Lori Esarey: Wellness is a practice, not just a word.

Kelly Engelmann: Welcome to the Synergee Podcast, where myself, Kelly Engelmann and Lori Esery shared by on powerful tools and topics that nourish your body,

Lori Esarey: and most importantly, feed your soul.

Kelly Engelmann: Welcome back Synergee listeners, we’re so glad you’re here. Where we believe we’re stronger together. Hold on to your seats because we have Cheryl Burdette here with us today and we are so excited to have her.

Lori Esarey: Cheryl Burdette, N.D. Is the founder of Person Logics Health Academy, an educational initiative designed to increase knowledge of integrative medicine for practitioners.

She is the Director of Education and the Naturopathic Residency Program at progressive Medical. She is the founder and educational director of a functional laboratory, precision Point Diagnostics, for which she designs clinical profiles and trains clinicians with utilization. She’s on the board of Advisors for Zymogen and Inc. 500 supplement company. She is a partner of TheraDura a physician line distribution in Germany. She serves on IRB Boards is involved in study design and translational research, and has lectured extensively worldwide. Her passion is teaching around the practices of integrated and naturopathic medicine to increase awareness of evidence-based natural therapies.

Let’s get started with Cheryl Burdette.

Kelly Engelmann: So welcome to the Synergee Podcast. We are so excited to be back together. Lori Esery and Kelly Engelmann hosting Cheryl Burdette today and, I have to tell you I have been the most excited about this podcast and I have been about any podcast in a long time, because if I could sit in one person’s brain, And absorb all of the information that she has up there it would be Cheryl’s brain. I have brain envy every time I’m around her, all of the biochemistry that swims around in there I just wish I could soak it all up, so I’m excited that she’s here with us today.

Lori Esarey: I’m gonna second that. Cheryl, thank you so much for being here. I can’t even say that any better. I feel like such a geek sometimes, give me everything you got.

Cheryl Burdette: You guys are too kind. I think I just it’s like company, so thank you for having me here.

Kelly Engelmann: Cheryl’s been in our world for a while. Lori and I are. Perpetual students since they were always in class and Cheryl’s been gracious enough to teach us live and virtually.

And so we are honored to have her here to share her wealth of information. We’re gonna dig into all things food sensitivity, intestinal permeability, those are big words we’re gonna break ’em down for you. We’re also gonna get into the whole idea of oxidative stress and how that plays out. What you can expect to feel or see when you’re experiencing some oxidative stress. We know if we have that, we’re not winning our game. So, Cheryl let’s dig in. It’s common, and I have to think back to when I first started doing food sensitivity testing. And I have to say the first, panel that I did for food sensitivities was a food sensitivity panel that looked at the response of the white blood cell.

And it tested multiple foods, and we would get that panel back and it would be, oh my goodness, how in the world am I going to eliminate all of these foods? And so at Precision Point, I absolutely love and adore the way that your panel is laid out so that as a clinician, we can look at that information through the eyes of a functional medicine practitioner and say, what is the immune system trying to do with this food source, and how do I take this information and help this patient navigate a diet that’s going to lead to healing and not lead to further nutrient deficiencies and ongoing food sensitivities. So help us understand a little bit more about how that panel is laid out in the intention of that panel.

Cheryl Burdette: So the panel came to be, through Precision Point Diagnostics as you said, but the lab came out of a clinical practice so, I practice at Progressive Medical and my partner, Dr. Gasagoli, it’s a large clinic about 10 docs, 10 to 11 docs all under the same roof and so but also PA’s and nurse practitioners and acupuncturists and dieticians and naturopathic docs and so, a lot of patient care progressive’s been around for 30 years and so really getting to see a lot of data come through there, and historically we used other food sensitivity tests as well even the one that you mentioned and from other places and we always felt like a little bit like Goldilocks, right? Like a little too hot or a little too cold, and I was like it’s not exactly what I want. And so we started a laboratory about 15 years ago for just this reason because, really when you sit toe to toe with a patient wanting to feel like you’re giving the best and that you’re really getting to the heart of the issue and so, it’s difficult in this world of food reactions because there’s a lot of disagreement and there’s not consensus. And if you approach more standard of care, they’ll there’s even the idea that there’s only one way that the body reacts to foods and that’s an allergy IgE and that’s what’s typically done, it can’t be done through a blood draw, but it’s usually done in offices when that’s the one that when people get stuck and the skin, and then you wait and you see. It doesn’t turn red, and if it doesn’t, then you probably don’t have a problem or you’re told you don’t have a problem. But even the best allergy test out there, it’s only positive 50% of the time when somebody has a symptom. And so what that tells us is 50% of the time we’re reacting to foods in a different way. So the allergies are important, and we wanna know if you’re gonna eat a strawberry and you’re gonna go into anaphylactic shock that’s an important thing to know. But it turns out also you can have lower levels of these immediate reactions that you might not even be noticing because they’re more subacute in terms of the threshold of how you feel.

However, they can still create inflammation in the body. And if you see a lot of reactions in terms of more allergies, even if you’re not feeling symptoms from them yet, it can tell you that you’re in more of what’s called an atopic direction, an allergic direction. This is where we’re more likely to get autoimmune conditions or eczema, things of that nature. But again, it’s only part of it.

