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#15 – How to Make Friends With Your Immune System, the Latest Research on Autism, and Rethinking Antioxidant Supplements with Dr. Theoharis Theoharides

Today, our guest is Dr. Theoharis Theoharides, a world renowned expert on mast cells and the immune system. Dr. Theoharides is a Stanford and Yale trained immunologist who currently serves on the faculty at Tufts University School of Medicine. Dr. Theoharides’ lab investigates the mechanism of selective secretion of cytokines and other pro-inflammatory molecules from mast cells, cells which the layperson can think of as the “military sentinels of the immune system.” When the body senses an invader, or even in response to stress, mast cells release a cocktail of weaponry designed to kill the intruder. In a state of good health, this mast cell activity is a benefit. However, when mast cells become chronically activated, the increase in immune activity contributes to many of the chronic diseases plaguing the western world. Dr. Theoharides is also the inventor of a luteoline / quercetin formula supplement designed for those suffering from mast cell problems. In today’s episode, we shine a spotlight on the work Dr. Theoharides has done with autistic children and discuss practical strategies for quieting down the immune system.

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This Episode Covers:

  • The only pharmaceutical drug that blocks mast cell activity [7:00];
  • Why mast cell activity tends to get worse with time [13:00];
  • Common environmental triggers that stimulate mast cells including mold [16:50];
  • The problem with supplements [24:00];
  • Autism and mast cells plus the tests to run for autistic children [30:00];
  • Heart disease, histamine, and mast cells [49:30];
  • The best nutrients for mast cells and phenol intolerance [57:00];


Dr. Theoharides: When I started talking about this about 10 years ago, no one believed us. Five years ago, some large epidemiological studies came out indicating that the only comorbidity of autism is actually eczema and asthma. And now, just next week, September 26, there will be an annual conference or what is called MAPS, Medical Academy of Pediatric Special Needs in Mesa, California. And I actually give the keynote address on mast cells and allergy, and autism.

John: Welcome to the “GeneFood Podcast.” I’m your host, John O’Connor. Hey, everyone. Today we have a world-renowned mast cell expert by the name of Theoharis Theoharides. Dr. Theoharides has been published in “The New England Journal of Medicine.” He has hundreds of peer-reviewed articles that have appeared all over the medical literature for a number of years now. He’s a Yale-trained medical doctor. He also holds a Ph.D. in pharmacology from Yale. And he’s on the faculty as a professor at Tufts University Medical School as well.

As I’ve alluded to, he’s one of the best-known commentators on all things, mast cell, histamine, immune system. And for people that are kind of coming on to this podcast and thinking, “Well, that sounds pretty technical and a little bit intimidating,” well, you can think of mast cells as these big cells that hold all of the weapons of the immune system. And when something like an allergen or parasite or something that comes into the body that the immune system doesn’t like, the mast cells release these weapons and they go and their job is to neutralize these invaders. The problem in our modern world is because of all the stress that we have and screens and technology and the pace of our lives, these mast cells, these military sentinels of the immune system, start shooting at things that they shouldn’t shoot at. They kind of almost become like a bull in their own china shop.

And Dr. Theoharides is going to give us a tour through the common conditions that mast cell activation is responsible for, mast cell activation can affect the development of children and autism, kids that are on the spectrum of those issues. As well as the nutrients and practical things we can do in our own lives to kind of keep our immune system quieted down and under wraps. So without further ado, here is Dr. Theoharides.

John: We feel excited to have you on it’s a real privilege and honor to speak with you because I know that your time you know, is very fully committed and you’re doing a lot of research. So I think the best way to start with you Dr. Theoharides is to talk about your current position, your current areas of interest, kind of giving the audience a flavor for the work that you’re involved with, who you are and how you became so interested in your research.

Dr. Theohalides: Sure. Okay, so Theoharis Theoharides. I was born in Greece. I came to Yale in the ’60s. I did my undergraduate two masters, a Ph.D. and my MBA degree at Yale. Then I came to Boston training Internal Medicine at New England Medical Center and started the Department of pharmacology at Tufts University School of Medicine where I am still a professor. And I had the Laboratory of Molecular Immunology and Drug Discovery.

Ever since my time at Yale, I was very interested in how secretory cells secrete their packages. And I use the mast sell as probably the best model, because even then, in the early ’70s, we knew that each mast cell contains about 500 secretory granules, little sacks that contain about 50 different molecules. And when the cell is stimulated, I prefer stimulated rather than activated because if we say activated it implies potentially also a proliferation of the cells. But nevertheless, you can use that term for the purposes of our discussion. So when the cells are activated, and then immediately within five minutes at most secrete their secretary granular content, and then over a period of six to 12 hours, they produce another 15 molecules or so.

And unfortunately, we have literally focused on the release of histamine, which was discovered in the late ’40s. And not on anything else that is being secreted from the mast cells until the middle ages or so, when another class of molecules called leukotrienes are produced, also fairly rapidly, but released over time, were discovered. And of course, we have anti-histamines and anti-leukotrienes drugs that are used in asthma.

And most recently, over the last five years or so, a drug has been developed that literally neutralizes circulating immunoglobulin E or IgE. Which is the main trigger of mast cells during allergic reactions, and that basically is an antibody that neutralizes Ig. So short of that, we have no other drugs to inhibit either the release or the action of the hundred or so molecules being released from the mast cells. And about half of them are either cytokines or chemokines. And we were the first literally to show when I was a graduate student at Yale, in articles that were published in the Journals of science and nature within a year of each other. That unlike what was thought, and unfortunately until recently still thought that the mast cell must degranulate or explored like a hand grenade to release all its granules.

So we showed the mast release either individual granules and may contain different molecules or individual molecules without ever releasing histamine or the enzyme tryptase that is unique to the mast cells. So we have been missing the forest for the trees for, you know, hundreds of years. And it amazes me that pharmaceutical companies have not been interested in getting into this area. Because if we were to just consider allergic reactions, meaning what do we call atopic dermatitis, or eczema, or allergic asthma, or allergic rhinitis, or food allergies. We’re talking about 40% of the population. In fact, what we read diseases, where the cytokines are involved, whether we call that inflammation or something else that we will discuss later. I think about 60% of the people at any particular time I have a problem related to the mast cells. And yet, we have no drug to block the release of molecules from the mast cells, including histamine.

I left this at the end, the only drug that is available it’s called Cromolyn or Gastrocrom because it’s used primarily to reduce gastrointestinal problems. And I published a paper in the “Journal Science” in 1978, showing the Cromolyn may inhibit [inaudible 00:07:30] mast cell, but repeatedly we and others have shown that is extremely weak inhibitor of human mast cells. And in fact, the body shows what we call tachyphylaxis within a few months of getting the drug, as a target cell basically become immune to the inhibitory action of Cromolyn that will go tachyphylaxis. And you keep on increasing the dose until such levels you will start having major side effects.

