Histamine Well Podcast: Exploring Histamine, Methylation & Holistic Health

Main Causes of Histamine Intolerance: What's Behind The Symptoms

• Joanne Kennedy • Episode 2

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High histamine levels are often a signal of deeper imbalances, and in this episode of The Histamine Well, we’re uncovering the hidden root causes that could be driving your symptoms. From SIBO and gluten intolerance to leaky gut and methylation issues, we’ll explore why histamine intolerance is rarely just about food and how addressing the underlying factors can lead to real, lasting solutions. 

Whether you’re managing your own health, supporting others on their journey as practitioner, this episode will empower you with insights that go far beyond symptom management, helping you get to the “why” behind histamine issues.

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Joanne Kennedy:

Hi, it's Joanne. Did you know histamine intolerance isn't just about the foods you eat? It's a common sign that something deeper is happening in your body. Histamine itself is a symptom. A signal of an underlying health issue. In clinical practice, we commonly see conditions like SIBO, gluten intolerance, digestive enzyme insufficiency, oxalates, mold, and estrogen dominance as common root causes of high histamine. So if you've been struggling with histamine issues for years without finding answers, this episode is for you. Welcome to the Histamine Well podcast designed for practitioners and patients alike. This is your trusted source for insights on histamine intolerance, methylation, gut health, women's hormones, and much more. I'm Joanne Kennedy, your host, naturopath, author, and educator, passionate about breaking down complex science into clear accessible knowledge. Whether you're a health professional or navigating your personal wellness journey, the Histamine Well podcast bridges the gap between cutting edge research and practical understanding to empower you with the tools to thrive. Welcome back to the second episode of the Histamine Well podcast. Today we are covering something really important, which is the understanding that histamine intolerance is caused from something. It's caused from something in the environment. It could be something going wrong with your gut. It could be your hormones. So we don't just rely on low histamine diets to fix our patients when it comes to histamine levels. We need to unravel the one root cause for you, the several root causes for you. Because more often than not, people have several root causes of high histamine in the body. So it's actually when I first learned about histamine intolerance, we were just putting patients on a low histamine diet. And like possibly giving them some digestive enzymes. Possibly doing a stool test to look at the microbiome in the large intestine, because you can have an overgrowth of histamine producing bacteria. And at the same time, an undergrowth of beneficial bacteria. And beneficial bacteria do many things, including regulating inflammation in the gut and inflammation increases histamine. So it sounds very convincing that you do these stool tests and then you reduce those histamine producing bacteria with herbal medicine, and then you increase the beneficial bacteria with prebiotics. And that that would fix the histamine issue. But what would happen in most of these patients is that after doing that. And they start to reintroduce the histamine foods, they would flare again. So this is where I really learned that there are a lot more causes of histamine issues stemming from the gut than just large bowel dysbiosis. So dysbiosis is that imbalance between good and bad bacteria. And some of that sort of bad bacteria was increasing histamine. And I still see this in clinical practice today. So I have a lot of patients come to me because they've done this. They've done these expensive stool tests. Done a gut protocol for the large intestine. And their symptoms are managed because they're not eating high histamine foods. And when they reintroduce them again, they flare. So I train practitioners all over the world. Germany, Austria, France, Dubai, US, Canada, and we all see the same thing. When it comes to histamine, just doing a large bowel gut protocol, very rarely fixes the issue. Now, if that has done that for you, that's wonderful. That's great. But if it hasn't happened, then I'm here to tell you that we need to dig deeper. So in this episode, I'll walk you through the common factors I see in my clinical practice every day that are driving up histamine levels. So for practitioners and students, this is where it all begins. Understanding these root causes is essential for getting your patients on the right track. getting the right testing done. Doing the protocols for the root causes and not just relying on a low histamine diet. And for students, especially, this is a call to dive deeper into your training. A lot of what I'm going to talk about today are the things that you really need to understand when you leave college. And I know that a lot of you are not learning about things like SIBO or mold or oxalates. And doing extra training whilst you're studying is going to really set you apart from your peers when you graduate. And for those of you suffering with histamine intolerance, I urge you to get a pen and paper out. If you're driving, obviously just wait until you get home. You can always come back to this episode and write down these main causes. And I want you to really think, have I actually properly investigated this issue? Have I done a test that's identified this issue and it's been ignored? Oxalates being a big one, I see. So people do organic acids tests and it shows high oxalate and it's so often ignored. The practitioner doesn't think it's a big deal. And I'm here to tell you that it is a very, very big deal. I'm just going to go through all the major causes we're going to talk about today. These include SIBO. Histamine producing bacteria in the large intestine and why I don't think that is where you need to focus. Digestive enzyme insufficiency. We'll chat about hydrochloric acid, pancreatic enzymes, bile acids. We talk about gluten intolerance and the difference between celiac disease, allergy to weight and non celiac gluten sensitivity. We talk about leaky gut, LPS toxins, helicobacter pylori, inflammatory bowel disease that's Crohn's disease and ulcerative colitis, oxalates, mold, estrogen, methylation issues, genetic polymorphisms and medication. So there's a lot to cover. It's quite a long episode, but stick with me as I'm sure you'll get a lot out of it. So, as I was saying, as someone suffering with histamine intolerance, I encourage you to leave no stone unturned. And if you're interested in learning more about this, I do have my e bundle, which is an ebook. It's really well researched, so you can manage this yourself. There's treatment options, or you can also take the ebook to a practitioner and say to them, Hey, can you please help me get this testing done? And a lot of them might actually be able to help you with the results and doing protocols around treating these root causes that you're going to learn about. We're going to start with SIBO. So when it comes to histamine, SIBO is a really big deal. So what exactly is SIBO? SIBO is small intestinal bacterial overgrowth. So essentially you have an overgrowth of bacteria in the small intestine. So it can be an abnormal type that's just there or it can be your own bacteria that's meant to be in the small bowel and it's overgrown. So essentially that's SIBO. And what happens with SIBO is