Jill Brook: [00:00:00] Hello, mast cell patients and wonderful people who care about mast cell patients. I'm Jill Brook, and today we have an episode of Mast Cell Matters, Deep Dives on Mast Cell Activation Syndrome or MCAS, with our incredible guest host, Dr. Tania Dempsey, world renowned expert, physician and researcher. Dr.

Dempsey, thank you for being here and which of your brilliant colleagues did you bring with you today?

Dr. Tania Dempsey: Oh, I'm so excited to have Dr. Todd Maderis here. We're gonna have, this is gonna be a treat. Uh, we have, we have so much in common. I'm really excited to, to, to pick his brain, but let me do a little bio on him. Dr. Maderis specializes in treating Lyme disease and tick-borne infections, mold related illnesses, autoimmune conditions, chronic viral infections and conditions associated with chronic complex chronic illnesses such as Mast Cell Activation Syndrome and Chronic Fatigue Syndrome,

ME CFS. He's a board member of the International Society [00:01:00] for Environmentally Acquired Illness, and a member of the International Lyme and Associated Disease Society, ILADS, uh, the American Academy of Environmental Medicine, the National Association of Environmental Medicine, the Arizona Naturopathic Medicine Association, and the California Naturopathic Doctors Association.

His approach to treating chronic illness is to identify all underlying causes of symptoms to provide a clear direction for treatment. With over a decade of experience treating Lyme disease, mold related illness, and complex chronic illnesses, he realizes each patient is unique and requires an individualized treatment strategy.

Welcome.

Jill Brook: Welcome,

thank you.

Dr. Todd Maderis: Yeah. Thank you. Glad to be here.

Dr. Tania Dempsey: So excited. Well, we're gonna, we're gonna dive in and what I'd really like to, you know, hear about is your journey to, to sort of finding Mast Cell Activation Syndrome and understanding it. What, what was your path to this, to to, to get to this, you [00:02:00] know, point?

Dr. Todd Maderis: Yeah. I, you know, it's, maybe I'll, I'll take it back a little bit further to the beginning. I, I, you know, I really was interested in environmental medicine when I was in doing my medical training. And, and after graduation and began my practice, I trained with Walter Crinnion, who was a environmental medicine doc, and really kind of loved that aspect that, you know, there was these outside environmental influences that could affect our health.

And, you know, over time I began seeing patients that were more and more sick. And one of those you know, one thing led to another and, and someone told me about a Lyme disease conference and, and really encouraged me to, to go. So, next thing I knew, I was on an airplane to a conference and took that on

as you know, that became a big part of my practice. And then, I think it was in 2017 when Larry Afrin spoke at [00:03:00] ILADS or, or maybe Theoharis Theoharides spoke the year before. And, and I got my first introduction to MCAS. Had never heard of it before, didn't know anything about it. But it, it definitely made a lot of sense and I started to see the association with my patients and, um, you know, joined the group online,

and the rest is history.

Dr. Tania Dempsey: Yeah. I think many of us, you know, realize that, wow, we've been seeing this, but we don't, we, you know, we couldn't put a name to it until we, you know, start to, to be more introduced to, to the topic.

So, so, you know, talk a little bit about, you know, the, the types of things you're seeing with MCAS in your patients. Are you seeing MCAS as a manifestation of the other things that you're treating, like the environmental illness and the tickborne infection? Are you seeing it as, as a root? Tell us what, what your experience is with, with MCAS.

Dr. Todd Maderis: Yeah. It's, it's, it's difficult to tease out sometimes, right, 'cause these you know, as we were just discussing before we came online, these, these [00:04:00] patients have a lot of, many, many symptoms. It's hard to know the timeline of events. What came first? What's, what's a result of, and what's a primary etiology?

You know, I, I tend to think that the body has this inherent wisdom and it's doing everything that it's should do to, in attempt to heal. The mast cells being a part of our immune system that, you know, there likely is some underlying cause that's, you know, irritating it. I, I describe it mast cells to patients as sort of a beehive and that there's likely something that's poking that beehive.

And we try to find the underlying root issue that, that might be contributing to that activation or dysfunction. Clearly people can have primary mast cell disorders. It's like, if I could draw an imaginary pie chart on, you know, where, what percentage of, of which underlying cause or even secondary manifestation is your makeup,

everyone's makeup's a little bit different. And and so I think it's a critical part, whether it's cause or effect. You [00:05:00] know, I really find it's important to, to modulate the immune system. I love, I love that word. It's like, you know, Goldilocks' porridge. You, you, you want your immune system to be just right.

And, um, getting the mast cells under control to minimize symptoms, I think is a critical part to their, their healing. Sometimes people are so reactive that we can't get any treatments on board until we calm their mast cells down or modulate their, their mast cells. So, it's a big part of my practice.

I think the immune system is fascinating. You know, I, I describe it to patients as the most fascinating system in the body. It's you know, and really remarkable. I think the more we learn about it and, you know, associations with things like even the mitochondria and mast cells, it, it's you know, really, I think going forward we're, we're gonna see a whole lot more immune related dysfunctions.

You know, we know autoimmune diseases have been on the rise for many, many [00:06:00] years, and it's, it's, you know, unfortunately just getting worse. So, critical part of recovery for sure.

I feel so grateful for Larry. You know, you get to practice with him every day, which I'm, I'm jealous of, um, learning from him and having learned so much, it's, and, and I. I'm near Mark Renneker here in San Francisco, and I learned a lot from him in the early days. And then just so grateful for the, the group that we have because everyone contributes and we learn so much from from one another.

Dr. Tania Dempsey: And we have to, because the reality is that as you know, because it sounds like you really have an individualized approach to patients, as I do, every patient is different. Every, every, you know, those connections that we're looking for in our patients are, are, are different. I mean, there's some flavor, right,

that's similar, but there are things that are, are different. And you know, unfortunately it, it almost seems like every patient is a little worse than the patient before. I, I, I really, I mean, we sort of talked a little [00:07:00] bit about this before, like we're seeing sicker and sicker patients, which is really unfortunate.

I have a lot of theories about it. I'm sure you do too. And so we have to be collaborating. We have to be thinking, we have to be researching all the time. Like, my brain never shuts off because I, I think that the answers are there, the solution's there. We have to help people. But we can't do it, you know, in a vacuum because this is not that type of medicine.