Lori Esarey: I don’t wanna interrupt, but I did have to ask this question for clarity. So what I heard you say. Is that 50% of the time, that a person has a allergy to something, a potential allergy to something, they may have a negative test. Is that right? Or is it just the opposite?

Cheryl Burdette: Absolutely. Yeah. And that the best allergy test out there, it can. It’s only predictive 50% of the time.

Kelly Engelmann: And that’s for IgE, that’s for immediate reaction, right?

Cheryl Burdette: Yeah.

Lori Esarey: So we have people that have inflammation. I mean, they come into our clinics all the time, as you just said. They’re clearly having some form of symptoms, inflammation, but yet they come in saying, I’ve had all these tests, and they’re negative. So this is why.

Cheryl Burdette: Yeah. It’s just, it’s not the greatest test. And then research has been very stifled in this area, a kind of because of how immunology gets taught and who knows, and maybe also because there’s been a reluctance on insurance companies part to pay for some of these things that does factor into it. So we got kinda left with a very, inadequate way of looking at how people react to foods, and I’m sure you guys feel the same way. One of our most powerful tools in terms of what we deliver to our patients is around diet and dietary therapy. So if that’s the case, if diet’s one of our most profound tools, then what do we do to make sure that someone’s on the least inflammatory diet possible, so we continued to work with other food allergy tests, food sensitivity tests, and like I said, oh, maybe this one shows everything all the time and this one seems to show no reactions and so, we really struggled and so we thought, you know what? We need a test that puts together all in one test, multiple ways that the immune system reacts to foods.

And so, like you mentioned the live cell analysis. That’s helpful. It shows this innate immune system reaction, and that’s part of it. But we also have this secondary immune system, and a lot of autoimmunity and a lot of chronic conditions are more driven by that. When we think about something like, rheumatoid arthritis, for example. We think about what’s going on there, and so in a condition like that there are antibodies that are confused and they’re attacking the patient’s tissue. Well, why did the antibody get confused? And often it’s because it’s reading a food wrong, that food has a similar amino acid structure and so, we create this antibody to a food that can cross-react to our own tissue. So if the immune confusion is something like a cross-reactive antibody, then you need to measure antibodies as well. That’s what we do on the dietary. P88 we look at antibodies, not ex only, but I’ll get there. So we look at those antibodies, liken an IgE reaction and allergic reaction, but what we’ve learned is that, we also have these delayed reactions to foods.

Three to 72 hours later, not immediate. So you’re having a bad day, you feel foggy, your head hurts, and you go, what did I have for breakfast this morning? And it’s really what you had for breakfast two days ago. And so this is why the sensitivities can be difficult to get from merely a history alone. It doesn’t happen immediately, it’s just that it’s delayed. And so IgG is something that’s often overlooked in standard of care. And I think, the reason for that is because in a standard of care approach, you want to measure something that tells you about a diagnosis, an ICD 10 code A label, and that’s important. We need a diagnosis that certainly helps us in a functional medicine paradigm as well. But IgG reactions, they don’t create a singular symptom. They don’t create a rash, they don’t create hives, they don’t line up with a particular diagnostic code. They create general inflammation that can make so many conditions worst. So in a standard of care world where you’re doing testing for a diagnosis, it doesn’t match what’s generally being done. Here we’re saying we care about the diagnosis, we want to do the correct testing to get to that point, but we also care about the process behind the diagnosis. And that process is so often inflammation, and a large part of inflammation comes from what we eat. And so if the immune system is confused and now fighting foods, we have this increase in inflammation and that can make almost any siner symptom worse. So we said, okay we need to look at allergies, but we need to look at sensitivities. But then as you dive into the immune system it continues to be, more and more complex, there are more and more pieces to it.

So what we realized, and oh, and largely from the world of desensitization in terms of allergies, so if we know that we have an anaphylactic reaction to a peanut, we can seek out desensitization like injections or even sublingual immunotherapy that’s done under the tongue. And when we do this, we take in a little bit of peanut and eventually become tolerant.

And so the mechanism of action of that is that it increases another type of antibody, something called IgG4, and so many tests out there just looked at all IgG together. IgG is that sensitivity, that delayed reaction 3 to 72 hours later. But there are four types of IgG, and so this was another kind of pushback, people would say, well, there are four types. They don’t all do the same thing. In fact, IgG4 does something completely different, it does, it’s not inflammatory, it doesn’t contribute to headaches or joint pain or bloating or these type of issues. In fact, it blocks an allergic reaction. So when you do something like desensitization, the whole point of that is to increase this antibody IgG4. And when we have enough of it, it will block IgE. That thing that drives the allergic reaction. So true, they’re all different. So pull it out, measure it. And this is very useful cuz now you can tell have you become tolerant to something you were allergic to. And now when we’re looking at IgG, we’re looking at subtypes one, two, and three that do run in the same direction, that do behave in a similar way. They’re, they create inflammation. But then, even that wasn’t the end of the story because it’s not just IgG that plays a role in these sensitivity reactions. It turns out that there is an amplifier and it’s something called compliment. And when compliment is there with this IgG antibody, it can amplify that reaction. Thousand fold even some say as much as 10,000 fold. And so, out of that clinical practice we would be looking at just IgG by itself sometimes, depending on what test we were using at the moment. And patients would say, the ones that are high, I don’t really get the most symptoms from that. But these medium levels, those tend to really kick in the headache or kick in the the depression or anxiety. So what’s going on there? Well, again, it’s because it’s not just IgG, it’s also this complement antigen, and when you have those together, amplifies the reaction. So he said, we need to measure that too. So we ended up with a test that looks at four independent ways that the immune system reacts to foods. Because again, if food is our most powerful tool, how do we create the least inflammatory diet for each person and a great start without any testing is of course to get the processed foods out and to eat more fruits and vegetables and focus on getting good quality protein and make sure you’re getting good fiber and so many people as they start to feel unwell.

