10 New Oxidative Stress & Gut Health Biomarkers to Know

Well, hello there and welcome to the Root Cause Medicine Podcast. I'm your Host for today, Dr. Kate Kresge, and we are sitting down with the incredible Dr. Cheryl Burdett. Dr. Cheryl is an instructor for us at Rupa University. She's teaching a course that starts next week called Food Sensitivities, Gut Health and Detoxification, A Functional Medicine Approach. Now, something new that she's teaching about in this course are 10 novel stress and oxidation markers, things like F2 isoprosteins, 8 OHDG, total glutathione, antizonulin antibodies, anti LPS antibodies, bodies, secretary, IgA, you name it, she's going to talk about it today and why you might want to consider screening your clients for it. The bottom line we now have the ability to simultaneously quantify intestinal permeability, microbial translocation and systemic oxidative damage using just the patient's mail in results. Dr. Burdette walks us through the evidence behind why we should be testing these biomarkers regularly in folks who show up with gut issues and chronic illnesses and what to do if they're elevated or abnormal. Before we get started though, I've got a special question for the healthcare providers in the audience. What if your supplement dispensing patient education and treatment planning all lived in one powerful platform built for whole person care? And what if that platform was free for both you and your patients while saving you hours each week on treatment planning and Follow up? Meet FullScript, the comprehensive care delivery platform designed to reduce administrative burden and enhance clinical impact so you've got more time for joy. From automated rebuilds, lab ordering with interpretations, to evidence based protocols calls and built In Adherence Support, FullScript integrates the tools that you need to streamline care and stay focused on what matters most your patients. In a recent survey, 74% of providers reported saving up to three hours per week using FullScript to create treatment plans. Are you ready to work smarter and elevate your practice? Visit fullscript.com to get started today. And one last important note. The views on this podcast are those of the hosts and the guests, and they don't necessarily reflect those of FullScript or any affiliated organizations. This podcast is for informational and educational purposes only, and it's not intended to be medical advice for your safety. Always check with your doctor or healthcare provider before making changes to your health routine. Now let's start the show. Dr. Cheryl Burdett welcome to the Root Cause Medicine Podcast.

Thank you so much for having me. Always a pleasure.

I know I should say welcome Back. We had a fantastic episode with you that folks should go listen to originally, where we heard a lot about your background and your work at this point. We are now on probably our fifth bootcamp with you, at least, where you have been teaching our practitioners for several years now. And we've got some really exciting updates that you're including in your next course, which starts very soon. And I personally find it fascinating. We're talking about oxidative and stress markers, and this might be new to practitioners in the audience. So today we're going to cover 10 biomarkers that you're going to be discussing in depth in your boot camp. But give us an overview. You know, what are you going to be talking about in this boot camp when it comes to gut oxidation and stress? And why are these things critically important to measure?

Yeah, absolutely. So when we get started with a patient, we would love to have every single piece of information possible if we could run an MRI on every single one. And also imagine that these things are non invasive as well. So if we could have all kinds of imaging and all kinds of blood work and every little bit of it, of course we would want that. But there are limiting factors and eventually maybe too much data or data that's not in the right direction can even be distracting. So how do we manage that with a patient? How do we look at the process behind the disease, which could be so many things. It could be nutritional, it could be inflammation, it could be oxidative stress, it could be mental emotional stress, it could be hormones. How do we look at all of that process behind what's going on so that we can individualize without overwhelming or without something that's just too much to even cover or financially has limitations too? So I have thought, what are those key things that I really want as I get started? And of course that varies from patient to patient. There's an individual nature to that. Based on a history, we're going to decide what we want to order. But in addition to that, with most people, we really want to rule in or rule out inflammation as a process of that chronic condition and or oxidative stress, the amount of free radicals. And another way of kind of saying that, is leaky gut driving part of what's going on in this patient, or are they at a toxic threshold and toxic body burden is driving what's going on? Or is it some of both? And there are very few instances where I don't want to know if there's a piece of that going on in a patient. So when we designed this profile. We thought, what are the go to markers that have probably the largest breadth in terms of covering cause for chronic disease? The most research, the kind of marker where I could go online and I could look at PubMed and look at peer reviewed research and say there are over a thousand clinical studies that say, yeah, this gives us impact about toxicity in the body. And so that was the origin story of the gut ox stress bundle that got put together.

I love it. And as someone who sat in your courses, I am familiar with how well researched every single biomarker you tend to discuss is. I love that you always have screenshots of these studies. You go through the mechanisms. It's really incredible the amount of evidence you've been able to include for practitioners. So they feel super confident that they're using the latest, most advanced, but also very evidence based tools. Let's talk about the 10 biomarkers that you are measuring with this test. So what are the analytes that you're looking for when you're assessing gut oxidation and stress?

Yeah. Okay. So one marker I'm very excited about are antibodies to lipopolysaccharides, lps. And the reason that that excites me is because when I think about gut based markers, I probably wish for most of them. But when I think about, okay, where is the strength of the research? Where is the data that talks about harm from dysbiosis, gut based inflammation? And there's no shortage of data. But when we drill down to LPS specifically, that is what leaks in over time and is responsible for a phenomenon called metabolic endotoxemia. And so that is the process that by which the inside of your vessels begin to not work as well. Because this lipopolysaccharide as it drifts in, it's damaging to the inside of the vessel. That same LPS damages even your lipids, it's like your LDL and puts them in a stickier state, oxidized ldl. So now you've got the perfect one too. You are damaging the inside of the vessel and also making the fat more oxidized. So that is a beautiful foundation for starting an eventual plaque in terms of atherosclerosis. So the depth of the research with LPS in particular is really quite strong. And that's just cardiovascular disease. It's important because it's our number one killer. And if there's a gut based connection, this is not something that's routinely looked at. So being able to see that is really helpful. But that's only for starters, that LPS is so bad for us that if I'm in a lab and I want to create an autoimmune model, I take a syringe and I fill it up with LPS and I inject it into that rat. And the reason it creates autoimmunity is because it down regulates what are called T reg cells, the ones that keep our immune system in balance. So now here we have this marker that drives cardiovascular disease, drives autoimmunity, crosses the blood brain barrier. Another thing they'll do if they want to create a depressive model of a rat in a lab, they use LPS for that too, because it crosses the blood brain barrier, creates inflammation that blocks tryptophan's ability to be moved into serotonin. And so it wreaks havoc in the system. And it comes from the gut, it comes from dysbiotic bacteria, and that is our bread and butter. This is the thing that we know to treat, and that really gets left out. Otherwise, it's associated with aging. It's hard on the mitochondria. So again, the depth of the research is really strong with that one.

