Hidden Histamine Threats with Dr. Theoharis Theoharides

[00:55] Dr. Linda Bluestein: Welcome back, every bendy body, to the Bendy Bodies Podcast with your host and founder, Dr. Linda Bluestein, the Hypermobility MD. As you may know, I have had aberrant mast cells my entire life, so I'm super excited to talk to Dr. Theoharides about mast cell activation and what we can do to help ourselves feel better.
Dr. Theoharides is professor and vice chair of clinical immunology and director of the Institute for Neuroimmune Medicine in Clearwater, as well as 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 Immunopharmacology 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.
[01:52] 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 ScholarGPS and Expertscape. He was inducted into the Omega Alpha Omega National Medical Honor Society, the Rare Diseases Hall of Fame, and the World Academy of Sciences. 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.
[02:35] I am super excited about this conversation with Dr. Theoharides. He is an absolute wealth of information when it comes to mast cells 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 you don't miss any of our special hypermobility hacks. Here we go.
[03:01] I am so excited to be here today with Dr. Theoharides, and we are going to have some excellent conversation. I hope your day is going well and that you're ready to dig into this.

[03:12] Dr. Theoharis Theoharides: Well, it's a real pleasure to be with you, and I'm looking forward to our discussion.

[03:20] Dr. Linda Bluestein: Terrific. So can you just start out — a lot of the listeners of this podcast are of course familiar with mast cells and mast cell activation syndrome, but can you give us a brief description of mast cells and their role in the body and in health and disease?

[03:37] Dr. Theoharis Theoharides: Well, that's an hour in itself.

[03:38] Dr. Linda Bluestein: Exactly. It is.

[03:40] Dr. Theoharis Theoharides: All right. 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. We used to think that each mast cell is the same, and definitely that is not the case. So depending on 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.
[04:18] We know for sure that they are present in tissues that are exposed to the outside world, such as eyes, nose, mouth, lungs, skin, and gut. However, a wonderful paper published about 5 years ago showed that the mast 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 they can be sensitive to whatever is happening outside and inside the body.
And they're also present in the meninges that cover the brain and in the central part of the brain — we call it the diencephalon — especially the hypothalamus, which regulates homeostasis, and the amygdala, which regulates behavior. In fact, the hypothalamus communicates with the pituitary — which makes all the hormones — via a small bridge they call the median eminence or the stalk. The number of mast 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.
[05:32] The second point is that each cell contains about 1,000 small spheres. I call the mast cell like a soccer ball filled with about 1,000 ping pong balls. Each one of those little ping pong balls contains as many as 100 different molecules. And when the mast cell is triggered, especially in anaphylaxis, all the small granules — secretory granules, little spheres — release their content. But over a period of 6 to 12 hours, the mast cell can make another set of molecules. In fact, some colleagues wrote a paper about a year ago — Dr. Afrin and colleagues — and collected about 350 molecules that the mast cell can make.
[06:24] The last point I want to make, to which we will surely discuss in more detail, is that histamine and the enzyme tryptase that have been typically associated with the mast cell are only the tip of the iceberg, because in most cases where the mast cells are activated, they're not released. Let me stop there, and we might come back to what the mast cells might be doing other than bad things in the body.

[06:53] Dr. Linda Bluestein: So this is already fascinating. When I think of phenotype, I usually think of clinical presentation and the differences in phenotypic presentations — or you might have a phenotypic presentation of, 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 not all mast cells are created equal, it sounds like.

[07:19] Dr. Theoharis Theoharides: Absolutely true. The mast cells obviously have in their nuclei information to make pretty much everything. Every cell in the body does, except that as we mature as individuals, as species, certain cells forget to do some things and do other things. And the reason I'm saying that is because mast cells have existed for more than 300 million years, long before we had an endocrine, immune, or nervous system. In fact, by virtue of the fact that they contain so many different molecules, other colleagues and I believe that they were kind of the multifunctional cell — they can release some hormones, some neurotransmitters, some immune material. At the time, as I said, there were no such systems developed. Fish, octopi, lizards have mast cells that don't get allergic reactions.
[08:10] So we clearly believe — and there is evidence to that — that as we grew and developed through evolution, functions of the mast cell became somewhat less useful. Give you an example. Let's say that we were walking in swamps. All kinds of parasites are going to come up the body, whether it's through the skin or through the anal canal. The mast cells actually have the ability to fight parasites and bacteria. In fact, they're triggered by such organisms. So millions of years ago, those were most likely the only defenses we had. Well, now we're pretty sterile in our environment. We get antibiotics. We just don't use those defenses anymore.
[09:03] To give you another example, we cannot actually heal wounds unless mast cells are involved. When we tried — and we published this with colleagues from the Joslin Diabetes Center at Harvard — we created diabetic wounds in diabetic mice, and we used either mast cell–deficient mice or otherwise normal mice. The mast cell–deficient mice took months to heal their wounds compared to just days. So we do know that they have very useful functions, within reason.
[09:40] My unfortunately late colleague Dr. Markus Maurer from Charité in Berlin — who died recently while hiking in Italy, where he'd been many times before — was a phenomenal guy, a 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 snakes, 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 regulates them. If we knew that, then clearly by the end of our conversation, we would have better ways to deal with conditions of mast cell activation.

[10:30] 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 going to get into right now, but they think, "If only I could just get rid of my mast cells." But that's not correct. They're essential. So can you explain what mast cell activation syndrome is and how that differs from allergic or inflammatory conditions like eczema or asthma?