that SIBO bacteria take foods that are known as FODMAPs and resistant starch and they convert those foods into gases. And these gases, where they're going to cause a lot of the bloating, which is a classic symptom of SIBO. And the gases cause Inflammation in the small intestine. And when there's inflammation, the cells release histamine. And at the same time, the DAO enzyme that breaks down histamine resides in the microvilli, the tiny little hairs of the small intestine. And inflammation can reduce the amount of microvilli you have. And if that occurs, then obviously the synthesis and excretion of the DAO enzyme can be reduced. So the net result is that you have too much histamine. Now I can hear some of you saying, Joe, I know SIBO. I've heard of SIBO, but the testing is not 100 percent accurate. My physician wouldn't test it saying it's not an accurate test, or potentially you've done a SIBO test and it's come back negative. Well, there are some reasons that you can get a false negative test result. I won't go into that now. I'll do a whole episode on SIBO, but if you are someone who has had a negative test result and you do really well on removing FODMAP foods from your diet. Then that could potentially be a false negative. So what I do in clinic is when I suspect a patient has SIBO, I get them to do the SIBO test, And then I get them to start the SIBO diet as soon as they've done that test. It's often a SIBO low histamine diet, and I do that for a few reasons. So first of all, I really want my patients to get some good results really quickly. To get some relief from their symptoms. And that diet can absolutely bring down inflammation and histamine levels really quickly. I'm also really interested to see how they do on the diet and our next consult, because if the SIBO test comes back negative and their symptoms are so much better on the diet, I need to think, were they just eating way too much gluten beforehand? Cause you do need to remove wheat and therefore most gluten in a SIBO diet because wheat is high FODMAPs. was it the gluten that's driving up a lot of the symptoms or was, did they just have a terrible diet. Way too much sugar, way too much processed foods, et cetera. So people try really hard on the diet, but it is easy to slip up, especially if you're eating out. So you might go to your in laws for dinner and you know, your mother in law is trying to really help you with this diet that you're on. You tell them about it, but inevitably they kind of get it wrong. They give you too much FODMAP vegetables. People don't understand like FODMAPs, they're in healthy plant foods. They kind of get confused about why you can't have these and you eat way more FODMAP foods than you're meant to. And you can get really bloated and you get a lot of symptoms. So when this happens, again, this is a real red flag for SIBO. And in this scenario, I do feel confident with treating SIBO, okay? Because the testing is not 100 percent accurate. If you know you have SIBO or you suspect you have SIBO, doing the SIBO diet and getting the histamines down at the same time can be really beneficial. So you might find that you need to do a SIBO low histamine diet. A combination of that is going to reduce inflammation really quickly and therefore reduce histamine. And especially if you're one of those people that can't tolerate supplements, getting inflammation down in the first place can then help you tolerate supplements better. So we can always rely on dietary intervention to help get the inflammation down first. And then you can start to introduce the supplements slowly and titrate up. But it's so often the case when there's just multiple food intolerances, that there's going to be multiple supplement intolerances. And it's very frustrating because the supplements can help you. So, if your one of these people, if you're interested, you can find the SIBO low histamine diet on my website. It's part of the e bundle. Simply go to joannekennedynaturopathy. com. You'll be able to find it there. The next thing I want to talk about is large bowel dysbiosis and the histamine producing bacteria that can occur in that condition. So large bowel dysbiosis is basically when you have Too much bad bacteria compared to good bacteria in a large intestine. And very convincingly, it seems like, wow, if I've got all this bad bacteria, it's producing histamine, that that's going to drive up my histamine issue. It's going to be the main cause of my histamine issue. And what I was saying at the beginning of this episode is that it really is the only thing that's causing the high histamine in the body. And simply focusing on fixing the large bowel with, sort of herbal medicine to kill off bad bacteria. Prebiotics to increase good bacteria usually doesn't result in great clinical outcomes. So we are moving on to gluten and gluten intolerance. So what is gluten intolerance? So basically, humans are pretty intolerant to gluten because it doesn't break down properly in the gastrointestinal tract. And what gluten does is that it causes zonulin to be released. Gut cells are held together by what we call tight junctions. They open and close to allow food molecules, ions, and water to get into the blood where they are meant to be. And they're held together by zonulin and gluten can dissemble the tight junctions and therefore zonulin gets released. And we can actually test for that in a stool test. We can see if you have high zonulin levels. And gluten is basically inflammatory and anything that's inflammatory is going to cause high histamine. When we're talking about gluten intolerance, it really refers to three different conditions. Celiac disease, allergy to wheat, and non celiac gluten sensitivity. So celiac disease is an autoimmune condition and occurs in genetically susceptible individuals. And these individuals, when gluten gets through a leaky gut into the blood, it triggers an auto immune response. And the inflammation that occurs is so severe that it flattens the microvilli in the gut, which are the tiny little hairs. And these tiny little microvilli, they secrete the DAO enzyme. So those with celiac disease can have significant issues with breaking down histamine effectively. This is a patient group that often requires DAO enzyme supplementation long term. Especially if there's been significant microvilli damage. I actually had a patient recently from Italy. You know, it's crazy. A lot of the research on gluten and zonulin is coming out of Italy because we think we can just go to Italy and eat gluten to our heart's content. But a lot of people are still reactive to it. A lot of Italians are still very reactive to it. This girl, she was about 40 and she's celiac. She was diagnosed late in life at 38, I think. And unfortunately being diagnosed so late in life and having that exposure to gluten for so long. Her microvilli are very flattened and I really don't think you can grow them back. So her DAO enzyme is really reduced. So she'll probably need to supplement with DAO enzyme long term. So this is just one of the conditions whereby it is very hard to correct, but most of what I'm talking about today, we can fix these issues. But from my clinical experience with gluten, I don't really see anyone thriving on gluten. And people will sort of argue with me as they might not have gut issues, but they have anxiety, they have migraines, they have depression, they have eczema. It's terrible for PMS. It's a major cause of iron deficiency. So it might not be showing as a gut issue. It can be showing as always systemic. issues and nutrient malabsorption. So there's not many people that are actually