Hidden Histamine Threats with Dr. Theoharis Theoharides (Ep 139)

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Introduction to Mast Cells and Guest Introduction

Dr. Theoharis Theoharides: So I usually describe the brain as filled with spiders. They make spider web and the spider web is basically the scaffolding onto which the neurons crawl and make their connections. If the microglia see danger, two bad things happen.

Dr. Linda Bluestein: Welcome back every bendy body to the Bendy Bodies Podcast with your host and founder, Dr. Linda Bluestein and the Hypermobility md. As you may know, I have had a Barrett mast cells my entire life, so I'm super excited to talk to Dr. Theo Haes about mast cell activation and what we can do to help ourselves feel better.

Dr. Theo Haes is Professor and Vice Chair of Clinical Immunology and director of the Institute for Neuro Immune Medicine in Clearwater, as well as [00:01:00] the executive director of the Center for Excellence for Neuroinflammation Research at Nova Southeastern University in Florida. He's also the adjunct professor of immunology at the Tufts School of Medicine, where he was a professor and director of molecular immuno pharmacology and drug discovery.

He received multiple degrees from Yale, including his PhD and md. He also received a certificate in global leadership from Tufts School of Law and Diplomacy, and a fellowship at Harvard Kennedy School of Government. He has shown that the unique immune tissue cells and mast cells communicate with the brain microglia and are critical for neuroinflammation.

Dr. Theoharides has over 500 publications and almost 50,000 citations placing him in the world's top 0.05% of most cited authors and the worldwide expert on mast cells by scholar GPS and expert scape. He was inducted into the Omega Alpha Omega National Medical Honor Society, the Rare Diseases Hall of Fame and the World Academy of Sciences.[00:02:00] 

He developed novel dietary supplements with unique combinations of flavonoids formulated in Mediterranean olive oil to increase absorption. He has received over 30 patents and trademarks. I'm super excited about this conversation with Dr. Theo Haes. He is a absolute wealth of information when it comes to mast cell and mast cell activation disorders.

As always, this information is for educational purposes only and is not a substitute for personalized medical advice. Stick around until the very end. So don't miss any of our special hypermobility hacks. Here we go.

I am so excited to be here today with Dr. Theo her and we are going to have some excellent conversation and I ho I hope your day's going well for you and that you're ready to dig into this. 

Dr. Theoharis Theoharides: Well, it's a real pleasure to be with you and 

Dr. Linda Bluestein: I'm looking forward to our discussion. Terrific. 

Understanding Mast Cell Activation Syndrome (MCAS)

Dr. Linda Bluestein: So can you just start out, I mean a lot of the [00:03:00] listeners of this podcast, of course, are familiar with mast cells and mast cell activation syndrome, but just can you give us just a really brief, uh, description of mast cells and the, their role in the body and in health and disease.

Dr. Theoharis Theoharides: Well, that's an hour in itself. Exactly. It is. Alright. So mast cells are unique tissue immune cells. They come from the bone marrow. Most of them, they show up in the bloodstream as precursor or progenitor cells and then they go into tissues. And we used to think that each must cell is the same, and definitely that is not the case.

So depending what tissue they go into and what microenvironmental conditions they encounter, they develop into a different, what we call phenotype. So their ability to respond and their ability to potentially be inhibited about which we might talk at the end is very different. So we know for sure that they're [00:04:00] present in tissues that are exposed to the outside world, such as eyes, nose, mouth, lung, skin, gut.

However, number one wonderful paper back about five years ago. Showed that the must cells throw filopodia between the endothelial gaps that make up the wall of the blood vessel, and they sense what's happening inside the lumen of the blood vessels. So therefore they can be sensitive to whatever is happening outside and inside the body.

And point number two, they're present in the meninges that cover the brain. And in the central part of the brain, we call it the cephalon, especially the hypothalamus or regulates homeostasis and the amygdala, the regulate behavior. And in fact, the hypothalamus communicates with a pituitary that makes all the hormones with a small bridge, they call them median [00:05:00] nce, or the stock, and the number of mu cells per unit volume in that little bridge is more than what we have on our skin.

Yet the brain does not get allergic reactions. So that's kind of one point of the overview. The second point is that each cell contains about 1000 small spheres. So I call the master like a soccer ball field with about a thousand ping pong balls. Each one of those little ping pong balls contains as many as a hundred different molecules, and with the master is triggered, especially in anaphylaxis, all the small granules, secretory granules, little spheres release their content.

But over a period of six to 12 hours, the ma cell can make another so many molecules. And in fact, some colleagues wrote a paper about a year ago, Dr. Rin and colleagues, and collected about 350 [00:06:00] molecules that the must cell can make. Now the last point I want to make to which we will I'm sure discuss a much more in detail, is that.

Histamine and the enzyme tryptase that have been typically associated with the muscle cell is only the tip of the iceberg. Mm-hmm. Because in most cases where the muscles are activated, they're not released, lemme stop there and we might come back to what the muscles might be doing other than bad things in the body.

Dr. Linda Bluestein: So this is already fascinating. So when I think of phenotype, I usually think of clinical presentation and the differences in, uh, phenotypic presentations. Or you might have a phenotypic presentation of, you know, for example, hypermobile EDS that may or may not have a different genotype. So you're saying that we can also think of phenotype in terms of the mast cells themselves and that they're not all mast cells are created equal, it sounds like.

Absolutely 

Dr. Theoharis Theoharides: true. The muscles obviously have [00:07:00] in their nuclei information to make pretty much everything, like every cell of the body. Except that as we mature as individuals, as species, as whatever, certain cells forget to do some things and do other things. And the reason I'm saying that is because the muscles have existed for more than 300 million years long before we had an endocrine, you know, immune or nervous system.

Mm-hmm. In fact, by virtue of the fact that that contains so many different molecules, other colleagues, and I believe that there were kind of the multifunctional cell, it can release some hormones, it can release some neurotransmitters, it can release some new, uh, material. At the time, as I said that there were no such systems developed.

So fish, for instance, occupied lizards of bus cells that don't get allergic reactions. So we. Clearly believe, and there is evidence to that, that as we grew [00:08:00] and developed revolution functions of the must, cell became somewhat not useful anymore. Give you an example. Let's say that we were walking in swamps and, and our feet were, you know, walking swamps, all kind of parasites are gonna come up our body.

Mm-hmm. Whether it's through the skin or through the anal canal, et cetera. The mu cells have actually the ability to fight parasites and bacteria. In fact, they're triggered by such organisms. So millions of years ago, most likely. Those are the only defenses we have. Well, now we're pretty sterile in our environment.

We get antibiotics, et cetera, because we don't use them anymore. To give you another example. We cannot actually heal wounds unless the muscles are involved. Mm-hmm. When we tried, and we published this with colleagues from the Joscelyn Diabetes Center at Harvard, we created, you'll allow me to say, uh, diabetic wounds in diabetic mice.

And we used either must cell [00:09:00] deficient mice or otherwise normal mice. The muscle deficient mice took months to heal their wounds as compared to just, you know, days. So we do know that they have very useful functions within reason. Um, my unfortunately late, uh, colleague Dr. Marcus Mauer from SHA in Berlin, who died recently while hiking in Italy where he's been many times in the past.

Uh, he was, he was really a phenomenal guy, great researcher and lecturer. One of his first papers was to show that. Proteolytic enzymes released from the mast cells immediately degrade toxins. It can be toxins from snake, from spiders, whatever, but if it keeps on going, then it becomes a massive inflammatory problem.