So we're going to go through the other markers here in a minute. Secretory IgA, zonulin, F2, isoprostenes. Before we go into those, I want to stick with LPS for a second. So what would you do if you found this marker and it was elevated? And how are we measuring this? Are we doing saliva, urine, blood? How are we checking for this?

Okay, so this one comes from the finger stick. And if I see that elevated, then I know that I need to reach for antimicrobials. I am probably likely to reach for a botanical that has berberine in it. There are lots of botanicals that have berberine, from coptis to goldenseal to Oregon grape. So using some type of berberine containing formula to treat that, because it kills the bacteria, that sheds lipopolysaccharides. But also, remember I said LPS drives metabolic endotoxemia. So now when we look at what berberine does clinically, well, we know, oh, it decreases lipids. Well, one of the major reasons we make lipids is when LPS goes to the portal vein and gets dumped on the liver, the liver goes and we start making all kinds of cholesterol and ldl. So makes sense that berberine would decrease lipids and that kills the lps. Berberine also does other things too. It helps with LDL receptors and it helps with reverse cholesterol transport. So it's a winner in that category. But then here is this marker that ties gut dysbiosis to cardiovascular disease. And then here's this botanical compound that one of the major things it does is it controls the microbiome and has all this rich metabolic data as well. So that's real high on my list for lps.

Oh, I love that. I think most people listening will be familiar with berberine helping, maybe with insulin resistance and insulin sensitivity, and might not know about this other critical role that it's playing.

Yeah, but you probably still think of it for elevated cholesterol and people on the metabolic continuum, and it just ties the whole story together.

Do you have a story of a patient who maybe had done everything else, had done all the other workup, but they discovered this biomarker was out of range, and when you treated it, they got better?

Yes. And unfortunately, it can show up even when things don't on stool test. My stool test, girl. And you will never get me to not want a stool test. But this adds to that. And so sometimes when we're trying to figure out, okay, we're getting started, what's most important, it's not a complete overlap. There's a synergy there, or a reason to do both of those, because sometimes you can see lipopolysaccharides and not see a huge amount of dysbiosis on the stool test. Otherwise, it's just tricky. No test is perfect. So that's why I like to add that in. And again, because the clinical research is so strong, again, you literally inject this stuff into rats to create so much pathology. So it's so tightly controlled with things.

Now, when you're looking in the blood, we're saying lps, are we actually seeing LPS or are we seeing anti LPS antibodies?

Okay, so, yes, good point. We are measuring the antibodies to lps, and there's a couple reasons for that at least. One is that they're very stable. So we like that in terms of the lab methodology, things aren't going to happen in shipping. It's just really hard to mess it up. The second is, is because it's more clinically meaningful for what we're talking about. You start to make antibodies out of range to LPS long before you have huge amounts of LPS floating around in the blood. The reason for that, it's more this immune activation that drives the inflammation, the metabolic endotoxemia. So the antibody, the immune component of it, is really the more important part. By the time you start to see measurable amounts of lipopolysaccharides. Now you're probably looking at a toxic patient, someone who's even septic. So that's what we think's going on. That's a refer out immediately. You know, that's going to be handled hospital side. This is what you see in the research associated with chronic fatigue, for example, or scleroderma or various conditions that are rheumatoid arthritis. It's interesting. If you biopsy the synovial fluid of a joint, you will find LPS antibodies there, often EBV antibodies too. So yeah, that's why we do the antibodies.

I'm glad you clarified that because I'm sure our clinicians with emergency room experience are thinking, well, I have run this and seen it on several patients. We're talking about the antibodies, we're talking about how can we screen the immune system for a reaction to LPS long before you get a super high burden of LPS in the blood. And I love that you clarified that. Now are we more likely to see these if a client does have leaky gut or can they sometimes be independent of each other?

Yeah. So just like we have to look at different lipids because they tell us different things, there are different ways the gut becomes leaky. Leaky. And when. So when I first learned of zonulin, my heart just went pitter pat because zonulin, it was discovered and it tells tight junctions to open. And so we found the biomarker that governs leaky gut. And it and Fasano's research talked about how it goes up even before the onset of autoimmunity. So I was like, here it is, it's wrapped up, put a bow on it, we're done, we've got it figured out. Horrible colitis patient comes in and their zonulin is normal. I'm like, what you'd like it like, ah, so what's wrong with this test? So, but nothing is wrong with the test. It's just that the body's complex and we do these things in different ways and not always all at once. Like you can have someone who has elevated triglycerides but not lipids. Probably. We often see it together, but you don't always see all of it. The same is true with leaky gut markers. So you could have an elevated zonulin but not have an issue with lps? Well, zonulin goes up for a number of reasons. We for sure it goes up in response. Response to gluten and bacteria. Some research even saying that zonulin might be triggered by also yeast and mold and that this might be the route by which our most mold toxic patients are having higher levels of exposure that make them more sick. Of course respiratory can initiate things, but then if tight junctions open and mold floods in from the gut, that's a big, huge exposure route. So different things can be going on, different people can have different weaknesses. And one that's really unique and why it's on there, diamine oxidase. So that is an enzyme that gets made in the gut lining. You could just have your gut lining atrophy. So like people that took too many NSAIDs, they wear the gut lining down so much they ulcerate. That is a very leaky gut, but it's not a zonulin mediated leaky gut. So yes, you could have one elevated and not the other. Even though sometimes we think, well, if the gut is leaky, shouldn't all of these be off? And I wish there were one. Tie it up with a bow, be done with it. But the body is complex.

