The Dr. Hyman Show - Mold, Lyme, Gut Health, and the Mystery of Histamine Intolerance

Episode Date: April 21, 2025

Many people struggle with mysterious symptoms like fatigue, brain fog, food sensitivities, and skin issues—only to be misdiagnosed or dismissed altogether. This conversation highlights how histamine intolerance and mast cell activation syndrome can be the hidden drivers behind a wide range of chronic conditions, and why they're often overlooked in conventional medicine. From the role of gut health, food triggers, and environmental toxins to deeper root causes like Lyme disease or mold exposure, it’s clear that personalized, Functional Medicine is key to uncovering real answers. Understanding the immune system’s role in histamine reactions—and how even “healthy” foods can be inflammatory for some—is a critical step toward healing. In this episode, I talk with Dr. Todd LePine, Dr. Elizabeth Boham, and Dr. Mark Pimentel about what histamine intolerance is, how it can be related to gut health, and why it’s important to address it. Dr. Todd LePine graduated from Dartmouth Medical School and is Board Certified in Internal Medicine, specializing in Integrative Functional Medicine. He is an Institute for Functional Medicine Certified Practitioner. Prior to joining The UltraWellness Center, he worked as a physician at Canyon Ranch in Lenox, MA, for 10 years. Dr. LePine’s focus at The UltraWellness Center is to help his patients achieve optimal health and vitality by restoring the natural balance to both the mind and the body. His areas of interest include optimal aging, bio-detoxification, functional gastrointestinal health, systemic inflammation, autoimmune disorders, and the neurobiology of mood and cognitive disorders. Dr. LePine enjoys skiing, kayaking, hiking, camping, and golfing in the beautiful Berkshires, and is a fitness enthusiast. Dr. Elizabeth Boham is Board Certified in Family Medicine from Albany Medical School, and she is an Institute for Functional Medicine Certified Practitioner and the Medical Director of The UltraWellness Center. Dr. Boham lectures on a variety of topics, including Women’s Health and Breast Cancer Prevention, insulin resistance, heart health, weight control and allergies. She is on the faculty for the Institute for Functional Medicine. Dr. Mark Pimentel is a Professor of Medicine and Gastroenterology through the Geffen School of Medicine and an Associate Professor of Medicine at Cedars-Sinai. Dr. Pimentel is also the Executive Director of the Medically Associated Science and Technology (MAST) program at Cedars-Sinai, an enterprise of physicians and researchers dedicated to the study of the gut microbiome in order to develop effective diagnostic tools and therapies to improve patient care.  Dr. Pimentel has over 150 publications in many high-profile journals, and he is the author of the book, The Microbiome Connection: Your Guide to IBS, SIBO, and low fermentation eating. This episode is brought to you by BIOptimizers. Head to bioptimizers.com/hyman and use code HYMAN10 to save 10%. Full-length episodes can be found here: Is Histamine Intolerance The Cause Of Your Mysterious Symptoms? What is Histamine Intolerance? Surprising Symptoms You Need to Know IBS: It’s Not In Your Head—Advances In Diagnosing And Treating, Bloating And Tummy Troubles

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And if you're looking for curated and trusted supplements and health products for your health journey, visit my website at drhymen.com. From my website store for a summary of my favorite and thoroughly tested products. Histamine is found naturally in the body. The body makes histamine. We also consume histamine. And the interesting thing about histamine is

it is also part, it's released by mast cells as part of our first response to offending organisms like viruses. So mast cells are like a white blood cell. Exactly, yes. Type of white blood cell. What type of white blood cells, yeah. And the also interesting thing is that histamine actually works as a neurotransmitter.

And when you think about this, this is really an interesting thing. And as I was preparing for this, I sort of stumbled upon some things which I thought was really quite fascinating, is that when you take antihistamine, what happens to you? You get drowsy. Exactly.

So histamine, when it's at high enough levels, it stimulates the brain. Histamine is actually involved in the sleep-wake cycle. Well, I mean, Tylenol PM or Advil PM, it's Tylenol, or Advil PM it's, it's Tylenol Advil plus Benadryl, which is an antihistamine. Right. So, so, so it's a balance like, you know, too much histamine is bad.

Too little histamine is also bad. So when you actually totally block histamine, you actually get sleepy. It'll actually involved with the sleep wake cycle and a modafinil, which is the drug that people take that actually works on histamine. Providual. Providual, exactly. Actually part of that works on the histamine.

So it keeps the histamine levels higher, so it keeps your brain sort of awake, if you will. Incredible. So most people are familiar with certain histamine conditions, right? If you get hives, if you have a peanut allergy, if you have this condition we call dermatographia, which sounds weird, but essentially it's if you scratch your fingernail on your skin, If you have a peanut allergy. If you have this condition we call dermatographia,

which sounds weird, but essentially it's if you scratch your fingernail on your skin, it'll create a red welt. Yes, yes. That's a, that's a. You can literally write your name on your back and it'll kind of have raised like letters. And that's actually a poor man's way, I oftentimes will use that with patients to determine

how much histamine they're having in the connective tissue because the mass cells are the type of white blood cells that are in the connective tissue of the body. And when they have excess amounts of histamine in them or they release histamine too easily, you will get this thing called dermatographism where you can take your finger and stroke on the skin and you will form a red line and it'll stay there and sometimes it'll get really welty and raised and that will tell you that there is a problem with excess amounts of histamine in the body.

Yeah and it's something that we've all experienced and when you get a bee sting or something like that you'll see this raised welts. Yep. But what happens for some people, they don't necessarily get the hives and they don't get these raised welts on their skin but they do suffer a whole range of symptoms.

So when someone walks in your office, what are the clues that alert you to the fact that they might have a histamine problem? Because by the way, most traditional doctors don't even know anything about this syndrome. Yeah, if you have allergies taking in histamine, but that's about it.

But there's a whole host of problems that people suffer from that are mostly misdiagnosed, poorly treated, and create so much suffering, which is unnecessary. Yeah. And there's a term out now, which when I was in medical school, we didn't even have it. It was called, it's now called MCAS, Mass Cell Activation Syndrome.

Like it's a real medical diagnosis. It's a real medical diagnosis. I mean, we're seeing a lot of it now. And the question is, is why are we seeing so much mass cell activation? And I've been puzzling on this myself. Yeah, I never took that class in med school. I know, right. Exactly.