John: Yeah, I know there’s so much to get into it’s really interesting to hear you talk about how these immune cells can selectively release histamine, which gets all the attention. That’s the area that we’ve been kind of most interested in. When you talk about the granules and the things that are getting released from the mast cells, and you correct me where I’m wrong. But for the listeners at home, who may be new to this topic, I think of this issue as the mast cells is almost like the garage that holds all of the military equipment of the immune system.

And when the immune system gets stimulated, it releases this weaponry out into the body and then that weaponry is then responsible for killing invaders or attacking things that aren’t supposed to be there. And when the weaponry is released, and the firepower is unloaded into chronic and circular way, it starts to cause issues and all sorts of myriad ways for people in their everyday lives. Would you say that is kind of like a mast cell for dummies good way of thinking about it?

Dr. Theoharides: You put your finger to it, although I will qualify it a little bit. I’ve said many times both in written form as well as in my lectures, that mast cell is literally a circulating pharmacy in our body. It contains most of whatever we would need actually, except for antibiotics to tackle diseases. So if I could actually direct the mast cell to release certain things and not others, I might not need to use drugs. So even though you correctly stated it organizes the immune system to let you fight invaders, let’s assume you have a parasite.

John: Right.

Dr. Theoharides: And mast cells are very involved in parasites and they talked to another cell type called eosinophils cell. But even the mast cells were to be releasing loads of histamine as they kill parasites, then you will be having all the problems that patients have with histamine overload, even though the parasites might be killed. So there’s got to be something else that has been released that allows recruitment of the other immune cells to do the job and not necessarily dump everything out.

Give you another example. We and others have published repeatedly, that mast cells accumulate around solid tumors, like breast cancer. And we published a paper just a couple of years ago that they accumulate around pancreatic cancer as well. But the mast cells around the cancers are not degranulated. In fact, something is being reused by the cancer cells that prevent the mast cells from the degranulating, in which case that will kill the tumor cell by releasing tryptase, histamine, and tumor necrosis factor. And instead, the cancer cells stimulate the mast cells to release only vascular endothelial growth factor VEGF which allows basically near vascularization and allows the cancer cells to basically feed themselves grow and metastasize. If I knew how the cancer cells do it, it would be an amazing basically discovery, and we still don’t know how to do it.

So we have to keep in mind that nature, God did not put the mast cells there for the occasion that they will release a lot of histamines and cause itching you know, runny nose or whatever. But what has happened, and we realized that and that’s basically the main focus of what we’re doing now, is that if the mast cell responds to certain triggers, it resets its threshold, and now it becomes much more likely to respond to sub-threshold triggers or to additional triggers that it never responded before.

John: Okay.

Dr. Theoharides: So it’s doing the job, and I think the mast cell is doing some useful function every day. For instance, we published a paper just recently with my colleagues from the Joslin Diabetes Center at Harvard, showing that if we block the mast cells in diabetic wounds, the wounds do not heal. So we know the mast cells are a major function in helping heal.

As I said earlier, histamine is also very important for motivation and learning. And surprisingly, the highest concentration, if not the only concentration of mast cells in the brain is what we call the basal ganglia, which is the hypothalamus and amygdala, they regulates homeostasis and behavior. I mean, I don’t think nature put them there just because.
John: Right, so what you’re saying is that if you have this increased immune activity via the mast cells, and they’re starting it sounds like they develop a trigger finger. So if they’ve gotten, you know, pissed off, for lack of a better term.

Dr. Theoharides: Sure.

John: And they’re irritated they’re gonna start shooting at things more than they would if they weren’t.

Dr. Theoharides: That is correct. And then what happens is some of the molecules that we don’t commonly discuss that are secreted from the mast cells act back on the mast cells. For instance, cortical dropping releasing hormone is the main hormone released under stress from the hypothalamus in the brain. Yet, we published that human mast cells release more CRH than even the brain. And what happens is we also published that the mast cells have high affinity, very strong receptors for CRH. So if CRH is released after the mast cells have actually been activated, it will be released it will act back on the mast cells. So what happens is the mast cell grows even more receptive for CRH. So the mast cells now are much more susceptible to stress. And we know that stress does a job in many of the patients have allergic-like problems. Let’s call them atopic problems. I would like to call atopic problems because, in my mind, atrophy is more general term and includes both pure allergy as well as other potential triggers such as mode that we will talk about later.

John: We will so let’s go back to you mentioned just a minute ago so there’s all this very interesting biochemistry. And you said even though this may sound to some listeners as something that sounds very technical you said a minute ago 40% of people are dealing with this allergy mediated mast cell issues.

Dr. Theoharides: Well, let’s call them mast cell activation because allergy is when truly you have specific Ig in your body or your being skin tested. And you turn out to have a positive skin reaction. But about half of the people I deal with, or my colleagues deal with, don’t have allergies. And get someone gets stressed and their turn red for instance, on their face, under their dorsal I can scratch someone on the skin, which we call a dalio [SP] sign and you get a wart where has scratched you. That means that the mast cell responded to pressure, the other people to respond when they actually just exercise. Other people cannot tolerate heat these are not allergic reactions. We do not have immune IgE in these conditions. So we’re struggling to call this patient something because they’re not allergic. So some colleagues use the word atrophy. And most recently, of course, we use the term mast cell activation syndrome. I tried to rename it mast cell mediator disorder. But in any event, these are logistics that, you know, we deal with among ourselves. The bottom line is that there’s a whole bunch of patients whose mast cells are activated, that may release histamine, but they definitely released cytokines and chemokines if they are not allergic. So what do we call this basis?

John: And that’s why you say that 60% of people have these potential issues.

Dr. Theoharides: Correct.

John: One of the things that comes up in these conversations, there’s basically two things that I think of right away that I would love to hear your thoughts on. One, it sounds like some of this mast cell activation, independent of allergy or these heightened immune responses could be caused by environmental pollutants. Stress, cell phones, lack of sleep, caffeine, running around cities, the changes in our modern lifestyle. And I want you to speak to that.

Dr. Theoharides: Absolutely. Yes. Well, let’s start with the simplest of all, as I said, mast cells can change their reactivity. So whether some of what you mentioned or what I will talk about, it stimulates the mast cells on their own, whether they changed the reactivity to other things, is almost immaterial for the purposes of our discussion. But to give you an example, we already discussed briefly that stress activates the mast cells directly and makes them more prone to other things. So any type of stress can do that.

And in fact, we publish papers where we measured CRH the stress hormone in the blood with patients to whom were given some decongestant State-Trait Anxiety Inventory, that within 34 questions are so gives you an idea how stressed individuals are. And CRH was very high in the blood and it was a very strong correlation with anxiety. So we know that. Therefore, any type of stress by definition is likely to stimulate the mast cells directly or make them more responsive either to new triggers or whatever triggers a patient might have had to begin with.

