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REPLAY: Mast Cell Activation Syndrome with Dr Michelle Woolhouse & Beth O'Hara

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REPLAY: Mast Cell Activation Syndrome with Dr Michelle Woolhouse & Beth O'Hara

Naturopath Beth O’Hara shares her experience of 20 years with MCAS, most of those years undiagnosed, which has fuelled her interest to become an expert in MCAS.  

Dr. Michelle Woolhouse delves into Beth’s health journey with MCAS and Beth generously shares her clinical pearls on the atypical presentations of MCAS, the relationship of mast cells and the nervous system, genetic variants (SNPs) predisposing someone to MCAS along with treatment options that range from micro dosing supplements, neuroimmunology, limbic system balancing and vagal nerve stimulation. 

Covered in this episode

[00:32] Welcoming Beth O’Hara
[02:31] What is MCAS
[05:51] Signs and symptoms of MCAS: piecing together the big picture
[12:23] Beth’s personal struggles with MCAS
[17:35] How Beth rebuilt her health
[19:57] Stabilising the nervous system
[25:53] The importance of safety during the healing journey
[30:23] Genetics and testing for SNPs that provide insights into MCAS treatment
[35:10] Functional pathology testing for mast cell mediators
[40:50] General protocol for sensitive people
[45:05] Additional resources for practitioners
[47:14] Thanking Beth and final remarks

Key takeaways

  • Mast Cell Activation Syndrome is a multi-systemic, immune dysregulation with atypical presentations which narrows down to knowing which mast cells and receptors are being dysregulated along with which mediators are being released. 
  • Mast cells line every nerve sheath and every nerve ending. They can release neurotransmitters and neuropeptides but also have receptors for these communication molecules, giving rise to communication between mast cells and the nervous system. The chronic excessive release of signalling chemicals (eg histamine, cytokines) can lead to hyperactive signs and symptoms as the cross talk between mast cell receptors and the nervous system is accelerated. 
  • Signs and symptoms that may or may not present in MCAS – 
    • MSK- general swelling/oedema, muscle and joint pain, hypermobility, connective tissue disorders, osteoporosis, osteopenia, food sensitivities, chronic pain 
    • Integumentary- itching, flushing, hives, burning skin, itching, poor healing, hair loss, rosacea, psoriasis 
    • Cardiovascular- chest pains, tachycardia, palpitations 
    • GIT- diarrhoea, constipation, reflux, dysphagia, burning mouth, IBS 
    • Nervous system- brain fog, headache, anxiety, depression, insomnia, numbness, tingling 
    • Respiratory- wheezing, asthma, shortness of breath, post nasal drip, congestion 
    • Eyes- redness around eye 
    • Reproductive/Urinary- endometriosis, dysmenorrhea, urinary pain
    • Autoimmune conditions 
  • People with MCAS can be particularly sensitive to supplements. Be super vigilant when considering herbal tinctures and begin with micro doses of therapeutics, the equivalent of a few grains of sand. 
  • Stabilising the vagal nerve must take into consideration a person’s sensitivities i.e. if one is sensitive to light and sound, avoid those therapies. 
  • Genetic variants to consider for MCAS: ABP1, AOC1, HNMT, EGT181, CYP21A2, HTC, MAO, NAT1, NAT2, KIT, IL-6, IL-13, SIRT2. 
  • Mast cell markers where a single elevation can indicate MCAS: tryptase, chromogranin A, prostaglandin D2, plasma histamine, urinary n-methyl histamine or urine histamine, plasma heparin. Urine prostaglandin D2 and prostaglandin F2, and leukotriene E4. 
  • Complete blood count (CBC) or full blood examination (FBE) eosinophil percentage >2% can point to excess histamine. 
  • Liver function tests (LFT) are an important marker to flag and manage for toxicities. 
  • Vitamin D (25-OHD) helps to stabilise mast cells.
  • Iron studies in accordance with RBC’s can aid with assessing inflammation due to excess iron or the need for iron.  
  • Treatment may take two to six years. Beth's recommend phases of treatment for sensitive patients are as follows: 
    • Phase one: Stabilisation of the nervous system (particularly limbic), the vagal nerve and mast cells. 
    • Phase two: Support sleep, stress, sex hormones and thyroid. Assess the root triggers. 
    • Phase three: Gentle detox 
    • Phase four: Treat any tick borne issues 
    • Phase five: Rebuild gut lining, bones, connective tissue 

Resources discussed and further reading

Beth O'Hara
Beth's website: Mastcell360
Research: Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review, The Journal of Allergy and Clinical Immunology: In Practice, 2021)
Podcast: The Emerging Importance of Psychoneuroimmunology with Dr. Michelle Woolhouse and Professor Craig Hassed
Research: Defining the Role of Cognitive Behavioral Therapy in Treating Chronic Low Back Pain: An Overview, Global Spinal Review, 2015

