What You Should Know about Histamine Intolerance

A lot of my patients are curious about this. I’m not going to say that we’re seeing more of it, because I’m not sure if that’s actually true. I think the awareness of it is higher, so we’re paying more attention to it. It may also be true that we’re seeing more of it, and there are some reasons why that might be the case, which will be revealed as we go through this answer. We’ll go into the basics of what histamine is and then we’ll talk about why histamine might be a problem for some people. Then I’ll finally get around to discussing diet for histamine intolerance.

Note: The Prescript-Assist supplements discussed in this article are no longer available. Please click here to learn more about a substitute, the Daily Synbiotic from Seed.

In this episode, we cover:

4:03  What Chris ate for breakfast
6:20  What is histamine?
11:49  Why histamine might be a problem for some people
17:36  Recommended diet for histamine intolerance

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Steve Wright: Good morning, good afternoon, and good evening. You are listening to the Revolution Health Radio show. This show is brought to you by 14Four.me, the 14-day healthy lifestyle reset program. If you’re someone who’s trying to put all the pieces of great health together that Chris talks about—such as diet, sleep, movement, and stress—but can’t seem to make them fit in your lifestyle, well, number one, I totally understand; and number two, this program is for you. So go check out 14Four.me, Chris’ new lifestyle reset program. You’re listening to the Revolution Health Radio show. I’m your co-host, Steve Wright from SCDlifestyle.com. With me is integrative medical practitioner, healthy skeptic, and New York Times bestselling author, Chris Kresser. Chris, how you doing?

Chris Kresser: Hey, Steve. I’m good. How are you?

Steve Wright: I’m tuned up, man.

Chris Kresser: I hear that.

Steve Wright: I got a big old workout in today, and I just got energy.

Chris Kresser: All right. I’d like to see that. Yeah, I’m not there yet. I’m going to the gym after this. So hopefully, I’ll catch up with you.

Steve Wright: Are you guys getting hit by the polar vortex right now?

Chris Kresser: It definitely feels colder than normal here. There’s no doubt about that. I feel the fall setting in, which is cool. I like the fall. It’s my favorite season. But yeah, I’m having to make a little adjustment. Because up until I left last week—I spoke at the Weston A. Price conference this weekend on the acid-alkaline hypothesis. When I got on the plane, it was like 75 degrees. When I got off the plane in Indianapolis, it was not 75 degrees, definitely. I was like, “Oh yeah, I live in a little bubble called California, where the weather is really different than other places.” Then when I came back, it was actually fairly chilly as well.

Steve Wright: You said fall. And I just looked out on my deck, and there’s six inches of snow out there.

Chris Kresser: You’re like, “Hey buddy, that’s winter.”

Steve Wright: Yeah.

Chris Kresser: Well, it’s all good. I mean, it’s sunny and nice out, but it’s just a little chilly. I’m not complaining. Of course, I have nothing to complain about. It’s all good.

Steve Wright: So how was the talk?

Chris Kresser: The talk went well. It was fun. It was well-received. You know, it’s another one of those myths that just keep sticking around despite a lack of evidence that really supports it. If this is new to anyone listening, you can Google “Chris Kresser acid-alkaline.” There are a couple of blog posts that we wrote about that a while back. I’ll probably eventually record the talk as a screencast and make it available for free, because there’s more updated and a deeper level of information in the talk, because it was a 1-hour-and-15-minute presentation.

Steve Wright: Wow. So are you saying that your myth-busting power got even stronger?

Chris Kresser: Took it up to a new level. The live talks, I like to do that. Also, I make an effort to make it accessible and fun, so that people aren’t bored out of their mind listening to me talk for 1 hour and 15 minutes. It was good. And it was good that I saw Chris Masterjohn. I watched him and he did a whole day on fat-soluble vitamins, which was pretty cool. I caught a fair amount of that. Then we had a couple of meals together. It’s always good to catch up with him. So it was a nice time.

Steve Wright: Were you referring to him by his new nickname, Professor J?

Chris Kresser: The Professor?

