Episode #188: Latest Insights on MCAS with Dr. Kelly McCann, MD and Beth O'Hara, FN

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Hello everyone and welcome to episode number 188 of the Better Health Guy Blogcast series. Today's guests are Dr. Kelly McCann and Beth O' Hara and the topic of the show is latest insights on Mast Cell activation Syndrome. Both of our experts today are prior podcast guests. You can find their full bios by looking at episode 142 for Dr. Kelly and episod 101, 109, 122 and 156 for Beth. Dr. Kelly works with patients with complex chronic illnesses and is an expert on Mast cell activation syndrome. Beth is a leading expert on Mast cell activation syndrome and operates Mast Cell360.com both of them are amazing practitioners and are people that I have been honored to collaborate with and be mentored by. They recently partnered up to host the Mastering Mast Cell Activation Summit, which runs in October. And now my interview with Dr. Kelly McCann and Beth O'. Hara. It is a great honor for me today to have Dr. Kelly and Beth with us to talk about the latest insights on Mast cell activation syndrome. They are each a powerhouse and their collaboration on their upcoming summit is certainly going to bring some powerful new insights. Thank you both for being here.

Thank you so much for having us. Scott.

It's a pleasure. I'm so excited.

Let's start by talking about how each of you started to focus on mast cell activation syndrome. How did you recognize that it was an important part of the chronic illness conversation or puzzle and what percentage of the populations that you each work with are somewhere on the mast cell spectrum?

Well, I started focusing on it because of my own health journey and having been ill with odd extreme allergy symptoms and various other GI symptoms, brain fog and so on from an early age. No one ever knew what it was, but I got shuffled to allergists and those medications made a difference and long, long journey and over 75 practitioners and hundreds of thousands of dollars. And then there was an interview Yasmina kellenston did with Dr. Theo Heredis and he described Mast cell activation syndrome. Well, it was still theoretical over 10 years ago. I was like, oh my Gosh, someone just laid out my whole life story. It all made sense, but we didn't have any. There weren't tools. There were no books that you could access. There were just research papers. And they were all over the map. They mostly focused on ige. But then Larry Afron's book came out. Don't. Don't Bet Against Occam. And that was, I think both of their work was just a real game changer in terms of getting recognition and of course, so many other people. But. But we had to start piecing together. How do we deal with this, how do we handle it? And did piece it together. And fortunately, now we have protocols and understanding that it's light years beyond where we were back in that first interview. And people can get better so much faster and with way less money, which is wonderful. Not that it's six months and I know people listening to this probably know that, but we're looking at 2, 5 years instead of 15 to 20, which is what I was dealing with. And my practice is 100%, I would say almost 100%, maybe 99% MCAs. Some people have a diagnosis when they come in. A lot of people don't. But if there's chronic inflammation, my philosophy is that if we've got chronic inflammation in two or more systems, we've got some level of mast cell involvement that needs to be addressed.

My practice is very different, and my journey was very different from Beth's. I'm med, peds trained, board certified medical doctor, did a lot of functional medicine, integrative medicine, and really started in the realm of environmental medicine with Walter Crinian, looking at the environmental toxicants. And then one of my colleagues said, hey, you should check out the shoemaker guy. He's talking about mold. And then realized my mold patients weren't getting better and I needed to explore Lyme disease and chronic infections. And then, you know, all of a sudden, these patients were getting sicker and sicker. And I ran into Larry Afrin, read his book and was the light bulb went off on all these very complex patients who were coming to me originally. And we were diagnosing them with mold and Lyme and then having to manage, learn how to manage the mast cell activation piece. And I have my own mold, multiple mold exposure journey, Lyme journey that triggered, you know, all these sensitivities and mast cell symptoms because I was an allergic kid and had all these issues growing up also. So it's been now, in hindsight, a personal journey and a professional journey to help more and more of these patients that are becoming sick with a variety of different total load issues. And so perhaps my percentage of the population I work with that's MCAS would be maybe 60, 70%. So I see a lot of GI symptoms, I see a lot of autoimmune conditions. But I do think similar to Beth, in large part, many of these folks do have some, some presentation of inflammation which could be managed as mast cell activation, even if they might have the worst case presentation or, you know, 20 symptoms, 20 systems involved.

Dr. Neil Nathan talks about the ultra sensitive patient, and some of the common themes in those patients are mold exposure, bartonella, mast cell activation syndrome, and then the limbic and vagal pieces that are so critical and often overlooked. Are there any other common themes that you want to add to that list that are maybe potential triggers for or drivers of being a more sensitive patient in general? And why do you think people seem to be so much more sensitive now than maybe the patients you might have working with? A decade ago?

I was one of those super sensitive patients, and I was somebody who could barely tolerate a sprinkle of gaba and it would make me more anxious. And I was having all these paradoxical reactions. Curcumin and quercetin made me more inflamed and gave me insomnia at this tiny little. When I say sprinkle, like a fairy dusting amount of it. And so I think those are huge drivers then. That's what in our clinic we specialize in now are people with hypersensitivities. So we do see quite a lot of particularly mold toxicity, bartonella, and then the limic and vagal dysregulation. But I have to ask, well, why, why are they dysregulated, the limbic and the vagal systems? And we see so much trauma, early childhood trauma particularly. And there's a much higher percentage of people in the chronically ill population with early childhood trauma than in the general population. So why does that matter so much that when we experience trauma, whether it's outright abuse, but even people forget that neglect is often the most severe form of trauma. Emotional neglect, physical neglect, it can be witnessing trauma, it can be witnessing someone being abused, it can be being bullied at school, it can be having a medical procedure at a young age and not understanding it, or an injury or an illness at a young age, there's so many drivers of trauma, and I think especially in the pandemic, the effects, I mean, that was a global trauma. And then what about the children that were reaching developmental age and going through social, developmental development. And. And everyone's wearing masks and they can't read faces and they're supposed to be learning how to read faces. And so we. We live in a traumatized society. And a traumatized society traumatizes each other. And it can compound and compound. So I think that's a huge driver. There's a lot of chemical toxins that I know Dr. Kelly can go into. But natural gas is one that I see quite a bit. Natural gas leaks that I'm looking at a lot more from natural gas stoves not being ventilated properly. Or they are. I rented an Airbnb and. And it just leaked without being on so much that it just filled the kitchen. And I had to keep the windows open and run air purifiers and run the vent hood constantly, nonstop the whole stay because of how much it was leaking. Benzodiazepine withdrawal is a big trigger. So this is one I see often because the receptors and sometimes SSRIs are the types of antidepressants. But those receptor issues can really trigger sensitivities. When we get into mold toxicity then we open the door for all kinds of things like oxalate issues. One of the drivers of histamine intolerance. Salicylate intolerance is often a big one. Sensitivities for supplements and foods that get missed. And I know we'll touch on that here in a bit. Covid is a huge driver and was a huge driver. Is still a huge driver of limbic dysregulation and one of the drivers of long Covid. One of the other things we don't talk about a lot is. But you've had a incredible podcast with Chandler Mars which is B1 deficiency. And we know mycotoxins greatly deplete B1. Stress depletes B1. We need B1 for the. The nervous system to fire properly. And when we get onto these super limited diets and even like a keto diet, it's very hard to get enough B1 because it mostly comes from grain. So we have to be cognizant about it. Or if people are. Have a lot of food sensitivities, there's. We get down to so few foods. Which is something that happened to me where I got down to 10 foods and I was counting sal and pepper and my herbs to make myself feel better. You lose the nutrient status needed to hold resiliency in the system. And that's when my sensitivities just skyrocketed. Was about three to Four months after I got that limited, because I didn't know what I was doing. I was just taking out any foods I was reacting to. I didn't know I had histamine intolerance and lectin and oxalate intolerance and fodmap intolerance and salicylate intolerance and issues with glutamate. And glutamate is another one. So glutamate will drive sensitivities. Another thing that will really. I see driving sensitivities over and over in these populations are people who are shutting down their intuition and their self, knowing about something really big and important in their lives. And our bodies. I love the title of the book. Our Bodies Keep the Score. And they, they will keep the score and always tell us the truth, whether we listen or not. And if we don't listen, it will show up all kinds of ways and sometimes it'll. It'll kill us. I mean, literally, I don't mean to sound dramatic, but people die of heartbreak. People die of stress. That's a form of stress. So those are, you know, those are some of the big ones that I think about as the drivers of these. I'm just thinking the real hypersensitivities where people are struggling with light, they're struggling with sound foods, they're not able to take hardly any supplements, hardly any medications. You can even get into issues processing conversation and things like that.

Yeah, I think that's amazing. And I like how you're really kind of putting the message out there that sometimes a really restrictive diet is not the right thing, particularly long term. I remember working with one client that was down to one food, and that one food was alligator. What do you find are the top triggers of mast cell activation syndrome itself? Are there specific triggers that kind of rise to the top that you think are maybe more common than others? Are there some that might surprise people? I know I generally tend to think of mold, parasites and EMFs, even though there's certainly a much longer list. What are some of the ones that you see at the top of the list?

