How to Fix the Vascular Health Crisis: The Endothelial Glycocalyx

We are living in times of great medical discoveries and advancements and today I am thrilled to talk about a relatively unknown structure: the endothelial glycocalyx (EGX). The EGX can profoundly affect overall health – after all, you can’t have healthy organs and tissues if blood vessels are not healthy. Today on New Frontiers, I am joined by Dr. Kristine Burke a board-certified family, sports, and functional medicine physician, and medical director for Diabetes Reversal Group-Sacramento, where we discuss the full breadth of EGX functions and why it’s critical for cardiovascular health and so much more. Dr. Burke shares her exciting clinical experience and impressive findings from her case study series using Arterosil for plaque regression in some of her toughest patients. It’s a fascinating and enlightening conversation, so tune in and get ready to take some notes! Plus, exclusive discounts for listeners! Thanks for listening, and for your support of New Frontiers. -DrKF

Is endothelial glycocalyx one of the more important discoveries of our medical era? And could it be profoundly affecting overall health? In this episode of New Frontiers, we are joined by Dr. Kristine Burke, who has practiced the full spectrum of family medicine since 1997, is certified in functional medicine and acts as the medical director for Help Your Diabetes Sacramento. Dr. Burke explains the many functions of the endothelial glycocalyx (EGX), various advanced lipid panels and biomarkers to assess EGX health as well as the causes and clinical signs of EGX dysfunction. She also shares fascinating results from case series based on her clinical practice of using Arterosil, a specialized sulfated polysaccharide, which led to over 50% vascular plaque regression! We also discuss how improving the functional capacity of our primary transport mechanisms benefits many areas of health and why Arterosil has a potential therapeutic role in conditions such as diabetic neuropathy, renal disease, macular degeneration, erectile dysfunction, and more.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And of course, today is no exception. I am really excited to be talking about all things endothelial glycocalyx. Really one of the most important and intensely researched areas in human health in years. I look forward to doing a deep dive today, and I will be talking to Dr. Kristine Burke. Dr. Burke is a board certified family medicine and sports medicine physician.

She is also fully certified in functional medicine. She’s the medical director for Help Your Diabetes Sacramento and has practiced the full spectrum of family medicine in California since 1997. Dr. Burke believes that the best medical care requires time, a trusting relationship, and a collaborative approach to achieve the most successful personal outcomes, good health, longevity, and a superior quality of life.

She truly enjoys caring for her patients and strives to guide them to wellness and prevention, as well as carefully managing their illnesses and medical conditions. Dr. Burke, you sound like a wonderful functional medicine doc, and I just really look forward to talking to you today. Welcome to New Frontiers in Functional Medicine.

Dr. Kristine Burke: Thank you so much, Kara. Thank you for the introduction. It’s really a pleasure to be here with you today.

Dr. Kara Fitzgerald: I also want to just tell folks, if you’re interested, I’ll have her full bio on our show notes because she’s a teacher. She’s an educator. She’s just involved in a lot of really cool stuff in the medical world and in the functional medical world. Please, take a look at that on our show notes. I’m always excited to learn more about the endothelial glycocalyx. I’m just really thrilled that we’ll get to focus on it. Of the content that we produce here at drkarafitzgerald.com, this one has probably garnered the most…

I would say maybe a top five level of interest from the professional community and people are hungry for this. Can you define the endothelial glycocalyx or EGX as it’s abbreviated? Just tell us what it is.

Dr. Kristine Burke: Yeah. I think if we start at the high level and work our way down into the details, that helps to bring in some perspective. For years, the research that’s been looking at direct visualization of blood vessel flow, we’ve seen this little invisible layer that seemed to keep the blood cells from coming into direct contact with the vessel walls. There were all kinds of theories about what that was or how that happened. Perhaps it was an electrostatic effect or some type of reflective barrier.

But as our digital image resolution got better and better and better, it could be seen that there was actually this layer of fine fibers, just a few microns thick, that creates an actual true physical barrier. Really like a slippery non-stick gel-like layer that we now know of as the endothelial glycocalyx. And that non-stick layer has a hugely important role in keeping the contents of the lumen of the vessels, so the white blood cells and platelets, from sticking to the arterial wall.

When we dive in a little bit deeper into the next layer, what’s it actually made of? It’s made up of all of these different polysaccharides, proteoglycans, glycosaminoglycans, glycoproteins, and they’re all actually anchored to the endothelial cells. That allows the fibers to sense the shear stress of the flow within the vessel. That creates a trigger for the production of endothelial nitric oxide, and we have this whole cascade of events that really come down to defining what is the health of the endothelium.

