Episode #115: Joint Hypermobility and EDS with Michael McEvoy

Welcome to Better Health Guy Blogcasts Empowering your better health and now here's Scott, your Better Health Guy. The content of this show is for informational purposes only and is not intended to diagnose, treat or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or or his information to facilitate self treatment. As always, please discuss any potential health related decisions with your own personal medical authority.

Hello everyone and welcome to episode number 115 of the Better Health Guy Blogcast series. Today's guest is Michael McAvoy and the topic of the show is hypermobility and Ehlers Danlos syndrome. Michael McAvoy is the founder of Metabolic Healing and co founder of True Report, a nutrigenomics assessment. Michael is recognized as a thought leader, systems creator, educator and integrator of diverse clinical modalities. Michael has created the Metabolic Healing Institute out of the need for deeper clinical applications and clarity of vision in the field of functional medicine and integrative health care. Through unique educational and teaching endeavors. Michael's objective is to assemble a network of the world's top clinicians to meet the demands and challenges of 21st century Functional medicine and to implement the analytical tools and frameworks required. And now my interview with Michael McAvoy.

This is a show that I've wanted to do for quite some time. Today we'll be talking about joint hypermobility and Ehlers Danlos syndrome. Michael McAvoy is an expert in these conditions and many others. I'm honored to have him on the show today. Thanks so much for being here, Michael.

Thank you for having me, Scott.

So first let's talk about how you became so passionate about finding solutions for complex chronic illnesses. Did you have some type of personal health journey that motivated you to really devoting your life to helping other people?

I did when I was in my early 20s, so I'm now 40 years old. I had a health crisis that was the result of traveling overseas and as a result of that my health sort of collapsed and that led me to a journey to want to learn everything I could possibly learn about making my health better. And consequently, as a result of all of this, I've been engaged in research over the last 15 years and with the advent of some of the more progressive research that's evolved, I've been fortunate enough to basically devoted my life to this work.

So in the realm of what we're talking about today, were there some specific mentors or key guides that kind of helped you put the puzzle pieces together around Hypermobility Ehlers Danlos, rccx. All the things that we're going to talk about next.

Yeah, I mean, I'd like to really say that I'm very grateful for the important research that has been done by so many pioneering scientists as well as collaborations that I've had with many very bright and brilliant people. And it's really important to be able to go deeper into the subject matter of complex illness. And by doing this it means that we have to constantly be pushing the boundaries of what we know and what is possible. And so I'd really like to personally thank the following individuals for their research and in some cases their collaboration. So, Deborah Cusack, I would like to thank her specifically as it's related to hypermobility syndromes and EDs. I would like to thank Dr. Sharon McGlathry for her elucidation of the RCCX theory. I'd like to thank Dr. Robert Navio for the cell danger response research that he's been pioneering. Dr. Eric Gordon for his collaborations. Lynn August for hers. Dr. Emmanuel Revici, who is a pioneer in the field of systems biology as it's related to chemistry and physics. Sandeep Gupta, Sean Bean and Keith Bernstein. So these are just a few of the many people that have greatly influenced me and are continuing to do so.

That's an amazing list. I mean, I get the chills just from hearing that list of people because they're all so brilliant. So yeah, that's fantastic. And thank you as well.

Yeah, I would also like to personally thank many of the unknown people that don't get credit for their contribution. And this has to also go out to many of the patients. I've learned more from working with people with complex illness than I have from any textbook or any scientific study that I've ever read. Because it's really their own subjective observations of what is going on with their bodies and their ability to report that that is so critical in clinical decision making. And so that really has to be put out there.

Beautiful. Let's start by talking about joint hypermobility syndromes. What is joint hypermobility syndrome and how is it assessed?

So joint hypermobility syndromes can be thought of as a sort of convergence of different either diagnosable or non diagnosable conditions that involves joint laxity. And the most commonly diagnosed joint hypermobility syndrome is known as EDs or Ehlers Danlos syndrome. And there's other conditions like Marfan syndrome which are considered to be similar. Now we have to also realize that there are many people in the population who have undiagnosed hypermobility syndromes or have been given an EDS diagnosis but actually may have something else going on. So eds as well as Marfan's disease or Marfan syndrome are essentially congenital conditions where it's believed that there's some genetic defect that has led to a breakdown of collagen or the inability to form certain types of collagen or collagen constituents. We know that there are 30 major types of collagen, but there are potentially hundreds of other collagen like components that are involved in the, the connective tissue system. And so it's often very difficult to appropriately distinguish between who has a congenital form of EDS versus who has some acquired form of joint hypermobility. And there's often a lot of overlap. So there's basically two major types of initial criteria used to diagnose the problem. And this is known as the Beighton Scale, which is an older model that is a very simple clinical assessment that you can do in an office setting in a matter of seconds or even a couple minutes. And the other is a more recent inclusion of this criteria known as the Brighton Scale. The Brighton Scale is a little bit more accurate because it includes the Beighton Scale as well as a number of other metrics and variables to help sort of overall diagnose the likelihood that there's something going on in the collagen system.

And these are tell us a little more about those assessment tools. So are they like looking at how far you can bend your pinky or your wrist or something along those lines?

Yeah. So very simply, we can actually go through the five major criteria for the Beighton Scale Hypermobility assessment. So it's a nine point scale that is usually done clinically and it's basically so that there's the pinky assessment where you bend the pinky finger back. And if the pinky finger can extend back more than 90 degrees, that's given one point for each hand and then the next one is the thumb exercise. With the thumb you press towards the forearm and if the thumb can touch the forearm, you add a point for each arm. The other one is the elbow extension with the palm facing out. If the elbow hyperextends on both arms, that's one degree or one point for each hand, arm and then the knees. If the knees hyperextend, that's one point for each leg and then forward flexion of the spine. If your palms can touch the floor with the knees straight, that's considered to be one point. So there's limitations with that, because there could be injuries that could have created a situation that led to those kinds of abnormalities from occurring. But there can also be many other things going on with the collagen system that that Beighton scale cannot appropriately catch. And so this is why the Brighton Scale was sort of put together. I should say. I'm not an expert at the Brighton scale. I know that this is something that's used. And they include a number of other types of criteria that look at the overall possibility that a person has something going on with their connective tissue system, which would either require an EDS diagnosis or something else.

What are the primary symptoms that you see in someone that has joint hypermobility syndrome?

It's important to point out that there's a number of overlapping comorbidities that people with joint hypermobility frequently have. And if you start to go into the research, you find that these comorbidities are very common and that in fact the so called joint hypermobility, that is the presentation physical symptoms, is only really the tip of the iceberg. And I would just say. So I'm going to just speak from my current clinical experience of what I've been witnessing recently with clients that have some type of joint hypermobility going on, that the most common overlapping symptoms and comorbidities include whole body pain, fatigue, postural orthostatic tachycardia syndrome, mast cell activation syndrome, autoimmune, some kind of an autoimmune disease, chronic digestive issues. And then the other one, last but not least, is Lyme disease bringing up the rear. There's probably a number of other ones, such as anxiety disorders and anxiety and depression, but particularly anxiety disorders. And that, that, that research has been sort of pioneered by Jessica Eccles out of the uk, who found that people with joint hypermobility tended to have abnormal brain structures. They were looking at studies that showed that the amygdala and the hippocampus were sized different volumes for hypermobile patients. And so that tended to overlap with the symptoms of anxiety. So as you start to sort of peel away the onion, you begin to realize that there's a lot more going on among people with joint hypermobility syndromes. And it often takes decades. A person could have joint hypermobility their entire lives and never are diagnosed with EDS until their late 40s or early 50s. And it sort of becomes a breaking point in their own personal understanding of why they've been so sick with so many different problems for so long. So in that sense the diagnosis is good because it helps to sort of more accurately pinpoint the overall problem. But I should also caution that with any diagnosis, you want to really kind of focus on what the underlying mechanisms are that are driving these symptoms. And that's what I hope that we can sort of come away with today.