So I would definitely want to add to the conversation and say environmental, environmental chemicals. And I know that's very obvious, but I think even though we have a sense that there's more pesticides out there and people need to eat clean and, you know, patients will come in and like, yeah, I eat a clean diet. I eat all organic, I'm gluten free, I'm dairy free, I'm sugar free. And they're still Having all these issues. It's because our world is becoming increasingly more and more toxic every single day. And you know, some of the, the recent studies that have come out looking at the bibliographic information about environmental chemicals is that, you know, we used to say, oh, there's like 85,000 chemicals, no, there's probably 300,000 chemicals in the environment today when we look at the information from all the different countries. And so we are in this toxic soup that is only getting worse. And if you layer that into a situation where, well, we're, all of our detox pathways are being gummed up by our environmental chemicals and we're nutrient depleted because we're avoiding all these foods. We're just compounding the problem. And so it's really no surprise when we think about it from that perspective. Our buckets are way over full and we're spilling over and we're having all these symptoms. And it's happening at younger and younger ages because moms are toxic when they have babies. Babies are born toxic. I mean, we know from the studies from 20 years ago that babies are born chops chock full of chemicals. You know, with some of the cord blood studies and those were 20 year old studies, babies were born with 200 chemicals in their cord blood. So it's just compounding. And we are standing at the precipice of a tsunami of chronic illness. In large part that's going to manifest as mast cell activation syndrome because of this whole toxic burden. So is it mold?

Yes.

We know that molds and water damaged buildings are huge. I live in Southern California. I've lived here for 14 years. I've lived in 10 different homes. All of them have been moldy. Every single one of them has been moldy. And two are so bad that they really should have been condemned. And I know what I'm doing, so. So I can't imagine, you know, if we have all these faulty buildings because people are scrambling to get a place to live and we're not, we're not aware of, of our exposures. The other primary exposures that we get are in our home. So we're making healthy choices with what we put in our body in terms of our foods. But what about the air that we're breathing? What about the water that we're drinking? What about the building material? So we've got mold, but then you've got all the high VOC paints and the particle board and the formaldehyde and all those chemicals in our furniture. Right. We go to Ikea and We think we got a great deal. Unfortunately that great deal is probably filled with some chemicals. It's particle board and that is adding to the total load. So I think it's a multifactorial trigger that's leading to these presentations, unfortunately. Pew. That was a mouthful. Sorry.

I'm so glad you mentioned that though because it is true. And we're not starting at the same starting point that we were three generations ago. And the generations, you know, I know we both, we all three work with families and generations and we see them that the children sicker than the adults and sicker younger. And so this is really continuing. And I think you mentioned some of the big drivers are the tick borne infections, of course and mold toxicity. I just, I feel like I'm always beating the same drum. But it's so important and even I don't see it enough. I cannot underestimate, estimate the amount of stress as a trigger. And we live these massively stressful lifestyles, even a normal lifestyle and normal what we consider a health.

What's normal death. What's normal anymore.

Really what we call normal. You know, it's like you, you get up at 6, you get the kids ready for school, you get their lunches packed, they barely have time to eat something. They get on the bus, you're off to work, you're late for work because you had to hit rush hour traffic and some kid forgot their, their gym shoes so you had to drop the gym shoes off and now you're worried you're going to lose job because you're related to work and you're dealing with the only health issues. You got brain fog. And then you know, there's layoffs coming and you've still got to get the kids picked up, you got to get dinner, you got to get homework. Oh, there's extracurriculars. This one kid's having some behavioral issues because they're not getting enough attention. And then you're trying to fall into bed at midnight and get up again at 6 and there's no time to breathe, there's no time to connect with nature. There's no time to listen to ourselves. And that alone breaks down our health. So those are some. Some. My top triggers of MCAs are tick borne infections, mold toxicity and stressors. And we conclude in their traumas.

I want to talk a little bit more. Kind of building on this trigger concept. Do you see mast cell activation as the core illness or root cause of these complex conditions or is it the result? I know there are some amazing leading people in the mast cell activation realm that kind of see mast cell activation as the core illness. And then I know there's others of us that think that if we can address these root causes, that we can move past it. So is mast cell activation the primary issue, or is it more secondary?

I think. I think. And I. Beth can weigh in too. I suspect she agrees with me. I think it's secondary. The vast majority of the time, there's this genetic susceptibility, right? In environmental medicine, we talk about genes, load the gun, the environment fires the trigger. And I think that that's really the case. I know that I have, you know, a genetic predisposition for autoimmune conditions based on my 23andMe and allergies for sure. But it wasn't until there was an external exposure mold that really just pushed me over the edge and probably lyme disease, too. So it was additive and it can be recoverable. Maybe not to the part where I get to be or a patient gets to be. I tell people, you know, you may not ever be a rock star and get to live a rock star lifestyle, but who would want to do that anyway? They all die in their 60s. So, you know, we get to the point where we're living a healthy lifestyle and our life has meaning and it's full, and we get to do the things that we want to do. And maybe you don't get to eat everything single, every single food on a smorgitz board, but you get to eat the healthy foods and you get to participate in a life full of meaning. And I think that that's a. That's a great goal. And it's an achievable goal for the vast majority of people who are willing to do the work, willing to do the things that calm down the mast cells, that calm down the vagus nerve, that, you know, address the limbic system activation, reduce their exposures, reduce their stress, and then eventually and. And address their thought patterns, their beliefs, their toxic relationships. And as those things get cleared out, the body can release the toxins and the dysfunctional patterning and come back into homeostasis and a much more full life as possible.

Coming back to the comments that you made about environmental toxicants, I do think heavy metals and pesticides and chemicals, I think they are significant contributors to our health. Health to mast cell activation syndrome. One of the things that I see people often wanting to do is to really aggressively detoxify if I'm toxic. And getting rid of those toxins is going to make me better. I want to be as aggressive as possible. My observation has been that those people that are dealing with mast cell activation syndrome, sometimes we have to detox much more gingerly, much more, not as aggressively, that sometimes that more aggressive approach can really backfire, that we don't want to be mobilizing lots of metals and other toxicants in the body because we may then actually activate or trigger the mast cells. What's your thoughts on how to best approach detoxification in someone that is dealing with mast cell related issues?

Yes, I agree Scott. Detox can absolutely backfire and for most people it really is a situation where we have to do what's pre tox. I can't take credit for that. I think that was Nafisa Parpia who coined that term. But prepare for, for, prepare for detox first. And by that we're really looking at how do you, how do you reduce exposures? We can practice avoidance and that's a way to begin to lessen the accumulation and very, very gently calm down the mast cells. I mean I think that's really what has to happen in any pre talks situation. From my perspective it's avoidance, it's calming down the mast cells, it's stimulating the vagus nerve, it's doing all those preparatory things that are going to enable somebody to eventually get to the point where they can detox, you know, in terms of like heavy metals. That's way down the line for most people. I, I want people to be about 70% improved from the, wherever they were when they walked in my door before I'll even look at metals just because it makes people so sick to try and pull out those metals.

For example, there is some conversation around abnormal methylation in relationship to mast cell activation syndrome. So is there a connection that you see between methylation related issues and mast cell activation?

There is and this is a multi layered question in my mind so we can think about just the base biochemistry which is one we have to produce. Same is a CO factor for histamine N methyltransferase HNMT and that's one of the better known enzymes, the top two enzymes that are talked about, although there's dozens. But the top two in terms of histamine breakdown are talked about are diamine oxidase DAO and this HNMT which I know you all know well. But for our listeners that requires a CME for methylation to activate it. It's a CO factor to break down that excess histamine. So if we have excess histamine then mast cells have histamine receptors on them. So do eosinophils, basophils, their basophils and inosophils will release more histamine in the presence of histamine and then all of that will trigger more mass activation. But then we can start to think also bigger picture about what is methylation really doing and you know, cell danger response. Just in my mind, this theory changed the field of what we're doing and looking at the biochemical changes when our bodies go into survival response and that these methylation changes are protective and necessary. And so part of that mechanism is a methyltransferase enzyme called DNMT3A and that's been identified in a lot of mast cell related disorders and there's papers out there on this. So we know that in cell danger response, methylation is often turned down. I mean, sometimes we see overmethylators, but a lot of times we see under methylators, we see aberrations in methylation and there's a reason it's happening. And so I wanted to take us to that context because methylation is so popular online, mainly because that got, that was like the holy grail at first of functional genetics, right? Like, oh, if we unlock methylation we're going to solve all these chronic illnesses. And what we didn't know at that time was about cell danger response and that this is happening intentionally to protect us. And the mast cell activation, the histamine and increased histamine production is being ramped up to create inflammation, to protect us from those toxins, to protect us from pathogens. So we want to be really careful about when we enter into methylation, especially for sensitive people, not for somebody who's super robust and they can do a glutathione IV and they like feel amazing and they, they can take whatever they want. That tends to be a different picture. But I'm talking about people whose resiliency in their system has come to a level where I see it, I'm a visual thinker, so I always see, just see biochemistry in pictures and I see when we get that level of loss of resiliency, it's like the biochemistry is all these interwoven spider webs and we make a change here and it reverberates everywhere because we don't have the resiliency and it really should be in a robust system to where these are strong connections and we make a system here and there's just a tiny little change. But in those who lost the resiliency, we drop in some methylfolate and everything rocks and sways and it's because we're working against that cell danger response. So I just want people to really think about the order of operations, especially if they're sensitive and when to introduce that, because that's the key to success and sensitivities and mass activation is to go in the right order at the right time for this person's body and their needs and their situation.

I don't want to spend a lot of time on testing, but we know there's lots of tests to look at mast cell activation syndrome. It doesn't seem to me that any of them are consistently reliable. I know some people will base their mast cell approach based more on history, clinical observation. So what are you using as your top testing approaches for mast cell activation syndrome? If anything, do you find that MMP9 correlates in your patients to those dealing with mast cell activation? What are your thoughts?