This is obvious. We all know, oh, I should eat better. I should exercise more. This isn’t news to most people out there. And so they went out, they went to Whole Foods, they changed what’s in their pantry, they ate more vegetables, but they still weren’t feeling optimal. And so what else is going on? Well, unfortunately, we can feel inflamed from healthy foods, and so looking at each patient’s blood, looking at their levels of reactions allows us to individualize diet and take it to that even next step to make the most powerful tool more exact.

Lori Esarey: Such a complex test.

Cheryl Burdette: It is.

Lori Esarey: I mean, I think about what it took to get there to figure all of this out and I know that there was a lot of medical lingo in that and we have a lot of followers that listen to this, that or that are our patients so, I think between Kelly and I, we’re gonna go through and I have a couple of questions, and I think I heard you say there are four independent ways that you guys have figured out how to look at the immune system, right?

Cheryl Burdette: Yes.

Lori Esarey: So you’re not just looking at IgE, which is that immediate reaction. But you’re also looking at delayed food sensitivities that could be 3 hours to 72 hours, but on top of it, there’s this layer of desensitization that can occur. Right. With you’re able to look at that, have you been in some ways desensitized that food? But then, do you also have a compliment that maybe amplifies, something that may not be a big deal or look like a big deal with your immune system but because of that, it amplifies that reaction so it’s a big deal. So that’s a lot of information and I can only imagine, the difficulty of interpreting that test so as not to overwhelm our patients. Kelly, I know that you see that all the time, right?

Kelly Engelmann: Yeah. I have to say, I have an example of a patient that had a test from a another functional medicine provider, a year ago. And she comes in to see me a year later, she’d been strictly following that elimination. These more significant elimination and I can’t remember how it’s worded on there, but the more restrictive diet on there. And a lot of those had eliminated her valuable oil sources, avocado and things like that. And so she’d gotten herself pretty nutritionally depleted with fatty acids. And she was having skin break down and having ongoing gut breakdown, right? And so you can, without working with a trained clinician, if you’re trying to do this independently, you can walk yourself into a worse situation. So it is a complex test. It is so, Unbelievably valuable to the clinician that can help someone walk through recovery from food sensitivities. But it does need to be respected in that this is not a forever way of living. Your immune system’s constantly changing. And evolving as it should be, and as a result of that, we have to be careful in how we counsel our patients on taking action on that testing, correct?

Cheryl Burdette: Yeah, and this is why, like you said, it’s very important to work with a clinician because it’s not just the piece of paper that’s a forever roadmap. And I like to remind patients that in fact the whole point of this test is not to restrict the diet more initially maybe, but long term, the goal is actually to open the diet up even more than before and be less reactive to foods in general. So the benefit of working with a clinician is they’re not just gonna say, here’s a piece of paper that says to remove foods. They’re going to look at those foods which ones are the most important for you, prioritize the plan, and at the same time do things to build the gut lining, do things to help the immune system become retrained so it’s not confused by those foods when it meets them, and then guide the patient as to when they should bring those foods back in, that’s one of the most important parts of the test is that’s step A. But you move and you progress. And the point is to be able to bring in more foods than before with less inflammatory reactions. Now, I don’t mean Big Mac or sometimes we’re probably gonna still keep things like wheat or dairy, more to a minimum, but we can see these situations where people are inflamed from chicken or avocado, like you said, or spinach or things that they need. And that’s not the state that we want them to stay in long term. We wanna open that diet back up.

Lori Esarey: And I think that’s so important too as we as clinicians are discussing that with our patients, cause I think so many times they come into that going, you’re just gonna take more foods out of my diet. And I wanna reiterate that that is not the goal. It’s to give you the appropriate removals that you need in that time to heal. And then understand how to also diversify and open it up to foods maybe you haven’t been taking in right? And now you’ve become nutritionally deprived, right? So it’s adding them in, so definitely important to address it that way.

Cheryl Burdette: I think to your point Lori, what usually ends up happening is people, Eat a different variety of foods. Like when we look at the a standard American diet, it’s quite possible that you’re getting wheat and dairy at every single meal. So now you’re opening up to other grains, almond, or maybe tapioca flour or various blends, like I think in general what we see is more diversification of the diet.

