335: Resiliency Radio with Dr. Jill: The Cell Membrane: Your Body’s Power Grid with Bob Miller

Hey guys, welcome to Resiliency Radio, your go-to podcast for the most cutting edge insights in integrative and functional medicine. I'm your host, Dr. Jill, and with each episode, we dive into the heart of healing and personal transformation. Join me as I interview medical experts, world leaders, innovators of all types, helping you on your journey to optimal performance and healing. Today you're going to hear from one of my um most repeat guests, some of the top episodes, Dr. Bob Miller, who goes into the genetics and different pathways. Uh today we're going to be talking about a protein you may or may not know on the lipid billayer. It's called cardiolipin. So stay tuned. And if you haven't yet heard Dr. Bob, um you will enjoy this episode. Before we do, I just want to remind you we are accepting new patients at Flat Iron Functional Medicine in Lewisville, Colorado. You can call us at 3039937910 to schedule or you can go to email info@flatironfunctional medicine.com. Um you can meet our providers with a 10-minute free call if you prefer or you can just get on the schedule and see one of us as an expert um medical detective to help you solve your clinical problems. Also, as you know, products and services I offer at drillhealth.com. You can check that out for more things for your health, for your gut, for your brain, for your long co or whatever you're suffering. Check it out there. Get 15% off your first order. And if you haven't yet ordered my book or check out the unexpected finding resilience through functional medicine, science and faith. You can find that anywhere books are sold. Um, one of the most common feedback I've heard um from the readers is I sat down and read it in one sitting. So, it tells my own story of overcoming uh Crohn's disease, cancer, and mold related illness and all of the battles and difficulties that I overcame, but also the the things that I learned in the process. Um the really practical tips, including things like how to deal with our old trauma and uh relationships and things that you might not expect. So, check it out wherever books are sold. If you want a signed copy by me, just go to Dr. Jill Health and order it there. Lastly, I just want to remind you that products and services at drjillhealth.com like our ultra hydrating boost booster are available. These are Dr. Jill beauty products that are clean and effective. They are some of our top selling products and I always want to remind people of that because they're some of my favorite things and I really love the beautiful labels um there as well. They just happy. They make me smile. So hopefully it'll do the same for you. Okay, let me introduce Bob Miller, a traditional naturopath specializing in the field of genetic specific nutrition. In 1983, he opened Tree of Life, a practice and served as a traditional naturopath for 27 years. He lectures nationally and internationally at seminars to educate healthcare practitioners about genetic variance. If you've been on this channel, you have heard him before, but let's dive right in with Cardiolipin with Bob Miller. Bob, we're back again. I don't know how many this is now. You probably have it uh the numbers of what we've done, but this is always such a fun episode. Um kind of different from our normal episode, but we're diving deep. and you've got some really profound discoveries about the cell membrane that we're going to dive into. So, I'm just going to hand it right over to you. And as always, um we're like we're like the talk show host, you know, back and forth. I'm going to let you kind of go with it and then I will comment clinically as I see interesting things that you're sharing with us today. >> Absolutely. And this is number 14. >> Amazing. That's pretty pretty amazing. >> Yes. So, you're seeing the screen? >> I am. Yes. Looks great. >> Yeah. We're going to be [snorts] talking about the cell membrane, your body's power grid. Now, what's absolutely fascinating, Dr. Jill, >> is that uh you know, we have been doing this, as I said, for a long time, >> you started all the way back in 2020. >> Wow. >> Episode number 16. And what's interesting is we've talked about you know things like the peroxy nitrite the over stimulation of NOx IL6 upregulation of that we call the carnahan reaction the he oxygenase pathway super oxide what's interesting we're tying those all together now into one piece and I think everybody's going to be very surprised how we've taken all those things and tied them together. So what we're going to learn, we're going to talk about the cell membrane. We're going to talk about ATP, a denisonin triphosphate, and we're going to learn how that's made in the electron transport chain, and we're going to look at all the things you need for that. The major focus today is going to be on an interesting membrane called cardipen. Possibly people never even heard of this. >> And by the time you're finished, you're going to understand why this cardioipin is more important than we ever realized. And then you also have what's called the lipid billayer and how they get damaged by what's called lipid peroxidation by peroxin nitrite and hydroxal radicals things that we spoke about in previous >> webinars. Then we're going to talk about that lipid peroxidation and calcium dysfunction, how it messes with how your calcium is used and then also how it changes your sodium potassium pump and the consequences that is. And then we're going to tie that into glutamate and anxiety. So, uh, put your seatelt on, folks, cuz here we go. So, I'm going to burn through these pretty quickly. I'm not going to read them all. So, the cell membrane is a thin flexible barrier that surrounds every cell in your body. It's made of a phospholipid billayer. Those are fats with water loving head and tails. It keeps the cells safe and stable. If you didn't have that, the cell would not be functioning. It controls what enters and leaves. It helps with communication. It supports the cell structure, enables specialized functions. So obviously without cell membranes, cell couldn't keep their contents, exchange materials or communicate with each other. We call it the foundation of life at the cellular level, keeping your body cells healthy, organized, and able to work together. Now the first step in making a cell membrane is the formation of a phospholipid eye layer. As we said, we've got the heads and the tails. And this creates a stable, flexible barrier that makes life possible. Now, this billayer serves as the scaffold for embedding proteins, carbohydrates, and other molecules. The functional plasma membrane that controls what enters and leaves the cell. Proteins need to go in and out, controls fluidity with cholesterol, the glyoproteins. And this chart to the right here shows what it actually looks like where there's uh places where the