Transcription
Hey everyone, and welcome, welcome, welcome, welcome to a Long Haul Syndrome presentation. I'm Dan Kalish, and I welcome you here. If someone could just raise their hand so I know that my sound is working, then I can relax with my technical setup here. Oh, thank you, Margo. Are we good?
So, we have a lot to talk about. I want to thank Genova for helping us put this on and sponsoring it and helping get the word out. Yeah, this is something that we're very interested in studying right now. And a little bit about myself, if you have not attended one of these before with me. So, um, oh gosh, so many things have happened. I don't even know what to call it. But anyways, my past life, you know, pre-COVID, I was, uh, I worked with the Institute for Functional Medicine for three years, um, setting up this practice implementation program, which we taught all around the country. I may have run into it at one of their conferences, but I was at all the modules for quite a while, uh, teaching the sort of practical aspects of starting a business in functional medicine. That was a really great experience. And I've worked with the BAM clinic on research projects. I've worked with Richard Lord. So you may know Dr. Lord was one of the original scientists that developed a lot of the work that we do. He was the first one to do amino acid testing, fatty acid testing, organic acid testing. He developed the GI Effects test. He's long retired, but he and I work together every week and have been doing that for seven years, which is really one of the biggest joys of my life, uh, to have such a brilliant teacher. I'm in practice. I'm actually certified through IFM. Been practicing. That's out of date. That bullet point. It's really closer to 30 years now, if you believe that. Um, and I've been teaching for a long time.
And so, um, what we have coming up, we've been working on this for a long time, is the Long Haul Syndrome Bootcamp. So if you're interested in the course that we're doing right now in this webinar, you think you want to spend a few months really diving into this pretty deeply, you may want to sign up for the Long Haul Syndrome Bootcamp. It starts, uh, June the 8th. It's a 20% discount for Genova clients if you use that code or passcode there, GD22. And, um, it's a two-month exploration of long-haul COVID, mitochondrial work, ACE2 receptor stuff, um, science, you know, sort of the clinical models and treatments, and mostly lab interpretation. So what we're seeing, you know, because I teach a lot of classes now, I have my mentorship program, and we have long-haul COVID patients literally in every class that I teach every week. And I meet, you know, five, six hours a week of teaching. And so we're seeing a lot of these cases now, and what doctors are doing, and what's working and not working, and want to get the word out because this is the state of the next decade, I think, for all of us. So anyways, that's coming up. If you're interested, you can sign up for that.
And today, we're going to kind of focus in on an area, one area of this, that may be one of the more important areas, you know, for a lot of patients, which is understanding how the brain is impacted by COVID and how the brain is suffering in long-haul COVID. And look, a lot of cytokines. And there's a study I was just reading this morning on COVID-19 and kynurenine and kynurenic acid. And like, I mean, there's what used to be, in my mind, kind of integrative medicine ideas are now very much in the mainstream. And this whole idea of cytokines being problematic, and, uh, you know, neuroinflammation being problematic, is now front and center. And we've got the testing for this. You know, we've been doing this for generations, literally. I'm like, probably the third generation of practitioner that's been doing this kind of work. So it goes back to the 70s and 80s. There's nothing new here, but we really can make a huge impact if we can figure out how to interpret these labs and help people. So I want to look at that. And we'll also have some time at the end to review labs, and I'll do as many questions as I can.
And so to start off with, I wanted to look at just models. I'm very, very interested in us all having models so you can communicate to patients. So if a patient comes in and you suspect they have long-haul COVID, you have a checklist of things that you're starting to think about. And, um, that can vary. This is, this is from a friend of mine's website, Dr. Schweig's website. He put this together, and I really like the graphics. They're kind of cool: viral persistence, autoimmune, mitochondrial impairment, and the cell danger response, dormant pathogens in the body, microclots, mast cell activation, brain function problems, and microbiome dysregulation. So just to point out that we're just looking at a subset of this, um, but an important subset of this, you know, rather large problem that we're now seeing people are confronted with.
And so when I, you know, in my practice as it is today, um, I've had, in the last even six months, more new patients come, more old patients come back as new patients than ever before, who had a problem that I solved 5, 10, 15 years ago, and now that problem's back. We've had a large number of new patients coming in who have, you know, acquired COVID and just haven't recovered. And so this is becoming probably three-quarters of the work that I do in my own practice. And we're seeing that in a lot of practices throughout the country. This is really going to just take over everything that we do. So we've got to figure it out.
And then the good news on it, on all this, is that like I said, for three generations, integrative practitioners have been dealing with post-viral syndromes. This is a unique virus. I know it's different than other ones that we've confronted in the past because it, you know, primarily affects the ACE2 receptors and the mitochondria and the cardiovascular system, and then it kind of also takes a hit at the immune system, autoimmunity, the microbiome, and all these other things. But, you know, it's, it's not fundamentally a whole new problem, uh, in the to the extent that a lot of these problems have been worked out before with other kinds of infections. So I think we have a good shot at helping people with this, just based on the history. And there are all kinds of different models that are being put together, and I just grabbed one or two here that I've been looking at. This is a nice one on viral persistence or inflammation or autoimmunity triggering all these things. I think what the conventional medical community is starting to struggle with as they attempt to deal with long-haul COVID is the, you know, multi-factorial systems medicine kind of approach that has to be taken here because it's not like any of these people have one symptom, and it's probably not going to be that any of these people have a single isolated cause to their problem. That's probably going to end up being a whole variety of things that we all need to look at.
And so when you look at the conventional scientific literature on this subject, it's really quite interesting that they're thinking much more in a systems way than, than, you know, typically would have happened before COVID. But we want to talk about for the most part now are cytokines and how all this works, and in particular, what happens when the body produces a large number of cytokines, and how that impacts tryptophan levels, and how that can impact the brain, and how you can measure for that on the tests. Okay, that's really what we want to look at.