Dr. Kara Fitzgerald: It’s absolutely extraordinary. It’s just extraordinary. Do you know approximately the year that the technology was able to perceive it?

Dr. Kristine Burke: I think it was in the mid 2000s that…

Dr. Kara Fitzgerald: Oh my gosh.

Dr. Kristine Burke: Yeah. I think it was in the mid 2000s that it was very clear. There’s been research on the endothelial glycocalyx for, gosh, probably 40 years now, but it wasn’t really visualized until about 20 or 25 years ago.

Dr. Kara Fitzgerald: That’s amazing to me. It’s extraordinary. The human body never ceases to reveal more.

Dr. Kristine Burke: Yes!

Dr. Kara Fitzgerald: It reminds me of the major recent aha of discovering brain lymphatics, for example, or certainly this is paramount to the work that you and I do in functional medicine, but really appreciating the microbiome and getting that it is really just a key fundamental central player in our health. Where would you say the endothelial glycocalyx kind of falls in thinking about some of these recent and important discoveries?

Dr. Kristine Burke: Yeah, I agree with you. I think that the discovery of not only the presence of the endothelial glycocalyx, but the complexity of what it’s actually regulating. The selective permeability within the vessel, harboring the extracellular superoxide dismutase, so that it has an antioxidant role, regulating what gets through the endothelial surface. All of those, I think, the discovery of this is going to turn out to be one of the more important discoveries of this era.

Just like the microbiome, like you mentioned, it opens a whole other world of understanding of how the endothelium has such an important role in vascular health and in health in general.

Dr. Kara Fitzgerald: Yes, yes, yes. It also brings to mind the blood brain barrier. It’s almost like nervous tissue and its sensitivity or the gastrointestinal barrier. It’s just really extraordinary. But a lot of us, alas, clinicians and patients alike, we’re not getting this piece of information. We haven’t quite integrated it into our thinking as clinicians in delivering care, or as patients in wondering about it or asking about it. Still we’re focused on cholesterol, lipids, et cetera. Thinking about this, a friend of mine, I was at the gym yesterday.

And of course, I’m sure this happens to you all the time. A friend of mine had just gotten his labs done and he wanted me to look at them. He had this lipid panel LDL and HDL and triglycerides and then a handful ratios. One of the probably oldest tools that we’re using and one of the tools that is desperate for updating, and yet we’re still leaning on that. I said, “Well, first of all, you need to get an advanced panel. We really can’t make good clinical decisions from this very limited data.”

I’m going to guess that the panel came out probably in the ’50s or the ’60s, and we haven’t evolved our thinking. Here we’ve got just this extraordinary potential of looking at the endothelial glycocalyx. What are your thoughts like bridging from this old, this archaic cholesterol panel to moving into thinking about EGX and other… Well, I guess I’m thinking about labs, but just talk to me about this and where we need to go and where we are.

Dr. Kristine Burke: That’s a big can of worms, right? One of the things that’s been really fascinating to me in my movement from practicing conventional family medicine into practicing primary care from a functional medicine perspective, we all know that that’s about root cause and looking more upstream, but it’s fascinating to me to have a conventional lipid panel and then the deeper dive into the advanced lipid panel and the number of times that the conventional panel is normal or near normal while there’s a disaster behind the scenes in the LDL particle count and the density of the LDL, all of those different components that we have in the advanced lipid profile.

I love pointing out to people like, look, if we were only doing the conventional standard of care, this lipid profile, everyone would be telling you that your numbers look great. But take a peak down here. Actually this is where our looming disaster is. That’s why for half of people, their first symptom of cardiovascular disease is sudden death.

Dr. Kara Fitzgerald: Yes. Right.

Dr. Kristine Burke: Right? We don’t have a lot of opportunity to intervene if we’re not looking for something before that happens. We’re just agreeing that we’re going to let half of people go from that. I think part of what’s missing from that conversation is inflammation. We know in functional medicine that inflammation is kind of the root of all evil. Most people still think of cardiovascular disease from that cholesterol profile or perspective as this progressive clogging of the pipes, if you will.

But when you look at the data, only about 15% of cardiovascular events occur via that mechanism. The other 85% happen because there’s plaque, vulnerable plaque, that ruptures, and then a clot forms in the vessel. Inflammation plays a pivotal role in that scenario. We’ll now take that a step further and now we understand part of what makes that vessel wall vulnerable to that plaque deposition in the first place. We have an opportunity to intervene at an even higher level.

