In Episode #16, PART 1: Dr. Jill Carnahan Interviews Dr. Bob Miller on Functional genomics and Perioxynitrite pathways and NADPH Steal
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.
A popular inspirational speaker and prolific writer, she shares her knowledge of hope, health, and healing live on stage and through newsletters, articles, books, and social media posts! People relate to Dr. Jill’s science-backed opinions delivered with authenticity, love and humor. She is known for inspiring her audience to thrive even in the midst of difficulties.
Featured in Shape Magazine, Parade, Forbes, MindBodyGreen, First for Women, Townsend Newsletter, and The Huffington Post as well as seen on NBC News and Health segments with Joan Lunden, Dr. Jill is a media must-have. Her YouTube channel and podcast features live interviews with the healthcare world’s most respected names.
Dr. Jill 0:12
Well, hello everyone! We’re live, and it’s so awesome of you to join me. I know I advertised this with my practitioner in a newsletter, which is a pretty large group of people, so you might be joining me from all over. If you’re a practitioner, you’re in for a huge treat today. As you always know with Bob Miller, we go deep and we go technical. If you’re just a person who found us on Facebook and doesn’t know what you’re getting into, be ready for a ride because this isn’t for the lightweight. We’re going to go deep into genetic pathways, peroxynitrite, and some really amazing things. But I promise you it’ll be interesting.
Dr. Jill 0:42
So I want to introduce our guest first, and then I want to ask him a few basic questions, and then we’ll dive right in. And he even has some slides to share because, when we’re dealing with this kind of stuff, it’s so much easier to have a visual. So I’m excited that he’ll be sharing that and telling us more about it.
Dr. Jill 0:57
Just a little housekeeping: Feel free to share as we’re live. This will be recorded. So you can find the recording here on Facebook, and you can also find it on my YouTube channel, “Dr. Jill Carnahan” on YouTube. It may be a day or so until it’s up, but it will be there as well.
Dr. Jill 1:14
I am delighted to introduce my colleague and esteemed friend, Dr. Bob Miller. Dr. Bob Miller is trained in naturopathic specialties. As you know, I think I’ve had more naturopaths on my Facebook Lives than medical doctors. I always joke that I was born with the heart of a naturopath because I love how we delve into the same things. And the solutions are not just drugs and surgery; they’re really based on a much more natural approach. I always find that I learn so many things from my naturopathic friends. They’re some of the smartest people I know.
Dr. Jill 1:46
So I’m delighted to introduce Bob Miller. He actually specializes in the field of genetic-specific nutrition. What you’re going to love about him is that he’s going to dive into pathways you’ve probably never seen before unless you’re a practitioner who’s studying this stuff. But it’s so relevant to some of the details. And if you’re out there listening as a patient, Bob is the kind of guy that can help you find hard-to-pin-down pieces of your puzzle and some of the pieces that might have been missing when your doctor treated you or a nutrient. Like, “Why did I react to that one?” So as we dive into that, some of that might start to make sense.
Dr. Jill 2:22
He earned his traditional degree from the Trinity School of Natural Health and is board certified through the ANMA. In 1983, he opened the Tree of Life Practice, where he served as a traditional naturopath for 27 years. For the past several years, he’s been exclusively engaged with functional nutritional genetic variants and related research, specializing in nutritional support for those with chronic Lyme disease. So for any of you listening out there, I know that hits a lot of you. And it’s sad—we’ll briefly talk about that at the beginning—but Bob, I know this is epidemic in its nature. And you’re in Lancaster, is that right?
Dr. Bob Miller 3:00
Yes, Lancaster County.
Dr. Jill 3:01
You’re in the heart of Lyme Country. Tell me just a little bit about how you got into functional genomics and your pathway even to naturopathic medicine.
Dr. Bob Miller 3:12
Sure, well, it’s an interesting story. Traditional naturopathy is my second career. I was in electronics in the cable TV industry. And in my early 30s, I came down with a very severe case of ulcerative colitis. That’s where the colon becomes very inflamed, and you’re bleeding. I was in the hospital for 21 days, lost half my blood, and then hemorrhaged. I remember vividly that night, [when] I wasn’t sure if I was going to make it till the morning. Of course, the recommendation was: Take out the colon. But here in Lancaster County, I’m a bit of a stubborn Dutchman. So I thought, “There’s got to be other ways.” So I started digging and just became fascinated and haven’t turned back yet. So [this was my] second career. And of course, having an electronics background, we think in schematics and pathways. So when I was introduced to genomics, it just made so much sense. This is just like an electrical circuit. And if you follow the electrical circuit, you can go back to where the dysfunction is. So that’s a little bit of the history.
Dr. Jill 4:14
Bob, I love this because I had no idea. We have some real parallels in our journey. First of all, I was in bioengineering. It’s not electrical, but [it’s] the very same idea of pathways. That’s why I love talking to you. And I think you know I had Crohn’s disease, which is a cousin to ulcerative colitis. I had the same thing. My doctor said: “You’re going to need drugs and surgery for the rest of your life. There’s no other way. It’s incurable.” Ironically, we have quite a similar journey, don’t we?
