Ugh... what did I do to deserve this?

“I can’t drink red wine: it gives me headaches.”
“I can’t drink white wine: it gives me headaches.”
“I can’t drink Champagne: it gives me headaches.”

You have probably heard this before. Some people just react badly to certain types of wine. The cynic would say it’s all psychosomatic, yet there exists a bona fide, though not well-understood, medical condition called “red wine headache.” What’s going on in wine that causes these headaches?

Sulfites

Sulfur dioxide and its forms in wine are generally referred to by the catch-all term “sulfites.” Lots of people have heard of them, but many do not understand why they are in wine in the first place. Sulfites have been added as an antioxidant and antimicrobial agent practically since wine was first made. Many consumers read bottles of wine that say “Contains sulfites” and assume that these chemicals are the cause of headaches.

They are not.

There is no evidence in any scientific literature that sulfites cause wine-related headaches. Sulfites do cause a trigeminal response (nasal irritation) if present in large amounts in wine. This stinging perception of molecular SO2, which smells like a struck match (a match head is basically sulfur and phosphorus) varies by the amount of total sulfites, pH, and other factors. A very small part of the population (about 1%, according to the FDA) is allergic to sulfites and can have respiratory difficulties with exposure, but headaches are not common.

The general mantra with sulfites is “harmless to many, annoying to some, dangerous to few.” Red wines generally have fewer sulfites than white wines (due to the antioxidant capacity of tannins and other polyphenolics found in reds).

Biogenic Amines
Less well-known in the wine world are another set of compounds, formed by the degradation of free amino acids by fermentation organisms. They’re collectively called biogenic amines, and they include histamine, tyramine, and the worst-sounding of the bunch, putrescine.

Their health effects in large doses include headaches, nausea, and other unpleasantness.

Many countries now have recommended (but not yet set in legal stone) limits on biogenic amines in wines. In spite of this, studies examining the safety of these compounds have found that their amounts in wine are below those which would cause such side effects. Biogenic amine concentrations in aged cheese are more likely to produce symptoms than in wine.

Also, anyone taking the prescription drugs known as MAO inhibitors (a much older generation of antidepressants, seldom used these days) should definitely avoid biogenic amines. MAO, or monoamine oxygenase, breaks down and eliminates detoxifies these compounds under normal conditions. In the presence of MAOis a person can go into a hypertensive crisis, which can actually be fatal. On that note, people with varying levels of MAO could have varying responses to histamine and tyramine.

Red wines are generally higher in biogenic amines than whites (practically all red, but significantly fewer white wines are go through malolactic fermentation [see inset] and more nutrients are extracted from the skins during fermentation of reds.)

Factors that increase biogenic amines in wine

  • Spontaneous malolactic fermentation: Commercial malolactic bacteria have been selected for lower production of these biogenic amines. Spontaneous MLF can contain malolactic bacteria that are more prone to biogenic amine production.
  • Yeast lees exposure: Exposure to yeast lees releases mannoproteins and amino acids in yeast, leading to BA production, so wines aged sur lie and in the methode champenoise will have higher BAs.
  • Brettanomyces: in a recent study, fermentations containing Brettanomyces bruxellensis (aka Brett) produced a larger amount of BAs than Saccharomyces. Many Old World wines (particularly unfiltered, low-sulfite wines) are susceptible to spoilage by Brett.
  • High nitrogen: high nitrogen in the must can lead to increased production of biogenic amines during fermentation and also contribute to BA production by spoilage organism in the bottle down the road.  Diammonium phosphate (DAP)  can be added to up nitrogen nutrients in must but is sometimes overused.

Tannins and other polyphenols
Since red wines contain tannins and white wines do not, these and other polyphenolic compounds are also a factor that is often targeted as a headache cause. Tannins do cause an astringent feeling in the mouth by interacting with mouth proteins (much more information on this topic can be found here at Palate Press.)