I think it also creates another way of explaining why these really important personalized lifestyle interventions that we work on with all of our patients, why and how those are so profoundly impactful in our health. Because if your vascular system, right, 60,000 miles of blood vessels, if that’s not healthy, then the rest of your tissues and organs also cannot be healthy. The vascular system can’t be healthy unless the endothelium is healthy, and the endothelium can’t be healthy unless the endothelial glycocalyx is healthy. It just becomes this domino effect that starts with the glycocalyx.

Dr. Kara Fitzgerald: Extraordinary. We’ll have to highlight and bold what you’ve just said. But it’s very elegantly stated and just a nice drill down and you bring us back to EGX. I’m assuming this is what you’re… Some version of this is what you’re expressing to your patients.

Dr. Kristine Burke: Yes, exactly. Part of what we do in our practice is an annual wellness assessment and focusing on cardiovascular risk, since about half of the population succumbs to cardiovascular disease. We really focus on cardiovascular prevention. And in that process, we’re looking at all of these components. We’re looking at the advanced lipid profile. We’re looking at the inflammatory markers, vascular inflammatory markers like Lp-PLA2, for example, or myeloperoxidase.

Those are giving us a sense of the inflammation that’s happening within the vessel wall. And also with myeloperoxidase, in particular, the fragility of that fibrous cap, right? We’re looking at that vulnerable plaque with that necrotic core, and that plaque tends to have a very thin covering, as opposed to a thicker or fibrous cap when plaque is stable, because we have all manner of different types of plaque and plaque deposition that we can have.

When we’re looking at those individual components, now we can start to understand, well, what puts this part of the vascular system at risk? We use CIMT, for example, carotid intima-medial thickness to assess the vascular age, and then whether or not there is plaque forming in the carotids, because that has about an 80% correlation with what’s happening in the coronary vessels and in the cerebral vessels. We can get a good sense of the risk profile that’s developing for any particular patient. Oh yeah, go ahead.

Dr. Kara Fitzgerald: I just want to ask you a couple things, because people, they’re vigorously writing or typing to capture some of what you’ve said. Two questions. One, can you give us the panel that you’re looking at just so I can put it on the show notes and people can see. You’re looking Lp-PLA and MPO, and you’re doing an advanced lipid panel. I’d love to just get some more granular details, and then you’re doing a CIMT and so forth, just so that I can let folks know what you do.

And then from that, and I think this is where you were headed, talk to me about what you’re seeing that’s flagging you for EGX dysfunction.

Dr. Kristine Burke: Okay. We’re looking at obviously the advanced lipids, as we’ve discussed. Specifically in there, we’re looking for the LDL particle number because that has the greatest predictive value for eventual major adverse cardiovascular event development in the future, much more so than total LDL. And as I was mentioning earlier, the number of times that I have a normal or near normal total LDL and massively abnormal LDL particle number. If we want, later we could go into that a little bit more, but really we’re looking at that advanced lipid profile.

It’s very important to also get the LPa. While that is predominantly genetic determined, and as yet, we have not been able to really move the needle on that very much with lifestyle interventions. Perhaps niacin can help with that. One of the mechanisms by which LPa leads to increased cardiovascular event risk, and in particular seems to be a big risk factor for stroke, is that it impairs the way that we can break down fibrin and fibrinogen.

That’s one of the things by regulating coagulation within that endothelial glycocalyx, that’s one of its roles, is regulating coagulation and host soluble fibrin. By addressing the endothelial glycocalyx, we can help to mitigate… Hopefully we can help to mitigate some of the risk by understanding how LPa creates risk, and then what we can do to mitigate that by making the endothelium healthier. That’s one of the things I like to look for.

Dr. Kara Fitzgerald: Let me ask you right there because we’ve got exactly nudging LPa is… It just really doesn’t happen. It’s pretty challenging. And therefore, mitigating risk is also what we’ve concluded as well. When you see an elevated LPa, would you start using Arterosil with that? Or would you focus on EGX automatically? Or would you look at the whole picture and evaluate risk based on your full workup?

Dr. Kristine Burke: Boy, that’s a tough question. I think kind of all of the above. I think we don’t have data specifically looking at targeting the glycocalyx and LPa or with what I use to target the endothelial glycocalyx, which is Arterosil, and we can talk a little more about that too. But just looking at it from a physiologic and mechanistic point of view, it absolutely makes sense to me that the more we can support normal and healthy function of the endothelial glycocalyx, the more opportunity we have to lower those risks.

Yes, I would definitely be thinking about turning to Arterosil, one of the things that I use to address the EGX. We’d also be doing all of the things that we normally do from a personalized lifestyle perspective and some of the nutraceuticals that we may be using to help with vascular inflammation and some of the biochemistry involved in that. And then looking at the person’s whole picture, because we know that one genetic abnormality doesn’t necessarily…

It’s not an inevitability that something’s going to happen. But the more of those that we have, or the less equipped we are in one particular area of the physiology to be able to deal with clotting regulation, for example, then the higher that risk becomes. It’s each of those things in their own way.

