53. Histamine Intolerance vs MCAS: How To Tell The Difference

Many people with flushing, hives, anxiety, brain fog, digestive issues, food sensitivities, and heart palpitations are told they have either histamine intolerance or Mast Cell Activation Syndrome (MCAS). While these conditions can look remarkably similar, they have very different underlying mechanisms—and understanding those differences is often the key to finding the right treatment.

In this episode, Joanne explains the difference between histamine intolerance and MCAS, why symptoms overlap, and why some people continue to react despite following a low histamine diet. Drawing on her clinical experience, Joanne explores how histamine is processed in the body, the role of DAO and HNMT enzymes, common triggers for mast cell activation, and why addressing the root cause is essential for long-term recovery.

She also discusses the connection between mould mycotoxins, gut dysfunction, SIBO, oxalates, nervous system dysregulation, and histamine-related illness, while sharing practical insights into how she approaches assessment and treatment in clinical practice.

In this episode, you'll learn:

• The difference between histamine intolerance and Mast Cell Activation Syndrome (MCAS)
• Why these conditions share many of the same symptoms but require different treatment approaches
• How DAO and HNMT enzymes help regulate histamine in the body
• Common causes of histamine intolerance, including gut dysfunction, SIBO, mould exposure, oxalates, and hormone imbalances
• Why MCAS symptoms are often more severe, unpredictable, and triggered by non-food factors
• The connection between mould mycotoxins, chronic inflammation, and mast cell activation
• Which laboratory tests may be helpful—and why some commonly recommended tests have limited clinical value
• Joanne's clinical approach to identifying and treating the root causes of histamine-related symptoms

Whether you're navigating histamine intolerance, suspect MCAS, or you're a healthcare practitioner wanting a deeper understanding of these complex conditions, this episode provides practical, evidence-informed insights to help you take the next step towards better health.