getting away with eating a lot of gluten. You know, I know in Australia and North America. It is different to Europe. I was in France recently and I can definitely eat more bread over there. But funnily enough, I did after a while eating it three times a day. I did find it impacting my blood glucose levels, actually. So I always think that sort of there is a limit to how much we can actually consume. We also have wheat allergy. So wheat allergy is a food allergy induced not only by gluten, but also wheat. Wheat allergy occurs due to gluten damaging the lining of the gastrointestinal tract. Unraveling the tight junctions. Releasing zonulin causing a leaky gut. When the wheat gets through into the blood, the body recognises it as an antigen, which is a toxin. And the body makes an antibody, often called an immunoglobulin E. it can cause immunoglobulin E. E is an extreme. I always remember that from studying E extreme as it's going to cause anaphylaxis. So the IgE antibody binds to the receptor on the mast cell and the mast cells are going to degranulate and release histamine really fast. So this is more of the anaphylactic picture. So I don't actually see a lot of these patients because it's normally picked up by the immunologist or the GP pretty quickly or yourself as you are actually rushed to hospital from eating wheat. So it's a serious condition when you're anaphylactic to wheat. Now, wheat allergy can also cause a different type of reaction. It's called a type IV hypersensitivity reaction. It's not anaphylactic. Anaphylaxis, it's really fast like really quick and it peaks at 30 minutes. Whereas a hypersensitivity reaction, it can take 12 to 72 hours to develop. And the common symptoms will be dermatitis, headaches and sinusitis. So this is sometimes hard for patients to pick up because it's like, wow, like I ate wheat two days ago and now I'm having this heightened response to it 48 to 72 hours later. If you suspect it is gluten and weight, like you'd very simply remove it from your diet for a month or so, and you'll be able to tell if it's significantly helping your overall health and your histamines. Cause what can happen is it's causing your histamine bucket to become really high in your body. And then when you eat a very high histamine food like tomato or avocado, you'll flare again and you'll blame the tomato and avocado, but it's actually the wheat and the hypersensitivity in your body that's causing your histamine reaction. Now, the other problem with wheat, it's also high FODMAP. So people with SIBO are also going to have adverse reactions to wheat because it's driving up that SIBO bacteria. I had a patient a few years ago from Germany. She was living in Sydney and she was a bucket of histamine. She was highly intolerant to histamine foods. She had to cook all her foods from scratch from home. She couldn't eat out at restaurants, no leftovers. In Germany, they're really into histamine and MCAS over there and CIRS. And they're very thorough with their testing. They put her through all the testing for gluten issues and everything came back normal. It said she didn't have a problem with gluten at all. And when I spoke to her, I was always like, well, you know, gluten in Australia is different. The wheat grown in a harsh environment. There's different proteins put in it. Potentially you're just hyper reactive to the gluten here. But she's like, no, no, I was having these issues in Germany. And so, she wanted me to test for the DAO enzyme. Which I did and it came back normal. So I didn't see her again. And then I ran into her at Pilates. Like a year later. And she came up to me and she's like, Oh my God, Joe, you were right. It was gluten all along. So she was just eating gluten like pretty much every day. It was stimulating her histamine so much. And then when she ate anything high in histamine, it would just really flare. So there's not really testing for it. We can just have issues with gluten because of how inflammatory it is with the gut. So I'm going to talk about a condition called non celiac gluten sensitivity. So basically it's a condition whereby symptoms occur from consuming gluten or wheat in a person for whom celiac disease and wheat intolerance are ruled out. Is this most people? Question mark. So clinically, I see gluten causing inflammation in the majority of my patients. And as we know, inflammation increases histamine production. It's also going to reduce DAO enzyme activity. So it just makes sense that gluten can really drive up your histamines. I'm now going to talk about leaky gut. And I know people are going to say, Oh, I don't believe in leaky gut. It is quite a contentious thing. The scientific research is there. It's called intestinal hyper permeability. You can look it up on PubMed or Google Scholar. You'll be able to find the research. I think people don't really Believe it or patients are a bit confused about it because a lot of practitioners are just testing for leaky gut and then doing gut healing nutrients like glutamine and zinc. Expecting that to fix the problem, but they're not addressing the root cause of why you have a leaky gut in the first place. So I just think patients come to me having done that saying, Oh, I've done that, but it's not actually fixed their health issues. We need to actually delve into the potential reasons you can have this hyperintestinal permeability. So what exactly is it? Intestinal hyperpermeability is a condition that occurs When the lining of the intestines become more permeable than normal. Allowing larger particles, such as food, proteins, toxins, and bacteria to pass into the bloodstream. This can trigger an immune response and inflammation in the body, which will contribute to the development of high histamine. And as I was talking about before, it's actually that the structure of the gut lining is held together by a complex called the tight junctions. The role of the tight junction is to allow beneficial ions, nutrients and water to pass into the circulatory system and at the same time prevent unwanted pathogens, toxins and undigested food from entering. So the tight junction complex is regulated by a protein called zonulin. And upon insult to the intestines from gluten and dysbiosis, zonulin is released. And this dissembles the tight junctions that hold the intestinal cells together. And studies show that people with histamine intolerance have elevated zonulin levels in this stool test. This is how you can get systemic symptoms of histamine such as hives, eczema, headaches, migraines, anxiety, insomnia, et cetera, from gut issues. So it is a real thing. Gluten will cause it. Dysbiosis will cause it, whether it be large bowel or small bowel. So SIBO can definitely cause issues with a leaky gut. When we get into the more complex areas such as oxalates and sulfur issues, this can also be a really big problem for gut healing. So oxalates will deplete the body of sulfur. And without sulfur you can't make mucin, which is a protective lining in the gut. It also makes your digestive enzymes. So it protects the gut. This is a really big deal when it comes to healing the gut. And I also just think about SIBO and the fact that it takes FODMAP foods and converts them into the gases. If you're curious to learn more about oxalate toxicity and its impact on histamine and methylation, I've got a 45 minute webinar covering exactly what oxalates are, why they accumulate, their symptoms, how they deplete sulfur, Lowering homocysteine plus I'll share safe strategies for moving oxalates from the body. This is a must know for practitioners, students, and anyone suffering with oxalate