The Cell Danger Response: Why You’re Not Healing (Yet)

Different diseases get you stuck in different places, and it can be happening in different— see, what's confusing is that we always want to make blanket statements, but it can be happening. You can have cells in your body that are stuck in the CDR1, and then you might have a lot of scarring and hypertrophy of tissue, or especially if it's CDR2, you'll get a lot of scarring. In CDR1, you'll have a lot of inflammation because there's usually— then you're still signaling the neutrophils to come come cause problems in CDR1 because that's, that's that, that, that, that acute phase of inflammation that in some people doesn't tone down.

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Hello, it's Dr. Kent Holtorf with another episode, and today we'll be talking with Dr. Eric Gordon. He's going to talk about metabolomics. Mitochondria, cell danger response, a new way of looking at these chronic illnesses and, you know, how they relate to health and how peptides can be used to kind of fit into the picture. But really like looking at different way of looking at chronic illness. And I think you really enjoy this. And I've known Eric for a long time and consider him a great friend and see him at almost every conference. And he's been around. He's president of the Gordon Medical Research Center and founder and owner of Gordon Medical Associates, a private medical practice in San Francisco Bay Area specializing in complex chronic illness. In addition to his clinical practice over 40 years— hey, he doesn't look over 30 to me though— but he's engaged in a lot of clinical research. He created a series of medical symposia bringing together thought leaders in the international medical community. Focusing on chronic fatigue syndrome, ME, Lyme disease, autoimmune disease, autism in a collaborative mode. And he really loves to collaborate and has innovative medical practice. He's a university researcher, which really has been his lifelong dream, is collaborating with these multiple forces. He did an amazing paper with Dr. Robert Naviaux on metabolomics. And we'll talk about what the heck that is. Mitochondrial function, chronic inflammatory disease, and is really bringing his dream to life with all this amazing new stuff and new ways of looking at things. In 2016, as I mentioned, he co-authored a paper, groundbreaking paper with Dr. Naviaux, on the metabolic features of chronic fatigue syndrome, published in the Proceedings of National Academy of Sciences, or prestigious journal. He's a medical advisor to Tech Bioscience and is the GMA collection site for Lyme disease biobank, providing samples for researchers. So he's really doing the right thing and really searching for, you know, what new ways to look at things and researching to find, you know, cures and treatments for these illnesses that people don't believe in. And it's interesting, if a doctor doesn't understand it or doesn't treat it, it doesn't exist. It's the patient's fault. And it's, it's interesting. We'll get into it where they did a study that they could tell the difference between chronic fatigue syndrome, fibromyalgia, normals, where doctors, oh, there's no studies. Although we do our, just our panel, we can pick out someone with chronic fatigue syndrome, fibromyalgia, chronic Lyme versus a normal about 70, 80% of the time and how bad it is. So it's kind of like, I think, the chronic fatigue syndrome diagnosis, fibromyalgia diagnosis, did a disservice to the patients, allowed doctors not to look at anything underlying. So you got this, here's an antidepressant. But, um, I'd like to welcome Dr. Gordon. Thank you for coming on our summit. Really looking forward to, uh, uh, talking about all your information, wonderful knowledge base, and sharing that with Thank you, Ken.

Thank you. It's a pleasure. It was really nice to hear how you, you know, just how difficult it is treating people who are not respected because the doctor doesn't understand. I mean, that's been the bane of my existence. I got into what we used to call alternative medicine in about 1990, '92, and it always— It always amazed me how the sicker the patient, the more the automatic eye roll of the doctor. Plan B. The positive review of systems. I mean, we have so many nice ways of saying that a patient is not sick or malingering. And it just broke my heart over the years to watch that. And we'd see these people, and the more you saw, the more you saw. You know, because in the beginning I was kind of the same way. It's like, can this be real? Yeah, you know, yeah.

And more and more, you know, that doctors— one patient, since you're in the ICU and the doctor orders a psych consult, says it's all psychological, you know, like, yeah, this psych consult.

I, I just had a patient unfortunately pass away last year, a young woman, 39. And, you know, that, that was, you know, she had been told at least 50 times that, you know, she needed psych consults. I mean, they, you know, in all the best places.

Oh yeah, and it's like, you know, I'm sure you have the same, is that, you know, people start crying just the fact we're working them up and believe them, and we're like, yes, we've seen this before.

Like, what?

You know, they told me this is crazy, you know, that I'm crazy. And then they start wondering if they are crazy, you know.

Well, that, that, that, that is, is, is the problem. And that's what so excited me about this metabolomics, okay, because I had been looking my whole life, as you, for for markers. What can we measure for people? You know, and, and we all, you know, we jump down, you know, we, we always jump on, on the bandwagon of measuring this test and that test, but at the end of the day, they still just tell us that the patient is sick. You know, we have a lot of innate immune markers now thanks to Dr. Shoemaker. You know, Rich has been a great help, but I have a little disagreement. I just don't think they're specific markers. These are just markers that you're in a— That's true.

