24. Histamine & Anxiety – How High Histamine Triggers Fight-or-Flight Symptoms

Can histamine be the hidden reason behind your anxiety?

In this episode, I break down how histamine acts as a neurotransmitter in the brain — and why an overload can leave you wired, anxious, and unable to relax. We dive into how methylation, estrogen, mold, and gut inflammation (including SIBO and oxalates) all feed into the histamine-anxiety loop.

Whether you're a practitioner treating patients with anxiety or someone who’s tried everything to feel better — this episode gives you a deeper lens into the hidden biochemical drivers of mental health symptoms.

If you've ever felt overstimulated, panicked, or like anxiety hits out of nowhere, you're going to want to hear this one.

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Transcript

Joanne Kennedy: 0:00

Hi, it's Joanne. What if your anxiety isn't coming from your mind, but from your gut, your hormones, and your histamine pathways? What if that sense of panic, the racing heart, the sleepless nights and that wide but exhausted feeling all stem from something deeper? Something biochemical. If this sounds like you stick around because we are diving into how histamine could be a major overlooked driver of your anxiety. 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 are 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. Hi everyone, and welcome back to the Histamine well. In today's episode, I'm going to be discussing how histamine can cause anxiety. We'll be looking at the main drivers of high histamine in the brain, including methylation imbalances, chronic stress, gut issues such as sibo, helicobacter pylori, oxalates gluten intolerance and digestive enzyme insufficiency, as well as the impact of mold exposure. This episode is a must listen for practitioners working with patients who have anxiety and chronic histamine issues. For students, this is core knowledge you'll absolutely need to know when you start practicing. And if you're someone dealing with histamine intolerance or anxiety yourself, I hope this episode gives you some valuable insights into what might be the cause of this for you. So let's get started. First of all, we need to understand that histamine acts as a neurotransmitter in the central nervous system. When histamine levels in the brain are high, it increases arousal, wakefulness, and vigilance. Essentially priming the nervous system for action. And this heightened arousal activates the sympathetic nervous system, which is your fight or flight branch of the autonomic nervous system. So the autonomic system, we've got fight or flight, or we've got rest and digest, which is parasympathetic nervous system. When the sympathetic nervous system is triggered, it releases noradrenaline, or it's also called norepinephrine direct directly from the sympathetic nerve endings in the brain, as well as the heart and blood vessels and other organs. So when the sympathetic nervous system is activated, it also sends a signal down to the adrenal glands to release adrenaline, which is also called epinephrine. And this gets released into the bloodstream. It's this adrenaline that gives you this more systemic impact. It really, really amplifies the fight or flight response. And it happens in multiple organs at once. So when this happens, we see symptoms such as sudden anxiety or panic. It can feel like it hits out of nowhere, racing thoughts. Irritability or feeling on edge, it can make you hypervigilant. So feeling overly alert or really jumpy. It can definitely cause insomnia. It can cause emotional reactivity. So crying easily, feeling overwhelmed. It can also cause intrusive thoughts or a sense of impending doom. It can cause mood swings or rage outbursts. And this is particularly common in perimenopausal women. You can also get cognitive symptoms such as brain fog. You can have difficulty concentrating or staying focused. You can feel really wired, but tired. And you feel really overstimulated when you're in busy environments. The physical symptoms include heart palpitations or racing heart. Which is tachycardia. Shakiness, or tremors. Muscle tension. You can feel really sweaty, cold, clammy hands. You can get shortness of breath or shallow breathing, diluted pupils. You can get headaches, lightheadedness, or dizziness, and then you can have the digestive. Issues such as nausea, urgency, or cramps due to blood flow being shunted away from the gut. So these are the typical fight and flight symptoms. But we've gotta understand that histamine can absolutely cause these fight or flight symptoms. So these are the symptoms that we would get if we're chased from a wild animal or if we're in a car accident or something like that. But histamine can absolutely cause these symptoms and you know, you might think, oh, not as severely, but sometimes absolutely it can cause people to have a quite a significant release of adrenal. Then we get this adrenaline crash, so the aftermath. People can feel fatigue or burnt out. You can get low blood pressure or dizziness upon standing, which is pots like symptoms. You can feel depressed or a real emotional flatness. You can also have salt