[10:59] Dr. Theoharis Theoharides: Sure. So first of all, we should be thinking about mast cell disorders in general. We separate those into 3 categories. One is the so-called primary mast cell disorders, such as systemic mastocytosis or cutaneous skin mastocytosis. Those by definition have more mast cells either in the skin or the bone marrow or some other organs like the liver or the bladder. Then we have the secondary mast cell disorders, which is the bread and butter of everyday allergy — allergic conjunctivitis, sinusitis, atopic dermatitis, eczema, asthma. And then we have the third category, the idiopathic. As is well known, when we don't understand something, we call it idiopathic. There we have idiopathic anaphylaxis, idiopathic urticaria, idiopathic edema, and mast cell activation disorders — not yet syndrome.
[12:04] Now, mast cell activation occurs in all these conditions. People with systemic mastocytosis have mast cells that are activated. If you've got eczema, you've got mast cells in the skin that are activated. If you've got asthma, you've got cells that are activated. So mast cell activation by itself applies to all 3 different categories, except that under the idiopathic category, we have mast cell activation disorders or mast cell activation unspecified — where someone without having many mast cells and without any known trigger such as an allergen, mast cells are activated.
[12:46] Now, why do we get stuck with mast cell activation syndrome? This is where the major confusion is. Our colleagues have indicated that one should be able to measure high levels of the enzyme tryptase in the blood. That is true in 90% of systemic mastocytosis patients. It is true in probably less than 10% in cutaneous mastocytosis cases, which is kind of interesting. And for mast cell activation — if tryptase, 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 itchiness or bloating or whatever, then we call it mast cell activation syndrome. So you have to have — not that I necessarily agree — tryptase elevated within 48 hours of an episode.
[13:49] But there are 3 problems with that. Number one, many individuals don't have tryptase elevation. In fact, Dr. Butterfield and colleagues from the Mayo Clinic have shown repeatedly that 24-hour urine levels of the metabolites of prostaglandin D2, prostaglandin F2-alpha, and leukotriene C4 are much more predictive than tryptase. They analyzed patients who, according to them, absolutely should be in the mast cell activation syndrome category, and yet 35% of them had absolutely no tryptase elevation, even though they fit all the other criteria.
[14:31] And to make things worse, a paper was published about a year ago — and our colleague Mariana Castells wrote a very nice editorial in the New England Journal of Medicine — where colleagues had measured tryptase levels on 105 individuals regardless of diagnosis. They found the astonishing result that about 30% of them had familial hypertryptasemia, and that's why tryptase was elevated. Another 30% had chronic kidney disease, which 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 discuss this paper, which I find very, very intriguing.
[15:28] In addition, while we started saying that for better or worse, serum levels of tryptase — we used to say about 2 years ago should be 11.5 nanograms per milliliter — as of a year ago, this was raised to 15 nanograms per milliliter because so many people just don't have the levels they used to. 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 tryptase within that period of time.
[16:03] So identifying even those patients who would qualify as mast cell activation syndrome is exquisitely difficult. So much so that a family recently from Tampa, Florida had to go to the emergency room because the lady had an anaphylactic episode. Her husband, by the way, is a physician. They mentioned to the emergency room personnel that she has a history of mast cell activation problems. And the answer, according to the husband, from the personnel was, "What's wrong with your breasts?" This was an emergency room in Tampa, 2 months ago, where they had no idea what we were talking about.
[16:51] So the field is very confusing. And unfortunately, we make it more confusing because we use different terminologies — mast cell disorders, mast cell activation disorders, mast cell activation unspecified, et cetera. As long as mast cell activation unspecified or mast cell activation disorders exists in the diagnostic codes — and it does — I will use those codes for a patient that doesn't have elevated tryptase, and I don't necessarily get stuck calling it mast cell activation syndrome if my colleagues insist that tryptase should be elevated. The approach to treatment is exactly the same, and what we expect to happen to these patients is exactly the same. So having the tryptase elevated doesn't make any difference in terms of treatment or longevity or other symptoms that one expects. But for some reason, most of our colleagues get stuck with MCAS rather than mast cell activation in general.

[17:55] Dr. Linda Bluestein: Yeah, that's very helpful. And I want to clarify — when you said about 48 hours, are you saying from the time of the episode?

[18:00] Dr. Theoharis Theoharides: From the episode. Let's say you have an episode right now that you feel coming on. From the beginning of the episode, you've got — according to the criteria — 48 hours to have blood drawn and show the tryptase is elevated, because then presumably it goes back down. But as we will discuss later, I hope, there are many, many triggers of the mast cells — which I will enumerate some of — that we absolutely know do not lead to tryptase or even histamine release.
[18:37] We published papers in the Journal of Clinical Immunology, the Journal of Immunology, and the Proceedings of the National Academy of Sciences showing that triggers such as viral proteins — we used coronavirus spike protein, and published that it stimulates release of cytokines without anything else. 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.
[19:15] So we've got now many patients with chronic COVID or long COVID who all of a sudden are allergic to everything — quote unquote allergic, because they can't use any other term. I suspect that — and I'm giving a lecture in Canada in about a month — multiple chemical sensitivity syndrome is actually mast cell activation disorder, but not necessarily with tryptase elevation, because in such cases we don't see tryptase elevation. So I almost believe that we should change the name "mast cell activation disorders" to something else, but that's for another time.

[19:53] Dr. Linda Bluestein: I mentioned the other day when I was recording an episode just by myself that I think it should be called "mast cell activation spectrum." That would be wonderful. I feel like it's such a spectrum of diverse presentations. And like you're saying, with the labs — you were commenting on tryptase, prostaglandin D2, and also leukotriene E4 in the urine. So in terms of the labs that you find most helpful and the diagnostic process that you use, can you share some of that detail with us? And if there are certain steps that need to be taken in order to make the labs show the most meaningful results?