Steve Wright: The Professor, okay.

Chris Kresser: Yeah, I was. And he’s settling into his new position. He likes it a lot. He’s super busy. You know, he had to prepare last-minute for a couple of classes he’s teaching. But it’s great. Great to see him getting that kind of position and recognition.

What Chris Ate for Breakfast

Steve Wright: Awesome. Before we dive into this week’s question, Chris, did you have anything for breakfast today?

Chris Kresser: It was pretty standard today, Steve. Nothing exciting. I had scrambled eggs, sauerkraut, and some bacon. Then I had some coffee with cream. What can I say?

Steve Wright: Gosh, Chris, I’m let down. I’m so sad.

Chris Kresser: I’ll try to do better next time. All right. We have a great question from Genevieve today. It’s about histamine, which I know is a hot topic. A lot of people want to know more about it. I think this is going to be a really helpful show for a lot of folks. Let’s give it a listen.

Genevieve: Hi. Just wondering what kind of diet you recommend most for histamine intolerance, because I know there’s a few out there. The typical low-histamine diet includes grains. I think The Low Histamine Chef limits animal protein. Then, of course, you have GAPS, which is full of nourishing foods, but many are high histamine. And that’s what kind of caused my problem to begin with, was the high-histamine foods on the GAPS diet. So I’m just wondering what you would recommend most to follow to try and heal it, if it can be healed, although I know sometimes it might be related to methylation. Thanks.

Chris Kresser: Thanks, Genevieve, for sending that in. As I said, this is definitely a hot topic. We receive a lot of questions about it. A lot of my patients are curious about it. I’m not going to say necessarily that we’re seeing more of it, because I’m not sure if that’s actually true. I think just the awareness of it is higher, so we’re paying more attention to it. It may also be true that we’re seeing more of it, and there are some reasons why that might be the case, which will be revealed as we go through this answer. But let’s talk a little bit about basics, and then we’ll go into—basics of what histamine is, and then we’ll talk about why histamine might be a problem for some people. Then I’ll finally get around to answering her actual question about the diet for histamine intolerance. But I think it’s important to kind of maybe correct some misconceptions and go over some of the basics before we do that.

Steve Wright: That sounds like a plan, man. What is histamine?

What Is Histamine?

Chris Kresser: Histamine is an organic nitrogen compound that’s involved in local immune response and systemic inflammatory responses. It regulates physiological function in the gut and it acts as a neurotransmitter. It’s produced by immune cells called basophils and eosinophils and also mast cells, all of which are typically involved in allergic responses, among other things. To bring this home, if you’ve ever been stung by a bee or bitten by a mosquito and you see the redness and swelling there, that’s histamine-mediated. So everyone’s had experience with histamine. What it does in the inflammatory response is increases the permeability of capillaries—which are the small blood vessels—to white blood cells and some proteins, so that those white blood cells can engage the pathogens or the toxin in the tissue. From a dietary perspective, histamine is derived from the amino acid histidine, which is found in many different foods, especially fermented foods. We’re going to talk more about that later. But it’s also produced by some of the species of bacteria found in our gut. That is actually one reason why it’s possible that histamine intolerance is on the rise, because of this profound shift that we’ve seen in our gut microbiota over the past several decades. So just as celiac disease and gluten intolerance is probably on the rise because of that, I think it’s at least plausible that other conditions, like histamine intolerance, might be on the rise because of that as well.

Steve Wright: When I think histamine, the first thing that comes to my mind is allergies. Is that a good association or are there a lot of other things going on? Because I know you used the bee analogy there.

Chris Kresser: It is a good association. Like I said, basophils, eosinophils, and mast cells are all very much involved in the allergic response, and histamine mediates that allergic response. The itchy eyes, watery eyes, itchy skin, all the things that you associate with allergy and atopy, those are definitely mediated by histamine. So if someone has a lot of allergies or they’re having kind of allergic responses that they don’t necessarily associate with any particular trigger, that could be an issue with histamine.

Steve Wright: When you say mediated, what does that mean?