And unfortunately, we do not know how to regulate the mast cells. We don't know how the body, our body regulates the mast cells. If we knew that, then clearly by the end of our [00:10:00] conversation, we would have actually better ways to deal with conditions of ma cell activation. 

Dr. Linda Bluestein: And I think that's such an important point that mast cells do things that are useful in the body.

Because I think so often people think, oh my gosh, I have mast cell activation syndrome. Which of course we're gonna get into what that actually is right now. But, but they, uh, but they think, oh my gosh, if only I could just get rid of my mast cells. But that's, that's, that's not correct. Yeah. Right. They're essential.

So can you explain then, what mast cell activation syndrome is and how that differs from allergic or inflammatory conditions like eczema or asthma? 

Diagnostic Challenges and Lab Tests for MCAS

Dr. Theoharis Theoharides: Sure. So first of all, we should be thinking about mass cell disorders. 

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: In general, and we separate those in three categories. One are the so-called primary muscle cell disorders, such as systemic mastocytosis or cutaneous skin mastocytosis.

Those, by definition have more mass cells, either in the skin or the bone marrow [00:11:00] or some other organs like the liver or the bladder. Then we have the secondary MA cell disorders, which is the bread and butter of everyday sort of allergy. So you've got allergic conjunctivitis, anes, uh, you know, atopic dermatitis, eczema.

My view is, and then we have the third category, the idiopathic, and as well known, when we don't understand something, we call it idiopathic. Mm-hmm. And there we have idiopathic anaphylaxis, uh, we have idiopathic TIC area, we have idiopathic edema, and we have must cell activation disorders, not yet syndrome.

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: Now, ma cell activation occurs in all these conditions. Clearly people with sustaining mastocytosis have muscles are activated. If you've got eczema, you've got masters in the skin, they're activated. If you've got asthma, you've got cells that are activated. So ma cell activation by itself. [00:12:00] Applies to all these three different categories, except that under the idiopathic category we have must cell activation disorders or must cell activation unspecified where someone without having many must cells and without any known trigger, such as allergen muscles are activated.

Now, why do we get stuck with muscle cell activation syndrome? And this is where the major confusion is. Our colleagues have indicated that one should be be able to measure high levels of the enzyme rease in the blood. That is true in 90% of systemic mastocytosis patients. It is true in probably less than 10% in cutaneous mastocytosis patients, which is kind of interesting.

And we will talk about the mast cell activation. If trip [00:13:00] days, according to the criteria as they stand now, is elevated within 48 hours of an episode, and you have all the other telltale signs of, you know, itchiness or you know, bloating or you know, whatever, then we call it muscle cell activation syndrome.

So you have to have, not that I necessarily agree, trip days elevated within 48 hours of an episode, but there are three problems with that. Number one, many individuals don't have trip days elevation, and in fact, Dr. Butterfield and colleagues from the Mayo Clinic have shown repeatedly that 24 hour urine levels of the metabolites or prostaglandin D two Prostaglandin, F two Alpha and leukotriene C4 are much more predictive.

Than trip days. They analyze patients, and according to them, they absolutely should be in the muscle activation syndrome [00:14:00] category, and yet 35% of them had absolutely no tryptase, even though they fit all the other criteria. And to make things worse, a paper was published about a year ago ago, and then our colleague, Mariana Castell, wrote a very nice editorial in the New England Journal of Medicine.

So our colleagues had measured tryptase levels on 105 individuals regardless of diagnosis. They found out the astonishing finding that about 30% of them had familial hyperemia, and that's why Triase was elevated. Another 30% had chronic kidney disease that blew everybody's mind, and the rest was actually.

Malignant mastocytosis or aggressive mastocytosis, hardly any mast cell activation syndrome was present. And yet we don't [00:15:00] discuss this paper, which I, I find it very, very intriguing. And in addition, while we started saying that for better or worse blood levels or serum levels of t tryptase, we used to say about two years ago, should be 11.5 milligrams per milliliter.

As of a year ago, this was raised to 15 milligrams per milliliter because so many people just don't have the levels that they used to be. And finally, unless you have an indwelling catheter to draw blood within 48 hours, and you go to some medical facility where they know what they're doing, no one can measure triptan within that period of time.

So identifying even those patients who would qualify as muscle cell activation syndrome is exquisitely difficult. So much so that our family recently, um, from, from Tampa in Florida, uh, that had to go to the emergency room because [00:16:00] the lady had an PHY episode. And your, your husband by the way was a physician.

Is a physician, and they mentioned to the emergency room personnel that she has a history of mass cell activation problems. And the answer according to the husband from the personnel was, what's wrong with your breasts? So this is emergency room in Tampa. Two months ago where they had no idea what we were talking about.

Dr. Linda Bluestein: Wow. 

Dr. Theoharis Theoharides: So the field is very confusing and unfortunately we make it more confusing because you, we use different terminologies. So muscle cell disorders, muscle cell activation disorders. Mm-hmm. Muscle activation, uh, you know, uh, unspecified, et cetera. So as long as mass cell activation, unspecified or mass cell activation disorders exist in the diagnostic codes, and it does, I will use those codes for a patient that doesn't have elevated drip days.

And I don't get necessarily stuck to call it mass cell activation [00:17:00] syndrome. If my colleagues insist that tryptase should be elevated there and the approach to treatment is exactly the same. 

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: And what we expect basically will happen to these patients is exactly the same. So having the tryptase elevated doesn't make any difference in terms of treatment or, or longevity or, or other symptoms that one, uh, expect, but for some reason, most are colleagues get stuck with MCAS rather than ma cell activation in general.

Dr. Linda Bluestein: Yeah, no, that's, that's very helpful. And I wanna clarify, when you said about 48 hours, so are you saying from the time that the blood is drawn from the patient until it's actually from the 

Dr. Theoharis Theoharides: episode. Let's say you have an episode right now that you feel like, you know it's coming. 

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: Uh, so from that, from the beginning of the episode, you've got, according to the criteria, you've got 48 hours to have blood drawn.

And so the treat taste is elevated because then presumably sort of it goes down. But as we will discuss later, I [00:18:00] hope, uh, there are many, many, many triggers of the mast cells, which I will enumerate some. Mm-hmm. That we absolutely know do not lead to three days or even histamine release. We publish papers in, in genealogy, clinical immunology during immunology for preceding Central Academy of Sciences, showing the triggers such as, for instance, viral proteins.

We used coronavirus spike protein, and we actually published that it stimulates release of cytokines without, uh, anything else. Um, we published that the first hormone released under stress. Corticotropin releasing hormone not only stimulates the mast cells to release only cytokines, but it resets the reactivity of the mast cells to other triggers.

So for instance, we've got now many patients with chronic covid or long covid that all of a sudden are allergic to everything, quote [00:19:00] unquote allergic. 'cause you know, they can't use any other term. Um, I suspect that, and I, I'm giving a lecture to Canada in about a month, that multiple chemical sensitivity syndrome is actually mass cell activation disorder, but not necessarily with a tase tagged it because in such cases we don't see tryptase elevation.

So I almost believe that we should change the name Mass Cell Activation Disorders to something else. But that's for another time. 

Dr. Linda Bluestein: I mentioned the other day when I was recording an episode, uh, just by, by myself, and I was musing on some different things that I think it should be mast cell activation spectrum because I That would 

Dr. Theoharis Theoharides: be wonderful.

Dr. Linda Bluestein: Yeah. I feel like it's such a spectrum of, you know, just the diverse presentations and, and like you're saying with the, with the labs. So you were commenting of course, on tryptase and prostaglandin D two and also leukotriene E four in the urine. So in terms of the labs that you find most helpful and the diagnostic [00:20:00] process that, that you do, can you share some of that detail with us?