And I also think, and this is something that, let me just draw on this for a second, that we understand when we're looking at organic acids and amino acids and fatty acids, we're looking at metabolomics. We're looking at the study of these small molecules or metabolites that are within cells. And so there's a context to it, though. So we have our genes and genomics, the study of the genes. And some of you probably already do testing for SNPs and whatnot. You may see some of that, some of the problems that we're talking about tonight revealed in, in the genetic testing. And then we have the proteins, or proteomics, right? The study of proteins, proteomics. So the genes encode for us to sling together these amino acids into sequences. For example, the ACE2 receptors are about 815, I think, amino acids put together, you know, um, and eventually then we run and regulate our metabolism through these proteins. And so what we're talking about now is some people may have a genetic tendency to have problems, some people may not. But all the people that we're going to look at are going to be struggling with the ability to make proteins properly and the ability to run their metabolism properly. And what I think you see all long-haul COVID scientists agree on is that there's problems with the blood vessels, there's problems with the mitochondria, and there's some major issues with the ACE2 receptors. So from there, things diverge, right? And some people are looking more from an autoimmune perspective, or some people are looking more from, you know, old infection that's being triggered perspective. But I think there's a few common things that we can see that we can all agree on here. And one of them is the cytokine issue.
So this is a little daunting, but just to show you, when this is really what we want to think about is up here, it's tryptophan. So tryptophan is used for a lot of different things. It's used to make serotonin, it's used to make melatonin, and you'll see in a slide in a minute, it's used to do a whole lot of other things. And it's used up or burned up or depleted when we produce a lot of cytokines. And so one of the common effects of having a lot of cytokines produced for a long time is that your serotonin dips or your melatonin dips. So you can have sleep problems, or you can have depression or anxiety problems that are a direct result of having acquired COVID in the past. We're not going to talk too much about the other side of this here.
And then if you haven't run across these papers and you haven't studied Dr. Robert Naviaux's work, I really encourage you to do it. Um, he talks a lot about the cell danger response in his work, and it's quite profound. I had the amazing pleasure of sitting next to him at a dinner in Phoenix a couple of months ago, of all places in the world, and, uh, I got to sit next to this guy. He's like one of the top scientists in the world. I got to sit next to him for like three or four hours over, you know, a couple glasses of wine and a really long dinner. And he's quite, quite a human being. He's a very gracious and amazing human being. And at the same time, he's one of the best scientists in our field right now, really quite remarkable. But his work has probably never been more important than right now in relation to COVID.
Here's a slide from one of his studies, and I'll just show you what the short version of the cell danger response. If you want to listen to his videos or read his research papers, much more eloquently put by him. But what, what happens when, um, in this, in the simplest way put, you know, simplest way we could put this, is that when the cell is first attacked, and it doesn't matter what attacks it. We're talking about a virus now. We could also be talking about people who have post-vaccine injuries, so someone who actually is suffering from the side effects of a vaccine to prevent the mRNA vaccines to prevent COVID, or it could be someone who had COVID, or it really could be any infection. The same mechanism kicks in, which is that when the cell is attacked, it goes through these three stages that he outlines as the CDR, or cell danger response. And the first thing that happens when the cell senses danger is that the mitochondria change. They change their behavior, they change their shape, they change their function, and they stop using oxygen to make energy, which is the main job of mitochondria most of the time. And instead, they signal the cell that the cell is under attack. And so it turns out that the mitochondrial production of ATP can be used as a signaling system as well as an energy system. So again, if a virus hits the outside of the cell wall here and starts to invade, the mitochondria instantly stop using oxygen to make energy, and they use that oxygen to generate oxidative stress. It's pretty profound. In other words, the mitochondria shift from making energy, and they go into, like, it's kind of like mitochondrial fight or flight, in a way. Or it's more like, you know, with all the wars going on right now, it's more like a war. It's more like a soldier. I think of it like a soldier who's walking around and they're polishing their rifle and polishing their shoes and marching around, and then all of a sudden a war happens, and then they grab their rifle with their buddies and they go out and start shooting at other human beings. They're in battle mode. They're engaged in, you know, combat, and they're not caring about whether the shoes are polished anymore. They're carrying about whether they have enough bullets or not. So your mitochondria flip as soon as the cell membrane is impacted and the electrochemical charges, they're changed a little bit, there's a little change there. Then the mitochondria stop making oxygen, stop using oxygen to make energy, and they start to create this massive amount of oxidative stress. And why does that matter? Because when that oxidative stress gets to be too large in amount, you know, then it's quite dangerous, and cells can die. And one of the characteristics of COVID is that when you get the infection, you can have this cytokine storm, or this huge amount of inflammation and oxidative stress that occurs. And what we're then concerned about is damage to mitochondria that could occur because of that process. Okay.
And here's more details on the cell danger response. Again, you can read about this later if you're interested. I think it's fascinating. But what we're talking about is when you're first exposed to the virus, your body tries to contain it, and your innate immunity kicks in, and your mitochondria are the generals that are coordinating this army of innate immunity, and they're telling everything else what to do. And if that goes on for a long period of time, you can get stuck in that CDR1. You can also get stuck in what he calls CDR2, cell danger response two, the second phase or second stage here. And there's different factors and all that. The main point is that the mitochondria get involved immediately, and they are regulating and controlling our innate immune response. And because of all the inflammation that's generated as a protection mechanism, mitochondria, in the process of protecting you, are damaged. And that becomes a really big problem.
So cytokines and transcription. And this is a really interesting quote here from this one article: "Transcription factors involved in the regulation of cytokines and their receptors, as well as transcription factors that are activated by cytokines." So, in other words, the activation of cytokines also starts to regulate your genes. So when we get inflamed, and this whole process kicks in, that has an impact on the genes, and this back and forth thing happens, okay? So the signaling systems in all of this are really key.
