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Medical accounts of red wine headaches go back to Roman times, but the experience is likely as old as winemaking – something like 10,000 years. As chemistsspecializing in winemaking, we wanted to try to figure out the source of these headaches.

Many components of red wine have been accused of causing this misery – sulfites, biogenic amines, and tannin are the most popular. Our research suggests the most likely culprit is one you may not have considered.

The common suspects

Sulfites have been a popular scapegoat for all sorts of ailments since it became mandatory in the 1990s to label them on wines in the U.S. However, not much evidence links sulfites directly to headaches, and other foods contain comparable levels to wine without the same effects. White wines also contain the same amount of sulfites as red wines.

Your body also produces about 700 milligrams of sulfites daily as you metabolize the protein in your food and excrete it as sulfate. To do so, it has compounds called sulfite oxidases that create sulfate from sulfite – the 20 milligrams in a glass of wine are unlikely to overwhelm your sulfite oxidases.

Some people point the finger for red wine headaches at biogenic amines. These are nitrogenous substances found in many fermented or spoiled foods, and can cause headaches, but the amount in wine is far too low to be a problem.

Tannin is a good guess, since white wines contain only tiny amounts, while red wines contain substantial amounts. Tannin is a type of phenolic compound – it’s found in all plants and usually plays a role in preventing disease, resisting predation or encouraging seed dispersal by animals.

But there are many other phenolic compoundsin grapes’ skin and seeds besides tannin that make it into red wines from the winemaking process, and are not present in white, so any of them could be a candidate culprit.

Tannin is also found in many other common products, such as tea and chocolate, which generally don’t cause headaches. And phenolics are good antioxidants– they’re unlikely to trigger the inflammation that would cause a headache.

A red wine flush

Some people get red, flushed skin when drinking alcohol, and the flushing is accompanied by a headache. This headache is caused by a lagging metabolic step as the body breaks down the booze.

The metabolism of alcohol happens in two steps. First, ethanol is converted to acetaldehyde. Then, the enzyme ALDH converts the acetaldehyde to acetate, a common and innocuous substance. This second step is slower for people who get flushed skin, since their ALDH is not very efficient. They accumulate acetaldehyde, which is a somewhat toxic compound also linked to hangovers.

So, if something unique in red wine could inhibit ALDH, slowing down that second metabolic step, would that lead to higher levels of acetaldehyde and a headache? To try to answer this question, we scanned the list of phenolics abundant in red wine.

We spied a paper showing that quercetin is a good inhibitor of ALDH. Quercetin is a phenolic compound found in the skins of grapes, so it’s much more abundant in red than white wines because red grape skins are left in longer during the fermentation process than white grape skins.

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