Dr. Kara Fitzgerald: Right, right, right. Taking a full picture and then layering on… Well, a full functional approach and then layering on additional interventions like Arterosil. We scratch our heads. I actually have a blog on LPa and interventions on my site I wrote quite a while ago, and I just feel like I should circle back and talk a little bit about the endothelial glycocalyx and Arterosil because it was exactly what you do. How do we approach this functionally and mechanistically? How can we support people who have really high LPa? Because it is difficult and there’s not a lot we can do.

Dr. Kristine Burke: Exactly. I think too, understanding that the inflammation and the oxidative stress or excess reactive oxygen species are some of the catalysts for hypercoagulability. We know that the EGX actually supports extracellular superoxide dismutase. It has a very important antioxidant role. You can imagine, I like to imagine the EGX is this kelp forest. This is like the little visual that I have in my head, and it’s this kelp forest that has an ecosystem. And within that ecosystem, we’ve got the extracellular SOD.

We’ve got maintenance of some of those coagulation factors soluble fibrin and maybe antithrombin. We have the protective, the physical barrier that the EGX creates. All of those play together. If you imagine the difference between this robust fluffy ecosystem of this endothelial glycocalyx kelp forest versus one that’s been stripped and maybe is denuded and it has bare patches or is very short and doesn’t have a lot of real estate, if you will, to support that infrastructure, you’re going to have a really different physiologic impact between those two things.

Dr. Kara Fitzgerald: Who is the person with a sheared endothelial glycocalyx? How are they presenting? I mean, there’s obviously a continuum. Just talk to me about that.

Dr. Kristine Burke: Yeah. We don’t yet have a way of clinically directly visualizing what’s going on in the EGX. We have to rely on indirect measures of that. One of the things I like to look at is ADMA as a measure of the ability of the endothelium to generate nitric oxide and to respond to vascular stress by being able to produce nitric oxide. If we back that up, what are the things that create a dysfunctional or an unhealthy EGX? It’s really all of the things that we focus on in managing lifestyle induced risk.

High levels of glucose and insulin, oxidative stress that we’ve just talked about, toxins, infections, stress, sleep deprivation, sleep apnea. It is a very, very dynamic structure, and it is unfortunately very easily damaged, sometimes even within just a few minutes or hours of exposure. But luckily on the flip side of that, it is also readily regenerated. Just like regenerating any other tissue, in order for us to be able to regenerate that, we need the building blocks to regenerate it. That’s where Arterosil, which contains this specialized sulfated polysaccharide called Rhamnan Sulfate, is a building block to make those fibrils that create the EGX.

Dr. Kara Fitzgerald: It’s just really cool.

Dr. Kristine Burke: It is really cool.

Dr. Kara Fitzgerald: ADMA, people, just to go back to that, that’s asymmetric dimethylarginine. When it’s elevated, that individual is inhibiting nitric oxide production. It’s a useful marker and we can actually get it covered by insurance, I think, pretty readily through Cleveland Heart Labs, right? Are they offering it through Quest, I believe.

Dr. Kristine Burke: Yeah, yeah, they are. And in fact, I use that Cleveland Heart Lab vascular inflammatory panel as a good profile. And that has the Lp-PLA2 and the myeloperoxidase. It includes the ADMA. It also looks at microalbumin creatinine ratio, which is a measure. It’s interesting now, because I’ve been doing those labs for a long time, and now to add in this layer of understanding of why those all reflect vascular health, literally each one of them is linked back to the EGX.

Looking at microalbumin creatinine ratio right, we’re looking at protein leak across an unhealthy endothelium. What regulates that selective permeability, it’s the EGX. We’re looking at ADMA as a measure of the ability to produce nitric oxide. Well, what regulates the production of nitric oxide? It’s the transduction, the shear stress assessment of the EGX that’s transmitting that signal into the endothelial cells to signal for the production of nitric oxide. They all circle back to the EGX, which I just love, right?

It’s like you take something you’ve been doing, and then now all of a sudden, you have this opening of your eyes to the reason why those all make sense as markers.

Dr. Kara Fitzgerald: What are you actually seeing? How long have you been using Arterosil in practice?

Dr. Kristine Burke: I’ve been using it for about three years now.