So in joint hypermobility syndromes, would you say that they are more common, congenital or acquired? And when they're acquired, what are some of the more common triggers that lead to the hypermobility syndrome?

Yeah, that's a very good question, and it's an important question to ask because there can be both acquired joint hypermobility as well as congenital, which is more common, is not entirely clear. There's a lot of cases of EDs that are made that are diagnosed even by geneticists that are misdiagnosed as EDs, when in fact, there's underlying infections that seem to be causing the symptoms that look like eds. And so, again, most of the. Most of the people that have been diagnosed with EDS have been done through, have been diagnosed by a geneticist. However, even still, most of the diagnosed EDS conditions are done without any genetic testing. And so a lot of this is done by observation, by looking at family histories, by looking at the overlapping symptoms that seem to manifest with eds. And the fact that genetic testing is actually very limited in diagnosing the most common forms of EDS tells you that we have to sort of look at the problem differently. And we know, for example, that certain types of infectious bacteria like Lyme disease and Bartonella can cause in some people what looks like eds, what looks like joint hypermobility. And there was a paper that was published a couple years ago, this was on a veterinarian, and she was diagnosed with Type 3 EDS, which is considered to be one of the most severe forms because it affects the vascular system. It turned out she had Bartonella infection. And so when she was aggressively treated with antibiotics for Bartonella, her EDS hypermobility resolved. So it tells you that there can be an acquired component that is due to some environmental vectors.

And would you say that things like mold illness or mold exposure, heavy metals, potentially, can those be triggers? What about certain medications like fluoroquinolones?

Yes, I do believe so. As you start to look at what is going on with the connective tissue, particularly the extracellular matrix, which we're going to talk about, is so integrally involved in the formation of our connective tissue collagen and our cellular scaffolding that sort of holds together the bag of our physiological tissues is you start to realize that there's a Lot of different environmental components that can be affecting our connective tissue. As you mentioned, fluoroquinolone antibiotics like Cipro and Levaquin, for example, one of the ways that they work is by causing a breakdown of collagen and connective tissue. And this can be a major problem, especially if there are people in the population that have genetic susceptibilities that could impair their ability to properly synthesize connective tissue. I've witnessed clinically how fluoroquinolone antibiotics used on these vulnerable people can cause lifelong problems that manifest in severe problems with connective tissue dysfunction. But there are other environmental vectors, like I believe that various toxins, according to the literature, mercury, for example, can cause disruptions in the synthesis of metalloproteinases, which can lead to the breakdown of the connective tissue. We know that Lyme and Bartonella, for example, can do the same. And so we have to be considering these things when we're talking about hypermobility syndromes.

In the clients that you've worked with. Would you say that if we look at the congenital group versus the acquired group, is one more difficult to treat, or do they both respond to treatment?

Both are difficult. The congenital form is probably the more difficult to treat because of the fact that there is supposed to be, or there supposedly is an underlying genetic component which predisposes them to not being able to make collagen in the right way or in the right amount. I would argue actually that the most difficult case is to treat with people that have both a congenital weakness as well as some other environmental factor that is at play. So, for example, I have people that have been diagnosed with classical eds, but they also have Lyme disease and Bartonella infection, and they have always been hypermobile, but suddenly their entire connective tissue system shuts down seemingly altogether after they were infected with the bugs. So those are probably the most difficult is that they have both going on.

Let's talk about the extracellular matrix. I know that's a topic that gets you rather excited. It's one that I've Learned about from Dr. De Keto Klinghardt for many years. So what are the functions of the extracellular matrix? What role does it play in joint hypermobility syndromes?

I want to start by taking a sort of big picture, 5000 foot overview of physiology and sort of where we are today. And I want to really, really emphasize why I think it's so important to begin taking a systems biology view to the problems that we face today with chronic disease. And it's because we sort of have this tendency as humans to sort of apply this linear and sort of reductionistic view to the human body. You know, we have in medicine, for example, specialists in every type of medicine. We have gastroenterologists, cardiologists, endocrinologists, etc. We have specialists that specialize in single systems. We have geneticists that specialize in genetics. And so the problem with that is that we will eventually get to a point where we realize that there are a continual interaction with all physiological systems. So, for example, I try to avoid even talking about the immune system as an immune system, because in actuality, the nervous system, the endocrine system, the immune system, the digestive system, are all very much related to one another. And so it's really important to try to see the bigger picture and to understand that the human physiology is a truly holistic system that is working in concert with all different, so called separate systems to respond to different threats of danger and to try to establish homeostatic equilibrium and balance as a sort of whole system. And so when we talk about the extracellular matrix, we have to apply that same type of thinking, because if we don't, we sort of are trying to like partition it off from how cells behave and function, when in fact, we can't talk about how cells behave and function and how they communicate and how they operate in a holistic system without talking about their extracellular environment. There is really a difficult, it's really difficult to separate out the barriers and the walls and where do the barriers begin and where do they end? And so I want to try to at least have that conversation as we're talking about this. What we know is that the extracellular matrix as a system is sort of the tissue that holds cells together. It provides the structural scaffolding, it provides the container for all of the relationships of different cells and cell types to exist. It helps to modulate the cell life cycle. So our ability for cells to undergo apoptosis, cell death, or to sort of maintain their function in a healthy way is largely held together by signals and cues from the extracellular environment. The extracellular matrix importantly regulates a number of different growth factors and how these growth factors are able to sort of go out and influence the physiology in different ways. So, for example, we'll look at this later. VEGF and TGF Beta 1 and IGF 1 and all of these different growth factors, fibroblast growth factors, all of these playing a diverse role through multiple physiological systems. They depend upon activation points within the extracellular matrix. In the connective tissue system. We know from some of the research of Pissinger and Hein, the Germans, that different immune cytokines are interacting directly with the connective tissue system. And so this has wide reaching implications on autoimmune disease and how our immune system responds to the threat of danger. And last but not least, the extracellular matrix provides the proper fluid balance and pressure gradients for maintaining the correct electrical charges that have to occur in order for systems to be able to function at optimal levels. We know that the charge dynamics are held together by water and fluid and electrolytes. The extracellular matrix plays an important role in helping to maintain this charge so that all electrical signaling is maintained.

I tend to also think of the extracellular matrix as kind of a sponge where environmental toxicity is stored in the body. And so it seems like it's also very sensitive to our environment, to the toxins that we're bringing into the body. Tell us a little bit about the constituents of the matrix. What does the tissue consist of?