Of course. And if there's certain steps that need to be taken in order to make the labs show most meaningful results. 

Dr. Theoharis Theoharides: Of course. Um, so I always say some labs are much more informative if someone doesn't have other comorbidities, but unfortunately many of these patients have comorbidities. What I mean to say.

We published and so did Doto Metcalf many years ago, and Dr. Riano from Spain, totally independently that at least in systemic mastocytosis levels of interleukin six in the blood were more predictive of the severity of the disease, especially bone involvement. Then trip chaser histamine, so this was published 15 years ago, three independent labs.

Wow. Different times. Now granted, someone will say, well, interleukin six, it's not a mass sub mediator specifically. Of course it's [00:21:00] not, but if you don't have any other comorbidities and IL six is of the roof, then I've got to take it seriously. Mm-hmm. Uh, a paper was published about two years ago that in chronic urticaria vascular endothelial growth factor.

It was very high, especially in those who were resistant to treatment. Well, VGF comes from the MA cells and we published, as I said earlier, that corticotropin ion hormone specifically, uh, induces release of VGF. So what I usually do is measure total IgE and I measure total subclasses of IgG because IgG one tends to be protective.

IgG four is involved in food intolerance, which is a little different. We can talk about it because many of the mass cell activation disorder patients do have food intolerance. Mm-hmm. Which is not picked up by IgE. There's a caveat doing the food [00:22:00] intolerance test, and I know many of my colleagues allergies don't really like to do it because if you eat something every day turns out to be false positive.

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: So I usually tell families, patients, if you can live with a little boiled chicken and canoa for three days, then do the test. Canoa doesn't have gluten, for instance, in it. I've never seen antibody allergic to chicken. So you kind of go, uh, a little bit on the safe side and then you can find out, you know, if there are actually insensitivities or intolerances.

In addition, before I go to the testing, we also have histamine intolerance, which is very different 'cause histamine comes from the mus cells, but it's also present in many foods. Avocado, tomatoes, peanuts, you know, spices, cheese, and therefore you can have a reaction to that histamine if you don't have the enzymes.

A breakdown histamine. The main enzyme is diamine oxidase. Mm-hmm. And we can measure diamond oxidase, gene polymorphisms in the United States. [00:23:00] For some reason, we don't measure activity in Europe. They measure activity as well. So if someone is polymorphisms and or uh, low activity, then you can give supplements like diamine oxidase supplements.

Mm-hmm. And there's a tricky part with these supplements because, you know, enzymes are broken down as many things by the acid in the stomach. So unless something is a TE coated or acid resistant formulation, it's all gone. And I get all kind of comments from patients that take Diamond Oxidate supplements and say they don't work.

Then I ask them, what was it? Well outta about 10 formula there. Only one is. Acid resistance. So you see how we misinform our patients. Mm-hmm. Uh, by, well, not we, the, the, the companies out there misinformed them, but we should be able to tell them also that enzymes will be broken down eventually. Uh, and enzymes, as we all know, don't get absorbed [00:24:00] from the gut.

Otherwise, we'll be giving insulin by mouth. Peptides are not absorbed. So the most benefit of the DAO enzyme supplements is what happens in your intestine, not in the rest of your body. So if the histamine is released in your intestine, then yes, DAO will work. And why is that important? Because histamine is broken down systemically within one minute, and then ends up as methyl histamine in your urine.

If however, histamine is produced by mast cells in the intestine, it will be intacted. And this is why, if I suspect patients starting backwards, especially the have GI problems. I ask for a stool analysis for total histamine, which can be done in the states and eosinophilic onic protein, which comes from eosinophils, but triggers the hell out of the mast cells and calprotectin, which I think is one of the best indices of inflammation rather than CRP or, you [00:25:00] know, erythrocytes intimidation rate, et cetera.

So I start with that. Now, in terms of blood that I'll do total IG subclasses of IgG, especially one and four, definitely I'll, I'll send for a tryptase unless I as chronic itching. I never ask for plasma histamine because it's really broken down very quickly. If, however, plasma histamine is elevated, that is important, and most of the time it's elevated and we can pick it up by doing the so-called basophil activation test or IG receptor.

Activation test, and these patients autoantibodies against the IG receptor on mu cells and on the circulating basophils and these antibodies, rather than blocking the reaction, they stimulate the basophils of the muscle. Three release histamine. This is probably the only time that I see histamine elevated in the plasma.

And when we do the [00:26:00] patient field activation test, which both LabCorp and Quest do it, except that they're buried inside panels. Mm-hmm. So you have to ask for chronic urticaria panel to find it. You cannot just unfortunately ask for it, you know, specifically. And then I do interleukin six and I do VEGF because at least these are measurable.

I would love to be able to do two more molecules. One is interleukin 31 because it is causing more itching than histamine. More aging, the tryptase. And right now there is actually a drug that blocks into the thick, into le at 31 receptors available in this, in the state. So we have some more drugs, especially for the aging part, but not for the other, uh, symptoms.

And then to the extent that it is possible, I will ask for the metabolites that I mentioned earlier. Uh, F 12 of a Prostoglandin D two, and the leukotriene, uh, C four. [00:27:00] Um, now we are trying to create a panel that is much better than what we just discussed for mass cell activation. But the difficulties, how do you validate it?

Because we can validate it systemic mastocytosis patients, because I have access to these patients by other colleagues. But much cell activation, as we just discussed, is a spectrum. So unless I have a very well defined set of. It's very difficult to validate a set of laboratory, um, uh, results. Anyhow, we're working on it, but, um, and clearly as we will discuss individuals that might have both, you know, POTS and EDS, et cetera, becomes even more complicated in terms of what do these comorbidities, uh, do to each other.

Dr. Linda Bluestein: I have so many follow up questions to that. Please, please do. Keep on going. It's wonderful. But, but I, but I [00:28:00] also know that, uh, we have so much more that I would like to cover than, than we're going to have time for. We're gonna have to do a part two for sure. Sure. So, so let, let me start though, with the DAO polymorphism and, um, if there's a specific lab that you order that through, and also the DAO supplement, you mentioned that there's one specific, uh, brand of supplement that is not, uh, digested by the acid in the stomach like the other ones are.

So I'm sure people would, are wondering which one that is. Okay. I, I've gotta look it up now. Uh, but if our, we can always put it in later in the, in the show. Yeah. If our 

Dr. Theoharis Theoharides: listeners actually assert for acid resistant mm-hmm. Or enter coated DAO, only one will come up. Okay. At least that I know is of about a month ago.

Okay. But I will. I'll find it. So I don't want us to break, uh, the, the, the sequence of, uh, thought here. The, uh, many of the laboratories that do [00:29:00] genetic analysis these days will give you, not only just Dao, they'll give you a whole bunch of things. So unfortunately in the United States, you've got it all, the whole list, and there are all kind of such companies that do it.

Um, but they don't give you only the Dao uh, in Europe. I can ask for only Dao and they'll give me only that. And that becomes obviously, you know, much cheaper for the, for the patients than doing the whole, the whole list. 

Dr. Linda Bluestein: I, I didn't know if, you know, now you can send a regular lab order to LabCorp Quest and you can put on there, you know, the MTH of R uh, you know, uh, polymorphism and, and they'll just do it.

You don't have to have a special lab for that like you used to have, so, correct. I didn't know if Yeah, 

Dr. Theoharis Theoharides: that's wonderful that they can do M-T-H-F-R actually they didn't used to. Uh, and in fact, they might have caught up. They might actually have, uh, they might be be using it, uh, now as well, uh, for the, for Dao.

