For the Greek philosopher Celsus, wine was the answer to endless ailments, from fatigue and fever to coughs and constipation. But despite its convenient healing powers, the grape, he conceded to his faithful readers, could bring about the odd headache.
Now, researchers believe they have hit on the reason why wine – red wine, in particular – causes such swift and undeserved headaches. When the liver breaks down a particular ingredient, it produces a substance that has the same effects as a drug used to make alcoholics feel dreadful if they drink.
“We think we are finally on the right track toward explaining this millennia-old mystery,” said Morris Levin, the director of the Headache Center at the University of California, San Francisco. “The next step is to test it scientifically on people who develop these headaches.”
Red wine headaches are a different beast from the hangover variety that set up shop the morning after the night before. Rather than coming on after a lengthy session, they can strike 30 minutes after drinking only one or two small glasses.
Since Celsus’s time, researchers have eyed all manner of red wine compounds in their search for the culprit. Tannins, sulphites, phenolic flavonoids and biogenic amines have all come under suspicion. So far, none has been nailed as a clear trigger.
Writing in Scientific Reports, the US researchers said they homed in on phenolic flavonoids, compounds that derive from grape seeds and skin and which contribute to red wine’s colour, taste and mouthfeel. Levels of flavonoids can be 10 times higher in red wines than whites, making them prime candidates for causing immediate headaches.
When people drink wine, the alcohol is metabolised to acetate in two steps. The first converts alcohol in the form of ethanol to acetaldehyde. The second turns acetaldehyde to acetate. Specific enzymes in the liver orchestrate each of these processes.
The researchers, including Prof Andrew Waterhouse, an expert in viticulture at the University of California, Davis, ran lab tests on more than a dozen compounds in red wine. One stood out. A flavanol called quercetin, found almost exclusively in red wine, is processed in the body into various substances. One of these, quercetin glucuronide, turned out to be particularly effective at blocking the enzyme that converts acetaldehyde into acetate.
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This could be key to solving the mystery. With the crucial enzyme suppressed, toxic acetaldehyde builds up in the bloodstream, the scientists believe. At high levels, this causes headaches, nausea, facial flushing and sweating. In fact, a drug called disulfiram blocks the same enzyme and is used to treat alcoholics by producing the same miserable symptoms if they drink.
According to the researchers, when susceptible people drink red wine with even modest amounts of quercetin, they can develop a headache, especially if they are prone to migraines. Why some are more affected that others is unclear: their enzymes may be easier to block, or they may simply be more susceptible to toxic acetaldehyde.
The team now hopes to test the theory with a clinical trial on the headache-inducing effects of red wines with different quercetin levels. The results could help people avoid red wine headaches in future. Grapes make quercetin in response to sunlight, so grapes grown in exposed clusters, such as Napa Valley cabernets, can have five times more quercetin than other reds. Skin contact during fermentation, fining processes and ageing also affect quercetin levels.
“It will be potentially very helpful for people who drink red wine to be able to choose wines less likely to cause headaches,” Levin said. “Also, winemakers may use our findings to reduce quercetin in their wines.”
