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In this episode, you will learn about the Cell Danger Response and explore a different perspective on recovering health from chronic illness.

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About My Guest

My guest for this episode is Dr. Neil Nathan.  Neil Nathan MD has been board certified by the American Board of Family Medicine and the American Academy of Pain Management. He is a Founding Diplomate of both the American Board of Integrative & Holistic Medicine and the International Society for Environmentally Acquired Illness or ISEAI.  He is the author of several books including "Toxic: Heal Your Body from Mold Toxicity, Lyme Disease, Multiple Chemical Sensitivities and Chronic Environmental Illness" and "Molds and Mycotoxins: Current Evaluation and Treatment: 2016".  He is internationally recognized as a lecturer and teacher in the field of integrative medicine.

Key Takeaways

  • Is the Cell Danger Response (CDR) similar in concept to the need for "rebooting"?
  • What are the triggers of CDR?
  • What are purinergic signaling and purinergic receptors?
  • What are the key changes that occur when we enter a CDR?
  • What are the various CDR states?
  • What treatment options are appropriate in each state?
  • What needs to occur to move from one CDR state to the next?
  • Is lab testing and exogenous supplementation at times going against the wisdom of the body?
  • How can the current CDR state be determined?
  • What metabolomic changes have been observed?
  • What is Suramin?
  • Are there natural treatment options that can help move through the CDR?

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Interview Date

June 12, 2020 


Transcript Disclaimer: Transcripts are intended to provide optimized access to information contained in the podcast.  They are not a full replacement for the discussion.  Timestamps are provided to facilitate finding portions of the conversation.  Errors and omissions may be present as the transcript is not created by someone familiar with the topics being discussed.  Please Contact Me with any corrections.  

[00:00:01.02] Welcome to BetterHealthGuy Blogcasts, empowering your better health. And now, here's Scott, your Better Health Guy.

[00:00:13.11] The content of this show is for informational purposes only and is not intended to diagnose treat or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice, or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.

[00:00:34.12] Scott: Hello everyone, and welcome to episode number 121 of the BetterHealthGuy Blogcasts series. Today's guest is Dr. Neil Nathan, and the topic of the show is Cell Danger Response. Dr. Neil Nathan has been board certified by the American Board of Family Medicine, and the American Academy of Pain Management. He is a Founding Diplomat of both the American Board of Integrative and Holistic Medicine and the International Society for Environmentally Acquired Illness or ISEAI.

He is the author of several books including ''Toxic: Heal Your Body from Mold Toxicity, Lyme Disease, Multiple Chemical Sensitivities, and Chronic Environmental Illness''. And ''Mold & Mycotoxins: Current Evaluation and Treatment 2016''. He is internationally recognized as a lecturer and teacher in the field of integrative medicine, and now my interview with Dr. Neil Nathan.

I have been looking forward to this conversation for quite some time; it's an honor for me to have Dr. Neil Nathan back on the show today.  I first heard him speak about Cell Danger Response at a conference five years ago. He is my first-ever three-time guest on the podcast and this is going to be a fun ride. Thanks so much for being here today Dr. Nathan.

[00:01:53.27] Dr. Nathan: Thanks Scott, no pressure.

[00:01:57.11] Dr. Nathan: Since you've been on the show before, I’m not going to ask my normal intro question. But I’m interested in how did you become aware of and interested in Cell Danger Response? And what was it about it that grabbed your attention? And then are you continuing your collaborations with Dr. Naviaux in his ongoing research in this area? 

[00:02:17.15] Dr. Nathan: Sure. Actually, I might not look good telling the story, but I’ll tell it anyway. I got an advanced copy of a paper that he wrote in 2013 called ''The Cell Danger Response'' and I read it. This kind of thing that you read casually, and then I read it, and it was the most phenomenal putting together of information that I’d come across in a very long time. It was biochemically super accurate, comprehensive and I was so impressed with the paper that I actually made a mini-presentation to the clinic I was working at the time.

I distilled it down to five pages of notes, and that was distilling it. And then I did what I always do, which is I reached out to actually talk to him. And he was not an easy person to get hold of. So I called him, I emailed him; I left messages, never returned any of my requests. Fortunately, I had a mutual friend who I know knew him and had access to him, and I asked her if she would introduce us so that I could actually get to him. So literally, and I am proud of this, I stalked him, I did. And I was giving a lecture at ILADS when I was in San Diego and Bob's lab is there.

And so I finally did reach him on call and said would you meet me for lunch. I just want to meet you, I think your paper is incredible, I just want to talk about it and he agreed. And so at that time, I was working at the Gordon Medical Center and Eric Gordon and Wayne Anderson and I had lunch with Bob. And it went for a very long time, we went on through the afternoon just sharing ideas and throwing ideas back and forth. It's the kind of dialogue that I eat up, for me, this is what I live for.

And out of that dialogue came one of the papers that Bob wrote, which is measuring metabolomics in chronic fatigue patients. Because we had a ton of patients with chronic fatigue, and we could provide the clinical material, he provided the metabolomics analysis and that became one of his more important papers that was published several years later on the metabolomics of Chronic Fatigue Syndrome. So with that meeting, Bob and I became friends. My wife in fact calls our relationship a “bromance” because I adore Bob, he's one of my absolute favorite people.

In addition to being one of the brightest men that I’ve known, he also has a renaissance mind. He thinks comprehensively, he's a lovely person and I’m honored that we basically will talk for about an hour at least one Sunday a month in which we're just tossing ideas back and forth. And I’m also honored that he respects my writing abilities so that he'll usually give me a draft of pretty much anything he's writing for my input as to how clearly it's written. Is he saying it the way he wants to say it, is this clear enough? And I’m absolutely honored to be able to work with Bob. So the answer is ongoing, one of my favorite people and we can talk about his work, yes.

[00:06:02.23] Scott: Yes. That's wonderful; it gives me hope that there are collaborations like that happening in the field that result in better clinical directions for people. So this is a little bit of a long one, but the idea of being stuck or needing to reboot is a concept that you've introduced in your book in Toxic. I kind of visualize the cells of the body much like a house with a hurricane surrounding it, and so we pull down the storm shutters.

But we get so afraid that we never open them again. And so, the Cell Danger Response model appears to be somewhat similar in terms of being stuck the potential need for rebooting. Dr. Naviaux has said that we need to signal that the war is over and that we can return to normal metabolism and use ATP for growth and recovery instead of starting endless wars. So with that, I’m interested at a very high level, how do you see the Cell Danger Response, what is it?

[00:07:02.11] Dr. Nathan: Well, I see it as a profound model that helps us to understand much of chronic illness. And by that I mean some of the biochemical underpinnings of chronic illness, now it's not all chronic illness, but much of it. Some of the named illnesses that we see most commonly Chronic Fatigue, Fibromyalgia, autism, neurodegenerative diseases; all of these share the Cell Danger Response as an underlying issue. And it's a very primitive millennial old way in which we are simply responding to threat.

So how do we respond to threat? Well, we shut it down, it's very simple. Your analogy of putting down the storm shutters in a hurricane or a tornado is valid; we shut it down. We want to hold whatever the threat is at bay until we can harness our optimum resources to deal with it and heal. And the second piece of it that you mentioned is particularly germane in the concept of the COVID pandemic that we're currently living with. Which is in response to COVID, we responded in a very particular way, we shut it down. And one of the concepts of the Cell Danger Responses, the way you deal with it is not necessarily the way out. So shutting it down is a way to start dealing with it, but we will be forever different and changed because of COVID. We are not just going to go back to the way we lived before, it isn't going to be simply okay, the viral threat's over, we're going to go back and live our lives. We're all changed, we're all different.

We all live in a different world; we all think of danger differently than we did. And this is a beautiful analogy to the way the Cell Danger Response works because once an organism and you can think of it as on a cellular level, you can think of it as a generic level. Once an organism has responded in a way it is primed for any other threat, and part of the aging process, and Dr. Naviaux writes about this beautifully, is that aging is essentially a process of having recurrent threats that we deal with, which leave us a little bit more metabolically compromised every time they happen.