Now, if we're going to kind of bring it down to a clinical application standpoint here, we're thinking about three different ways that the neurotransmitters can get thrown off: stress, which of course, plenty of people have now. We're looking more at toxins or biotoxins, the inflamed neurons that happen when you're exposed to an infection. But then we also want to consider genetic factors, okay? So those three are kind of all coming together. And these are the types of symptoms that you guys, I'm sure, are familiar with: depression, fatigue, brain fog, and things like that. So there's a series of chemicals, and when we get to the lab portion, I'll show you how you can measure for all this, that are going to be that will indicate to you if the brain is inflamed. And it's not that hard. You'll see markers like kynurenine, quinolinate, picolinate. You'll see, um, a whole series of other markers that have to do with the tryptophan itself. There's markers for serotonin production, whether they're high or low, and there's markers for tryptophan, whether it's in the normal range or low. So you can get a read on these pathways from a whole bunch of different angles all at the same time. But it revolves all around this kynurenine molecule and what's happening with this particular pathway here.
So in general, when kynurenine levels go up, we know that there's some kind of chronic inflammatory process going on that's impacting the brain, and it's very often infection-driven. When kynurenine goes up, it also stimulates the overproduction of this other metabolite that we can measure called quinolinate. And quinolinate is neuroexcitatory. And so this is a normal response to inflammation and infection. See, we have inflammation and infection here. We have this pathway. There's our tryptophan converting into kynurenine, and then converting into quinolinate. And that quinolinate goes to the brain. In the brain, it stimulates these NMDA receptors, which become overly excited and make people feel not that great, right? So that would create anxiety or depression or brain fog or problems with sleep. So this is the brain when it's inflamed. And we actually can measure these markers. You can measure the tryptophan itself, you can measure for oxidative stress and inflammation, you can test the kynurenine and quinolinate. And when you see these levels are high or out of balance, then you know that there's a specific problem that you can address. And there's some really simple solutions. Like, if quinolinate is high, you can use magnesium. Obviously, if tryptophan is low, you can use tryptophan. If the body is inflamed, you can use curcumin. So there's some very real treatments here that can impact people rather dramatically. It's really extremely rewarding to do this. Again, when quinolinate levels go up, you have this impact, very negative impact on the glutamate or glutaminergic related neurons, okay? And that's going to create just an agitation and depression that's very uncomfortable for people.
Now, this kynurenine pathway, as we saw right here, is driven by, is from tryptophan. Let me just show you that one more time. So tryptophan converts into kynurenine. So if you're making a lot of these inflammatory cytokine, you know, responses, a lot of these are happening because you're inflamed from an infection, then tryptophan levels can drop. You'll see this quite frequently. And tryptophan, when it drops, becomes a really big problem. And I thought this was a little bit funny when I first found it. It's actually an International Journal of Tryptophan Research, but these people are pretty serious about tryptophan. And they talk about, you know, tryptophan's basic role. So if tryptophan is depleted because you have an infection and you're fighting an infection, that's the least of your worries. What really happens that's a bigger problem is that you cannot make proteins. Remember, we're talking about proteomics and genomics and metabolomics. When your body's making tons of kynurenine to fight and deal with an infection like COVID, you're going to not only lose the ability to make serotonin and melatonin and get depressed and have sleep problems, but it's also going to interfere with tryptophan's main role in the body. Tryptophan's main role in the body is protein synthesis. I love how in this journal article, they put this first: "The principal role of tryptophan in the human body is as a constituent of protein synthesis." The principal role of tryptophan in the human body is as a constituent role, uh, constituent of protein synthesis. So there's 20 amino acids you need to make proteins, and if you don't have enough tryptophan, you're going to be in trouble. And this is one reason why when you get an infection like this, you can have all kinds of problems throughout the body because now you can't make proteins adequately.
And here's another diagram on tryptophan. I think that might be a little bit helpful because it's never what you think it is, you know, when you're studying this stuff. So here's our tryptophan. Out of the tryptophan, most of the tryptophan is going to produce proteins throughout your body. Some of the tryptophan turns into niacin, believe it or not. You make vitamin B3 out of tryptophan. What were, and here's the kynurenine pathway there, right? And then a small percentage of the tryptophan goes over to 5-HTP, which goes over to serotonin. And most of that serotonin actually is produced in the gut, and the gut uses it to increase peristaltic contraction. And actually, in the gut, and a tiny little bit of the remaining serotonin ends up in the brain. Okay. So tryptophan, where we think of it as most famous for the serotonin effect on the brain, its main role is in the production of proteins. All proteins in the body except for collagen require tryptophan. So you can, here's where this gets interesting, is you can have a depletion of tryptophan because you have an infection, right? And then that depletion of tryptophan can cause all these other problems. And all you have to do is the test to measure the tryptophan, and you're giving them tryptophan, not only to improve their serotonin and to improve their melatonin so they can sleep and they're not depressed or anxious, but also so they can start to synthesize body proteins.
And here's, if we're going to kind of hone in on the serotonin part of this, because obviously you want people to feel better, here we have our tryptophan again. Most of it's going over here in protein synthesis. If you have an infection, here's your kynurenine, you see that there? And so it goes over and it goes down to quinolinate. Why? If there's inflammation or an infection, then tryptophan takes a turn down this way, right? That's what we're worried about. And these are the very inflammatory cytokines that we talk about when we talk about a cytokine storm. So here and here, and then these chemical compounds, these metabolites, are also neurotoxic, neurodegenerative, neurodamaging. So when quinolinate goes up, it damages the brain. That inflammation causes a real, a negative impact. So what we want to do is stop the inflammatory process, shut this down here, so we can use our tryptophan for the good stuff, to go over this way to 5-HTP to serotonin, so your gut is happy, your brain is happy, you can sleep well. That's what we're shooting for.