cravings or an electrolyte imbalance. There all the symptoms that can happen when the histamine is driving up the adrenaline. What causes all of this buildup of histamine in the brain? Both over methylation and under methylation can potentially lead to high histamine levels in the brain, but for different reasons. We'll start with under methylation. We need to understand that histamine is broken down in the brain by the histamine n methyl transferase enzyme. The HNMT enzyme. And it uses SAM E as its cofactor, and SAM E is a methyl donor. So because it's called a methyl transferase enzyme, histamine, n methyl transferase enzyme, it needs a methyl group to work. Now if you are an under methylator and you have low Sam e available and a slow methylation cycle, this can lead to you not having enough methyl groups to break down histamine in the brain. And this will cause the histamine to build up in the brain. And some common reasons for this are genetic variants such as MTHFR, MTR, MTRR. As well as you can have a variant, a mutation on the histamine and methyltransferase enzyme itself. Or you can have nutrient deficiencies. So there are certain nutrients that are methyl donors such as methylfolate, methyl B12, choline and methionine. These are all really important nutrients you need to make these methyl groups. To make the Sam E. Things like chronic stress and chronic illness can also deplete the body of these methyl donor nutrients. So essentially when with under methylation, it's super simple. You don't have enough methyl groups to break down histamine in the brain. Over methylation can also cause high histamine. So paradoxically, in some people pushing methylation too hard by taking methyl donor nutrients like methylfolate or methylcobalamin or Sam e can upregulate histamine release from the nerve cells. And this is because these methyl donors, they stimulate neurotransmitter synthesis and turnover. So remember, histamine is a neurotransmitter. And when people are over methylating, it increases all the neurotransmitters in the brain. Including dopamine and serotonin and the norepinephrine. When the norepinephrine is high, when the brain senses that it's high, it causes it to become in fight and flight, and then the adrenals get the message to release adrenaline. This is why sometimes it's hard to tell if someone's over or under methylating, what's going on with histamine in the brain. Some people are just over methylators due to other genetic variants. Estrogen is definitely pushing a lot of women into being over methylators. Cortisol can do it as well. So it's a bit nuanced. If you are taking these methyl donor nutrients and that's happening to you, then absolutely you need to stop them. But often people are not taking these methyl donor nutrients and they're over methylating and they're not actually aware that they are over methylating. So this is why I'm always testing methylation in my patients in real time with the mood sense test. Mood Sense is an at home saliva swab test for methylation. It shows you if you're over or under methylating, and once you do the test, you enter that information onto the online portal. And the company tell you what supplements you need to take. It's very simple. There's only a few supplements and I've been using it in clinic and getting amazing results. For listeners of this podcast, I've secured you a 10% discount. If you use the code HISTAMINEWELL10. And you can get access to that test via my website. Let's just recap that. If you are an under methylator, you're just not breaking the histamine down via that HNMT enzyme. This seems to be like chronic buildup of histamine in the gut. Like just low grade, but chronic anxiety. Insomnia. It can also cause migraines and dizziness and vertigo to build up in the brain. Whereas when someone is over methylating it's basically all the neurotransmitters in the brain can be jacked up. And we are seeing people with like high dopamine symptoms like agitation, serotonin syndrome, such as really bad depression. And then the high norepinephrine triggering the adrenaline. These people are often really the jittery anxiety. The heart palpitations. The early morning waking. If you feel irritable or anxious after methyl supplements, this is a classic sign that you are over methylating and you should not be pushing your methylation. So what do you do? You absolutely need to test. What are the other things that can cause high histamine in the brain? So when there's too much histamine in the gut from things like gluten intolerance, low digestive enzymes, helicobacter pylori, sibo, candida, oxalate, all of these things can set off inflammation in the gut. And this inflammation sends messages to the brains in two main ways. Firstly, it's via the vagus nerve. So the vagus nerve connects the gut to the brain. When it detects inflammation or high histamine, it sends a signal to the brainstem which then activates the brain's own histamine producing neurons. Causing a buildup of histamine in the brain. The second way is through the immune system. Inflammation in the gut triggers immune cells to release chemical messages called cytokines. These cytokines travel in the