Dr. Todd Maderis: No, yeah. Yeah. It's, it's, um, you know, and I, I love to learn as well, and so I keep, you know, it's, it's like I love when I discover something new or make an association. I think the connections are where we, how we can, you know, help people and, and you know, really attempt to crack the codes of these, these chronically ill folks.

But you know, I, we have this like general understanding of mast cell disorders. And, and then, you know, the other day I, I recently started running genomic profiles on patients and, and I hadn't [00:08:00] really done a whole lot of that testing. I think back in the day, everyone got excited about M-T-H-F-R and some of the mutations we were looking at, and then we realized, well, maybe they're not as impactful.

It's more of that epigenetic, you know, influence that that's regulating how the genes express themselves. But in these genomic profiles, they look at just, you know, hundreds of genes and, and even looking at the mast cell genes, the genetic variants that could influence mast cell activation, I found fascinating. You know, I didn't know there was an an IL interleukin 13 gene variant that basically causes

B cells from switches it in from producing IgG and IgM antibodies to producing IgE. Right? So then it, you have this increase binding to mast cells and mast cell trigger. So, there's an, there's an a interleukin four genetic variant that does basically the same thing. So when you learn that, you go, okay, there [00:09:00] could be environmental influences like we discussed earlier, or infectious triggers, or, you know, stress and a variety of other things.

But there could also be this genetic predisposition towards mast cell activity that's different than a monoclonal disorder. So it, it's fun when you learn something like that. Like, oh, great, there's, you know, knowing this about the patient, it makes complete sense that they have a propensity towards mast cell reactivity.

Dr. Tania Dempsey: Yeah. So what kind of genomic testing are you doing?

Dr. Todd Maderis: Yeah. You know, I, so I've been running the Intelex DNA genomic profile, which, yeah, and we learned about them, I think, you know, through ILADS.

And so that was sort of my intro too, and started running on patients. And kind of that unique patient, you know, one of the first patients, I, I mean, I've had a couple really interesting ones,

like a, a young woman with autism and had a diagnosis of Lyme disease, came here with a positive Lyme result, but wanted to explore some other, like what else could be contributing. And we decided [00:10:00] to do a genomic profile on her. And, and, and sure enough, she has I forget the, I think the gene is called a SHANK3 gene.

She's, she's homozygous for it. And you know, it occurs in like 1.7% of the population and it predisposes her for developing autism. And you go, wow. It, so the, for the audience, the less the less common the gene is, the more, you know, impact we think it has. And, and so, you know, for her it was, she was like teed up to get autism and then she had the environmental influence that sort of, you know, probably tipped over the edge.

Because she's homozygous, you know, her mom is likely, her mom talks about their whole side of the family, kind of having people on the spectrum. And but clearly she had to get a copy from her dad as well. Her mom and dad are fine, but because she's homozygous it's, it's, you know, put her into this, this state

where she experiences these symptoms, I should say. And, um, I've seen it with PANS and [00:11:00] PANDAS kids too, right? That, that they have the infections, yes, but then when you look at their genomic profile, you'll see these genes that, that basically they're, you know, by default they're almost, they're gonna have these autoimmune, you know, an autoimmune encephalitis presentation.

Dr. Tania Dempsey: Yeah, it's incredible. But I, I think that's an important point. And I, and I talk a lot about this on, uh, I, I, I did a little Reel recently on, on social media on this. The, the fact that I think you need multiple hits. I think you need a, a genetic propensity. Now, now the reality is lots of people probably have these various, you know, uh, variants or polymorphisms and we wouldn't know 'cause we wouldn't test them because they're quote unquote normal, right?

So we don't really know what what's really going on in the, the normal population. But, but we know that, you know, there [00:12:00] is some, you know, predisposition and then there is some early exposures. And, um, you know, who's doing amazing work on this is, um, Dr. Claudia Miller in at UT San Antonio. I, I'm hoping that she's gonna speak at ILADS this year.

I'm, I'm working on it because she is amazing in the work that she's doing. She's the one who really put TILT on the

map, Toxicant Induced Loss of Tolerance. Um, and she then sort of has, you know, she's been collaborating with Larry Afrin and I, and, um, really came to realize after 40 years of, of doing the, the, the work that she was doing, that mast cells were at the root of, of the development of chemical intolerance and chemical sensitivity.

But what she's finding is that there's some kind of, again, probably some genetic vulnerability and then there's an early hit to like, uh, you know, uh, uh, a child who in [00:13:00] utero maybe exposed, um, maybe the mother was exposed to some chemicals, petrochemicals, pesticides. You know, there are all these different right toxicants in, in the environment that the mother's exposed to.

Then the baby is exposed in utero, maybe even exposed after birth. And that is, and, and what they, what they showed was that. The incidences or what she's trying to show is that the incidence of autism is higher in mothers who are chemically intolerant, chemically sensitive, higher rate of

autism. That's because the mothers are exposed, triggering their mast cells, which is then then an early exposure and an early activation of mast cell in the, in the mother, and the exposure in the infant or embryo or however early that's happening is then sort of tipping things over.

And I think that makes sense to me.

Dr. Todd Maderis: Yeah, absolutely. I mean, it, it, you start to think about it and put [00:14:00] it together and they published on that, right? That paper has already been, yeah, I, I saw the paper. It was fascinating to see the connection, 'cause you know, again, it's, it's like the people that, you know, argue that, you know, vaccines are such a touchy thing,

do I wanna say the word, but,

you know, we're in good company. You know, that they can trigger, well the kids that maybe developed autism following a vaccination. It might be hard to point the finger at the thimerosal that was in it, the mercury preservative, the, the potentially there was a genetic underpinning,

right. That predisposition you just mentioned. And I, I, you know, I think of it the same way. It's like we have this genomic or genetic susceptibility plus an environmental trigger equals illness, disease. And you know, kinda like the young woman I was just mentioning that's, that's on the spectrum, you know, makes you, I, I fast forward and think and go well,

it's all this cross pollination that we're doing, the people that are getting together and then having children, you know, and, and all of a sudden having a homozygous [00:15:00] child of some that increases their risk for a condition or disease. Maybe we should run genomic profiles before we start dating. It could be part of our, uh, you know, in people's dating profiles now so that we, you know, those people don't come together and produce someone.

But there's also beauty to, I mean, I don't think being on the spectrum is such a bad thing right. There, like, there, I've seen headlines lately about, you know, Lyme disease is really the, the trigger to, you know, a, a big contributor to autism. And, and it likely does trigger something there, but is it the only trigger?