So one of the important things, obviously, is you want to shut down inflammation. That may involve testing and correcting the gut. There's a lot of different things that go into that. And of course, I just had to mention fatty acids because it's a, there's a very good chance that the person is going to need omega-3 fatty acids. We can also test for that. You might, and these days, with with the current patients I'm working with, I give them omega-3s to almost everybody. Keep an eye out for that. But again, you can test for the omega-3s and 6s quite easily on the labs.
So in summary, and then I want to look at some tests in a moment now, but when we're balancing the brain, we want to look at the inflammatory pathways by which serotonin is depleted. That's through excess kynurenine production. You want to reduce inflammation also. So you may need to test and correct the gut. You may need to do a few other things. And I'll, I'll just mention also briefly that with long-haul COVID patients in particular, there's a couple of patterns that are seen when there's brain involvement. So one of the patterns is that a bacteria, a kind of famous bacteria that's on a stool test, like a GI Effects test measures for this, is *Faecalibacterium prausnitzii*. If that is low, and which it can be easily in a long-haul COVID patient, you're not going to have the production of butyrate that you need. Okay? So there's this gut microbiome connection. So butyrate is a short-chain fatty acid that's made in your gut by certain good bacteria, and they make it in response to you eating fiber. And *Faecalibacterium prausnitzii* is the one that's been the most strongly associated with long-haul COVID. So if that one is low and you're not making enough butyrate, you're going to have major problems with this whole gut-brain connection.
So butyrate is the main fuel supply for the intestinal lining cells. 60, 70 percent, maybe more, of the energy that the intestinal lining cells use comes from butyrate. So that's important for that reason. But when butyrate travels to your brain, it has a very magical effect. And I'll ask this as a question: Does anybody know what butyrate does in the brain? I'll give you like maybe 10 or 20 seconds. See everyone types in the right answer. What does butyrate do when it hits your brain? So you have *Faecalibacterium prausnitzii*, this good bacteria in your gut, which you can measure on a GI Effects test from Genova, and it makes butyrate. When butyrate goes to your brain, it stimulates brain-derived neurotrophic factor, BDNF, which generates the production of new brain cells. So if *F. prausnitzii* itself is low, you're going to struggle to generate new brain cells. That's one of the profound gut-brain connections. So as you're doing the metabolic testing, and you're doing your neurotransmitters and organic acids and all that stuff, you also want to combine it with the GI Effects because if the commensal bacteria are low or the butyrate is low on a GI test, then you're not going to have that stimulation of BDNF that you need to make new brain cells.
And one of the hallmarks of long-haul COVID in the brain, independent from the whole inflammatory pathways we're talking about here, is that brain cells die when people have long-haul COVID. And there's a series of studies they did in, in the UK where they, and these are really, these are devastating. So there's two big studies they did. One was on MRI. So they had 40,000 people that had had MRIs at this huge data bank of MRIs, and they took, I think around 800 of them, and they had them repeat their MRIs. So they had these MRIs before they had COVID, and then they redid them after COVID. And then they separated them, obviously, into two groups: ones that had COVID, ones that didn't. And the ones that had COVID on the second MRI had about a 30% decrease. Oh, I'm sorry, 30% of the people that they tested, 30% of the people in the follow-up MRI had a measurable decrease in brain size. In other words, brain cells have been destroyed. The brains had shrunk. 30% of the people they tested, they could see on MRI that their brains were smaller, not working as well. And then on a different study, they also did in the UK around the same time on long-haul COVID patients, they found about 30% of the people that had had COVID had a reduction in spatial memory and other, you know, tests of brain function. So this virus, one of the main things it can do is impact your brain in a very negative way. And not all these people had severe symptoms initially. Many of these people had very mild or moderate symptoms in the beginning when they first had COVID, but it goes up through your nose, right? And you, some people lose taste and smell, and then it's in your brain, and it's not a good thing for that to happen. So that is a pretty profound implication of what's going on here.
And when COVID is in the brain, it destroys brain cells. And then, in addition, this sort of separate, independent, separate and horrible problem from what we're talking about tonight primarily, which is the whole inflammatory response, the whole gut-brain inflammatory response. So both of these things can happen. You can have the kynurenine pathway activated, quinolinate going up, and have all the cytokine production that's causing a problem, and low tryptophan. And then at the same time, you can have problems with the brain cells actually dying or being destroyed. And one of the main ways to get them to grow back is to increase butyrate. So you can, you can test GI Effects tests will show you if they have low butyrate. You can give them butyrate as a supplement, as well as give them prebiotics and fiber products so that *F. prausnitzii* levels come up because that bacteria is making butyrate for you. It's a little butyrate factory. But in the short term, I'm supplementing everyone with butyrate, as well as doing the GI testing and fixing the microbiome. Okay? So that's a super important aspect of getting the brain to work well.
All right. So now let's take a look here at some tests. It's a crazy world, you guys. So much going on right now. So I'm going to just show you a couple of labs and then how this all ties back on a practical level. So hopefully, when you guys look at your tests, you can start to make sense of this. And in some ways, this isn't that hard. In some ways, it's really hard. I sort of struggle with that. I think you can get tripped up with these things pretty easily. All right. Let me find, hang on one second. I got to blank out my screen for one sec. I want to shift gears here. Here we go. This should pop up on your screens in a second now. This is, as you can see, an I-CHIP. And bingo, you should see that right now. Now you can look at the, at the front page here, the summary page, and see a lot. And let's go, here's what my plan is. Let's see if we can do this. Just go through a couple of labs and design a couple of programs, and then I can get the questions at the end. Okay? So type your questions in, and we'll try to cover as many as they can.