issues. You can find the webinar at joannekennedynatropathy. com. Just go to shop webinars and you can use the discount code OXALATES to enjoy 20% off. Now FODMAP foods are prebiotic. So prebiotic foods are really helpful for feeding the bacteria in the large intestine. And they're meant to get down to this, the large bowel. And those beneficial bacteria will take those foods and convert them into short chain fatty acids. And short chain fatty acids do many things including providing a fuel source for the cells of the gut to regenerate and repair and rebuild. So if you've got SIBO and you're not getting the FODMAP foods down to the large intestine, that's not helpful for the integrity of the gut lining to help repair the cells. So this is obviously going to be contributing to leaky gut. So it is a real thing. We just need to be getting to the root causes of all the reasons why you can have this intestinal lining that's hyperpermeable. Now we're moving on to LPS toxins or lipopolysaccharide toxins. So LPS are found on the outer membrane of gram negative bacteria. The LPS, the lipopolysaccharides, once they're released from these gram negative bacteria, they become toxic. And they're released when the bacteria die or multiply. And therefore they're recognized by the human immune system as a danger signal because they're a toxin. And the LPS toxins are going to trigger inflammation. And as we know, inflammation is going to drive up histamine. So these LPS toxins are another major cause of high histamine levels. A common gram negative bacteria is Helicobacter pylori. And there are several SIBO bacteria that are also gram negative bacteria. So moving on to one of my favorite topics, which is hydrochloric acid. And I think this is because I actually did this really deep dive one day. I was just fascinated by it. I was reading about the evolution of human stomach acid and why humans have such acidic stomachs. Way more acidic than a lot of other mammals. And in fact, just as acidic as vultures. It's because Paleolithic man. Our ancestors cavemen. And we still are like, let's face it. We're exposed to our feces. And they were probably eating animals that were rotting. Well, I'm sure that they were eating animals that were rotting. They probably had even stronger hydrochloric acid than we do today. And the reason being is that it's highly antimicrobial, right? So when I work that out, I say, wow, like hydrochloric acid is your first line of defense. If we are low in HCL, it's going to really expose our gut to pathogens. So, what is HCL? Hydrochloric acid is a strong acidic fluid and it's secreted by the cells of the stomach to break down proteins. It also suppresses the growth of ingested bacteria, thereby limiting the number of bacteria that pass into the small intestine. So when you eat your food, hydrochloric acid is released. It's going to break down your meat. If you don't break down your meat, it's going to sit, rot and ferment in the gut. This will cause a lot of histamine. Hydrochloric acid also is really important when it comes to other digestive enzymes. So I think about it as the conductor of the orchestra. When hydrochloric acid is released, a signal is sent to the pancreas to take pancreatic juice into the small bowel. Pancreatic juice is alkaline. So that alkalizes the small bowel and an alkaline environment is where the pancreatic enzymes will work. So they're not going to work well in an acidic environment. They work in an alkaline environment. So hydrochloric acid, it's starting the process of getting the small bowel alkaline. At the same time, a message is sent to the gallbladder to release bile. Now bile is going to help you break down fats. But bile is also a natural laxative and also has antimicrobial properties. So when there's a reduction in hydrochloric acid, there's a knock on effect with a reduction in all your other digestive enzymes. And the net result of this will be SIBO. So simply an acidic environment in the small intestine is a breeding ground for SIBO bacteria and candida for sure. It will definitely cause SIFO or small intestinal fungal overgrowth. So some of the major causes of low stomach acid are stress. I see that all the time. So when you're in fight and flight, you're not in rest and digest. It's very simple. You'll also see B12 deficiency as being really common as a symptom of people with low hydrochloric acid. There's proton pump inhibitors. They're medications that block stomach acid. Zinc deficiency can also lead to deficiency in hydrochloric acid as we need zinc to help make hydrochloric acid. So essentially you need to be sitting down, chewing your meal, chewing your meat effectively and properly, releasing the stomach acid. You need to not be taking these medications that block your stomach acid. You need to make sure your zinc levels are good. This will ensure that you're getting enough hydrochloric acid. And as I was saying, we also need these pancreatic enzymes. So these pancreatic enzymes, they also break down protein. They also work on fat, carbohydrate, and starch. So they're a really big player when it comes to digestion. And when there's dysfunction in hydrochloric acid production, then you're not going to be getting enough pancreatic enzymes or the environment is too acidic for the pancreatic enzymes to work properly. So in essence, if you're not breaking down your food, then there's more food for the SIBO bacteria, allowing them to dominate. Making SIBO way worse. And at the same time, if you're not breaking down your food, it will sit rot and ferment and increase your histamine. So let's chat about bile acid. Bile is quite complex actually. But when it comes to SIBO, what can happen is that the SIBO bacteria can deconjugate bile acids. That means it breaks them apart, causing them to be unavailable to break down your fats. With SIBO, you can often have fat malabsorption, which can cause nausea and pain or lose stools or diarrhea. Going in and pushing bile acids when you have SIBO is probably not going to be a good idea. You need to get the SIBO bacteria down first. So when it comes to digestive enzyme insufficiency, we just really need to be aware of it. I actually had a patient a couple of years ago now,. And when I look back, I just should have picked up how stressed he was. But he was an Aussie guy, he was a tradie, he was a surfer. Real sweet guy but tough. You know, quite stoic. And he was full of histamine. He had skin issues, anxiety, insomnia. He had some bloating and highly reactive to histamine foods. So right away I'm thinking, Oh, you've probably got SIBO. So I sent him off and he did the SIBO test. But it was negative. The same time we did some blood tests and it came back with his B12, which was really, really low. And he was eating a lot of animal protein. So I was thinking, wow, that your hydrochloric acid is just really, really low. And another symptom that he didn't really understand when I met him was he was chronically constipated. So although he was going every day, he had incomplete emptying and he just wasn't sort of aware. Well, he didn't know. He didn't know that it was incomplete. So he didn't know that he was constipated. And as soon as he started taking the hydrochloric acid, his bowels started to move. and his histamine started to really clear up. So the hydrochloric acid was breaking down his foot and his bowels were moving. The gut is just a long tube, isn't it? It was blocked. It was stuck. He didn't have SIBO. He just had these histamine issues driven from his gut, driven from low hydrochloric acid. And when we got talking, when he got to know me better and trust me, he