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[Mentorship Miniseries] Lab Interpretation: Longitudinal Case Study Review on Immune Function

The Kalish Institute of Functional Medicine56:22

Transcription

Hi everyone, and welcome, welcome to our mentorship mini-series. This is my new favorite thing to do. I love these little classes. They're mini classes to get you, I don't know, oriented towards different topics, I guess, is probably the best word to say.

And so, format for those of you that, for whom this is the first time, I'm going to talk about this. This one is a little different than actually the other one. So, this one, we're going to look at a couple of slides, but not really look at slides. I want to show you guys a case, a very interesting case, and go through each of the different sets of labs. So you can see, we call it like a longitudinal case study. You'll see how the labs change over time, which I think is quite interesting. In fact, it's the most interesting part of the job. So I think it's worth looking at.

And, you know, I had been in practice for, I don't know, like 20 years until I really started to get into longitudinal analysis of labs. I mean, it seems like a kind of obvious thing you should do. So, if you're, if you're not doing this, you should do it, right? Because this is like the most obvious thing. And probably a lot of you already are. But, you know, now I have like five, six years of organic gases tests on the same patient. And, you know, you always learn more from the second test than you did from the first test. You always learn more from the third test than you did from the second test, and so on. So it's, um, pretty incredible to watch the labs change and to look at the physiology behind that change and what's happening kind of mechanistically. So I strongly encourage you guys to, to, you know, always retest organic acids and fatty acids and amino acids. And, you know, as you start to piece together the biochemical changes that are occurring on the lab and you look at the patient, you see how they're feeling, you know, you can figure out a lot of new information that might not have been available to you otherwise. So that's what we're going to talk about. So we'll look at, um, these examples. We'll have time for questions at the end.

And then, um, oh, and then I just thought I'd start off with like the biggest picture imaginable in all this, right? So the biggest picture is that when I think back on my original training with Dr. Timmins in functional medicine lab analysis in the 1990s, really, if you just, if we were playing some kind of drinking game, you know, and we were doing shots of tequila or something, and it was like the fourth shot of tequila and someone's like, "Okay, we're going to play this game. I'm going to name a doctor, and you just say what comes to your mind first." And if you said Timmins, I would say parasites, for sure. I mean, not to categorize this brilliant man's amazing career in a single word, but that's kind of what he was about. Or maybe a more accurate, if you, if it was a drinking game, you have two words. I would have said, "Someone say Dr. Timmins," I would say, "Chronic infections." So meaning that what he really taught me was that most of the patients that we work with have chronic infections. And that these infections are often, you know, dormant or have been present for so long, the person doesn't even know they have them. None of their other doctors know they have them. And that when you do GI testing and other types of testing, you can uncover these chronic infections and help people change their health. And the whole first 10 years of my career, and all the many years I worked with Dr. Bill Timmins, was all about finding chronic infections. That's really what his thing was.

And, um, that was the basis of my practice for a really, a really long time. And, um, and for those who had never met Bill, he was one of the original guys that did the salivary adrenal hormone testing. He helped start a lab company called, that's still around, called Diagnostics. He was a, a partner in crime with a man named Dr. Elias, who was the, uh, founder of Diagnostics. And those two guys just ran around like a bunch of 10-year-olds, you know, talking about labs, and just, they just loved this work so much. And, um, that really rubbed off on me in my very, very first years of doing this kind of lab analysis stuff. So anyways, and then I, I worked for Dr. Timmins' lab company, and I used to have like 500 doctors that were under my account. And I would, you know, analyze labs for them and all that stuff. And that's kind of how I got started in teaching lab analysis was with Timmins. But anyways, the foundation of any good analysis, and I'm sure you all do this every day for a functional medicine, you know, workup, is to check for chronic infections. And so what we're talking about today is the exact same thing, susceptibility to infections. But, you know, it's both how we're going to react in the short term to an acute infection, and then the functional medicine version of it, you know, being what we're looking for with chronic infections. But we've always dealt with infections in functional meds in a variety of different ways, right? And the primary way that Tim taught was to strengthen the host before you even get the infection, right? Why not strengthen the host? And to that end, he, you know, set up and ran two different lab companies that analyzed adrenal hormones. And, you know, was a strong advocate of testing secretory IgA and making sure that we are testing and correcting adrenal hormones, as well as, um, getting secretory IgA and the immune response, that first-line immune response corrected. And then, obviously, the microbiome testing and the GI testing was another big part of the work that he did.

