 Well, good afternoon everybody. Welcome to another episode of Dr. Jill Live. You can find all other episodes on YouTube, on Stitcher, on iTunes, or wherever you watch or listen to podcasts. Hopefully you're enjoying this and I hope you do subscribe and leave some reviews there for us. Today, I have a special guest who is no secret to you all if you've been watching Dr. Jill Live. As I've heard some of the reviews, he's one of your favorites because we go deep and we go into the mechanistic pathways. And today is no different. Every single time I talk to Bob, we have some new groundbreaking information on these enzymatic pathways and how they affect our health, especially if you're listening and you've dealt with chronic Lyme disease or mold toxicity or post-COVID or symptoms after Epstein-Barr virus. It's real common that often these genetic pathways are the secret to why you're suffering or why you can't figure it out. And you're going to learn something really exciting today about hemoxygenase. Before I jump in, again, you probably know Bob, but I'll give a brief introduction. He's a traditional naturopath specializing in the field of genetic specific nutrition. He earned his traditional naturopathic degree at Trinity School of Natural Health and is board certified through the ANMA. He recently opened, actually not recently, about 20 years ago, Open Tree of Life practice and served as a traditional naturopath for 27 years. And then lately in the last over years, he's been engaging exclusively with functional nutritional genetics. And if you're a practitioner listening, which we have lots of practitioners, you have probably used his test or seen his test. I don't know of anyone who hasn't been familiar with some of these pathways. Bob, welcome, welcome. As always, it is absolutely a pleasure and an honor to have you here today. And I'm super excited about our path. Before we jump in, any just brief little teaser on what we might find today with the hemoxygenase or why it's important to the listener? Oh, sure. You know, the we've been looking at some of our other podcasts on how we make inflammation. And we've looked at, you know, things like glutathione and superoxide, dismutase and all those helpful things. And I was really surprised to learn that we're going to talk about today is a major pathway that we use for detoxification and reducing inflammation. So as you so aptly said, if you've got mycotoxins or Lyme or some other chronic inflammatory, this may be one of the pathways that that might be disrupted. And we need to work on. So hang on, put your seatbelt on because we're going to we're going to go for a ride here today. Super excited. Take it away, Bob. All right, we're going to do a slide screen share here with the slides. And let's see. I think you got the slides there. I see screen. There we go. Looks good. OK. All right. Our topic is why the hemeoxygenase enzyme is critical for your health. And of course, we're not practicing medicine here. We're just giving you information that's a literature review. And people have seen this before. So I said hemeoxygenase another 3D chess game played underwater and the environmental and genetic factors that impacted. Now, I just drew this little diagram from the literature that we found. We're going to be talking to you about an enzyme called hemeoxygenase. And just in case anybody doesn't know, your DNA is instructions on how to make enzymes and enzymes either make something or clear something or have some other function inside the body. And when they're mutated, they most of the time don't do the job as well, but sometimes they do their job too well. Neither one can cause a problem. So let's take a look up here. You see that the hemeoxygenase can decrease the oxidative damage to the pancreas. It helps kidney function. It's actually can help reduce joint swelling and inflammation. It's actually involved with non-alcoholic fatty liver disease that can be associated with obesity and diabetes. Can help reduce gut inflammation and reduce the secretion of pro-inflammatory cytokines. Helps with the cardiovascular system and metabolic function. There's very few enzymes that have such a myriad of impacts upon the body. Now, I wanted to show this first because as you know, Dr. Joe, we are seeing such an increase in autism. I believe it used to be one out of a thousand and I think the latest might be one out of forty-four or forty-five or something like that. Someone did a study of low hemeoxygenase serum levels in children with autism. And the conclusion is, this study suggests that oxidative stress is higher in children with autism and that hemeoxygenase levels are insufficient. To achieve oxidative balance. That one was quite surprising because when you talk to elementary school teachers have just taught five years, even aside from autism, we're just seeing so much ADD, ADHD inability to concentrate. It's becoming a very serious problem. And clearly, this isn't the only issue that may be neuro-inflammation from other factors, but the hemeoxygenase may be playing a role in helping to reduce it. Now, you did an excellent article and I'm encouraging everybody to read this article to learn about the hemeoxygenase benefits. It's on your website. You call it hemeoxygenase one can boosting and help in auto-immunity. And you very well described in one sentence what hemeoxygenase is. It's an enzyme involved in a process known as heme group degradation. And we're going to talk about what a heme is and it breaks down and dissembles it, the type of molecule known as heme. It's an important role in various biological processes. It's bound to be, it's designed to be bound to other compounds and I'm going to show you what it does. And when it's not, it becomes a potent inducer of inflammation. However, your body has an anti-onatural built-in defense mechanism and that's the hemeoxygenase. So this might be a topic for another show. So I'm going to go through this one very briefly. But what happens is that glycine and succinyl COA go through eight steps called the heme cycle. The very last step, the FETCH enzyme puts iron on the heme and you've got your heme. Look on the right here, heme plays a role in hemoglobin, myoglobin, neuroglobin, cytochrome P450, that's your phase one detox. Cytochrome C electron transport, peroxidase, catalase, these are catalase, major anoxam, NADPH, as you know we did a whole show on the importance of NADPH. Tryptophan for your serotonin, nitric oxide synthase. And you know we did an entire show on nitric oxide in the infamous Carnahan reaction. And then the Suox enzyme, which is a sulfite to sulfates. So it's pretty amazing what this is involved with. And you can have genetic mutations anywhere along the pathway here or possibly glyphosate might be impacting glycine. And if your mitochondria is not doing a very good job, you may not have enough succinyl COA. So there's a lot of things here and in our genetic health consulting, we are finding that many people who are struggling may have some genetic issues along the pathway or lead, lead will impede this as well. So this is a diagram that shows all of the enzymes and these are your cytochrome, cytochrome P450s. Every one of these are dependent upon heme to function properly. So cytochrome P450 is many of your phase one detoxes that clears medications is also involved with your steroid hormones and is involved in many, many processes. We're just beginning to learn the extent of the CYPs. You also see the bottom, your nitric oxide is involved, your Suox is involved. So if we don't have enough heme, we can have no mutations on these. And whatsoever, they're not going to work because it doesn't have what it needs to work. It makes so much sense, Bob, as far as why it's such a big deal, which is exciting that we're talking about this. Absolutely. Now, again, I really encourage you to read this article. You go into the details. I just gave the key points here. Cytoprotective, antioxidant, immunosuppressive. And it's like, what, why is that good thing? You explain that anti-inflammatory support in autoimmune and inflammatory diseases and antimicrobial. So go to your website and read the whole article. You really did a fantastic job on that, Dr. Joe. Thank you, Bob. And I just have to credit you because you were the one who got me thinking about it. I thought I'm going to start writing about this. And I think it was based on some of the articles we shared. So believe me, it was really on your instigation. And I just love I want to mention the immune thing because I think people are learning this and understanding if you're a practitioner, you're seeing this. But really, at the crux of so much of the chronic complex, whether it's mold or Lyme or long COVID, it is either overactivated immune system or underactive. It's this dysfunction of the immune system. And we're going to dive into that