nutrients go in and out based upon what's called the the change in the in the gradient. The your cell membrane is your life gate. That's why we call with that. It lets in glucose, amino acids, your sodium, potassium, calcium. keeps out toxins, maintains membrane potential, houses receptors for your hormones, cytoines, neurotransmitters. And if this gate fails, here's what happens. Dr. Jill, there goes your energy, your communication, and your structural integrity. The cell membrane is your life bait, lifegate, because it controls energy flow, information flow, the ion balance, inflammatory signaling. If it's healthy, the cell adapts, repairs, and survives. If it's damaged, the cell becomes inflamed, disregulated, and eventually dies. And that is the dying process when the cells start falling apart. All right. I know I burned through that pretty quickly, but I want to talk about >> Well, that's so important, Bob. I just want to just we've talked before about these things but this is at such a core level of every cell in the body how it communicates how it um um acts in conjunction and we've known for many many years as well that all I'm sure you're going to go into all the things that damage these membranes but this is really a core concept so I want people listening to realize that this is at the core of so so many complex chronic diseases go on >> absolutely well we want to talk about ATP a denisonin triphosphate People have probably heard that. I mean, they learned that in in high school biology, but it's it's good to review. Your brain, your lungs, your kidneys, your digestive system, your immune system, reproductive, all your cells, the nervous system, the skin, the skeletal system, the muscles, the liver, the heart, they all need ATP. And if we theoretically had an ATP switch, which we don't have obviously, but if we switch that to off, everything would just stop >> because everything depends upon that ATP. >> And that's what we're going to be talking about in this webinar. All right. Now, we just spoke about how ATP is so important. Now, I know many times if we talked about ATP in the past, we said, "Oh, yeah, that's responsible for your muscle energy." But look at this list. Not only energy, if the low ATP, you're going to have increased inflammation, lowered repair, lowered resistance, >> fatigue, your sodium potassium balance goes off, your calcium regulation goes off, you're going to become anxious, and we're going to talk about that a little bit. There's something called gal cells that'll give persistent inflammation. >> So, Bob, pause right there really quickly. ATP, we know about energy. You've got these incredible lists, but you just said something that I think you're going to talk more about later. problems with ATP could actually cause anxiety. Is that true? >> Yes. >> Brilliant. >> Yep. So, we're going to get into this. Impaired neurotransmitter balance in neurons creates anxiety, impaired gal cell function, impaired protein synthesis, reduced antioxidants, cell loss and organ dysfunction, decreased immune function, reduced muscle function, impaired digestion. restore ATP and you restore life. >> Wow. >> I'm gonna tie this into why the three major things that we're seeing today is mold getting stronger, >> Lyme disease, spike protein, and I'm going to tie that all together >> into why that's attacking our ATP. Now, we're going to talk now about how you make ATP. There's something called the electron transport chain. And we'll try to make this simple. They're called complexes and there's five of them. And what happens is electrons that come from something called NADH flow through what's called an iron sulfur cluster. We're going to talk about that. It also needs heem. And then what happens is these protons get pushed into the inner cell membrane and each one pushes a little bit out and then they come back in in number five >> and make your ATP. >> So what we're going to be talking about today, Dr. Jill, is what can go wrong here and there's a heck of a lot that can go wrong. So NADH now I would I would encourage people to go back and look at one of our the last webinar we did and that was on the importance of NAD NADPH. So your NADH is what provides that electron that pushes it. So that's that's how it's made. Now look what happens if we have low NADH which many people do. In our clinic, we measure >> the NAD NADPH. And if you got low NADH, you're not going to be pushing those protons up and you're going to have low energy. So, it's episode number 270. I would encourage people to go back and watch that one. We really dig in deeply into NAD, NADPH. We don't have time for it today, but encourage you to watch episode number 270. So that's if we have low NADH. Now on the other hand, in episode number 270, we talked about that you can have too much NADH if it doesn't get turned back to NAD. That can be just as bad >> because the electrons back up >> and then it'll actually come back to a complex one. And we'll talk about this later. the electron leaks off and makes a free radical called super oxide. >> Yes. >> Now again, I would encourage everybody go back and watch our video. I think we spoke like for an hour and 15 minutes on super oxide. >> So you see how this is all tying together. So if we have balanced NADH, sort of like Goldilocks and the three bears, not too much, not too little, then the protons fly out, they come back in, and we have plenty of ATP. >> So it's really critical that we have this NAD, NADH balanced. Again, episode 270, watch that to learn all the complexities of that. Now, CoQ10, I'm sure most people have heard about CoQ10. CoQ10 is part of the shuttle that takes that electron. So, you can see one and two here start donating. They hand it over to three. And we could probably do a whole episode on CoQ10, >> but just briefly, it's in two forms between reduced and oxidized. So, we have to have enough CoQ10. >> Yes. >> Well, guess what? You can have genetic snip single nucleide polymorphisms that impair the efficient creation and utilization of CoQ10. So if you don't have enough CoQ10 here, you're not getting the whole way down here and you're going to be tired. >> Mhm. Now also he now what's interesting episode number 119 we spoke about he and he plays a lot of roles but I'm just referring to it right here you can see it's in complex 2 complex 3 complex 4. So if you don't have enough heem then you're also not going to have those protons go up and make your ATP. So here we say inadequate he can therefore impair electron flow, lower ATP production and increase electron leakage and oxidative stress. And guess what? You can have genetic weakness in the hem cycle and we talk about that in episode number 119. Now here's u what we spoke about in that episode. But I'm not going to go through it here. But this is the pathway in which you make that heem. And for example, you can have lead exposure which will impair