Well, I love that. That's why you screen for multiple different root cause analytes, so that you can actually see what's going on and then the treatment's gonna be different. So let's actually start talking about Zonulin a bit. You mentioned the mechanism of action and that Zonulin tells these tight junctions to open up. When you see that high in one of your clients, what's the next step?

Yeah, so when zonulin goes up, then I want to figure out do I think it's more bacterial or do I think it's more gluten? I'm probably going to work on both of those together, but I often get a sense from the history. So if I think it's more bacterial like we also see some LPs. Now we're back to thinking about our antimicrobials, but if it's gluten or maybe it's something that we're not even sure. I really love immunoglobulins for treating lps. And so immunoglobulins can be sourced from serum, they can be sourced from colostrum. Of course, there's even some egg derived immunoglobulins out there. I don't know that this commercially available, but I was reading a research study where they were deriving immunoglobulins from camels. I haven't seen that yet in a bottle, but so anyway, the point is that these immunoglobulins do a lot for treating leaky gut. Think of this. When I think of breastfeeding, if we took breast milk and we looked at what it was high in, one of the things that it has a lot of our immunoglobulins, I mean, this is why we source them from colostrum, from animal sources. But as an animal, we also have very high levels of immunoglobulins in our breast milk. And when the gut linings, because we come onto this planet with a leaky gut, that's why we don't introduce foods initially, because it's just part of it. We've got to wait a minute till that lining heals. And. And of course we know if we introduce foods too early, we can have more allergies. And so really this idea of leaky gut we've all known for forever because we don't introduce food right away. So those immunoglobulins from breast milk, they actually look a lot like a molecule of zonulin. And so they'll sit in the receptor where zonulin was trying to bind and block it from doing so. And so it has this immediate ability to shut down tight junctions. But it's this nice, wonderful, gentle therapy. Because immunoglobulins build your immune system, they increase secretory iga, they wall off bacteria. So instead of it lysing open and creating a die off, just kind of decreasing adherence, lowering the level. So it's a nice way to step in with these patients that tend to often be sensitive to treatments as well. So I love immunoglobulins when I see an elevated zonulin. But insert all your favorite leaky gut treatments, because any leaky gut treatment will build up the lining, will help to decrease zonulin over time. That's just one that has a nice directed activity for it. I love it.

And it ties in really well to another analyte that you're measuring on this test, secretory iga. So tell us what that is.

Yeah, so when we go in for our yearly physicals and we get CBC and a chem screen, because that's about all in a standard visit that you would get, the CBC will show you a white blood cell count. And we look at that and we go, okay, our immune system is fine, or our immune system is not fine, as the case may be. But it's interesting that that's the one we look at because as we know, 85% of the immune system is in the gut and that is secretory iga. And that is our first line defense. And that does Kick back at bacteria, and that does kick back at lipopolysaccharides. And so it's a really important thing to know. I know we know treating the gut is where 80% of the immune system is, but it really crystallized in my head one day when I thought, you know, our go to immune treatment, it's not a beta glucan, it's not a licorice, it's not a vitamin C or a vitamin D. Our go to immune treatment is normalizing gut health. That is our most powerful tool in terms of improving immunity. And so this is why we're often doing this, you know, looking at our LPS or in our stool tests and all this in our, for example, Lyme patients and mold patients who are so chronically ill. It's not because, you know, per se, the bug in the gut, we know they have other bugs too, we have to deal with. But if we're going to tip the scales in their favor and allow the immune system to really do its job, you have to look at Secretory IGA. And I could argue that it affects 95% of the immune system because it also sends signals through dendritic cells to prime the rest of the immune system to decide, are we going to make a T reg cell, are we moving towards TH17 really inflammatory? And so it's a director too. It changes how we interface. I mean, for example, if you have a low secretory iga, you will have a higher titer to foods because the rest of your immune system says, our front line is worn down, it's not doing its job. The rest of us better overact. And so these people will pull out the foods, they'll do a really good job, but their titers are still elevated. And they're like, why? Well, because that if that first line defense is down and the rest of the immune system stays amped up. And so that could be a food reaction, but that could also be like that post Lyme autoimmune kind of thing too. We stay amped up when that front line is degraded because, well, somebody's got to do something. So might even get a 90 to a 95 score in terms of how much of the immune system it is. Wow.

What types of cells are making secretory iga?

So our peyer's patches there and the in the GI lining creating that secretory ig. And it's very energy intense. You need lots of protein to do it. Vitamin A is excellent for increasing our production of secretory iga. So nice, easy one to reach for. And we knew that already. We knew vitamin A was good for the immune system. It's also antiviral, but this is another way that it acts. Zinc also helps our production of secretory iga, part of that barrier defense, and probiotics of course too. So it's an important one to look at.

Absolutely. I would imagine, particularly for your celiac patients who are at increased risk for deficiencies in both zinc and vitamin A. This is cool already. This bundle of biomarkers together tells you so much. And we haven't even gotten halfway through.

And sometimes I'll see a marker I'm really excited about, but then I'll go research it. I'm like, well, there's one study and that just isn't enough. I mean, like an example of that we worked through in our integrative community was for a long time we all measured 2:16 ratios, 2 hydroxy estrone to 16 hydroxy estrone in the urine to look at metabolites. And there was one study that, that said that, and then we all ran with it. But then the original researcher said, oh, I messed up, it might really be four. He didn't mess up. He just did more research and learned more things. That's different than messing up. But then he found four hydroxylation was really more of the culprit. And as more research came in, about 16, it was like, well, sometimes it's bad, sometimes it's not. It was more iffy. But we really ran with that one study and as we got more research we saw, okay, there's probably a better way to do this. So these are markers that again, just have thousands of papers, every single one of them, a real depth of study.