Yeah, so that's a great point you brought up. And I think we have to think about this in a kind of chemistry sense. So the sulfated polysaccharides that make up the large percentage of the extracellular matrix, so we're looking at the glycosaminoglycans, for example, heparin sulfate, dermatin sulfate, hyaluronic acid, which is the so called webbing that kind of holds it all in place. These sulfated polysaccharides are anionic. And so when we look at different cationic metals, for example, like mercury or aluminum, we are having to think about the potential for attraction. And so that chemistry plays out in a real way, in an important way, I think. And it can probably be one of the reasons why, as you brought up, is a good way to think of this, is that the tissues can become like a toxin sponge, where we're simply creating an attraction between certain molecules which shouldn't necessarily be in the body in high amounts, but are now, because of environmental toxicity, has reached a very dangerous level. And so these, these proteoglycans and glycosaminoglycans are largely the constituents of the ecm, and we have to think about their breakdown and they do begin to break down during inflammatory signaling. And this is probably one of the reasons why autoimmune diseases are so overrepresented, are so common in people with joint hypermobility, is because there's a toxin component, there's a genetic component, the sort of decreased ability to Synthesize the ECM constituents in a normal regulatory fashion, coupled by the fact that inflammatory signaling can start to cause a breakdown and degradation of these tissues. So when we start to look at the ECM as a whole, we start to see that there's a lot of different components. As I mentioned, water, fluid, electrolyte, sulfated glycosaminoglycans, as well as the proteoglycans are the sort of major constituents here.

What is the connection between the immune system and the matrix? So if we look at things like the mast cells, the fibroblasts, macrophages, and so on, how do they interplay?

Yeah, good question. So in the tissues, the main cell type that forms our extracellular matrix constituents is known as the fibroblast cell. The fibroblast cell has got a very active mitochondria continuously spinning out, as I like to call it, the webbing. So we can think of the fibroblast cell as like a spider and that it's constantly spinning out the web of the matrix. All of these different constituents are being laid out and they're constantly in a process of being broken down, remade. New cells are being formed, old cells are dying. It's a continual life cycle that is happening in real time. The fibroblast cell, importantly, is interacting with a number of other cells in the local environment that includes neighboring immune cells like macrophages and. And it also includes a relationship with neighboring mast cells, which are found abundantly in the loose connective tissue. And we know obviously that mast cells can degranulate and release histamine. And in the chronic disease world, we often see that mast cell activation syndrome is a common problem. But what most people sort of don't see is the fact that mast cells are integrally involved in the formation and the sort of repair processes of the extracellular matrix and are working together with the neighboring fibroblast cells. For example, mast cells are storage sites of heparin, which plays a role in clotting as well as in is actually heparin sulfate is one of the glycosaminoglycans. Mast cells also will release growth factors such as Fibroblast Growth Factor 2 and 7, and these play an important role in signaling messages between different cell types of the connective tissue system. So, as I've mentioned, there's a lot going on in the tissues and with respect to immune function. So outside of just the fact that different types of cytokines, growth factors, such as TGF beta 1, which is arguably the most important immunosuppressant cytokine depends upon different constituents in the matrix. We also know that when the collagen begins to break down during inflammatory activities through the infiltration of metalloproteinases, that this starts to break apart different proteoglycans in the connective tissue. And these proteoglycans, decarin, biglycan, they start kind of, they're floating around and then they get picked up by different immune cells. And this is what stimulates the assembly of what's called the inflammasome. So we know that the toll like receptors get stimulated. These are receptors on the surface of immune cells and they then can stimulate this inflammasome assembly. The inflammasome is then what triggers the subsequent formation of inflammatory cytokines. Interleukin 1 beta, interleukin 17. Downstream of that you have TNF alpha. And these are the sort of beginning stages of a virulent inflammatory process which if can't be adequately controlled. We have autoimmune conditions. Autoimmune disease that are, that arises is IL17 is a major kind of shift towards the autoimmune program. So there's many reasons why immune dysregulation can occur directly as a result of the breakdown of the ECM constituents.

You mentioned that mast cells actually are involved in tissue repair. So do attempts to stabilize mast cells to help make people feel more comfortable in their body, less symptomatic from the inflammation that may be produced from activation of the mast cells? Are those potentially kind of going against our healing process?

Yeah, that's another very good question. And I say that it's a delicate balance. So clearly mast cell activation syndrome is a major clinical challenge in a clinical symptom that affect so many patients today. And it can be a very debilitating condition. And I'm very sympathetic towards patients that have that condition. I will point out a fact that most of the anti histamine and mast cell stabilizing medications that are being used today are also anticholinergics. And so anticholinergics inhibit acetylcholine signaling. Acetylcholine in turn is the most abundant neurotransmitter that the vagus nerve uses. And it's one of the most important neurotransmitters for cognitive function. So there has been concern and publications about the use of antihistamines, including simply Benadryl because of its association with dementia and Alzheimer's disease. This was published, I believe in Harvard last year. But we have to think about the sort of double edged sword of treating mast cell activation syndrome by trying to inhibit the degranulation of mast cells. On the one hand we're trying to alleviate and ameliorate symptoms, but on the other hand, by doing so with certain medications, we actually may be causing far more problems than we realize. And because postural orthostatic tachycardia syndrome and dysautonomia actually common among EDS and hypermobility patients, using these kinds of medications may be counterintuitive. But I think it sort of illustrates a bigger problem. Something that a systems biology viewpoint can help us to understand better is that mast cell activation may be part of a bigger problem which is related to the body's healing cycle or cell danger response even, and how we need to sort of view the mast cell situation more as a repair process that is not able to be completed. And I think if we look at it from that perspective, we'll have more solutions in the future as to what we really need to be doing to prevent that from happening. And I have a few ideas about it.

Yeah, and it's interesting when you look at all the potential triggers for mast cell activation, probably the one that's stands out for me that I think over time will become more recognized is the exposure to EMFs in our environment. And I know you were in the audience at the same conference last year where Dr. Theo Horridis mentioned that mast cells are 10 times more active in the presence of a cell phone. Which really caught my attention even being aware of this for a long time. I mean, that's a pretty significant statement.

Yes. I will have to say that most of the people that I have, that I work with that have EDS or joint hypermobility, they tend to be sensitive to emf. And it's an interesting phenomenon. And we live in a very complex world now where it's now becoming almost impossible to not be exposed to emf. But I tend to think of the extracellular matrix as a sort of barrier between the worlds, if you will, where we have electromagnetic fields from the outer environment that is affecting our own bodies, magnetic fields. And so there's. I think that when we think in terms of fields and physics, we're talking about the different ways that the body is sort of receiving signals and is able to, or not able to sort of hear signals, hear certain signals or be affected by other signals. So I think that's a really important point. And from experience I have to say that most people with hypermobility seem to be hypersensitive to EMFs, even more so than the others in the. In the general population.

You mentioned Bob Navia's work with cell danger response. What's the role of the matrix in terms of the cell danger response?

So for those who are not, we'll give a very brief overview of that. And Dr. Robert Navio is one of the most important scientists, in my opinion, and he should be nominated for a Nobel Prize within the next three to five years. He probably will be. This is again, a systems biology way of looking at complex illness, which is a very needed shift in worldview that has to occur in medicine to make medicine more personalized, more accurate. But basically, the cell danger response is the body's response to the threat of danger. And as he's pointed out in his more recent papers, the cell danger response is actually the body's healing cycle, of which there are three major stages. The inflammation phase, which is phase one, the sort of repair and cleanup phase, and the new cell formation phase, which is phase two. And then the CDR3 checkpoint, which is the sort of place where you have to get past in order to get back to normal mitochondrial function. So the problem seems to be that people get stuck in one of these three phases. And if you're stuck in one of these three phases, you can't complete the cycle. You can't get back to normal homeostasis, normal healthy equilibrium. So we know. So basically, one of the major takeaways from Dr. Navio's research, of which there are so many, is purinergic signaling. Purinergic signaling has to do with the fact that during all phases of the cell danger response, including the initial phase of inflammation, the mitochondria will change their function. In CDR1, for example, the inflammatory phase will occur when the mitochondria stop their normal ATP synthesis. The respiratory chain reduces its production. It reduces its consumption of oxygen. So as a result of that, oxygen builds up in the cell and we have the generation of free radicals from oxygen buildup. This is a necessary part of the inflammatory process. Free radicals are run amok. And we have, as Dr. Revici calls it, entropy. We have chaos and disorder that is a coordinated effort of cells. The key part of this, the ATP that was used and being produced by the mitochondria is now effluxed out of the cell, and it's leaving the cell through these different purinergic receptors, such as the P2X7 receptor, which is a purinergic receptor. So the ATP leaves the cell and that becomes A neurotransmitter like molecule, that extracellular ATP begins to signal to neighboring cells that we have danger, we have inflammation, we're changing the whole scenery and function of cellular activity. So we know that the fibroblast cell, which is the main cell that is what is producing our connective tissue constituents, we know that that fibroblast cell has on it purinergic receptors. And in fact those purinergic receptors are integrally involved in this cell danger response. They will basically be affected by the levels of ATP in and out of the cell. And we know from research at the UC at University of California, San Diego that was done that in fibrosis, tissue fibrosis, that purinergic signaling is integrally involved in this inflammatory process. We need more research to be done in hypermobility syndromes to demonstrate the specific coordinated phases of how fibroblast cells are responding to the threats of danger. But we know that they are and we know that that's front row center in what's going on here. So as it comes to the cell danger response, the connective tissue is front row center. Yeah.

