Mentorship Miniseries: Metabolomics 101

Hi, and welcome to our Spring Mentorship Mini-Series. Dan Kale is here, doing a talk on Metabolomics 101. Oh man, so much going on in our worlds right now, aren't there? People, like, we are busy, busy, busy, busy doctors. So much happening. This is pretty relevant, maybe more relevant than even before.

So, for those of you that are new, that have the first time you've attended one of these, introduced myself a little bit. This is, uh, Dan Kalish. I've been in practice for like, a really long time, since 1992. Um, I've worked with the Mayo Clinic. We did a research project together. We had a group of Mayo Clinic doctors take this class a decade ago or so, and we decided to collaborate. Have a copy of the study if any of you are interested. It's on adrenal and GI function, and it's directly out of what I teach in the mentorship class.

I've been working since 2015 with Dr. Richard Lord, who, those of you that are older, been in practice for 30 or more years, know Richard really well. Those that are newer, he is the scientist that developed organic acid testing, amino acid testing, fatty acid testing. He was the guy at the bench in the lab that made all these things, all these tools for us. And it's been the greatest privilege of my career to be working with Richard these last seven, eight years full-time, developing curriculum. It's an amazing experience. A lot of what we're going to talk about tonight is based on his work. Um, and, you know, I've worked with IFM, I've done a lot of different things in the industry, and I'm really interested in lab interpretation and lab training and lab skills, lab skills development. And so, I want to do a talk, and then I want to look at some labs, and then we can do some questions.

All right, and we have some things coming up for you that are brand new this year. In June, uh, Dr. Richard Lord and I have put together a Long Haul Syndrome Lab Interpretation Bootcamp. This is really the best of Richard and Dan. We've never worked together in this way, but he's done all the research, pulled all the studies, done all his science intensity. Those of you that didn't know Richard can appreciate what I'm saying. And then I get to do the fun lectures. So, it's going to be science-heavy but clinically oriented at the same time. You get 20% off if you use that discount code. And this is the next decade of our careers, isn't it? Working with people that have side effects from or long-term effects from having had COVID, or some people who are having vaccine reactions as well.

And then in April, we also have our Advanced Lab Interpretation Class. This is the one-year full-on program for those of you that really want to get serious about learning how to interpret labs well. And to get a thousand dollars off, $999 off if you use this code. And you guys that have been thinking about it for a while, jump in. Is it no time to waste? You know, the, the year goes quickly. You'll learn how to interpret labs. You come out at the other end feeling totally confident in adrenal hormone testing, female hormone testing, GI workups, all the microbiomes. So, if we get into intercourse, organic acids, metabolomics, all that, it's a pretty intense experience. And people come out of it understanding how to interpret labs at a pretty high level. If you're interested, get that going. If you're not interested in a year-long commitment, the bootcamps are our short things that you can get into.

So, now let's talk about this, uh, gosh, I have a lot of slides. I don't know if we can get through them all, but I wanted to have some take-home, you can use them right away messages in all this. So, that's kind of the theme. And we'll talk about lab-based things and some practical things that you can do, especially around patient treatments based on these tests. So, we're going to look mostly at organic acids for now, and thinking about mitochondria, brain toxins, maybe a little bit on gut microbes.

For those of you that are new to organic acid testing, these tests were first developed, uh, when Richard was a young man, for screening, uh, for newborn babies with gene, for genetic disorders that are life-threatening. Dr. Lord came along in the late '60s and thought, you know, we could use the same testing technology to look for metabolic dysfunction in adults, couldn't we? And 20 years later, he and Andy Braley, you know, set up a lab and started doing that. That lab no longer exists. It's called Metametrix. It's been incorporated into Genova Lab now. And, uh, the thought there was that you can see the genetic and environmental and dietary control that nutrients have over our metabolism by using organic acids. These tests are so specific, these tests are so scarily accurate. You, you know, I can't even tell you the, if you don't understand that, it's because you don't know how to interpret them. So, like when I met Richard in 2015, I thought these were pretty good tests, but now that I really know how to interpret them, it's like this whole other level of understanding has opened up. It's like you can literally see into the person's mitochondria and into their cells, into the very chemical processes of their body. And then correlate that exactly with what, with why they're having high cholesterol, high blood pressure, high stress levels, high, whatever, you know, or low levels of energy, low, you know, low libido, low, whatever. You can just see it literally on these tests. Okay.

Um, let's see. Oh, somebody is asking, oh, for the code. Here, here, here, uh, for this. Here's the code for the, uh, and if you, if you just get interested in doing these classes later, you can always email my office. But the code for the thousand bucks off is MINIAPRIL22. Okay, that was for Angie.

So, the, the role of these tests in practice. Like, I got by my first 15, 10, 15 years of practice without really understanding these labs. But now that I understand them, I just can't imagine how I could even proceed with a patient without knowing these things. And so, hopefully today, I'll just kind of inspire you to, to pick up more, um, more like, uh, know depth of just the sort of the passion for understanding labs over time. Okay.

So, who do you use these tests with? You can really test anybody with these labs. You can test somebody who wants a wellness checkup. You can test somebody who's got depression and anxiety. You can do with kids, older people, younger people, men and women, people who are pregnant, people who are athletes. You can use them pretty much with anyone. And in fact, you know, a lot of the dogmas that maybe that there were, a lot of the concept around the more advanced testing like organic acids or amino acids is that, oh, we use those with chronically ill people who are hard to solve, you know, hard to solve cases or complex cases. But absolutely not. You know, we have all these patients that we're working with now. We have a professional poker player who's an amazing patient, and he's fine, he's healthy, but he wants to play poker better. We have a surfer who wants to surf better. You know, we have lots of women who want to get pregnant, they just want to be healthy before they get pregnant. So, you don't have to limit these tests to people who are chronically ill by any means. In fact, they're probably more effectively used in a preventive kind of way. So, super, super important.