You know, I've vacillated a little bit on this. I do check, you know, when I'm doing a routine panel, I will check histamine levels. I know they're not a perfect marker, but I do check histamine levels, Chromogranin A and Tryptase. And those are the ones that you can get through blood work through any National Lab, LabCorp and Quest. And very often I can get multiple, I can get elevation in histamine levels. And that combined with a history, a clinical history will often be enough to make me feel like, okay, yeah, we have mast cell activation syndrome. I think one of the more useful markers in somebody who has had a biopsy, either of an endoscopy or a colonoscopy, and we do the special stains, the 117 stains. So that CD117 stains, these are not routine stains. They have to be requested specifically by a physician to have the pathologist look at that. And if the way that they report it is if there is greater than 20 cells, mast cells stained with CD117 stain in a high power field that is suggestive of a mast cell activation syndrome. It's not, again, a perfect test, but I do find it very helpful. If somebody has, you know, high power field, 60 cells and they have lots of symptoms that really correlates and, and then patients feel validated. Other practitioners, particularly their conventional doctors, feel more validated in that diagnosis. I don't tend to use the MMP9 so much and there's no particular reason for that. I have used the more extensive testing that is taught by Dr. Larry Afrin. I Think one of the challenges is finding a, a location that has a refrigerated centrifuge and a pathologist and a team that's willing to go the extra mile so that that chain of custody of the blood and the urine from the patient in a refriger, you know, drawn in a refrigerated tube in a refrigerated centrifuge and hold down the line to get the specimen where it needs to be. So it's an adequate specimen. I do find that it's worthwhile, again, with some people to do that, especially if they're in a flare, especially at the beginning of the journey. But at the same time, we're looking at maybe a dozen different markers and there are thousands of mediators. And so getting a negative test does not rule out mast cell getting a positive test. Everybody breathe a sigh of relief that that's actually what you have.

Excellent. Very, very helpful. How might mast cell activation syndrome lead to or contribute to neurocognitive issues? Maybe brain fog. Do mast cells in the brain itself play a role? Or is it that mast cells throughout the body are releasing various mediators that then cross the blood brain barrier and impact our cognition, leading to brain fog, maybe even contributing to inflammation and resulting anxiety and, or depression?

I think there are mast cells in the brain, but they're not as many as there are outside of the brain, obviously. And so when we start to get an inflammatory situation, we're going to get breakdown of the blood brain barrier, and those mediators are going to be able to, to better pass into the brain, causing even more inflammation in the brain. And so, yes, the, the mediators being released outside is really one of the primary drivers. Although, you know, there are some mast cells in the brain. And I've been recently, recently wrote a, read a book by Dane Goodenow about breaking Alzheimer's, right? And he talks about plasmalogens in the brain. And I, I do really think that this is a huge component of brain fog. So we've got inflammation in the brain, we've got oxidative stress in the brain from whatever toxic exposure, Lyme disease, Bartonella, mold, mast cell activation symptoms. And in the brain, we have our plasmalogens. And there are three primary purposes of plasmalogens. One, they make up 90% of myelin. Two, they are antioxidants. And unlike things like glutathione and vitamin C, we can't regenerate them. Once they get used up as an antioxidant, they're done. And so we have to make more. And we make them in what's called the peroxisome. So in our cells, we have mitochondria, which are the most famous organelle other than the nucleus, which holds the DNA. And we also have the peroxis and those peroxis exosomes. Their job is to beta oxidize lipids and create more phospholipids for our cell membranes, and they create plasmalogens. And then the third very important thing that plasmalogens do is that they are in the cell membranes, in the presynaptic cell, and they are responsible for releasing those neurotransmitters. So we literally cannot release our neurotransmitters without those plasmalogy, which translates into brain fog. Right. So, so we're using up our plasmalogens. We don't have enough in our presynaptic neurons. We can't release those neurotransmitters. We can't make connections in our brain, and our brain is foggy. So I have been using plasmalogens in some of my patients, which are generally very well tolerated, and it's been really helpful at bringing people's brains back online with that brain fog dog. It's pretty cool stuff.

I love that. I interviewed Dr. Goodenow, I think, two episodes ago, and I'm excited about his Prodrome Neuro and Prodrome Glia products. I will tell you, my brain felt like it had been thoroughly exercised after having a conversation with him because he is so incredibly intelligent.

Yes. Yes, he is.

That's awesome. I'm excited that you're, you're using that. I didn't know that that was the case, so thanks for sharing that.

That, and just to add to this, so I got Covid a year ago September and had terrible brain fog afterwards. I mean, for me, I'm like, you know, not quite all there. And I did his Prodrome scan and my plasma levels were low, and I started the Prodrome Neuro and, you know, couple weeks back on fires. So it, I, I, I'll be a testament to that. That.

Love it. Love it. How does the salicylate conversation overlap with the mast cell and histamine conversation? Are salicylates themselves triggers for mast cells? Is it common, uncommon? Are there ways to test for it? And how might we approach treatment or how might treatment be different if someone is salicylate intolerant? And I'm going to first say that this probably could be a whole nother podcast that Beth and I could do at some point in the future. So we're going to have to stay a little higher level on this one, but interested in how that that ties into the mast cell conversation, Let me.

First define salicylates for those of you listening who have not heard that term before. These are the phenolic compounds, the colorful compounds in most herbs, fruits, vegetables. And so there are some herbs, fruits and vegetables that don't have salicylates, but most do. So we think about high salicylates as being things like quercetin, curcumin, these are going to be pretty high. Whereas GABA L theanine, being an amino acid, they're not plant derived. Those are going to be pretty low salicylate. We're going to find a lot of salicylates in foods like rosemary and basil and thyme. Interestingly, a lot of our antifungal foods, we're going to find high salicylates in raspberries, blueberries and things like that. Whereas lettuces tend to be lower, cauliflower is lower, there's a lot of foods that are lower. So it's not like there's nothing to eat. But the interesting thing in terms of salicylates and mast cells is salicylates can both stabilize mast cells or degranulate them, Depending on what 1, what receptors are being affected by the mast cells, since There are over 200 receptors and in mast cell activation syndrome, some of those receptors can get overly sensitive to different things inappropriately, but they can also stabilize them. And that's where a lot of our phenolics have a really a big impact on supporting the mast cells. This relationship with histamine intolerance, one, when we get salicylate, it's also an intolerance like histamine. So it's if the bucket fills and the pathways that drain it out are not working properly, or we're overflowing into that bucket by over consuming or in the case of histamine, can also be overproducing. Then we're going to get this buildup. We've got too much. And in salicylate intolerance, you'll often find people who are pretty sensitive to aspirin, which is a salicylic acid. Aspirin is sometimes mast cell stabilizer in some people. So it's one of those fairly tricky ones to use and it's one that people should be really cautious with unless somebody has a prior experience to aspirin in the, in the mast cell population. But when those salicylates start building. They can start. If they, they cross that threshold, they can start triggering the mast cells to release more histamine and trigger more other mediators to be released. So what's also interesting about salicylates is they tend to be detoxed by the same pathways that detox molds, particularly glucuronidation, which you have a podcast on, and sulfation, glycination, glycine, and also microbiome degradation of salicylates. There's just like with oxalates, they, there are bacteria in our guts that break these salicylates down and convert them into different things like nutrients. So mold toxicity is one of the biggest triggers I see of salicylate intolerance. The good news is when we clear up the mold toxicity and we take the load off of those salicylate clearing pathways, people salicy intolerance usually completely reverses, which is wonderful. Now, there are some instances of extreme genetic variance, but I hope people start to take out of these conversations that just because you have genetic variants, it's not a life sentence, because genetic expression is so much more important. It's rare that there be genetic variants that really impact people if they have a great lifestyle, a great diet, and they're managing their stress and they're really rebooting the nervous system.

Time I have taken my Beth o' Hara formulated glucuronidation assist today for those listeners that are listening to us talk about glucuronidation. Still have one more dose to go today. I want to talk a little bit then about oxalates as well. So we know that those can come from food sources, but we know that they also potentially come from internal fungal colonization. So if we take the fungal mycotoxin component maybe, maybe out of the conversation. Do oxalates themselves trigger the mast cells?

They do. And oxalates are really fascinating to look at under a microscope. They have sharp types of structures and they have all kinds of structures, but they can look like shards of glass, they can look like little razor blades. And they're microscopic, but they are making, creating tissue damage one of the ways that we often. And oxalates will be really high. For anybody who's not come across this before, they'll be, they're super high in sweet potatoes, beets, spinach, plantains, chocolate almonds, Swiss chard, rhubarb. Those are some of our most high oxalate foods. And just one or two servings of those foods a day can far exceed the amount that the kidneys can filter out of oxalate. So this is how I got myself into so much trouble with oxalate, is that when I started cleaning my diet and going gluten free, I went to almond flour. I started eating seasonally. And what you, what, what do you get in the winter? You get sweet potatoes, you get Swiss chard, you get spinach. And I was so overloaded, and I would get this intense joint pain and be unable to walk. I'd have to just barely be able to make across the room with a cane just to go to the bathroom. And so that was a huge game changer. And, and one of the ways that oxalates would trigger the mast cells, whether it's coming from dietary or it's coming from aspergillus colonization in the gut, is that these microscopic sharp molecules will scrape the tissues as they go through. So they tend to deposit in areas of injuries. So you think about people who have osteoarthritis in a particular area, there's often an oxalate component. Not always, but often. And interstitial cystitis is. Often has a. It's not always oxalates, but frequently. And there's. That's. This, is this relationship with IC and mast cells and oxalates. The oxalates will scrape the urethra and even the bladder, and then the mast cells are going to be inflamed, they're going to produce inflammation because they also respond to injury. And then you can get into these cycles. So that's just a little snapshot. There's lots of ways that oxalates can affect, can affect all of this.