But it's true. It's a big thing now. We're seeing a lot of it. And it's not like there's one cause for mass cell activation. There are multiple causes. I actually even deep dived into the literature, one of the things that I stumbled upon was the effects of EMF on mast cells. EMF is electromagnetic frequency. Like your cell phone, cell towers, Wi-Fi. Absolutely. There's some work by a woman, Johansson, out of, I think it's Sweden, who's done some work on the effects of EMFs on mast

cell degranulation. And there's some good studies showing that EMFs are one of the things in susceptible individuals that cause their mast cells to release more histamine that drives this allergic inflammatory response. So that's fascinating. And so what, what are the sort of symptoms that you see people coming in with? Well, they oftentimes will react to every food. They're sort of the people who they can't, they have a more and more restricted diet

because the more foods that they eat, it'll trigger because lots of foods contain histamine or will get broken down. Histidine is an amino acid and that when you consume foods that are high in histidine, things like meats have a lot of histidine, your body will actually break it down into histamine. And normally the body can process that, but when you have problems with either too much ingestion

or too much production of a histamine or not enough breakdown of the histamine, then you'll have problems with histamine intolerance. And these are typically a lot of people who have food allergies. And Mark, I think you've done this yourself. This is really interesting is the old way of treating food allergies was what?

Chromaline sodium. Yeah. Remember using that? And that's actually quite, it's actually a pretty good treatment for people who are really, really reactive to foods and the way that chromaline sodium, because chromaline is actually used for patients with asthma. Yeah, you inhale.

It's an inhaler. It's an inhaler, exactly. Yeah. It's a very effective drug. For really bad cases, chromaline sodium can be very, very helpful for patients who have severe histamine responses to foods. It's true. And people can come in with all sorts of weird symptoms that are misdiagnosed. They have headaches. for patients who have severe histamine responses to foods. And it's true, and people can come in

with all sorts of weird symptoms that are misdiagnosed. They have headaches, they get migraines, they have congestion, sinus issues, fatigue. Brain fog. Brain fog, digestive problems, menstrual cycle problems, nausea, vomiting, and if it's really severe, you can get really bad cramping, you can get irdema, tons of fluid retention, palpitations,

anxiety, your temperature regulation is off, dizziness. So a lot of people come in with all these weird symptoms, I don't know what's wrong, I'm taking an antidepressant. Yeah, exactly. But there is a way to diagnose this. And so if you're suffering from any of these issues, there may be a chance that it could be a histamine issue. it may be that there may be a chance that it could be a histamine issue. Yeah. And when you have someone who comes in

with all these symptoms, and by the way, a lot of people have edema and fluid retention. You can just stick your finger in their body and their tissue, because it's puffy and swollen. You can get edema in the legs. You can see just people carrying a lot of extra weight and fluid. Yep. It's often some type of histamine activation there.

Well, sure, because the mast cells, which are the cells that contain histamine, they're actually found in the spaces, the interstitial spaces in the connective tissue of the body. So that's why they get puffy, because those are where those cells that are high in histamine reside. And it can really be something

that leads to chronic fatigue syndrome, this mast cell activation issue It's a big deal and and most of the time it's just completely missed. Yeah, I mean you ask the average doctor say doc I think I have mast cell activation syndrome. Can you please get me the test and diagnose me? They're gonna know Yeah, you know, let me check your histamine levels so so when you have a patient with this, how do you begin to think about? So when you have a patient with this, how do you begin to think about diagnosing this? Because it can be a big deal for people. And I wanna share a case later,

you're gonna share some cases of some patients who've suffered for decades, decades, and finally get better when we treat them. Yeah, well again, we talked on the last podcast about the role of leaky gut in the microbiome. Interestingly, when you have dysbiosis, some of the bacteria will actually cause more of your body to produce excess amounts of histamine. So that's another thing where when the histamine is in excess in the digestive tract,

that can be related to food consumption, which are high foods in the histamine, or the bacteria are actually causing the breakdown of histidine as an amino acid to go into histamine. So dysbiosis is one of the things that can trigger excess amounts of histamine. That old nasty gut thing again, where we're just talking about the gut here on the Doctors Pharmacy podcast

and especially on our House Call episodes because it's such a fundamental thing and it's connected to everything. And the microbiome is so critical in so many aspects of our health. And I remember when we started doing this, Todd, decades ago, and we'd say, oh, people have a leaky gut or there's problems with their gut floor,

they have dysbiosis, they would just laugh at us. Literally, doctors would just laugh at us and think we're completely crazy. And yet it is now one of the most important areas of research in medicine is the microbiome and understanding leaky gut. And you see all kinds of papers in scientific literature using the term leaky gut. Wow.

I literally remember sitting, it was in 1997 and I was at Canyon Ranch and I was having dinner with some guests and there was some doctors in the crowd and we were having nice dinner and I was talking about leaky gut and this woman was an allergist. So her specialty was allergy and things like this to me. And she looked at me and she says, you're just completely nuts. There is no such thing as leaky gut.

This is just a bunch of, you know what? And I just was like, looked at her and I'm like, oh boy. And it's now 25 years later and medicine's really come along. It takes a long time, but people are still struggling. And I think the obvious, the worst sort of case scenario of a histamine reaction is obviously anaphylaxis. Anaphylaxis, yeah.

But it doesn't have to be that. So talk about how we begin to diagnose it. We look at what tests, besides the SIBO test, we look at. Well, you can measure histamine in the blood. You can also measure tryptase, which is another marker for mast cell activation. You can also measure, there's another test which in my preparation for this, I've not measured it. I haven't found the lab that does it, but it can be measured as N-methyl histamine,

which is a breakdown product of histamine. That's another one that can be done. And then again, I think one of the tests for me is dermatographism. I find that a very helpful clinical test to determine if a person's math cells in interstitial spaces are overly reactive and releasing lots of histamine.