Vagal Treatment

Research: Running Head : Frequency Specific Microcurrent Therapy as a Healing Modality 1 Potential of Frequency Specific Microcurrent Therapy as a Healing Modality Submitted (Wickersham, 2020)
Research: Polyvagal Theory: A Science of Safety, Frontiers in Integrative Neuroscience, 2022


Michelle: Welcome to fx Medicine, bringing you the latest in evidence-based, integrative, functional, and complementary medicine. I'm Dr. Michelle Woolhouse. 

fx Medicine acknowledges the traditional custodians of country throughout Australia where we live and work and their connections to land, sea, and community. We pay our respects to the elders, past and present and extend this respect to all Aboriginal and Torres Strait Islander people today.

Today we're going to explore the complex but very important syndrome called Mast Cell Activation Syndrome, or MCAS for short. And how by breaking it down into simple constructs can help us as practitioners navigate patients through this windy road back to health. We're also going to look at the whole system's approach to healing and by using basic principles that help us manage the overwhelm faced by both patients and practitioners alike. 

Joining us on the line today is Beth O'Hara. Beth is a U.S. based functional naturopath and functional genetic analyst. She's a doctorate in Naturopathy, and has a master's in Marriage and Family Therapy. After her own health journey and setbacks, she specialises in the genetic analysis, functional naturopathy, and emotional wellness for those experiencing MCAS. She's passionate about helping and teaching others to do the same. 

Welcome to fx Medicine, Beth. And thanks for being with us today.

Beth: Thank you so much for having me on. And I think this will really be a significant game changer for some practitioners. Because as we know, pre-COVID population studies of mast cell activation syndrome showed it was affecting up to 17% of the general population. We suspect it's much higher, because of the trigger, mast cell trigger that COVID is higher today.

Michelle: Oh, I'm excited to get into that. So, I'm going to start with a question I'm assuming you get asked a lot, which is what is MCAS? And how does it present? And also, why you became so interested in this space?

Beth: Sure. So, we'll start with what is MCAS? So, mast cell activation syndrome, it's an immune dysregulation. And it's defined as multi-systemic, meaning it affects more than one system. And it can present with or without allergy. And it can present with or without anaphylaxis. And with or without hypersensitivity. There are myriad of different kinds of symptoms that people can experience. And this comes down to which mast cells in the bodies are dysregulated, which receptors are affected, and which mediators are being over released.

So, we know that the mast cells are in every tissue in our bodies except the retina. And then there are over 200 receptors on the mast cells for everything from various pathogens, whether we're talking about Lyme bacteria, we're talking about Bartonella or we're talking about Shigella or something like that. For viruses, whether it's COVID, or flu, or cold virus, Epstein-Barr, for moulds, for parasites. There are receptors for chemicals, for hormones, for stress and injury, for cytokine signalling from other immune cells. And we could spend a whole podcast just on those receptors.

Michelle: Yeah. I like that.

Beth: And then with the mediators, people know about histamine, and that's very well known, but there's over 1,000 mediators. So, these include mediators like prostaglandins, interleukins. There's a whole class of different inflammatory and anti-inflammatory cytokines, substance P. And one of the mediator classes I want people to just tuck into the back of their mind because we'll come back to it is that mast cells also release some neurotransmitters and neuropeptides. So, there is the continual communication loop with the nervous system. And they actually reside along every nerve sheath and every nerve ending. So, they're the interface between the nervous system and the rest of the body. And that's very important when we get into how do you work with people who are having these kinds of issues and particularly those with hypersensitivity. 

But then there are so many locations, so many receptors, so many mediators. Those types of symptoms that can show up are really based on what permutations of those are occurring for this particular patient, and what triggers are happening for them. And when I think about symptoms, I like to think per system, and there's no way to go through all of them. That would also take the whole podcast just to do that, but I'll hit some highlights, and then point people to some resources.

Michelle: That would be great.

Beth: When we think just systemically, we can have symptoms like chronic fatigue is one of the most common, chronic pain, muscle pain, joint pain, common. Sensitivities aren't always there. But if somebody has a lot of sensitivities, if they're the person who's holding their breath to try to get down the laundry aisle of the grocery store, or they're struggling with supplements and medications and most of these things are triggering them, and they're having food reactions, it’s not a guarantee that it's mast cell activation syndrome, but it's a good clue to at least dig and find out.

And people can have general inflammation, they can have general swelling, they can have water retention. In the musculoskeletal system…we talked about muscle and joint pain, they can have a bone pain and mast cells are actually made in the bone marrow and then migrate out. There's a relationship with mast cell activation syndrome and hyper mobility of both the joints, but also skin and other connective tissue. Osteoporosis, osteopenia, have been linked. And people won't have all of these symptoms, most likely. They'll have some combination of them.

