The surprising truth about histamine intolerance

We've probably all heard of “antihistamines,” medications that can ease symptoms of hay fever and other allergies. 

But what is “histamine”? It’s a vital chemical that our bodies produce, and it plays a role in a number of functions that support our health. 

In today’s episode of ZOE Science & Nutrition, Jonathan speaks with Dr. Will Bulsiewicz, ZOE’s U.S. medical director, to learn more about this flourishing area of research — and the best ways to identify and treat histamine intolerance.

Will is a board-certified gastroenterologist, and New York Times bestselling author of the microbiome book Fiber Fueled.

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Episode transcripts are available here.

Transcript

[00:00:00] Jonathan Wolf: Hello and welcome to ZOE Shorts, the bite-sized podcast where we discuss one topic around science and nutrition. I'm Jonathan Wolf. Today I'm joined by Dr. Will Bulsiewicz, and our subject is histamine intolerance. 


[00:00:18] Will Bulsiewicz: Histamine intolerance is a fairly new and flourishing area of research. It's likely that a number of people aren't even aware that they suffer from it, and more importantly, how they can treat it. 


[00:00:30] Jonathan Wolf: So Will, my questions then are, what is histamine intolerance and if you do suffer from it, is there anything that can be done? 


[00:00:39] Will Bulsiewicz: Well like I said, Jonathan, this is a very active area of research, and we have some exciting studies that could be a real game changer for people. 


[00:00:47] Jonathan Wolf: Sounds like there's no time to waste. Let's get into it. 

So Will, I don't know anything about histamines, but the name does sort of ring a bell. And now I'm thinking of it, I'm thinking about anti histamines. You know, the pill that you pop when you're trying to relieve the symptoms of hay fever or allergies. So, that makes me think maybe I'm not a fan of histamines, if they're responsible for my puffy eyes, and snotty nose, and the fact that, you know, hay fever has tended to ruin many picnics in my summer. 


[00:01:53] Will Bulsiewicz: Yes, that was a quite graphic description, so I can tell that you really have lived with those issues before. So, you know…

[00:01:59] Jonathan Wolf: Absolutely. 


[00:02:00] Will Bulsiewicz: It's not fun when that's the case. This is all true, Jonathan, and it's important to know that histamine isn't all bad. In fact, histamine is an essential chemical that we need to carry out a number of healthy bodily functions. 


[00:02:17] Jonathan Wolf: Okay, so I'm willing to maybe give you that, but I'm going to need a bit of convincing, because, you know, my view of histamine at the moment is like, you know, picnic-ruining, can we get rid of it? So what does it do that's so important? 


[00:02:29] Will Bulsiewicz: Okay, so, Jonathan, my apologies before I start, because I'm about to nerd out here. But trust me, I think this is going to be worth it for people to understand this. 

So, histamine is a signaling molecule that is produced by immune cells called basophils and mast cells. So you can think of it as like these cells are trying to communicate with each other and histamine is how they do it. It's a message. And it moves around the body and it binds to histamine receptors in different locations, including your brain. lungs, your heart, even your bone marrow. And when it does this, it basically will activate some sort of process. 

So for example, in the lungs it could be stimulating the muscle that lines the lung tissue, or in the stomach, it could be actually increasing stomach acid production. 
Or in blood vessels, it could be helping to relax those blood vessels. Now these, in different contexts, depending on what's happening in the body, these can be very important, necessary things. 

In women, histamine actually increases estrogen production. And in men, histamine plays a role in having an erection. These are important things! 


[00:03:50] Jonathan Wolf: So now I can see I need to rethink my entirely negative view about histamine. Thank you, Will. That's, you've definitely forced me to rethink my approach. 


[00:03:58] Will Bulsiewicz: I couldn't help but be a bit vigorous there with my enthusiasm. I apologize to you and the audience. 


[00:04:05] Jonathan Wolf: So I can see that it's important, so basically you're saying it plays this really important role in a whole bunch of functions in the body. 


[00:04:12] Will Bulsiewicz: Yeah. And you know, really importantly, this is a fundamental part of how our immune system works. So, you know, when something invades our body, histamine actually triggers the mechanisms in our body that allow our immune system to basically attack. And eventually get rid of that invader. 