And so when I think about what we're going to about to look at today, we're applying the same basic kind of information, but a little more targeted and specific towards mitochondrial function instead of adrenal function. So you have adrenal function and gut function tied together inextricably, right? So the, when we're stressed, we degrade the intestinal tract lining, trying to get amino acids. We go into a catabolic state. We chew up the intestinal tract lining. Also, when we're stressed and cortisol is out of bounds, we, um, you know, the secretory IgA levels become abnormal. So our immune defense in the gut lining weakens when we are stressed due to how cortisol responds, right? So we've got now leaky gut from the catabolic state that the person is in. They're chewing up their gut lining for fuel. All that glutamine is getting chewed up for energy, right? The gut lining, all those tissues and proteins are getting chewed up. And then secretory IgA levels are off. So you've got damage to the gut lining itself and a weakened immune response. So there's this direct link between stress in the adrenals and gut function. With what we're talking about tonight, there's a very similar direct link between mitochondrial function and viral infections that cause problems with that, with inflammation, inflammatory cascades that cause problems in people who have issues with a huge oxidative load already, okay? And we want to try to tie together how a chronic virus, not a chronic GI infection, can kind of tie into the adrenals. That's the work that we do a lot in the mentorship. There's a whole first six months of the mentorship class. But now, you know, in the era of COVID, I also want to look at how mitochondrial function and a viral infection can be related. And kind of, that's what tonight's case is about. There's a lot of research going on about this all around the world. And I'm just having a, one, one little case study here. We go over tonight to kind of open, uh, up the, um, the vision as to what we're going to be seeing with a lot of these, uh, chronic COVID cases that are coming in.

So, um, who am I? If you're new to this, I'm the founder of the Kalash Institute. Okay? It's not a very creative name, but whatever, it kind of worked at the time. Kalash is dancing. Okay? Trained a thousand or two thousand practitioners. Been doing this for a while. Been worked with Mayo Clinic. We had Mayo Clinic doctors doing my mentorship a whole bunch of years ago, right? Right now, I'm working a lot with Richard Lord, who's one of the originators of the, of the labs that we do in our industry. He's the man that did the GI Effects test and organic acids and fatty acids and all around brilliant top scientist in our field. And I've been in practice for a long time. I actually practiced, I don't know, it seems like all week, but it's only Tuesday and Wednesday. I practice two days a week. It's still kind of deep in the trenches. We have a mentorship program where I'm trying to mimic the experience that Dr. Timmins gave me in the 1990s, which is a one-year kind of immersion experience where you get through this curriculum that's online. You get through, um, live Q&A calls like tonight, where we, we go over the labs that you're running on your patients. You have a group of people that you can connect with. And we have Zoom tours available. If you want to do a free Zoom tour with Jennifer, you know, you can check out what the mentorship might be like. If you're a candidate for that, it makes sense to you right now. And we have classes starting May 24th. And if you're in this mini-series, which you must be if you're hearing this, you get a $699 discount off the mentorship. And if you take one of our boot camps that are coming up, then you get an even bigger discount of $11.99. Okay? And those are the codes there. And if you forget any of this information, just remember the word "discount," and you can email the office, and we'll help you figure out, uh, what you might want to sign up for. Okay? So we have these short boot camps. They're two-month courses. And then we have the full one-year program. And, um, we'll be starting that one-year program, uh, the end of May.

Okay, so for today, I want to talk about, oh, hang on, that's not, that's the wrong slide. Was it? No, that's the right slide. Okay. Yeah, for today, I want to look at this rather complex study, a rather complex case. Okay? I'm just, we're just going to go straight up to the labs. We're going to look at lab and lab and lab and discuss what's going on. And you guys can ask questions. Okay? So this is more of like a workshop lab review, not like a lecture kind of thing. So let me just pull up the first lab. We'll get to it all right here.

Here's lab number one. And hopefully, most of you are familiar with these to a certain extent. You know, these are organic acids tests. You're going to see some other fatty acids and amino acids also in a moment. And we're going to start off with the initial test that the patient did and talk about some of the key markers, especially in regards to mitochondrial function, right? So when the mitochondria are stressed, they shrink in their populations. Dr. Lord calls this mitochondrial retraction or a hypometabolic state. And you want all the mitochondria you can get. It's not a good thing if your mitochondrial populations are dropping. And so when you look at organic acids here, the way that these tests were originally designed was to look for high markers, right? And an extraordinarily high marker implies that there's a genetic disorder, right? And so in the '80s, well, really back in the '60s, Dr. Lord thought, well, wait a minute, if we're using organic acids to find these really rare genetic or disorders in newborn babies, maybe we could look for, you know, adult-onset versions of these similar problems. And so historically, in both conventional medicine and in pediatrics, when they test newborn babies, and also in integrative medicine, a high marker on any one of these metabolic tests here that we're about to look at is a bad thing, okay? And then, in general, low markers are just sort of dismissed as being, "I'm not sure," or "It looks fine to me," basically. It's the, "It looks fine to me" marker, okay?