this. You can have genetic snips mutations. All of that will impact your body's production of heem. So here's another way that your ATP can be lowered. Now this is one that I'm absolutely fascinated. >> Now Bob, I'm gonna ask really a quick question about hee. Um, and this may be a silly question, but I bet if those people listening might have the same question, he how is that related to iron and feritin directly? If you're measuring that in the blood, is he a different part particle or is it actually >> I do believe. >> Yeah, I do believe it's it's different than your your iron or feritin. Yes. >> Um, we might want to go back to that episode and watch that. I think we >> in there. Yeah. >> Now, this one I'm absolutely excited about. Nobody's talking about the iron sulfur cluster. Mhm. >> And what that means is that iron and sulfur combine together four irons, four sulfers and make an iron sulfur cluster. And you can see here it is in complex one, two and three. And if we don't have the iron sulfur cluster, this is what helps those electrons flow. >> And if you don't have that, this isn't going to flow. So, I'm sure Dr. Jill, one of the most, you know, biggest complaints you hear from some of your patients is they're tired. >> Yes, >> they're fatigued. Well, you can see there's a lot that can go wrong here. So, here it says when iron sulfur clusters are deficient, electron transfer becomes less efficient, increasing the leakage and super oxide formation while reducing the proton gradient needed to make ATP. >> Yeah. So again, you don't have these protons going up to come down here to make ATP. Then on top of that, the electron leaks off and I'm going to show that later making super oxide. And again, please go back and watch our episode on super oxide so you understand the significance of that. >> Now here is how we make the iron sulfur cluster. This is complex Dr. Jill. So you'll see up here we have iron import and these are what are called solute carriers >> that create the mitochondrial iron pool. Then there's an enzyme called FXN feritaxin which you can also have genetic snips on that provides the iron. Then you need cyine >> and through the uh enzyme NFS1 you can have snips here provides the sulfur. Mhm. >> But you also need an electron NADPH. >> So if you're having trouble with your NAD and you're low in NADPH, you're not donating the electron. >> Yeah. It's like a little recipe equation. >> So then these are the genes. We won't get into this, but these are the ones that actually assemble. And when it comes out of here, it's two fees, two S's, two sulfers. M >> and then through this process we get it into the four fee 4s. But look who's here. Glutathione redoxase number five. >> So if we don't have enough glutathione we don't get from two to four. >> Mhm. >> And then through these enzymes right here and if you want and you can have genetic snips here, you can have genetic snips here. It hands it over to complex one. Now, what we've been seeing as we're looking at this, I am stunned for how many people this is their issue. >> And when we're uh at the end, we're going to you're so brave. We're going to look at your genome and I'm going to show you why this might be something you need to look at, Dr. Jill. >> Oh, excellent. >> Now, here's what we need. If we have iron that's too high and cyine too low, you're going to have not enough clusters and you're going to be making what are called hydroxal radicals. We spoke about that in our very first webinar. If ideally they're balanced, everything's good. You're going to have adequate ATP, low inflammation, everything's going good. If you would have low iron and high cyine for your sulfur, again, you're going to have a problem. And if they're both low, you're going to have a problem. >> Okay, this is fascinating. Again, it's so clear. And I want to just mention people out there might not know cysteine. NAC is a form of cyine that we take as a supplement. And this is why I've always known in clinical practice and you and I have talked about other scenarios, Bob, where it's goldilocks. Um, sometimes you just think, oh, I need NAC because it's a precursor of glutathione and everybody takes it or they take a lot of it. And in this scenario, for example, number three, if you took too much and you had low iron, it may be a problem. >> You're right. Goldilocks, not too hot, not too cold, just [laughter] just right. >> Right. >> All right. Now, here's what can happen. We're living in a different world. I often tell people that uh I was born in a different world in 1954. We didn't have so many of the things that we have now today. >> We have the spike protein. This very well may have changed things dramatically. >> Yes. >> There's a lot of people that do believe micotoxins are getting stronger. >> Mhm. >> And then Lyme disease seems to be rampant. Now, there's many things that'll trigger this, but these I think are the the big three. >> Yeah. >> And that stimulates tumor necrosis factor, which is an enzyme that's inflammatory part of your immune system, but again, Goldilocks, if it's too active, we have a problem. Then it stimulates NFCAPPA B. This is the core enzyme that starts putting off inflammation. It stimulates NOx. Again, this was one of our u this was one of our webinars early on. It stimulates ins. This is carnean reaction that we thought >> where too much NOS 2. So if you get super oxide nitric oxide, we get peroxy nitrite. Ironically, oh no, is the uh is the symbol for it. That will then start destroying the iron sulfur cluster. That isn't the end of it. That iron gets released and iron is your best friend unless it's your worst enemy because if it's floating around well on its own, it can be very inflammatory and it will come back and stimulate TNFA. Then through the fentin reaction, hydroxal radicals combine and make hydroxal radicals that does more damage to the lipid billayer. So here you can see if you got plenty of iron sulfur clusters, everything's going good. If you don't impaired electron transfer, proton leak, loss of gradients, reduced ATP, increased reactive oxygen species, and when those electrons leak off rather than make energy, going to show you later how that can create quite the problem. And then you're going to have loss of that membrane integrity. And remember, we said >> that membrane integrity is one of the most important things we need to have. Now, if you wouldn't think that's enough, there's there's more. There's something called the Krebs cycle. And this is really important because this is part of our energy production. It makes many of the things that your electron transport chain needs. But interestingly, there's an enzyme called AC2 and it needs the iron sulfur cluster to turn what's called cisacetate into isocitrate. And if that happens, you're going to have adequate NADH production. You're going to support your ATP. Everything is going good. But look what