I [00:30:00] mean, but there are things, for instance, uh, there's Genome Mind that does, you know, such analysis. Uh, there is Intel xxx, DNA that does, but they will do all of them, though, not, not just one. Um, there's vibrant wildness that will do, you know, such analysis. Um, uh, there's something called neo screen. Uh, there's something called tempus genetic.

There are many of them. And, and the price vary actually. E even, uh, 23 and Me will do it, except that they don't tell you the results. They, they, so you need someone else, like a geneticist to explain the results, uh, to you. Um, now in terms of, there's another problem with the DAO supplements. Uh, as you will see, and I'm sure our listeners will see, they say units and it's amazing because one, someone might say 1000 units and the other might say 30,000 units.

[00:31:00] Well, you know, I mean, what, what are we talking about here? So they're not standardized at all. Obviously the more units, the, the battery will be, and all of them except for one, come actually from a million source, from from pork. And many people, either because they're vegetarians or ethnic groups, don't wanna do that.

And there's only one company called na. Tao, N-A-T-U-R-R-T-E at the end, Tao Naro Dao. And that is actually from, um, bin Sprouts. Uh, but according to colleagues, it's not very active in spite of the fact that they list many units. Um, so I would not necessarily, I don't wanna discourage people from using them, but I just would like our listeners to do a little searching in terms of, you know, what they find, how they use it.

If it doesn't work, just switch basically the brand. And as I said, I'll try to create a little table and send it to you, [00:32:00] if not today, maybe tomorrow, because I think it will be very useful. 

Dr. Linda Bluestein: That would be amazing. And, and definitely I encourage people to look at the show notes 'cause we'll put some information in there after the fact.

So, so that's great. Thank you. 

Mast Cells in the Brain and Neuroinflammation

Dr. Linda Bluestein: Okay, so we're gonna take a quick break and when we come back, we are going to talk about the role of mast cells in the brain and neuroinflammation and, um, how all of this actually fits together in the, in the human body. So we'll be right back.

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Okay. I'm back with Dr. Theo Haes and we are covering some really great information about mast cells mast cell activation, trying to understand the difference between mast cell activation, mast cell disorders. Histamine sensitivity, all of these different things that I think often tend to be lumped together.

So I, I really appreciate you, uh, explaining all of that, you know, kind of at the beginning and, and when you talked about mast cells being in different parts of the brain, you know, really what, what came to my mind right away when you were talking about the amygdala, you know, that's the fear [00:34:00] center of the brain, right?

And we know that a lot of people with mast cell problems with connective tissue disorders, um, anxiety is a, is a common problem. And, and I have hypermobile EDS by the way, and, and I have very active mast cells, um, and, and anxiety. So I've, I've, I fit that description myself. So, um, so I would love to talk more about.

The, the role of the mast cell in the brain and also in neuroinflammation and how mast cells contribute to things like brain fog, migraine. And now we're gonna go outside the brain, um, you know, bladder pain, but also, uh, neurodivergence like autism. So, oh my 

Dr. Theoharis Theoharides: goodness. 

Dr. Linda Bluestein: Yeah, I know. Big question. Sorry. 

Dr. Theoharis Theoharides: Alright.

No, no, no. It's okay. So in 1990, um, I wrote a review and I called the muscles cells, the immune gait to the brain. Mm-hmm. And the reason I did that, which holds is outside the brain. As I said earlier, we have two endothelial cells that make the wall of the blood vessel in the [00:35:00] brain. We have another set of cells called pericytes, and they literally make up the blood-brain barrier, which is protective.

What do you know, the must cells literally hug this blood-brain barrier. Uh, so we've published electro microscope pictures showing that. Half of this blood-brain barrier is covered by one mass cell or another. Now, what is critical here is that the mass cell contains molecules that will open up the blood-brain barrier if it's released.

So if you get, let's say, a severe mass cell activation instance, whatever the trigger might be, the muscle will be activated around the blood-brain barrier and will make it leaky. So like leaky gut, it will be leaky brain basically. So molecules will come now inside the brain, either because they were circulating in the blood, which they should be going into the brain, or for the must cell itself.[00:36:00] 

And the mediators of the must cells are well known to trigger the brain defenders, the microglia. So I usually describe the brain as filled with spiders. They make spider web and the spider web is basically the scaffolding onto which the neurons crawl and make their connections. If the microglia see danger, two bad things happen.

First. The good thing is it will try to attack the invader. That's fine, but they go overboard. So now they don't make scaffolding anymore. So we lose the connections, which I believe very strongly. We've shown it, uh, as recently as this year to be true in autism. And they will also lead to auto inflammation in that localized area where the problem basically is now, molecules from the must cell are not necessarily bad all the time.

Histamine, for [00:37:00] instance, which is found in ma cells, is also found in neurons. We call them histamine, heric neurons. And histamine is very important for motivation, learning, and memory. So I always tell my colleagues and patients, if some antihistamine helps, you don't necessarily go overboard and take 300 milligrams a day because eventually you will plow your brain and even the non-sedating antihistamines, once you start pushing, the amount will get into the brain.

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: So the so-called second generation antihistamines are good, let's say Zyrtec at 10 milligrams. Mm-hmm. We always say you can go four times the recommended dose. Mm-hmm. Once you start reaching the dose, your brain is affected. So we don't want necessarily to block the mast cells, as we said earlier in the brain, or block all the histamine, uh, in the brain.

The MUS cells [00:38:00] are found also plentiful, not only around the hypothalamus and the amygdala, but also around the pineal gland that regulates our diurnal rhythm. Mm-hmm. So again, antihistamines can affect basically our sleep pattern as well as a lot of histamine, and who knows what else might be released.

Before I got involved in brain MA cells, other colleagues from Sweden had published that they saw collection of ma cells in the brains of individuals with multiple sclerosis, for instance. And that is critical because as we know, much of the problem in multiple sclerosis is that immune cells that are circulating.

Yet through the blood-brain barrier in the brain, they recognize the myelin that covers the nerves as foreign, they attack it. Mm-hmm. And that's where I have [00:39:00] basically disability. That might be at various parts of the, you know, it might be tongue, Chis, you know, hands, et cetera. For many, many, many years, millions of dollars had been spent trying to convince everybody that beta amyloid plaques are the beginning and end in Alzheimer's.

Dr. Linda Bluestein: Mm. Mm-hmm. 

Dr. Theoharis Theoharides: All of the studies have failed. And now our colleagues say that it's inflammation against the plaques and some individuals have more inflammation than others. 'cause 30% of the people that die of old age have plaques, but they don't have dementia necessarily. 

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: So this is why I worry about the mass cell activation, that it may be contributing to inflammation and if people are super sensitive.

Such as muscle cell activation disorder patients. Mm-hmm. That might be more likely to suffer of such neuro immune conditions. We're finding now that individuals with long covid not only have a lot of quote unquote allergic [00:40:00] problems, as we discussed earlier, but they also have a lot of neurologic problems, such as brain fog that you mentioned earlier, et cetera, and colleagues have published in the past that systemic mastocytosis patients do have a lot of cognitive problems.

They cannot concentrate, they cannot remember, et cetera. And even though earlier I said that mastocytosis is primarily a diagnosis of bone marrow mast cells, as you quite nicely asked earlier, how about the bladder for instance, or the GI tract. We published almost 20 years ago that in this sterile condition called interstitial cystitis, it's a basically sterile bladder inflammation.