No, it's not. You know, so it's, it's fascinating and yeah, I think we're learning more and more about, you know, medicine is too complex, or at least the patients that we treat to, to, to be myopic, right? You have to be open to everything that's out there, and the more you keep looking into it and under, you know, discovering and learning, it's like, well, yeah, of course it [00:16:00] makes sense that there's this genetic predisposition and then we have these, so we can't control that, but we can control the environmental piece and, and, you know, hopefully minimize those exposures to, you know, kind of tamp down that phenotypical expression.

Dr. Tania Dempsey: But that's, that's difficult, right? I mean, how, how do we control the environment? I mean, I, I do, I just did like a masterclass for, uh, for my audience, you know, for like, you know, how to detox your home, right? Mm-hmm. And, and lower the toxic load. And we, we try all that. We teach all that. But reality, not to sound like a pessimist, but the reality is that it's, it's really hard to control some things, right?

There are people who are living in environments where, you know, drinking out of a stainless steel water bottle is not gonna change anything because, you know, I think about exposures like, um, you know, if there's a, if there's a toxic explosion of stuff like, you know, the, there was, um, a [00:17:00] trained derailment in Ohio. Well, those people I just read an article about, it's two years later, and the toxins from that train are still found in the air, in homes, you know, miles away. And these people either cannot move back to their homes or they're living in their homes and are so ill.

And so that's where I really think like we've gotta, we've gotta start to figure out how to protect people better. How to right, like

really detox these toxins from our environment.

Dr. Todd Maderis: Quite a big undertaking. But you're right, it's, it's looking at more of how are we producing things, what are we, what are we using for packaging? I think it's, you know, it's starting to happen clearly, but we've gotten ourselves in such deep holes for, you know, decades now that it's gonna take a while to, you know, to reverse that.

And, and, you know, a lot shifting in the, you know, on, on, on the government level federal level from a [00:18:00] health standpoint. So who knows what's gonna happen, but yeah, it, it's, you're right. It's, it's a big undertaking. And I don't know the solution for you, you probably are familiar with the German lab

IGL. Were you guys ever sending blood over? Yeah, we, we did. Yeah. We, so did we until we, until they, we couldn't send blood samples there anymore when they, they restructured. But we, you know, they had that IEP profile, I think it was intracellular erythrocyte, you know, they were looking at toxicants inside of...

Dr. Tania Dempsey: Oh, yeah. Yeah. Yeah.

Dr. Todd Maderis: Intracellular toxicants.

It's kind of a unique way to measure things, right? And almost every sample we sent, people would come back with elevated toxins, these profiles of, I think 24 different toxins. And it was like we're all living in a toxic environment and, you know, I loved that lab. There was a lot of other aspects that we do mitochondrial panels, and I thought it was really fascinating and we, we do a lot of, um, I use a lot of phosphatidylcholine in my [00:19:00] practice intravenously.

Yeah. We love, love doing IVPK stuff where it just really helps with detoxification and, and repairing those damaged cell membranes, basically, I think of it like, um, flushing toxicants out of cell membranes and then we'd repeat the IGL profile after they went, you know, patients went through a course of treatment and we'd see their, their cell membranes come back nice and healthy, you know, kind of, without the toxin burden.

Dr. Tania Dempsey: I was just gonna say we saw some DNA adducts that were mind blowing. You know, one, um, patient had a very unusual pesticide that has been outlawed apparently for years. And, and I think he was probably, the kid was about, I don't know, 16, 17. And, and this pesticide has been outlawed for like, greater than 20 years, and it was sitting on his P53 gene.

Dr. Todd Maderis: Oh, wow. Yeah.

Dr. Tania Dempsey: Which is, which is the gene that's sort of like supposed to help prevent cancer, [00:20:00] right?

It's one of our cancer prevention genes. Right. And I mean, that was mind blowing. Yes, we did some PC and, and uh, you know, IV oral and it seemed to go away, but you wonder where people, even young people are being exposed to this stuff.

Dr. Todd Maderis: Yeah, yeah. Yeah. I think of them like the, the persister toxicants and then the non persisters, and that's what I was always taught. It's like, you know, things like DDT has a halflife of, I don't know if it's 40 years, it's a long DDT been banned for, maybe it's been banned for 40 years, but it has a really long halflife and uh, PCB,

some of these persisters will still, you know, be in the human, uh, or non persisters, like VOCs and, and other things, you just kind of remove the exposure and, and they hopefully go away. But the DNA adduct thing is very fascinating. You know, when you look at it on that level, sort of a, you know, a, a single strand of the DNA has this, this covalently bond toxin that's, I think of it [00:21:00] like coming in and, and blocking genetic expression.

Whereas one of my, my colleagues says, it's like putting the wrong document in a, in a Xerox machine, and then you're printing it over and over again. The wrong information is coming out and, but the good news is you can correct that. And I think that's what, when we, we talk about illness or when we started doing that running the IGL test, it, it kind of, it, it dawned on me one day it, it's like we'd get the cell biology health, you know, their markers back and we look at in someone who's young in their twenties and, and, um,

I would say this is what you would expect to see in someone who's in their sixties or seventies. Right? And so then I kind of had this moment like, well, maybe chronic illness, what, you know, what chronic illness really is, is sort of this, this, you know, premature, this aging, this damage to cells. And of course we know that oxidative damage and reactive oxygen species, all these things that that's really what is happening.

And mitochondria are affected. And, and some people have better antioxidant [00:22:00] capacity than others. And so there maybe they're more protected. But, but ultimately that's, uh, you know, I think what we're seeing in chronic illnesses like this, this, this rapid, you know, it's damage to tissues in cells, which is, which is sort of like advanced aging.

And, and that's why people feel the way they feel. They're just, they're, they have a ton of inflammation. They're affected on a cellular level. When I would describe those results to patients, I'd say, you know, we're, we're looking at your cellular health and you've got, you know, your, your cells are what make up your tissues.

Your tissues are what make up your organs. You've, you've got about 50 trillion of these cells in your body, and if we can repair them and heal them, then it, it can improve how you feel. Then the, the tissues in the organ start working more effectively. You know, you've probably familiar with Robert Naviaux's work with the mitochondria and cell danger response.

