 Well, hello everybody. It's another episode of Dr. Jill Live. As you know, you can find us on YouTube on Stitcher and iTunes or anywhere that you watch or listen to podcasts. And today we're back with my good friend, Bob Miller. Many of you have seen our podcast and know Bob well. We were just talking before we got on that your podcast episodes, Bob, are some of our most watched and favorite episodes. And what's interesting is we go really, really deep and really technical, but people seem to really like that. So hopefully if you're out there joining us today live or if you're listening to the recording, you will enjoy diving in. This is one of those podcasts I'll kind of give a little warning. You might wanna watch it because Bob's gonna share some slides. There's some very intense in very fun, I say intense, but you and I love the intensity of the diagrams, right? Exactly. So we're gonna actually be having some visuals that you might wanna tune in. So if you're listening in your car, don't go off the road, but later on if you get a chance, you might wanna specifically watch this one on YouTube because there's gonna be some cool graphics and things that might explain. What I'll try to do is just add in if you're out there listening and not watching, I'll try to explain if there's one or two things that need explanation. So Bob Miller, again, a well-beloved guest and wonderful friend of mine. He is a traditional naturopath specializing in the field of genetic specific nutrition. In 93, he opened Tree of Life Practice and served as traditional naturopath for 27 years. For the past several years, he's been engaged exclusively with functional nutritional genetic variants and related research specializing in nutritional support for those with chronic Lyme disease. And I'll really say it goes way beyond that chronic infections, mass selectivation, even mold exposure, but definitely these complex chronic infections and toxins. And I could go on, Bob, you've got so many accolades, but what I love is your mind and what you bring to the table and how you look at things. So welcome to another episode. Always a pleasure to be here. And first let me say congratulations on your book. What an incredible publication. And I know you must be impacting the lives of so many people as they read it. So best of luck and continuing to promote it and changing the lives as people learn some of the wisdom you're passing on. Oh, thank you, Bob. I mean so much. Yeah, it's quite a ordeal and I'm glad I'm on this side of it now getting it out there. So today our topic is called a lesser known cause of mass selectivation. So many of you may know, I'll just frame this and I'll give it right over to Bob. Mass selectivation, these primordial cells that have been around for probably for any of other parts of the immune system are often reactive to our environment. And so what we're seeing in this post pandemic error and error with an all time high load of toxins in our environment. So parabens and phthalates in your makeup and beauty products, the heavy metals, maybe when you get the silver amalgams in your mouth or lead in the old paint or as you sand off some old materials in your house or now fluorinated compounds, these PFA's are found in Colorado where I live in all of the water supplies are now contaminated with these forever chemicals. I could go on and on about the toxic load in our world but the significance of this is that it's driving our immune systems to be a little crazy and to act out more than they are supposed to. So this toxic load plus infectious burden is a perfect storm that's causing us to see more and more and more cases of something we didn't even talk about 10 years ago called mass selectivation. So the topic of our conversation today is gonna be for Bob to really dive into some of the pathways behind this and explain something you may not have heard about relating to another cause of mass selectivation. So take it away, Bob. Okay, what a great introduction. I mean, you just gave like a two hour class on mass cells in 45 seconds. Excellent, excellent. So our topic here, and are you seeing the screen okay? Yes. Okay. So our topic is lesser known cause of mass cell activation and as Dr. Jill said, there's so many things impacting us but today I think we're gonna take a really deep dive and look at what might be the mechanisms for all these environmental toxins causing this but then more importantly, what we can do to maybe slow that process down a little bit. Now, there's a lot to be said about mass cells and what we're gonna be talking about is how they come from intracellular calcium which probably is surprising many people. It's like, wait, calcium, that's supposed to be good from something that probably no one has ever heard of that's the aryl hydrocarbon receptor, the NMDA receptor and then of course the last one most people have heard about and that's EMF. And as we've said many times, this turns out to be the 3D chess game that's played underwater. Now, here's what we're gonna talk about mass cells 101 and I mean just really basic as Dr. Jill just explained it but then we're really gonna dig into some of the causes excess intracellular calcium and we'll do a little bit on EMF and then something very fascinating the NMDA receptor stimulation and how glutamate's involved then we'll get into the aryl hydrocarbon receptor causing this problem which is absolutely fascinating. Then we're gonna look at the various chemicals that stimulate this aryl hydrocarbon receptor a little bit of genetic predispositions and then an action plan of lifestyle things you can do that may be able to slow down the possibility of this happening. Now, we're gonna be spending about two minutes on what mass cells are. One of the experts on mass cells is Beth O'Hara, functional naturopath and Dr. Jill has interviewed her twice. So if you really wanna dig into the mass cells really encourage you to go back and listen to number 78 where they took about mold and 29 both of those triggers and treatments for mass cells. So 43 minutes, 52 minutes mass cell 101 in case this is a new subject for you because we're gonna blow through it pretty quickly and then spend our time on wine. Also have to do a shout out to a good friend Dr. Harold Landis he graduated from University of Maryland dental school in 83 and then he went on to do integrative medicine at the University of Arizona in 2021. And he and I have been, we call each other the geezer geeks as we get into all of this and study it together and Dr. Landis is now participating in my webinars that I have for physicians every other Thursday evening. So we're just having a good time. So I'd be remiss if I didn't mention his valuable contribution to some of this information. Okay, we're gonna blow through mass cells here. Important role in innate and adaptive immunity. As Dr. Jill said, they recognize harmful antigens by binding to them. And then once they bind to the cause the release of inflammatory mediators. One of my favorite phrases is, is that a good thing? Yes, unless it isn't, meaning that if it's overactive. Again, it's very valuable innate and adaptive immunity, coordination of the immune defense when we have a virus, bacteria, mold, candida, even venom detox, wound healing, recovery of connective tissue after injury, formation of new blood vessels and vasodilation, homeostasis of tissues and organs, neurogenesis, angiogenesis, regulation of menstruation, regulation of pregnancy, all these good things. However, we can get what's called mass cell activation syndrome where they're dysregulated. They become overactive and over-release inflammatory mediators. When these slides were made up, which was some time ago, likely present in nine to 14% of the population. Dr. Jill, for the people that come in to see you again, which is a, you know, you're seeing more of the tougher cases, what percentage would you say you think are having some level of mass cell activation? Yeah, you know, Bob, that's why I mentioned that 10 years ago, because 10 years ago I didn't even know what it was. And nowadays I would say 25 to 30% have some piece of it. So it's a huge percentage. And if you haven't watched, I know you didn't mention this today, Bob, but we did a presentation on the Carnahan reaction, the INAS pathway. And one thing I learned recently that I didn't know is mass cells are also regulated by nitric oxide, which if it's uncoupled when there's oxidative stress will actually cause more reactive oxygen and less mass cell regulation. So this is all connected. And if you haven't seen our previous episode on the INAS pathway, that's another one to watch. Absolutely, yes. We named it after Dr. Carnahan. It's called the Carnahan reaction. Here's a brief look at a chart that shows how when the mass cells get activated, they give off histamine. It's what are called interleukins. They stimulate a very powerful inflammation creator tumor necrosis factor. And again, this is a good thing unless it's overactive. Now mass cell activation is when things are getting carried away. And that began the evolution of discussions about other forms of mass cell disorders, which became Noma's mass cell activation syndrome. Now, when this occurs, we can have allergy, some sub types of autism, asthma, anaphylaxis, gastrointestinal disorders, many types