 Okay, we're live Bob Miller. It's great to be back with you and today I have been so excited about this topic because it's so relevant not only to the stuff we've seen in the past with endotoxemia and Lyme and mold etc but with COVID the IL-6 pathway has been predominantly on the news in the research and today we are going to dive into IL-6 and Bob's going to give us a lot of background on what is it, what pathways it affects, where it goes and why it's relevant to pretty much all of the chronic inflammatory processes that we're seeing. So if you've been on our Facebook lives, first of all, you can watch this. It'll be recorded. You can go to my YouTube channel to get these videos later anytime. There's four now. I think this is our fifth. So you can watch all of those. I'll be sure and put a link in the comments. If you have any questions as we're going, feel free to comment and I'll try to watch those. And Bob Miller has just been a fixture. He's part of TRIA Life Health. I don't have his formal bio up today. I feel like people might know you by now but just a real great ability to put together synthesis of complex pathways and to look and find new data that helps us as clinicians try to figure out what's happening in our patients' bodies. So thank you, Bob, for coming again today and joining us with this new information. I'm going to make sure your screen share is on and I will just let you take it away with IL-6. Okay. Well, always a pleasure to be with you. We have so much fun as we geek it out, so to speak, on some of these pathways. And I must say, you know, all the other things we did were fascinating. We spoke about peroxanitrite and we spoke about the importance of NADPH and then the NADPH steel. And then we talked about the homocycle where this thing all just cycles together. What's interesting is what I'm going to do today is pull it all together as to how this may be many, many cofactors in creating a very inflammatory cytokine called interleukin-6. And as you mentioned, you know, this is getting in the headlines because of COVID because it's upregulated in the cytokine storm. But even if we put that aside, this is a very important molecule that we have to be very aware of because it has so many implications and I think people will be really blown away by all the negative things that too high a level of IL-6 does. So let's do a screen share and get started. Okay. I believe we're sharing the screen. Yeah. And the title is IL-6, the good, the bad and the ugly. And of course we want to mention that this is for educational and informational purposes only. We're not telling anyone that this diagnosis is a disease or treats any disease. So I call this the 3D chess game played underwater. And you can see over here we have some scuba divers playing 3D chess game. And the reason I had an artist make this is because this is how complicated this can really be. We tend to think what is the gene related to fill in the blank? And I think what we're going to find, that doesn't exist. There's multiple factors that go together. Genetics and possibly more important, the environmental factors that are impacting it. And it's often been said genetics loads the gun, but environment pulls the trigger. And we have to look at this complex equation to truly understand what's happening. Now we're going to be talking about what are called interleukins. And I have a sneaking suspicion, Dr. Jill. We're going to be doing something later on IL-13, IL-4, because all of these are so very important. And the reason we started with IL-6 because of the news that has gotten on COVID, but again, if we even put that aside, this is very, very important. Just a little bit of interleukin 101. There are chemical mediators involving signaling between cells, particularly your white blood cells. The words here intermeeting between lukin referring to leukocytes. There are types of cytokine, which is derived from a combination of two Greek words, cytomeaning cell and kinos meaning movement. And there are signaling molecules that aid cell-to-cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma. As we're going to learn, they're not bad. We've had many, many conversations. This is our fifth one. Common theme that we seem to have is there's a balance. Too little of something is a problem. Too much of something is a problem. Same with cytokines. Use properly, they're not our enemy. And there's evidence showing that certain cytokines are involved in not only the initiation, but the persistence of pathologic pain by directly activating sensory neurons. So what they do is they're involved when there's nerve injury or inflammation. And so when we have a cut or a burn or something like that, they come to the rescue to help us out. So there's two pathways, classical signaling pathway, when the white blood cells, it occurs in the white blood cells and the liver cells. And it promotes an acute phase inflammatory response and potential anti-inflammatory actions. Interesting. It can be inflammatory or anti-inflammatory. Then there's another one where the IL-6's binding leads to what's called dominalization on cellular membranes increased bioavailability. And this actually promotes pro-inflammatory activities. So what's interesting, CRP, C-reactive protein, which is very inflammatory. It's a mediator of acute phase inflammation and is measured to evaluate underlying levels of inflammation. I'm sure it's something you measure on a regular basis with many of your patients. However, IL-6 is a major regulator of this CRP expression and appears to be essential for the induction of it. Now, we're probably going to spend about five minutes talking about the good and then we'll probably spend about 50 minutes talking about the bad. But our immune systems and our white blood cells, they're critical for protection against pathogens and development infections. So IL-6 is an essential messenger within the immune system. So when we get some foreign invader inside us, IL-6, along with other things, corresponds to the rescue. Now, this acute inflammation signals for tissue repair and inflammatory responses designed to initiate healing or protection from invaders. However, unresolved chronic inflammation is associated with many health concerns. Now, what's interesting, if we get rid of IL-6 completely, they're susceptible to various infections. So IL-6, again, is not our enemy unless there's too much of it. Now, here's paper and most of our slides, by the way, Dr. Jill, are going to be peer reviewed studies for those who aren't familiar. This is all from PubMed. It tells you where it was published. These are the authors and all of these have to be peer reviewed. So we're not making any of this up. This is all peer reviewed information. Rather than go through this in any detail, what they found is that IL-6 levels appears to be critical for proper lipid regulation. So they did some experiments with mice and they found it's a very important thing to have. Now, when we exercise moderately, it appears IL-6 is released in a circulation from the contracting muscles, and then that may have a role in gastric functions in response to exercise. Now, we're going to talk about exercise later. We all know that moderate exercise is very important. However, if we over exercise, it can be to our detriment. We'll get into that a little bit later. Now, the authors found in this study, an IL-6 blockade induced muscle inflammation in the mouse model of muscular dystrophy. So IL-6 may have some beneficial roles with some conditions. And again, what we're going to find is we need some, but we have a problem when there's too much. Now, here's an article that talks about IL-6 appears to have a specifically important role in wound repair. The analysis suggested IL-6 may have an important role in macrophage infiltration, fiber and clearance and wound contraction. Now, those are some of the good and there's probably more, but as I said, we spent five minutes on the good. Now we're going to talk about when IL-6 goes rogue when it starts to create some problems. I'm starting out with this one because this was a study that was done in a senior study. And the term inflammaging is when there's too much inflammation in the body. And as we age, low-grade chronic inflammation is a risk factor for the development of age-related diseases and frailty. So they did this study to find out what was happening with interleukin-6 C-reactive protein and the health of the elderly. And we all want to age gracefully. Here's the bottom line. When comparing successfully aging individuals to those with aging related diseases or disability, there was lower IL-6 levels in the successfully aging group. Even longer survival was associated with lower concentrations of IL-6. So what was the conclusion of the study? IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entirely, entire elderly population and successfully aging individuals. So I'm sure a lot of the viewers watching today say, well, that's for me. I want to age successfully and not spend the last years disabled, frail, being a burden on their relatives. Now this was interesting. This study showed interleukin-6 from systemic inflammation predicts all-cause mortality in men. Bottom line, IL-6 was consistently related to all-cause mortality independent of the level of adjustment and showing a dose-response relationship between IL-6 and risk of death. It's a powerful predictor of all-cause mortality in male elderly community dwellings. To me, I found this fascinating, Dr. Jill, when I came across this. This is huge. Whenever you say all-cause mortality, that's a big deal. Absolutely. Now one of the things I've been doing over the last probably four to six weeks is I'm doing my health coaching with folks and they tell me I'm struggling with fill-in-the-blank and I just go like, hmm, I wonder if there's a study on interleukin-6 and this. Wow. And I have a sneaking suspicion. I'm going to show you a lot of slides here today, but we're probably just scratching the surface. So this data suggests that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice. So we're talking about pulmonary hypertension and lung inflammation. So there's many causes, of course, for hypertension. Lung inflammation or lung issues is one of them. And here's where interleukin-6 plays a role. Now look at this one. This is your cardiovascular disease. IL-6 contributes to endothelial dysfunction. We're going to show a chart a little bit later. By the way, we've made a new chart that will be premiered here. It's produced as a response to angiotensin-2. Now for those of you who are practitioners, you understand the R-A-A-S, the renin angiotensin system. And we're going to show this and explain it. So if you're a little lost now, that's okay. IL-6 is associated with hypertension and a higher incidence. Again, all cause mortality. Now there's a very nasty free radical called superoxide. And if you want to learn about this, go to our very first interview that we did. Probably sometime I think June or July. It's on the Dr. Jill's Facebook. And we talk about how this nasty free radical superoxide combines with nitric oxide. Nitric oxide is needed for good blood flow to create one nasty little oxidizing agent called peroxynitrite. And our first webinar was on peroxynitrite. I encourage you to go back and listen to that. Then you'll understand why it's so important to keep this peroxynitrite down. Then what that does, that further lowers your nitric oxide bioavailability. And nitric oxide won a Nobel Prize for its study back in the 1980s, because it's so important for that opening of the blood vessels, making sure that the blood is flowing properly. And it also has so many other properties that we don't normally think of. A good indication of low nitric oxide is cold hands and feet, or hypertension, because as your blood vessels constrict. And also for men it relates to erectile dysfunction because there's not enough blood flow for the penis to become erect. By the way, that's what Viagra and Cialis does. It stops the breaking down of nitric oxide. This one I found mind-boggling. Dr. Jill, it's increased in the cerebellum of the autistic brain. Mm-hmm. So, bottom line, conclusion, increased IL-6 expression may be partially responsible for some of the issues of autism. Clearly, autism is going through the roof. You know, the statistics are used to be one out of a thousand. And what's it down to now, Dr. Jill? 45 or 50, something like that? Yeah, I think it's incredible that how it keeps going down, down. I think it won 45 was the last number that I heard. Yes. And predictions are that it's going to even get worse, and affecting boys more than girls. Again, in our health coaching, we work with a lot of parents with autistic children. You know, what I should have done is I got