You know, he, I love his statement. The, you know, the [00:23:00] chronic disease persists because healing is incomplete. And I'm sure you've seen this with your patients, it's like they're maybe positive for, for bartonella and mold, and you, you get rid of the Bartonella and you clear the mold, but the patient still can remain symptomatic.

Maybe they're better in some areas their headaches are less severe and their energy. But they might still experience fatigue or inflammation or brain fog. And, and I think that's the cellular healing. You know, he's sort of referring to something else. But I think that's what we're doing with the PK protocol is we're, we're, you know, with phosphatidylcholine repairing cell and mitochondrial membranes and which of therefore we're healing tissues in organs and, and they're working better.

And then of course people feel better. Um, so that, that's, uh, you know, in the last few years in my practice, I've really, you know, I, I always, I'll describe it to patients, you can remove the underlying cause, but people can remain [00:24:00] symptomatic and, it's almost a, you know, sometimes when people, uh, we probably have a lot of Lyme, you know, colleagues, that someone still is symptomatic and they have a history of a tickborne infection, they'll keep kind of chasing the bug.

And, and ultimately we have to know when to pull out and not attempt to kill bugs, but try to repair damaged tissue and heal, get the, you know, get 'em outta that cell danger response. Get 'em, you know, back on the, the road to health.

Dr. Tania Dempsey: That's gonna actually be a, a big focus of our, uh, upcoming ILADS conference in October is sort of understanding this relationship between the terrain,

which is the host of bugs and all the stuff, right?

And so trying to understand, you know, how much it's, it's a, it's a little bit of a dance is what I say with my patients, right? If you have persistent infection, it's gonna be very hard to heal. So sometimes you still have to go after the infection, right? And even though you've [00:25:00] been chasing that infection for 20 years, we know these infections persist.

There's no question about it. But there's a reason why the immune system is not clearing the infection too, right? It's not just about the bug. It's about the, that immune response. And so, you know, trying to, to understand that and figure out ways to you know, and I like how you said that earlier, modulate the immune system, right?

Not increase the immune system, but modulate it so that even if there is infection there, maybe maybe the immune system can handle it better. Maybe the, the healing has allowed right, things to, to sort of fall into a balanced state.

Dr. Todd Maderis: Yeah.

Dr. Tania Dempsey: So that's, that's where I think, like, that's where I think the future of this, of this field is going.

Jill Brook: So I was just wanting to ask for all of us who have never heard of this PK protocol or

the phosphatidylcholine thing, if people are having their ears perk up saying, what, what is this?

Is, is, [00:26:00] can you say again, what is the name of this if people wanna Google it, or where could

people learn more?

Dr. Tania Dempsey: So, we call it PK Protocol because it's named after, uh, Patricia Kane, who sort of was a pioneer. Her and her husband were the pioneers of understanding membrane, basically it's membrane medicine, so understanding the, the cell membranes.

And, um, they started their work, I believe, in treating severe neurodegenerative diseases like ALS, MS and then, and then PANS/PANDAS, and some other, some other, uh, neurologic conditions. And they found that, you know, through their work, that using this compound phosphatidylcholine, which we can explain a little bit about that we knew that our, our cell membranes are cell membranes are basically the thing that goes around the cell,

that that needs to be fluid. It needs to allow garbage out. It needs to be able to pull [00:27:00] nutrients and other important things in, right? So, so the cell membrane you need, you need it to be sort of happy and the cell membrane is made up of certain types of fats, phosphatidylcholine is one component, big component of the cell membrane.

If you don't have enough of it and the cell membranes are kind of stiff, well what happens is then the garbage builds up in the cell and the cell becomes sick, um, or it can't absorb nutrients into the cell. And often viruses and infections and things like that kind of stick into the cell membrane. And also that they, they actually sort of damage that cell membrane and make it stiffer or make it leakier,

right? There's, we also talk about leaky cell membranes that are, that are also not, kind of, not allowing the right amount of fluid in the cells. A lot of patients will say this is classic, right, I can drink all this water and I never feel hydrated, right? That's 'cause their cells are not able to suck up the water because their cell membranes are [00:28:00] actually damaged.

Um, and so the PK protocol, or I, or phosphatidylcholine can be given or it could be given orally it, and it should be probably given in a mul multiple ways, orally, IV. Sometimes and often combined with other compounds to try to rebuild. And one of the things that it does in addition to rebuilding the cell membrane is that it sort of can bind to toxins and help the body pull those toxins out and detox.

Tell me if there, if I missed anything and fill in the gaps.

Dr. Todd Maderis: Oh yeah. No, that was perfect. I, I, you hit it on the head. Um. Yeah, I, I've, I wrote an article about phosphatidylcholine 'cause I, I just, I love phospholipids are, you know, phosphatidylcholine and I think phosphatidylethanolamine are the two primary phospholipids that, that make up your cell and mitochondrial membranes and yeah, they, they get damaged by all the garbage that we're exposed to on a daily basis.

And, you [00:29:00] know, infections, toxins, you name it. And then they don't work as well. And, and like you were saying, they become stiff and rigid and they don't do the job they're supposed to do. So it's, I think it's a big, big piece of the puzzle. And there is a healing, you know, I've, I've had patients with, you know, positive infections and then we treat them and like it doesn't really move the needle.

And we're like, well maybe, you know, let's try, let's go on to the next step. 'Cause that, I mean, we could, we could do a whole podcast on testing, right, and, and what are we really looking at? We're, look, you know, some of the tests we use, we're looking at antibodies and can you have an antibody, were you one of the authors on the paper, the mast cell paper and, you know, spurious antibodies, right?

Dr. Tania Dempsey: I was.

Dr. Todd Maderis: We can make antibodies to things and, and you know, is there an active infection there? When we do direct methodologies, like under a microscope, of course that's, that's an active infection. But, um, you know, something I was gonna say earlier when we were talking about, the infections and sort of that [00:30:00] total accumulation of thing and, and hitting on what you mentioned earlier, Tania, was that that multi hit model, and I, I would agree.

I, you know, you hear that time and time again from patients. Or you're talking about Claudia Miller in the work, in, in exposures in utero. And, but you'll see in patients too that might have, you know, maybe they got Epstein Barr in high school and then they had a head injury in college.

They fell off a scooter when they were drunk in college. And then they you know, got COVID in their twenties and all of a sudden they're symptomatic. And, you know, it, that's, that's the tricky part is Dr. Naviaux would say, you know, the road from chronic illness back to health is, is not the same, just removing the path that got you there.