of malignancies, cardiovascular disease. They play a significant role in the TBIs, PTSD, Alzheimer's, MS, ischemic entries. They might even be playing a role in autism spectrum disorder. They are really creating a lot of havoc. So what we had in our body to help us is now turning on us. Eczema, chronic dermatitis, migraines, neurological disorders, GI, including Crohn's and IBD, some autoimmune diseases, vascular inflammation, unexplained multi-system illness. And I tend to think there's more people struggling with this than they realize. Would you agree with that, that some people are chasing symptoms, not realizing it may be mass cell activation? Yeah, it's really Bob at the root of so, so many things. As you can see this whole skew, it could be skin, it could be gut, it could be heart, it can be, and part of that's because histamine, one of the many mediators from mass cells affects every tissue in the body. Absolutely. And I'm not gonna read all of these. You know, if you're watching the video, you can pause it if you wanna look at it. But you can see it's widespread, all of the things that can be created by excess mass cells. Again, I'm not gonna read this. If someone's watching, they may wanna pause if they wanna read it all. Overall fatigue, muscular skeletal systems might be related to osteoporosis and osteopenia, skin symptoms from the histamine, itching, flushing, hives. By the way, Dr. Jill and I did an excellent podcast on histamine. And if you go back and look at that one, we really cover histamine quite well. Cardiovascular, feeling faint, digestive, mouth burning, gum inflammation. Again, I'm not gonna read the whole list, but this is the who's who of digestive symptoms. Rain and nervous system symptoms, lungs and respiratory symptoms, eye symptoms, trouble focusing, blurry, itchy, watery, irritated. Reproductum system symptoms, endometriosis, painful periods, urinary tract issues, anaphylaxis, itchy hives, flushing or pale skin. As you can see, this is a very, very broad list of things that can be happening. Fibro, chronic fatigue, IC, certain cancers, as we said, Crohn's disease. Heller's Danlos, where people are super flexible. Pots, where you get dizzy when you stand up quickly, as we mentioned, autism. And even some forms of auto-immunity, such as rheumatoid arthritis, lupus, Hashimoto's. The list goes on and on. All right, now, what's the real problem? As you so succinctly said in the very beginning, it's many of the toxins that we're exposed to. And it may even be an expression of what's called the cell danger response where the cells go into somewhat of a shutdown. So we went along in a pretty good clip there because I just wanted to give a brief overview of mass cells. And again, go back and watch some of those other videos if you really wanna dig into it. But we've now established that mass cells can be a problem. Now we're gonna dig into some new research as to why this might be happening. Probably pretty surprising that I'm gonna be talking about calcium because everybody knows, well, calcium's important, right? It helps form your bones and teeth, helps maintain body strength, assists in the movement of muscles, assists with nerve messaging, helps blood flow as vessels relax and constrict, releases hormones and enzymes that support the body functions. We must have calcium. In the glands, it triggers the secretion. In nerve cells, triggers the release of neurotransmitters. In muscle cells, it triggers muscle contraction. In cardiac muscle, it prolongs heart contraction to ensure adequate ejection of the blood. All really important things, you'll notice down here I have the word unless. There's now convincing evidence that the calcium ion can play a critical role in cell killing under certain conditions. This peer reviewed study, the calcium ion and cell death. Who would have thought that something as important as calcium could actually, under the wrong conditions, turn on us? And what we're gonna be talking about is when excess calcium comes into the intercell, the intercell calcium, there needs to be a balance between the extracellular and the intracellular. And you need a lot extracellular, just a little bit intracellular. And when too much comes in, that's when we start creating problems. So here's a peer reviewed study. It is well known that mass cell activation is critically regulated by intracellular calcium ion. Now I don't want anybody listening to this and saying, oh my gosh, I gotta stay away from calcium because it causes mass cells. Not what we're saying at all. We're saying it's when calcium is used improperly that we're gonna explain in a little while. You know, we also did some videos on iron. I mean, iron is critical. Without iron life doesn't exist. It carries your oxygen through your red blood cells. However, iron can become a bad boy too and cause all kinds of problems. So now we're gonna be exploring how the mechanisms are that cause calcium to be disrupted and actually do some harm rather than be good for you. Now this chart here shows us, and I'm gonna try to get the annotation here and draw. Let me get the drawing tool. So here's what's called a calcium channel. So what you're seeing here is the cell wall and there's channels where calcium comes in. And the keyword here is if there's calcium overload, if there's too much inside the cell. So this is outside the cell over here. This is inside the cell here, the intracellular. mitochondria dysfunction, oxidative stress, generation of free radicals, DNA damage, and cell death. If too much calcium comes intracellular. And again, we're not saying calcium is bad, but when it's misused and comes into the cell inappropriately, that's when it creates a problem. Now this chart, again, we're not gonna go into the detail here, but it shows three different ways that this calcium flux can cause mass cell activation. Here's the second one, here's the third one. And we have the citation here, if anyone wants to look this up and read it, it's a long article. Somebody really wants to get into the specifics of how this causes the mass cell activation. So here's another article. If matrix calcium increases beyond physiological demands, it can prove the opening of the mitochondria permeability transition pore and trigger apoptic or necrotic cell death. In other words, the cells can be killed if too much calcium comes inside the cell. Here's another article, the role of calcium in cell injury. And the bottom line is, it can result in the membrane damage and mitochondria calcification and mass cell activation. So now the story is going, well, if that's the case, how does that occur? We're gonna get into that, but first let's look at, this has been linked to neurodegenerative disorders, Alzheimer's, Parkinson's, even some thought that it might be related autism spectrum disorder, attention deficit hyperactivity disorder. I mean, if you talk to an elementary school teacher who's been teaching for five years or more and you ask them, how are the students doing? I don't know if that's happened to you as well, Dr. Jill, but everyone I've talked to says, there's a difference in the last five years. The children can't pay attention, they're more rumbunctious, they're more agitated. And at the worst, it can even go to schizophrenia. Are you noticing that same thing in children, Dr. Jill? Yes. Hey everybody, I just stopped by to let you know that my new book, Unexpected, Finding Resilience through Functional Medicine, Science and Faith is now available for order wherever you purchase books. In this book, I share my own journey of overcoming life-threatening illness and the tools and tips and tricks and hope and resilience I found along the way. This book includes practical advice for things like cancer and Crohn's disease and other autoimmune conditions, infections like Lyme or Epstein Bar and mold and biotoxin related illness. What I really hope is that as you read this book, you find transformational wisdom for health and healing. If you wanna get your own copy, stop by readunexpected.com. There you can also collect your free bonuses. So grab your copy today and begin your own transformational journey through functional medicine in finding resilience. Dr. Jill? Yes, yes. For a multitude of reasons, which some of which you already talked about, absolutely. I feel like there's a big exponential difference in health, mental health of children and adults and all the things we're discussing. Absolutely. Okay, now we're looking at even heart failure. They're saying that mitochondrial calcium overload is a key determinant in heart failure. Now, here's one of the ways that this can happen. This gene right here is CACNA1C. This is called your calcium voltage channel. And this line right here is the cell wall. And we need calcium to come in to the cell. We need some in there. It's stimulated by voltage. Now, what's happening to us? We are living in a sea of electromagnetic fields like never before. No matter where you go in houses and businesses, on the street with cell phones, we're being exposed to EMF. More and more research is looking at, is this EMF triggering this calcium voltage channel to bring calcium in? And that's an area that's being researched quite a bit. Now, we're gonna spend a little time on this chart right here that we made. It's just a little dense, but