Okay, now we have these four, I call them four horsemen of physiological damage: inflammation, catabolic physiology, insulin resistance, and oxidative stress. And these are four mechanisms that just absolutely destroy our cells, our tissues, our bodies, our minds, right? And then the question becomes, okay, we can all agree on that. The inflammation, being catabolic, being insulin resistant, and having a ton of oxidative stress is just going to take you off this earth and put you into the ground. That's not really like debatable. But then the question becomes, like, how can you figure out where it's coming from? Is it coming from mitochondrial problems? Lipid-related problems? DNA-related problems? How is the, like, is the oxidative stress hitting what, you know, the mitochondria? Is it hitting your lipids? Is it hitting your DNA? Is it insulin resistance manifesting in what way? And what these labs start to do is they show you both if the person's insulin resistant, they also can show you if that insulin resistance is, you know, damaging a certain tissue in the body. Okay. And so, that can be very specific. You can even see these inflammatory markers with the brain, uh, you know, the brain and being inflamed.

So, when you think about a damaged metabolism, enzymes are not working properly, so that the pathways that our body relies upon aren't working properly, like beta-oxidation or the burning of fat, or glycolysis, or the citric acid cycle itself. And one of the main reasons why these enzymes can be damaged and the metabolism can become damaged is because of environmental toxin exposure. So, we have to make sure that we clear detox pathways. We have to check antioxidant markers so we can protect the tissues. You can now actually then measure specific enzymes and see which ones are damaged. That's how intense this is. You can see the actual enzymes and then you know exactly what to target and what nutrient to use to fix the problem. And I think one of the biggest struggles I had in my first five or ten years was not really knowing if what I was going to do, if what I wanted to do was going to work or not. You know, just thinking, well, I don't know if I give this patient a whole bunch of glycine, how do I know that's going to work? And I was kind of scared a lot because I didn't want to sell somebody, you know, a six-month supply of glycine and it didn't help. And so, I think part of my role now is just to say, okay, I've been doing this 30 years. The teachers that taught me have been doing this for 30 years before that. This stuff works so well on a clinical level that it is mind-numbing. And in fact, every day in my practice, I just see things that I can't believe. Even this week, I saw two or three cases where I'm, I didn't say this, but I'm just thinking, wow, that is insane that all that stuff just got better. You know, all your nerve damage is gone, you can walk. All these things happen to people when you do these programs properly that will absolutely blow your mind. And so, it's not only a matter of not worrying about, is it going to help? But it's like, you can't really even anticipate the level to which these protocols, when done properly, will completely change your patient's physiology and completely change their mental health and completely change their energy levels and all these different things. So, again, I see this every day in practice. There's a little bit of faith involved in the beginning when you haven't done this for a while. But if you can look at me as like a second, maybe third generation practitioner, you know, there's a lineage behind this. People have been doing this for a long time, and it's been a very successful undertaking for all of us. And the lab testing and the protocols are just getting better and better. So, if anything, you have an advantage over someone like myself 30 years ago, or an advantage over someone like Dr. Lord or Dr. Timmins, who were doing this stuff in the 1980s, you know. So, you can be confident, totally confident.

The underlying causes, we want to figure out. And there's so many of them, right? Let's not even worry about that right now because there, but that slide is just for me to remember to say that there are underlying causes. We're getting into the weeds on the lab results and markers, but of course, you want to think big as well. So, think macronutrients before you think micronutrients. In other words, you know, if you're getting really obsessive on zinc and B6 like I do, then also make sure that their diet is figured out, right? That the macronutrient ratios are working. And we're not going to talk about that much because we're assuming you guys are working with nutrition and you're working with lifestyle and all that. And we're going to spend our time today mostly focused on the labs.

So, when I look at my patient base and I see also, I have the privilege of teaching this mentorship course, so we have like a good five hours a week where I'm in class with doctors, and they're submitting lab after lab of their own patients. And I look at all those every week. So, I see hundreds and hundreds of these tests every month, and have done for, you know, over 20 years. And after you see something 10, 20, 30, 50, 100,000 times, you start to get some patterns in your head. You start to realize, well, these are things that we see a lot: better oxidation problems, glycolysis problems, neurotransmitter issues, methylation defects, mitochondrial problems, oxidative stress, toxin-related issues. These are things that you're just going to see every day. And so, I try to focus on the things that are the most common that you're going to, you know, have to figure out how to fix. And once you figure out how to fix these things on one person, it's not like it's going to be that different on the next person. So, if you're just getting started with this work, if you're just getting started with this work, then you can design really simple supplement programs based on one or two supplements per section of the test that's screwed up. And then as you get better, you can go up to Defcon 10 here and, you know, get up to this level where you're doing high dosages of all kinds of complicated things. But you can absolutely get very good clinical results in the very beginning if you choose maybe two supplements per category to really hit the person with. If this is a big IF, you get them on a therapeutic dose of whatever it is that you're using. If you underdose people on a million things, there's no effect at all, except for the fact that they buy all these supplements and they're kind of pissed off because they don't get better. If you are specific and you isolate the mitochondrial problem, or the blood sugar regulation problem, or the neurotransmitter problem, or the urea cycle problem, and you really target it, you're going to start to move the needle for people, even with a couple of products per section. And as you get better and better at interpreting the labs, you can make more and more elaborate programs. But sometimes the simple programs are better, even if you have a deep level of understanding.