[20:35] Dr. Theoharis Theoharides: Of course. 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. We published — and so did Dr. Metcalfe many years ago, and Dr. Escribano from Spain, totally independently — that at least in systemic mastocytosis, levels of interleukin-6 in the blood were more predictive of the severity of the disease, especially bone involvement, than tryptase or histamine. This was published 15 years ago, 3 independent labs, different times.
[21:17] Now, someone will say, "Well, interleukin-6 is not a mast cell mediator specifically." Of course it's not. But if you don't have any other comorbidities and IL-6 is through the roof, then I've got to take it seriously. A paper was published about 2 years ago that in chronic spontaneous urticaria, vascular endothelial growth factor was very high, especially in those resistant to treatment. Well, VEGF comes from the mast cells. And we published, as I said earlier, that corticotropin-releasing hormone specifically induces release of VEGF.
[21:55] So what I usually do is measure total IgE, and I measure total subclasses of IgG, because IgG1 tends to be protective and IgG4 is involved in food intolerance, which is a little different. Many of the mast cell activation disorder patients do have food intolerance, which is not picked up by IgE. There's a caveat to doing the food intolerance test — many of my colleagues, allergists, don't really like to do it because if you eat something every day, it turns out to be a false positive. So I usually tell patients: if you can live with a little boiled chicken and quinoa for 3 days, then do the test. Quinoa doesn't have gluten in it. I've never seen anybody allergic to chicken. So you kind of go a little bit on the safe side, and then you can find out if there are actually sensitivities or intolerances.
[22:51] In addition, we also have histamine intolerance, which is very different because histamine comes from the mast cells, but it's also present in many foods — avocado, tomatoes, peanuts, spices, cheese. And therefore, you can have a reaction to that histamine if you don't have the enzymes that break it down. The main enzyme is diamine oxidase. We can measure diamine oxidase gene polymorphisms in the United States. For some reason, we don't measure activity here. In Europe, they measure activity as well. So if someone has polymorphisms and/or low activity, you can give supplements like diamine oxidase supplements.
[23:38] There's a tricky part with these supplements, because enzymes are broken down — like many things — by the acid in the stomach. So unless something is enteric-coated or an acid-resistant formulation, it's all gone. I get all kinds of comments from patients who take diamine oxidase supplements and say they don't work. Then I ask them what they're taking. Well, out of about 10 DAO formulations out there, only one is acid-resistant. So you see how we — or rather, the companies out there — misinform our patients. We should be able to tell them also that enzymes will be broken down eventually. And enzymes, as we all know, don't get absorbed from the gut — otherwise we'd 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, that will work.
[24:41] Why is that important? Because histamine is broken down systemically within 1 minute and then ends up as methylhistamine in your urine. If, however, histamine is produced by mast cells in the intestine, it will be intact. This is why, if I suspect patients have GI problems, I ask for a stool analysis for total histamine — which can be done in the States — and eosinophilic cationic protein, which comes from eosinophils but triggers the mast cells intensely, and calprotectin, which I think is one of the best indices of inflammation rather than CRP or erythrocyte sedimentation rate. So I start with that.
[25:28] In terms of blood, I'll do total immunoglobulins, subclasses of IgG — especially 1 and 4 — and definitely I'll send for a tryptase test. Unless someone has 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. Most of the time it's elevated and we can pick it up by doing the so-called basophil activation test or IgE receptor activation test. These patients have autoantibodies against the IgE receptor on mast cells and on the circulating basophils. These antibodies, rather than blocking the reaction, stimulate the basophils or the mast cells to release histamine. This is probably the only time that I see histamine elevated in the plasma. And when we do the basophil activation test — which both LabCorp and Quest do, except that they're buried inside panels, so you have to ask for the chronic urticaria panel to find it — you can't unfortunately just ask for it specifically.
Then I do interleukin-6 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 causes more itching than histamine and more itching than tryptase. Right now there is actually a drug that blocks interleukin-31 receptors available in the States. So we have some more options, especially for the itching part, but not for the other symptoms.
[27:11] And then, to the extent that it is possible, I will ask for the metabolites I mentioned earlier — F2-alpha for prostaglandin D2, and leukotriene C4. Now, we are trying to create a panel that is much better than what we just discussed for mast cell activation. But the difficulty is — how do you validate it? We can validate it in systemic mastocytosis patients because I have access to these patients through other colleagues. But mast cell activation, as we just discussed, is a spectrum. So unless I have a very well-defined set of individuals, it's very difficult to validate a set of laboratory results. Anyhow, we're working on it. And clearly, as we will discuss, individuals who might have both POTS and EDS, et cetera, makes it even more complicated in terms of what these comorbidities do to each other.

[28:18] Dr. Linda Bluestein: I have so many follow-up questions to that.

[28:20] Dr. Theoharis Theoharides: Please, keep on going. It's wonderful.

[28:23] Dr. Linda Bluestein: But I also know that we have so much more that I would like to cover than we're going to have time for. We're going to have to do a part 2 for sure. So let me start with the DAO polymorphism — is there a specific lab that you order that through? And also the DAO supplement. You mentioned that there's one specific brand of supplement that is not digested by the acid in the stomach like the other ones are. I'm sure people are wondering which one that is.

[28:54] Dr. Theoharis Theoharides: I've got to look it up. But if our listeners search for "acid-resistant or enteric-coated DAO," only one will come up — at least as of about a month ago. But I'll find it because I don't want us to break the sequence of thought here.
[29:21] Many of the laboratories that do genetic analysis these days will give you not only DAO, they'll give you a whole bunch of things. So unfortunately, in the United States, you've got to do the whole list. There are all kinds of such companies that do it, but they don't give you only the DAO. In Europe, I can ask for only DAO and they'll give me only that, which is obviously much cheaper for the patients.

[29:54] Dr. Linda Bluestein: I didn't know if — now you can send a regular lab order to LabCorp or Quest and put on there the MTHFR polymorphism and they'll just do it. You don't have to have a special lab for that like you used to. So I didn't know if they might have caught up with DAO as well.