Michelle: What you're telling us is it gives us some clues, because we often see patients with food sensitivities, or chronic pain, or fatigue. I’m thinking of a couple of patients at the moment that are really sensitive to supplements. So, it's a great way to kind of take those top end kind of symptoms and sort of see them as potential clues.

Beth: Yes. And these are the patients who are going from specialist to specialist to specialist, and nobody can piece together the big picture. So, there are these...often thought of as these mystery cases. And part of it's because this has been so mystifying with...there are thousands of possible presentations that can show up. 

If we think about the skin, if that's involved, we're going to see things like itching, flushing, hives. We can see burning, skin burning. We can see slow healing of skin. Hair loss is actually quite common because of inflammation of the hair follicles and not being able to hold on to the root.

And then the autoimmune types in conditions like rosacea and psoriasis, you can also see eczema. There's some misinformation out there. It used to be thought that everyone with mast activation syndrome had to have skin symptoms. Now we know that's not true. And there are people with MCAS without the skin involvement. But I just wanted to put that out there for people.

With the cardiovascular system, we might have chest pains that aren't heart attack related. We might have a rapid heartbeat or heart palpitations. You see a lot of GI symptoms and this is very common. Anything from diarrhoea or constipation, acid reflux, trouble swallowing, and throat tightness is common. Mouth burning I see a good bit of, irritable bowel syndrome and all of the inflammatory bowel issues have been linked with mast cell activation syndrome. We think about if there's chronic inflammation, there's a mast cell component there somewhere. 

With the brain and nervous system, brain fog is super common, trouble with word recall. I see a lot of headaches, the anxiety, and depression, and insomnia. Tinnitus is common. Just ear ringing is one of the most excruciating symptoms, if people have that. May get numbness, tingling. 

With the respiratory system, if that's involved, we get things like wheezing, we can have asthma, shortness of breath, a lot of post-nasal drip is common, sinus congestion. Again, people may not have that system involved so we always have to keep open to which systems are involved here. 

We can have irritation, redness around the eyes. Reproductive tract can be involved in particularly things like endometriosis, painful menstruation, hormonal balances. The urinary tract, inflammation in the urinary tract. Bladder burning and pain is common in both men and women. And then, if lactic reactions can occur, not everyone has those. 

And almost every form of autoimmunity that I've seen...every form I've seen, there may be some that haven't been associated, but I'm pretty confident based on the mechanisms of the immune system, that we'll eventually find that every autoimmunity is linked to mast cell activation syndrome. Ehlers-Danlos is closely related, POTS, Postural Orthostatic Tachycardia. Autism spectrum disorders are related. Rheumatoid arthritis, Hashimoto's, multiple sclerosis, any of those if there's autoimmunity, or these kind of chronic inflammatory issues, we want to trace back and see are the mast cells dysregulated?

Michelle: I mean, what you've just presented there is just an enormous...and obviously having thousands of receptors in nearly every system of the body apart from the retina be involved. Are we talking about mast cell activation syndrome being the mechanism for the symptomatology? Or is it a distinct symptom on its own? Can you have something like an autoimmune disease and not have MCAS being the underlying causation of it?

Beth: That's a great question. And I think it traces back to how are we going to define mast cell activation syndrome, and that diagnostic code only became official in 2016. So, the diagnostic criteria is still in flux. But I think what we could officially say is there will be mast cell dysregulation, and then whether or not it qualifies concretely as mast cell activation syndrome, depends on what state we're in, and the evolution of that diagnostic criteria, which is still being debated. But if there's chronic inflammation, there's going to be some mast cell involvement. And that's what I'm most concerned about. The diagnostic criteria for my purposes are just too new. And I consultant, I don't diagnose. But I'm looking at getting people back, getting their health and their lives back.

Michelle: I'm going to get to the diagnosis in a second, but I really wanted to find out why you became so interested in this space.

Beth: Yes, this is a journey of my own health. I started developing health issues around age eight. We had moved to an old farmhouse in the country. I thought it was a great adventure, and it was. There were really fun aspects of it. But my health started unravelling. And no one knew back then. I mean, this was the early '80s. No one knew about mould toxicity. Barely anyone knew about Lyme disease and we were bitten by ticks. And when I was a child, I would be covered head to toe in hives and then scratching until it bled. I had a traumatic brain injury when I was nine, and that set off all of this brain inflammation for decades.

And I developed severe insomnia, anxiety, dark depression. And I was very academically inclined, though, so I kept pushing academically and pushed way too hard. I really wanted to become a neurologist. I was on track to go to medical school. And my senior year of undergrad, I had burned the candle at both ends. I had gotten scholarship offers, and I had to turn them all down because I was so ill at that point, I could hardly get out of bed. And it was just devastating. I didn't have a backup plan. That was all I could envision myself doing. 

