In Episode #42, Dr. Jill interviews Bob Miller on IL-6: Everything you need to know about this cytokine: The Good, The Bad, and the Ugly.

Dr. Jill is your Functional Medicine Expert specializing based out of Louisville, CO. She has countless free resources on mold, autoimmune health, detoxification, brain health, and more.

More Reading: The Dynamic Role of Interleukin-6: https://www.jillcarnahan.com/2020/09/21/a-fascinating-look-at-the-dynamic-role-of-interleukin-6-in-inflammation/

Dr. Jill

Dr. Jill Carnahan is Your Functional Medicine Expert® dually board certified in Family Medicine for ten years and in Integrative Holistic Medicine since 2015. She is the Medical Director of Flatiron Functional Medicine, a widely sought-after practice with a broad range of clinical services including functional medical protocols, nutritional consultations, chiropractic therapy, naturopathic medicine, acupuncture, and massage therapy. As a survivor of breast cancer, Crohn’s disease, and toxic mold illness she brings a unique perspective to treating patients in the midst of complex and chronic illness. Her clinic specializes in searching for the underlying triggers that contribute to illness through cutting-edge lab testing and tailoring the intervention to specific needs. 

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The Podcast

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The Transcript

#42: Dr. Jill Interviews Bob Miller about Interleukin 6 (IL-6)

Text:

Dr. Jill  00:12
Okay, we're live! Bob Miller, it's great to be back with you. 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, Lyme, mold, etc., but with COVID, the IL-6 pathway has been predominantly on the news in the research. Today we are going to dive into IL-6. Bob is going to give us a lot of [information] about what it is, 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. 

Dr. Jill  00:50

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 are 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.

Dr. Jill  01:12

Bob Miller has just been a fixture. He's part of Tree of Life Health. I don't have his formal bio up today. I feel like people might know you by now. But [he has] a real great ability to put together a synthesis of complex pathways and to look [for] 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. 

Bob Miller  01:44

Okay. Well, it's always a pleasure to be with you. We have so much fun as we geek out, so to speak, on some of these pathways. And I must say, all the other things we did were fascinating. We spoke about peroxynitrite, the importance of NADPH, and then the NADPH steal. And then we talked about the Holme cycle, where this thing all cycles together. What's interesting is that 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, 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. I think people will be really blown away by all the negative things that too high a level of IL-6 does.

Bob Miller  02:39

So let's do a screen share and get started. Okay, there. I believe we're sharing the screen. 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 diagnoses a disease or treats any disease. So I call this the 3D chess game played underwater. As you can see over here, we have some scuba divers playing a 3D chess game. 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 [is] that doesn't exist. 

Bob Miller  03:24

There are multiple factors that go together, [such as] genetics and, possibly more importantly, the environmental factors that are impacting it. It's often been said: Genetics loads the gun, but environment pulls the trigger. 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, that we're going to be doing something later on IL-13 and IL-4 because all of these are so very important. And the reason we started with IL-6 is because of the news that this has gotten on COVID. But again, if we even put that aside, this is very, very important. 

Bob Miller  04:07

Just a little bit of interleukin 101: There are chemical mediators involving signaling between cells, particularly your white blood cells. The words here, ‘inter' meaning between, ‘leukin' referring to leukocytes. They're a type of cytokine, which is derived from a combination of two Greek words, ‘cyto' meaning cell and ‘kinose' meaning movement. They're signaling molecules that aid cell-to-cell communication in immune responses and stimulate the movement of cells toward sites of inflammation, infection, and trauma. As we're going to learn, they're not bad.

Bob Miller  04:41

We've had many, many conversations. This is our fifth one. The common theme that we seem to have is that there's a balance: Too little of something is a problem; too much of something is a problem. The same [is true] with cytokines. Used properly, they're not our enemy. And there's evidence showing that certain cytokines are involved in not only the initiation but [also] the persistence of pathologic pain by directly activating sensory neurons. They're involved when there's nerve injury or inflammation. When we have a cut, a burn, or something like that, they come to the rescue to help us out.

Bob Miller  05:19

There are two pathways. The classical signaling pathway 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 IL-6's binding leads to what's called dimerization on cellular membranes, or increased bioavailability. This actually promotes pro-inflammatory activities. What's interesting is that CRP, or C-reactive protein, which is very inflammatory, is 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. 

Bob Miller  06:19

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 are critical for protection against pathogens and the development of infections. IL-6 is an essential messenger within the immune system. When we get some foreign invader inside us, IL-6, along with other things, comes to the rescue. Now, this acute inflammation signals tissue repair and inflammatory responses designed to initiate healing or protection from invaders. However, unresolved chronic inflammation is associated with many health concerns. It's interesting that 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. 

Bob Miller  07:11

Here's a 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. 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 a proper lipid regulation. They did some experiments with mice, and they found it's a very important thing to have. 

Bob Miller  07:45

When we exercise moderately, it appears that IL-6 is released into circulation from the contracting muscles. That may have a role in gastric functions in response to exercise. We're going to talk about exercise later. We all know that moderate exercise is very important. However, if we overexercise, it can be to our detriment. We'll get into that a little bit later. The authors found in this study that an IL-6 blockade induced muscle inflammation in a mouse model of muscular dystrophy. So, IL-6 may have some beneficial roles with some conditions. Again, what we're going to find is that we need some, but we have a problem when there's too much.

Bob Miller  08:32

Now, here's an article that talks about how IL-6 appears to have a specifically important role in wound repair. Analysis suggested IL-6 may have an important role in macrophage infiltration, fibrin 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. 

Bob Miller  08:53

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. The term ‘inflammaging' is when there's too much inflammation in the body. 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 and 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 disabilities, there were lower IL-6 levels in the successfully aging group. Even longer survival was associated with lower concentrations of IL-6. 

Bob Miller  09:50

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 entire elderly population and in 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, and being a burden” on their relatives. 

Bob Miller  10:21

Now, this was interesting. This study showed that interleukin-6 from systemic inflammation predicts all-cause mortality in men. The bottom line: IL-6 was consistently related to all-cause mortality independent of the level of adjustment, showing a dose-response relationship between IL-6 and the 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 it. 

Dr. Jill  10:55

Oh yes, this is huge. Whenever you say all-cause mortality, that's a big deal. 

Bob Miller  10:55

Absolutely. Now, one of the things I've been doing over the last probably four to six weeks is doing my health coaching with folks. And they tell me, “I'm struggling with” fill in the blank. I just go, “Hmm, I wonder if there's a study on interleukin-6 and this.” 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. This data suggests that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice. We're talking about pulmonary hypertension and lung inflammation. There are many causes, of course, for hypertension. Lung inflammation or lung issues are one of them, and here's where interleukin-6 plays a role. 

Bob Miller  11:49

Now, look at this one. This is 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 premiere here. It's produced as a response to angiotensin II. Now, for those of you who are practitioners, you understand the RAS, 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 of all-cause mortality.

Bob Miller  12:24

Now, there's a very nasty free radical called superoxide. If you want to learn about this, go to the very first interview that we did, probably sometime in June or July. It's on Dr. Jill's Facebook. 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. 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.

Bob Miller  13:05

Then what that does is further lower your nitric oxide bioavailability. And nitric oxide won a Nobel Prize for its study back in the 1980s because it's so important for the opening of the blood vessels, making sure that the blood is flowing properly. 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. 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 do. They stop the breakdown of nitric oxide. 

Bob Miller  13:48

This one I found mind-boggling, Dr. Jill. It's increased in the cerebellum of the autistic brain. So the bottom line, in conclusion, [is that] increased IL-6 expression may be partially responsible for some of the issues of autism. Clearly, autism is going through the roof. The statistics are that it used to be one out of a thousand. And what's it down to now, Dr. Jill, 45 or 50 or something like that? 

Dr. Jill  14:14

Yes, it's incredible how it keeps going down. I think 45 was the last number that I heard. 

Bob Miller  14:21

Yes, and predictions are that it's even going to get worse, affecting boys more than girls. Again, in our health coaching, we worked with a lot of parents with autistic children. What I should have done is… I got permission to share the clip from the mother. The mother was almost in tears, thankful for the way her child was improving, and all we were doing was doing things to decrease interleukin-6. 

