Transcription
Hello everybody and welcome. I am Dr. Dan Kalish, and I am here in conjunction with Genova to talk about the most important thing that you can imagine for your patients: insulin resistance. So, super excited, uh, to be working with Genova to put this class on, and super glad that you guys are here. Um, I'm just kind of watching the ticker thing here. People are streaming in from all over the world. It's really exciting. These have been our super most, uh, popular, I guess, is the word, or enthusiastically received classes that I've done in a long time.
So, there's a companion to this class, which, if you didn't hear it, we did last week, which is, I'm sure, posted all over the place. You can ask for that recording. It's on beta oxidation. This is a companion, and we'll tie these two subjects together. We're going to talk about insulin resistance. So, I'm going to introduce myself, talk a little bit about the background that I come from, and why I do these talks. And then we will get into some cell physiology, biochemistry stuff. I'll promise to keep that short, 20 or 30 minutes. And then we're going to look at some labs. So, you can learn the biochemistry and then apply it. That is the whole point. Applied physiology, applied biochemistry. You want to, everything that we learn in biochemistry, I want you to know as information that you can apply to your patients. That's the goal. I promise I would never talk about a pathway that is not clinically relevant. Promise.
So, I am Dan Kelly, for those of you that are new, uh, to these kinds of webinars. And I founded The Kalish Institute back in 2006. I've worked with a lot of different people over the years. A group of Mayo Clinic physicians took my training program 10, 12 years ago. We ended up collaborating together and doing a research study. I've worked extensively for the last 10 years with Richard Lord, who is a scientist that developed organic acid, amino acid, fatty acid, and nutrient testing. Pretty much everything that we're talking about tonight is from the bench of the science department of Richard's original lab. And I've also been in practice for a really long time. Like, I'm on my 30th year of practice right now, and I still see patients one day a week and still kind of experience the ups and downs of what it's like to be running a clinic. And my main goal since I created The Kalish Institute was to build successful functional medicine practices because I've always felt that there's a shortage of successful practitioners due to a lack of practical application education. And so, I come from a very academic background. My, uh, you know, father was a professor. I grew up in Berkeley, California. And I'm not, you know, down on academics at all. But my role in this world has really been to teach people how to apply the information they have to a patient practice so you guys can be successful. So, The Kalish Institute, we have boot camps that last for like a month. We have mentorship programs that last for a year or two. We have business classes. We have classes in everything that you can imagine to make your practice super successful. And that's my main goal for all of you. And I'm glad to have you here.
So, now we're going to jump into the topic today, the Nutrival. And just so you know, we are starting a Nutrival. It's the first time we've ever taught this class, first ever getting started interpreting the Genova Nutrival boot camp. And that starts in a week. We've got two or three spots still available. If you guys are interested in signing up for this small and elite group, you get 20% off with this Genova Diagnostics code: GDX23. And you can sign up for it right now. And, um, come back and listen to the rest of the lecture later. So, this is going to be, uh, an intensive review of the Nutrival. It's like, this is a big test. What am I going to do with this test? How do I even use this thing? It's a beast. And each one of these markers, you could spend years studying. But how do you apply this right now in a practical way that's going to give you clinical results that'll blow your mind? That's what this class is for. I've spent, I don't know, depending on how you look at it, at least a year creating this boot camp for you guys. And we're going to just smush it all down into a matter of weeks. So, there'll be lab review sections of the boot camp. There's lectures that I put together for you. An overview of the test, but again, with the eye towards immediate practical application. You don't have time in your practice to wait for three years to do some kind of academic thing before you start treating patients. We want you treating patients now, in real time. So, anyways, I hope some of you will join that class. That's starting next week. And you get 20% off if you're a Genova referral.
So, the problem is kind of obvious. I'm just going to show some graphics so we can all agree that cardiovascular disease is a big problem. It's still the number one killer. And insulin resistance is the setup for development of cardiovascular disease. Sugar consumption is on the rise. It's astronomical how much sugar people consume. Diabetes is on the rise. Even as heart disease is dipping down a little bit, still the number one killer, diabetes going back up. So, we could say we've slightly better managed some aspects of cardiovascular disease, but diabetes is just on a rush upward. Obesity on a rush upward. You just see these graphs all day long. Everything's going up. And what we're, and this is the worst side of all this, is like kids. This is young kids, 10-year-olds. Look at their diabetes rates. That's not acceptable in a modern culture. We have safety. We have, you know, we're not in the middle of a civil war or some kind of crisis. There's water. There's food. You know, there's no reason why our kids should be on a diabetic curve like this. This is insanity defined. We have to stop this, okay? Somehow, with adults is one thing, but to see the rates and increase in childhood diabetes is just insane.