permission to share the clip from the mother. The mother was just almost in tears, thankful for the way her child is improving. And all we were doing was doing things to decrease interleukin-6. Wow. Clinical anxiety, cortisol and interleukin-6, you're saying clinically anxious participants exhibited significantly lower levels of morning cortisol. Now, let's talk about that a little bit. Cortisol is made by the adrenal glands, and one of the things it does, it calms down histamine. One of the things that IL-6 does is create excess histamine. So I would encourage you to go back and listen to the last Facebook live that we did on Dr. Jill's Facebook page, or her YouTube page, because we spent a whole 50 minutes talking about histamine. And we talked in there about, we tend to think of histamine as itchy eyes, runny nose, rashes, but it's significantly more than that. So as IL-6 is stimulated, we're going to show you later charts that it makes histamine. We need cortisol to knock that down. So I'm sure we're all seeing this. Anxiety is going through the roof. The ladies that work in my office, sometimes they come back and say, Bob, these people are driving me crazy. They're screaming at me because a package didn't go out as supposed to, or something like that. I like to talk to people at the grocery store. They say, tell me, how are people behaving? They're all like, oh my goodness. They're just so anxious. They get so upset over everything. So it appears as though we are becoming more anxious. And of course, turn on the news for 10 minutes. And it's like, what? Now, look at this one. I mean, this one blew me away. Role of interleukin-6 in depressive disorder. Animal studies and clinical studies have demonstrated that IL-6 may have a special role in depressive disorder. Once again, Dr. Jill, we are just seeing so much more people, not only anxious, but people depressed. I think I saw Bob, that prescription, I don't know, was 600% increased in antidepressants. And obviously, we have COVID, we have pandemic, we have isolation. There's many other reasons, but this is definitely playing into it. And especially because we know infections and COVID and many other things will also increase IL-6, which I'm sure we're getting to. But the increase in depression is astronomical this year. Absolutely. Now look at this. The role of cytokines in suicidal behavior. Whoa. This one really blew me away. Elevated IL-6 was the most robust cytokine finding associated with suicidal ideation and both non-fatal suicide attempts and suicides. And I don't know if suicide is on the increase, but clearly, there's more than we should be seeing. So clearly, I mean, there's so many factors, not just IL-6, but this is a factor in suicidal behavior. Now, one of the saddest things is when someone's dealing with anorexia and bulimia. And I talk to parents sometimes are just heartbroken by, my child is so skinny, I worry about them and they still think they're fat and they restrict their food, putting themselves at tremendous risk. Look at this. Conclusion, tendency toward increased IL-6 production. And I didn't know this. Suppresses food intake in animals, in individuals who severely restrict food intake, suggest a potential role of these cytokines in anorexia nervous. Yeah, I'm just blown away by all of this. Now, one of the biggest fears that we have as we get older is Alzheimer's disease. So what they found is they enrolled 41 subjects in a disease group and 40 in the normal group. So the majority of the subjects in the disease group had mild Alzheimer's disease. There was elevated levels of IL-6 and decreased levels of plasma trail in the group. So plasma IL-6 was identified as a potential biomarker of Alzheimer's disease at an early age. And of course, makes sense. You know, the brain, 80% fat, the more inflammation we have, the more brain inflammation we're going to have, and the more the brain is going to deteriorate. Now, look at this breast cancer. Several studies have demonstrated IL-6 and its signaling in tumor growth, the growth of the cell, and therapeutic resistance. Therefore, it seems that targeting IL-6 or its receptor in combination with other potent anti-cancer therapies may be a potent therapeutic approach for breast cancer therapy. Absolutely astonishing. Colorectal cancer. And of course, this is on the rise. Several experimental and clinical studies have linked the cytokine interleukin-6 to the sporadic and inflammation associated colorectal cancer. The increased IL-6 expression has been related to advanced stage of the disease and decreased survival. So here again, inflammatory bowel disease. As you know, that was what got me interested in this kind of work. A severe case of inflammatory bowel disease when I was in my mid-30s, lost half my blood, then I hemorrhaged, didn't know if I'd make it to the next day in the hospital for 21 days. And that was about 32 years ago, and my colon is now just doing fine, but got to work at it. And I was told, the colon's got to come out. If you don't have this colon, you're an idiot. There is growing evidence that pro-inflammatory cytokines interleukin-6 plays a crucial role in the uncontrolled intestinal inflammatory process. Now, what I'm understanding is the amount of children that are getting inflammatory bowel disease, and once again, skyrocketing. And they're saying, again, the colon cancer, and of course, as we know, long-term inflammatory bowel disease leads to colon cancer. So, interesting study for a peer-reviewed study, but a villain in the drama of pancreatic cancer development. Conclusions, IL-6 emerges as a key player in pancreatic cancer development and the progression. So here we're talking about chronic inflammatory proliferative disease, same thing. Several diseases including rheumatoid arthritis, systemic onset, juvenile chronic arthritis, osteoporosis, psoriasis, amazing, all these things that it's involved with here. I was really stunned when I started dating and found all these peer-reviewed studies. Here we go, insulin resistance and type 2 diabetes. There's a relationship between stimulation of IL-6 and insulin resistance, and there they go into what causes it. So, by blocking IL-6 and IL-6 signaling may be an effective strategy for the treatment of insulin resistance. So, as we know, when I was a kid, we used to call it adult onset diabetes because you were usually, you know, a little obese and over 40, and now we're seeing children with diabetes. I'm sure in your practice you were seeing young children with diabetes, Dr. Jill. With type 2, yeah, and then so interesting because this pathway with endotoxemia we've talked just a little bit about where the LPS coating of the bacteria goes into the blood and we know that triggers IL-6 and we know that's associated with diabetes and heart disease and obesity and mood disorders. This is all playing together and you kind of wonder which came first. We talk about that LPS and these infections, but what if really the common denominator is IL-6? It's certainly looking like that's part of the story. Absolutely. Now, listen to this. Thyroid hormone concentrations. The data reveals a statistical relationship between elevated serum IL-6 concentrations in alterations and circulating thyroid hormones. So, of course, you know, we're not even talking about Hashimoto's here, they're just talking about low thyroid. And so, since this is related to autoimmune, I probably should look, I didn't find any, I didn't look for them, but I wouldn't be surprised if there's a relationship to Hashis. Now, one of the things that we're talking about, and I think you and I spoke about this before, that early in our careers we didn't even talk about mast cells all that much. And mast cells or white blood cells that again are there protect us. However, when they become overactive, they're a problem. And at my conferences where we teach physicians, you know, I often say, how many of you have seen a dramatic increase in what's called mast cell activation in the last five, 10 years? Virtually every hand goes up. That people are coming in with more and more mast cells. Again, mast cells are not our enemy. They're there to protect us unless they're overactive. What percentage of the people who come see you, Dr. Joe, because you see some of the people who are really struggling, what percentage would you say you believe that the mast cells are overactive? Oh, gosh, I would say at least 25% maybe more, but that's one in four. So yeah, exactly. And when you started your career, what was it? Maybe 5%, 5%. Absolutely. So here they're saying IL-6 increases mast cell proliferation and formation. And we suggest IL-6 blockade might ameliorate the mast cell related symptoms and pathology in mast cell related diseases associated with elevated IL-6, including the high levels of mast cells. This one just blew me away. I mean, I never thought I'd find something like this. As I said, as we dug into the, I'd be at the office until one in the morning. It's like, no, I got to go. I was so, a long parallel to you looking as we talked about IL-6. I wanted to, and same thing, I just kept going down rabbit holes of there's so many studies with IL-6. It's unbelievable. Not surprising, but it really is. I wonder if there's anything that's not related. Well, I was thinking the same thing because, you know, in traditional naturopathic philosophy, it's excess inflammation. That's the initial trigger. And if this does that, it probably is related just about to any degenerative condition. You know, it was just funny. I talked to a woman who had hot flashes and I said, hmm, I wonder. And I thought, no, I won't find anything. Lo and behold, serum IL-6 concentrations in perimonopausal women with severe hot flashes were significantly higher than the concentration of women without hot flashes or with mild and moderate hot flashes. So it's even playing a role in the dreaded hot flashes. And again, another person had vitiligo and I thought, hmm, I wonder. And increasing the production of pro- inflammatory cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role in that cytotoxicity. So they're saying that the cytokine production might be involved in the vitiligo. Now COVID-19, now again, we're not saying by knocking down interleukin-6, you're going to prevent getting COVID. This is not a cure for COVID. What we're talking about is when you get COVID, as you know, some people have no symptoms. They didn't even know they had it. Others are, okay, I had a cough and a sore throat and others are gasping for breath and on ventilators. Much of the literature now is pointing to interleukin-6 and bradykinin as part or, you know, in part or in whole of that cytokine storm for the lung inflammation. So this is just a review. It says during a meta-analysis, elevated IL-6 levels were found to be significantly associated with adverse clinical outcomes. 2.9-fold increase in mean IL-6 concentrations in complicated COVID-19 cases. Now I should have grabbed this slide, but I didn't find it, but or didn't have time to do it, but there appears to be some studies that show the higher the IL-6 is before you get COVID, the potentially more probability have of going into the cytokine storm. Now again, we're not saying keeping IL-6 down prevents COVID, not at all. We're just saying it could be, you know, potential that it's a factor in how severe the cytokine storm could be. Now, Bob, that's that's one reason why I said we can't wait to talk about this because that's been my theory is that again, this is not medical advice, but the priming of someone who has IL-6 for LPS endotexemia for another infection for all these many reasons. I suspect that those who are primed with higher IL-6 is before they get this infection tend to bear worse because that whole systemic inflammatory cascade is already going and primed. It's like priming the well. Back in the days when you pumped water, you primed the well. And interestingly, as you and I were talking about this before our presentation, there is some new data that ivermectin is being used in clinical studies and research this old use of drugs and ivermectin has activity in preventing LPS induced IL-6 increase. So again, these are all just interesting observations, but that one I thought, wow. So I suspect that any drug that would have an effect on IL-6 could potentially help some of these chronic infections. Absolutely. Again, not cure the COVID, but not PS severe. Now, this is another one, interleukin-6 in patients with COVID-19. Just going to read the study. Evidence shows that pro-inflammatory cytokines play a pivotal role in the lung damage in people affected by COVID-19. A lot of patients affected by COVID-19 developing a damaging immune reaction sustained by cytokines leading to the lung infiltration by macrophages and monocytes. Interleukin-6 