Okay, so most of what we're talking about now are organic acids. There's a lot of information out there about them. There's all kinds of studies. But most of the research has been done on genetic disorders or in, inborn areas of metabolism that are life-threatening, that are screened for newborn babies, right? So, every newborn baby gets a heel stick, they look at the blood, and they see, oh, you have a urea cycle defect. Well, we're going to have to talk to the parents about this, aren't we? Because if this child starts to eat normally, they could have neurological problems. And what we're talking about today are mild versions of these inborn areas of metabolism combined with nutrient deficits from bad diet, lifestyle, toxin exposure, those kinds of things. So, whereas the inherited metabolic diseases and the screening for them is what started off this kinds of testing, now we see both the shadows of mild genetic disorders mixed in with nutrient deficit-related problems. And that's part of the joy of the testing. And when you're from a practitioner's standpoint, is once in a while, you're going to see a really clear genetic disorder pop up. Once in a while, you're going to see a nutrient deficiency related to diet pop up. And if you can start to differentiate between those, you're going to be at this sort of mastery level of understanding. It is very satisfying. This happens in the mentorship class, like, every few weeks when a doctor discovers their first metabolic disorder that has a genetic basis. And because those patients, they will never forget you. You will never forget them because you're going to completely change their lives. You will also find many patients along the way that just have the general nutritional deficits from bad diet and lifestyle and those kinds of things, and you can help those people dramatically too. But it's nice to be able to do both. Okay, if you really can look at a deeper level of understanding on these labs.

So, I thought I would just break this out so we can just look at two or three things that you guys can wrap your minds around: mitochondria, maybe some insulin resistant stuff. If we have time, we can look at the urea cycle. All right. Well, that kind of takes your breath away, doesn't it? So, I guess we're talking about, uh, mitochondria first, and then the, yeah, okay. So, we get into mitochondria and insulin resistance. Let's at least do those two.

All right. So, I don't know, this is not like meant to be memorized. This is just meant to make you realize, wow, this is kind of complicated. But what are we looking at even? Okay. This, so this is a mitochondria, and within the mitochondria, all these things are going on. But we're measuring these things on organic acids. We're measuring pyruvate, we're measuring citrate, isocitrate, alpha-ketoglutarate, succinate, fumarate, malate. That's what the organic testing is. It's measuring these markers. If you get into amino acids, you can also measure valine and isoleucine and leucine and the actual amino acids. You can measure the process of fatty acids getting into the mitochondria through the carnitine shuttle. Can all be tested for. So, what we're really doing with the first, you know, with the mitochondrial-related sections of organic acids is looking to see, can the person burn carbohydrates well? Can the person burn fatty acids well? And what the heck is going on with the citric acid cycle? That's a lot of information, and there's a lot of potential problems in here. You see how complicated all these pathways are? Wherever there's complexity in the body, there's room for things getting messed up, uh, you know, in regards to genetic problems and variations that are going to really change things for people. And then there are certain parts of these pathways that are like super sensitive to environmental toxins, like the one, I don't know, it's almost a defect is succinate, the succinate dehydrogenase enzyme. It's like a sitting duck for every environmental toxin out there. So, you got an environmental toxin out there, Zeus comes into the body, takes out that succinate dehydrogenase enzyme, and then boom, you got a defect in your mitochondrial functioning. Not a good thing. Not a good thing. And there's certain, uh, pesticides and herbicides, probably the most notorious one is Roundup, that can cause some really severe problems in this regard.

So, another process that we're going to look at then is glycolysis and how we burn up glucose and how glucose gets into the citric acid cycle. And this is a way to look at insulin resistance. I'm sure you're all familiar with that term before. It may show up on other labs. And so, we can look at markers for pyruvate in particular. And so, the way this works is, yet, you have glucose, it gets into the cell, you start to go through glycolysis, you get into the mitochondria as the pyruvate is being produced. And if this process isn't working well, then everything goes over this way, and we start to make more lactate or lactic acid. And you can measure this on the lab. So, if pyruvate is high, it means this process isn't working well. If lactate is high, it means this process isn't working well. So, you can see the early formation of insulin resistance with either high pyruvate or high lactate. And that is really, really helpful. Because if people are becoming insulin resistant, there's a big problem there. There's inflammation, there's lots of oxidative stress, there's potential for cardiovascular disease, potential for high cholesterol, high triglycerides, maybe a fatty liver, maybe a person is obese, maybe they're pre-diabetic. They may, so many things can go wrong if this process isn't working well. And I just think these things look pretty. So, I just, this is almost like a break in the talk to just look at what we're talking about. This is what the pyruvate dehydrogenase enzyme actually looks like. Can't believe they can actually diagram this thing out. These are all the amino acids kind of spun together in their double helixes and all these different structures. So, when we say the enzyme, let's just kind of clarify what that means. So, in order to turn glucose into pyruvate, and in order to get pyruvate into, uh, you know, the energy production pathways, you have to have enzymes. And pyruvate dehydrogenase is going to move things along here. And if pyruvate dehydrogenase isn't working, then pyruvate levels are going to go up. So, if you see a high marker on an organic acid like pyruvate, it means that the enzyme related to that marker is not working well. Okay. There's an enzyme that's dysfunctional. And guess what? Every one of these enzymes requires certain vitamins and nutrients to work right. So, if you can figure out what enzymes are messed up by which markers are high, you know what nutrients that person needs to get their metabolism to work right. How amazing is that? It's like a magic trick. And you've got to have a little belief and trust and faith that this actually really works. I know it's very theoretical sounding when you're first learning about it, but it actually really works.