Kelly Engelmann: Yeah. And that’s what we absolutely need in order for that gut microbiome to repair the gut lining, right?

Cheryl Burdette: Yes, it is complicated, but then there is a page that says, stay away from these foods and eat these foods so it does get boiled down a little more simply, but it’s always best when there’s an interaction between patient and clinician, because you’re gonna be able to take that to the next level.

Kelly Engelmann: Absolutely. So timing of doing a test like this, right? Because the timing of the test in working with the patient is important into knowing how to implement, right? So to your point earlier. You mentioned we want to eliminate processed foods that are inflammatory, if you’ve got a patient that’s complaining of inflammatory symptoms, headaches, muscle aches, fatigue, insomnia, the list goes on and on brain fog, right? Those are inflammatory symptoms. We wanna get the obvious, food’s out of the diet first, right?

So I love the fact that you’re a clinician, and in the lab. You get both sides of the equation. When do you recommend, that a food panel will be done on a patient? Like what’s in the perfect world? If you could have a perfect world of timing of testing in relationship to working with the patient that’s pretty naive to making food changes, where would that fall?

Cheryl Burdette: So when we first meet with the patient, and like I said, there’s a team of dieticians that I’m lucky enough to work with. We will start on some dietary change, pretty immediately. That’s done at the first visit, and we often use something that we label it a detox diet, but I think that it could equally be called a detox, gut microbiome diet and so we do, we have people come off foods that tend to be more inflammatory as a trial, we take them off the wheat, we take them off the dairy. Caffeine goes alcohol glows, we talk to them about hitting targets with fiber, making sure you’re getting 15 to 20 grams of fiber which, even the best of us can struggle with even when we have vegetables all through our diet, so really working on that piece and then, From there when people come back at the next visit, if they’re still experiencing some symptoms, that’s when we’ll say, okay, now let’s do a food sensitivity test and many times people really want to do this because they wanna transition from that, in general here are things that are often inflammatory to people to exactly what is going on in my body. Where’s the inflammation in my system so they’re often eager to do this, to know what’s gonna be most appropriate for them. But I do lean on this test a lot and so I’ve had patients come in that say, oh, I had a friend who was here, last week or the week before, and you ran this test on them as well. Do you just run this test on everybody, and no, not everybody, but many people and again, the reason is because I want every patient to have the least inflammatory diet possible. And, one of the major ways we can retrain, boost the immune system retrains a better word, because if it’s overactive, put it back into a normal zone, is by working through the gut. And if we are eating foods that we’re sensitive to, you will continue to degrade the gut this is where we house 85% of our immune system and even the part that isn’t there in the gut, the immune system that starts in the gut communicates with the rest of our immune system as well, so if we’re thinking about any condition where there’s an immune imbalance, any condition where there’s gut-based distress, any condition where there’s inflammation, then working with gut and foods becomes an important part of that. So I do run this test quite a bit because like I said, I want every patient to have the opportunity to have the least inflammatory diet possible.

Lori Esarey: So what I hear you saying is very similar, Kelly. You and I in our independent practices working with patients to what we call a reset diet, right? So it’s deloading their body, removing those common inflammatory foods, those common food intolerances and or allergies out of the diet, giving them time to really get used to and get their body kind of offloaded as you will, and then meeting back with them. And I think from a timing piece, that’s great because then your kind of like if they already begin to feel quite better in that time, I think that excites them to see that food alone helped them make a change in how they felt, right? So I think that that kind of makes them first more curious and I think that makes them more motivated to, okay, what’s next? What can I do next? So I did hear you say something that I wanted to kind of circle back to too. You had said cause I think we all threw around the boosting of the immune system, and I heard you go back and you corrected that. So I kind of wanted you to go back and explain what you meant by that for our listeners.

Cheryl Burdette: Yeah. So we all are familiar with, oh, being under more stress and didn’t quite eat right, and then that cold happens and we’d go, yep. Our immune system was down and so got this infection not feeling quite well but, also the case of the immune system being overreactive and this would be like in an autoimmune condition like rheumatoid arthritis or even Crohn’s disease, and this is the case where the immune system has become confused, it’s hyperreactive, it’s going off to foods and to even maybe bugs in the gut, and so now rather than too little immune function we’re in overdrive. So there are also immune cells that help to put the immune system back in balance and they have a good name for what they do they’re called t reg cells like regulator. When we quit eating foods that we’re sensitive to it helps the gut lining to repair. And I always think of that as a barrier, and as that barrier gets stronger between the foods we eat and the immune system reacting, it helps those t reg cells to improve their function as well. If we look at a standard of care model in the world of autoimmunity, what is done are to take various medications that are immune suppressive. And then you have to deal with that, those side effects it’ll say right there, there’s an increased risk of colds or flus or catching various bugs because of that immunosuppressive part. But the nice thing about natural therapies and working on normalizing gut health and working on normalizing tissue is that it puts the immune system in balance. So we are not stuck with, we can either suppress the immune system or boost the immune system, when we work on gut-based inflammation, it helps all these immune cells to work together it helps these two reg cells to gain ground and put the immune system back in balance, and I love that about what we do because we don’t just have to suppress or move the body all in one direction. When you make the system healthier, it begins to do what it should do more naturally. And so if something, if parts of the immune system are high and parts are low, then we can move them all back to the middle to be more functional. And that’s what we’re trying to do is restore that function.