is one of the main mediators of inflammatory and immune response initiated by infection or injury and increased levels of IR-6 are found in more than one half of patients with COVID-19. Levels of IL-6 seem to be associated with inflammatory response or respiratory failure needing for mechanical ventilation and or intubation and mortality in COVID-19 patients. Again, if somebody wants to find the study, just type interleukin-6 as a prognosticator in patients with COVID-19. PubMed, not Bob Miller's opinion, this is a PubMed peer-reviewed study. Now, we're not going to have time to get into all of this, but this is some of the things that IL-6 will do. If somebody wants to pause this or take a look at it, they can. But what I'd like to point out is that it does increase the CRP, does reduce the albumin, increases the hepsidon which decreases iron and has all kinds of effects. So, you know, this could be a whole day course on all of these things, but just wanted to point out all the things that IL-6 does. Now, this is probably just a fraction of the things that IL-6 does. Now, I'm sure everybody's saying, well, that's really good information, but what do I do or don't do? So now we're going to get into some of that. So, what's one of the risk factors for, you know, more of a cytokine storm? High blood sugar. So, inflammatory cytokine concentrations are acutely increased by hyperglycemia. So, here's the summary. High blood sugar for diabetes. Acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with impaired glucose tolerance. So, what we're going to find here as I go through this, this is going to be the good health 101. Things that natural health professionals have been talking about, not on natural health, but medical doctors have been talking about for a long time, things we have to do to stay healthy. What's stunning to me is, oh, how this ties into interleukin-6. So, clearly, taking the steps you need, diet, medications, well, whatever you need to do to keep your blood sugar under control is an important factor in not having interleukin-6 be upregulated. Obesity, and of course, obesity is on the rise. Have you ever seen any people post a picture of like a crowd back in the 1950s or 1960s, and they say, note that you don't see anyone who's obese, you know, do that. Today, obesity is on the rise. Adipose tissue is one of the main sources of inflammatory mediators, including interleukin-6. So, if someone is obese, one of the most important things they can do is get down to a healthy weight so they make less interleukin-6. Now, obesity isn't, I mean, IL-6 isn't the only factor with obesity, but it is one of the factors to consider when being overweight. Now, one of the things we've talked about before, when if you go back and watch our videos on the NADPH deal and the home cycle, there's this NADPH oxidase, and this is an important enzyme. When we are faced with a pathogen, NADPH oxidase says, whoa, we got an enemy here. Iron, give me some oxygen. NADPH, give me an electron, and let's kick up a storm here. Let's make some superoxide, hydrogen peroxide. Let's make some mast cells. Let's make some cytokines. Let's make some histamine, and take out this invader. We didn't have that. We die of infection. But the thing that I've been talking about for years, I believe environmental factors are up-regulating this enzyme. Lo and behold, interleukin-6 induces expression of the NADPH oxidase number two, and you'll find studies on COVID that it's the up-regulation of NADPH, or NOx2. These are abbreviation as NOx. NOx2 is behind the cytokine storm. Again, putting COVID aside, all the things that this could do by having these two talking back and forth to each other is significant. So IL-6 was found to increase NOx2 activity in concentration and time-dependent mechanism. So NADPH oxidase is stipulated by interleukin-6, and I'm going to show you a chart later that it's a crosstalk. Interleukin-6 stimulates NOx2. NOx2 stimulates interleukin-6, and you have a positive feedback loop that just keeps feeding upon itself. Now, we're going to show a chart in a little while. In the RAS system, they were saying angiotensin-2, when that's increased, was found to induce interleukin-6, and then subsequently NOx once again. And in an IL-6 knockout, it was found to inhibit that angiotensin-2 increased NOx activity in VEGF expression. And again, for the layperson, they're going to be like, what in the world is all of this? But I'm going to show you a chart that shows you how this plays together. Oxylates, lo and behold, oxylates, stimulates IL-6 production. So oxylates, in case someone doesn't know, they are like little razor blades in some of the healthiest foods. Have you ever heard anyone, Dr. Jill, said that I wasn't feeling well, so I started to eat healthy, and I started doing spinach and kale and beets, and I got worse. And almonds and all these wonderful foods? Yes. Absolutely. So what happens here is some of these very healthy foods, for their own self-protection, have these little razor blades inside them, so insects don't eat them. If our gut is doing okay, they just pass right through. But for some individuals with gut issues, or there's actually even genome genetics that may give indications you don't break them down as quickly, these oxylates get inside the body and these people are in pain. There's some thought that fibromyalgia is related to this, and these are the folks that if you just, you know, touch their arm a little bit, they're in pain. Massage is torture. So oxylates up regulates the expression and secretion of IL-6 in the kidneys. So absolutely astonishing. And many people don't think about oxylates. That's why I think it's important to do the, you know, the Great Plains Oat Test and see if there's oxylates that are occurring. Homocysteine. You know, a lot of doctors don't measure that probably as much as we should, and I'll never forget reading the book, and it's excellent reading. It's called the H factor. It's written for the layperson, and the bottom line of it is the higher your homocysteine, the sooner you die from all causes. And chapter after chapter talked about studies that show how homocysteine can increase all kinds of mortality. There might be other mechanisms, but elevated homocysteine increases IL-6. So the study is in favor of an association between homocysteine and IL-6 production. Now, what's interesting, we can't vilify homocysteine because that is what the body uses to make the master antioxidant glutathione. So here we go, Dr. Jill, back to Goldilocks and the three bears. Not too little, not too much, just right. Without homocysteine, you don't make glutathione. Too much homocysteine, you die sooner from all causes. Do you have a range of, of homocysteine that you prefer, Dr. Jill? Yeah, I'd like to see a below nine for sure, and ideally below seven with Alzheimer's and Dale Brighton's work. But then if it gets really low, like below four, it can be an issue too. So there is an optimal range. So I'd say four to nine would be ideal. Absolutely, I would agree. Some people in the functional like six to seven, but it might be hard to get it there. Perhaps a subject for a different time, but this is related to methylation. Homocysteine is taken by methyl B12 and methylfolate to recycle it back to make something called SAMI that's involved in a lot of processes. And if you go back to our talk on histamine, you'll see that the HNMT, histamine methyl transferase gene, needs SAMI to methylate histamine. So then if we have too much histamine, as you'll see in a little bit, that'll create more IL-6 and we're on another hamster wheel. So elevated IL-6, homocysteine and low folic acid was found in patients with acute heart disease. Dopamine increases interleukin-6 release. Wow. So dopamine, of course, is going up. And this might be in a subject for another talk, but here it says dopamine increased basal IL-6 release and potentiated IL-6 release stimulated ACTH LPS, IL-1 beta. So here it says dopamine through dopamine receptors regulates the release of interleukin-6 and tumor necrosis factor from adrenal cells. And clearly, dopamine must be going up because people are getting angrier and more frustrated. And one thing I was going to mention with dopamine is when you have excess, so first of all, gut dysbiosis is getting worse and when you have excess clostridia in the gut, they will produce false neurotransmitters in excess dopamine. And we see this all the time with behavioral disorders, autistic spectrum disorders, mood disorders. And so that's just one small functionalism and reason for elevated dopamine. And there's many more. I love the idea. We could do a whole lecture on dopamine and causes of high neurotransmitters. Sure. Sounds like we're going to be at this for a while. Yeah. So in mice, IL-6 administration was found to produce profound elevations of both serotonin and dopamine activity in the hippocampus and prefrontal cortex regions of the brain. Now, another interesting thing, there's an enzyme called COMT that is used to clear dopamine. It's weakened by estrogen, strengthened by testosterone. So what's happening? We're being exposed to all these plastics that are Zeno estrogens. And that's why we're seeing, you know, testosterone levels dropping in young boys, possibly why, you know, when I talk to college professors and I say, tell me about the freshmen, one term that everyone keeps using is fragile. They're just not, you know, confident they're fragile. So we've talked before about mTOR and autophagy. And in case anyone doesn't know, there's two processes inside the body that are equal and opposite. One is called mTOR, the growth of new cells. If we didn't have mTOR, the sperm and the egg would never become the baby. The baby never become the adult. We need mTOR to make new cells. It's called a mammalian target of rapamycin. However, there's a inverse to that. And that's called autophagy, the cleaning of the cells. If you Google autophagy Nobel Prize, who's the Nobel Prize in medicine, was given for the study of autophagy in 2016. We need a balance between these two. And my research has shown that there's so many environmental factors that are up regulating mTOR, which then down regulates autophagy. I give the analogy, think of mTOR as the construction crew, autophagy the janitorial cleanup crew. And mTOR suppresses autophagy. A couple of things that would do that. You know, I think we're going to look back some day and say, what were we thinking? Giving animals growth hormones so they get fatter faster. Seriously? What were we thinking? That stimulates the mTOR. All of the plastics, they're xenoestrogens. So that's why I believe people are seeing such good results with intermittent fasting and the ketogenic diet. Because what it's doing when you go intermittent fasting, when you take the nutrients away, the mTOR says, hey, construction crew, I don't have any materials. Take a break. Okay, janitors, come out and do your thing. Now, this is interesting. This is a little, you know, like a 3D chess game here about itself. But interleukin 6 influences stress by reducing the expression of an mTOR inhibitor. So when you reduce an mTOR inhibitor, that allows mTOR to go rampant. And mTOR is a very dutiful replicator. It will replicate healthy cells, cancer cells. And I don't have a slide on it here, but COVID uses mTOR for replication. So that's why I'm thinking now is not a good time to be doing things that upregulate your mTOR. Now, if that's not enough, autophagy, the cleaning of the cells, IL-6 inhibits autophagy again by a signaling pathway. So what happens is the IL-6 stimulates something that slows down autophagy. So taken together, these data indicate that IL-6 inhibits starvation induced autophagy. So theoretically here, if someone would try to do intermittent fasting to try to boost their autophagy, if they've got a lot of IL-6, that's working against them. To me, this was like mind-boggling. It's like, oh my goodness. So if we have this IL-6 going, we're going to crank up mTOR. We're going to weaken autophagy. And that is going to set us up for all kinds of inflammatory cascades. And one of the best ways to see if your autophagy is not working is the amount of age spots you get sooner rather than later. As you know, when people get older, they get those age spots. One of the things they are is when the dead cell that is being reproduced is not cleared properly. So I many times see people in their late 40s filled with age spots. You know, ideally we wouldn't get them at all, but let's say it's probably okay if we're 85. But the sooner you get those age spots, and I'm not talking about freckles, I'm talking about age spots, the sooner you get those, the more indications there are that autophagy may not be as robust as it should be. Yeah, I was