So, then the third subject area, we'll just touch on for a moment because this one, no one ever talks about, are urea cycle disorders. Nick is identified in the scientific literature as a metabolic problem for adults. And what we're doing in this class is saying, hey, we're going to measure for it. And I'll show you a lab example in a minute that detected a urea cycle defect in an individual patient. And then I'll show you what you can do to start to correct it. And so, let's talk a little bit about, we have time. Yeah, we're good on time. Look at me. Okay, let's go through these, and then we'll look at some labs, and we can come back to the protocols at the end.

So, here's the process again. It's a little bit like being in high school biology. But we take a glucose molecule, we cut it in half, we make a pyruvate, we make, I guess, two pyruvates, really. And then that pyruvate goes into the mitochondria into acetyl-CoA, right? And then the citric acid cycle, we start to break it down more. And then through oxidative phosphorylation, the electron transport chain, and then we end up making energy. What we're going to focus on just for today's class is what happens if the pyruvate dehydrogenase enzyme isn't working well. Pyruvate goes up. But that means this whole process has been blocked. Lactate, as I mentioned before, can also go up on the labs. So, if you see high lactate or high lactic acid or high pyruvic acid, sometimes called pyruvate, that means that this process of glycolysis isn't moving forward in the right direction. So, then what happens? Well, you have all this excess energy that can't get metabolized for fuel. And so, does it just disappear? No. You know, it ends up getting converted into fat. Triglycerides go up, cholesterol goes up, you get fatty liver, of course, you get insulin resistant because your carbohydrate metabolism is damaged, right? This whole system is not working well. So, not only are you tired and craving sweets all the time, but you start to get fat and a little depressed and, you know, just kind of off your game. This is happening. And if you can identify the enzyme that's not working right, like if the pyruvate dehydrogenase enzyme, then you can know exactly what nutrients you need to fix it. Okay. And there's B1, B3, lipoic acid, fix that one. Okay. And you just, this is not like me making stuff up. You just can look at lists of that. Eventually, you'll probably memorize them. Okay. Again, here's the enzyme. Remember, if it's not working well, B1, B3, lipoic acid, etc.

Now, here's, uh, oh, the second thing that we were supposed to talk about. Let me see. Um, was, let me go back here. Yeah, mitochondria. So, one of the, one of the main ways, if not the main, that's not the only way, but probably the primary way that mitochondria are damaged is when we have too much oxidative stress and we can't protect the mitochondria. Then the enzymes that run the mitochondria are nuked, like the one that we just saw, pyruvate dehydrogenase, or the succinate enzyme that I mentioned earlier. So, if there's a lot of oxidative stress and we can't protect the mitochondria, enzymes are destroyed or damaged. Of course, environmental toxins will drive this process incessantly because they generate a lot of oxidative stress. And so, you need glutathione levels to be adequate to protect yourself from all this oxidative stress. If there's excess oxidative stress, the whole process of methylation is also thrown off, and things just get worse from there. So, when you see mitochondrial damage, suspect that there's a lot of oxidative stress. And the tests measure oxidative stress. You see all the oxidative stress markers there. There could be like five or ten oxidative stress markers on a typical lab that we do. You can measure glutathione, you can measure vitamins E and A and beta-carotene, you can measure CoQ10, you can measure all these different variables. You can measure 8-OHdG, all these different variables that have to do with oxidative stress can be measured. Okay. Then you can also get into like nitty-gritty genomic, you know, deep layer stuff. And that's what this slide is supposed to be reminding me to tell you. For those of you that are really into the advanced work or already been doing a lot of lab interpretation, really, what's the next step is to understand the genomic interpretation of organic acids. We're not going to really do that today, but this is just to remind me that, you know, that's a pretty cool thing to do.

So, let's take a look here at, uh, protocols first, and then let's look at some labs. Sorry, I'm skipping around a little bit, but I want to talk about a protocol for the mitochondria. And so, remember, you can use these simple programs that are listed on the board here. If you see on a lab that there's a variety of mitochondrial markers that are not doing well, you don't have to know exactly how the succinate one is different from the fumarate one, is different from the malate one. And I mean, yeah, you can look all that stuff up if you want. But if you just see a large number of mitochondrial enzymes not working well, if you simply use CoQ10, magnesium, B complex, free-form amino acids together at a, at therapeutic dosages, it's going to start to make people feel better. And then later on, you can add to this the complexity and the PQQ and this and that. But this general program, as soon as I say mitochondria, you should think CoQ10, magnesium. CoQ10, magnesium. This should be the first thing in your brain. Someone says mitochondria, you should think CoQ10, magnesium. Those are the main nutrients you have to have present. And these are medium dosages. So, CoQ10, I've got it here at 200 a day. You could easily go to 400 a day on CoQ10 if you really want to move the needle more. Magnesium, 200 twice a day. You could go up from there if you needed to, for sure, as long as they don't get diarrhea from it. B complex, usually one a day. If you know the specific Bs they need, you can add in individual Bs as well. Okay. And then the free-form amino acids, once or twice a day to get things going. There are might, there are combination products that each company has also that are even simpler. And it's always called Mito-something, Mito-Boost, Mito-This, Mito-Plus, Mito-That, you know. So, you can use those combination products as well. If this is too complicated for you, just get a therapeutic dose of one of the combination products and hit the patient pretty hard with it, and you'll notice the mitochondrial symptoms starting to improve. Anything from depression to headaches to weight gain, etc. All right. So, that's one protocol.