Bob Miller  14:50

Clinical anxiety, cortisol, and interleukin-6—here it's 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 is calm 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 YouTube page because we spent a whole 50 minutes talking about histamine. We talked in there about how we tend to think of histamine as itchy eyes, a runny nose, and 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. 

Bob Miller  15:46

So I'm sure we're all seeing this: Anxiety is going through the roof. The ladies that work in my office sometimes come back and say: “Bob, these people are driving me crazy. They're screaming at me because a package didn't go out when it was supposed to” or something like that. I like to talk to people at the grocery store and 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?' 

Bob Miller  16:29

Now, look at this one. This one blew me away: The 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 many more people [who are] not only anxious but [also] depressed. 

Dr. Jill  16:53

I think I saw, Bob, the prescription… I don't know if it was a 600% increase in antidepressants. And obviously, we have COVID, we have the pandemic, and we have isolation. There are many other reasons, but this is definitely playing into it. And especially because we know infections, 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. 

Bob Miller  17:20

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 in both non-fatal suicide attempts and suicides. And I don't know if suicide is on the increase, but clearly there are more than we should be seeing. Clearly, there are so many factors, not just IL-6, but this is a factor in suicidal behavior. 

Bob Miller  17:54

Now, one of the saddest things is when someone's dealing with anorexia and bulimia. I talk to parents sometimes. They're 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: The tendency toward increased IL-6 production—and I didn't know this—suppresses food intake in animals. And individuals who severely restrict food intake suggest a potential role of these cytokines in anorexia nervosa. I'm not just blown away by all this. 

Bob Miller  18:36

Now, one of the biggest fears that we have as we get older is Alzheimer's disease. They enrolled 41 subjects in the disease group and 40 in the normal group. The majority of the subjects in the disease group had mild Alzheimer's disease. There were elevated levels of IL-6 and decreased levels of plasma TRAIL in the group. Plasma IL-6 was identified as a potential biomarker of Alzheimer's disease at an early age. And, of course, it makes sense. The brain is 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. 

Bob Miller  19:17

Now, look at this [regarding] breast cancer. [There are] several studies demonstrating IL-6's 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. 

Bob Miller  19:42

Colorectal cancer. And, of course, this is on the rise. Several experimental and clinical studies have linked the cytokine interleukin-6 to sporadic and inflammation-associated colorectal cancer. The increased IL-6 expression has been related to the advanced stage of the disease and decreased survival. 

Bob Miller  20:05

So here again: Inflammatory bowel disease. As you know, that was what got me interested in this kind of work. I had a severe case of inflammatory bowel disease when I was in my mid-30s. I lost half my blood, then I hemorrhaged. I didn't know if I'd make it to the next day. [I was] in the hospital for 21 days. That was 32 years ago, and my colon is now just doing fine. But I've got to work at it. I was told: “The colon's got to come out. If you don't have this colon out, you're an idiot.” 

Bob Miller  20:34

There is growing evidence that the pro-inflammatory cytokine interleukin-6 plays a crucial role in the uncontrolled intestinal inflammatory process. Now, what I'm understanding is that the amount of children who are getting inflammatory bowel disease is skyrocketing. And they're saying, again, colon cancer [too]. And of course, as we know, long-term inflammatory bowel disease leads to colon cancer. 

Bob Miller  21:02

So, an interesting study for a peer-reviewed study, but “a villain in the drama of pancreatic cancer development and progression”. Conclusion: IL-6 emerges as a key player in pancreatic cancer development and progression.

Bob Miller  21:18

Here we're talking about chronic inflammatory proliferative disease—the same thing. Several diseases, including rheumatoid arthritis, systemic onset juvenile chronic arthritis, osteoporosis, and psoriasis—amazing, all these things that it's involved with here. I was really stunned when I started digging and found all these peer-reviewed studies. 

Bob Miller  21:46

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. Blocking IL-6 and IL-6 signaling may be an effective strategy for the treatment of insulin resistance. As we know, when I was a kid, we used to call it adult-onset diabetes because you were usually a little obese and over 40. And now we're seeing children with diabetes. I'm sure in your practice you're seeing young children with diabetes, Dr. Jill. 

Dr. Jill  22:23

With type 2, yes. It's so interesting because in this pathway with endotoxemia, we've talked a little about where the LPS coding of the bacteria goes into the blood. We know that triggers IL-6 and we know that's associated with diabetes, heart disease, obesity and mood disorders. This is all playing together. You kind of wonder which came first. We talk about LPS and these infections, but what if the common denominator is really IL-6? It's certainly looking like that's part of the story. 

Bob Miller  22:52

Absolutely. Now, listen to this: Thyroid hormone concentrations. The data reveals a statistical relationship between elevated serum IL-6 concentrations and alterations  in circulating thyroid hormones. Of course, we're not even talking about Hashimoto's here. They're just talking about low thyroid. So since this is related to autoimmune… I probably should look. I didn't find any papers; I didn't look for them. But I wouldn't be surprised if there's a relationship to Hashimoto's. 

Bob Miller  23:25

One of the things that we're talking about, and I think you and I spoke about this before, is that early in our careers, we didn't even talk about mast cells all that much. Mast cells are our white blood cells that are there to protect us. However, when they become overactive, they're a problem. At my conferences where we teach physicians, I often say: “How many of you have seen a dramatic increase in what's called mast cell activation in the last five, ten years?” Virtually every hand goes up [in agreement] 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. Jill—because you see some of the people who are really struggling—would you say you believe that the mast cells are overactive? 

Dr. Jill  24:18

Oh, gosh. I would say at least 25%, maybe more. But that's one in four, so that's a lot.

Bob Miller  24:23

Yes, exactly. And when you started your career, what was it? 

Dr. Jill  24:27

Maybe 5% [or] 10%. 

Bob Miller  24:30

Yes, absolutely. So here they're saying that 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 research, I'd be at the office till 1:00 in the morning. It's like, “No, I've got to go.” 

Dr. Jill  25:03

Yes, I know. I'm parallel to you. The same thing: I just kept going down rabbit holes. There are so many studies with IL-6, it's unbelievable. It's not surprising, but it really is. I wonder if there's anything that's not related. 

Bob Miller  25:18

Well, I was thinking the same thing because, in traditional naturopathic philosophy, it's excess inflammation that's the initial trigger. And if this does that, it is probably related to just about any degenerative condition. It's funny; I talked to a woman who had hot flashes and I said: “Hmm, I wonder.” And I thought, “Nah, I won't find anything.” Lo and behold, serum IL-6 concentrations in perimenopausal women with severe hot flashes were significantly higher than the concentration in women without hot flashes or with mild and moderate hot flashes. So it's even playing a role in the dreaded hot flashes. 

Bob Miller  25:56

And again, another person had vitiligo and I thought: “Hmm, I wonder.” An increase in 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 cytokine production might be involved in the vitiligo. 

Bob Miller  26:21

Now, COVID-19. Again, we're not saying that 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 [like], “Okay, I had a cough and a sore throat,” and others are gasping for breath and on ventilators. Much of the literature now points to interleukin-6 and bradykinin as in part or in whole of that cytokine storm for 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.” [There was a] “2.9-fold increase in mean IL-6 concentrations in complicated COVID-19 cases.”

Bob Miller  27:14

I should have grabbed this slide, but I didn't have time to do it. But there appear to be some studies that show the higher the IL-6 is before you get COVID, the potentially higher the probability you 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—potential—that it's a factor in how severe the cytokine storm could be. 

Dr. Jill  27:42

Bob, that's one reason why I said we can't wait to talk about this, because that's been my theory. Again, this is not medical advice, but the priming of someone who has IL-6 for LPS endotoxemia for another infection for all these many reasons makes me suspect that those who are primed with higher IL-6 since before they get this infection tend to fare 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 [on] this old use of drugs. And Ivermectin has activity in preventing LPS-induced IL-6 increases. So again, these are all just interesting observations. But on 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. 

Bob Miller  28:40

Absolutely. Again, [it will] not cure COVID, but it probably will not be as severe. Now, this is another one: Interleukin-6 in patients with COVID-19. I'm 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 develop damaging immune reactions sustained by cytokines, leading to 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 IL-6 are found in more than one half of patients with COVID-19. Levels of IL-6 seem to be associated with inflammatory response, 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. 

