amounts of drinking.
Here the impact of acetaldehyde becomes messier than the supplement ads let on. Genetic deviations that impair the processing of alcohol turn out to be associated with lower rates of alcoholism. “My interpretation is that a buildup of acetaldehyde is, in fact, aversive,” Edenberg told me. In other words, spikes in acetaldehyde seem to nudge people to stop drinking. (Indeed, Antabuse, the first drug marketed for alcohol-use disorder, deliberately inhibits ALDHs, increasing acetaldehyde levels and making people feel ill when they drink.) Rodent experiments seem to back up this interpretation. When scientists decreased the rate at which acetaldehyde is processed in mice, they wound up drinking less alcohol. And when scientists helped the mice process acetaldehyde faster, “they continued drinking,” Yanina Pepino, a professor of ingestive behavior at the University of Illinois Urbana-Champaign, told me.
New discoveries continue to be made about acetaldehyde. Although scientists long presumed that alcohol is converted to acetaldehyde in the liver, Pepino said that recent research in animals found that up to thirty per cent of acetaldehyde is transported over to the intestine through bile, and processed to acetate there instead—with unknown implications. Other scientists have noted that when alcohol reaches the brain, it is metabolized into acetaldehyde there; they wonder if, rather than make us feel bad, it can make us feel good. In animal models, the compound has been shown to bind with the neurotransmitter dopamine to activate the brain’s reward system.
The causes of hangovers are no less complicated. “It’s very simplistic to think that only acetaldehyde plays a major role,” Pepino told me. In people who produce normal ADHs and ALDHs, she said, there’s no evidence that acetaldehyde levels are linked to the severity of hangovers the next morning. Even if a connection exists, researchers would have a hard time documenting it. “Acetaldehyde is one of the most difficult molecules to measure that I have ever encountered,” Pepino said. On its own, the molecule doesn’t stay in the bloodstream for long. It’s highly reactive with many other molecules, so measuring its levels in the body is difficult. At room temperature it’s a gas, so in the laboratory it tends to vanish into the air.
So what causes a hangover, really? I was surprised to learn that scientists still don’t really know. Alcohol is a diuretic, so dehydration presumably plays a role—but rehydration isn’t enough to cure a hangover, so it can’t be the whole story. Jonathan Howland, an emeritus professor of emergency medicine at Boston University, who has studied hangovers and people who are mysteriously resistant to them, thinks that one possible source of the condition is methanol. The alcohol that generally makes a person feel drunk is ethanol, but adult beverages often contain small quantities of methanol, which build up while the ethanol is being processed by the body. He’s not certain enough to recommend any hangover deterrents, however. “Coming up with an intervention when you don’t know the mechanism in the first place is kind of dicey,” Howland told me.
Ignorance hasn’t discouraged humans from trying to stop hangovers in millennia past. One of the oldest known treatments, a string of shrubby leaves meant to be worn as a necklace, appeared in the text of a fraying piece of ancient Egyptian papyrus. Since then, raw egg yolks, pickle brine, cumin seeds, six-packs of Coke, and greasy breakfast sandwiches have all been credited with easing our post-drinking ailments. As Joan Acocella wrote for this magazine, in 2008, a suspicious number of cures happen to include alcohol as a main ingredient.
Some scientists speculate that acetaldehyde might trigger a release of the immune-signalling chemical histamine, leading to alcohol-intolerance symptoms. Pepino suspects that hangovers are the result of a broader immune response. Many classic signs of a hangover—headache, fatigue, nausea—also crop up when we have the flu. And it’s known that, after heavy drinking, markers of inflammation in the blood tend to spike, just as they do when we’re sick. “It’s so complex,” Pepino said. “That’s why we still don’t have a very crisp, clear grasp of what causes a hangover.”