going to mention with mTOR, Bob, but you mentioned this, and just so people who are listening, things that up-regulate mTOR would be anything that increases growth hormone. So some of these newer peptides are actually taking growth hormone or taking any anabolic types of steroids that would be testosterone or of course any illegal substances, even some of these peptides and amino acids. So leucine and isoleucine in these. So if you're taking amino acid, you're doing testosterone, you're taking peptides, you could be a higher risk for this mTOR being excessive and lack of autophagy. Absolutely, and throw glutamine in there as well. And we talked about this before, but it's worth mentioning. I believe too many well-meaning health professionals are suggesting too much glutamine, which can then up-regulate mTOR. Now the reason they take it is because it heals the gut. Well the gut is one of the fastest reproducing cells. So yes, glutamine will help the cells reproduce, but we may have what they call those unintended consequences that it may up-regulate your mTOR and actually make more glutamate, which we're going to show you in a little bit, actually can inadvertently up-regulate IL-6. Here we go, histamine. If anyone hasn't listened to our last talk, go back and listen to the talk we had on histamine. This one blew me away. IL-6 levels significantly increased following histamine stimulation, and guess what IL-6 does? It makes mass cells that makes histamine. So I think now is a good time for me to swing over a little chart, and if we can, I will put this in the comments later this evening so that somebody can download this PDF. So here you can see IL-6 in the center, and you can see that it stimulates NOx, stimulates mass cells, stimulates histamine, that then further stimulates interleukin-6. And then I'll show later that I listed on the left all the things we spoke about that will stimulate IL-6. We're still getting through these endogenous, and then later we're going to talk about the inhibitors, but I mentioned earlier we were going to talk about angiotensin. Maybe now is a good time to do that. The renin system, the ren gene, when it's stimulated, and look what stimulates it, superoxide, mass cells, histamine, dopamine, testosterone, stimulates angiotensin-1 and angiotensin-2, stimulates interleukin-6, superoxide, CRP, as we said mass cells and histamine, they all come back and what I'm calling the home cycle to re-stimulate this, but this time I put IL-6 in the center showing how all the factors that do that. And I'll be speaking about bradykinin in a little bit, but I'll come back to this when I do that, but very important how this histamine feeds back in this positive feedback loop. I found that very, very surprising. Bradykidin induces interleukin-6 production by human airway smooth muscle cells. So the bradykinin by the bradykinin-2 receptor induces IL-6 expression. IL-6 excretion by bradykinin is sensitive to cortical steroids and is regulated by the TH2 derived cytokines. So let's talk about bradykinin just a little bit because there are studies out there that indicate high bradykinin is part of the cytokine storm, but look what it does. It stimulates interleukin-6. Now look at glutamate. Glutamate inhibits ACE-2. Why is that important? ACE-2 is what takes these inflammatory molecules, angiotensin 1 and 2, turns them into angiotensin 1-7. So what I'm finding in our health coaching based upon functional genomics, when people have a lot of mutations in ACE-2 and maybe they have some mutations in H-Mox 1 that knocks this down, they've got a lot of inflammation going on. If they also have glutamate, the glutamate will inhibit ACE-2. Now let's look at the, now let's look at the, oops, didn't want to do that, hold on. I was just going to ask you, blow it up to potential inhibitors, Bob. We're going to get to those. Okay, we're all, we're getting comments already. What do you do then? Hang on, don't get stressed out because it'll put up your dopamine. We don't raise your IL-6, so hang on. So bradykinin will stimulate IL-6. The ACE enzyme takes this bradykinin down inactive fragments, CPN1 that we've just started to measure in our software, and just observing, many people with ADD and ADHD seem to have this, but just an observation. That turns it down to this molecule and then again, ACE-2 puts it into inactive fragments. Well, what does COVID do? Comes in using ACE-2 and we can eat. But aside from that, when you've got mutations here or high glutamate, you're going to have more bradykinin. Now, just an interesting thing that I just recently learned, we know that, you know, one set of drugs is called ACE inhibitors to bring down blood pressure. I just assume that they reduce the angiotensin 2. No, they don't. They slow the bradykinin to inactive fragments, and that's why some people get a cough on ACE inhibitors. So I wasn't aware, were you aware that that was the action of ACE inhibitors? No, I would have agreed with you at the receptors. I didn't think about the bradykinin piece. Yeah, I was very surprised by that because I just figured, well, ACE inhibitor, this is where you make, and I don't have it on this chart, but aldosterone would be up here, which causes you to hold on to sodium and excrete potassium. But this is where a lot of people get edema when, you know, the swelling of the legs when that occurs. So bradykinin induces this IL-6 production. Now, this one really blew me away. Estradiol decreased levels of IL-6 in a dose dependent manner. And this data suggests the hypothesis that at least part of the anti-resortative action of estrogen in humans is mediated by decreased production of IL-6. So we always talk about, you know, estrogen needed for bone health. There might be multiple pathways for that, but this is one of them. Keep in mind this is estradiol. Estriol has an elevation in serum IL-6 following an LPS challenge. So the saying these results suggest that the estradiol can have significant quantitative tumor necrosis factor IL-6 effects on inflammatory monokines produced in response to an endotoxin challenge. So absolutely fascinating. So, you know, we work with your, you know, with your primary care physician or whoever you work with on hormones to make sure that these two are balanced. Any thoughts on that, Dr. Jill? Yes. You saw me like, I was like really salivating on this one. This is new to me, but I would comment, number one, we use estradiol thinking it's like, we call it caboose hormone, end of the line because your body can't make four hydroxy and two hydroxy, some of the metabolites that can damage DNA. So we often use estradiol in breast cancer survivors or patients who need just a regulator of vaginal dryness by itself. If this is true, we have to think about this as part of the player of that activity because typically the good news is it's used transdermally. So I'm assuming there's not a huge amount of systemic absorption, but even so we, in my mind, I consider estradiol to be very weak and not potent. But if it were to in someone with elevated IL-6 already actually make that worse, we're just talking, we're postulating, we don't know, but according to the study, that's possible. I think we need to watch that. I would recommend if you're watching this, get your doctor to do some sort of quantitative metabolite panel. I like Dutch hormones. There's others because it will look at all the metabolites and then you can know for your body, what are your levels of estradiol, what are your levels of estradiol, what are your levels of esterone, and what are the levels of the four hydroxy and the two hydroxy. Just like Bob talks about pathways, it's really critical to talk to your doctor and get testing so that you know where the estrogen is going and what it's doing in your body. Yeah, good point. I mean, this is not all bad. I mean, as you said, this has many important functions that if your physician says you need it, I wouldn't go off of it. Obviously, follow their direction. But this is just another piece of the pie that might even be, who knows? I mean, just speculating might even be the ratio between the two. We're not saying you can't have this or shouldn't have this. It's just that perhaps if the ratio gets off, perhaps as it relates to progesterone, who knows? I mean, those are all speculative things that are probably yet to be discovered. Now, this is interesting. Regular physical activity, keyword moderate intensity improves cardiovascular risk factors, including low-grade inflammation. Back to Goldilocks and the three bears. Acute vigorous exercise such as marathon running resulted in marked increases of circulating pro-inflammatory markers. So we found an up regulation of tumor necrosis factor alpha in IL-6 in the plasma during vigorous exercise. So again, exercise is good for you. Can you overdo it? You bet you. And then does it start working against you? Yes, Bob, I would love to comment on this one, because I had a personal, so again, in medical school, we're taught calories in, calories out, exercise more if you want to maintain healthy weight and metabolism. So I, for decades, was doing very high-intensity, either like orange theory, high-intensity interval or running. So I would get up, get out of bed at 5.30, be on the road, be at the exercise by 5.45, do an hour of a pretty intense workout and come back and go to work. And about a year and a half ago, I started working with a trainer and she encouraged me to stop all the high-intensity and actually just do movement, and I did functional movement for several months and rehab my back. And then when I started exercising again, I did a little bit of free weights and walking, which to me was like nothing. I had to laugh. I'm like, and literally this is 40 years of doing the high-intensity types of exercise. But what happened, Bob, was not surprising, but to me, miraculous. My percent body fat went down by 8%. I got in the best shape of my life. And I always joke, I basically stopped working out and gotten the best shape of my life. And I love to tell my colleagues and women in their 40s like me about this, because here I am. I was a medical doctor. I've been through physiology, biochemistry, understand exercise. And I did not understand that number one, I was raising inflammation every day. Number two, I was raising cortisol, which was working against me. And all of a sudden I ate the same. I did less and I actually gotten a lot better shape. Now I actually have better muscle, less body fat. And it's almost without trying. All I do is walk or hike a couple times a week and do a little bit of free weights. And I'm talking very minimal exercise. And this is really important for people to hear, because it is a big deal. And I'm not saying you shouldn't be active, because I am active with walking. But I did not know this as far as how much it was affecting inflammation in my body. And so if you're getting stuck on weight loss in your woman over 40, maybe you're working out too hard. I'll bet you there are some people that are right now saying, bless you, Dr. Jill. It's very freeing because now I don't have it. It's funny, Bob. I have to say this too. There was no compulsion. I loved my workouts. I enjoyed it. It wasn't I wasn't over. I didn't feel like I was overtraining, but because it was just joyful. I loved it. But now that I know the truth, I think I was I think the truth was my body would have told me if I would have listened. This is too much. So absolutely. But perhaps you have a little bit too much glutamate, do you think? Probably. Probably the cortisol glutamate and inflammation. So it's amazing to me. Yeah. Yeah, that glutamate gives you that drive. Oh yes. And dopamine. We talked about this already. Now let's talk about the environmental factors. And then by promise after this, we're going to tell you what to do. So don't get stressed out. Air pollution and inflammation. Oh my goodness. I have a lot of clients in California. As the fires raged, I get the calls. Yes. I talked to you a year ago. I was doing fabulous. Thank you so much for your help. And now I'm in crisis because all that air pollution. Here it says the particulate number concentration exposure was reported to have an immediate impact on circulating IL-6 levels in heart attack survivors. Five-day cumulative exposure to the particulate matter was associated with increased fibrinogen concentrations. This suggests the role of air pollution inflammatory conditions. So results indicate an immediate response on the IL-6 level. So those poor folks in California, and I believe in your neck of the woods too, Dr. Gill, wasn't there some fires in Colorado as well? Oh, there was. And we also saw TGF beta, which is right along the lines of these cytokines. I'm measuring that because of a mold illness. I'm not measuring IL-6 