Yeah, that's fantastic. We, we touched on benzodiazepines a little bit earlier in the conversation. On the one hand, they potentially can help stabilize mast cells, but on the other, it seems like using them can become a bit of a slippery slope. So do you find that these benzodiazepine medications are helpful or do you find that they further complicate an already complex illness picture both.

You know, as a, as a medical doctor who can prescribe. I do prescribe benzodiazepines. And sometimes it has been a game changer for some people in stabilizing their mast cell symptoms when, you know, very few other things were found to be stabilizing for some patients. And then, you know, flip side, I have a mast cell patient who doesn't look like your standard allergy mast cell patient, but, you know, he went through a very, very long taper and now is having terrible issues with withdrawal Months and months after being off the benzodiazepines. So. But we didn't know he had mast cell when he was put on the benzodiazepines, which I actually didn't prescribe initially anyway. So yeah, it, it can be, it can be a game changer and very, very helpful and then also can be problematic.

You mentioned earlier, Beth, your experience in an Airbnb with a gas stove. So how much of a concern should we have around gas stoves or ranges or gas ovens? We know they can release some chemicals like benzene, but can exposure to these types of sources of gas be triggers for the mast cells? And how common do you think that is that people with mast cell activation are being triggered by my exposures to gas?

Still unsure how many. It's something that really started getting my attention earlier this year. I probably should have gotten my attention sooner, but, you know, you can only pick up so much at a time. But I have had some people who had worked so diligently on mold, on the VOCs, on the not making sure they didn't have off gassing furniture, all of this stuff, but they never looked at the gas and they were so sensitive and they were having eye burning, you know, sound sensitivity, all these different, lots of brain fog. And it would turned out to be a gas leak somewhere in the house. And part of, I think this is a much bigger problem today than it was even 40, 50 years ago. We think about, I mean, when I was growing up, everyone had gas stoves and people didn't have these tightly built houses. Houses were drafty. And now we have these tightly built houses, so we're trapping it all in here and we don't open our windows and we don't have a lot of airflow. So this is why I had installed a fresh air exchange on our H vac system. Even though it lowers our energy efficiency, it improves our air quality dramatically. Because I do have a gas stove and I actually love cooking on gas. But I think what allows me to do that is I have a massively powered range hood where you can't talk when it's on high because it's so loud. But I'm really great grateful for it. And it vents all the way outside and some of these hoods bent just to the attic and then it's still in your house, so that's really important. And then it's an open space, so it's like an open kitchen, dining area, great room. So there's. That's different than a closed off area. Where it's going to build and build and build. But if somebody cooks on my stove and forgets to turn the fan on and I walk into the room, I'm instantly ill. Just very quickly, and I mean to, to a point of if I don't leave within 30 seconds, I'm going be non functional. And I'm pretty far along in my health recovery. So I can just. That's anecdotal evidence from my own experience, but just clinically and personally, I think it's bigger than we've been getting credit for. And I'd love Kelly's thoughts because she's the real environmental chemical expert here.

Twenty, 30 years ago, there was a condition called multiple chemical sensitivity or toxic induced loss of tolerance tilt environmental illness. And I think that was mast cell activation. We just didn't recognize it at the time. And you know, finally, people like Claudia Miller, who wrote whose life work has been chemical sensitivity, who developed the queasy questionnaire to figure out if you have of chemical sensitivity. She and Dr. Afrin and a bunch of other people at, you know, colleagues of ours got together and wrote an article, overlap between multiple chemical sensitivity and mast cell activation. And it really does seem that if you have multiple chemical sensitivity, you have mast cell activation. And the reason that I'm going into this history is because one of the biggest drivers of multiple chemical sensitivity is, you know, gas, petroleum, you know, sort of gas exposures. That's one of the biggest ones, along with pesticides. And so it makes sense now with, you know, piggybacking on what Beth was saying, that this is a huge trigger for mast cell activation because I think it's always been a trigger for mast cell activation. We just didn't call it that at the time.

I want to talk a little bit about infections. So we know that there is potential for viruses, bacteria, fungal overgrowth, parasites to potentially be triggers for mast cells. Wondering which of the infections you think are the most relevant in this conversation? We've talked about Bartonella. We've talked about COVID Does treating these infections over time also seem to reduce the severity of the mast cell activation syndrome in your patients? What is the split in terms of internal or external? When we're talking about triggers that may be triggers of or stimulators of mast cells.

Let's see, where to start? You know, I think so many of our patients are multiply infected that it. It often becomes really challenging to sort out. Oh, bartonella is triggering things 25%. Or maybe it's the fungal colonization. It is. It is an infectious soup. And sometimes we don't even know which are the biggest triggers until we've resolved them. And we can say in hindsight, when I treated this, these percentages of symptoms got better. When I treated this, these percentages got better. So, you know, it's kind of yes to all of the above, Scott? Yes, Covid absolutely triggers mast cell. Yes. Bartonella and lyme absolutely trigger mast cell in some patients who have, you know, what we call chronic Lyme disease. But it's really a Babesia infection that can certainly trigger mast cell activation. And absolutely, fungus internal fungal colonizations can trigger mast cell. You know, I've only occasionally dabbled in the parasite realm, and I do find that treating parasites can help with mast cell activation. I know we're going to talk about biofilms a little bit here shortly, but biofilm colonization is huge in triggering mast cells.

I've had Dr. Ann Courson and Dr. Ruth Chris on the show previously talking about hypercoagulation. We know that heparin is one of the materials that some people test for to explore the potential for mast cell activation. Why are the mast cells releasing heparin? And then in someone that is hypercoagulated, would it not be a good thing that the mast cells are releasing heparin, which is actually then blood thinning? So wondering if you can talk a little bit more about the connection between mast cell activation syndrome and hyper per coagulation.

Sure, I could try. So it's interesting. I've learned a lot from Ruth and Dr. Ann Corson as well. What I'm finding is that many patients who are chronically ill have a genetic predisposition separate from their mast cell to have a hypercoagulable state, whether that's factor 5 Leiden prothrombin G mutation or something called PI1 plasmagen activator inhibitor. They could have an elevated LP or elevated homocysteine or MTHFR. Gene variants can also contribute to a hypercoagulability. So there's this hypercoagulability genetic predisposition that somebody has. I mean, I'm testing virtually everyone in my practice, and I'd say about 90% of my patients seem to even have just the PI One variant. So it's a quite hefty number of people in my, my chronic illness patients. I, I do suspect that, you know, if we think about the mast cells as being the, the cells in our body that are really trying to protect us and doing their best job to protect us, maybe releasing heparin is a way to counterbalance the hypercoagulability that's being triggered by the bartonella or, you know, the mold that's triggering the hypercoagulability. So who knows, Maybe that's a weird way to think about it.

Or.

No idea. I definitely don't have any research on that. But we do know that Heparin release is one. I know Dr. Afrin thinks of it as one of the markers that's most sensitive and specific. I don't tend to test it very often because I haven't found a lab that has a decent enough reference range to verify that it's actually present in my patient population. But that's one way to think about it.

So if we build then on hypercoagulation, I want to talk a little bit about biofilm. So I tend to think of biofilms as maybe a more extreme presentation of hypercoagulation, kind of another spectrum of sorts. I know some people maybe think of them completely separately, but to me, there seems to be some overlap. And I've always felt like we need to be very careful about aggressively breaking open biofilms. I see people all the time, early on in their treatment that want to do biofilm breaking and start taking enzymes and doing those things. And so my concern has been that as we open Pandora's box, so to speak, and we release more infections and more environmental toxicants and toxins that can activate the immune system, activate the mast cells, that. That potentially could make things worse. So what is the connection between biofilms, biofilm treatment, and mast cell activation?

Let's go back a little bit and talk about what biofilms are. For those of the listeners who may not know, a biofilm is, I think about it as a force field or a mucopolysaccharide gel that bacteria, fungi live in when they are hanging out together. And the truth is that they hang out together everywhere. It's the scum on a pond. It's the ring on a glass. When you let the water evaporate, that. That mineral content that's left in the glass, that is the residual of the biofilm that was from the bacteria that was in the water. It's the slime at the, you know, in the path of the snail. So biofilms exist everywhere. And that also means that we have a biofilm in our nasal passages where we have bacteria. We have a biofilm in our gastrointestinal tracts. We have biofilms in our vagina, if you're a female, and our bladder and. And what I'm Starting to see. And what I've learned from Ruth Chris is that the hypercoagulability piece reinforces the biofilms that are being created by the bacteria. Now I don't know if it's the person's physiology laying down those fibrin clots in the biofilm or the fibrin particles or if it's the bacteria saying, oh, we want, we want some of that fibrin. I don't know who was doing it, but the hypercalubility is reinforcing that biofilm, making it that much more resilient and resistant to being broken down. And so what I'm finding actually with a lot of patients who have interstitial cystitis or even just, you know, dysuria or like urinary frequency, they often have a biofilm or a colonization and they're hypercoagulable. So they have this double whammy. I had a 50 year old fireman who used to complain that he would have to like keep a empty soda bottle in his, in his cab because he wouldn't know when he'd have to go. And he'd have to go so badly he couldn't get off the, you know, the highway and go, he'd have to urinate it right there in the, the fire truck cab. That's not normal. And it turned out that sure enough, he was positive homozygous for the PI1 gene variant and had a biofilm film in his bladder. Treating the biofilm in the bladder and treating it with biofilm busters and antibiotics, a couple courses of that, he has no more symptoms. So cool. And I've had other patients who have had, you know, similar lifelong rashes, terrible mast cell, terrible joint pain and at, you know, and I've gotten them better and they're more stable. And now we add in the, the, the piece of, of breaking down the biofilms and breaking down the sticky blood, as I call it, and people just keep getting better and better and better and the mast cells calm down more. So it seems like these biofilm colonizations are contributing to the low level inflammation that's happening. And as we clear it up, the mast cells can calm down, the inflammation can calm down, down and it has a systemic effect in many people. So it's really cool stuff.