and why the heme is so important to that. Absolutely. Very well said. So here's what we're going to do today. We're going to really move quickly. We're going to review the inflammation pathways discussed in platelet activation and ranties pathway. That was episode number 102. I would really encourage people to go back to that one because we go into detail. I'm going to do the cliff notes in about two minutes of what we carried it covered in an hour and a half. Then the purpose and function of heme oxygenation. And this is going to surprise people. It makes small amounts of carbon monoxide, which may be protective. And people might be thinking, no, wait, isn't that what kills you? Yes. But a small amount of it that the body makes can actually be helpful. Converts your iron into ferritin. If we don't do that, we have a real problem. And the most thing we're going to talk about today is making the powerful antioxidant, Billy Rubin. Now, a lot of people say, no, wait a minute, isn't that what people have too much of? Sometimes like Gilbert syndrome or when babies are born, they're yellow and they need to go under a light. Yes. But interestingly, at the right amount, Billy Rubin is right up there with glutathione as an antioxidant. How it protects us. Why NADPH, one of my favorite subjects, is so important that we're going to talk about a new enzyme, POR. Then we'll talk about the environmental and genetic issues, the various snips. And then we're going to take a look at your heme oxygenase pathway, sharing it with the world. You're brave, Dr. I always love being the guinea pig, Bob. And thank goodness I have so many good genetic mutations. We give lots of, we'll have hours and hours of discussion. And then the bottom line, what can we do, lifestyle-wise, diet-wise, or supplementation that might be beneficial? Now, this is a somewhat revised map from what we had before. And oops, I want to make this a little bit bigger. There we go. So this is what we covered in the previous podcast. And I'm going to go through this very, very quickly. There's an enzyme called TNFA, tumor necrosis factor alpha. And this is our friend, unless it's not, because this will be stimulated by any kind of lipopolysaccharides, mycotoxins, virus, clostridia, any eborellia, all of those will stimulate. And that's OK, unless it's overactive. And you can have mutations on this that are gain of function, iron, critical for life. But there are genetic mutations that you can absorb extra. And that will also stimulate TNFA. Then it stimulates another nasty free radical producer called NF-Kappa B. And maybe I shouldn't use that name because we need it in some instances to kill pathogens. Then it stimulates the NOx enzyme, NADPH oxidase. And we did a whole webinar on this on how this is our friend because it makes mass cells to kill pathogens. But if up-regulated, we have too many mass cells and we have mass cell activation. And we've spoken about this before, that 20 years ago we barely saw any of this, and now it's rampant. What percentage of the people that you see as a functional doctor do you think have extra mass cells going on? Oh, Bob, I think it's upwards of 50 percent. It's almost always coexistent now with all things we talk about, the chronic infections, the toxicity, the mold, the lime, etc. Many, many people, I'd say half of them have mass activation as part of the picture. And mass cells are our friends unless they're not. If they're overactive, that's a problem. The CERT enzyme, CERT-1, inhibits NF-Kappa-B, inhibits NOx. You can have genetic mutations on here, or unfortunately, high fructose corn syrup inhibits it. We can have mutations in the KIT gene that will make more mass cells. Then we make histamine, and we did a whole recording on histamine. And when that's in excess, we have enzymes called HNMT, MAOA, MAOB, the aldehydes. There's a UGT-1A4, there's dynaminoxidase that clears histamine. And you can have issues here where you don't clear your histamine. Or lipopolysaccharides can stimulate HDC enzyme to make more histamine. Then here comes the infamous Carnahan reaction, okay? Where the histamine stimulates an enzyme called INOS. Now, I really encourage everybody to watch the video we did on INOS. Just go to your YouTube channel or any other place where you have them and just search for the INOS. We really do a deep dive as to what happens when this gets up-regulated, down-regulates the INOS. You lose your BH4. Then rather than making nitric oxide, you make superoxide. Then you make peroxanitrite. This is called NOS on coupling. Very common, you know, people have rain odds or just circulatory issues, have this. Then we... From a conservative perspective with INOS, what we see is we love nitric oxide. Athletes try to make more by taking BH juice. It's really popular to enhance nitric oxide for blood flow, for basal dilation. However, too much is the Goldilocks principle, like always, right? Too little, too much is not a good thing. And for many people, like myself with the INOS mutations, it's up-regulated. So they produce too much. And how that could present clinically is syndromes like POT. So many people have heard of postural orthostatic tachycardia, where you basically basal dilate, you drop your pressure to 85 over 45 or 50, and you have hypotension, you have dizziness, fatigue, and that's very commonly related to this INOS up-regulation, especially is it INOS 2, right? The one you just showed us. Yes, INOS 2. Or it's, yeah, it's NOS 2 or INOS. Got it. So it's INOS or NOS 2. Now, there is some of the recent researches indicating that it may not be the extra nitric oxide, but it's this running too fast, running out of BH4, and we're making superoxide rather than excess nitric oxide. So you'll see literature on both. But the current scientific thinking is that, well, yes, the INOS is running, but it may not be the nitric oxide, it may be the superoxide. Either way, it's semantical, which one it is. It's a problem and it's inflammatory, but I just want to point out there's debate as to which one it is. OK. But any time INOS runs too fast, you're going to have a problem because you get NOS on coupling, then we activate our platelets. And as you know, thick blood, there it goes, veins, clots and strokes is on the rise because these platelets get activated. Then it creates something called ranties. And again, we're not going to cover that. Watch our platelet activation video for that. But then we need our good fats. We need our omega-3s used by the fads enzymes to make what are called protectants and resolvents that can calm this down. We didn't talk about this in the previous webinar. We didn't have this information, but NADPH is the cofactor for these. So if NOx is constantly being upregulated, we may not even be able to use our fats properly. And using the omega-3s could actually be pro-inflammatory. Then to wrap it up, TNFA stimulates an enzyme called PLA2. And I have to admit I'm enamored by this because I believe this is really being upregulated where it pulls arachidic acid out of the cell membrane. Now, arachidic acid plays important roles in the body. It's not all bad. But when it's pulled out of the cell membrane, it can go down through multiple pathways to make inflammation. The one we're just going to show here is there's an enzyme called 5-LOX that makes leukotrines. And what's interesting, we're finding that there is one SNP that has a gain of function on 5-LOX. And there's a CYP4A2, I'm sorry, CYP4F2 that inhibits leukotrines. And what we're finding is when people have this upregulated, this downregulated, they have inflammation that they just can't seem to get under control. And we'll show that when we look at your map. Then I'm not going to go into this, but just very briefly, it can stimulate interleukin-6. And it can stimulate angiotensin-2, which is involved with blood pressure, but also stimulates interleukin-6. And I'm just mentioning that because hemoxidinase can calm that down as well. So that is the problem that we identified. So when we talked about platelet activation, we gave the problem, but I didn't realize at the time that hemoxidinase plays a very important role in calming all of this down. And I have that in the next slide here. But before we do that, I just want to show, when the heme is made, here's your hemoxidinase enzyme, and we need NADPH to turn that broken down heme into carbon monoxide. And yes, that is the one that kills us if we get too much of it. Helps your iron go into ferritin, so it doesn't become a free radical. And then our emphasis today is going to be on the biliverdin and the bilirubin. And again, we think of bilirubin being too high as a problem, sure it is. But I think people are going to be stunned that bilirubin is right up there with glutathione as an antioxidant. Now we're going to get into the iron here. We're just going to have a couple