So that's what COVID is going to be doing to us. We're not going back to the same world that we started two and a half months ago, the world that we enter will be more fearful. We'll all have PTSD for a while, and we'll all cope with it in different ways. And metabolically, our immune systems may be different than how we interact as people will be different. So it is hard, it's a way of understanding threat and how the body responds to that biochemically so that we can understand how to orchestrate a response to that threat.

[00:10:44.15] Scott: In your clinical experience, what are some of the top triggers or activators or initiators of the Cell Danger Response? What do you most commonly see in your patients that activates this entire protective mechanism?

[00:11:00.11] Dr. Nathan: Well, without any question, in my world the two biggies without question are Lyme with its co-infections and mold toxicity, those are the biggies. Other big players are other environmental toxins, and that includes chemical toxins, heavy metal toxins. Includes EMF exposures, and I have to include stress as a major threat to the system. So other things that we focus on I don't find generate this type of response quite the same way, for example, there are other infectious agents, lots of viruses, parasites, other bacterial infections.

But these are the ones that tend to trigger this type of response because it's really important for people to understand that not every infection triggers a profound stuck Cell Danger Response. So any virus will trigger that response, it's really simple. The virus is perceived on a cellular level as a threat, and within seconds the cell with the mitochondria being the sensors of threat, the cell goes oh, we got a problem here and it goes through a series of orchestrated almost like a dance of biochemical shutting down to allow the body to heal until we get on top of that virus.

Take a cold, okay. So we get a cold, we deal with it successfully. We haul out our cytokines, our immune system fights the cold successfully and then we bounce back. So we don't take much of a hit from that, that's pretty straightforward. We haven't really fully engendered the stuck part of the cycle, we've just used the beginning part of the cycle to harness our immune response and we get better, it's great.

But in stealth infections or in toxins that may be difficult to get rid of, that quick response, quick in and out immune system up and running, get this out of here we're done, we don't engender that quick response. It's a much more prolonged response. We start it the same way, we get it off the ground, the Cell Danger Response gets going, but then we haven't gotten rid of the infection.

Lyme disease, the Lyme bacteria is one of the slower-growing bacteria, almost all of the bacteria in the Lyme world that we call co-infections are intracellular organisms, they get inside the cells, they are not as easy to get rid of so they stick around. Our immune system has to deal with it in a prolonged way. And once we get prolonged, that's when this thing kicks in, that's when the Cell Danger Response goes beep, beep and it doesn't turn off, it's like a car alarm that doesn't turning off. It gets very annoying when you have to listen to that.

[00:14:21.22] Scott: When we think of Cell Danger Response, I think most people think that the entire body is either stuck or not stuck. But can various groups of cells or tissues or organs be in a Cell Danger Response when others maybe are not? Or possibly some areas in the body are in a different phase or stage of the Cell Danger Response? Is that possible?

[00:14:48.09] Dr. Nathan: It is. Generally, what is affecting a cell ultimately will affect the whole body. However, and Dr. Naviaux uses the term mosaic to describe the process that at any given moment in time, you can have certain tissues of the body in Cell Danger Response 1 and other tissues will be in Cell Danger Response 2, and others will be in Cell Danger Response 3. So it is not a clean, we're always in the same thing in a uniform way. Different parts of the body are operating in different ways with different capacities, with different genetics. So it's a tad more complicated than just every cell in the body is going through this at the same time, not quite.

[00:15:42.25] Scott: You mentioned mitochondria, so let's talk about that a little bit about ATP. I think many people think that to heal that we need to support the mitochondria that we need to produce more ATP. But that may not necessarily be the case in this Cell Danger Response model. So talk to us about extracellular ATP, the role that it plays as a danger signal. Can that be measured in some way, and why might attempts to create more ATP potentially backfire?

[00:16:14.26] Dr. Nathan: Okay, wonderful questions. So we all know that ATP is the major energy molecule of the body. And accordingly, we think of it as a good thing exclusively. Which is if we're fatigued, make more ATP, that's a nice, simplistic answer. However, as an intrinsic part of the Cell Danger Response, one of the first things that happen when a cell feels threatened is it changes ATP from an energy molecule to a signaling molecule.

So it stops using it for energy. And think of this in terms of let's say you have a flu, your body grounds you, you're exhausted, absolute fatigue, malaise. Don't want to get out of bed, that is a part of the healing response, it's part of these Cell Danger Response to convince the organism to not attempt to overdo or do what you can't do. You don't have the ATP resources, you don't have the energy right now, shut it down, rest, go to bed, sleep that is a part of the healing response.

So we're stopping the way we use ATP, and instead, it is leaving the cell as a signaling molecule, and it is the creator of beep, beep danger, it is the molecule that's doing it for us. So when the extracellular percentage of ATP goes up, that is a signal to the entire body we're under threat right now, shut it down. And Dr. Naviaux has outlined beautifully a host of other biochemical changes that accompany this. And so you're absolutely right, to tell someone with a chronic illness that they have a mitochondrial dysfunction, tells us nothing.

Of course, you have a mitochondrial dysfunction, it comes with the territory. You have to, your body is changing the way you use energy to deal with this chronic illness, regardless of which threat it is, the body doesn't care, it's going to do this anyway. So if you use strategies to stimulate the body to make more ATP, it will either do nothing or make you worse, it's the wrong way to go. And I see a ton of people referred to me who are on all kinds of mitochondrial building materials. They're taking Coq10 and L-taurine and L-carnitine and D-ribose and malic acid, whatever your favorite products are, and their physicians are baffled that it's not doing anything.

Well, you're dealing with an organism that can't use it, it's on survival mode, it can't use that. And so one of the most important concepts of the Cell Danger Response is, it's really important to try to figure out which part of that response that organism is in, or you're going to be giving treatments that will either do nothing or hurt the person, and you're going to spin your wheels for a long time because you're not addressing the cause.

[00:19:57.26] Scott: Is there a way to measure extracellular ATP or is that not available?

[00:20:02.10] Dr. Nathan: Not clinically no, not yet. I know that Dr. Naviaux's working currently on a variety of things that may help us to understand what stage of the Cell Danger Response you're in, but we don't have that currently available.

[00:20:17.22] Scott: So before we jump into the shallow end of the pool because we'll never get into the deep end of the pool in this topic in 90 minutes. Talk to us about what is purinergic signaling, what are purinergic receptors? How do they fit into a Cell Danger Response discussion?

[00:20:34.10] Dr. Nathan: So ATP is a purine, so purinergic simply refers to ATP and some of the similar molecules of which ATP is the best known. A purinergic receptor is one that like all receptors, you've got a structure on the edge of every cell and that cell is intended to bind to ATP when it comes around. So a purinergic receptor simply accepts ATP.

There are 19 known purinergic receptors, and they respond to ATP in such a way that they participate in this shutting down process. So if we're talking about using a medication like Suramin, which is an anti-purinergic, it blocks the receptor site so that it the ATP can do its job and is no longer blocking. In other words, it reverses this process and has the capacity to turn off that danger signal.

[00:21:41.29] Scott: At a very high level in some of your prior talks, you talk about eight key changes that happen when we enter this Cell Danger Response. So can you tell us what actually happens, what are these eight key changes that we see?

[00:21:54.16] Dr. Nathan: Well, sure and these all occur virtually simultaneously and almost instantaneously once it gets triggered. So just to tell you how it gets kicked off, the mitochondria in a cell are exposed to a threat, either a toxin or an infection. They immediately register that threat as a drop in voltage in the cell, and that drop in voltage triggers the body immediately to go into what we call oxidative shielding. Now for years, people have talked about oxidative stress in which there's free radicals that are produced, reactive oxygen species that come into play and that's always been thought of as the cause of the illness.

In point of fact, that isn't necessarily the cause of the illness, in one of Dr. Naviaux's profound papers is literally titled ''Oxidative shielding versus activated stress''. Where he's trying to shift consciousness that this oxidative shielding is the oxygen level in the cell rises, shutting off a whole lot of other processes inside the cell and that is protective. It's not intended to harm the cell, it doesn't need to be treated.

So in the same way that we just talked about maybe treating mitochondrial dysfunction isn't the right strategy initially, maybe using antioxidants isn't the right strategy, we are messing with the body's innate intelligence and it's knowledge that no, I’m creating the correct milieu, chemical milieu in which healing can occur. Don't mess with me, and again by understanding this we can make progress. So once that gets triggered, there are eight specific things that are a part of that. One is that the body immediately changes its metabolism, it goes from what's called polymer metabolism to monomer metabolism.