blood until the brain's immune cells to make more histamine. So both of these pathways will increase histamine levels in the brain. We don't actually need histamine itself to be crossing into the brain from the gut. It's doing it by these chemical messengers and the vagus nerve. Now, if the inflammation becomes really chronic, it can actually make the blood brain barrier more permeable. The blood brain barrier is a protective layer that normally keeps substances in the blood out of the brain when it's more permeable. Histamine from the bloodstream can get into the brain and add to the histamine that's already being made in the brain. So it's gonna cause excess histamine in the brain. So clinically, I see this all the time. People come in with gut issues, SIBO and oxalates, and digestive enzyme insufficiency, gluten intolerance. And they are getting these mental health symptoms from their digestion. Anyone that has gut issues and high histamine in the brain can attest to. Absolutely. When my gut's out, when I eat high histamine foods, I get a worsening of my anxiety. I get a worsening of my heart palpitations. I can't sleep properly, et cetera. What do we do about the histamine in the gut? Obviously you need to get to the root cause, but what you can do quickly put yourself on a low histamine diet. It really does reduce that histamine load quickly. Most people with gut issues do have sibo. It's so common. It's caused from stress, it's caused from digestive enzyme insufficiency. It's caused from mold, it's caused from eating processed foods. It's caused from antibiotic use. So if you suspect you have sibo, I do have on my e bundle, the sibo, low histamine diet as part of my E bundle, so that diet can get your histamine bucket down super fast. There's lots of recipes as well, so that's really helpful. You can also take the DAO enzyme. There's many commercial products available. I often recommend Seeking Health Histamine Digest, so it's the DAO enzyme. The DAO enzyme breaks down histamine in the gut. It's absent in the central nervous system, but if you've got the gut issues causing the histamine to get up into the brain, then you wanna take a load off the gut. And taking D Enzyme can really help. Taking saccharomyces boulardii can upregulate the DAO enzyme, making it more available. You can also consider Procetin or vitamin C to stabilize mast cells that release the histamine. So doing all of this whilst you get to the root cause often can give you a lot of relief from your histamine gut symptoms. Therefore, the neurological symptoms including anxiety of high histamine. Before we go any further, I want to speak directly to the practitioners and students listening. If you're intrigued by histamine and methylation and eager to expand your knowledge in this fascinating area. 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. We cover sibo, hormonal imbalances, oxalates, M-T-H-F-R, the four pathways of methylation, including the folate pathway, methionine pathway, tetrahydro biopterin pathway, and the all important transsulfuration pathway and much more. The program is delivered by detailed online webinars and handouts for you to keep. And for eight weeks you'll meet with me for live coaching calls in a private community space with other practitioners from all over the world dealing with histamine and methylation issues in their patients every day. Together we learn so much. To learn more and apply, visit joannekennedynaturopathy.com. The next thing I'm gonna talk about is estrogen, and how estrogen can increase histamine, both systemically and in the brain. Estrogen released from the ovaries, it moves into the brain, it's meant to. And we have. Estrogen receptors on the histamine, neurons in the brain. So when estrogen attaches to the histamine neurons, especially if estrogen is a little bit too high, it will start firing off histamine in the brain. And as we know, histamine in the brain when it's too high, causes an increase in epinephrine because the brain thinks it's on high alert for threat. The fight and flight system kicks in. And then the adrenaline kicks in from the adrenal glands causing anxiety. Estrogen can also stimulate mast cells to release histamine. Mast cells that are in the blood and they're also found in the gut and other organs, they will start to release histamine. And as we know, the more histamine we have in the gut, the more histamine we can get in the brain. Estrogen also downregulates the DAO enzyme that breaks down histamine. We can see that when you are both high histamine and high estrogen, it's this really vicious cycle. And this is why women so often get heightened anxiety at ovulation if they're estrogen dominant. Too much estrogen compared to progesterone or if they've got a pre-existing histamine issue. And then before their period when progesterone drops and estrogen is unopposed, this can also cause a heightening of anxiety. So what do we do about this? Obviously you need to try and get the histamine down in the gut. You need to detoxify your estrogen. Calcium D Glucarate is a great supplement for that. You need to support the production of progesterone. Nutrients for progesterone