slides on iron and then a couple on carbon monoxide, but then really focus on the bilirubin. So iron-derived reactive oxygen species are involved in the pathology of numerous vascular disorders. And that is the iron in the heme, which is dangerous when it escapes from its physiologic site. Then the endothelial cells upregulate this enzyme, heme oxygenase, and ferritin. And what they're saying is that has been shown to be effective in the protection of the endothelium against the damaging effects of heme and oxidant. Heme and oxidants lack of adaption in an iron-rich environment led to extensive endothelial damage in humans. So what they're saying here, to sum it up, the heme oxygenase takes what could be a nasty free radical, that iron, and puts it into something safe. And here is a chart that shows it. Here's your heme oxygenase 1 and 2. And we're saying it's degraded by heme oxygenase, leading to the generation of this ferrous iron. However, the heme oxygenase activation also increases ferritin expression, which can bind the ferrous iron and detoxify its pro-oxidant effect. So here you can see as it goes into the ferritin, it can negate that pro-inflammatory. So you can see here, if you don't have heme oxygenase working, this iron can be very, very inflammatory. And I believe one of our early recordings was on the dangers of iron. And we talked about the Fenton reaction. Where iron combines with hydrogen peroxide. Yeah, Bob, I always love to talk about, to patients to give them a really clear, it's like if you have an old car and it starts getting rusty, the iron rust and that becomes, that's basically what can happen in your body is this oxidative stress creates rusty iron. I'm exaggerating a little, but the idea is this oxidative stress in the body with iron combined with iron is really nasty. And so many docs and people are like, oh, everybody of a woman should be on iron supplements. Yes, there's a place for it. We need iron clearly, but if you have excess iron or if you're not binding iron or you have oxidative stress, iron can be very problematic too. It's not, it's a neutral place where it's very good for us, but there's a problematic place where it becomes very dangerous. Absolutely. And you know as we've had these discussions over the years, we keep coming back to the same thing. Too little or too much of anything can be helpful or harmful. There's that Goldilocks, as you said, that spot in the middle where everything is balanced. And I wanted to just mention this is just from memory, so I may be quoting myself a little wrong way back 20 years ago in med school, but with carbon monoxide, there's a big shift with the acid alkaline of the body, the pH. And so I'm suspecting one of the ways that it could be beneficial is enzymes are all regulated by pH in the blood and there can be just the smallest 0.1 change of the pH and there's shifts in enzymes opening up or closing or active or non-active. And I'm guessing in this situation the benefits of a little carbon monoxide are actually changing the pH of the blood in a beneficial direction. Sounds like a plausible thought to me. So here it summarizes, takes care of the iron, makes a little bit of carbon monoxide, which is vasodilates, anti-inflammatory, anti-thrombotic, and then also makes the biliverdent that turns into the bilirubin that we're going to be talking about shortly. Now, clearly, carbon monoxide is a killer. Okay. It kills many people every year. And way back in the 19th century, they figured out that it might be overcoming the oxygen. So therefore, we're fixated. So clearly, I mean, this is a killer, no doubt. You know, no one would do it, but don't go exposing yourself to carbon monoxide. I think you're doing something good because your body makes it in very small amounts. So please don't think that you're going to help yourself by breathing carbon monoxide. So here it's talking about, it's a gas a second messenger produced when hemoxygenase catabolize heme. Now, what's interesting, here they're saying low concentration carbon monoxide has the neuroprotective agent for combination of treatment of stroke. And its beneficial effect would be at least partially mediated by activation of the NERF-2 pathway. So I've been pondering this a little bit and you can't find any literature that's definitive, but I'm wondering if its effect isn't that it just gives a little kick to NERF-2. And I know we've spoken about this before, but if someone's knew it's worth repeating, NERF-2 is what stimulates the production utilization and recycling of your antioxidants. It's also involved with all of your detox pathways. So there might be multiple like you mentioned as well, but it may also stimulate NERF-2. It makes sense. And the other thing that's really interesting, Bob, is anything in excess oxygen can kill too, right? Because reactive oxygen, too much oxygen. So in my mind, this could also help modulate if there's too much reactive oxygen, especially neurologically, because that's such a problem with oxidative stress in the brain. Absolutely. So here we're saying carbon monoxide can quell inflammation, defend tissue from oxidative stress, prevent cell death and more. So at high levels, it causes a cell death at the low level. Again, created by hemoxygenase, not anyone using it on their own can actually prevent cell death. And this is an interesting quote here. It helps with lung transplants, lung fibrosis, ulcerative colitis, cancer, heart disease. And here's a quote from a lung disease expert at Cornell Medical College. There is no molecule that's been shown to be this cytoprotective in just about every orient tissue. The brain, the lung, the pancreas, the heart, the kidney, you name it. When I was preparing for this, I was really surprised at this because we all think of carbon monoxide as a killer. And now here's this article that was printed back in 2011. Carbon monoxide-activated NERF-2 pathway leads to protection against ischemia. So that's why I believe that there might be a component of this, and they're even actually saying the beneficial effect would be at least partially mediated by activation of the NERF-2 pathway. All right, carbon monoxide induces vasodilation and nitric oxide release. Now, interestingly, high levels inhibits nitric oxide synthase activity. Lower concentrations releases nitric oxide from a large intercellular pool and therefore may mimic the vascular effects of nitric oxide. So here again, it's dosage, and I've probably said it too many times, but just again, it's what your body creates, not what you'd expose yourself to. Now, here's an interesting chart that shows that the carbon monoxide stimulates the antioxidant response element for your KEEP-1 and NERF-2, which then increases your antioxidants. And as we'll talk about later, NERF-2 stimulates and controls hemoxygenase. So it's like we've got a loop here. And fascinating how the body works. Now, we want to get into what Billy Rubin does. So, remember, we very quickly went through it, though we talked about the dangers of tumor necrosis factor alpha being too high. Again, we need it, but when it's excessive, this is when you get your autoimmune diseases. Your NF Kappa B, we need it, but an XS can be very inflammatory. By the way, just as a clinical observation, Dr. Jill, those who seem to be incredibly ill from Lyme disease were finding that they have a homozygous mutation on the one NF Kappa B that's a gain of function. The NOx enzyme, again, creates the mass cells. And interleukin-6, I think the video we did on IL-6 is still your most viewed video. I do, too. Yeah, people are really loving that one. So, all of these are pro-inflammatory. CERT-1 holds it back. Look what Billy Rubin does. It inhibits TNFA. It inhibits NF Kappa B. The hemoxidase enzyme supports CERT-1. Billy Rubin puts down nitric oxide, the NOx enzyme, NADPH oxidase, and it inhibits interleukin-6. And I don't have it on this chart because it's way down the chart, but it also inhibits INOS, Carnahan reaction, all from Billy Rubin. I mean, I was quite stunned when I started researching what it does. So, here's the hemoxidase enzymes. And then what we're going to do today is we're going to talk about how this is all controlled by NERF-2, which is controlled by KEEP-1. And then we're going to talk about one of my favorite subjects, NADPH, because we're going to talk about how there's an enzyme called POR that donates the NADPH to hemoxidase. Now, let's think about this a little bit. If you've got the NOx enzyme chewing up your NADPH, you may not have enough over here. Then you can also have genetic mutations in G6PD and ME1. And by the way, this is one of the most worldwide common mutations there is. You may not be making enough NADPH for the enzyme to give there. NERF-2 turns these guys on. KEEP-1 shuts them down. There's a whole lot of things that can go wrong here. And clinical