Now to translate that into English, polymer metabolism is we are making proteins out of our amino acids, we're making complicated sugars that we work with and polysaccharides. Well, the microbes that are trying to infect that love that, because they can't make all of that for themselves. Literally, they are hijacking our chemistry to make those materials, so we shut it down intentionally. So we shift from making those complicated materials that they can't make but need, and we instead shift to monomer metabolism which is simply simple sugars, simple amino acids, simple fats, that's one. Another thing that we do is we change the way we metabolize sulfur.

Now that's much more relevant in terms of glutathione, one of the most important sulfur-containing materials in the body. We need glutathione to help process toxins; we need glutathione to help with oxidative reduction reactions. And unfortunately, we use it up very quickly in the initial stages of the Cell Danger Response. So how do we make glutathione? With methylation. So the cell intentionally shuts down methylation to stop making glutathione, so that the body can't harness methylation either.

For example, viruses can't replicate unless they hijack our ability to methylate, our ability to make histones so that they can replicate their DNA which is what they do. They can't do it, unless we're offering them here, methylate to your heart's content you know make all the materials you need, we shut it down. So again another area that is often misunderstood is oh, you're not methylating very well. Well duh, of course, you're not methylating well, it's part of the deal. So again, many practitioners have discovered that attempting to give methylation early on in the course of illness will backfire.

In my patients who tend to be very sensitive, the vast majority can't take methylation materials, it'll make them worse and for other people, it won't do anything. So do you need to methylate? Eventually. But not in the beginning phases, because we shut it down. We shut down, we change tryptophan metabolism. We make tryptophan into, there are two different big pathways you can take depending on the enzyme that's working on the tryptophan, which is just an amino acid.

We can either make serotonin from which we make melatonin, or we can make kynurenic acid and quinolinic acid. Now the latter will trigger IL-6 it's inflammatory and it's long associated with a great deal of psychological issues like anxiety and depression. Obviously, serotonin helps us to cure depression and feel better. Which pathway does the body use, that depends on that person's innate chemistry and genetics, but that's another part of the deal. It changes how we process vitamin D. The enzyme that normally we utilize to bind and work with vitamin D shifts.

So our vitamin D levels drop, it changes the way we metabolize B6, the biome changes. There's an automatic shift in the biome through the Cell Danger Response because it is becoming less open if you will to all of these exogenous issues. An interesting paper by the way on the biome reboot, Dr. Naviaux did a paper with mice that can be autistic. And he took Suramin and he gave them to the autistic mice, and he measured a whole host of parameters including their biome. One injection of Suramin normalized the biome completely in these mice doing no other interventions. So again, we do elaborate treatments to reboot our gut. We are taught in functional medicine, the gut is the most important area that needs to be treated first.

Well, you're going to find for example if you have mold toxicity that you won't be able to fix that biome until you fix the mold, because it's triggering the Cell Danger Response, you're just not going to do it. Fix the Cell Danger Response in many ways the biome will often reboot itself. So the wisdom in Dr. Naviaux's work here is it's helping us to understand when we need to intervene with our knowledge of functional medicine.

It's not enough to know what's deficient, we need to know when is that organism able to use that in the service of healing, or are we just piling up a whole bunch of supplements that it's got a process, it's on survival mode, it can't possibly deal with that. So those are some of the eight basic principles that this contains.

[00:29:46.13] Scott: I want to bring in the seasonal cycle conversation, and understand how that fits into the Cell Danger Response. So historically, we were more impacted by natural seasonal cycles. We feasted in the summer; we were hungry in the winter. But that's not the case with our modern lives; we have access to things all the time.

We can essentially confuse our metabolism. So if we look at modulators of metabolism like mTOR which is more summer and protein synthesis and growth versus winter which is more AMPK activation, stimulating autophagy or the cellular cleansing. Is there some benefit to us attempting to approximate these seasonal cycles on a daily basis through the use of fasting for example? And how does this perspective on metabolism tie into a conversation on the Cell Danger Response? 

[00:30:43.20] Dr. Nathan: Okay, all good points and very nicely stated. So just to rephrase that a little bit, summer metabolism, let's say we have a primitive tribe and nutrients are rich in the summer. We've got all kinds of growing plants to harvest; we've got easy access to fish and wild game and all the things we eat. So we can eat to our heart's content during the summer.

In the Native American traditions, for example, they would have their end of season hunt and they would cut buffalo and they would take blueberries which were ripe at that season and they would make pemmican for winter use, which is a mixture of those two. But basically, they would literally pig out during that season, knowing that winter was coming and they weren't going to have any access to that at all. Now, as you're pointing out, we don't go through winter anymore. So if I want to eat blueberries or kiwis or anything at any time of the year, it's in the store. I can eat anything at any time. In those days, they only ate seasonally. And what it did to their metabolism is you tended to gain weight and fill out and grow during the summer, and in the winter you're regrouped.

Metabolically, regrouping meant autophagy for example, where we're going to cleanse the system. We're going to get rid of stuff we don't need, we're going to fix things, we're going to repair things. Kind of like viewing the pioneers during the cold winter months in South Dakota, unable to get out of the house from adrift so that's when we repair things. We fix the clothes that are torn; we fix the boots that needed fixing. Any tools that needed fixing; this is when we do there. So the thing is we don't do that anymore on a body, cellular level we just grow.

And our obesity epidemic is very well documented because we don't ever get a chance to regroup which is an intrinsic part of healing. So for the Cell Danger Response, that growth period corresponds to being stuck in a phase where you can't move out. And partly to help move out, you need to shift your metabolism into the AMPK portion. So fasting is one of the best ways of doing that, and one of the ways that you're alluding to is modified fasting, where you can for example build into your daily routine, not eating for 16 hours and then eating a couple of meals thereafter.

You can do it in lots of different patterns; all of them are written about. You can do it two days a week, just to kind of help boost it, you can do it for a longer period of time. But either way, it helps to get rid of the inflammatory process of growth by harnessing the anti-inflammatory process of rebooting or reworking our metabolism. 

[00:34:05.28] Scott: So let's dig a little deeper now into the three stages of CDR:  CDR1, CDR2, and CDR3 and talk a little about what's happening in each stage, what's unique about the stage. What needs to happen to move out of that stage and to the next stage, and what are some of the treatment interventions that potentially make the most sense for a given stage.

So if we start with CDR triggering, we move from the health state to CDR1. So what happens in CDR1 metabolically, what's the focus of treatment and what should we then be looking for to move from CDR1 to CDR2? What are the criteria that need to be satisfied to move to the next stage or phase?

[00:34:53.11] Dr. Nathan: Well, given our previous discussion, what we've been talking about virtually exclusively is CDR1, that's a threat. So the body moves from health to having some kind of a threat, and we deal with that threat through this elaborate process of changing our metabolism, changing our immune system, changing the way we see the world and we stay there until the threat is gone. So again if you got a cold, you can get through that quickly and we're done.

But if you have Lyme disease, if you have mold toxicity, if you have other toxicities which you're not aware of that you're not attempting to get out of your body, it's not going anywhere. You're going to stay in the Cell Danger Response 1 mode forever unless you deal with the threat. So one of the difficulties in conventional medicine seen through this lens is that given that Lyme disease has only recently been recognized a bit by the conventional medical establishment.

Mold toxicity, not even as much, there's even less recognition of its importance. You're dealing with literally millions of patients with chronic illnesses, who are under threat, but conventional medicine hasn't yet embraced this, nor does it know how to even begin to measure it. So those patients are being told I’m sorry, I don't know what you have. You've got so many symptoms; it's got to be psychological. So you have an SSRI deficiency or a benzodiazepine deficiency, have a nice day, see a psychiatrist, I’m not the guy for you and as an aside to the family, they're not really sick.

So this adds immeasurably to those patients illness, because now not only are they sick, but their family doesn't believe them anymore, their doctor doesn't believe them anymore. So sorry for that digression, but couldn't help it. They're stuck, because the healthcare system that they're hoping will identify what's making them sick by and large isn't embracing this newer information that would go ah I know why you're stuck, and if I’d fix this then we can move you along and along this pathway. So this is all Cell Danger Response 1.