And it's interesting with cell danger response, I wonder, is it always an actual threat or danger or is it a perceived threat or danger? Getting us into the realm of the limbic system, the amygdala, into Annie Hopper's work. I think in some cases the threat may actually not be as significant, but we just need to reboot the limbic system. Any quick thoughts there?

Phenomenal question. I love it. It's off the cuff. I love it. And I think that's absolutely an imperative point point. With hypermobility syndromes, as the research from Jessica Eccles. I hope I'm pronouncing her last name correctly. She's pointed out, and she's a UK based researcher, she looked at brain volume discrepancies in hypermobile patients versus non hypermobile patients and they found that the sort of linear relationship between anxiety disorders and hypermobility relative to amygdala variations. We know that the amygdala is a part of the limbic brain that is prone to what's called kindling, meaning that stressful life events or traumatic life events, especially early life events, can cause patterning in how the brain fires and behaves and responds to different stimuli in terms of different threats that can occur later in life. And sort of the sort of pattern that gets placed at the earlier years of life can affect what's going on 30 years down the road. The same can occur Theoretically, in a chronic disease state, if somebody has been exposed to Lyme disease at some point, their body goes into a whole kind of danger response state. That kind of a loop of danger in the brain and nervous system can be repeated again in the future if a similar threat was sort of perceived, whether real or not, by the brain and the nervous system. And so we have a sort of situation, as Scott is alluding to, that could be saying that there may not actually be a real physical threat. It may be a sort of loop that is gone, that is going on within the brain and nervous system in some way. But we believe that the people that are hypermobile, whether it's EDS or just acquired joint hypermobility, they tend to have brain and nervous system imbalances in the sense that there's something going on there that is leading to, that is leading to these sort of loops. And I think the Ecklis research points to that as a probability. A lot of the people that I work with that are hypermobile, they not only are prone to anxiety and high heightened stress responses. High stress responses, as McLathrie points out, a brain wired for danger, quote, unquote. I think that that is sort of giving us an interesting look into the phenotype of these types of patients. And that leads me to thinking about how what we really need to be looking at from a brain regulation standpoint, a nervous system regulation standpoint, are as I call them, self regulatory practices that help people to volitionally control their brain and nervous system's ability to respond to the threat of danger. This is almost like reverse engineering the problem by using things like breathing practices and meditation, as well as brain training practices, to sort of, quote, unquote, biohack your nervous system's response. And I think if we start approaching it from this standpoint, we're gonna start to see some very interesting and important results as a result of this.

Let's talk a little bit about Gerald Pollack's work with exclusion zone water, or EZ water. The modulating effect on the matrix. Is there a role here for infrared sauna photobiomodulation? What are your thoughts on that?

The research of Pollock is very important. And there's a lead up of many scientists for many years that were looking at water research. And until Pollock came around, most people didn't take water research very seriously, unfortunately. But he sort of opened the door for really looking at water research legitimately. And we know that near infrared light between the 810 to 850 nanometer spectrum has been shown to increase what's called exclusion zones in water. And exclusion zones is a type of water, as Dr. Pollack points out, the fourth phase of water, which is essentially negatively charged gel like water, that exists on the surface of all lipophilic surfaces, including within vessels. And there's. It's really amazing because some of the earlier German research was pointing to the probability that the matrix water is in fact very similar to the type of water that Dr. Pollack has discovered. So that leads us to sort of understand that near infrared light in the light front, which is part of the sun's natural spectrum, does in fact play a very critical role in the connective tissue water, and the ability for that water to maintain a negative charge. And that negative charge is likely playing a very important role in everything from intracellular function that's occurring in the cytosol of cells to the mitochondria to tissue hydration and charge elements.

As we move into talking more about Ehlers Danlos syndrome, let's talk a little bit about the similarities or differences between joint hypermobility syndrome and Ehlers Danlos syndrome. Are all cases of hypermobility considered EDS, and do all cases of EDS have a hypermobility component?

So there are 13 forms of EHLers Danlos syndrome which are all believed to be congenital. So they're genetically diagnosed, they're typically diagnosed by a geneticist. But not everybody with joint hypermobility necessarily has eds. There is a critical need right now to make the distinction between who has a real genetic EDS versus who has some acquired form of it. Most of the people that I've worked with in practice that have been diagnosed with genetic eds have never actually had any formal genetic testing done that is confirmed that they have a congenital form. They just assume that it's a congenital form. So that's sort of a, sort of a big missing piece of the puzzle in the scientific research. But not everybody with eds, not everybody with joint hypermobility has genetic EDS per se.

So let's then talk a little more about Ehlers Danlos syndrome. You mentioned 13 different types. What are the more common types that you see in your clinical practice?

So the classical form and then the non classical form or what? I think the hypermobility is probably one of the most common forms. But not all forms of EDS necessarily feature hypermobility, although most of the forms that you're going to hear from the diagnostic side do in fact feature some type of hypermobility or skin hyper elasticity is another component. And the other forms of EDs are not as common I don't really come into contact with many people that have some of the like type 10 or type 11 forms of EDS. Those are, those are considered to be far more rare. You're mostly encountering people that have been diagnosed with hypermobile EDS that have been done so diagnosed by a geneticist on a non, you know, on an observational basis primarily.

You talked earlier about the symptoms of joint hypermobility. Are there unique symptoms of Ehlers Danlos or are they pretty much similar?

The most common forms are similar joint subluxation pain syndromes. There may be. Typically you're going to see other people if there is a genetic component. There is other people in the family that have similar traits and characteristics. I think that that's an important distinction that sort of separates the congenital form versus the non congenital form. If you're the only person in the family that has hypermobility, then it's likely possible that something acquired and it isn't necessarily congenital. So you have to look at the overlapping symptoms that are associated with the congenital versus the non congenital forms to make that distinction.

And would you say the triggers for EDS are similar to the ones that we talked about earlier for hypermobility or are there some unique triggers? Triggers. And when we treat those underlying triggers, does that often result in the resolution of the Ehlers Danlos syndrome?

So yeah, I just want to be clear again that EDS is considered to be strictly a genetic condition and so there aren't triggers for a genetic condition other than the so called genetic associations. If a person has hypermobility, this does not necessarily mean that they have a genetic hypermobility. So I wanted to just be clear about that.