And so I, I think you're right about the future. It's this constant, you know, these, the accumulation as, Amy Proal, who's a researcher, she calls 'em successive infections, right? And you can have, whether it's all [00:31:00] viral or all tickborne or whatever it is, it's that successive exposure, um, that ultimately the body at some point can't, you know, it, it, it just, it breaks and it, it's difficult to unravel that.

So I think part of, there's a healing aspect to this as well, besides just removing what triggered it in the first place.

Dr. Tania Dempsey: Exactly, and that's why we, we turn to some of these, these treatments. So again, it doesn't, it doesn't help everybody, right? And that's, that's the problem. That's why I keep bringing in new modalities and always looking for other things to do because it can help a lot. What I use since, since we can't use IGL, um, anymore, or maybe we can, I don't know, but I haven't looked into it recently.

What I find is I, I use a, uh, BIA, Body Impedance Analysis or a, uh, we have a, a machine called the Bodystat and it measures the phase angle.

Dr. Todd Maderis: Hmm.

Dr. Tania Dempsey: And you can use the phase angle as a surrogate marker for cellular membrane [00:32:00] membrane health. The lower the phase angle, the more likely the cell membranes are damaged.

Dr. Todd Maderis: Ah.

Dr. Tania Dempsey: And so a lot of, a lot of my patients, we, we do these, we, we do these on everyone who we put on, let's say a GLP-1, 'Cause we worry about, 'cause it measures body fat and, and muscle and, right. I wanna make sure that they're not losing muscle. But the nice thing about the machine that we have is that it also measure measures phase angle.

So it's measuring like all the things that they wanna know. But for me, what I wanna know is what their, their cellular health is like. And, and this is a very rough sort of estimate. And what I have found very interesting is that in a, in a subset of patients who are taking GLP-1s, their cellular health is improving.

Dr. Todd Maderis: Hmm.

Dr. Tania Dempsey: And I'm not treating them with phosphatidylcholine or, I mean, some of them I am, but, but I have this subset that I'm not, and they are becoming less insulin resistant and they are you know, losing some body [00:33:00] fat. Some of them are even gaining muscle. I know there's a lot of literature about loss of muscle with GLP-1, but I have patients who gain muscle on GLP-1 because they're a little bit more strict about exercise and, and I'm on them and I'm microdosing and I'm not, you know, giving crazy high doses, but they're, but then their cellular health looks like it's getting better, which I would love to, to figure out how to really, you know,

test and understand.

Dr. Todd Maderis: Yeah. Oh, that's fascinating.

The things we discover sort of incidentally, right. You use SOT in your practice. We're talking about trying to kill these bugs and having antibodies and testing and how it's difficult, but how, how's I, we've been using SOT since last year in my practice, and I've found it to be remarkable for both tick-borne infections and chronic viral infections.

How, I'm curious what your experience has been.

Dr. Tania Dempsey: Yeah. I, I, I think it's, uh, it's been incredible. It [00:34:00] certainly has allowed us to use a lot less antibiotic and other, right, antimicrobials. Um, and especially for patients who really can't tolerate, um, those things. It's been, it's been amazing. Supportive Oligonucleotide Technique, SOT. I think they just renamed it, and it's called Q-REstrain

now. It's essentially a, um, a protein that's created for whatever, you know, infection that you're trying to kill. If it's a, if it's Lyme, if it's Babesia, Bartonella, Epstein Barr, various herpes viruses, it can be made.

There's a, there's a long list of infections that they can make, uh, a protein that matches the DNA essentially of whatever infection you have. And, um, and it's infused. And that, that little protein, it's almost like an RNA molecule, it's a short, uh, strand. It basically goes into the cell, binds to, to [00:35:00] the cells, not your cell, but the cell of the infection and basically shuts down the, the, the multiplication, the replication of the, of the infection, and essentially kills,

kills the, the infection. The way I look at it is that I think it's reducing load. You know, it's not gonna kill all of everything in one shot. Most patients do need multiple rounds. They often have multiple infections. So the patients who have done the best, my best cases, and I have quite a few now, are the ones that have done, let's say, they, they have, and we have, and a lot of these, you know, I use a lot of molecular testing.

So these are not an antibodies, right? This is, they're FISH-positive for Bartonella henselae. They're, they're FISH-positive for, you know, Borrelia burgdorferi. They have Epstein Barr, PCR positive. They have, you know, so, you know, right? So they have a lot of these things.

And if you, you know, sequentially [00:36:00] do these SOTs for these various infections, repeat testing, do another round. Sometimes, sometimes you need two or three of these SOTs spaced out for each infection, the load goes down. The load goes down, the load goes down, right? And the more the load goes down, the more the mast cells, the immune system,

you know, the cellular healing, all this stuff just has a chance to, to work. And that's what I see. Like I had, I had a, um, I have a, a, a patient who, uh, is in college and a few years ago we didn't even know if she'd be able to go to college. Uh, she actually is out west in California now. She has so many severe symptoms from infection with auto, like an autoimmune encephalopathy type PANS situation with a lot of you know, cognitive issues and, and lots of other stuff in her, in her, you know, early twenties, late late teens.

And we had done [00:37:00] antibiotics a few years before. We had done other things, and she just kept, you know, relapsing. Um, and then, you know, we just, you know, like S-O-T-S-O-T-S-O-T and her family was a hundred percent on board. And so, you know, we've done a number of them over the course of the last couple of years now and she is thriving.

Thriving. And actually she's, she's just finished her junior, I think it's her junior year that she just finished. She was in yesterday. Her mother's like, let's repeat testing. I wanna do more SOTs over the summer, 'cause I just wanna make sure by the fall she's good to go. Right. That's how like...

Dr. Todd Maderis: Yeah.

Dr. Tania Dempsey: It is just, you know, now I don't know if everyone needs to keep doing SOTs, but, but I do think that a lot of people do better when they have a little bit of a, a like a little refresher.

Like just in case a little bit. I don't know what you found so far.

Dr. Todd Maderis: That's interesting. Yeah. Yeah. Yeah. I think this next week we're, we're I've treated a, a, a gentleman I've been treating [00:38:00] someone a guy, kind of same thing with antibiotics, you know, off and on over the last couple years. And he grew up on Martha's Vineyard and, you know, multiple infections.