And do you find that you have to be very intentional about the timing of introducing biofilm therapies in that it could also potentially, you know, create more triggers being released into the system that then ultimately make the mast cell activation piece worse for A period of time.

Yes, I'm cognizant of that. But it is rather surprising how well tolerated some biofilm busters are. I mean, you know, with my very, very sensitive patients, that's not where we're going. But you know, I have a. Unlike Beth, I have a larger, more hearty constitution practice. And with those folks that we can go there fairly quickly, surprisingly, and they do really well. And it moves the needle very quickly. But yes, of course it's always important to be aware of the level of sensitivity of someone and you know, put that later just like we put the metal removal later. We have to be cognizant.

How much of an overlap is there between mast cell activation and immune dysregulation? Is it reasonable to perceive mast cell activation as an indicator of a lack of likely TH2 dominance? And are tools that are broadly immunomodulatory in rebalancing TH1, TH2, TH17, Treg? Do those commonly have a positive impact on the mast cell activation piece?

Absolutely. One of the really very simplified ways we could think of mast cells is that they're some of the frontline sensing, defending cells, but also orchestrators of the immune response response so that we could think of them as the conductor of the orchestra. And the orchestra is these. All these various neuroendocrino gastro immunological responses that are happening. And the mass cells, I and I, I frame it that way because the mass cells sit at the interface of the nervous system, the rest of the body, and they line the nerve sheaths, they are at the nerve endings. They have a really connected, an essential role with nervous system signaling. And we can't even segregate out immune dysregulation from nervous system signaling. So we've got to. We're really in this cutting edge area of rethinking these systems as independent and seeing them as not segregated at all. But all that to say a lot of this comes out of the work of Dr. Sam Yanek, who I think of as is one of our, maybe the father of functional immunology. And he talks about how mast cell activation is going to happen when a mechanism for it happening is when the TH1 pathogen killing side of the immune system gets overwhelmed. So this TH2 chronic inflammatory side dials up and those work like a seesaw. So either our healthy state is inflammation down, pathogen killing high, but when we've been onslaught, onslaught and affected by mold toxins and chemical toxins and stressors and traumas, then it can get flipped. And when we're in this flipped survival pattern which is a part of cell danger response. So again, protective mechanism, then that opens the door for the signaling to start to go awry. So what, what signaling goes awry? Autoimmune signaling. So every form of autoimmunity has been linked to. If there's autoimmunity, there's a mast cell dysregulation because the mast cells are opening the door for that TH17 signaling. And we can think about even things like cytokine storms. Now, cytokines are not limited in any way to mast cells, but mast cells are a big orchestrator of those cytokines. And there's. I have studied, you know, study illustrations showing the relationships between the mast cells and all these various B cells and T cells cells and lymphocytes and, you know, you can. Natural killer cells and all that. All this cytokine signaling that goes on. Well, if you think about mast cells, again, as being a major conductor, not the only. But they're such a big one. We, we tend to highlight them and emphasize them if your conductor is wonky because it's been onslaught by constant battle with toxins, pathogens, stressors. 24, 7 never gets to rest, just like any of us. If we didn't get to sleep, we would start to think strangely and not behave well. It's really hard to conduct an orchestra when you're really dysregulated, which is what. What's happening there. So that opens the door to all kinds of difficulties with managing infections, with managing inflammation and autoimmunity and even cancer.

Beth, you and I did a podcast on secondary porphyria and so wondering, is there a connection connection between porphyria and pyroluria and mast cell activation syndrome?

Yes, it's one of my favorite topics. So pyroluria is a form of porphyria. So we have to remember that when we're talking about porphyria pyloria, we're talking about the heme pathway where there's eight enzymatic steps and HMBS is the enzyme. I'm not going to even try to pronounce that whole word because it's very complicated. But, but what's called hmbs, that enzyme, when that enzyme gets blocked, you get the buildup of the pyls. And we tend to very loosely use the word porphyrins or really porphyrin bin and different words for these intermediates in this pathway, but we kind of loosely call them porphyrins and these porphyrins. So. So that pathway is creating Hemoglobin, it's creating all the other mitoglobin, cytoglobin, that delivers oxygen to tissues. It's also the base molecule for some of our antioxidants like sod. It's a base for catalase. So those that are breaking down superoxide, breaking down hydrogen peroxide, so resolving inflammation, particularly in the presence of pathogens. And it's the basis of nadph. So I just wanted. Which recycles glutathione and is has a role in dozens and dozens of really important pathways. So I wanted to drop those parts of the heme pathway in for people because you have such a loyal listenership and they're going to start connecting to some of these other podcasts that you've done. When these intermediates that we're loosely called porphyrins build up, they are highly toxic and they do trigger mast cells. And this is where you get symptoms. Visceral hypersensitivity and extreme abdominal pain that's diffuse. That can get confusing if somebody has something that's also tender. Like you could have a swollen spleen and your spleen hurt and have diffuse abdominal pain. But it tends to be that there tends to be extreme anxiety because these porphyrins block the GABA receptors. Well, mast cells also have GABA receptors. I have not come across anyone who studied it yet, but I want to if the perforins will block the GABA receptors on the mast cells in addition to the neurons. But we do have clear evidence that it is triggering mast cells. And it depends on the tissues. So it can be triggering in the skin, it could be triggering the mast cells around the nervous system can be triggering in the GI tract, various other tissues.

The last question before we get into some cutting edge intervention conversations is the connection between mast cell activation syndrome and Ehlers Danlos syndrome or hypermobility syndromes. Do we think that mast cells being activated can themselves have a negative impact on our structural integrity? How strong is that connection?

There is. There is definitely a connection, and I think it's bi directional. And so people who have a hypermobile physiology, because they. They do have actually EDS or they have EDS hypermobility, they tend to have a greater likelihood of developing mast cell activation if they're put in a situation where they have exposures to mold or Lyme or Bartonella or some of the other triggers that we've talked about. And then I do think that the mast cells which get released then can tenderize the ligaments and the tender and exacerbate the Underlying genetic predisposition. I'll let Beth continue.

I think that was great. I think what I could add is that mast cells, and this came from the work of Andrew Maxwell. Mast cells release elastase 2. And elastase 2 tends to make connective tissue more lax. And so when we think about connective tissue, we can think about the skin, we can think about the joint tissue, but we also think about the blood vessels. Vessels. We have to think about the lymph system and any of the other connective tissue we can start to have trouble with. Well, interestingly, and I don't have it tied to Elastase 2 yet, but I've been digging. We know that bartonella mycotoxins can both degrade the connective tissue better, but faster than the body can build it. What's really fascinating is that there are different forms of eds. Several forms are known as genetic. But the. The more common hypermobility form still does not have a single genetic marker that can be attributed to it. There's a collection of collagen markers and so on that can be loosely associated. But in terms of it being a primary genetic condition, we don't know that for sure. And I have seen people reverse it, and I've reversed it myself. Took from quite extensive hypermobility to where an osteopath was working on me, and I warned him ahead of time, I'm hypermobile. You gotta be really gentle. And he examined me and he said, I see no evidence of hypermobility. I think you've reversed this. And then I had two mold exposures, and it came right back. So again, we're back to pathogens. Bartonella toxins, mycotoxins, and then stressors can also trigger mast cell activation and release more of that elastase too. So we've got to think about those in terms of. In terms of how we're going to address eds. But there is a lot of hope. And having gone from somebody who could barely even carry a wallet because the hypermobility was so intense and the associated muscle spasms and everything that was going on with it, to being somebody who can function normally and pick up a basket of clothes or carry in the. The groceries or, you know, carry a heavy cooler that's loaded down is. Is. I just can't tell you how happy I am. And. And I see this in our clients, too. And so there is a huge amount of hope, particularly in the secondary hypermobility type of EDS or just where we are on the hypermobility spectrum. But even those who are genetic. And I've worked with people with genetic hypermobility. If we take the load down on the connective tissue, we may never get completely out of EDS if it's genetic, but we can certainly improve the symptoms and the functioning and there's a lot that can be done there.

Let's talk about some of the more cutting edge interventions in the mast cell activation arena that you are both finding helpful. Many people think quercetin when they consider mast cell activation and histamine intolerance. One of our listeners suggested that quercet works in the same pathway as estrogen and makes her histamine issues worse due to poor estrogen pathways. Do you see mast cell activation become more of an issue in puberty when estrogen and other hormones increase? Have you seen quercetin poorly tolerated in those that seem to have more hormonal contributors as well? And then is there an upper limit to how much quercetin one should take in a day before we're potentially creating problems within our microbiome?