Bob Miller  29:48

Now, we're not going to have time to get into all of this. But these are 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 hepcidin, which decreases iron, and has all kinds of effects. This could be a whole-day course on all of these things, but I just wanted to point out all the things that IL-6 does. 

Bob Miller  30:25

This is probably just a fraction of the things that IL-6 does. 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 more of a cytokine storm? High blood sugar. Inflammatory cytokine concentrations are acutely increased by hyperglycemia. So here's the summary: High blood sugar, or diabetes, “acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with impaired glucose tolerance.” 

Bob Miller  31:09

So, what we're going to find here as I go through this [is that] this is going to be good health 101—things that natural health professionals and medical doctors have been talking about for a long time—things we have to do to stay healthy. What's stunning to me is how this ties into interleukin-6. So clearly, taking the steps you need—diet, medications, or whatever you need to do to keep your blood sugar under control—is an important factor in not having interleukin-6 upregulated. 

Bob Miller  31:43

Obesity. And, of course, obesity is on the rise. Have you ever seen people post a picture of a crowd back in the 1950s or 1960s and say, “Note that you don't see anyone who's obese”? 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. IL-6 isn't the only factor with obesity, but it is one of the factors to consider when being overweight. 

Bob Miller  31:43

One of the things we've talked about before, if you go back and watch our videos on the NADPH steal and the Holme cycle, is this NADPH oxidase. This is an important enzyme. When we are faced with a pathogen, NADPH oxidase says: Whoa, we've 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 and hydrogen peroxide. Let's make some mast cells. Let's make some cytokines. Let's make some histamine and take out this invader. If we didn't have that, we'd die of infection. 

Bob Miller  33:07

But the thing that I've been talking about for years [is that] I believe environmental factors are up-regulating this enzyme. Lo and behold, interleukin-6 induces the expression of NADPH oxidase 2. And you'll find studies on COVID [show] that it's the upregulation of NOX2—the abbreviation is NOX—that's behind the cytokine storm. Again, putting COVID aside, all the things that this could do by having these two talk back and forth to each other are significant. IL-6 was found to increase NOX2 activity in concentration- and time-dependent mechanism. So NADPH oxidase is stimulated by interleukin-6—and I'm going to show you a chart later that [shows that] it's a crosstalk—interleukin-6 stimulates NOX2, and NOX2 stimulates interleukin-6. And you have a positive feedback loop that just keeps feeding upon itself. 

Bob Miller  33:07

We're going to show a chart in a little while. In the RAAS system, they were saying angiotensin II, when that's increased, was found to induce interleukin-6, and then subsequently, NOX once again. In an IL-6 knockout, it was found to inhibit angiotensin II, which increased NOX activity and VEGF expression. And again, for the layperson, they'll 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. 

Bob Miller  33:07

Oxalates—lo and behold, oxalates stimulate IL-6 production. Oxalates, in case someone doesn't know, are like little razor blades in some of the healthiest foods. Have you ever heard anyone, Dr. Jill, say, “I wasn't feeling well, so I started to eat healthy, and I started doing spinach, kale, and beets, and I got worse”? 

Dr. Jill  28:40

Like blueberries and almonds and all these wonderful foods. Yes.

Bob Miller  35:05

Yes, absolutely. So what happens here is that 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, which give indications that you don't break them down as quickly, these oxalates 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 who, if you just touch their arm a little bit, are in pain. Massages [are] torture. Oxalates upregulate the expression and secretion of IL-6 in the kidneys. So, absolutely astonishing. And many people don't think about oxalates. That's why I think it's important to do the Great Plains OAT test and see if there are oxalates that are occurring. 

Bob Miller  36:04

Homocysteine. A lot of doctors probably don't measure that as much as we should. I'll never forget reading the book—it was an excellent read—called The H Factor. It's written for the layperson. The bottom line is that the higher your homocysteine, the sooner you die from all causes. 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 [is that] 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 [makes] you die sooner from all causes. Do you have a range of homocysteine that you prefer, Dr. Jill? 

Dr. Jill  37:11

Yes, I like to see it below 9 for sure and ideally below 7 with Alzheimer's [considering] Dale Bredesen's work. But then, if it gets really low, like below 4, it can be an issue too. So there is an optimal range. So I'd say 4 to 9 would be ideal. 

Bob Miller  37:26

Absolutely, I would agree. Some people in functional [medicine] like 6 to 7, 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 methyl folate to recycle it back to make something called SAMe that's involved in a lot of processes. If you go back to our talk on histamine, you'll see that the HNMT histamine N-methyltransferase gene needs SAMe 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. Elevated IL-6, homocysteine, and low folic acid were found in patients with acute heart disease. 

Bob Miller  38:19

Dopamine increases interleukin-6 release. Wow. So dopamine, of course, is going up. And this might be a subject for another talk. But here it says dopamine increased basal IL-6 release and potentiated IL-6 release, stimulating ACTH, LPS, or 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. 

Dr. Jill  38:57

And Bob, 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 and excess dopamine. We see this all the time with behavioral disorders, autism spectrum disorders, and mood disorders. So that's just one small functional medicine reason for elevated dopamine and there are many more. I love the idea. We could do a whole lecture on dopamine and the causes of high [dopamine] and neurotransmitters. 

Bob Miller  39:26

Sure. It sounds like we're going to be at this for a while. 

Dr. Jill  39:29

Yes. 

Bob Miller  39:31

So in mice, IL-6 administration was found to induce profound elevations of both serotonin and dopamine activity in the hippocampus and prefrontal cortex regions of the brain. Another interesting thing [is that] there's an enzyme called COMT that is used to clear dopamine. It's weakened by estrogen and strengthened by testosterone. So what's happening? We're being exposed to all these plastics that are xenoestrogens. That's why we're seeing testosterone levels dropping in young boys. It's possibly why when I talk to college professors and I say, “Tell me about the freshman,” one term that everyone keeps using is ‘fragile'. They're just not confident. They're fragile. 

Bob Miller  40:20

We've talked before about mTOR and autophagy. And in case anyone doesn't know, there are two processes inside the body that are equal and opposite. One is called mTOR, or the growth of new cells. If we didn't have mTOR, the sperm and the egg would never become the baby; the baby would never become the adult. We need mTOR to make new cells. It's called the mammalian target of rapamycin. However, there's an inverse to that and that's called autophagy, the cleaning of the cells. 

Bob Miller  40:51

If you Google “autophagy Nobel Prize”, you'll see a Nobel Prize in medicine was given for the study of autophagy in 2016. We need a balance between these two. My research has shown that there are so many environmental factors that are upregulating mTOR, which then downregulates autophagy. I give the analogy: Think of mTOR as the construction crew; autophagy is the janitorial cleanup crew. And mTOR suppresses autophagy. A couple of things would do that. I think we're going to look back someday and say: “What were we thinking by giving animals growth hormones so they get fatter faster?” Seriously? What were we thinking? That stimulates mTOR. 

Bob Miller  41:40

All of the plastics are xenoestrogens. That's why I believe people are seeing such good results with intermittent fasting and the ketogenic diet. What it's doing when you do intermittent fasting and take the nutrients away [is that] the mTOR says: Hey, construction crew, I don't have any materials. Take a break. Okay, janitors, come out and do your thing. 

Bob Miller  42:04

Now, this is interesting. This is a little like a 3D chess game here in itself. Interleukin-6 influences stress by reducing the expression of an mTOR inhibitor. When you reduce an mTOR inhibitor, that allows mTOR to go rampant. And mTOR is a very dutiful replicator. It will replicate healthy cells and cancer cells. I don't have a slide on it here, but COVID uses mTOR for replication. That's why I think now is not a good time to be doing things that upregulate your mTOR. 

Bob Miller  42:46

Now, if that's not enough—autophagy [which is] the cleaning of the cells—IL-6 inhibits autophagy. Again, by a signaling pathway. So what happens is that IL-6 stimulates something that slows down autophagy. Taken together, these data indicate that IL-6 inhibits starvation-induced autophagy. Theoretically, 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 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. 