Yeah, and we also do a test for a DAO deficiency. Yes, yeah. So talk about what that is. DAO is an enzyme, right? Yes, so DAO is a diamine oxidase. So this is an enzyme that our body has and it helps to break down histamine. So histamine has to be consumed, it's used, and then it has to be detoxified. And if this enzyme is lacking in a person, for whatever reason, the enzyme may be turned off, you will have problems with the enzyme it's used and then it has to be detoxified. And if this enzyme is lacking in a person

for whatever reasons the enzyme may be turned off, you will have problems with detoxifying histamine, especially in the gut. So, and there are enzyme products that you can use, DAO enzymes that you can use that patients respond very, very well to this. Yeah, we do that here at the El Chivano Center. You get people histio and enzyme support.

And it's interesting, there's a lot of things we do every day that block DAO production. Absolutely, yeah. Alcohol, black tea, green tea, which is a good thing, mate, energy drinks, these all block DAO production. So it's gonna increase your histamine intolerance. Yeah, exactly, yeah. And then you can use antihistamines.

And the other thing, we had another podcast earlier on migraines. And I found this also very interesting, is one of the things that is a histamine blocker is Butterbur. And Butterbur is used in migraines. And the reason why Butterbur works in migraines is that it actually is working on an antihistamine level. Because you can get an allergic brain, if you will.

We know about that, where you get fuzzy in the head and you can get headaches and things like that. So excess amounts of histamine has an impact on the brain. Yeah, and so when you see these patients, you can do some of the genetic testing, look for these DAO deficiency issues. You can look at histamine levels, you can look at some of these byproducts, you can do tests for DAO deficiency issues. You can look at histamine levels. You can look at some of these byproducts.

You can do tests for DAO deficiency. You can look at some of the other factors that might be causing it like leaky gut, food sensitivities, all that is really part of what we do here at the El Chihuahua Center when we check these patients' history and we look at their lab tests. And then when they come in and you have this suspicion, because sometimes it's hard to diagnose you have this suspicion, because sometimes it's hard to diagnose, you have a suspicion, it's pretty easy to test and try different approaches that allow people to see if it's an issue.

So what are the dietary things that we'd start with? Because a lot of histamine triggers are in the diet. And so we can have a low histamine diet. So what's a low histamine diet? Well, foods would- Or what actually are, put it this way, what are the foods that have the highest histamine that we should be avoiding?

Yeah, so basically the way to think about it is bacteria produce histamine. So if you have food that's old, if you have food that's sitting in the refrigerator for a couple of days, guess what happens? The bacteria actually break down histidine, the amino acid, into histamine. So no leftovers for these people.

Leftovers, exactly. Oh boy. Leftovers, exactly. Oh boy, I live on leftovers. Right. Maybe just like the next day. And then fermented foods. Fermented foods are fermented by bacteria.

So anytime we have food that's old or fermented, things like Parmesan cheese, aged meats, et cetera, cured meats, et cetera. They have high histamine and that's part of the fermentation process. So you get- And yet we talk about fermented foods being so good for you, like sauerkraut and kimchi and natto and miso and-

Exactly. And this is where- And all this yogurt and- This is where these really good foods in someone who has histamine intolerance is like putting gasoline on a fire. And they'll say, well, I'm getting worse. It's like, well, no, you should be getting worse.

These are good foods for you. No, you have histamine problems. What is that saying? It was good for the gooses and good for the g well, I'm getting worse. It's like, well, no, you should be getting worse. These are good foods for you. No, you have histamine problems. What is that saying? It was good for the gooses and good for the gander, right? I think this is so critical what we're talking about here, Todd, because functional medicine is personalized medicine. Absolutely, yeah.

It's precision medicine. And it's not only medicine, it's precision nutrition. So it's really important to understand that even though this way of eating may be great for some people with fermented foods and eating Avocados and having you know delicious shellfish bone broth bone broth. That's another one, right? We think all these are great foods, but you might be killing yourself Of course alcohol and beer and all that is a problem wine

But but you know, we're we're we're really here focused on what is right for you. And I think dietary dogma really interrupts personalization approach to nutrition. Some people do great on vegan diets. Some people do terribly. Some people do great on keto and some people do terribly. So there's no one size fits all approach. And what really frets me Todd and probably I imagine you too, is that, you know, there's all these people out there on the web and internet and promoting this and that approach and this and that diet, and they're not seeing patients. Yeah.

And the thing about seeing patients is it's incredibly humbling. If you've seen tens of thousands of patients, you know, you can't be dogmatic. Absolutely. You can't say, this is the way. You have to be vegan or you have to be vegan or you have to eat Yeah, you have to eat fermented foods or yeah, it's like you go. Wait a minute. Everybody's different Yeah, and what works for one may not work for another. Yeah, one man's food is another man's poison

That's right and even good quote good foods, you know, we're talking about good foods Yeah And so I think I think this is a really important point, particularly people who have histamine issues, which is a lot of people at some level or another, they should consider trying a histamine free diet. And also other foods that we think are also great may be triggering histamine like papayas and chocolate, oh my God, chocolate, which I love,

would be terrible to get this condition. Dried fruit, certain nuts, food dyes, additives, wheat germ, wheat germ is supposed to be health food, right? Tomatoes, bananas, all these things may really cause increased histamine production. And sadly, in order to get this under control, sometimes you need to be restricting some of these foods for a while for your body to heal. It's not forever. That's the thing is, I think you're absolutely right. An elimination diet is not something that you do forever. A low histamine diet is also something that you don't necessarily have to do forever.

I think that the key thing is really working with a really good, well-trained, experienced functional medicine nutritionist who can help you navigate all of the nuances of what to eat, what to avoid, what to take in terms of supplements can be very, very helpful. Absolutely. The things that we want to focus on if you have a histamine intolerance or foods that are low in histamine like fresh Really fresh food is the key right not old food. Like you said fresh meat freshly caught fish Yep, not fish has been sitting around for a while or canned fish is not as very good Food that's not citrus fruits. Uh, eggs are great. Yeah, not gluten grains get away from the gluten but quinoa and black rice.