in every patient, but I probably should be. But we saw same thing in elevation of other cytokines as well. And I'm just passing on what Dr. Klinghart said. He believed that during the California Gold Rush days, they used mercury to extract the gold from the ore and that mercury got into the system, into the environment, and now as the trees burn, perhaps some of that mercury is being released. And to what degree that's happening, I don't know. I'm just passing on what his hypothesis was. But this is why it's so important to make sure that you've got good air purifiers and make sure that you don't have mycotoxins and any source of dust and dirt is cleaned up. And it's a huge problem, stimulating the interleukin-6. Now, I have a frowny face here. Why? Why? I couldn't think of crying coffee. Yes. My favorite, I always say Bob, I want to introduce about chocolate and coffee, the flavonoids in the gut. I say, these are my two favorite food groups, chocolate and coffee. Men who consumed greater than 200 milliliters of coffee, I mean, I couldn't believe this, had 50% higher interleukin-6. Women who consumed greater than 200 milliliters had 54% higher in aisle 6. You know, I thought 200 milliliters. That's got to be a lot. Well, it's like six ounces. Oh, darn it. When would we get a shot of espresso? Now it's saying this relation could explain the effect of increased coffee intake on the cardiovascular system. Now, when I present this, some people say, is it the caffeine or the, you know, would decaffeinated not have an effect? I haven't seen any literature, but let me just speculate and hypothesize. The caffeine does jack up the dopamine. So I'm saying, I wonder if that is the mechanism or if there's another. But I didn't find any literature as to what it was about the coffee, but yeah. So to me, that was like bad news because I love my morning coffee and and I don't normally drink coffee, but just to keep make sure my brain was functioning, I had just a little bit here with me. So you know, Bob, just an idea. So you brought this slide about menopause symptoms in hot flashes and women in aisle 6 and we're all like, wow, that's crazy. Well, with hot flashes, they're worse with dopamine and norepinephrine elevation and the coffee same thing would elevate dopamine and norepinephrine. I wonder again, just totally thinking outside the box, there could be, maybe there's a correlation with neurotransmitter elevation because that would be a commonality between hot flashes and coffee. Absolutely. So I'm sure there's a lot of people now are just saying, I wish I wouldn't have listened to this. I know. Sorry, turn it off. All right. One of the subjects that you and I are both interested in is EMF. I just recently had a physician tell me he said, he believes that we're going to look back someday on all the EMF and Wi-Fi as we did cigarettes back in the 1940s. You know, you can find, if you just want to be entertained or saddened, you know, go on YouTube and search for cigarette commercials in the 1940s. And you will see either doctors or somebody, an actor pretending to be a doctor saying that more doctors smoke camel cigarettes because it's soothing to their throat. And pregnant women should smoke if they're stressed because that will help them. And of course at the time, you know, you could smoke cigarettes for a year and say, look, I'm fine. Nothing happened. Right. But smoke cigarettes for 15, 20 years, lung cancer. So I think we're having the same argument with cell phones and Wi-Fi. And, you know, clearly our cell phones. I mean, in our hand, we have more information than in the Library of Congress. It's our camera. It's our texting. It's our phone. It's our calculator. It's all the apps. But we are constantly being exposed to electromagnetic fields. And if people go back to the first webinar we did, we talked about how EMF can stimulate the calcium voltage channels, which are worse if they're mutated, to bring extra calcium in combined with superoxide and nitric oxide to make, once again, peroxynitrite, which damages the DNA and depletes your glutathione. So here's a study. 112 employees of a power plant, they looked at the exposed group and 138 unexposed. They were enrolled in the study. Interleukin-6 and the tumor necrosis factor were measured. Long-term exposure to EMFs probably affects immune responses by stimulating the production of pro-inflammatory cytokines. So I know this is hotly debated. You know, if you listen to Martin Paul, he talks about, you know, how it comes in, what I just described. You will find the industry vehemently saying that this isn't a problem. But we're going to be participating in a conference. I think it's third week of January. It's two or three days completely on the negative effects of Wi-Fi. And there is concern that, you know, it's 5G rolls out. That could even be worse. And I've now talked to enough people that when I see they have mutations in these calcium voltage channels and I bring up EMF, they're not faking it. They're saying, yes, I can be definitely affected by cell phones and EMF. I'm sure you've run into that as well, Dr. Jean. Yeah. 100%. So this may be, you know, one of the things that's causing it. And there's no easy answers to this. I mean, we're not going to get rid of our cell phones. But there are simple things to do, like try not to keep it on your body. Don't charge it next to your bed. Put your Wi-Fi on a timer. Make your home as dumb as possible. You know, I'm very concerned about streaming to smart TVs. When you stream video, I mean, you are giving off massive amounts of EMF. You know, when you send a text message or you're in a phone call, yeah, that's a little bit. But when you stream video, wow, that's a lot. So I would encourage people to, I always encourage people, if you're going to watch, you know, streaming video throughout the internet, wire it to your television. Don't stream it. I couldn't do it anymore, Bob, because we don't have to give up our conveniences and things, but you can get wired networks in your house very easily now and same with wired TV, at least you minimize. And then there is a difference. For example, I have these beautiful shades that go up and down with Wi-Fi. It's a very, very, very tiny little dose. And it only happens when the shade's going up for 10 seconds. But the streaming of live video is a whole different thing. And if you're worried about this, you can get a building biologist. We have a local one in Boulder and they will come. And she actually came to my house, measured the voltage on my body with and without different electrical circuits on. And I'll tell you what, in my bedroom, I don't really have a lot there. I have a couple bed night stand lamps. There's no Wi-Fi router there. And my voltage on the body was 3,000 when the meter was on. And it was 300 when I turned the breaker off. So her recommendation was to get a master switch with a remote so that at night I could turn that off. She also recommended a router cover in my office here right next to me. It looks like a net, like a laundry bag over my router. And that decreases the signal just enough to protect me so that I'm sitting here. It's not much exposure, but I still have plenty of Wi-Fi in the apartment. So these are kind of simple things you can look at. I will say I'm not a fan of grounding mats or sheets anymore because there can be some controversy over if they actually potentially make the problem worse. But protecting yourself from devices is a great idea. And don't ever put your phone in your bra ladies or your phone in your pants men because those are by impressionable organs. And it does affect breast testicles, reproductive organs as well. Oh, absolutely. I've had some good results and I have no affiliation with these folks that there's a called 5G block VLOC bag. And it's a sleeping bag. So it's not grounding. So I agree with you on grounding. You might just be the antenna. But there's actually they're made out of silver threads. And I curl into that every night and I swear I sleep better. I love that because that's a simple thing. You don't have to plug it into that. One other thing, Bob, I don't know if you know much about pulsed electromagnetic frequency or PEMF. To me, this is kind of new. I got my own mat. Anybody who's followed me has seen me on the mat because I love it. But that has been a game changer for my health and physiology. And I think any of us who are sensitive, I feel like it is one of the remedies for EMF sensitivity. It kind of provides the hurts of the earth's frequency. So I lay on my mat 20 minutes every day and I find it to be really helpful. Absolutely. That's going to be one of the slides coming up. Oh, yeah. Careful of that EMF. My office right now, you know, I probably can't see it, but the mouse is wired. The computers are wired. Trying to expose as much. I have less exposure as possible. No surprise here. Glyphosate exposure increases inflammatory response. And it increases IL-6 after glyphosate exposure. So I'm sure glyphosate does many other things. I mean, it may substitute for glycine. It may impact the heme cycle. Who knows what else it does. But in that interesting, the glyphosate will actually increase the interleukinase. It just shows all this load, Bob, right? Whether we, none of these things by themselves are totally toxic. But what happens is the load. So we have glyphosate in our, you know, organic wines from California. We have in the dog food, the molds, and we have the EMFs in the house mold in the house. So it's this combination of everything that's really causing the issues. Yes. So sodium sulfide increased LPS stimulated secretion of IL-6. Our curcumin decreased IL-6. So curcumin, you know, we don't know all the properties, but that's one of the things it does. It decreases the interleukin-6. Now, one of the subjects that you and I both love, and by the way, the talk you gave at our microtoxin conference was incredible. And we're going to mention that one more time that people could get those recordings if they want them. Here we're talking about the production of IL-6 increased in response to microtoxin exposure. We can influence bad effects on fetal development. So let me just jump to another slide here. Pro-inflammatory effects of ochrotoxin A on nasal epithelial cells. A microtoxin from mold significantly increased IL-6 and may promote inflammation in the nasal cells. Then just last evening, I do a, I do a webinar every other Thursday evening for physicians. And by the way, if any physicians are watching this, just contact us. We'll get you the information on how you can be part of it. Last night, one of my guests was Dr. Andrew Campbell. Again, he was one of the speakers at the microtoxin conference. And this is his test from my micro lab. And he heard my talk that I gave to physicians on IL-6 last week. And he said, Bob, you piqued my interest. I've started going through the literature. In the published studies, Dr. Andrew Campbell has reviewed the following microtoxins are the strongest drivers of IL-6 secretion. Of the 12, he measures nine very strongly stimulate IL-6. So absolutely amazing. If there's any health professionals watching this and they'd like to see the webinar, just contact us and we can give you the link where you hear, he talked about 20 minutes about all of these, but all of these microtoxins will increase interleukin-6. And I'm sure you probably have some thoughts on microtoxins, Dr. Jill. Yes. So we just see this massive inflammatory response with microtoxins. So this does not surprise me at all. And you remember my little story about exercise? Well, I was recovering from mold with that too. So again, these layers, what happens is if we have glyphosate in our food and we're not eating organic, and then we have EMS in our home, we have mold exposure in our home, it's just going to create this inflammatory pathway. And Bob, I think that's why we're dealing with a pandemic is because people have been primed for maybe a decade or more longer than that, but it's just getting increasingly worse with these toxic load creating issues. And there's been some studies that show potentially in more air polluted areas, there's more complications of COVID as well. And could that be again from the toxic nanoparticles and environmental load? Like you mentioned with the smoke and all of that priming the body for IL-6 production, I think it's probably related. Oh, no doubt. I mean, that's possibly why New York was hit so hard. Possibly why by some of them, when you look at some of the cities that were hit the hardest, they seem to have the most air pollution. And again, I don't think it affected whether you got COVID or not, but I think it affected possibly the severity of it because the IL-6 was already up regularly. So, and if you're interested, if you're