 Bob Miller, it is so good to have you back. You get the honor of being my first guest. It gets at number two, and we're going to do a number three next month, too, because we had the most views of any of the live episodes so far was the last one. So any of you who are watching, first of all, welcome. I'll introduce Bob Miller if you don't know him already in just a minute. But his first episode, you can find on my Facebook page or on my YouTube channel. And my YouTube channel now has over 20 episodes, and they are great, but Bob's is one of the best. I know you're going to enjoy it. So please be sure to go back there, watch our first episode. Today we're going to talk about NAD, and we're going to dive into what that is, what it means for your health, and why it might be the most important thing that you hear this year in regards to your health and overcoming chronic disease. Just a little background. You can get free blogs, free information on my website, just jillcarnihan.com. And later we're going to be talking about an upcoming conference that Bob is putting on, and his events are just fantastic. So we will talk about that. You'll definitely want to save the date. This will be recorded here, so you can watch it. You can share it with your friends or your colleagues. And of course, it will be on my YouTube channel. So welcome, Bob Miller. And I'm going to give a little introduction in case anyone didn't hear the first one. You've got such a wonderful bio. He's Bob Miller's a traditional naturopath specializing in the field of genetic specific nutrition. And what you'll find about Bob is he goes, D, he's got the mind of an engineer, electrician we talked about. And I love that because I do too in its pathways and its processes, and these things all come together and give us really great information on how to help our patients and clients. He earned his traditional naturopathic degree at the Trinity School of Natural Health and is board certified through the ANMA. In 93, he opened the Tree of Life Practice where he served as traditional naturopath for 27 years. For the past several years, he's been engaged exclusively in functional nutrition genetic variants and related research. And some of the pathways he puts together, some of the conclusions about what causes what, what intervenes nutritionally at this pathway level. It's been so helpful to practitioners like myself because we get these complex patients and the medicine we're taught at least in my allopathic background is a one size fits all. And as we know more than ever, it doesn't work that way. Every patient that we see in front of us is different genetically, spiritually, emotionally, physically. And so this really takes into account the genetic and individual variation of our patients. And I find Bob that a lot of the stuff you teach and that we learn with these pathways helps us to make little tweaks and breakthroughs that make all the difference in their care. You can find his full bio on his website, which what's your website, Bob? Oh, tolhealth.com. Perfect, tolhealth.com and information there. But we will without further ado jump in to everything about NAD. And if you wanted to share your slides, we can do that now as well. Okay, we're going to do a screen share. And again, what a pleasure to be to be back here. We had so much fun. The last time it was absolutely, absolutely incredible. And I'm so honored that so many people watched it. So we're going to dig right in. As you said, we're going to we're going to geek out here a little bit. We're going to be talking about why supporting your NAD plus and NADPH levels may be your key to longevity and and health. Now, we're going to talk about these molecules. But first, I want to say they're critical for many things, first for detoxification. And as you know, Jill, we're living in a world that's more toxic than it's ever been. We need to have energy production. We're going to talk a little bit about mTOR and autophagy, the growth of cells and the cleaning of cells, supporting the search ones, which perhaps a lot of people haven't heard about, and recharging our anti oxidants. Now, let's just get into a little bit of the theory behind it. In metabolism, NAD plus, nicotamide, adenine, dinonucleotide, it's involved in redox reactions and transferring electrons. Because when you really get down to it, we really are an electrical being. You know, Einstein told us a long time ago equals mc2 energy and mass are interchangeable. A little hard to grasp, but that's what we are. Now, NAD plus is an oxidizing agent, and it accepts electrons from other molecules and becomes reduced, and this forms NADH, which can be used as a reducing agent to donate electrons. And of course, we all know that in the Krebs cycle, at the top of the electron transport chain, that's how we make our RATP. So they have a critical role in maintaining homeostasis. And then we're going to be talking about NADPH, which is actually synthesized from NAD, and has similar functions. Now, let's talk a little bit about these. They're fundamental common mediators of various biological processes. As we said, energy metabolism, mitochondria, that's where we make our energy, calcium homeostasis. To me, this is the key one right here. Antioxidants, it actually takes your antioxidants after they do their job, they become oxidized, and talk about this more later, and recycles them. But it wears two hats. You will actually generate oxidative stress. And I'm going to just get into that a little bit today, but that's going to be the primary thing we're going to be talking about in our August interview, how NADPH is actually used to make free radicals. And why I believe that this is getting out of balance because of genetic and epigenetic factors, all the things that we've done. We're going to look back someday on some of the things we've done to our environment and say, oops, what were we thinking? Yeah. And Bob, I just want to comment here, because in my mind, I always think about like glutatham, we've known about oxidized reduced. It goes in this cycle. Would you say that we're looking at it's totally different, but it's a parallel cycle of we need oxidized reduced states. And if either one of these states gets imbalanced, we lose our ability to basically recycle those enzymes. Is that correct? Absolutely. Let's take a peek here while we're on that subject. Perfect. So here is glutathione, the master antioxidant. We have to have it. It's part of glutathione conjugation. I'll be talking about that a little bit. After it does its job, it becomes oxidized. So if it sits here and doesn't recycle, it will combine with oxygen to make superoxide. Then it'll combine with nitric oxide to make peroxanitrite, a very strong oxidizing agent. So for this to happen properly, you know, what we have to have here is adequate amounts of NADPH because that NADPH takes your oxidized back to your reduced. So if that doesn't happen, boom, down here into an oxidizing agent. So that's why