Then we go into all kinds of, let’s say, heavy metals. There many publications not from us, that both lead and aluminum stimulates the mast cells. The other publications that PVC stimulates the mast cells, Bisphenol A stimulates the mast cells. Glyphosate, which is as you know, “Roundup” one of the most, you know, common herbicides, Atrazine is one of the most common pesticides that stimulate the mast cells.

And then we go to things like, you know, we would never expect this or at least we don’t talk about it. But you probably know what polyethylene glycol is. Polyethylene glycol is very basically to every drive, every food substance, every cosmetic you know, you can think of. And I’m looking at a paper right in front of me that was published last month. The polyethylene glycol is a cause of IgE mediated anaphylaxis. Who would think that people that now the reactivity is lowered will respond to polyethylene glycol, which is found in lipstick, for instance, in mascara, etc.

So we’re literally surrounded by potential triggers, which by themselves if the overall population might not be enough, in certain part of the population may be enough. And if the mast cells now become more reactive, these materials might now be triggers for those individual were never suspected. We always suspected that mold might do a job and everybody was looking, you know, everybody you know, black mold in your tiles.

John: Yeah.

Dr. Theoharides: But as it turns out we had two publications last year in the “Journal of Clinical Therapeutics.” One was a review the other was a case reports were mold not necessarily black mold releases volatiles toxins are called mycotoxins, they stick to everything clothes, carpet, drugs, etc. You can’t get rid of them. And it’s very hard to measure them as well. So, I had patients that I begged to go away for like two to three weeks to some other relative or you know, go on vacation or whatever to an environment where there was no mold 90% of the symptoms disappeared okay.

And this type of mold reaction cannot be treated by drugs or block mold. You know, we have drugs like flucytosine and Amphotericin B. Those are for systemic fungal infections they don’t deal with mold that you inhale. So, the only thing that we can use for so, for the time being, is certain supplements that can actually reduce the activity of such mycotoxins. So berberine sulfate is one, oregano oil is another I’m just giving you some examples.

John: You’re saying these are antifungal aimed at stopping…because that was a very good list of the different substances, chemicals and bad actors that influence mast cells to release their cytokines and different granules, etc. But you’re saying that in some cases, and this is something functional medicine doctors talk a lot about is the idea that some systemic mold toxicity could be causing these mast cell issues for some people. And so when you talk berberine and oregano are these…these are antifungal compounds that are more gentle?

Dr. Theoharides: They are antibacterial, but they appear to actually have additional properties that we don’t understand they reduce the reactivity to the toxins. I don’t have the science to give you that but their publications that seem to be very helpful to patients who have been exposed even though patients might not continue to be exposed.

And they’re also publications that such mycotoxins or bacteria such as Borrelia lyme or Babesia, stimulate mast cells to release all these cytokines.

John: Okay.

Dr. Theoharides: Now, histamine are not ribcage no degranularization. So we just have to think that the mast cell can participate. And then cytokines can make them the reactivity of the mast cells to release histamine, of course, greater. I’m not necessarily discounting histamine at all. I’m just saying that there is a class of molecules that seem to be released by triggers unrelated to allergy. And those can either activate the mast cells alone or make them more susceptible to dry Ig-mediated.

So for instance, the editorial that I just mentioned, says the polyethylene glycol is the cause of IgE-mediated flax, in other words, polyethylene glycol doesn’t stimulate the mast cells directly and makes them more responsive to Ig, in other words, to an allergic reaction.

We published a paper a long time ago that stress meaning CRH we add CRH to human mast cells they become much more responsive to Mercury, for instance, okay. And this is an area that just not being discussed, that the mast cells must have some threshold that is being reset. Because I have so many patients who basically say, “Something happened, and all of a sudden I’m allergic or I respond to everything.”

John: Yeah.

Dr. Theoharides: So what happened? I mean, obviously, that event, whatever the event was, must have reset the mast cell so mast cell response to these triggers that this patient never responded to before. And mold is very high in mycotoxins and colleagues now have a new definition of a new disease actually, it’s called Chronic Inflammatory Response Syndrome. Where basically toxins are high on the list. So you’ve got a chronic inflammation not related to histamine because of certain toxins that might be released either from mold or bacteria or insect bites or bee stings or whatever.

John: Yeah. One physician that’s written about this is Dr. Ben Lynch, who is a genetic researcher. He’s a natural path in Seattle. I actually wrote about this as well just to kind of give a real-life example at to hear your reaction to for our listeners. I shared this on a previous podcast, but I had a situation where I was living in Austin, Texas, which is an environment that I actually had to move away from because I was so allergic to all the cedar and the grass. I had some traditional allergy panels that were run and some of my traditional IgE reactions to certain species of grass were just like off the charts high.

And I would take in Austin a supplement like lion’s mane, which I believe increases nerve growth factor. And correct me if I’m wrong, but I think via mast cells, I think mast cells release nerve growth factor. And so I would have a reaction to that supplement in sitting in Austin, Texas where I’d get you know, the itchiness and all that. Take the same supplement, literally a few weeks later in the Bay Area, a place where I have no allergies. And I have a phenomenal reaction in the supplements and it’s a great new topic and everything.

Dr. Theoharides: Really, oh, wow.

John: Yeah, I mean, I’ve seen. So speak to that for a minute a situation.

Dr. Theoharides: Let me just reply generically, first of all.

John: Okay.

Dr. Theoharides: I’m worry about supplements.

John: Good. Yeah.

Dr. Theoharides: Even though I know I’ve helped create some supplements, which I may come to later. But why do I worry? So I think that supplements should be regulated at least to the extent of number one being produced in good manufacturing practices, certified facilities, GMP certified facilities. And to the extent that they should, at least, list both the purine and the source. I’m not talking about you know, doing double-blind studies necessarily, etc. I believe that.

And let me give you an example. Quercetin is one of the most popular flavonoids and, in fact, inhibits mast cells and we and others have published that. However, the cheapest source, of quercetin is peanut shells. And they don’t tell you that.

John: Really.

Dr. Theoharides: Oh, yeah. If someone is allergic to peanuts, you’re doomed. The second cheapest source is actually fava beans. And about 20% of those Mediterranean extractions like myself, you know, Greeks, Italian Jews, North Africans, they lack an enzyme, which is called G6PD. And if you’re lacking this enzyme and you eat anything for fava beans, you get what we call hemolytic anemia, which means all your blood cells go to pieces, and then you start searching your tail going to hematologist, etc. And I can go down the list of various sources of supplements, which are not pure. So, let me tell you, for instance, you know, they have 100 milligrams of something, as you know, about 80% of whatever you take either in a capsule or in a pill are feelers.
So if something is very impure, you’re likely to respond to the impurities. And one particular problem that I’ve been dealing with is with many patients that have “Brain fog” you know, they forget they cannot, you know, multitask, they cannot, you know, find the right words right away, etc. We give them four reasons that we can go into calcium folinate, not folic acid, folinic acid, because they have a mutation or some mutations in the enzyme MTHFR that takes folic acid and mixing it to tetrahydrofolate. So the available sources of calcium folinate in the United States at least they come in a pill form, and many patients respond to that adversity.