And so, we want to talk about the big picture here. And I want to just present, before we get into the slides, just the two biggest picture concepts that you should be able to take home. One is from the earlier talk on beta oxidation. So, go back and listen to that. That's the slow-twitch muscle fibers. I see how I slowed down there. Is that clever? Slow-twitch muscle fibers. I'm going to ask one quiz question right now. See if anyone gets it right. What's arguably the most important slow-twitch muscle in the human body? Anyone want to take a stab at that? I'm just going to do, see if anyone types in an answer. The heart. Your heart is a really big slow-twitch muscle. Period. So, we want our slow-twitch muscle fibers to use oxygen to make energy and to burn fat. That's the whole point. There is this other glycolytic system where we're burning glucose. And when you think of it from an exercise perspective, when you're intensely exercising super hard and you couldn't breathe fast enough to, you know, fuel the whole oxygen-related fuel system, then you have to kick gears over to burning glucose, obviously. And that's what we're going to be talking about today. Fat burning system, slow-twitch muscle fibers, glycolytic system for an athlete that would center around the fast-twitch muscle fibers.
Why does that matter? Because the whole point of functional medicine is that we're doing lifestyle medicine. But it's not just lifestyle medicine. It's not like, you know, just someone nagging you, "Oh, you should go exercise more," or "Why don't you eat your vegetables?" It's not nagging medicine. It's lifestyle medicine based around labs. That's what functional medicine is. So, if you run a lab test and you see high pyruvic acid or high lactic acid, which is the, the two markers that we're going to focus on tonight, high lactic acid or high pyruvic acid, that is a clear, horrible sign that this person is not burning glucose appropriately. And so, then what do you want to do? You want to fix those enzymes that are broken with nutrients. And we'll look at that in detail in a moment. And then you want to, to make that actually work, you want them then to exercise. Literally use their glycolytic system. So, you can't just give somebody a supplement and say, "Oh, yeah, if we give you enough B5, this is going to work out. Just take a bunch of carnitine and you'll burn fat." Absolutely not. That's the nutrient that the pathway requires. But to get the pathway to work is the whole point of the lifestyle stuff. So, you need to learn about Zone 2 and Zone 5 exercise. You need to learn how to stimulate fat burning and mitochondrial function in Zone 2. And how you can, once in a while, once or twice a week, stimulate this glycolytic system where you're burning glucose. So, you not only give the nutrients for that pathway, but you force that pathway to work. In this case, with exercise, you could do it in a lot of different ways too, if you want. I mean, there's other things you can do to improve blood sugar regulation. But the combination of exercise and supplements in diet, obviously, is, you know, what we're after here. You'll, your results if you just give the supplements to fix this pathway that has, you know, the lactic acid and pyruvic acid pathway, will be okay. They'll be good. They'll probably be better than most people that are trying to treat this stuff, probably. But if you combine that with the exercise, you got it made. You'll be like super advanced mastery level for all this stuff.
All right. So, now we talk about why this is happening in the first place. Well, one of the main reasons is environmental toxin exposure because environmental toxins damage mitochondrial enzymes. They damage these glycolytic enzymes related to glycolysis. And that causes some pretty big problems. You will see high markers on the Nutrival when an enzyme is damaged. And we're going to go into detail on how enzymes work in a minute. Excess energy consumption, that's overeating, basically forces the body to store the extra calories. You have to do something with them. And then again, the lack of muscle tissue makes this whole thing that much worse. It's like having an earthquake and then there is already a flood and then there's a fire that breaks out. Just like boom, boom, boom, boom, boom. Environmental toxin exposure, excess calories, and lack of muscle tissue. Those things just stack up. And and that's why this is happening. That's why kids' diabetes levels are impossibly high because we've exposed them to environmental toxins. I take the blame of that. My generation caused that problem. There's no 10-year-old kid that triggered the environmental crisis that we're in now. They're eating too many calories, probably also our fault for preventing sodas and whatnot. And they don't have the muscle mass that they need. That's the heart of the problem.
So, over time, this creates insulin resistance, oxidative stress. Then you head into the things like high blood pressure, heart disease, diabetes, metabolic syndrome. All that stuff starts to happen. On the patient side, in terms of what people are complaining about, people don't usually walk in and say, "Oh, you know, I feel like I have too much oxidative stress," or "I think I have metabolic syndrome." That's really rare. But people walk in and say, "I'm depressed. I'm tired all the time. I have brain fog. My whole body hurts. I have pain in my joints. I'm bloated." All, you know, these are the kind of symptoms that people are experiencing when all this stuff is happening. So, we want to then solve for this by testing carbohydrate metabolism, testing for environmental toxins and the pathways that clear those toxins, and testing for oxidative stress. And then fixing what you find in those areas. That's the key. We're just focusing on carb metabolism because we only have an hour. But clearly, you need to address these other issues too.