Dr. Kara Fitzgerald: Okay, okay. I know you did. You collected a case series. I mean, when you started to use it, did you see evidence on labs and clinical response that you were actually making a difference in these numbers? I mean, I know you have your foundational lifestyle piece, and that’s essential,  diet and lifestyle. Of course, foundational. We know that you do that as a functional medicine physician, and then you’ve layered in over the last three years Arterosil. What have you seen?

Dr. Kristine Burke: When I first learned about Arterosil, I came back to my practice and was like, all right. Like I generally do to new products, which is super unfair, is I try it in my hardest people, the ones that I haven’t been able to get success with, with everything else that I’m doing. It’s like, all right, you think you can add something to the mix here? You’re going to perform on the toughest cases. That’s what I did. I started with one of my patients. She was 70at the time. She had a really big load, a big eccentric plaque burden. Her cardiac cath looked clean, but her vessels were loaded. She had a calcium score, a coronary CT calcium score, of like 1,500, which is massive.

Dr. Kara Fitzgerald: Wow!

Dr. Kristine Burke: All of her plaque was basically eccentric, going back to what we talked about at the beginning, right. A massive plaque burden, but not obstructive. Just high risk for a rupture. I had been managing her as best I could with all of the tools in the toolkit, resveratrol. I can’t even remember the kitchen sink I had thrown at her. And then I added in Arterosil and we got like a 50% reduction in her plaque in about six months. Obviously I was blown away by that. I just started adding it to a bunch of the people in my practice that I called the tough nuts.

I had a 50-year-old high level athlete with a bad family history of cardiovascular disease, multiple sudden cardiac deaths in their fifties. I had like a 70-something year old diabetic with known coronary artery disease. And then I had like this 62-year-old executive with autoimmune disease. A lot of different reasons why people had this final common pathway of cardiovascular disease. I just started adding it.

And then when I repeated their studies and we actually did this as a retrospective case series, we had on average this greater than 50% reduction in plaque. I had multiple years of carotid evaluations on all of these patients, and most of them I was able to stabilize. Stop their plaque from continuing to progress and continue to accumulate. Fantastic accomplishment. In a few of them I had some regression.Maybe I think on average the number came out to be about 22%. Then we add in Arterosil and we’re way over 50% plaque regression. Like literal regression.

Dr. Kara Fitzgerald: Extraordinary.

Dr. Kristine Burke: Yeah.

Dr. Kara Fitzgerald: That’s extraordinary.

Dr. Kristine Burke: It really was extraordinary. When something can come in and perform in those most difficult cases, that really gets your attention. From a lab perspective, we did go back and analyze the laboratory numbers. The only one that was statistically significant in that small… Our case series was just 10, so hard to achieve statistical significance with such a small number. But for Lp-PLA2, that lipoprotein phospholipase 2, the inflammatory marker that’s released from the foam cells.

When the macrophage eats up the oxidized LDL and becomes a foam cell and releases that Lp-PLA2, we use it as that marker of vascular inflammation. That did actually significantly reduce in the patients who were taking Arterosil. Now, it’s a retrospective series, right? So causality, difficult to say. But just understanding the mechanism, it makes sense that if we’re restoring and repairing the EGX, that we’re replacing that non-stick lining, we’re going to be changing the ability…

Those bare patches become sticky spots where leukocyte adhesion occurs, platelet adhesion occurs, cholesterol or LDL adhesion occurs. All of those are the gateway to those things getting through the endothelium and into the vascular wall where they create that inflammatory process that ultimately ends up in plaque development.

Dr. Kara Fitzgerald: Just really fabulous work. I encourage you. I mean, 10 of your toughest cases, I know in the world of large clinical trials, it’s small. In the context of clinical process, it’s extraordinary that you put this together and you did such careful analysis. I just really applaud you, because I know it’s challenging to track and do it. I hope that you write it up. If I can support you in any way, you need a postdoc in your practice, but I would love to see it published. It’s really important what you’ve found.

Dr. Kristine Burke: Yeah, I think you’re right. I have interns in my practice that do a medical scribe internship in their gap year between college and while they’re applying to medical school. I just started doing that a few years ago, and it has really brought in another layer of enthusiasm and really interesting expertise in these young doctors-to-be. We’ve been trying to work on improving our data collection processes and getting some of those ducks in a row so that we can start to hopefully put out some of this clinical research, even if it’s just descriptive like this, right?

Showing what we did and what changed and what our understanding is of why that happened. I think that’s important info to get out.

Dr. Kara Fitzgerald: Oh, it’s extraordinary. I mean, speaking to the choir, I published in 2011 a collection of case studies. So yeah, 100%. 100%. We’re continuing to do research looking at epigenetic changes, DNA methylation, and we just finished a cohort of seven that I would like to publish as a case series. I really applaud you and support you, anything I can do in that place to kind of elevate what you’ve done. It’s very important. It’s the first line of inquiry. We’ve got to get it out there even though some trialists perhaps poo-poo it. It’s essential.