Bob Miller  43:37

One of the best ways to see if your autophagy is not working is by 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 [caused by] is when the dead cell that is being reproduced is not cleared properly. Many times, I see people in their late 40s filled with age spots. Ideally, we wouldn't get them at all. But let's say it's probably okay if we're 85. 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. 

Dr. Jill  44:15

Yes, I was going to mention, Bob—you mentioned this, just for people who are listening—things that upregulate mTOR would be anything that increases growth hormone. [That includes] some of these newer peptides or 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 [such as] leucine and isoleucine. So if you're taking amino acids, you're doing testosterone, and you're taking peptides, you could be at higher risk for this mTOR being excessive and a lack of autophagy. 

Bob Miller  44:50

Absolutely. And throw glutamine in there as well. 

Dr. Jill  44:53

Yes. 

Bob Miller  44:54

And we spoke about this before, but it's worth mentioning: I believe too many well-meaning health professionals are suggesting too much glutamine, which can then upregulate mTOR. The reason they take it is because “Well, 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 unintended consequences. Then it may upregulate your mTOR and actually make more glutamate, which we're going to show you in a little bit. It can inadvertently upregulate IL-6. 

Bob Miller  45:27

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 mast cells—that makes histamine.

Bob Miller  45:49

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. Here you can see IL-6 in the center, and you can see that it stimulates NOX, stimulates mast cells, stimulates histamine, and then further stimulates interleukin-6. 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 as I mentioned earlier, we were going to talk about angiotensin. Maybe now is a good time to do that. 

Bob Miller  46:31

The renin system, the REN gene, when it's stimulated—and look what stimulates it: superoxide, mast cells, histamine, dopamine, testosterone—stimulates angiotensin I and angiotensin II, stimulates interleukin-6, superoxide, and CRP. As we said, mast cells and histamine [too]. They all come back in what I'm calling the Holme cycle to re-stimulate this. But this time I put IL-6 in the center, showing 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 it is very important how this histamine feeds back into this positive feedback loop. I found that very, very surprising. Bradykinin induces interleukin-6 production by human airway smooth muscle cells. So the bradykinin [produced] by the bradykinin-2 receptor induces IL-6 expression. IL-6 excretion by bradykinin is sensitive to cortical steroids and is regulated by Th2-derived cytokines. So let's talk about bradykinin just a little bit, because there are studies out there that indicate how bradykinin is part of the cytokine storm. But look what it does: It stimulates interleukin-6. 

Bob Miller  47:51

Now, look at glutamate. Glutamate inhibits ACE2. Why is that important? ACE2 is what takes these inflammatory molecules, angiotensin I and II, and turns them into angiotensin 1-7. So what I'm finding in our health coaching based on functional genomics [is that] when people have a lot of mutations in ACE2 and maybe they have some mutations in HMOX-1 that knock this down, they've got a lot of inflammation going on. If they also have glutamate, the glutamate will inhibit ACE2. Oops, I didn't want to do that. Hold on. 

Dr. Jill  48:31

I was just going to ask you to blow it up to potential inhibitors, Bob. 

Bob Miller  48:36

We're going to get to those here. 

Dr. Jill  48:37

Okay. We're getting comments already: “What do you do then?” 

Bob Miller  48:43

Yes, hang on. Don't get stressed out because it'll put up your dopamine and IL-6. [laughter]

Dr. Jill  48:48

You don't want to raise your IL-6, so hang on. [laughter]

Bob Miller  48:51

So bradykinin will stimulate IL-6. The ACE enzyme takes this bradykinin down to 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—turns it down to this molecule. And then again, ACE2 puts it into inactive fragments. Well, what does COVID do? It comes in using ACE2 and weakening it. But aside from that, when you've got mutations here or high glutamate, you're going to have more bradykinin. 

Bob Miller  49:24

Now, just an interesting thing that I just recently learned. We know that one set of drugs is called ACE inhibitors to bring down blood pressure. I just assume that they reduce angiotensin II. No, they don't. They slow the bradykinin into inactive fragments. That's why some people get a cough [when] on ACE inhibitors. I wasn't aware. Were you aware that that was the action of ACE inhibitors? 

Dr. Jill  49:49

No, I would have agreed with you about the receptors. I didn't think about the bradykinin piece. 

Bob Miller  49:53

Yes, 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. And this is where a lot of people get edema, the swelling of the legs, when that occurs. So, bradykinin induces this IL-6 production. 

Bob Miller  50:18

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-resorptive action of estrogen in humans is mediated by decreased production of IL-6. So we always talk about the estrogen needed for bone health. There might be multiple pathways for that, but this is one of them. Keep in mind that this is estradiol. Estriol has an elevation in serum IL-6 following an LPS challenge. So the same. These results suggest that the estriol can have significant quantitative tumor necrosis factor and IL-6 effects on inflammatory monokines produced in response to an endotoxin challenge. Absolutely fascinating. So work 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? 

Dr. Jill  51:22

Yes. You saw me; I was really salivating on this one. This is new to me. But I would comment that number one, we use estriol thinking it's like—we call it caboose hormone—end of the line. [This is] because your body can't make 4-hydroxy and 2-hydroxy—some of the metabolites that can damage DNA. So we often use estradiol in breast cancer survivors or patients who need 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 that it's used transdermally, so I'm assuming there's not a huge amount of systemic absorption. But even so, in my mind, I consider estriol 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. 

Dr. Jill  52:12

I would recommend that if you're watching this, get your doctor to do some sort of quantitative metabolite panel—I like DUTCH [test on] hormones, [and] there are 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 estriol? What are your levels of estrone? And what are the levels of the 4-hydroxy and the 2-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. 

Bob Miller  52:41

Yes, good point. I mean, this is not all bad. As you said, this has many important functions. 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. Who knows? I'm just speculating. It might even be the ratio between the two. We're not saying you can't have this or shouldn't have it. 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. 

Bob Miller  53:11

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 upregulation of tumor necrosis factor alpha and IL-6 in the plasma during vigorous exercise. So again, exercise is good for you. Can you overdo it? You betcha. And then does it start working against you? 

Dr. Jill  53:50

Yes, Bob. I would love to comment on this one. So again, in medical school, we're taught: Calories in, calories out; exercise more if you want to maintain a healthy weight and metabolism. So for decades, I was doing very high intensity, either Orangetheory, high-intensity interval [training], or running. I would get up, get out of bed at 5:30, be at the exercise by 5:45, do an hour of a pretty intense workout, and come back and go to work. 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 movements. I did functional movement for several months and rehabbed 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. 

Dr. Jill  54:36

Literally, it's 40 years of doing high-intensity types of exercise. But what happened, Bob, was not surprising, but to me, miraculous: My body fat percentage went down by 8%. I got in the best shape of my life. And I always joke: I basically stopped working out and got in the best shape of my life. I love to tell my colleagues and women in their 40s like me about this because I was a medical doctor. I've been through physiology and biochemistry. I 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. 

Dr. Jill  55:11

And all of a sudden I ate the same, I did less, and I actually got in a lot better shape. Now I actually have better muscle and less body fat and it's almost without trying. All I do is walk or hike a couple of times a week and do a little bit of free weights—and I'm talking very minimal exercise. This is really important for people to hear because it is a big deal. 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. So if you're getting stuck on weight loss and you're a woman over 40, maybe you're working out too hard. 

Bob Miller  55:47

I bet you there are some people who are right now saying: “Bless you, Dr. Jill.” [laughter]

Dr. Jill  55:53

It's very freeing. And it's funny, Bob, I have to say this too: There was no compulsion. I loved my workouts. I enjoyed it. I didn't feel like I was overtraining because it was just joyful. I loved it. But now that I know the truth, I think I was. I think the truth was that my body would have told me if I had listened: This is too much.

Bob Miller  56:14

Absolutely. But perhaps you have a little bit too much glutamate, do you think? 

Dr. Jill  56:18

Probably. Cortisol, glutamate, and inflammation. So it's amazing to me. Yes. 

Bob Miller  56:24

Yes, that glutamate gives you that drive. 

Dr. Jill  56:26

Oh, yes. And dopamine. We talked about this already. 