Lori Esarey: So boost versus suppress versus balance.

Cheryl Burdette: Yeah. Exactly.

Kelly Engelmann: Yeah. I wanna talk about the gut lining, intestinal permeability. We’re blessed also to be able to look at that. So tell us a little bit more about how that plays into food sensitivities and how we can assess for that.

Cheryl Burdette: Yeah, it’s a podcast, but so I, it’s hard for me to refrain from using my hands. So now I’ve got some hand gestures going on here, but, and so with patience, I used to draw the picture, but now I acted out more cuz it’s a little bit faster. But so as we think about gut-based permeability it even sounds weird. Leaky gut. It sounds weird, right? I remember when I first learned about it 20 plus years ago, I thought the same thing. That sounds weird. I’m gonna go look it up in the scientific journals and I’m gonna see if I can find some stuff about leaky gut. And if I can’t, then this isn’t real. And when I did that 20 plus years ago, There wasn’t a, a lot of data, but I couldn’t make it out of a naturopathic medical school without having to realize that probably there was something to this. And so I was working with an ulcerative colitis patient. She was having 20 plus bowel movements a day. She couldn’t leave her house, she couldn’t go out to eat. She and what they had suggested her next move be would be, we’ll just remove part of your colon. And for sure that’s gonna decrease the inflammation, but I’m gonna guess that most of us would like to hold onto our body parts and there would be some other issues there when we remove the colon. So instead, we got started doing things that treated this phenomenon of leaky gut, gut-based permeability, and changed her diet and figured out foods that were inflammatory to her and as we did that, her bowel movements went back to normal and she wasn’t having 20 bowel movements a day and she didn’t have to remove her colon. And she was able to go out to dinner with friends and family and she got to that point of being able to even expand what she was eating, and this was because we were working on this concept of leaky gut. And so, now if I go to the literature and I look up gut-based permeability, I can find thousands of studies, and not only can I find lots of data that supports this and connects leaky gut to things like depression, connects leaky gut to things like insomnia, connects leaky gut to things like cardiovascular disease and neurologic conditions. Not only can I find the data, but now we’ve even figured it out biomarkers things we can measure in the blood that tell us if this is going on. And so, 20 years ago we didn’t know these biomarkers existed, so we couldn’t measure it, we couldn’t tell where someone was at, but now we have the opportunity to do so.

And so Alessio Fasano is instrumental in this story. He’s a researcher. He was at Boston, now he’s at Harvard, and he popularized this marker zAnion and zonulin you can measure in the blood, it can also be measured on stool testing, and it is what tells those that gut lining to open up. So there are these little things called tight junctions and think about kind of legos or linking logs, locking together, that’s how the gut lining works. And this zonulin tells those locks to open up and when the gut opens up, now things get into the body that shouldn’t be there. Your food doesn’t get broken down as much as it should. Little bits of bugs, bacteria, because we have more bacteria in our gut than there are stars in the Milky Way, little bits of this bacteria begin to leak through into our body, and our body goes that’s weird, that shouldn’t be here, I’m gonna create immune reaction, and boom we develop these sensitivities and it creates this inflammation that can be part of something like I mentioned, like depression or even neurologic, condition.

So historically we would treat this, we would see people get better, we called it leaky gut or gut-based permeability. We knew that it worked, but we weren’t really able to measure it or define it. Now we’re able to actually measure markers in the blood. Some go up, some go down, but that changed direction from normal. When the gut is more leaky and zonulin is one of these, so we can measure it in the blood. And Allesio Fasano went on to say, He said, you know what? This is the environmental trigger that causes autoimmunity. You’re not born with rheumatoid arthritis. You’re not generally born with Crohn’s disease, we get there eventually. So what caused that gene to express itself? Well, he went on to show that zonulin goes up before the onset of autoimmunity, before the onset of things like celiac disease or even Crohn’s disease. And so what he said was this gut becoming leaky, is what causes the immune system to run crazy, run wild, run amok in terms of being overly inflammatory, and he said also the good news is once it’s high, when if we do therapies to lower it, we can put that genie back in the bottle, we can keep the immune system from being overly reactive. And so once we could measure it, then it became much easier to diagnose, it becomes easier to treat. I mean our patients always rightfully want to know, well, how long do I need to do this treatment? How long will I be on these particular supplements? And now we can say, till zonulin is normal, because that tells us the gut is no longer leaky. But it gives us a way to really rule these things in and out more appropriately. And it gives us some benchmarks to know if our treatment is working or not. So it’s fascinating. The science really caught up to what we were doing, we’ve been doing treatment of leaky gut for decades and decades, and now the science says, yep that’s a known phenomenon. We can measure it, we can treat it, and we’ll, we can see health conditions improve when we do so.

Lori Esarey: So let me ask if we can measure it in different ways, like stool or blood. Is there one that’s more preferred over the other or should one be used at different times than the other? What is your philosophy on that? What is your belief on that?

