IRA FLATOW: This is Science Friday. I’m Ira Flatow.

FLORA LICHTMAN: And I’m Flora Lichtman. It’s the season of merrymaking. And that means you’re always looking for a gift to bring to somebody’s holiday party, right?

IRA FLATOW: Right.

FLORA LICHTMAN: Lots of times I feel like a bottle of wine is perfect. It fits the bill.

IRA FLATOW: It is absolutely true. And I was just thinking about that, which makes me wonder. Are you, Flora, a red or a white wine person?

FLORA LICHTMAN: Thank you for asking. I’m a both person. You’re safe with me with either. But I have noticed this weird thing with red wine, the head pain that comes along with it.

IRA FLATOW: That’s right. I think everybody gets that, the dreaded red wine headache. And you don’t know what it is because it feels sometimes like a hangover, but it’s not quite that, right?

FLORA LICHTMAN: Right. Well I learned that’s exactly it. It’s completely different from a hangover. And there’s been a breakthrough in what might actually cause it. So this comes from Dr. Morris Levin, Director of the Headache Center at the University of California San Francisco Medical Center.

Dr. Levin, welcome to Science Friday.

MORRIS LEVIN: Thanks very much. Thanks for having me on your show.

FLORA LICHTMAN: OK, first of all, I just want to clear this up. So a red wine headache is not a hangover?

MORRIS LEVIN: Right. It’s a different kind of thing. Hangover headaches, as you know and as everybody knows, happen a number of hours after drinking, tend to happen the next morning, and they tend to happen when one over drinks, more than just–

FLORA LICHTMAN: Yes, I do know.

MORRIS LEVIN: –drinking a little bit, right.

FLORA LICHTMAN: And this is different?

MORRIS LEVIN: This is quicker. It happens in the first couple of hours, and it can it sometimes occur after just drinking a little bit.

FLORA LICHTMAN: And does it happen with all alcohol, or is this a red wine specific headache?

MORRIS LEVIN: It’s really specific to red wine, hence the name. And I think people can get it after drinking white wine or after drinking another kind of alcohol. But it’s kind of rare. And it’s been a mystery as to why this happens with just red wine for hundreds, maybe thousands of years.

FLORA LICHTMAN: Thousands of years, really?

MORRIS LEVIN: Right, right.

FLORA LICHTMAN: Has it been referenced in literature?

MORRIS LEVIN: Well, I don’t know. But I think it probably has occurred to people. I know it’s been referenced for the last couple of hundred years.

FLORA LICHTMAN: It seems like there’s a lot of misinformation about what causes or might cause red wine headaches, like I’ve heard that sulfites in wine are bad. Are they responsible?

MORRIS LEVIN: Right, Flora, it’s been a lot of things. It’s been tannins that have been proposed, histamine, sulfites, tyramine, alcohol itself. And each one of them made some sense. But each one of them has in succession been ruled out and disproven pretty convincingly. And now, as you gathered, Andy Waterhouse, a wine chemist, and I have settled on this compound that’s found particularly in red wines.

FLORA LICHTMAN: Yeah. Talk to me about your theory.

MORRIS LEVIN: The theory is that a compound called quercetin, which is present in red wine in much higher concentrations than it is in white wine and other alcoholic beverages is the culprit, although it’s not a direct culprit. It actually inhibits an enzyme that is responsible for detoxifying alcohol in our systems. And the problem is when that enzyme doesn’t work properly, there is a buildup of a toxin called acetaldehyde. And it’s a pretty nasty toxin that not only causes headaches. It causes a number of other symptoms and the more I look into this acetaldehyde, I think it’s not just toxic in terms of things like headaches and maybe a little nausea and so on. I think it’s toxic to a number of organs, and might be kind of dangerous, more dangerous than thought.

FLORA LICHTMAN: So if you have a red wine headache, does that mean other bad things are happening in your body?

MORRIS LEVIN: Good question. I don’t know. I think it might. Of course, like anything else, like any other toxin, the more you take in, the worse it is. And I think probably the occasional red wine is not going to hurt anybody other than maybe giving them the headache.

FLORA LICHTMAN: I’m glad to hear that. What is this chemical do? Is that the right word, chemical, for quercetin?

MORRIS LEVIN: Yeah, it’s an interesting compound. It’s not in itself dangerous. In fact, it’s marketed as a nutritional supplement because it’s an antioxidant. It’s a member of this family called flavonoids. And they are healthful and can be helpful for people. But it’s when taken in in concentrations that are kind of high in conjunction with alcohol, ethanol. That’s where it can be a problem.

FLORA LICHTMAN: What does it do in the grape? What’s its purpose in the grape?

MORRIS LEVIN: Yeah, it’s an interesting question. It’s found in a lot, this flavonoid, this quercetin, it’s found in a lot of fruits and vegetables. And it’s a pigment. And so it is found in grapes and other foods that are colorful. For example, it’s found in onions, but only the onions that are colorful like yellow onions, found in other vegetables and fruits. And it’s probably not bad for you at all, unless it’s taken, like I said, with alcohol.

FLORA LICHTMAN: How interesting. I mean does the fermentation process have any effect on its concentration, or how it’s working in the body?

MORRIS LEVIN: We don’t think so. But what seems to happen is that when grapes are exposed to a lot of sunlight, which is a good thing in the winemaking business, the more sunlight grapes are exposed to, the more sugar and the better they ferment, and I gather that particular happenstance allows grapes to turn into very, very good wines. And so one of the things that we’ve noticed is that the better wines that have this kind of high sun exposure, high sugar content to the grapes, makes the best wines.

