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In Search of a Cure for the Dreaded Hangover

Can science help defeat the physical aftereffects of drinking too much alcohol—if not the regrets?


Since the invention of fermented beverages, curing the dreadful aftermath of overimbibing them has been one of humanity's morning-after quests. Ancient Greeks ate sheep lungs and two owl eggs to cure such a hangover, a cure tweaked by Roman Gaius Plinius Secundus, better known as Pliny the Elder, who suggested raw owl eggs or a fried canary. Sicilians recommended dried bull penis although Mongolians prefer tomato juice and pickled sheep’s eyes.
 
But what do scientists say? After all, hangovers cost the U.S. alone some $224 billion a year in workplace productivity declines, drinking-related health care expenses, law enforcement, and motor vehicle accident and fatality costs, according to the U.S. Centers for Disease Control.
 
Beyond the fiscal damage, scientists take the hangover seriously for more reasons than helping postdrinking pain. “Studying alcohol can tell us how the body works in its normal fashion,” says Michael Oshinsky, director of preclinical research at Thomas Jefferson University in Philadelphia, who studies hangovers to better understand migraines. When the body is pushed to its physical limits to metabolize alcohol, it helps show what causes headaches—one of the common components of the hangover.
 
Hangover cause
Shortly after a person starts consuming an alcoholic drink, the liver gets to work. The enzyme alcohol dehydrogenase (ADH) metabolizes the ethanol (that's the type of alcohol in alcohol) into toxic acetaldehyde. From there the liver enzyme aldehyde dehydrogenase (ALDH) metabolizes acetaldehyde into acetate, a less toxic compound that breaks down into water and carbon dioxide. According to the Department of Health and Human Services, some alcohol metabolism also occurs in the pancreas, gastrointestinal tract and the brain, but the liver does the bulk of the work with its two enzymes.
 
The problem is: all this takes time and, the next day, the drinker suffers.
 
That dreadful feeling the next day is the condition often called a hangover, which the journal Alcohol and Alcoholism characterizes as “general misery” with symptoms of drowsiness, concentration problems, dry mouth, dizziness, gastrointestinal complaints, sweating, nausea, hyperexcitability and anxiety. Most of these symptoms have been linked to elevated levels of acetaldehyde.
 
In a 2000 study “The Role of Acetaldehyde in Actions of Alcohol,” which was published in Alcoholism: Clinical & Experimental Research study, researchers determined elevated acetaldehyde levels caused increased skin temperature, facial flushing, increased heart rate, lower blood pressure, dry mouth, nausea and headache. The researchers reported that heavy drinking leads to elevated acetaldehyde levels, which leads to inhibited ALDH enzymes, and in turn causes these adverse effects. The alcohol does not properly metabolize.
 
Japanese researchers further studied the role of acetaldehyde but specifically in Japanese workers whose bodies could not break down the alcohol. Specifically, they studied participants with the allele (mutant gene) aldehyde dehydrogenase-2 and those with inactive ALDH2. This enzyme mutation is what leads many of Asian descent to turn red when drinking. The study concluded acetaldehyde may be the culprit behind hangovers after discovering acetaldehyde quickly metabolized with normal ALDH enzymes, but participants with the enzyme mutation experienced cardiovascular complications, drowsiness, nausea, asthma, facial flushing and were at greater risk for hangovers.
 
Whereas this study was limited to Japanese subjects, prominent researchers continue to note that acetaldehyde likely causes the hangover. In a 2014 Food & Function paper, “Effects of Herbal Infusions, Tea and Carbonated Beverages on Alcohol Dehydrogenase and Aldehyde Dehydrogenase Activity,” Chinese scientists determined acetaldehyde is the “primary mediator” of the hangover’s “adverse effects,” adding the compound is linked to lesions and tumors of the large bowel. These scientists also said the second metabolite, acetate, may provide protective health effects associated with the regular moderate consumption of alcohol.
 
But research in hungover rats suggests that the buildup of acetate is not a good thing, and may be responsible for hangovers. “Because acetaldehyde is a very reactive compound and toxic to the body, your body has an efficient mechanism for handling that. It changes it into a very stable compound, which is acetate,” Oshinsky says. “Your body is filled with acetate and there are lots of other biological processes that have acetate as a by-product.” Too much acetate can trigger a nasty headache. Oshinsky published his work in the peer-reviewed PLoS ONE in December 2010. His findings are backed up in principle by dialysis research. Doctors working with patients with failed kidneys used sodium acetate to buffer the dialysate, one of the two fluids in dialysis used to clean the blood, and discovered significant headaches in about 30 percent of the patients. After the dialysis researchers switched the buffer from sodium acetate to sodium borate, Oshinsky says, the headache rate dropped to less than 2 percent. This evidence supports the fact that acetate, not acetaldehyde, causes the hangover, he adds, or at least the hangover headache.
 