we're gonna slow her down here and show you what can happen. Absolutely fascinated by this. There's something called the NMDA receptor. And there's a glutamate binding site. Now, glutamate is a neurotransmitter that makes you intelligent, highly motivated. Go get her. Too much of it though, you're anxious. Glycine is an amino acid and it binds on here. And if there is too much stimulation of this NMDA receptor, look what it does. It brings in calcium into the cell. Again, this is the outer cell up here. This is the inner cell here, creating massed cells. Now, why might that be a problem? We're gonna show you a little in a little while. Lifosate, which is roundup, will drive the NMDA receptor. And also, homocysteine. This is something that I believe should be measured more often than it is. But it's a molecule that needs to be recycled through a process called methylation into something called SAMI. And many times this homocysteine is too high and it will also stimulate the NMDA receptor. Now, this gets a little bit more complex. Calcium, when it comes in, can be blocked by magnesium. And many of us are low in magnesium. So you can see here this little green right here is magnesium blocking it. Also, the amino acid tarin will inhibit it. So that's why we've been looking quite a bit magnesium tarate perhaps is the good magnesium source when this is an issue. Now, what's interesting, there's something called quinolytic acid. And we're gonna have a slide for this, but it is neurotoxic and it will cause what's called NMDA, it will cause some lipid peroxidation, but it will also stimulate NMDA. And this comes from something called the chironine pathway that we're gonna show you a little bit later. Now, Dr. Jill, we have found a SNP that I've now put into my top 10 list. There's an enzyme called ACMSD, right? There's the RS number, okay. And that converts quinolytic acid into picolytic acid. And picolytic, we're gonna show you a slide, is quite helpful and it's very much needed for the proper use of zinc. So if we don't have enough picolytic acid, and we're gonna show you can also have genetic mutations on the transport of zinc. So maybe if you don't get enough from your diet, you don't convert quinolytic to picolytic. You don't get enough zinc, you have trouble carrying zinc. You do not have the ability to hold back this NMDA receptor. So as you can see here, there's multiple, multiple factors involved here. So you've gotta make sure this quinolytic acid isn't too high. And by the way, this interestingly, this nasty molecule turns into something called NAD by these enzymes. And NAD actually inhibits mast cells. So Dr. Jill, that's why we're putting a lot of emphasis recently on making sure that this quinolytic acid isn't too high. And we are looking at, we're in the research phase now, we're not there yet. We've gotta figure out how to get that quinolytic to come over to picolytic so that our zinc can hold this back. This is amazing, Bob. I wanna comment on two little things that came up as you were talking. First of all, we've known for just cardiovascular disease in general, there's kind of four main nutrients that I always think about for heart health. Magnesium is one, tarine is number two, then there's carnitine and CoQ10, but magtarate has always been a huge cardiovascular. And as we know from your slide just previous, this calcium channel is very important for cardiovascular disease and prevention and regulates blood pressure and all kinds of other things as well. So that's interesting that on this other level, this magnesium and tarine are so key. So that's number one. Number two is as you mentioned, quinolytic acid is total excitotoxic. You'll probably talk more about this, but I'll just frame it from a clinical perspective. When I see elevated quinolytic acid in the urine, it is literally the number one red flag for neurodegeneration for a bipolar, schizophrenia, ADHD, any sort of excitotoxic disease where there's a mental component or a nervous system component, because literally quinolytic acid elevated will kill nerve cells and there's a whole another pathway that's not shown here again, you'll probably show it to us that steals from our happy serotonin, right? Again, you know this well. So this is such an important pathway Bob that you're talking about and I want our listeners to know that this is involved in a lot of depression, anxiety, bipolar, mood disorders and learning disorders and neurodegeneration because it literally elevated quinolytic acid will be so excitotoxic that it will kill your neurons and your brain cells. Absolutely, we're gonna show a little later how it actually stimulates the inflammation. So this just shows the way we've got to be very careful with glyphosate, why we need to check our homocysteine and if it get it down. This is why some people do not do well on glycine and this is also why some people as you said are so anxious. So we're looking at this NMDA receptor as being a big problem. And again, we're talking about mass cells but as you pointed out, it's way, way beyond that. Okay, now here we're saying that massive activation of the glutamate receptors we just talked about can result in excessive rises in the calcium that's thought to underlie the fundamental processes leading to neuronal death. Preventing such cellular calcium rises in the brain may reduce considerably the neuronal damage either that's produced by stroke, head trauma or epilepsy. Here again, another study. If anyone wants to read the whole study just go to a search engine and just type in that title and that will pop up the whole study. I just took like the one sentence that summarizes it, excessive or prolonged exposure to glutamate causes an elevation of intracellular calcium levels that can ultimately trigger neuronal death. Now, I've been talking about glutamate probably for the last 15 years. From a standpoint of yes, it makes you intelligent, highly motivated, go get her, but it can make you anxious and it can lead to a little bit of ADD, bipolar, schizophrenia. Only recently have we dug in and realized this is also a very powerful way to create inflammation inside the body and we'll be connecting those dots a little bit later. So here that's saying just another study that says the activation of the NMDA receptors produces prolonged increases in that intracellular calcium concentration. All right, now we're gonna get just a wee bit deeper here. So you'll see on the right here, that's what you just saw, okay? So we went through all of that. Now what I'm gonna talk about is glutamate. So right here is glutamate, makes you intelligent, highly motivated, go get her, okay? And it's made from glutamine and they're actually genes that are enzymes that will cause the glutamine to turn into glutamate. Glutamate will go back into glutamine. There's an enzyme called DAO that when there's mutations on it, it will cause the glutamate to go even higher. There's enzymes called glut and gut that will turn glutamate into alpha-ketoglutarate which is energy inside the mitochondria and you can have mutations on glut, and one of the things, Dr. Joe, I'm very excited about recently is oxioacetate. This shows up in the Krebs cycle and it takes glutamate and turns it into alpha-ketoglutarate. Now, this is surprising. I mean, we just literally learned this in the last couple of months. Something called pyruvate turns into oxioacetate. And one of the B vitamins is biotin. And if you speak to most people about biotin, it's like, isn't that for the hair, the skin, the nails? You know, yeah, sort of. I've just begun to learn recently, biotin is much more important than we ever realized because the pyruvate carboxylase enzyme will take biotin and turn it into oxioacetate to clear the glutamate. So for some individuals, if you have a genetic mutation that you don't transport the biotin, that you don't recycle the biotin, that you don't use the biotin to turn the pyruvate, your low on oxioacetate, which also impacts your Krebs cycle, but this glutamate is allowed to run wild. And Bob, there's a product, I'm not going to mention brand names on here, but there's an oxioacetate that I've been starting to use in clinical practice because it was talked about with the cell danger response, which is kind of related to mass selectivation and the studies on this oxioacetate using high doses can decrease that cell danger response and decrease the mass selectivation, but I did not know this pathway. Like now that I see it, it's like an aha, because of course that works. And of course you can do it with more biotin or pyruvate in the right person too. I'm sure you'll tell us about that, but this is fascinating. Yeah, absolutely. I'm starting to use that product as well with very good. Yes. You know, and guess who else on this call? That would be like me, has high glutamate. Yeah, both of you. I know I'm like, I'm on this. Love it. Now, what gets interesting then is that glutamate will stimulate the NMD receptor that we just talked about, but there's even more. Now this really surprised me. So this line here is your cell wall and there's something called lipids that have to replace the cell wall and build the cell wall. So as you all know, we're made of cells and we've got this cell wall and it's made up of from lipids, our fats. Well, what can happen is