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Transcript

0:00

Hi, it's Joanne. One of the most common questions I get asked is, do I have histamine intolerance or do I have mast cell activation syndrome, MCAS? And it's a great question because on the surface they can look almost identical. Both can cause headaches, flushing, hives, anxiety, brain fog, digestive issues, heart palpitations, and reactions to food. Both can leave people feeling miserable, and both are often misunderstood, under-diagnosed, or lumped together as if they're the same thing. But while the symptoms can overlap significantly, the underlying mechanisms are very different, and understanding that difference is often the key to finding the right treatment approach. So in today's episode, we're going to break down histamine intolerance versus mast cell activation syndrome, explore the root causes behind each condition, discuss why some people don't improve on a low histamine diet alone, and talk about what I see most commonly in clinical practice. 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. Hi everyone. Welcome back to The Histamine Well. I'm so glad you're here today because we're diving into a topic that I get asked about constantly. And honestly, one that even a lot of practitioners get confused about. Histamine intolerance versus mast cell activation syndrome, or MCAS. These two conditions look remarkably similar on the surface. Both can cause headaches, flushing, hives, brain fog, gut issues, heart palpitation, disrupt your hormones. Both seem to get worse with certain foods, and both are widely under-diagnosed. But they are not the same thing. The root causes are different, the triggers are different, and the approach to managing them is very different. If you've been trying to just cut out high histamine foods and you're still suffering, this episode might explain why. So let's break this down. What is histamine intolerance? Histamine is a molecule your body actually needs. It's involved in your immune response, your stomach acid production, your neurotransmitter signaling, your sleep-wake cycle, and a myriad of other beneficial things. It's not a villain. It's just a molecule that needs to be properly managed. The problem with histamine intolerance is essentially a bucket problem. Your body is accumulating more histamine than it can break down. Histamine gets broken down primarily by two enzymes, the DAO, diamine oxidase, which works mainly in your gut and breaks down histamine from the food you eat, as well as from the gut issues that can cause histamine, such as oxalates or SIBO. The second is histamine N-methyltransferase enzyme, which works inside your cells. When DAO is low, whether because of gut damage, mold, genetic variants, certain medications, nutrient deficiencies, and your bucket of histamine coming in from food or gut issues in particular, then histamine isn't cleared efficiently. It builds up, and once your bucket overflows, symptoms start. So this is histamine intolerance. It's dose-dependent and cumulative. A little bit of aged cheese might be fine, but aged cheese plus red wine plus leftover chicken that's been in the fridge for three days, that in combination with what's going on in your gut is going to overflow the bucket. So common symptoms of histamine intolerance are digestive issues, heartburn, bloating, diarrhea, nausea. Skin issues such as eczema, flushing, hives, acne. Neurological issues such as headaches, migraines, insomnia, anxiety, brain fog, cardiovascular, heart palpitations, low blood pressure. Then you've also got like a lot of the sinus allergy picture as well, symptoms. And just it causes havoc with hormones as you have would've learnt about on this podcast. So let's now talk about MCAS, mast cell activation syndrome. Mast cells are immune cells. They live in your tissues, your gut, your skin, your lungs, your brain. Their job is to act as first responders. When they sense a threat, whether that's a pathogen, a toxin, a bee sting, even stress, viruses, mold mycotoxins, they degranulate. They release a chemical storm that includes histamine, but also other inflammatory mediators. Prostaglandins, leukotrienes, cytokines, and dozens of other mediators. In MCAS, mast cells are hyperactive. They're triggering inappropriately to things that shouldn't be threats: foods, fragrances, temperature changes, exercise, emotional stress, EMF exposure, even barometric pressure changes for some people. The mast cells are essentially a car alarm that goes off if a leaf falls on the bonnet. I love that analogy. So they're just hyper, hypersensitive. And because mast cells release many mediators, not just histamine, the symptom picture in MCAS is often much broader and often more severe. It can also be more unpredictable than histamine intolerance. MCAS symptoms can include everything in the histamine intolerance list, plus anaphylaxis or near-anaphylaxis reactions, bladder urgency and pain like interstitial cystitis. Bone pain, osteoporosis. Neurological symptoms such as tremor and cognitive dysfunction, extreme fatigue, reactions to non-food triggers like smells, heat, cold, vibration, and reactions that don't follow any obvious dietary pattern. So that last point is important. MCAS reactions can be wildly unpredictable. Some might eat a food one day and be fine and then react to it the next day. That inconsistency is a hallmark of mast cell involvement, and it's different from histamine intolerance where the pattern is more related to the load. Now, I know I said mold mycotoxins, guys. So mold can cause mold allergy. The mycotoxins can cause MCAS and something called chronic inflammatory response syndrome, which I'll discuss on another episode. But CIRS-- it's a chronic inflammatory response syndrome. The immune system gets very dysregulated, and it can just cause histamine intolerance as well. But generally, when we are seeing an MCAS picture or a CIRS picture, the common thing we see is it's mold mycotoxins. I just wanted to flag that. So what do we do? We treat mold. That's what we do. We do a full mold workup, and we treat the mold. And we look at the fallout from mold. So mold causes SIBO. It causes oxalate issues. It causes nervous system dysfunction. It disrupts the whole terrain of the gut, et cetera. 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, MTHFR, the four pathways of methylation, including the folate pathway, methionine pathway, tetrahydrobiopterin 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 Now, let's just move on. so will testing be useful? When it comes to what I do in clinic is if I think there's a mold issue driving this MCAS issue, I will do a mold mycotoxins test. If there's sinus issues, a MarCons nasal swab test, and most of the time I'm gonna do an organic acids test because let's just move on the fallout of mold. So the organic acids test will show us like what has actually been the fallout in the body from the mold. Potentially SIBO testing, potentially a complete microbiome map to look at sulfur issues. So this is, I think, something that is not just unique. Well, it's not unique to my clinic, but I know that a lot of this full workup with mold is just not being done. That's how I approach it because 99% of the time, if you're pushing into MCAS or if you've been told you've got MCAS, then we need to get the mold dealt with. We need to get the mold out of your body, and we need to fix the fallout from it. Now, to get more of like an official diagnosis of MCAS, like if it's official that you have it, there are some gold standard tests. One is serum tryptase. So it can be elevated during a reaction, but often normal between reactions, which makes it frustratingly insensitive for diagnosis. You can do a 24-hour histamine prostaglandin D2 and N-methylhistamine test. These need to be collected during or right after a reaction to be meaningful. And then there's this serum chromogranulin A, which is another mast cell mediator. These are t-tests that are gonna be done from a doctor, an integrative doctor specializing in MCAS. So often people will think they've got MCAS. It might have been thrown around. A practitioner might have said you got MCAS. These tests haven't been done. I am gonna go straight for the root cause because that's just what we do in my clinic. And when we deal with root causes, it's just usually mold that I see for MCAS. This is where we're starting to see some real improvement in our patients. Now, reading up on all of this online, right? There is just such overkill in some tests. So if you look online or even ask AI, it's gonna tell you that you diagnose histamine intolerance with serum DAO enzyme activity, whole blood histamine, and genetic variants. And I'm here to tell you it's just not right. It's just not clinically useful. There's a whole article here saying serum DAO enzyme activity, this is the most clinically useful. It's just not. Most people with histamine intolerance just are a bucket of histamine from oxalates, digestive enzyme insufficiency, gluten intolerance, Helicobacter pylori, SIBO, estrogen, right? Their DAO enzyme's fine. They've just got too much histamine. Why I know this is actually 'cause we just don't really test for DAO in Australia. In Germany, everyone gets tested for DAO. I see so many Germans, they're right into histamine intolerance over there. And my colleague Mariella Gebhardt, she's a practitioner in Vienna, and she sees a lot of Austrians, German. They all test it. Most of the time it's fine. And they're a bucket of histamine, right? It's actually not low. They're making sufficient amounts. It's just overloaded. So it's not that useful. And then there's the genetic testing for DAO and HNMT variants. Well, you can have a double mutation on both of those variants and have no histamine issues because you don't have any of the main causes. Or you can have no mutations on those genes, and you are full of histamine from the causes that I've spoken to you about. So those tests are actually not that useful. One other thing I forgot to mention with MCAS/mold is that there's often significant nervous system dysregulation. The mold mycotoxins cause issues with the limbic system, the vagus nerve, poor vagal tone, and this is why you can get a myriad of different gut issues. The vagus nerve is just not performing its function throughout the entire gastrointestinal tract. I hope this makes sense because I know it's quite confusing because with MCAS, you've got to get to the root cause. Look, it can also be caused from Lyme disease, Epstein-Barr virus. We don't see the Lyme so much in Australia, but I know in the US and Europe it's quite big. So in my patient base it's usually going to be mold mycotoxins, and often they don't have to go down the route of more testing for MCAS and mast cell stabilizing medication. If we identify the mold, you've got to get the mold out of the house. You've got to get it remediated or move. I know it's a real stress, but you have to take mold seriously, and then we do a big mold detox and often people feel a lot better. So I hope that makes sense. I hope you got a lot out of that episode. If you would like to make an appointment to see us, we see people online globally. You can easily make an appointment via my website, joannekennedynaturopathy.com 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. If this podcast has supported you, one of the most impactful ways to help us reach more people is to leave a review on Apple or Spotify. Take a quick screenshot and email it to us at info@joannekennedy.com.au and as a thank you gift, we will send you a copy of my histamine intolerance e-book. Until next time, take care and be well.