Dr. Bob Miller 4:42
Dr. Jill 4:43
That’s amazing. Well, I’d love to talk about, first of all: What is peroxynitrite? And feel free to share your slides whenever you want. And let’s get [down to] the basics: What are we talking about here? And how does that relate to diseases?
Dr. Bob Miller 4:59
Yes. I’m trying to share, and I’m getting a message that “the host disabled participants’ screen sharing.”
Dr. Jill 5:03
Okay, let me do this. Yes, okay. I think I just corrected that. See if that works.
Dr. Bob Miller 5:07
There we go.
Dr. Jill 5:08
Dr. Bob Miller 5:09
Dr. Jill 5:10
It’s like childproof door locks, right? [laughing] Your door locks were on; now they’re off.
Dr. Bob Miller 5:17
There we go. So again, our subject today is functional genomics and peroxynitrite. And here’s what we hope to learn today: What is functional genomics? What is peroxynitrite? And then we’re going to very quickly get into five pathways [by which] peroxynitrite might be made. And of course, the disclaimer: We’re not geneticists here. We’re using functional medicine to help physicians as a clinical assistance tool. And of course, we’re not giving any medical advice here.
Dr. Bob Miller 5:51
Now, here’s the basic premise: Poor diet and environmental factors, when combined with genetic variants in our DNA, might cause an increase in toxic substances and then a decrease in critical nutrients and molecules needed for optimal health. So here’s functional genomics. It’s no longer that model of treating or [saying], “Take this for that.” So rather than suppressing a symptom, we’re focusing on either refining a potential nutrient deficiency or an excess of a toxic or harmful compound in the body. We think of genetics as: Where did I come from? What diseases might I be susceptible to? Functional genomics isn’t that. We’re looking at pathways, and it gives you clues because genetics is just a predisposition, as I like to say. So when you see these genetic mutations, you use that as [a guide] to where to put your detective hat on and dig deeper with labs. Then, as we compensate for those nutrient deficiencies or support the detoxification, the body returns to homeostasis.
Dr. Bob Miller 7:02
Now, this is one of my favorite sayings: This is a 3D chess game played underwater. Some people like to think, “Oh, what SNP do I have, and what do I need to take for that?” I think we’re going to find that that’s way oversimplified, and it’s not quite that simple. Thinking that you need methyl folate because you have MTHFR sometimes does more harm than good. And we have to be looking at this globally, from a genetic, epigenetic, and cofactor [perspective], because there are so many things that come into play.
Dr. Bob Miller 7:37
Now, in the traditional naturopathic philosophy, I had this picture drawn, and it says, “When the house is burning down, don’t wash the windows and mow the lawn.” I’ve seen this way too many times from practitioners: Someone is really inflamed, and they start trying to support methylation or get the mitochondria going, and it backfires because they’re in such a state of inflammation. Now, for those who are new to this, we’re just going to go very briefly through genetics. Our genes are what make us human, and just minor variations make us unique. Now, a gene is nothing but a section of DNA that provides instructions for protein synthesis. One of the things I’m amazed at—what a miracle we are in our creation!—[is that] we eat fats, carbohydrates, and proteins; we drink water, we breathe air, and we’re exposed to sunlight, and everything gets made from that. I just sit back and just marvel at the miracle of that, how that all works. Well, it’s the DNA that makes the enzymes that make that happen.
Dr. Bob Miller 8:48
Many people have heard of SNPs. That stands for single nucleotide polymorphism. That can make us a little bit unique. It’s a variation in a gene. That SNP can then sometimes lower the function of that enzyme. As we said, enzymes take one substance and turn it into another. And if we have SNPs, that’s not optimal. Now, this is inherited from the mother and father. Each parent passes on one of their two sets of genes. And this is how it works: If a father has a gene variant and a mother has a gene variant, there are a couple of options that can occur. That’s why the same parents can have multiple children, and their genetic patterns are quite different. And here’s another one, a homozygous genome, and how it gets passed on to the children. So that’s why sometimes parents can be carriers of disease; both parents are fine, but the child has a problem.
Bob Miller 9:49
Now, our genes are not our destiny. I didn’t coin this phrase, but I love it, and that is that “genes load the gun, environment pulls the trigger.” I believe that we’re being exposed to so many environmental factors that our parents and grandparents weren’t exposed to. I believe that’s why we’re seeing such an increase and so many concerns. So epigenetics means the addition of changes to the genetics. And that’s all the things that we’re exposed to: The plastics, the electromagnetic fields, the genetically modified foods, the growth hormones given to animals, the degassing of some of the materials that we use, and the lead that we used to put in our gas. All of those things are having an impact on us.