You see it in a lot of things.

Yeah. Yeah. I mean, we started measuring his stuff back in 2004. And they are exciting, but there's so much like that out there. We have so many tests that tell us the person is sick, but we don't know— they still doesn't really tell us what's wrong, just their immune system is triggered. And that's been the problem with getting our patients respect. Without a test, we're kind of left to that, well, we know that these people are sick. There are very few diseases, as I mean Horowitz was very good at pointing out, there are very few diseases that give you transitory arthralgias. It just doesn't happen. That's why we don't—

you know, I mean, they'll basically say a standard Texas disease doc, nope, they don't have Lyme. But they've lost the power of basically exam and review of systems and history. Like, what else does that? Well, nothing else. Well, no, your test is negative. So what's explaining it? I don't know. It must be psychological.

Yeah.

So what the heck is metabolomics?

Okay. So metabolomics, I mean, you can say it any which way you want. I don't know the— metabolomics, metabolomics. I don't know myself. I guess it comes out of me as metabolomics.

And then I did a George Bush there.

Yeah.

Nuclear.

Nuclear. Yeah. OK. This is looking at the small molecules in the body. They call them small. They weigh about less than 1,000 Daltons, which make them like the amino acids, glucose, the small— the smaller small proteins, but most— and the fats. You know, and these are— we always looked at those as your basically your raw materials for the body, but they're also the end products of metabolism. So metabolomics measures, you know, the raw materials of metabolism and most of the end products. You know, if you think of it, the genes are the blueprints, okay? The enzymes tend to be the machines, and the metabolites because that's what we're measuring with metabolomics, is the metabolites, are the raw materials and the end products. And what has been so interesting about looking at metabolomics is you start to see that they are what is controlling a lot of the information. This is the mechanism that allows for epigenetics. We talk a lot about epigenetics, but epigenetics basically is whether you methylate or acetylate or demethylate or deacetylate the histones. You begin to expose different parts of DNA, which then will give you another—

Just so the viewers, like, with epigenetics, it's how the environment affects the genes. So if you have a gene for, like, diabetes, let's say, that if you— someone, two people have the same gene, one person eats great but other person not so much, that person will get it. But someone who doesn't have a gene, but they eat terrible, they'll still get it. So the environment affects the genes that are produced.

But yeah, so that's it. And metabolomics is the way that this is— is the intervening step. Okay, like, because I said, if you have too much glucose, you begin to glycolate— glycolate— cause glycolation of proteins, and you also change how much insulin is made. You know, that happens because you're turning genes on and off. Um, and so Dr. Naviaux got into this because he initially was doing a lot of work with inborn errors of metabolism. That's usually lipid disorders in kids, things that will often cause death in the early— in the first 10 years of life. And of course, he was doing a lot of genetic work. That's what he's mostly doing. But as the more he did, the more he saw that genetics doesn't predict much. 'Cause even two kids with the same gene defect have vastly different prognosis. And we see that all the time. Take thalassemia or anything. You have the gene, but some people have symptoms and many people are asymptomatic. It depends on whatever else is happening in the environment. And that's where the metabolome directly talks to the genes, turns them on and off.

And when you're looking at the metabolome, the metabolomics, Are you looking at, like, it's basically taking all these things, measuring the amount of certain things, or you look at specific markers? Because there's so many. How do you interpret that?

Well, that's the thing, is that, I mean, whether there's 2,000, 3,000, or 5,000, they're still arguing. What generally, what can be measured is somewhere between 500 and 1,000 relatively easily. You can measure and know what they are. 'Cause in metabolomics, you can do— metabolomics is done using, these days, using mass spectra, mass specs. And it's the kind of device that you can get a ton of information, but you just know something is there. You don't know what it is. But when you measure chemicals and identify them, usually you're measuring about 400 or 500, and you can really identify what the chemical is. And what we've been looking at, and we'll take the chronic fatigue as an example, is at that point, Dr. Naviaux— and I just want to make it very clear, that paper, which is a brilliant paper, was— it's— I supplied the patients, Dr. Naviaux supplied the brains.

I know you did more than that, so you're very—

but basically, you know, I mean, I just want that clear. Um, it's, uh, he had— he is an amazing thinker. I really think that if you actually look at his website and some of his ideas are just really, really, I think, groundbreaking because he's got a very eclectic background. He was originally— he's an MD who got a PhD in virology and then went into inborn errors of metabolism and has a great interest in evolutionary biology as well. So he brought all those together, very broad. And there's some— his recent articles, um, that on the cell danger response and, uh, on the healing cycle, I think are really worth looking at to get a broad view. And we'll come back to that.

But just, just so patients, people out there can get a fine copy of those articles, look up Cell Danger Response.