Okay, so yes, I see that quercetin is not perfect for everyone. You know, one of the things that I think is most important when helping patients manage their mast cell symptoms, and Beth alluded to this earlier, is really that, that intuition. And so I really try and encourage my patients to learn how to tap into their own intuition is, you know, we start with testing for supplements and trying to figure out what are the supplements that are going to be most useful. And many times quercetin is not the go to thing, you know, whether that's because of their intuition that they know it's going to not be great for their, for their hormone estrogen pathways. And in patients who aren't interested in doing muscle testing, you know, if they don't see a benefit, then we move on to other things, things. So although it's, you know, touted as one of the best things, I use it with some people and not with, not with everybody. I definitely see mast cell becoming an issue with hormones for a variety of different reasons. We know that mast cells have hormone receptors. And what's interesting too is I also see that patients who are mold exposed have hormone dysregulation. So many, many of my young, 20, 30, 40 year old women who are not menopausal will be amenorrheic, meaning they don't have a menstrual cycle. And, or if they do, if they do have a cycle, they have horrific cycles. And it turns out that they're often sensitive to their own hormones. I had one Young woman, she would get a mast cell flare right before her menstrual cycle. Kind of full body hives, terrible fatigue and lethargy. Couldn't go to school because it was so debilitating for her. And what we figured out was that she had a sensitivity to progesterone. We were able to desensitize her to her own progesterone. And now she has normal menstrual cycles, takes no antihistamines, has no problems with it. And, you know, it was a pretty profound and relatively simple way to treat that. So there are lots of interplays between the hormones, the triggers of hormonal dysregulation and mast cell.

And in that scenario with the desensitization piece, were you using something like NAET or something like sublingual immunotherapy or low dose immunotherapy? What was that?

Yeah, we did sublingual immunotherapy to progesterone. But yes, I've used that for people who have histamine intolerance too. So they have, have mast cell, they have overabundance of histamine. And we figure out that they have a sensitivity to the histamine exacerbating all of those symptoms. And we can treat with sublingual immunotherapy. It's pretty awesome stuff.

And do either of you have any concerns about too much quercetin negatively impacting the microbiome? I seem to remember Datis Kharassian talking about with some of the flavonoids and polyphenols and things that we don't want to do too many of them.

You know, Dr. Theo Hereides talks about this as well and you know, he has a pretty unique formulation that is focused on better bioavailability over increased quantity. Now, I've done both. I've used that approach. I've used higher dose straight quercetin. And some people can take a lot of it, some people can take a, only take a little of it. Some people can take none of it. Some people can take the form that's in the soft gel, some people can take more, the powder form and capsules. And I think it just comes down to bio individuality. But it is a prebiotic. And so for those who have sibo, particularly an overgrowth with things like Galactobacillus, bifidobacteria bacteroides, then it's a prebiotic for those and it can. And I've seen that increase. I've also seen Perilla and some of the Other phenolic herbs that we use sometimes increase gas and bloating people with SIBO and sometimes not at all. But this is where you've got to get in and look at the case and why there are just no blanket protocols for this. We can have frameworks, but then everything needs to be individualized because every case of MCAS is completely different. Different.

Dr. Kelly mentioned that quercetin isn't always a go to. So I just want to do a quick rapid fire for each of you, knowing that everyone is unique and your approach is very personalized and individualized. What are your top three to five interventions in working with your mast cell populations?

Honestly, I often start with H1 and H2 blockers. I know it's not as popular if people want to be more natural, but we know, we know how it works, we know why it works. And so I do use H1, H2 blockers. I do find them very helpful. I use a lot of LDN with patients as well because oftentimes they'll have that autoimmune piece that needs to be managed. Let's see, I've. I've recently started trying oxytocin. So stay tuned. It's pretty, pretty cool little molecule to play around with. And you know, I, I think, I know you wanted this rapid fire. Let's see. Pick, pick. Alginol is another one of my favorite ones. Pyramine. I'll use resveratrol. Resvoxitrol. And then, you know, it has to. It has to be. That's just the mast cell piece. So we have to do the vagus nerve. We have to do the limbic system retraining. We have to do the emotional spiritual reconnection with one's intuition. So that's. There's my top interventions.

Love it, Beth.

I mean, I could go big picture or I could go into individual. So I think I'm going to go. Go just really big picture here because so much, again, depends on the case. And we get such variety of like this person's salicylate intolerant. Oh, this person has pretty significant sibo and this person has alpha gal. And this person, you know, is. Can take all kinds of things. This person's struggling to even drink water. And so what I time and time again come back to is the big picture of, of dialing down the nervous system through the limbic. The vagal retraining and emotional grief processing is a big part of the nervous system because there's so much grief in chronic illness, so much loss of the lives that we had and loss of relationships, loss of being seen, of being understood. There's a lot of grief. And then one thing I did want to touch on trauma that would fit in here is we soothe the trauma. We don't go back and revisit when people are in the thick of things because it can stir it back up and feel retraumatizing. We just work on ways of soothing it in the body rather than telling. And telling the story of talk therapy or even EMDR is usually too much. So that's the ner. I'm going to put that in the nervous system category, nervous system, neurological, emotional category. And then we have, we've got to remove the triggers. So this can take some time and it requires to get well. And people really can get well. And it's remarkable what happens. But people have to have the courage to do whatever it's going to take. And that may mean I let go of my toxic hair dye. If that's causing me anaphylaxis or hives. I let go of having my router on overnight. And yes, my teenage son is going to be unhappy or I'm going to get him a higher data plan or everybody's going to be offline at 10:30 so that we can reduce the MF. The mold remediation is often the biggest for people and the most challenging. But we've got to think about the chemical toxins, we've got to think about the food triggers. Are we drinking clean water? I love how Jill Carnahan makes it very simple. Clean air, clean water, clean food. And so we look at this clean relationships. What I think about what's happening biopsychosocial for people and that's why we call it 360, is we got this whole view, you know, of the whole person and then we go into a gentle detox. So those are my three nervous system remove triggers, gentle detox. And if we can get through those three phases, then things like doing sibo, things like going after tick borne infections go much smoother and they're easier because we just took the big heavy hitters out.

Wonderful. Love it. Low dose naltrexone is one of the tools that I have found very interesting over the years for immune modulation. We've used it for many years in the chronic Lyme realm in the mold illness arena. Does it have a role in mast cell stabilization and if so, how might the application of low dose naltrexone be different in that scenario?

You know, I don't know if I necessarily think about it differently in the MCAS patient population because oftentimes they have mold and they have Lyme and they have autoimmune conditions. And so I'm using it in a multifactorial way to help calm down that immune system. Perhaps the major difference would be in how I'm dosing it. I might start at a much, much lower dose in a very sensitive mast cell patient. So we're starting out like 0.1 milligrams and they're opening the capsule and they're taking little tiny granules of that. If they're really that sensitive, as opposed to when I first started with Lyme and autoimmune, I was like 1.5 and then quickly titrate up to 4.5 and no mast cell patient could tolerate that. So that's the biggest difference that I find in using it.

Another favorite immune modulator of mine personally is black seed oil. Wondering if you've used black seed oil in your patient population populations with immune dysregulation with mast cell activation and does it hold up as a helpful intervention in your clinical experience?

I find it's, I mean, it's definitely powerful. It has immunomodulation properties. It has very specific properties with mast cells. It's been shown to really help with allergies, which we know mast cells have a relationship with. It helps reduce COX2 prostaglandins, leukotrienes. So there's quite a bit of research about the thymoquinone that's in black seed oil or sometimes black seeds. And sometimes it's called Nigella sativa or black cumin seed. It's also one of the things, this is again one of those, the right thing in the right order at the right time for this person because it's also antibacterial and antifungal. And so some people who have a high fungal or tick borne infection or other, you know, pathogen load that's responsive to black seed oil, that can blow them out of the water. Other people who are really robust love it and they do great on it. And so we just want to take that sensitivity level and account for people. But it is just one of many. And we could probably list hundreds of possible nutraceuticals that support the mast cells, but that's, that's a top one for people who aren't super sensitive.

What role do peptides play in supporting those with mast cell activation? Are there specific peptides that you find most helpful? Are you using BPC157 or KPV or amlexanox or others in your patient populations?

I'm not using a lot of peptides in my patient population. I do know that BPC157 can be very helpful, helpful orally for gastrointestinal system and calming down the mast cell and then as an injectable for tendon issues, joint pain issues. And then the KPV also is used, but I don't, I don't use it a whole lot.

We talked a little bit about slit therapy or sublingual immunotherapy. There's also low dose immunotherapy. Are you finding low dose immunotherapy helpful in modulating the immune system and thus benefiting those people dealing with mast cell activation syndrome?

You know, I'm using more of the LDA or low dose allergy therapy, which is a form of immunotherapy taught by the American Academy of Environmental Medicine to treat more global reactions, food reactions, in what they call inhalant reactions. And so these are grasses, molds, trees, dogs, cats, dust mites, et cetera. And then they do have a chemical mix as well. And so it is a very simple, very broad spectrum way of calming down the immune system. It's inexpensive, it, it doesn't require any testing and it has been a wonderful addition to helping quell that immune dysregulation in a mast cell patient. And, and it's administered either sublingually or intradermally once every two months. And so it's a very doable thing for most patients. Now, you know, patients in Beth's practice probably wouldn't be ready for it if they're super sensitive, but the ones who are, are a little progressed, can benefit greatly. It takes down that reactivity and can be used in conjunction with slit therapy, the sublingual immunotherapy, for more targeted interventions of phenolic reactions in food or hormonal reactions that people might have and then with the ldi. So that's low dose immunotherapy developed by Ty Vincent. That's going to be more targeting. I find the infection piece of that. So that would be Lyme, bartonella, et cetera, to really try and calm down that immune disposal dysregulation due to those infections. So that's how I use it predominantly.