Dr. Jill 10:37
And Bob, if I could just make a quick comment. Gosh, I just want to stop here, because environmental toxicity and mold are such a big deal for my patients. I really see this as the elephant in the room, so that’s the thing that’s different from even 10 years ago—for sure 50 years ago. But I remember when I first started [about] 15–20 years ago, I’d have a very simple case of Hashimoto’s, hypothyroidism, or some other autoimmune disease, and it would be fairly straightforward. They get well fairly quickly. And nowadays we have this set of very complex infectious loads and toxic burdens. I didn’t want to interrupt you, but I wanted to make sure that our listeners knew. This toxic load, if you’re wondering: “Well, why is it so much worse now? Why are so many more people getting sick from the virus?” This is part of the puzzle: Our environmental toxic load is overwhelming our natural immune defenses, and we’ve finally gotten to that tipping point, haven’t we, Bob?
Dr. Bob Miller 11:31
Absolutely, yes. I would concur completely. And that’s why—I will talk about this later—I’m having a conference for health professionals from September 18–20, three days on mycotoxins. I’m like you. When we see those people who are having challenges, 8 times out of 10, they’re being exposed to mold and mycotoxins. And actually, I’m going to be showing you the enzyme that is up-regulating, which I think will be quite fascinating.
Dr. Jill 11:56
Bob, I can’t wait! I’ll be there. And if you’re a professional—we’ll talk about this at the end, and we’ll share links—stay tuned for September 18–20 because you’ll want to be there. Bob, I want to just say something else. The mold is such a big deal. I’m the mold expert; I deal with mold all the time. But even for me, I’m always careful to go in with a blank slate with my patient and not assume there’s any mold. But over and over and over again, we get to the end of the puzzle and realize: “Oh my goodness! This patient too has a mold exposure.” So thanks for saying that 8 out of 10 [figure] because it’s so common.
Dr. Bob Miller 12:31
Absolutely. Now, this slide is showing us that when we do have that mutation, stepping in with compensatory things actually brings you back into balance. This is just a quick study on how riboflavin has an impact on the status of the homocysteine-lowering effect of folate in relation to the MTHFR genotype. All right, to answer your question [about] peroxynitrite: This is just one of the many things that puts the house on fire, so to speak. There’s a very important molecule called nitric oxide, [which] we need for circulation—we’ll talk about that—and then a rather nasty free radical called superoxide. This has an important role in chronic inflammation, immunity, and aging. And I’ll show you how mycotoxins actually stimulate the production of peroxynitrite. It’s hypothesized to play a key role in various degenerative states.
Dr. Bob Miller 13:30
Several analyses suggest that selenoproteins, particularly the selenium-dependent enzyme glutathione peroxidase, may have an important role in detoxification and elimination. I find it interesting that the symbol for peroxynitrite is ONOO. Broad-spectrum antioxidants—vitamin E and melatonin—may be, in part, preventing the formation of peroxynitrite. Peroxynitrite formation rises 100-fold for each 10-fold increase in superoxide and nitric oxide production. So what we’re saying here is that superoxide generation is a potential mechanism that disrupts nitric oxide. We’ll be talking about that. And I’ve been talking about superoxide for probably 10 years. Probably within the last two to three months, I’ve looked at it anew and said, “This is likely more significant than we realized.”
Dr. Jill 14:30
Bob, would it make sense that the theory that I’ve been hearing [about] why antioxidants like zinc, vitamin C, and even minerals can be so powerful with viral infections is that this free radical state is part of what allows pathogens to proliferate?
Dr. Bob Miller 14:51
Yes, absolutely. That goes back to the traditional naturopathic philosophy [from] 75 to 100 years ago, when traditional folks said, “These people are quacks that should be in jail.” But now the science is coming out and proving it to be true.
Dr. Jill 15:05
We were right all along.
Dr. Bob Miller 15:07
Yes. Nitric oxide—I’m sure people have heard of it. It’s in the cardiovascular and nervous systems. It has a very short half-life. And this actually won the Nobel Prize all the way back in 1998. Nitric oxide is critical for blood pressure, preventing thrombosis, preventing leukocyte adhesion to vessel walls, increasing the flow of nutrients to critical organs, and improving the efficiency of waste removal. Now we’re going to talk about superoxide. Inside the cells, sometimes an electron flies off and combines with oxygen, making what’s called superoxide. This superoxide has been hypothesized to be a potent key player in the aging process.
Dr. Bob Miller 15:51
All right, now we’re going to start to geek out here, so hang on to your hat. Here we go. Okay. I’m going to get my drawing tool here, and we’re just going to have a great time. So one of the things that we need is this nitric oxide that we spoke about. The nitric oxide is down here. [It’s a] vasodilator and electron donor. Now it’s quite a complex process to get there. We need a substance called BH4, tetrahydrobiopterin. Now, things can go wrong here. Aluminum can suppress that. Well, there’s something called the urea cycle in the kidneys that clears ammonia. These are the genes involved in that. If we have any genetic mutations or anything else that goes on, that excess ammonia will also use BH4 to be cleared. That’s why ammonia levels are so important. Now we’re going to talk later about NADPH, my favorite molecule.