And instead of going to become a neurologist, I became a chronically ill patient, and my health kept cycling downward until by the time I was 28, I was hobbling with a cane. I could barely even walk from excruciating pain. I didn't sleep for four years. I had daily panic attacks. I was itching head to toe. I had severe GI distress daily basis. I'd gotten down to 10 foods that I could tolerate, and I lost my tolerance to medications and any supplements. So even a little sprinkled curcumin would give me extreme anxiety, flushing. A little bit of quercetin would worsen my insomnia.

Now I know about salicylate intolerance, but I didn't understand that then. But even GABA, just a little sprinkle of GABA would send me out of my skin. And I totalled up at one point, I'd seen over 75 practitioners. Nobody knew what to do with me and I exhausted traditional medicine, holistic medicine, functional medicine. We didn't have a word for mast cell activation syndrome back there. 

And everyone I saw, the compassionate ones said, "You're the most sensitive person I've ever met. And I'm so sorry, I just don't know what to do.” And the ones that were frightened and didn't know how to handle it told me that I was crazy, that it was in my head, that my lab work was normal, and I got a referral to psychiatry. And somehow, I kept going. If I'm nothing else, I'm tenacious. And I kept going. And the last time someone said, "I don't know what to do," was the most experienced functional medicine physician at the time I could get to. This was before telemedicine. That didn't exist.

Michelle: Yeah.

Beth: And I sobbed the whole way home and sobbed the whole rest of the day. And I woke up the next morning and said to myself, "Beth, what else are you going to do? You can lie here and die or you can figure this out." And I had the pre-med background. So, any moment my brain would start to focus, even if all I could do is read two sentences of a research paper, that's what I would read, and try to piece together what it was saying. And it took me a total of about 20 years to put the pieces together, but I figured out the root triggers.

Once I learned about mast cell activation syndrome, then I was off to the races because I had something to focus on. And it was still in its research phases as of that point. But I did, I put it together. I met Dr. Neil Nathan who has influenced me tremendously and is my close mentor and learned about the root triggers, and addressed those. And I went back to graduate school later in life and built a practice. 

I just like to share with people some of the wins, but I just came back from a trip to go see my husband's grandchildren, and I got to play with them all day. And I could pick them up and pack them around. And I can go hiking these days, I haven't used a cane in years. And my brain is fully functional. So, it's been a huge, huge turnaround.

Michelle: Yeah. What an inspirational story. I mean, I think it really does, it gives that deep merit when you've actually been the patient yourself. We talk about that quite commonly, but to build yourself up from really, the end of the line, essentially, is what you've just described, and back up to being fully functioning, dropped the cane. It's one of those inspirational stories, I think all of us love to hear. 

So, obviously you know MCAS from the core all the way in which to kind of rebuild a body. So, for you, how did you start after finding out that? What were the first things that you did to turn that around for yourself?

Beth: Well, after running into a brick wall many, many times because I didn't know what I was doing and it was all experimentation. Eventually, what started turning things around was, one, getting out of mould exposure. I didn't even know that I've been exposed most of my life even after I had left home. And started working on my nervous system. That was what started turning it around, so that I could start to tolerate things. And when I began to start supplements again, I started with extreme micro dosing. 

And just to give people a sense of what this means...a lot of times I tell people, "You're going to start small with some sprinkles.” And then they come back and I review what they were doing and I'm like, "Well, how much did you actually take?" And they'll say, "An eighth of a capsule." I'm like, "No, no, no." Because it'll backfire on really sensitive people. When I say sprinkles, I mean literally the equivalent of three or four grains of sand.

Michelle: Yeah.

Beth: Like a dusting. And I started with just the very first thing...I mean, it might've been a B vitamin because it was so long ago. I don't really remember. But I started single ingredients. And I'm pretty sure I started with B vitamin because herbs I couldn't handle at the time probably because of salicylate intolerance and extreme micro load that I had. But anything that I could handle...I remember using B2. 

Now it's not where I would start people today. But I would open the capsule for this little dusting in water and just do that for two months. And then I would start with the next...

Michelle: Oh, two months.

Beth: ...thing I thought I could layer in. Like B1. I put the tiniest little dusting of B1 in with the B2. And over about four or five years, I built myself up to where I could do these little sprinkles of...I had about 30 different things and I'd make myself this little sludge every day twice a day. And I could get that down. 

Now we have a whole method and the whole system of how to guide people through. And so, well, I call it the first step, the stabilisation phase. So, we really start with stabilising the nervous system, particularly the limbic, and the vagal nerve, and we stabilise the mast cells.