Now this is great when we're fighting infections. But unfortunately, our immune system can sometimes be a bit trigger happy. And start to release histamine in response to harmless things. Like peanuts, or animal fur, or pollen. Perhaps you're picking up on the trend here. 


[00:04:51] Jonathan Wolf: I am, and now I understand the pollen as the culprit of these ruined picnics and how histamine fits in. Though in all seriousness, presumably in the case of you know, allergic reactions, this can be really bad and potentially life threatening. 


[00:05:10] Will Bulsiewicz: Yeah, so to be totally clear, I was describing a different, a series of allergens and you know, allergic symptoms can be caused by this surge of histamine from the immune system in response to something that it perceives to be a threat. 

So like leaky nose and itchy skin and stomach cramps, or even these potentially life threatening allergic reactions that we're talking about, they can all be manifestations of your body trying to banish a non-existent foe. And the thing is, you can't punch a ghost, but you could hurt yourself if you try to. And this is when those histamines, those antihistamines that you mentioned earlier, Jonathan, they come in actually quite handy because they can stop the extra histamine that's in the body. 


[00:05:55] Jonathan Wolf: Got it, because basically your body is like overreacting to this, it's just pollen, it's actually not some horrible infection, and so your antihistamine is sort of lowering the level of your reaction, which is why, you know, if I take them every day during the summer, actually, I probably can go to a picnic. 


[00:06:10] Will Bulsiewicz: That's right. Yeah, and it's sort of like your shields blocking the histamine that's been excessively produced. 


[00:06:16] Jonathan Wolf: So is this what we're referring to, Will, when we're talking about histamine intolerance? This allergic reaction to certain substances?

[00:06:26] Will Bulsiewicz: No. So we are building up towards histamine intolerance and we're starting with sort of the classic histamine reaction, which are these allergic reactions to things. 

But there's an important distinction to make. So, you know, allergies help us to understand the excess histamine, but allergies and histamine intolerance are actually two different things. And to understand histamine intolerance, we have to take a look at the other way that histamine can enter our body. And that's actually through the food that we eat.

[00:06:58] Jonathan Wolf: Well, I think talking about the food that we eat is sort of the reason for this podcast, so where do we start? 


[00:07:05] Will Bulsiewicz: Okay. So I want to take you on a little journey, Jonathan. You know, I love to take these little journeys with you. And we're going to start with something called histidine. So it's a little bit different. 


[00:07:16] Jonathan Wolf: Okay, so, histidine, not histamine? 


[00:07:21] Will Bulsiewicz: That's right. So histidine is one of the 20 amino acids that are the building blocks of protein. Now, when histidine comes into contact with an enzyme, again, I apologize for being such a nerd, but L-histidine decarboxylase, for my nerds out there, it converts histidine into histamine. 

And many species of bacteria have this exact enzyme. 
And this conversion process is a normal part of the life cycle of our food. So what that means is as foods ripen ferment and eventually decay. Histamine is being produced. 


[00:08:03] Jonathan Wolf: Okay, so then I eat this ripe or fermented food and the histamine ends up in my stomach? 


[00:08:09] Will Bulsiewicz: That's right. But our journey doesn't end there because histamine then will move from your stomach into your small intestine where it comes into contact with an enzyme called the DAO or diamine oxidase. Now, DAO is our defense system within the intestine to neutralize histamine in our diet. Before the histamine is able to get into the bloodstream by crossing the epithelium. 


Now the epithelium is a single layer of cells that lines the intestine. So with the single layer of cells, if what's inside the intestine, like the histamine, can cross to the other side, it can enter the bloodstream, and then it can spread throughout the body in a matter of seconds. 


[00:08:58] Jonathan Wolf: So I'm now imagining this DAO a bit like the security check at the airport, you know, it's operating the x-ray machine, you know, it's gonna remove sharp objects or liquids or any of the things that your small child thought would be funny to put in your bag at the last minute, like a big pair of scissors. And it's going to in fact, in this case, check for histamine and like rip it out of there before allowing the bags through to the other side. 


[00:09:26] Will Bulsiewicz: Yeah, that's right. And I think one of the important things is that your body already is producing histamine, right? So the outside histamine, this is not something that we need from a dietary perspective and it can spoil the balance. 