observation, those people who are really struggling with Lyme or mole or mycotoxins, they usually have some issues with their hemoxidase or the delivery of NADPH or the heme cycle that delivers the heme. So this really is the 3D chess game. And you could see people having low bilirubin or low hemoxidase, you could probably have 30 to 50 different ways you got there. KEEP-1 Yeah. NERF-2 So there isn't a one-size-fits-all. There isn't a, oh, take this herb for that. It's complex. We like simple answers. It wouldn't be nice if it was, but there aren't when it comes to this. It's rather complex. KEEP-1 You know, Bob, I just want to comment, I was giving a lecture for a group this morning, and one of the comments was, is this substance good or bad? And I had to laugh because it depends, right? And that's the answer for most of the stuff is it really, the more we do personalized precision medicine, the more it really is important because you could have tumor cause histamine in someone or be the best antioxidant in another person. So there's never a one-size-fits-all. And we have to kind of become uncomfortable with that uncertainty that there isn't just a protocolized approach. And the best treatment is this real individualized deep dive. KEEP-1 Yes. When somebody, I tell my clients, if somebody says everyone should. NERF-2 Yes. KEEP-1 If that doesn't include drinking water, anything else other than drinking water and breathing air get very worried. NERF-2 Absolutely. I agree with you. KEEP-1 Yes. So here's a little more detail. The heme cycle helps make the heme. Now that's what we talked about earlier. So, succinyl COA, that comes from our Krebs cycle. Glycine comes from our diet. It's amino acid. And this is controversial. Stephanie Seneff talks about how glyphosate, she believes interferes with glycine. You will see other sincere, you know, scientists say we don't think so. NERF-2 Stephanie Seneff talks about how glyph... So we can have glyphosate, possibly... KEEP-1 I don't know how glyphosate. NERF-2 I'm sorry, Bob, let's give me one second. Let me turn off the mute here. KEEP-1 You will see other sincere, you know, scientists say we don't think so. NERF-2 Okay, there we go. The thing just popped on and gave our echo again. So let's go, keep going. I'm sorry. KEEP-1 Yes. So I don't know how much we lost there. So I'll just start over. NERF-2 Second or two, yeah. KEEP-1 So succinyl COA, which comes from the Krebs cycle, and glycine that comes from our diet, starts the process and goes through these eight steps to make heme. As I was saying that, you know, that maybe got interrupted, glyphosate are roundup. Some very sincere people say that it interferes. Some people say they don't think it does. So it may or may not, I tend to think it does, but, you know, I want to hold open the thought that it may not be totally accurate. But nonetheless, it's not good for us. NERF-2 So if we don't have enough heme, we then don't have the ability to make the carbon monoxide take the iron and break it down. And I'm looking for literature, and I didn't find it yet. I was hoping to find it before this podcast, but I couldn't find it. But it would make sense that if heme oxygenase isn't working quite well, this heme in the iron then just becomes very inflammatory. But I couldn't find any papers on it, but I'm sure it's there. NERF-2 Then as we talked about, ME1 and G6PD delivered to the POR enzyme, and we're going to talk about this one. We've never talked about POR before, but I'm really blown away by how important this is, because it donates the heme oxygenase, it donates the NADPH to the heme oxygenase. So we can have perfect heme oxygenase. We can have all the heme we want. NERF-2 can be functioning. But if we don't have NADPH being delivered, like having a brand new car without any gas. NERF-3 Now I am very enamored by riboflavin. NERF-4 And I think we've spoken about this before. NERF-5 Riboflavin is needed to make FAD, which is needed for the POR enzyme to work. NERF-6 And you can have genetic mutations on these transporters or the FAD1 enzyme that makes the FAD. NERF-6 So there's a heck of a lot here that can go wrong, Dr. Jill. NERF-6 And so I think it's important for the functional doctor to be able to see where the problem is, because yes, there's herbs that stimulate heme oxygenase. But if you're not getting G6PD and ME1 to deliver the NADPH, it's not going to help. If you don't have this cycle working properly, you're not going to have the supply of heme and stimulating this isn't going to help. Really a complex situation. NERF-6 Yeah, and Bob, I just want to comment. From seeing a lot of organic acid tests, we talked about this before, too. I know you're now incorporating those results into your testing. But glutaric acid is a marker on organic testing that shows riboflavin deficiency. And I will say it is probably one of the number, not one of, it is the number one deficiency I see on organic acids. And I think I just speak, you know, honestly, I think a lot of colleagues ignore that, oh, riboflavin is not that big a deal. And I find it is a big deal, especially in something like migraines and many other processes, that riboflavin is huge. And we tend to give the glory to the methyl B12 and the methyl folate. I think riboflavin is just right up there with the importance. NERF-6 Oh, absolutely. I've been doing some webinars for doctors on methylation. And I call it get your ducks in a row. And that is don't even think about giving methylfolate if you're low in riboflavin. Because riboflavin is one of the cofactors for the methyl group to wander the folate. And you hear this all the time that some well-meaning person either on their own or through a practitioner says, oh, I've got MTHFR, therefore I need to take methylfolate. And they feel phenomenal for 10 days. And then it's like, what just happened to me? They get irritable, they get inflamed. Just as a side note, and maybe this could be another show we do, but the histamine and methyl transferase gets stimulated by methylfolate. If the downstream from that, the MAOA and the MAOB can't handle it, it actually makes the situation worse. So we have to be real careful with methylfolate. I tend to think in the functional world it's being given just a little too much. Now, obviously somebody's pregnant, we've got to have it. If you've got a high homocysteine that's related to this, maybe it's time to be done. But other than that, I think we're overdoing it just a bit. Bob, I agree. And I just want to comment and clarify what you just said with the histamine intolerance mass selectivation. A lot of these are poor breakdown of histamine, among other things, and methylation breaks down histamine. But like you just said, I just want to clarify, because if you're having a poor MAO or one of those other enzymes, you can actually be in a worse situation with histamine if you give too much methylfolate. And is that what you're basically saying? Exactly. You got absolutely right. So when people have mutations in MAOA and MAOB, or the cert one that controls it, I tend to think if there's any chance that you're creating excess histamine, take care of that first before you support methylation. So I've done some webinars on that effect. And I think I actually presented that for great planes one time. I called it Getting Your Ducks in a Row. And in addition to histamine, you also have to be careful with dopamine, because folate and sami can drive dopamine. Anyways, I said we need fat also for the PPOX enzyme. And there's other cofactors along here. And we're investigating how maybe we can help practitioners making a custom supplement that may not only give the succinyl, CO, and the glycine, but where they have weakness find where the cofactor help is needed. So that's one of the things we're researching. But as I said, lead will impact some of these. And glycine deficiency, just as a little side note. Again, clinical observation. When people have difficulty here, unless they have a dairy problem, they love ice cream. Because it provides the glycine and the carbohydrate. And here we go. And when people have trouble in here, they often get what we call hangry, where the intermittent fasting on our ketogenic diet is a disaster, which goes back to what we just said. Intermittent fasting can be fabulous, but if this pathway isn't working, it bombs on you. Same with keto. It can be fabulous. But if you don't have these, these people need carbohydrates on a regular basis. So that was a little side trail there, but probably worth putting in. Actually, really important, Bob, because again, right now, there's so much emphasis on intermittent fasting for everyone, right? And keto diet for everyone. And I agree with you. There are many patients who do not tolerate that and actually do far worse. So you really have to know who you're dealing with in order to use those kinds