And then remember, we talked a lot about pyruvate and lactate. If they're high, this is it. B complex, one or two a day. Lipoic acid, a couple a day. Magnesium is always required for this stuff. You can add in some chromium and biotin if you want. Every company that we work with has blood sugar regulating supplements. And you'll see, if you look at the list of what's in that stuff, it's a combination product. It'll have B vitamins, lipoic acid, magnesium, chromium, and biotin in it. So, you can buy these in a single, you know, capsule if you don't want to go through the complexity of five different supplements for a patient or six different supplements. Getting one of the combination blood sugar support products that has all this stuff in it, super simple. And like I said, in the beginning, one or two products for insulin resistance combined with one or two products for the mitochondria can make a huge difference for people. These full protocols they have here are ideal. But if you want to start simple with one or two products, just use the combination products for blood sugar with a combination product for the mitochondria. And right off the bat, you have two supplements there that can make a huge difference for the person, if you also do the lifestyle changes.

Okay, now, and we'll do questions towards the end. I think those, those are good ones to start with. And we're right at the half an hour mark. So, let's look at some labs. Oh, I'm going to, gosh, up a couple of tests here. Look at that. We've got some really good ones from class, too. If we have time to go over a little bit today, I can show you some other ones. But let's start off with the ones that are, I'm supposed to be showing you here. All right. Let's see if that should pop up on your screen. Uh, yes, I think you can see that now. All right. So, this is Diagnostic Solutions. This is their OMAx profile. And not surprisingly, that includes metabolomics, hence the name. And they have a handy-dandy chart at the beginning that gives you a clue about what to look for here. But that's kind of cheating. We want to actually look at the important parts of this, which is the raw numbers. Okay. Oh my gosh. Now, I didn't do this on purpose. This was a kind of like a random and coincidental, what do you call that? I think they call that serendipity, don't they? When that happens? Serendipitous. Uh, there we go. I'm gonna pull up a protocol here so I can make up one for you guys, too. Um, so now we're gonna think about cases, you know, uh, from what do you call it, from a treatment standpoint, right? And what are ways that you can design protocols? So, one of my personal obsessions for the last 30 years has been figuring out how to design protocols that patients will actually do. So, I spent a long time learning protocols in their idealized form from all my teachers. And then at some point, I figured out, oh, wow, you know, I design these perfect programs, but people don't do them. So, maybe I should focus on programs that people will actually do. And that's what I try to do myself in my own practice now, and that's what I try to, um, teach. So, here's a health plan, here's a lab, and let's go at it.

So, right off the bat, succinic acid is high. Remember we looked at that enzyme in this citric acid cycle? That enzyme is damaged, the succinate dehydrogenase enzyme is damaged. And so, we want to get it working again. And it relies upon B vitamins, in particular, vitamin B2. And you never want to give B2 by itself. You'd always want to give the B complex. And if you're worried about it, you could give some additional B2 on top of B complex. Again, if an enzyme marker, if if an organic acid's marker is high, it implies that the enzyme is not working well. Now, you could be born with a poorly functioning succinate dehydrogenase enzyme, which means that you just need a lot more B vitamins than everybody else does. Or you could be exposed to an environmental toxin, as we all are, and that toxin could come out because you don't have enough of a protection of a barrier of glutathione. That toxin gets in and wacks your succinate dehydrogenase enzyme, and then the succinic acid goes up. So, it could be environmental toxin related, could be genetically related. You could have, as one of my old patients years ago did, like a Burger King diet. She ate Burger King three times a day, which is disgusting, but she was still alive. She was like 26, 27 years old. And, you know, if you eat a diet totally bereft of nutrients, no vegetables, no beans, nothing like that, you could have a nutrient deficit that would cause this marker to go high too. Really bad diet, genetics, environmental toxin exposure. And you can't tell from the lab which one it is. You can't tell from this marker. But that's part of the fun of this is you go, oh, okay, I see that marker's high. Why is that happening? What's nuking that enzyme? Can I find what the underlying cause to that is? And that's where this stuff gets kind of exciting.

So, we can kind of cruise through here, and this person's not doing that well. Okay, a sec. Let me get this to be a little bit better here. Uh, yeah, okay. So, we're not really talking about beta oxidation. Let's try to focus on, see if any other markers on this one show up that are relevant. Well, these are pretty important. We can come back to those if we have time later. Histidine, I mean, so many markers. You know what? We can, yeah, that's enough. Well, this, this combined that with one other thing because one of the things showed up on this test, it's kind of obvious. You see that 5-HIAA there, 5-hydroxyindoleacetic acid. That's quite low. That's a marker for serotonin. So, when that marker goes low, it implies that serotonin is low. Okay. It's a urinary byproduct of serotonin. Now, if we go up to the other section of this test, because I can show you how you can combine markers here, you can see how this kind of comes together. See the tryptophan levels are also low. Hmm. Okay. So, tryptophan is low, 5-HIAA is low, and kynurenate is high. So, what does that mean? When, when the brain is inflamed, kynurenate levels go up, and that can deplete tryptophan, and that can deplete serotonin. And that's what's happening in this person. They have a lot of brain inflammation. How do I know that? Because kynurenate is going up, and they have low tryptophan and low 5-HIAA. So, they're losing their serotonin and they're losing their tryptophan as a result of that.