Cheryl Burdette: Yeah, there’s a lot of overlap there. So when you’re measuring it in the stool, you are measuring the largest pool of where zonulin is created because most zonulin is created in the gut. If you measure it in the blood, you’re capturing part of other places where we make zonulin and we make zonulin in the liver. We make zonulin at the blood-brain barrier. And the blood-brain barrier is just what it sounds like, it’s the tissue that separates the rest of our body from the brain to protect it.

So interestingly, zonulin made in the liver can be a reason for an increase in lipids like cholesterol and triglycerides and zonulin at the blood-brain barrier can be a reason for things like brain fog. In fact, I was fascinated when I read that, one of the things that is causing brain fog in Covid long haul is a leaky blood-brain barrier governed by Zonulin. And so there’s a lot of overlap. I would say there’s about 80% overlap between the, feacal or a stool zonulin and a blood zonulin. But the blood zonulin will capture those other places as well and those contribute to pathology too. So if you already had it on a stool test, I wouldn’t bother retesting it on in the blood until you’ve treated it. But if there’s symptoms that have to do with like brain fog or depression or anxiety or even cardiovascular issues, then the serum might be preferable because you’re gonna capture zonulin that would be related to those places in the body and can be contributing to those things.

Lori Esarey: Excellent.

Kelly Engelmann: So you mentioned some symptoms of leaky gut, so if I’m a patient and I’m wondering, is it possible that I have leaky gut? As a clinician, I have found those symptoms may be. Just those traditional inflammatory symptoms. So what do you say?

Cheryl Burdette: Yeah, and it’s a little bit tricky and this is why measuring can be useful at times as well, because we would think, okay, leaky gut, that must mean that I’m bloated or have constipation or diarrhea that I have pain in the gut. And often that’s true, often there will be some bloating or, you eat certain things and you don’t feel right and kind of thing so gut-based symptoms of course, but even ankylosing spondylitis. So a condition where bones fuse in your back. The part of how that starts is when the gut becomes leaky, when zonulin goes up and so there’s this association between leaky gut and even that. And so in that scenario, somebody might not have been having lots of constipation or diarrhea, but they could still have leaky gut that’s contributing to symptoms that they’re feeling. Maybe an even more common one is depression. You might not necessarily have diarrhea, constipation, gas, or bloating, but you’re depress.

Well, gut-based permeability or the gut being leaky creates inflammation that’s hard on the brain. That inflammation even impairs our ability to make certain neurotransmitters like serotonin that make us feel good, make us feel less depressed. And so now being able to measure these markers of leaky gut, but can be really important then, because you’re like, no, it’s in my head. I feel blue. I don’t have any problems with things I eat. But it’s the leaky gut that creates the inflammation that causes the depression to express itself. So when someone’s gut is leaky, there’s inflammation that’s created from that. And inflammation kind of washes over our genetics and causes probably our areas of weakness to more expose themselves. So we can have symptoms that aren’t even related to the gut, that can be a direct result of that gut-based permeability.

Kelly Engelmann: So what I heard you say brain symptoms are very common, with leaky gut, right? Brain symptoms are very common, and your areas of weakness, having exacerbations in challenges that perhaps joint pain, skin issues that may or may not be gut related or gut related symptoms at all. You may not have any gut related symptoms and still have full-blown leaky gut, and that’s hard for patients to conceptualize. Because we say leaky gut and they’re like, but I have a bowel movement every day and I don’t have any bloating, right. So that can be difficult for them to kind of put those two and two together.

Cheryl Burdette: Yeah. So it’s nice when the science catches up and we can measure these. Markers to say, this is a part because let’s go back to the example of depression. Maybe a zonulin is making the blood-brain barrier leaky, and this is causing depression. And that’s one way to get there. But maybe you are producing less of certain or are transmitters, maybe it’s serotonin, maybe it’s dopamine, those. Both being low could either or cause depression or maybe you have issues in terms of something called methylation. And so we have to methylate our neurotransmitters to turn them on and make them more active. And so that can be another reason for depression. So the fact that we can measure these markers of leaky gut to say what is your cause for depression is very useful, cuz now we can treat more accurately.

Kelly Engelmann: Absolutely. So in the way of intestinal permeability panel, because one of the markers that I absolutely love on there is DAO.

I see so many histamine related challenges because of, you that micro villa and the small intestine being damaged and they’re not able to make enough d a o. And as a result of that, they’ll have histamine symptoms which drive them banana’s. Itching, insomnia, anxiousness oftentimes that come with lack of d a o. So tell us more about that.

Cheryl Burdette: Yeah, I love that one too. And because it is such a game changer for people when that’s the marker that’s off and you identify it and you treat it, you can see a lot of improvement in quality of life, interestingly so, diamine oxidase, it’s the enzyme that degrades histamine and we make it in the gut. So this is another thing that gut-based work does for us, not only putting that barrier in place so that there are foods and bugs are separate from our immune system, but as you repair that gut lining, as you plump up the microvilli, as you said, they produce what are called brush border enzymes and also diamine oxidase in right there in the gut lining.