of things. Yeah, just clinical observation. When I've seen people that have a lot of issue here, I say, did you ever try keto or intermittent fasting and did it go poorly? And it's like, how did you know? So again, it goes back to everyone should is not a good thing to say. All right. Now, let's get into the crux of the matter. What's a bilirubin? It's the result of the breakdown of red blood cells. Now there are conditions that you can have high bilirubin. This is a problem. Once in the liver, the bilirubin becomes conjugated. This means it's water soluble and the body can excrete it. And we're actually going to look at the glucuronidation enzymes that turn it into something that can be removed. Because unconjugated is toxic, and it's usually not because it can come out of the body as long as nothing is interfering with its removal. All right. When it's too high, this is when the liver is not working properly and it can't make the bilirubin water soluble. Then it builds up in the liver. Causes can be hepatitis, alcoholic liver disease, some medicine overdoses, autoimmunity. All of those things can cause the bilirubin to go too high. We get yellow, yellowing of the whites of the eyes, dark colored urine, itchy skin, pale stool. We can have nausea, vomiting, stomach pain, bloating, weight loss, headaches, confusion, fatigue, drowsy, all from bilirubin to high. Now, this is probably the slide that's going to blow everybody away. Everybody knows about glutathione and how wonderful it is, and everything you've heard is absolutely true. So in this study, which some people might want to just, you know, put these words in and read the whole paper, water soluble glutathione primarily protects water soluble proteins, whereas the lipophilic bilirubin protects lipids from oxidation. Whoa. When I saw that one, it's like, seriously? And this was published all the way back in 2009. So in my opinion, in the functional world, the functional doctors need to be aware of this and not always look to glutathione as being the savior every time. I love that, Bob. And I'm wondering about, because we're doing tests that show lipid proxides, right? Which shows oxidation of lipids. So with someone who shows those high lipid proxides, this is something we need to really be thinking about. Absolutely. So in mice, they deleted the hemoxygenase enzyme, which generates the biliverton, and they displayed greater lipid than protein oxidation, while the reverse holds true for the glutathione depletion. So this is something that I believe the functional world needs to start looking at. I was quite surprised. Now, there's even more. Bilirubin scavenges superoxide. One nasty free radical. It inhibits one of my favorite subjects, NADPH oxidase. Very quickly, Nox or NADPH oxidase is our friend, because when we have a virus or bacteria or a pathogen, it kicks in and says, we've got an enemy here, we've got to fight and kill. Without that, we die. But I believe there's many environmental or genetic factors overstimulating the Nox enzyme. And here we have it, that bilirubin will calm that down. So what they're saying is, expression of inducible form of hemoxygenase, this is the one that kicks in when it's challenged, can be boosted by oxidative stress, sometimes from the NADPH oxidase activity. And then it puts the protection in. It starts creating the bilirubin that feeds back to quell this oxidative stress. So if something is stimulating, the Nox enzyme, and we don't have the bilirubin, that's when things can get carried away. And I keep going back to, I believe a major thing we're seeing today is upregulation of the NADPH oxidase enzyme. It's our army. It's what kills the pathogens, but it hurts us if it's running too fast. And I believe we did a Facebook live just on that subject of all the things that upregulate the Nox enzyme. Yes, we did. And there's a lot. There's a list. And again, this is our environment. We're all swimming in toxic soups. So part of what we're seeing is we are all getting exposed more and more and more to higher levels and then what can our bodies handle and those who have genetic mutations are starting to get ill. Absolutely. As we've said many times, genetics loads the gun, but the environment pulls the trigger. So here's an article says bilirubin inhibits the activation process of the NADPH oxidase. We said the same thing, but another article just reinforcing that concept. Now this really surprised me. It's a potent antioxidant that can protect the cells from a 10,000 fold increase of excess hydrogen peroxide. And hydrogen peroxide, again, can be used to kill pathogens, but too high creates a problem for us. So it says bilirubin acts as an antioxidant. Then it's oxidized to biliverin and then recycled by biliverin reductase back to bilirubin. And we'll show that on the charts when we look at your DNA. There's more. Inhibited the secretion of tumor necrosis factor and inner leucon-6, indicating the inhibition of the NF Kappa B pathway. I mean, it just keeps going on what this does. It could therefore be considered an endogenous regulatory molecule modulating inflammation. Now this is fascinating. This was, let's see, I don't see a published date. Oh yeah, September of 2009. Moderate high bilirubin is associated with reduced incidence of cardiovascular disease, including hypertension. Now we talked about this more when we talked about the home cycle. So we don't have time to get into it today, but the angiotensin-2 is what can create the body to hold on to sodium and excrete potassium. Moderate daily high bilirubin prevents that angiotensin-2 dependent hypertension. So there we go. And of course we're seeing so much high blood pressure and we see the sodium retention with the edema that goes with it. Bilirubin exerts renal, renal is a kidney, in the angiotensin hypertension. As we know, the hypertension can affect the kidneys. And we're saying they conclude that the bilirubin exerts renal protective effects on the angiotensin-2 dependent hypertension. Unconjugated bilirubin modulates nitric oxide production via INOS regulation. As we said earlier, this is the Carnahan reaction. And we're going to show once again where you inherited from both mother and father mutations on the two INOS that makes it overactive. And they're saying here that created a significant reduction of INOS gene expression. So there you go, Dr. Jill. We now have a way to help reduce the effect of the Carnahan reaction on you. Unbelievable. This is amazing. Now, we spoke about CERT-1 and I don't think I put a chart in this time, but CERT-1 also helps you make superoxide dismutase and INOS as well as knockdown inflammation. And it's saying that hemoxazinase has the ability to restore cellular redox and rescue CERT-1. So you can see there's a relationship between CERT-1 and hemoxazinase. They help each other out. In a feedback loop. Now, this is something we're just beginning to research and we don't have a lot of data on this, data on this, but when Billy Rubin is released into the plasma, it is taken up by albumin which serves as its transporter throughout the body. The binding is extremely high and under ideal conditions, unconjugated Billy Rubin is seen in the plasma. I was hoping to get a little more research on this done before our broadcast here, but I didn't. But this is an interesting study and just published in February of 2020. The role of the Billy Rubin to albumin ratio as a predictor for mortality in critically ill patients without other problems. So they were saying that high Billy Rubin and low albumin are frequently appeared and associated with poor prognosis in critically ill patients. Their conclusion was a higher Billy Rubin to albumin ratio is related to the unfavorable prognosis and mortality in critically ill patients. Well, maybe sometime we can come back when we have more information on this to learn how the albumin carries it around. I'll be honest, I don't have a strong understanding of this yet, but we need the albumin. So if the albumin goes down, then we don't get the positive effects of the Billy Rubin. As we know, Gilbert syndrome is a condition where people have occasional and short-lived episodes of yelling of the skin and whites of the eyes caused by a buildup of Billy Rubin in the blood. And we'll show this in the software. There's an enzyme called UGT1A1 which is part of a process called glucuronidation where it takes the unconjugated Billy Rubin, conjugates it, and then excretes it. So if we have genetic issues here, we may not be able to excrete it properly and then the Billy Rubin becomes. A problem. Interestingly, homocysteine down regulates the hemoxygenase 1 enzyme. And we could do a whole show on homocysteine. There's books out there that says high homocysteine virtually causes so many things that will cause you to live longer or less long because it does so much damage. And I knew some