Not dairy. Avoid dairy, but you can have coconut milk or almond milk. Lots of veggies, but no tomatoes, avocados, spinach or eggplant, right? So you've got to be smart about this and it's a little complicated and often you need help with the nutritionists. All the good oils and fats that we like. Those are all great. So, you know, it's pretty much how I eat. I mean, I do eat avocados and certain things, but I really pretty much eat protein vegetables, and it works so well for these patients. So Todd, when you see a patient like this, tell me about a case that you might've had

where it sort of kind of got you thinking about this and allowed you to really drive down into really the diagnosis and the treatment. Well, you bring up an interesting thing, because as I have seen more and more patients, and I think we are seeing more patients who have histamine intolerance, call it mast cell activation syndrome, to what degree,

is there are certain individuals who can be a little bit more predisposed towards this. So people who have Ehlers-Danlos syndrome, the hypermobile people can actually have, for whatever reasons, will have a higher incidence of histamine intolerance. The other thing in the case I recently had was a patient who came in to me

with severe mast cell activation syndrome. It was on a whole bunch of different medicines, including chromium, which we talked about earlier, to decrease food reactions to histamine. And I saw the patient and he gave a very interesting history. He had this skin lesion which sort of like morphed into this almost like a scarring type ulcerated lesion on his back area. He saw multiple dermatologists, had a biopsy, had part of the area removed,

and was ultimately diagnosed with some type of form of scleroderma, sort of like a malignant scleroderma, which is sort of interesting and like, oh, what's that related to? But he was also having all of these histamine type reactions. And then when I asked him a bunch of questions, I started thinking about, well, guess what? Lime disease is also associated with histamine intolerance because lime bacteria resides in the connective tissues in the body. It sort of hides there. And that in turn can actually

activate those mast cells, which mast cells are the first line defense or one of the first lines of defense against infectious agents. And when I asked him, because he had a lot of fatigue and brain fog type symptoms too, but maybe that was related to something else. So I asked him about potential exposure. So lo and behold, he ended up having a low CD57 count, which is oftentimes a marker. It's not diagnostic of Lyme, but it tells you that the immune system is not working so well. When I did advanced testing on him, he had actually had conventional lab testing. I think we talked about that in another podcast, how regular conventional lab testing for Lyme

disease is not that helpful. But I did a specialized T cell Eli spot test on him. And his Lime Eli spot test lit up like a Christmas tree. Wow. Right. So he had Lyme disease. He had Lyme disease, which was actually triggering a lot of his mast cell activation type symptoms.

So I've been working with him for a while and he did very well. I put him on a supplement, which is a combination of quercetin, which can help with- It's like a natural antihistamine. Natural antihistamine. Turns out it's really good for COVID too.

Yeah, yeah, exactly. Very powerful phytochemical. And he did very well by adding nettles along with quercetin in supplement form. He also worked with nutritionists, got on a low histamine diet, dramatically made a huge, huge improvement. His brain was working better and his energy was better, but he still wasn't 100% better. So that's where I went to the next level.

And he's currently actually being treated for Lyme. And it's in the medical literature. And I sort of stumbled upon this, because I had this patient come into me. And she had the same thing. She had severe mast cell activation. She was on Zolair injections for. It was like 20 grand a year. Yeah, yeah, exactly.

Yeah, 20 grand a year. 20 grand a year. To control the histamine, which could be controlled by diet and these other things. Exactly. And her condition actually turned out to be the same thing. It was actually undiagnosed Lyme disease. And this is, I think, one of those things

where you have to think about it, not that Lyme disease causes everything, but Lyme disease is such a tricky condition that you've gotta be thinking about it. Anybody who comes in. It's a great masquerader. It's like syphilis, exactly. It's like the great masquerader. And people can come in.

I've seen people with Parkinson's symptoms. I've seen people with brain fog. I've seen people with rheumatoid, seronegative rheumatoid arthritis. Chris Christopherson at Alzheimer's quote Alzheimer's. Exactly. Exactly.

I had one patient with fibromyalgia who is quote unquote fibromyalgia, whatever that means, it means you heard all over. And so Lyme can actually mimic fibromyalgia. Yeah, so you really gotta think about it. And it doesn't present as one, you know, neatly little boxed diagnosis. It's really, you gotta really think about it.

Well, that sort of speaks to one of the foundational concepts of functional medicine is that one disease can have many causes. Yeah. Right, medicine is that one disease can have many causes Yeah, right like histamine intolerance could have many causes Yeah, and one cause like Lyme disease can create many diseases Yes and create like, you know Lyme disease can cause neurologic issues and joint issues and skin issues and chronic fatigue and Alzheimer's and Mass Effectivation Syndrome, you know, uh, you know pots and all these weird

Diagnoses that doctors treat as if they're the thing but actually is something else, right? Like some symptoms of histamine intolerance will include things like headaches or migraines congestion congestion after you eat, especially. Digestive issues are really high on the list. Abdominal pain and bloating, diarrhea, constipation. We talked about the rashes that can happen, urticaria, hives, rashes that can happen. But we also know that histamine intolerance or high levels of histamine can cause a lot more systemic things as well.

So, or other systemic symptoms. So things like low blood pressure, heart palpitations, dizziness, vertigo feelings, anxiety. So sometimes people will feel more anxious when their histamine levels are high, chronic fatigue. And so, you know, histamine intolerance. And get a lot of nasal congestion, right? And sometimes even asthma symptoms.

Absolutely, right? Absolutely. Brain fog and it's like everything, right? So it can be dismissed as, you know, people don't put the dots together and the doctors don't often put the dots together and these symptoms are often seen as disparate or not connected, but they're all really connected, right? They are, right, they are.

And it is, you know, to be honest, I've often not put the dots together, right? So it is not always easy. We're always like, oh, this person has headaches. Why are they getting headaches? Or they're having digestive issues. And then all of a sudden you go, oh, this is all related. And I've got to be thinking about histamine.

And so we've learned a lot over the years too to be able to help people as well. So I think of mast cell activation syndrome, it's more systemic. There can be a lot more things going on and and and you know when we say the word histamine intolerance, we're really thinking a lot about that, you know that reaction that happens from eating a food and and and that histamine reaction or that histamine imbalance that occurs after a meal where there's just too much histamine around and the body's not able to break it down. And, but you know what, it's often a clinical diagnosis, right? So it's often based on looking at that person's story

and understanding, you know, really understanding their timeline and what their symptoms are and looking for those interconnections that can really help us to determine if this is what's going on for them. Because the testing is imperfect. Yeah, that's right. I mean, like in terms of traditional medicine, what would be the traditional approach to diagnostics, testing, and then treatment? And then let's sort of talk about how we would approach this from a functional medicine perspective. Right. So, you know, you can measure histamine levels, right? So whether you can measure histamine levels in the blood, so you can measure something called histamine and tryptase

in the blood, and you can measure histamine in the urine. It's called a methyl histamine urine test that's done. And that test is often done, both functionally and conventionally. And it can be helpful if the levels are high. So if the levels are high, you go, oh, this person has an issue with histamine. But what's a problem with this test is that the levels fluctuate a lot during the day and depending on what you just ate and the amount of food you ate and how we'll talk about this later. It's not super reliable, right?