What does this have to do with headaches? Not much. One argument against tannin-related headaches is the fact that tannins are naturally found in all kinds of foods from tea to chocolate to nuts. In fact, many wines with added tannins (yes, you can do that in some places) contain tannins derived from nuts.

The basis of the argument stems from studies that suggest that tannins in cotton can induce the release of serotonin, a neurotransmitter which constricts blood vessels, leading to headaches. However, a recent study found that red wine is actually a vasodilator, and it is likely that the mechanism of vasodilation is related to the polyphenols in wine. So if anything, the polyphenolic content of a red wine should work to alleviate headaches. Thus, the evidence of tannin as the culprit seems a bit weak.

Glutamate
Another suspect one might think of as a cause of wine headache is glutamate, the amino acid responsible for the umami flavor found in many wines.  After all, many people report headaches and other symptoms after eating Chinese food, typically a hotbed of MSG (monosodium glutamate).  Again, though, recent reviews of decades of literature have shown no clear connection between MSG and such symptoms.  Thus, a connection between the glutamate naturally found in elevated levels in some wines and headaches is not likely.

Alcohol
Normally, the alcohol by volume in table wine can range from 7% in crisp, light Mosel Rieslings and Vinho Verdes to 16% in Zinfandels and some Alsace Gewürztraminers. So a night of drinking wine will leave one far more dehydrated than a night of light beer. Indeed, I am sure that many wine headaches have a simple explanation: hangovers.

Though the hangover itself is not very well-understood scientifically (despite the money to be made with a cure!), many of its symptoms are similar to those of dehydration. Alcohol inhibits proteins called aquaporins, which concentrate urine, conserving the body’s water supply. Thus, you might make several trips to the bathroom during a night of drinking, then wake up parched. Dehydration and many of the other adverse effects of alcohol can add up to a killer headache… for which my favorite cure is a Bloody Mary.

Psychology
Allow me to present another possibility. Our perception of wine is highly influenced by psychology and context. This explains how hilariously inaccurate results can come from blind tastings, even with professionals. Some studies involving red wine and headaches have indeed been discounted due to the researchers’ inability to properly blind participants, suggesting that a placebo effect may have influenced the participants’ claims of headaches caused by red wine. If a person really believes that red wine can give him headaches, then ingestion of red wine may work him up into a headache regardless of the contents of the wine in question.

I’m not trivializing what is widely recognized as a genuine medical phenomenon. I’m simply suggesting that not as many people actually suffer from headaches triggered solely by ingestion of red wine as we might think. Headaches are very common and medically mystifying, so sometimes it is hard to tell the true causes of many headaches.


Avoiding headaches

So far, there is no conclusive determination on what component of red wine causes the dreaded “red wine headache”. This is likely due to the fact that funding for the detailed studies needed to isolate the cause(s) is hard to come by.

Wine is such a complex chemical mixture that we may never understand the complicated combinations of factors that cause headaches in certain people. Each of us is unique and likely possesses different sensitivity to the thousands upon thousands of different molecules in wine. Migraine sufferers, in particular, can have an array of environmental triggers, from certain foods to bright lights.

In general, though, given the factors that influence biogenic amine production, if you are susceptible to “red wine headache”, it may be wise to avoid wines prone to Brett, spontaneous MLF, and long yeast exposure. Keeping meticulous tabs on the wines we drink (and our reactions) can be helpful, too. I guess when it comes to avoiding headaches, we can always rely on the old Henny Youngman gag: “Doctor, it hurts when I do this!” “…Then don’t do it!”

For now, though, all this medical research is giving me a headache. Time to pop open some wine.


Further Reading:

Tom Mansell

Tom Mansell is a PhD candidate in chemical engineering at Cornell University in Ithaca, NY.  He is borderline obsessed with the science of wine and winemaking. His blog, Ithacork, focuses on Finger Lakes wines and always includes a “Science!” section, which gets down to technical details for the hardcore wine geek. Follow him on Twitter @mrmansell.