happens if your iron sulfur cluster is damaged. It doesn't happen. There's going to be citrate buildup, reduced KB cycle flux, less NADH, lowered ATP, more oxidative stress. When we came across that one was like that's a big deal. >> If your KB cycle is not spinning, you're going to be tired. >> And then people try to take all kinds of stimulants and other things >> and either they don't work or they backfire. >> Yes. >> Because you're I'm sure you've heard that many times. Oh, I took I can't take vitamins because they I react to them. >> Yes. >> There's many reasons, but this could be one of them. When you start pushing this and you're stuck here, >> right, >> it's not going to go. >> Exactly. >> It's not going to go. Now, I'm not going to read each of these, but I I'm going to burn through them very quickly, but it just shows all the body systems that are impacted by the iron sulfur cluster. We're going to start with the lungs. If it's damaged, we're going to have electron leaks, ATP declines, lung stress and dysfunction, fatigue or exercise intolerance, airway irritation, pulmonary stress. The brain, same thing. Brain fog or neurotransmitters, excitability imbalance, neuroinflammation risk, neurodeenerative stress. All that happens if you don't have enough iron sulfur clusters. that affects the brain. >> Here's the kidneys where reabsorption, electrolyte imbalance, fluid dysregulation, kidney injury and risk. >> Then [clears throat] here we have the liver fatigue or detoxification, fatty liver risk, metabolic stress. All if you don't have that iron sulfur cluster delivering those electrons. Now, this is probably going to be the most important thing we're going to talk about in this podcast. >> Yes, >> cardiolipin. It's a specialized phosphoipid found mainly in the inner mitochondrial membrane where the electron transport is located. Now, I'm not going to read all these enzymes. These are the ones that make it. It helps organize, this is key points. This may be the most important thing we're saying in this whole webinar. helps organize and stabilize the electron transport chain complexes. And we'll talk a little bit about super complexes, supports efficient electron transfer and proton pumping, and helps maintain the membrane structure needed to generate ATP. So now I'm beginning to believe that having adequate manufacturing of cardipen and not destroying it might be one of the most important things we should put to the top of our list when we're dealing with dysfunction. Hey guys, just a reminder you can find products and services at drjillhealth.com. Things like the detox bundle, the Epstein bar bundle, and many other things for your gut, for your brain, or for whatever might ail you. Go to drjillhealth.com. Get 15% off your first order. And let's get back to the show with Dr. Bob. Yes. And Bob, in clinical experience, I'm sure you're gonna go to this. But what I see since spike, since mold, since that I'm actually regularly testing every patient for anti-cardipin antibodies because as you have this damaged membrane, the body's like, "Whoa, what's going on with that?" And again, I'm sure you'll explain more about this. Then often you get auto antibodies to that. And to me that's a sign not of lupus although that can be but more of damage to these membranes and I have to actually intervene and um and think about what needs to be done. So there are tests that can measure some of these processes to the cardioipin. >> Yeah. You can't measure cardioipin itself but as you said you can measure the cardipin antibodies. >> Yeah. >> So if the cardioipin falls out of the membrane the immune system says who the heck are you? >> What's going on? Exactly. Exactly. And won't you Oh, sorry. Go ahead, Bob. >> Oh, and then you start attacking what one of the most important molecules might be in the body. >> Yes. And again, you can uh speak to this later when you talk about my genetics. I always share to you guys listening out here who haven't heard of Bob and I episode. I always put my genetics right out there for the public to see. Really transparent. But what I was going to say is after my first um significant COVID infection, I developed anti-cardipin antibodies. Surprise, surprise. >> Well, that's interesting. >> Yeah. So here we go. Neurological disorders, neuroscychiatric disorders, mitochondrial issues, cardiovascular issues, metabolic disorders, skeletal muscle disorders, immune disorders, autoimmune, gastrointestinal, liver, kidney, endocrine, fertility, aging. >> Wow. >> And aging is cumulative cardipan oxidation. Even cardipan abnormalities can have a complex relationship with cancer and vision disorders. >> Wow. hearing disorders, pulmonary disorders, blood disorders, rare genetic disorders, all of that can be related. Now, cardipin isn't the only piece, but it's likely a contributing factor to all of those conditions. So, that's why our research team is saying, you know what, we need to really make sure we are making and taking care of our cardip. >> Yeah. because when it's exposed, it can even directly talk to NLRP3. That's we spoke about that in another webinar, helping recruit and activate the inflammosomes and trigger more inflammatory signaling. That's why we have our little yikes over here. >> Yeah. >> So, you can see how this thing just keeps spinning. So, mitochondrial stress leads to the NLRP3 recruitment, inflammosome activation. So look at all cardioypin helps to do organizes the inner mitochondrial membrane anchors the electron transport complexes stabilizes the super complexes. So let's talk about that a little bit. As I showed you before there's a little space between the complexes and that's where electrons can leak off. When there's adequate cardipin, they get closer together and there's less chance for leakage. So, you're going to have more ATP. It's believed that people who are naturally athletic have that going on that their complexes are close to each other and there's plenty of ATP and not having the u and not having the leakage. So improved electron transfer efficiency, leakage, decreasing your super oxide production, maximizing your ATP, supporting the proton retention, regulating aptosis, the death of the cells, supporting autophagy and the recycling, and maintaining the structure of the membrane. All of that's related to cardipen. Now we could probably do a whole webinar on on just cardioipin but there's something called cytochrome C which is also part of the u which is also part of the electron transfer and if there's not enough cardipen cytochrome C falls out of the inner membrane and then that is really making apoptosis where when mitochondria are actually damaged. Interestingly, this is where red light therapy is shining. >> Ah, >> no pun intended, right? >> Yes. Yes. >> The the red light helps keep that cytochrome C into place. That's why red light therapy has become so popular. >> Now again, we we could spend