A study published in 2023 provided new insight into why some people develop headaches after drinking red wine.
Researchers from the University of California, Davis, and the University of California, San Francisco proposed that a naturally occurring grape compound may interfere with the way the body metabolises alcohol, potentially triggering headaches in susceptible individuals.
The findings offer a credible new hypothesis, but they do not yet prove that this compound causes red wine headaches in people.
Red Wine Headaches
Headaches are remarkably common. A global review estimated that approximately 15.8% of the world’s population experiences a headache on any given day. Alcohol is also a recognised headache and migraine trigger, particularly when consumed in larger quantities.
However, some people develop a headache after drinking as little as one or two glasses of red wine, even when small amounts of other alcoholic beverages do not produce the same reaction.
These red wine headaches can begin within 30 minutes to three hours of drinking. Although several wine components have previously been suspected, researchers have struggled to identify a specific chemical mechanism.
A Possible Cause
The researchers focused on quercetin, a phenolic compound found naturally in grape skins and many other fruits and vegetables.
Quercetin belongs to a group of compounds known as flavonols and is generally regarded as a beneficial dietary antioxidant. The researchers proposed that the problem may arise not from quercetin alone, but from the way it is processed by the body when alcohol is also present.
Red wine generally contains considerably more quercetin than white wine because the grape skins remain in contact with the juice during fermentation. The amount can vary between wines according to grape variety, sunlight exposure, vineyard conditions and winemaking practices.
What the Researchers Found
When quercetin enters the bloodstream, the body converts much of it into a metabolite called quercetin-3-glucuronide.
In laboratory testing, the researchers found that this metabolite inhibited ALDH2, an enzyme that plays an important role in breaking down acetaldehyde during alcohol metabolism.
Andrew Waterhouse, wine chemist and study co-author from UC Davis, explained that this interference could slow the body’s metabolism of alcohol.
Why Acetaldehyde Matters
The body metabolises alcohol in two principal stages.
First, ethanol is converted into acetaldehyde. The ALDH2 enzyme then helps convert acetaldehyde into acetate, which the body can process more readily.
If ALDH2 does not function efficiently, acetaldehyde can accumulate. Acetaldehyde is a toxic and inflammatory compound associated with facial flushing, nausea and headache.
The researchers proposed that quercetin-3-glucuronide may inhibit ALDH2 sufficiently to increase acetaldehyde levels and trigger a headache in susceptible people.
Why Are Some People More Susceptible?
Professor Morris Levin, a neurologist and director of the Headache Center at the University of California, San Francisco, suggested that people with migraine or another primary headache condition may be particularly susceptible to this mechanism.
Individual differences in alcohol metabolism may also help explain why one person develops a headache while another can drink the same wine without experiencing any symptoms.
Researchers do not yet know whether the ALDH2 enzyme is more easily inhibited in people who experience red wine headaches or whether those individuals are simply more sensitive to acetaldehyde accumulation.
What the Study Did—and Did Not—Prove
The study demonstrated in a laboratory that quercetin-3-glucuronide can inhibit the ALDH2 enzyme.
It did not involve participants drinking red wine, measure acetaldehyde accumulation in those participants or demonstrate that quercetin directly caused their headaches.
The researchers therefore described their finding as a hypothesis requiring human clinical testing. A suitable trial would compare wines containing different amounts of quercetin in people who regularly experience red wine headaches.
In Summary
The study suggests that quercetin in red wine may be converted into a compound that interferes with the body’s metabolism of alcohol.
This could allow acetaldehyde to accumulate, potentially causing headaches, flushing or nausea in susceptible individuals.
It is a promising explanation for the long-standing mystery of red wine headaches, but it is not yet a confirmed cause. Human trials are needed to determine whether the proposed mechanism occurs outside the laboratory and why it affects some people but not others.
Read the full UC Davis explanation of the study.