It's awesome. I would love to move into some of the more markers of oxidative stresses where I would put them. I'm curious if you would agree with but the F2 isoprostenes, 8oHDG glutathione. Can we talk about those and why we would measure those and how you're measuring them in this test? Are you actually measuring them in the gut through the stool? Where are we looking for those?

Yeah. Okay, so those, the 8 OHDG and the F2 isoprostane, those are done through urine because they're metabolites. And then the glutathione comes from finger stick. And 8.0hdg is one of my go to favorites. And I'll quote Joe Pizzerno, he talks about it a lot too. He says it's probably the best go to detox marker. He also talks about and studies that show that 8G, we know it goes up when there's DNA damage. And obviously there's DNA in the nucleus, but there's a lot of free radicals, a lot of reactive oxygen species around that nucleus in the mitochondria as well. So a big part of the production of it comes from the mitochondria. There's really good research that associates a high eight ohdg with mitochondrial damage. And now if we couple that with glutathione, that's on there as well. And so in general, our mitochondria will function well if we have good levels of antioxidants, if we have high levels of glutathione. And so yes, we're getting even now to the place where we can do different genetic tests in terms of mitochondrial markers and really dig into the various parts of the process. But as we're getting started with somebody, if they don't have adequate glutathione, the mitochondria is not going to function like it should anyway. And in most people, if we can get that the glutathione adequate, they're going to do so much better. Such a good, logical place to start. 8 OHDG. I could say a thousand peer reviewed articles, but it's probably more like 10,000 or hundreds of thousands. And it's so correlated to when the DNA hits toxic body burden. So when we look at aflatoxins, when we look at carcinogens, when we look at PCBs, when we look at all the things in our environment, we can tick through all of those that I just mentioned, of course, cigarette smoke. And there, there's a big association with they will cause an increase in 8 OHDG. And so for example, I can think of this one patient, just extremely healthy in general, everything Great. But yet her 8 OHDG was high. And it was just such a surprise given just her vitality in general. And we went through many things, but that led us to think about implants and it turned out they were very mold. And this was a reason and we just really wouldn't have figured it out unless we were trying to figure out where her toxic exposure was coming from. But the thing is, we know we're all exposed to toxins, but are you exposed to a level that your DNA can handle, that your diet, that your antioxidants can handle, or are you out of balance? And that's what it tells us.

Awesome. So adohtg will go up because it's basically a product that is being released into the body when DNA is damaged, or so literally kind of breaking apart. Is that true?

I guess I did say that. But if I'm going to be absolutely, perfectly correct about it, it's part of the repair mechanism. So after it's damaged and the body's trying to get it better, that's where it comes from. But yes, in general.

Amazing. So you can infer, okay, the body's working really hard to repair a lot of DNA damage. Where's the damage happening? Where's it coming from?

And then when you look at what causes 8oHDG to go up, you see mold. Aflatoxin does that. You see, of course, cigarette smoke does that. You see, of course, indoor sickness, which is Primold. Again, you see all the carcinogens, even heavy metals, cause that too. So you don't know what the toxin is, but you do know you're at threshold. So do your detox work? Change the diet, get the antioxidants up, look at it again. If it's in normal, we don't necessarily have to go look for any other zebras out there.

Yeah. Now, you mentioned glutathione and how it helps with detox. But, you know, so many of our listeners may not have had a biochemistry class that really taught them about how glutathione works, and they might just have heard about it on Instagram in the same way they kind of hear about, like, a detox tea. And so I almost feel like it's worth grounding ourselves a little bit in the biochemistry of glutathione. Why is it helping with detox? What does it do in the body?

Yeah, I feel the same, too. And sometimes my brain would get kind of lost with this detox question, because, like, those studies that talk about the umbilical cord of a newborn having more than a thousand chemicals in it already. And so part of my brain wants to go, okay, thousands of chemicals out there, environment. What is the thing that pulls every single one out? You know, like, which combination of this and that do I need to have? And so I took some time and I sat down and I said, okay, what are the major toxins in the environment that we're exposed to? Like, you know, what is the top 10 list out there? And then I went through and looked at and how are they removed from the body? And really, anything in that top 10 list is removed from the body as glutathione goes up. So we talk about phase one and phase two detoxification phase one or your cytochrome P450 enzymes. Phase two are glucuronidation, where we take that toxin. So as we know, the toxin comes into our body, it goes through phase one, and then it can create these hydroxyl intermediates that are even more toxic than that original substance. This is why we have to have good phase two, because it soaks those things up, attaches it to a conjugate, moves it out of the body, clears it so we're not bouncing around with an even more like cigarette smoke, doesn't even become carcinogenic until it goes through phase one. So that's why we need adequate phase two to keep up with this. So when you tick through, okay, there's glutathione conjugation, there's amino acid conjugation, and that one probably relies on little heavier on glycine, but there is sulfation and that's sulfur containing amino acids, which glutathione is. There is methylation. Lowering your oxidative stress helps methylation to work better. And did I already say glucuronidation in there as well? So when we really tick through the major toxins and the major way we eliminate things from the body, it comes back to a lot of glutathione. So rather than get lost in the muck of which of the thousands of the chemicals are there, just like really locking in on, like, what do we like for increasing phase two, how are we increasing glutathione, and then how are we measuring it to make sure that we have adequately treated that person, that they're getting enough antioxidants for their toxic exposure? And so sometimes we think, well, as we treat them, that's going to get better anyway because it's the Lyme using up the glutathione or whatnot. And in part that's of course true, but at the same time, it is a part of your therapy. It's not just a cleanup act. For example, glutathione is highly antiviral, decreases viral replication. We saw a lot of studies during COVID that came out talking about that. We know that glutathione also will calm down T cells. So when we are in that TH17, that more inflammatory branch of the immune system, good glutathione helps those cells to calm down. So it's not just reactionary. It's fine, though, that reaction is getting toxins out, but it's also often treating part of the cause too.