many times people are so confused. They've got inflammation, some well-meaning practitioner says, oh, I'm going to fix you up. I'm going to give you some glutathione. They feel better for a couple of days, and then they start tanking. And sometimes people are told, well, that can't be happening because this is a master antioxidant. If you don't have enough of this guide, you're going to go down this pathway. So that's why I'm so excited about NADPH. So I'm glad you brought that up because that's a critical, critical piece. And Bob, I just want to mention, because again, you hit the nail on the head for probably so many people watching today. And I'm one of those people we've talked about this before, where I had this massive mold exposure 2015, got so sick, and of course, glutathione. What do you do? Well, I did not tolerate it at all. And back then, five years ago, I didn't understand why. All I knew was I got way, way worse when I would take glutathione. And I know some of you listening are having that experience, and it doesn't make sense. This is part of understanding why that happens and why you need to really make sure it's like carts and horses, and you have to have things in order. And if you just push the end product, you may not get where you want to get. And you may actually cause more harm or more damage. Now, I'd have a question real quick here. What I found for my personal journey that was that precursors of glutathione were fairly safe and tolerated, like glycine and vitamin C and selenium and any any C and even alpha-lipoac acid in small amounts. If someone's trying to replenish their NAD, would that be a safer way to go than giving loads of glutathione? Well, let's first talk about your selenium. You know, your selenium is part of recycling your glutathione as well. So selenium will help the glutathione peroxidase recycle. So again, for low on selenium, could they also have trouble with the recycling? Oh, sure. Yeah. Well, I don't have a chart right here, but the selenium is part of recycling what's called glutathione peroxidase, which clears hydrogen peroxide. Now, you talked about some of the precursors, glycine right here. So glutathione is made from glutamate, cysteine, and glycine. Now, one of the interesting things is the, sometimes people have a genetic mutation that on this gene right here, GCLM and GCLC, if they do, that cysteine does not come down here. And in some instances, this can combine with iron to make hydroxyl radicals. So then cysteine doesn't work. And then also, glycine sometimes stimulates the NMDA receptors and can make the person more anxious. And then finally, here's the GSS enzyme. If this enzyme is not working properly, you're not going to make the glutathione from. And then to make it just a little bit more complex, something called NERF2 and KEEP1 control all of these. So if you've got weakness in KEEP1 and NERF2, they're not turning these enzymes on. And let me just mention what a miracle we are. I give the analogy NERF2 and KEEP1 is kind of like a sprinkler system. In a rough sense, think of KEEP1 as the sprinkler, NERF2 kind of like what turns on the water. So when oxidative stress comes along, KEEP1 says, hey, we got a fire here, folks. Let's turn on these enzymes to make more glutathione. I mean, what a miracle we are, the way the body actually responds and reacts. Mutations here can impact that. And that's why I call it the 3D chess game played under water. So many factors that intertwine. And there just aren't easy answers. There really aren't. Well, and I want to comment, if you're a practitioner listening or a patient, what's so easy to do is you want a one-size-fits-all. You want the hook book. What's the formula, Dr. Jill? And I just want to reiterate what Bob's saying here is there is no formula. It really has to be individualized. And I always get nervous when people have a one-size-fits-all trick. It just doesn't, none of those things work for everyone. And this is why some of the variants that we have genetically in processing different nutrients and our depletions and things and our toxic exposures all play into this. Absolutely. 3D chess game played under water, as we said. Now, let's talk about NADPH in some of the other things it does. I'm sure people have heard of nitric oxide. Nobel Prize winning back in the 1980s, not only is it vasodilative, but it's also anti-inflammatory and does many other processes inside the body. If we don't have enough NADPH, we don't make nitric oxide. And this is where people have cold hands and feet or rain odds, high blood pressure, erectile dysfunction, cardiovascular disease. Many people have never heard of triadoxin, but it's a very important antioxidant. And again, it takes the oxidized back to the reduced. Not enough NADPH, that doesn't happen. Now, we just talked about glutathione. However, many people don't know about this. NADPH just needed to take heme and turn it into ferritin. So heme is where the body takes iron by the FETCH enzyme and makes the heme. And when the heme is aged, what's called the HMOX enzyme, takes heme, puts it into ferritin. Well, if we don't have enough NADPH, that doesn't happen. So the iron gets dumped, becomes a free radical, and the ferritin is low. And then if you think, oh, my ferritin is low, let me take more iron. If that's what's happening, you can just again make more inflammation. Then heme also makes something called bilivertin, which is a very powerful antioxidant that actually calms down mast cells. And so many individuals now, everyone's talking about mast cell activation. Well, this could certainly be because of environmental factors. That'll primarily be what we're talking about in August. All of the environmental factors that stimulate the mast cells. But we need bilivertin to calm that down. And then we also turn heme into carbon monoxide, which interestingly stimulates the nerve too. So now you can see why I am so excited about NADPH when you look at all the functions that it does. Now, this is fascinating. You know, 12, 15 years ago, we started learning about MTHFR and C677 and A1298. And everything you've heard about that is correct. It's what puts a methyl group on the folate. And we all know that we need folate for so many things, for making our semi, our methylation, you know, it's needed by pregnant women. And I won't go into all the details of this, you know, somebody can read this slide later. But what's interesting, if we don't have enough NADPH, taking folate actually shifts the balance towards oxidation. So once again, somebody says, oh, I have MTHFR, I need to take methylfolate. They feel great for two or three weeks. And then they start feeling anxious, angry, and inflamed. Yes. And they don't know why. And to this day, I still see people that, oh, I saw somebody and says I have to, I have MTHFR, I need to take methylfolate. My answer is maybe. Because if you don't have things lined up properly, folate will actually stimulate what's called mTOR, mammalian target