Dr. Kristine Burke: Yeah, it’s the first step.

Dr. Kara Fitzgerald: It’s the first step. I’ve got more questions for you. I want to eventually guess to your thoughts. But before that, I’m going to throw in some other questions around cardiovascular disease, but eventually I also, so I don’t forget, want to put a pin in thinking about where you’re using Arterosil elsewhere. I had an awesome conversation with Holland Messier, and we ended up just sort of looking at it mechanistically and thinking about using it in intestinal permeability and for other indications. I would like to see if you’ve moved there.

But before we go there, I first want to ask you how you’re dosing Arterosil in these tough patients and in general. Are you using the recommended dosing? Answer that one first.

Dr. Kristine Burke: Okay. I do typically use the recommended dosing, which is one cap BID, twice a day. Some patients get weary of the multiple times per day dosing. I have even used it as just two caps once daily and seem to get equivalently good results. But what’s been studied is one cap twice a day, if we want to stick with that. In neuropathy in particular, which, there has been a study on diabetic neuropathy specifically, and in neuropathy, it seems to be more effective at a higher dose. That’s two caps BID in that instance.

Dr. Kara Fitzgerald: That’s still not bad.

Dr. Kristine Burke: No, no, it’s not bad at all. When you start expanding the way you look at the mechanisms by which these disease states develop, and you’re thinking about it from the perspective of the organ and the tissue can’t be healthy without healthy blood flow, and then that whole cascade that we talked about at the beginning with the endothelium and the endothelial glycocalyx, you start to just see potential for Arterosil or attention to the EGX everywhere, right? In renal disease, renal insufficiency, in visual change.

Macular degeneration is a target that we’ve talked about looking at. These are all speculative at this point, but it makes sense that these things that have to do with abhorrences in the health of the vessels are going to, at least in some part, be improved by attention to the EGX, which is the thing that keeps the vessel healthy.

Dr. Kara Fitzgerald: Any anecdotal experience you can share in using it in renal disease or macular degeneration or any other condition where you’ve used it sort of “off label?”

Dr. Kristine Burke: Yeah. I’ve seen improvements in the MACR, the microalbumin creatinine ratio. Oh, and another place that it performs well, literally and figuratively, is in erectile dysfunction actually, which ultimately is a plumbing problem. There definitely you see clinical benefit. I’m trying to think off the top of my head. Those are probably the main ones where I feel certain that I have seen a direct impact of Arterosil. Others are more subtle, I think, right? You see overall improvement, or you see reductions in…

It’s kind of like asking, how do we prove that this or that lifestyle intervention has improved this particular individual’s health, life, or longevity, and short of the epigenetic methylation, which now we are able to start proving it. I love your work in that.

Dr. Kara Fitzgerald: Thank you.

Dr. Kristine Burke: I think that’s going to be another interesting target, right? Like looking at it before and then bringing in an intervention like Arterosil, and then looking at what happens afterwards, because all of these things fill up that bucket of inflammation and of resilience.

Dr. Kara Fitzgerald: Yeah, absolutely. I love the other ways that you’re using it. Diabetic neuropathy, renal disease, macular degeneration, erectile dysfunction, and still dosing it as directed on the label in general.

Dr. Kristine Burke: Yes, in general.

Dr. Kara Fitzgerald: Which is so simple.

Dr. Kristine Burke: Yeah. And then from a practical standpoint, people can get a little bit weary of their supplement regimens. I have, again, off label, used it at a more maintenance level when maybe I don’t have active plaque, but I have family history of risk. The inflammation markers look good, but we still want to add this in. I will sometimes drop it down to one cap daily just to keep people engaged, keep those building blocks available to repair the EGX as damage occurs with what we do in life.

Sometimes I’ve done pulse dosing when cost is an issue for people. Most of the studies that Calroy Scientific has done using Arterosil have been looking at eight week treatment intervals. And that’s where we’ve had like profound reduction in that vulnerable plaque, that necrotic fatty core in the plaque, or reduction in plaque in the aorta in an animal study. These shorter term interventions have these big results.

I’ll do it for two months, and then have them maybe stop for two months, and then bring it back for two months, and just kind of keep pulsing it at what I know has been proven to work. Just anything to be creative to keep them engaged and keep them using it.

Dr. Kara Fitzgerald: In your retrospective analysis, was it an eight-week interval that you saw these really big shifts?