No, it's not. And so a lot of times these tests come back negative, meaning they look normal, but that doesn't mean the person doesn't have issues with histamine. So just because these tests are negative, it doesn't mean, oh, you can check that box and say histamine is not an issue. So in addition to those tests, we're always looking a little deeper. So we can measure things like, we can now measure things like DAO levels. So you can actually measure that

enzyme level, which is many times helpful. We can look at things like, is there increased intestinal permeability? By doing some tests that look at antibodies against zionulin and lipopolysaccharides, because that can give us an indication that this may be an issue. And we also-

Zionulin is like the gluten marker for excess gluten and lipopolysaccharides are toxins that bacteria make that create inflammation. So those are bad things that happen in your gut and that can trigger this. Right, and then when the body makes antibodies against them, that means that there is increased intestinal permeability. So it's a test that we do to give us a sense of,

is there increased intestinal permeability and is that where we need to work to help improve this person's health? And we also look at genetics. We look at genetic markers all the time, that can influence how well you make that DAO enzyme as well as how well you break down histamine through methylation.

So there's a bunch of different genetic SNPs we will evaluate for that will also give us some information about like, how much is this person at risk for having issues with histamine? Yeah, it's interesting. And I think people have even weird symptoms like dermatographism, where you kind of scrape your skin with a fingernail and it'll just like,

welped up and look bad. So you can write stuff on your skin and it's like graffiti. Right. But these are really, a whole host of really disparate symptoms. And again, this is a spectrum, right? System intolerance, mass cell, activation syndrome,

they're all part of a continuum of dysfunction of your immune system, overreaction of the allergic response in the body, and triggers all this cascade of downstream symptoms. The problem is traditional medicine doesn't do a very good job of this and throws a lot of medication at it. Antihistamines, things like Allegra, Claritin, Zyrtec or what we call H2 blockers, another histamine receptor like Pepsid or Tagamet. And then they use, you know, mast cell stabilizers which actually I think

can be helpful like chromol and sodium which we use. You can take it orally as a liquid before you eat to kind of decrease any reactions to food. And I find that extremely helpful during safe medication. But there's more serious ones like Singulair for leukotriene inhibitors, which are strong medications, steroids. So that's really kind of the toolkit.

And it's a very limited toolkit and often doesn't really solve the problem, it just masks the symptoms. So the beauty of functional medicine is that it helps us really start to think about the symptoms. And as you mentioned, we do a deeper dive. We look for things like leaky gut, for food intolerances. We look at dysbiosis, what's happening in the gut.

We also look at mold and environmental toxins and hormone levels and all the things that we know really are relevant when it comes to sort of trying to understand the root causes of overactive histamine response. So I think it's an area I think we have a lot of success with and a lot of different approaches than traditional healthcare.

I think the interesting thing about histamine is that it also is in food, right? So people have to eat. You make histamine in your body, but you also get histamine from various foods. And maybe you could sort of share what initial approach would be from a functional medicine perspective. You know, we do with the deep diagnostics, as we mentioned, you know, look for leaky gut, look for dysbiosis, look for hormone imbalances, toxins,

look for food sensitivities, look for mole issues. We do, you know, genetic testing, look at histamine related enzymes like DAO and maybe even urinary histamine levels. So we do a whole range of tests, but then once we find out someone has this, what's kind of the general approach they would take to dealing with the root causes?

So right, we wanna calm down the body and calm down this reaction, this overreaction that's happening in the body. And so we will often do a trial of a low histamine diet and it can be very effective, as I mentioned, with this patient with migraines and how effective it was. But what's important, I think really important to just start off with is this is not a lifelong diet

because there's a lot of really healthy foods that have histamine in it, right? Or even can cause histamine to be released in somebody's body. So what we ultimately want to do is decrease the body's reaction to these foods and heal leaky gut. But let's start talking about this low histamine diet, because it is a really great tool that we are using often. And just for a bunch of reasons, one to see how much is this histamine related to this person's symptoms? And then how can we help start to calm down the body's immune reaction? And then over time, we work to relax the diet. So what we always do is we do phases, so we're not overly restricting foods. And it's, you know, because it's important to recognize that

the amount of histamine in a food varies significantly depending on how long that food has been sitting there, how long that food is, you know, how long it's since it's been picked or caught and or prepared. We know that foods that have been the longer they've been sitting there, they will, histamine levels will go up. And so it's important to think about a lot of different things when we're doing a low histamine diet. So in terms of the phases, what we start with first is removing alcohol, especially beer and wine and champagne. Those, as you mentioned earlier, are foods or drinks that are high in histamine

and they also block the body's ability to break down histamine. So we pull those away first. And we also work with people to make sure that they are not keeping a lot of leftovers around. They're eating foods that are fresh, very newly prepared. If they do have leftovers, they want to freeze those foods right away because the longer the food is is sitting there, the more histamine it will produce. For example, we also know like with fish, for example, you want to try to eat fish 30 minutes after

it's been caught. Well, you know, because that will have the lowest level of histamine. Exactly. That's so hard to do. So a lot of times people have frozen fish, which is good because those fish are often frozen very quickly after being caught. Oh, that's interesting. Yes. And they're gonna be lower in histamine. But the key is when you defrost your fish,

you wanna prepare it right away and consume it right away because the longer it's being defrosted or the longer that, you know, if you eat that food, two days after you prepared it, there's gonna be higher levels of histamine in it. So all of that can be really complicated. So I will always recommend, and we do this at the Ultra Wellness Center,

we have what, seven nutritionists now? I always recommend people work with a nutritionist. I work with a nutritionist because it can be such a complex process to figure out and to remove and you want to do it in a healthy way where you're not overly restricting, but it can be really helpful. So you want to have fresh foods, minimally processed foods, and you want to have foods without those additives in it that like sulfates and MSG,

things that can trigger more of a histamine response in the body. No, it's just like, you know, the aged cheeses, fermented foods, alcohol, those are all really full of histamines. You have to be really careful with those endpoints. Absolutely, we put a lot of those in phase two. So if phase one isn't enough to calm down the body,

then we'll move and pull away the canned and smoked fish anchovies, which unfortunately is one of my favorites. But again, this is not a lifelong food restriction. Processed and fermented meats we pull away, aged cheeses, pickled and fermented foods, which like sauerkraut, kimchi, yogurts, kefir, mustard, ketchups, vinegars, soy sauce.