[00:09:41] Jonathan Wolf: Got it, so I don't want that because I'm managing the right amounts in the right place and this is all going to mess with it. So when everything is operating normally that's happening, what can go wrong? 


[00:09:54] Will Bulsiewicz: Okay, so the first thing I want to talk about is something that's called histamine intoxication. And this is a form of food poisoning that occurs after the consumption of foods within an unusually high histamine content. And the histamine overpowers the degradation mechanisms in the small intestine. 
And basically, you are flooding the bloodstream with an excessive, massive amount of histamine. 


[00:10:20] Jonathan Wolf: So the team did a bit of research on this because histamine intoxication sounds quite exciting after all, you know, alcohol intoxication is something that many of us have tried from time to time. Apparently it wasn't always called this, Will. It had the rather less appealing name of scombroid fish poisoning, 


[00:10:40] Will Bulsiewicz: Yeah. 


[00:10:42] Jonathan Wolf: This is because, I am told, it is closely related to the consumption of spoiled fish in the Scombridae family, which includes tuna and mackerel. However, over the years, the World Health Organization has instead recommended the use of the term histamine intoxication. I assume partly because it can be brought on by eating other types of fish and certain cheese also because I think nobody other than like seven biologists know what the Scombridae family is, so I guess they've gone for slightly clearer terminology. 


[00:11:16] Will Bulsiewicz: Yeah. No one knows what that is, but we all know that a bad piece of tuna is not a good thing. And so you want to avoid the bad tuna if you can. 


[00:11:23] Jonathan Wolf: I love it when the World Health Organization tells you not to eat fish that's gone rotten. That's really helpful. 


[00:11:31] Will Bulsiewicz: Start with the fundamentals of a healthy diet here. So, that's right. So 98% of these histamine intoxication cases are caused by bad fish and the remaining 2% is attributed to cheese. Now this is not like the routine cheese that you get at your store. So there's no reason to be fearful of your cheese.

But these are sort of rare cases where these things have unusually high histamine levels due to their interaction with certain bacteria. And it's interesting to note that unlike other types of food poisoning, histamine intoxication outbreaks have increased over the last 10 years and it's considered actually one of the main problems of global food security. That's a surprise, right? 


[00:12:12] Jonathan Wolf: That's amazing. So, what does histamine intoxication feel like, if you have it? 


[00:12:19] Will Bulsiewicz: It's not fun. So I want our listeners to picture this around 20 to 30 minutes after eating some funky tuna, you develop a throbbing headache. You start to feel nauseated and then a wave of explosive diarrhea comes hard. face is flushed. You're having palpitations like your heart is beating out of your chest and you are sweating profusely. 
Okay. What I just described lasts for about half a day. It's not fun. 


[00:12:53] Jonathan Wolf: It sounds terrible. 


[00:12:55] Will Bulsiewicz: Yes. And once again, what we come back to is don't eat the funky tuna. But in all seriousness, histamine intoxication is intense as you can tell. But the good news is it's a one time event. 

So this is a little bit different though than histamine intolerance because histamine intolerance is not just a one time event, this is a chronic condition, so it will occur more frequently and even can be caused by seemingly normal food at times. 


[00:13:22] Jonathan Wolf: And it's funny. It just reminds me of the thing that my mum always said, which is, don't mess around with the fish, you know, if you think it might have gone off, don't eat it. And I guess this is, you know, this is sort of the story of why you make sure that if you are eating fish, like it's fresh, um, because nobody needs that sort of intoxication. 


[00:13:41] Will Bulsiewicz: That's right. 


[00:13:42] Jonathan Wolf: So you're now moving us on to intolerance and histamine intolerance. What does that mean? 


[00:13:48] Will Bulsiewicz: Yeah. So this word intolerance, we've heard it on this podcast when we talk about food intolerances. And food intolerance is not an allergy, but instead it's some sort of hypersensitivity to a specific component of our food. So in this case, the hypersensitivity is to histamine. To understand one of the ways that someone can be hypersensitive to histamine, we have to take a look at the DAO enzyme in our small intestine, because remember, that is our histamine shield. 


[00:14:18] Jonathan Wolf: Ah yes, this is the airport security check in my guts. 