a whole webinar on talking about this, but this is how your cardioipin gets made. the final step being here. But you also need some of your essential fatty acids and they're controlled by fads two and fads one. One of the things we are finding is that people who are really struggling have genetic snips in fads 2 and fads one. >> Therefore, they're not getting the polyunsaturated fatty acids over here. >> So this final step, they call this TAZ. It combines these two together to make your mature cardipen. So we oftentimes see people that I just spoke to a a 40ome year old woman today who her sister died of a heart attack at 44. She's having heart problems. >> Wow. >> She was homozygous on just about every fats. >> Mhm. >> So she was not making cardio liip >> and creating all kinds of of problems. So now lipid peroxidation again this is probably the key thing we need to focus on today that's where reactive oxygen species here we go back to what we spoke about six years ago >> yes >> hydroxal radicals super oxide and peroxy nitrite attack the fatty acids within the cell and mitochondrial membranes this Dr. deal might be the most important things we've said today. When that cardioipin gets damaged, it de destabilizes the membrane proteins and ion transport, impairs the electron transport chain, lowers ATP, increases electron leakage and super oxide generation. Then it makes aldahhides such as 4 HNE and MDA which can further damage proteins, enzymes, DNA and mitochondrial structures contributing to calcium dysregulation that we're going to get to next. Inflammation, oxidative stress, and progressive cellular dysfunction. See how this is all tying together here, >> Dr. Jill? >> This might be one of the more important slides we're going to show as well. So here's your cell membrane, your lipid billayer. Here's your cardioipin. And when we make super oxide from NOX, I think this is our second webinar we did. When the electrons leak, when we combine to make peroxin nitrite, or if we get iron combining with with hydrogen peroxide, we make hydroxal radicals. There's another one called alux that we won't get into today. They will start damaging the billayer by grabbing a hydrogen. We call that the spark. By the way, this is Mr. Sparky over here. >> Ah, yes. >> Then the propagation where it just keeps feeding on itself until we bring out the firefighters. And that includes things like vitamin E. I particularly like Delta Gold, K2, >> aazanthin, CoQ10, and glutathione. >> They're the firefighters. Particularly aazanthin. It actually protects the entire cell membrane where a vitamin E just protects part of it. >> So, we've been finding pretty nice improvements when you turn off the blowtorrch and you bring out the firefighters. This very well may be step number one. So, I know a lot of folks are like, "Oh, you've got mold. We've got to detox mold. Oh, you've got candida. Oh, you've got heavy metals." Well, if this is malfunctioning and the eliminating organs aren't getting the power, it can be very difficult to do. >> Yes, that makes sense. >> So, I'm putting out that hypothesis that maybe this is step number one. >> Yeah. >> Before you try to do anything else too heroic. And I think this is why Patricia Kane's work on cell membrane restoration has been so powerful in all of these years of any practitioner doing these kind of mold or lime or glanccoid because it focuses on this very topic which is cell membrane restoration. >> Yes, I've been posting this on my my Facebook page and she's actually been jumping in and giving >> Yay. She's probably like, "Yes, Bob, you're bringing evidence to what I've been doing for years. It's amazing." But I mean, you've got the she she obviously knew it worked, but you're bringing a whole new level of understanding to the topic. >> Yeah. And I believe when when CO came along, that's stimulated this. The micotoxin stimulate this. Lime stimulates this >> perfect storm. >> So I believe that's why we might be in a new world here. >> That things that maybe worked in the past aren't going to work quite as well >> until we address this. >> Yeah. >> Step number one here, Dr. Jill. All right. Now, here's another This is one of my favorite pictures. When Here's the complexes again. Here's the protons. Here's the electrons flowing. Here's CoQ10. Here's cytochrome C making the ATP. This represents your cardioipin. If cardioipin gets damaged, these electrons don't make ATP. They leak off. Mhm. >> This is important. Combined with oxygen to make super oxide, then combined with nitric oxide to make peroxin nitrite. By the way, nitric oxide isn't a bad guy. It's very good for us, right? >> Except that when it combines with super oxide, >> then it becomes, oh no, peroxy nitrate, >> and there was some thought that peroxin nitrite wasn't as dangerous, but we're now finding it it really is with new scientific research. then oxidizes your cardiolipin, damages the cardipin. And what do you have here, Dr. Jill? A feedback loop. >> Mhm. >> A vicious feedback loop that as you damage the cardipin, there's more leakage. More leakage leads to more cardioypin. And around we go. >> This may be the key point of this podcast. >> Wow. If this is going on, you got to stop it because if you don't, many things that you're going to try may not work >> work correctly. >> So stopping this is critical. Isn't that uh absolutely fascinating, Dr. Joe? >> It makes so much sense, Bob. I love how we keep going. It's like the Russian dolls you said. We keep going um you know lower into you open one and they're like, "Oh, there's more. Open one. There's more." more and as you get to the depth of this and this is such an essential cell membrane even the cell danger response by Navio was all around when cell me cell membranes get damaged and ATP leaks outside the cell it triggers this response which this is at the core if we can prevent this cardioipin from being damaged so tell us more how do we how do we deal with this >> okay here we go so this is just a little drawing on how the cardiolipin gets damaged from pronoxin nitrite Here again spikes micotoxins lime stimulates microglea M1 TNFA NFCappa B here's your inflammosomes stimulates noxinos then peroxin nitrite oh no damages the cardipen lipid peroxidation and again genetic snips if you got gain of function on TNFA gain of function on fcappa B gain of function NRP3 gain of function IL6 gain a function here. Two people could be exposed to the same thing. But if one person has genetic gain of functions here, they're going to be more impacted. That's why two people can live in a moldy house. >> Yeah. >> One person is sick and the other one says, "But I don't feel anything." >> Mhm. >> There's the difference. Then here comes your hydroxal radicals. Again, I think this was our first our first podcast six years ago. We spoke about how hydrogen peroxide combines with iron in the in the fentin reaction and makes these