So it's amazing that we can Measure this. Right? It's so cool. And I'm curious when you see, let's say glutathione's low. There's so many products out there. Like there's patches, there's liquids, you know, there's things you can rub on your skin. You could get a glutathione iv. How do you think about maximizing someone's glutathione intake and what are some of the strategies you'll use?

Yeah, so I always want to think about diet and lifestyle. I mean, we've seen those studies that talk about if you just eat an organic diet for three days, something like 90% of the toxins go down in your urine. So it's a good indication that we need to do more in terms of looking at our clean 15, staying away from our dirty dozen, really giving patients good lifestyle advice as well. And that's what's so nice about these biomarkers is they are lifestyle biomarkers, which there's a huge absence of in normal standard of care care. But then in addition to that nice thing about having a lab is you get to see how a lot of these things work. And then you can call your friends up and be like, what were you doing? That is an amazing jump in glutathione kind of thing. I've been pleasantly surprised with nac, which is the major rate limiting asset in terms of making glutathione. It's not super expensive. It does a pretty good job helping to boost glutathione in most people. And then from there, the industry as a whole has figured out some good delivery methods for glutathione too. So your acetylated glutathione and your liposomal glutathiones, they have really overcome some of this idea that that gets broken down into the constituent amino acids at the brush barrier. So again, having a lab got to look at a comparison IV glutathione to for example, an S acetylglutathione. And while the oral acetylated did not not get as high as the iv, nor would we necessarily expect it to, it got pretty close. And it was handling the markers of oxidative stress in a competent way as well. And you know, it's nice to use these things together if you're going to do an iv, do things to support on days that are when you're off. But you'll see it and then sometimes you don't see it go out because that is the nature of patient care. Right. It's not always perfect, linear, lovely relationship like we'd like it to be. And then these are your patients that you're saying, okay, something else is going on. Is there a chronic infection that's really just keeping you depleted? Kind of a lot. Like we think about adrenals too. You can, some people, you'll just give those glandulars and they just stay flatlined, but it's the infection. And then as you deal with that, boom, that's when they pop. So even a level that doesn't go up tells us something. Test are both to rule things in and to rule them out. Sometimes we don't get to rule in what we thought we were going to, but the. That's why you were doing the test. I know it can be frustrating, but.

It'S also a good plug for repeat testing. So, you know, this isn't a panel that you would run just once. You would run it, do interventions, run it again so that you can see are your interventions actually getting the clinical impact that you want them to have. When you rerun a panel like this, how soon do you generally do it? Is there a rule of thumb, like, you know, three months, six months More.

At that three month benchmark. I tend to also fold in. How's the patient doing? So, and, you know, maybe if someone's just doing fabulously well and all their symptoms are gone, then maybe we are a little more conservative with retesting. But when that isn't the case, this is when we need to look. Well, did your glutathione improve? Have we seen some change in F2 isoprostane? If not now, we need to change our therapies, because that, that is just the nature of it. Nothing works the same in everybody all of the time. Which is why we do need these biomarkers.

Awesome. Now, we mentioned F2 isoprostenes. This one might be newer for folks who particularly maybe aren't in the research all the time. And I'm curious if you can explain what that is. And this is another urinary biomarker. Why did you decide to include it?

Yeah, because it's looking at a different compartment in the body. So just like you can have different tissue that responds to stress differently in your body. Like, I'm a firm believer for my, myself that I can handle it pretty well here in my brain, but my adipose tissue does not like stress at all. Like, I definitely think that there's. I've got a little bit of a difference there. But in the same way, you can have different parts of your body that are more fragile in the face of free radicals. And so for some of us, maybe you already started off with some DNA that was a little more fragile. So that's where your oxidative stress shows up. But for others of us, the deoxidative stress shows up in our fat compartments, and that is F2 isoprostane. It is a marker. So it starts off already as a bad fat. It started off as arachidonic acid, and we know that's that angry, inflammatory fat. This is why we lower meats and men with prostate cancer, red meat, because, you know, too much arachidonic acid can drive those things more inflammatory. Okay, so it was already bad. Now it gets charged with the reactive oxygen species, and it becomes F2 isoprostane. And so when that is high in the body, it mucks up your fat, and your fat is your brain. And so, for example, if you take DHA, an omega 3 fatty acid, and you're hoping it's going to help brain chemistry because it gets converted into what are called neuroprostains that are helpful with cognitive function, F2 isoprostane shuts that off. So in terms of. So it's associated with more neurologic conditions, but also anxiety, depression, because it's giving you an indication that there's too much oxidative stress in the brain. So our neurotransmitters aren't working like they should. That could be Parkinson's, but that could also be things like focus. So that's one area. Another area where we think of fats doing damage is, of course, atherosclerosis. If I biopsy a plaque, it's fats. It's angry, inflamed fats. And so one that you'll find in that plaque is often that EP2 isoprostane. It is vasoconstrictive. It's irritating to the vessel wall, and it will charge ldl. So it's part of that plaque formation. And then the next place I think of it, too, is myelin sheath. For example, if F2 isoprophane is elevated, you will not incorporate Omega 3s into the myelin sheath as well. And you also see that research with oxidized ldl. You want to look at that in your Ms. Patients. There's some group that says you've got to start thinking of this as a lipid disorder. And so to incorporate lipids into the myelin sheath, they've got to be in this nice reduced form. And so EP isoprostane Tells us if your fats are in a healthy place.

Wow. It's incredible that if this was high, even if you're thinking, I want more healthy fats, I'm going to take Omega 3s. This might actually block that from being effective.