Michelle: So just going to stop you there, Beth. When you say stabilise the nervous system — because there's obviously so many things that can support that — what do you do to stabilise the nervous system? How would you start with that?

Beth: Yeah, so I want to reach back towards the podcast you had on psychoneuroimmunology. And I was so excited to see that. That's what I did like my master's research in.

Michelle: That's what I did my post grad in too. It's my passion.

Beth: Oh, great. Well, we're going to have fun here. So, for people who aren't as familiar with this, or they haven't listened to that podcast yet, I really want to encourage them to listen to that, because it's essential in understanding, really, really understanding the mast cells and how they function. So, to go back to how they line every nerve sheath and every nerve ending, I talked about how mast cells release neurotransmitters and neuropeptides. They also have receptors for neurotransmitters and neuropeptides. So truly, it's this constant communication feedback. And particularly for people who are not tolerating anything, supplement wise. I get a lot of people who can't handle anything orally, their skin is a mess, they can't do patches or anything topical. And they're not ready for the dosage of an IV.

The nervous system is a way that we can enter and calm the mast cells down in an incredible way. And especially for sensitive people, it's about at least 50% of their healing process. There are two important parts of the nervous system that we focus on, the limbic system, and the vagal nerve. And a lot of times people will tell me, "Well, I'm using the Calm app or Headspace app, or I'm listening to meditations on YouTube, or I'm doing yoga, breathing and meditation." And that's great and definitely continue those. But the limbic system and vagal nerve have a lot of power involving how the mast cells regulate, or dis-regulate.

And particularly because both of those systems are highly involved in monitoring for safety. And the mast cells are all about monitoring for safety. And that's how they work in conjunction. And there are mast cells in the limbic system, inside the brain. And with the limbic system, particularly, it's very important to have a method where we are exercising, going from our fight or flight, anxious state, and the mental ruminating that we all do and shifting that very deliberately and consciously into a deep state of calm, and peace, and safety.

And there are different ways of doing that. But we have to do it repeatedly. We have to train those neural pathways just like we might train for a marathon, where you're going to build up slowly over time, and you're going to have a daily practice. And you wouldn't just do one day of it and then go run a marathon. You're going to train over time over several months. And the best programs I found for that have been Annie Hopper's, DNRS, or Ashok Gupta's Gupta Program and both are fantastic. And I tell people, "Look at both of them and see who you resonate with, whose voice feels safer to you, who do you feel most relaxed with." And there are few others. There's one now called The Primal Trust Academy that's come up and another called Direct Your Own Care. A few other programs that are starting to come and be available. There are limbic programs but there are not many of these. They're very specific. 

On the vagal nerve, there's so many modalities that people can use, and we have to hone them for their sensitivities. Some people have a lot of light and sound sensitivities, so they may not be able to use those modalities. So, they may have a lot of EMF sensitivities. But it's great as a practitioner to have a whole toolkit to choose from because the more vagal support people do, more different kinds of ones, the faster they can reboot that system from dysregulation back to regulation.

Some of my favourites are BrainTap, which is an audio program that has different sound modulations in each ear. They have a lot of programs, but they're particular ones for healing, and relaxation, and targeted at the vagal nerve. And they make a head start with light. And it's even more effective if people can tolerate the light. There are things like alpha stem. I actually just got to try this last night. And it's the current thing you put on your ear lobes. And it runs a particular frequency. And it's very calming, and it's oriented towards the vagal nerve, I really liked that.

Michelle: That sounds good.

Beth: There are things like frequency specific microcurrents. And that's one you have to do as a practitioner. So, when people have a physical location, and that's a wonderful one to look into getting certified in because then you can bring people into your office and give them those kinds of treatments. It's called frequency specific microcurrent.

There are other things like vagal acupressure that's helpful. There's another listening program that we use a lot in our clinic we have a practitioner administer. It's called the Safe and Sound Protocol. It was developed from Steven Porges polyvagal work. And those are just a selection of some of the ones that are out there.

Michelle: It's brilliant to talk about that psychoneuroimmunology component of the treatment because I think that's often being missed over the treatment programs that we've kind of supported people through and understanding with that significant sensitivity that working with the body rather than working against the body. Because really mast cell activation syndrome, a little bit like autoimmunity, is almost like the body fighting.
And so rather than joining the fight, and it’s that sort of almost philosophical way of ‘you can't cure anger with anger’ kind of thing. It's really working within and sort of coming around and really stroking the body and keeping it safe and creating trust. And that way has a profound shift in our immunity and therefore our overall nervous system health. And so, it's fascinating for me for you to actually bring this as almost the first component of your healing mechanism when you're dealing with somebody that is in that state of severe sensitivity.