Yeah, it's N-A-V-I-A-U-X, you know, and he pronounced it Navio. If you just stick that in and Cell Danger, or just even CDR, your paper will show up. It's there. I mean, the same thing, chronic fatigue, put in chronic fatigue and Naviaux and the paper will show up. He's also done a lot of work with autism, and I'll touch on that at the end if we have a minute. But what we, what we did in chronic fatigue, he looked at between 400 and 500 chemicals in 40 patients, 20 males and 20 females. And that's one of the important things about metabolomics is that sex and age matter, okay? And it's not just the sex hormones. Men and women are significantly different, even subtracting out the sex hormones. And it's just like they say, women are a little more complicated. I think if I remember correctly, if we, if we, we can hit a very good differentiation of chronic fatigue patients from healthy patients in men, looking at about 8 chemicals. In women, it took at least 12, and even then we probably— because they're a lot more complicated than we are. But that was the beauties. What we saw is that, you know, we found basically about 40 chemicals that were 2 standard deviations from the mean, from normal, in people with chronic fatigue. The other thing that's very interesting about— and he's done this in PTSD using people from, you know, in the Navy before and after, you know, Afghanistan and Iraq. He did it, he's done it in depression with a large group from Denmark. He's done it in Gulf War syndrome, you know, chronic fatigue, and he's now working on a Lyme cohort.

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You know, when we look at our panel, you know, you're just looking at 400 things and we do like 35. They think we're crazy. We do, you know, so many things, but it's, we see that the Lyme patients, the autistic patients, Gulf War Syndrome patients, they look the same, you know, that immune system, that, you know, uh, everything just like, wow. They have this common pathophysiology, what we'll talk about.

Yeah, the common is inflammation in different— inflammation stuck in different parts of path— in different pathways. Because one of the things— I mean, this is just an aside— it's that we're seeing is that we did two chronic fatigue studies with— only one of them has been published so far. The other one is kind of in the can waiting to come out. And one of them was done almost all with my patients. I shouldn't say my patients, patients from my clinic. And the other one was predominantly patients of Paul Cheney. I don't know if you know, a lot of people don't know about Paul anymore because he's kind of gotten quiet, but Paul was one of the original people that, you know, Paul Cheney and Peterson, you know, basically woke everybody up that this was happening.

Yeah, he got a lot of arrows too. Yeah, yeah, yeah.

But, but the thing, but What's interesting is that Paul doesn't quite believe as much in chronic Lyme as we do.

That's interesting.

Yeah, you know, and one of the things is that I— we did— a lot of the people in our— in the chronic fatigue group started off with Lyme disease years ago. We treated their Lyme and their joint pains went away. A lot of their symptomatology went away. What they were very— we were very careful to exclude anyone who had typical Lyme symptoms. What they were left with was, to me, the hallmark of chronic fatigue, you know, post-exertional malaise. They couldn't— their lives were limited if they did, you know, whatever it was. If they did 2 hours, 4 hours, whatever, if they passed that, they crashed the next day or later that day. To me, that's when they— there's so many of the academic articles on chronic fatigue are not talking about chronic fatigue. These guys, the people in academia, don't do not understand chronic fatigue.

Yeah, yeah, I'll wholeheartedly agree with that.

Yeah, they confuse— I mean, there's no way you can confuse a depressed person, okay, with someone with chronic fatigue. Yes, some people with chronic fatigue get depressed, but you know, when your family abandons you, when you don't— you can't function, you can't—

you wouldn't be depressed.

You may get depressed, but that's not what's wrong with you, you know. And anyway, I— this is So getting back, so in our panels, what was so interesting is that what we saw was these group of chemicals called sphingolipids, sphingomyelins, and ceramides, things that I had never heard of. I mean, I'd heard of in medical school vaguely. Actually, when I was in medical school, I don't know if we even talked about them. I don't know.

They just invented fire. Yeah, OK.

Right, pretty much. I mean, you know, I always laughed. The— oh, what is it? See, I'm getting so I can't remember things. Anyways, it doesn't matter, but I would just— there were— the library was not as big in the 1970s. It really wasn't. Prostaglandins— there was maybe 3 paper-thin volumes on prostaglandins when I was in medical school. Okay, now you could fill a library with things on prostaglandins. That's how far we have come with information. We haven't learned that much, but we got a lot of information. So the thing is, is that these lipid— these glycolipids, okay, are a lot— which have a lot to do with exosomes, interestingly enough. You know, the exosomes are made up of these glycolipid envelopes with a little bit of few proteins inside. Well, these are what's abnormal, significantly abnormal in people with chronic illness, because they're the— they, they are the signals that there's chronic inflammation in the bloodstream. See, because that is one of the problems of metabolomics, is we're looking again at the blood when many times the dysfunction is in an organ. And so we're still looking at just the drainage from the system, and that's why a lot of signals get lost. Because if it's your liver, you know, or your kidneys that aren't doing so well, but the rest of the body is doing okay, if you're You know, obviously if you're measuring the end product of what the liver does specially or the kidney does specially, you can discriminate, but sometimes you can't tell when it's just a little dysfunctional or maybe 20% of your liver is not working well. That's where the money is. Someday we'll figure out how to really check that.