So, and what are we actually measuring? Well, we're measuring metabolism. And what does metabolism mean? Well, we're breaking down food. What are the foods? Well, there's fatty acids, there's fats, carbs, and proteins, right? The three macronutrients. So here you have fatty acid metabolism. Here you have carbohydrate metabolism. And then down here, you have the B complex markers, which are measuring amino acid metabolism or protein metabolism, okay? That's what B vitamins do. So again, we have fat metabolism, carb metabolism, and the protein metabolism markers. Now, in between here, we have something called the citric acid cycle or energy production, the Krebs cycle, some people call it too. And that's where we're making energy inside the mitochondria, all right? And so I'm going to just show a couple of slides just to kind of orient all of us so that we're clear on what we're talking about. And here's a nice summary slide right here. All right, let's see. Hang on a sec. Uh, so we take fats, carbs, and proteins and convert them in a whole variety of pretty complicated ways into something called acetyl-CoA, which then enters the citric acid cycle so that we can make ATP. And when I ask patients, kind of jokingly, but kind of not, like, "How important is this?" I'll say, "Well, why don't you try holding your breath? Let's see how long you last." Because the reason why you're breathing right now is to provide oxygen for the final step of energy production that we call the electron transport chain. So once they hold their breath for like 10 seconds, they start laughing usually. But the point of the matter is that this is not like an optional process. This is the reason why we breathe.

So to bring it back home to what this is really about is survival, right? If this is not working, we die. If on an individual cellular level, energy production is not going well, then the cell can die from too many reactive oxygen species, right? From too much oxidative stress. So there's a spectrum. Too much oxidative stress, cells die. That's from, you know, aberrant metabolic functions, right? And then you can have, on the opposite end of that spectrum, inadequate production of energy. That would be accompanied by low levels of oxidative stress, believe it or not. But that is not a good thing, right? Because the mitochondria are just not even present. They're not making energy. And that's what we're worried about. And so the way that you can, you know, if you had, if someone came to you like it was like, um, like a Mike Myers movie, I don't know if you guys know Mike Myers. He's this comedian, and he always says this thing. Is his little finger, you know, he's paying the creepy bad guys. So Mike Myers came to you and said, "I want to destroy the world." Then what should we do? You know, you could say, "Well, why don't we invent a disease that causes hypoxia that limits oxygen supply for a little while?" And then Mike Myers would go, "Oh, that's a good idea." Now, why would that be so messed up? Because if you don't have enough oxygen for a little while, the mitochondria sense that, right? And they retract. They decrease their production. And if you combine that with a disease that generates a whole boatload of oxidative stress or inflammation, you've got a perfect storm. You've got mitochondria that are already on the ropes, and then you've got all this inflammatory cascade or cytokine storm or inflammatory response, whatever you want to call it. And that combination is, you know, deadly, literally, right? And so we're thinking about something like COVID. You can see, and, you know, you can Google this and research this later this evening if you're curious. You just Google "COVID fatality rates and glutathione levels," and you'll see all the research that's being done on that. And it's pretty clear now to the scientists that the lower your glutathione levels are, the lower your ability is to defend against oxidative stress, the higher your chances are of dying from COVID. It's a direct relationship. And in fact, the people that have robust glutathione levels do quite well with COVID. People that have very low glutathione levels can suffer extreme problems from it, okay? So COVID can do a whole bunch of things. But the important point here too is that it's not just COVID, right? It's, it's how the immune system is reacting with this inflammatory response that's really at the heart of what we're talking about. And the more inflammation that there is, the more oxidative stress that there is, the weaker that the body's, uh, the weaker the body's ability becomes to run these mitochondria properly.

So again, if you were like some evil dictator in a Mike Myers movie and you wanted to undermine the mitochondria of the American population, you would say, "Well, why don't we, you know, cut back on their magnesium levels a little bit? Why don't we create a culture where they don't eat vegetables very often? And let's invent something called fast food." You know, so that people just, and the majority of Americans now are low in magnesium, right? Everybody knows that. I mean, that's like research. I remember Joel Evans teaching me that like 20 years ago. This is, and has not gotten any better, okay? Most, most people that we work with are low in magnesium. Low levels of magnesium are also going to cause an interference with the ability of the mitochondrial function. And then, of course, the killer of all is low levels of CoQ10, okay? So magnesium, oxygen, or CoQ10, any of those things that drop, there's many other examples, right? High oxidative stress, it's going to limit the ability of the mitochondrial function. So as we look at these labs in a second, we're going to look at this person's fat and carb and protein burning capacity, as well as the citric acid cycle itself. And we're going to look at the levels of oxidative stress on the test also. And remembering that high levels of oxidative stress, that means we have a ton of free radicals and we have damage to the system, damage to the mitochondria from that. What you should have is over here, you see abundant ATP being produced and a few free radicals that your body's glutathione just deals with. What happens to patients is not enough ATP, huge amounts of free radicals, right? And that's a pretty big problem. If your glutathione levels are low, you're going to have some serious consequences from that.