[30:11] Dr. Theoharis Theoharides: That's wonderful that they can do MTHFR now — they didn't used to. And in fact, they might have caught up with DAO as well. But there are companies like Genomind that do such analysis, IntelxxDNA, Vibrant Wellness, something called NeoScreen, something called Tempus Genetic — there are many of them, and the prices vary. Even 23andMe will do it, except that they don't tell you the results. So you need someone like a geneticist to explain the results to you.
[31:06] Now, there's another problem with the DAO supplements. As you will see, they say "units," and it's amazing because one supplement might say 1,000 units and the other might say 30,000 units. They're not standardized at all. Obviously the more units, the better. And all of them except for one come from a mammalian source — from pork. Many people, either because they're vegetarians or for ethnic reasons, don't want to do that. There's only one company called NaturDAO — N-A-T-U-R without the E at the end, DAO — that is actually from bean sprouts. But according to colleagues, it's not very active in spite of the fact that they list many units. So I don't necessarily want to discourage people from using it, but I would like our listeners to do a little searching in terms of what they find and how they use it. If it doesn't work, just switch brands. As I said, I'll try to create a little table and send it to you — if not today, maybe tomorrow — because I think it will be very useful.

[32:27] Dr. Linda Bluestein: That would be amazing. I definitely encourage people to look at the show notes because we'll put some information in there after the fact. So thank you. Okay, we're going to 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 how all of this fits together in the human body. We'll be right back.

[33:48] Dr. Linda Bluestein: Okay, I'm back with Dr. Theoharides, and we are covering some really great information about mast cells and 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 really appreciate you explaining all of that at the beginning.
[34:14] And when you talked about mast cells being in different parts of the brain — what came to my mind right away when you were talking about the amygdala is that it's the fear center of the brain, and we know that a lot of people with mast cell problems and connective tissue disorders have anxiety as a common problem. I have hypermobile EDS, by the way, and I have very active mast cells and anxiety, so I've fit that description myself. I would love to talk more about the role of the mast cell in the brain and in neuroinflammation, and how mast cells contribute to things like brain fog, migraine, and — now we're going to go outside the brain — bladder pain, but also neurodivergence like autism.

[35:01] Dr. Theoharis Theoharides: Oh my goodness.

[35:02] Dr. Linda Bluestein: I know, big question. Sorry.

[35:04] Dr. Theoharis Theoharides: All right. So in 1990, I wrote a review and I called the mast cell the immune gatekeeper to the brain. The reason I did that — and it holds — is that outside the brain, as I said earlier, we have two endothelial cells that make the wall of the blood vessel. In the 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 mast cells literally hug this blood-brain barrier. We've published electron microscope pictures showing that half of this blood-brain barrier is covered by one mast cell or another.
[35:48] What is critical here is that the mast cell contains molecules that will open up the blood-brain barrier if released. So if you get a severe mast cell activation instance — whatever the trigger might be — the mast cell will be activated around the blood-brain barrier and will make it leaky, just like leaky gut. Molecules will now come inside the brain, either because they were circulating in the blood — which they shouldn't be going into the brain — or from the mast cell itself. And the mediators of the mast cells are well known to trigger the brain's defenders, the microglia.
[36:33] I usually describe the brain as filled with spiders that 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: they will try to attack the invader. But they go overboard. So now they don't make scaffolding anymore. We lose the connections — which I believe very strongly, and we've shown it as recently as this year, to be true in autism. And that will also lead to autoinflammation in that localized area where the problem is.
[37:17] Now, molecules from the mast cell are not necessarily bad all the time. Histamine, for instance, which is found in mast cells, is also found in neurons. We call them histaminergic 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 cloud your brain. Even the non-sedating antihistamines, once you start pushing the amount, will get into the brain. The so-called second-generation antihistamines are good — let's say Zyrtec at 10 milligrams. We always say you can go up to 4 times the recommended dose, but once you start reaching that dose, your brain is affected. So we don't want necessarily to block all the histamine in the brain.
[38:17] The mast cells are also found plentiful not only around the hypothalamus and the amygdala, but also around the pineal gland, which regulates our diurnal rhythm. So antihistamines can affect our sleep pattern as well, as can a lot of histamine and who knows what else might be released.
[38:46] Before I got involved in brain mast cells, other colleagues from Sweden had published that they saw collections of mast cells in the brains of individuals with multiple sclerosis. That is critical because much of the problem in multiple sclerosis is that immune cells circulating in the blood get through the blood-brain barrier, recognize the myelin that covers the nerves as foreign, attack it — and that's where you have disability that might manifest in various parts of the body: the tongue, eyes, hands, et cetera.
[39:32] For 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. All of those studies have failed. And now our colleagues say that it's inflammation against the plaques, and some individuals have more inflammation than others — because 30% of the people that die of old age have plaques but don't necessarily have dementia. So this is why I worry about mast cell activation potentially contributing to inflammation. And if people are super sensitive — such as mast cell activation disorder patients — they might be more likely to suffer from such neuroimmune conditions.
[40:18] We're finding now that individuals with long COVID not only have a lot of quote unquote allergic problems, as we discussed earlier, but they also have a lot of neurologic problems such as brain fog. And colleagues have published that systemic mastocytosis patients do have a lot of cognitive problems — they cannot concentrate, they cannot remember. And even though earlier I said that mastocytosis is primarily a diagnosis of bone marrow mast cells, as you nicely raised earlier, what about the bladder or the GI tract? We published almost 20 years ago that in the sterile condition called interstitial cystitis — basically sterile bladder inflammation — mast cells are activated. In fact, one of the ways to address this condition is exactly what I say for everybody else: avoid histamine-rich foods, and then use some supplements to which we might get later if we have time, such as Cystoprotect that we developed 20 years ago. It's the only product — drug or otherwise — that has been consistently helping these patients all along.
[41:34] So once the mast cells 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 an antihistamine for this, an antileukotriene for that, an antiprostaglandin for something else, anti-VEGF, et cetera. So our effort has been for 40 years: how to regulate the mast cells. I don't necessarily say to block them, because as we said earlier, we don't want to block them altogether.
[42:03] But fortunately and unfortunately, some of the newer drugs — especially for systemic mastocytosis — induce mast cell apoptosis. They basically make the mast cells die. Now clearly, if someone has horrible aggressive mastocytosis, that's the way to go. But I'm hearing increasingly from patients who have mast cell activation syndrome — whether they do have it or not — that they would like to try these drugs. And I'm telling them: they're injectable, they have horrible side effects, they're going to basically get rid of all your mast cells in the body. You don't necessarily need that.
[42:42] So what I see is a lot of behavior in individuals that have mast cell activation problems — and I don't say necessarily bad behavior, I just say behavior. I remember I used to travel around the world with a lady who had mild systemic mastocytosis, indolent systemic mastocytosis. As you know, when you land in another country and 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 she had to go through — until we realized it and she wore a mask. I don't know why anybody would force people to go through duty-free, obviously to sell their products, without thinking of what else we're doing to these patients.
[43:34] So the mast cell does not have receptors that we know of for odors. So what happens? We did and published the following experiment. We put an indwelling catheter in individuals who were allergic to just one aeroallergen. And we measured cortisol — meaning activation of the hypothalamic-pituitary-adrenal axis — over time. We simply sprayed them with a trigger. They got cortisol elevated within 2 hours. 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 — and we used as a control individuals where we just put a clothespin on their nose so they couldn't breathe. Cortisol was not elevated. So clearly, mast cells in the nose, triggered by the aeroallergen, were releasing molecules that would travel up the olfactory nerve, stimulate the hypothalamus to release everything that stimulates the HPA axis. You see how the mast cells can be involved in different ways.
[44:44] And very recently, I published an editorial — actually a letter to the editor — to the Journal of Allergy and Clinical Immunology, and I called it "Skin Mast Cells Under Stress," because they communicate with sensory nerve endings. A number of dermatology journals have published papers showing that the mast cell can release molecules that sensitize the nerve endings, and then the nerve endings release substance P and CGRP, et cetera, which stimulate the mast cell — creating a reaction cycle. So we have to regulate the mast cells.