include zinc, B6, iron iodine, and Vitamin D. When you are low particularly in iodine or iron or Vitamin D,'cause you can test all these things. You will have symptoms of low progesterone. It's so common. So you need to make sure you get those nutrients up if you are perimenopausal, starting to take bioidentical progesterone can be really, really helpful and. The fact that estrogen is detoxified via methylation means that you need to support methylation. So you need to understand if you're an over methylator or an under methylator. And that mood sense test, the at home saliva swab test for methylation is the best and easiest way to do that. Now we are moving on to mold. So when you're exposed to mold, the mold can release toxins called mycotoxins. And these mycotoxins can get into your body through the air you breathe, the food you eat, and even through your skin. And once they're in your system, these mycotoxins cause inflammation in the gut and the respiratory tract. And that inflammation can set off the same gut brain communication pathways that I was talking about via the vagus nerve and the immune system causing high histamine in the brain. The vagus nerve is sensitive to inflammation and irritants such as mycotoxins. When mycotoxins trigger inflammation in the tissues it connects to, the nerve itself can become irritated. This irritation can change how the vagus nerve signals between the gut, the brain, and other organs. It also increases the activity of brain histamine pathways. Mycotoxins can also get into the bloodstream. And if the blood brain barrier becomes more permeable, they can then pass into the brain. And once inside the brain, they will stimulate these histamine, histaminergic neurons to release histamine causing spikes in anxiety. Mold is a big problem. You would've heard me talk about this a lot on my podcast, especially when it comes to nervous system dysregulation and high histamine. The first thing we need to do is you need to assess your home for mold. Like, trust your nose. If your bathroom, your laundry, your wardrobe smell musty, that classic damp smell. It's often a sign that there is mold and there is mold mycotoxins. You need to look for past water damage. Has there been a history of leaks, flooding, burst pipes, roof damage? Is there condensation around the windows? This can definitely be a big red flag for mold. You need to check your house for ventilation. Mold loves dark, damp, still air. Think bathrooms behind furniture, under kitchen sinks, wardrobes. It's in air conditioning units or old mattresses. And observe how you feel in different environments. Do you feel worse at home and better when you leave the house, when you go to work? Or when you're on holidays or when you're just spending more time outdoors. This is a really interesting pattern. I've had a lot of patients recently, several patients just recently with mold illness that they have no idea that they've got mold illness. And they're so sick they've had to leave work, and then they've spent weeks at home trying to get better and they get worse and worse and worse because they're not leaving the house. And they'll often say, oh, like I put on this t-shirt, and it smells like all musty and moldy. That is a classic sign that you have a big problem with mold. It is a serious condition. If you're looking to work with a mold specialist, my colleague Melanie, is a world of knowledge when it comes to mold. So she sees patients globally except for the US and Canada, I'm afraid. But if you are looking for a mold specialist, I can highly recommend Melanie. The US people. If you go onto Dr. Shoemaker's website. Surviving Mold, I'm pretty sure it's called Surviving Mold. He has a list of well-trained practitioners that you can work with. What we also need to understand about mold is that it can cause MarCons. Which stands for multiple antibiotic resistant coagulase negative staphylococci. It is a type of staph bacteria that lives deep in the nasal passage, and it's often caused by mold exposure. MarCons will cause inflammation in the nose. When that inflammation in the nose builds up, it triggers histamine locally in the nasal passage. It's very close to the brain, isn't it? And it sends a danger signal to the brain. So the vagus nerve and the immune messengers carry the inflammation messages from the sinus into the brain. And this can activate the brain's own histamine producing neurons which is gonna build up histamine. All of the chronic inflammation can cause a leaky blood brain barrier which is going to make this issue way worse. So whenever I have patients with mold exposure, any nasal issues, even if it's a little bit of a drippy nose and neurological histamine symptoms, including anxiety, I'm definitely testing for MarCons. It's a nasal swab test. So if you're in Australia, we test for MarCons all the time. You can book yourself in for a consultation with Melanie. She can help you get that sorted. Or if you're in the US there's a lab called Microbiology DX, which tests for MarCons. I'll put that information in the show notes for you. Another major cause of high histamine is chronic stress. When I first started as a practitioner, you