One more example, and then again, just kind of set the stage for the labs that we're about to look at. This is the electron transport chain. Remember this, Complex 1, Complex 2, Complex 3, Complex 4. The electron transport chain is located, it's embedded, it's like stuck in the mitochondrial membrane, the inner mitochondrial membrane, okay? So if the mitochondrial membranes are not doing well, this ability to produce energy is not going to do well, right? Or ATP is going to kind of falter. And what the, what the electron transport chain should be doing is generating these protons, remember this, the little H+ as it's generating electrons. And then this all magically comes together and turns into ATP and water at the end of the process, which is kind of remarkable. And then there's another little process over here, which is important, fatty acids, okay? And a fatty acyl-CoA and beta-oxidation, that's the burning of fats for energy. And then, of course, the burning of glucose for energy. Glucose converts to pyruvate, and then here's our citric acid cycle right here, okay? So this is what we're measuring. As you look at the lab in a second, you're going to see all these markers. You're going to see that we're measuring succinate and fumarate and pyruvate and acetyl-CoA. We're measuring this. It's, it's a miracle that you can do this. The scientific breakthrough, you can measure succinate, you can measure the, you know, the different, um, complexes, Complex 1, 2, 3, and 4, you can measure them, okay? And that's what we're doing. And we want to see, hey, how is this person's mitochondria working and what's happening to them, okay? So that's with that as sort of a, the pre, what do you call it, a preview. Let's look now at the markers and see if this helps.

All right, so right off the bat, we're back to the test here, and we can see the fat metabolism markers look fine. This is the first test, remember? Now, the carbohydrate metabolism is pyruvate, beta-hydroxybutyrate. Those are DL, which means underneath the detected limit. And then as we go down and we see other aspects of the test here, we see, oh, wait a minute, there's other markers that are quite low. So there's, like, we start to add up how many markers are low. Well, there's one, there's two, there's three, there's four. So, you know, so a couple of low markers is fine. There's five. But we're starting to see a pattern of low. We're starting to see a really clear pattern of low. Six, seven, eight, nine, ten. And you see how many of these markers are low? So when there's that many markers low, more than six out of these first 21 are low, we start to get suspicious that this might be hypometabolic. This might be mitochondrial retraction. This might be not enough mitochondria present, okay? And so that's sort of step one.

And then in this particular case, with this patient, we then went on and did another, you know, we did a program. And I'll write out the programs. Well, maybe I should write out right now. Why don't I just write it out right now? My way. So we did a program. We do when somebody's mitochondria are all not doing well, all you do a pretty straightforward but pretty sophisticated program. Use free-form amino acids. And you typically want to use 8 to 10 grams. You don't want to do this with cancer patients, but you can do this with anyone else on an empty stomach. And you can do that either once or twice a day. You want to use CoQ10 at, let's say, at 200 milligrams, at least twice a day, if not more. So let's just say that for now. And remember, magnesium is part of this. You want to use magnesium. And you want to use magnesium in a chelated form. So I just call it magnesium chelate. It might have a magnesium glycinate or citrate or multi-chelate, whatever your favorite is. Say, also maybe 200 milligrams. People like to take magnesium before they go to sleep at night. It's kind of relaxing. And then you want a really complex multi. Then usually in addition to most multivitamins, you want some additional B complex too, because the Bs are very important for this, okay? So this would be a basic. And if you want to get extra fancy, you can use this stuff called PQQ. If you want to get extra, extra fancy, you can use one of these products called NAD+. Okay? So that would be like the fancy, fancy program. You don't have to do all these things, but that would be like the complete program if you're wondering, right? And the, um, free-form amino acids are going to help stimulate the body to repair and build more mitochondria. That's kind of what we're after here, okay?

So let's go back now and look at what was the second test. So on the second test, so we're fast-forwarding like a year here, okay? And then I also want to point out that we've got a patient who has more energy, who is up and around, who is feeling a heck of a lot better, who is starting to exercise and participate in the world as she hadn't done for a while. And it's, you know, you fast forward 40 years later, and it's easy. People come in and say, "I feel great." I'm like, "You look great." "I know, I've lost weight, I'm exercising, finally, the fatigue is gone, my depression is gone, I feel so much better." So what would you expect with more physical activity, with more mitochondrial activity? So some of these markers have gone up, which is okay. That's kind of what we want to have happen, right? And now we say, "Oh, okay, there's still some that are low. Carbohydrate metabolism is still a problem." One, or is one, two, three, four, five, six, seven. There's still some markers that are low, right? But in general, when you look at the trend, things are coming up. Patient is feeling better. We're kind of heading in the right direction and on the right track. And so if you want, you know, as much as I try to follow up with people, um, we didn't follow up very well. This patient just kind of disappeared for a while. Okay? And then something really bad happened, and she got COVID. And then she retested herself in kind of the deep desert of a post-COVID extreme fatigue situation. So we had taken her under active mitochondria back in 2016, got them back on track to the point where she's feeling energetic and like her life is back. So much so she stopped taking most of the supplements, just kind of felt like things were okay. And then COVID hits, and then we retest her. And then this is what happened, maybe three or four months after she got COVID. And so, and then the caveat also, she acquired the infections, she got moderately ill, say, not hospitalized or anything like that, but then after the infection was gone, she had this, you know, deep and profound fatigue that was quite a bit worse than when she first came in.