Bob Miller  56:31

Now, let's talk about the environmental factors. And then, I promise, after this, we're going to tell you what to do. So hang on; 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 got calls: “Bob, 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 of 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 a role of air pollution of inflammatory conditions.” “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. Jill, weren't there some fires in Colorado as well? 

Dr. Jill  57:29

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 the same thing in the elevation of other cytokines as well. 

Bob Miller  57:43

Mm-hmm. And I'm just passing on what Dr. Klinghardt 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 environment. And now as the trees burned, perhaps some of that mercury is being released. 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. Make sure that you don't have mycotoxins and [that] 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 [inaudible] coffee. 

Dr. Jill  58:31

Yes. Bob, when I introduce [information] about chocolate and coffee, the flavonoids and the gut, I say, “These are my two favorite food groups: Chocolate and coffee.”

Bob Miller  58:40

Yes. I'll drink to that. 

Dr. Jill  58:43

Yes, me too. 

Bob Miller  58:44

Men who consumed greater than 200 milliliters of coffee—I mean, I couldn't believe this—had 50% higher [levels of] interleukin-6. Women who consumed greater than 200 milliliters had 54% higher [levels of] IL-6. I thought, “200 milliliters, that's got to be a lot.” Well, it's like six ounces. 

Dr. Jill  59:04

Ugh, darn it. I can't even have one cup. Well, what if we get it from a shot of espresso? [laughter]

Bob Miller  59:11

Now, it's saying this relation could explain the effect of increased coffee intake on the cardiovascular system. When I present this, some people say: “Is it the caffeine, or would decaffeinated not have an effect?” I haven't seen any literature, but let me just speculate and hypothesize that caffeine does jack up dopamine. So I wonder if that is the mechanism or if there's another one. But I didn't find any literature as to what it was about the coffee. 

Dr. Jill  59:40

Interesting.

Bob Miller  59:41

Yes. So to me, that was bad news because I love my morning coffee. I don't normally drink coffee, but just to keep making sure my brain was functioning, I had just a little bit here with me. 

Dr. Jill  59:53

You know, Bob, just an idea. So you brought this slide about menopause symptoms and hot flashes in women and IL-6 and we're all like, “Wow, that's crazy!” Well, with hot flashes, they're worse with dopamine and norepinephrine elevation. And [with] coffee, the same thing—it would elevate dopamine and norepinephrine. I wonder again, just totally thinking outside the box: Maybe there's a correlation with neurotransmitter elevation because that would be a commonality between hot flashes and coffee. 

Bob Miller  1:00:17

Absolutely. I'm sure there are a lot of people now who are just saying, “I wish I wouldn't have listened to this.” 

Dr. Jill  1:00:22

I know.

Bob Miller  1:00:25

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 believes that we're going to look back someday on all the EMF and Wi-Fi as we did cigarettes back in the 1940s. If you just want to be entertained or saddened, go on YouTube and search for cigarette commercials from the 1940s. You will usually see a doctor or somebody, an actor pretending to be a doctor, saying that more doctors smoke Camel cigarettes because it's soothing to their throats and pregnant women should smoke if they're stressed because that will help them. And of course, at the time, you could smoke cigarettes for a year and say: “Look, I'm fine. Nothing happened.” But smoke cigarettes for 15–20 years—lung cancer. So I think we're having the same argument with cell phones and Wi-Fi. 

Bob Miller  1:01:19

And clearly, [with] our cell phones in our hands, 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 calculators, [and provides] 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 peroxynitrite, which damages the DNA and depletes your glutathione. 

Bob Miller  1:01:58

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. If you listen to Martin Paul, he talks about 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 the third week of January. It's two or three days completely on the negative effects of Wi-Fi. And there is concern that, as 5G rolls out, that could even be worse. 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 definitely be affected by cell phones and EMF.” I'm sure you've read into that as well, Dr. Jill. 

Dr. Jill  1:03:04

One hundred percent. 

Bob Miller  1:03:05

So this may be one of the things that's causing it. And there are 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. I'm very concerned about streaming to smart TVs. When you stream video, you are giving off massive amounts of EMF. When you send a text message or even a phone call, yes, that's a little bit. But when you stream video, wow, that's a lot! I always encourage people: If you're going to watch streaming video from the internet, wire it to your television; don't stream it. 

Dr. Jill  1:03:52

I couldn't agree more, 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 the same with wired TVs; 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 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. She actually came to my house and 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 of nightstand lamps. There's no Wi-Fi router there. My voltage on the body was 3,000 when the meter was on and it was 300 when I turned the breaker off.

Dr. Jill  1:04:42

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. I'm in my office. Right next to me, it looks like a net, like a laundry bag over my router. That decreases the signal just enough to protect me so that I'm sitting here, [and] it's not much exposure. But I still have plenty of Wi-Fi in the apartment. So these are 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 whether they 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 impressionable organs. And it does affect breast testicles and reproductive organs as well. 

Bob Miller  1:05:28

Oh, absolutely. I've had some good results—and I have no affiliation with these folks—there's [something] called 5G Bloc[Wave] Bag. It's a sleeping bag, so it's not grounding. So I agree with you on grounding. It just might just be the antenna [inaudible]. But they're made out of silver threads. I crawl into that every night and I swear I sleep better. 

Dr. Jill  1:05:49

I love that because that's a simple thing. You don't have to plug it in. 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 for any of us who are sensitive, I feel like it is one of the remedies for EMF sensitivity. It kind of provides the hertz of the earth's frequency. So I lay on my mat for 20 minutes every day and I find it to be really helpful. 

Bob Miller  1:06:18

Absolutely. That's going to be one of the slides coming up. So be careful of that EMF. In my office right now, you probably can't see it, but the mouse is wired. The computers are wired. I have as little exposure as possible. 

Bob Miller  1:06:36

No surprise here: Glyphosate exposure increases the inflammatory response and it increases IL-6 after glyphosate exposure. So I'm sure glyphosate does many other things. It may substitute for glycine. It may impact the heme cycle. Who knows what else it does? But isn't it interesting that glyphosate will actually increase interluekin-6?

Dr. Jill  1:07:01

Fascinating! It just shows all this load, Bob, right? None of these things by themselves are totally toxic, but what happens is the load… We have glyphosate in our organic wines from California. In the dog food, we have molds. We have the EMFs in the house [and] mold in the house. So it's this combination of everything that's really causing the issues. 

Bob Miller  1:07:24

Yes. So sodium sulfide increased the LPS-stimulated secretion of IL-6; curcumin decreased IL-6. So curcumin—we don't know all the properties, but that's one of the things it does. It decreases the interleukin-6. 

Bob Miller  1:07:42

Now, one of the subjects that you and I both love… And by the way, the talk you gave at our mycotoxin conference was incredible. And we're going to mention one more time that people could get those recordings if they want them. Here we're talking about how the production of IL-6 increased in response to mycotoxin exposure, which can influence [and have] bad effects on fetal development. So let me just jump to another slide here. Pro-inflammatory effects of ochratoxin A on nasal epithelial cells. Mycotoxins from mold significantly increased IL-6 and may promote inflammation in the nasal cells. 

Bob Miller  1:08:23

I do a webinar every other Thursday evening for physicians. By the way, if any physicians are watching this, just contact us. We'll get you 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 mycotoxin conference. And this is his test from MyMycoLab. He heard my talk that I gave to physicians on IL-6 last week and he said: “Bob, you piqued my interest. I started going through the literature.” In the published studies, Dr. Andrew Campbell has reviewed the following mycotoxins as the strongest drivers of IL-6 secretion. Of the 12 he measures, nine very strongly stimulate IL-6. Absolutely amazing. If there are any health professionals watching this and they'd like to see the webinar, just contact us and we can give you the link. He talked for about 20 minutes about all of these. But all of these mycotoxins will increase interleukin-6. And I'm sure you probably have some thoughts on mycotoxins, Dr. Jill. 

Dr. Jill  1:09:25

Yes. We see this massive inflammatory response with mycotoxins, 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. [With] these layers, what happens is if we have glyphosate in our food and we're not eating organic and then we have EMFs 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: 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. There have been some studies that potentially show that  in more air-polluted areas, there are more COVID complications 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. 