hydroxal radicals. Now, if we're able to have enough catalase, thyroid or glutathione peroxidase 4, we can burn that off. But again, you can have genetic snips in these guys that you don't clear the hydrogen peroxide. You're going to be more prone for this. And what do you have? Cardiolipin oxidation. Then impaired electron transport efficiency, more electron weak leaks, weaker proton gradients, less ATP and around we go. Now what happens next is fascinating. We we all know that calcium is, you know, critical for the body. It builds the teeth and the bones, but it's also a signaling molecule. It'll signal things. So [snorts] when you move your hand or or uh or your heart beats, the calcium is the one that signals it to do that. But anything can be excessive. Back to our Goldilocks. And there's an enzyme called R Y R1 that takes calcium from something called the endopplasmic reticulum, which does a lot of things, but one of the things it's the storehouse for calcium. And when stimulated here it says when it's excessively stimulated the cytolic calcium rises creating a stronger calcium signal near the mitochondria. >> The mitochondria then take up more calcium through this enzyme increasing and then they're saying excessive matrix calcium can promote oxidative stress impair the electron transport chain and reduce efficient ATP production. So calcium can be your best friend or your worst enemy like everything can be. So this R YR1 can be stimulated by lipid peroxidation. >> Whoa. >> Yes. >> So lipid peroxidation will tell this guy dump out calcium. Well then what does it do? So it says um >> and Bob have we actually see hypercalcemia um in the serum or is this just a process that's intracellular that we could measure? Do we know? >> I'm not sure but just interestingly now this is just >> clinical observation this is all it is >> when I point this out these people do have high calcium in the blood. Huh? >> Well, we already know like cancer situations and and we call them metanoplastic syndromes, which are things that go alongside um not that that always means there's cancer, but um when there's damage and um growth in the body, often this hypercalcemia is one of the things that can happen um again among other things. So, that makes sense. >> So, here we go. Lipid peroxidation generates reactive oxidants and aldahhides that can modify that Ry R1. Oh my goodness. Let me say that again. Lipid peroxidation modifies RyR1 making the channel more prone to calcium leakage from the endopplasmic reticulum. The resulting rise increases mitochondrial calcium uptake primarily through that MCU and that increases more reactive oxygen species, promotes mitochondrial permeability changes, disrupts electron flow through the electron transport chain, and here we go, decreases your ATP production while increasing leakage and oxidative stress. You see how we've got a couple of feedback loops going on here, Dr. Jill? >> Yes. All right. Then here's what happens when we get that calcium overload. Here's your endopplasmic reticulum. Ry R1 becomes overactive. Puts too much calcium in the cyto cytoolic area. Goes into the mitochondria and then that creates mitochondrial dysfunction, oxidative stress, er stress. There's something called cow pain that we can get into later. Inflammation, excitability problems, muscle dysfunction, cardiac stress, cell injury, and apoptosis. [clears throat] >> All of that can occur when this guy is pumping out too much calcium. >> Wow. >> And then we'll talk later. There's an enzyme called NCX, which helps take the calcium out, but that will be weakened if there's not enough ATP. That's where we're going to go here next. So now we're going to move over to the sodium potassium pump. And quite simply what that does, it keeps the balance of sodium and potassium. So you need potassium inside the cell and not too much sodium. And this pump is an ATP dependent membrane that moves three sodium ions out of the cell, two potassiums into the cell, maintaining the electrical and chemical gradients needed for normal cellular function. Look what it does. Nerve signaling, muscle contraction, nutrient transport, cell volume control, secondary transport system such as calcium and neurotransmitter handling. Talk about that stress a little bit later. >> Yeah. When the pump is impaired, sodium can accumulate inside the cell. Potassium gradients weakened, calcium regulations become disrupted, and neurons and muscles may become electrically unstable, contributing to impaired signaling, weakness, excitability, and further cellular stress. And guess who this guy runs on? >> ATP. >> So, we're not going to read all of this here, but here's the here's the sodium potassium pump. taking out sodium, bringing in potassium, running off ATP. Consequences, brain and nerves, heart, muscles, kidneys, intestines, all of those can be impacted if we don't have this guy doing its job. Now, over here you see the enzymes that are part of that and genetic snips here can further impact how the sodium potassium pump does its job. So, one of the easiest ways to see that is when people have edema, the swelling of the ankles. They're they're getting that sodium potassium >> out of balance. Now, here's how we take care of the calcium. Okay? There's an enzyme called circa that puts the calcium back into the endopplasmic reticulum. But look who it's dependent upon. ATP. >> Seems like a common theme here, Bob. We need that ATP. >> We sure do. [laughter] So then if your sodium potassium pump doesn't work, it doesn't create the right gradient. So NCX can take the calcium out and then you're going to have all this cellular stress, impaired relaxation, mitochondrial strain, dysfunctional injury if circa is not doing its job, and the sodium potassium pump is weak. All dependent upon ATP. So this is just another drawing of the circuit that if [snorts] you got adequate ATP, you're going to put this calcium back into the endopplasmic reticulum. Okay? If it's not doing its job, it stays in the cytool creating all the problems that it creates. Now listen to this. It makes neurons more excitable >> and that's going to make you stressed. So you can see how this just becomes a chain of events that keeps impacting. So the brain and nervous system, the lungs, the muscles, the intestines, the heart, they're all impacted if that's not working properly. So here's and again I'm not going to read all this. We could spend a whole webinar on this one, but it just shows how the sodium potassium pump's going to affect the neurons homeostasis and enabling every thought, signal, and movement in the brain. Um it's the foundation for stable neurons, healthy signaling and brain resilience for the heart. It um it may it's the foundation for healthy rhythm contraction and cardiac resilience. Then also for the lungs supports healthy airway function, cellular stability and lung resilience. for the muscles supporting