The Science Behind Red Wine Hangovers

Amanda Buerger

When in South Africa, do a wine tour!

That’s what I thought, anyway. This month, I was lucky enough to attend the Society of Environmental Toxicology and Chemistry Africa joint meeting with the Society for Risk Assessment in Cape Town South Africa. Prior to presenting my research, I took a little day trip to Franshhoek for wine tour, which got me wondering about the chemistry of wine and that infamous “red wine hangover” people talk about. Red wine headaches have been reported for centuries, and a 1988 blinded study found that 9 of 11 patients prone to migraines from red wine had a migraine following exposure, while 0 of 9 had a migraine from vodka (Littlewood et al. 1988).

What is it about wine that leaves some people so hungover? Sulfites? Histamines? Tannins? Let’s take a closer look! 

Figure 1: Photos taken along the Franshhoek Wine Tour, clockwise starting top left: barrels at La Bri (a female owned and operated winery), vineyards at La Bri, ship-themed bar at La Couronne vineyards, and view of the main building at Glenwood vineyards.

​Hangovers (in general)

First, let’s talk about what causes a hangover before moving on to why red wine hangovers are just so bad. Alcohol is readily absorbed into the blood through the gastrointestinal tract, where it travels throughout the body to the main site of metabolism, the liver. In the liver, alcohol dehydrogenases metabolize ethanol (the active component of alcoholic beverages) into acetaldehyde, and then aldehyde dehydrogenases convert acetaldehyde into acetate (Heit et al. 2015). Acetaldehyde is highly toxic and a carcinogen, while aldehyde is relatively harmless and is quickly converted to CO2 and H2O for excretion. Due to the importance of the liver in the metabolism of alcohol, this is why you should never take acetaminophen to cure a hangover, as that drug can cause liver damage when combined with alcohol!

Some alcohol makes it into the brain, where it is metabolized by catalase or cytochrome P450 2E1 (CYP2E1). While alcohol can cause long term effects through its carcinogenic metabolite, the immediate hangover is mainly a result of dehydration. Ethanol decreases your body’s production of antidiuretic hormone (vasopressin), which decreases the kidney’s ability to re-uptake water and can cause you to expel up to 4 times more liquid than you take in (Swift and Davidson 1998). This dehydration and subsequent imbalance in electrolytes is the main reason you feel so bad after a night of heavy drinking.
So, what makes a red wine hangover different? 

Red Wine Hangovers

Sulfites

Let’s start with sulfites. Sulfites are used to preserve food products and help prevent wine from becoming vinegar (which happens to wine that’s been open for too long). In the United States, wine can contain up to 350 parts per million (ppm) of sulfites, and any wine containing more than 10 ppm must be appropriately labeled. While most consumers believe that sulfites are the cause of wine headaches, the Federal Drug Administration (FDA) has found that only 1% of the US population is actually “sulfite sensitive” and sulfites are likely not the reason for most red wine hangovers, as many other foods contain levels of sulfites in excess of those in wines. Additionally, red wines actually contain less sulfites than white wines. For more information about public perception of headaches from sulfites and the willingness to pay extra for “sulfite-free” wine, see this article. 

Histamines

Histamines are proteins released by the body during allergic reactions and can lead to adverse effects, such as headaches (Maintz and Novak 2007). Histamines can also be ingested from food products. These histamines are degraded by diamine oxidase (DAO), so if levels of DAO are low or the level of histamines is high, one may experience symptoms of allergic reaction (Maintz and Novak 2007). So, what does this have to do with wine and headaches? Well, red wines have 20 to 200 times more histamines in them than white wine, which suggests that this may be a reason that red wine triggers these hangover headaches, though Krymchantowski and Jevoux (2014) found a lack of literature supporting this mechanism. That being said, for the small percentage who are histamine intolerant (those with no DAO or reduced DAO activity), this is likely to contribute to red wine headaches (Panconesi 2008).

​Tannins & Flavonoids 

So, sulfites and histamines are likely not the culprits (at least for most people), but what about congeners? Darker colored alcohols have more congeners, or impurities, than lighter colored alcohols. One famous group of congeners is tannins, which are bitter compounds that come from grapes. Red wines generally have a higher tannin content than white wines, as they are in contact with the tannin-containing grape skins for a longer period of time, and this contributes to their unique astringency. While red wines have a higher level of tannins and are associated with migraines, mechanistic evidence for this relationship are lacking and further studies are needed (Krymchantowski and Jevoux 2014).

Tannins themselves belong to a larger class of congeners called flavonoids, which are naturally occurring phenols and polyphenols that can form radicals (compounds containing an unpaired electron that are highly reactive and therefore toxic) (Figure 1). Phenols can inhibit phenosulphotransferase (PST) enzymes, leading to the accumulation of free radicals and their subsequent toxicity, which can manifest in headaches. Red wines contain up to 50x more flavonoids than white wines, and it has been shown that even heavily diluted red wine can inhibit PSTs by up to 50%. Around 30% of the flavonoids in red white are thought to contribute to its color, which is why they are in lower levels in white wines (Krymchantowski and Jevoux 2014; Panconesi 2008). 

Furthermore, certain flavonoids found in red wines can cause platelets to release 5-hydroxytryptamine (serotonin), and this release is unique to red wine compare to white wine and beer. Once released following red wine consumption, reuptake and binding of serotonin is inhibited. Though the inhibition of serotonin binding to its receptors is unclear, this may be the cause of red wine headaches (Krymchantowski and Jevoux 2014; Panconesi 2008).

Figure 2: Phenols (shown left), such as flavonoids, can become highly reactive radical compounds that are toxic to you.

Methanol

Lastly, methanol is a common congener that occurs in red wines more often than white wines (Swift and Davidson 1998). Methanol is a type of alcohol with one fewer carbon and two fewer hydrogens than ethanol. Though methanol is metabolized by the same enzymes as ethanol, its metabolites, formaldehyde and formic acid, are more toxic. Interestingly, ethanol is metabolized faster than methanol, which may be why hangover symptoms take so long to kick in.

In the end, what’s causing your red wine headaches? Probably a combination of things. But congeners such as flavonoids and methanol seem the most likely culprits for most people. I think I’ll stick to my white wine, thank you very much.