told me that he had a lot of childhood trauma. He was dealing with a lot of anxiety. But the histamines were making it way worse. His trauma and anxiety had flicked him into a fight and flight response in his body chronically. Thereby not producing adequate hydrochloric acid. and thereby not being able to break down his food. So it's really interesting where the nervous system is such an important part of digestion. And it's actually a really important part of how the immune system reacts. Because when the nervous system is out of whack, when it's challenged, it's hyper responsive. The immune system will get involved as well. Obviously causing inflammation and histamine can be released. Before we go any further, I want to speak directly to the practitioners and students listening. If you're intrigued by histamine intolerance and eager to expand your knowledge, particularly around methylation and how to apply this understanding in clinical practice, we offer the Histamine and Methylation online group coaching course. The only program of its kind. It covers everything you need to know about histamine and methylation, providing both the theory and guidance you need to treat these issues effectively in clinical practice. To learn more and apply, visit joannekennedynaturopathy.Com. That's digestive enzymes. So we're going to move on to inflammatory bowel disease. There's two diseases that fall under that umbrella. Which are Crohn's disease and ulcerative colitis. And as the name suggests, inflammatory bowel disease causes significant gastrointestinal tract inflammation and inflammation results in a reduction in the synthesis of the DAO enzyme and at the same time is going to release histamine. Research shows that people with Crohn's disease and ulcerative colitis have significantly less DAO enzyme activity in the gastrointestinal tract compared to healthy individuals. If you have IBD, taking DAO enzyme might be an important part of your treatment. So if you're in a flare, especially when there's a lot of gastrointestinal tract inflammation and you're having histamine symptoms, then taking the DAO enzyme before meals might be a really good idea to help you tolerate more high histamine foods. We're going to move on to Helicobacter pylori, which is actually an infection. It's different to SIBO. SIBO is your own body's bacteria. That's overgrown in numbers that are problematic. Whereas Helicobacter pylori is an infection, which means that you can pick it up from other people. It's also gram negative. And remember those gram negative bacteria release the LPS toxins, which are highly inflammatory. Also causing high histamine. Helicobacter pylori can cause chronic gastritis and gastric ulcers, and the mucosal damage that occurs in helicobacter pylori, chronic gastritis and peptic ulcers, that is gonna stimulate cells to release histamine. And what I find clinically is that it is a bit of a roadblock. Helicobacter pylori can be a bit of a roadblock. Because this is kind of what happens. So when you have H. pylori, a lot of histamine is being produced in the stomach, stimulating hydrochloric acid. You might get a lot of reflux and heartburn. Then you'll be put on a proton pump inhibitor. So that will be symptomatic control. At least until you sort out testing and treating the helicobacter pylori, which includes the proton pump inhibitor and the antibiotics. If you have SIBO as well, that is probably going to make SIBO worse. So this is where it gets a bit complex. So what I find hard here is that people with SIBO really need to take hydrochloric acid to get on top of their nutrient absorption and to really help SIBO treatment. So what I found clinically is that if you do a SIBO low histamine diet at the same time as treating Helicobacter pylori. Getting your histamine bucket down can really help with those that are getting way too much hydrochloric acid production with that combination of Helicobacter pylori and SIBO. It's a patients that actually have a lot of bad burning pain, right? What you don't want to do is go in and give them hydrochloric acid because that can cause pain that can last for days. So I actually don't treat a lot of helicobacter pylori. I often send them off to the doctor to get the triple therapy also. Cause I know it can actually lead to cancer. And they do that. And then I work with them. As soon as they've done that to like heal the stomach. get the SIBO under control. And then if they do need hydrochloric acid, it's a better sort of safer environment to do that. Now, I know a lot of practitioners do work with Helicobacter pylori. That's fantastic. If you need help with H pylori, I'm sure there's a lot of gut naturopaths that are getting great results with it. It's just because I think the patient groups that I see are usually severe presentation. They often have a bucket of histamine. And we just need a clean slate to work with. Now we have a really big topic. And this alongside mold, I would say is the hidden cause of histamine. I say it's hidden because no one knows about it and it's oxalates. So what exactly are oxalates? Oxalates are natural occurring molecules found in many plant foods at varying amounts. They are also in several species of mold. if you know you've had mold illness. If you've been exposed to mold, then you really need to look into oxalates. Hopefully at the same time that you're dealing with your mold or at least afterwards, once you've realized there's an oxalate problem, because it can actually be making you feel worse than even the mold. Also our bodies make oxalate as part of the breakdown of glycine and hydroxyproline. So these are actually two amino acids that are particularly abundant in collagen. And what's everyone doing? They're supplementing with collagen because social media telling women they need collagen. So rightly so. However, If you have an oxalate problem, adding more collagen into your diet might not be helpful. It can potentially be causing a buildup of oxalate if you can't break it down properly and also flaring of histamines. So when collagen goes to liver, it gets broken down in the liver and then it gets converted back into glycine and hydroxyproline. And they are then converted into a compound called glyoxalate. And glyoxalate can then be further metabolized into oxalates. In the liver and then they're excreted via the kidneys into the urine. But there are certain conditions that can hinder that process and drive up oxalate in the body. The other thing we need to know about oxalates is that the gut microbiome breaks down oxalate. Oxalates coming in the gut, right? So oxalates coming in from the diet, we need a healthy microbiome to break down oxalate in the gut. So when we have really low beneficial bacteria, we're going to have problems breaking down dietary oxalate. What then happens is that you get a buildup of oxalate and essentially they are very sharp crystals. They deposit in the gut, in the joints, in the bladder, in the urethra. They can get into the thyroid. They can even get into the brain and they cause chronic inflammation. Which will drive up histamine. And not many people know about them. If you are in the oxalate world, of course you know about them. But I can't tell you how many organic acids tests I've seen of patients that have high oxalates and it's ignored. It's completely ignored. I actually had a patient recently, she's living in Asia and she's so unwell. She has every symptom under the sun and she's living in mold. She's been living in mold for a long time and she did an organic acids test five years ago and all her oxalate markers were high. And not one practitioner