So now we see her amino acids are completely depleted. Look at this. Just low, low. Oh my gosh. Look at this. This just makes you want to cry. Gotta take a deep breath on this one. Low lysine, that's going to interfere with immune function. You know, beta-oxidation, low tryptophan, it's going to interfere with protein synthesis, it's going to interfere with serotonin production. Low, low branched-chain amino acids, that'll interfere with the ability for the muscles to do their job properly. Phenylalanine, low, that can cause depression. Taurine and glycine, low, those are two amino acid, sulfur amino acids that are critical for, um, for detoxification. The entire, almost the entire neurotransmitter section of this test is low. Three main markers there, low, to do with the brain chemistry. And it gets worse, really. When the, the thing, why I thought this was the reason why I thought this was so interesting in particular, is that we had the original test where she was quite depleted. We got her better symptomatically, and the labs looked a hook, a heck of a lot better too. And then we were able to see, okay, well, after COVID hit, what happened? And look at the fatty acids. Check out. Let's look at this. This is incredible. And oh, yeah. Oh, my gosh. This is bad too, right here. So magnesium levels are low. Okay? Not all this was caused by COVID, but some of it was. Antioxidant level is now low. Omega-3s are okay, but the omega-6 is not so good because sixes were wiped out. And then the part that we really want to focus in on is what we talked about from the other tests, which are the mitochondrial markers. So now we see this pattern emerging of high markers. Remember, fatty acid metabolism, those markers were normal for both the previous tests. Now she's not doing beta-oxidation very well. She's not doing beta-oxidation very well. What does that really mean, even? Well, it means that when we're at rest, like we're all sitting around right now, just, you know, thinking and talking and watching the computer monitor or whatever, 90% of your energy is being produced by the burning of fat from beta-oxidation. She can't do that. So when she's just sitting around nowadays, she's unable to burn body fat adequately. And so she's going to feel pretty, not so good, right? Just physically exhausted. And let me just show you real quick here what's supposed to happen. Was supposed to happen when we're making energy is this. And then, of course, the kicker is, where does beta-oxidation occur? In the mitochondria, right? So this is what we're talking about is a metabolic problem that COVID induced, or a mitochondrial problem that COVID induced. And so what's supposed to happen is when you're sitting around, 90% of your energy is coming from fat burning. That slide looks a little weird, doesn't it? There we go. And so what your body's supposed to take the fat and attach it to a carnitine molecule and then pull it into the mitochondria and make energy out of it, okay? And it's carnitine that does that. And on her system right now, this is not working properly at all, okay? So she's not going to be able to make energy from fat very well. You can see all three of these fatty acid metabolism markers are high. Adipate, succinate, methylmalonate. That entire mechanism is not working. Previously, the carbohydrate markers were low. They were undetectable, I think, on both those previous tests. Now they're both high. Now we're seeing that these enzymes aren't working very well. Her mitochondria are back. They're not working very well. And then if you look at her energy production markers right below there, under the citric acid cycle, you can see there's one, two, three, four, five of them are high. The B vitamin markers, two or three of them are high. So now every one of these high markers represents a part of the body where the mechanism is not working properly, but there's an enzyme that's broken, or a pathway that's not conducting signals properly. And that's what she's left with at this point. Of course, it's going to make you incredibly exhausted because you cannot make energy. And the other thing that's really quite remarkable is the oxidative stress marker is quite high now. The reference range is up to a 0.66. She's five times the reference range, so a huge amount of oxidative stress going on in the body.

All right, so I'm just going to take a step back here for a second. Let me show you a few more images here to kind of tie together what we just talked about, and then we can go to questions, okay? Here. Just a quick reminder. My computer is not working very well. Come on, you can do it. I'm going to, I'm going to shut the camera down because I think it's taking up too much bandwidth. There we go. That work? Let me open it up for questions while we're waiting for my computer to behave. Sorry, this is not working at all. I mean, if I hit the right button, it would be better. There we go. Okay, just a quick reminder here before we, uh, go to questions. I'm going to show you what we're doing here at the Kalash Institute real quick. Number one, the big picture in functional medicine is dealing with chronic infections. And what we're going to see, I think, in the next five, eight, ten years, is a lot of people who had COVID who are, you have mitochondrial problems as a result of COVID and are somewhat devastated from that. So we should all learn how to interpret these labs so we can fix these problems because people are going to need the help more so than ever before. Okay? So quick little note on what's happening at Kalash Institute, then we can go to some questions. We have our one-year mentorship that's starting at the end of May. You guys can sign up for that now. You can book a Zoom tour with one of our staff, and they'll help you go through the curriculum. And you can, you know, talk with other doctors that have taken the class and get a sense of if it's appropriate for you. And there's a couple of discounts that we're offering. You get $699 bucks off if you have attended one of these mini-series. And if you end up doing one of the boot camps that we offer every couple of months, you can get a $199 discount with the boot camp codes. That's about what the boot camp costs. So I don't know, my staff came up with that one. I think they're being kind of generous there. All right, so that's the detail there.