[00:37:39.00] Scott: So talk to us a little bit then about some of the treatment interventions that you generally think of in CDR1. Is this where we're using antimicrobials, implementing detoxification strategies? And then what is it that finally signals to the body ah, we can move from CDR1 to CDR2?

[00:38:00.19] Dr. Nathan: What signals it is when the mitochondria no longer feel under threat. It's not a psychological issue. The mitochondria, those little organelles inside every cell of our body, those mitochondria have to be reassured there is no threat. You can't convince them that that's the case, they have to sense oh, the chemistry is getting right now, I’m not under threat anymore, I no longer sense the toxin that caused that energy drop. I no longer sense the presence of those microbes that triggered that voltage drop that set me off in the first place.

So we're dealing primarily with Lyme disease and co-infections, other infections as well potentially. So got to treat it, however, you treat it. Whether you use antibiotics, herbals, homeopathic all of the above, effective treatment has to be applied. We have mold toxicity, we have to use the right binders to pull the mold toxins out of the body. If mold has started growing in the body, in the sinus or gut areas, we've got to use antifungals and other supportive measures to get it out. And we have to support the body's ability to detoxify for both infectious illnesses and for toxins of every type. So as we kill infectious agents, it releases toxins and that's one of the things we've learned in the last 20 years, which is you can't just cure Lyme disease by giving antibiotics. You've got to include a detoxification strategy, or those toxins will accumulate and that toxicity looks a lot like Lyme. So you may have actually cured the illness and you're dealing with toxins now, and if you're not addressing it, that patient is not going to get better. Now, as per Cell Danger Response, same deal.

As long as far as it's concerned okay, thank you for getting rid of the microbe. But now I’ve got these toxins which are still triggering me, I’m not going away. Heavy metal toxicity, we've got to use the right chelating agents to bind it and get rid of it. EMF toxicity, we have to limit exposure, quiet the system. And super important is the limbic system and the vagus nerve, parts of the brain that control our perception of safety have often been targeted and come into play now. So that many patients can't get better until you quiet the limbic system and the vagus nerve also.

So it isn't a simple thing of saying okay, this triggered you, I’m simply going to do that and then you're going to get better, we have to look at the bigger picture. Using all of these strategies, the cell will slowly shift to a point where it goes I’m safer, not necessarily completely safe, I’m safer.

Now I’m ready to begin the process of repairing all of the damage that's been done, and reconnecting with my fellow cellmates from whom I purposely disconnected myself, so that I could isolate myself, literally commit harakiri if I had to in the service of my whole organism.

[00:41:42.01] Scott: So let's follow up on a couple of CDR1 related things then before we move on to CDR2. So in some of your past lectures, you've talked about the fact that detoxification, at least native or inherent detoxification, is really more of a CDR3 type process, that the body may have difficulty releasing intracellular toxins in CDR1 for example. On the other hand, in your book Toxic which for listeners if you have not read it, you should get it.

It's absolutely the best aggregation of all of the information around mold and Lyme and co-infections, you really need to read that. In that book, you outlined the use of binders for example very early on in addressing the toxins that you just talked about that can be triggers for the Cell Danger Response.

So my question is are there certain types of detoxification and drainage potentially strategies or interventions that make sense in CDR1? Versus maybe others that make sense in CDR3 for example? Are there some things we don't want to do in CDR1 in terms of too aggressive detoxification?

[00:42:57.03] Dr. Nathan: Very astute, very important and very complicated question. Sorry, if one wants simplicity, work at a HMO. If you want to help people who are sick, you're going to have to wrap your mind around complexity. The answer, unfortunately, is complicated. If we don't begin to bind and get rid of toxins in CDR1, we're never getting out of CDR1.

So we do have to start immediately. It may not be optimal detoxification, because the body may not be able to use those things optimally. For example, one feature of the basic eight features of Cell Danger Response that I didn't mention is that, because the redox potential of the cell and there's more oxygen than that cell than before. There is a mandatory interference with our ability to remove heavy metals. So in that state, the body starts to sequester heavy metals rather than being able to get rid of them. If you will think of it as it doesn't have the energy to get rid of it, it's on survival mode just can't do it. So most patients will if you measure them, have elevated levels of heavy metals when they're sick in Cell Danger Response 1.

Again, many people think of this as oh, that's what's wrong with you, that's what I want to treat. It's not necessarily the cause, it's making them worse, but it's not necessarily the cause it's what triggered it in the first place. So although it does need to be dealt with, not necessarily at that stage. So heavy metal toxicity, if you can deal with it in CDR1, great. And here's where individual chemistry genetics and capacity come into play.

There's no test that I know of that is yet on the market that can tell me how capable is my patient of responding to what I’m trying to give them, it's literally trial and error. So I will give the materials that should help them in very small amounts and see how they do with it. If they can take the ball and run with it if they can take those materials, great. That will help move them forward to healing, getting them out of Cell Danger Response 1.

But if it makes them worse, they're telling me no, not ready for that yet. So the simple answer to your question if there is one Scott, is my patient will tell me by their response or reaction to what I’m giving them how ready are you for this intervention for right now. So we start these interventions in Cell Danger Response 1, slowly, cautiously not the way you would for patients who are constitutionally strong. And we watch what happens and then we move on from there totally paying attention to their reactions.

[00:46:36.02] Scott: Let's talk then about CDR2, do we generally spend most of our time in CDR1 or can CDR2 or even CDR3 be really dominant long-term phases? What's happening that's different in CDR2? What types of treatment strategies are you thinking about? And then what's the exit criteria from CDR2 into CDR3?

[00:47:05.10] Dr. Nathan: Again, this is a spectrum. Although, Dr. Naviaux talks about a gate, literally a blockage gate that has to be passed to move from one to the other. It's more of a process than a strict, we're going to line you all up at the gate until the ferry is ready to be loaded and then you all get on the ferry and move, doesn't quite work that way. Most of my patients spend a humongous amount of time in Cell Danger Response 1. Once they start to get better, and this is tricky, we don't yet have any tests that I’m aware of that can tell us with precision ah, you're moving into Cell Danger Response 2, now I can use other strategies.

Generally, when a patient tells me they're about 50% better or more, I will see if they're ready for the next stage by trying the supplements that didn't work in Cell Danger Response 1. Let's take mitochondria; at this point, I might try Coq10, L-carnitine, L-taurine, and D-ribose, okay. If there is no response to it whatsoever or worse, okay you're not ready yet, you haven't made that transition. However, if they're going oh you know, my energy has definitely picked up since you gave me those supplements, I go great.

Now I know with a little more accuracy that we've moved from Cell Danger Response 1 to 2, and that I can pick up, focus a little bit more on detoxification strategies, nutrition. Now maybe I can reboot that gut, now maybe I can work on SIBO. Now maybe I can use those supplements that I was not able to use before. Now maybe I can start working with methylation supplements.

Unfortunately, all on a trial and error basis. I don't have any way to do it other than using your clinical judgment. And I know that that's frustrating, but that's the most honest straightforward answer I’ve got for you.

[00:49:26.23] Scott: So CDR1 is about removing the trigger or triggers, is it true that CDR2 then in part is about restoring or repairing or rebuilding after the threat itself has been removed?

[00:49:42.22] Dr. Nathan: Yes. The entire metabolism changes from glycolysis in Cell Danger Response 1 to aerobic glycolysis in stage 2. Now the difference between those two is profound, using glycolysis you can only get a couple of ATP molecules from anything you're metabolizing. Whereas, in aerobic metabolism, now we can get 38 molecules of ATP out of the same substance.

So there's a profound improvement in our ability to extract energy from the food we're eating and to make progress in that regard. But we've got a lot of healing to do, we've gotten deconditioned, our muscles aren't working very well, we're weaker. And so slowly and steadily, we begin to add things that will help make us stronger. But again, our metabolism has changed profoundly, the actual structure of the mitochondria seen under an electron microscope have changed, now we're able to do more. What we haven't done yet which is Cell Danger Response 3 is we haven't yet rebuilt the lines of communication with our other cells.

Now, if we've been in this state for a long time and we know that there are patients who've been sick for 15, 20 years who were helped, and now are much better than they used to be. But those lines of communication are shut, how does a cell know how to communicate with another cell? Well, it turns out they're taught. It's a wisdom passed down from older cells to younger cells.