Dr. Jill 16:53
Dr. Bob Miller 16:54
Yes. NADPH combines with BH4, oxygen, and something called arginine. Then the enzyme NOS takes it all and makes nitric oxide, unless something goes wrong. After BH4 is used, it turns into BH2. We can have genetic mutations in these enzymes that don’t allow it to come back. We’re going to talk later about ‘NADPH steal,’ where NADPH is used to actually make free radicals. You’ll notice there’s also heme right here. Heme is a cofactor. There are eight steps that we need [in order] to make that heme. And look who we have here: Glyphosate. Glyphosate can impact the glycine that’s needed for this heme cycle. These are people who often get hangry. They get very upset and angry if they don’t have food on a regular basis. So what happens if something goes wrong here? Oops, we make superoxide. That combines with that very important nitric oxide for ONOO, peroxynitrite. Guess what that does? It further suppresses BH4. And this feedback loop just keeps going. That’s why sometimes people will take L-arginine, thinking, “Oh, I’m going to build my nitric oxide levels,” and all they do is hurt [themselves] and get some viral infections.
Dr. Jill 18:33
Bob, I just want to make a few things that are aha [moments] for me clear, because I bet your listeners are saying the same thing. First of all, aluminum—sources of aluminum are super common, right? I can think of obvious [things like] cooking in tinfoil or using aluminum antiperspirants, which is why we should only be wearing deodorants. Do you know any others? I mean, vaccines nowadays contain a lot of aluminum. And again, I am not your anti-vaccine person, but we have to think about the load and all of this. I’m actually checking the aluminum levels of every patient right now. You would not believe the load of aluminum I’m finding. So that’s a really big deal. Ammonia—I know the gut can produce it, [as well as] some sorts of dysbiosis in the gut, especially bacterial and parasitic. Any other sources that are common for ammonia in patients that you know of?
Dr. Bob Miller 19:21
Well, sometimes eating too much protein, not chewing well, plus genetic mutations in the urea cycle [can cause that].
Dr. Jill 19:27
Okay. And then glyphosate is clearly in non-organic food. So if you’re not eating organic, you’re going to get that. And now we know even organic California wines have traces of glyphosate, so you can’t be too careful with that.
Dr. Bob Miller 19:39
Absolutely. And I forgot to point out lead. Lead inhibits NOS. And of course, we had lead paint many years ago and lead in our gasoline. So if you have aluminum and lead, your ability to make nitric oxide is compromised. This is where people get cold hands and feet, Raynaud’s, and high blood pressure. And we’ll show later how important nitric oxide is.
Dr. Jill 20:01
And L-arginine is not the solution. I just want to reiterate that. There’s a way bigger pathway here that you’re going to explain to us.
Dr. Bob Miller 20:08
Absolutely. So here’s the potential genomics. I’m not going to read them. Those are all the things that could go wrong and make it difficult: Lead, aluminum, and glyphosate. And here again, we can support the function. Okay, SAMe, S-adenosyl-L-methionine, methyl folate, [and] royal jelly can actually help you make more BH4. Yucca, larch, L-citrulline, and L-ornithine can help that urea cycle. Interestingly, witch hazel and rosemary will scavenge peroxynitrite. SOD will help you neutralize that superoxide so you don’t chew it up. Pomegranate, green coffee beans, garlic, and hawthorn all support the NOS enzyme. There’s a lot that can go wrong in there. That’s why, when we train our doctors on how to do this, looking at this is one of the first things we look at. Again, cold hands and feet, early varicose veins, hemorrhoids—all of those things can be related to that NOS uncoupling.
Dr. Bob Miller 21:12
Now I’m going to move over to iron. We all know that iron is critical. I mean, if we don’t have iron, we don’t carry oxygen, and life doesn’t exist. However, something can go wrong, so let’s look here. There are genetic mutations that people have very high in English, Irish, and Ashkenazi Jewish [descent] that cause them to over-absorb iron. That was actually adaptive. The Irish, during the potato famines, if they absorbed more iron, actually did better. But today we don’t have famine, and we’re putting a lot of iron in foods. So what can go wrong here? Again, we talked about [how] the body will make superoxide, sometimes on its own. We need superoxide dismutase to turn that into hydrogen peroxide. However, then we need something called catalase to turn that into water and oxygen. We need glutathione peroxidase to turn it into water. And we need thioredoxin to turn it into water. Now, glutathione and thioredoxin donate electrons. And you’ll hear this a lot. Look who’s needed to keep recharging: NADPH!
Dr. Jill 22:32
Is this where hydrogen can be helpful—because that’s a donor—either the hydrogen tablets or the inhaled? Would that be in this [inaudible]?
Dr. Bob Miller 22:41
Absolutely. Yes, right here we are. So what happens is when that iron—whether it’s in excess or not—combines with hydrogen peroxide to make what’s called a hydroxyl radical, which damages proteins, carbohydrates, and DNA. So here’s where your hydrogen water can come in and neutralize that hydroxyl radical. But we need NADPH, glutathione, thioredoxin, [and] catalase. A lot can go wrong in here. This is the most common thing I see. And actually, it’s what won me the research award in 2016 at the Helsinki ILADS meeting, showing that those with chronic Lyme were five times more likely to have one of the genes that would cause them to absorb more iron.