John: Yeah, negatively yeah. I wanna get into that in a minute. I think we should devote a decent chunk of time to talking about problems with supplements. I completely agree. I just wanna wrap up and basically we’ve I feel like we’ve established what mast cells are. We’ve talked about environmental and other factors that caused them to get angry and release this stuff into the body that’s causing damage to people. I wanna also before we get into the kind of the solutions for quieting down mast cells and kind of continue with this supplement conversation. I wanna just give people out there listening what are the top like five conditions or like the top five signs that you could look at and say, “Okay, maybe this is something that I’m when I’m out of balance I’m kind of steering in this in this direction with these mast cell problems.”

Dr. Theoharides: You’re talking about diseases.

John: Diseases, I mean, for example, we have an article on the blog about seems like there’s a least a fairly clear or at least emerging or at least plausible link between allergy, allergic rhinitis and anxiety, allergy and stress, right histamine. You talked about you know, having skin issues or you know, your bug bites swelling up, just things of that nature that people would…that if you heard somebody or you’re just you had to do a top five list you were on you know, Letterman or something that you had to say.

Dr. Theoharides: So first of all, if you’ve got chronic itching what we call chronic prostatitis, that’s definitely mast cells. Even though 50% is allergic and 50% is not allergic, it’s still mast cells. And any worse is with stress, and so does chronic rhinitis that you mentioned but 40% is allergic, the other we call it perennial or angiotensin. Meaning there other factors are involved. And especially in patients who antihistamines don’t seem to help. Take Solaris, Solaris is associated with a tremendous amount of itching okay, but antihistamine don’t seem to help with these patients. If you’re actually end-stage dialysis patient before you go dialysis you itch like crazy. And we published 20 years ago that this is due to high parathyroid hormone. So PTH will stimulate the mast cells.

So anytime you have chronic itching or what seems to be an allergic-like reaction would smack mean you know, mast cell problems. So going back, atopic dermatitis or eczema, chronic rhinosinusitis, chronic asthma are very high on the list.

John: Okay.

Dr. Theoharides: Then we go into psoriasis. Or we showed, by the way, that it’s not histamine that causes the itching it is interleukin 31. And Interleukin 31 is much more pruritogenic meaning causes much more itching than histamine and it’s not blocked by antihistamines, and there’s no drug right now to block interleukin 31.

And then you go to conditions where there’s chronic inflammation and a lot of neuropsychiatric involvement. So, fibromyalgia, chronic fatigue syndrome or myalgic encephalomyelitis, chronic inflammatory response syndrome, chronic Lyme disease. All of these conditions have either skin related problems, whether it’s itching or douching, or flashing. And a lot of neuropsychiatric problems some of them get a little better with antihistamines, but they get a lot better when we try to block the mast cells.

And over the last three years or five years, as you know, we have been discussing and writing that mast cells are involved in the pathogenesis of autism. When I started talking about this about 10 years ago, no one believed us. Five years ago, some large epidemiological studies came out indicating that the only comorbidity of autism is actually eczema and asthma. And now, I, you know, just next week, September 26, there will be an annual conference, which is called MAPS, Medical Academy of Pediatrics Special Needs in Mesa, California. And I actually give the keynote address on mast cells and allergy and autism.

John: And that’s a good list. That’s an interesting list itching, allergic reactions, flushing and then some of these kind of more defined, you know, chronic illnesses that some people out there do have issues with. On the autism front that was on our list to discuss. Okay, so you know that there’s an issue with mast cells for children that suffer from autism. What do you do with that information? How can you take that information and make it actionable to help your child if this is something that your child is…?

Dr. Theoharides: Many different ways.

John: Okay.

Dr. Theoharides: We’ve got about 5,000 children over the last few years, you know, kind of doing what I’m about to say.

John: Okay.

Dr. Theoharides: So first, of all, you make absolutely sure that there is a problem you identify the problem. It could be true allergy, or it could be food intolerance.

John: Right

Dr. Theoharides: And in my mind, it doesn’t make any difference are all mast cell-related.

John: But let’s stop you there though. So there’s somebody listening because this is so with food intolerance, you’re gonna go to an allopathic like a traditional allergist, you’re gonna get their IgE panel done.

Dr. Theoharides: Well…

John: And then…

Dr. Theoharides: Okay, so let me speak to that. So when you do an allergy panel, a traditional allergy panel, you have to ask for specific testing. So I usually ask for about 10 different potential triggers. So I go casein, I go gluten, I go on alpha-gal which is found in meat primarily, you know, beef and pork, not chicken. Now, we have a lot of patients allergic to alpha-gal. Then I do dust mite, then I do any pollens that might be close to wherever they leave, it might be pine tree it might be cypress trees, it might be you know, whatever. Okay, and then I do a pot of about five molds.

John: Okay.

Dr. Theoharides: So about 10 different things because you have to ask specifically for each one of them. So that’s the typical panel. I also always ask for a total IgE because if the total IgE is high, they’re more likely to respond to potentially other triggers that are not on the list of the 10 that I mentioned.

Then, if the patient or the child or the parents indicate that there’s a lot of gastrointestinal problems, like bloating, diarrhea, you know, the stool smells badly, it’s very yellow, which happens often. Then we’re dealing with three potential conditions. I’m sort of simplifying things. But one could be that someone has what we call screws or gluten enteropathy. In which case, you don’t necessarily go and scope someone right away. But you can measure in the blood things like gliadin or zonulin or transglutaminase, which are high if, in fact, your gut has been affected. And you know, your mucosa now is flat rather than having villi. Goes without saying that if you have that gluten is one of the major problems, but we would have seen that on the gluten IgE panel anyhow, but I measure them just to make sure.

John: That’s interesting. So you do a literal traditional IgE we panel.

Dr. Theoharides: Yes.

John: Okay. But some of these tissue transglutaminase and test, I think those celiac markers they look at IgA don’t they? Localized to this.

Dr. Theoharides: Well, you can look at IgA I was going to come to the IgA right about now.

John: Okay.

Dr. Theoharides: So the reason why I asked for as I said, zonulin and gliadin and transglutaminase is because you could destroy the mucosal of the gut, not necessarily due to gluten enteropathy other things could destroy it, which case the gut-blood barrier becomes permeable. And we’ve been thinking all the time that is only to gluten, but it’s not only to gluten, parasites can do that, inflammation in the gut can do that okay. So that to me, that’s an indication that the gut-blood barrier is down is disrupted and I have to deal with it okay.

Then I worry about the makeup basically of the gut, whether it’s a bacterial or fungi and IgA is very important. So if IgA is very low, I worry. And I would send actually for stool analysis. And a stool analysis typically we do parasites and over eggs for the parasites. But I also ask for leukocyte count. In other words, they count the white blood cells, if the white blood cells are there, that means inflammation, even though we might not know in response to what.