[00:14:22] Will Bulsiewicz: That's right. So someone with histamine intolerance could have impaired DAO activity. So to use your analogy, maybe the x-ray machine is faulty or the border guard is daydreaming and thinking about something else. This means that the active histamine can get past the DAO, get through that single layer of cells, the epithelium and cross into the bloodstream. 
And then it over stimulates those histamine receptors and it triggers this physiologic response. 


[00:14:51] Jonathan Wolf: So it sounds like it's pretty important that our DAO enzyme is sort of doing its job properly. What could be causing it to be less effective? 


[00:15:00] Will Bulsiewicz: So naturally, one of the possibilities is that a person could be born with a gene that alters the function of DAO. And this will then affect their ability to break down histamine in their food. But DAO can also be affected by certain medications that people use or alcohol consumption. Or certain foods or even certain conditions like celiac disease or Crohn's disease or irritable bowel syndrome. 

But it's not just down to the inadequate DAO. The other thing that's really important, we've been talking about the single layer of cells, the epithelial barrier, and this plays an important role too, Jonathan. 


[00:15:39] Jonathan Wolf: And what does that mean, Will? The permeability of our epithelial barrier. Most of us didn't even realize we had an epithelial barrier 15 minutes ago. 


[00:15:48] Will Bulsiewicz: Yes. So this is, this is the wall that's lining our intestines, and we've heard about a concept perhaps called leaky gut. And so the permeability is referring to how effective this wall is at keeping things out of our body that aren't supposed to be entering into our body. 


[00:16:06] Jonathan Wolf: And am I right in saying that your microbiome, like all of these trillions of bacteria in your gut, can influence this? 


[00:16:13] Will Bulsiewicz: That's absolutely correct. We actually touched on this topic, by the way, when we did our episode about inflammation. So we're talking about the same area and the same kind of thing. Damage to the gut microbiome can break down this gut barrier. Making it easier for histamine that's inside your intestines to cross into your bloodstream. 


But what's exciting is that the opposite can also be true. So if we heal the gut, then we can actually restore competence to the epithelial barrier. And when we do that, we are actually going to hold the histamine where it's supposed to be in the intestines and prevent it from getting into our body. 


[00:16:57] Jonathan Wolf: And we'll, you know, what happens if too much of this histamine is sort of transferring from our food and into our body?

[00:17:07] Will Bulsiewicz: This is where histamine intolerance starts to trigger these symptoms, these sort of classic histamine symptoms. So researchers found that the most common manifestation is abdominal distention or bloating. 

In a study of people with histamine intolerance, they found that 92% of them reported having this type of symptom, either bloating or abdominal distention. But then it can manifest in many different ways that can literally affect us from the top of our head to the tip of our toes. 

Now, the average person with histamine intolerance reports a myriad of symptoms. An average of 11 different symptoms. So this is affecting people in many different ways. So it's hard for doctors to diagnose histamine intolerance because, you know, as an example, Jonathan, you’re at your gastroenterologist for your bloating. You go to a neurologist for a headache. You go to a cardiologist for heart palpitations. And the issue is that there's this one diagnosis that pulls them all together. But what if these specialists don't see that one thing that's pulling all of these different systems together? We need a whole patient approach in order to understand this. 


[00:18:16] Jonathan Wolf: And so if you suspect someone has a histamine intolerance, can you test for it? 


[00:18:21] Will Bulsiewicz: So unfortunately, there's not an easy test. There's things that we can do, but there's not an easy test. There's not a blood test or a poop test or a CAT scan that we can use to make this diagnosis. 

The way that we do it is to use an elimination diet. So specifically, we will do a low histamine diet. Now, it's important for our listeners to understand there's no such thing as a zero histamine diet. All food contains some level of histamine. And histamine levels also can change in different foods at different stages of sort of the food cycle or the maturation process. So it becomes tricky to define what a low histamine diet is, but we do have ways that we do this. 


[00:19:08] Jonathan Wolf: So what are your top tips to actually follow a low histamine diet? 


[00:19:12] Will Bulsiewicz: Well, we know the histamine increases as the food matures in its life cycle, you know, as it moves progressively towards ripe. So eat fresh food whenever possible. Perishable food has the least histamine at harvest, and then the levels will continue to rise. Most fresh fruits and vegetables are totally in play. 