So the gut lining makes the primary enzyme that degrades histamine. And that’s great news for like this time of year when the spring in pollen and we’re like, ah, how could I degrade more histamine. Well, your gut-based strategies help with that, but what what’s fascinating is that this is not the only place histamine affects us, we have histamine receptors in the brain, we have histamine receptors on the heart, and so when diamine oxidase is low and people aren’t degrading histamine like they should, this could be a major reason that they are having headaches, those histamine receptors in the brain in fact, 83% of people with migraines have low diamine oxidase. And we think about migraines, they’re horribly painful. The medications that are utilized are given in small amounts because they’re can be addictive. So it’s hard to get that particular medications that pull you out of pain and yet 83% of people could have benefit in terms of gut-based work and degrading histamine more. And so when we see diamine oxidase is low, we can treat it, we can give it and for example, all use supplements that have diamine oxidase and then even at the onset of a migraine. And I’ve seen great success with this in terms of not even needing to use something more invasive, not needing stronger pain medications to break the cycle of pain. I’ve seen arrhythmias turn around with increasing diamine oxidase levels, and again, the heart has histamine receptors and so even helping the heart stay in rhythm more. It gets back to how well we degrade this histamine, but histamine can make us not just itchy but again, it’s your area of weakness. So for some people, histamine might make you really agitated. For some people, histamine might cause a headache. For some people, histamine causes an arrhythmia. And so if we can identify your ability to degrade histamine then we have another way to treat that’s very low invasive. That’s back to that gut-based work. Back to building up that lining and keeps you from needing more and more medications over time. And so, yeah, you’re right. This one is just really nice tool to have. Often the picture is that person who’s kind of non specifically reactive to so many things. They can’t quite figure out what the trigger is, and it’s even confusing from foods because they’ll go, oh gosh, but I ate this food two days ago and I didn’t get the symptom. Well, that sounds like a food sensitivity, first of all could be that. But the second thing is as food sits, it degrades and part of degrading is it starts to have more histamine in it. So you’re thinking, well it couldn’t be this food I ate this exact same thing the other day and have no problem. Well, now your leftovers have more histamine, and if you can’t degrade that histamine, there are a number of ways that that can affect people but it so treatable, and so it gives us another avenue to pull people out of a highly inflammatory state by using more natural therapies.

Kelly Engelmann: Yeah. So Cheryl, I wanna go back to what you said about histamine and headaches, because oftentimes we’ll see premenstrual headaches, right? I mean, I know that histamine’s a part of that, but I never even considered adding D A O just during that time of month, to see how to help them navigate that, right? I just hadn’t put that together until you just brought that out, so thank you for that.

Cheryl Burdette: Well, yeah, and you’re right, progesterone will work. Most of the time for most patients that have that presentation, because as we know, have progesterone drops. That’s what causes the lining to shed, this is why we have a period, and for those patients it’s probably dropping too much. And progesterone stops swelling around the nerves in our brain and so progesterone even binds to what are called GABA receptors that are the major way we rest and relax. So progesterone is a very calming effect on the body and it’s a great therapy. But now and again, you’ll have those people that you’ll use progesterone for a headache before their period and then they’re still getting a headache. Your test and their level looks okay. So actually diamine oxidase drops off around our period too. And so when the people are non-responders to progesterone therapies, using diamine oxidase can be a really great thing for keeping people from having a headaches.

Lori Esarey: Well, I could spend the whole entire afternoon talking to you.

Kelly Engelmann: I know, right? We could spend all day here. I wanna spend a few minutes talking about oxidative stress. We produce oxidative stress as we do life as we should, but oftentimes we have a burden of oxidative stress that we’re not taken care of in a healthy way, and that causes oxidative damage.

So you guys have a way to measure. Oxidative stress burden. So tell me about that.