But yeah, yeah, when you have— yeah, on cell signaling on the, on the cell surface, how do you get blood to check that?

You know, yeah, we're checking the whole system, but we can see patterns, and that's the important thing— the pattern of inflammation. And what's interesting is the patterns— so the patterns are similar enough amongst different symptom groups, like the Gulf War Syndrome are significantly different from the Lyme people, from the chronic fatigue people. Okay, but they're all in that same ballpark. The sphingolipids are off, but they're off sometimes in slightly different ways. And what makes it even more interesting, okay, is that amongst the people— and I said we had about 40 metabolites that were abnormal, you know, in the chronic fatigue group, and about, you know, 25% were— had to do with having chronic fatigue, were shared. But 75% of the abnormalities We're individual. We're based on that person's biochemistry, genetics, and environmental exposures.

Right, all the other things that they have.

Exactly.

Now, can someone order these tests, or is this all still recent?

Not yet. I mean, there are people selling small panels, but not yet. I mean, there's a company called Metabolon, which you can order your, your your metabolomic panel from, but they're giving you— I don't think you get really much information.

I guess the thing, how do you interpret it without looking at the rest, comparing it to the rest?

Right. So at this point, metabolomics is, is still in the experimental field. I mean, we had the TechBio that you had mentioned. We started TechBio with the idea that we were going to measure— we were going to be selling metabolomic testing. This was back in 2000 '16 when we first— the first paper came out. Oh my God, we got to be doing this. And then we turned around and we discovered something is that the information really didn't give us in chronically ill people a lot of treatment help. Yeah.

What do you do? Thanks. I'm sick. I know I'm sick.

Exactly.

Yeah.

We would have had to charge $1,500 for the test and it would have just told you you have chronic fatigue. Now, if we had had a big enough sample size and I could have made an FDA diagnosis, You know, then maybe it's still a lot of disability, but hey, exactly. But it really— see, because what I had hoped, okay, just like I'm sure you, is that if you give me enough numbers, enough chemicals, I'm going to make— I'm going to change things. Yeah. And this goes back to the big lesson that has a lot to do with the cell danger response, but the big teaching for me is that what we saw is that just because something was high or something was low, correcting that didn't change the system. Sort of like we talked about in the beginning, the right supplement doesn't always change the system when somebody is chronically ill because what we're dealing with is compensation.

Yeah, and it's not a cause, it's a result.

Exactly. Being a doctor, we got so used to if you're bleeding or if you're low in blood, we give you blood. Right. Your blood pressure's high, we lower it.

Everything's a vicious cycle and, you know, where— what caused what, you know, the genes create these and then they affect the genes. So what, you know, where, where do you go and everything, every system seems to be affected in these patients. And, and where do you start? You know, one causes the other and causes the other and kind of doesn't matter what the initial thing is. Now it's this big vicious cycle. But with like the cell danger responses we'll talk about, but mitochondria are key.

Right. And actually, let me just— another Dr. Bob aphorism is, you know, like, the path to health is not reversing the path to disease. You know, again, because that is the way we often approach medicine, because our medicine is based on a trauma, the story of trauma. You know, we're really good if you're broken, traumatically, we put you back together because the instigating event was the trigger and we just have to repair, you know, just remove it and let the body heal. Unfortunately, with chronic illness, that doesn't happen because the instigate— the thing that's making you sick is your body's response to the trauma, just like we see with our Lyme patients. You know, there's a, I don't know, a significant number of people, you'll kill the bug they're better. But there's even more that we get stuck with. You kill the bug—

yeah, they're still there.

They're still there. So anyway, so the story of the mitochondria, of how to think differently about disease, and is the mitochondria— is mitochondria have different forms. I mean, obviously we know you have like different mitochondria in your heart than in your fibroblast.

And let me just mention that, you know, mitochondria in the cell taught early medical school. They're basically an evolutionary organism that was probably separate and came into the cells, but they were taught they make the energy for the cell. That's kind of what they do. That's what we're taught in medical school, and that's what— if you ask, you know, 99% doctors, that's what they're going to say. So I just want them to explain what that is.