Yeah, they do. They like to sit in your hormone receptors and block hormones from binding. And so it's like just, it's this idea, this is what makes us who we are. Again, we would never just even give a beautiful bioidentical estradiol by itself. We would be thinking, but what is the health of that person? And so in this case, if you have high F2 isoprostane, you're, you know, moving your estradiol up, you're maybe giving more, even though it's safer. The least amount is the least invasive. So yet you have to push it and they're still not getting symptomatic relief. It blocks that binding. So and this is why we've got to clean the terrain, right? It's not just the therapy, but where the therapy is going. And so these markers get a lot at what is that terrain? And therefore, look, let's build the person up so that the therapy response is better.

It's beautiful. You mentioned arachidonic acid being sort of the building block of that F2 isoprostene. How would you help someone to reduce levels of F2 isoprostenes if you found it in the blood?

So it makes me think fat soluble antioxidants. So some of our mixed tocopherols and tocotrienes and of course CoQ10. And that makes sense. We would have already thought of CoQ10 for things neurologic and for cardiovascular disease. So it's another situation where the treatments really fit nicely. But you don't only have to use fat soluble antioxidants like compounds from broccoli, the glucosinolates that get converted to sulforaphane, they're very effective at lowering F2 isoprostane. And we know that they're very effective at lowering oxidative stress in the brain. So that makes sense. Like if you give a rat sulforaphane and then cut them open to see where it goes. It super concentrates in the brain and a couple in the reproductive tissue. That's why it tends to be protective there. So if that fat is damaging in the brain, then something that crosses the blood brain barrier makes good sense for treating it. And you see it come down nicely too.

Are there any foods besides red meats that you would advise someone to maybe be mindful of consuming in moderation. If you think arachidonic acid might be high.

The red meat and the dairy are your two biggest offenders. So limit those. Take the diet history, see if they've got a lot of that. And then, of course, getting our omega 3s up. But just like you said, even your omega 3 doesn't work as well in an environment with high F2O isoprostane. So this is that, kiddo. That maybe they had A horrible omega 3 fatty acid index and they have attention deficit disorder. And we're like, oh, yeah, there's so much research about omega 3s and brain health. And we do all that and it's like nothing. This can be one of the obstacles.

So would you say this is gut oxidation and stress, or would you say this is the gut comma, oxidation, comma, stress? How do you think of. Because I'll tell you why I'm asking this. I'm sitting here thinking, you know, my specialty was mental health. And every biomarker you're mentioning, I'm like, check, check, check, check, check. Even if I never even thought about the gut, if someone came in with depression and anxiety, I'd want to measure these markers.

I've been reaching out to my psychology friends, colleagues for sure, because gut brain access and oxidative stress. And if you tick through every one of those markers, if I go glutathione and depression, ADoHDG and depression, LPS and depression, you can find things that can connect those together. So, I mean, even zonulin. Yes, I talked about a leaky gut, but we all know it also modulates a leaky blood brain barrier. So there's a whole subset of brain fog that responds to therapies that treat zonulin versus, like, boosting more neurotransmitters. So, yeah, they really do reach a lot of places.

I can't let you go without asking you about two more things. One, anytime I see you, I just want you to, to spread the word about how to accurately assess food reactions because you are, in my opinion, the world expert on this. And I think we still need to get more people in front of you because you have created a panel and a list of biomarkers that you really like for assessing food reactions. And I know you're going to talk about this in the course as well. I want to ask you, you know, our conventional providers are going to be familiar with IGE food allergies. Our functional medicine providers may also be familiar with things like iga, you know, Maybe IGG reactions. You have a very nuanced way of looking at food reactions. What additional biomarkers have you learned about through your research and clinical experience that go beyond the ones I just mentioned? And why should we be measuring them?

Yeah, so these fields develop and science develop. Fascinating to watch it unfold. So we've learned a lot about these various antibodies. We continue to learn about them. We've learned that there's not just IgG, that there are subtypes of IgG. And so I think one important thing that we do is we tease out IGG4. So there's some types 1, 2, 3, tease out type 4 and then look at type 1, 2 and 3 together. And so the reason for that is they are completely different. It would be like looking at HDL and LDL and saying, well, they're both cholesterol. Well, they're basically the exact opposite. And that's the case with IGG4 versus IGG1, 2 and 3. Subtypes 1, 2 and 3 bind to complement. They drive sensitivity reactions, those reactions that are three to 72 hours later that we're all very familiar with. But yet subtype 4 blocks IGE from being able to bind to a basophil or a mast cell. It's what creates tolerance to allergies. So this is why there's been a criticism of igg. If you look at, like a position paper from Clinical Chemistry, they say, don't do igg testing because it's a marker of tolerance. And that would sound very curious to a lot of it because we go, no, the sensitivities we know, we take these foods out, people do better. Well, they're sort of right. And it's a bit sloppy science to state it that way. IgG subtype 4 is a marker of tolerance, but 1, 2 and 3 drive inflammation. So just breaking those apart answers this major criticism that's gotten in the way of looking at igg, which we know creates inflammation in the body. And by the way, it is more common to do it in other countries, starting to be. So sometimes that's a nice lens to look at things through, but unfortunately, that's not the only way we react to foods. You could have an IGE reaction to food, which is more immediate. And what we learned from some research in terms of polio is what they were looking at was who got most symptomatic when they got polio. And so they were looking at titers. And the assumption was, well, if you make a bigger titer, you must have more of an Infection, you're going to have more symptoms. But they were like, it's not always titer that predicts the most symptoms, like who's going to be paralyzed. So what they saw was when complements affixed or binds to igg, that amplified the reaction a thousand to ten thousand fold, which is a real big difference, I guess a 10,000 fold difference. But so if we can measure where complement is binding to igg, we have a much more sensitive test for which foods are really creating reactions. So we do that on the igg side as well. And again, we also do ige looking at those immediate reactions and then right at the moment where that seems way too overwhelming and oh my gosh, four different ways you react to food foods. Then we go, here, eat these, don't eat these. And we even do one page where we just list them. Here's your most reactive food, down to your least reactive food. So if you have someone who's just lit up like a Christmas tree, we do the best we can. You go, okay, focus on these top 10 foods. Or I like that list too, because you'll see all the things they're not reacting to. Look at the bottom of this list and work up because these are things you're having no inflammation to. So really pull these into the diet. So a lot of information which can be overwhelming, but we shouldn't stick our head in the sand like I always say. Of course an MRI is more complicated than an X ray, but it doesn't mean we wouldn't want the mri. Right. So, yes, complication, but hopefully delivering in a way that it's still meaningful to the patient.