Beth: It's so critical. And we also have a psychologist on staff who's well versed in this area and mind-body approaches and she works with emotional support coaching, right. But from emotional support perspective, also just having that support of feeling safe with another person and witness. Because the reason I share the part of my story that I was told so often I was crazy, because it's so common. And it's traumatising for people, and they've heard it many times, unfortunately.

And even that, being witnessed in that, "Yes, your symptoms are real," in a way that isn't encouraging them to be a victim, but is empowering them to say, "Yes, your symptoms are real. Yes, you are experiencing this. And there are things you can do about it." And to have somebody do that in a way that's compassionate and gentle, and then help them feel safe in their bodies again, is huge. So, this is the whole foundation for moving forward, especially for the hypersensitive people.

And while we're talking about safety, bringing in as well emotional safety, safety within our relationships, whether it's our family relationships, or friendships, other social relationships, or work. It's amazing how many people with chronic illness are in a relationship with somebody in some way that's disordered. And that's also not safe. 

So, I've had times where people have gotten out of mould, they've done all of the stuff. But they're not improving. And when we start digging, we start to realise, "Oh, you're being emotionally abused on a regular basis." So, I just going to open some of these pieces for practitioners dealing with the patients who are like I was, and there's all these components to it. And if we start thinking about outside of the box, outside of this, "Well, give them some quercetin, or give them an H1 blocker, or something like this, what are the actual triggers going on underneath and how do we help them navigate it?” Because this is a lot of work to do what we're all doing with these really chronically ill patients.

Michelle: And it's interesting, what you say too because we're talking about emotional safety maybe in relationships, maybe in the workplace, maybe in intimate partner relationships, but also, you alluded to mould. So sometimes when the environment is unsafe as well. You were nine years old or eight years old when you moved into a mouldy environment. And I think in my experience with some patients that have had an external parasite, or bacteria, or virus really impact their body over a long period of time, how unsafe they feel, and how angry they feel at that external stressor. And I just think that it's often with mast cell activation syndrome, you can see these multitude of causation factors. And so, what you're teaching us is to look at the whole, and by piecing together and accepting every single part of the pie, and knowing when to start and when to move is really the art of the practitioner and the patient relationship.

Beth: That's absolutely it, yeah.

Michelle: So, I want to take you back to a few more practicalities. Because I know that you have an expertise in analysing genetics and genetic sensitivity, and you find that really powerful, important part of your practice. Tell me about some of the testing that you consider or that you find really helpful in which to confirm or embellish your thinking as a practitioner.

Beth: First, I want to frame the genetics in terms of thinking about it as epigenetics. And when we have these underlying triggers that affect our genetic expression like mycotoxins, like Lyme or these other co-infections or metals, chemical toxins, stressors, all of these affect their genetic expression. The way I look at the genetics is that we'll have these weak points, that once the genetic expression is affected will be highlighted. But also remembering that when the triggers are removed, it's amazing how the genetic expression can correct itself. And often these genetic variants are not a big deal.

And just a case in point, I'll use myself again. I have significant genetic variants on the heme pathway and had acute intermittent porphyria when I was really ill as well. And those attacks happened repeatedly until I got out of the mould exposure and got partway down the detoxification and got some of this out, and the Lyme handled and the co-infections handled.

The only time I have any trouble with that pathway now is if I'm at elevation and low oxygen can be a trigger. And I just increased my carbs slightly, and I'm fine for somebody who had severe attacks, historically. So that's just an example. 

And I see a lot of things turn around for people. The genetic testing that I use, I use Bob Miller's functional genomic analysis. And I find that his software for practitioners is quite comprehensive. And he has all kinds of ways of presenting the data and their biochemistry maps in there with the genes laid right in there. That's very powerful.

Some of the snips that I look at, some of my top ones are the ones for histamine, the ABP1 AOC1 genes for diamine oxidase, which is different by the way than the DAO gene and that gets mixed up sometimes online. The DAO gene is for the amino oxidase, not diamine oxidase. So, for DAO, diamine oxidase, it's AOC1 or ABP1. The HNMT genes, the histamine receptor genes I find really helpful. And ones...some of the others involved in histamine breakdown. So, these are going to be a glucuronidation gene, EGT181.

There's CYP 21a2 that has to do with converting progesterone to cortisol. That's mast cell stabilising. Let me come back to histamine for a second though.

Michelle: Yeah, do.