It's a pattern of knowledge and chemistry that the older cells have witnessed because they were around when things were good. And the younger cells don't know about those, they weren't around then. They don't know how things worked in the good old days. And so literally during Cell Danger Response 3, we're re-establishing our ability to communicate neurologically and endocrinology.

So the endocrine system which gets shut down in Cell Danger Response 1 intentionally, now we're putting it back online and we literally need the older cells to teach the younger cells, well son, in my day you know I used to talk to your pancreas quite a bit. But had been a couple of years now that I’ve, my cell phone batteries haven't been able to be recharged, but now my cell phone batteries are up and I think we ought to give your grandpa a call. Sorry for being metaphorical.

[00:52:33.01] Scott: No, it's great; it helps for the illustration for sure. So before we jump more into CDR3, we talked about in CDR2 this process of rebuilding or restoring, there's also as I understand the concept of certain cells that have too much damage and thus they become senescent, they need to be disposed of so to speak.

So is there a place in CDR2 for things like black tea extract or even quercetin that can help to support the body in clearing out these senescent cells? Because as I understand part of aging and illness over time as well as the accumulation of these senescent cells. So can you talk to us a little about that aspect of CDR2?

[00:53:20.08] Dr. Nathan: Sure. What you're talking about another word for it is autophagy, where we realize we've got some damaged stuff here beyond repair. So I can't keep hanging on to them, if you don't want to be a hoarder, you don't want to have all this stuff lying around in your living room and you can't even walk around it, because you've got all that stuff there, you got to get rid of it. And so yes, there is definitely a role for improving autophagy in our body and getting rid of those things.

Now that's a natural process, I want to emphasize that we're just beginning to understand this. Our bodies understand this already, they know what to do infinitely better than we do. So I’m never going to be smart as my body is. So if it knows it it's got some dead stuff lying around it has to get rid of, it'll do it as long as there are no impediments to that. So if we can enhance that in any way, absolutely this is the time to do it.

[00:54:30.14] Scott: Does the CDR cycle itself move in only one direction? So if I’ve gone from CDR1 to two can something happen that ships those same cells or organs back into CDR1? Or is that essentially a different overlapping cycle?

[00:54:49.18] Dr. Nathan: No. And you've all had patients who were doing great, they were healing, they were better. They would tell you they were 80% better, and then something happened. It could be a psychological or emotional stress; it could be an exposure again to mold or some sort of exogenous toxic material. It could be a surgical procedure; it could be a severe viral infection.

For those people with mast cell activation, it could be a flare-up of that. So absolutely people can regress and go back in their stages and it's not linear, it's a fluid process and as I mentioned earlier, we have mosaics. Certain tissues of the body can be in one Cell Danger Response, and other tissues can be in another place.

[00:55:42.27] Scott: So you introduced CDR3 and talked about the re-establishing of communication as the healing process kind of moves forward back to the health state. What are some of the interventions or strategies from a treatment perspective if any, that are implemented to support CDR3, or at that point is it the body itself is taking over again and moving things forward?

[00:56:10.20] Dr. Nathan: Once again it varies. For many people, they will reboot automatically at any stage. In other words, once they get rid of the toxin, they're going to reboot themselves. They don't have to do anything; they're going to heal themselves. For other people, and we don't know how to identify them yet, we can't tell you why yet.

But there are certainly some people where once the toxins or the infections are gone, they're still sick and they need to be rebooted. And then we need to be using all of those wonderful tests we have to define what the biochemical issues are. Is it a deficiency that needs to be addressed? Is it magnesium? Is it zinc? Is it copper? The toxin is gone, but the whole detoxificational system needs to be rebooted.

The liver needs to be strengthened, the gallbladder needs to be strengthened, the kidney needs to be strengthened, lymphatics. Is it structural? Do you need work from an osteopath or a chiropractor to remove the physical impediments to structure? There's a whole ton of structural issues that come into play. For example, we observed in our sick patients that the majority of them had lymphatic issues.

That the lymph drainage was profoundly infected, that the chronic inflammation had kind of gunked up the lymph channels, not much is moving. And so we have to come up with strategies of how do we get it moving. It can include exercise, massage, Frequency-Specific Microcurrent all of these things. Almost all our patients have hormonal imbalances, and before it was hitting a moving target, now we can be much more precise about ah, you need a little bit of thyroid.

You have your adrenal gland rebooted; you need some more sex hormones on board in order for that to happen. So now we can get more precise. Now if your methylation hasn't rebooted itself, now it's going to be helpful. Now if your mitochondria need feeding, that will be helpful. Now if your limbic system and vagus nerve need treatment and you weren't able to respond before, now we can reboot those systems as well.

[00:58:46.05] Scott: Yes. So when the threat is still present in the earlier stages, the body's shutting down a lot of these systems to protect itself, the threat has now been addressed and so there isn't a reason that it needs to continue to remain in that protective mode. But we need to restart those systems because they've been essentially offline for a period of time is kind of how I’m interpreting what you're saying. Is that reasonable?

[00:59:12.03] Dr. Nathan: Absolutely. And that brings up something I know you're going to address, which is what about habitual changes, which is one of Dr. Naviaux's wonderful points that he makes here. Is the body can become so habituated to functioning in a compromised biochemical way. That if you fix it, it may interpret that as a threat and react to it. From an addiction point of view, for example, it looks like the body is almost addicted to its physiological state of functioning.

And if you make it better, initially it may look like a Herx or a die-off, because that's the way those things look biochemically. So what this means and I think it's a profound observation, with many of our patients when we would give various substances, various supplements later in treatment, sometimes our patients would respond to them very badly and we go oh, that's bad I’ve got to back off here. Sometimes, we simply have to ride that out, because the patient has gotten habituated.

If you give it a little bit of time, the body will go oh yes, I just didn't recognize this as a good thing, I only recognized it as a change and I’m really leery about changes. So I’m going to be really careful about that. That adds a whole other dimension to complicating our perceptions of where our patients are responding to what we do. So this is where clinical judgment starts to come in, whereas a clinician you watch someone's reaction to what you're doing and going I’m not sure that's a Herx, maybe we'll hang out here for a bit longer and see if this smooths out with time.

And I think all practitioners have seen that sometimes if you keep doing something that seemed to be a reaction, it settles down and the patient accepts it and makes progress. And sometimes you do the same thing and they get worse and worse and worse and worse. So if you can be a smidge more courageous and not shut it down with any possibility of reaction, I think that many practitioners are going to start to find that some things that you do may be okay if you go gentle and keep gently plugging away at it.

[01:02:04.18] Scott: So our “dis-ease” so to speak becomes our new normal, and attempts then to shift the body back towards health are perceived as unfamiliar or uncomfortable, and thus we may react negatively to treatment interventions that are actually very health-promoting.

[01:02:23.23] Dr. Nathan: Yes.

[01:02:24.06] Scott: I wanted to just quickly come back to your comments about reestablishing cellular communication and then giving marching orders to the new cells that were created in CDR2. How do we know that the marching orders given to new cells are health-promoting and that those new cells don't receive marching orders from other bad guys so to speak?

[01:02:48.23] Dr. Nathan: An interesting question. My first answer is I don't know, my second answer is trust the body's wisdom. We're using metaphors and analogies right now; we don't know to what extent this happens. But I believe that our bodies instinctually know good information when they get it.

And the truth is, if you get the wrong marching orders and you establish a less than healthy connection, you'll know it because you're going to have symptoms from it. Your thyroid isn't going to work as well, your adrenal is not going to work as well, you're going to have symptoms from it. My best answer is trust the body's wisdom.

[01:03:43.18] Scott: I think that's actually a great answer because I think that's something we don't do enough, right? We think we have to solve every problem, we have to take a pill for every microbe or toxin or whatever. Where really we just need to unburden the body enough that its own innate intelligence and wisdom will always be better than any pill we can take.

[01:04:07.12] Dr. Nathan: Thank you. Well said, I'd love to emphasize that. I have long believed in the body's innate intelligence, and I know how little I know and I know how smart bodies are, often they just need a nudge. Now when some of these more complicated newer illnesses to epidemics of mold and Lyme and so on need more than a nudge, unfortunately. But at some point, when we feel like that body is beginning to turn around, I personally tend to do less.