Cheryl Burdette: Yeah. And so oxidative stress maybe might sound foreign, I could call it a reactive oxygen species and make it sound even more biochemistry, weird. But really people are very familiar with this concept. It’s really simply, are you getting enough antioxidants for your body and we all know antioxidants. We know that that’s what’s in fruit and vegetables, and we know this is why we should eat them because they’re good for us and antioxidants squelch free radicals. And so another name for free radical is a reactive oxygen species or oxidative stress. And so we’re familiar with the idea that if we don’t get enough antioxidants, that we’ll have too many of these free radicals and that can even do things like damage our DNA. And this is how we get those mutations that could eventually become a cancer. But reactive oxygen species or free radicals, they can muck up a lot of things in the body. It’s not just a cancer. They interfere with enzymes that will help us in terms of making our more active thyroid hormone. Or they can interfere with our ability to produce neurotransmitters or they can create pain in the body, or they can damage our lipids, our LDL and make it even stickier and more plaque forming so, these reactive oxygen species or oxidative stress, is really at the heart of much chronic pathology out there. And you probably had this experience, like you go in you do your once a year wellness exam, and then you go, now what on here tells me if I’m at risk of cancer. And there’s really not a marker on there that does that it tells you that your kidneys are functioning and that your liver is functioning and those are good things and that you’re not anemic, and those are good things for us to know, but our number two causes of death, cardiovascular disease, and cancer and so it’s interesting that routine screening doesn’t really do something to assess this. Well, some of those markers of oxidative stress that we look at, again have funny names 8-OHdG is one of them, but it is a marker that goes up when there are more free radicals. When there’s more free radicals than your body can handle. And it goes up when DNA is being damaged. And as it goes up, we have more risk of cancer. If it’s elevated and you get a cancer, you’re, it’s likely that your cancer will be more aggressive. It’s likely that you’ll have more metastasis. And so we do have very validated ways to measure. Are you getting enough antioxidants to control inflammation or reactive oxygen species in your body? And these markers of oxidative stress, again, are associated with yes, risk of cancer, but also risk of cardiovascular disease. When you have more oxidative stress, like I said, this can impact your ability to, for your neurotransmitters to function so it can interfere with and cause things like depression or anxiety. Can certainly contribute to more pain. So, if we wonder are we getting enough from our diet to control what’s going on in our body to keep us in the best state of prevention? Well, we don’t have to just wonder. We can very easily measure these markers and we can get us a snapshot of Yeah, what I’m doing dietary is enough or, no, it’s not. I’m sure you’ve had this experience where, we’ll, maybe we’ll recommend maybe something that has like green tea or has broccoli sprout extracts that they, because they’re so helpful in terms they’re very potent antioxidant. And someone will say to you, yeah, but I eat broccoli. And then I’m like well, but is it enough to control your pathology? And if they’re sitting there with symptoms, then we already know the answer is no. But again, how much, like every time you read, there’s a different antioxidant, there’s different studies, different amounts, well how much and how many should I take? Well, we can answer that pretty simply by measuring your level of oxidative stress. And that will tell us, are you getting enough antioxidants to control signs and symptoms that you’re experiencing?

Kelly Engelmann: Yeah, I’ll oftentimes find that test can be really eye-opening for patients that, to your point, think they’re getting enough.

And I’m like, okay, well let’s check and see. Let’s see what your level of oxidative stress looks like. Let’s see what your level of glutathione looks like. Are you able to have enough reduced glutathione? Those kind of questions we can have answered by looking at that oxidative stress panel so, that has been a game changer for people that, to your point think they’re good enough.

Cheryl Burdette: Yeah. Hey, it can really help that those lifestyle things hit home. This a younger gentleman who worked in the lab who exercise hot Tai Chi really well. What was a cigarette smoker, and I’m sure that he knew cigarettes were not good for him and he did this on himself, and he saw that 8-OHdG was so high and he would always try to cover up the cigarette smoke, but if you’re not a cigarette smoker, it’s very hard to cover hat up. So I could always tell it, he just smelled like cigarette smoke and cologne when he came. So anyway he was asking what could that be? And I was like, well, there are various lifestyle things that can contribute. Cigarette smoking is an example of that. And anyway, so a few months later he showed me his result again, and now it was very low. And I was like, oh, what did you do? What did you change? And he said, oh, I changed some lifestyle things, so because he is, he didn’t wanna talk to me about the cigarette smoking and that’s fine. But and again, I’m sure he is a very smart human being. I’m sure that he knew that cigarettes were not good for him, but seeing it there and seeing the damage it was doing to his body and, he was in his early twenties and so already that happening. So it was eye-opening for him and motivating to make the lifestyle shift he needed to make

Kelly Engelmann: Great story, was Cheryl, we could spend the rest of the day here together. Go ahead Lori.

Lori Esarey: Yeah, that’s what I was gonna say. We could, and I just wanna personally thank you not only for your contribution of being here today with us, but your contributions not only as a clinician, but in the lab, developing tests that help our patients and our community live better and live optimally. I mean, we covered three tests today, and it was a lot. We didn’t even get to go in the nitty gritty of all of them, but we talked about the P88 test, we talked about the intestinal probability test. We talked about the oxidative stress test as well, and I think we could have probably spent an hour or more on each of those.

But it was very, very enlightening. I just really appreciate that you’ve carved out time and just what you have contributed. Years and years and years of practice. We call medicine, obviously the practice of medicine, but also getting in there in the lab and being a pioneer and being and willing to put yourself out there. I know that it’s taken countless hours and ongoing.

Cheryl Burdette: Well, I wanna thank you guys too because I think lab tests and all that, the most important part of medicine is education. And so things making something like this available so people can just understand more about what’s going on in their body is really the primary thing that we need to do and like you said, we’ve known each other for quite some time, so I know like, You’re out there giving up your weekends. You guys are at every conference, constantly trying to learn the next thing and how to help the next patient. And so very lucky to be here today and spend some time with you, and thank you for all that you do to help each patient feel better.

Lori Esarey: Thanks so much for listening to today’s episode. You can find more information about Synergee at Synergee for Life. That’s S Y N E R G E E, the number four life.com.

Kelly Engelmann: And then Synergee Connect is our Facebook. And then please make sure to follow us on your favorite podcast app so that you make sure you get future notifications of episodes.

Lori Esarey: The purpose of our Synergee podcast is to educate. It does not constitute medical advice by listening to this podcast. You agree not to use this podcast as medical advice to treat any medical condition in either yourself or others, including, but not limited to patients that you are treating. Please consult your own physician for any medical issues you may be having.

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