Dr. Bob Miller 23:28
Now, one of the ironies is that many times people say, “Well, I can’t be absorbing more iron because I’ve always been told I’m anemic.” Well, of course. If this is happening, if this excess iron is coming down here, you’re making more hydroxyl radicals. And then, if a well-meaning practitioner says, “Oh, I’m going to make you feel better by giving you iron,” if this is occurring, you’ll actually make the person worse. So what we have to do is get these pathways going, and then you have all the iron that you need. This is called the Fenton reaction, named after Dr. Fenton, who discovered this in 1895. Now, what continues to happen here? This OH- will stimulate iNOS, which is another form of nitric oxide, to make peroxynitrite. Now, on this drawing, we showed how this also leads to something called a carbonate radical CO3, which oxidizes your DNA. This is actually DNA damage that can occur. This is a very dangerous process. That’s why, as we said, hydrogen water, those tablets, the air that you breathe, or hydrogen machines can be some of the most important things. If someone said to me: “Bob, you can only take one thing. There’s a new law that [says] you can only take one thing. Call it.” I’d have to say hydrogen water.
Dr. Jill 24:56
Bob, I couldn’t agree more. People forget that they’re cheap and easy. Now the inhaling machines, which I have in my office, when I’m doing charts two or three days a week, I use it. I love it. I feel so good. That’s a $5,000 machine. Not everybody can get that, but everybody can afford hydrogen tablets. So I agree; I highly recommend those as adjuvant therapy and an easy thing [to do].
Dr. Bob Miller 25:17
Absolutely. I was just using my hydrogen machine before the call, just to make sure my brain was 100%. [laughing]
Dr. Jill 25:21
I love it. [laughing]
Dr. Bob Miller 25:24
All right, I’m not going to read these, but these are all the genetic mutations that can cause this to go awry. Again, glyphosate, hydrogen water, skull cap, clove, and alpha-lipoic acid can support the proper use of iron. SOD [and] catalase [also]. We’ll talk about this later: Nicotinamide mononucleotide supports the production of NADPH. Also, copper is needed to make ceruloplasmin. And many times there are also mutations in beta-carotene [conversion] to vitamin A. We need vitamin A and, of course, selenium for your glutathione peroxidase. Now, the beauty of looking at genomics is that you can see where you need support.
Dr. Bob Miller 26:07
Now, EMF—there’s just more and more information coming out about this. I think we’re going to look back someday and say, ‘oops!’ I often give the analogy: Think of asbestos. What a wonderful thing because the houses didn’t burn down and people didn’t die. But then there’s that unintended consequence. We thought lead would make our world better by making our paint better and our gasoline more effective. Oops!—I’m afraid we’re on the same path. Now what happens is that we have membranes that store electrical potential across their membrane in the form of an iron gradient, and this stores the electrical potential. Well, what happens when we’re exposed to EMF? That electrical potential goes up. This is a new chart we literally made days ago. So here’s calcium, and there’s a gene called CACNA1C that’s responsible for the calcium coming in. Now, once it gets in, it turns into calcium/calmodulin. I’ve never seen a genetic mutation more accurate than this one. Mutations on this—I’ve never seen anybody who didn’t have it, who didn’t tell me that they’re sensitive to EMF. They’re more impacted by EMF. And this, of course, creates inflammation on its own.
Dr. Bob Miller 27:37
But since we’re talking about peroxynitrite, what does the EMF do? It creates nitric oxide from the superoxide in the EMF and makes the peroxynitrite. It’s yet another method to cause inflammation inside the cell. One of the things July and I question—I’m not saying this is a fact, but Bob Naviaux has done some great work on the cell danger response—and I have to wonder [about also is] if this is not a factor involved in the cell danger response when the body is just kind of in that half-shutdown trying to preserve itself, because inside the cell all of this is going on. That’s why making sure you’re not sitting next to your router all day and not carrying your cell phone on your body [is important]. Use the speakerphone or earbuds—not the type where you put the transmitters in your head, but at least those wired or air ones. I often tell people who have this as their severe problem: “You need to make your house very dumb. Do not have a smart home.”
Dr. Jill 28:45
Yes, I couldn’t agree more. I would say if you are sensitive, you need to get wired internet, of course. I still have Wi-Fi, but I’m actually not as sensitive. I probably should. A lot of my friends just recently said, “Jill, you know better; you need to get wired” [internet]. So I’m probably going to be doing that, but right now I have a router cover that protects me. And I had a building biologist come to my condo here and check everything out. There’s a meter they’ll put on your body to see the voltage, and then they’ll check as they turn switches and check the electricity. My measured body meter voltage was over 3,000 on the bed—I just laid in my bedroom on the bed—with no special lights, nothing special on. When I turned the master bedroom switch off, it went to less than 200. That was a shock to me, which means I have an appointment to get a master switch with a remote so that at night I can turn off the electricity just in my bedroom by remote. And I would highly recommend, if you have the resources, getting a building biologist to come check your home as well.
Dr. Bob Miller 29:44
Well, you said it was a shock to you—no pun intended.