All right, so let's do a little program design for this person. So, problem number one was mitochondrial, mitochondrial issues with high succinate, right? Now, that doesn't sound like a lot, but that means a lot. That means that you can't make energy effectively in the citric acid cycle. So, that person needs what? Well, as soon as I say mitochondria, you should say CoQ10, magnesium, and B vitamins, because it's a mitochondrial issue. So, right off the bat, you know you need that. If you want to get specific, you can say B2 for this one, but you don't even have to. B2 is in every B complex, so don't worry about it. You didn't have to think about that specific thing as long as you do the B vitamins, a lot of problem. Now, we also have a neurotransmitter program. We have, it's called the NT problem. And what they have, low tryptophan, low serotonin, and high levels of inflammatory cytokines. That's the kynurenate pathway. Kynurenate, let's just abbreviate like that. Okay. So, now you have a couple of different options. We want to keep it simple. Use CoQ10, 100 milligrams. Do one or two of these twice a day. You gotta do your magnesium. I like magnesium glycinate. It usually comes in around 200 milligrams, sometimes 100 milligrams, depending on which one you're using. Let's just say you got a, yeah, you can get 100, 200 milligrams. So, in that range, let's say you get 200 milligrams worth, however many pills that is, and then you do that here and do that here at night. Helps people sleep well. And then you want some kind of a multi. The ones I'm using now a lot are mitochondrial, Mitochondrial ATP from Pure Encapsulations. Anywhere from two to four of those. That's like a mitochondrial multivitamin, basically. And then some B complex. And if you're using the Mitochondrial ATP, you don't need B complex. So, I'll put a compound question mark by that because it's got the B vitamins in it. You can probably omit that. Okay. So, the B vitamins are in the Mitochondrial ATP. I would take that out. And then any kind of a multi that you like, a good quality multi-pack to round things out. So, that would be the mitochondrial component. And then for neurotransmitters, that's pretty easy, right? Because they're low in tryptophan, so you're going to give tryptophan, you know, a fair amount of it. Um, it usually comes at a 500 milligram. Let's say you get at least three of those at night. And then they're clearly going to need some things for, you know, control of inflammation and whatnot. And that's kind of outside what we're talking about now. So, you need to investigate more why is the brain inflamed? Environmental toxins? Gut problems? Very likely this person has a gut problem. You're going to want to work with it. And these protocols are usually done for three to six months. So, then you stop and you re-test, and then you make adjustments on the new lab.

All right, and let's see here. I'm going to do one more protocol and then we'll open it up for questions. So, here is another case. This, let me go back to the beginning here. Is a Neutral Valve from Genova, also has organic acids. It also has a summary page. You can see quite clearly here, oxidative stress levels, super high. Mitochondrial dysfunction, pretty high. Problems with the omegas, we're not talking about toxin exposure, pretty high. And these things are not unrelated. That's what we've been talking about this whole time. So, in other words, if you have a lot of environmental toxins, that's going to generate oxidative stress. And the oxidative stress is going to hit your DNA. Not good. It could hit your lipids. That would have a cardiovascular ramification. If the oxidative stress hits your lipids and you have oxidized LDLs, that's kind of what we call heart disease, right? And then it can also hit your mitochondria, which would be a metabolic problem. So, lots of toxin exposure, which we all have, generates oxidative stress. And then is it your DNA getting hit? Your lipids getting hit? Or what we're talking about today, your mitochondria getting hit? Just a matter of how your body is taking the blows. I hate to oversimplify human suffering, but this is, you know, probably three-quarters of my practice. Let me, let me back up and say one more thing here, because it's not, so I would say either environmental toxin exposure or gut problems. Either environmental toxin exposure or gut problems. Either of those, sometimes both. Either of those generating oxidative stress and then damaging mitochondria. That's like boom, boom, boom, one, two, three. Tons of gut problems generating oxidative stress, damage mitochondria. Tons of toxin-related problems causing oxidative stress, damaging mitochondria. That's like 75% of what I do with patients. I hope I don't really want to completely oversimplify and minimize what I do, but that's, let's see. Oh my gosh, this person needs a lot of help. Look at this. But let's look at the fun part. You can figure these parts out yourself. You can look at magnesium and figure out they need magnesium. But the complicated part, I think, is more important to look at because it's harder to understand.

So, here, let's say, zoom out for a second. This is the mitochondrial section of this test. And they make it easy for you. They color code it so you can't really miss it. So, let me get out my colored pen set here. And this person is not burning fat very well, right? Adipic acid, suberic acid are high. That means that beta-oxidation is not working. Beta-oxidation not working. Pyruvic acid high. This is insulin resistance. This person can't burn carbs very well. Can't burn fatty acids very well. That's a really bad problem. That would be like if you're driving your car and you've got a flat tire and you're trying to get to the freeway off-ramp, you know, without stopping so you don't get killed by the side of the freeway. And then your other tire went flat. It'll be like, okay, boom, I'm stuck in this, you know, fast lane of the freeway and I can't go anywhere. Okay, you have acids not being able to make energy from hydrates. This is the worst thing. Poor little mitochondria. And then when you get into the citric acid cycle itself, you see all the yellow guys here. These are like milder problems. But look how many of them there are. They're four. So, there's four different enzymes in the citric acid cycle that aren't working. A couple of enzymes up here, a couple right here. I mean, it's just not a system that's working. Got a lot of problems.