A lot of these, as we talked about earlier, are really healthy foods. So we wanna be able to add them in in the future, but sometimes again, we pull them out for a period of time to see how much that helps somebody's symptoms improve. And they typically will see improvements in two to four weeks. So it's like a two to four week removal

to get a sense of how much things calm down in the body. There is even a phase three where we have to restrict even more and pull away some plant foods like avocado, spinach, tomatoes, pineapple, citrus foods that can also trigger some histamine reactions in some people's body. And so, again, we do it in phases. And we can attach this handout, I think, right Mark,

to the people? And the show notes will put a handout on the different phases so people can listen in and actually figure out what to do by looking at this handout that we have provided at the El Tribuano Center. We'll put a link to it. And I think it's kind of a good guide on how to get started on your own. But one of the challenges is that even if you do all that stuff, I always say we need to figure out not what you're sensitive

to, but why you're so sensitive. And that's sort of the next phase. You can get people immediate relief by removing histamine and by giving them DL enzyme and maybe some other things that sort of are mitigating symptoms, whether it's antihistamines or chromalin or whatever you're gonna give them. But at the end of the day, to really resolve this, you have to dig deep into the root causes

and to try to deal with those things that we really are good at in functional medicine but are not so great at in traditional medicine. That involves everything from optimizing and fixing the gut, whether it's spectral overgrowth, fungal overgrowth, leaky gut, inflammation, healing and repairing the gut, which we have a whole program, four and five hour program in functional medicine. I've done many podcasts on the gut. Optimizing nutritional status

that affects their immune system, whether it's vitamin C, B6, magnesium that support histamine metabolism, and also the stress reduction part, which is really key because that activates everything, getting regular sleep, exercise, but then also diving, see what do you have mold, do you have environmental toxins,

do we have heavy metals causing this, do we have something else going on that we need to treat directly, and how do we upregulate your detoxification system? So we really treat both the histamine syndrome itself, but also then dive into root cause treatment so that people don't have to suffer with this their whole life.

So we now believe that, and you sort of brought this up as part of the introductions, is that we now believe that food poisoning starts the whole process. So you, and eating is part of it. You know, back in the day, meaning like 40, 50 years ago when we were in kindergarten, we would sit in a sandbox and eat the sand.

Now we eat salad out of a bag until we go to Club Med. And for the first time in our life, we see salmonella or, you know, we go somewhere and we get travelers diarrhea or we get food poisoning or whatever. We start to explore the world of food. But food poisoning triggers this and we now have identified the toxin in food poisoning, the CDTB toxin that trips off some antibodies in the human body that then cause your nerves of the gut to fail or to be impaired. And so when the flow of the gut is slowed by this impairment, bacteria build up. And there's two bacteria that just flourish when it's a little more swampy.

So I used to watch survivor shows on TV on Discovery Channel, you probably watched those. And they always say- I like the loss, I used to watch loss, which was kind of like survivor It's a little bit different There's a little more raunchiness story with survivor. You just kind of try trying to make it to a road somewhere, but The point was that he he always this guy on the Survivor show would always say if the water is not moving

Don't drink it if the water is flowing fast drink it Because it's cleaner and the same thing with the small bowel. If the small bowel stagnates it becomes swampy and bacteria grow in it and the same thing is happening in the human small intestine and so it's a sequence. So food poisoning, the antibodies and then you develop the bacterial buildup. So you're almost saying it's like an autoimmune disease of the nerves of the gut that develops that kind of makes them sluggish. So this is a kind of a radical idea

that irritable bowel is an autoimmune disease, isn't it? I mean, this is kind of not what most doctors typically think of when they think of IBS. They think of IBD or inflammatory bowel disease, but they don't think of irritable bowel being autoimmune. The interesting thing about contrasting IBD to IBS, so the antibody that we discovered is an autoantibody that is directly related to the pathology. So the higher that antibody is, the sicker you are.

The antibodies in IBD are markers of IBD. They're not directly implicated in the pathophysiology. The antibody to vinculin that we discovered is directly related to the pathophysiology. We can make rats have IBS just by giving them this toxin. And so that's very cool because it allows us to study new drugs and new therapies coming in. Not so cool for the rats though. No, not so cool for the rats though. Not so cool for the rats. Wow.

So this is fascinating. So you were saying there are different kinds of bacteria. Can you explain, you know, what are the kinds of bacteria? And then what type of food poisoning is it any? Like if you get Giardia or if you get Salmonella, Shigella, Kempelbacter or Entamoeba? Or like, you know, what are the kinds that typically cause the problem? Well the four horsemen of the apocalypse of IBS are chemplobacter, salmonella, shigella, and some E. coli food poisoning type of E. coli pathogenic E. coli. Giardia can do it too. It turns

out it has vinculin in its structure and so maybe that that's how you get the antibodies from Giardia. The viruses are less likely to precipitate IBS. So the four horsemen, Campylobacter, Salmonella, Shigella, and E. coli. So that's, and it occurs about, starts to occur about three months after you get sick. Patients will remember, some don't remember, and they'll say, well, you know,

they have a couple of days of diarrhea and they don't pay much attention to it. But they remember going on a trip to Hawaii and they end up in the hospital with bloody diarrhea. And then ever since then, nothing's been the same. I have heard that story so many times. You know, I went to Thailand or India or, you know, Jamaica and like, and sort of trip the whole thing going. Yeah, or the taco truck in Venice, yeah. So, a lot of possibilities. Wow, so this explains like sort of 60%, you say, but you know, not all of it, right? What are the other things that may be driving irritable bowel syndrome?