So we don't have to be fearful of our plant based foods, but there's a couple that are classic high histamine foods that people need to be aware of. That includes spinach, tomato, avocado, which makes me sad because I love them, and eggplant, which I believe some people refer to it as aubergine. 


[00:19:54] Jonathan Wolf: A few of us do. 


[00:19:54] Will Bulsiewicz: Yeah, it's confusing to me at times, but nonetheless, these are all higher in histamine. Now cooling slows down histamine production. So like your refrigerator will slow it down, but actually your freezer slows it down even more. If you can freeze a product immediately after harvest, then that actually protects it. 


The other thing is that heat increases it. So like frying our food, grilling our food, high heat cooking increases histamine levels. The last thing is that we mentioned that the microbes produce histamine. All fermented foods are high in histamine. So that means alcohol, and even chocolate, vinegar.
Believe it or not, these are fermented foods, and unfortunately they're all off the menu. 


[00:20:44] Jonathan Wolf: So I'm now feeling incredibly sorry for people with histamine intolerance because it's like there's no alcohol, there's no chocolate, there's no avocados, there's no tomatoes. I mean, this is pretty miserable and that is before you get, that's just from the taste perspective, that's before talking about the health benefits. And we know the health benefits of all of these foods supporting your microbiome, so that doesn't sound too good either. 


[00:21:11] Will Bulsiewicz: Yeah, I agree with you. I mean, it's not fun for me to sit here and say that I'm taking away everything that's fun and delicious from your life. Particularly the avocados. It just kind of pains me to say that. 

But also bear in mind that this is a temporary thing. We're not using an elimination diet as a permanent diet. It's used to make the diagnosis and the way that we make the diagnosis, so to be clear, the way that we make the diagnosis is if you have two or more symptoms of histamine intolerance that improve or resolve on a low histamine diet, that's how we make this diagnosis. So this is again a temporary diet for the purpose of the diagnosis. 


[00:21:55] Jonathan Wolf: And, Will, do we know, or are there any estimates of how many people are living with this sort of histamine intolerance? 


[00:22:08] Will Bulsiewicz: Well, Jonathan, research would suggest that about 1 to 3% of the population has this condition. Which by the way, to me, that's actually quite a high number. That's more than there are people with celiac disease. And we talk about celiac disease all the time. 

That being said, I think this percentage might actually be underestimating it because as we get more knowledge and have better diagnostic tools for histamine intolerance, we'll be able to know more. 


[00:22:37] Jonathan Wolf: And is there anything, because it sounds like this is, again, in one of these areas is very emerging, is there anything that you can do about this histamine intolerance if it turns out that you have it? 


[00:22:51] Will Bulsiewicz: Yes. So the good news is that there are things that we can do. Ultimately, the goal is not just to diagnose it. The goal is to treat it and improve it and put it into remission. 

And an example of something that you can do are DAO supplements. So we've been talking about how DAO breaks down the histamine. Now these supplements, they, let me first say, they are not well studied. That being said, like the expectation is that by using supplemental DAO around mealtimes, you can help to break down the histamine rich foods. 

Unfortunately, they're very expensive. And also, they come from a source that's a little bit bizarre. They're made from the kidneys of pigs. Now, there's an alternative choice that actually I think is really cool and exciting. And those are sprouted legumes. So it turns out that rather than eating the kidneys of pigs, you could eat kidney beans or lentils or chickpeas and sprout them. And actually, when those legumes sprout, they produce a very large amount of DAO. Peas have the largest, the highest amount of DAO activity. In fact, peas have more DAO when they are sprouted than you will find in pig kidneys by 77%. 


[00:24:11] Jonathan Wolf: Wow. So, if you do need this, that sounds like a pretty interesting way to go. Is there anything else you can do? 


[00:24:18] Will Bulsiewicz: Well, there's been some recent research about improving the gut barrier. And actually there was a study where they showed that by improving the gut barrier, which is what we've been talking about, they actually were able to lower blood histamine levels. Now this is early phase research, but I still think it's very exciting to prove this concept that if you can heal the gut barrier, you can protect yourself from histamine intolerance. 


[00:24:47] Jonathan Wolf: Well, Will, there's a lot more to histamines than I thought at the beginning of this conversation. What are the key takeaways for the audience? 