that iron and hydrogen peroxide, and by the way, this might be another podcast sometime just to dig into this, what's called ferroptosis, it will damage this lipid. And if it joins the cell wall, it damages the cell wall. And I was hoping to have another graph made up just couldn't get it done, but there's a dance between this damage to the cell wall and the NMD receptor and something that we're going to talk about later. Maybe that'll be our part two at some point. But what happens is when this lipid gets damaged, there's an enzyme called GSS that makes something called glutathione. And then an enzyme called glutathione peroxidase number four that takes the glutathione and fixes this guy. So he can join the cell wall in a healthy way. It's called lipid peroxidation or ferroptosis. So you can see glutamine comes in, cysteine comes in, and as you all know, the glutathione is a tripeptide. So it's got lysine, glutamine, and glutamate. But interestingly, look at this key point right here. Glutamate inhibits the enzyme that brings the cysteine in to make the glutathione. Whoa. To me, that was a big deal. And then also cysteine, if it doesn't turn into glutathione, it can actually be inflammatory by, especially if it can't go through what's called suox, and that'll actually make inflammation. So people might be taking cysteine like NAC, thinking, oh, cool. That's going to make me more glutathione. But if it's blocked, and you might have problems with something called the suox enzyme that's downstream down here, you can actually make inflammation by taking NAC. Ate when that happens. Bob, I love that you mentioned it. I just want to emphasize because, and a quick question. Well, first of all, NAC is a precursor of cysteine. So everybody out there has probably heard of NAC. Many of you are taking it. And I would totally agree. Clinically, I have seen people get worse, and they have underlying infections, inflammation that's not controlled, and too much NAC can be a problem. So be very aware. All these nutrients have their good sides and bad sides. I have a question that you may or may not be answered to you, but that alpha-ketoglutaric acid or gluterate at the top left there, I see your arrows going from glutamate. So I'm assuming your body can convert glutamate to that, and that's a good pathway because that converts to energy. Does taking alpha-ketoglutarate do anything to the glutamate itself? Is there any back pathway that you know of? Well, I mean, I've never studied that dug into it, but I mean, it would just make clinical sense that if you would take too much of it, it may cause the glutamate to back up. So which, you know, we've said this many times, you know, not too much, not too little, just about everything. Yeah. And then another question real quick, lipid membranes there. I'm assuming this could be measured with lipid peroxides, which we can measure in the urine and blood of patients. Yes, like the OGHD or something like that. Yep. So if you have had done organic gases and you have high lipid peroxides, which is a sign that your membranes are being damaged, and this is what Bob's talking about with that inflammation and the lipids being oxidized there at the bottom left. Yes. And, you know, when we get breakdown of the cell membrane, that's when the body breaks down. Because we live and die at the cellular level. Yeah. So you can see now why I have a new appreciation for glutamate not just makes you anxious and gives you nightmares. It can actually do serious damage to the body. Any other thoughts, questions on this before I move on? Just one more caveat. If you're out there and you or a loved one has cancer, these pathways can be active in cancer, especially one thing I always look at if someone has cancer is are they making lipid peroxides or 8DH DOH is, which 8D oxy. Can't remember the full name there, but those two markers are related to oxidative stress and definitely related to DNA damage, which is a precursor of cancer. So this is relevant not only to inflammation, muscle, but patients with cancer. Well, let me talk about one of my other pet peeves. A lot of people think they have an upset intestinal tract, which they might. And too many times people reach for are suggested glutamine. I'm not anti glutamine. It does stimulate mTOR. It will rebuild the gut. But if you've already got this overactive, you can be throwing fuel on the fire by taking glutamine. And that can include things like bone broth. Chinese food, collagen, all of those things that we tend to think are good for us, like bone broth. Well, that can't be bad for you. Well, if you've got too much glutamine being made, in some instances, that could happen. Now, again, I'm not anti bone broth. You know, it has a lot of benefits. But if this is an issue, maybe some caution is warranted. Bob, I love that you said that. One thing that you find on labels and health foods and different things is otalyzed yeast extract. In fact, it creates a great flavor in our brain. It's almost like a natural MSG. And the same thing goes for that. That's a precursor of glutamate. And MSG is as well. MSG is glutamate. So anything with MSG, anything with otalyzed yeast extract, anything with collagen or bone broth, those things can trigger this pathway. Absolutely. And now there's times that it's absolutely necessary. But if we're concerned that this guy is too upregulated, caution might be warranted. All right, quinolinic acid, and you did a good job talking about how dangerous it is. It's an agonist meaning it supports or stimulates that NMDR receptor. So it's a brain excitotoxin. And they're saying it's a neurotoxin, glyotoxin, pro-inflammatory mediator, pro-oxidant molecule. It can alter the integrity and cohesion of the blood-brain barrier. How often, I know you do look at a lot of organic acid tests. How often do you see that elevated, Dr. Jill? And I check pretty much every single person for this. It's on my organic acid panel. I would say on this, it's probably 10 to 20%, which is still, you know, one or two in 10. Not as high as just the mass selectivation, but let's say even 10%. It's significant. And like I said, there's a few red flags in my practice that I see. And this is one of them that I'm like, oh, this is very bad. This will long-term lead to some sort of neurodegeneration and mood disorder or some long-term sequelae. So it's a really big deal if you have this elevated. Absolutely. Just another that kind of says the same thing, implicated in the cause of many human neurological diseases. All right. Now, picolinic acid. Now, if you remember back to my chart, I showed you there's an enzyme that turns quinolinic into picolinic. And I'm very intrigued by this because we found a study that when that one that AM SSD that I showed you, when it's homozygous, a much higher rate of depression and or even suicidal ideations. So that quinolinic acid is really playing havoc on us. And I think we found the one RS number that can really impact it. Now we're way early on this, but what I'm finding is in many autistic children, they have a homozygous on that one. They can't convert the quinolinic to the picolinic. So on the other hand, picolinic comes from a tryptophan that I'll show you in a little bit. I repeat that gene real quick. I know you said it. I want to make sure people hear it. And then I heard it. The gene that converts quinolinic to picolinic is what? ACS. Got it. D. Thank you. And there's the RS number two, one, two, one, three, three, seven. And I didn't, I don't think I put that slide up, but there is a slide that this is related to depression. Well, that would, that would certainly make sense. Yeah. So if anyone can check their genes for that, that's a good one to look at. So as I said, we're seeing that quite often in autistic children. Okay. Now the. Okay. Picolinic neuro protective, immunological anti-proliferative effects. Picolinic acid increases the turnover of zinc in addition to enhancing the absorption of excretion. So it has implications for uses in zinc deficiency. So think about how this becomes the perfect storm. If you don't turn your quintalink into picolinic, you're going to stimulate the NMDA, then you might be inhibiting the one mineral that calms it down. Perfect storm. Now just clinical observation only. We're seeing many individuals who have difficulty converting quintalink to picolinic along with trouble transporting zinc as almost like the perfect storm. So we've been trying to put these people on a lot of zinc picolinate. And Bob, there's a German researcher who's doing DNA addicts. What he's doing is he's testing your DNA for things that stick to the DNA and damage the DNA that could be aspergillus like mold that could be metals that could be all kinds of chemicals and toxins. He literally does a panel of the DNA for these adjuvants, but the core thing that he finds is low intracellular zinc is the thing that triggers the worst reactions, which goes back to probably this research here and why zinc is so core and so important for detox. Absolutely. I'm glad you pointed that out. That's very valuable. All right. Homocysteine. We mentioned this earlier is known as an agonist. Again, that means it helps it. It's an agonist means it goes against it to that NMDAR. So it's so important to keep your homocysteine levels in check. And I'm sure you