of rapamycin, which of course is needed for the growth of new cells. So that's why pregnant women needed. But interestingly, a lot of people don't know this, but the COVID virus hijacks mTOR for replication. So if our mTOR is running too high, there's the potential here that we could give COVID an opportunity to replicate too fast. So that's why before I give people folate, it's like let's make sure we've got enough in ADPH. And I'm sure you've probably seen lots of people that were told they need methylfolate. They took it and they felt worse. Yeah, Bob. And I just want to comment because back when I was 25, a long time ago, I had breast cancer. Well, that was three years ago, right? Yeah, just three years ago. I love you. So anyway, all that to say, I found I had methylation issues. I had one copy of the C677. I was low in B12 and methylfolate. And of course, what do we do? And this was years ago, I didn't have all the understanding that we do today. I took methylfolate. And this was after the cancer. But as we talked about through mTOR, can actually without NAD appropriate levels, which I'm sure I've been depleted all my life until recently, I actually created more cells and had more breast lumps that they thought were potential for issues. And that was all because I had really pushed some high doses of methylfolate. So you can really get into trouble with even cancer or pre-cancerous or fibromas or cystic things with this process as well. And you want to work with a practitioner who understands and not just push methylfolate without the other precursors. The other thing you said that I think is very relevant is the mTOR is hijacked by COVID. Now, we've seen some evidence that perhaps patients who are really into bodybuilding and pushing mTOR with amino acids and some of the peptides and rapdomycin. So there's all these things that a lot of the anti-aging groups are doing to push mTOR. And could it be that some of those people are a little higher risk for complications of COVID? We don't know for sure, but some of the evidence is pointing to the fact that that might be true. And this is why. Yeah, now's not the time to be pushing mTOR in my opinion. If it doesn't make any difference, well, it doesn't matter. But if it does, I'd rather be safe than sorry. Yes. Yes. So I'm sorry to interrupt you again, Bob. I just want to mention our practical terms. The opposite mTOR is autophagy when your body, when your cells are actually eating up the bad guys that are doing the wrong signaling and going to go down a wrong pathway. Your body says, Hey, you need to kill yourself. And that's autophagy. So autophagy and mTOR are always balanced. And we want that balanced. And one of the things, and Bob, I'd love to know if there's other things that you know of. But one of the things that helps autophagy is fasting. So that's one reason why intermittent fasting can be helpful to balance that mTOR autophagy pathway. Sure. Well, let's let's take a quick peek at that over on that subject. Let me just pull in the maps and charts here. So let's take a look. You are so good at finding the details that I love it right on the spot. But I think it's important and practical for those listening. So I love that you brought that up. There we go. The beautiful mTOR chart. Yes. So let's look at the mTOR chart. So this is actually what I did when I on one of my studies in 2018 on Lyme disease. So and one of my things that I that I really believe is happening. As you said, mTOR is the growth of new cells. Okay. So we have mTOR growing new cells and we have autophagy cleaning the cells. And interestingly, autophagy, we believe takes out the virus as well. Now, what have we done in our environment? We have all these plastics that are creating xenoestrogens. What do they do? They stimulate mTOR. So as you said, some of these protein drinks and things. And I think we're going to look back someday and say, what were we thinking, giving our animals growth hormones? Well, they'll get fatter faster and we can make more money. Yes, but that gets passed on to more mTOR. Higher levels of glucose and insulin, iron will stimulate it, methionine and sami, glutamate, and of course, folate. And that's why, of course, women who are pregnant need folate because if they don't have fast reproduction, they're not going to make the new baby. So they do not get pregnant, have a miscarriage or deformity. So during pregnancy, you want to push that mTOR. But if you're not pregnant and you're concerned about inflammation, pushing mTOR too much can be a problem. So you talked about intermittent fasting. Well, of course, when you stop amino acids, the carbohydrates, the iron, the glutamate, the folate, I give the analogy, think of mTOR as the construction crew. And it's building. When you take away the materials, it says, well, I can't do any building. Okay, janitors, come out and do your job. And that's what they do. The janitors, so to speak, come out and start cleaning. And I found in my one study on Lyme disease, those that were chronically ill with Lyme had epigenetic and genetic factors that threw them into mTOR dominance. And I think you said intermittent fasting, right there, ketogenic diet, but also resveratrol, turmeric will slow down mTOR, while lithium, vitamin D and berberin support the AMPK enzyme that supports autophagy. And I believe we have just done so much in our environment and even cytokines. You know, we're getting more cytokines now because of inflammation. They're all stimulating the mTOR to our detriment. Again, that's why I believe we're seeing such great results with intermittent fasting and the ketogenic diet. Thanks for going over that. I think that's so important for people to understand the balance. Absolutely. Yes. I'm glad to go down that little bunny trail there. It was a good one. Now, this is how we make NADPH. So tryptophan, which, you know, most people know about that's, you know, what we get in our turkey. Most people know that goes into serotonin, but it will also go down this direction by TDO, IDO1 and IDO2. Well, if we've got genetic mutations here, this pathway may not be as robust. And there's a scientist doing some research. I'd love to do an interview with him, but he believes when there's mutations here, this is where you get the excess serotonin and you don't get it moving down through here. And this is the de novo pathway, more enzymes, more mutations there, and then quinolinic acid. Now, this induces NMDA receptor mediated lipid peroxidation and anxiety. So when people have mutations in QPRT, these are the people that are getting hit in two ways. Their quinolinic acid is too high and then they're not getting the NAD that they need. Now, a lot of people are learning about nicotamide riboside and nicotamide mononucleotide and even niacin. Okay, this is what comes down through NMNAT. And as we age, this is what weakens for us. And therefore, we don't get as much NAD. Now, interestingly, NAD then NAD plus can go up to NADH or it can come