just have to get good at the tools of your trade. You have to learn how to treat gut issues. You have to learn how to balance hormones. You have to learn how to support immune system. You have to have lots of tools in your toolkit to get people's bowels moving. You need to understand what happens when people take the vitamin D or get their iron up when their zinc is low. All these things. You start to practice what you learn at university and what you learn from your mentors and what you learn from courses. But now that I've been doing this for a long time, I can just see how much chronic stress is causing so much illness in people and also really, really increasing their histamine load. So what is happening? When we are chronically stressed, it keeps the body in a switched on state. And over time, that state drives up histamine via a few connected pathways. Firstly, when stress is ongoing, the fight or flight system stays active. That raises the noradrenaline and the adrenaline, which primes mast cells and neurons to release more histamine. It increases the arousal circuits in the brain. And they stay switched on. Early on in this piece, cortisol will run high. Later on, it becomes erratic or low. And both patterns increase inflammation signals that nudge these histamine pathways in the brain to create and release more histamine. So the chemicals our body releases when we are stressed directly stimulate mast cells in the gut, on the skin, and in the sinuses to dump histamine. This adds to the overall load that signals the brain via the vagus nerve and the immune messages that there's too much histamine. Too much inflammation, too much histamine. That's gonna add more histamine into the central nervous system. Ongoing stress and inflammation can lead to a leaky blood brain barrier. Leading in more inflammatory mediators and more histamine over time. Chronic stress is a major cause of low hydrochloric acid and without hydrochloric acid, you can become very deficient in vitamin B12. And in particular, methylcobalamin methyl B12 is a really key nutrient you need for methylation. So it works on that histamine in methyltransferase enzyme to break down histamine in the brain. I can't tell you how many patients I now see where this stress is their major, major driver of their histamine. For sure, the stress is also causing hormonal imbalance. It's causing gut issues like sibo, but it becomes very chicken and egg. So you really need to start supporting your nervous system. And clinically we find doing really gentle somatic exercises from either Irene Lyon or the Workout Witch the best places for you to start. It's interesting when you listen to Irene Lyon's work, if you do her course, her 21 day reset, she talks about how practices like deep breathing and meditation are actually more advanced practices. It's not saying that they're not good, but sometimes people's nervous system doesn't wanna relax like that because it's so stressed out. The exercise that she starts with is literally orientating yourself in your present environment. That simple. But people can become so stressed out in their nervous system, so taxed that they're not even present. So just to recap, what do you need to do? First of all, reduce histamines in your diet. If that is helping your anxiety, there is definitely a histamine component to your anxiety. If that helps a little bit, but you've still got gut issues, then potentially you've got sibo. I've got a sibo low histamine food list and recipes as part of my e bundle, which you can purchase via my website and obviously you can work with me regarding sibo. I see lots of SIBO patients. You need to assess for mold if you suspect mold, if you smell it, if there's dampness, if there's been water damage, if you feel better out of the house. Definitely need to think about mold. If you have chronic nasal issues, look into MarCons. Ladies, balancing your hormones is really important. I see so many women with estrogen dominance, low progesterone methylation issues, gut issues disrupting their hormones. Histamine driving up their estrogen. So if you need help with your hormones, I'm here to help. Also, if you suspect methylation issues. Most people are having methylation issues. If you're listening to my podcast and you've got some chronic health issues, you've got some high histamine, you need to be looking at methylation. You can do a mood sense methylation test. You can purchase that via my website. And I was saying you can get 10% off for your first and subsequent orders using the code HISTAMINEWELL10. And stress. You need to work on your stress, whether it be going for a walk, meditating. Or if that's not really cutting it, there are some really great resources, Irene Lyons course or the workout, which she's actually got an app that is quite helpful to download and helps you to do some really calming somatic exercises. So thank you for joining me. I hope you found this episode beneficial. Be sure to subscribe to the histamine well so you don't miss an episode. Leave a review and you can also share this episode 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. Until next time, take care and be well.