They may not be he result of overconsumption, but what are the causes of red wine headaches, asks Dr Erik Skovenborg.
Hangover headaches—which are the deserved result of binge or excessive drinking—are not the topic in this review. The focus is on “the undeserved hangover”—headaches after consuming even just one glass of red wine. The task here is to look for clues to possible causes of “undeserved hangovers” in order to help sufferers of undeserved headaches with suggestions of suitable solutions.
Some innocent usual suspects
Red wine headaches have been attributed to sulfites, but there is little evidence linking sulfites directly to headaches. White wine and many foods contain comparable levels of sulfites to red wine without headache complaints. Sulfite oxidase enzymes in the body catalyze the transformation of toxic sulfite from our metabolism of sulfur-containing amino acids to around 2,500mg of sulfate per day. In comparison, the 20mg of sulfites in a glass of wine is small beer for your sulfite oxidases. Asthmatic patients who are sensitive to sulfites are, however, recommended to limit their intake.
Tannin could be a plausible suspect, since the quantity in white wines ranges from 40 to 1,300mg/l, with an average of 360mg/l, while red wines contain from 190 to 3,900mg/l, with an average of 2,000mg/l, which amounts to 25–480mg of tannin in a glass of wine. Little evidence, however, links tannin directly to headaches. As a phenolic compound, tannin is a good antioxidant that is unlikely to trigger inflammation and headache. In comparison, a typical cup of black tea contains 30–100mg of tannins.
Related
With the verdict of not guilty of headache for sulfites and tannin in mind, we have to look elsewhere for responsible factors for red wine headaches. Some headache types suggest clues to a plausible culprit, and if you suffer one of the types of headaches listed below, you will find suggestions for which wines of which to steer clear.
Migraine
About 25% of migraine patients report that their attacks can be provoked by food and drink, with red wine heading the list. Littlewood and colleagues studied 19 patients with classical migraine, attending the Princess Margaret Migraine Clinic, who believed that their headaches could be provoked by red wine but not by vodka or gin. An intake of 10 fl oz (300 ml) of a Spanish red wine provoked a migraine attack after about three hours in 9 of 11 of those migraine victims, whereas none of the 8 patients challenged with 10 fl oz (300ml) of a vodka-lemonade drink of equivalent alcohol content had an attack.1 The major difference between red and white wines lies in their content of phenolic flavonoids, including the anthocyanins that give red wine its color. Many red-wine-sensitive migraine patients are able to enjoy light rosé wines, and some studies have found a threshold around one glass for intake of red wine that may provoke an attack.
Biogenic amine (histamine) headache
You may belong to the 8 to 10 out of 100 wine lovers who are histamine-sensitive if you have experienced headaches accompanied by symptoms like nausea, vomiting, diarrhea, and itching after a glass of red wine. Histamine is produced in the body and has vital functions as a signaling substance released from mast cells in response to allergic reactions or tissue damage. Histamine is also found in some fermented foods and drinks such as cheese, fish, and wine. Intake of a low amount of histamine through food is normally not harmful, because it can be detoxified by amino oxidases (MAO and DAO) in the gut. A weak histamine degradation activity due to genetic factors, however, increases a person’s sensitivity to histamine, and, in sensitive individuals, the consumption of wine with a high level of histamine can cause headaches because the activity of MAO and DAO is further inhibited by alcohol.2
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In the process of vinification, histamine is produced by lactic acid bacteria during malolactic fermentation. Meticulous research by Sophie Parker-Thomson for her MW research paper showed that these bacteria are acutely sensitive to sulfite. So, the recent trend toward deliberately making wine with very little sulfite creates the perfect environment for bacteria that produce biogenic amines to flourish. The story is told by Jancis Robinson MW in her article “A light shone on wine intolerance.”3
The key finding was that when as little as 30mg/l of sulfur dioxide was added before alcoholic fermentation, the biogenic amine level in the resultant wine was inconsequential and the different winemaking techniques had little bearing on final concentrations. But biogenic amine levels were highest, at levels certain to cause reactions in sensitive individuals, in wines either with no added sulfites or sulfites added only late in the winemaking process.
A few countries have recommended an upper limit for the histamine content in wine: 2mg/l in Germany, 3.5mg/l in the Netherlands, 8mg/l in France, and 10mg/l in Switzerland and Australia. If you are sensitive to histamine, you should probably opt for young white wines that have not undergone malolactic fermentation and light, young red wines fermented and stored in steel. It would also make sense to avoid wines produced with no or very low SO2 additions and wines that have spent very extended time on lees.