Bob Miller  1:10:17

Oh, no doubt. I mean, that's possibly why New York was hit so hard. When you look at some of the cities that were hit the hardest, they seem to have the most air pollution. 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 upregulated. And if you're interested, if you're a practitioner, just contact MyMycoLab. These are IgG antibodies that they run.

Bob Miller  1:10:43

Now, we talked before about lipopolysaccharides from gram-negative bacteria. They induce tumor necrosis factor and IL-6. So, Dr. Jill, I'm sure you have a couple of comments on this. 

Dr. Jill  1:10:55

Yes, absolutely. This is interesting because we often measure tumor necrosis factor and LPS. And this is where I've seen the most data, like thousands. I remember when I first presented on LPS-induced endotoxemia and 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 endotoxemia—”those are the ones that are having more trouble with complications” because 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, etc.—then you're going to have more leakage of the LPS into the bloodstream, creating this inflammatory pathway. 

Bob Miller  1:11:43

Absolutely. Now, this one blew me away. Borrelia: “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.” 

Dr. Jill  1:12:03

Wow. 

Bob Miller  1:12:04

Wow is right. 

Dr. Jill  1:12:06

That's big.

Bob Miller  1:12:10

Lyme disease has possibly been around forever. But clearly, 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; perhaps it already did that before but now this load 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. 

Dr. Jill  1:12:41

Yes. And Bob, I tell people all the time, “Well, why now?” 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, spiders or mosquitoes and gotten tick-like infections, which would include Borrelia, Bartonella, Babesia, Ehrlichia, Anaplasma, rickettsial diseases, etc. 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 and never have symptoms.

Dr. Jill  1:13:15

So a lot of you 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 get polluted smoke in the air from fires for months and months. You have mold in the home and exposure that weakens the immune system from trichothecenes, which are mycotoxins or mycophenolic acid, which is a toxin that also suppresses immunity. And then all of a sudden, that limbo bar of the immune system drops, [and] an old Epstein bar—which was not bothering the person—old Lyme, Borrelia, Bartonella, etc. pop up.

Dr. Jill  1:13:46

So often, I would say, the 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. 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 in coming back online, because if that happens, you may not even need to aggressively treat the Lyme for that patient to be well.

Bob Miller  1:14:14

Absolutely. And as you know, we've done eight studies now on Lyme disease, just looking at the genome of 243 people who have chronic Lyme. The same thing keeps coming up each time. The first study that we won the award for in 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 showed that there was difficulty with bile production and synthesis, so there was an inability to detox. So we found eight different patterns that seem to be significantly higher in those with chronic Lyme. 

Bob Miller  1:14:53

And you hit the nail on the head. I think they found that the iceman that they found had Lyme inside of him. So I think it's just that we're overreacting. Again, because of our entire mast cells, this whole system of cytokine production is being upregulated. And this becomes a straw that breaks the camel's back. Yes, that one just blew me away—that there might be some LPS in the spirochete. And again, as you said, 50 years ago, it wouldn't have mattered. 

Bob Miller  1:15:25

Now, this is no surprise: Active smoking and a history of smoking are associated with higher levels of interleukin-6. That's almost a no-brainer on that one. So now is a good time to stop smoking. Interaction between smoking and interleukin-6: The potential role of the IL-6 gene in the inflammatory response associated with smoking. So what they're saying here [is that] there's a polymorphism—what that means is a genetic mutation—in the IL-6 gene. Here's the RS number. That's the actual location of the gene. 

Bob Miller  1:16:00

And what we're finding—and we're studying this, and we have it in the software that measures this—is that many of these mutations are upregulation. So what I'm finding [is that] 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 that the results indicate a potential role of the IL-6 gene being mutated in the inflammatory response associated with smoking. I mean, you hear stories all the time of somebody who's 90 years old, smoked for the last 50 years, and they're healthy as a horse. That makes a nice news story, but possibly they don't have any other co-factors or any of these mutations. You'll see somebody else who's smoked for 10 years and has lung cancer. So [there are] multiple, multiple reasons. And this wouldn't just be it, but this could be another factor that, if you've got this upregulation, smoking is going to have a much higher impact on you. 

Bob Miller  1:17:03

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. It strongly supports the functional relevance that IL-6 promoter SNPs affect basal regulation and carcinogen-induced IL-6 secretion. So again, that goes back to how you could probably have 10 people who work in a uranium mine, and two might get lung cancer from it. And what they're saying is that many of them had this genetic mutation that caused them to upregulate to radon. I've always known radon is 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. Are you in Denver County, Dr. Jill? 

Dr. Jill  1:17:56

I'm in Boulder County. 

Bob Miller  1:17:58

Boulder County. Well, anyway, I guessed wrong. But you can just put in the county and it'll tell you on average how many results are higher than 4, which is the rate, [and] how many are 2 to 4. So I would encourage everyone after this webinar to go to radon.com, find the county that you live in, and see where it's at. 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. 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. I think this is yet another contributing factor. Any thoughts on radon, Dr. Jill? 

Dr. Jill  1:18:56

No, I love that you bring this out. The air quality people who came to test my EMF actually talked about radon, and this is something that's very relevant and very common. So if somebody is focused on mold, I forget to think about asking patients if they've checked. This is brilliant. And thanks for sharing the website. 

Bob Miller  1:19:14

Yes, I'm fascinated. What I've been doing now is consultations. If I'm doing it interactively, I'll say, “Well, let's find your home.” And it's interesting. I just had somebody in New Jersey today on the shore. And this was like 2% and then in other areas, it's like 50%. This comes from granite. So the more granite you have, the more potential there is for this. 

Bob Miller  1:19:39

Now, volatile organic compounds. Interestingly, my first client this morning was someone who was doing quite well. They said: “Well, I was really doing well, and I 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. Then they had somebody come in and spray fumigants for insects. We could probably do a whole webinar on this or the main substances causing multiple chemical sensitivities. The authors found exposure to VOCs significantly increased NOS activity—that's nitric oxide synthase—and IL-6 and decreased glutathione concentrations. It was suggested to be the result of increased NOS activity.

Bob Miller  1:20:31

Now, this gets very confusing because we said the NOS is important. Well, it is, unless it combines with superoxide. So I'm totally speculating here, but I would imagine what they missed here is that this probably also increases superoxide, and then when it combines with the nitric oxide, it creates the peroxynitrite. So we've really got to be careful with these VOCs. I literally put this in today based on a consultation. Again, I learned this from my client today. Ten best picks and ten worst picks for volatile organic compounds. This person bought a four-year-old car, but the car made them sick. And I'm not pro or con any of these cars. But they're telling you which ones seem to have the least amount of volatile organic compounds. So you can go to this website, ecocenter.org, and you can find these charts.

Bob Miller  1:21:35

If you're very, very sensitive, part of your decision-making process in your car might be: 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 would have thought that your car purchase could have an impact on your inflammatory levels? 

Dr. Jill  1:22:00

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 car smell, that means there are VOCs. 

Bob Miller  1:22:14

Absolutely. I'll be curious, is anybody sending comments like, “Oh my gosh, I never would have thought of that?” 

Dr. Jill  1:22:22

Let me go back to the comments here because I've been watching them. Oh, yes, radon. 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?—the granite in the earth.

Bob Miller  1:22:32

Exactly. Exactly. 

Dr. Jill  1:22:33

Yes, and then formaldehyde they mentioned, which is a VOC that is also in materials and things. 

Bob Miller  1:22:40

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, [which] increased the secretion of production of interleukin-6. Thus, both PCP and DDT have the potential to produce chronic inflammation by stimulating the 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. So we really need to be careful with this pesticide exposure, particularly if we have upregulated interleukin-6. 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. 

Bob Miller  1:23:31

Heavy metals. Induction of IL-6 by aluminum-induced oxidative stress. They're saying that happens, and they're saying it'd be prevented by selenium. And what they're saying here is that selenium is the cofactor 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 the decrease in glutathione could be prevented by coexposure to selenium. I'm not sure that's true all the time, but we don't have enough selenium. If you don't want to take a selenium supplement, just eat some Brazil nuts. They're an excellent source of selenium. 