Dr. Jill 29:47
Right, exactly. [laughing] And Bob, the funny thing was that I would tell you: I’m not really EMF sensitive. I mean, I do wear bioelectric shields. I protect myself. I do a lot of things, but I don’t feel that physically ill from it on the spot. However, as soon as she turned the breaker, my heart stopped fluttering and went still, and I didn’t even notice it. It wasn’t like I had tachycardia or anything, but I felt the physical sensation of the change, so it’s very real.
Dr. Bob Miller 30:13
Absolutely. And these teenagers who keep their cell phone under their pillows to hear if a text message comes in—
Dr. Jill 30:17
Unbelievable! [They leave it] by the brain. There are glucose metabolism studies that show the distance from your brain absolutely affects brain glucose metabolism, and it’s exponentially… So if you have your phone right next to your head, it’s a very, very bad situation.
Dr. Bob Miller 30:32
Yes, I recommend getting [something] like a battery-powered alarm clock rather than using your cell phone. People tell me, “Yes, it’s right by my head because I use it as my alarm.” I think there are going to be serious unintended consequences from that. So, potential genomics, the CACNA1C that we talked about: Making sure you have enough superoxide dismutase, NOS is working okay, and you have enough glutathione. Of course, the epigenetics is the EMF. I’ll never forget [when] I heard a lecture from Dr. Sinatra, and he said, “If you come to our house, we have princess phones on the wall.” [laughing]
Dr. Jill 31:10
I love it! [laughing]
Dr. Bob Miller 31:13
So magnesium, witch hazel, melatonin, rosemary that we talked about, and superoxide dismutase. And I think so many people are using [things] like Netflix, which they stream to their television. I think it’s a good idea to have your TV wired rather than streaming it because you’re exposed to so much EMF when you do that.
Dr. Jill 31:34
It just adds up, so anything that you can do to decrease [it is beneficial]. And I noticed Rosemary is coming up over and over and over again. I’m a 19-year breast cancer survivor. That’s a big one for breast cancer, and there’s no doubt there’s a connection to this pathway because of the DNA-damaging effects, right?
Dr. Bob Miller 31:50
Oh, absolutely, because it’s taking care of that peroxynitrite. Now, glutathione—most people know about this—is a major antioxidant. It neutralizes superoxide. It neutralizes hydroxyl radicals. It’s one of the powerhouses of the cell. It regenerates vitamins C and E. It’s involved in detoxification. Aging and degeneration—as we age, our glutathione levels go down. So we tend to think of glutathione [as]: “Cool, the more the better!” And I’m sure, Dr. Jill, have you ever given someone glutathione and they had a negative response to it?
Dr. Jill 32:24
Oh, yes, Bob, and that’s my story. I just talked to a colleague. I was like, “I was like that for two years.” So tell us more, because I’m one of those people.
Dr. Bob Miller 32:33
Yes, well, here’s what happens. Glutathione—up here, we just show how it’s made for fun. It’s N-acetyl cysteine. Up here would be your glutamate [and] your glycine, and then the GSS enzyme makes your reduced glutathione. And then glutathione, through glutathione S-transferase, does what’s called phase II glutathione conjugation, where we take out toxins and put them in the stool or the urine. Then, also, glutathione peroxidase neutralizes free radicals, so we tend to think the more the better. However, some people take glutathione and they’re like, “That is the most wonderful thing I’ve ever had.” And then other people are like: “I can’t take that. I feel horrible when I take that.” So let’s look at what happens.
Dr. Bob Miller 33:23
Glutathione does its job, donates an electron, and it becomes GSSG, or oxidized glutathione. Look what oxidized glutathione does. You’ve heard this before. It combines with oxygen to make superoxide, then chews up more of your nitric oxide to make peroxynitrite, ONOO. And then we have to even use some glutathione to deal with that. Here’s why I think NADPH is so critical and not enough people are looking at it. NADPH donates an electron to the oxidized glutathione to take it back to the reduced. And again, these are just some of the things that’ll make the NADPH. And I’ll be talking later about the ‘NADPH steal.’ So when you take glutathione and it doesn’t recycle, you have a problem. Isn’t that fascinating?
Dr. Jill 34:24
Yes, that makes so much sense. I find that when we do give people the donors to make NADPH, it does help with these pathways.
Dr. Bob Miller 34:33
Absolutely, yes. That’s why I believe that we have to learn if somebody has an NADPH deficiency and support this before we start putting this in.
Dr. Jill 34:44
I was just going to say that the first piece is often not what you think of, like you said in your analogy of the house and the fire and what to do first. I love that because many practitioners are just [doing] this protocolized thing where it’s glutathione and liver support and detox. Patients aren’t ready for that if they don’t have the nutrients in place. And with your genetic testing, you can tell exactly what things people might need more of beforehand.