The Red Wine Headache
Herbert S Kaufman, Clinical Associate Professor of Medicine at the University of California, San Francisco School of Medicine, investigated the Red Wine Headache (RWH) in a number of studies. The RWH syndrome was complained of by a significant number of subjects known to the author’s practice. Twelve sufferers of RWH took part in a test consumption of red wine. After 3.4 fl oz (100ml) of red wine, 9 of the 12 confirmed the development of a dull, deep headache, while a dose of 6.8 fl oz (200ml) of red wine caused headaches in 11 of the 12, with maximum headache severity reached within one hour.4
When a dose of 650mg sodium salicylate was given 30 minutes before ingestion of 6.8 fl oz (200ml) of red wine, only 2 of the 12 subjects experienced a headache. The author found no signs of allergy in the participants and no specific characteristics of the headache-provoking red wines. The best diagnostic test for RWH was an in vivo challenge. Acetyl sodium salicylate was the drug of choice to prevent the RWH. In a later study, 200mg ibuprofen (NSAID) functioned nearly as well as 300mg aspirin in inhibiting RWH, but 500mg paracetamol did not, and a placebo was ineffective.5
Red wine flush headache
The metabolism of alcohol happens in two steps. First, the ADH enzyme converts alcohol to acetaldehyde—a highly reactive and toxic substance, which is immediately converted to harmless acetate by the enzyme ALDH. In the body, acetate is used as an energy fuel in skeletal muscle and used for synthesis of lipids in the liver. The fast detoxification of acetaldehyde is a testament to the impact of its reactivity. Around 30% of people of Chinese, Japanese, and Korean ancestry, however, have inherited at least one ALDH2*2 allele, which results in a less functional ALDH enzyme. After drinking any kind of alcoholic beverage, they will typically develop a flushing on the face and body, often accompanied by headache, nausea, and general physical discomfort.
Andrew Waterhouse, Professor of Enology at the University of California, Davis, and his colleagues scanned a list of phenolics in red wine while looking for a substance in wine that might inhibit the effect of the ALDH enzyme and explain the association of headache and red wine consumption. They spotted a paper showing that quercetin is a good inhibitor of ALDH, and a subsequent inhibition assay in test tubes confirmed that quercetin was indeed a good ALDH inhibitor. When quercetin enters the bloodstream, it is converted into quercetin glucuronide, and quercetin glucuronide was the supreme test-tube winner. The next step could be to give human “red wine headache” subjects two red wines that are low and high in quercetin, respectively, and ask whether the high-quercetin wine induces more headaches.6
People who are prone to headaches and migraines appear to be particularly susceptible to red wine headaches. If human studies confirm the hypothesis of a red wine flush headache due to quercetin inhibition of the ALDH enzyme efficacy, Waterhouse and his colleagues are on the right track. But there are still many questions to be answered, they admit, in an interesting review in The Conversation.7 “So, if quercetin causes headaches, are there red wines without it? Unfortunately, the data available on specific wines is far too limited to provide any helpful advice. Grapes exposed to the sun do, however, produce more quercetin, and many inexpensive red wines are made from grapes that see less sunlight. If you’re willing to take a chance, look for an inexpensive, lighter red wine.”
Another option might be to dump the reds and go for whites. Quercetin is found in grape skins where it absorbs ultraviolet light as a sort of sunscreen for the grapes. During the vinification of white wine, the grapes’ skins are removed before fermentation, so white wine doesn’t have quercetin. Light rosé wines might also be safe to drink.
NOTES
1. JT Littlewood, V Glover, PTG Davies, C Gibb, et al. Lancet 331 (1988), pp.558–59.
2. D Doeun, M Davaatseren, M Chung, “Biogenic amines in foods,” Food Science and Biotechnology 26:6 (2017), pp.1463–74.
3. https://www.jancisrobinson.com/articles/light-shone-wine-intolerance
4. HS Kaufman, “The Red Wine Headache: A pilot study of a specific syndrome,” Immunology & Allergy Practice 8 (1986), pp.279–84.
5. HS Kaufman, “The Red Wine Headache and Prostaglandin Synthetase Inhibitor: A blind controlled study?” Journal of Wine Research 3:1 (1992), pp.43–46.
6. A Devi, M Levin, AL Waterhouse, “Inhibition of ALDH2 by quercetin glucuronide suggests a new hypothesis to explain red wine headaches,” Scientific Reports 13 (2023), 19503.
7. https://theconversation.com/why-does-red-wine-cause-headaches-our-research-points-to-a-compound-found-in-the-grapes-skin-243869