And are they also related to SIBO, or is it all something else? Well, so based on culturing the bowel, we've been able to isolate that 60% of IBS is SIBO. The other 40% is a mixed bag. So for example, and you probably talk about this now, Ehlers-Danlos syndrome, Potts syndrome, we're starting to recognize those illnesses

as characteristically GI-centric, at least in their early presentations as well. Some of the leftover, 40 percent have Ehlers-Danlos syndrome or POTS, or some of them are celiac that we've missed. Some of them are food sensitivities, some of them are histamine sensitivities. It's a mixed bag of a number of other disorders,

and some of them are fungal overgrowth. So we see that in about 6% to 10% of that 100 pie. So there's still more to unpackage. We're not ignoring the other 40. We're trying to figure the rest out. But it's a little bit harder to unravel. So let's pause there for a minute, because you just said something that I think might slip by, which is this whole idea of fungal overgrowth or what often is referred to as

CFO, small intestinal fungal overgrowth. In my coming of age as a functional medicine doctor, basically people would laugh when we talked about yeast overgrowth or anything like that and candidiasis and it was just a quacky alternative concept. But it seems to me, you know, now understood as potentially playing a role in some of these cases. Can you talk about the current understanding of this

and actually some of the treatment? And then I'll sort of loop back to the, how do we start to treat and think about IBS differently? Yeah, I mean, Satish Rao, Dr. Satish Rao in Georgia has done a lot of the seminal work in this. But more recently, we've done a lot of the seminal work in this, but more recently we've done shotgun sequencing of the small intestine and we've been seeing this fungal overgrowth.

That doesn't mean you shoot somebody in the gut with a shotgun. No, shotgun sequencing means we sequence every single piece of DNA we can find and then characterize it and see what organisms it represents. Yeah, and it represents fungus About 10% of time and that when the fungus is higher your your The patients are experiencing more abdominal pain and more diarrhea. So there is a subclass of these patients that it is fungal but it's Smaller than some would like to believe but larger than those who are naysayers as you've probably heard And so it is there, it's real, but it's a little more challenging to identify. There's no breath test for it. You got to go in and chase it. And that's the challenge.

Chase it by doing stool cultures or? Well, chase it. It could be by stool, but if you want to find small intestinal fungal overgrowth, you got to get into the small intestine and that's really- Sample it. Because you have endoscopy and all of that. That's how Dr. Rao identifies it. Yeah, and any particular species of fungus or is it sort of a broad array?

So what we found in this quote shotgun sequencing is Candida albicans is a big part and a little bit of Candida glabrata. And there's a few other Malassezia and all these other organisms that are very minor, but they generally aren't at a high number that we think are as consequential as the first two I mentioned.

Yeah, no, I definitely have seen that on cultures. And, you know, in my experience, maybe it's not universal, but it tends to lead to more constipation. And so people tend to have more constipation. And also I can tell, because they might have other fungal symptoms. They might eat tons of sugar and starch.

They might actually have fungal rashes on their skin or dandruff or other kind of clues that they have kind of a yeasty kind of situation going on. But I think it's important that it's been identified. And going back to kind of the treatment of that, how would that normally be treated? Well, generally in allopathic medicine, we try an antifungal. There are natural antifungals as well, and you're probably better versed in those than I am, but we do use fluconazole.

We do use niacin. Occasionally, we use more radical, more advanced antifungals, but those are the typical first two choices. Yeah, sometimes you can take what we used to call amphoterrable, which is a horrible first generation antifungal, but it's not absorbed. So if you take it orally, it's not absorbed and that can be effective. Exactly. Yeah.

Oh yeah. And then in terms of the bacterial stuff, you talked about these three different bacteria, right? You've got methane producing, hydrogen producing, sulfide producing, and they all are a little bit different. And you said the methane producers are not really bacteria, they're archaea. But, you know, for simplicity's sake, let's call them bacteria. And I don't think most people know what archaea is. It's arcane, right? So the, yeah. So what is your approach to starting to kind of differentiate these? And then how do you determine what the right treatment is

for a patient and can kind of guide us through what to do, both in terms of lifestyle, diet, and any kind of supplements that might be helpful and medication? Yeah, so first of all, we helped develop the first three gas breath tests, so just full disclosure, but it's changed my practice because there are patients

who fell through the cracks without knowing hydrogen sulfide. So unpacking each, the hydrogen positive breath test patients are generally, we actually just published this paper, it came out literally yesterday. There are two bugs, that's it, that cause the hydrogen overgrowth. It's Escherichia coli, the non-pathogenic one, and Klebsiella pneumoniae. Those two characters, when they come into town, everybody leaves because they're so opportunistic and bullies and we think they produce even toxins to the other bacteria

around them to try and get rid of the inhabitants. So it's like you've got a gang that comes into the small town and everybody leaves. So it's a disruptor of the microbiome and then they rise very high in number. So that's the hydrogen one. The second category is the methane or methanogens. And those characters live both in the colon and the small bowel. And we have a paper coming out showing exactly where they're living. And it's pretty universal in a lot of these patients. So hence, we call it intestinal methanogen overgrowth and not SIBO methane, because it's not just the small bowel, it's colon also.

And when they produce methane, it gives you a lot of constipation, a lot of gas, and you can't pass the gas, and these people are quite miserable. And then the third is the hydrogen sulfide, which is the new kid on the block, which has changed my practice, because some of those patients, we didn't know.

Breath test is normal, everything looks fine. And then the hydrogen sulfide's positive, we get rid of it, and all of a sudden sudden they feel better than they have in their life. And for some reason when you get rid of hydrogen sulfide, it doesn't come back so quickly, which is beautiful. I have patients who have gone a year or just one treatment and they're done. And so I'm really excited about that. So I mean, I could talk about the treatments if you like now or-

Yeah, yeah, yeah. Because you know the treatments can be real different. And this is important to understand for people because, you know, just because you have a real bowel, it's not like a one-size-fits-all approach. You've got to differentiate what type it is. And these tests that Dr. Pemminton developed, the tests for anti-CDTB and anti-viculin antibodies are really important. And then the breath test that allows you to look at hydrons, methane and sulfur. So can you talk about what are the different treatments for each of these?