Dr. Bob Miller 35:09
Yes. And the most common thing I see in those who are suffering the most is that they’ve got either NOS uncoupling or a Fenton reaction along with NADPH deficiency. It’s the most common thing I see. So we need to look at some of the enzymes that are involved in making NADPH. I didn’t mention it in that chart, but there’s something called NERF2 and KEAP1 that control all the glutathione and NADPH genes. GSR, I should mention, is the enzyme that uses NADPH. So even if you have enough NADPH and GSR is not working, this isn’t occurring. The double whammy is NADPH deficiency and GSR problems. So glyphosate can be a problem. Nicotinamide mononucleotide, pau d’arco helps NADH to NAD+, and grape seed extract helps the quinolinic acid move down the pathway. And then a few things for NERF2: Milk thistle and broccoli seed extract to support NERF2. But again, if you support NERF2 too quickly, it can actually put people in inflammation. So again, sometimes it’s like: “NERF2! Yes, it’s so important!” People support it, and they get worse.
Dr. Bob Miller 36:26
All right, now this is probably the most important thing I’m going to talk about: NOX, NADPH oxidase. It’s my favorite subject. I’ve been talking about this for two years. It’s the only enzyme whose sole purpose is to make superoxide and hydrogen peroxide. Now we tend to think, “Well, why would it do that?” Well, again, the wisdom that God put in the body is absolutely astonishing. So when we’re hit with a bacteria or some other pathogen, the body [in essence] says: “Whoa, we’ve got a problem here. We need to create some superoxide and hydrogen peroxide, stimulate some mast cells, stimulate some cytokines, make some histamine, and let’s go in for the kill.” If we didn’t have that, we’d die of infection. [It’s been seen] in animal studies where they take it out. So this is an important process. I give the analogy: It’s kind of like the military. You want a military that protects you, but you don’t want a military that’s turning the guns on the citizens. And one of the areas that we’re researching is our epigenetic factors—stimulating this NOX enzyme to start shooting when there isn’t an enemy—and that’s one of the areas that we continue to research.
Dr. Bob Miller 37:41
Now, we’re really going to bend your mind with this chart. What I’m going to do is pull this one over so we can look at it just a little more closely. So the NOX enzyme is needed to create this cytokine storm and mast cells when we are faced with an outside invader. However, histamine will make it go. Oxalates will stimulate it. Excess iron will stimulate it. Glutamate will stimulate it. Smoking or particulates will stimulate it. Aldosterone, which I’m going to speak about in a minute, stimulates it. Homocysteine, dopamine, sulfite, and something called mTOR stimulate it. So when it gets stimulated, it gets oxygen from iron and an electron from NADPH. Now, keep in mind that we just learned we need NADPH for nitric oxide. We need NADPH for glutathione. We need NADPH for thioredoxin. So that’s why I coined the phrase ‘NADPH steal.’ This NADPH is being used excessively to create this storm. So then it creates the mast cells, and here are mycotoxins. Here are Lyme disease, EMF, and xenobiotics. The mast cells will then create cytokines and stimulate these interleukins, tumor necrosis factors, and histamine. [These are] all good things when we’re fighting a battle and we have somebody to take care of [or] to take out, [but] when it’s running amok, we have a problem.
Dr. Bob Miller 39:28
Now, this is some of the latest research that I think is very exciting. We have something in the body called renin, and that stimulates angiotensin I. The ACE enzyme makes angiotensin II. That stimulates aldosterone, which then stimulates the NOX enzyme. And of course, we know this is what’s behind hypertension. There’s an enzyme called HMOX that calms this down. When people have mutations in HMOX, they can’t calm this down. Now, there’s an enzyme called ACE-2 that takes these pro-inflammatory vasoconstrictive molecules and turns them into angiotensin I-7, which is vasodilative and anti-inflammatory. As a side note, COVID-19 comes in using ACE-2.
Dr. Jill 40:17
I was just going to say that I know where you’re going with this because a lot of the side effects we see are from that vasoconstriction, correct?
Dr. Bob Miller 40:24
Absolutely. So this angiotensin II then stimulates interleukin-6, which is behind the cytokine storm. Interleukin-6 stimulates NOX, and it goes around. But here’s what’s really exciting. I just presented this to my doctors last night at a webinar. Histamine, mast cells, and peroxynitrite—remember, whenever you have superoxide, you’re going to get peroxynitrite; hold on to your hat—stimulate renin. And here we have a positive loop that just feeds upon itself. High glucose, peroxynitrite, histamine—[there’s] conflicting information on dopamine—but also testosterone stimulate the renin. This might be one of the mechanisms behind the cytokine storm. So for example, if something kicks this off, like if a child gets a strep infection and then goes PANS and PANDAS, or, as you said earlier, we’re not anti-vaxxers, but if you get aluminum and the aluminum stimulates this, this could be one of the mechanisms that causes this to feed upon itself. Now, what’s interesting is that nitric oxide and oxytocin calm down NOX and mast cells. And if your nitric oxide is being destroyed, we don’t have it. And of course, oxytocin is the love hormone. So go hug somebody or at least hold your cat or your dog to get your oxytocin.
Dr. Jill 41:57
Bob, we’ve had social isolation for two months, and [things are] starting to come back, but we’re not frequently hugging one another. Hugging is one of the main mechanisms that’s not breastfeeding or sexual that increases oxytocin. For months, I’ve said: “Yes, I agree with what’s happening. We need to take precautions. But we’re not thinking about the fact that social isolation is a huge risk factor for immune dysfunction.” And now you’re telling me it’s a huge risk factor because you have less oxytocin production for the blocking of this enzyme.
