Why does red wine cause headaches? New study offers clue

By Kristen Rogers, Nov 23: Scientists may be closer to understanding the culprit behind the consumption of red wine causing headaches for some people, according to new research.

A flavonol naturally occurring in red wines may interfere with the body’s ability to metabolize alcohol, causing an accumulation of toxins that can lead to swift headaches, suggests the study published in the journal Scientific Reports.

Quercetin, the flavonol, is a plant compound found in fruits and vegetables including grapes, berries, onions and broccoli.

“When (quercetin) gets in your bloodstream, your body converts it to a different form called quercetin glucuronide,” said study coauthor Andrew Waterhouse, a wine chemist and professor emeritus in the department of viticulture and oenology at the University of California, Davis, in a news release. “In that form, it blocks the metabolism of alcohol.” 

Red wine has a tenfold higher amount of phenolic compounds, especially flavonoids, than white wine, which makes the beverage a “primary contender responsible” for headaches, the authors said.

Waterhouse and the other researchers aimed to uncover why headaches after imbibing just one or two glasses of red wine can even happen to people who don’t get headaches from other alcoholic beverages — so they studied how the flavonol may affect a genetic variant of an enzyme called ALDH2 that’s involved in the body’s metabolism of alcohol.

Nearly 8% of the global population has a variant of the enzyme that isn’t particularly active, and the deficiency is highly prevalent among people of East Asian descent — affecting around 40% of this population. Having a dysfunctional ALDH2 variant has been associated with skin flushing, heart palpitations and headaches after drinking.

When people drink, the alcohol is broken down in the liver by the enzyme alcohol dehydrogenase, which turns it into the compound acetaldehyde — a “well-known toxin, irritant and inflammatory substance,” said lead study author Dr Apramita Devi, a postdoctoral researcher in the department of viticulture and oenology at UC Davis.

The presence of acetaldehyde in the body is supposed to be short-lived since the enzyme ALDH2 transforms it into acetate, which is less toxic.

Using lab tests, the authors found that a derivative of quercetin — quercetin glucuronide — inhibited the enzyme variant. The interference, they hypothesized, would lead to a buildup of the toxin acetaldehyde — and headaches — in people who are more susceptible.

An untested mechanism

But experts who were not involved in the research urge caution, characterizing the study as a proposition of a theory rather than proof.

“The study was only done in a lab, and the substances were tested outside the human body in concentrations several times higher than that in blood after a few glasses of wine,” said Dr Jonas Spaak, an associate professor of cardiology at the Karolinska Institute in Stockholm, Sweden, via email.

This kind of research can generate ideas about the potential processes involved in the relationship between red wine and headaches, he added, but “ideally, the researchers should have included samples and tests from humans to verify this mechanism.”

Doing so is especially important since, in natural contexts in the human body, the quercetin derivative the authors used is something generated in the liver and excreted by the kidneys, said Dr. Vasilis Vasiliou, chair of the Department of Environmental Health Sciences at Yale University. Neither Spaak nor Vasiliou were involved in the new study.

What’s next in the study of red wine headaches

The authors plan to test their hypothesis in a small clinical trial of people who develop these headaches, by comparing red wines with high amounts of quercetin with those that have little.

“It is important also to mention that all alcohol consumption (is) for enjoyment only, and that there (is) no solid evidence for any positive health effects (of) red wine or alcohol, but solid evidence for dose-related harm,” Spaak said. “If you drink, do so in moderation.”

To minimize headaches, you can also experiment and try wines made by a variety of producers and grape varieties since the “levels of compounds that may trigger headache in red wine vary substantially between different wines,” he added.

Quercetin is produced by grapes in response to sunlight, Waterhouse said. “If you grow grapes with the clusters exposed, such as they do in the Napa Valley for their cabernets, you get much higher levels of quercetin. In some cases, it can be four to five times higher.”

As a result, you may have better luck with cheaper red wines or with white wines, which have a lower flavonol content overall, according to the study.