Yeah, right. And that type of mitochondria, that form is Bob has labeled M2, and you can ignore the, the numbering. I usually get them confused anyway, but he did. So, but this mitochondria, this is the mitochondria that's functioning normally in your body, and its job is to produce ATP efficiently. Okay, energy, right? Energy, energy. And, and it makes some of the raw materials that allow your— that your body needs for, for growth, but its main function is to take the energy that's produced in by burning glucose and make that efficiently into a lot of energy, okay, by passing the electrons down the electron transport chain. Now that's the M2 form. Now what happens is that if that, if that mitochondria starts to sense that it's not getting its share, its normal amount of raw materials it browns out. My analogy is that it's like the old days when you knew, you know, the Vandals were coming, the, you know, the barbarians were invading. You would like burn the fields, retreat into the castle, and seal the walls. And so hopefully they would— they wouldn't be able to survive long enough to lay siege, and they'd move on. And so we do the same thing. That mitochondria when it senses that it's not getting enough energy, it stops making as much ATP. And by doing that, it increases— since mitochondria, when you make ATP, is when you use oxygen, that's when your body's using oxygen, okay? You can burn, you can burn sugar without using oxygen, but— and we call that anaerobic glycolysis. But when the mitochondria are involved, it's aerobic, it's using oxygen. So when that stops, oxygen concentration goes up in the cell, and that creates a very oxidative, um, rich environment. And so you have to— your nucleus then starts to pour out your antioxidants as a response. Okay, so, but the other thing that's happening at that time is the mitochondria also start to take some of the ATP that it's still making and put it onto the cell surface, and it becomes a signaling molecule. And ATP, adenosine triphosphate, and, and all of its derivatives, especially things like— things that we think about like adenosine, are cell signaling molecules. These work like paracrine hormones. They're giving information to the immune system and to nearby cells that there's danger here, there's a problem. In fact, this happens on an ongoing basis. I mean, this is kind of how we learn. When our cells actually put a little more ATP on the outside, if it's a nerve cell, you learn faster, okay? Because you focus. I mean, you can't focus on every input that comes into your body, so you have to know which ones to focus. And danger focuses you at all levels, because this is a very conserved— this has been happening since we were amoebas. Okay, this is the first thing. And what happened— and it creates what we call sickness behavior. You're fatigued, you withdraw socially, you lose your appetite. You know, I mean, all these things are happening because you're making less energy.

Yeah, and it's like, until people get the flu, it's not the virus causing symptoms, it's your body's response.

Exactly. And what happens is that the mitochondria are directly involved in creating what they— the increasing interferon the interferon-1 group, which is made intracellularly and starts to make the inflammasome and the thing that makes you feel sick. Okay, so that's the normal— well, that's what happens when— so you have the normal mitochondria are making energy, then it goes to this M1, which is like this battleship form of the mitochondria, okay? And it also causes changes in the cell membrane. The cell membrane thickens. It starts getting less permeable because it's defending itself. It's less— you stop communicating. When a cell is really injured, like an injury, it stops communicating to the cells next to it because it's got to heal. So this is what's happening when it's healing. And then the next stage is what we call the M0 stage. Is— and this is, this is what happens when you're making energy by burning sugar, but the mitochondria have turned on again and are now using oxygen. So there's no longer oxidative stress, but you are now using that ATP to make— you know, you're not making ATP, you're using the electron transport chain to make intermediate chemicals, the things that make all your pyrimidines, which is part of your DNA and RNA. you know, and also chemicals that will help make hemoglobin and acetyl-CoA to help burn your fat. So you're making all kinds of things that help the cell grow. This is what happens in a cancer cell, okay? But this is also what's happening in your normal cells when they are rebuilding after injury, okay? And at that point, they're not communicating well with each other. And this is, this is one of the things— if cells— and then if the next step is they go back and the mitochondria are now operating normally, But now you're in what we call the third stage of the cell danger response, and the cells are just beginning to begin to communicate with each other. And if they don't fully go back to normal communication, we now have senescent cells, which is one of the dangers of aging. It's not the dangers, that's probably how we do a lot of this aging process of slowly falling apart, is that we have more and more Cells that haven't been able to come fully back online, they're working. They just don't have enough energy and they're not communicating. You see, this is the thing, it's communicating. Oh, remember that cool— you're old enough— Cool Hand Luke, you know, what we have here is a failure to communicate.

And it's interesting, and you know, with the mitochondria, I think you ask almost every person who's chronically ill what's their body temperature you know, it's low. We'll check everyone's basal metabolic rate. They come in, the sick patients, they're usually 25% lower, you know, so they're burning less oxygen, making less heat. You know, you're making energy, you're creating heat, and they're all low. And they don't eat anything and kind of, you know, they'll gain weight unless they have, you know, terrible gut issues where they can't eat anything. But it's, it's interesting. So yeah, we see that commonly. I think more and more even on a subtle level where people, they don't feel horrible, but very low metabolism, or they're kind of that early phase.