[45:17] Dr. Linda Bluestein: That is just so fascinating. I was going to ask about triggers, and I know you wrote an excellent paper — I believe it was called "The Impact of Psychological Stress on Mast Cell Activation." Correct?

[45:34] Dr. Theoharis Theoharides: Yes, very close.

[45:36] Dr. Linda Bluestein: It's fascinating because when I was a child — I mentioned I have hyperactive mast cells — my parents used to think that my asthma was psychological, because if I was at a friend's house laughing, or under more emotional stress, I would have more asthma attacks. My parents are lovely people, but I remember them definitely framing it that way.

[45:58] Dr. Theoharis Theoharides: A lot of physicians say — we used to call them psychosomatic diseases, and now we call them functional disorders because "psychosomatic" doesn't sound very good. But we're still saying the same thing. Except that we now know that CRH will do this. There's no question about it. And since our publications, a lot of other colleagues have shown that CRH is released in the skin, in the bladder, and in the gut. And it's pro-inflammatory rather than anti-inflammatory.
[46:31] Now, in terms of regulation — just to make this topic even more interesting — as you know, mast cells accumulate around solid tumors, especially breast cancer. However, the cancer cells make the mast cell not degranulate, but release only angiogenic factors that make new vessels grow so that the tumor cell can feed itself and metastasize. If we could make the mast cell release, let's say, tumor necrosis factor or tryptase, we'd kill the cancer cell. So the cancer cells are smarter than us. That's why I dislike supplements that say things like "flavonoids to boost the immune system." I don't necessarily want to boost the immune system because it might cause more inflammation. I want to regulate the immune system. That's why we created some supplements such as PureLut or Neuroprotect that contain natural flavonoids — pharmaceutical-grade purity — but they're mixed with olive oil to increase absorption from the gut, because otherwise we cannot get enough into our system. Maybe we'll have more time for this later.

[47:38] Dr. Linda Bluestein: Yeah, I definitely want to make sure that we have time to come back to that. I'm going to link your website in the show notes, which is drtheoharides.com, so people can see all the great information you have there. And I know people are going to want to look at that.
[47:54] So a couple of 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 you can also tell us: among those lists, are there foods that are specifically more reactive in more people, and do you have any general guidance? Because I think sometimes it can be really challenging — people can end up eating just a couple of foods, which we don't want.