And then just a quick review on what we just talked about. Uh, fats, carbs, and proteins being burned up for energy. What we saw with this person was she developed a carbohydrate metabolism problem after COVID that she didn't have before. That means she's not burning glucose very well. Her pyruvate and lactate went through the roof. Her ability to run glycolysis and to convert glucose to acetyl-CoA was damaged, uh, by, we are assuming, by the infection. The fatty acid metabolism or beta-oxidation was similarly damaged. So now you got a patient who's understandably tired because while she could burn fat and carbohydrate before, the mitochondria weren't so great. When we first worked with her, we got all that working. And right after getting COVID, a few months after COVID, all of a sudden she has this new problem with beta-oxidation and this new problem with glycolysis, and she's profoundly fatigued, even worse than she was prior to the 2016 set of labs. So again, patient who came in with fatigue, got better, and then slid back deeper into fatigue for different reasons than the initial fatigue. The initial fatigue was a lack of mitochondria, right? Now she's got problems with fat metabolism, problems with carb metabolism, and these mitochondrial markers were the preponderance of them were high this time, right? We saw these high markers, not low markers. So now these pathways are struggling to be run properly. The mitochondria are there, they're just not working very well. And there's this profound sense of fatigue. And again, the damage then is occurring to the mitochondria themselves from oxidative stress. And you can also and should really assess glutathione levels and antioxidant levels to help protect the mitochondria from further damage. That's a super important part of all this. You want to make sure glutathione levels are good, fat-soluble antioxidants are good. And remember the cell membranes, those inner membranes, those are fats. Those are, that's a phospholipid bilayer. The, all the membranes that are running these mitochondrial energy pathway things with electron transport chain, remember it's embedded in this fat membrane. So it's fat-soluble antioxidants protect that membrane. The fat-soluble antioxidants are low, which she had on the test, remember she had low fat-soluble antioxidants. That means that those membranes are going to be damaged, and that means the mitochondria are damaged. It's like when you're watching, uh, you know, a medieval movie and they're attacking the castle and the castle walls are being destroyed gradually by some catapult thing. It's kind of like that, but it's the actual membrane that's housing all these proteins that run the electron transport chain. So if I'm going to say that one more time, so if your fat-soluble antioxidant levels are low, what's getting oxidized or damaged are your fats. And the fats that we are absolutely not wanting to get damaged are the ones that form this membrane because that's where our metabolism is sitting. You know, it would be like if you're in the castle example and someone was attacking a castle and the people inside the castle put, you know, all their most precious things on the top of the castle wall so it could get to, you know, would be stupid because it would get destroyed, right? No, you wouldn't, you'd hide behind the wall. In this case, the wall or the membrane is housing everything that we're worried about getting damaged. So if you have a lot of oxidative stress from an infection, there's a lot of inflammation, these fats in the, in the membrane, the fat-soluble antioxidants take a hit, right? So glutathione drops, E drops, you know, CoQ10 levels drop. And all these things that are in the membrane trying to protect us, you know, weaken. And so then, of course, this membrane is not going to work very well, which means your electron transport chain is going to fall apart. This is where it's housed. It's literally sitting in there. Got another picture of that. I'll show you. You see it graphically. It's like, whoa, he's not kidding. It's actually in there. Um, let me see. Uh, there, this picture. Yeah, so there's one of the, this is a Complex II, I think, the electron transport chain sitting in the cell membrane or the mitochondrial inner membrane, sorry, not the cell membrane, the mitochondrial inner membrane. Okay? That membrane's made out of fat. That fat is damaged. This thing's not going to work very well. It's a very delicate structure. And, you know, what's cranking through? We just were talking about this this afternoon. In one cortical neuron, one brain cell, one brain cell generates 4.7 billion units of ATP, not like in a day, but in a, in a second. So this thing that we're looking at here, this electron transport chain, it's generating 14 billion, with a B, okay, units of, units of, uh, no, 4.7 billion units of ATP. But that translates into around 14 billion times CoQ10 has to move electrons around, right? It's like 14 billion times of electron pair is moving. It's a super high volume stuff, okay? It's easily damaged. It's a very delicate and complex system that's easily damaged.