It's so much information for anyone who actually wants the holistic in depth view and not just a snapshot of part of the story. I think it's a beautiful panel where you can check all of that out at once. I also want to get your take on something that I feel like is coming up more often as we talk about metabolic endotoxemia, which is something that you mentioned in the beginning of the podcast. There's a lot of talk about looking at bile acid production. When you're looking at that picture, you mentioned things like fat soluble vitamins like vitamin A that can help with immunity. Are you thinking about enzymes, bile acid production when you see some of these markers out of range?

Well, and we're also thinking about development of that. So we're just starting that. So please don't call the office looking for it yet. But I'm with you. That's a lot of really fascinating, fascinating stuff. And so, like, if you asked me about bile five years ago, I would have said, yeah, it helps us detox. That's the way we get metals out of the body. Fat absorption. We certainly need it. I wouldn't have said, yeah, and if we conjugate it correctly, it becomes undecylic acid, and then that is a key mitochondrial driver or I wouldn't have said, and, yeah. Did you know we have bile receptors in our breast and we have bile receptors in our brain, and if we don't conjugate it well. Well, there's a connection between what our bile is doing and fibrocystic breast tissue and that there's a. Right. And bile's a part of all this Glip1 signaling too. So bile helps us to produce GLP1, and so it's involved in that as well. So, yeah, shout out to bile. It's more than just for detox. We're looking at developing some testing around this, too. However, you could still get a picture of that from this test. You would be seeing if 8ohTG is high. So that would give you some of that kind of mitochondrial peeing. We know that bugs can grow more in an environment where we're not fully digesting things, so maybe a little bit of an indirect piece in that direction. But, yeah, I think it's a very interesting area.

I can tell that people are just loving learning from you and are going to go sign up for your course because you're so informed, you're so enthusiastic. You could tell that you really care about your clients and are staying on the leading edge and that the reason you're so interested in these things is.

Because they work and there are medicine. They tell us you need to be doing better with diet, you need to be doing better with sleep. And these are the things that we know are more in the research than any statin ever was. Right. I mean, that just is true. There's more positive data with exercise than probably almost anything out there. There's more positive data with, like, sleep and bmi. And so all of these things are tied to those lifestyle pieces. Inflammation. How do we manage inflammation? Inflammation.

People might have heard you say GLP1. They might be more familiar with GLP1.

Same thing.

Yes. I happen to know you gave a presentation for us at Rupa. You did a webinar on GLP1 in the gut. And people might be thinking, hang on, that's something that you take. It's a prescription. You inject it or you take it. Is it in the gut. And does it have anything to do with the conversation we're having today?

Absolutely. If you are producing more lipopolysaccharides, you see the clinical data that associates them with, with weight gain and they're damaging to the gut lining. So you'll produce less GLP1 less GLP1 on your own. So a hundred percent, like in terms of semi glutides, I think they absolutely have their place. People need support. But I think for most people, even if they use that to jumpstart, they're going to want to transition off. And so one of the ways to help that transition off is to manage these other things that, that would cause us to, to gain more weight or to decrease our own Glip1 production. And lipopolysaccharides are a big deal there. And then if you absorb them, it upregulates these LOX receptors that tell you to store more fat too. So fine, people need a little extra support. Let's, let's get them started. Let's get them on either Glip1 or even some natural GLP1 agonists and then build up in your body so that you can produce your own. So as you transition off, the weight doesn't just come back, you're not in the same place again.

People's ears might have perked up when you said natural Glyp1 Agonist. What do you mean when you say that?

Okay, this is wild. So just like we have obviously bitter receptors in our tongue, if I go down into the small intestine and biopsy the area that makes our own Glip one, that the structure there looks a lot like a bitter taste receptor. And so basically we have receptors for bitter in our small intestine. And so when something bitter hits our gut lining, that's one of the signals for making our own Glip one. So this is why we see berberine show up in that capacity or hops you're starting to see in some formulations in terms of Glip one. So think bitter. And even just, you know, with our patients have them if they're like, I eat too much at dinner. Bubbly water suppresses appetite a little. And then put some bitters in it because that's going to increase your own Glip1. Now, now, other things that help us just nutrients improve Glip1. So for example, if I eat a bag of potato chips, which I would never. But if something happened and my. An alien invaded my body, so. And then I'm not full from that because there's no nutrition in it. B vitamins, vitamin D nutrition signals glip one fiber with a good healthy microbiome. More short chain fatty acids produce more Glip1. That's what's interesting. Glutamine helps us make more Glip1. So there's a lot of things that we can do naturally and they kind of what you see that they fold back into what's happening with the gut. Wow.

Okay, we're gonna link the webinar you did in the show notes because again I think people are gonna wanna go see that now. You teach for a living, you treat. Talk to us a little bit about you for a second. I mean you're so knowledgeable and I have to imagine you're so busy cause you're seeing patients. You're also building these incredible courses that I happen to know you give frequently to other clinicians. What are you up to these days? Where can people find you?