[48:20] Dr. Theoharis Theoharides: Well, let me tell you an example of something that happened just an hour ago, actually. We should keep in mind that food supplements, drugs, and cosmetics contain numerous substances, and many of them are not necessarily disclosed.
[48:37] Starting with histamine — at least we know, as I said earlier, that tomato, avocado, cheese, peanuts, sardines, and spices have a lot of histamine. And it so happens that many of these food substances have high salicylates. To remind our audience, acetylsalicylate is aspirin. Bayer added the acetyl group, so it's not as corrosive to the stomach, and it became aspirin. But if you use herbs, a lot of herbs have salicylates — barks of various trees, and foods like cumin, and curcumin have a lot of salicylates. And the reason I'm saying that is that curcumin is anti-inflammatory, but only 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. Same thing with cumin — cumin is a spice, and out there you'll see on the internet that cumin is safe, but it has a lot of histamine. So it is safe if you're not histamine-sensitive.
[49:55] I was talking to a company — a very well-known company that makes dietary supplements — earlier today. I was saying how I go to extremes for the supplements I helped develop with this company, Algonaut, A-L-G-O-N-A-U-T, to avoid anything that I know is going to hurt people. For instance, all the Algonaut supplements are tested for glyphosate. Glyphosate is a herbicide known as Roundup. It stimulates the mast cells intensely. And so does atrazine, which is another herbicide. Yet we're selling these substances widely and no one is telling people they're likely to trigger the mast cells. I told them I want supplements to be tested for glyphosate being one of them.
[50:42] The other major problem we're having these days is what I'm sure you know — alpha-gal syndrome. Alpha-gal is found in most mammals, not so much in humans, but not in chicken and not in fish. So beef will have it, pork will have it. What happens is you might be bitten by a tick — you might never get Lyme disease or other diseases like Bartonella — but the tick will carry alpha-gal from whatever it had bitten before: squirrel, deer, cow. Now you become allergic. And we don't routinely test for alpha-gal. We can — you can send to LabCorp and request alpha-gal — but the companies don't send for it.
[51:27] I had a case recently of someone who showed up with very red lips and swollen tongue. We sometimes call it allergic tongue syndrome or whatever — we always come up with syndromes. Well, she was using chopsticks that had mammalian gelatin in them, and the gelatin had alpha-gal. She was sensitive to alpha-gal, and it was reacting locally on her face just by using chopsticks. The same thing could happen with lipstick, with mascara, with whatever. And unfortunately, companies don't disclose that. They don't list it, they don't test for alpha-gal, they don't say it's gelatin. So you wouldn't know unless it said "fish gelatin" or something. That's another set of things to be aware of.
[52:13] Then we know that a lot of preservatives affect those who have mast cell activation. For instance, polyethylene glycol or PEG can trigger people. And unfortunately, some vaccines — including the Pfizer vaccine — have PEG. So I usually tell people: just try some Miralax, which we use for constipation. Miralax is PEG. So if PEG doesn't bother you, then you can try something that might contain PEG. We've got to help our patients find their way through this — not just scare them by saying you can't use X, Y, and Z, because then they won't be able to eat anything.
And then there are the red dyes, all kinds of dyes. As you know, Red 3 has been banned because it's carcinogenic. But red dyes trigger a lot of allergic-like responses. And as I'm sure you know, one of the Benadryl preparations has red dye in it. So why would an anti-allergic formulation have any dye in it is beyond me. I usually tell patients and families: try to get clear gel capsules if you can. Many of these products now exist as clear gel capsules, but they're hard to find. Many pharmacies just don't carry them, so you kind of have to order them.
[53:31] Finally, in terms of foods in general: if you suspect something bothers you, you have to pay attention to it. And the last point I wanted to make is what we call phenol intolerance. There are many substances that are phenolic. Chocolate is phenolic, strawberries and blueberries are phenolic, pomegranate is phenolic. And many substances have more phenolic groups than others. Pycnogenol has 15 phenolic groups. Quercetin has 5. Those individuals who are phenol-intolerant — which 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 much polyphenolic content. For instance, olive oil — which is wonderful — the more pure the olive oil, the more phenolic it is. People do promote it as a polyphenolic anti-inflammatory olive oil, and we use olive oil in all the Algonaut preparations, but I don't want polyphenolic oil because 30% of the people have phenol intolerance. They're not going to know it and they might get jittery.
[54:47] So you see how you really have to go through all of this before saying, "I really have a problem that needs medication." And then I usually go for some antihistamines, obviously, as long as they're tolerated, because many individuals cannot tolerate some antihistamines. About 15% of people get wired on antihistamines even though they're supposed to be primarily sedating. At the same time, I will look for pure flavonoids such as the ones made by Algonaut, especially liposomal, because that increases absorption. And please — I tell everybody — try to avoid the motto "if something doesn't get absorbed, I'll give you a lot more." So for instance, if I give you 2,000 milligrams a day of any combination of flavonoids, only 10% — 200 milligrams — will be absorbed. 1,800 milligrams will stay in your gut and shut down your gut flora. So now you get SIBO and you start chasing your tail, wondering why you have small intestinal overgrowth. Too much of something is not necessarily good, as we spoke about histamine and antihistamines as well.

[56:07] Dr. Linda Bluestein: I'm so glad that you mentioned the gut microbiome, because that is something I did want to ask you about specifically. The gut microbiome is so important, and if possible, we should be eating a diversity of foods. How does the gut microbiome interact with any of this? And what about probiotics or prebiotics — is that a good idea?

[56:30] Dr. Theoharis Theoharides: So there are mast cells in the gut, no question about it. If we have a parasite, we get an allergic reaction, they're going to fire. As I said earlier, you can measure histamine in the stool as an index of whether they're actually misbehaving. If they are misbehaving, they will affect the gut-blood barrier, which will allow more molecules to enter the blood, and our immune system will be responding to those as well. So we need to calm the mast cells there.
[57:00] But the gut, as you well know, communicates with the brain either through molecules that go through the gut-blood barrier into the blood and then into the brain, or through the vagus nerve, which sends all kinds of branches down to the GI tract, stomach, et cetera. So we have to keep our gut as normal as possible. And we don't. Our diet in general is miserable in the Western world. Many of the foods we eat either trigger the mast cells or at least don't quiet them down.
There are so-called anti-inflammatory foods — foods that basically have flavonoids in them. But again, we have to remember that you cannot build up too much of those because you can affect everything else in the gut. There are also the so-called good probiotics. Those contain bifidus. Bifidus does help break down histamine, so I like it. And I watch out for the lactobacilli, especially in individuals who are allergic or sensitive to milk, because lactobacilli comes from milk and these preparations are not necessarily pure. I've heard of people using lactobacilli-primary probiotics and getting all kinds of reactions, and then I trace it back and they're sensitive to casein found in milk.
[58:26] So I'm a proponent of using probiotics of any kind as long as one is not sensitive to a particular kind. And stress is a 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, and it affects, as I said, mast cells in the skin and the brain.
[58:50] I usually recommend — other than avoiding the stressors if possible, or doing some exercises like yoga or meditation — the herb ashwagandha, which is fairly safe. I recommend it in children as well, except that it is a little bitter. So unless you swallow a capsule, if you put it into some liquid, just taste it first so that people would comply.
And then, unless somebody has systemic mastocytosis or a history of anaphylaxis or asthma — in which case they might need an epinephrine pen for a reaction — I like the drug propranolol. Propranolol, one of the trade names is Inderal, is a beta blocker. We use it a lot in people with hyperthyroidism, to lower the pulse. But I like it because it works within 30 minutes, it's out of your body in about 3 hours, you don't get used to it, and it doesn't cloud your mental abilities. So I recommend it to students and performers and others. And you don't have to use it every day. You can take it just before what you think might be a very difficult day and just take it for a couple of days and then you're off it. And now that we have oximeters, it's very easy to titrate, because the oximeter gives you your pulse. If your pulse is 100, you've got to drop it at least 10 points lower. If you take 10 mg propranolol and it doesn't do it, jack it up to 20 and you'll see. If your pulse drops, you're at the right dose. You don't have to bother your physician necessarily.