Chris Kresser: It means that histamine is probably causing the symptom. The excess production or the inability to break down histamine is causing those symptoms. And it’s not just doing it to irritate you. Histamine actually, like I said, plays an important role. It increases the permeability of capillaries to white bloods cells, so that the white blood cells can do what they’re supposed to do and they can get there. So we need histamine. The problem isn’t histamine itself; it’s when people have problems breaking it down or they’re overproducing it. I do want to point out that this phrase we’re using of histamine intolerance, if you look it up in the scientific literature, you’ll find a couple of papers that talk about it, but it’s not a legitimate medical condition, like diabetes or something, that has a clear etiology and pathology, and a clear treatment. A lot of people will argue that histamine intolerance doesn’t exist and it’s imaginary. I think just like adrenal fatigue and some of the other things that we talk about, it’s true that it doesn’t exist as a distinct disease entity. But it’s also true, and there’s plenty of research to support this, that there can be problems with histamine breakdown. And if that’s the case, excess histamine can certainly cause symptoms, and that’s well-established. So we use the phrase “histamine intolerance” just as a colloquial way to talk about it. But just understand that if you go to doctor and start talking about histamine intolerance, they’re probably going to look at you strangely. There’s actually a new term that’s been proposed for this syndrome. It’s mast cell activation syndrome (MCAS), which we’re going to talk about in a second. There are a few papers that have been published about that. So if you want to impress your doctor with a fancy term and show him/her some scientific papers that support this, you can bust out the MCAS term. All right.

Steve Wright: Just dropping it!

Chris Kresser: So I’ve mentioned that the real issue with histamine is—well, let’s go back to the background. Once histamine is produced, it’s broken down by two primary enzymes. One is histamine N-methyltransferase, and the second is diamine oxidase. For a long time, it was thought that diamine oxidase played the major role in breaking down histamine. And it probably does. But lately, there’s been a little bit more focus on histamine N-methyltransferase. If you recognize that term methyl, you know, we’ve been talking about methylation and methyl donors lately on the show. That’s another hot topic. They’re definitely related, which we’re going to discuss. So the key thing to understand here is that for most people, histamine is not a problem. Histamine is a normal part of the physiological response. If you get exposed to something, histamine can help the inflammatory reaction, and then the diamine oxidase or methyltransferase breaks it down. That’s the end of the story. You never need to think about histamine, it’s not an issue. That’s what’s true for most people. But there are potential issues that can make histamine a problem for some people.

Why Histamine Might Be a Problem for Some People

The issues are broken into two categories. One would be overproduction, so making too much histamine. The second would be inability to break it down properly. Let’s look at each of these in turn. Overproduction typically would have two main causes. The first could be gut dysbiosis, because we know that certain types of bacteria produce histamine and certain types of bacteria degrade it. So if we have an overrepresentation of the kinds of bacteria that produce histamine, then you could theoretically have excess histamine production. That could cause some of these histamine intolerance issues that we’re talking about. The second cause is something called mast cell activation syndrome, which I just mentioned. This is still a relatively poorly understood entity. There was a paper. I think the first papers were published on it just a couple of years ago. There’s one kind of review paper in 2013. Basically, it involves an overactivation of mast cells, which are the cells that primarily produce histamine. We don’t really know what causes this. Certainly, genetics play a role. There are a lot of mutations that can affect mast cells and the production of histamine. But there are likely other causes that haven’t been well-defined at this point.

Steve Wright: Chris, how many mast cells do we have in our gut?

Chris Kresser: I don’t know the specific number, but there are lots of mast cells all throughout the body. The production and breakdown of histamine is particularly notable in the gut. This is why histamine intolerance can lead to gut issues, and disturbance in the microbiota can lead to excess production of histamine or inability to break it down. So speaking of inability to break it down, that’s the second major problem. That can be broken into three subcauses. One would be impaired methylation, because histamine N-methyltransferase requires methylation to function properly, that enzyme. So if you’re not methylating properly, you won’t break it down. Second, not enough histamine-degrading bacteria. So dysbiosis, again. The third reason would be a genetic issue with diamine oxidase production. Some people just genetically don’t make enough diamine oxidase to break down histamine. So those are the main problems with histamine and the causes of those problems.

