For the Greek philosopher Celsus, wine was the answer to endless ailments, from fatigue and fever to cough and constipation. But despite its convenient healing powers, the grape, he admitted to his faithful readers, could cause the odd headache.
Now researchers believe they have hit on the reason why wine – especially red wine – causes such quick and undeserved headaches. When the liver breaks down a certain ingredient, it produces a substance that has the same effect as a substance used to make alcoholics feel terrible 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 than the hangover variety that set up shop the morning after the night before. Instead of coming after a long session, they can hit 30 minutes after drinking just one or two small glasses.
Since the time of Celsus, researchers have looked at all sorts 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 have been nailed down as a clear trigger.
In Scientific Reports, the American researchers said they were at home in phenolic flavonoids, compounds derived from grape seeds and skins that contribute to red wine’s color, flavor and mouthfeel. Levels of flavonoids can be 10 times higher in red wines than white, making them prime candidates for causing instant headaches.
When people drink wine, the alcohol is converted to acetate in two steps. The first converts alcohol in the form of ethanol to acetaldehyde. The other converts acetaldehyde to acetate. Specific enzymes in the liver orchestrate each of these processes.
The researchers, including Professor Andrew Waterhouse, an expert in viticulture at the University of California, Davis, ran laboratory 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, was found to be particularly effective in blocking the enzyme that converts acetaldehyde to acetate.
This may be the key to solving the mystery. With the crucial enzyme suppressed, toxic acetaldehyde builds up in the bloodstream, the researchers 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 may develop headaches, especially if they are prone to migraines. Why some are more affected than 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 levels of quercetin. The findings may help people avoid red wine headaches in the 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 aging also affect quercetin levels.
“It would potentially be very helpful for people who drink red wine to be able to choose wines that are less likely to cause headaches,” Levin said. “Winemakers can also use our findings to reduce quercetin in their wines.”