So, the solutions here, maybe we'll just look at this page and kind of make the program based on this. For the fatty acids, you use carnitine, magnesium, and B vitamins. But magnesium and B vitamins, we're giving to everybody, don't worry about that. Carnitine would be the specialty product for that. Pyruvic acid, B1, B3, and especially lipoic acid. And then citric acid cycle, we already talked about. So, let's go back and we can actually look at our old protocol here. And so, is there a mitochondrial problem? Yep. So, first thing you think of, CoQ10, magnesium. Done. But remember, this person also had the fatty acid issue. So, you want to use L-carnitine. And that can come in a 300 or 500 milligram capsule, somewhere in that range. And you want to give a total of around 2,000 milligrams a day. So, it's just depending on what kind of product you get, it may be two, something like that, two capsules twice a day, three capsules twice a day, somewhere around there. You wanna do 2,000 milligrams a day of the carnitine to really get that fatty acid metabolism going. And then this person also had the problem with pyruvate being high. So, you wanna use lipoic acid. You can usually get that in 300 milligram and do either one or two of those twice daily. Okay, sometimes as much as 1,200 milligrams is required. And then again, this person had the pyruvic acid problem. So, they need a B complex. You could give extra B1 and B3, but you don't really have to in the beginning. I would just try B complex and see if that's enough. If one a day doesn't seem to be doing anything, you can give two a day. That's kind of a lot, but I'd probably start with one a day and see how they respond. If the enzymes are really sluggish and not working well, they need more B vitamins. And you can escalate and give single dose B vitamins, you know, like just B1 or just B3 or something like that. But generally, in the beginning, these programs are enough. So, this would be a combined mitochondrial support program with a blood sugar support program. And there's certainly many additional things you can do. I'm trying to keep this simple and realistic so you guys can actually try these things with patients and, uh, get well.

So, here's my general advice then. If you haven't listened, if you've heard me talk a lot before, you can just go surf the internet for a second, read the news or whatever. But if you haven't heard this before, this is super important, which is that this is why I say this every time I give a talk. The biggest problems that I see in functional medicine now, I'm just going to draw it for you because I see this every day and it drives me insane, is we'll get a new patient coming in, they'll say, oh yeah, I saw this functional medicine doctor and, you know, I did this program and, you know, it didn't really help. And I'll look at the protocol and it'll be one of these, one, one, one, one, one, one, one, one things. And they'll be like, 500 milligrams of N-acetylcysteine. Never helped anybody with anything. You might as well just hit your head against a rock. Okay? It's not gonna do anything. Uh, what else? Maybe an enzyme or something like that. But, you know, what drives you even more crazy and more ballistic is they'll, they'll pick some beautiful like gut product, like say it's Formula AC, Formula Two, that's from

Pure, that's a really beautifully designed candida product. And they'll give them like one twice a day. I don't know, maybe that's what it says on the label, but that's not gonna do anything for anybody. So you get these programs and it's like this list of ones. That means that you're not giving the patient enough of anything. It's like torturous to see that. So sometimes there's every product picked out carefully and accurately, but everything massively underdosed and nothing happens. It's very frustrating for patients to experience that.

Okay, so we don't want you guys to do that. We want you guys to not, certainly don't want you to ever hurt anybody. You got to be careful and be, you know, know what you're doing. But at the same time, you don't want to just perpetually underdose everybody, or you will just be frustrated and you'll think this stuff doesn't work very well.

Okay, so I'm going to answer questions in a minute, but let me just tell you what's happening around the Chaos Institute. So we have two things coming up. In case you started late and missed this part, we have the Long-Haul Syndrome Boot Camp that Dr. Lord and I have put together for you guys. So it's all of Richard's research and sciencey stuff, and then my clinical application. We unfortunately have a lot of long-haul patients in my practice right now, and unfortunately, we're all learning how to deal with this. You get a discount, 20% off if you use that code for the mini, uh, of your mini-series attendee.

And then we have the Super Class coming up in April. And hopefully, a few of you are going to sign up for this. This is why sort of my most exciting thing that I do with my week is this mentorship with advanced lab interpretation. So this is a year-long course. We have live weekly calls. We review your labs from your patients, talk through every case that you have. We have small groups of doctors all together, and there's just, you know, four, five, six cases every hour. Sometimes there's one or two, but man, there's just so much learning going on. You really learn how to interpret labs at the end of this because you're going to see your labs that you run plus all the other doctors in the class. You're going to see their labs, you see my labs. If we have time, I can show my stuff in the class once in a while when I get a really interesting case. And you get a thousand bucks off with a discount code there if you want to sign up for the year-long course. And if you really want to have, if you want to be a half-decent functional medicine practitioner, you have to learn how to interpret labs at some point, you know? And I'm trying to make this as easy on you guys as you can. You don't even have to leave your house, it's all online. You don't have to fly around the world and sacrifice anything too big. And these courses are really quite effective. We've been doing them since 2006, and they work. People get out of these classes and they're confident in how to interpret labs. Okay? And the labs that we look at are adrenals, female hormones, a lot of GI testing, and organic acids in excruciating detail because that's usually the hardest part to learn, right?

So, um, let's take a look here at stuff. Questions. All right, now let's go and see. Uh, does the mentorship include transcripts or notes? Well, you know, everything is recorded. Everything is recorded, so you go back and listen to it over and over. When I was learning this stuff from Dr. Timmins, I had cassette tapes. This kind of dates me a little bit, but I taped everything that that guy ever said. I have boxes of tapes of his, literally boxes and boxes of them. And I would listen to these tapes in my Walkman, you know, five, ten, twelve times. If he had a really good adrenal thing that he did, there was a good adrenal case, I would just listen to it over and over. I just memorized everything he said over the course of six or seven years. And so, absolutely, all the things that we do in the mentorship are recorded. You can listen to them over and over. We can probably get you transcriptions if you really want, you know, as well.

The 20% off slide on the, uh, please say it. The code is miniapril22. Let's see. That is for, oh, sorry, hit the wrong button there. Miniapril22. And then for the Long-Haul Syndrome class, it's mini22. So if you want to do the Long-Haul class, you get the discount, it's mini22. And if you want to do the mentorship and get the thousand dollars off, it's miniapril22. And if you can't remember that, or you write it down, you forget where you put it, just email my office. And Jennifer, who's our wonderful salesperson, does Zoom tours for doctors. She'll give you a tour around all the courses and, and, you know, kind of orient you to what we're doing.