And my visits with patients are more involved with looking at their whole life, whether they're reincorporating their life the way they want to. For many patients, they've for years had living illness behavior, now they have to embrace and this is very difficult. They have to embrace being well again. Oh my god, I have had a built-in excuse to not do lots of things I didn't want to do for a very long period of time. Well, but now I don't have an excuse anymore, so that's scary.

And so early on, I often begin the discussion with my patients I say okay, as you're getting well, how are you envisioning living your life? What are you going to do that you've wanted to do that you haven't before? How are you going to embrace that? How are you going to transit into that and move into that? And that's not about giving them a supplement.

You know what, a lot of physicians, practitioners of every type sort of have this idea that if you come to me, I got to do something; I’ve got to give you something during this visit. And I don't think that's true, sometimes what I give people is hope, a pep talk, perspective.

I think these are very valuable and all my patient needs at that point, I don't have to stick one or two more supplements on an already huge supplement list that they're taking. And I think it's a tendency that people have that I hope we can begin to shift into valuing what we're giving people that is not necessarily a substance.

[01:06:49.00] Scott: Some of my next questions will be a little bit of review on some of what you've already said. So the Cell Danger Response itself challenges a lot of the paradigms that we normally think about running a test, looking for things that are low, exogenously supporting them, taking vitamin D, methyl donors, thyroid, antioxidants you mentioned a lot of these already.

One of the areas that I’d like to get your thoughts a little bit more is in the area of materials to reduce histamine and the activation of mast cells. And so my understanding is there is an increase in histamine as part of this Cell Danger Response in CDR1. Is that also protective, and is the implementation of mast cell stabilizers or histamine reducers, is that also potentially counterproductive early on? Or is it necessary to calm the inflammatory cascade?

[01:07:48.29] Dr. Nathan: Yes. Your ability to ask 12 questions in a run-on sentence is legendary here, you've done it again, thank you. And I’ll see if I can follow it all. So first of all, a histamine problem is intrinsic to the Cell Danger Response in several different ways, and I don't really want to call it a problem. Remember that all of these responses are therapeutic and protective and healing if they occur quickly like with a cold. It's when they keep going that it becomes an issue.

So there are two mechanisms to mention here for histamine, one is the activation of the Cell Danger Response stimulates the B6 dependent enzyme histidine, which is converted into histamine. So there is intrinsically a greater amount of histamine being made as a part of the Cell Danger Response. Also, we metabolize histamine using methylation.

If we are shutting down methylation, then the histamine which is being made in greater amount is being metabolized less and we get even more histamine. So as a process, and keep in mind this has value, we use histamine as a part of communicating between our immune system and our nervous system and it's therapeutic, we use it to fight off parasites, for example, another threat to the body that we need to work with. But as this thing becomes ongoing, now we have a histamine issue.

So a very high percent, greater than 50% of my patients have a mast cell activation issue and do have a histamine problem. Generally, that has to be dealt with sooner rather than later, because this adds another whole component of inflammation to an already inflamed system, not good. So generally treating it early in the course of illness really matters, but again patients will tell us if it's too early. For example, I’m sure all practitioners have had the experience of using mast cell activation materials and strategies to quiet it down and finding their patients couldn't take them.

And so for those patients, this is almost like defining it as no, I’m so shut down right now that unless you work on the limbic system and vagus nerve, we're not going anywhere. You have to allow that cell/organism to feel safer or it won't even let you take the materials you need to treat the mast cell activation. But with that exception, treating mast cell activation early in the course of illness is mandatory or you're going to have trouble making progress.

[01:11:09.22] Scott: Beautiful. In some ways, the idea of the Cell Danger Response is somewhat akin to the idea of the bugs in chronic Lyme disease being gone but people still having symptoms because they have “post Lyme syndrome”.

And so how do we know that the triggers are really gone, and the body is now stuck in absence of any actual ongoing stressor? It seems like there's some overlap here between the model of CDR and what we used to think of as “post-Lyme syndrome”, and yet now we're suggesting well “post-Lyme syndrome” may actually be the persistence of Lyme and co-infections. So how do we tease that out?

[01:11:49.23] Dr. Nathan: Again, very good question. Again, the different causes we can measure with varying degrees of accuracy. So if I’m talking about mold toxicity, I can accurately measure when I’ve gotten mold out of that body. If I’m dealing with some other toxins like heavy metal toxins, I can accurately measure that I’ve gotten it gone.

Lyme, not so much. So our testing for Lyme is still at a stage where it is very difficult to ascertain have I really eradicated the bug, or are they better. Now in terms of the phrase “post-Lyme syndrome” which is mostly used by the IDSA, not by people from ILADS. The easy distinguishing thing for me is if it was simply a recurrent syndrome that was represented this stuck place, then the majority of our patients would not be responding as they do to long-term antibiotics and other treatments.

So as long as a patient is responding with positive improvement from taking antibiotics and other treatments that is specific for the organisms that I believe they have, then this is not technically “post-Lyme syndrome”, this is still chronic active Lyme disease.

At a certain point when that patient has improved to a certain extent, maybe we could talk about the use of that term which from my perspective is misused. It is simply a chronic condition that we still haven't fully rebooted yet. And maybe these are people when we get access to Suramin, that we will be ultimately able to do some more rebooting.

[01:13:45.16] Scott: If we think about DNRS or Dynamic Neural Retraining System, Annie Hopper's work with the limbic system which you've also termed a tool for rebooting, you talk about in your book Toxic.

How much overlap is there in terms of a looping limbic system where there's an inappropriate assessment of safety and the concept of being stuck from a Cell Danger Response model. In other words, once we move out of CDR1 and into CDR2 and 3, is something like DNRS potentially then rebooting the Cell Danger Response?

[01:14:23.09] Dr. Nathan: Yes. I usually use it in CDR1, and then I have my patients if possible carry through to 2 and 3 where it's even more effective. The reason for that is there's a certain degree of stuckness that will prevent people from taking and responding to what I want to give them in Cell Danger Response one if they don't feel safer. Safety is the issue, so it's really important that we use whatever tools we have, and I’m a big fan of Annie Hopper's DNRS program, in that I’ve used it in I don't know 350, 400 patients at this point with the vast majority clearly telling me that was really helpful in letting me get going on what you're trying to do here.

[01:15:24.21] Scott: Do you find that using DNRS if someone is in a water-damaged building, do you find that they need to fix the environment first? Or is it okay to reset the limbic system and essentially say that our surroundings are safe if, in fact, they're not?

[01:15:45.25] Dr. Nathan: DNRS will help in a toxic environment, but it won't hold. And patients will get frustrated because they will expect more from it than it's capable of doing. So you can't get well if you stay in a toxic environment, I can't say that often enough, it's not possible. You can get better, you can improve for example.

Many of my patients who are really sick in a toxic environment are so cognitively impaired that they can't even make the decisions and judgments they need to get out. So if I can improve them a bit by using DNRS and using binders, it can make enough of a difference that they can be able to remove themselves from that environment. Otherwise, I watch them spinning their wheels and going I can't even think about moving, can't do it.

[01:16:44.27] Scott: Talk to us about the metabolomic testing that Dr. Naviaux has created. What were some of the patterns that you saw; you referenced the work that you did together in the Chronic Fatigue Syndrome realm. Are most of these metabolites indicative of a low or hypometabolic state? And then is there a difference between men and women in terms of the observed patterns?

[01:17:09.04] Dr. Nathan: So yes, yes, and yes. In our study that we did on Chronic Fatigue Syndrome patients, we had equal numbers of men and women in equal controls and the men and women were different. There was a bit of an overlap in terms of the biochemical abnormalities that we saw, but there was a whole lot of non-overlap. And one of the important findings of this study was in the past, many research studies have been done predominantly with men. And now we're realizing the conclusions of those studies cannot be applied unilaterally to women based on those studies.

We've got to be studying women equally, we do not have the same chemistry and we need to be aware of that, so we can make the right decisions. One of the outcomes of that study Scott was that we were able using 11 metabolites in women, and 8 in men to be able to distinguish from controls chronic fatigue patients with an accuracy of 94 to 96%.