John: Okay.

Dr. Theoharides: And the final part is the food intolerance. Now, many of my colleagues these are the bonafide allergist if you wish don’t do food allergy panels, and for two reasons, one, because he has never, never really been validated. And therefore, you know, we don’t know what to do with it.

And second, because many times you have tremendous false positives. Now, why do you have false positives? First of all, the food panel measures IGG for antibodies, and it’s a subclass of the IGG. And I like to measure IgG1 and IgG4 both the total, just like I said, total IgE I ask for total IgG1 and IgG4, because those have been associated with all kinds of, you know, immune problems. And most of the laboratories measure only one. There’s one laboratory I have nothing, you know to do with a laboratory financially, it’s called pinner test P-I-N-N-E-R, in New York. Where they send you basically a kit, you prick your finger, you send it back, and they measure IgG1 and IgG4. And I happened to send blood from a number of patients to three different labs, and there’s turned out to give me more accurate of what turned out to be clinical problems at the end.

John: Okay.

Dr. Theoharides: But the most important thing wherever you do a food intolerance panel is not to eat, if possible, any of the suspected foods for at least three days before you draw blood. Because, for instance, if you eat egg every day, it was turned out to give you false positive to the egg. And many times families tell me especially for children, “Well what am I gonna, you know, feed them they’re going to starve? Well, a child’s not gonna starve first of all, and most of the time, I don’t see reactions to chicken and rice, sometimes to rice, but they’re the safest. So if someone can feed you to themselves or a child, you know chicken and rice, maybe for three days, at least you avoid all the others. And then I will believe the results. So the highest the number is some laboratories give you numbers from one to I don’t know 40 or so. Some they give you one plus, two pluses, three pluses. One plus, I’m not gonna pay any attention to unless the family tells me that they absolutely have a problem with it. But if you’ve got two pluses, three pluses, I will at least do a few months of avoiding those substances.

John: Okay. And do you find that that really improves their verbal their?

Dr. Theoharides: Well, look, every child is different. I cannot expect that any particular approach will be the single approach to help them. So what I usually do for every child after having done what I told you, and…Well, when I say in the United States, I work with other colleagues, I don’t see patients in the States anymore. But I do see patients in Cyprus, in Greece, in London, etc., for all kinds of reasons it’s a little easier to do it that way. And the testing sometimes it’s easier to do, but be as it may I would exclude such problems first, or any other trigger if I think the child has an atopic like problem. And one of the ways for me to get a suspicion of whether a child or an adult has a problem is look at their eyes. If they have any black circle under the eyes.

John: Yeah.

Dr. Theoharides: For me 99% of the time they have an allergic-like or topic like problem unless they haven’t slept for, you know, four or five days, of course. Okay. So that and then what I would do is basically scratch the underarm with my nail straight line and wait for about a minute. If that scratch turns out to become red, which called dario [SP] sign or dermatographia. I’m absolutely 100% sure that there’s a problem somewhere that has not been identified. So, depending on what the outcome of the results the laboratory results was I will try to deal with them first with some antihistamines whatever they can tolerate. And it might be a combination of antihistamine some at night, some in the morning. For instance, if they cannot sleep or give them an antihistamine that can help them sleep as well.

And here is a problem Benadryl comes actually as red pills, many patients respond to the red. I don’t know why anybody in their mind will put a red dye in an antihistamine. So I tried to get the clear capsules soft gel capsules of Benadryl, for instance, not the pills they have a coloring just to give you an idea. If I want to help them sleep, there is Atarax or hydroxylysine that is both anti-anxiety and put you to sleep as well and give that at night, etc.

If they’re asthma you my end and then to leukotriene like singular. If they have horrible itching older children you know, over eight years, or older adults I might give them you know, Xolair which is you know, the neutralizing Ig molecule. And in the meantime, I’ll try to block the mast cells as much as possible. And there comes the supplements that I have to develop that contain the flavonoids luteolin. Keeping in mind they’re both question luteolin, Pycnogenol, curcumin, they’re all phenolic and about 15% of the children respond to phenols and they become hyper.

So hyperactivity is high on my list because hyperactivity is not part of the diagnosis of autism. So I have to figure out why they’re hyperactive? Do they release more epinephrine and norepinephrine? Or their snips indicate that they cannot actually break it down. So that is very important. So if they’re not breaking down, they’re going to be intolerant to phenols. And there are actually some enzymes specifically for phenols. So if that’s the case, I will try to reduce their hyperactivity. And their drugs that can do that although sometimes I start with things like you know, primrose oil, or various tea like oils that can be, you know, sort of sedating, but those are very short-lived.

And then you can use drugs like propranolol, which is a beta-blocker which we use to reduce blood pressure, but it’s one of the best anti-anxiety drugs, unlike, you know, Prozac or you know, benzodiazepine is what we call them okay. That then blocks the activity of the epinephrine and norepinephrine at the receptors. Other colleagues use clonidine, that blocks the release of epinephrine, norepinephrine. And eventually, you might need to use drugs like you know, Risperdal and Strattera, especially the children are very self-destructive, etc.

So it all depends on what kind of child you’re dealing with. But after dealing with all of this and trying to reduce hyperactivity, reduce histamine reactivity. I will give them about 2000 units of vitamin D3 because about 40% of the children have been reported to lack vitamin D3. And vitamin D3 is also anti-allergic. Two years ago, we had a whole symposium in the “Journal Clinical Therapeutics about it. If they have MTHR of permutations, I’ll give them calcium folinate or methyl folate.

And then I’m left with the inflammation. And ever since we said there might be a connection between mast cells and reactivity and autism. And not only the epidemiological studies showing a connection, but they’ve been studies indicating that there is inflammation in the brain. And these studies focused on the immune defender of the brain called microglia, the brain does not have circulating immune cells have only microglia. Microglia is helpful because unlike the spider and the neurons climb with the spider web that makes for connections, etc. But if the microglia see an invader because the blood brain barrier opened up that could be environmental, it could be from inside the body, it could be circulating new cells are getting. The microglia freak out and they become like, you know, the clones on “Star Wars.”

The start actually growing like crazy and they tried to contain that area. But in their effort to contain the area they create inflammation. So they literally short track with the system. It’s like the spark plugs are now arrested. So my approach is, on the one hand, to remove the rise by giving natural anti-inflammatory and the other gives them gas with high octane, which will be the calcium folinate, basically. So that’s kind of the approach all the way from, you know, laboratory measurements to diagnosis, to addressing the diagnosis that can be addressed to inhibiting the mast cells. And the supplement neuroprotek, neuroprotek phenol now in about two weeks it will be available something called [inaudible 00:44:40] or pyrithione [SP], for instance, address exactly that. Trying to keep it the mast cells in various parts of the body with luteolin being more soluble and getting into the brain than Quercetin, for instance.