of the damage that homocysteine did. I was not aware that it down regulated hemoxygenase. So measuring that homocysteine is so important. I'm sure as a functional doctor you do that all the time. You probably look at people's homocysteine. I do routinely and totally agree with you. I've seen someone in people's in the 20s and it's very concerning. Absolutely. And the catch 22 is sometimes it's full late in B12 but then that can backfire in other ways. So it really becomes a tight rope as to how you bring that down safely. What percentage of your patients do you think have high homocysteine that you see? This is definitely less than mass cells. I'd say maybe 15, 20 percent. It's still like maybe one in five but not as high. Yeah. And unfortunately it's not measured very often. And often when I do you know consults with folks in our health coaching who say have you ever measured your homocysteine? They never heard of it. No one's ever measured it. And it can be very, very important. And just if you're listening out there I like to see below nine but in the breadism protocol with dementia and those kinds of things we're going below seven even. So but then on the other hand below four is an issue too. So there's a happy medium as well. Yeah absolutely because we need homocysteine to go down through transulfuration to make our glutathione. So again everything every time we do a show here we talk about not too little not too much. So I now want to focus on the POR enzyme. I'm very intrigued by this guy because it donates NADPH to hemoxygenase 1 but not only hemoxygenase 1 most of your cytochrome P450s use POR to donate the NADPH. So you can have genetic mutations and I'll show you those when we look at your genome. You can have mutations in G6PD, ME1. We mentioned this earlier you need FAD to be the co-factor not enough riboflavin causes that. Then you can have mutations in G6PD or ME1 or they can be just fine but if you've got nerve two issues or keep one issues they don't get stimulated they don't do their job. Let's go back to riboflavin what is your what is your favorite dosing for riboflavin? Well you know it's funny because a lot of times some like riboflavin by phosphate is the active form and it comes in like 30s which is I think way too little. I usually start at 100 and with migraines I'll go up to 400 per day. Hmm okay. All right. That was curious what your what your dosing was there. Now people probably have never heard of the PORG and I think we need to look at this gut because it provides instructions for making the enzyme cytochrome P450 oxiriductase. 50 enzymes depend upon this and they're involved with the synthesis and breakdown of various molecules and chemicals within cells. So if we don't have those CYPs working these are folks that have all the negative effects with with medications or they're exposed to any chemicals and they can't handle it. As we said it's involved with the metabolism ingested substances such as medications in the liver. Now this is going to surprise you. It's involved in your drug metabolism your steroid metabolism your xenobotics and your hemoxygenase. So if this guy doesn't have a source of NADPH or it's got mutations that it doesn't have the FAD it's not going to do this job. Now we're not going to spend a lot of time on this one but look at this guy. This is a chart of how POR is involved in all of your hormones. Here's your cholesterol your pregnenolone your progesterone your testosterone every time you see this little orange here POR is involved. So you're going to have hormonal disruption. And then here it talks about bone formation the steroid metabolism we just talked about drug metabolism detoxification your hemoglobin metabolism and your cholesterol all controlled by POR. And I just want to illustrate again the importance of NADPH because NADPH helps recycle your thriadoxin your glutathione your catalase helps DHFR deliver folate helps the POR but here's NOx NADPH oxidase NOx will use it to make free radicals and if this guy's up-regulated likely all of these others are going to suffer and that's why I keep going back to we got to be looking at the NOx enzyme so again I talked about this a little bit but just a a quick review the Susano COA comes from the Krebs cycle dietary efficiencies or possibly glyphosate may impede it mutations in any of the heme cycle enzymes may lower it lead may lower it and then the porphyrins go from one to another through the cycle then they may block the GABA receptor sites is where people get hangry where it's like I'm upset I'm frustrated I got to have some food they feel better after they eat now action steps and again I would encourage people to watch our episode 102 remove exposure to mold in your environment can't emphasize that enough and I'm sure you talk to people about mold and they'll tell you oh I don't have any mold in my house yes and because they don't see anything black growing on the walls that doesn't mean you don't have mold it can hide in many places and I know you've you've done other webinars on on mold that encourage people to to watch them but take it seriously make sure you don't have any virus or clostridia or any source of lipopolysaccharides here's a couple of nutrients that can support TNFA black human milk thistle EGCG and Oswellia all of those can help with TNFA NF Kappa B remove exposure to mercury treat virus consider reducing exposure to glyphosate reduce TNFA over stimulation we're just beginning to dig into this because we may make a supplement for NF Kappa B but the vitamin E gamma version curcumin fish oils alphalopoic acid NAC but you got to be careful Rashi mushroom green tea and resveratrol home down NF Kappa B in other words what we're doing here is we're saying let's not stress hemoxygenase as much NADPH oxidase take care of the histamine the oxalates glutamate get away from air pollution I remember you saying when you had the the big fire in your town that it really impacted people yeah we saw NF alpha and TGF beta and all kinds of things rise just from the smoke exposure because it was so toxic keep homocysteine at a healthy level keep dopamine at a healthy level keep sulfites at a healthy level keep aldosterone at a healthy level IL-6 m-tornotophagy there's a lot there but all of those have to be taken care of curcumin spirulina and then any lifestyle and nutrients who would support healthy levels of the stimulators listed above IL-6 again when I copied this there was 3,300 people who viewed that and that's where we spoke about IL-6 and probably the interest comes from that's the cytokine storm everybody was trying to to look at mold Lyme disease the lipopolysaccharides EMF radon and air pollution particulates lead mercury aluminum the life is safe the omega-6 is particularly canola oil VOCs pesticides in an EM-tour stimulator those will all stimulate IL-6 so what we've talked about here is how do we take the pressure off of hemoxidinase okay then I'm not going to read these if somebody's watching they can just pause it and write these down but all of these things will again stimulate IL-6 and then you can have genetic gain of function on IL-6 and here's some of the things that can reduce it hydrogen water thiamine and riboflavin black human apigenin pine bar PEMF I'm going to have a slide just on that I know that's one of your favorite subjects Dr. Jill yeah vitamin D EPA and DHA hyperbaric selenium because it supports glutathione make sure your blood sugars are controlled healthy weight and moderate exercise then how do you support SIRT so SIRT supports endothelial nitric oxide the good blood flow supports a major antioxidant knocks down those two inflammatory enzymes so reduce or eliminate high fructose corn syrup we're going to look back on this someday and say what were we doing yeah SIRT 1 is part of our anti-aging high fructose corn syrup inhibits it intermittent fasting again if you don't have problems with the the heme cycle support heme oxygenase because that supports it this is dependent upon NAD and reduce the overstimulation of it Ms. Veritrol and Terra Stilby and Bob I was going to say this is where people are talking a lot about autophagy autophagy is basically cell programmed death so it prevents those cells that go rogue from becoming cancer and it's very very important for anti-aging because the senolence of the cells as they become older if they're not dying off that's the most common thing that causes aging so everything you're describing here I just want to put in practical application is basically anti-aging and prevention of cancer two other drugs that I don't recommend but do have also CERT-1 activity and autophagy is a rapamycin and metformin so those are the popular in the some of the now they have side effects too so again you wouldn't want to use those without a physician helping but this is all about anti-aging and prevention of cancer