Now to my knowledge, there's never been an actual biochemical test, blood test that would tell us yup you've got Chronic Fatigue Syndrome. So it takes it out of its old place in medicine as a psychogenic illness. It is not a psychogenic illness; these are biochemical changes that we can measure.

So that measuring eight materials in men alone allows us to identify those patients with an accuracy of 94%. So this is pretty profound, it changes the territory putting Chronic Fatigue Syndrome as a real illness, not feigned, not imagined, and not psychological, it really puts it on the map. 

[01:19:08.24] Scott: And if you do repeat testing, does the treatment of the initiating trigger meaning primarily CDR1, does that begin to shift the metabolomics back to a healthy fingerprint? Or does it require us to get through CDR2 and 3 before it starts to change the fingerprint?

[01:19:31.13] Dr. Nathan: We don't know yet, the answer is those studies have not yet been done. They are planned; I know that Dr. Naviaux has that in mind. And in fact, we're recruiting I think at this point I think it's pretty close to happening, we need to be able to not only have the measurement arm that we did, but we then need to have a treatment arm and see where changes occur. Honestly, we don't know yet, we have some pretty good guesses as to what's going to happen.

We think that chemistry will simply move from, and you can plot it out on a Venn diagram. We believe that they will move from being a toxic pattern that we can actually measure for different illnesses. Dr. Naviaux has measured this for PTSD, for traumatic brain injury, for Gulf War Syndrome, not just chronic fatigue and several others. So with each group that he does, what we've learned is you can distinguish these biochemically, and they're all a bit different from each other.

At some point, we will be able to separate these out once we've done the studies. These are very expensive studies; these studies are complicated and difficult. Dr. Naviaux is doing about as much as any human being can do to get all of this done as quickly as possible. So we need a lot more information to answer your question.

[01:21:13.22] Scott: I know at the ISEAI conference where he spoke, he was talking about doing the same type of study for Lyme disease, for PANS and PANDAS and also Alzheimer's. Do we know if those studies have started?

[01:21:26.12] Dr. Nathan: Not yet.

[01:21:28.29] Scott: Okay. So the last few minutes that we have I want to get into your thoughts treatment-wise. You mentioned Suramin, so talk to us a little bit about Suramin. Do we know if it is potentially going to be available at some point? And then when we're thinking about Suramin, do we still need to remove the initial trigger or threat or infection or toxin that led us into CDR1? Or can we ignore all of that and use something like Suramin and expect to move back to the health state? 

[01:22:03.20] Dr. Nathan: Complicated question again. Suramin Is made currently by Bayer in Germany, and they are reworking their factory, it is not available for anything other than research purposes at this time. And they monitor it very closely.

I am told by Dr. Naviaux that there is a US-based company that is planning on being able to make Suramin as well, and we may be able to get out from under that difficult umbrella that Bayer is using to not allow us to work with this the way we would like. For listeners, I would like to add, Dr. Naviaux did a phenomenal pilot project using Suramin in autistic children. It's a small pilot project; the second one is being done as we speak right now in a much larger study.

There were five children that were controls, and there were five children that got Suramin intravenously one dose. And I would encourage listeners to go to Dr. Naviaux's website and look at the videos of the children before they got Suramin and after they got Suramin. All five children that got Suramin had spectacular improvements in their psychological status that are so obvious that it's heartwarming. And this tells us what Suramin is capable of. Now, neither Dr. Naviaux nor I believe that it would work well in a state of threat, meaning I believe you've got to be at least some ways out of Cell Danger Response 1 for it to work.

And one of his concerns is that it will be used as a panacea rather than being used responsibly, and people will start using and go well-tried it didn't work. It needs to be used with an understanding of the entire process that we're working on. So I hope that we'll have access to it soon. One thing I can comment is I recently had someone send me a research paper showing that Chinese skullcap root has some purinergic blocking activity. Now, this is to my knowledge the first herb that I am aware of with some actual research telling us that this has the ability to reboot.

[01:24:39.24] Scott: Do we know how many of the 19 purinergic receptors it might affect?

[01:24:44.15] Dr. Nathan: I don't know that was studied, all I know is that it does have some purinergic activity.

[01:24:51.05] Scott: Without something like Suramin, can a patient move completely out of the Cell Danger Response. Meaning CDR1 to 2 to 3 and back to a healthy state. Or is there a need for Suramin to finally reboot the overall danger response? 

[01:25:10.27] Dr. Nathan: Well, I believe that I have helped the majority of people I’ve treated for the last god knows how many years, and I believe that many of them gotten well having been really sick. People have gone out of wheelchairs that are living normal lives that are well now.

I absolutely believe it is possible to reboot them. I would add to that statement though, I’m not sure that all of them have been completely rebooted. So I would love to have another tool that would get that last bit of rebooting material done if it were able to be done in a reasonable, quick, healthy fashion.

[01:25:58.08] Scott: Yes. I mean it sounds appealing, at the same time I have to think that we don't need to rely on or put all of our hopes on Suramin or be discouraged because we don't yet have it. If we look at plants, my understanding is even plants have a Cell Danger Response and I’m guessing that they manage to get out of it in some way without taking Suramin.

[01:26:19.18] Dr. Nathan: For most people, if you get them to a point that they're stuck places are gone, and unfortunately I mean not just biochemically but structurally, but emotionally and spiritually. But if you can get people to a place where their stuck places are pretty much gone, their natural healing ability will take place and they will finish up the job on their own.

[01:26:44.17] Scott: Where does something like lysine fit into the Cell Danger Response model? Is it effective because of its anti-viral properties or does it also potentially help move the CDR process along?

[01:26:59.21] Dr. Nathan: I think it plays a minor role. I think in the first paper, Bob emphasized it because it was one of the eight materials that become deficient in the Cell Danger Response, it has an anxiolytic effect. And he thought at that time that would be one of the things that would be instrumental in reversing this. One of the things that we've all found as we've studied this more and you pointed us out, this is worth emphasizing.

Our old model of looking at health which was I’ll measure what's going on in your body, and I’ll give you what you lack. You're low on magnesium, I’ll give you magnesium. Low in zinc, give your zinc. Low in lysine, I’ll give you lysine. Those are absolutely insufficient to move you out of the Cell Danger Response pattern because none of them address cause. They're not dealing with the threat. So I think lysine falls into that category. 

[01:28:05.18] Scott: And let's talk briefly about P5P so that as I read is another potential tool that can help minimize a sustained Cell Danger Response. So how might P5P be helpful, and is there a connection between P5P from a Cell Danger Response discussion and the loss of B vitamins including B6 and P5P in people with kryptopyrroluria or KPU?

[01:28:33.04] Dr. Nathan: Okay, two different areas. I mentioned before that activating the CDR stimulates the B6 dependent enzyme histidine to make more histamine. So B6 is an integral part of it. Well, we use it up, so it's going to happen that we're going to become deficient. Again, depending on where the patient is and their responsiveness, some patients will respond to P5P or B6, and some it'll set them back.

So it isn't a matter of just saying ah, you're deficient I’m going to give this to you. It's are you ready for it, is this something your body wants to be doing. And I do believe that all of this ties into the pyro urea that we do see more often in Lyme and mold patients because that has to do with another piece of the Cell Danger Response which has to do with heme metabolism. And I didn't mention that initially, but now is a time that I can mention that too.

The basic part of the Cell Danger Response shifts how we deal with heme, which is not only an important part of hemoglobin, but I’m going to remind everyone that heme is a major constituent of the CYP enzymes of the liver that are involved with energy generations. So if we are interfering with that type of metabolism that predisposes to our inability to process hemoglobin later on when we're breaking it down.

To be more clear, we recycle our red blood cells every three months. So we're constantly destroying our red blood cells and making new ones. Well, when we have all of that hemoglobin that we've got to recycle, if we are compromising our ability to metabolizing it and in case in patients with polyuria or in patients with porphyria, both we're going to be accumulating those materials and adding to the toxic and inflammatory burden.

[01:30:57.12] Scott: For people interested in that topic, you can go back to a podcast that I did with Beth O’Hara a few months back on heme dysregulation and porphyria, and we do get into that in more detail. Sphingolipids are one of the items that have been observed in that metabolomic testing to be low in Cell Danger Response, does that potentially mean that certain lipids like phospholipids or other fats could actually make the chronic microbial burden worse? Or are there certain dietary foods like milk or dairy products that contain them that could make things worse at the wrong stage of Cell Danger Response?