Muscles are activated. In fact, one of the ways to address this condition is exactly what I say for everybody else. Avoid histamine rich foods for one thing, uh, and then use some supplements to which we might get to, you know, later if we have time. [00:41:00] Uh, such as cyto Protect that we developed 20 years ago.

And it's the only actually product drug, otherwise that has been helping, uh, the patients all along. So once the muscles are activated, this is my worry, it's very difficult to turn them back. And since they release so many molecules, we cannot be coming up with antihistamine this or rine this, or Interpros gland that mm-hmm.

Or anti VGF, et cetera. So our effort has been for 40 years how to regulate the mast cells. I don't necessarily say to block the mast cells. Mm-hmm. Because as we said earlier, we don't block them altogether, but. Fortunately and unfortunately some of the newer drugs, especially for cyst mastocytosis, induce mass cell apoptosis.

So they basically, the muscles die. Now, clearly if someone is horrible, aggressive mastocytosis, that's the way to go. Mm-hmm. But I'm hearing and have been approached [00:42:00] increasingly by patients that have must cell activation syndrome, whether they do have it or not, it doesn't matter that they would like to try these drugs.

And I'm telling them they're injectable, they have horrible side effects. They're gonna basically get rid of all your muscles in the body. You don't necessarily need that. Mm-hmm. Um, so what I see is a lot of behavior in individuals that have ma cell activation problems. And I don't say necessarily bad behavior, I just say behavior because they're different behaviors.

Uh, I remember I used to travel. Around the world with a lady that had systemic, mild systemic mastocytosis, indolent, systemic mastocytosis. And as, as you know, when you land in another country and if you come into the US you go through customs, but then you go through duty free, they force you to go through duty free.

This lady would faint because of all the smells mm-hmm. That she had to go through until [00:43:00] we realized and she wear a mask. I dunno why anybody would force people to go through jail, obviously to sell their products. Yeah. You know, we don't think of what else we're doing, uh, to these patients. So here you go.

The must cell does not have receptors that we know of for odors. So what happens? So we didn't publish the following experiment. We put an indwelling catheter, individuals that were allergic to just one IRO allergen. And we measured. Cortisol meaning activation of the hypothalamic pit, adrenal axis over time.

And we just basically spray them with a trigger. They got cortisol, you know, within two hours elevated. So before we got the paper published, the reviewers said, well, it's the stress, because now their nose gets all stuffed up. So we said, good point. So we used as a control individuals that we just put a close speed of their nose so they go to breathe.[00:44:00] 

Understanding Mast Cell Activation and Stress

Dr. Theoharis Theoharides: Cortisol is not elevated. So clearly my cells in the nose triggered by the arrow allergen were releasing molecules that would travel up the olfactory nerve, stimulate the hypothalamus to release everything that stimulate the HPA axis. So you see how the MUS cells can be involved in different ways. And very recently I published an editorial, actually it was letter to the editor, uh, to genealogy clinical immunology.

I called it skin MA cells under stress because they communicate with sensory nerve end index and a number of dermatology journals have published papers showing that in fact, the muscle cell can release molecules are sensitized, the nerve end index, then the nerve end index release, substance P and CGRP, et cetera.

The stimulant, the MO cell started having a reaction. So we have to block the most cells. 

Dr. Linda Bluestein: I mean, that's just, uh, so fascinating. And I, and I was gonna ask next about, about triggers. And I [00:45:00] often will tell people about stress, and you wrote an excellent paper, I believe it was called The Impact of Psychologic Stress on Mast Cell Activation.

Correct? I'm not gonna to tell this slightly, right? No, no, it was, it was very close, yes. Yeah, it's, it's, it's fascinating because when I was a child, I, I mentioned that I have, uh, hyperactive mast cells. My, my parents used to think that my asthma was psychologic, because if I would be at a friend's house and I would be laughing, or, you know, if I was under more emotional stress, I would have more asthma attacks.

So I, I, my parents are lovely people, but I remember them. No, no. De they, a lot of Ians 

Dr. Theoharis Theoharides: say, see, we call this, we used to call them psychosomatic diseases. Right. And then now we call them functional disorders. Mm-hmm. 'cause psychosomatic in it doesn't sound very good, but we're still saying the same thing, except that we now know that CRH will do this.

That there's just no question about it. And since our publications, a lot of other co colleagues have shown that CRH is released in the skin and it's [00:46:00] released in the bladder and it's released in the gut and it's pro-inflammatory rather than being anti-inflammatory. 

The Role of Diet and Supplements in Managing Mast Cell Activation

Dr. Theoharis Theoharides: Um, now in terms of, you know, regulations, just to make this topic even more interesting, as you know, must cells accumulate around solid tumors, especially breast cancer.

However, the cancer cells make the must cell. Not de granulate, but release only angiogenic factors that make basically new vessels grow so that tumor cell can feed itself and metastasize. If we could make the must cell release, let's say tube necrosis, vector, or treat days, we're gonna kill the cancer cell.

So the cancer cells are smarter than us. That's why I hate supplements that they say, let's say, flavonoids to boost the immune system. Well, I don't necessarily wanna boost the immune system because it might cause more inflammation, uh, than not. I want to regulate the immune system. That's why we created some supplements such as Pure Loot or Neuro [00:47:00] Protect, uh, that contain natural flavonoids pharmaceutical grade purity.

Uh, but they're mixed with olive oil to increase absorption from the gut. 'cause otherwise we cannot get, uh, enough into our system. Mm-hmm. Maybe we'll have more time for this later. 

Dr. Linda Bluestein: Yeah, well I definitely wanna make sure that we have time to, to come back to that. So I, I'm going to link your, uh, website in the show notes, which is dr theo her.com.

But I'll, I'll, I'll put the link there so people can see it because you have so much great information on your website as well and I know people are gonna wanna look at that. So. Sure. A couple things I want people to go there specifically to look at. One is your extensive list of triggers and extensive list of things to avoid, but maybe if you can also tell us, um, amongst those lists, if there's foods that are specifically, you know, more reactive and, and more people.

Sure. And if there's, if you have any general guidance, because I think sometimes it can be really challenging. People can end up eating just a couple of foods, right. Which we don't want them to do that either. 

Dr. Theoharis Theoharides: Uh, and I'll tell you an example of something that happened just an hour ago actually. [00:48:00] Uh, so we should keep in mind that food supplements, drugs, cosmetics, contain numerous.

Substances, and many of them are not necessarily disclosed. So starting with histamine, at least we know, as I said earlier, that tomato, avocado, cheese, peanuts, sardines, spices have a lot of histamine. And it so happens that many of these food substances have high salicylates. And to remind our audience a subtle salicylate is aspirin.

Mm-hmm. Okay. So Bayer added the ACE group, so it's not as corrosive to our stomach and it became salicylate. But if you use herbs, a lot of herbs have salicylates, for instance. Barks of various trees, have a lot of salicylates and foods like cumin, for instance, like curcumin, have a lot of salicylates. And the reason I'm saying that is [00:49:00] we know the curcumin is in anti-inflammatory.

Mm-hmm. But the same anti-inflammatory. If you really get it very pure, if you have a partially purified extract, there will be a lot of salicylate in it, and that might make things worse. 

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: Same thing with cumin. Cumin is a spice out there. You'll see on the internet the cumin is safe, but it has a lot of histamine.

So it is safe if you're, if you're not histamine sensitive. So I was talking to a company, very well known company that makes actually dietary supplements earlier and, and I was saying how I'm going to extremes, uh, for the supplements I helped develop with this company, Agon, A LGO, and OT, to avoid anything that I know is going to hurt them.