down to NADPH. One of the mutations that we find very clinically significant is NQ01 because this is the NADH to NAD plus. And when these are out of balance, this is when people are in a hyperstate, tremors, migraines, because they're not getting down through here. Now, I'm going to talk about this more, but NAD plus also supports PARP, which is DNA repair. So as our DNA gets damaged, PARP jumps in and says, I need to do some repair. So bottom line is here, there's a lot that can go wrong here in making your NAD plus. And again, same thing. We are learning about all the benefits of NAD and I'm going to talk about more of them. So we tend to think, gee, the more nicotamide riboside or more nicotamide mononucleotide I take, the better off I am. Sometimes. Same as methylfolate. So let's dig just a little bit deeper. And this is a complex chart that we really don't need to get into a lot of the details. But NAD plus stimulates what's called the search ones, which are involved in longevity. And part of it is because they make SOD and catalase. And I'll be showing a chart on that in a little bit. These are major antioxidants that neutralize free radicals. And if you've got way too many free radicals going on, you know, you're going to age prematurely. And as we spoke about, here's the NADH and energy production. And then my favorite NADPH. And I want to get into this again later, recycle your antioxidants or free radical production. To me, that is what is so fascinating. This guy will either help you make antioxidants or make you make more free radicals. To me, that's fascinating. And the whole premise of our research being that I believe epigenetic factors is tilting that balance, that this NOx enzyme is being unnecessarily upregulated, pulling away from all those good things and making excess free radicals. Now a lot of people tend to think, well, free radicals, they're bad. No, they're not. They kill the pathogens, they're signaling. Without them, we die of infection. But if they're in excess, that's when we have a problem. Bob, I just want to ask you a question real quick. So that SOD you mentioned with catalase, which is really critical for decreasing free radicals. I noticed there's an SOD mutation. I happen to have that. Is that related to a down regulation of the production of SOD in catalase? Absolutely. Well, just SOD. There's cat genes that make the catalase, and then there's SOD genes that make the SOD. And what we find is that when people have a lot of mutations on SOD, they're really struggling. And if you remember when we talked about peroxanitrite a month ago, we many times showed that superoxide combines with nitric oxide to make peroxanitrite. Yes. And if we don't have enough superoxide dismutase that feeds upon itself, and peroxanitrite is a very oxidizing agent. Would that make sense? Again, I'm just always wondering, and based on some of my personal and clinical experience, I definitely have a lot of SOD mutations. And I've noticed that like hyperbaric chambers and ozone, anything that creates some oxidative stress, I don't tend to tolerate well. Do you think that's correlated with the SOD types of mutations? Oh, absolutely. Yes. Because I'll be showing a map a little bit later on here that shows how we need the SOD to turn some of those things into hydrogen peroxide. And well, why don't we just jump there now? I love this that you go on rabbit trails with me. Now, one other question. Now, H2 in the LD, I know we both like that. And I use it almost every day after work for about 30 minutes. I love it. But I'm assuming that is a pretty safe bet for someone like me with SOD mutations. Is there any way that that pathway could be overdone? No, I don't think so. Hydrogen is very safe. So here is your free radical superoxide. We need SOD to turn that into hydrogen peroxide. Then we need glutathione peroxidase that we spoke about. Thriadoxin to turn this into water. And then we also need NADPH to keep recycling these guys. So if we don't turn this into water, and here's catalase that turns it into water and oxygen, it'll combine with iron to make your hydroxyl radicals. And that's where the hydrogen water or the breathing hydrogen will neutralize these hydroxyl radicals. Because look what this guy will do. Combine with nitric oxide to make ONO peroxynitrite. And the same way here, if we don't have enough SOD, we make our ONO peroxynitrite, which suppresses the immune system, leads to osteoporosis, inflammatory bowel disease, on and on, and depletes our glutathione. So yeah, that's why I'm a big fan of hydrogen water and breathing hydrogen. I just, in prep for the show, I always try to like to have my brain as clear as possible. So I did about 20 minutes of hydrogen about an hour and a half ago just to, you know, on the top of my head. I love it. And like I said, I do too. And I know people are always asking, so I'm going to get a practical really quick. I know you have hydrogen tabs for sale in your line of products. So do I at my store? So make sure and check out Dr. Bob's on those. They're super easy. They're not expensive. You can put a couple tabs in water. And while it's fizzing within about 90 seconds, you just drink it down. And I find that people who do that, this is a much more simple, cheap way to do it than inhaled. The inhaled is probably more powerful for sure. But the machines cost in the thousands of dollars. I got mine from high tech health. I'm curious as to where you got your machine Bob. So you can go to high tech health if you're interested. But they are, yeah, they might be run upwards of $5,000 for the machine. So you can get the tabs for a while less. Absolutely. So these NAD levels decrease with age. And that's why the aging process takes a toll on us. Now, one of our researchers found it absolutely fascinating. They found that perhaps the best time to take NAD is around three to four PM from a, you know, an oscillation standpoint. Now, probably a lot of people have never heard of Sertuans. And we're not going to get into a lot here, but there's a process called acetylation and deacetylation. In a normal cell, these are balanced. In an abnormal cell, the acetylation is weakened and the deacetylation is strengthened. And all of these, this is dependent upon adequate amounts of NAD. Now, we spoke about PARP and that is DNA repair. So when peroxynitrite or other free radicals damage our DNA, again, what a miracle we are, Dr. Jill, we have the ability for the repair team to come out and start to fix us. And PARP does that, but look what it needs. It needs NAD plus to repair the DNA. So if we don't have enough NAD plus when the cells get damaged, we don't have the ability to do the repair. So that's why that NQ01 is so important because if you're stuck in the energy production and not down in the NAD plus, you don't have the ability to do that. So now would probably be a good time for me to swing in another chart here. And it shows the, all the things that the NAD plus does. So let me bring this guy