Babesia, Bartonella. I think at one point he was positive for Lyme too and kinda same thing. Maybe some little bit of progression with, with the different regimens, but never really, like, his main complaints would never fully resolve. And he responded really well to SOT. And he, he has this, a young boy, an 8-year-old that has PANS and PANDAS and, and positive for Bartonella and Babesia and

this dad has done so well with the SOT that next week we're administering SOT to this 8-year-old. And, um, he'll do two rounds, he'll do both, we've drawn him already for Bartonella and Babesia, and it's, it's remarkable. You know, I, the way I think of it too, it's not like you, you're not swallowing an antibiotic every day, twice a day for months and months and months.

Those organisms, as we know, like the, they, they shut down as soon as the [00:39:00] back, the antibiotic is on board and the antibiotics only work when the bacteria are replicating. So there, I think there's limited success. We've, it's been the main tool that we've all had for a long time, but there's other tools out there, and I think that's part of medicine, right, is staying, you know, looking at areas that can help us advance and, and, and be better.

So it's, it's, I'm excited about it. I, I wasn't an early adopter. I kind of sat back and wanted to see how it unfolded and then once we started using it, we've just been, it's been great.

Dr. Tania Dempsey: But like everything else, right, I definitely have patients who are not, you know, responding the way we, you know, we want, we would like, and that's when you have to look at the why. You know, what's different about that patient? Why is it, is it not about the infection or the load? Is it more about, you know, an immune dysfunction that somehow is you not, not even allowing the SOT to, to work? For some patients, it's because, you know, [00:40:00] it's, it's not cheap.

So, you know, if you have financial constraints sometimes the patients can only do one, two, and they really need three or four. And so they stop treatment too early, then they don't get the full effect. And that, you know, that's unfortunate, 'cause they, they might have been a, you know, be, been able to, to react well, but you, you know, they, they can't do that many.

Um, so there are lots of different reasons. So like everything else, it's, it's just been an amazing tool. Like we've been doing it since we started in, um, 20 18, 20 19 and then had to shut down a little bit. You know, 2020 was a, was a, was a rough year. Um, but then since then it's just been like, yeah, it's just been incredible.

Dr. Todd Maderis: Yeah, yeah.

Dr. Tania Dempsey: So, but you know what I wanted to, I really was really looking forward to talking to you about some of your work in the, um, like blood coagulation stuff and the blood clotting, 'cause [00:41:00] I've been really interested in this as well, and I, I definitely have seen some very interesting profiles on patients.

And so I'd love to hear what you are finding, what's the relevance is, what, what you're testing. Let's talk about blood clotting.

Dr. Todd Maderis: Yeah. Yeah, I know. Funny that we would even never thought I would be so fascinated in hemodynamics. Um, but I, I you know, I, I think going way back there, I remember there was a chronic illness conference in Arizona probably 10 years ago. And there was a guy named David Berg that kind of introduced this concept.

I think the profile at the time was called the ISAC profile, ISAC. And he had founded a lab called Hemex, I believe, and then, um, sort of knew of it, didn't really get dive too deep in it then. Probably about five years ago it kind of [00:42:00] resurfaced for me or came, you know, crossed my path and I, I started to explore it more and began testing patients.

Um, Hemex had gotten sold to a lab called Esoterics, and then LabCorp went on and purchased Esoterics, so I think that's their hematology division. And the panels, you know, the blood markers aren't your traditional, you know, D dimers and, and PTTs and things you're gonna get with an acute event that we're concerned

someone might have a, you know, is having an MI, a heart attack. But they're looking at more of the fibrin side of the coagulation panel or pathway. I always show patients, I have a great little diagram on my computer and I'll pull it up. And, you know, on one side of, of this coagulation pathway, we, we make fibrin and on the other side we break down fibrin.

And it's this constant, this dynamic state that's always occurring. Once again, Goldilocks's porridge. It has to be in balance. [00:43:00] If you make too much fibrin or you don't break it down readily or both, then you're gonna be in a hypercoagulable state. We have genes that influence the fibrin production, right?

People that are Factor V Leiden or have a Factor II gene mutation. And that would cause us to make too much fibrin. On the fibrinolytic side of that pathway there's a PAI-1 gene or plasminogen activator inhibitor one. And if someone has a deletion there, they don't break it down as easily.

But the, even without the genes, all the conditions that we've been talking about so far, uh, anything that drives inflammation can also contribute to this hypercoagulable state. And so the, you know, being hyper, you know, sort of having hypercoagulability is, can cause its own symptoms. It can, you know, I think it's a big contributor,

pOTS and dysautonomia. I, I screen all my patients that have POTS. It can [00:44:00] contribute to things like, uh, you know, definitely fatigue, brain fog, almost like a cerebral hypoperfusion. You'll see decreased or poor circulation, they always get cold hands and feet. Yeah, I have, I have Renaud's right and my thyroid's normal.

So you'll see some symptoms from, you know, when, when people are hypercoagulable, but what I think the connection that shows up a lot in our world is that fibrin also contributes to biofilm production. And so apparently in the general population, about 20% of people have one of the genes. And I think it's a little bit more, I think the PAI-1 people, there's, it's more common than the Factor II and Factor I V.

But out of all the people that I am testing, the people that are walking in my door, I would say close to 80% of people have one of the genetic variants. And so it, it got me, it got me very curious and wondering if 80% of the people that I'm seeing with complex [00:45:00] chronic illness have one of these genetic variants, could it be playing a bigger role or hypercoagulation playing a bigger role in the, either the persistence of their illness or maybe the you know, contributed to the onset of some of their symptoms?

So I, I think it's a, you know, it's become a, a, you know, a important variable I would say in in my patients. And even the connection with mitochondria, 'cause I started to think, well, all these people that, that have excess fibrin or they, they, um, you know, they don't break it down readily, they're all fatigued.

Like, fatigue was like the through line for all of 'em. And so, of course when you look at, you start thinking about mitochondria and, and oxidative phosphorylation, you go, oh, of course the cell needs oxygen for energy production. And they're basically in a hypoxic state. So, you know, I start diving into this stuff and you just go to, in your [00:46:00] favorite AI source and type in hypoxia, mitochondrial dysfunction, and you'll see a whole lot of, of good information.

So, again, I, I think it's probably playing a much bigger role in, you know, our, many of the conditions that we see in folks.