has stopped and thought, wow, this is a big problem when it comes to the priority of things. So oxalates really are one of the first things we need to get under control because they're disrupting your sulfur. In complex ways, they reduce the body of sulfur and sulfur is the second most abundant element in the body. It's essential for so many processes. It helps make the lining of the gastrointestinal tract. It helps make your digestive enzymes, your ligaments, connective tissue. It's key for the sulfation pathway, which is a liver detoxification pathway, and it makes glutathione. So super important. So if you're low in sulfur, wow, like we really need to fix that. If you've got an oxalate problem, then this is something we need to work on as a priority. So if you are someone with histamine issues and you've gone down that SIBO pathway. Tested SIBO. You've treated it or tested it, it came back negative. You've got gluten out of your diet. You've done lots of work on your hormones and you've done many other things and you're still not well. Then it could definitely be worth your while looking at oxalates and mold. So mold it's everywhere. It causes havoc in the body in a lot of people. Some people are more genetically susceptible for not being able to process mold. So how I look at my histamine cases, it's like a process of elimination. And so if I see a patient come in and I look at their diet, I'm like, how much gluten are they eating? Are they sensitive to gluten? We go through SIBO symptoms. Right. So I think about SIBO. Do they have a low symptoms of SIBO? Yes. No. Then I think about all the symptoms of oxalates. But when I often get patients that come in and have done every test under the sun, especially if I've got their gene reports. People that do gene reports are unwell. They're sick and they've sort of, they've been unwell for a long time, they're trying to find answers. So they come in. They've done gene reports. They've done Dutch hormones. They've done SIBO, stool testing. Nothing found. And I can see these patients from my form. They tick every box. I've got every symptom. You know, a lot of histamine symptoms, pain symptoms, fatigue symptoms. They can't eat anything. They have multiple food intolerances. They have multiple chemical sensitivity. And these are so often the mold patients. And when I'm training my practitioners, I talked to him about this. It's like, when it's not a simple SIBO or gluten intolerance case, when hormones are balanced, they're eating well and there's chronic illness and chronic histamine load, you just got to get your head around mold and oxalates. I don't stop until I'm convinced someone doesn't have a problem with it and they usually do. So if mold not picked up, it's going to keep on driving histamine. It's just going to keep on driving up your histamine bucket. Disrupts the microbiome. Really taxes the immune system and the nervous system. So we can't ignore it. We need to really, really make sure that we pick up mold in our patients. You know, mold, it's common. It's found in the environment on plants, soil, decaying organic matter. And so when mold is growing indoors on damp surfaces, such as walls, ceilings, and floors, this is when it can be very harmful to humans. And when it is growing indoors, it produces high levels of spores called mycotoxins. And mycotoxins can get into the blood and wreak havoc. You can't see these mycotoxins, they're microscopic, they're everywhere. They're released into the environment, they get onto the walls, into your bedding, into your body. They love natural fibers, carpets, a couch, they're everywhere. And as I was saying, they cause chronic inflammation in the body, they'll really drive up your histamine. Mold mycotoxins can lead to a condition called CIRS. Chronic Inflammatory Response Syndrome. It's a multi symptom, multi system illness. a lot of histamine symptoms. And what happens in CIRS is that normally when the body detects something, so an environmental toxin like mold mycotoxins, it triggers the innate immune system. So the innate immune system is the first part of the immune system that gets triggered when there's a threat and it causes pain and inflammation. There's a lot of white blood cells that are involved. And cytokines, which are inflammatory mediators, are also involved. And then the mast cells get involved. And they're going to release histamine. And when this part of the immune system kicks in, you start to feel unwell, which is a trigger that there's something wrong. So it's telling you, stop doing that thing, remove yourself from that thing, that environment. It's like a warning, warning, warning. Right? And as I said, this part of the immune system has mast cells. So they're going to degranulate and they're going to release a lot of histamine and other inflammatory mediators. And then what is meant to happen on around day four is that your adaptive immune system is meant to kick in. This is your antibody antigen part of the immune system. So your body will produce an antibody against an antigen. An antigen is another word for a toxin and there's an antibody created for each type of toxin. So it's a very robust part of your immune system. I think of it like the special services. It's like highly trained soldiers and these antibodies, they know exactly how to deal with their specific antigen. But what happens in CIRS is that you do not mount an antibody response. So the adaptive immune system does not kick in. And your innate immune system, this is the first part of the immune system with those mast cells. They just don't stop. It remains active. So you're continually releasing inflammatory mediators, including histamine from those mast cells. So that's part of the picture of CIRS. Like it's quite complex. But when it comes to CIRS, one of the major causes of CIRS is mold and mold mycotoxins. And then we've also got a condition called mast cell activation syndrome or MCAS, and it's a condition characterized by abnormal activation of mast cells. So individuals with MCAS, the mast cells are overly sensitive and react inappropriately to a wide range of triggers, including mold mycotoxins. So CIRS and MCAS, a lot of the causes of CIRS and MCAS are mold. And I see this a lot clinically. I see people diagnosed incorrectly with MCAS a lot. They're told they've got MCAS. Whereas they've actually got histamines being released from their hormones or from digestive enzyme insufficiency or from SIBO. I do see that a lot clinically whereby it's just different cause it's a different mechanism. What's going on and obviously different causes, therefore different treatments. I'm now going to talk about how methylation is important to know when it comes to histamine. Methylation is a biochemical process in the body whereby a methyl group. So a methyl group is a carbon atom. And it's got three hydrogen atoms attached to it and a spare arm. So if you just write on a piece of paper, a C and then North, South, East, West, a H and then one, and then put a H on three of those, and you'll see a spare arm. That's a methyl group, right? And that spare arm, it goes around the body. And it attaches to a substrate, which can be DNA, RNA, proteins, neurotransmitters, hormones, immune cells, and nerve cells. And when this occurs, that chemical compound has been methylated. And when it comes to histamine, there is an enzyme that requires one of these methyl groups. And that enzyme is called the histamine N methyltransferase enzyme. The HNMT enzyme, and that breaks down histamine found inside the cell. The DAO enzyme deals with histamine outside the cell and the histamine N