John: That’s an interesting protocol. I guess the one thing that some people are listening are probably wondering is you know, how the heck are you supposed to get these kids with autism to change what they eat. It seems very difficult. I have a good friend whose son has a mild form of autism I spend a lot of time with him and he’s a really sweet kid. He’s…it’s hard for him though he has stuff he likes to eat and stuff he doesn’t like to eat and.

Dr. Theoharides: I know.

John: Yeah.

Dr. Theoharides: And go through that phase. There’s no question that goes with that phase. And from my experience is not worth forcing them to eat. Because what happens is, if I were to give them hydroxylysine the antihistamine at night, that actually increases appetite. And to the extent with the might be able to tolerate or give them in a form that can be mast Omega-3 or fish oil that increases the appetite. So by reducing some of the triggers, and increasing the appetite, you might actually introduce foods that the child will not have tolerated otherwise. But some of the pickiness if you wish is behavioral. So as the children become more responsive and more engaging, they also become, you know, better eaters as well. So it’s a combination of things.

John: You know, as their health improves, they become more open to eating different types of food.

Dr. Theoharides: Right. Let’s just imagine if a child, for instance, eat something and their tummy’s bloated.

John: Yeah.

Dr. Theoharides: They’re gonna hate it. They cannot tell you because you’re not verbal yet but they’re gonna hate it.

John: Yeah, okay.

Dr. Theoharides: Which I’ve seen many times. If children become constipated, their whole behavior is hardly affected. Because they cannot tell you that they’re hurting and we forget about that. So I tell parents, make sure that the child moves their bows at least once a day if they’re doing good by the second day, you’ve got to intervene. And if you let it go for a few days, basically the whole gut get stuck there and they might need an enema to clean them up. This is the most common problem of a sudden change in behavior that is at least addressable fairly quickly. And one of the benefits of some of the supplements that have been developed that I mentioned is each capsule is 50% the Luteolin the flavonoid and 50% olive oil. So the olive oil itself helps actually with constipation without having to go to other extremes. Acetylcysteine, for instance, is very useful, you know, in my mind, because it’s very good for loosening the stool and it contains caprylic acid and caprylic acid is very good antifungal.

John: Mm-hmm. Would you recommend just rather than going straight coconut oil which also has I think like lauric acid and a few other.

Dr. Theoharides: I don’t think anybody can go wrong with you know, good quality coconut oil.

John: Okay, so you wouldn’t even go for the MSM and all that you just.

Dr. Theoharides: Unless, of course, again, a child response. Anybody can respond to anything. So I always tell patients parents, just try one thing at a time for two, three days and see where you stand. If you can tolerate it then you continue.

John: But if there’s a response you back off pretty much indefinitely.

Dr. Theoharides: Absolutely. And in the kind of approach that I told you, I don’t expect anything before at least a month is up. I don’t see behavior immediately even though some parents say so. So by one month to three months, I see better eye contact, better sociability, respond to more complicated, you know, tasks, etc. It’s usually six months to a year that I started seeing language improvement or new words. And what happens which is absolutely fascinating to me, is at the beginning of the might be a couple of syllables that might be a verb, and then all of a sudden you see whole sentences and you scratch your head. These children have not been speaking up to nine year old and now all of a sudden they communicate. They don’t start with what linguists have been telling us we have to teach them you know, A, B, C, D, from scratch. So they basically are very smart. They absorb everything and something in their brain, even though has shut them off and they cannot communicate opens up another converse.

John: Yeah. It’s really funny with my friend’s son every so often he’ll have a breakthrough. So he’ll speak in a series of sentences that far exceeds what his communication have been prior to that, and it’s incredible to see. I mean, he’ll just break out with a few senses and then he…

Dr. Theoharides: Right, and then they shut down again.

John: Exactly, yeah. Okay, so we’ve established I think quite a bit here so far. You know, you have the conditions the mast cells effect very interesting. I know that’s been a subject of your research lately with this whole issue of autism. That’s such important work. I would like to touch on heart disease actually briefly to though, you know, let me ask you this very sort of targeted question. Is it possible to develop heart disease meaning arterial plaque from mast cell activity alone without having had a sterile or an errand, you know, piece of cholesterol deposited into what the cardiologist call like the subendothelial space. Basically something that gets beneath your endothelial cells are not supposed to be there?

Dr. Theoharides: I doubt it.

John: Okay.

Dr. Theoharides: I doubt it. The mast cells can participate in coronary artery disease in at least five different ways. So number one, it’s been reported many times that in those who have coronary artery disease, if you sample the coronary sinus, there is much more histamine in the coronary sinus, much more tryptase we published it. And much more interleukin 6 we published it. But not necessarily in the overall circulation, which means that the local mast cells in the coronary arteries and in the heart can do that. So that’s number one. And strangely enough, even though histamine is vasodilatory for the blood vessels everywhere else, it is constrictive for the coronaries. So keep that in mind. It’s something we don’t understand. So the histamine must be acting on different receptors on the coronary arteries and causing constriction and not dilation, number one.

Number two, we know that the molecules that are extremely constrictive and that is angiotensin 2. That’s the most venture constricted molecule known. That’s why we have so-called ACE inhibitors because they block the conversion of angiotensin 1, angiotensin 2. What is amazing is that the enzyme that converts angiotensin 1 to 2 is plentiful in the mast cells. So therefore, the mast cells can participate in constriction of the coronaries by virtue of the fact that they produce angiotensin 2.

John: Is that how they regulate blood pressure then?

Dr. Theoharides: While you regulate blood pressure, but you have too much angiotensin 2, you’re gonna have high blood pressure, you’re gonna constrict the corners as well.

John: Right. Yeah.

Dr. Theoharides: Okay. Number three. The mast cells are plentiful in the pacemakers of the heart. So we have one pacemaker in the atrium and one peacemaker in the ventricles. So if the mast cells there, get actually stimulated, they can short circuit the system. And that has been reported very often by a colleague of mine, a professor of Cardiology in Greece by the name of Kounis, K-O-U-N-I-S and in fact, this is known as Kounis Syndrome and I had the honor to publish with Dr. Kounis a number of times. So that mimics a heart attack without having atherosclerosis without have anything else other than responding to a trigger of the mast cells.

John: So you’re saying you can have a mast cell…a heart attack caused by mast cell activity minus a atherosclerosis.

Dr. Theoharides: Correct. No much atherosclerosis whatsoever. So that’s three. Four is that the mast cells release interleukin 6, that is very pro-inflammatory. And as you know, it is the secondary loose inflammatory plaques developed against the stable, atherosclerotic plaque that break often calls the infarct. So if your coronaries constrict, that’s plugged in, which is, of course, important, but he just plugged in, you don’t just don’t get enough oxygen. But if a plaque breaks off to and goes to smaller coronaries, that’s what causes the myocardial infarction.

John: Yeah.