check that. Don't you, Dr. Jill? I do on every patient. And my ideal is below nine. If you're healthy below seven, if you have neurodegenerative disease. Absolutely. And I'm surprised how many doctors do not check it. It's often when you're, when we're consulting with folks, it's what's your homocysteine. I don't know. There's a book out there called the higher your homocysteine, the sooner you die from all causes. And we're going to show you very briefly another pathway that homocysteine can stimulate what's called the, the fentanyl reaction where iron becomes a free radical. Okay. Just another article here. Homocysteine dependent and MDA receptor stimulation and the resultant calcium influx leads to rapid and sustained plus four elation glyphosate. Again, peer reviewed study. You can look these up. If you type all these words in the whole thing will pop up. Our results strongly suggest that activation of the NMDR pathway together with its downstream calcium is caused by glyphosate. Brutus modifies the NMDA receptors and can make up seizures worse. So what have we done in the last 40, 40, 50 years? One of my, by the way, one of my favorite jokes is I was born in 1954 and when I'm speaking to younger people, I'll say, yeah, I was born on a different planet, meaning that we didn't have all of these things that we have today. So we have high fructose corn syrup. Then we have the glyphosate. No wonder we're seeing so many people struggling and anxious. Now this is the fascinating. It's called the arrow hydrocarbon receptor. Not many people have heard about this yet. And I think in the functional and naturopathic world, we really need to dig into this because in my opinion, this is a big deal. Now we're going to, this is the cell. This is the cytosol and this is the nucleus. A ligand is defined as any molecule or atom that binds to a receiving protein otherwise known as a receptor. So here's a ligand. It attaches to the AHR enzyme. It then goes into the nucleus and it binds with something called ARNT. And hold onto your hat. Depending upon what the ligand is, it can be pro-inflammatory or it can be antioxidant. As you know, Dr. Jill, most enzymes we look at, they can create free radicals or they'll create antioxidants. This one is a different animal. So I think you can see why I'm very intrigued by this guy. Then there's another one called AHRR that will calm this down. Now we are really in the early stages of this. Now I know a lot of holistic health practitioners watch your videos and my message to them would be, you need to start looking at this because this is a big deal. So what it does, a ligand here is defined as any molecule that binds to a receiving protein molecule and the aryl hydrocarbon receptor is ligand activated that takes in environmental, dietary, microbial, metabolic cues to control complex transitional programs. And we say complex. This is still now being researched by the scientific community and data is coming out. I mean, there's so many papers being written on this. This is being looked at. But I'd like to bring attention to it, to the functional world because I think it's a missing piece. This is a little dense, but I do want to go through the whole thing slowly. It's a transcription factor and receptor for small molecule chemicals including dioxins, environmental pollutants. Now, as you pointed that out very succinctly in your opening comments, but it will also take in things such as flavonoids, byproducts of intestinal microbiomes and drugs. Now, once this ligation occurs, it translates to the nucleus. In other words, it goes into the nucleus. Then this big word here, the direct interaction between at least two different functional receptors forming a complex with specific biochemical and functional properties different from those of the component receptor unit. Boy, is that a mouthful? With the AHR nuclear translocator ARNT, binds and regulates the expression of target genes. In other words, it will determine based upon what the ligand is, what it does. Now, one of the things that it turns on is CYP1A1 and CYP1A2 and 1B1. And that's called cytochrome P450 or phase one detox. Is that a good thing? Yes, unless it's excessive, because what happens is this takes toxins, turns them into something that can be absolutely worse if it's not cleared by what's called phase two. So if your phase two enzymes are not doing their job properly and you start simulating phase one, you can have a little bit of a problem. So the reactive oxygen species are generated during this process by these cytochrome P450s or this is a wild antioxidants through NERF2. NERF2 is what turns on all your antioxidants. So you can be turning on more inflammation or anti-inflammatory. And there's also, to make it a little more complex, there's an aero hydrocarbon receptor repressor and we haven't even begun to dig into that. There might be some ways to turn this on. So as you can see, this is incredibly complex. So perhaps someday when we have all of this down, we could do a whole podcast just on how this guy works. But look at this visual. If you get some dioxin or other bad chemicals, it'll stimulate the CYPs and make oxidative stress that does DNA damage and inflammatory cytokines. Or if the right flavonoids go in, it turns on NERF2, the master antioxidant and has antioxidant properties. So Jill, do you a little surprised by how this one guy can do two different things? This is amazing, Bob. And I knew you told me there was some really cool thing you're going to share today. And once again, my mind is blown. And you're right. I feel like I know a lot of what's going on. I have not studied this mechanism. Yeah, I think we really need to. I think those of us in the functional world really need to understand this because as we'll talk about later, some of these nasty chemicals that we know that we weren't exposed to 50 years ago is stimulating it. So here we are, these aero hydrocarbon receptors. They control mast cells. Ta-da. They result in calcium and reactive oxygen species dependent enhancement of mast cell activation. EHR is critical in controlling mast cell homeostasis. So I'm sure you're already in your mind thinking this through. So Bob, how do we not have it stimulated to the inflammatory side and how do we stimulate more of the antioxidant side? And we're getting to this a little bit. But again, this is all brand new and we have a couple clues, but we're going to be learning a lot more as we go along. So here's that EHR and look what it's doing. Stimulating the calcium channel to bring in calcium to combine with arachidic acid, which is one nasty, nasty bad boy and makes inflammation. And here again, this is just another chart. Here's the citation. If somebody wants to dig into the article as a whole article here, our EHR stimulates mast cells. Now what's interesting is EHR wears two hats. It can stimulate interleukin-6, which is inflammatory, tumor necrosis factor. It can stimulate IL-2 and IL-4. But look at this. It stimulates NQ01, which is anti-inflammatory. Stimulates NERF-2. And again, stimulates that CYPs. So it's amazing how this one enzyme here can have all these different properties. So what I believe is happening, I mean, this was again part of the wonderful creation that the body is and it works fine until we muck it up with all these environmental factors. So here's another slide that shows some of the things that will stimulate it. Vascular disturbances, impaired blood-brain barrier integrity, neuro-inflammation, neurotoxicity, immune suppression, circadian disturbances. Oxidative stress increased angiotensin-2. That's what puts your blood pressure up. Decreased nitric oxide, vascular inflammation, cellular sentinence, inhibition of autophagy, the cleaning of the cells, messing up with our circadian clocks. All of that can be affected by this EHR being out of whack. Sleep disorders, metabolic disorders, immune disturbances, decline in autophagy, decline in the mitochondria. We spoke about these and also then, you know, bottom line decline in the lifespan as this gets over stimulated. I'm not going to read you. Bob, I want to mention really quick on that slide before there, that IDO enzyme, which is related to the quinolinic acid conversion. And years and years ago, when I was a big, probably 15 years ago on that IDO because it converts to quinolinic acid, which is our, we know the bad boy, we just talked about. And there's many things that stimulate IDO enzyme, but one weird one that we haven't talked about, I want to mention is parasites. And I have seen a correlation with parasite infestations and sleep disturbances. And as you mentioned here, this is to me is another aha today because I'm like, oh, this might be the pathway or one of them by which parasites that you have in your intestines that you maybe don't know about is impairing your circadian rhythm and impairing your sleep. Absolutely. And I had some slides in here that I took them out. But as you know, some research has been done at Stanford on how the IDO-1, when stimulated by a tryptophan, goes along for a little bit and then it conks out. So if somebody has mutations in the IDO-2, that can create something called metabolic trap. But I took those slides out because I thought we were getting into a little too much today. These are all the parts of the body. And