[00:24:56] Will Bulsiewicz: Alright, so I think that the key takeaways for our listeners are that number one, I'm not here to vilify histamine and make it sound like this categorically bad thing. It's actually crucially important for many parts of our bodily function, including our ability to fight off infections. 

So we really need histamine and when it's in balance, it is not a problem. The issue is when there's too much and this can happen when there's an allergic reaction. This can happen when you have a Scombroid poisoning. And this can happen when you have histamine intolerance. 

And histamine intolerance is another form of a food intolerance. We've talked about many types of food intolerances, including the FODMAP intolerances that people can have on this podcast. 

The majority of people who have histamine intolerance are middle aged, they typically will have a damaged gut and they will have these symptoms that include bloating, but could affect from the top of their head to the tip of their toes. Headaches, migraines, runny nose, sinus issues, palpitations, heart issues, respiratory, like rapid breathing, skin issues, rashes, all of these things can be manifestations. 

So we want to pay attention, particularly if our food is triggering these symptoms and particularly with these high histamine foods, like fermented foods or seafood or spinach and tomatoes and avocados and aubergine, I did that for you, Jonathan. So think about the whole body. Don't just go to different specialists for individual symptoms. 


Think about the whole body and know that the way forward is first to diagnose it with a low histamine diet and second to heal the gut. And in healing the gut, we can actually overcome this issue, but in the process of healing the gut, we may want some additional or supplemental DAO. And believe it or not, sprouting our legumes can be the way that we accomplish that. 


[00:26:55] Jonathan Wolf: And well, one of the things I'm struck is we, we spend a lot of time talking on the podcast and in terms of the ZOE product and program, basically how to take all of us from what tends to be, you know, very poor Western diet that we've had, generally very poor gut microbiome in terms of the number of good bacteria that we want. 


And really that the essence is to add more things in and particularly more plants and different sorts of plants and the right ones for your body. And that often by doing that, you can actually improve your health and then it will actually allow you to manage foods that maybe you struggled with before and improve your health. 


And here with histamine, it feels like we're talking a lot about removing all of these things and ending up on a diet that I fear is, you know, very easily going to end up like something sort of ultra processed and denuded a lot of good things. 

Is that sort of inevitably where you end up? Or actually, here again, are you saying that often if you can improve somebody's gut health over time, actually you could potentially reduce or even, you know, stop these symptoms completely? 


[00:28:08] Will Bulsiewicz: Yes, so I am so glad that you asked this question because I think that this is crucially important. You know, I'm here pounding the drum of eating a wide diversity of plants and a diet of abundance, not restriction. 

Restriction is never the path to better gut health. And it's important to be completely clear that when you have histamine intolerance, any dietary restriction is intended to be temporary. 

So for example, this low histamine diet, you don't do a low histamine diet and stay on a low histamine diet. You do it purely for diagnostic purposes, typically on the order of two weeks, at the most four. And then you come off of it. What we're doing, Jonathan, is we're taking one step back so that we can take two, three, four, five steps forward. And the way that we accomplish that is by understanding our body. 

So you do need to understand your body. And the reality is if you have histamine intolerance, those fermented foods are going to make you miserable so the way that we fix this is first to diagnose the issue and second to correct the issue and there is a path to do that. 
So we don't want to take them away, what we want is ultimately to bring them back in a way that we can tolerate them and enjoy them.

[00:29:22] Jonathan Wolf: Amazing. Well, if you've been listening to this and thinking that you're really interested in understanding how to change what you eat in order to improve your gut health, then you may be interested in becoming a ZOE member. 

You know, as one part of that, you will get a gut microbiome test to actually understand the individual good and bad bugs inside your gut, which is something I do regularly as I look to try and improve that. And most importantly, you'll receive a personalized program based on your body, what you eat, and where you are to understand how to make step-by-step changes that can improve how you feel now and in the long term – not just your gut health, but your overall health over time. 


Go to zoe.com/podcast to discover a little bit more about ZOE, and there you can also get 10% off your membership. As always, the ZOE Science & Nutrition podcast is not medical advice. It's for general informational purposes only. If you have any medical concerns, including the sort of topics we've been talking about today, please consult your doctor. I'm Jonathan Wolf. 


[00:30:29] Will Bulsiewicz: And I'm Will Bulsewicz. 


[00:30:31] Jonathan Wolf: Join us next week for another ZOE podcast.