But another study suggests the alcohol’s congeners [related substances] are more likely the hangover perp than the metabolites. “[Congeners] occur in alcoholic beverages, mostly as a result of the processes used in fermenting and aging,” says Damaris Rohsenow, research professor at the Behavioral and Social Sciences Center for Alcohol and Addiction Studies at Brown University School of Public Health, which makes them more prevalent in barrel-aged beverages such as brandy, wine and whiskey. Congeners include acetaldehyde itself as well as acetone, fusel oil, furfural, methanol's metabolites, polyphenols, histamines, esters, tannins, amines and amides, among others. All have been linked to the alcohol’s intoxicating effects.
 
According to Rohsenow’s “Intoxication with Bourbon versus Vodka: Effects on Hangover, Sleep, and Next-Day Neurocognitive Performance in Young Adults” published in Alcoholism: Clinical & Experimental Research, healthy heavy drinkers 21 to 33 participated in two drinking nights after an acclimatization night, building a mean blood alcohol level of 0.11 percent on vodka or bourbon one night with matched placebo the other night. The study found congeners increased hangover severity, with people feeling worse after bourbon. Bourbon whiskey has 37 times the congeners as vodka because bourbon ages in oak barrels, leaching out various molecules. But it’s not all bad news for bourbon. “Some whiskey congeners, particularly butanol, actually protect the stomach lining from damage [gastric mucosal damage], so potentially [it] might protect against feeling nauseous,” Rohsenow says
 
As for the hangover, Rohsenow says ethyl alcohol itself may still be the primary culprit. “Our study comparing beverages with high versus very low congener content showed most of the effect of drinking on hangover was due to the ethanol itself, with the other chemicals increasing hangover significantly but accounting for a much smaller percentage of the effect on hangover,” she says.
 
Hangover cures
Now the part you’ve been waiting for: Modern scientists have almost as many cures for hangovers as have been handed down from antiquity. Last year Chinese researchers from Sun Yat-sen University in China, the Food & Function paper co-authors, studied 57 different herbal and carbonated drinks' impacts on the enzymes that break down and rid the body of acetaldehyde and acetate, respectively. They discovered that some drinks, namely an herbal infusion called “Huo ma ren,” which consists of hemp seeds, increased ADH levels. That accelerated the breakdown of the alcohol in the first place but also inhibited the enzyme responsible for getting rid of acetate. The study showed that although green teas are rich in antioxidants, they “seriously prohibit” the metabolism of alcohol. The researchers wrote it’s better not to drink tea products during or after excessive alcohol consumption.
 
On the other hand, four beverages increased ADH and ALDH activity, helping to metabolize the toxins more quickly. Xue bi, which is similar to the popular soft drinks Sprite and 7-Up, showed the greatest increased ALDH activity and breakdown of acetaldehyde. The paper said the common soft drink additive taurine promotes efficient elimination of acetaldehyde. Thus, this research pointed toward Sprite or other soft drinks with taurine as being the optimal hangover cure.
 
Sticking to the liquid cures, Oshinsky’s study credits a morning cup of coffee and an aspirin. “The way we block the headache in the rat is five hours after we exposed them to alcohol, we gave them the caffeine,” Oshinsky says. “Nonsteroidal anti-inflammatory drugs also block the headache in the rat and those have a much longer half-life, so you can treat the animal much earlier, three or four hours before the headache.”
 
Moving past the over-the-counter antidotes, University of California, Los Angeles, chemical engineer Yunfeng Lu is using nanotechnology to mimic the liver’s enzymes and speed the elimination of alcohol from the body. Lu’s team showed that polymer capsules just tens of nanometers in diameter containing enzymes that break down alcohol could reduce blood alcohol levels in intoxicated mice. The team published their work in Nature Nanotechnology. Lu plans further research before testing this technology on humans but indicates the nanocomplex has far greater implications than just curing the hangover. In the study Lu concluded, “Considering the vast library of enzymes that are currently or potentially available, novel classes of enzyme nanocomplexes could be built for a broad range of applications." (Scientific American is part of Nature Publishing Group.)
 
It's complicated
But not everybody is ready to hail the nanomedicine as the future and decisive cure for all things, especially doctors who specialize in the hangover.
 
Anesthesiologist Jason Burke runs the Las Vegas–based mobile clinic “Hangover Heaven” and treats hangovers with IV fluids, the nausea medication Zofran, pain and inflammation drug Toradol, and a proprietary blend of vitamins. He remains skeptical of any and all hangover studies. “My biggest issue with hangover research is the way that most of these studies view hangovers,” he says. “When you actually look at the severity of the hangovers in most of these studies, they're not that bad.” He adds that “Las Vegas–sized” hangovers would not be considered ethical or safe by the review boards that approve medical experiments. Studies based on rats or humans who drank four beers won’t help the 24-beer client with a 0.3 blood alcohol level, he notes.
 
Still, Burke admits Lu's hangover nanopill intrigues him. “People want to feel better now,” he says. “This is America, the land of the magic pill.”
 

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