in the end absolutely well here you can see CERT-1 inhibits mTOR which inhibits autophagy so that's why CERT-1 is one of my other one of my favorites and when people have homozygous on CERT-1 they're usually struggling you know they've gone to 20 clinics and nobody can figure out what's happening makes sense all right how do we support hemoxygenase support KEEP-1 and NERF-2 particularly when I see a homozygous mutation on the KEEP-1 overactive these folks are in trouble here's your sulfora pain milk thistle turmeric was virtual again support adequate NADPH by not having an overactive NOx we call that the NADPH steel spirulina calms that down a little bit again adequate NAD but after you've calmed down NOx and then hops panlex ginseng sage rosemary turmeric and broccoli and probably others support the enzyme but again I go back to if you think you're going to take care of it all just by doing this as we as you learn there's so many other pieces to this puzzle that you have to take care of all right I thought you would enjoy this Dr. Jill the pulse electromagnetic field increases hemoxygenase 1 and superoxide disc mutase yeah wow and I believe you have something on your website that the the PMF that you recommend yeah I love the hairdos it's actually if you look right down there on the floor down there I use it every single day and I'll tell you something else about that's related to the whole stuff we talked about platelet activation rentase my theory and I have evidence to back it up is it actually helps with viscosity of blood so people who are struggling after COVID or after lime or this with blood viscosity I think it actually helps circulation and I almost wonder if sometimes that's the most important thing that we feel because our blood is flowing better because that it's like a magnet that actually helps the blood flow circulation sure well if you go back to that that video we talked about it's the up regulation of the INOS that activates the platelets so if upstream you're able to slow that whole pathway down that would make sense that it's going to improve the circulation yeah we've also talked about molecular hydrogen okay so what they're saying is that hydrogen rich water reduces reactive oxygen species production by inhibiting the NADPH oxidase activity so that then of course is going to you know take some strain off of your your hemoxygenase in case anybody doesn't know you can get machines that'll knock the hydrogen lose from your water or you can get some capsules that's what we have here Bob this is a hydrogen machine I thought I should I have it right next to my desk here because you and I I know we love to use this absolutely you can keep explaining but I want to show they are expensive but they are for me and probably for you too I think they're so worth it because it neutralizes these reactive oxygen into water so it's very very safe absolutely so you can breathe the the the hydrogen or there's actually little tablets that you can drop into water that'll at least knock it loose from the water and it inhibits the NADPH oxidase activity plus a lot more so here we have molecular hydrogen against sepsis it upper like upper regulates SOD hemoxygenase 1 catalase and suppresses NADPH oxidase activity so I've been asked already it said Bob if you could do one thing if there was something that said Bob you get a choice you do one thing from a functional standpoint what would it be I think I'd picked hydrogen Bob I agree I want to just pause there because I just had this vision like what if an ICU is in a hospital is like every bedside had the breathing like think of how much you just talked about sepsis and prevention I wonder how much really severe illness we could prevent if we got these ill people breathing hydrogen or taking the tabs but the breathing it is even more powerful wouldn't it be amazing yeah I mean look at all it does it neutralizes rocks and nitrite the oh no here's your hydroxyl radical slows down I-NOS slows down NADPH oxidase increases SOD hemoxygenase and catalase all from number one on the periodic table of elements hydrogen yeah so simple so simple and maybe that's why we're not talking about it much um a little bit of exercise will increase the hemoxygenase as well okay now we come to A looking at you are you ready for this I'm ready okay here you are and this comes from the functional genomic analysis software and this is the whole what we call the the ranties map so each of these circles is an enzyme and what we can do is we can click on any one of these and it'll actually show us what's happening so you can see here Dr. Joe your tumor necrosis factor see it pop up on the side here you're fine but we talked about this before in the Carnahan reaction you do have one mutation on the HFE which causes you to absorb a little bit more iron we didn't talk about this before because we didn't have it but you do have gain of function on one of the NF Kappa B's and just for those watching if you've known if your doctor may tested you for hemochromatosis that HFE is one of the main genes for that if you have two copies you have hemochromatosis but as we're talking here carrier one copy does make a difference even if you don't have full-blown hemochromatosis absolutely it can cause you to absorb a little more iron incredibly common and people of English and Irish descent so then we continue down the pathway and we need cert one to hold it back and you're fortunate you do not have the cert one what we're finding the people that are just really struggling might have TNFA HFE weakness insert one exposed to mycotoxins and Lyme disease these are the people that are just struggling so badly then we stimulate the NOx enzymes then there's an enzyme called KIT that will cause the mass cells to be a little overactive and I don't know if we spoke about this but you've got one little heterozygous on a kitchen that could cause your mass cells to be a little overactive then we make histamine and again watch our video on histamine and here's the histamine and methyl transferase enzyme and I don't have it on here but that's what we spoke about if you've got histamine and you take full 8B12 or SAMI you'll make more N-methyl histamine and then if you're MAOA and MAOB can't handle it this is worse than the original histamine yeah and in my experience Bob in the early days right from my breast cancer I realized I had methylation issues MTHFR one gene mutation and I took a lot of methylfolate and it did not go well as you can imagine now later on as I've detoxified and done other things with the genes I can definitely tolerate a milligram or two but in the early days it was disastrous just like you said yes and then histamine carboxylase this actually causes the body to take the amino acid histamine and make histamine you do not have any of the evidence-based ones in other words these are the ones where there's literature that says this really impacts it however when we look at the ones that there's no evidence for there's still a few but we don't know what they do but they could be gain of function but we don't we don't know for sure then here we go the carnahan reaction the NOS2 is what makes a lot of nitric oxide to kill pathogens and you've got an up regulation see this lets them have you're a little hard to see but there's an up arrow here mother and father gave you mutation up arrow here mother and father gave you mutation and then that will stimulate the NOS1 coupling which makes the superoxide that makes our ONO peroxide nitrite which then further depletes the BH4 and it's worth noting that BH4 is needed to make your serotonin and is involved with your your dopamine as well so many times people are depressed because they don't have enough BH4 all right then we come over here and we activate the platelets oops what could I just do there we activate the platelets and then we need our our good fats to let me just make that a little bit bigger we need our good fats made by the the fads enzymes and you're not too bad here you just have a little bit on fads 2 nothing on fads 1 and 1 on ELOVL 2 which is the EPA to DH okay now and there Bob because you mentioned this I think is important for people listening that protections and resolvents you basically bypass that pathway if you have issues and those are the SPMs SPM active SPM supreme there's a lot of them out there I found that to be incredibly helpful for me with inflammation and it makes sense because I'm bypassing all of those FAD enzymes and the riboflavin for me for 20 years now I know why but I've always taken at least 100 or 200 a day of riboflavin for years because I really do better with the riboflavin which makes sense with the FAD enzyme absolutely now this could be a future show to talk about this because I'm really becoming enamored by arachidinic acid the tumor necrosis factor through PLA 2 brings out the arachidinic