So number one, long, when when you get COVID and don't recover, there are many mechanisms. I showed you that slide. There could be autoimmunity, it could be persistent infection, it could be reaction to a vaccine, it could be an old infection that's coming back, it could be the, the spike protein still circulating in your body, it could be just an inflammatory response that you can't quiet down. So a whole bunch of things can happen. But there's two things that always happen with one, which is that the ACE2 receptors are damaged or deficient, and the other is that the mitochondria are impacted. And the way that that occurs, the reason why those things, the reason why the mechanisms behind how that all occurs, is because there's this rush of cytokines and there's this rush of inflammation/oxidative stress. Okay? And so we're just looking at one narrow aspect of this so we can kind of get something concrete to teach in an hour, but I just want to see the bigger picture. Oxidative stress is through the roof. It has to be in all these patients. That's the main problem. Remember, the cell's attacked. The body's response to that is for the mitochondria to stop using oxygen to make energy and to use that oxygen to to increase oxidative stress within the cell. Why does it do that? Well, because that makes the cell a really hostile environment for the virus to survive. So the massive amount of oxidative stress that's generated is your body trying to protect itself from the infection. And of course, with that goes overboard, people end up, you know, in the emergency room, and they're in some serious trouble. But if there's a mild infection, this is what most of my patients have had. I have, I haven't yet had any patients who have been hospitalized with COVID. All the long-haul cases I've had were mild. They didn't go to the hospital for any reason. They were just sick for a few weeks, and then they were okay, you know, until they realized they weren't. So that oxidative stress damages mitochondria and damages the pathways in the brain that we're talking about.
So here we see lipid peroxides are high, 8-OHdG is high, cysteine is low. That would be the classic picture of this oxidative stress or this inflammatory response. So now let's go look at how that ties back to the brain markers. Well, first, let's look at tryptophan, just to be fair, and let's look at the end of this lab where the amino acids are. Here we go. So this lab, first of all, if you, we're looking at the amino acid section of the neurotransmitter valve. Now, in the long-haul COVID patient, uh, it's kind of interesting. Look, histidine is low, lysine, tryptophan, arginine, cysteine. Each one of these means something different, you know, but this, we could talk about them all for hours, but oh, glycine, look at that. Okay. So let's talk about the super essential ones. There's, um, if you want to just try to focus here, I have like a lab interpretation, uh, kind of like I want to try to cover all of it at one time. It's like, oh my god, that's not gonna happen. Okay. So this is, we're gonna ground ourselves here and just talk about glutathione. So remember, there's three amino acids you make glutathione from: glutamine, which is just barely borderline low; cysteine, or cystine, which are low; and glycine, which is low. So that fits perfectly. All three amino acids that this person needs to make glutathione, which is the master antioxidant that's trying to stop all this carnage, right? If the infection is triggering this kynurenine-quinolinate nightmare, it's glutathione that's trying to stop it. It's trying, your body has a mechanism to try to stop the cytokine storm, obviously. So those three amino acids need to be replaced to get the glutathione up, or you could use glutathione, or both. And you can see tryptophan is low. Okay, so low tryptophan. So you're going to want to support with tryptophan. There's many reasons why you might want to use 5-HTP, but if the person's low in tryptophan, 5-HTP is not going to ever bring tryptophan back up. You have to just use real tryptophan. Okay? And the dosages should be at least 1500 milligrams a day. And if it makes them drowsy, you know, give it to them at night. There's other ways you can do it during the day. You can combine it with tyrosine, you know, so they're not as tired. But anyway, so that's, that's one section here. So glutathione, the master antioxidant that's going to protect the inflammation, protect the brain from the inflammation. So cysteine, glutamine, glycine, or a lot of people use NAC, or N-acetyl cysteine, for this purpose. Maybe 3,000 milligrams of NAC, maybe 3,500 milligrams from that range of NAC. That's to get the glutathione up. You could give another 3,000 milligrams of glycine for this particular person. Get the glutathione levels up with NAC and glycine. That's going to protect the brain, knock the inflammation down because you got to stop this pathway. It's act, it's overly active. You don't, you got to stop this kynurenine over-expression thing, right? You can also use curcumin. But in this case, the NAC and glycine would be perfect. So now you're like, okay, we're dealing with the original problem here. We're calming this system down. Now we're going to look at the kynurenic acid. Let's see. And you can see here, let me do the highlighter thing here. You see here, here are the highs. Xanthurenic acid is high too. So this is a marker for B6, and B6 is very strongly related to the production of all these different chemicals that we're talking about. So this person is deficient in B6, and they've got these neuroinflammatory markers that we're talking about. This kynurenic acid, or kynurenine, is through the roof. Quinolinate, or quinolinic, quinolinic acid also high. Okay. So you want to get those down and support with the tryptophan. That's kind of a one-two punch. And you, how do we get these down? Well, we just saw that they have all these problems that are related to glutathione. Now, that's one of the better anti-inflammatories out there. It'll directly address this and put a stop to these markers being so high, along with magnesium. Whenever you think glutathione, you immediately, the second part should be magnesium. Glutathione by itself doesn't work very well. You always want to combine it or couple it with magnesium. There's some complicated reasons for that. But let's see, um, oh, and while we're at it, I can just show you one more marker because it's right in front of us. We're saying, um, glutathione levels are screwed up. We saw cysteine, glycine, and glutamine all low or borderline low. Those are the three amino acids you make glutathione from. And here's a direct measure of glutathione itself. Pyroglutamic acid is high. That's another confirmation of the low glutathione. So low glutathione will drive pyroglutamic acid high. So classic case here: low glutathione, high inflammatory markers in the brain, and, and the low tryptophan. And then don't forget B6. So a million years ago, I was working with this one lab company. This is like my son was in eighth grade. I was 15 or 20 years ago, something like that. And I did this, they did this kind of informal study, shall we call it, where they are trying to figure out why certain patients weren't responding to 5-HTP treatments and others were responding really well. It just didn't make sense to the scientists that I was working with. And so, and they were all taking vitamin B6. And so they actually tracked all these people down. And this is a small town in Minnesota that they did the study, which is kind of funny. But they, um, they found out where these people were buying B6 and what kind of B6 they were buying. And it turns out that if you give the person the perfect amount of 5-HTP and the perfect amount of tryptophan, and they go and buy a cheap B6 somewhere that doesn't work, the whole thing gets undermined. I'm just circling xanthurenic acid here because this is a B6 marker. So B6 is a critical step to making serotonin. You can't make serotonin if your B6 levels are low. So no matter how much 5-HTP or tryptophan you give this particular patient, if you don't give them 100 milligrams of B6, maybe even 200 milligrams of B6, it's not going to work. I wouldn't randomly give people 100 milligrams or 200 milligrams of B6, but when you see the xanthurenic acid high, they're deficient in B6 already. You're going to give them this tryptophan, maybe some 5-HTP to get the serotonin up, they're going to need even more B6, and they're already deficient. So at least 100 a day to get things moving there, K of B6, and that is super important.