strength, relaxation, and muscle resilience. As people get older, that's one of their biggest concerns that they don't have the strength to stay stable, to walk properly, to fall because, you know, one fall at a certain age can really be serious if you break a hip. So, if you want those muscles to be working, you got to make sure they have enough ATP. And this sodium potassium pump is doing its job. And finally, the intestines supports motility, absorption, and intestinal resilience. And finally, the kidneys, healthy kidney cells, balanced electrolytes, stable blood pressure, long-term kidney protection. All of that is dependent upon that. >> Mhm. >> So, when that's inadequate, loss of membrane stability, calcium may be cleared less effectively, cells may swell. I'm sure you see a lot of people, they've got >> Yes. swollen ankles, nerves, muscles, heart tissue, and other high energy organs may function less efficiently. And as the ATP falls, bump function slows. All right. Now, you had said earlier you were excited about stress. >> Yeah. >> Okay. So, there's something called an astroite, and astraittes take glutamate. Now, glutamate makes you intelligent, highly motivated, go-getter. But in excess creates anxiety, neuroinflammation, can't sleep. It's a mess if the glutamate is too high. Again, Goldilocks. >> Yes. >> Not too much, not too little. So, if we have adequate ATP, you see that up top here, it actually creates a gradient where what happens is that sodium grabs the glutamate and brings it in. If there's low sodium inside here and then this enzyme the u takes the u the glutamate turns it into glutamine which is an amino acid that actually helps make glutathione and goes back out as glutamine. So the excitatory glutamate turns into the helpful glutamine through the afterite >> that's contingent upon the sodium potassium pump keeping that sodium and potassium balanced so that it will flow in. So what happens if we don't have it? Oh, and by the way, I forgot to mention that it's not just um glutamate, it's ammonia. So, there's some researchers that believe this is why autistic children do flapping because of the ammonia and the glutamate together. So, wouldn't that be something if autism was actually an ATP problem? So now here is the astrite where we don't have enough potassium and we have too much sodium. The glutamate remains outside, doesn't come in here. Very little goes out as glutamine and then you're going to have pulling less glutamate in and then the glutamate remains high and you're going to be stressed. That's the aststerite. Now, here's the neuron. So, the neurons, I'm sure everybody's heard of GABA. GABA is the don't worry, relax, be happy. And some people take GABA and they're relaxed. And some people take GABA and say it made me worse. Did you ever hear that? >> Oh, yes. Because I know this pathway well. I do have patients that can't take GABA. >> So, what happens? GABA has one job and one job only. It opens up the GABA receptor so chloride can flow in. But for the chloride to flow in, you have to have low chloride inside. And guess who does that? There's enzymes called KCC2 and NKCC1. So KCC2 keeps the intracellular calcium low. NKCC1 brings it in. Guess who controls it? the sodium potassium pump that needs ATP. So if everything's working fine, GABA hits, chloride moves in ah relaxing. However, if we don't have enough ATP and the sodium potassity balance gets off, there's high chloride inside. GABA hits chloride rather than going in moves out and that's excitatory and we want to do some research on this but this very well may be happening with a lot of anxiety disorders and even uh autism not saying that yet but that needs to be researched >> that makes a lot of sense because I find glutamate being high and in this GABA issue in patients who have like you said it's sometimes on the spectrum or um other things and this this glutamate gaba thing are all about mood disorders and sleep. >> Absolutely. So, as we said, that's why people can take GABA. Somebody tells them, "Oh, you're stressed. Take GABA." And it's like, "It made me worse because it did what it's supposed to do." GABA has one job. Open up this channel. >> Yes. >> And if the chloride is low inside, it flows in. It's relaxing. If it's high inside, it goes the other direction and it's excitatory. Mhm. >> Yeah. So ATP doesn't just power the cell, it determines which systems fail first. So we need to start asking which ATP dependent systems are failing. So here's the cardipen story. Cardipin organizes the electron transport chain. Then it produces the ATP, powers nearly every biological process. When cardio liipin is damaged, they fail in predictable patterns all the way to clinical manifestations physicians see every day. It's a compelling system biology narrative that ties together mitochondrial function, inflammation, organ dysfunction in a single network. So when you got low ATP, it forces cells to reduce non-essential functions, preserve membrane integrity, maintain ion gradients, limit biosynthesis. Physicians often see the downstream effects. Fatigue, organ dysfunction, metabolic inflexibility, sometimes without recognizing the mitochondrial origin. So, ATP deficiency, we talked about the electrical failure, neurological, muscular, immune failure, genetic failure, structural failure, recycling failure, detoxification failure, organ failure. Now, this is a chart that I just literally finished last night. >> Wow. >> And maybe I'm being a little brave here, but I'm saying redefining functional medicine. So, here's your infections, your lime, your micotoxins, your spike protein, your EMF, your pollutants, chronic stress. They stimulate microgle M1, two necrosis factor, NFCappa B. Here's carnean reaction. Peroxin nitrite damages the cardioipin lipid billayer. Mitochondrial damage electron leak. Super oxide that then combines with hydrogen peroxide. Hydroxal radicals. Lipid peroxidation. Okay. And feedback loop. Then iron sulfur clusters. If they're not doing their job, more iron may participate in the fentin reaction. Then again, electron transport chain activity goes down. All of it pointing to low ATP production. That's going to affect the sodium potassium pump. Then we get a problem there. And then comes the calcium. And then here's your impaired aststerytes and neurons. anxiety and hyperbility, hyperexitability and anxiety, and then that glutamate dysregulation causes more cellular damage and around we go. So, I literally just had this >> fascinating. I love it so much. Makes so much sense, Bob. >> Yeah, I'll probably be redefining this a little bit over time, but I think this captures the bulk of I was going to say this is so much that I think we should have a part two and kind of go over like in a few months of what has changed if there's been any little because this is just fascinating. I think the cell membrane concept ATP at the core is really where we