Beth: The HTC gene is the helpful one. And that one has to do with converting histidine to histamine. MAO genes break down histamine, [inaudible 00:37:25] genes, NAT, one and two, break down histamine. On the mast cell side, I look at the KIT gene. I like to look at IL-6 and IL-13 with interleukin. Those are some of the top ones that I like to touch on. And then anything that's inflammatory can impact...if we have iron dysregulation issues, if we have issues with copper transport to where copper is accumulating, which is really common in this population. We have issues with glutathione. Oh, I want to touch on one other which is SIRT2. And SIRT2 is the signaller and it signals to inflammasome production. One of the really interesting things about SIRT2 is that you can modulate that with resveratrol. You can also modulate it with bicarbonate. And one of my first entry points for really sensitive people is actually if they have low blood pressure, use baking soda…

Michelle: It's pretty cheap.

Beth: ...for that inflammasome modulation.

Michelle: So, all of those genetics, I mean, for a new practitioner, that sounds quite complicated. But is there particular pathology tests that you can use or even the standard kind of tests like looking at the full blood examination, looking at zinc and copper levels, looking at urinary and liver function tests. Is there other kind of pathology tests that can highlight some of these issues?

Beth: Well, why don't we talk about the ones that are diagnostics for mast cell activation syndrome and then I'll talk about what I find to be most useful.

Michelle: Okay great.

Beth: In this current diagnostic criterion, there are 10 markers that are mast cell mediators and 1 of the 10 has to be elevated. These are tryptase, chromogranin A, prostaglandin D2, plasma histamine, urinary N-methyl histamine or urine histamine, plasma heparin. And then you can also measure prostaglandin D2 and prostaglandin F2, and leukotriene E4 in the urine.

The challenge with those is that all of those samples have to be kept chilled until processing. And they have to be cold centrifuge processed, which most labs, at least in the States, don't have. I don't know about Australia. And most of the time, these tests don't get run correctly. They don't get analysed or processed correctly. Dr. Efrain, who's one of our leaders in this field, he believes that if it's processed correctly, one of those is going to be elevated.
One of the questions I keep coming back to is if there's over 1,000 mediators, and we only have 10 we can measure, how do we know they have an issue with 1 of those 10 and not the 990 plus others? So, I don't know the answer to that. I don't usually ask people to run those other than sometimes it's nice to see the plasma histamine and N-methyl histamine. But I do ask people to get CBCs and CMPs every six months. And this is because we deal with so much toxicity, and so much tick-borne infections and we need to track these. I look at, in the CBC, the eosinophil percentage.

Michelle: So that's what...

Beth: And if it's over 2%.

Michelle: So, I was just going to say, Beth, we use the term FBE for CBC. So just for clarification, but go on.

Beth: Okay. Thank you. So, I look at the eosinophil percentage. So, the eosinophil...there's two other cells, besides mast cells that make histamine, eosinophils and basophils. If those eosinophils are over 2%, then that can be a good case for using Ketoprofen or Rupatadine. And those are both anti-eosinophilic as well as have other mast cell stabilising properties. So that's one for people to keep an eye on. And then why are the eosinophils elevated? 
With the CMP...is that the right term for Australia?

Michelle: Okay, yeah, UNEs and LFTs.

Beth: Okay, so with your UNEs and your LFTs, generally, I see kidney markers stay in a good range in the population I see. And I can only speak to that population. But really watch those liver enzymes. Because again, there's so much toxicity in people who are really chronically ill, and make sure they're getting liver support if they need it. 

There's a few other blood tests I ask people to get routinely. Vitamin D 25-OH. Vitamin D is mast cell stabilising. And in the mast cell population, we want that — now we're going to get into trouble with the units of measurement — but in the units of measurement we use here, we want it between 60 and 100.

Michelle: I think it's the same.

Beth: Then...okay. Then the iron markers. I always look beyond ferritin because ferritin is only showing us 10% of our iron stored, and can also be a marker for inflammation. Just because ferritin's low...I've seen a ferritin at six or seven, and the red blood cells were fine. So, we're going to look at those red blood cell markers to see if they're trending low. And then also look at your total iron, your iron binding capacity, the percent iron saturation transferrin. And it's not uncommon to see people dealing with mould toxicity, and tick-borne infections, and mast cell activation syndrome, to tip into true iron deficient anaemia. 

This is why you really want to make sure, because if their iron is fine and the red blood cells are fine but the ferritin is three or four, that may be high, high inflammation. And if you give that person iron, that iron will be inflammatory and can worsen the inflammation state. But if their red blood cell markers are low, and we're talking about their haemoglobin, their haematocrit, MCH, those markers, then if they don't get the iron, they're going to be in trouble. And our immune cells rely on iron to function properly. So that's another pearl I can share with people.

Michelle: So, looking at those markers, if we identify a very sensitive patient, and whether they're expressing that through their nervous system, through their immune system, through chronic pain pathways, fatigue, etc. And then going about and using things like psycho neuroimmunological tools, mind-body medicine, essentially. So vagal tone stimulation or support, and limbic system support, and an overall, I guess, empathy from a practitioner to know that to go slow is really important, to look at all of the underlying principles of health and well-being. So, the healthier the body, the more able the mast cells can stabilise. And looking at either chronic infections, such as mould, or chronic Lyme, or other kind of stealth-like infections, is that way of kind of very slowly supporting the body back to health and well-being all the while using continually mind-body medicine techniques to reinvigorate and re-energise the body that is often been unwell for quite a long time.