So let me see here. Oh, gosh. Uh, let me do a little program design, and then I can answer some questions. And, you know, when, when you do these protocols, um, they start to be really similar after a little while. So let me just show you an example here. So for this person that we just talked about, you could use a tryptophan. It would help if you spelled it right. Tryptophan. T. It usually comes in 500 milligrams. Um, it knocks people out, so you probably want to do it before bed. And then, we said NAC. Let's say you do a thousand milligrams three times a day. Why? Because you want to get the glutathione up. And NAC, this is the boost glutathione. This person was also low in glycine. So what the heck, let's just do it all. I would give them a glycine at a thousand milligrams three times a day. You might want to do the glycine on an empty stomach. NAC is always given with food because it can upset your stomach. So now we've got our glutathione covered. We're doing these two are going to have a massive anti-inflammatory effect, and we've got our tryptophan covered. But now we also need B6. So I would do a B complex plus a total of 100 to 200 milligrams of B6, depending on what company you're using, you know, you can kind of figure that out. Of course, you always want to use a multi. And then anytime you're even saying the word glutathione, you're thinking magnesium. I usually use magnesium glycinate. That comes in like 100 milligram capsules. So when you use glutathione, one of the effects besides what we're talking about in the brain here is that it's going to improve mitochondrial function, okay? Because it's going to start to protect the mitochondria. And in order for the mitochondria to actually work better, you need magnesium. So glutathione is not going to be fully effective without magnesium in the equation in terms of how it affects mitochondria. The opposite is true too. If you've given someone magnesium for a year and they're just not really responding well, magnesium will not promote the repair of mitochondria or the ability of mitochondria to make more energy if glutathione levels are low. Your body has a way to sense this. It has mechanisms, and it's like, okay, we're getting all this magnesium, but guys, guys, guys, let's not make ATP because if we do, we're going to generate a lot of oxidative stress. The function in the body that generates the most oxidative stress is the production of ATP. And so your body simply will not make tons of energy, even if you give magnesium, if glycine levels, if glutamine, glutathione levels are low, because you don't have the protection, right? Glutathione is protecting the mitochondria, just like it's protecting the brain, the brain cells. So you have to pair magnesium and glutathione together. And there's a whole section in Dr. Lord's book about that. It's called the Magnesium-Glutathione Dyad, if you want to read about it. Okay. And let's see where we're at. Let me get to a few questions and then we'll, um, time for one more lab. Okay. Uh, let's see. Um, yeah, you guys all get recordings of this for sure. They'll send out a recording. If you only see me talking, it means that you have a, a problem on your side. There. If inflammation, do you not give tryptophan? So if, yeah, you can still give tryptophan. Danielle got the BDNF thing right. Ten points for Danielle. Do you give 5-HTP to support tryptophan, or does it drive more quinolinate and could not urinate? So usually, if the tryptophan is low, I would always give tryptophan. If that's not enough to boost the serotonin and they don't respond with an improvement in sleep or an improvement in depression or anxiety after a month or so, you could add 5-HTP in addition to the tryptophan. Remember, I showed you almost all the tryptophan goes to other purposes than making serotonin. The vast majority of tryptophan is going to be used for protein synthesis. So you can absolutely give tryptophan, and if necessary, separately give 5-HTP. You don't usually need to do that, but you can. How long do you give an antioxidant program before an omega-3, 6 program? I start them at the same time, usually, which I can understand why you might want to wait, but I do them together. If you supplement with tryptophan, the person has inflammation, will you just be supporting more inflammation? Absolutely not. Because remember, look at all the things that tryptophan does. Let me see here. Let me show you. This is pretty important. Remember tryptophan. Remember there's a journal of tryptophan that I thought was kind of funny. Remember tryptophan's major role. Look, most of what tryptophan is doing is making proteins. There's no way that taking tryptophan is going to make you more inflamed. If you're deficient in it, it's going to make your, your body able to heal and repair. The inflammation is coming from an infection in the gut. The inflammation is coming from COVID. Inflammation is coming from an inflammatory response that's kind of stuck. But you're going to deal with that with the glutathione, with the curcumin. Part of the job is going to be to put the inflammation out. So you can absolutely use tryptophan. Now, if you were ignoring their diet and ignoring inflammation, then maybe the tryptophan makes somebody a little bit worse, but we're not doing that because we're doing these other things at the same time. Okay. Let's see. I think I answered the magnesium question. Oh, ACE2 receptors. We didn't really talk about that. We can know. And you can absolutely give glutathione for any of these situations. You can give 100 to 200 milligrams of glutathione twice a day. And for people that are really sick, I would do that. I would do both. I would do NAC, glycine, and glutathione, at least for the first couple of months, so they really start to stabilize, you know. Um, yeah, and it's, it's not the tryptophan that's driving kynurenine production, it's the inflammation, right? So it, that's, that's one thing. Okay. And then, um, let's see here. And there is, uh, let me try to answer this other one. Um, let me see if I can do this easily. I use the liposomal glutathione from Quicksilver, just simply because patients don't complain about the taste as much as they do with the other ones. So I think the liposomal forms are better. A lot of them taste really bad, but Quicksilver makes one that people.