So, for instance, all the agon supplements are tested for glyphosate. Mm-hmm. Glyphosate is a herbicide known as Roundup. It stimulates the hell out of the mast cells [00:50:00] and so does Atrazine, which is another herbicide. Yet we're selling them like crazy. And no one is telling them that they're likely to trigger the must cells.

So I told them that I want supplements to be tested for X, Y, and Z, glyphosate being one of them. The other major problem we're having these days is what I'm sure you know, it's called Alpha gal syndrome. So Alpha Gal is found in most mammals, not so much in humans, but not in chicken and not in fish. So, you know, beef will have it, pork will have it.

And what happens is you might be beaten by a tick. You might never get Lyme disease or other diseases like Bartonella, you know, et cetera. But they will carry Alpha Gal from whatever they had beaten before square old, dear, you know, cow to you. Now you become allergic. We don't test for Alpha Gal, we can test, we can send to [00:51:00] LabCorp request for Alpha G, but the companies don't set for Alpha G.

So in a case recently of someone who showed up with very red lips and swollen tongue and they couldn't figure out, sometimes we call it, you know, allergic tongue syndrome or whatever. We always come up with, you know, syndromes. Well, she was using chopstick that had actually all the chopsticks have mammalian gelatin in it.

And the gelatin had Alpha Girl, she would send it to Alpha Girl and it was reacting locally in her face. Mm. Just by using chopstick. And the same thing could be with lipstick, it could be with mascara, it could be with whatever. So we, and unfortunately companies don't say that, that don't list, you know, they don't test for alpha gallon, they don't say it's gelatin.

So you wouldn't know unless it like fish gelatin or something. Um, so that's another set to worry about. Then we know that a lot of preservatives affect a. Those that have muscle activation, for instance, polyethylene glyco or PEG [00:52:00] mm-hmm. Can trigger people. And unfortunately some of the vaccines, including Pfizer vaccines have PEG.

So I usually tell people, just try some MiraLax that we use for constipation. MiraLax is pg, so if PG doesn't bother you, and you can try something in my pg So you've gotta help, you know, our, our, our patients kind of find a way through, not necessarily to scare them. You can't use X, Y, and Z, they won't be able to eat anything.

And then it is the red dyes, all kind of dyes. As you know, red three has been banned everywhere because it's carcinogenic. Uh, but red dice trigger a lot of, uh, you know, allergic life of responses. And as I'm sure you know, one of the Benadryl penetrate preparations has red dye in it. So why would an antihistamine, antiallergic formulation have any dye in it?

It's beyond me, 

Dr. Linda Bluestein: right. 

Dr. Theoharis Theoharides: So I usually tell. Patients families try to get clear gel cups if you can. And many of these products now [00:53:00] exist as clear gel cups, but it's hard to find them. Many pharmacists just don't carry them. So we kind of have, uh, to order it. Then finally, in terms of, you know, foods in general, if you suspect, that's what I tell people, that something bothers you, then you have to pay attention to it.

And the last point I wanted to make is what we call phenol intolerance. So there are many substances that are phenolic chocolate phenolic, strawberries, blueberries are phenolic. Uh, pomegranate is phenolic. Uh, and many of the substances have more final groups than others. So Pycnogenol has 15, uh, finale groups.

Cetin or cetin, however you pronounce it, has five. The reason I'm saying that is those individual are pH intolerant, which again, we can test by doing polymorphisms on the relevant enzymes become very irritated. They cannot sleep at night. They get very anxious if they take too [00:54:00] much polyphenol content.

For instance, the olive oil, which is wonderful. The more pure the olive oil, the more pheno it is and people. Promo is a polyphenol anti-inflammatory olive oil, and we use olive oil in all the agon preparations. But I don't want the polyphenol oil because 30% of the people have phenol intolerance and they're not gonna know it, and they might get, you know, jittery.

Um, so you, you see how you really have to kind of go through all of this before starting saying, well, I really have a problem that needs medication. And then I usually go for some of the antihistamines, obviously, as long as they're tolerated. 'cause many individuals cannot tolerate some antihistamines. 15% of the people get wired on the antihistamines, whether they're supposed to be primarily, uh, sedating.

And at the same time, I'll look for pure flavonoids, such as the ones made by algon, [00:55:00] especially liposomal, because that increases the absorption and Algon uses olive oil for that. And please, I tell everybody, try to avoid the motor. Something doesn't get absorbed. I'll give you two, you know, a lot more. So for instance, let's say I give you two grams a day, 2000 milligrams a day of any combination of flavonoids, only 200%, I mean 200 milligrams, 10% will be absorbed.

1800 milligrams will stay in your gut, shuts down your bio flora. So now you get sibo, you start chasing your tail. Why do you have small intestinal, you know, overgrowth? Um, so too much of, of something is not necessarily good as we spoke about, uh, histamine and antihistamines as well. 

Gut Health and Mast Cell Activation

Dr. Linda Bluestein: And I'm so glad that you mentioned about the gut microbiome, 'cause that is something that I did wanna ask you about specifically.

Um, I know that gut microbiome is, is so important, and if, if possible, we should be eating a diversity of foods and things, um, it, how does the gut microbiome interact [00:56:00] with any of this? And also what about probiotics or prebiotics? Is that something that's a good idea. 

Dr. Theoharis Theoharides: So there, my cells in the gut, no question about it.

Mm-hmm. If we have a parasite, we got allergic reaction, they're gonna fire. We said earlier, you can measure histamine in the stool, for instance, as an index. If they're actually misbehaving. If they are misbehaving, they will actually affect the gut blood barrier, as we said earlier, which will now allow more molecule strength into the blood.

And our immune system will be be responding to those as well. So we need to shut down or calm the muscles cells, uh, there. But the gut, as you well know, communicates with the brain either through molecules that will go through the gut blood barrier into the blood, and then into the brain or through the vagus nerves that sends all kind of branches, uh, down to the GI tract, stomach, et cetera.

And they go, you know, kind of back and forth. So we have to keep. Our gut as normal as possible, [00:57:00] and we don't, our diet in general is miserable in Western world. Mm-hmm. Um, and many of the foods we do either treat or the muscles, or at least they don't quite down the muscles. Um, so there are the so-called anti-inflammatory foods.

These are foods that have basically flavonoids in them, but again, we have to remember that you cannot build up too much of those because you can affect everything else. Uh, in the gut there are the so-called good probiotics, as I call them. Those are the contained bifidus. So the bifidus does help break down histamine.

So I like the bifido and I watch out for the lacto bale, especially in individuals who are allergic or sensitive to milk. Lacto comes from milk, and these are not necessarily pure. So I've heard people using lacto Basa, primarily probiotics, and they're getting all kind of reactions. And then I chase it down and they're s ca uh, found in [00:58:00] milk, uh, uh, et cetera.

So I'm a proponent of using probiotics, uh, uh, of any kind as long as, you know, one is not sensitive to a particular kind, uh, or another. And, uh, the stress is a major, major, major factor, as you've kindly indicated for yourself, because it will affect our absorption from the gut. It will affect how the gut works.

Uh, it affects, as I said, mass cells talking, uh, in the skin and the brain. And I usually recommend, other than doing, avoiding the stress if possible, or doing some exercises like whether it's yoga or meditation or whatever, I usually recommend the herb ashwagandha. Mm. Which is fairly safe matic in children as well.

Uh, except that, uh, it is a little bitter. So unless you swallow a capsule, if you put it into, you know, some liquid, just taste it first because it is a little bitter. So, you know, people don't, uh, [00:59:00] so that people would comply. And then unless somebody is either systemic mastocytosis or hyster of anaphylaxis or asthma, in which case they might need an EpiPen epinephrine pen, you know, for a reaction.