I love to, to run the coagulation panel on, on all of my patients. I always do it through LabCorp. There's a retired nurse practitioner named Ruth Kriz. And, and Ruth is amazing. She's one of the most generous ladies. She's just fantastic. I've learned so much from her.

And she created a panel with LabCorp. The, the test code for the listeners, it's, it's 5 0 5 4 4 3 and you could get your GP or anyone to order the test. You know, there's preferred reference ranges, which I have on my website. People can find it on my website. Those are David Berg reference ranges, I believe.

And because a lot of the, well, the LabCorp reference ranges include the people that have the [00:47:00] genetic variants. So you, that really skews the range. But, you know, finding out if you're an over producer of fibrin or you don't break fibrin down, you know that that guides treatment, right? So people go, well, can I just take my fish oil?

Or what about you know, I take an aspirin every day? Well, as we know, those work on platelet aggregation, that's completely different mechanism of clot formation. Clots form with, with both platelets and, and fibrin. And people have a fibrin issue. Or they can have a fibrin issue and not a platelet issue.

So anyhow, you wanna know if you're making too much fibrin or not breaking it down.

Dr. Tania Dempsey: I couldn't agree more. I think I, and I think that's part of the persistence of infection as well, because if everything is in this biofilm, then you can't, you're never gonna reach it, right. Even with the best SOT or whatever, you just, you've gotta, you've gotta deal with this. So I think I agree. I'm onto this too, and I've, I've seen some [00:48:00] really interesting things.

So, so what's your, what's your approach? So if you, let's say you have a patient with PAI-1. By the way, I have so many homozygous PAI-1 patients in my practice. It's blowing, it's like blowing me away. I can't believe it. Basically right now, I don't think I have anybody who does not have some polymorphism of PAI-1.

They're either 4G, 5G or they're 4G, 4G. I don't think I have anybody who's 5G, 5G, which would be the normal.

Dr. Todd Maderis: Yeah. Wow.

Dr. Tania Dempsey: So, I'm curious, is that similar to what you're seeing by any chance, or do I have a skewed...?

Dr. Todd Maderis: Yeah, I, I've seen patients with normal 5G deletions or not have the deletion but they still might have elevated markers. So the way I sort of interpret the results is like, someone could have a Factor II mutation, and in this whole thing, it's, it's really it'll tell you what's most fascinating is when you [00:49:00] just,

for me, I then I think, well tell me like, let's talk about family and, and you know, how are your, so we've seen, I have a patient with ME/CFS. He's, he's uh, probably, I think he's had a about 15 years and, and once we learned about his Factor II, he has a Factor II and a PAI-1 deletion, and I said, well, tell me about your, like how are your, how's your parents' health?

How was your, you know, your siblings? And he goes, well, my sister who's my age, so she's in her sixties, she had a stroke when she was in her twenties and we never knew why. And it's now 40 years later. And so he knows, he has a Factor II. Of course she's an, she happened to be an internist. Never knew she had the Factor II until I diagnosed.

And I've, there's been other scenarios like that. I mean, just the other day I picked up a Factor V on an 82-year-old and I'm like, this woman has been alive for 82 years and never knew she had a Factor V mutation. And you start thinking back 'cause people will miscarry, you know, the, there's a [00:50:00] variety of symptoms that can occur over time.

A woman that, you know, basically kind of lives on antibiotics for her, chronic tick-borne infections. Every time she stops 'em, everything comes back. Well, what's going on there? Well, she, she's a, she's a Factor V. She's 75 years old, and now we figured it out. So I, yeah, I use low dose Eliquis if they're, you know, Factor II or Factor V, or they, they have an elevated prothrombin fragments 1+2, or, you know, on the PAI-1, if they have a deletion, I'll put 'em on typically Boluoke, which is lumbrokinase,

or if they have elevated alpha-2 antiplasmin, I'll use Boluoke as well.

Dr. Tania Dempsey: And how much Boluoke are you using?

Dr. Todd Maderis: I typically do two caps at the same time once a day. There's a kind of a guide based on alpha-2 antiplasmin levels. You can, you can definitely do more, but Boluoke is expensive. And, and, um, I think two a day, and I'll repeat testing.

I wanna see those markers come down, but [00:51:00] the, you know, I don't repeat the genes. You don't have to repeat the genes, but...

Dr. Tania Dempsey: No, no. I just don't think it works like, as well in some patients. And so I'm really trying to figure out what else I can use to, to break down. A lot of them it's, it's, they're not breaking down the fibrin. Well, again, it could be both, but, but I have them on Boluoke. You know, we can't get it in the US but I, I definitely have a few patients who have been able to, to source, uh, sulodexide which, you know, you can only really get from like Italy and Russia and

other things, which is an oral heparin, which

I think does seem to be somewhat helpful. In the past, I, I have used injections of heparin or, you know, a low molecular rate heparin, uh, like Lovenox for subset of patients who, you know, there's some research, you know, way back for about Lyme and, and the use of heparin. So [00:52:00] I think this is based on on this, but you know, I'm just wondering what else can you do beyond the Boluoke for a lot of these patients?

Dr. Todd Maderis: Yeah, yeah. Yeah. It's, I think reducing inflammation is, is also a big part of it, right? Like, um, and, and, and even the mast cell connection. I mean, I, I think maybe it was the 82-year-old that she was a referral from someone at UCSF here and, um, uh, with my mast cell referral. And, um, and so she said, well, can my mast cell be,

you know, could it be, could the hypercoagulation be contributing to the mast cell dysfunction? And of course, I went to AI and did a little and of yes, there's an interconnection that they call it a, well, the result that I read was a bidirectional loop, and that mast cells will, you know, they'll irritate the endothelial or the mediators will cause sort of an irritation of the [00:53:00] endothelium and then contribute to a hypercoagulable state. Hypercoagulation can also exacerbate mast cell activity. So it just, it,

it's

a vicious little cycle and, right, so I hear what you're saying. Some of these people, you know, don't respond and, and, but I think a lot of the chronic infections we see, it's not just the tick-borne or systemic infections.

It's like chronic sinus, uh, colonization from mold exposure, or even the PANS and PANDAS kids, those, there's likely a biofilm there. SIBO, my SIBO patients, I, you know, how many times do you have to retreat SIBO, like most people do. And, but if you put 'em on a biofilm agent, I think, or especially if they're, they have one of these genetic fibrin issues, then the biofilm agent's gonna help them.