Dr. Kristine Burke: No, that’s funny that you ask that. No, it was a hot mess. Because when I started off recommending Arterosil to these patients, it was in my mind kind of experimental. And then it wasn’t until I had that first couple of cases where I had these profound results that I decided to go back to study those patients at this point in time, which was about six months or so after I had started recommending it. When we looked at how people had used it, most of them had used it as directed.

But oh my gosh, some of them had used it like for just two months and then hadn’t used it again, or had used it sporadically over the six month period. Initially when we were looking at the data, I thought, well, this isn’t even going to be useful. And then I started thinking, well, this is real life. This is the reality of clinical practice. I mean, patients don’t always do exactly what we ask them to do despite our best efforts. Even in that real world reflection, we still had really amazing results.

Dr. Kara Fitzgerald: That’s just so cool. I appreciate you saying that, because it is true. You are still wrapping your head around its power. I can imagine how you speak to your patients about it now has changed.

Dr. Kristine Burke: Yes.

Dr. Kara Fitzgerald: I mean, we can improve adherence considerably when we’re really clear of how essential an intervention is. If our patient actually gets that, I think we can see adherence rates really skyrocket. Initially you were still sort of putting your toe in the pond, and I’m thrilled that people hung with it long enough and that you were able to go back and look and see these extraordinary findings.

Dr. Kristine Burke: Yeah, exactly. There’s a huge difference between saying, “Hey, let’s try this. The research behind it is really amazing,” which is still motivating for people, especially people like this who you’ve been working with for a long time. They’re super engaged already.

Dr. Kara Fitzgerald: Yes, yes, they trust you.

Dr. Kristine Burke: But the difference between that and, “Hey, I’ve had these unbelievable results and I want the same thing for you,” those are two very different deliveries.

Dr. Kara Fitzgerald: Yes. Yeah, that’s right. I’m really excited for your work. It’s just really cool. I think you’ve already alluded to this, but the continuum of plaques and risk profiles in general, the different type of plaque, you’re just… I mean, you’re seeing extraordinary benefit, regardless of the starting point or the risks.

Dr. Kristine Burke: Yeah, we are across all different varieties of plaque. Mind you, in the clinical setting, I’m really, for the most part, just looking at the carotid CIMT. We don’t have the research level definition or detail like in… One of the studies that was done by Calroy on Arterosil looking at vulnerable plaque, and in fact, the study that helped it get patented for the regression of vulnerable plaque, that uses a technique called MRI plaque view. Right now that’s still only available in the research setting.

It will, I’m sure eventually, have a clinical application because it gives you so much more detail about the morphology of the plaque. I don’t really have the capacity in my practice to see, does it look necrotic? Does it look this, that, or the other? We’re really only able to measure the burden of plaque. We can see whether plaque is soft or heterogeneous or calcified. It was very interesting because we saw a shift of the plaque morphology into predominantly heterogeneous. Nobody really knows what conclusion to draw from that.

We certainly didn’t see that that created any increased risk of events or anything like that. We had no adverse events at all in any of the studies actually, which is an important thing to point out is the safety of Arterosil is phenomenal. Literally no contraindications and no adverse events to speak of. But I thought that that was very interesting. Because if nothing else, it at least illustrates that we’re definitely getting remodeling of the plaque. And then when the more detailed analyses are done with MRI plaque view, that is exactly what we see that there’s significant remodeling within the plaque itself.

Dr. Kara Fitzgerald: Just very exciting. As we head towards home, I wanted to just touch on… I want to see where we’re headed with EGX and maybe future research directions, et cetera. But you made an important point about nutrient delivery and needing a functional endothelial glycocalyx for that to happen. Here you are treating your patient with awesome, full-on functional medicine. They’re on a perfect diet, and they’re taking extra nutrients as you’ve prescribed. You see evidence for it, et cetera.

But they’ve got a really damaged endothelial glycocalyx. I mean, would you say that’s a fundamental piece? It’s almost like healing an intestinal barrier that nutrient delivery is greatly compromised. Do you suspect just clinically that repairing EGX helps your foundational functional interventions actually work better?

Dr. Kristine Burke: Oh boy! I mean, intellectually, I would expect so. That’s a really hard thing to measure. Like so many things in functional medicine, we’re doing so many things at once, which is what makes proving our work challenging. But it certainly makes sense that if you’re improving the functional capacity of one of your primary transport mechanisms, that it only stands to reason that, of course, you’re going to have improvement in delivery.

Dr. Kara Fitzgerald: Yes. Yeah, it does. It really does. Maybe one day we’ll be able to analyze that. I don’t know, look at certain tissue levels of nutrients and see if we can visualize a change based on treatment with Arterosil. Yeah, that would be cool, but perhaps a far off pipe dream.