over here. So here's your NAD plus, which we spoke about earlier. But now in this chart, we show the downstream effect. Here is your PARP enzymes, DNA repair. And in our talk on peroxynitrite, we talked about how the peroxynitrite creates the carbonate radical CO3, which oxidizes the guanine. And then here's the sirtuins, SIRT3. And look what this guy does. Turns glutamate to alpha-ketoglutarate, which is energy, helps the ureocycle, clear ammonia, stimulates the foxos that makes your SOD and catalyze. So are mutations in SOD important? Sure they are. Okay. But if the SIRT3 is not working, or it doesn't have enough NADPH, you could have perfect SOD here, and you're still going to be low in superoxide dismutase. So that's why we have to look at this globally. Not just SOD mutations, that's important, but it starts all the way back here. NAD plus feeds SIRT, feeds foxos, feeds SOD. So that's why I believe this NAD plus is so important. But hang on to your hat. Look what happens here. SIRT3 supports autophagy. SIRT1 inhibits mTOR. So we talked about this imbalance of mTOR and autophagy. So an inadequate NAD could actually be one of the contributing factors to this imbalance between mTOR and autophagy. And as you said, mTOR replicates cells. It's like a copy machine. It doesn't care whether it's a healthy cell, cancer cell, or a virus, it replicates it. And these two have to be balanced. Many factors that go into this, like over here is those enzymes we spoke about, and AMPK, there's a lot that gets involved in here. NERF2 regulates them all. But for now, we're just pointing out how NAD lack of that could lead to an imbalance of mTOR and autophagy. Good question, Bob, for your clinicians like myself. I'm assuming like insulin growth factor in the blood would be a way to measure like an offshoot of mTOR. Is there anything else that would tell us if we were measuring in the blood or serum or urine that would tell us status of mTOR versus autophagy in a real life patient in real time? That's the only one I'm aware of, but I'm hoping that we're going to learn more as time goes on. Now again, 3D chess game, the sirtuins that we've talked about do all this protective things. PARP is needed to repair your cells. So the more you're damaging your cells with peroxanitrite or other agents, the more your NAD gets tied up in PARP and is not available to sirt. So not only do we have to make sure we have enough NAD, we want to make sure that we're doing all we can to minimize damage to the cells. And again, I'd encourage people to go back and listen to that other interview that we did a month ago where we talk about the myriad of ways, even including EMF, that can cause the damage from peroxanitrite. And here's just showing how peroxanitrite stimulates the PARP activation. So when the body makes that peroxanitrite, it says, oh, damage is occurring. PARP comes in. Again, what a miracle we are. And God put us together, the miracle of being able to repair. But if we overwhelm that with too much peroxanitrite, we just can't keep up. And that's when people break down quickly. You know, I'm sure we've all seen people that are say like 50 years old, and somebody looks like they're 35 and another one looks like they're 70. The difference being is the oxidative stress to the cells and the ability to repair. So again, that's why big fan of NAD. Now, we already spoke about the production of it. I just thought I'd show that one more time. These are the steps. And these are the genes, TDO, IDO1 and IDO2, tryptophan, chironine to quinolinic acid, QPRT, a big one, grape seed extract, interestingly can support. So it's amazing how people can reduce their anxiety and make more NAD just by grape seed extract if they've got mutations in QPRT. These are your final steps. And I already spoke about NQO1. And interestingly, there's an old herb from South America, polyarco. And it's a source of the beta-latchocone, which supports that conversion. And I've seen many people like have tremors and other things improve dramatically when they start taking polyarco. So, Bob, I love that. I just want to comment again, clinical perspective, quinolinic acid, that's a bad one. I always hate to see that, especially with neurological neurodegenerative diseases, we can actually measure in the urine, kinurinate, quinolinic acid, and 5-HTP metabolites and see what's happening here. But just like you were mentioning there, I find it hard in clinical practice to say, what can we do to stop that fire? It's a fire on the brain, fire on the nervous system. You mentioned grape seed, so that's a powerful one. I've heard magnesium and NAC may have some, is there anything else that we could do with quinolinic acid from a nutrient perspective? That's all I'm aware of. Now, here's why it's so important that we understand this, because if you just start taking nicotamide mononucleotide or nicotamide riboside, and you're stuck up here, you can actually make things worse. Just a quick clinical study, I had a gentleman with tremor. Nothing medically worked. I mean, they were ready to put probes in his brain, which he wasn't too excited about. We put him on polyarco, about an 80% improvement. Then I said, okay, let's put a little bit of nicotamide mononucleotide in, and as soon as we did, the tremors came back. So we actually had to back off here and just keep going with polyarco. So that's why it's so important to know if you've got NQO1 mutations, because you can think you're doing well by throwing this in, because we all know the benefits of it. But if we're stuck here, we can make things worse. Hate when that happens, right? Yes. And again, I love putting these clinical things in, because again, I'm a wealth of guinea pig experience. When I first got NAD, I was like, wow, this stuff is amazing, and I felt so good. And just like you're talking about, you need folic acid, NAD, and you need all of these different pathways. Well, again, as we already know from the comment I mentioned before, I tend to be lower on my methylated B vitamins or historically have been. And after about a month or so, I started feeling more tired and more depressed and more a lack of stamina, like lack of energy. And of course, as you know, where I'm going, I was depleting my methyl donors. And so patients who are very, you know, more, I would say fragile, although I don't like that word like myself, they kind of walk this fine line. I find it's real important to make sure they have TMG, methyl folate, methyl B12, a few of the methyl donors along with, especially nowadays, we're pushing really high doses of this. So you've got to make sure you have any comment on that. And is that an experience you've seen happen as well? Absolutely. People who are low in methyl groups, I mean, this really is a form of niacin. Yes. So you do need the methyl groups. And again, that's for the people that are, that are under-methylators. For the people that are over-methylators, it probably helps them by depleting some of those methyl