[01:31:41.24] Dr. Nathan: Theoretically, I’m more aware of the use of phosphatidylcholine intravenously and orally for most of my sick patients, it is a wonderful tool to help reboot all membrane physiology, remove toxins and help heal myelin sheaths, which is often involved for some of our patients. I love intravenous phosphatidylcholine.

But in terms of could, it be potentially a problem? Our most sensitive patients often can't take even the tiniest bit of it. So I may start my patients on a half a CC of intravenous phosphatidylcholine, and for a few patients, they can't even do that. So that may be an example of what you're suggesting that might not be a strategy that will work right off the gate. But I also want to add that that's fairly rare. Most patients can at least take tiny doses like a half a cc, one cc, and then very slowly build up to higher doses where it becomes very helpful, very therapeutic.

[01:32:57.01] Scott: I want to just mention in this Cell Danger Response conversation, the importance of exercise, the importance of focusing on sleep. Let's talk just for a second about exercise; we know how important it is in healing, promoting disease-free health, promoting reserves, and resilience. At the same time, many people that are in the Cell Danger Response can't really tolerate it. So what are your thoughts? Are there particular types of exercise that can help move them out of Cell Danger Response, while at the same time not pushing them beyond the limit of what their body can handle at that time?

[01:33:33.03] Dr. Nathan: I don't think exercise plays much of a role in Cell Danger Response 1, it more often backfires. A large percentage of patients in that category have post-exertional malaise and myalgia which are barometers of overdoing it. Essentially, a post-exertional malaise which is where if you attempt to do something could even be something simple, some physical activity of some kind and you get wasted for the next day or two.

That's your body's way of saying you have no energy reserves, yes. By willpower alone, you can do anything you want to do, that you're going to pay for it. And the price is you're going to have to wait until you get enough energy reserves back that you can do anything. So exercise is great, wonderful, healthy, absolutely, and here comes the but. It can only be done to the extent that your body will allow it, and this is not a matter of discipline, it's not a matter of mind over matter. So if you can walk to the mailbox and back every day, great, as long as it doesn't waste you.

As long as you're not worse for a much longer time afterward. If you can walk around the block, great. Whatever amount of exercise you can do, that's wonderful. But if you overdo it, you will not damage yourself, but you're going to set yourself back. And this is something that requires careful titration on the part of the patient and the practitioner, then I can assure you that the majority of patients overdo a lot. It's something they have to learn over and over and over again. And I’m fond of one of my favorite phrases is, I told you so.

[01:35:34.11] Scott: Or if some is good, more is not necessarily better.

[01:35:38.14] Dr. Nathan: There is that one, indeed.

[01:35:42.17] Scott: I want to talk just a little bit about Frequency Specific Microcurrent. You've talked about that as a rebooting tool; we know it can help the limbic system, the vagus nerve, so many of these things that you talked about. At the same time, we know that just the use of FSM can increase ATP very significantly.

So do you find that because of that increase in ATP which could then lead to more extracellular ATP, and a louder danger signal? Do you find that FSM also needs to be timed later? Or do you find that it's generally well tolerated throughout the CDR phases?

[01:36:20.10] Dr. Nathan: Rarely causes problems other than in the most sensitive patients, especially people who are electrically sensitive. It's a rare problem; I mean FSM is an extremely versatile tool. It can help with quieting the vagus nerve, rebooting different parts of the brain. It can help with detoxification specifically. You can literally program in various mold and Lyme frequencies and the organs of elimination to help that work, very nice tool.

My most sensitive patients, especially from an EMF perspective, sometimes can't handle FSM even in minuscule amounts. And again, there are some tricks to that you can without even putting it on the body. If you simply turn it on in the room, you may be able to get them to tolerate it in small amounts and move them on from there. So like everything, rarely would that theoretical consideration come into play.

[01:37:21.15] Scott: I know you've talked about the success you've had with some patients using BrainTap as kind of a parasympathetic tonifying tool, maybe some overlap into the limbic system realm, maybe different mechanisms. Do you think BrainTap has a place in helping to move us through the Cell Danger Response back to the health state? 

[01:37:44.06] Dr. Nathan: I do, it's one of my more favorite tools along with FSM in doing that, used early. So especially in my really sensitive patients. I know you did a program on brain tap; it consists of basically, looks like a virtual reality headset with earplugs. And basically uses different frequencies of light and sound that reboot the inflamed parts of the brain.

I’ve used it now and well, at least a hundred patients and the vast majority report that it significantly helps quiet down that inflamed nervous system, and makes them less anxious, sleep better. It takes that, it adds another level to that safety factor which begins settling out that Cell Danger Response.

[01:38:39.16] Scott: I heard a rumor that your book Toxic is now or soon to be available as an audiobook, which I’m sure people will be interested in, tell us about that.

[01:38:47.18] Dr. Nathan: Oh, very excited. Toxic is an audiobook, at this point, it's been done and should be out within a month. And one of the fun parts for me is I’ve always wanted to read some of my own books. And so they were okay with my reading, the dedication, and acknowledgments. So my voice will be in the book. So I’m really excited about that, I know that a number of people have told me that their cognitive ability to read has made it difficult for them to actually read the book, so I’m very much hoping that on audio they'll be able to at least get some of that and process it.

[01:39:32.15] Scott: Beautiful. My last question is the same for every guest and you've answered it twice before, but I’m sure things have changed since then. What are some of the key things that you're doing on a daily basis in support of your own health?

[01:39:43.22] Dr. Nathan: I don't know if my answer is going to change too much. I attempt to do Tai Chi meditate on a regular basis; I walk almost every day, a couple of miles a day. I eat organic and healthy. I would probably tell you that Cheryl the love of my life and my new puppy Sasha, and my older puppy Joey give unconditional love to me, that is the foundation from which everything flows. And I’m very fortunate; I live in one of the more beautiful parts of the world.

I literally live in a redwood forest, and the pacific ocean is two miles away where all of us walk as close to every day as we can. More recently, I have been doing a type of media meditation recommended to me by one of my teachers which involves basically lying on the ground with no expectations. But simply allowing myself to connect to the earth in a non-verbal profound way. It's kind of a new meditation; I’ve been doing it for the last six months.

And I am very impressed with what the ground has to teach me non-verbally. It's a way to connect to the natural world in an even more profound way. After doing it for a while, I discovered that I can feel a flow pattern in my body from the natural world that is both restorative, and I believe allows me to be more in touch with my intuition and my instinct which I hope will translate into helping me be more effective as a healer.

[01:41:59.07] Scott: Absolutely beautiful. Disneyland is closed during this shelter in place time; this was much more fun than going to Disneyland would have ever been for me. I enjoyed this conversation immensely and really looking forward to it. I’ve said it before, but I think that you really are a pebble in the pond that creates such amazing positive ripples for everyone whose life you touch. And I thank you so much for your time and sharing with us today, Dr. Nathan.

[01:42:26.20] Dr. Nathan: Thanks, Scott. I feel the same way about you; you're up to 121 of these podcasts, that's pretty amazing. And for those of you out there, you'll probably cut this out, but I’m going to say it anyway. For those of you out there who don't know, Scott researches all of these, he does an incredible amount of work before we have this.

So I have in front of me a six-page, single-spaced outline not only about what we're going to talk about, but that goes into vivid detail about all of the things that we've discussed here. So your preparation shows and your podcasts are wonderful, thank you for that.

[01:43:07.29] Scott: Thanks Dr. Nathan, be well.

[01:43:09.23] To learn more about today's guest visit NeilNathanMD.com that's NeilNathanMD.com. NeilNathanMD.com.

[01:43:21.08] Thanks for listening to today's episode. If you're enjoying the show, please leave a positive rating or review as doing so will help the show reach a broader audience. To follow me on Facebook, Instagram, or Twitter you can find me there as better health guy. If you'd like to support the show, please visit Betterhealthguy.com/donate. And to be added to my newsletter visit Betterhealthguy.com/newsletters. This and other shows can be found on YouTube, iTunes, Google Play, Stitcher, and Spotify. 

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