should be at really molecular medicine but personalized precision this is where it's at. >> Absolutely. Now, I don't know if you want to share. We've got about five minutes left, so you can decide what's most priority. But, um, >> what we'll do, we'll go through action steps very quickly and take a quick peek at you. >> Okay. Reduce those inflammatory triggers, >> the TNFA, restore calcium homeostasis, protect the cardipin, the uh support cardipin synthesis, limit hydrogen peroxide, support the electron transport co-actors. And we could probably do a whole webinar on that. Uh just very quickly if anyone wants to take a peek at the genetic side, that's what we do. We do functional genetic testing. And if somebody wants to get our clinic, here we are. Treeoflife Health [snorts] toalth.com. We can measure your genetics, do a consult, find out where your weakness is. And then for practitioners, if they would like to do this, >> here's where a practitioner can go ahead and uh and do this. Functionalgenomicanalysis.com. Now, let's take a really quick peek at you, Dr. Jill. >> Sounds good. And I just want to say, Bob, your work here in training physicians and helping patients has been so profound. So, I'm really glad to share this information every single episode that we do because it's that going to this level often gives an insight or aha into these small like the Carneahan reaction, right? One of these things that Exactly. >> Okay. Now, this is Dr. Jill and this is on our functional genomic analysis. So what triggers it is if we absorb extra iron and if you remember your hetererozygous or the hemocromattosis gene. >> Yes. >> Then you also have SLC481 that could give us more iron. This would be a topic all itself, but there's an enzyme called HP >> that helps take the Fe2 into the Fe3. And you can see you got a couple snips there that stimulates TNFA NFCappa B interlucan 6 and here's carnahan reaction. >> These two right here increase excess super o n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n n nitric oxide. Again, nitric oxide is not bad. People get very upset that they're saying nitric oxide's bad. Not at all. But when it combines with super oxide that's when it makes the peroxy nitrite that damages the cell membranes. Then over here if we don't clear hydrogen peroxide and you can see here you've got one homozygous on catalase you'll get hydroxal radicals that makes lipid peroxidation and you're in one feedback loop here. Now remember we said that stimulates the R YR1 enzyme >> to push calcium in to the mitochondria. >> So this is your complexes here. So no matter what's going on with the ingredients that are needed for this if that calcium comes rushing in it shuts it down. >> Okay. >> Then here you can see these are the enzymes that make the cardipen. But you also, if you remember, I told you you need the longchain polyunsaturated fatty acids. >> Yes. >> And you can see it's not real bad, but you have some snips here on fads 2. Your fads one is looking fine. So, you really don't have any trouble, I don't believe, getting the nutrients there to make the cardipin, but your challenge might be that because of the lipid peroxidation, the calcium's coming in. Now, I'm really excited about the iron sulfur cluster. >> Uh-huh. >> So, here you can see the making of the iron sulfur cluster. >> Okay. >> Now, we've not identified which of these are are evidence-based yet. So, we don't we don't know. But you can see here you've got two little snips on the guy that delivers the u the NADPH to make the iron sulfur cluster. But remember I said once you make it, you can oxidize it. And again, not a diagnosis, but a predisposition here, Dr. Joel, >> that because you got a little weakness on nerf on nerf 2 and you got a little weakness on Hmox and little extra push on NFCAPPA B. But here's the one, the NOS 2. >> Yes. If you're making any super oxide, that's going to make peroxin nitrite, which is going to damage your iron sulfur cluster. >> Then this guy right here, you can see you've got a homozygous on all three of them. That's the one that takes the iron sulfur cluster and delivers it to complex number one. >> Wow. >> So now you can see Yeah, you can see there's a second component here to the uh >> Yeah. to that NOS too that and again not a diagnosis but a potential that you might be um damaging those iron sulfur clusters just a little bit. >> Wow. Makes sense. We just like we said we just keep getting deeper and deeper and more um layers and this is fascinating. So if you're out there listening like I said Bob started in the beginning please go back. It's almost like we've created a whole course of episodes. go back to to to the episode that he first mentioned and uh listen to that. He has them all listed in earlier in this. You can just rewind if you're listening uh audio or video. And then um this to me though is the cherry on the top, right? Like this is one of those things that you told me beforehand would be profound. And because I'm also seeing this in clinical practice with more anticardiipen antibodies and um more inflammation and just lipid membranes in general being the core of how we often reverse some of this complex chronic issues. I really love going to that level versus being up here and the infections and toxins. Right. >> Yeah. I think that's the whole point of this. We uh perhaps we're just going too far down and I wouldn't be surprised that co has made it happen. >> Yes. that that is that's what's driving it now. And then mold getting stronger, lime getting stronger, and we're just when I I help doctors many times go through the genetics and they keep telling me things that used to work in the past don't work as well. >> Yes, that's exactly. I often say, you know, I'd have these very simple patients in three months, they'd be well 20 plus years ago and now it doesn't happen that way. It's way more complex and more layers. So Bob, as always, I am so grateful for you, for our friendship. I'm so grateful for the brilliance that you bring to this and I love these very special episodes because they really dive deep and those people who want that are watching and listening and if you guys have enjoyed this or find it helpful please share it with a friend or your physician please pretty please um Bob as always we're going to do another we're going to do round two or round three or round 27. So >> we can do a couple rounds on every because we really just touched the sur we could do >> exactly I was like this is so good and it's so deep like I'm going to have to go and watch it again. So if you're out there listening, you may want to rewind and listen again. But as always, thank you for your brilliant research. Thank you for bringing this to the field. And I hope to see you upcoming in person at one of the conferences. >> Absolutely. All right. Well, take care, my friend, and we'll we'll talk again soon. >> Thank you, Bob. >> [music]