So even though EDS may always have a genetic component, is it still possible then that something, whether it's a microbe or a toxin or whatever, is the trigger for it to then become more expressed and the person to become more symptomatic as a result of their genetic.

Situation, that situation likely is occurring. And there is not a lot of published research about those compounding two factors together. But clinically having seen those two together, I would say that's a very difficult type of a person to treat. But you have to address the. If there is an environmental trigger that is making the EDS symptoms that they have worse, you have to address, I would say the tree and the branch. So you have to address the environmental component and, and you have to address the underlying connective tissue weakness. I would probably prioritize it where you treat the Lyme or the Bartonella or whatever that environmental vector is and address that as a primary and then actually the EDS is a secondary. Because if it's the environmental trigger that's setting off the cascade, making the whole system go haywire, you've got to be able to control that danger signal.

It seems that EDS is becoming more common, which if it's truly genetic, may not necessarily be true. So do you think we're recognizing it more? Why is it more common now than previously?

I definitely think that the environmental toxin component is probably one of the overlying themes that is contributing to all of this equation. We really do not know how to study the effect of 83 billion pounds a year of chemicals that are being produced in the world and the effect that that is having in a synergistic way on human biology, especially among the more vulnerable populations of people such as those with hypermobility.

So would we then say that if Ehlers Danlos has this genetic component, but we're suggesting that environmental toxic toxicity plays a key role. Is that to say that even if they have this genetic underlying genetic issue, that it may not be expressed until there's another epigenetic factor like the environmental toxicity? Can we have the genetic scenario and yet have none of the actual symptoms of Ehlers Danlos syndrome?

I think that that's very possible because I think that there are many things that are. There are epigenetics, histone modification and DNA methylation that probably can contain certain genetic variations and can suppress gene expression to some degree. I do think that there is a distinction between individuals with genetic haploinsufficiency which is sort of diagnosed as or is way to look at. That is, there are people with true genetic diseases that do not make enough of an enzyme product because of a full blown knockout of a particular gene. Those are cases that are considered to be more rare. And so we should not group together those people with the people that have a lesser SNPs. SNPs, for example, variations in certain genes that may kind of interact but may not. There are different gradations within genetic diagnostics that I think should be treated very carefully.

A listener asked if there is a connection between some vaccinations and Ehlers Danlos syndrome, for example Gardasil. Have you seen any connection there?

I've not seen any personal connection with Gardasil vaccines and hypermobility development or eds. However, it should be pointed out that vaccines contain adjuvants such as aluminum and aluminum. As a vaccine adjuvant is known to stimulate the toll like receptors on immune cells which can stimulate the inflammasome assembly and this occurs through the formation of damage associated molecular patterns or pathogen associated molecular pat. Aluminum as well as other toxins for example, can stimulate the inflammasome leading to a cascade of danger signaling.

In the SIRS or chronic inflammatory response syndrome world, many people are familiar with TGF beta 1 transforming growth factor beta 1. You've mentioned it. How does it fit into this discussion and our attempts to down regulate or lower TGF beta 1 when it is elevated? Is that potentially going against the body's innate wisdom and healing process?

Great question. Transforming growth factor beta, probably the most ubiquitous cytokine growth factor that you'll ever research about. It's in everything, doing everything and when I say everything I'm sort of generalizing, but it sort of shows up in so much research that it's really remarkable. So it's clearly not black and white. TGF beta has so many functions that it's just impossible to say we need to raise it or we need to lower it. As mentioned, it's an immunosuppressant cytokine, but it also can be pro inflammatory in certain instances. It's critical in stem cell differentiation. So making new cells, you need TGF beta to be present and it's doing different things things as it comes to the connective tissue in the extracellular matrix, TGF beta, it interacts with type 1 and type 2 collagen and it also is activated through the tanaskin X which is a part of the RCCX gene cluster and the Tinaskin X is critical for this sort of adhesion anti adhesion function of tissue. We have to think about things in a different way. Clinically speaking we're saying oh, this is high, this is low, and that's really not an appropriate way of looking at the problem because we have what I like to say, quality and quantity. So because something is high or low doesn't necessarily mean we want to raise or lower it because there are qualitative things that occur at the level of the tissue. Qualitatively speaking, if there is a lack of certain proteoglycans or a lack of certain ECM constituents that can impair the qualitative function. The qualitative effect, the ability to utilize TGF beta in different systems because of a lack of connective tissue or a problem qualitatively in the relationship between the tissue and the growth factor, these are things that you can't necessarily detect by looking at so called levels of TGF beta or other growth factors. You have to sort of apply a systems biology approach to sort of understand these complex interactions. So I don't know if I really answered the question well, but it's difficult to call it a black and white thing on the surface, but we have to pay attention to scientific research needs to really advance in its way of looking at complex problems. And the growth factor signaling component is huge with respect to the connective tissue and the immune system and the nervous system and neural development. It's huge. It's absolutely an immense component. But we need new models of looking at the growth factor cytokine systems, because it's not just about highs and lows.

You talked about collagen, so let's talk a little bit more about that. Is there in some cases an oxygen autoimmune response to our own collagen playing a role? And then if we're thinking about taking exogenous collagen, is that helpful? Is that harmful? Is it better to provide the building blocks and let the body produce the collagen? What are your thoughts on collagen?

You can definitely make antibodies to host tissues and that can certainly include the connective tissue. This is another area of research that needs to be expanded upon. Would love it if somebody came up with a very extensive panel of ECM constituents and autoantibodies that form. That's something that we really need to be looking at. Again, the immune system will create inflammation and collateral damage. And part of the collateral damage of the inflammatory process is the degradation of the extracellular matrix. Metalloproteinases, for example, are integral in the sort of boring apart, the sort of drilling through the ECM and that frees up all of these proteoglycans are floating around the immune system. Immune cells can sort of pick these up and then that sort of stimulates more inflammation. So you've got this sort of CDR one cell danger response, one cascade that's sort of creating this sort of entropic situation. In terms of actually utilizing supplemental collagen under these conditions, I've not actually seen that that has. I've not actually seen that giving collagen supplementally actually has any positive or negative effect on hypermobility per se. If it's having any effect, it's very minor. I think that it's probably overall better to provide the. If you're going to try to provide, use some sort of a therapy to provide the sort of basic ingredients so that the cells can start maybe making their own collagen. I think in that sense polysaccharides would probably be a Little bit of a better thing to be looking at.

Deborah Cusack is well known in the EDS world for putting together a protocol based on her own health journey. Been used by lots of people. What are some of the key elements of the QSAC protocol that you found helpful in your clinical work? And are these managing symptoms or are they addressing the underlying root causes at the same time?