Dr. Jill  1:24:13

Yes. Two or three of those per day, except that you have to watch for molds, so 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 doctors who have patients in India and have had some consultations 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, here in the US, we're getting exposure.

Dr. Jill  1:24:40

So if you're listening and you use aluminum foil or aluminum deodorants—usually it's antiperspirants—those are things that are easy; just get rid of them. Make sure your cookware [is not aluminum], that you're not using aluminum foil and that you're not using it in the antiperspirants. It's an adjuvant in vaccines because it stimulates the immune system. Again, I'm not anti-vaccine, but sometimes the load and 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 is related to SNPs. That would be interesting. 

Bob Miller  1:25:10

No, I don't. Now, what we're going to do for our next conference—that'll probably be next September—aluminum, lead, and mercury are going to be on our agenda. 

Dr. Jill  1:25:21

Good.

Bob Miller  1:25:23

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? 

Dr. Jill  1:25:31

Yes, I know, right? And then it's right by the breast tissue for women, and it's such an absorbable area. The other thing I want to mention here is that chlorella can be a good chelator of aluminum. I know that's Dr. Klinghardt's recommendation. And zeolite. So those are the two that I tend to use more as binders in metal issues. There are 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. There's a whole-blood aluminum level. It's pretty simple. 

Bob Miller  1:25:59

Mm-hmm. And some people use hair analysis for that as well. So I would encourage everybody to use at least a deodorant or some of those natural things. Some of those rocks are incredible. And we're going to look back: Why were we smearing aluminum into our armpits? So it is elevated. And interestingly, aluminum stimulates NOX—NADPH oxidase—which then [triggers] this whole cascade that we were just talking about. 

Bob Miller  1:26:27

No surprise here: When you've got lipopolysaccharides, the interleukin-6 is worse when you've got lead. The heavy metal lead markedly augments the lethality of endotoxins in laboratory animals. Lead-exposed mice showed an altered IL-6 appearance in the brain in that the levels of IL-6 in the brains peaked at four hours rather than three hours after they were exposed to the 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 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-1 beta, interleukin-6, and tumor necrosis factor were significantly higher in the group of workers chronically exposed to lead by 38%, 68%, and 57%, respectively. It indicates that chronic occupational lead exposure promotes inflammatory processes by the induction of pro-inflammatory cytokines. There they are once again. Now, here we go. What do we do? 

Bob Miller  1:27:50

Okay, curcumin; we talked about that earlier. During a meta-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 the dose or duration of supplementation. Now, we know that turmeric, or 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 supports? 

Dr. Jill  1:28:19

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. It can be anti-pain and anti-inflammatory in that way, so I'm guessing it may be either anti-mast cell or anti-prostaglandin. 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. 

Bob Miller  1:28:47

And it slows down mTOR. Now, pycnogenol—we've been talking about this for years. The French maritime pine bark was found to decrease CRP and reduce interleukin-6. Thiamin 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. 

Bob Miller  1:29:23

Now, one of the things that we've just added to the software that can be used by health professionals—we're looking at the transporters for riboflavin and thiamine. What we're noticing, again, just observing, is that when people have mutations in riboflavin and thiamine, such as myself, their IL-6 can go up. I have to wonder if this is possibly why I was more prone to ulcerative colitis at an early age. [There were] probably multiple factors. But I've now started taking riboflavin and benfotiamine, 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. 

Dr. Jill  1:30:07

Bob, I love this. I just want to comment because I have somehow intuitively 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 are different mitochondria: Part one, two, three, and four. And in parts two and three, if patients have deficiencies in those—again, they're like the sections of the mitochondria; there's another name for it—number one, riboflavin and thiamine are key and critical to those. And number two, 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 me.

Dr. Jill  1:30:48

For me, this has probably been a decade where I've been on probably 300 to 600 of thiamine, high doses, and then at least 400 of riboflavin. It's been a literal game-changer. And again, now I know more about why that is. But it's really a big deal. The other thing I see is that 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. And people don't really remember. They think about methyl folate and even P5P or B6, but riboflavin is like Rodney Dangerfield: “I don't get no respect.” I love riboflavin. And it's produced by gut bacteria. If you have had gut issues and have a decrease in the 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 doctors aren't really thinking along those lines. They're game changers for patients' health and [for] myself. 

Bob Miller  1:31:41

Absolutely. And I've been observing and I'm seeing that when people do have mutations in the thiamine and the riboflavin transporters, oftentimes putting those back in makes a game-changing effect. Now, in Ayurvedic medicine, [they are] big fans of black cumin seed oil. Obviously, they're stretching it here quite a bit, but in Ayurvedic medicine, they'd say that black cumin cures everything but death. It's obviously not true, but that's how impressed they were with it. So the black cumin seed oil significantly reduces IL-6. 

Dr. Jill  1:32:16

And you know what else it does, Bob? It's very unique because I don't know any other natural substance that works on clostridia. So I use black cumin seed when I have clostridia overgrowth and I don't want to use vancomycin or some of the heavy hitters. It really does work, especially for autistic children. I'll often have them on black cumin seed oil. It's very effective. 

Bob Miller  1:32:35

Absolutely. Apigenin—many people are like, “What's apigenin?” It's found in parsley and chamomile. This just about knocked me off my chair: It 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 Nrf2. That's what causes the production, recycling, and utilization of your antioxidants. It strongly decreases interleukin-6. Parsley, for goodness sake, and chamomile. So again, I'm formulating a product that's going to have parsley in it. 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? The things that God put on the earth for us are there, and we sometimes forget all about them. 

Bob Miller  1:33:42

Now, oxytocin, the love hormone. Interestingly, oxytocin attenuates NADPH-dependent superoxide activity and IL-6 secretion. You can see the charts there. 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% 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, or when there's human-to-human contact. What are we doing now in a lockdown? We stay six feet away from each other. I think this is why we're seeing such an increase in the adoption of dogs. I can't say for sure, but I would imagine that when you hug your dog or your cat and you feel that bond between them, you probably increase your oxytocin. 

Bob Miller  1:34:38

Interestingly, there's a genetic marker that shows—and it's incredibly accurate—that people have a more predisposition towards empathy based upon 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?” 

Dr. Jill  1:35:04

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—

Bob Miller  1:35:10

It's one of the OXTRs. I can get you the actual… 

Dr. Jill  1:35:16

Maybe you have it in your matrix? 

Bob Miller  1:35:18

It's under neurotransmitters. 

Dr. Jill  1:35:19

Got it. Okay, that's all I needed to know. I can find it. I'm just curious. 

Bob Miller  1:35:24

If anybody wants to look it up if they have their genome, like from 23andMe or something, it is RS number… Here, I'll just pull this over. 

Dr. Jill  1:35:32

Oh, you're amazing. 

Bob Miller  1:35:34

OXTR and the RS number is 53576. That's 53576. When it's homozygous—very empathetic. What I love to do when I talk to young girls—their 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?” They'll typically say no. And I'll say, “That's it.” That's the word. When people are very empathetic, narcissists find you and take advantage of you. They know how to gaslight you and really convince you that if you don't do everything they want, you're the problem. And it can just totally ruin your life.

Dr. Jill  1:36:31

Bob, this is funny. If you guys stay tuned on Facebook Live in probably a month or two, Sarah Gottfried and I are doing a whole episode called “Bad Boyfriends”. So two OXTR double homozygous [individuals] are going to actually talk about this to the public. 

Bob Miller  1:36:51

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 co-factors. I may put my research team on this. Is there something we can do from the  standpoint of nutrients that may stimulate the production or co-factors? I really don't know, but that would be fun to find. But I think our oxytocin is dropping during these stressful times. 

Bob Miller  1:37:42

Hydrogen water. The news on this just keeps going on and on and on. If anybody doesn't know, there are little tablets that you can drop in a glass of water. They fizz. As you know, water is H2O. So what it does is knock the hydrogen loose. As soon as it's done fizzing, you chug this down. And look at this: Hydrogen water lowers interleukin-6 and tumor necrosis factors, therefore exerting a protective effect. And I know you're a fan of hydrogen water as well, Dr. Jill. 