They still might need multiple rounds, but it, I think it, you know, moves them along further along the spectrum.

Dr. Tania Dempsey: Oh, no, I, I, I agree. I just, I [00:54:00] think it's just, it's a little complicated, but I think this area, uh, with this coagulation fibrin and all that stuff, I think it's super important. And I'm so glad that you're, you're in, you know, you're, you're looking at this and studying it and, you know, hopefully, we'll, we'll find more stuff, right?

Dr. Todd Maderis: I mean that's, that's the beauty of medicine is there's no shortage of, well, people can get complacent. I, I had an email from someone today that just through my website that said, thank you for an article I had just written. And he said, I am I'm pleased to see that you have gone swimming upstream against the general complacent medicine.

It's a funny way to put it, but yeah, I don't, it, you know, we, you can get into your little world and just keep doing the same thing over and over again. I think obviously with our patients, that's not the case. There's there, we can't, there's no other option. If you wanna help them get better, you have to keep, you know, stay curious.

And that's, that's sort of my motto and it, I, I [00:55:00] love it. It makes it really fun, actually. So yeah, the coagulation is, is, um, another piece of the puzzle.

Dr. Tania Dempsey: I think it's a very interesting and, and very important piece of the puzzle. And that's the whole point. You know, I always, I use this analogy with patients all the time, right? That, that they're like an onion and we've gotta peel, you know, the layers. And so I think this coagulation piece is a layer.

And it's, it could be like, the thing could be multiple layers for some patients, right? But maybe it's, uh, for some others it's, it's, it's a layer. It, it does something. But then once you've removed that, then, then you are able to deal with the other layers, right? So it's just lots of different, you know, until you get to that, you know, middle where you're, you're done.

Dr. Todd Maderis: Yeah. I, I think, you know, unfortunately, a lot of times I see new patients that have been sick for a period of time for like a lot of us, they, you know, in their, we're their sixth doctor or their 12th doctor, whatever, that, you know, they [00:56:00] potentially have not been assessed properly. Like they've, there've just been some, there's some gaps in their workup.

And if you've missed something and, and you know, again, I you, you approach it with humility, you go, well, maybe it is something that I, you know, and, and you look at the whole, you know, I love to cast the broad net when I do testing and, um, and, and sometimes you pick, you pick something up and you go, wow, this, this, I mean, I, I have a, a woman right now that sounds like a, it's almost, um, she's sort of been sick with a tickborne infection for about seven years.

Been treated by some wonderful, really great docs. But they at some point she really felt like she should be tested for mold and was sort of asking for the mold test, finally got a mold test. It was slightly positive, but not really remarkable. You wouldn't think like, oh, it's, and so I happened to see her soon after, I just brought up heavy metals. She had lived in Japan for two years and at some point, like a decade ago, it'd been a while. And so I thought, oh, well we should [00:57:00] just screen you for mercury levels, a lot of fish and in Japan. And we, we did, and she, she collected a urine toxic metal test and her result came back the highest level of mercury I've seen in 16 years of practice,

and I've been doing environmental medicine since day one. So I was blown away. You don't think it, you know, she struggled in this Lyme kind of looking through the Lyme lens for seven years and she had basically mercury toxicity that was, was overlooked for a long time. And, you know, it's just one of those things where I wouldn't, I, I think sometimes we can easily forget about the, like even the metals, right?

Like, oh, that's so 1990s or whatever. But, but for some people it could be part of their picture, it could be another tack in their foot. And, and in the interest of getting these people better, we need to know everything about them. So I, I just, I think half the battle is a proper [00:58:00] assessment. And then the, the second half is just finding the treatments to, to address those.

Dr. Tania Dempsey: Yeah. Definitely, very, very similar approach. So we are, you know, sort of near the end here, so, is there anything else that you'd love to share with our audience? Anything else you're excited about or anything else we should leave a message, you wanna leave with them before we finish up?

Dr. Todd Maderis: yeah. Well, we talked a lot about the things I'm excited about currently for sure. Who knows what next week we'll bring and. But I, I, I, I always love to offer a just a sentiment of hope. You know, I really, I think, you know, on the patient side of the desk, they've been in it for so long and they've, they've really struggled that it's hard to, they, they begin to wonder if they ever will get better again, or, you know, can they get better?

And, and I truly believe that [00:59:00] everybody has the ability to, to get better and to heal and improve. And so I think that, you know, my words of encouragement would be keep at it. You know, keep looking for someone that can be your partner and helping you get better. And, and, you know, so it's, it's, don't get caught up in, in, you know, a Facebook group where those are the people that aren't getting better, will commiserate together and they can be really great resources for people

but, you know, I, I find that everyone's different and, and not all the information that people get, uh, whether it's through social media or, or wherever, it's maybe not applicable to them. So keep keep searching. You can heal, you can recover. We're learning more. Us, you know, doctors like yourself and me, that we're, we're learning more every day.

So it's, it's possible.

Dr. Tania Dempsey: Great, great sentiment. Um, so where can people find you? Tell us about, um, your social media stuff and...

Dr. Todd Maderis: Yeah, I, um, [01:00:00] I enjoy writing, which I, I don't do as much as I'd like to, but I, I have a website, which is drtoddmaderis.com, and I like to post what I'm seeing in my clinical practice, so I get to share with people that are out there maybe that don't have access to, to docs like you and I. And on social media

i, I also, I post a lot of current research on Instagram and on X.

Dr. Tania Dempsey: You post great stuff. I love, I love all the

articles.

Dr. Todd Maderis: Thank you. Thank you. Yeah. It's, I enjoy it. It keeps me, keeps me, you know, at the forefront or reading the research too

forces me to do it. Yeah.

Dr. Tania Dempsey: Well, thank you so much for being here. This was, this was great. We could go on for another few hours.

Dr. Todd Maderis: Thank you for having me.

Jill Brook: We will put all those links in the show notes. So listeners, you can just go there and find it easily. And Dr. Dempsey, Dr. Maderis, this was amazing. Thank you so much. All these new things. Thank you for staying curious. Thank you for [01:01:00] not just settling into, uh, the routine and going with, what was it, the, the current of, uh, conventional all all the complacency.

Oh my gosh, we appreciate it so much. You guys are amazing. I know we went a little long. Thanks a million for your time. And okay, listeners, that's all for today. We'll be back again soon with another episode. But until then, thank you for listening. Remember, you're not alone, and please join us again soon.