groups. Again, one size does not fit all. Everyone's unique. So besides the MTH of our gene, is there any of the things you'd look at with poor methylators versus, so under-methylators versus over-methylators, is there a few of the top genes you would look for with that? Well, yeah. I mean, COMT uses, let's just take a quick peek here. So COMT, catecholamide nomethyl transferase, needs SAMI. Okay. So if you've got a lot of mutations here, you may not be using the SAMI, possibly putting your methyl groups up. Now, I don't have a chart on this, but SAMI also turns into creatine, which is needed for your muscle strength. So if you've got mutations on the genes that make the creatine, you can also have excess methyl groups. And then, conversely, if you've got difficulty with your MTHFR, MTR or MTRR, you may not take this homocysteine back up through, and then you'll be low in SAMI. Now, everyone looks at MTHFR, but you've got to look a little bit deeper. You've got your folate receptor sites, your DHFR, your MTHFD1. Is MTHFR important? Sure. But I've seen people with MTHFR mutations, and they're doing just fine. I've seen people without them, and they're not because the problems weigh over here. Or, you know, you might be chewing up all your methyl groups because you're desperately having, trying to have histamine and methyl transferase get out all this histamine. So if we don't have enough COMT activity, this is where your dopamine comes in. Now, look what weakened COMT, quercetin. So for some people, if their COMT is low, quercetin can make them worse. Estrogen, and of course, we're living in a sea of estrogen, and tyromine foods like cheese. Interesting. Yes, I've got another quick example for that. So I love my quercetin when I have allergies, and I remember when I used to take that. And all of a sudden, my cycle, I'd get breast tenderness, Bob. And guess what? I was inhibiting COMT and creating less detoxification for my estrogen. So I realized for me, again, there was a very fine line between too much quercetin and not enough if you have a COMT mutation. Absolutely. And then your testosterone supports COMT. So what's happening in the world today? We're living in a sea of plastics, we're swimming in estrogen. And when I talk to physicians who specialize in hormones, they tell me, particularly in the young men, testosterone's dropping. Yes. And that's possibly why when you talk to college professors and you say, tell me about the freshmen coming in, you know, they're sensitive, they get upset quickly, they anger quickly. Well, if you're not clearing your dopamine, that could be happening. Now, there's many factors. Before we started the show here, we talked about how people are getting so angry. Speculative here, but perhaps if this is being weakened, we're not clearing our dopamine and people are just getting more angry. I mean, it's clearly multifactorial. But that could be a factor in what's happening. And stress will affect COMT because you're going to produce more of those hormones too. So that's probably a factor we're seeing right now in this environment as well. Sure. Absolutely. Spot on. G6PD, extremely common in people with Italian background, particularly Southern Italian, Native American, African, very, very common for G6PD mutations, which makes your NADPH. And interestingly, just clinical observation when people have Northern European descent and they make a lot of free radicals from iron, and they also have Southern Italian that they don't have enough G6PD. These are the people that are often very inflamed that nobody can seem to figure out. Pattern that we see all the time. Excess hydroxyl radicals, G6PD mutations. Interestingly, I'm in Lancaster County, Pennsylvania, where I work with the Mennonite and the Amish. And there is one group called the Martins that, while it's back up, the Mennonites are primarily Swiss German. And however, there was three brothers whose name was Martino from Sicily who converted to the Anabaptist Mennonites. And their ancestors have these G6PD mutations. And fascinating how you can actually, when I talk to people in the region, I'll say, is there a Martin in the background? And they're like, okay, how did you know that? Wow. Now, Bob, this goes really close to home because I grew up in Central Illinois with a, I was still like Christian was the background of my family, but they were close, close Swiss German Mennonite relatives. So very, very similar from my background. I know that group. I know that people very well. And I know that these mutations do exist. And we have a lot of Martins that were neighbors. So very fascinating to hear that today. Yeah. Yeah. I'm sorry. Go ahead. Go ahead. Well, I wondered too. So the G6PD, we talked about Southern Italy. And in my studies, it seems that there is a correlation with the complications and infectiousness of COVID in relation to this gene. Do you have any insights into that? Well, sure. Let's think about what that does. That recycles your glutathione. So as we, well, not the G6PD, but the NADPH. So purely speculative hypothesis that the more G6PD variants you have, the less you're going to be able to recycle your glutathione, the more likely you might be for that cytokine storm. Again, potentially my hypothesis, maybe this is why African Americans have more trouble because the G6PD mutations are significantly higher in African Americans. Yeah. Again, really speculative, but that was my thought with Italy and the real difficulty they had in the beginning was, I bet there's this genetic variant that's playing into that as well. Yeah. Well, keep in mind Southern Italy particularly was closely tied to Northern Africa as people migrated over. ME1 is also involved. IDH is also involved. So mutations in any of these could impact your NADPH. And again, I just summarized them here. Genetics involved in that production. So how can we support it? Niacin, nicotamide riboside, nicotamide mononucleotide, grape seed extract for that quinolinic acid to NMN, and or potoyarco for the NADH to NAD+. Now, phase one detox, maybe people have not heard of this, but there's something called the cytochrome P450s. And they're the very first step in detoxification. And what they do is they take toxins and they make them into something fat soluble. And then phase two comes along and puts them into water soluble. Look who we have here. NADPH is needed for that cytochrome P450 to work properly. So everywhere you turn around is the NADPH. So if you don't have enough of that, even your phase one detox, maybe not as robust. We spoke a little bit about glutathione conjugation. And the GSTs is the glutathione S-transferase. This is what takes the byproducts of CyP450 and then turns them into something water soluble. So if you have any mutations in GSTs, that's not going to work very well. So here you can see what's happening here. Here's your CyPs, making your xenobotics. And then your GSTs through phase two glutathione conjugation put these toxins into stool or urine. But