All right, so let me open it up for some questions and see if you guys are wondering about anything. Uh, we have time. Yeah, we're right on time. So I like it when it's right on time. You see, um, here, let me get this going here. There we go. All right, slip that into there. And I'm going to go for question number one here. All right, uh, the patient who's not tolerating tryptophan, that could be for a lot of different reasons. If you're not, if they're not tolerating tryptophan, I would just wait, work on the liver, usually, and see if you can get the liver working better first, and then you come back and try it again. Um, free-form amino acids on an empty stomach to stimulate mTOR, correct? So that would be for the hypometabolic state that where that woman was when we first tested her. Just curious if her oxidative stress was so high due to COVID or something else? I guess you can't tell. I mean, probably have to take a thousand people and test them and then give them COVID and then retest them to be sure. But I don't know, it seemed pretty intuitively obvious to both her and I that she was doing great right up to COVID, and then immediately after COVID, all these problems started. But I know this is not like a, you know, double-blind, bloody blah. But we were talking about this the other day with some prominent researchers and academicians that back in the old days, medicine was built on individual case studies. That's what doctors did. They worked up a case, they got success, and then they told other doctors about it. So I think it's okay that, you know, you have a successful case, or in this case, an unsuccessful case, you share it with your colleagues, you know? Um, there's so many different variables, but we've kind of almost been trained to not pay attention to common sense, I think these days. Um, besides low B2 and carnitine, what else can cause issues with beta-oxidation? So damage to the cell membrane, I'm sorry, damage to any kind of lipid damage is going to damage beta-oxidation. So the lipids, the fats, the fatty acids have to be pulled across the outer and then inner membrane of the mitochondria. And so if there's damage to those membranes, the system is not going to work very well. So again, you're right back to oxidative stress, especially the fat-soluble antioxidants. I was trying to emphasize those are the really big ones. Let's see. How long to treat with free-form amino acids? At least six months, typically. Could you use free-form amino acids plus a mitochondrial support program? Yeah, absolutely. Use those together. It's really great. Yeah, so all these test results were from organics profile, as correct? Yep, on the same patient. So originally she was in a hypometabolic state. We got her mitochondrial populations back. Then those mitochondria took a hit, and so we saw high markers on the third test. That was the kind of progression there. Yeah. Would you prescribe additional B2 if she has a problem with beta-oxidation? Absolutely. You can give B complex, then an extra 100 or 200 milligrams of B2 on top of that, maybe even more if you want. I'm just trying to scroll through the questions here. If someone comes from eating the Standard American Diet, would these labs be beneficial? Oh yeah, absolutely. That's, that's like the main purpose of these labs is to find out. I mean, if people start to eat healthy and they feel great, they don't need labs, right? These labs are really designed for people who, you know, the lifestyle changes haven't been enough to really make them feel like they're a million bucks. And this test, again, from an organic acids profile from Genova Diagnostics. Should the low across the board amino acids on a test be replaced? Yes. So when you have low amino acids like she did on the second test, then you give usually around five grams of amino acids twice a day on an empty stomach to rebuild the amino acid levels. That's a little different than what you do when you're in a hypometabolic state. Oh yeah, and I forgot to show you the treatment plan. I'm going to bring that up in a second here. So let me, let me write down the actual programs here. I mean, I told you I was going to do that, but I did it. Oh, no, I did. Look, look at me there. That was the original one, right? This is the one to stimulate mTOR and get mitochondrial populations back. Now, in the, for the third test, her amino acids were low. So you can also just replace amino acids with amino acids, right? That has nothing to do with mitochondrial populations. It's just like getting more amino acids in the person. So these supplements are all about the same. Now, but in this case, there's a couple of things that were different. She doesn't need the PQQ anymore necessarily. Probably doesn't need the NAD+ anymore necessarily. As one of you just said, B complex plus, you can do some extra B2 if you want to really push the fat-burning mechanisms. And then she also had, remember, a high pyruvate and lactate. So those relate to thiamine and niacin. So you could also give extra thiamine and niacin. And then also when pyruvate and lactate go high, it shows a person needs lipoic acid. So that would be, let's say, 500 milligrams, three times a day. It's like that. And the thiamine and niacin, you have to experiment with, you know, 100, a couple hundred milligrams a day of each extra if you want to push the pyruvate and lactate levels back down. And, uh, so those would be the differences, I guess. Yeah. Yeah, those are the main. Oh, and carnitine, sorry. I forgot the most important thing. Carnitine, usually that's like, let's say, a 500-milligram pill. And let's say you give two of those, three times a day, okay? So that would be the follow-up program. Again, if you didn't catch this, we used amino acids in the beginning to stimulate mTOR. We used the amino acids in the final program because she was low in amino acids. So a good example of that is like, you can use magnesium in someone who's deficient in magnesium to get their magnesium levels up. But you can use magnesium and someone whose magnesium levels are fine just to lower their blood pressure because magnesium is a vasodilator. So you can use a supplement like you would use a drug. You can use arginine in someone who's low in arginine so they can clear ammonia and do all these other kinds of things that arginine does, right? But you can use arginine and someone who has normal arginine levels just to bring up their nitric oxide and keep their blood vessels like super clean and healthy. So you can use a supplement to replace a deficiency, or you can use a supplement to have, you know, sort of a drug-like effect. Either way, you can do it. Oh, Suresh is asking a good question. That's a really good question for us. Rush is thinking, telling you guys should all take the mentorship. Suresh took the mentorship, and now he's asking like a really smart question, okay? Because he's thinking through this stuff. All right, so here's the dealio. So Suresh is asking, well, wait a minute, why are these fat and carbohydrate and amino acid markers going up, right? If they're not taking place inside the mitochondria? I guess there's a reason for that. So when your citric acid cycle itself is not working inside the mitochondria, right? The feeder systems that go into the mitochondria back up. They stop because if they didn't, think what would happen, Suresh? If you just kept dumping the metabolites, you kept dumping pyruvate, if you kept breaking down glucose and dumping pyruvate and lactate into the mitochondria, I'm sorry, if you kept dumping pyruvate into the mitochondria, or if you kept dumping tons of fats into the mitochondria, and the citric acid cycle was not working, the cell would die. The cell would just blow up. It would be.