Good, challenging questions. So Deborah Cusack, she needs to be given credit for the development of what she's calling the Cusack Protocol for eds. And she's basically kind of figured out that for herself and her family and now for a huge percentage of people, that there are some very simple nutritional things that can be very, very helpful and beneficial for people. And this is commonly referred to now as the QSAC protocol. And if anybody's listening to this that has either themselves or family members with EDS or hypermobility to check it out and to start looking at this. About a year and a half ago I began to pull her online Facebook forum of which there's thousands of people in there, all that are self treating or are working with different people. And I wanted to basically poll the audience to see what is it that, what's working for people. I wanted to try to get as much data as I can. So we had hundreds of responses and I literally went down checklist by checklist, writing off everything and then figuring out what are the top 10 or 11 things that have worked well for people in this hypermobility field forum. And surprisingly I'll go through the list one through 11. So number one, magnesium. Number two, aloe vera, which is aloe vera contains the polysaccharides, the sugars that the connective tissue system uses to form these different constituents of the collagen. Number three, cbd, probably for pain management. But there's other things that CBD appears to do is including there's some evidence that it modulates the fibroblasts and it's also got immunological signaling mechanisms as well. Number four, hydration and electrolytes. Again that makes sense to me because the tissues, the ecm, you have to have charge, you need to have fluid and electrolyte dynamics to maintain proper electrical gradients. Number five, vitamin C. Vitamin C plays a crop role in collagen synthesis. Most of the people that I work with with EDS tend to respond well to vitamin C and typically higher dosages of vitamin C. Next on the list are mushrooms, polysaccharide containing maitake and lion's mane. And so these have, these are also polysaccharides Some people clinically don't respond well to aloe vera for some reason, and that's not exactly clear why. It could have something to do with aloe vera possibly interacting with the clotting system that's been proposed. Not entirely clear. Some people respond better to lion's mane and maitake. We know that there's possible effects on the immune system with the mushrooms as well as on, you know, neurotrophic growth factors like BDNF and ngf. Next on the list for people on that forum that were getting benefit, probiotics, gastrointestinal function. A lot of people with EDS have digestive related concerns. Then bringing up the rear, Vitamin D, turmeric, physical therapy and then smoking cannabis, I think was number 11. The physical therapy component is probably something that is not looked at enough. But I do have reports from other clinics and colleagues that treat people with eds that they work closely with physical therapists and they find that the physical therapists that do resistance training with the patients get great results. And I think we have to really be looking at this as a major component.

Based on your clinical work with a number of people with Ehlers Danlos syndrome, what are you finding are some of the top interventions? Are there differences from that list that we just went over and then specifically around kind of the growth factors support. What are some of the key areas that you like to support in your clients?

Yeah, so the clients that I work there are very complex because they usually have overlapping comorbidities, including Lyme disease, mold, heavy metal toxicity. So that on top of the EDS diagnosis, makes things very complicated. I think it's also important to look at circadian biology. And I found that there are some people with EDS that seem to have an exacerbation of their symptoms through some circadian based rhythm and that may include menstrual cycle. The hormone component is overlooked in eds. There are some people that are now really beginning to look at the balance of progesterone and estrogen and the importance here in actually the overall role that these hormones are playing in the tissues. So that's actually something that as of the last six to 12 months I really started to pay more attention to because in some cases it has shown to be very significant. The circadian biology plays a key role here I think as well. And this is something that might take years to elucidate on because the circadian clock genes of the body are found largely in the brain, in the SCN of the hypothalamus and from Clinical experience. I think that we need to be looking at the circadian rhythm component because the circadian rhythms are sort of organizing the expression on a daily basis of all our biological processes include mitochondria will turn on and turn off during certain times of the day, inflammation will turn on and turn off during certain times of the day. Person with an autoimmune flare up sometimes they experience that cyclically at a certain time between 4 and 6am every day. That clearly tells us that there are changing diurnal rhythms that are going on here. And we need to be paying closer attention to those rhythms because that could actually more specifically mean that we have to target certain protocols during certain times of the day, certain times of the month, even maybe certain times of the year. I have a client right now who is always with, with so called hypermobility EDS like characteristics who is always worse between December and March and the rest of the year is much better. So that there's clearly something going on there with regards to some circadian rhythm. So we need to be looking at these. This again this is systems biology is going to help to really elucidate these things going forward in the future. So some of the other things that I pay a lot of attention to are vitamin C, magnesium, copper, which gets overlooked. The mushrooms overall I like actually better than using the aloe vera. Overall the mushrooms, my taki shiitake combination seem to have a better overall effect. In terms of pain. I like to, I like to try to take an overall diverse approach. I actually find that electrolytes and fluid and electrolyte balance can be a huge regulator of pain, including fibromyalgia like pain, connective tissue like pain. I think that fsm, I've referred people out for that, that definitely has helped in many cases. And I know that Dr. McMaken's work is shown the ability to attenuate the connective tissue with frequency specific microcurrent therapy and the ability to actually improve and even increase the synthesis of collagen. So if there's a way to sort of find out how to synergize FSM with some of our so called biochemical protocols, I think we'll really be looking at good things. Some other things that I've been playing with lately in terms of mast cell activation, one thing I wanted to mention is that one of the things that doesn't get enough attention is the blood gas ratio and we sort of overlook the fact that oxygen and carbon dioxide are really the most kind of fundamental gases in the body and Oxygen is sort of the most important nutrient that there is. You don't exist without oxygen, but you don't make free radicals without it either. So there's a dynamic there. And we know from some anecdotal reports that breathing exercises have actually been able to control mast cell activation syndrome in some people. And that's a really important thing to look at. The other thing that people use for some of the brain related problems like the intracranial hypertension and even some of these other brain related conditions is a drug called Diamox, which is acetazolamide. Basically that's a carbonic anhydrase inhibitor. So it leads to an increased buildup of carbon dioxide. Carbon dioxide, as it turns out, is the most regulatory factor in the perfusion of the brain by a huge factor. Way more than oxygen, way more than nitric oxide. And so when you start to play with blood gases, namely carbon dioxide, you start to really realize that there's a lot going on here anyway. The blood gas thing is a huge component. I think that's not being looked at. Somebody needs to really look at the PAC CO2, which is done through a capnometer, measuring the actual blood gas CO2 levels of these patients. I'm going to bet you. My guess is you're going to find some abnormalities that can probably be corrected either with a medication like acetazolamide or even breathing techniques or things that are going to modulate the perfusion of oxygen to the tissues, including even nitric oxide therapies. That's an interesting dynamic that we haven't discussed, but I want to throw out there for growth factors. I'm looking at polysaccharides, I'm looking at certain amino acids. I like the MAP amino acids supplement just because it provides a bioavailable amount of amino acids. If a person has digestive problems, absorption issues using that particular product has been shown to be very helpful. And I've had a couple of clinical case studies where that product was actually critical in helping to sort of reorganize the inflammation and even the connective tissue laxity that was occurring. There's another product that we've been sourcing from Europe, Mega Complex gf. This is a purified chicken embryo product that contains in it something like 25 different growth factors, including the FGF growth factors. Clinical reports from clinicians suggest that it's helping with things like mast cell activation, it's helping with pain, and it's helping with digestive problems. And it's likely that when you're Sort of providing growth factors directly. You're able to sort of support the body's own physiological processes, is the way we like to look at this.

Are there any contraindications when we're supporting these growth factors relative to, let's say, if someone had an active cancer, is that a potential concern?

I would probably say if you have active cancer, you would probably want to be really cautious with things that are going to promote growth factor signaling.

Yeah. In Borrelia or Lyme disease, we know that Borrelia loves collagen, and collagen and structural integrity can be impaired without joint hypermobility or Ehlers Danlos syndrome. So do you think that a lot of these strategies that we've talked through, do they make sense in those with chronic Lyme disease, even without hypermobility?

So it really comes down to the danger signal. Right. And I think that if there's a danger signal, like a virulent stealth pathogen like Borrelia, which does in fact love to live in the connective tissue as well as elicit the immune system to start breaking down the connective tissue, you need to sort of. You need to really address that as a primary. And if you don't address that as a primary, that danger signal will continue to perpetuate, at least theoretically it will. And you may continue to try to support the system with all of these different ECM supplements and protocols, but you might not actually get any benefit from it. So it's one of those things where you have to sort of put the cart before the horse, so to speak, and treat the current process. But as I like to say, you sort of eventually need to be looking at both of these and you need to treat the branches of the tree as well as the roots of the tree.