a practitioner, just contact my micro lab. These are IgG antibodies that they run. Now, we talked before about lipopolysaccharides from gram-negative bacteria, induced the tumor necrosis factor and IL-6. So, Dr. Jill, I'm sure you have a couple of comments on this. Yes, absolutely. So, this is interesting because we actually often measure a tumor necrosis factor in LPS. And this is where I've seen the most data like thousands I remember when I first presented on LPS-induced endotexemia and I saw IL-6. And then as I started seeing the COVID data, IL-6 came up. That was my first inkling back in March or February that, oh, no wonder, diabetics, obesity, high blood pressure, all the same things that we see in relation to LPS-induced endotexemia. Those are the ones that are having more trouble with complications because, again, there's a priming effect of this on the body. And it's sadly really common because as we have more leaky gut, which happens with mold and Lyme and permeability and chronic illness and et cetera, then you're going to have more leakage of the LPS into the bloodstream and creating this inflammatory pathway. Absolutely. Now, this one blew me away, Borrelio. These results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro and in vivo. It is likely that this molecule plays an important role in the seriousness of Lyme disease. Wow. Wow is right. Now, you know, one of the questions that comes up is, you know, Lyme disease has possibly been around forever. But clearly, I mean, more and more people are getting hit harder by it. So the question becomes why? And I don't say that this is the reason, but this could be a factor that perhaps it already did that before. But now this bloat has gone up. Lyme is like the straw that breaks the camel's back. Combine that with mycotoxins. I'm sure you see this yourself when somebody has mycotoxin and Lyme. These people are nailed hard. Yeah. And Bob, I tell people all the time, I'm like, well, why now? Why, you know, this or that? And how I think this is just my clinical experience thinking outside the box. But here's what I see. I think tens of thousands, maybe hundreds of thousands of people have been bit by ticks or spiders or mosquitoes and gotten tick like infections, which would include Borrelia, Bartonella, Obesia, ehrlichia, anaplasma, rickettsial diseases, et cetera. And they're going around because these are actually low virulence infections, which means if you have a robust immune system, you could get those infections and never know it, never have symptoms. And so a lot of people are walking around without symptoms. But if you were to test them, they would come back positive for Lyme or co-infections. However, then you go polluted smoke in the air from fires for months and months, you have mold in the home and exposure that weakens immune system from trichocytines, which are mycotoxins or mycophenylic acid, which is a toxin that also suppresses immunity. And then all of a sudden that limbo bar of the immune system drops an old Epstein bar, which was not bothering the person old Lyme or Borrelia, Bartonella, et cetera, they pop up. And so often I would say majority of the time the people who come in with active symptoms of Lyme disease and test positive, it's not just the infection, it's the infection plus a weakened immune system. And so part of my treatment plan is not just hitting the infection with tons of antibiotics, although sometimes it's appropriate, we actually need to go to the root cause and support that immune system and coming back online because if that happens, you may not even need to aggressively treat the Lyme for that patient to be well. Absolutely. And as you know, we've done eight studies now on Lyme disease, just looking at the genome of 243 people have chronic Lyme. Same thing keeps coming up each time. The first study that we won the award for at Helsinki Finland in 2016 showed that they had dysregulation of iron. But what's that going to do? That's going to increase the inflammation. Another study showed an imbalance of mTOR and autophagy. And on and on, the last one we did show that there was some difficulty with, with bile production and synthesis. So there was inability to detox. And so we've found eight different patterns that seems to be significantly higher in those with chronic Lyme. And you hit the nail on the head. I mean, I think they, they found that the Iceman that they found had Lyme inside of it. And so, you know, and I think it's just that we're overreacting. And again, because our entire mass cells, this whole, this whole system of the cytokine production is being upregulated. And this becomes the straw that breaks the camels back. Yeah, that wouldn't just blew me away that, that there might be some LPS in the spirochete. And again, as you said, you know, 50 years ago, it wouldn't have mattered. Now, this is a no surprise. Active smoking and a history of smoking are associated with higher levels of interleukin-6. So that's almost a no-brainer on, on that one. So now's a good time to stop smoking. Interaction between smoking and interleukin-6. Potential role of the IL-6 gene in the inflammatory response associated with smoking. So what they're saying here, there's a polymorphin. And what that means is a genetic mutation in the IL-6 gene. Here's the RS number. That's the actual location of the, of the, of the gene. And what we're finding in, we're studying this and we have it in the, in the software that, that measures this, that many of these mutations are up regulation. So what I'm finding when I, when I see people who have massive amounts of inflammation, many times they have what are called homozygous, both mother and father gave the mutation, and that IL-6 is overactive. So here they're saying the results indicate a potential role of the IL-6 gene being mutated in the inflammatory response associated with smoking. I mean, you, you hear stories all the time of somebody who's 90 years old, smoked for the last 50 years, and their health is a horse. And you know, that makes a nice new story, but possibly they don't have any other cofactors or any of these mutations. You'll see somebody else who smoked for 10 years and has lung cancer. So multiple, multiple reasons. And this wouldn't just be it, but this could be another factor that if you've got this up regulation, smoking is going to have a much higher impact on you. Radon. Now, we've all known that radon is not a good idea, but here again, another IL-6 promoter variant was associated with lung cancer in uranium miners. Strongly support the functional relevance that IL-6 promoter SNPs affect basal regulation and carcinogen induced IL-6 secretion. So again, that goes back to, you could probably have 10 people who work in a uranium mine, two might get lung cancer from it. And what they're saying is many of them had this genetic mutation that caused them to upregulate to radon. So, you know, I've always known radon's a problem, but it's now come to my radar screen a little bit more that perhaps we should be a little more vigilant. There's a website, www.radon.com, and you can put in your county. And are you in Denver County, Dr. Jill? I'm in Boulder County. Boulder County. Well, anyway, I guess wrong, but you can just put in the county. You just put in the county and it'll tell you on average, how many results are higher than the four, which is the rate, how many are two to four. So I would encourage everyone after this webinar, go to radon.com, find the county that you live in, see where it's at. And if you have a basement that maybe has some cracks in the floor, or you have some drains, you can inexpensively get a radon test kit. And I just personally bought an electronic one. It was like $220 or something. And I'll give it to my clients locally to use and say, you know what, go check the radon in your house. And it's the silent killer. You don't know it's there. And the remediation is not all that difficult. You just get some pipes and fans and take the radon out. And I think this is yet another contributing factor. Any thoughts on radon, Dr. Jill? No, I love that you bring this up because like the air quality people that came to test my EMF actually talked about radon. And this is something that's very relevant, very common. And I'm so sometimes focused on mold, I forget to think about asking patients that they've checked. This is brilliant. And thanks for sharing the website. Yeah, I'm fascinated. What I've been doing now is I do consults. If I'm doing it done on interactive, I'll say, well, let's find your, and it's interesting. I just had somebody in New Jersey today on the shore. And this was like 2%, you know, and other areas, it's like 50%. So it depends upon this comes from granite. And so the more granite you have, the more potential there is for this. So now, volatile organic compounds. Now, interestingly, my first client this morning was someone who was doing quite well. And they said, well, I was really doing well, and I've really tanked. And they said it happened after I got another car. It wasn't a new car. It was just a new car for them. And then they had somebody come in and spray fumigants for insects and volatile organic compounds. And we could probably do a whole webinar on this. Are the main substances causing multiple chemical sensitivity? The authors found exposure to VOC significantly increased NOS activity. That's nitric oxide synthase and IL-6 and decreased glutathione concentrations. And it was suggested to be the result of increased NOS activity. Now, this gets very confusing. We said, because we thought we said the NOS is important. Well, it is unless it combines with superoxide. So totally speculating here. But I would imagine what they missed here is this probably also increases superoxide. And then when it combines with the nitric oxide creates the peroxynitrite. So we really got to be careful of these VOCs. And I mean, I literally put this in today based upon a console. Wow. It's fantastic. And again, I learned this from my client today. 10 best picks and 10 worst picks for volatile organic compounds. Now, this person bought a four year old car, but the car made them sick. So now before they ever get a car again, you know, and yeah, I'm not pro or con any of these cars, but they're telling you that which ones seem to have the least amount of volatile organic compounds. So you can go to this website, echocenter.org, and you can find these charts. So if you've got, if you're very, very sensitive, part of your decision making process in your car might be, you know, what is the release of the volatile organic compounds? So it was curated by the ecological center, and ratings were based on the presence of potentially toxic compounds such as bromide, chloride lead, and other chemicals. So who'd have thought that your car purchase could have an impact on your inflammatory levels? Wow, that's amazing. I remember the term years ago in biochemistry, methyl methacrylate, well, that's the smell of new car leather, but that's a VOC. So even though you like that new new car smell, that's, that means there's VOCs. Absolutely. I'll be curious. Is anybody sending comments like, Oh my gosh, I never would have thought of that. I've been wanting to go back to the comments here because I'm watching this. Oh yeah, they're right on with what they said, what if you live on the second floor? It's usually more of the lower levels because it comes from the earth, correct? Like the granite in that. Exactly. Yeah. And then formaldehyde they mentioned, which is a VOC that is also in materials and things. Now, again, we just researched this today. I'm sure if we really dug into it, we'd find a whole lot more. But here's a pesticide, and I'm probably not even going to try to pronounce that, increase the secretion and production of interleukin 6. Thus both PCP and DDT have the potential to produce chronic inflammation by stimulating production of IL-6 by the immune cells. So this poor client today bought a new car, then had pesticides put in her house and was feeling terrible. And so we really need to be careful with this pesticide exposure, particularly if we have operated interleukin 6. So that's why in my opinion, it's very important to know what your interleukin 6 genes are looking like. If they're mutated, they might be overactive and you need to take special care to keep that interleukin 6 down. Heavy metals, induction of IL-6 by aluminum induced oxidative stress. And they're saying that happens. And they're saying it'd be prevented by a selenium. And what they're saying here is that selenium is the co-factor for glutathione. Short-term exposure to aluminum resulted in an increase in the systemic inflammation parameters of IL-6. Glutathione decreased upon aluminum exposure. Both the increase in IL-6 and decreasing