don't seem to mind so much. Um, oh, and then to also mention, uh, kynurenate is also a B6 deficiency marker. So when you see high kynurenate, it can indicate neural inflammation, or it can indicate B6 deficiency, or it can indicate both, right? So you have to be a little careful though. But if you only see kynurenate elevated and quinolinate is not elevated, oftentimes that would be a B6 deficiency, not a neuroinflammatory problem. Because really, they should be elevated together. If you look here, if kynurenate is high, then quinolinate should be high along with it. So if only kynurenate is high and quinolinate is not, it may then be a B6 indicator. Okay, vitamin B6 deficiency. And you can sometimes verify that with xanthurenic acid because if that's high, then you know they have a B6 problem.
All right, so, um, let me answer this one question here. Let's look at one more lab and then I'll stay for an extra few minutes to talk about H2 receptors if you guys are so inclined. Somebody asked about that, but that's not really about tonight's talk. So let's look at another test here and see. The job is getting harder, I'll certainly say that. Since COVID hit, our job has gotten a lot harder. You know, I'm not saying it's impossible now, but it's certainly a lot more work. Oh, sorry, I hit the wrong button there. Let me just turn this off and I'll find it. Um, okay, here it is. This should pop up on your screen in a moment. And what we have here is another neutral valve. Although I would encourage you guys, as I mentioned, to do GI Effects tests on all these patients. And you're looking, remember, for that fecalibacterium prausnitzii organism in particular, and you're looking for butyrate levels. Okay, so here's another long-haul COVID example. Again, super high levels of oxidative stress. We're not surprised by that. We'd expect that may manifest in slightly different ways in this person. It's manifesting with lipid peroxides being high and ADOHDG being high. And then let's look at the well, and I should just briefly actually, you can see this on this other diagram. They have a really nice picture of this later in the lab here. Let me show you. So remember that started off, I think it was like the second PowerPoint slide was a was a cell membrane. It was a cell with a membrane around it. And so when the body first gets infected with COVID-19, your mitochondria, in a millisecond, senses that there's a problem with the cell and it stops making energy. And the oxygen is diverted towards oxidative stress. So your body intentionally makes a ton of oxidative stress. The other thing that the mitochondria signal is for the production of crappy quality fatty acids. Your body starts to make trans fats. Your body starts to make really bad fats. And the mitochondria is directing all this. And the mitochondria is sending these bad fats into your cell membrane, making the cell membrane brittle and stiff and horrible. And guess what? That traps the virus inside the cell. The cell is committing suicide here, right? The mitochondria is like, okay, we got a virus in here. This is not a good situation. We're going to screw up our cell membrane. So it starts making really bad fatty acids and sending them to the membrane, which stiffens it up so nothing can get in and out. At the same time, it generates all this oxidative stress, which is brutal. It is totally like a war. Uh, now this particular patient has high lipid peroxides. You see that high lipid peroxides? That means that the cell membranes are not doing well because that's oxidation or damage of the membrane. Okay. And that's the membranes for the mitochondria. It's a membrane for the cell. It's all those things. And the ADOHDG is also high. So that's one of the key indicators of oxidative stress. So now we know the systems. And of course, neurons have huge amounts of fat that are associated with them, right? So if lipids are being damaged, neurons are not in good shape either. It's not just like a kind of a cardiovascular mitochondrial kind of problem.
All right, then we can kind of scoot down and look at the portion of the test that's related to the brain. When I look at these labs, sometimes I just, it's just a miracle that some of my patients are even alive. You know, it's amazing how much your body can handle before you completely give up. Okay, so here's our amino acids. Let's see what's happening over there. Tryptophan's borderline low. Threonine and lysine, histidine and arginine are outright low. And let's see. Okay, so it's not like the last one, a little different. And then, oh, look at this. This is perfect. I didn't really plan this, you guys, but this is perfect. Okay, so remember the tryptophan was like borderline but not technically low. But look here at the serotonin marker, incredibly high. And look at the inflammatory markers, both high. Okay, now in this case, the B6 marker is all right. So now we've got someone who has added this kind of answer is a question that someone asked a minute ago, someone who's got adequate tryptophan but whose serotonin marker is crazy high and it has a lot of neural inflammation. So for this person, you could potentially give 5-HTP and the anti-inflammatories that are appropriate, antioxidants that are appropriate based on the lab, and maybe a little bit of tryptophan or none at all. Okay, so you can vary these programs based on the lab. And let's look and see one more time here at the, um, oxidative stress markers here. Yeah, let me show you that section. So we're talking about like the anti-inflammatory part of this to shut down kynurenate and quinolinate and those markers going high. There's many different ways you could do this. But here, pyroglutamic acid is high. So you could use the NAC and glycine like we did last time. The lipid peroxides were high. So let me show you how you can handle that. I see, oh, you see that? Look how high there, lipid peroxides are extremely high, literally off the charts there. So when you see lipid peroxide super high, what do you want to do? Okay, here's another quiz question for you. What kind of antioxidant do you want to use with lipid peroxides being high? Would you want to use vitamin C? No. Nothing against vitamin C, but you'd want to use, Brian nailed that pretty fast, fat-soluble antioxidants. So you have your choices, E, A, beta-carotene, and the kind of super famous one called CoQ10. So when you see lipid peroxides high, you want to protect lipids. So you want to get an antioxidant that's going to have an affinity for fatty acids, not be afraid of them, not be fat-phobic, but fat-friendly. So E, A, beta-carotene, or CoQ10 are usually used. So in this patient's case, that would be an important component to reducing the inflammation and all the tissue damage that's going on in terms of the cell membranes.