[1:00:40] Dr. Linda Bluestein: Well, I'm thinking we've gotten through about half of what I wanted to talk about, so I think we're going to have to come back and do a part 2. But I'm thinking I'm going to have to start taking propranolol and ashwagandha before our next chat, and then I can fill you in on how that's going. Before we wrap up and get to the hypermobility hacks, can you tell me about ashwagandha — who would be a good candidate for it, what kind of benefits would someone see, and if you're willing to share any details about doses?

[1:01:10] Dr. Theoharis Theoharides: You get mild relaxation quite easily, but it's not the kind of molecule that if you push it, you're going to get much more. So for an adult, it would be 500 milligrams twice a day, and that's it. If it doesn't help them, it's not going to help them. For children, I usually go 100 to 200 milligrams a day — usually in some applesauce or honey, something like that, so it's not as bitter. And I've used it myself. When I have some difficult days, I always carry a little propranolol in my pocket just in case. Whether it's a patient, the university, or just life in general, we get hit every day with all kinds of stressors. We used to have much more time, maybe, for friends and others to vent. Now we don't. Sometimes we just have to deal with it ourselves, and it's not helpful. And the older you get, the more you worry — or at least I worry.

[1:02:11] Dr. Linda Bluestein: Me too. I could totally relate to that. So I think we should probably have a second conversation specifically about treatment — really getting into how people can sort out what kinds of foods might be causing them problems. Because I think some people are going to say, "Wait — olive oil? Sometimes it's good, sometimes it's not? Blueberries — that's supposed to be really good for us." So I feel like there are some details in there that we need to come back and revisit. You've given us such a wealth of information and so much to digest. And I bet there are going to be some questions from—

[1:02:50] Dr. Theoharis Theoharides: We haven't spoken about EDS yet.

[1:02:52] Dr. Linda Bluestein: I know.

[1:02:53] Dr. Theoharis Theoharides: So we have to.

[1:02:55] 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 hack that you can think of for people with hypermobility and any of these associated conditions that you would like to share before we wrap up, that would be great.

[1:03:14] Dr. Theoharis Theoharides: I would like to urge people with hypermobility, whether they have been diagnosed or not, to do a very simple test — scratch their arm, the underside of the arm, 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.

[1:03:45] Dr. Linda Bluestein: Okay. Are we looking for dermatographism?

[1:03:47] Dr. Theoharis Theoharides: Yes. Because if they do show it, and many people do, that will be enough for me to start chasing mast cell activation. Because that means that only the pressure stimulated the mast cells — there's no allergen, there's no stress, there's no other trigger. I would say 90% of the time I'm correct that there's something to be discovered. And no one has ever done that as a study — how many people have dermatographia, for instance, et cetera. And that might be quite interesting. In fact, if you would like to do a poll with your listeners, 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 dermatographism than the general population without having a well-diagnosed mast cell activation disorder.
[1:04:48] I don't know whether you can do that. Usually in order to publish something, you can't just send it open-ended. You've got to send it to, let's say, 100 people, and if 60 people or more respond, then you've got some decent results. Otherwise, it might look like only those who were interested replied. But that's something you might want to consider since you have so many listeners, and it would be quite helpful for all of us.

[1:05:13] Dr. Linda Bluestein: Oh, I think that's a great idea. And I'm looking at my arm and it does look red.

[1:05:17] Dr. Theoharis Theoharides: Oh, it does. Bring it a little closer. Oh, yes, it is. It will disappear in about a minute or two. The longer it stays, the more reason to investigate.

[1:05:29] Dr. Linda Bluestein: And I do test people for dermatographism in their in-person visits. But I usually do it a little bit differently than how you do it. I would make like a letter or something rather than—

[1:05:46] Dr. Theoharis Theoharides: No, you don't have to. You can use the back of a tuning fork. You can use the back of a reflex hammer, or a pen with the writing tip retracted. And I usually tell patients: don't do it if you've got long fingernails, because you might break your fingernails and then I'll be hearing about it forever.

[1:06:11] Dr. Linda Bluestein: Yeah, exactly.

[1:06:13] Dr. Theoharis Theoharides: But most of the time, just using your fingernail is good enough.

[1:06:20] Dr. Linda Bluestein: Okay. Well, so many great ideas that I would love for us to follow up on. I'm just really grateful to you for being so generous with your time. And before we go, could you let people know where they can find you and where they can learn more about your work?

[1:06:38] Dr. Theoharis Theoharides: So you kindly indicated one website, which is drtheoharides.com. There's another website that is much more involved — that's why I created the second one — which is called mastcellmaster.com, all one word, M-A-S-T, mast cell master. And I would urge people, if they have the time, to watch on YouTube an episode from 12 years ago called "My Mystery Symptoms and Mast Cells." It's easy to find. There are two ladies — I happened to be lecturing in Denmark, and one patient who had been after me was in Copenhagen and she had a television station. So they taped her saying basically her case. And then a lady I was traveling with that I mentioned earlier, who also had problems, would interject, and I would talk about mast cells and how they relate to some of the symptoms. It's quite informative, actually. Because there are also two patients talking about their issues as we discuss mast cells, it's easier to relate the mast cells to some of the symptoms they have. So — "My Mystery Symptoms and Mast Cells."
[1:08:06] 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. The reason I came down — two reasons. One is because they're very interested in integrative medicine. And my colleague Nancy Klimas has been at the forefront for Gulf War illness and chronic fatigue, myalgic encephalomyelitis, et cetera. So if you search "NOVA Center of Excellence for Neuroinflammation Research," you will see a new site with a lot of information about what we're doing research-wise right now.