Does the mentorship help with setting up a functional messaging practice? That's, yeah, that is the whole point. This is my practice. So the mentorship is everything that I do in my practice dumped into your lap over the course of a year. It's literally like what Glenn did for me when, when I was first learning how to do this work. Glenn Feeder came up to me after I'd been working for him for about six months. He was wearing shorts, an aloha shirt. I'm like, what's up, Glenn? We're supposed to be at work. He literally handed me the keys to his clinic and said, "I'm taking Wendy and the kids and we're going to Bali for two months. It's all yours." You literally like handing me the keys, like physically. I had the keys in my head. I was like, oh my god, I can't believe I'm trying to mimic that experience, but it's online and you don't get my physical keys, but you get everything that I do in my practice. And the mentorship, that's the whole point. And that's why it takes a year to get all the information over.

Uh, what are the companies? Oh, so you can, there's a, you can use Diagnostic Solutions for the lab testing, and they have the Omics test. And you can use Genova. They have the NutraVal. Let's see. If you're an RN, can you take the mentorship? Absolutely. We welcome nurses. That is not a problem. We've had a lot of nurses take the class. If you're not using Ions anymore, you can use NutraVal or the Omics test. They're roughly equivalent. The Neutrophils, if you want to stay with Genova, it'd be the same company. Do you have lifetime access? No, I think we have, I think you have two years of access to the mentorship now. Once you sign up, you get a year of access and you get an additional year after that.

Let's see. Lisa, oh, I see you can't see the code. Maybe you can see it now. Sorry, I think that was a formatting problem. That's why everyone was asking about that. I hope you can see it now. Mini22 is the code for the Long-Haul class. And then miniapril22 is the code for the other one. And again, if you can't see those, just email the office. And sorry about that. I'll put those up higher next time.

The Long-Haul COVID Boot Camp, be for those in advanced mentorship too? Yeah, I may be somewhat redundant, but I'm not sure. Jennifer, I'm not sure about that. Um, it may seem a little redundant in some ways, but in some ways, probably not. Let's see. I'm trying to cover all these questions here.

So patients with breast cancer should for sure do these tests. Super important. Of course, you don't want to give them any hormones at all, but you want to make sure you do the testing. Oh, if pyruvic acid and lactic acid are low, whoo. If you see a pattern of low mitochondrial markers, it can mean the person's hypometabolic. That's like the deep end of the swimming pool, okay? So hypometabolic means there's not enough mitochondria physically present. That's a big problem. Does it mean that the mitochondria are not working? It means they're physically not there, okay? It's like the difference. I always think, I don't know, because I think about cars all the time, anyways, this is why I think about this way, but it's like a car that has an engine that's not working, that would be high mitochondrial markers. Or a car that just physically doesn't even have an engine in it, not going to go anywhere, is it? That would be a hypometabolic state. When a preponderance of these mitochondrial markers are low, that is a huge problem because you have to rebuild the mitochondria in order to fix that particular situation, okay? That's a good question from Brown, Brown Win, Bronwyn, sorry, I don't probably not pronouncing your name right.

How do you know if they need additional B complex? Well, you run the labs, and then if the B vitamin markers show up, you put them on a B vitamin. Give them three to six months, re-run the labs, and you should see the markers normalize. If they don't normalize, then you bring the dosages up accordingly. You know, you can absolutely give B vitamins by themselves, but you always want to give a B complex with the additional B2 or B complex with the additional folate. In general, is considered not a good idea to give an individual B vitamin unless they're also on a B complex. And there's complicated reasons for that because if you stimulate one part of the process with B2, you need all the other B vitamins to make the metabolic pathways work. So if you just give an individual B vitamin without the B complex, it's not going to be very successful.

So if someone holds up as take supplements before a test, the results show lower levels, how would you know if the existing supplements are the correct dose? That's complicated, but if you do a series of tests, one or two, or sometimes three labs, you very clearly will see patterns that'll let you know if you're dosing the person right or not, okay?

Um, so environmental toxin labs. So, uh, Great Plains has several, you know, toxin screens for mold and environmental toxins. They have one for glyphosate. Um, so they're probably the leader in that area, you know, if you want to do some testing specifically for those. But you also still want to know which detox pathways aren't working and make sure that you get that done. So it's not so much that you're treating the individual toxin, usually, as it is that you're treating the pathway overall.

Would you treat this one before the other? So in general, I think it's good to get the cell physiology normalized. And once that's happening, then to work on cleaning out environmental toxins or doing whatever needs to be done. But if you start to detox someone's mercury and their basic metabolic pathways aren't working, the outcome could be not so great.

Can this test be used as a wellness protocol? Absolutely. That's the best use of it is as a wellness protocol. That was me asking that question. Super important. In fact, I wish that we could all just have a wellness practice and that's all we did, you know?

Um, let's see. Okay, I'm going to wrap things up. I think I see what happened why everyone was asking this question because the slide wasn't, was too far at the bottom of the slide. So anyways, the code for the discount for the Long-Haul class is mini22. Mini22. And then the code for the advanced class mentorship class is mini, miniapril22. Okay? And if you guys are interested at all, contact the office. Talk to Jennifer. She can give you a Zoom tour and get you started. This is a mentorship mini-series. That means there's more of these coming up. So if you want to attend the next one, that would be great as well. And I hope to see you there. Okay, bye for now. You.