Beth: I'd love to share just the overall method we use for sensitive people in a nutshell. It's very brief, and this isn't what everyone needs. And if people aren't sensitive, there's many ways. I'm not saying this is the only way. I just want to offer this way of thinking as a possibility for people. 

The way we move people through is that we started with before the stabilisation phase, where we stabilise the nervous system and the mast cells, and we remove the triggers. And we do that before we ever start detoxing, because the people that we see are the ones that keep falling through the cracks, and they're failing the regular protocols, or failing the detox protocols. Nothing’s working, they can't handle glutathione. They're struggling with binders. And then we'll do what we can to support sleep, to support cortisol, and their sex hormones, and thyroid. Knowing that that's a moving target, while you're getting the triggers addressed. 

Then, while we're doing that, we're assessing what our root triggers are so that we can put together a plan for the order of operations. And it’s the order of operations, these really sensitive people make a difference for them. So, when there's mould toxicity, which we almost always see in this population that we're working with, we start with the mould, because it's so neurotoxic, disruptive to the immune system. It's almost impossible with a large level of mould illness and mould toxins and colonisation to get rid of SIBO or to clear tick-borne infections, or Epstein-Barr or these other things, parasites even, when the mould is still there. So, we go through a really gentle detox with them. And it takes longer than it does most people. But it's better to take longer and they can actually get through than they only make it a couple of months and they crash. 

Then we'll move on to the tick-borne layer. And usually once those two layers are addressed, most of the people — at least in our practice — start to clear Epstein-Barr and parasites on their own. Not exclusively, but most of them. And then when we get to the other side of that, we can start to rebuild things like the gut lining, the bone health. If there's been issues with osteopenia, now they can actually make headway, they can rebuild their connective tissue. I see Ehlers-Danlos, not the genetic kind, but the hyper-mobility form, we see it reversed quite a bit. It reversed for me, and I don't have signs of it at all anymore.

And definitely, just optimise and we do that genetic optimisation and get them on a wellness plan. That may take two years on the short end to five years or six years if it's a really complex case. But that's way shorter than 20 years. And people usually...95% of people will feel better, better and better as they go through.

Michelle: Yeah, that right.

Beth: I just want to give that order of operations as an option for these sensitive people. They're so challenging.

Michelle: That's such a good point. And I think too, I mean, hope is really important. And progress is really important as well. So if somebody is getting better all the time, then they can maintain that motivation as well. 
So, Beth, such a wealth of knowledge. Is there any go-to resources, or websites, or courses, if people are really interested in this, they can help themselves navigate this space better?

Beth: Yes, I'd love to share. Our website is mast, M-A-S-T as in Tom, C-E-L-L 360. So mastcell360.com. We have so many resources on there. We have a lot of practitioners who come. It's written for a lay audience, but I try to put the little pearls in there for the practitioner.

Michelle: Great.

Beth: And then we do have three courses. Many practitioners have taken them. There's the nervous system course all about these different modalities and how to choose and a lot of practitioners have used that to learn how to walk their clients through picking these different types of modalities and put a program together. There's a supplement course, the top eight mast cell supporting supplements. And then a real flagship course that practitioners love is the MC360. That's the name of the method, MC360 Precision Mold Master Class.

And it starts from the very beginning. When somebody comes in, where do you start with them? How do you walk through? And all of these courses have the research on them as well. So, I go over the studies and you get all the citations. But in the advanced one, it takes them through the entire mould detox for a sensitive person with mast cell issues. How do you get their mast cells stabilised so they can detox, the order of the detox. A lot of troubleshooting to handle things like stubborn constipation, other types of digestive issues, pregnancy and breastfeeding. And then there are three case studies that I go through their entire protocol from start to finish and what really got them well. Three people with quite significant illness and sensitivities.

Michelle: Beth, thank you so much for being with us today to discuss all things MCAS. It's certainly a complicated presenting issue. But the way that you shine that light on how we can walk through those complexities over a long period of time and the basic principles, you have given us so many tools to work with and helped in our understanding. And hopefully we can pass that on to many more patients in Australia and on this side of the world. So, I'm really grateful for you to be here sharing with us today.

Beth: Thank you so much for having me. I'm really happy we can partner to help more people get this out to those people that are suffering.

Michelle: Thanks, everyone for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's episode on the fx Medicine website. I'm Dr. Michelle Woolhouse. And thanks for joining us. We'll see you next time.


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