again, I'm not going to read them for time, I mean it's just about everything can be affected when this EHR is out of whack. My summary there is the pizza's bad if you look like a slice of pizza, right? Yeah, bad pizza there. There you go. All right, here's another map that I made that we're going to spend a little bit of time on. So let me get the drawing tool. So this is called the chironine pathway where tryptophan and amino acid, we just, Dr. Joe just spoke about IDO-1 and IDO-2. They'll make something called chironine. And then it'll go through a whole other process here where it ends up with your quinolinic acid and there's that ACMSD. And then that eventually end up in NAD which will calm down the mast cells. But for now let's look at what happens when this chironine or any of those substance stimulates EHR and here's the one that suppresses it. This is where it combines and stimulates the aryl hydrocarbon receptor. Now you'll notice that mycotoxins stimulate it. Arachidic acid stimulates it. Now we're going to talk about polycystic aromatic hydrocarbons as well as homocysteine. We'll all stimulate this receptor. And then what I did here I just drew all the things that will happen but it will stimulate interleukin-6 and we spoke about this and I believe in our Rante's discussion then stimulates the NOx enzyme, then stimulates KIT which stimulates mast cells. But hang on to your hat. It also creates increase in intracellular calcium concentrations. And then as we spoke about earlier here's the map that we showed earlier how the glutamate through NMDA upregulation stimulates the problem and then we could have EMF, voltage-gated calcium channel creating this intracellular calcium. So there's a lot that can go wrong here. And then of course we show up here the CYPs, you know, xenobotics will be turned into carcinogenic compounds. And I'm going to show you a little study later that upregulation of the RO hydrocarbon receptor can actually cause weight gain. I'm sure many people have looked at crowd pictures from the 1960s and if they look closely it's like there's not many people that are obese. You look at a picture today and do you know the statistics of how many people are now obese, Dr. Jill? Oh gosh, I think about diabetes which is closely related and it's like one in three I think is predicted or even currently. And I want you to just repeat what you just said about that body mass just because I think this is such an important point today of is it the cytochromes that are just repeat what you just said there I think it's so important. Oh, the cytochromes or the body mass gain? The body mass gain. You know what, I have a slide coming up. Okay, perfect. One or two slides which shows it in detail. So we have all these chemicals now including chinearine and I didn't put them in here but there's genetic mutations that can get the chinearine stuck when we actually look at the map cause we're gonna, Dr. Jill's gonna be brave we're gonna look at this mapping her again so we'll take a peek at her map so there's just so many things that stimulate this. Now just very quick clinical observation we are noticing that when people have mutations on here they're very inflamed because we believe that even like the good flavonoids are not carried in to stimulate nerve 2 but that's just all speculative at this point but I think how everybody can see why we're really excited about this the potential for how we can alter this by what we're exposed to. So here they're talking about that chinearine promotes mass cell activation and what we're doing is we're talking about this guy right here and I probably should have put it in there's enzymes here genetic mutations you can have that you get stuck here but you can see that chinearine will promote mass cell activation through that aryl hydrocarbon receptor here we go this is what we were talking about chinearine induced aryl hydrocarbon receptor signaling in mice causes body mass gain liver stenosis and hyperglycemia isn't that astonishing all right then here's another one inhibition of the aryl hydrocarbon receptor prevents western diet induced obesity so this may be the key as to why everyone's gaining so much weight I mean it's diet and it's lack of exercise and many things but this could certainly be a factor so you can see that this leads to the obesity so this study showed that inhibition of the HR blocks the cycles output to prevent obesity again if anyone wants to read the whole article just type that in on Google and up will pop the entire article with all of this if anyone wants to really dig in and learn more anything else on that Dr. Jill oh your microphone's off we go sorry I got a tool got all hooked up there and tangled okay all I was going to say is this makes so much sense as we started with toxic load increase in obesity this is one of the mechanisms you've just described as far as how all these chemicals in our environment are contributing even if you're eating the same thing exercising the same amount to the increase in body weight gain fatty liver and obesity absolutely so the gut microbiota activates tryptophan metabolite can there any to mediate this case are talking about some kidney cancers but we need to really dig into this because tryptophan can turn into something called tryptomine that stimulates the RO hydrocarbon so we would like to see if we can find maybe some probiotics that would inhibit that but that's research for another day now I'm not going to read all of this but these cyclic aromatic hydrocarbons or PHs they're made whenever substances are burned coal gas sites breathing smoker coming into contact with contaminated soil exposed us to this now what's been happening I don't know if that's happening in your neck of the woods but here in Pennsylvania we really got impacted by those California Canada rather forest fires I don't know I guess you weren't affected by that in Colorado were you slightly but we have our own so many fires last year it's just starting this year and of course we're recording this just days after the beautiful town of Lahaina and Maui was burned to the ground so I know they're experiencing and our love and prayers go out to all those people in Hawaii who lost homes but I want to mention something really important we think mold is bad and I test the labs like TGF beta after mold exposure after the forest fires here and the wildfires here in Colorado I was seeing the lab values actually much much worse from the smoke and fire exposure than even from mold exposure so I have actually seen objective data that this inhalation of smoke is as bad or worse as a mold exposure for most of my patients absolutely this is the names of them and if somebody wants them they can you know pause the video and get them but if they come throughout the environment in the air water in the soil they can persist for months or years PAH's short for polycyclic aromatic hydrocarbons numerous carbon atoms join together as at least 10,000 difference of them they can come from animal matter carbon fuel such as coal or petroleum they can come from the city parts of smoke or ash automobile exhaust industrial emissions smoke from burning wood charcoal and tobacco interestingly grilled smoked and charbroiled foods are sources of some PAH exposure and here's an article that's saying that the they're created by incomplete combustion and they induce the cytochrome we feel P450s that we just talked about through activating the aero hydrocarbon receptor all right now off to dioxins again through the activation of the aero hydrocarbon receptor are potent toxic substances wildly distributed in the environment so this could be doing it as well they're often harmful to human health they're sometimes called persistent organic pollutants because they take many years to break down some of this even comes from food animal products dairy meat and seafood it can get into the drinking water according to the EPA it can come from different sources it's mainly the result of industrial processes and the EPA has listed dioxin as one of the 30 hazardous air pollutants that pose the greatest threat to urban areas and this chart shows how the dioxins come into the cell they combine with the EHR and with the RNT and stimulate reactive oxygen species through cytochrome P450 high levels of dioxin is in cigarette smoke so this might be one of the mechanisms that cigarette smoking can be so bad for us and you know we're stating the obvious if you're a smoker a really good idea not to now I just put this in for fun this is my office and I just snapped these pictures in my office I have something with a carbon filter something called molecule and by the way this is not a promotion for them at all by any stretch there's lots of them out there and a dioxin so I just mentioned when people come in my office they look around it's like you've got three air purifiers yep that's the door coming in this is next to my desk this is a little countertop Bob I have three in my 1400 square foot condo and I have five in my office so I totally am right there with you alright this should suggest that AHR has tumor suppressor like activity for human lung cancer so I know this guy isn't all bad but arsenic can throw a monkey wrench into it and again we're getting arsenic from I believe we can get that from chicken and