So Andy Waterhouse is thinking that if you want to avoid this kind of headache, maybe drink, the less expensive, the cheaper wines.

FLORA LICHTMAN: Music to my ears.

MORRIS LEVIN: Right.

FLORA LICHTMAN: So does that mean it’s found in the skin of the grape, and that’s why you see it more in red wine than in white wine?

MORRIS LEVIN: I think that’s right. And then, like I said, the grapes that are treated in certain ways have more quercetin. And interestingly, white wines just don’t have much.

FLORA LICHTMAN: So where did this theory come from? I mean, what sort of science do you have to back it up, and what would it take to know for sure that this is what’s causing the red wine headache?

MORRIS LEVIN: That’s the key question. And right now, it’s just a theory. So we do have to prove it. We think, first of all, the way we came up with this idea and it wasn’t our first idea, but the way we came up with it is to look at what is present in red wine and not present in any other type of wine or other alcoholic beverages. And this passed muster for something that is very high in red wine and low in other beverages.

So after thinking about and excluding some other culprits, potential culprits, this just seemed to be obvious.

FLORA LICHTMAN: And what would it take to prove it?

MORRIS LEVIN: We could and we have designed a few experiments that we’re waiting to do because we need to get funding for doing such things. But a simple experiment that I think might work is to simply ask people to try wines with low quercetin compared to wines with high quercetin, and these would be people who do get red wine headaches, and see what happens.

And then down the line we’ll look at particular concentrations. We’ll probably evolve ways to have quercetin entered into the systems of people in other ways and see what happens. And I think it’ll work, one way or another, prove or disprove this theory. And of course, it’ll be real helpful to people who’d like to drink red wine, and we hope it’ll be helpful to wine producers, and that’s nice. But what really appeals to me is that this is my focus of my career for just about my whole career, one of my main foci.

And what I’m hoping is that if we can learn more about this, we can learn more about what causes some headache types. We can learn about the big question in my practice, which is, why do some people have much worse and much more frequent headaches than others?

FLORA LICHTMAN: Oh, I wondered about that. If there are different kinds, different categories of headaches, or if every headache is the same.

MORRIS LEVIN: No, there are. And of course, the most common headache condition is migraine. And even though we’ve been studying migraine, we meaning the medical world has been studying migraine for hundreds of years, there’s still a lot of unanswered questions. One of the things I’ve noticed about red wine headaches is that my patients with migraines seem to be particularly prone to red wine headaches. But yes, there are a number of headache types from tension type headache, to cluster headache, post-traumatic headaches, and so on.

FLORA LICHTMAN: When I have a headache, what is actually hurting? Is something happening in my brain? Is it around my brain? Where’s the pain coming from?

MORRIS LEVIN: Yeah, that’s a good question. You probably remember that the brain itself doesn’t feel pain. It’s insensate. But the linings around the brain called the meninges are very pain sensitive, and the skull itself, even though it doesn’t feel pain, the linings around the skull are very sensitive. The scalp is very sensitive. Blood vessels around the brain and around the head are very sensitive. We think the pain from migraines comes from a pain producing process in the linings around the brain called the dura.

But red wine headache is still a little mysterious. I think it’s probably similar to migraine in some ways. But we’re not sure.

FLORA LICHTMAN: When you say that there’s a pain process happening, does that mean that there’s swelling or there’s inflammation? What’s actually causing the pain?

MORRIS LEVIN: Yeah, you said it, inflammation. Probably inflammation with associated swelling, and blood vessel changes, and chemicals that get secreted that produce pain.

FLORA LICHTMAN: Are there headaches that don’t have a trigger?

MORRIS LEVIN: Yeah, good question. I think everything is part of a process. Everything in the headache world is part of a process that has a beginning and hopefully an end. But yeah, I mean there are headaches that just seem spontaneous. Some of my patients are very good, for example, at identifying all their triggers, whether it’s weather changes, foods, or stress. Other patients will tell me that for no particular reason they have gotten very bad headaches.

FLORA LICHTMAN: How did you get into this red wine question? Are you afflicted personally?

MORRIS LEVIN: You know I drink wine. I don’t drink very much. And I like it, but I don’t have a big tolerance for wine yet. I know that I have to be careful with red wine, in particular, because I will get a red wine headache. But that’s not how I got interested in it. I was just approached by Andy Waterhouse with this idea that we should really try and find out the cause of it.

FLORA LICHTMAN: Is there a big headache mystery that you’re dying to solve?

MORRIS LEVIN: Oh, so many. I think like I said, we’ve come a long way in terms of understanding how migraine, the most common headache type, exists and why is it that some people like me, for example get a migraine attack once a month or so. It’s not so hard to abort the attack. And we go on with our day. And other patients, especially some of my most difficult patients, have headaches more days than not? Why is that? Why are some people so disabled? Why are there many, many patients who don’t just have headaches, but they have a lot of accompanying symptoms, like cognitive changes, mood changes, terrible nausea, visual changes, et cetera? So I could go on and on.

There are lots of mysteries. But that’s the way science is, medical science, especially. We solve one mystery, and two more pop up.

FLORA LICHTMAN: Fascinating. That’s all the time we have for now. I’d like to thank my guest, Dr. Morris Levin, Director of the Headache Center at the University of California San Francisco Medical Center. Thank you for joining me.

MORRIS LEVIN: Oh, it’s been a pleasure, Flora. Thank you.

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