And do you find, in some cases. So a listener asked if their EDS symptoms, so we know it's genetic, but if their symptoms were triggered because they moved into a house that had a mold issue in some cases. Is addressing the mold issue enough to resolve the EDS symptoms, or do they need to do more than just fixing the original trigger?

Complex question. It's sort of. It's unknown. I think there's no one answer to that. I think it depends on a lot of inter individualistic variables, genetic strength and weaknesses, etc. I would still address that problem from. Again, I would try to do both. I would try to. Obviously, getting the mold out of the system, getting into a safe living environment is becoming a very difficult thing these days. And mold is one of these sort of problems that prevents that from happening. But at the same time, we need to be able to help our bodies to kind of clean up the damage that has been done. And if we can help the body do that using basic nutrition and some of these other specialty supplements and protocols, then great, and I hope it really works for people. But we have to realize that everyone is really unique, so we have to just go one by one on a case by case basis.

There's a lot of excitement around peptides these days. So things like BPC157, for example. Do you think that peptides ultimately will play a role in eds?

Yes, I do. There's not enough clinical data yet, but I am a big fan of BPC157, and I've seen it work in some cases really, really well for acute injuries. I really think that the oral form of BPC157, which is being used now, has a lot of beneficial effects on some of the gastrointestinal symptoms that are common. And I think that it's something that we really need to keep moving this research forward, not only with BPC157, but with the other peptides as well. Thymus and beta 4, Thymus and alpha 1. And there's a whole kind of underground world of peptides that has been sort of percolating under the sea, so to speak, for a long time, but is now starting to gain wider acceptance. So that research is critical going forward.

So as we start wrapping up our conversation, I want to get a little bit into RCCX. So Dr. Sharon McGlathery, who you mentioned, talks about RCCX and how they are involved in these complex conditions like eds, like mast cell activation, like pots and so on. So what are the RCCX genes and how are they related to what many listeners might know as the HLA genes from the chronic inflammatory response syndrome world? With the hla. Doctor, for example, can we.

Can I speak for another three hours?

Sure.

Obviously that's a joke, but I know you could. Well, yeah, so getting into RCCX theory is very complicated stuff. This is arguably the most complex region of the human genome, and it's a cluster of four genes on chromosome 6, and it sits right in the middle of the HLA region and chromosome 6, which is by itself considered one of the most complex regions. So this is the most complex region within the most complex region of the human genome. So it's a copy number variation gene cluster, which means that it's a rare part of the genome, only 4 to 10% of our human Genes are copy number variations and RCCX is one of these. A copy number variation means that the genes that run in tandem, there's four of these, they tend to produce duplications of themselves and then the duplications produce these things called pseudogenes. And so you have these sort of complex problems that arise in the different copies and pseudogenes. As it turns out that these four genes are integral in some of the most important systems of the body. You have the Tinaskin X gene or tnxb, which is the connective tissue component part of the cluster. Tinascan X deficiency is actually one of the forms of EDS classical like eds, which is the second EDS form I believe, and that often produces symptoms of skin hyper elasticity, joint hypermobility. But there's some complex things that occurs within tnxb, but know for now that it is, it's also linked to schizophrenia and it's also linked to neurological conditions. And there's been some recent studies that have shown that. And so the other genes on this cluster sitting right next to TNXB, you have CYP21A2. This is the gene that produces cortisol and aldosterone directly from 17 hydroxyprogesterone biochemically. And because of its position next to TXB, you often see interesting overlapping comorbidities that seem to tell us more about certain patients. There's actually a paper published about the CAHX syndrome 2016 by Chen and Morissette and that paper was looking at how certain EDS patients actually have also congenital adrenal hyperplasia, which is the disease most associated with CYP21A2. And that's really fascinating from a genetic standpoint, but it shows that it illustrates the complexity that it can occur when two genes overlap and share genomic regions. So the other thing is that there's a lot of, I believe, a lot of under diagnosed a lot of undiagnosed conditions and symptoms attributed directly to CYP 2182. They've only studied one single disease, CAH, with respect to 21 hydroxylase. But the fact is that cortisol is probably one of the most talked about and researched molecules and physiology. It's central to the body stress response. We know that it affects the brain, we know that there's cortisol that that gene expresses in the brain and in different regions of the brain and even the spinal cord. So it's got to be involved in neurological responses. So this RCCX modular research that Dr. McGlathery has sort of pioneered in Many ways, it's leading to a number of very important questions. And I believe somebody someday in the future is going to win a Nobel Prize for really putting all of these pieces together. The third gene on the cluster is complement C4, which is a link to autoimmune disease, as there's about, I think, eight to 10 different autoimmune diseases that are directly linked to some variation of C4, whether it be low C4 protein levels or C4 genetic variations or anomalies that occur within our CCX cluster. And the complement C4 as a protein is integral in the innate immune system. As part of the complement immune system, we talk about C4A as it's related to things like anaphylaxis, mast cell activation, Lyme disease, mold, but it comes from the parent protein, which is complement C4. Actually, it turns out that not only is complement C4 integral in the innate immune system, but it's actually critical in synaptic and dendritic pruning. So it's trimming synapses in the brain. And that's why two different research papers found that about 30, about nearly 40% of autistic patients showed variations of the C4 gene, which leads to aberrant pruning of the brain and synapses in the brain. So it implicates not only autism, but potentially other neurological diseases that are involving pruning. So aberrant pruning, like schizophrenia, for example, or other diseases like bipolar or neurological conditions. So there's an enormous field of research that could open up just as a result of looking at the RCCX gene cluster. The fourth gene, RP1, is the STK19 gene. It's not known. We don't know exactly what it's doing, but we do know that all of these genes together equals a big problem. And one of the biggest problems is actually being able to sequence the RCCX cluster. Currently, there's no commercial lab that can do the deep read on all of these genes. And you can't simply look at your 23andMe data and say, oh, I've got this SNP, I've got that SNP. In fact, because of the complexity with the pseudo genes in rccx, there's a lot of high frequency of what called false reads, meaning that the lab like 23andMe, reports somebody's homozygous for a SNP, but actually that's not correct because they can't account for the pseudogene which is causing this miscommunication. The genetic reading of It So currently you can't sequence this RCCX cluster. And even if you did sequence the modular genotype, you still aren't able to account for the extraordinary depth of complexity that's occurring. I think that eventually RCCX is going to be recognized as a critical part of the human genome that played a critical role in human evolution. And I think that that's going to have to do with the ability for certain individuals to be able to adapt to environmental stresses versus not to adapt. And what's interesting about RCCX is that there is a subclass of people in this population that is highly subject to genius intelligence. And we witnessed this, we've observed it, we've interviewed people that have genius iq, that have family members with extraordinary complex comorbid diseases that go on for generations. And if we look at the trail of research and evidence, it all points to the RCCX gene cluster. So I think that RCCX actually represents something even more profound than we're even able to sort of realize. Genetics research tends to look at things, and I'll kind of leave it at this. Genetics research tends to, from a medical standpoint, tends to look at what are the disease associations with certain genes. But we need to take a different viewpoint because as it turns out, there's always a flip side to a coin, right? A genetic configuration usually leads to something that is an undesirable trait, but there's always some sort of an advantage to that genotype. Disadvantage, advantage. Two sides to a coin. We can use many different examples of genetics research to demonstrate that fact. So when we look at complex genetic diseases or complex genetic associations, we should also be taking into and asking the question, whether we're talking about EDS from a genetic standpoint or RCCX from a genetic standpoint, what are the advantages as well as the disadvantages? And I think that once you start asking that question about what are the advantages are you're going to start to find out what are some of the solutions to some of these more complex health problems that arise from the disadvantages of the genotype. If we emphasize what's good and we study what the good things are, we may learn about what to do with the bad things.