I just want to point out, before I go to the symptoms, that there are other mutations and genes related to the methylation pathways that can cause histamine issues. One is monoamine oxidase (MAO). If you’ve done a 23andMe gene profile and then you’ve run it through Genetic Genie or MTHFR Support or something like that, if you look on there and you’re homozygous for MAO, then there’s a decent chance that you may be sensitive to histamine. So that’s something to be aware of. The symptoms of histamine intolerance are very similar to some of the symptoms of allergies. You have itching of the skin, eyes, ears, and nose; hives; tissue swelling, especially facial and oral tissues; a feeling of throat constriction or tightness; hypotension, like a drop in blood pressure, especially you get dizzy when you stand up quickly; tachycardia, so rapid heartbeat, increased pulse rate; palpitations; symptoms that kind of resemble anxiety or panic attack; chest pain; nasal congestion; runny nose; seasonal allergies; conjunctivitis, which is irritated, watery, reddened eyes; some types of headache, like migraine can be related to histamine; fatigue; confusion; irritability; digestive upset, especially heartburn and reflux; and much more rarely, occasional loss of consciousness, blacking out just for a few seconds that’s unexplained by other causes.

Steve Wright: So Chris, that’s like a list of symptoms that if we stack them on like a severity scale, goes from annoying to life-threatening.

Chris Kresser: Yes.

Steve Wright: Would it be safe to assume that the lower you are maybe on your health ladder, the more this could be an issue for you? And as you sort of have more things in balance as far as health-wise, maybe histamine issues are going to be more on that annoyance scale?

Chris Kresser: I think the health status is one factor that determines sensitivity. But there are other factors that don’t necessarily relate to current health status, which are genetic. So if somebody has homozygous MAO mutation and they’re also homozygous for MTHFR mutation and they have very poor methylation because of that, and then they also have a defect in diamine oxidase, an inability to break down histamine once it’s produced, and then maybe they even have defects that lead to overactivation of mast cells and production of histamine, that person’s probably going to be pretty sensitive to histamine even if they’ve got everything dialed in. I don’t know how many of those people there are that have that unique constellation of things together; probably not that many. But they may always need to be careful, for example, with fermented foods, and some of the foods that we’re going to talk about that are high in histidine, and therefore, histamine. And/or they may need to use some natural antihistamine support or take some diamine oxidase as a treatment.

Recommended Diet for Histamine Intolerance

Now, let’s talk about the low-histamine diet, because this is something that can be really helpful symptomatically. Of course, for longer-term healing, you want to address the underlying cause and things like that, dysbiosis or methylation problems, but the diet is an important part of the treatment always and getting some symptom relief. Fermented food, as I mentioned, is the biggest offender. That’s because the bacteria during the fermentation process produce histamine. So things like wine, cheese, yogurt, kefir, vinegar, all of which are healthy foods otherwise, are like kryptonite for people who have serious histamine intolerance. I’ve often had patients come and say, “God…” They’ll fill out the diet survey and they’ll mention something about how they’re intolerant of these things. It’s kind of a revelation for them to learn about histamine, because they’d never been able to figure out what the common thread is between all of these foods that they’re reacting to. Seafood, unfortunately—I say unfortunately because it’s such a healthy food, and it’s underrepresented already in many people’s diets—but seafood, shellfish, finfish, fresh, particularly smoked or canned seafood, is also really problematic from a histamine perspective. Eggs; processed, cured, smoked, and fermented meats like bacon, sausage, salami, pepperoni; leftover meat, because after meat is cooked, the histamine levels increase due to microbial action as the meat sits; all fermented milk products, of course; citrus fruits; berries; dried fruit; spinach; tomatoes; artificial food colors and preservatives; certain spices like cinnamon, chili powder, cloves; herbal teas; alcohol; chocolate; cocoa; and then vinegar and foods containing vinegar, such as pickles, relishes, ketchup, and prepared mustard.