Dr. Jill  1:38:12

I'm a huge fan. I know you and I, usually before our shows,  we breathe it through our machines. I just did that this morning. I have it on my favorite meditation chair. So I'll just sit and read and meditate, put on my hydrogen prong, and do 30 or 40 minutes. That's super-powered. But the little tabs are excellent as well. 

Bob Miller  1:38:31

Yes. So if somebody said to me, “Bob, you can take one thing and one thing only,” I would probably choose hydrogen water. 

Dr. Jill  1:38:37

Yes. And I've never seen anyone react to it; I don't know about you. It's very, very gentle. 

Bob Miller  1:38:42

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 aches, bloating, or gas, just stop—that indicates you've got SIBO. But it's very rare. I'd say it's like 1 out of 100. But just in case anybody tries hydrogen water and it's like, “Oh my gosh, I feel horrible,” talk to your health professional and get checked out for SIBO. 

Bob Miller  1:39:05

We talked about this earlier: Pulsed electromagnetic fields suppress IL-6 transcription. That's possibly what you're doing when you're laying on your pulsed electromagnetic field. The pro-inflammatory factor IL-1α significantly promoted IL-6 transcription over time. It indicated that the inductive effect of IL-1α on IL-6 could be significantly inhibited by PMF treatment in a time-dependent manner, as early as two hours after stimulus initiation. 

Dr. Jill  1:39:40

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 I have an immune deficiency as well; I'm in great shape despite all of this—I have always had low protein no matter how much protein I eat because I think I have the protein-wasting enteropathy 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. If I look at my labs—I get them drawn every month—the protein albumin [levels] are always just a little low. 

Dr. Jill  1:40:12

Within 10 days of me using the PEMF 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 are like: “Okay, Jill. Shut up about the mat.” But I've done a lot of things; you know how I biohack myself. And that PEMF 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 still don't know the mechanism, if it was a decrease in IL-6. Or I actually think it helps with cellular healing, so it was probably one of the few energetic things that actually healed the enterocytes. I don't know. But isn't that interesting? 

Bob Miller  1:41:03

Absolutely. And do you drink your hydrogen water and breathe your hydrogen while you're on the mat? 

Dr. Jill  1:41:07

I do that before, but the same thing. Sometimes I do, actually—same time. 

Bob Miller  1:41:13

Yes, multitask here. So all right, vitamin D; no surprise here. Vitamin D administration can significantly reduce the IL-6 in the ventilator-assisted [inaudible]. So we could do a whole show on vitamin D, but I think everybody knows that. Now, what's the range that you like for vitamin D? 

Dr. Jill  1:41:34

Yes, 50 to 80 is super safe. I'm okay if people go above 80 as long as they're not above 100 with hypercalcemia. 

Bob Miller  1:41:41

Yes. In my opinion, I think we need to take vitamin K2 with it if, particularly, we have the calcium voltage channels where that extra calcium from the vitamin D will go in and create peroxynitrite. You could potentially create more inflammation if you create more inflammation if you create more calcium absorption under those conditions. So again, Goldilocks and the Three Bears: Not too little, not too much. 

Dr. Jill  1:42:06

Yes.

Bob Miller  1:42:08

Arachidonic acid. This is your bad fats. 

Dr. Jill  1:42:11

No surprise, right? 

Bob Miller  1:42:12

Yes. And for anybody who really follows good health, they're like: “Duh! This is the who's who of good, healthy things to do.” So arachidonic 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. 

Dr. Jill  1:42:38

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 carbohydrate, trans-fat diet sometimes need omega 6 and omega 3. So I'll often give evening primrose or borage with it. But in general, most American diet eaters need exclusively supplementation of omega 3s because they already have plenty of omega 6s and other types of fats. 

Bob Miller  1:43:02

Absolutely. Now, this next slide is not going to surprise you. EPA and DHA reduced levels of pro-inflammatory cytokines in aging adults. So that's your EPA and DHA. That has a significantly lower effect on interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha after just four weeks of therapy and an even greater lowering effect after eight weeks of therapy compared to the control group. There was a slide that I almost made up, but I lost track of it. They talked about why in Japan, they seem to live healthier and longer. And possibly [there are] multiple factors. But one of the thoughts was that the EPA and DHA from the fish intake might have been a factor. 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 the treatment of hyperbaric oxygen. 

Dr. Jill  1:44:12

Excellent. I will mention that 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 hyperbaric [oxygen therapy]. So you want to treat that and get that under control first, because you may flare if you do it and you're not controlled. 

Bob Miller  1:44:29

Absolutely. Selenium [is] inversely associated with interleukin-6 in the elderly. And of course, we don't get enough selenium. I'll never forget how many, many years ago I talked to somebody who was head of the agricultural department of Pennsylvania. He actually got soil from Africa and used it 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 confounders. And again, I think the effect here is that it helps recycle your glutathione. 

Bob Miller  1:45:11

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 Holme's hypothesis, where all of these things that we spoke about upregulated the NOX enzyme and it'll create this process. So rather than just going along, go back and watch that other video where we talk about the Holme's hypothesis, where multiple environmental factors upregulate renin and interleukin-6 and begin a cascade of inflammation. And there is the Holme cycle. We talked about this in the other show, where many environmental factors upregulate NOX and make superoxide, hydrogen peroxide, mast cells, and histamine. They all come back and stimulate renin, angiotensin I and II, IL-6, more aldosterone, and 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. 

Bob Miller  1:46:10

Now, what do you do? Here we go. Make sure you're in a mold-free environment. If mold is suspected, consider mold remediation. Work with a health professional, check mycotoxin levels, and detox appropriately. Consider functional genomics to identify a potential weakness in detox pathways. Consider air purifiers if [in 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, and the KRAS. All of these can create high glutamate [levels]. Limit glutamine supplementation.

Bob Miller  1:46:54

And I love Honokial and magnesium threonate. They help with glutamate. Check your glyphosate levels. Take steps to reduce exposure. Consider eating organic. Consider checking for radon and mitigating it if it is high. Check for C. difficile and [use] 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 molybdenum. Check out if you have high oxalates. If you eat spinach and 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. 

Bob Miller  1:47:40

I encourage everybody to watch our video on histamine. Consider dietary changes in nutrients to reduce histamine. These are the genes, HNMT, MAOA, and HDC. This is a whole subject in and of itself. Histidine decarboxylase, when upregulated, creates more histamine. There's more. Check for heavy… That should be, I'm sorry, not ‘heavy meals', heavy metals. Typo there. And take appropriate steps to detox. Check the CACNA1C genes for potential EMF sensitivity. Consider caution with EMF. Consider measuring dopamine and taking steps to lower it if it is high. Check the DBH and COMT functional genes. Have your medical professional measure your homocysteine. Take the appropriate steps. 

Bob Miller  1:48:24

These are the enzymes that, if they're mutated, can result in higher homocysteine. Healthy weight and normal blood sugar. A healthy balance of good fats. EPA and DHA versus bad fats. As we spoke about, appropriate exercise, not overexercise. Stop smoking. You may want to check your glutathione and SOD genes—that's superoxide dismutase—for proper function and compensate if needed. Check the renin, ACE2, IL-6, 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—Dr. Jill was a speaker—if anyone would like to listen to this, they can just go to nutrigeneticcresearch.org/2020-conference and order the three-day conference. Again, thank you, Dr. Carnahan, for being a part of that. That was excellent. 

Dr. Jill  1:49:19

That was a great conference, Bob. Thanks for putting it on. You really had great content and great speakers, as always. 

Bob Miller  1:49:25

Yes. Now, I'm going to speak for a moment to health professionals. If someone says this is really cool, the NutriGenetic Research Institute does online education and live conferences. We created software that analyzes genomics. We have our own genetic test and we work with a line of custom-made formulas that can help bring this into balance. NutriGeneticResearch.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 is the director. And if anyone wants to get a hold 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. 

Dr. Jill  1:50:22

That was fun! Oh, my goodness. I couldn't wait for this, IL-6. We've talked about it for maybe six weeks or four weeks or something like that, and I knew it would be good. Bob, as always, you packed in so much good information. 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 to 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. 

Bob Miller  1:51:04

Absolutely. I hope many people got some aha moments tonight as to how they can reduce inflammation and age successfully. 

Dr. Jill  1:51:12

Thanks. And we will see you next time!