I like the drug propranolol. So propranolol, one of the trade names is indol, uh, is a beta blocker. We use it a lot in people with hyperthyroidism because our pulse is very high to lower the pulse. But I like it because it works within 30 minutes. It's outta your body in about three hours. You don't get used to it and doesn't cloud your mental abilities.

So I recommended it to students and performers and others and you don't have to use it every day. You can start just before when you think that might be a very difficult day, for instance, and just take it for a couple of days and then you're off it. Another, with oximeters, it's very easy to titrate it 'cause the oximeter gives you your pulse.

So if, let's say your pulse is a hundred, uh, you've [01:00:00] gotta drop it down to at least 10 points lower. And if you, if you take 10 milligram for parol, it doesn't do it, then you jack it up to 20 and you'll see, uh, if your pulse drops, you're at the right dose. You don't have to kind of bother your physician necessarily.

Dr. Linda Bluestein: Well, well, I'm thinking. So, so, uh, we, we got, we've gotten through about half of what I wanted to talk about, so I think we're gonna have to come back and do a part two, but what I'm thinking is I'm gonna have to start taking Propanolol and Ashwagandha before our next chat, and then, and then I can fill you in on how that's going.

Um, before we, before we wrap up and get to the hypermobility hacks, uh, can you tell me, with the ashwagandha, who would be a good candidate for that? What, what kind of benefits would someone see? And if you're willing to share any additional details about like, dosing, you get mild 

Dr. Theoharis Theoharides: relaxation, uh, okay. Quite easily, but it's not the kind of molecule that you push, you're gonna get much more.

So I usually, for an adult it will be 500 milligrams twice a day and that's it. Okay. If it doesn't help them, it's not gonna help them. [01:01:00] Okay. Uh, for children, I usually go a hundred to 200 milligrams, uh, a day. Usually in some applesauce, you know, some honey something, so it's not, you know, that bitter. Mm-hmm.

Um, but, and I've used it myself. So I, I, I, I know, I know when I have some difficult days, I always carry a little propanol in my pocket. Oh, really? Just in case. No, I do, because, you know, whether it's a patient or whether it's the university or whether it's life in general, you know, we get hit every day with all kind of crazy stuff.

Dr. Linda Bluestein: Mm-hmm. Uh, 

Dr. Theoharis Theoharides: and you know, we used to have much more time maybe for friends and others to vent. Mm-hmm. Now we don't, and sometimes we just have to deal with ourselves and it's not helpful. And the older you get. The more you are here, just, I worry. 

Dr. Linda Bluestein: Yeah, me too. Me too. I could totally relate to that. So, okay.

Practical Tips and Future Directions

Dr. Linda Bluestein: Well I think that we should probably have a second conversation about treatment specifically and, and really get into, you know, how [01:02:00] people can really sort out what kind of foods might be causing them problems. Because there's probably some people that are gonna be saying, wait, what? Olive oil? Sometimes it's good, sometimes it's not blueberries.

You know, that's something that's supposed to be really good for us. Right. So I feel like there's some details in there that we need to come back and revisit. 'cause you've given us such a wealth of information and so much that we, that we need to digest. And I bet you there's gonna be some questions from listeners.

And we haven't spoken 

Dr. Theoharis Theoharides: about eeds yet. 

Dr. Linda Bluestein: I know. 

Dr. Theoharis Theoharides: So we have to. 

Dr. Linda Bluestein: Yes. So I like to end every episode with a hypermobility hack, and you've already given us so many, of course, but if you have another like, uh, hack that you can think of for people with hypermobility and any of these associated conditions that you would like to share, um, before we wrap up, that would be great.

Dr. Theoharis Theoharides: I, I would like to urge people with high mobility, whether they have been nest or not, uh, to basically, uh, do a [01:03:00] very simple test, uh, which is to say, scratch their arm, the underside of the arm. Mm-hmm. With our, with a finger of the other hand or a dull object, one continuous line from the elbow towards the wrist, just like that.

And then wait a couple of minutes and see if that will turn red. Okay. 

Dr. Linda Bluestein: Okay. Are we looking for graph? 

Dr. Theoharis Theoharides: Yes. Because if they do, and many people do. That will be enough for me to start chasing muscle cell activation after that. 

Dr. Linda Bluestein: Mm-hmm. '

Dr. Theoharis Theoharides: cause that means that only the pressure simulated the muscles. There's no allergen, there's no stress, there's no other trigger.

Uh, and I would say 90% of the time I'm correct that there's something to be, uh, discovered and no one has ever done that. Uh, you know, as a study, I mean, you know how many people have dermatographia, for instance, uh, et cetera. And that might be also quite interesting. In fact, if you would like to do, uh, a, a, [01:04:00] a, a poll with your, your patients, that would be, it will be almost publishable because from what I said earlier, there might be something lacking in the skin.

We might find out that more individuals have. Than the general population in general without having, you know, well diagnosed muscle activation disorder. Mm-hmm. I dunno whether you can do that. Usually in order to publish something as, you know, you've, you can't just send it open-ended, you know, you've gotta send it, let's say, to a hundred people and, you know, if 60 people or more respond, then you've got some decent results.

Uh, otherwise I might say only those that were interested, you know, replied. But that's something you might, you might want to consider since you have so many, uh, listeners and it would be quite helpful for all of us. 

Dr. Linda Bluestein: Oh, I think that's, I think that's a great idea. And I'm looking at my arm and it does look red.

It does. I don't know. You probably can't. I can't bring a little 

Dr. Theoharis Theoharides: Oh yes. It's, it's, it will disappear in [01:05:00] about a minute or two. The longer it stays, the more. Reason to be chased 

Dr. Linda Bluestein: and, and I do test people for Domato, grm or I, or have been, and, and the, their in-patient visits or in-person visits, not inpatient.

I'm glad, but, but I usually do it a little bit differently than, than How do you do it? Like a Well, I just would, would like make like a, like a letter like that or something rather than No, you 

Dr. Theoharis Theoharides: don't, you don't have to. So you can use, uh, you know, you can use the back of a tuning force. You can use the back of, uh, you know, a hammer if you have those, you know, for exam, uh, or you know, the, like a, a pen without, uh, the, the part of the pen that writes, you know, Uhhuh.

And I usually tell patients, don't do it if you have got long fingernails because you might break your fingernails and then out. You know, 

Dr. Linda Bluestein: I'll 

Dr. Theoharis Theoharides: be hearing it forever. 

Dr. Linda Bluestein: Yeah, exactly. Exactly. But 

Dr. Theoharis Theoharides: most of the time, just using your, your nail of the, of, of a finger, it, it's, it's good enough. 

Dr. Linda Bluestein: Mm-hmm. Okay. Okay. Well, so many great ideas that, [01:06:00] that I would love for us to follow up on.

And I'm just really grateful to you for being so generous with your time. And before we go, could you, uh, let people know where they can find you, where they can learn more about your work? 

Dr. Theoharis Theoharides: Okay. So you kindly indicated one website, which is, uh, d rt o harid, T-H-O-O-H-A-R-I-D-E s.com. There's another website which is much more involved.

That's why I created the second one, which is called must sell master.com. All one word, MAST must sell master. And I would urge people if they have the time, uh, to watch on YouTube, an episode from. 12 years ago called My Mystery Symptoms and Must Cells. It's easy to find. Uh, and there are two ladies. I happened to be lecturing in Denmark and one patient that had been after [01:07:00] me, uh, was in Copenhagen.