Steve Wright: No wine, no pickles, and no chocolate. We have to help these people.

Chris Kresser: Sorry, I just removed all of your favorite foods. Don’t hate me. It’s not my fault. I didn’t make this stuff up. If you didn’t get that down and you’re listening to this in your car, don’t worry about it. If you Google “Chris Kresser histamine,” you’ll see a blog post that has this list. Also, don’t freak out if you have to remove these foods for a period of time to feel better. Because in most cases, when you do address the underlying causes—like the gut dysbiosis and methylation—then most people are able to add some of these foods back in without any ill effects. Now I do want to point out that there’s a huge spectrum in terms of histamine intolerance. You were probably hinting at this, Steve. But there are some people who, red wine, they can’t tolerate. But almost everything else on this list, they do okay with. Then there are people on the far end of the other spectrum—and there are a lot fewer of these, but I’ve had some patients who fit this profile—who, the only meat they can tolerate is meat that’s literally been slaughtered. Like, they have to go to the farm right after it’s been slaughtered and get it, because if the meat even sits for a little bit, the time that it takes to get to the store and sit in the meat case at the store, it’s already got more histamine that they can tolerate. A couple of my patients have had to go on almost like a completely plant-based diet, because all of the animal products, they haven’t been able to tolerate. Over time, fortunately, that changed a little bit for them. And they were among the sicker patients that I had. So again, like I said, it’s not very common. But just know that there’s a big spectrum, and you need to really experiment a lot with this stuff to figure out what works for you and what doesn’t work for you.

Steve Wright: I think Chris points this out in the article, but if we have anything that can help you with that, just remove it all at once. Just remove it all at once. Just take the pain. If you think of it as painful to get rid of some of these foods, which I’m sure some people do, just do it all at once. Don’t just mess around and say, “Okay, I won’t do wine for a little while or chocolate for a little while,” because you’re not going to figure it out.

Chris Kresser: That’s never going to get you anywhere. That’s a great point. You have to just suck it up, take it all out, and then start adding stuff back in one by one. That’s the only way to do it. It’s really laborious, but it works. And both Steve and I know this from experience, working with a lot of people. You can get your diamine oxidase levels tested actually. It’s a serum test. So you can get diamine oxidase. You can get serum histamine tested. Serum tryptase, T-R-Y-P-T-A-S-E, is considered one of the most sensitive markers for mast cell activation syndrome. So you can run some tests, and that might be helpful in seeing where the problem lies. For example, if you run the test and your diamine oxidase levels are normal but your histamine is very high, that means that you may not have an issue with breaking down histamine. It may be more of an issue of overproduction of histamine due to gut dysbiosis, for example. In that case, fixing the gut and doing a low-histamine diet would probably be enough, without any additional intervention. However, if you get tested and your histamine levels are normal, but your diamine oxidase is really low, then that suggests you have possibly a genetic deficiency of diamine oxidase. And what’s probably going to help you more is to take diamine oxidase, which you can take as a supplement. Seeking Health sells it as Histamine Block. There’s also DAOSin, D-A-O-S-I-N, from Swanson. There’s Histame. They’re all basically the same thing. It’s actually taking diamine oxidase, the enzyme that breaks down histamine. You take it with meals. That can help a lot. Then there are some natural antihistamines that are probably a better idea for excess histamine production. Those include quercetin; bromelain, which is an enzyme; pine bark extract, which is also known as Pycnogenol. That’s pretty expensive, but it can be effective. Then there are, as I said, certain species of bacteria that break down histamine and certain species of bacteria that produce histamine. So Lactobacillus casei, Lactobacillus delbrueckii, and Lactobacillus bulgaricus, which are typically in yogurt and fermented dairy products, those are notorious histamine producers, which is why fermented dairy can be like kryptonite. Lactobacillus plantarum and Bifidobacterium infantis are two histamine degraders. It’s quite difficult though to get Bifidobacterium infantis separately as an individual strain, without other strains that are also in it. But it is possible to get Lactobacillus plantarum that way, just as a single strain, pretty easily. So that can be a good one to take. Then soil-based organisms like Prescript-Assist, which I like for many other reasons. This is another reason that I like it. There’s not a lot of research on this, but my experience is that soil-based organisms tend to be neutral or even histamine-degrading. They tend to be tolerated pretty well by people with histamine issues. That’s it, Steve. I hope that was helpful, Genevieve, and that we answered your question.