Yeah, so I mean, if I have an IBS patient with diarrhea or a patient with diarrhea and bloating, my practice now, I do the antibodies because I wanna be able to say, was it food poisoning or not? And if the antibodies are really high, it makes it harder to treat. But also you travel travel you better take

Prophylaxis because you could get into further trouble with these antibodies going higher So I universally do that like prophylaxis like what like the facts and I give that facts and prophylaxis That's what I do in my practice and a lot of the GIs now do that Because if the antibody goes higher The damage to the nerves of the gut is more intense or the effect on the gut is more intense, at least that's what we're seeing in our clinic. So we're very careful with those patients who have the antibodies positive. When it comes to, then we do the three gas breath tests in all of our patients.

And if it's hydrogen, and we all know Rifaximin got FDA approved for IBS with diarrhea on the basis that IBS was in part of microbiome disease and now we understand that microbiome condition is SIBO so I give refaximin for that. If it's methane we have one double blind study that we can lean on and it's refaximin plus either neomycin which is what the double blind study covered, or rifaximin and metronidazole. And then the third category is hydrogen sulfide. And we give rifaximin, but we give it with bismuth, because bismuth is an anti, it blocks some of the synthetic functions of hydrogen sulfide in the sulfate reducing bacteria. Point is, the hydrogen sulfide goes down, the bacteria

are reduced and therefore the patient's normal bacteria take over and things get better. More permanently in that group it looks like. And that's basically Pepto-Bismol. Yeah, Pepto-Bismol. Yeah. Yeah. Interesting. So in terms of diet, is there in a different approach to each of these in terms of what you would recommend from a food perspective? We haven't sorted out and or had time to sort out the different diet approaches, but I envision smarter people in the end diet

will come up with a way. What we do now is what we call low fermentation eating. So we don't use low FODMAP in our practice because you can't do it indefinitely, but low FODMAP will reduce the amount of calories you're providing to bacteria and therefore they'll ferment less and and that might help. But long-term low FODMAP hurts your microbiome and can cause nutritional deficiencies so you can't stay on the full low FODMAP indefinitely. And FODMAP is like fermentable oligosaccharides that yeah, fermentable oligosaccharides that basically

Yeah, fermentable oligosaccharides, monosaccharides, et cetera. And basically it's too restrictive. But you've probably, most people have probably read about FOD, low FODMAP diet. It's very popular in the last few years. But we use what's called low fermentation eating, not as restrictive. And the philosophy of that was with a low fermentation diet, you can go to any restaurant in the country and you'd find a meal. So it's, you know, you don't want to be the person at the table just because you have

IBS that spends 10 minutes with the, with the, you know, trying to explain your dietary restrictions on a low FODMAP diet. So you know, that's part of the reason. We want our IBS patients to feel as normal and as socially non-isolated as possible. And that's part of it. What is a low fermentation diet? So it's basically restricting non-digestible carbohydrates.

So low fiber, no dairy, and then none of the artificial sweeteners because of course they're easily fermentable. And then spacing your meals, so you don't eat for five hours between meals because the damage of the nerves, we talked about that earlier, the damage of the nerves causes a reduction in cleaning waves of the gut. So the cleaning waves only occur when you're not eating. So your gut is sort of like got two computer programs, eating mode, cleaning mode. If all you do all day is spend time in the break room, taking a bite of a bagel

that's in the break room, you never go into cleaning mode. So, so in addition to the construct of what to eat, we tell you when to eat and to try and space your meals up. So anyway. It's interesting, you know, the typical dietary recommendation when I was in medical school for IBS was more fiber, like Metamucil basically. What you're saying is that you wanna restrict

soluble fibers that are digestible. And low fiber diets seem to be, you know, it seems like a contrary notion when you wanna create a healthy microbiome because it's good bugs in the stomach. soluble fibers that are digestible. And low fiber diets seem to be, you know, it seems like a contrary notion when you want to create a healthy microbiome because good bugs also live on fiber. So how do you navigate that? Well, you know, I may be punished

for saying something like this, but everything has fiber in it now. Even Cheerios, they put fiber in it because it prevents colon cancer and it's colon health and all this stuff for 20 years. How much have we heard about colon health and fiber? A lot. What have we got now? We've got colon cancer happening in the 40s and we're doing screening colonoscopy at 45

now. I'm not saying it's fiber causing that, but all the fiber we've been pounding and the cardboard we've been eating hasn't really done as much as we thought it might. So I'm a little unclear about fiber. But from the point of view of bacteria, you put more fiber, you're going to have more of the bacteria. If you had bad bacteria to begin with, there's going to be more of them. For a healthy person whose microbiome's healthy, no problem.

But not for these patients with these microbial conditions. Now, if you've gotten, you know, these antibiotic treatments, you know, you've gotten diagnosed, you've gone through the testing, you've gotten the personalized treatment, you do the course of antibiotics, what prevents the bacteria from coming back? And in my experience, it often does. So, how do we manage the sort of recurrence that occurs? Because you don't want to keep giving people antibiotics because intuitively people go, wait a minute minute antibiotics are bad for the gut so why are we giving antibiotics to someone who's got a gut problem seems counterintuitive well uh i can answer in two or three ways but i'll try to touch on a little bit of each we looked at refaximin

before and after treatment the small bowel and when you get rid of the bullies in the town all the inhabitants of the town come back. So it goes opposite of what people think. We're not, you know, being cataclysmic. It's getting rid of the E. coli and the Klebsiella incibo that allows the regular bacteria to re-flourish, repopulate, and take over again for a period of time. But remember, the problem is those cleaning waves are not working.

So it is possibly going to come back, depends how badly damaged. And that's where that antibody comes in. Because if the antivinculin, which is that auto antibody for the autoimmune disease of IBS, is very high, the neuropathy is more high or more intense and you're going to relapse or reoccur more frequently. So that's where we were able to have some further strategy. But first of all, take the antibiotics. They actually repopulate the town counter to what you think. We've never seen

antibiotic resistance to rifaximin so far. Knock on wood. It's a very unique chemical drug. And then we get them on the low fermentation eating diet. That's what we do. and for those where the antibodies high or those who relapse we do put them on a prokinetic. So they space their meals. Everything's going right, but we want to stimulate those cleaning waves at nighttime because that's the longest time you're not eating and make you clean up as much as possible at night so that

the bacteria don't have a chance to come back. So we don't do all three things for everybody. It depends on, you know, if somebody relapses in two years, we don't need to put them on a drug every day to prevent. But if they relapse every three months, then we can stretch it out to a year by adding the prokinetic or doing more aggressive diet strategies.

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