rice if I'm not mistaken so again homocysteine activates the AHR pathway I am really becoming fascinated with arachidic acid this is one bad boy and it actually plays an important role inside the cell membrane and I'm going to show you a little chart and this could be another topic to discuss the genetic and epigenetic patterns that causes arachidic acid to come outside of the body but the bottom line is it will stimulate the AHR from the arachidic acid this is a test called your omega 3 index and this shows your omega 3 and you can see from this individual it's low in the red this is the omega 6 to 3 ratio it's high and here you can see the arachidic acid EP ratio high and we are seeing individuals you can see this goes up to 32.1 and it should be 2.5 to 11 I'm seeing this in the 50s, 60s and 70s in some individuals and I believe it's one of the bad boys that's really creating a lot of problems now just very briefly we'll show how we can get arachidic acid and we spoke about this if somebody is really interested we did the video a couple months ago on Ranties and we talked about the tumor necrosis factor and by the way this is held back by something called hemoxygenase so if you get a chance watch the video Dr. Jill and I did on hemoxygenase because that holds this back mycotoxins, virus, clostridia, beryllia, lipopolysaccharides stimulate TNFA you can also have genetic issues with the TNFAs overactive it'll stimulate an enzyme called PLA2 that pulls arachidic acid out of the cell membrane and then here's where it does its damage you can create histamine, you can go through cox2 and make pain and fever this is the one I'm very intrigued with we'll have to talk about it another time through 12 blocks in a process called ferroptosis or through cox1 and make something called thrombotane which can activate your platelets and make your blood to thick so that's why I'm very intrigued by arachidic acid and as we said it stimulates that arohydrocarbon receptor but it's also responsible in a process called ferroptosis where iron combines with the arachidic acid to again damage the lipid membranes you spoke about this thoroughly in the opening aflatoxins and mycotoxins stimulate the arohydrocarbon receptor the endocrine disrupting potential of pesticides will stimulate the arohydrocarbon receptor these are talking about hepsidon deficiency which resulted in iron overloading and hemo-accumulation again promotes the AHR mediated oxidative stress so again iron critical and we didn't have iron life wouldn't exist but in excess we're used improperly in addition to doing some other things it promotes this AHR enzyme we all know lead is not good for us so this is another one that lead will stimulate the AHR and the CYP1A1 to create more inflammation and as we all know many years ago we had lead in our pain, lead in our gasoline and so lead toxicity is a huge problem I would imagine, I don't know if you do with everyone but you probably do some testing for lead I would imagine Dr. Jones I do at some point I test everyone for lead as well yes, how prevalent is it you know I think less than when we didn't know about the we know that a chipping of paints and things are a big issue but I think it's less than an issue than it used to be but I still see it absolutely, mercury stimulates this process anyone who's in functional medicine knows this is the who-who of bad things who are now learning one of the effects it might be having by stimulating this arohydrocarbon receptor it's a testing chart that we kind of sort us all before but this pulls it together a little more effectively so here's tryptophan an amino acid and it needs to turn down into serotonin and then it'll actually also turn into melatonin which we need for sleep there's a substance called BH4 which is needed to turn that tryptophan into serotonin it's also needed to make platric oxide so I encourage you to go watch the video Dr. Jill and I did on INOS and the Carnahan reaction where we looked at how what's called the NOS2 enzyme can be overactive and chew up your BH4 so if you chew up that BH4 you're going to be slightly depressed and then you may have more too much tryptophan well that tryptophan through IDO1 and IDO2 comes down through here makes canarynein and if you remember earlier we talked about how that can stimulate the arohydrocarbon receptor there is one evidence-based SNP I don't have the SNP number here but it will cause things to be blocked right here so we don't go down this pathway and make something called NAD we're also finding there's some mutations on this KYNU that also put the brakes on so we don't get down to this in case anyone doesn't know NAD is critical for life it makes it's part of energy production inside the cell it's responsible for making NADPH and I think Dr. Jill we did a video on NAD and NADPH in the NADPH steel so if we don't get enough of this we have a problem we can also have genetic mutations on QPRT and MNAT that we don't get enough NAD well the NAD suppresses the mast cells so you can see how this canarynein pathway and this whole pathway is becoming so important I don't think we've put enough emphasis on it in the functional world and here you can see NAD boosting molecules suppress mast cell degranulation so you can see if you go back to this map here if we get clogged up right here not only do we stimulate the aryl hydrocarbon receptor that makes more inflammation than mast cells but we don't have the NAD that helps knock it down that's why we're beginning to believe this pathway is so vitally important Resveratrol has antagonistic activity on the aryl hydrocarbon receptor so it may even help with the dioxin toxicity now this is totally fascinating vitamin B12 and they're saying folic acid but they probably mean folate alleviate the symptoms of nutritional deficiency by antagonizing or against the aryl hydrocarbon receptor so what they're saying is only these two substances B12 and folate will actually slow down that aryl hydrocarbon receptor so you can also have genetic mutations that I'll show in a couple minutes here that you may not transport your folate or you may not transport your B12 then if you add to that dioxin exposure or other environmental toxins you've created the perfect storm we've talked about this many times hydrogen, number one, periodic table of elements and there's tablets that you can drop in a glass of water and they fizz, and I know both you and I are big fans of that and I know you also breathe hydrogen as well so who'd have thought that lowly hydrogen, number one on the periodic table of elements will slow down that aryl hydrocarbon receptor aren't a joke, who'd have thought aren't a joke has something in it that induces through AHR and the NERF2 the good side of it so we're going to be learning so much more about this and I'm sure as research goes on there's more things that are going to come to us but aren't a jokes up-regulates NERF2 that's what turns on all your inoxidants one of my favorite enzymes NQ01 which neutralizes superoxide and also helps properly use NAD so here they're saying that it's activating it but it's activating it in the antioxidant side so it all depends what goes in what it does milk thistle prevents the expression of the CYP1A1 and COX2 which are genes targeted by the aryl hydrocarbon receptor indol3 carbonyl it will actually also slow this down it diminished the lipopolysaccharide induced pro-inflammatory gene expression of INOS many of these others and it slows down the aryl hydrocarbon receptor rosemary inhibits activation by dioxin so if you're exposed to dioxin the gentle little herb rosemary can help you out a lot to be learned so I kind of summarized what you can do try to limit exposure to oxins and PAHs consider high grade air purifiers if you're smoking for gosh sakes stop work with your doctor on home assisting and make sure that's okay make sure you have healthy levels of omega-3, 6 and arachidic acid make sure you don't get exposed to lead, arc, snake or mercury try to eliminate exposure to mold and mycotoxins and Dr. Jill has lots of videos on mycotoxins and if you are filled with mycotoxins work with a qualified health professional if you need it might be a good idea to measure the quinolilic and chironine levels in the organic acid testing and again work with a qualified health professional to normalize without a balance make sure your phase 2 detox pathways are working make sure you have adequate levels of folate and B12 but you've got to be cautious we've talked about this before too much folate can stimulate histamine consider hydrogen water, indole 3, carbonyl milk thistle, resveratrol and artichokes and if you really want to go deep look at functional genomic testing to see if any of those things are there now again we're not giving any medical advice here this is just for educational informational purposes but for those who want to know how you can lower the risk of that overactive EHR there's some common things that just you know everybody knows makes sense but this would be some of the things to look at so anything to add to that Dr. Jill? No, fascinating what a wonderful list one thing you mentioned with B12 and folate we know that homocysteine stimulates B12 and folate lower homocysteine so I wonder if that may be just related to lowering homocysteine who knows but