About The Author

Tom Mansell
Science Editor

Tom Mansell is the Science Editor here at Palate Press and a member of the Editorial Board. He has a PhD in chemical engineering from Cornell University, where he also learned to love the wines of the Finger Lakes. He is also the Science Editor for The New York Cork Report. Tom is currently living in Boulder, CO, where he is a researcher at the University of Colorado. Follow him on Twitter @mrmansell.

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  • http://www.enjoyfinewines.net M. Yee

    Thanks! Very informative article. I’ve done casual research and have been quite interested in this topic because I experience certain symptoms myself (fluid in ears). This is frustrating since I am in the in wine industry. So, thanks for posting this. I work as a wine steward at a retail store and many customers have told me about their symptoms. Now, I can explain more knowledgeably some possible reasons why, that every person is different and wine is a “complex chemical mixture”, and that sulfites is not the cause.

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  • http://www.ulcellars.com Steve

    Excellent article, well researched and very informative. Two comments:
    1) As a winemaker who IS allergic to sulfites I can attest that they do not add to headaches. I need to be very careful during crush to not contact must that has been sulfited or a wicked rash ensues.
    2) One other source of headaches is residual sugar in combination with alcohol.
    Great job!

  • http://www.1001vins.net yannik

    Excellent post. thank you. I heard from few wine producers that sulfites destroy your B12 vitamins. The B12 is apparently helping your system to absorb alcohol. Is it true ? I don’t know. If it is, that could be one explanation

  • http://www.foodandwinechickie.com Veronique Deblois

    Great post with tons of useful info/data. Cheers!

  • Gregg

    In my experience, people are really allergic to the histamines from the wine production process, as is the same issue with certain beers (hoppy and/or barrel-aged). The process might cause congestion and sinus headaches.

  • Rich Marrocco

    Tom,
    Nicely written article! I suffer from red wine headaches, but I also can get them from white wine, beer, or Absolut vodka (in small amounts yet!). Because of the “purity” of the vodka, I am pretty resigned to the idea that my cerebral blood vessels hate alcohol. If wine causes them to constrict, I might get a headache from tissue anoxia. If vessels dilate, they stretch and activate pain receptors. It’s probably not both for me because my headaches occur hours after the alcohol has metabolized, and I have never of people that get immediate but brief headaches. Maybe we can’t use migraine headache models to explain wine-induced headaches. Maybe it’s all serotonin’s fault. But, do people on SSRIs get fewer headaches? Would foods high in tryptophans help reduce headaches?
    The one thing I do know is that with a one-glass limit, I have started drinking much more expensive wines.

  • http://www.winesooth.com Arthur

    @ Greg
    You can’t be allergic to histamine.
    Histamine is a chemical mediator used by immune cells and is responsible for the symptoms we associate with allergic reactions: runny nose, itchiness, watery eyes etc. Allergy medications block histamine receptors to prevent/reduce the symptoms. So it may be that someone has a heightened sensitivity or, more accurately, a heightened response to histamine and molecules that mimic it.

  • http://www.thomaspellechia.com Thomas Pellechia

    One other possibility that isn’t discussed much could be mold that might have spores living in wood (oak) the cork, or in the wine cellar itself.

    After having gone through this subject in a variety of ways over many years, I am nearly (but not completely) convinced that the wine headache is a combination of reaction to amines or mold, or both, with a strong dose of psychological phenomenon.

    Having said that, I do know people who either sneeze or turn beet red after a glass of red wine. In fact, I’m one of them who sneezes, but not after all red wines that I consume, and then, after the second glass, the sneezing ends. Go figure.

    Tom, we shall add your “sulfites don’t cause headaches” to the zillions of others of us who have said and written those words over these many years, yet the power of myth is stronger than the truth and so, I’m certain we’ll have to keep saying it.

  • http://www.sondrabarrett.com Sondra Barrett

    Great post full of very useful information. I am also glad that Arthur responded to say you can’t be allergic to histamine, one of our bodies own chemicals. In addition, I don’t think you can be allergic to sulfites either. Allergies are a specific response involving antibodies, a protein, against the offending chemical. In my ancient training in immunology, small molecules, on their own, cannot trigger allergy response. That said, I would suspect, reactions to sulfites are also heightened sensitivities, metabolic responses. Responding to an irritant, like sulfite, histamine, a burn, is different from an allergy.