Steve Wright: Nuh-uh. I’m not letting you off the hook just yet, Chris.

Chris Kresser: All right.

Steve Wright: I have one question here to follow that up. So that was all, like, at the mast cell level. But the mast cells and everything we’re talking about here is part of—the inflammation pathway is part of the immune system. And I feel like this podcast would not be complete with at least a couple minutes about me asking, is there some play here with maybe improving your hormone levels, maybe your anti-inflammatory hormones—cortisol, for instance, if you’re having adrenal issues—something like that, that would be part of this whole equation as well, that people with histamine intolerance could get lost in the forest?

Chris Kresser: Yeah. No doubt, Steve. The reality is, we do these 25-minute shows—or 30 minutes—and we focus on a single topic. But that’s never really how it works in practice, right? There’s always a person that’s attached to one of these topics, and they don’t just have histamine intolerance. They have several other issues: adrenal fatigue, autoimmune disease, and whatnot. Certainly, all of those things have to be addressed for a successful outcome. It’s a great question. It’s true that mast cells, basophils, and eosinophils are part of the immune system. And if you have a hyperactive or underactive or swinging between hyperactive and underactive immune system, then that is going to exacerbate the problem. If you have high cortisol, low cortisol or inappropriate production of cortisol throughout the day, that’s going to cause an inflammatory response and affect probably histamine production in different ways. Certainly, imbalances of sex hormones can affect that. And as we mentioned, dysbiosis, but also several other gut issues. So SIBO and parasites and intestinal permeability and all of the potential things that can go wrong can affect it. There are probably the things that we’re not even thinking about at this point that can affect it as well. So certainly, you need to always consider the entire picture. But I can say with some confidence that the things that we’ve talked about in this show are probably the most important from the histamine perspective, and will give at least some relief while you’re working on those other bigger picture concerns.

Steve Wright: Awesome. Thanks for wrapping that up and bringing it back up to the top.

Chris Kresser: Sure. Good question. A couple of announcements. The paperback version of my book is coming out on December 30^th at the end of this year. It’s been renamed as The Paleo Cure instead of Your Personal Paleo Code, which is the hardcover title. There are a number of reasons behind that, which I’ll talk about on a later show. But it’s the same book, just a different cover, different name. We’re going to be doing some cool stuff around the book launch in December, so keep an eye out for that. We’ll be back with some more details. 14Four has been just a blast to see how many people have signed up. I think almost 2,000 people have signed up. Lots of folks are well into their 14-day reboot now. They’ve been through the preparation phase, and they’re starting. They’re having a great experience with it. We’re getting incredible feedback. There’s just a ton of activity in the Facebook group and community building around it. It’s just really exciting for me to see that this is really hitting in the way that I wanted it to hit. I know, from my own experience and from working with so many people, that it’s not really about information. Like, a lot of people know what to do at this point. It’s just about implementing it in your life. That’s the hard part. And that’s really what 14Four is about. So it’s just really—I’m excited to see the success that people are having and putting all these things together. If you haven’t checked it out yet, it’s 14Four.me. Keep the questions coming. We’ll talk to you. We’ll be back next week.

Steve Wright: Thanks, everyone, for listening. In-between episodes, if you’re wondering what Chris is researching—when he’s preparing for these episodes and his blog posts, a lot of times, he’s posting new things that he’s discovering on Facebook and Twitter. So if you’re not, I would encourage you to go over to Facebook.com/ChrisKresserLAc and Twitter.com/ChrisKresser to get updated ideas and things that he’s working on and things that he’s found. Thanks for listening. We’ll see you on the next show.

Chris Kresser: Thanks, everyone. Bye-bye.