Dr. Theoharides: So the development of inflammation due to either interleukin 6 or other molecules is very important. And then finally, the mast cells do a double job as follows. On the one hand, they release enzymes like tryptase, like CapOx [SP] peptides, etc, they break down the plaque, and therefore they’re more likely to cause coronary artery disease. And they prevent basically macrophages from eating the plaque and removing it. So they basically stimulate the production of foam cells, they collect a lot of lipids and more likely to cause inflammation.

So basically, I gave you six reasons why. And if you go to PubMed, some years back I published in “Trends in Immunology” or “Trends of Pharmacology” I forgot. An article entitled “Mast cells squeeze the heart and increase the gird” because adipocytes are also release molecules that affect the mast cells. And if you look into the adipose tissue, the adipose tissue is interspersed with mast cells okay. And we are just not addressing the mast cells at all, in cardiology.

John: Yeah, that’s something you never really hear about. I mean, I think some of the more sophisticated conversations surrounding causes of heart attack and these diseases of the heart. Do establish that it’s the subsequent immune system activity that’s attacking these breaches of the, you know, of the artery wall.

John: Yeah, that’s something you never really hear about. I mean, I think some of the more sophisticated conversations surrounding causes of heart attack and these diseases of the heart do establish that it’s the subsequent immune system activity that’s attacking these breaches of the, you know, of the artery wall.

Dr. Theoharides: Right. Peter Libby, L-I-B-B-Y is a professor of Cardiology at the Brigham Women’s Hospital at Harvard in Boston. And he was one of the leaders in talking about inflammation of the coronary arteries. In fact, about 10 years ago or so he had a wonderful article in “Scientific American” called “The Fire Within” talking about the importance of inflammation, and we still don’t have any anti-inflammatory drugs and, of course, no mast cell blockers. But increasingly, evidence has shown that taking a baby aspirin every day might not be only because it is anti-clotting, but because it’s actually anti-inflammatory. And subsequent studies have shown that the statins that we use to decrease cholesterol also have anti-inflammatory activity. But I’ve yet to see any drug that would address inflammation, especially in the coronaries.

John: And I think that’s a nice segue to this more practical way to close the conversation. Because people at home, some of which may be unfortunately suffering from, you know, very serious mast cell disorders or very acute chronic illness. But I think it’s more likely that at least, you know, a good majority of our audience are probably looking for ways that they can safely and smartly in a sophisticated way, kind of optimize. And if they feel that this is a way that they are potentially getting out of balance, whether it be you know, some kind of allergy issue or some kind of mild skin thing. There’s all this stuff on the internet about these different supplements that are blockers of mast cells and that they are, you know, this supplement, you know, helps degrade histamine this one doesn’t. I think the question thing you mentioned is really, really, really, really interesting.

Let’s do a tour of the different, you know, phenols and nutrients and things that people can take. Maybe starting with, you’ve talked about phenols intolerance, you touched on it with the autism conversation, but I think phenols intolerance is a really interesting place to start.

Dr. Theoharides: First of all, the audience, my colleagues should realize what are phenols? I mean, right now, in most medical schools, they just don’t teach any structures anymore. They don’t teach, you know, any interactions anymore. It’s really pathetic. I mean, I’ve taught students in the last few years that they probably know as much pharmacology as they’re gonna read from the television advertisements, unfortunately.

So phenols are found in seeds. They’re very plentiful in grapes. And then berries. And just to give you an idea, even Tylenol is phenolic. But Tylenol has only one phenol group quercetin 15, luteolin has four, Pycnogenol has 15, curcumin has two and the list goes on. So if patients or you know, otherwise normal people start loading up with many of these, you know, they eat grape seed extract and curcumin [crosstalk 00:58:33].

John: Resveratrol. Yeah. Super popular. Yeah.

Dr. Theoharides: They’re gonna build up actually with a lot of phenols. They’re gonna make them very irritated. I mean, I’ve got patients basically telling me, “I have Mastock psychosis.” I mean, they go crazy.

John: Because they’re taking too many antioxidant supplements basically?

Dr. Theoharides: Yeah. So they should, in general patients should have and should physicians have at least a table [inaudible 00:58:58] corte [SP] foods are rich in histamine. And corte foods are rich in salicylates. And as you know, salicylates is part of the aspirin. Aspirin is acetylsalicylic acid okay. We have a lot of patients who cannot tolerate salicylates. And of course, then you have, you know, all kinds of ingredients are going to supplements like preservatives, etc., like polyethylene glycol that we mentioned.

So, even though patients might not tell you, “I’m phenol intolerance,” they wouldn’t know. So I would actually tell them, “Does anything on this list bother you?” Because they go this list bother you and you go this list bother you. And if they do, then we’ll just remove them. But you’ve got to recognize their phenol substances everywhere and not necessarily in foods.

John: Just practically speaking, like David Sinclair, is this anti-aging researcher at Harvard and he’s very smart guy. He’s kind of on the cutting edge of longevity research, he’s promoting a book. He’s doing a podcast circuit. So I heard a couple of his interviews. I like his content. I just think he’s relatable and smart. And one of the things that he talked about as part of his anti-aging regimen, in fairness to him is he’s not he was very clear to tell people “Look, I’m not saying you should go do this.” But it’s kind of implied in these conversations. He’s taking like I think about a gram a day of resveratrol.

Now, I heard you phenol compound derived from grapes supposed to be an explanation for the French paradox, all that you know why French people tend to live longer. One theorized thing. And I’ve heard you do another interview where you said, “If you are gonna take these phenol compounds, you wanna make sure most people you wanna limit that in total.

Dr. Theoharides: Correct.

John: To at most a gram a day.

Dr. Theoharides: Correct.

John: Because if you’re taking more it can mess with you said menstrual cycles.

Dr. Theoharides: Okay, let me just address this in three different ways.

John: Okay.

Dr. Theoharides: So number one, there’s no question that if someone is phenol intolerant, he gives him a gram of whatever let alone Resveratrol, they’re gonna have a problem. The problem might not be allergy might be irritability or you know, neuropsychiatric kind of problems, which, of course, might be not evident to anybody that does come because someone’s taking supplements.

Number two, all phenolic compounds, whether it’s as I said curcumin, Resveratrol, Tylenol, etc. They all inhibit your liver enzymes and your gut enzymes and you need those enzymes to detoxify. So if you start pushing more than a gram a day, my colleague Dr. David Greenblatt has published numerous papers showing that citrus juice for instance, and pomegranate juice etc., block these enzymes and you cannot metabolize. And I’m sure you’re looking at snips for what we call CYP 3 enzymes. Those are the enzymes that detoxify the body, and he’s shown that these enzymes are inhibited by phenolic compounds. So you’re likely not to be able to detoxify, you’re likely to have your sex hormones stay high. And I’ll give you an example of something in a second.

John: Are you talking about which sex hormones would stay high? Because in some cases, I mean people generally want higher testosterone free testosterone. Are you talking about like sex hormone-binding globulin or?