    And let’s face the sulfite story – it was a political vendetta against alcohol that named it dangerous on wine bottles. Isn’t there more sulfite in dried fruit?

  • http://ithacork.com Tom Mansell

    Thanks all for your thoughtful comments.

    Steve: It’s part of the “common wisdom” that sweeter drinks lead to worse hangovers, but is it known in the scientific literature? Apparently, alcohol mixed with sugar can cause increased hypoglycemia in the hours following consumption. So, it’s possible, I guess.

    Yannik: Interesting point! Apparently, B12 can reduce asthmatic response in patients that present a sulfite allergy. It’s recommended for sulfite allergy sufferers, so maybe Steve should up his B12 intake during crush. :)
    Sulfites in food can in fact eliminate the activity of vitamins like B1, B12, C, and K in foods. Not sure about how they would affect vitamins already in the body though. Maybe a future Palate Press piece on sulfites will address this in detail….

    Rich: In college, I knew a girl who was basically allergic to alcohol. Anything more than one drink of anything and she had serious issues. Some people, Asians in particular, are deficient in acetaldehyde dehydrogenase, which allows acetaldehyde to build up during drinking. As for serotonin, I just don’t think there is enough information out there in the form of scientific studies.

    This is probably because there is already a cure for wine and alcohol-based headaches. Unfortunately, it’s “not drinking”.

    Arthur: I think I read that the response to biogenic amines is not IgE-dependent, but I would have to look at that again.

    Thomas: Thanks for chiming in. The “sulfites don’t cause headaches” may be well-known and well-repeated, but I’m not sure a piece like this could avoid mentioning them up front.

    Perhaps the sneezing, if not due to sulfite sensitivity, could be due to nasal irritation from alcohol and/or sulfites. I sometimes get a little nose tickle with, say, a 16% Shiraz. The beet red reaction could be also be reaction to alcohol (see acetaldehyde dehydrogenase, above)

    Interesting perspective vis-à-vis mold spores. I assume the proposed mechanism would be mycotoxins? I know that sulfites do destroy some mycotoxins under certain conditions.

    Sondra: It’s convenient to say “allergic”, but you’re right. Most sulfite allergies are thought to be caused by deficiency in sulfite oxidase. However, a small percentage of sufferers (those who get rashes, like our pal Steve) actually DO have IgE-mediated response, indicating a true allergy.

  • http://www.winesooth.com Arthur

    Tom
    I think you are right. Biogenic amines can act directly on receptors – thereby affecting some physiologic response. Thus my point, offline, that they should be called ‘bioactive’ amines.
    That was my point to Greg, that one can’t be allergic to a mediator of allergic response.

  • http://www.thomaspellechia.com Thomas Pellechia

    Tom,

    My sneeze is definitely induced nearly immediately, and mostly with red wines, but not all of them.

    As a teen, I had a series of allergic reactions (mainly hives) that were treated with strong antihistamines.Never determined what caused it, and as I grew older, the problem dissipated out of existence.

    All of this is to say that I am convinced through personal experience that something in wine–especially red–causes a reaction in my nose. And like the other allergic reactions I’ve had, after enough desensitizing to whatever is in the wine, by the third glass, the problem has abated. It’s the fourth, fifth and sixth glasses that cause the headache the next day…

  • Kevin

    What’s interesting to me is that I’ve consumed red wines for years with no negative side effects. It seems that within the last year or so, I’ve begun experiencing RWH after one glass of red wine. I live in California and tend to consume mostly California and Washington reds, leaning towards cabs, zins and syrahs. Happen to be headed to Paris for an anniversary with my beautiful wife of 20 years — sounds like a trip to the Burgundy region is in order for a little experimentation!

    This article has been very helpful as I’d begun to feel as if the answer might be that I needed to give up red wines.

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