Dr. Bob Miller 42:27
Absolutely. So I’m really excited about this pathway. And clearly, there are way too many genes to go into here, but these are all the genetic mutations that could contribute to that. Here are all the epigenetics that could combine to it. And then luteolin, PEA, and Boswellia calm down the mast cells. Quercitin can support the histamine response. [There’s also] methylation support if [you have] elevated homocysteine. And as we said, mold remediation is so important. Air purifiers and superoxide dismutase—we spoke about those before—can support the NOS enzyme. So I believe this might be behind why we’re seeing such a rise in autism. Dr. Theoharides from Tufts University believes that mast cells are stimulating the hypothalamus. That may not be the whole answer, but there’s the potential that this could be an issue that needs to be researched. So I think for anyone who’s doing functional medicine, trying to determine if any of these factors are up-regulating this is critical. And now you can see why I call it the 3D chess game played underwater.
Dr. Jill 43:40
I should say, Bob, that is a key [slide]. Go back one more time to that slide. We have a minute. This is so key, I just want to hone in on it. I’m having about 101 aha [moments] now as I think about this. I think about what we just went through with the pandemic, [what we] have ongoing, and the types of risk people have—whether it’s a predisposition, diabetes, or heart disease—have to do with a lot of these pathways. And the same cytokine pathway is active with lipopolysaccharide endotoxemia, which is a long technical word for leaky gut when you have bacterial coatings leaking into the immune system. They stimulate the same IL-6 pathway as well. And I feel like a lot of the risk factors we’re seeing with heart disease, diabetes, and age are more likely to have some of these things already primed. And then you just gave us a list on that other slide of the allergies, mycotoxins, and Lyme disease. These are all likely to lead to more inflammatory states, more risk of infection, and probably more risk of the virus becoming an issue.
Dr. Bob Miller 40:41
Absolutely. And that’s why sometimes bodybuilders who are trying their best to keep their testosterone high and stimulate their mTOR might be at the highest risk right now.
Dr. Jill 44:51
Dr. Bob Miller 44:53
Yes. Now, one of the things we just heard was that there was a drug that was discovered in England that seems to get people out of the cytokine storm. We immediately researched this, and what we found is that it inhibits the NOX enzyme.
Dr. Jill 45:07
Wow. And I think you sent me that study. I remember us talking back and forth. If not, I would love to see the research. That sounds so familiar because of the peroxynitrite and the cytokine storm. The cell danger response—it’s almost like we’re all looking in our areas at the same thing and describing it, but it all comes together with such cohesiveness because it makes sense. And to pull it back together for a practical takeaway—otherwise, this is overwhelming—first of all, if you can get with a functional medicine doctor, especially one that’s been trained by Bob, they can help you walk through these pathways. I know Bob consults himself, but do you mostly teach doctors, Bob?
Dr. Bob Miller 45:48
Yes, mostly. We have online certifications for doctors. I do a lot of one-on-ones with doctors where they’re like, “Bob, I need help with this,” and I’ll walk them through it to give them the guidance they need. And I can just say that if someone is a doctor and they’re interested in the software, there’s the website, DNASupplementation.com. Yvonne Lucchese is the executive director. She can help. And if someone wants to contact our office, there we are Tree of Life Health. There’s our phone number and our website. Also, there’ll be links there to our conference, September 18–20. And I have an online certification course for doctors—we have probably around 30 hours of instruction—that step-by-step takes them through that NOS uncoupling, the glutathione, and the mast cell activation. So if doctors want to learn this, we have a resource for them [to do so].
Dr. Jill 46:46
Excellent. Bob, I’m going to share this with my practitioner list. And I’m going to ask you guys, if you’re listening, if you have a doctor you know on Facebook, or another medical provider, or someone who is in the functional medicine realm, please share this information. Share this lecture with them. I think everybody should get to know Bob Miller. He is one of the brightest stars out there. And what I love about Bob is that you can tell he’s brilliant. I love talking [about] pathways [with him], but even more than that, he’s got a really great heart. He really cares about people, and he cares about finding solutions. Every single time we talk, Bob, I learn something new. I am so grateful for minds and hearts like yours that are out there just continuing to do the science because this is the kind of thing that really pulls it together. And as we both know, this is the only thing that’s really going to change our system. A drug itself might be a potential solution, but a drug is not going to help 100% of the population because of these genetic variations. So we have to have solutions that are more personalized.
Dr. Bob Miller 47:44
Absolutely. And let me also say that I think the world is very fortunate that you’re out there leading the way and helping educate so many doctors. I think when the books on functional medicine are written, there’ll be a large part talking about Dr. Carnahan. You have a beautiful heart as well; you want to help people get well. So I have the utmost respect and admiration for you.
Dr. Jill 48:04
Thank you so much, Bob. This has been a real treat. Please be sure to share. I’m going to include in the links the things that you saw on the slide as well. So if you missed it, you can also watch this again, but I’ll be sure to include it all. Thank you!
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