Yeah, well I have a really good support all around me. So none of these things are done in isolation. So Progressive Medical in Atlanta, Georgia, that is where I practice and with a large integrative team and we all get to work together under one roof. And like I said, it's been just a real blessing to be able to work there. And then at Precision Point Diagnostics is where clinicians are probably, probably be more likely to reach out to me. And that's some of the testing that's on rupa's platform. Getting it full scripts from RUBA platform getting it there as well. In addition to that I Origins incubator and this is where I teach a practice management group. So if this is interesting to you and you would love to get involved, but you're like what are the nuts and bolts of how do I charge cash and what is a webinar funnel and how do I market and do all that piece? I'm in partnership with Scott Ratigan, a functional lawyer and doctor Linda Mattioli who had a wait list after moving to a new city six months making a six digit figure, only working eight to three while her kiddos were at school. So she teaches all the things that she did to get started in such a successful way. And then I teach the clinical curriculum. It's a year long program. And so as you have case studies and you're wondering what test, what supplement, you submit them and we go, we meet every week and go over them. So. So I really enjoy what I do there because there's so many people that want to add this style of medicine to their practice. But just the logistics are overwhelming. So we're like, here are all the tools that we needed. Here's everything that we did. Boom.

Awesome. I can tell that you are, like, insatiably curious almost, and that you do really care because you need those two ingredients to spend as much time researching as you clearly do. I mean, you come prepared with stacks and stacks of studies. And guys, this is before ChatGPT and perplexity. Nobody was building this list for Dr. Cheryl. She was going out and reading the papers and finding it and looking on PubMed and reading the journals. I'm curious. Can we do some, like, quick questions for you? So we have a section that we call a rapid fire segment, and I want to get your thoughts on some of these before we let you go.

Go.

You've been so generous with your time so far. Let me ask you, if you had to have a career, but it could not be medicine, nothing to do with medicine, what would you love to do?

Maybe it's cheating to say ethnobotany. That might be a little too close or some type of PhD that's probably too sciency as well. But if it was going to be like, really nothing really like that. I've always thought I wouldn't mind being an aerobics instructor. Not that I'm particularly all that, but that I just get paid to get my exercise in. Every day can go around reminding people of how important it is. And even if you are not like the most ripped person out there, it's still so much benefit and whatnot. So, yeah, maybe jumping around on a.

Bench, that is so awesome. I'm not surprised you would do something with exercise. Okay, we're moving on to the questions a little more in your specialty. So what do you think is the single most predictive biomarker in early gut barrier dysfunction?

Jim? It's a little bit hard, but. But I really do think the one that has like the most studies is that LPS that we talked about because it does drive our number one disease. And they say that it's not that you get older, that you have heart disease, it's that you have more metabolic endotoxemia and that does damage over time. And so. So there's just such a depth of research and it is one of the most important things. And then it's tied into autoimmunity and cognitive function as well. So I really weight that one strongly. In terms of gut, you probably were expecting me to say zonulin because of my jumping up and down, but it's a Little more targeted, it's a little more autoimmune, and that one's a bit more broad and tied into so much of what we do.

I think we're going to look back in about 10 years and see that you and Jeff Land, there's a couple key people talking about LPS and metabolic endotoxemia who are really on the leading edge. And, you know, you guys probably feel like it's old news because you've been reading the thousands of studies for a long time, but it hasn't been widely adopted as a biomarker yet. And so I think we're going to look back and say, like Dr. Sheryl, Dr. Bland, there were some people on the forefront.

Well, you put me in some really nice company there, but that is exactly how I felt. And that like when I saw 8oHDG and then I saw literally thousands of studies and they said it's the most predictive for risk of cancer. If you get a cancer and it's high, it's more likely to be aggressive, you're more likely to have more metastasis, it's more likely to cross the blood brain barrier. And I was like, so heart disease and cancer one and two. And what is it that we're doing when we go in once a year that tells us anything about our risk? And that marker also tells me if I'm getting enough antioxidants, and it tells me about the mitochondria. And it's got such depth of clinical research that I was just like, it's a shame that this isn't done once a year on everybody. Sometimes people say, I like to buy a world of coke. I know I'm from Atlanta, but I'd like to buy a world an 8o HDG, I think.

I'm thinking some of the clinicians listening to this are going to start to do it once a year. And your panel makes it pretty easy and it's pretty affordable. So I really love that you've packaged these up like this. This has been a master class. It's amazing that. I mean, I feel like I've learned so much. We've been talking a while. Your course is overseas. Six hours of material. That's a deep dive into this. It's starting really soon. Do you want to tell people what else they're going to get in the course, where you'll go deeper with them?

Yeah, absolutely. So we scratched the surface with these topics, but in terms of food and food sensitivities, really taking the deep dive into where is the science, where is the research? Because I think that that is what we need to move the conversation forward. So we're going to compare different types of antibodies. You know, why igg? Why iga? We'll go into complement pathways more specifically and of course, some of my very favorites. We'll talk a lot about treatment, what you want to do when you see that these things are off, because removal is one thing, but there are things that we can do to speed that process up. And that's why I'm always so grateful that they're working with your platform, with clinicians, specifically, because I don't like to see people get left in that online world of order a food test, take foods out, never bring them back in. That really wasn't ever the intention, any of that testing. So in that capacity, and then we will look at how these various markers relate to different conditions. We'll walk through why, what you want to look for in terms of LPS with rheumatoid arthritis versus lupus versus others in the autoimmune continuum and really drill down in terms of multiple ways to treat these things as well.

Awesome. Thank you, Dr. Sheryl, so much for being with us today.

Yeah, it was such a pleasure. Thank you.

And so I want clinicians to know you're going to see me in the audience a bit in this course. I am looking forward to learning. Dr. Sherrill is who I go to learn from. So please join us. You can find more details details on rupeeuniversity.com and we will see you there. Oh, my gosh. Thank you so much for listening to today's episode. I've got one quick favor to ask you before you go. If you love today's episode, would you leave us a five star review on whatever podcast platform you're listening on right now? Our whole goal is education and to reach more people with this show. So you sharing your review helps more people discover this and learn something new. Thank you so much. You are the best. We so appreciate you. We'll catch you next time on the Root Cause Medicine podcast.