And, um, she, uh, had a television station. So we taped, or rather they taped us her, uh, saying basically her case. And then, uh, a, the lady that I was traveling with and I mentioned earlier basically that also had, uh, problems and that I would interject and talk about MA cells or how they relate to some of the symptoms.

Uh, it's quite informative, uh, actually, and because there are also two patients talking about their issues as we are discussing MA cells, it's easier to relate the MA cells to some of the symptoms they have. So my mystery symptoms. And past cells. Okay. And now, I used to be at Tufts University, as you know, for 36 years now.

I'm down at Nova Southeastern University in Fort Lauderdale, Florida. Uh, and the reason I came down, uh, two reasons. One is because they're very interested in [01:08:00] integrative medicine. Mm. And my colleague, Nancy Klima, has been, uh, at the forefront for Gulf War illness and, uh, chronic fatigue, myalgic, encephalomyelitis, 

Dr. Linda Bluestein: mm-hmm.

Uh, 

Dr. Theoharis Theoharides: et cetera. So, uh, if you go Nova Center of Excellence for Neuroinflammation Research, uh, you will see now a new site with a lot of information and a lot of what we're doing research wise right now. So, Nova Center of Excellence with neuroinflammation research. 

Dr. Linda Bluestein: Okay, great. Okay, well we will have like, we're gonna have lots of links in the, in the show notes and, uh, so much excellent information for people to really chew on before we do part two.

And go ahead and, and I should actually add, 

Dr. Theoharis Theoharides: not so much for promoting anything, but at the website of algon.com, A-L-G-O-N-O-T-I do have actually scientific blogs and those are much simpler than some of the sites [01:09:00] that I have. Hmm. So you'll see, for instance, a blog about bladder health. I. There's one, I don't have anything for EDS yet.

I thought we will do it together. I'd, which is why I wanna talk to you. Yeah, I would love to do that so seriously, because very few people know about hypermobility in itself or EDS or what we call now, the triad. Mm-hmm. So it's, you know, EDS, uh, and it's pots, you know, or mm-hmm. Dysautonomia and muscle cell activation.

And I, I think a lot of people should be aware of, of this because they do go together and, uh, I'm working very hard with a colleague from New York. We basically searched, uh, a particular IBM, uh, database for health, and we have incredible results of how much more prevalent, uh, muscle cell activation is in EDS.

Uh, we will be publishing it either as a letter to the editor or editorial. Uh, but we really went over about 10 million [01:10:00] cases. Really? The difficulty, yeah. The difficulty in searching for the results is that these database, as many databases using diagnostic codes and, you know, years back we didn't have diagnostic codes like muscle cell activation or muscle activation syndrome, et cetera.

So it, it's hard to search for all the data. Uh, but we use different terms, different different diagnostic codes. And at the end of the day, it was, I can tell you it was any, anywhere between four and 20 times more prevalent than the average population. Uh, but we're doing some fancy statistics right now to make sure that we're not missing anything.

But hopefully we'll submit it within the month or so. 

Dr. Linda Bluestein: Wow. A adding to your incredible, uh, literary, uh, contributions. I mean, I just like to read and write, Linda, that's all, uh, it, which is wonderful because, uh, some of us are not as good about writing, that's for sure. Well, you've gotta balance, 

Dr. Theoharis Theoharides: you've gotta balance everything.

Yep. But I, I've come to realize though, [01:11:00] that many, you know, gps don't read the scientific journals that, you know, we might publish. Mm-hmm. You know, whether it's allergy, whether it's inflammation, et cetera. So, for instance, right now with two colleagues, I'm writing a different article about autism, but we will send it to family practice, the journal family practice.

Mm-hmm. Uh, again, I, I dunno how many gps will be looking at that journal, but we've gotta get the word out to the colleagues. Yes. Um, uh, two years ago I sponsored a conference here in Florida on interstitial cystitis. Oh. It was, it was a day conference. Uh, there were three. Of the best people that know about interstitial cystitis, they have not retired yet as speakers.

I was the moderator. We send out emails and regular USP United States Postal Service invitations to every urologist in Florida. It was free, it was in [01:12:00] Tampa, Florida. Accessible. You didn't have to stay overnight. Only one OLA came out about 500. Yeah. I mean, that tells you how desperate the patients are and how horrible we as physicians are.

Dr. Linda Bluestein: Yeah. 

Dr. Theoharis Theoharides: We just don't wanna learn, you know? Yeah. Either because it's time consuming or because, uh, we're worried, uh, that, that we don't know enough. 

Dr. Linda Bluestein: Right. 

Dr. Theoharis Theoharides: But we should not be telling patients as they had told you earlier on. Oh, it's, it's all in your mind type of thing. You know, when you, you complaining about stress and asthma.

For instance, and stress worsens interstitial titis, we know that. 

Dr. Linda Bluestein: Mm-hmm. 

Dr. Theoharis Theoharides: Um, et cetera. So if, if the colleagues are not willing to learn, I don't know how we will get to them. That's, that's my worry. 

Dr. Linda Bluestein: Yeah. Yeah. Uh, and, 

Dr. Theoharis Theoharides: and some of us, uh, you know, for better or worse, you know, are, are dropping out, let's say for ma cell disease, [01:13:00] Dr.

Battlefield in May, he retired. Uh, Dr. Schwarze Virginia retired. Dr. Met at NIH retired, uh, Maria Castels, uh, either is living or, or just left Harvard. Uh, there's only one Jamma in Michigan that's kind of left that really knows what they're talking about. And when some of these colleagues left and patients were shifted to younger allergists, I get all these emails saying, they tell me there's nothing wrong with me.

Right. So all the work they have been done by our colleagues. They retired. It's just not carried anymore by younger people. They should be even more open to these problems than, than we were when we were never taught any of this. Mm-hmm. You know, back in our day. So 

Dr. Linda Bluestein: yeah. It's really crazy. And the whole, you know, uh, myth about tryptase elevations and that's the, the only thing that matters is so frustrating for patients because they're suffering.

And so, so many times we can do things right that are very right, very [01:14:00] low risk. And it's like, why not try ab Absolutely. 

Dr. Theoharis Theoharides: Abs. Yeah. Look, I'm not against measuring it. Mm-hmm. And if it is high, then I'll pay attention to it because I'm on my needle, bone marrow biopsy and other things. Right. Right. Exactly.

But to say to someone, there's nothing wrong with you because you don't have high tase when you have all the other symptoms. 

Dr. Linda Bluestein: Right. 

Dr. Theoharis Theoharides: It's, it's. It's unethical, basically. 

Dr. Linda Bluestein: Yeah, it is. It is. Yeah. And a lot of people have been traumatized by those kinds of appointments and myself included. So really it's so wonderful, the incredible work that you're doing and thank you.

We are, we are. I know. I can speak for all the listeners. We are so grateful for you and thank you so much. And are so grateful. That's what 

Dr. Theoharis Theoharides: keeps her going. Absolutely. So stay well. God bless you. You too. God bless all the patients and hopefully we'll be back again. 

Dr. Linda Bluestein: Yes, I look forward to chatting with you again.

Thank you so much for taking the time to talk to me today. 

Dr. Theoharis Theoharides: Thank you.

Dr. Linda Bluestein: I have been wanting to talk to Dr. Theo Heriz for so long, so I'm [01:15:00] so excited that this finally happened, and I hope you will stay tuned for part two of this conversation on mast cell activation and what you can do to help your mast cells be happier. Thank you for listening to this week's episode of the Bendy Bodies.

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