glutathione could be prevented by a co-exposure to selenium. I'm not sure that's true all the time, but and we don't have enough selenium. And if you don't want to take a selenium supplement, just eat some Brazil nuts. Yes. Excellent source of selenium. Right. Two or three of those per day, except that you have to watch some molds. You want to get them fresh, keep them in your fridge or freezer. And then I love this because Dr. Klinghardt also talks a lot about aluminum exposure and levels are so high. I've treated a few docs who have patients in India and have had some consults there and 100% of the patients that I've treated there so far have excessively high aluminum levels. I don't know if that's the cookware or what all it is, but I think again in the U.S. here we're getting exposure. So if you're listening and use aluminum foil or use aluminum deodorants, usually it's antiperspirants. Those are things that are easy. Just get rid of them. Make sure you're cookware. You're not using aluminum foil. You're not using it in the antiperspirants. It's an adjuvant in vaccines because it stimulates immune system. So sometimes a load, again I'm not anti-vaccine, but sometimes a load of the amount of aluminum if you have a poor detox pathway. And Bob, I'd love to know in a second if there's any specific detox related to aluminum that you know related to SNPs. That would be interesting. No, I don't. Now what we're going to do for our next conference, there'll probably be next September, aluminum, lead, and mercury are going to be on our agenda. So we're going to be good. Now you said it, but I think it's worth emphasizing. I think we're going to look back someday. What were we thinking smearing aluminum into our armpits? Yeah, I know. Right by the breast tissue for women and it's such an absorbable area. The other thing I want to mention here is chlorella can be a good key leader of aluminum. I know Dr. Klinghart, that's his recommendation. And zeolite. So those are the two that I tend to use more as binders in metal issues. There's many more ways, but those are two little simple things that patients can use if they suspect aluminum. And you can actually have your doctor check aluminum levels in the blood. It's a whole blood aluminum level. It's pretty simple. And some people use hair analysis for that as well. And so I would encourage everybody to use at least a deodorant or some of those natural things. Rocks, they're incredible. And you know, we're going to look back. Why were we smearing aluminum into our armpits? And so it is elevated. And interestingly, aluminum stimulates NOx, NOx, NADPH oxidase, which then this whole cascade that we're just talking about. No surprise here. When you've got lipopolysaccharides, the interleukin-6 is worse when you've got lead. So the heavy metal-ed markedly augments the lethality of endotoxins in laboratory animals. Lead-exposed mice showed an altered IL-6 appearance in the brain and at the levels of IL-6 in the brains peaked at four hours rather than three hours after they were exposed to lipopolysaccharides. So the amounts of IL-6 were found to be higher in the brains of lead-treated mice. Now, lead has so many negative effects, as does aluminum. Aluminum can stop so many enzymes from doing their job. But you know, for this talk, we were just focusing on IL-6. The influence of occupational chronic lead exposure. So here they're saying the serum levels of interleukin-beta-1 and interleukin-6 and tumor necrosis factor were significantly higher in the group of workers chronically exposed to lead by 38, 68, and 57 percent, respectively. That indicates that chronic occupational lead exposure promotes inflammatory processes by induction of pro-inflammatory cytokines. There they are once again. Now, here we go. What do we do? Okay, curcumin. We talked about that earlier. During a beta-analysis and systemic review of nine people, curcumin was found to reduce circulating IL-6 concentrations. The IL-6 lowering capacity was not dependent upon dose or duration of supplementation. Now, we know that tumoric curcumin is very anti-inflammatory. It may have other properties other than lowering interleukin-6, but this is one of them. Are you aware of other pathways that curcumin is supportive? Oh gosh, there are a lot of anti-inflammatory pathways and I'm thinking TNF-alpha is one of them. Again, this is off the top of my head. I know it can be anti-pain, anti-inflammatory in that way. So I'm guessing maybe either anti-mass cell or anti-prostate glandin. And they have some anti-cancer benefits. So I don't know if that's mTOR. Again, I'm just speculating. I don't know all the pathways, but it's got a lot of anti-inflammatory, anti-pain, anti-cancer support. And it slows down mTOR. Now, pycnogenol, we've been talking about this for years. The French Maritime Pine Mark was found to decrease CRP and it reduces the interleukin-6. Thiamine and riboflavin. Now, I'm surprised by this one. They inhibit the production of cytokines and increase the anti-inflammatory activity of cortical steroids. So conclusion, riboflavin and thiamine help the anti-inflammatory activity of dexamethasone, which is a drug, to knock down NOx2 and reduce the production of tumor necrosis factor and interleukin-6. Now, one of the things that we've just added to the software that can be used by health professionals is we're looking at the transporters for riboflavin and thiamine. And what we're noticing, again, just observing, that when people have mutations in riboflavin and thiamine, such as myself, their IL-6 can go up. And I have to wonder if this is possibly why, you know, I was more prone to ulcerative colitis at an early age, probably multiple factors. But I've now started taking riboflavin and benphotamine, which is the active form of thiamine. Don't miss it. And we're going to be working on some formulas that will be sold by supplement companies that are going to include riboflavin and thiamine. Bob, I love this. I just want to comment because I have intuitively somehow stumbled upon things that have really helped me. And back in the day when I found out they helped, I didn't always know the pathways. But thiamine and riboflavin have been game changers for my own health. And I do know there's mitochondria, different part 1, 2, 3, 4. And the part 2 and 3, if patients have deficiencies in those, again, they're like the sections of the mitochondria. There's another name for it. But the 2 and 3, if you have deficiencies there, number one, riboflavin and thiamine are key and critical to those. And number two, if you don't, if those don't function as well, you're more prone to fungal infections, which are number one correlated to Crohn's and colitis as well, which would correlate to you and I. And for me, this has probably been a decade where I've been on probably 300 to 600 thiamine, like high doses, and then at least 400 of riboflavin. And it's been a literal game changer. And again, I never, now I know more why that is, but it's really a big deal. The other thing I see is riboflavin is one of the key ingredients in methylation, but it's the one that's kind of forgotten. I think of it as the ugly stepsister. You know, people that don't really remember ribo, they think about methylfolate, methyl, and even P5P or B6, but riboflavin is like the Rodney Dangerfield. I don't get no respect. So I love riboflavin and it's produced by gut bacteria. So if you've had gut issues and you have decrease in maybe diversity of gut bacteria, it's probably an issue with riboflavin production as well. So I'm a huge fan. I love that you're including these because a lot of docs aren't really thinking along those lines and they're game changers with patients health and myself. Absolutely. And I've been observing and I'm seeing that when people do have mutations in the thiamine and the riboflavin transporters, that is oftentimes putting those back in makes a game-changing effect. Now, in arovetic medicine, big fans of black human seed oil, you know, obviously they're stretching it here quite a bit, but in arovetic medicine, they'd say the black human cures everything but death. Obviously not true, but that's how impressed they were with it. So the black human seed oil significantly reduces IL-6. And you know what else it does, Bob? That's very unique because I don't know any other natural substance that works on clostridia. So I use black human seed when I have clostridia overgrowth and I don't want to use vancomycin or some of the heavy hitters and it really does work, especially in the autistic children. I'll often have them on black human seed oil. It's very effective. Absolutely. Apojenin. Many people are like, what's apojenin? It's found in partially in chamomile. This, just about knocked me off my chair, enhances the expression of glutathione synthase, catalase and superoxide dismutase. These are the three major antioxidants, but there's more. It inhibits NADPH oxidase. That's what we've talked about. That's what stimulates the inflammation. It increases NERF2. That's what causes the production of, the recycling of and the utilization of your antioxidants. It strongly decreases interleukin-6. Parsley for goodness sakes and chamomile. So again, I'm formulating a product that's going to have parsley in it. And this is one of those bioflavonoids and these things are quite miraculous. But who would have thought that something like lowly parsley could be so powerful? You know, the things that God put on the earth for us are there and we sometimes forget all about them. Now, oxytocin, the love hormone. So interestingly, oxytocin attenuates NADPH-dependent superoxide activity in IL-6 secretion. You can see the charts here. I won't bother going through these, but there was a 36% decrease in IL-6 secretion when LPS-stimulated macrophages were treated with just a little bit of oxytocin and a 50% increase or decrease when they were treated with a 10 times higher amount. Now, oxytocin is what we get when we hug each other, when people kiss, when there's human to human to contact or what are we doing now in a lockdown? We stay six feet away from each other. And I think this is why we're seeing such an increase in adoption of dogs because I can't say for sure, but I would imagine when you hug your dog or your cat and you feel that bond between them, you probably increase your oxytocin. So interestingly, there's a genetic marker that shows and it's incredibly accurate. It shows that people have a more predisposition towards empathy based on their oxytocin status. It is spookily accurate. When people have those two mutations, I'll do a consult and it's like, Bob, are you sure you're not too tired to do this? What's the name? I remember you showing me that one. What's the name of that gene? I went back to look for it and I couldn't... It's one of the OXTRs. I can get you the actual, I can get you the actual... Where do you have it in your matrix? It's under neurotransmitters. Got it. Okay. That's all I need to know. I can find it. I can get... If anybody wants to look it up, if they have their genome, like from 23N or something, it is RS number... Here, I'll just pull this over. Oh, you're amazing. OXTR and the RS number is 53576. That's 53576. So that's the one related to... When it's homozygous, very empathetic. What I love to do when I talk to young girls, I'll say to them, especially other parents, are there with them and they're maybe 12, 14, I'll say, I'll tell you what, the old man has an important word I need you to learn. Do you think you know what that word is? And they'll typically say no and they'll say that's... That's it. Yeah. That's the word because when people are very empathetic, narcissists find you. And they take advantage of you. And they know how to gaslight you and really convince you that if you don't do everything they want, you're the problem and can just totally ruin your life. Bob, this is funny, but there's this... If you guys stay tuned on Facebook live and probably in a month or two, Sarah Gottfried and I are doing an whole episode called Bad Boyfriends. So, 2-O-X-T-R, double homozygous, this is going to actually talk to this to the public. You know, if that resonates with anybody, there's a really cool YouTube channel called Surviving Narcissism. It's Dr. James Carter and he puts out little 10 to 12 minute videos on narcissists and how to deal with them. The basic approach is if you want the cliff notes run when a narcissist comes into your life. But if you've been entangled with one, it really gives you good clues as to how to deal with it. But anyway, we need to do some things to boost our oxytocin. I'll be honest, I don't know the mechanisms. I don't know the cofactors. I may put my research team on this. As there's something we can do from a standpoint of nutrients that may stimulate the