what do they need? They need glutathione and they need proper function of GLRX. And you need the master control, nerve two and keep one, telling everybody to do their job properly. Now once again, after it does that, it's oxidized. We'll go on and make peroxynitrite if we don't. And here's our NADPH once again to the rescue to bring this guy back. So if we don't have enough NADPH, even this phase two glutathione conjugation won't be working. And this is one of the pathways that we take out many toxins, but particularly mold. And I know that's something of tremendous interest to you, Dr. Jill. Yes, fascinating. So important. Oh, and this is just some of the genes related to the glutathione production. Now I jumped ahead, but I'll just take a peek at this again. Many people, particularly English, Irish, Norwegian have genetic mutations with the overabsorb iron. Interestingly, this was by natural selection during times of famine. The people who overabsorb the iron were healthy enough to have babies. So in times of famine, overabsorption of iron was helpful. Today, we don't have famine. We put a lot of iron in foods. So if you have that genetic predisposition to overabsorb the iron, and then you don't clear the hydrogen peroxide, hydroxyl radicals. Now, this is what we're going to talk about in a month, but I just wanted to give a preview of what's coming up. There's a fascinating enzyme called NADPH oxidase or NOx. Interestingly, it's got one job, and it's to make the oxidizing agents, superoxide and hydrogen peroxide. Now, why would we want to do that? When we're hit with a bacteria or a parasite or some other pathogen, again, God put in is the ability to put on a fight to kill. So that's why all free radicals are not all bad. If we didn't have NOx, we would die of inflammation. It's helpful. However, the overexpression or overactivation is a major rule in oxidative stress and aging prematurely. So we have to, again, have everything in balance. Too much of anything can be harmful to us. So if we have an increased cardiovascular disease, neurodegeneration, organ failure, cancer, and even autism. And here is a study that said targeting these reactive oxygen species sources with natural compounds may be an important tool. Now, here you can see, this is what we're going to get into in a lot of detail in our next talk. That's what I mentioned now. I'll put this on as well, Bob. But so if you're listening, stay tuned August 28. It's about four weeks away. Same time, 3pm, mountain, 4pm central. We'll be back. And this is what we'll be talking about on August 28. Yes. And the reason I wanted to point it out now, because I don't want someone to listen to this lecture and say, boy, I see all the importance of this. I'm just going to start taking some NAD plus. Because what can happen? As we said, NADPH does all those good things that we talked about. However, when we're hit with a pathogen, the NOx enzyme says, hey, we got an invader here. Iron, give me some oxygen. NADPH, give me an electron. Let's make some superoxide, hydrogen peroxide. Stimulate the mass cells. Stimulate some cytokines, some interleukins, and histamine. And we're going to kick up a fuss here, and we're going to kill this pathogen. Is that needed? Absolutely. Without it, we die of infection. So what we're going to talk about in August is all of the epigenetic factors. We'll look at the studies on them that can artificially up-regulate this. Kind of like the military that starts shooting the citizens rather than the enemy. And look who's here, nitric oxide and oxytocin. Actually, calm it down. Now, this is our latest research, and we've just started to talk about this. So your people are some of the first to hear this. There's a substance called renin that is produced in the body to stimulate something called angiotensin-1. And then the ACE enzyme makes angiotensin-2, and that's why sometimes, I'm sure as a physician, you give people ACE inhibitors for their blood pressure. Then it makes something called aldosterone. And aldosterone causes you to hold on to sodium, excrete potassium, and hold on to water. But it stimulates NADPH oxidase, which then stimulates superoxide, stimulates hydrogen peroxide, stimulates mass cells, stimulates histamine. And again, when we've got a pathogen to cure after, that's a good thing. But if this is running rampant, this is where we create a problem. By the way, I put down here COVID comes in using ACE2. And ACE2 takes angiotensin-1 and angiotensin-2 and turns it into angiotensin-1-7, which is anti-inflammatory. Now, hold on to your hat. High glucose, peroxynitrite, histamine, dopamine, and mass cells all stimulate renin. And if you have genetic mutations in renin, it overreacts. If you've got genetic weakness in ACE2, it runs faster down this pathway. And I believe this research that we've done here is very clinically significant because, well, let me first say that I call this the NADPH deal. I've given it this name. That when the NOx enzyme is overstimulated, the NADPH in a sense is stolen away from its all of its other good functions. So what do you think happens if NOx is upregulated and somebody also has genetic weakness that they don't make enough NADPH? They're inflamed and they can't detox. Now, I've just been presenting this at some other medical conferences. But I think this is very clinically significant. I found literature on this, and we just didn't come up with this on our own. There's peer-reviewed literature that shows that peroxynitrite stimulates renin. Mass cells stimulates renin. Histamine stimulates renin. So what do we have here? A vicious cycle of inflammation. And I've just come up with the name, the home cycle. This is somebody that was a relative of mine that was influential. So I thought I'm going to call this the home cycle of these three guys coming down, stimulating renin. So what does this do? This just feeds upon itself. So the more peroxynitrite we make, the more aldosterone. The more mass cells, the more aldosterone. The more histamine, the more aldosterone. This thing just feeds upon itself. And of course, I know you're a big fan of making sure we have enough mycotoxins. Well, the mycotoxins stimulate the mass cells. Lime stimulates the mass cells. So all of these things can kick this off. And that's why I believe some people, they're told that their Lyme disease might be gone, but they still feel horrible, purely hypothesis. But I have to wonder if this thing is just not feeding upon itself. I think so much sense. And I love this. And I'm so excited that we get to hear your brilliance here today as some of the first listeners on the topic, because I know this is going to be big. Now, one thought is we can measure aldosterone in the blood. And I have done that. And you and I have talked about different patients and said, you know what, we should probably measure. Is renin, do you know if we can measure renin? I've got, yeah. And I don't know what they are, but apparently there's proper ratios that