Dr. Kristine Burke: I know.

Dr. Kara Fitzgerald: Something we can talk about at the IFM, AIC, in the chat this year or whatever. What are you most excited around? I mean, there’s lots here to be really thrilled. Where do you see research heading? Are you going to continue to involve your clinic in research? I mean, where’s this world going, the world of endothelial glycocalyx care and Arterosil and some of the science.

Dr. Kristine Burke: I mean, it’s heading to be a foundational piece of what we do just like the microbiome and helping to improve and augment the health of the microbiome has far reaching effects in immunology and neurology and all these different fields. I think the same is going to be true of the EGX. I think because of what I do so much in my practice, I’m really excited by the idea that focusing on the EGX and the health of it has the capacity for such phenomenal plaque regression. I think it creates such a compelling target for therapy and for intervention.

But the ability to impact things like neuropathy, which is so debilitating and difficult to treat, I think that’s amazing. We talked a little bit about macular degeneration, if we could have something that we can do that could impact the ability for people to maintain their sight and their vision. The big possibilities are really life changing for people. It’s like you said at the beginning, this relatively unknown structure has been discovered. And now we’re opening up to this world of huge impact on human health. I just think there’s much more to be discovered here.

Dr. Kara Fitzgerald: Well, I certainly hope you and I have another conversation, and I’m sure that our listeners would like that to be recorded on New Frontiers or, in some way, be able to disseminate it out to clinicians and just regular people alike. It has been great, Kristine. You’re such a font of knowledge and you’re doing such good work in your clinic. Again, thank you so much for joining me today.

Dr. Kristine Burke: Oh, thank you so much for having me. For the listeners who are interested in learning more about Arterosil, they can go to arterosil.com/newfrontiers. Arterosil is spelled A-R-T-E-R-O-S-I-L. Arterosil.com/newfrontiers. There’s a discount available for listening to the podcast and lots of great information, including links to all of the research, if you want to learn more about it.

Dr. Kara Fitzgerald: And we will splash that far and wide on our show notes and on our email send as well. If you didn’t get a pencil and write that down, just head over to the show notes page and you’ll see a link to it there. Again, Dr. Burke, thank you so much.

Dr. Kristine Burke: Thank you, Kara.

Dr. Burke, medical director and CEO of the True Health Center for Functional Medicine in El Dorado Hills, CA, specializes in family, sports, and functional medicine. She also has served as chief of family medicine at Mercy Hospital of Folsom, assistant clinical professor of preventive medicine at Loma Linda School of Medicine, and as an educator and facilitator for the Institute for Functional Medicine. Additionally, she contributed to the development of the COVID-19 Virtual Care pathway for VirtualPractices.org and The Institute for Functional Medicine’s COVID-19 Task Force. Dr. Burke received her M.D. at University of California School of Medicine in Davis, Calif., and is board certified in family medicine, sports medicine, and integrative medicine.

Dr. Kristine Burke bio

Dr. Kristine Burke Lab Panel, done at Cleveland Heart Lab:

• • Advanced lipid panel with NMR (includes LDL particle number)
  • Lp(a)
  • Inflammatory markers (hsCRP, LpLA2, myeloperoxidase)
  • ADMA for endothelial dysfunction
  • Microalbumin/creatinine ratio
  • Markers of oxidation: F2-isoprostanes, oxidized-LDL
  • Fasting Glucose
  • GlycoMark®
  • Hemoglobin A1C (HbA1c)
  • Fasting Insulin

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Studies:

Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function. (Wiley Interdiscip Rev Syst Biol Med, 2013)

Effect of the endothelial glycocalyx layer on arterial LDL transport under normal and high pressure.
(Journal of Theoretical Biology, 2011)

The Role of the Endothelial Glycocalyx in Advanced Age and Cardiovascular Disease. (Curr Opin Pharmacol, 2019)

The endothelial glycocalyx promotes homogenous blood flow distribution within the microvasculature.
Am J Physiol Heart Circ Physiol. 2016

Endothelial glycocalyx and severity and vulnerability of coronary plaque in patients with coronary artery disease. (Atherosclerosis, 2020)

Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo, Diabetes, 2006.

The endothelial glycocalyx: a potential barrier between health and vascular disease.
Current Opinion in Lipidology. Opinion in Lipidology, 2005.

The endothelial glycocalyx: composition, functions, and visualization. (Pflugers Arch – Eur J Physiol, 2007)

Vascular Endothelial Glycocalyx as a Mechanism of Vascular Endothelial Dysfunction and Atherosclerosis., (World Journal of Cardiovascular Diseases, 2020)

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