So with these RCCX anomalies, would we say that when Someone has specific SNPs or mutations that that leads to a determined outcome, that that absolutely will be expressed, or are these genes also still impacted by epigenetic factors?

Yeah, that's a complicated question. I believe that gene expression is controlled by many different is Influenced, I should say, is influenced by. There's many different variables of influence and there's different gradations of genetic expression. There are people with true genetic diseases where they exhibit haploinsufficiency and those are more rare but more severe. And then there are people with more, with less of a genetic problem, so to speak, and are more sort of influenced by these epigenetic variables as we're all being influenced by epigenetics on some level. So there's different gradations of that, the answer to that question and we can very much, I like to end with an empowering note that we can in many ways influence our gene expression by affecting our epigenetics. And really the science and study of epigenetics is about how we are able to control or modulate or influence our heritable genes. And I am hopeful that in EDS research that we're able to eventually learn how we can better serve ourselves and others by affecting our epigenetic influences. And I think when we look at basic things like basic health parameters, diet, exercise, sunlight, toxin exposure, if we're able to control for the things that we can control for, I do believe even in people with genetic eds, that we can still make positive and powerful improvements.

We know with things, for example, like mthfr, which I'm not a huge fan of, I think it has a big marketing department and it's probably less important than a lot of other things, but we know we can use things like folate and B12 and help influence its expression. Are there nutritional interventions that can help influence the expression of this RCCX genetic region?

Yes, definitely I tried. When dealing with a complex problem like rccx, I try to avoid simple linear solutions because I think that we have to approach it from a systems viewpoint. The thing that I would really pay the closest attention to and the thing that I'm really most interested in studying right now with respect to RCCX, modular theory, comorbidity disease theory, is brain regulation research and the ability for us to exert more voluntary control over our physiology in different ways. And I refer to these as self regulatory practices. I believe that in many respects, and this is now being proven in some studies, that we can control our gene expression in ways that we previously didn't think were possible. We could literally employ different types of breathing exercises which have been proven to influence and modulate our innate immune system and our nervous system. We can employ different types of meditation practices which alter our brainwave frequencies. We can utilize different types of therapies that help to retrain the brain and to modulate how our nervous system influences our how our physiology is able to communicate holistically. We're able to use different self regulatory practices to control our gene expression. And that to me represents the bigger win because in many ways the brain and nervous system do play a very critical role in communication with all of the physiological systems. And if we are able to influence how our brain and nervous systems respond and how they are doing the quote unquote thinking and feeling and experiencing through other practices. But I think that we're going to really see the new openings in the new medicine going forward.

Beautiful. My last question for you before we start wrapping up is in the CFS me arena, we've seen a few people recently go through pretty major surgical procedures for CCI or craniocervical instability. I'm interested in your thoughts on is there likely a connection between CCI and hypermobility and eds? And from your perspective, are there any non surgical tools that you think are available or will emerge to help those dealing with cci?

Yeah, that's a great question and thanks for bringing that up. Scott. CCI is a cervical cranial instability and some of the other lesser known and lesser understood conditions. Bilateral eagle syndrome is something that doesn't get a lot of pressure. Cerebral spinal fluid leaks. There are patients that are suffering with cerebral spinal fluid that leaks out of their ears, their nose and their different orifices. And this can cause all kinds of problems. Intracranial hypertension. The work that Dr. Driscoll has done on this is very poignant and important and it is a common problem in eds. And I definitely am wanting to talk about that. At least acknowledge that that problem exists. The upper cervical spine is house to There's a lot of things going on in the upper cervicals and the different cranial nerves that we have all kind of are all up tied up in the occipital region in general. And so in Dr. Not Dr. But Stanley Rosenberg's book Accessing the Healing Power of the Vagus Nerve, one of the things in there that he really illustrated, which is an important point, is that mild subluxation of the cervical spine can cause an impingement upon the vagus nerve. And I think that that's really an important how the structural component plays into the nervous system response is something that we need to really be looking at here. The vagus nerve comes up all the time when you're dealing with EDS and hypermobility. And I think it's because the connective Tissue. The myelinated and unmyelinated fibers of the vagus nerve are really, really central to this whole puzzle. That's probably a whole podcast in and of itself. What can we do about cci? That's another difficult question. There has been some positive reports of surgery, fusion surgery, actually resolving some complex symptoms with cci, but I don't know if that's going to work for everybody. I think we need to be proactive in sort of approaching the problem from a systems viewpoint, which is that there are multiple influencing variables and vectors that are converging. Remember that a lot of people with spinal degeneration may have undiagnosed Lyme disease. I've seen it, I've witnessed it, and I know that that exists. The connective tissue in the ligaments in the spine are part of the Type 1 collagen system, for example. So we have to approach that like we do with other problems that are associated with EDS on an individual basis, and realizing with the knowledge that if we can sort of apply the understanding of how environmental vectors are influencing these different systems, we'll have better understanding. I like recommending cranial osteopathy, because I have seen that work really, really well. This is a type of a treatment that involves the manipulation of the. Of the bone. But there's different forms of osteopathy, as there are different forms of cranial sacral therapy. Biomechanical versus biodynamic. Which of those is best for who sort of depends on each patient. But I think that that's one particular treatment. I think FSM is a particular treatment for CCI. Dr. McMakin, if she's listening, we'd love to sort of. I'd love to collaborate to maybe develop a protocol that could be used in conjunction with fsm. What can we do to make that synergize better? The possibility of. Again, this I'm kind of spitballing here, but injectable peptides could be useful. There are clinics that are trialing hematopoietic stem cell injections into different joint cartilages. This is being trialed. There's possible benefits to this. I'm looking at ways of actually helping those stem cell therapies possibly work better by also including other basic therapies like NAD therapies, like growth factor therapies, to be sort of synergistic. So with the issue of cci, we have to kind of take a systems approach and looking at different ways of supporting the collagen system there. And with the hopes that we can make progress because CCI is a very complex problem.

You have shared so much great information in our conversation today. I know you have some courses that you've put together as well. So if people people want to take a deeper dive into these topic areas, tell us a little bit about the courses and how they can access them.

Metabolic Healing Institute we created this a few years back and I've been creating practitioner based training programs for the last six years or so and metabolichealing.com that's www.metabolichealing.com and you can learn more about these courses. We are planning on releasing non practitioner based courses for the for the general lay public and one of the first that we are hoping to release sometime the next year or so is a course on joint hypermobility for the general public. We do have a course on RCCX for clinicians to become more familiar with this as well as what kind of therapeutics might be useful going forward.

So my last question for you. What are some of the key things that you do on a daily basis in support of your own health?

Good nutrition, hydration, meditation, exercise, sunlight and getting on my bicycle and riding on Westcliff Drive and looking at the Pacific Ocean.

Beautiful. And I think probably you're living in your purpose and passion as well, helping other people, which certainly is helpful for your own health. Also, you are such an incredibly brilliant practitioner, certainly have been a mentor of mine over the last several years, and I just appreciate all that you do to help people with complex chronic illnesses and to help minimize their suffering and to really dive into the research and come up with solutions. So thank you so much for your time today and for sharing with all of us.

It's a pleasure and it's a pleasure to be of service.

To learn more about Today's guest, visit metabolichealing.com that's metabolichealing.com metabolichealing.com thanks for your.

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