acid and there's a couple of pathways and I don't have that chart ready but one of them is to take the ALOX enzyme and make lucatrine B4 which is a nasty nasty lucatrine and you don't have any mutations here but some people have gain of function and the CYP this one right here calms down lucatrines clinical observation when somebody has homozygous here and homozygous here they've got inflammation that they just can't seem to figure out why so we're researching that so you're fortunate that you're clean as a whistle there all right now drum roll we're going to look at your hemoxygenase so here you can see your your HO1 and your HO2 make the biliverton and bilirum and you can see that you've got a homozygous and two heterozygous on your Hbox1 then you've got homozygous on Hbox2 now you are incredibly lucky because you do not have the gain of function on KEEP1 it's the folks who have this one either one or two particularly the twos that they they're these are the people that sometimes are even bed written from microtoxin exposure and you're very fortunate I don't see this very often you're perfect on all your nerf twos so you don't see this often perfect on KEEP1 perfect on nerf 2 so but you do have weakness on Hbox1 and Hbox2 now tell you about riboflavin here are the riboflavin transporters and you can see perfect perfect and flad1 which is making your your POR perfect so you really lucked out here your POR enzyme perfect G6PD not a thing not one little thing ME1 perfect and as I said the nerf 2 and KEEP1 so you really when I look at these very seldom is this area this good so you're very fortunate there because it could have been worse had you had issues here let's look at your heme cycle you do have a couple upon ones which clears your glyphosate have you ever tested for glyphosate oh yes Bob this is back and again a group on a farm organophosphates glyphosates massive exposures I think contributed to some of my history of illness and when I first tested when they very first came out with testing I was three times the normal limits of farmers on application day so and that was with actually an organic diet a pretty clean lifestyle so this is absolutely very valid for me as far as exposure and accumulation of glyphosate yes have you tested recently I'm better I'm low now finally all the detox have been good good good so with these pond one which which by the way that stands for peroxinase that clears the pesticides you know you've got to be very careful you know one of the things that I'm sure maybe it's not so much anywhere where sometimes people go golfing and some people will smoke a cigar and they'll put the cigar on the grass you know it's like not a good idea so you know Bob we're talking with Dale Bredesen about writing golf course Alzheimer's because there's so much related to the exposure on golf courses and pesticides in the brain and so it's a very real phenomenon I always ask people where do you live do you live near a golf course because they're likely going to be exposed to a lot more pesticides absolutely now your aline enzyme you can see here you've got two heterozygous mutations then on the UROS you've got one and on the CPox this is a new one that we've just added I mean literally in the last couple of weeks and this is a rather significant down regulation of the CPox enzyme so we could make an argument there's again keyword is potential that you may not be doing this as strongly as you should then you get over to the hemox and it's you know not doing its best but again you're very fortunate extremely fortunate one nerve two POR G6PD so what's interesting is the you know you really got hit hard on the INOS but you did I would say that probably one out of a thousand if not less that has everything perfect right here so you're very very fortunate there and that is that is you for this section and just said you might have a little extra because of the HFE and the NF Kappa B this could be pushed a little bit fortunately your assert's good but for you supporting this hemox as an ACE might be to your your advantage and I believe you did start a couple of things that support didn't you some sage or something or I did I'm trying to think of what we talked about because first in INOS was lysine and resveratrol I added back in I did SPMS and I'm thinking recently with hemox B5 was that one of the co-factors pyridoxine or maybe thinking about adrenals maybe I think you're thinking about adrenals okay okay well there there you go we can now see why you had some of the struggles that that you had and I'll just say one little thing about that because we've been talking on every it's kind of this pathway as we keep learning new things and you share all your amazing knowledge and I think I've shared on other with the INOS video that we did about how I was struggling with low blood pressures and all of this and I just told you before we started but I want to say this for people who are thinking oh there's no mold in my house I'm kind of the mold queen I'll just say it I love mold I deal with mold I really like help so many patients with mold and it's one of my favorite things to do and just recently Bob I told you two or three weeks ago I found ketomium which is one of the nasty of the nasties behind my fridge because there was a small leak in my home and now I am feeling so much better and I'm only just saying this because here I am I know mold I know how to prevent mold I do all the right things and even me in my home I found mold recently and there's no doubt all the stuff we've been talking about the last six months with the low blood pressure and the fatigue and some of the symptoms I was having related to that INOS pathway we're related to the mold in my kitchen so if you think there's no mold in your house check again because often there's these hidden things even for the best of us who know what to do that are causing illness absolutely well I'm so glad you found it and I'm sure it was a relief for you to know that there was a cause behind this right yeah all right just a little commercial if you're a health professional this is not for the general public the software the maps we looked at were made by the software your functional genomics and if you'd like to check us out just go to functionalgenomicanalysis.com we have a online certification and you can save $100 by using the code Dr. Jill the first couple modules are free then there's a charge and you can save $100 by using the code Dr. Jill somebody wants to talk to us here at the office for our health coaching tolhealth.com 717-733-2003 again the software functional genomic analysis and Yvonne Lucchese or Chrissy can can help health professionals so there we go that's that's a really quick why we need to be aware of hemoxygenase so to wrap it up what we need to do is take away the environmental factors that would stress it not have the enzymes that also stress it up regulated and then find out if the hemoxygenase enzyme needs help if the heme pathway needs help or we need NADPH through the POR enzyme Bob thank you as always this is just I love going deep and I know so many of our listeners do I think this is going to get thousands of more viewers I'm going to share it everywhere that I can I just want to thank you for your work I always love promoting and helping you get more practitioners trained because truly I feel like this personalized approach is the thing that's the game changer for my most complicated patients and I know you've seen that as well so I just want to thank you publicly again for all of your hard work all of your brilliance and helping us find the pathways even my own health has benefited from you and I want to say that publicly because we're just all grateful with all the work that you do and that you continue to educate and I really believe this is the future you know I've said before with I have a book coming out next year in a documentary and I would say I want to teach the teachers and influence the influencers because the more we can impact those who are out on the front lines like the functionalists and doctors and you're one of those people you're one of those people who teaches the teachers and influences the influencers in a very positive way that's changing health and the world so truly thank you for your work I'm so grateful well my pleasure and I do have to give also credit I'm very fortunate my son is following in my footsteps and he always has his masters in pharmacogenomics so a lot of these things that I pointed out today he's the one who pointed them out he pointed out the POR found the gain of function in the five locks so we're having fun geeking out together and working on it so that is even more beautiful that's my generation so as always thank you thank you all for listening leave some feedback share with your friends and we'll see you next time okay a pleasure to be here you