production or cofactors, I really don't know, but that would be fun to find. But I think our oxytocin is dropping during these stressful times. Hydrogen water. The news on this just keeps going on and on and on. So, if anybody doesn't know, there's little tablets that you can drop in a glass of water. They fizz. As you know, waters H2O. So what it does, it knocks the hydrogen loose. And as soon as it's done fizzing, you chug this down and look at this. Hydrogen water lowers interleukin-6. Glucose factors, therefore exerting a protective effect. And I know you're a fan of hydrogen water as well, Dr. Jill. I'm a huge fan. And I know you and I usually before our shows, we breathe it through our machines. I just did that this morning. I have it in my favorite meditation chair. So I'll just sit and read and meditate and put on my hydrogen prong and do 30 or 40 minutes. That's super powered, but the little tabs are excellent as well. And I'm a fan. Yeah. So if somebody said to me, Bob, you can take one thing and one thing only. I would probably choose hydrogen water. Yeah. And I've never seen anyone react to it. I don't know about you. I just, it's very, very gentle. Well, if somebody has certain kinds of SIBO, they have a bad reaction. It's very rare, but I always warn anybody, if you get stomach ache, bloating gas, just stop. That indicates you got SIBO, but it's very rare. I'd say it's like one out of a hundred. But just in case anybody tries hydrogen water, it's like, oh my gosh, I felt horrible. Talk to your health professional and get checked out for SIBO. Excellent. We talked about this earlier. Pulse electromagnetic fields suppress IL-6 transcription. So you're, that's possibly what you're doing when you're laying on your pulse electromagnetic field. Pro-inflammatory factor IL-1A significantly promoted IL-6 transcription over time. It indicated that the inductive effect of IL-1A on IL-6 could be significantly inhibited by PMF treatment in a time dependent manner early as two hours of stimulus initiation. Wow, Bob, you have to send me this. So I'll tell you a little story. I haven't told this to the public yet, but because of my history of Crohn's, which is healed, and then my, I have an immune deficiency as well. And I'm in great shape despite all of this. But I have always had low protein no matter how much protein I eat, because I think I have the protein wasting entropathy from the gut damage from chemo and all this. I've never figured out for sure why that is, but it is. And I just accept it. And my labs, if I look at, which I get them drawn every month, the protein I'll be given are always just a little low. Within 10 days, I'm using the PMF map for the first time in five years, they were totally normal. And I thought, well, that's interesting. Maybe it's a coincidence, but I've had three labs since, and every single one of them is continuing to be higher back in the normal ranges. So to me, this is like cellular integrity, which probably relates to IL-6 levels and inflammation. But that's why, again, people who've heard me talk about my mat, they're like, okay, Jill, shut up about the mat. But I've never seen, I've done a lot of things. You know how I biohacked myself and that PMF mat changed such an objective data point that I couldn't help but understand there's something pretty big going on here. So this is really interesting. I don't know still the mechanism if it was decrease in IL-6 or I actually think it helps with cellular healing. So it probably was one of the few energetic things that actually healed the enterocytes. I don't know, but isn't that interesting? Absolutely. And do you drink your hydrogen water and breathe your hydrogen while you're on the mat? I did that before, but I do the same thing. Sometimes I do actually same time. Multi-task care. So all right, vitamin D. I mean, no surprise here. Vitamin D administration can significantly reduce the IL-6 in the ventilator assisted pneumonia. So we could do a whole show on vitamin D, but I think everybody knows that. What's your range that you like for the vitamin D? Yeah, 50 to 80 is super safe. I'm okay if people go above 80 as long as they're not above 100 with hypercalcemia. Yeah, and that goes back to, in my opinion, I think we need to take vitamin K2 with it. Particularly, we have the calcium voltage channels that that extra calcium from the vitamin D will go in and create peroxide nitrite. You could potentially create more inflammation, create more inflammation if you create more calcium absorption under those conditions. So again, Goldilocks in the three bears. Not too little, not too much. Yes, yes. Arachidamic acid. This is your bad fats. No surprise, right? Yeah, and you know, for anybody who really follows, you know, good health, they're like, duh, this is the who's who of good healthy things to do. So arachidamic acid stimulates interleukin-6 release, and it doesn't take very long for it to do that. That's your canola oil and some of your other bad fats. I'm sure you give your patients advice on how to balance those fats. I do. And usually, we're giving omega-3s to make sure. Now, it's interesting because those patients who really eat a low refined carb-trans fat diet, sometimes they need omega-6 and omega-3, so often give evening primrose or barrage with it. But in general, most American diet eaters need exclusively supplementation of omega-3s because they already have plenty of the omega-6s and the other types of fats. Absolutely. Now, this next slide's not going to surprise you. EPA, DHA reduce levels of pro-inflammatory cytokines and aging adults. So that's your EPA, DHA, that a significant lower effect on interleukin-6 interleukin-1 beta and tumor necrosis factor alpha after just four weeks of therapy, an even greater lowering effect after eight weeks of therapy compared to the control group. So there was a slide that I almost made up, but I lost track of it, but they talked about why in Japan they seem to live healthier and longer and possibly multiple factors. But one of the thoughts was the EPA and DHA from the fish intake might have been a factor. So we've known for a long time that these fish oils are helpful, likely more than this, but I'm just pointing out that it helps reduce the interleukin-6. Hyperbaric oxygen. And of course, a lot of autistic children use this with success. IL-6 levels declined over time with treatment of hyperbaric oxygen. Excellent. Now, I will mention if you're listening and you're thinking hyperbaric oxygen is amazing, which it is, if you know that you have babesia, that's a contraindication to hyperbarics. You want to treat that, give that under control first because you may flare if you do it and you're not controlled. Absolutely. Selenium, inversely associated with interleukin-6 in the elderly. And of course, we don't get enough selenium. I'll never forget many, many years ago, I talked to somebody who was head of the Agriculture Department of Pennsylvania and he actually got soil from Africa and used that for his crops because it had higher levels of selenium, because we've depleted the selenium in our soils. So selenium was significantly inversely associated with interleukin-6 after adjusting for potential co-founders. And again, I think the effect here is that it helps recycle your glutathione. Yeah. So I spoke about this before, so I'm not going to read this, but I encourage everyone to go back to the video where we talked about the home's hypothesis, where all of these things that we spoke about up-regulated the NOx enzyme and will create this process. So rather than, you know, this is going along, go back and watch that other video where we talk about the home's hypothesis where multiple environmental factors up-regulate, renin, interleukin-6, and begin a cascade of inflammation. And there is the home cycle. We talked about this in the other show, where many environmental factors up-regulate NOx, make superoxide, hydrogen peroxide, mass cells, histamine, they all come back, stimulate renin, angiotensin 1 and 2, IL-6, moreldosterone, stimulate NOx, and we've got one nasty cycle. So what we've done is we've just built upon this by putting a little more emphasis on the IL-6. Now, what do you do? Here we go. Make sure you're in a mold-free environment. If you're in a mold is suspected, consider mold remuneration. Work with a health professional and check mycotoxin levels and detox appropriately. Consider functional genomics to identify potential weakness in detox pathways. Consider air purifiers if an area of smoke exposure or air pollution. Now, I think I pointed this out before, but glutamate will inhibit the H2 enzyme that will allow more production of interleukin-6. So if you want to do functional genomics, check these, the DAO, the GLUD, the GAD, the CRAS, all of these can create more high glutamate. Limit glutamine supplementation. And I love Hinokial, magnesium 3 and 8. They help with glutamate. Check your glyphosate levels. Take steps to reduce exposure. Consider eating organic. Consider checking for radon and mitigating of high. Check for C. diff and appropriate treatment. If things like wine and sulfur foods are a real problem for you, you may want to check your sulfation genomics, such as the suox gene. Maybe you need a little bit of melendimum. Check out if you have high oxalates. If you eat spinach, kale, and hurt or just someone grabbing your arm hurts, get your oxalates tested with a medical professional, and then follow their direction to reduce oxalates and or any supplements that may help. And encourage everybody to watch our video on histamine. Consider dietary changes in nutrients to reduce histamine. These are the genes, HNMT, MEOA, HDC. This is the whole subject in of itself. Histidine decarbalase, when upregulated, creates more histamine. There's more. Check for heavy, that should be, I'm sorry, not heavy meals, heavy metals. Type O there. And take appropriate steps to detox. Check the CACNA1C genes for potential EMF sensitivity. Consider caution with EMF. Consider measuring dopamine and take steps to lower of high. Check the DBH and COMT functional genes. Have your medical professional measure homocysteine. Take the appropriate steps. These are the enzymes that, if they're mutated, can result in higher homocysteine. Healthy weight and normal blood sugar. Healthy balance of good fats, EPA and DHA versus the bad fats. As we spoke about appropriate exercise, not over exercise, stop smoking. May want to check your glutathione SOD genes, that's superoxide dismutase, for proper function and compensate if needed. Check the renin, ACE2IL6 and HMOX genes that have the potential to increase interleukin-6 and take appropriate compensations. Now, in regards to mold, I'd like to mention that, you know, Dr. Jill was a speaker. If anyone would like to listen to this, they can just go to NeutrogenicResearch.org slash 2020 conference and in order of the three-day conference. And again, thank you, Dr. Carnahan, for being a part of that. That was a great conference. Bob, thanks for putting it on. You really had great content, great speakers, as always. Yes. Now, I'm going to speak just a moment to health professionals. If someone says this is really cool, the Neutrogenic Research Institute does online education, live conferences. We created software that analyzes the genomics. We have our own genetic test, and we worked with a line of custom-made formulas that can help bring this into balance. NeutrogenicResearch.org is where we do the research. We have an online certification course for health professionals. And if someone would like to learn about the functional genomic analysis, again, health professionals only. Sorry. There's the website. Yvonne Lucchese, Executive Director. And if anyone wants to get ahold of us for health coaching, our phone number is there, 717-733-2003, tolhealth.com. So I know that was a boatload of data there, Dr. Jill. That was fun. Oh, my goodness. I couldn't wait for this. I also talked about it for maybe six weeks or four weeks or something like that, and I knew it would be good. Bob has always been packed in so much good information. And I just appreciate all the research you do in bringing us all the data points. And then for us to just jump back and forth on ideas, because it's fun to hear this and say, oh, I wonder if this is why this is happening. So thank you as always. I so appreciate it. I will be sure and share this on YouTube. If you guys haven't subscribed to my channel, I put a link there on Facebook. Please do, because you'll get this and lots of other free stuff. And check out Bob's pages as well. I just greatly appreciate you and all that you do. Absolutely. I hope many people got some aha moments tonight as to how they can reduce inflammation and age successfully. Thanks, and we will see you next time.