methyltransferase enzyme deals with histamine inside the cell. So if you want to know more about this, you can go to episode one, where I talk about all about the science of histamine and how we make it and how we break it down. What we need to understand about HNMT is that you require the methylation pathway to be running. So it's complex. I'm going to be doing a lot of episodes on methylation, but what you need to know is that there are many environmental things that can hinder that pathway. And the funny thing is that a lot of the drivers of high histamine that you've learned about are common disruptors of methylation including digestive enzyme insufficiency. Why? Because if you don't break down your food properly, you might not be getting adequate vitamin B12 or methionine. Both are what we call methyl donor nutrients. They're nutrients required for methylation. If you've got SIBO, you can have malabsorption of folate. and vitamin B12, both important for methylation. If you've got an oxalate problem that can drive down your homocysteine. This complex, but homocysteine is required for the production of SAMe, which is the body's major methyl donor. So it goes around the body and it donates these methyl groups. So SAMe is the co factor for HNMT. The co factor is there to, support the functioning of that enzyme. It actually allows it to work properly. It's interesting just to say that What drives up histamine can so often disrupt methylation. And this is what I teach my practitioners is this framework. It's understanding that histamine in methylation. These links, it's so important to understand this in clinical practice as it can really help you pinpoint and nail down that problem really, really quickly in your patients. Another thing that's important to know about HNMT is that it's the enzyme that breaks down histamine in the central nervous system and the DAO Enzyme is absent in the central nervous system. So histamine symptoms such as vertigo and migraines, anxiety, insomnia, and inability to control your body temperature, motion sickness. Well, we need to think about not just what's going on with histamine, but what's going on with methylation. If you have neurological histamine issues and you've tried taking SAMe or methylated nutrients and it's helped you, fantastic. But if it hasn't, these nutrients can often cause side effects because it's breaking down histamine in the brain. But you need to address. It's why you have high histamine in the brain in the first place. It's often not a genetic issue. It's usually environment. It's epigenetics. It might often be due to the things that we've already discussed. So histamine in the gut can cause histamine in the brain, oxalates wherever they're depositing in the body and driving up systemic inflammation can definitely get into the brain. Eating gets in the brain. If it's too high, it can cause too much histamine in the brain. So when you break it down quickly with a methyl, sam e or methyl b, methylfolate. It can come out as an adverse reaction because it's actually just not addressing the cause. So you can be doing it too quickly. So I rarely put my patients with high histamine or methyl straight away. We need to get it down first. Oh, do you know what I forgot to talk about? It's oestrogen. So there is a really interesting link between histamine and oestrogen. So histamine stimulates the ovaries to release estrogen. And then estrogen can increase histamine in a few ways. So firstly, we need to know that there are estrogen receptors on mast cells. So estrogen can attach to these mast cells, causing histamine to be released from the mast cells. There are also estrogen receptors on nerve cells in the brain. So when estrogen gets into the brain, it's meant to, but kind of when it's too high, it can cause too much histamine to be released from these nerve cells in the brain. And this is why we can see women with hormonal migraines or hormonal anxiety. Like I know the anxiety progesterone. But if you got low progesterone, you might likely have unopposed estrogen causing a buildup of histamine. Too much histamine being released. this is why you might see a worsening of your histamine symptoms at ovulation when estrogen is peaking, or before menstruation when your progesterone is dropping. Estrogen also reduces DAO enzyme activity. So we can really see there's a very vicious link that goes on between histamine, estrogen, histamine, estrogen. And when women go into perimenopause, you might actually find yourself more sensitive to histamines. Definitely more sensitive to alcohol. It's a few reasons for that, but just histamine foods in general, you might start getting migraines for the first time when you're in perimenopause because when perimenopause your progesterone is dropping and your estrogen is often unopposed. So you might not be low estrogen yet, and that excess estrogen compared to progesterone is increasing your histamines. So if that's ladies, if that's happening to you, potentially you've always had some niggling histamine issues. I urge you to look into all the causes of high histamine. But in some women, it is just for the first time in perimenopause because of the disruption in the cycle and the low progesterone. And potentially, this is where you can start looking at supplementing with bioidentical progesterone. Ladies, if you'd like to learn more about how hormonal imbalances can drive up histamine levels and what to do about it, I have a 40 minute webinar on this fascinating topic. In this webinar, I cover What hormonal imbalance actually means, how estrogen can drive up histamine levels, the signs and symptoms of estrogen dominance and progesterone deficiency, the estrogen detoxification pathways. This is a must know for practitioners and students, as well as my favorite supplements for hormone imbalance. And much more. You can find the webinar at joannekennedynaturopathy.com. Just go to shop webinars. You can also use discount code HORMONES to enjoy 20% So we also have genetic polymorphisms. And I know I do MTHFR, I promote that I do that and I do. But one of the main reasons I do is that there's so much misinformation on MTHFR. People will say, Oh, grandma said I've got MTHFR or this practitioner or lady in the health food shop, you got MTHFR, you have to take methyl Bs for the rest of your life. And it's actually not necessarily true. Or they blame their MTHFR gene mutation on their chronic health issues. they blame it on their histamine issues. But what we need to understand about these genes is that it's the environment causing dysfunction in the enzyme in real time in your body. It's called epigenetics. And the genes that we're looking for in the genetic tests that people are doing, they provide the code for the enzymes in the body to function. So the MTHFR gene provides the code for the MTHFR enzyme. And it's that enzyme that takes folate from food and converts it into methylfolate. And methylfolate is really important for methylation. But just because you've got an MTHFR gene mutation doesn't mean that you have a deficiency in methylfolate necessarily. You might. Right? But there are other things that can cause low folate levels. So if you're not eating any green leafy vegetables and you're not consuming any folate. You need folate to be converted into methylfolate. Or if you're taking a lot of folic acid. It's fortified in wheat in a lot of countries in a lot of supplements, it blocks the uptake of your natural folate from food. So if you're blocking the uptake of your natural folate, that can cause a reduction in the amount of methylfolate you have. SIBO can reduce the