Yeah, it's, it's, it's where you get stuck, you know. That's the thing. Different diseases get you stuck in different places, and, and it can be happening in different— see, what's confusing is that we always want to make blanket statements, but it can be happening. You can have cells in your body that are stuck in the CDR1 you know, and then you might have a lot of scarring and hypertrophy of tissue. Or especially if it's CDR— I'm sorry, CDR2, you'll get a lot of scarring, you know. In CDR1, you'll have a lot of inflammation because there's usually— then you're still signaling the neutrophils to come cause problems in CDR1 because that's, that's that, that, that acute phase of inflammation that in some people doesn't tone down. Um, so it helps us think a little bit about this, what I'm hoping it's going to do eventually is help us treat people. As we can measure metabolomics in enough people and eventually even be predictive. I mean, to me, the really hot thing is if I can measure your metabolomics at age 30 and see where you're headed, especially through the lens of the genetics. We've all been frustrated by the genetics because remember, 20 years ago, we thought, oh boy, we're going to open that book of genetics. And get all the answers. And lo and behold, we open the book of genetics, and we mostly get confusion.

You know, and that is, that is a problem. And like, all especially all these genetic tests going out, which I do like them, is that really correlating them with, you know, with metabolomics, and, you know, or if you're seeing the results, like, people have, you know, myself, I have like every gene for— that's terrible, I should have high homocysteine, but I don't, you know. And so it's, yeah, it's interesting. I think, yeah, using it and correlating it with what's happening.

With what's happening, because we— I mean, genetics is a mess because we didn't realize how much is variable. How, you know, we thought it was a binary system, on/off, and it's not at all.

That's a good way of putting it, yeah.

Yeah, and but if we combine it with the metabolomics and the history of what we see, we can see where things are important and then treat appropriately instead of putting people on 35 supplements. You know, my whole thing in life, because I said I went through too many years with the shopping bags. People would literally walk in with 2 shopping bags full of supplements. Yeah, yeah. And I hate that. You know, I made a lot of money doing that for a while, but I didn't like it.

And it kind of goes into like treating a healthy person versus chronically ill, where let's say treating the mitochondria, that you can give them all these things, CoQ10, and— but if it's not working, it's not going to help. Where a healthy person may get a little boost if they're low, right? But it's chronically ill, you got to look at it a little differently.

Absolutely. You know, it was just some of the things we were talking about there. There, you know, there are some of those— the peptides that seem to work just in a very benign manner. They always help almost everybody, or they don't hurt. And there are some of the peptides that seem to have some double-edged swords to them, and that's because I think they're the ones that will work powerfully in that CDR2 mode when the body is in that place where it is acting actually like a cancer cell. But we want, you know, that, that's a time when using some of the, some of the interventions that will help the cell not kill itself is really good because you don't want to lose a lot of brain cells or a lot of heart cells, you know, until you're waiting for the vasculature to rebuild. You know, you'd rather not lose them because they grow back but not really well. So you would like to prolong their life, and so there are some peptides that will help do that, which is really great. If you have a stroke or a heart attack, but if you've got a tumor, it might feed the tumor because it's that same metabolism. The tumor is in that same metabolic phase of burning sugar to grow and using the mitochondria only to make raw materials, not using it for energy production. Because it's— so it's that— that's the important thing of, of, of where I think Understanding metabolomics, and this was understanding metabolomics, but thinking about the cell danger response, thinking about these cycles of what's happening in the body. Now, it's not easy because it's just, we're just, we're making it up, learning it all at the same time. But getting that thought process going of like, am I dealing with a person who is going through just a normal healing process? OK, after an injury, there's that 6 months. It could be a normal healing process, or am I dealing with somebody who is stuck in the early phase of inflammation and we can't get them out of there? And that would be a time— I think something like the BPC-157 is because I think that's what it helps do is help mobilize and get you to continue the healing phase.

Right, right. Yeah, and it— you have so many, uh, things that it does. It helps, yeah, basically heal and rejuvenate, lower inflammation.

Yes.

What, what other peptides do you like?

Well, the BPC-157 is one of my favorites because I— a lot of, a lot of the patients— I don't see a lot of patients anymore, okay? And the patients, a lot of the ones that I have are people who have failed not just what everybody else does, but also what I do.

I send them out and they come back and, you know, and they've tried everything.

Yeah, mentally, you know, 10% better here, 20% better there. I don't live in the world of home runs anymore. I miss that. But anyways, with those folks, often so many things are inflammatory, you know. So the BPC 157, I've been amazed that even people with major mast cell issues have been able to tolerate it.

Yeah, and that's more and more becoming a big issue with these patients with POTS. But really, I think it has to do with so many of these chronic infections. You know, basically mast cells are the allergic cell, but they— we've learned that they basically excrete tons of inflammatory products, not necessarily just histamine, and that cause allergic reactions. So Yeah, calming those down actually, in part, a lot of mast cell, mast cell migraines, they're still stuck on directly inhibiting mast cell, but really looking upstream and affecting the immune system, which affects the mast cells, I think is a much more effective means.