should be in place. So again, mutations on renin will cause it to be overactive. Mutations in ACE2 will cause this to be underactive. And then, you know, we're stimulating NOx and, and off we go. And of course, anti-otensin. IL-6 in there too, which is a big player with COVID, which is a big player with many of my inflammatory patients. And also is a genetic issue too for people. Oh yeah. You can have genetic mutations on IL-6 that are up regulation. And I was just going to point out, maybe it's a little hard to see here, but anti-otensin 2 stimulates IL-6. IL-6 stimulates NOx and then NOx stimulates IL-6. Feedback loops all over the place. And I don't have it on here, but vitamin D helps calm down IL-6. And then H-mox, hemoxygenase, also calms down anti-otensin 2. So mutations on here can be a problem. And hemoxygenase also calms down mast cells as well as lutealin. So I think we may have come across something very significant here as to how these patterns occur. Now purely hypothesis speculative, but when a child gets strep throat and perhaps starts this up, could that be a factor in why they go into pans pandas? I have no idea, but I'm just throwing that out as a hypothesis. Does something like that kick this off? And are many of the people that are inflamed that can't seem to get out of it possibly going into that cell danger response have this going on? So again in August, we're going to dig into histamine, oxalates, iron, glutamate, and how all of them stimulate NOx. And then we might talk a little bit about interleukin-13 because when interleukin-13 is stimulated, if it's mutated, it actually comes back and makes more mast cells. And then if we have difficulty breaking down histamine, we can't break down that histamine. So again, 3D chess game played underwater, so many moving parts. So one of the things we're doing is we're experimenting with things that support ACE2, superoxide, dismutase, things that calm down the mast cells, things that calm down the histamine and preliminarily very, very good results. So stay tuned. This is not a hypothesis. There's peer-reviewed papers on all of this. But the hypothesis is, you know, is this something that's common that feeds upon itself? And we've got to continue to research that. But my hunch is it is. Gosh, Bob, I love this. This is so practical. And again, as a clinician who treats some of the toughest cases in the United States, this is the kind of stuff that we need as clinicians and patients need because it's the game changers. And if I were to kind of summarize big picture thing, I remember 10, 20 years ago when I started, I would get a patient coming in with hypothyroid Hashimoto's or menopause symptoms or sore throat, simple straightforward, we do an intervention and within two or three months they're better. I never see those anymore. And part of it is the complexity. But part of it is what you just laid out here at the core is infectious burden and toxic load in our environment. How I see it as the toxic load, whether it's EMFs or chemicals or estrogen disruptors, chemical, you know, endocrine disruptors, all of these things are getting more and more in our environment. The stress is more and more. And our food supply is more and more adulterated. And then we have these old underlying infections. Number one, tick-borne infections are getting more prevalent because the encroachment of the the types of vectors that Kerry ticks are coming into the city areas and the city areas are coming out into that area. So most of the swaths of places where you can get them now are widening. But all that to say this toxic load is weakening our system, allowing old infections or new infections to become a bigger issue. And no greater example is it then right now with the pandemic, part of the reason why it's such a big deal is our systems are more weak than they used to be 100 years ago. So all that just to put it into place that toxic load infectious burden. But I don't want to leave you hopeless. Great researchers like Bob are finding this answers clinically. And there are ways to decrease inflammation and change these pathways. So thank you so much for bringing this. And yes, I wanted to mention the conference. Tell us about the conference coming up. Yeah, September 18 to 20. We were going to hold it live. But of course, now we can't because of COVID. So we're so thankful you're going to be one of the speakers. But Stephanie Seneff, who's brilliant. She's going to be talking about a fascinating subject and that is deuterium and how to get deuterium depletion and how that's related to some of these inflammatory pathways. She's doing new research that she's going to present for the first time. Neil Nathan, you know, known for his mold, Sandeep Gupta from Australia, speaking on mold remediation. Two of the people at Neutrogenic Research have actually done literature reviews on the pathways that clear the mycotoxins. So in other words, various mycotoxins, which pathway might need to be supported. Of course, this histamine wears out the adrenals. Joel Rosen is going to speak about that. McKay Ripley, again, part of the research team is going to be talking about IL-13, Bill Shaw from Great Plains, mycotoxins 101. A new good friend of mine, Andrew Campbell, is going to be talking about mycotoxins and illness and some of his testing. Beth O'Hara on mycotoxins and mast cells, Emily on oxalates, relationship there. And then I'll be talking about the cytokine storm. So since it's, you know, across the United States, we're speaking, we're starting at 8 a.m. Pacific, 11 Eastern. So the people on the West Coast don't have to get up too early. And three days and $385, which we think is very reasonable. Very good. Yeah. Bob, I can't wait. I am excited to be part of it. I have been very, I'm writing my book, which will be out in about a year. And so I've been very selective at who I've told yes to. And you are, you are among the top because I love what you do. I love your platform. I love the information you're bringing. And you always bring together really, really quality information. So thanks for what you do. Absolutely. Final thought here. Someone wants to talk to our clinic. Here's our phone number. If a doctor is watching this and says, you know, I'd like to do this genetic work. There's the website online certification. Here's our technical support and the supplements that we've needed can help the professionals only. They're not available to the general public. So if somebody wants to learn this, I have a link, the online certification course that teaches the functional genomics. So what a blast this has been, Dr. Jill, like always. As always, so much fun. Thanks for going down the rabbit trails with me to get some practical information for people listening. I was looking at questions as they're trying to monitor that as we went. Thank you as always. I hope you guys will join us next month. And Bob, have a great afternoon and evening. Okay, my pleasure. And looking forward to the next one.