This essay is shared with permission from The Conversation, a digital platform focusing on contemporary research.

Historical accounts of headaches caused by red wine trace back to Roman times, though the phenomenon likely dates to the inception of winemaking over 10,000 years ago. As chemists with a focus on viniculture, we’ve taken interest in uncovering the root cause of these headaches.

Various components of red wine have been blamed for these adverse effects, including sulfites, biogenic amines, and tannins. However, our research points to a less considered, more likely suspect.

Supporting Science Journalism

If you appreciate this content, consider supporting our distinguished journalism by subscribing. Your subscription helps sustain the future of our in-depth coverage on the breakthroughs and ideas that shape our contemporary world.

The Usual Suspects

Sulfites have often been accused of causing various health issues since it became a requirement to list them on wine labels in the U.S. during the 1990s. However, the evidence linking sulfites to headaches is sparse, and other foods that contain similar levels of sulfites do not provoke the same reaction. It’s worth noting that white wines generally contain just as much sulfite as red wines.

Furthermore, the human body naturally produces approximately 700 milligrams of sulfites each day as part of protein digestion, which it then excretes as sulfate. The body utilizes enzymes known as sulfite oxidases to convert sulfites to sulfate; thus, the 20 milligrams found in a glass of wine is unlikely to burden these enzymes substantially.

Biogenic amines have also been indicated as potential culprits behind red wine headaches. These nitrogen-containing compounds are present in many fermented or spoiled foods and can induce headaches, but their levels in wine are typically too low to cause issues.

Tannins are another plausible cause, given that white wines contain minimal amounts, whereas red wines have significant levels. Tannins are phenolic compounds that naturally occur in all plants, helping to fend off diseases and deter predators, or encourage animals to disperse seeds.

However, red wines derive additional phenolic compounds from the grape skins and seeds during the winemaking process that aren’t found in white wines, so any of these could be responsible. Moreover, tannins are found in other common items like tea and chocolate, which typically don’t cause headaches. Additionally, phenolics are known antioxidants and are unlikely to stimulate the inflammation associated with headaches.

The Red Wine Flush

Certain individuals experience a red, flushed complexion when consuming alcohol, which often accompanies a headache. This type of headache is due to a delayed metabolic reaction as the body processes the alcohol.

Alcohol metabolism involves two stages. Initially, ethanol is converted into acetaldehyde. Subsequently, an enzyme called ALDH transforms acetaldehyde into acetate, a harmless substance. For those who experience flushing, this second stage is less efficient due to suboptimal ALDH function, leading to an accumulation of the slightly toxic acetaldehyde, which is also implicated in hangovers.

If a particular substance in red wine could inhibit ALDH, thus slowing this second metabolic step, it could result in elevated acetaldehyde levels and consequently, a headache. To explore this possibility, we examined a roster of phenolics prevalent in red wine.

Our attention was drawn to a study indicating that quercetin is an effective ALDH inhibitor. Quercetin, a phenolic compound, is more abundant in red wines than white wines due to the longer contact with grape skins during fermentation.

Testing the Enzymes

The next logical step was to test ALDH activity. We set up an inhibition assay in test tubes to measure how quickly ALDH could break down acetaldehyde. After introducing potential inhibitors like quercetin and other phenolics into the mix, we observed how they affected the process.

These tests confirmed quercetin as a significant inhibitor. Other phenolics showed varying effects, but quercetin glucuronide stood out. When ingested from food or wine, most quercetin is converted to glucuronide by the liver to facilitate rapid elimination from the body.

Our findings suggest that quercetin glucuronide interferes with the body’s alcohol metabolism, leading to increased acetaldehyde levels and causing inflammation and headaches. This points to a secondary, or synergistic, effect, which is harder to identify because it requires the presence of two interacting factors to manifest.

Further research could involve giving human participants red wines with low and high quercetin levels to see if the higher quercetin wine triggers more headaches, which would confirm our hypothesis.

Regarding finding red wines low in quercetin, the available data is limited. However, grapes that have less exposure to sunlight produce less quercetin, and many inexpensive red wines are made from such grapes.

If you’re looking to avoid the risk, you might consider trying a cheaper, lighter red wine.

This article was originally published on The Conversation. Read the original article.