Dr. Theoharides: I’ll give you an example. One of the most common over the counter antacid is Tagamet even though now we use, you know, others. But Tagamet blocks, liver enzymes, and it’s been reported many times that if you take…if males take Tagamet or Cimetidine for more than three months they actually get reversible impotence.

John: Geez, wait so is that because of the phenolic compounds in that or?

Dr. Theoharides: That’s because the molecule Cimetidine inhibits the liver enzymes, it’s not phenolic. What I’m telling you is high-level of phenolic compounds will do the same thing, will inhibit the liver enzymes. And males also have a little estrogen so if you don’t break down the estrogen, estrogen builds up and it causes reversible impotence gynecomastia.

John: Damn.

Dr. Theoharides: So if someone is given two grams a day of phenolic compounds, they’ll definitely gonna shut down like Cimetidine does even though through a different mechanism. And they’re gonna have all kinds of problems they’re gonna start chasing a urologist because they won’t know what is going on.

John: Because that’s happening all I don’t I can’t speak to the gynecomastia or the transient impotence or any of that. But I can tell you that just running a website like what I run, we hear all the time from people I actually wrote a blog post titled “Are your supplements making you sick? Because all the people that are really into this space, they’re looking for natural compounds.

Dr. Theoharides: Yes.

John: I mean you’re in the supplement industry yourself I wanna talk about your product. But it’s what do you see all the time with people is they’re taking 500,000 milligrams a day curcumin. Then they’re taking, you know, 1,000 milligrams of resveratrol, then they’re taking Cimetidine, they’re taking NAC.

Dr. Theoharides: And the unfortunate thing is that I have colleagues who recommend five grams a day, of quercetin.

John: God, yeah.

Dr. Theoharides: Okay. And I’ve gone public, and I’ve written to them saying bio…”Please, don’t,” because everything is gonna change. And then the floor in the gut is going to change. The ability to, you know, break down all kind of drugs and other substances is going to change. I…but anyhow.

John: Quercetin is one to just have for a couple more seconds here to kind of flush out a little bit more because that is like, what is it, Chromatin you mentioned earlier? Is it called Chromatin?

Dr. Theoharides: Cromolyn.

John: Cromolyn I saw just in preparation for this podcast, just doing a little bit of browsing around PubMed. You know, there’s a paper out there I think it was posted in like 2018, saying that supposedly quercetin is more effective than Cromolyn at stabilizing mast cells.

Dr. Theoharides: That is actually my paper.

John: Okay.

Dr. Theoharides: When we use cultured human mast cells and we stimulate them, dose per dose, quercetin is much better than Cromolyn inhibiting. Except that quercetin is a supplement, Cromolyn is a drug and physicians like to use drugs, not supplements.

John: Right.

Dr. Theoharides: So that’s one. You know, one benefit of Cromolyn I’m not necessarily counting down Cromolyn. If a patient responds, by all means, they should take it, we just should know that it’s not, you know, a panacea. But one good thing about Cromolyn is not as phenolic as quercetin, for you know, if you were to look at the structure.

John: Okay.

Dr. Theoharides: But then we published that luteolin is much better than quercetin. And then recently, we published that [inaudible 01:05:39] luteolin has no phenol groups and it’s much better than even luteolin. Except, function of luteolin is very hard to get and therefore it’s almost impossible for the time being to put it you know, in some sublimate by mouth. But we managed to put it in a skin lotion called GentleDerm which a lot of patients that cannot tolerate in the skin can tolerate it without a problem.

John: But with Cimetidine, though sounds like the dose makes the poison is the idea that A you need to try to identify whether you have a phenol sensitivity number one. Number two, you don’t wanna just be taking probably ever more than 500 milligrams a day of quercetin I mean.

Dr. Theoharides: By keeping it. Let me just mention this, I should qualify the statement that less than 5% of quercetin in powder form gets absorbed. So even though I know more than a gram, that doesn’t mean that all the gram is absorbed.

John: Okay.

Dr. Theoharides: That’s why I say if you keep on adding, then it becomes worse. One of the reasons why the supplements I helped develop contain all of olive canola oil is because we create rudimentary liposomes like little lipid spheres that increase the absorption by fivefold or so.

John: So let’s talk about your product. You’ve done the research on Rutin basically, and that’s the micronutrient that you have shown has the most promising stabilizing mast cells is that go-to?

Dr. Theoharides: No, no, no Rutin is quercetin glycoside. Quercetin in nature does not exist as quercetin exists attached to a sugar and that’s called Rutin. So if the sugar come off the Rutin in the gut that generates quercetin, so we call quercetin aglycone, because it doesn’t have the sugar part, okay. And so Rutin by itself can if you give Rutin to isolated cultured must cells cannot do anything, because the sugar prevented it from getting into the cells. So it’s got to cleave the glucoside off and only the gut bacteria can do that, gut enzymes. So the reason why the supplements I helped develop contain both Rutin and quercetin and [inaudible 01:07:53] is as follows. Assuming that you’re not phenol intolerant the Rutin will be cleaved in the gut and you will keep the enzymes kind of busy. And if there is inflammation in the gut, as there is many times in children, especially with autism will help with that.

Quercetin, again, whether it’s generated from Rutin or in itself added to the supplement will actually inhibit the mast cells everywhere pretty much in the body except for the brain. And it will be very quickly metabolized because the more phenolic rings that you have, the easier it becomes to metabolize, and hopefully, it will allow luteolin to escape and get into the brain. Otherwise, if I were to give only purely luteolin, then most of the luteolin will be broken down before it can get you into the brain. So the phenolic groups you have, the more likely you will get through the blood brain barrier.

John: Okay.

Dr. Theoharides: That’s why we just developed pure loot, which will be pure luteolin, for that 15% of the children that cannot tolerate phenols. So we started with NeuroProtek that has 100 milligrams luteolin only about 70 milligrams of quercetin 30 minutes or rutin. Then we created NeuroProtek low phenol once we realize that many children and adults were responding that still has 100 milligrams phenolic, but I have 30 milligrams quercetin and only one milligram of rutin and I’m sure luteolin will be 100 milligrams of luteolin and nothing else.

John: Okay.

Dr. Theoharides: All of them still in an olive canola oil base to increase absorption.

John: Well, Dr. Theoharides we certainly appreciate you coming on. It’s been a really fun conversation lot that we got to very much value your time and your commentary on these issues I know a lot of people are looking for this information. So just again, thank you. It’s been a pleasure chatting with you.

Dr. Theoharides: Thank you very much for letting me share my thoughts with you and your audience.

John: Absolutely, we will be in touch.

Dr. Theoharides: Okay. Bye.

John: The “GeneFood Podcast” is our attempt to synthesize the latest developments in the fields of genetics, nutrition, and medicine, and offer you practical tips and stories you can use in your own unique health journey. If you enjoyed this podcast, you can find more information online at

John O'Connor

John O'Connor is the founder of Gene Food. Read his full bio here.

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