Yeah. Excellent. Love that. Are there specific minerals that make mast cell activation syndrome better or worse? How do zinc and magnesium fit into the conversation? What about iron or copper? Whether deficiency or toxicity? Is there a place for talking about.

Minerals in this conversation definitely there's so many nutrients that the mast cells need and it's astounding. But they, they do need zinc. Zinc's really important in terms of modulating that TH one response to allow us to dial down. So if we boost TH1 because the seesaw effect, we're gonna help modulate down the TH2 chronic inflammatory side that can drive some mast cell activation. So zinc I find is a big one. It's often quite well tolerated, but I find it tolerated in the sensitive population really well. It's not a starting point for me with the hypersensitive, but those who are sensitive, they can take some things. They may be taking two or three supplements at small amounts or more and they've got number foods as opposed to hypersensitive or people who probably not taking anything or they're taking a tiny sprinkle of one or two things and they're down to very few foods. And sometimes we have to build them up to the, that sink. Iron's another really important one. And iron is a sweet spot mineral. And so by that I mean if it's too low, you're in trouble. If it's too high, you're in trouble. So we tend to think about iron deficient anemia, which that in itself is a whole thing. And I'm sure you've got podcasts on what, how to truly define that, that we're not just looking at ferritin. So if anybody studies thinks they have iron deficient anemia, make sure to watch that podcast because there's a lot of educating to be done around that. And if you give someone with mast cell activation syndrome iron when they don't need the iron, it can cause a huge amount of excess inflammation. But if you have somebody who is truly iron deficient, where you're looking at the labs correctly, you're looking at the cbc, you're looking at the red blood cell markers, then if they truly need iron, then that can be a game changer in terms of stabilizing. And then of course you have to track because you can start to flip. And this iron picture where we're getting out of balance with iron is another aspect of that cell danger, survival response. We have to remember this is happening for a reason and we only want to intervene when we're getting into trouble, but we want to monitor. So I always find anybody who has mold toxicity as tick borne infections or any kind of serious chronic illness should be doing a CBC and a cmp. So complete blood count and a complete metabolic panel every Six months because you can catch a lot of things and it's easier to turn around a rowboat than a cruise ship when you let it go on for two years. And that's where that simple blood work that most people with chronic illness comes back normal. But sometimes you'll start to see trends if you watch it over time. And then we have copper. Copper is a fair weather friend in this population. We need copper for so many functions. One of them just relevant to this conversation is that copper is a base molecule for diamine oxidase. And so if we don't have copper, we can't make that diamine oxidase, that DAO enzyme to break down histamine in the gut. The same time, an increase in copper is going to decrease zinc, which is going to decrease our TH1 boosting, which can increase our mast cell activation. So we have to be really careful with copper. Copper in our population, it's one I've maybe only recommend somebody supplement two or three times ever, like two or three cases where we worked with that because mold toxicity there there plenty of published research showing how mold toxins are highly depleting of zinc and zinc and copper. Work with Cecil.

While not exactly a mineral, shilajit does contain many trace minerals, humic and fulvic acid. Have you found a place for shilajit or other products with humic and fulvic minerals beneficial in mast cell activation?

I do use a good bit of humic acid, particularly ion, to be able to repair the. I find that it repairs the gut lining in part not alone. I don't find it as a standalone in the levels of gut lining disrepair that we see. But I find it really good and I really like it as a nasal spray to start repairing the blood brain barrier. So I think that's excellent. Fulvic acid does have some binding properties for a variety of different toxins. I've not used the silajit very much at all myself because it's complex, because it's hard to get a good source. I know there are good sources out there, but it's quite complex and I tend to do simpler formulations in the sensitive population, which is who we're seeing. However, I'd probably use it a lot more if I had more of a heavily weighted robust population.

What is the overlap between mast cell activation and elevated IgE, which we think of more as traditional allergy? And then are there specific flavonoids or other nutrients or medications that might be IGE blockers, but may also have some beneficial effect in Mast cell activation.

You know, in all of my mast cell patients, I probably have only a handful with elevated IGE reactions. And, you know, of those, most of them are, you know, 150, 200 max, 300, and then like two or three that have, have IGEs in the thousands. And so for the ones who have IGEs in the thousands, I'm referring to an allergist. And oftentimes they're getting things like Xolair, and usually that can be extremely helpful for those with the IGE levels in the, you know, 200, 300 range, myself included. I use a lot of LDA. I don't, I don't necessarily find that there are flavonoids or nutrients per se that are going to help lower that ige. I'm really trying to reduce the immune reactivity in general for those patients and choosing the mast cell stabilizing options based on how they tend to respond best.

If I could just add in here, because we do get a bit of elevated ige and there's just a handful of things I have found to be a game changer for some people. Particularly the paraprobiotic holoimmune has IGE blocking properties. And I've seen that particularly getting up sometimes these elevations into two to three capsules twice a day, which does get pricey. But it's cheaper than xolair out of pocket if people have the ability to try that first and they're not too anaphylactic. Sometimes zolaire just needs to be done. But there's also bioflavonoid available. Been experimenting with for about a year now called biofisetin. That's also an ige blocker. Zinc's an IGE blocker, quercetin's an IGE blocker. So I find if we're going to go on the nutraceutical side, the synergy can help dial it down some.

So many good things. I love it. I want to just get a couple more thoughts on Zolair, because that is something that I'm hearing more and more people talking about asking me about the being suggested by their practitioners. And at the same time, it seems like people have reservations about it because of potential side effects. So what are your thoughts? Are there significant side effects? Is it clinically helpful? What are the things that we need to consider when making that decision?

Like I said, I don't often prescribe it. I'm referring to the allergist to prescribe it, mostly because it is a insurance hoop that needs to be jumped through and it's much easier to get it covered by an allergist than by a primary care or an internist. So that's one thing to think about. And then getting the dosing right too. So there's a wide variety of dosing that has to be looked at. Yeah.

And we've got a great talk with, with Dr. Tanya Dempsey where she talks more about her views on Xolair. I understand the hesitations because it's a biologic and you can get into things like one of the, one of the things we talk about, and I just want to point people towards the summit on this, is that histidine is one of the inactive ingredients. Well, histidine gets converted to histamine in the body and so there are ways to preload to reduce some of the side effects of Zaire. And Dr. Dempsey talks about that in her, in her talk.

Awesome. Awesome. I have to say that over the years I've been a little disappointed with people's response to supplemental dao. It doesn't always, always seem to make a shift. Wondering what your experience has been in your patient populations with supplemental dao.

One of the breakthroughs that I had with DAO was finding out that B6 is a cofactor. And so people don't have enough B6, they can't utilize it. And all of our enzymes have cofactors that are often not in the formula. So for example, digestive enzymes have mineral cofactors. And so, so we get so many people who are nutrient and mineral deplete. And I think this is sometimes why these different enzymes aren't working. I did formulate a DAO with a tiny 1mg of B6 in it and it's very clean and we've not seen a lot of reactions. Now, of course, somebody's pork sensitivity. DAO is pork derived, so that may not work if somebody has alpha gal, but that one I tend to get some, some improvements in. And not all DAO is made the same. So, for example, there is a nature DAO that comes from peas and I've had some people swear by it. But then there was recently some unpublished laboratory testing that showed very little DAO activity with it. So I think there's a lot we're still learning about availability, the CO factors, the way it's metabolized and who it's going to work in and who, who it's not going to work for. And does this person even have histamine intolerance?

Is there a place for IV therapy in mast cell activation? And if so what are some of the IV nutrients or materials that you might consider for supporting that patient population?

So I love phosphatidylcholine. That is my favorite. Go to IV oral medication or not a medication supplement. So Shameless plug.

We did a podcast on that before Dr. Kelly and I.

So yeah, check out my podcast. We go, we talk about full fat in that one. So yeah, I love phosphatidylcholine. And one of the things that's so amazing about it is that it's often generally well tolerated, even in mast cell patients. Probably not the hypersensitive, but the sensitive people IV because we're bypassing a lot of the locations where the mast cells are, so people don't tend to react quite as much. And it's great for treating many of the triggers, environmental chemicals, mold exposure, as well as Lyme and chronic infections. And so I just love, love, love phosphatidylcholine. Of course, many other nutrients are great. You can give extra B vitamins and zinc and things like that. But yeah, PC is my favorite.

And some of the, the go tos I've seen for flares also are if there's low blood pressure to just get some normal saline, get that up. Magnesium, a corn free vitamin C. This comes from, this cocktail, comes from Alex Bingham, who's a great functional medicine physician in this space. And then adding in a little bit of B1 and a little bit of B2 because those are needed for that proper nervous system signaling. And a lot of times people are sensitive, they could just start with normal saline and the next time they get some magnesium chloride and everything has to be preservative free. And then the next time they can do, you know, they can, they can build on the cocktail. So then they can bring in the corn free vitamin C, tapioca based, for example, it's preservative free. And then the next one, they add a little B1 to the mixture.