Okay, so what, some one of those, or what are some of those? So I just give you ideas. So like I use vitamin E a lot. Why not? It's cheap, it's easy, every company makes it. You can do like 400 IUs two times a day. You could probably give more if you wanted. I don't use A that often because you've got to monitor it. It's got to be a little careful with A because people can overdose on it. And I use CoQ10 with tons of people. CoQ10, you can do, let's say, 200 milligrams two times a day. You really get the fat-soluble antioxidants up with this person. And this person, we're saying, hey, maybe we could use 5-HTP with them instead. You can get that in a 100 milligram capsule, give three of those before sleep. And you could still use the NAC and glycine. They didn't need the extra B6. You could probably get away with just a B complex. So you kind of adjust their program. It could look something like this. And in terms of the CoQ10, I'm using ubiquinol now.
All right, let's see here. Let me get through a couple other questions. Oh, combo product. Yeah, there's a, there's a lot of companies have combination antioxidant products. Or if you know the easy way to do it too, is you can just go high with the dosages of one thing. Like you could use like lipoic acid if you want to do, just not too many products, but you want a ton of antioxidant potential there. You could use CoQ10 and lipoic acid, just those two. Because lipoic acid comes like in a 300 milligram capsule, and give that two times a day. And the CoQ10, and you can get CoQ10 in a 200 milligram pill. I just ordered a bunch for myself. Um, so if you want to keep the capsules down, you could give one 200 milligram CoQ10 a day, two lipoic acids at 300 a day. And that's a ton of antioxidants right there. If you want to keep the number of pills down, that's not cheap. CoQ10 at that dosage is expensive. But then you're getting a lot out of it, you know? So glutathione would help somewhat with lipid peroxides, but it's probably not the first go-to one because it's considered more on the water-soluble side, you know? Although I think these things are somewhat artificial distinctions, but you definitely want to get some fat-soluble stuff in there. Yeah, am I taking new patients? We're taking a very few new patients right now. I've cut my practice way back. I'm practicing a couple days a month. But if you guys have referrals, we do take a couple people a month. You know, I'm happy to do that. Let me see other ones.
Okay, and let me look at the lab one more time. See if we missed anything here. Yeah, there's one or two other things that are worth mentioning, right? Like with this person here. So another thing that we're going to have to do with all these long-haul COVID people is fix the mitochondria. And so with this person, you can see, uh, adipic acid and suberic acid, pyruvic acid, all high. So you're going to need to work with carnitine and the B vitamins and lipoic acid also to fix all that. So, you know, some B complex and carnitine, probably around the, let's say, two thousand, three thousand milligrams a day range, something like that, to get that working. These programs get pretty extensive. And then I want to show you one more thing too. There are non-lab-based long-haul COVID patients. Um, oh, yeah, yeah. And here's, here's an important question. Jessica asked, CoQ10 and glutathione levels all looked okay. All right, thanks for asking that, Jessica. So this just brings up, this is such an important thing, and I didn't really understand this until recently. So let me try to explain this, and if you guys can understand this now, you'll be like 27 years ahead of me. So absolute deficiency and relative deficiency. So an absolute deficiency of CoQ10 is the lab says you're low on CoQ10, you give someone CoQ10, their levels of CoQ10 come up. Absolute deficiency of water is you're thirsty, you're dehydrated, drink a glass of water, it's over. A relative deficiency means that you need more of a given product than the average person because XYZ is happening. So let's say you have high lipid peroxides, you can still use CoQ10 to lower their lipid peroxides even though they're not deficient in CoQ10. That's the independent variable. So in other words, you can have high lipid peroxides and need CoQ10 to lower that without having an absolute CoQ10 deficiency. So you can use CoQ10 to change a pathway or change a mechanism or change a process in the body even though they're not deficient in it. I think magnesium is the easiest, easiest example of this. So like if someone tests and they're low in magnesium, or they have like a bunch of mitochondrial markers, so you know they're low in magnesium or they need magnesium, you can give them magnesium. If all their magnesium tests look fine, you can still give somebody magnesium as a vasodilator to help prevent migraines or to help prevent cramping or to help with a million things, you know? So you can be with clinical nutrition, you can be replacing a nutrient that's missing, or you can be using a nutrient for an intended effect on a pathway. Another good example is mitochondria and free-form amino acids. So if someone's low in amino acids, like we've been talking about all night, you of course you give them amino acids to fix that. But I use amino acids all the time in people that are not low in amino acids to have an intended effect. I hope that makes sense. So it was a simple example of that. Let's say their gallbladder's screwed up, you could give them glycine and taurine, not their, not because they're deficient in glycine and taurine, but because glycine and taurine are going to force their body to make more bile and their gallbladder will get better. Now, they may or may not be low in those amino acids. That's an independent variable.
Okay, um, let's see a couple other questions here. And then let me remind you guys, if you joined us late, what we got going on here. There, there, so sorry we're going over time here, but we covered the gist of the webinar. So just quick reminders, we have a long-haul syndrome boot camp that's starting in June. And if you guys are interested, you get a discount for being a Genova referral, 20% off, G D two two one. Thank you, Genova, again. I've been working really closely with them in the last few years, and it's a great group of people. And their lab testing is just at the absolute pinnacle of our profession. I just rely upon their labs every day in my practice. Can't really imagine, uh, life without Genova. So they're just a critical component to our industry. I just want to give them a shout out for all these decades of hard work. That's not easy to run a lab either, you know? It's a lot of work. It's a lot of hard work to run a lab testing company, and they do a really good job of it. And, um, let's see, we got the long haul thing.