like having a wood stove and you know containing it in like a garbage can with a lid on it and then dumping in a bunch of jet fuel that probably just blow up right so your body's like hey i don't think so not today mitochondria aren't working so well we're not taking on any extra fuel right use keep your fuel out there this is why people get fat right when they eat too much because let's say that you you just eat a ton of food and your insulin levels all off and your body's got all this fat circulating everywhere you know they it can't all cram itself into the mitochondria your mitochondria like i don't think so there's all these intense regulatory mechanisms that would keep excess fat from getting into the mitochondria so it stays outside the mitochondria and we just get fat it's the same kind of mechanism right all this stuff is highly regulated there's even one really cool one i learned about the other day where when as there's an oxygen sensor right at pyruvate this is so cool there's this whole research group that works on this it's like people spend their whole career studying this one abstract thing and you just read this article it's so cool but anyways there's a little oxygen sensor system at pyruvate so as soon as your oxygen levels drop boom pyruvate levels don't convert into acetyl-coa your body just knows not enough oxygen we are not cramming that pyruvate into the mitochondria we're not going to make a ton of acetyl coa because that would damage the cell it's the cell protecting itself see pamela's asking why why are the free for amino acids do you ever have reactions with histamine i'm sure you could i haven't never had that problem i'm sure it could happen though so i'll be careful about that um why were the amino acids low yeah that is not clear to me i'm not sure i like barbara's theory as much as anything maybe because they're being used for making atp uh absolutely that could be it but i'm not sure do you think you'll see mitochondrial damage from the vaccines i don't know i really honestly don't know about that i got my vaccine as soon as i could i got mine back in february um let's see how do you choose which pathways to repair first oh that's a really good question that's a very good question so usually i'm thinking about what i actually do in practice if we see beta oxidation and glycolysis both screwed up we just usually fix them both at the same time it's it's doable it's not it's not an overwhelming amount of stuff so i don't know that'd be like choosing your favorite child or something for me it'd be like choosing my favorite bicycle like i don't know i got nine but it's called i don't know which one i just you know i use them all i think you could probably just do them both at the same time that's almost that's pretty much what i always do so if a patient's on an ssri does a trichome cause an issue absolutely it can so you have to be careful if patients are on ssris you really have to know what you're doing if you're going to use tryptophan or refer out to someone who doesn't know what they're doing you know [Music] so how long would you take three grams of lysine with an indicated low so you want to be about six months on three grams of lysine if you see low lysine stop and then retest so they don't want to give people lysine forever and high tryptophan can mean a lot of things usually it means that you don't have enough b6 in the system okay how many grams of arginine so usually with arginine we start with around 3 000 milligrams and can go up to as many as 6 000 milligrams depending on what the patient response is like okay so yeah you can use um i use uh you can you can use any of the different forms of b vitamins i typically use the company peer encapsulations their bees are really good or the company called designs for health and whatever is available from those two companies is usually more than enough sometimes they don't have some of the super specialty items but usually they do and then carnitine you can use it in a liquid form designs for health has it in liquid or designs and pure both have it in a capsule form if you're worried about cardiovascular disease problems and tmao is all over the map you can use acetyl-carnitine acetyl-carnitine instead of regular carnitine some people prefer that all right let's see heavier use it i've never used the elemental diet with free four amino acids i'm not sure what that would do okay see we have one more one more minute a couple more questions here um let's see lindsay's asking if someone has ammonia detox issues that appears to be genetic would you use arginine and definitely no absolutely not no so you want to use the arginine until the problem the markers start to normalize and then stop let's see if they need a maintenance dose or not but even with the genetic defects you don't necessarily want to keep people on those but anywhere from three thousand to six thousand milligrams a day of arginine sometimes the six thousand makes people kind of six you have to be careful to use that much okay uh so a patient with mast cell disorder and intestinal permeability oh gosh i don't know that's one of these people that you'd have to just see yeah i don't know i can't answer that question that's too complicated you know when you have super but i could say you know we have super complicated patients and you have all these lab values showing that things are wrong you want to figure out what's your entry point you know what's the one thing or two things that you can do that are really going to start to make them better and most importantly probably not make them worse right complicated stuff all right so i'm going to wrap it up for now thank you guys for coming to our mentorship mini series if you're interested in the real thing you want a year of lab review and tons of classes to get into in a whole community you can think about signing up you can talk with one of our staff and we have some discounts for you and a class starting in a couple weeks okay so i hope to see some of you in the mentorship and if not we'll catch ups at some other venue okay bye for now you