Some of the ingredients found in hangover supplements are intriguing, Pepino told me. DHM is found naturally in Ampelopsis grossedentata, a Chinese vine tea, and in Hovenia dulcis, an East Asian fruit tree. Zhijuzi, as the seed of the tree is known in traditional Chinese medicine, appeared in China’s first pharmacopoeia, in the year 659; according to one folk saying, it was credited with keeping a person sober through “a thousand cups.” In rodent studies, DHM seemed to clear alcohol from the animals’ bodies, reduce liver damage, and alter alcohol’s effects on the brain. Scientists are now trying to develop DHM as a treatment for alcohol-use disorder.
The DHM supplements being marketed on social media have some problems, though. For one thing, they have not been studied clinically in humans. Instead, they’re being sold as dietary supplements, which means that companies don’t have to prove to the Food and Drug Administration that they work. For another, they come in a different form than the DHM used in the mouse studies. Scientists dissolved the DHM into a solution and then injected it into the gut, which meant that the mice could absorb most of it: fifty to seventy per cent of the compound was deemed “bioavailable.” Daryl Davies, a neuropharmacologist at U.S.C. who researches the compound, told me that in the capsules and powders sold online the bioavailability of DHM drops to five per cent—if you’re lucky.
Davies hopes to develop forms of DHM that are more bioavailable—but not necessarily for hangover treatments. Instead, he hopes that the compound might help people drink less. He and other researchers have gathered evidence that DHM interacts with receptors in the brain that make people feel relaxed and disinhibited; it may make alcohol feel less rewarding. If it helps the body metabolize alcohol, then it could also make drinking less fun. As a result, Davies thinks that the compound shows the most promise for serious alcohol-use disorder, or for people with liver damage—even if those conditions are less likely to inspire Instagram ads. “Of course, it’s easier to market it as a hangover remedy,” he said.
In June, I tried two DHM-based hangover supplements. Drinking Buddies is a liquid that claims to contain DHM along with an acetaldehyde-busting amino acid, herbs such as milk thistle, and B vitamins. I went to a dinner party and had several glasses of wine; when I got home, my husband and I debriefed at the kitchen table as we drank a sour cider together. For the sake of the experiment, I probably imbibed more than I normally would have. Then, as instructed, I took the supplement. When we woke up in the morning, my husband groaned. He said that his hangover was at full strength. I felt a little more clearheaded than him, but as the morning dragged on I felt a familiar lethargy and fatigue fall over me.
The second time, I tried Gush, a hangover product made from a Korean pear juice that was supposed to be naturally high in DHM. I tried not to change my drinking habits that evening: I drank only what I wanted, two glasses of wine at an early dinner, and I went to bed at a reasonable hour. When I woke up, I felt just fine. In both cases, I recognized a kind of karmic balance. I felt lousy in proportion to how much I’d drunk. Maybe no supplement was capable of changing that.
When I spoke to Davies, in mid-August, I happened to have a slight hangover once again. The day before had been my birthday, and I’d had several plastic cups of wine while lounging with friends in the park. Later, at a bar with a friend, I’d sipped a Manhattan while opening presents. As Davies talked about the effects of drinking, I experienced a tinge of guilt.
Still, I wasn’t sure that I wanted my hangover, or my guilt, to magically disappear. I pointed out to Davies that maybe the hangover was my body’s rightful revenge—a sort of checks-and-balances system that moderates our immoderation. Davies observed, however, that most of us aren’t very good at learning our lesson; by the next time your friends invite you for spritzes, the memory of suffering is likely to have faded.
Henry Jeffreys, the author of several books about drinking, including “Empire of Booze,” told me that there was something cosmically wrong about wanting to feel unaffected by a big night out. The drinking was the first act; the hangover the second. But Jessa Ramsay, an acquaintance of mine who works as a sales representative for a spiked coconut-water beverage , disagreed. She often feels that she has to drink as part of her job, and she wishes that she could dull its effects. For her, the dream of a hangover cure lives on. “In my mind, it’s like asking, Can you ever have joy without sadness?” she told me. “I think you absolutely can.” ♦
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