The Quest to End Hangovers

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.