yeah we don't know it very well may so what we're going to do now we're going to very briefly look under the hood of Dr. Jill who's very brave I'm the big pig for health so I yeah genes to science here so here is a map of Dr. Jill's data now when we click on any of these here it will show up so very briefly extremely briefly I want to encourage you to go back and watch the video we talked about the Carnahan reaction because there's an enzyme called NOS2 when it's up-regulated will cause you to make too much nitric oxide that can be damaging and to pleat your BH4 and Dr. Jill both mother and father gave her mutation on two of the genes that cause this to be up-regulated and that's why we call it the Carnahan reaction because everyone knows Dr. Jill's health history and how she struggled and this wasn't all of it but this had to be a piece of it so that depletes your BH4 and by the way another topic for another time but fair optosis so it depletes our BH4 you can actually have genetic mutations that you don't make enough BH4 but now let's go up here so and actually Dr. Jill you're pretty good shape up here so you don't have the one enzyme that degrades tryptophan so if someone doesn't degrade excess tryptophan they can actually have extra here's that IDO2 you do have a homozygous on one of them and you can see here it's not that all uncommon it occurs in 25% of the population but it's called the metabolic trap where IDO1 if it gets pushed it works and then all of a sudden it just kind of conks out and stops working so if we have mutations on IDO2 we may not come down this pathway to make our NAD now there's nothing evidence based here but there's a couple that are slightly out of whack here but I don't think that's serious so here's your canirne and then you are a clear sailing I mean look at all that green I mean there's not a thing that went wrong oh it's highly likely that looks that good so this is the one that we talked about the one ending in 37 this is I'm going to put this on my top 10 list of SNPs that are dangerous that inhibits your body's ability to take winolinic into picolinic so we'll go back up here if that picolinic is high we show how that will stimulate the NMDA receptor site and as I mentioned if somebody's got that one plus if they have difficulty controlling zinc and you can see here Dr. Gemley you're perfect on your zinc transport no problems there whatsoever obviously everybody knows you're brilliant so there's genes called grin and you don't have the ones that are considered pathological but you've got a few SNPs here that could increase your NMDA increase your glutamate a little bit we spoke earlier about the oxyoacetate and you do have an interesting mutation on the gene that causes you to recycle your biotin into biocitin and you can see here this only occurs in 4.3% of the of the population so that's why it'd probably be a good idea for you to take biotin but you can see you don't have any other serious issues other than you might make a little more glutamate which again, no surprise because you are one of the more brilliant functional doctors in the United States and that's why because you've got a little bit of extra glutamate there and then when we dig into your aryl hydrocarbon receptor really non-event here I mean you don't have hardly anything on the enzyme itself just clinical observation when people have a lot of mutations on the AR and T many times they're not bringing it in here and they don't have the antioxidant capacity so but you're clean as a whistle here if we do make some interleukin-6 you could have a slightly over overactive interleukin-6 you do have one of the ket genes that you know if stimulated, mast cells could get carried away a little bit and then what we did is remember I said that B12 and folate is necessary to calm this down so what we put in here we put in the whole well not the whole just an abbreviated methylation and you do have one little copy of a folate transporter DHFR MTHFR C677 so maybe a little bit of folate would be a good idea again not pushing the histamine and then interestingly on your B12 there's something called gastrointrinsic factor that's the absorption of B12 the transport of B12 you've got a homozygous here and the MTRR that puts the methyl group so possibly a little bit of B12 and folate you know could be beneficial but we got to be real cautious because as we said that folate can stimulate histamine you've not talked about that that people get a home test and it's like oh my god I got MTHFR and they start taking 3 to 5 milligrams of methylfolate they feel great for 10 days followed by what the heck just happened to me because they've pushed it too hard and that makes so much sense always when we talk because I have been on injectable B12 since my Crohn's and my cancer because I was severely deficient before I knew any of this 20 years ago and I do so well but I need my B12 and it always was the same thing with the methylfolate and it's the same with patients I always want to replete B12 before methylfolate because if you overdo the methylfolate and you have a deficiency of B12 things get way worse and this was the case for me because years ago right after breast cancer I realized oh folic acid anti-cancer at that point I said just like what you're describing and I should say methylfolate was the one I took but for years that B12 has been critical I think it was probably a small contribution to my cancer and Crohn's just a severe deficiency and then you mentioned biotin I've been on that for years and intuitively have known there's something important beyond hair, skin and nails and you just told me recently about that pathway and that biotin gene and it makes so much sense. Sure and just to reiterate this is where we need that oxylacetate that turns that glutamate into alpha-cletary and we're just going to get clinical observing, just observing biotin can help some people with anxiety if they've got high glutamate and if they may need to turn some of that glutamate into alpha-cletary so we can't say that biotin's anti-anxiety I think that's where we get into trouble we try to pin a nutrient to a condition and somebody can be anxious and if this isn't the issue biotin won't hurt but it won't help so that's why we have to get into precision care where we see exactly where the need is so Dr. Jill although you didn't do too well on the nitric oxide side as we pointed out over here you had a little trouble over here you were better than most very rarely do I see anybody who's got clear sailing all the way down through here so just some typical things like avoiding some of those toxins a little bit of E12 and biotin like you're doing would probably be all you need so there you go so thanks for being brave and letting everybody see you you're welcome hopefully listening out there getting some of this great information you're probably going to want to watch this again and tell us where we can get more about what you're doing where we can find you this slide is for health professionals so if you're a health professional and would like to look at the genetic information we have software called functional genomic analysis that creates that map that you just saw we have supplements and we also have a saliva test that measures the DNA so if you're a health professional and you find this interesting just go to functionalgenomicanalysis.com get a free trial of the software we also have an online certification course that talks people through it's like 24 hours of instruction to learn it all first three modules are free if you're not a health professional and you just want to listen to it just for fun you certainly can I mean there's no certification or anything but a lot of lay people just say this sounds cool I want to learn it I want us to go on a certification if you use the Dr. Jill coupon save $100 it's only $5.95 save $100 and again this you know if you don't have some health degree this doesn't you can just a lay person can't get this and then start practicing this is for the person who's already qualified to just add that add that to it and if someone wants to talk to us gilifehealthtolhealth.com we still do consulting although I've now been told I'm booking out to November but we're still taking on new folks to try to help them so there is our information that if you want to go to our website give us a call and again health professionals can go here so I think that is the end of the presentation let me find how to stop the sharing there it is awesome Bob is always what a great tour to force of a new round of the aero hydrocarbons I can't wait to continue diving in and I'm sure we'll be doing this again in a few months on the next level thanks for all the work that you do in the world thanks for the brilliance you bring thank you all for listening again you might want to go back and watch this one again if you were listening on audio you might want to watch the actual video on YouTube and all the things we mentioned with basic like methylated bees oxalate I'm going to put links to places where you might find some of those things in products if you're interested Bob thanks again for joining us today it was a lot of fun did I with my promise true that this would be fascinating it was fascinating I love it thanks so much and thank you everybody for joining us