absorption of folate. Okay. So we need to be thinking about environmental things as well. We've also got the DAO genetic mutations. So I've had quite a few patients in Germany and some of the practitioners I train are in Germany and Austria. They do this testing all the time and collectively we don't actually see that many patients come back with an actual DAO deficiency in the enzyme function. You might have a gene mutation on DAO, but it might not necessarily be showing up as a deficiency in DAO. Does it mean you're not full of histamine? You might be producing a lot of histamine. You might be producing DAO enzyme, you might be producing it. But I'd say it's overloaded with histamine. Or your histamine issues are neurological where you need methylation and HNMT enzyme to deal with the histamine. So it's just not a test I do a lot because We normally just need to spend our money and focus on identifying the cause and freeing up that DAO enzyme, like just not overloading it with too much histamine. So you can also have a gene mutation on the histamine n methyl transferase enzyme. Okay? So remember the gene provides the code for the enzyme. And I have had people say to me. The only reason you would have neurological histamine issues is because of a gene mutation on HNMT. And it's just not correct. There are many causes of why there can be high histamine in the brain. Not just a deficiency in that enzyme due to a gene mutation. Having a gene mutation on HNMT might mean that you are going to do worse than your neighbor that doesn't. Right? But if your neighbor, your friend has no mutation on HNMT, it does not mean that they are completely risk free of getting any neurological histamine issues. Because they can simply have way too much histamine in the brain from gut issues, from estrogen, mold, marcons, which I will talk about in another episode. It's an overgrowth of particular bacteria in the nose, or at least a lot of histamine that can get into the brain. With or without this gene mutation you can have issues with the amount of histamine in the brain. So I hope that makes sense. We have these gene mutations that are interesting to look at, but it's the environment that is the really big thing we need to think about. And that's good because we can do something about it. You can spend time and money doing the functional medicine tests that help us get to the root causes rather than just doing gene testing and supplementing for an enzyme. I've seen this a lot. People do gene reports and they're told by these companies, you need to take SAMe. You need to take methylfolate. You need to take vitamin C. You need to take copper. You need to take the coenzyme for that gene. And often it is wrong. So for instance, you're told to take some methyls, you're a bucket of histamine, it can make you way worse. You're told to take vitamin C, it actually reduces methylation, it also increases oxalate. For instance, you might be told to take copper, but your zinc levels are really low. And you need the balance of zinc and copper that needs to be in a one to one ratio. So there's many reasons why you shouldn't just be supplementing from a gene report. What they're telling you to do is to take the co factor to support how that enzyme works in the body. But we need to understand why the enzyme is not working well in the body. It's just often sluggish. Really mainly due to chronic inflammation. I hope that makes sense. Finally, we need to chat about medications as there are some medications that can increase histamine. Now I urge you do not stop these medications because I say so. You really need to work in conjunction with a doctor if you're thinking about reducing or coming off any of your medications. But there are many drugs that can either stimulate the release of histamine or inhibit DAO enzyme activity. So some of them include muscle relaxants, Analgesics, including morphine and non-steroidal anti-inflammatory drugs. Some are local anesthetics, anti hypnotics, antihypertensives, antiarrhythmics diuretics, many different antibiotics. Bronchiolytics, H1 receptor antagonists, H2 receptor antagonists, antidepressants, anti diabetic medication, proton pump inhibitors, and antacids. So these are the common classes of drugs that we see impacting histamine. I'll put this list on my website in the show notes. If you'd like to take a look, you'll be able to see this list of medications. And I urge you to always check with your prescribing doctor if you want to change any medication. So that's a wrap. That is all the major causes of high histamine that I see in my clinical practice. These are very common issues that we're dealing with. in the patient base that are presenting to my clinic. So essentially, these are the issues that drive up inflammation in the body. And what is chronic illness? It's inflammation and it's driving up histamine. For someone suffering with histamine intolerance, I encourage you to leave no stone unturned. There are many things that are commonly missed. Commonly missed things are oxalates and mold. That's just a starting point. If you've gone through this list and you don't put a tick next to everything that you've definitely gone through all these conditions and made sure that you've had proper treatment and you're still getting issues, then please dig deeper. We're open for business. We see clients all over the world. We're And you're more welcome to see us for an appointment. And again, I've got my eBundle. So the eBundle is an ebook. It's very well researched on all the different causes of high histamine. There's my treatment protocols in there as well. So you can tackle this yourself, or you can take it to your current physician, naturopath, nutritionist, functional medicine doctor. You can take it to them and say, Hey, can you help me get these tests done? You can then work in conjunction with them getting the test done and hopefully they can come up with the treatment protocols to treat the root causes on the back of what the testing finds. So it's all about treating the root causes. So practitioners and students, these are must know conditions, especially if you're going to be treating histamine issues. And especially if you're going to be dealing with methylation. Supporting methylation in your patients because these are also major drivers of methylation disruption. If you're a practitioner or student, again, you're most welcome to join the Histamine and Methylation online group coaching course. It's the only course of its kind teaching you everything you need to know about histamine and methylation in clinical practice. It's not just theory. It's 12 years of my clinical practice. We have live zoom calls each week. So you will learn so much from me and also so much from other practitioners who are dealing with these issues in their clinical practice. Thank you for joining me on this deep dive into the major causes of histamine intolerance. I hope this episode has provided you with valuable insights into the science and key factors contributing to histamine issues, empowering you with the knowledge to support your work as a practitioner or your own health journey. If you've enjoyed this episode, be sure to subscribe to the Histamine Well. Leave a review or share it with someone who could benefit. If you have any questions you'd like answered or have a topic you'd like me to discuss, please go to my website, joannekennedynaturopathy.Com, where you can provide us with that information. So I'll see you next time where I interview my colleague, Melanie Peers, who has an absolute world of knowledge on oxalates. Until then, take care and be well.