[1:08:54] Dr. Linda Bluestein: Great. We're going to have lots of links in the show notes, and so much excellent information for people to really chew on before we do part 2.

[1:09:08] Dr. Theoharis Theoharides: And I should add — not so much for promoting anything — but at the website algonaut.com, A-L-G-O-N-A-U-T, I do have scientific blogs, and those are much simpler than some of the sites that I have. You'll see, for instance, a blog about bladder health. There's not one for EDS yet — I thought we would do it together, which is why I want to talk to you.

[1:09:32] Dr. Linda Bluestein: I would love to do that.

[1:09:35] Dr. Theoharis Theoharides: Seriously, because very few people know about hypermobility itself, or EDS, or what we call now the triad — EDS, dysautonomia or POTS, and mast cell activation. A lot of people should be aware of this because they do go together. And I'm working very hard with a colleague from New York. We basically searched a particular IBM database of health records and we have incredible results of how much more prevalent mast cell activation is in EDS.
[1:10:07] We will be publishing it either as a letter to the editor or an editorial. We went over about 10 million cases. The difficulty in searching for the results is that these databases use diagnostic codes, and years back we didn't have diagnostic codes like "mast cell activation" or "mast cell activation syndrome." So it's hard to search for all the data, but we used different terms and different diagnostic codes. At the end of the day, I can tell you it was anywhere between 4 and 20 times more prevalent than in the average population. We're doing some careful statistics right now to make sure we're not missing anything, but hopefully we'll submit it within the month or so.

[1:11:04] Dr. Linda Bluestein: Wow. Adding to your incredible literary contributions.

[1:11:10] Dr. Theoharis Theoharides: I just like to read and write, Linda.

[1:11:13] Dr. Linda Bluestein: Which is wonderful, because some of us are not as good about writing, that's for sure.

[1:11:19] Dr. Theoharis Theoharides: Well, you've got to balance everything. But I've come to realize that many GPs don't read the scientific journals that we might publish in — whether it's allergy, whether it's inflammation, et cetera. So right now with two colleagues, I'm writing an article about autism, but we will send it to Family Practice, the journal. I don't know how many GPs will be looking at that journal, but we've got to get the word out to colleagues.

[1:11:53] Dr. Linda Bluestein: Yes.

[1:11:54] Dr. Theoharis Theoharides: Two years ago, I sponsored a conference here in Florida on interstitial cystitis. It was a day conference. There were 3 of the best people who know about interstitial cystitis — who have not retired yet — as speakers. I was the moderator. We sent out emails and regular US Postal Service invitations to every urologist in Florida. It was free. It was in Tampa, Florida, accessible — you didn't have to stay overnight. Only one urologist came out of about 500. I mean, that tells you how desperate the patients are and how horrible we as physicians are. We just don't want to learn — either because it's time-consuming, or because we're worried that we don't know enough. But we should not be telling patients, as they had been told earlier on, "Oh, it's all in your mind," when someone is complaining about stress and asthma, for instance. And stress worsens interstitial cystitis — we know that. So if colleagues are not willing to learn, I don't know how we will get to them. That's my worry.
[1:13:15] And some of us, for better or worse, are dropping out. For mast cell disease specifically — Dr. Butterfield from Mayo retired, Dr. Schwartz in Virginia retired, Dr. Metcalfe at NIH retired. Mariana Castells either is leaving or just left Harvard. There's only one person in Michigan who's really left that 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." So all the work that had been done by our colleagues who retired is just not being carried on anymore by younger people — who should be even more open to these problems than we were when we were never taught any of this back in our day.

[1:14:08] Dr. Linda Bluestein: Yeah, it's really frustrating. And the whole myth about tryptase elevations being the only thing that matters is so frustrating for patients, because they're suffering. And so many times we can do things that are very low risk — it's like, why not try?

[1:14:25] Dr. Theoharis Theoharides: Absolutely. I'm not against measuring tryptase. And if it is high, then I'll pay attention to it because someone might need a bone marrow biopsy and other things. But to say to someone, "There's nothing wrong with you because you don't have high tryptase," when you have all the other symptoms — that's unethical, basically.

[1:14:44] Dr. Linda Bluestein: Yeah, it is. And a lot of people have been traumatized by those kinds of appointments — myself included. So it's so wonderful, the incredible work that you're doing. We are — I know I can speak for all the listeners — we are so grateful for you. Thank you so much.

[1:15:02] Dr. Theoharis Theoharides: That's what keeps us going. Absolutely. Stay well. God bless you. God bless all the patients. And hopefully we'll be back again.

[1:15:09] 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.

[1:15:11] Dr. Theoharis Theoharides: Thank you.

[1:15:19] Dr. Linda Bluestein: I have been wanting to talk to Dr. Theoharides for so long. I'm so excited that this finally happened. And I hope you will stay tuned for part 2 of this conversation on mast cell activation and what you can do to help your mast cells be happier.
[1:15:36] Thank you for listening to this week's episode of the Bendy Bodies with the Hypermobility MD Podcast. You can help us spread the word about joint hypermobility and related disorders by leaving a review and sharing the podcast. This helps raise awareness about these complex conditions. If you would like to dig deeper, you can meet with me one-on-one. Please check out the available options on the services page of my website at hypermobilitymd.com.
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