Yeah, I'm with you. I mean, that was something when Dr. Afrin first started writing about it, I had dinner with him. He has changed. The first dinner I had with him, He didn't quite get how important it was to deal with the infections, but now he does. It's really— I mean, I'm really impressed with that man because not many people learn, okay?

Yeah.

You know, especially when they think they have the answer, you know, and he kept learning. You know, he really did.

Yeah, I posted on that group. I said, you can kick me out of the group, but this is what I found that works, you know. It's against what even these guys consider A lot of smart, dedicated people in there, too, and I've seen you post a lot, too. Yeah.

Yeah. It's nice to see. But anyway, the mast cell— see, that's the other thing that's a fun thing that Bob pointed out to me. The mast cell is the original immune cell. When you have a multi-organ system, the first immune cell that popped up long before T cells and B cells and macrophages was the mast cell. So that's why it is so— it seems to be everywhere and do everything to our patients because it's primitive, but it makes like 200 different chemicals. And, you know, it's— so again, and treating it, I love your idea. You have to go a level, one or two levels up to really help. So fix the immune system. And probably the most important thing, the hardest, but sometimes the hardest thing is get that sympathetic nervous system off the roof. Because that's what, you know, when you, when you stay ill, you can't help it. You're activated. You're, you know, the parasympathetic gets turned down, the sympathetic gets turned up. But if we can turn that down, we can often really ameliorate the mast cell issue as well.

It's just a And a little pearl I lecture on is that one major stimulator to mast cells is corticotropin-releasing hormone. So, you know, basically the sympathetic nervous system, you're going to stimulate cortisol, which corticotropin-releasing hormone stimulates ACTH, then secretes cortisol. So these patients will have even high normal cortisol, but their ACTH is very high. So they're just, you know, on fight or flight. But if you give a little more cortisol, lower that ACTH, so it lowers that CRH, oftentimes the symptoms get better.

Yes, and that's the wise use of low-dose cortisol is a true art.

And yeah, you gotta— and some people, you know, it's— yeah, that can't tolerate.

In a way, when you think of it, that really is, you know, let's see, you know, cortisol is really not an amino acid peptide therapy, but same idea, same idea, small amounts in the right places.

Yeah, and actually BPC will actually lower that CRH or lower the ACTH. We can't check CRH. And when they're high cortisol and you're like, I don't want to give them cortisol, but their ACTH is even higher, BPC will actually—

Oh, thank you. That's a really interesting pearl. Yeah, I like that. I, you know, like many people, I started off using BPC, you know, focused on the gut.

Yeah, and as the gut is very— like, you know, we're finding more and more that, you know, gut brain-gut-everything axis. And it's really, again, that epigenetics, you know, goes along with that. And you just kind of getting close to ending here, like the thymosins.

Oh, I love— yeah, the thymosins. And again, in my population, I'll often start off with the thymosin beta-4 before I'll use the alpha. You know, I just find that, you know, it's often in people who are really— have very reactive systems. I need to mellow the immune response a bit, you know.

And then just kind of for everyone watching that, so if you, if you look at this oversimplification, you have kind of Th1, which is the intracellular immunity, and Th2, which includes Th17. But, and usually everyone's out of balance, so this is kind of the inflammatory autoimmunity. BPC lowers this. TB4 kind of is modulator of both. Thymosin alpha 1 really increases, which is good, but it also is— can really kill infections and you can have more reaction to that. So it's often good to start with the BPC that lowers that, that Th2 and lowers that inflammation that people can tolerate. And just a little side note too, thymulin, probably it's much more anti-inflammatory than all the other thymosins. And for Herx is that we use that. So just a little side note.

You know, that is always important because it's balance. I mean, and you know, when somebody is staying ill for a long time, you know, occasionally, you know, there's no rules. You know, I always want to make rules, but there aren't any because it's the same thing with like the LL-37 stuff, you know, which is a really nice immune, just goes out there and like gives information to the immune system, you know, kind of kill. But, you know, in a lot of people, it's really easy. But in my patients, I go very, very, very, very gently. And unfortunately, I don't think we can get that anymore.

Yeah, you can, but it's hard to get harder and harder. But just so everyone knows, it's antimicrobial peptide. So it's very broad spectrum viruses, bacteria, yeast, but also like BPC, you don't think of it as antimicrobial peptide. But it kills viruses, Candida, and, you know, one study showed that it killed the herpes virus in 1/100th the dose of acyclovir. We will have BPC with KPV, which is alpha melanocyte stimulating hormone, which is like melanotan, makes you tan, lose weight, got Barbie doll peptide. It's a small fragment of that which doesn't cause the pigmentation but amazingly anti-inflammatory and antimicrobial.

I would love that because, you see, in the old days we used, and I still occasionally used, you know, when we could get— before now we have to use the melatonin, but used to get MSH, you know, along with VIP. Those are— I mean, this is another contribution of Shoemakers, you know. I mean, like, those again, they really help reset the imbalanced immune response. You know, I was very, very, very impressed with those. So I mean, I think that's— those are really, those are really important ones.