We've talked about so many nutraceuticals and medications in this conversation, but are there any other medications or supplements that we don't commonly hear discussed in the mast cell realm that you are familiar finding helpful with your patients?

Well, I can just put out a couple. I mean, catotofen is talked about more and more, but that one has so many properties in terms of being a selective H1 receptor blocker. It's anti eosinophilic, which means it's going to reduce histamine production and it's anti liqu And I don't Prescribe myself. I consult and make recommendations. But that's one that often is, is helping a lot of people that we have educational conversations about. On the medication side, repatidine also you have to get it. You can get out of Canada and it has a coating that you can take a wet rag. And again, this came from Alex Bingham. Wipe that coating off for people are sensitive to the coating. And then on the supplement side, so simple. But one of my go to is this baking soda. I get a lot of people with low blood pressure doesn't isn't not not the right thing in high blood pressure. But they can use potassium bicarbonate and bicarbonates modulate a Cert 2 mechanism that drives inflammasome production that drives mast cell activation. So in a way it's actually reducing mast cell activation. People think of baking soda as being so simple, but it's, it's quite amazing what those bicarbonates do. And Tanya Dempsey goes into a lot more. I want to hear what Dr. Kelly has to say, but I just want to to make sure we put a plug in there for her talk.

I love ketotifen. I find that for many, many of my mast cell patients it works really, really well. And you can start at teeny, teeny tiny doses, you know, 05025 once or twice a day and work up to. I have one patient who has takes 8 milligrams twice a day, has to be compounded, which is a little bit challenging. I do also use a lot of compounded H1 blockers as well. So we find that for those sensitive patients, they can't tolerate the inactive ingredients in the commercially available products. But they do really respond great to the pharmaceutical itself. So we do a lot of compounding medications. I also love rupatidine. It's a platelet active factor inhibitor and so it has some unique properties in addition to the H1 block activities.

With EMF exposure seemingly becoming an increasingly significant part of the mast cell activation conversation, have you found any tools that are really helping your mast cell populations? Obviously mitigation or reduction of exposure is critical. But then there's also the conversation potentially about harmonization as well. What's working for your patients?

Well, definitely when you do the mitigation, get that, you know, make sure there's no dirty electricity, that we're not too close to the large transformers, we're not sleeping next to where the parallel lines come into the house. That's all critical. I've not seen a lot of success in my population with harmonizers. Some with blocking clothing. And I wear blocking clothing myself when I go, if I'm staying in a hotel or if I'm traveling, especially on an airplane. And I really make sure I get a hood and I, I cinch it down and I look weird as heck but I don't care because my brain doesn't hurt when I do it it. But one of the things that I recently learned about is this quantum field technology and this is actually what I'm wearing here. And this has been a, a game changer for me, my, myself. And then there's also this larger home unit that creates a quantum field. And it's actually this is very solidly research backed. There are studies on it, there's studies showing how it works. Whereas, you know, I know we've talked before about how stickers and the pendants and all this stuff when we don't know doesn't seem to be doing much. We don't have enough evidence, but there's clear evidence. And then we have a talk on this. I hope people listen to it because I think it's a game changing talk with EMFs and protect changing the dialogue away from getting rid of all of them, which we've got to mitigate what we can. But we're not going to be MF free even if we go live in the desert anymore because we've got Starlink. So what are we going to do? This is one of the things that we can do that is accessible and without having for all of us to live inside a canopy and try to work inside a canopy. So I hope people watch that talk.

And for people that want to dive deeper into that as part of the summit. I believe that's your interview with Dr. Roger Billica, correct?

That's right. Yeah.

Yeah. Excellent. Very, very exciting. As we start wrapping up, I wanted to just get your thoughts on limbic system retraining tools like DNRs. Gupta Primal Trust is becoming very popular and their potential to calm mast cell issues and lead people to being less sensitive and better able to tolerate the environment around us and other treatment interventions. What are your thoughts on the importance of limbic system retrainings?

I find that it's an essential piece of it. But the patients really have to understand that they have to be active participants. They're not going to do the program and have the program make them better. It doesn't work that way. So I do think that there's a little bit of a misunderstanding for some people that they actually really have to participate and even more so than just going through the motions. So it can be a critical, important, important component, you know, and, and ultimately what I find is that just like we have to tailor the diet, we have to tailor the supplements and the medications, each individual has to tailor the tools that they're using. So, you know, it may be that Gupta or DNRs is the thing that's going to move them from one place to the next and then they need a different tool and then they may revisit those tools that they, they've learned in the limbic system retraining at some point in the future when they're going deeper and deeper into the traumas or their own emotional healing, their spiritual journey, what have you. And so it's, it's. I see treating mast cell activation and have witnessed my patients experiencing this as a complete transformation of their, of their lives. And, and they are learning how to listen to the messages of the body and tap into what the body is saying and the intuition that they have been ignoring. And as they're healing those things, you know, first you have to heal the medical trauma and then you kind of are able to go deeper and gathering tools from various different places, whether that's an energy healer or a medical intuitive or a sound healer or reiki practitioner or brain gym practitioner and all of these limbic system retraining programs and developing their own spiritual practice. It is a layered exploration and transformation.

Beautiful. Beautiful. The two of you are such a great team. I know you recently paired up on the upcoming Mastering Mast Cell Activation summer summit, which will be linked in the show notes. Who are some of the people you've interviewed and what are a few takeaways that might surprise us or enlighten us?

Some of you know the ones, they've all been amazing. But Dr. Theo. Theo here, Theo Heredis talks about some cutting edge approaches in MCAs, but also wove in Covid and talked about some more in depth about the quercetin and the microbiome. And I think that one's a really important one to listen to. So I, I'd love for people to hear all of them. Neil Nathan really brings us the big picture of why are people becoming so sensitive and what do we do about it? And gets into a lot more detail than what we were able to cover here today. A couple other ones I'd love to point people to just would be Trudy Scott and about GABA support versus benzodiazepines. Really important conversation. And we mentioned the, the talk on ems. Don't miss Tanya Dempsey's talk on advances in medication and nutraceutical approaches and complex MCAs because there are some things that will be quite surprising. I don't want to give it away and we don't have time for me to do it justice but to catch that because there's some, some game changer things for both patients and practitioners and really all of these lectures but those are just a few of the top of my head head.

I have to give a few extra plugs. Andy Maxwell's talk, he's a pediatric cardiologist and the spiky leaky syndrome and really tying in the hypermobility mast cell environmental toxicant piece. It's just an awesome conversation. And then Jeffrey Smith spoke about GMOs which was fascinating to me. I learned a lot. Lynn Patrick is always so brilliant with her explanations of environmental chemicals and the weaving in that environmental medicine piece. And then we had a roundtable with Darren Ingalls and Tom Warcroft on Lyme disease and Bartonella and that was really fun to have that back and forth conversation with the four of us. And of course I have to plug Beth's talk to too. This talk was fantastic.

I think, I think both of ours and don't miss Kelly's because you really framed that we have to come back to love for ourselves and that just I think that's the bottom line is we get in these places because we're not loving ourselves, we're not loving the planet and if we come back into that love, we do have the courage to do what we need to do to heal ourselves. And if we heal ourselves then we have the courage to make the changes that can change the world that's driving MCASC for so many people. And we can change whether our great grandchildren are going to have the same lives that we've been living. And it's really up to us.

Wow.

I don't even know what to say to that. That was so powerful. Thank you, Beth. My last question is the same for every guest and we can be brief because we've covered so much already. But what are some of the the key things that each of you do on a daily basis in support of your own health?

I always do something for my nervous system. A listening app, some limbic work. I, I'm really loving NuCalm. I'm really loving safe and sound protocol. Kelly, you got me into Resimax which is one of my daily and frequency specific microcurrent. I do my supplements, I do my protocols. I love my sauna. But I, I may not get in the sauna every day. I don't get in the sauna every day, but what I do every day is to go out in nature. Nature and connect with the earth. And I'm lucky to live by a nature preserve and have a little area that's secluded and quiet and that will make or break my day if I go out and. And get in contact with the earth because it reminds me of why we're doing what we're doing, that it's so much bigger than I want people to get back to eating their chicken or eating, you know, cassava or eating, eating cucumbers or whatever it is. But really, it's about us all coming together in our oneness and in our humanity and remembering our humanity.

Okay, what do I do? Yes, I. I try and walk every day and do yoga as much as I can because that is not just the physical practice, but the mental practice. I love to do hard poses because it, it builds my trust in myself and my resilience and my strength. And I take my supplements every day and I try and spend time with the people that I love every day.

Wow. I love it. You are both amazing people making such a significant, positive difference in the world and really working hard to minimize the struggles of so many. I want to thank you both for being here and I just adore you both.

Thank you so much, Scott.

Back at you, Scott. This is just so fun. I love the three of us being together and I really love both of you.

To learn more about today's guests, you can find Dr. Kelly at drkellymccann.com that's D R kellymcann.com drkellymcan.com and find can find Beth at mastcell360.com that's Mast Cell360.com masscell360.com thanks so much for listening to today's episode. If you're enjoying the show, please leave a positive rating or review as doing so will help the show reach a broader audience. To follow me on Facebook, Instagram, Twitter or TikTok, you can find me there as Better healthguy. If you'd like to to support the show, please visit betterhealthguy.com donate to be added to my newsletter, visit betterhealthguy.com newsletters. This and other episodes can be found on YouTube, Apple Podcasts, Spotify, Google Podcasts and Amazon Music.

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