Yeah, it's nice. So that, that should be out probably the next month. But yeah, great studies on inflammatory bowel disease and autoimmune. So yeah, a lot of literature on it, which is nice.

Yeah, yeah. No, no, that, that is, that is, is fascinating. It's fascinating stuff. And you know, the microbiome, just to say, Is that that's the other thing we can see a reflection in the microbiome. We can— there's about 30, probably more chemicals that we can measure in the metabolome, in metabolomics, in your blood that are clearly from— your body doesn't make them. It was the bugs in your gut. And a lot of them obviously—

And it's interesting with this gut-brain axis that it goes both ways, that the gut You know, basically influence the brain, the rest of the body, but also rest of the body, the brain influence the gut. So it's like you give all these probiotics, but then all of a sudden they're back to the way it was, you know, because they influence the other way of what's going on in the system. So it's, it's interesting. Yeah, everything's a chicken or the egg.

Everything, you know, that my, my favorite thing to say is, yeah, two favorite quotes. One of them is everything works sometimes.

I've used your line. You gotta actually lecture me on that.

I just have to say, I mean, like, I love— I've worked with some brilliant practitioners over the years who have much more patience than I do and are able to, like, stick to one therapy for a while, and you really get to see the full beauty of what it can do. I, on the other hand, tend to be a, you know—

I'm like you. I'm ADD. I'm moving on.

Yeah, moving on. Okay, that didn't work. You know, I mean, and which is a shame because I have learned Thankfully, I have these people around me, so I watch and I learn through them that many times if you wait 3 months, it does work.

Yeah, that's about the max I give. But, and that's the problem too, it gets very complicated. If you do treatment A, it works, it doesn't work, uh, then you do treatment B, doesn't work, and treatment C doesn't work, but then do it together, it worked, you know. And so there's so much to it. Yeah, something doesn't work.

I was going to say, that's one point I was going to make, is that when we're— when people are stuck I just— it's not me. I just fully— I really believe that so much of chronic disease can be ameliorated, maybe not cured, but ameliorated and helped if people pay more attention to the fascia and the connective tissue and the musculoskeletal system, because that is often where you're getting that— where the glitch is in the feedback from the central nervous system to the organ and vice versa is because those nerves are often very sensitive to fascial tension. And to be honest, just like, you know, the acupuncture meridians are probably flowing through the fascia, and if that's all tight, that's when your acupuncture just, you know, doesn't do much.

Yeah, and it's interesting. I know Dr. Neal has talked a lot about the fascia, and going along with that, with just practical, we have a stem cell doctor and he comes. Let's say you have rotator cuff, right? Normally you want to inject in there right next to the stem cells, right into where the, you know, where all the problem is. He just does it sub— kind of subcutaneous into the fascia, right? And you're like, how is that going to work? And 10 minutes later, the people have full range of motion. It's incredible. We're thinking like, okay, this is ridiculous.

But, you know, it's sort of like neural therapy. Yeah, you know, I mean, basically neural therapy you know, is where we put information right below the skin that feeds into the sympathetics, and they're going right to the brain. I mean, it's— this body is just so amazing. I mean, like, you know, doesn't matter. I mean, that's my dream, is to have the team of people who can dance, who can treat different ways, but who could actually work together. One of the difficult things I'm sure you have seen over the many years that you've had your clinic is how hard it is to get the A-team willing to work together.

Yes, herding cats.

Yes, yes, yes, yes.

So yeah, you're good at doing that, which is— so I think we're running out of time here.

Okay.

And just want to say it's—

yeah, I hope people learned something. I, you know, it's often hard to convey new complicated ideas, uh, in, yeah, in a short time, but I think the main message is that there are more forms of mitochondria than we knew, than we've thought about before. And one— yeah, and they do actually change shape in the mitochondria while they're changing. When they're in the normal form, the M2, they're long strings. They kind of connect to each other. When you go into that danger zone, they break apart, they stop connecting.

And yeah, I think there was a study, very old study, where they did muscle biopsies in chronic fatigue syndrome patients and their mitochondria were very different. Oh yeah, about 80% of patients.

Another conversation one day that isn't directly related to peptide is a riff on a recent study of showing that serum from chronic fatigue patients actually has some interesting effects on normal people. But anyways, there's so much to talk about, Ken. You, you are—

you make them sick.

Yeah, yeah, you actually make them healthy. Not healthy, you make them resistant to viral infection. Interesting.

So yeah, so it shows it's all set up to fight.

Yep, yep, it's at a price, at a price.

Yeah, yeah, nothing's free. Well, always wonderful to talk to you, always new things, so we really appreciate you being on with us and thanks so much.

Okay, my pleasure, Ken. Great.

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