So, the use of supplement programs and lab markers is how you get the lifestyle changes to work. Because everybody knows that they should stop eating sugar. But if you can run a lab and say, "Oh, I don't know, this looks kind of scary. Your pyruvic acid and lactic acid are high. Let me show you what that means in terms of this pathway about how you burn." And then you're like, "Do you crave sugar?" "Be like, oh, yeah, I do." Well, it makes sense. You crave sugar because that's the problem here. Getting people to stop sugar and alcohol for a few months or forever requires some force. You have to force them. You have to meet, you have to meet their sugar cravings and alcohol cravings with the equal or greater force to stop it. And that's the point of the labs. Everybody knows they should not drink as much alcohol and not use much sugar. But to have a reason to do that, that's the point of the labs.
So, when you're thinking about all these things, whether it's heart disease, number one killer, diabetes, metabolic syndrome, obesity, they all have a very similar origin. And that's what we're talking about now. It's kind of the origin story for all of these things: insulin resistance. And you can see the early signs of insulin resistance on the Nutrival or the metabolomics test from Genova. So, for those of you that don't know, the Nutrival includes a blood draw and a urine draw, a urine sample. And it's a much more comprehensive test. The metabolomics is kind of handy, though, and it's becoming very popular. And it's one I order in my practice all the time. It includes most of the Nutrival, but there's a urine sample only. So, it's a little easier for patients to do it. So, either a Nutrival or a metabolomics can work really well. The Nutrival is the classic and complete test. The metabolomics is sort of the up-and-coming new test, but it's easier to do. It's a little less expensive. Either one is totally appropriate for what we're talking about now.
So, now I think about what are vitamins in the first place? You know, and I thought a lot about this for a lot of years, actually. You may, I don't know if that's a good thing to admit publicly or not, but it's an interesting subject to me. So, there are things that are not produced internally by your body. So, you have to get them from your diet. There's 13 of them, odd number. There's four that are soluble in fat: A, D, E, and K. We're not really talking about those. There's nine that are water-soluble: C plus the eight B vitamins. So, the eight B vitamins, you actually really need to focus on and you need to memorize and you need to learn inside and out: thiamin, riboflavin, niacin, pantothenic acid, B6. I, we call it B6. I know because it's hard to say, peroxyl five phosphate or whatever. But folate, B12. They're grouped together not because they're similar structurally, but because they're all water-soluble. They're made by plants. They're also present in animal products. As a simple example, B6 is essential for survival based on its functions in 140 different enzymes. So, like, we couldn't even cover the roles of B6 in a week-long class. Probably 140 different enzymes that are all throughout the system that are required for life depend on B6, just as a simple example. That's just one B vitamin. Pantothenic acid, I think it's my favorite B vitamin. It's, I know you shouldn't have a favorite B vitamin, but I do. Pantothenic acid is my favorite. It's a cofactor in 4% of all mammalian enzymes. Four percent. It's also the heart and soul of what we're going to talk a lot about today, which is acetyl-CoA, CoA, coenzyme A. Pantothenic acid.
So, these are not negotiable nutrients. These are must-have to survive for the next 30 minutes kind of nutrients, or even 30 seconds kind of nutrients. I think if you stripped all the B1 out of your body, I don't know, you, it's probably similar to draw, you know, all the blood leaving your body at the same time. You would be dead instantly. So, these are important, important, important. They're not a nice-to-have or "I'm going to take my B vitamins to be healthy." They're required to maintain cellular function. Super, super important. I would never prescribe a B vitamin without a lab test, however. Because to quote Richard Lord, my favorite quote after 10 years of working with this man, right, you guys should write this one down. This is not my, this is Richard's exact quote. "Every nutrient, every nutrient can be a toxicant." "Every nutrient can be a toxicant." Richard Lord said that to me 10 years ago. Every nutrient can be a toxicant. So, that means that you just give B vitamins to everybody? No. You have to test people and see what enzymes are working and which ones aren't and which B vitamins they need. And you need to know when to start, how much to give them, and then when to stop. The testing shows you when to start and how much to give. The re-testing or the follow-up test is the only way you're going to determine when you should stop. The patient feeling better is not the moment that you stop. You stop when the lab work is normal, when you've fixed the B vitamin deficiency based on the test. Super important.
So, now let's look at insulin resistance. And I know sometimes I slip, I kind of skip around with slides depending on the questions that are coming in and what I think I might want to focus on. Um, the concept here is that insulin resistance involves muscle, liver, and fat. The stores of fat that we have: muscle, liver, and fat. And if you're insulin resistant, you have problems eventually with a fatty liver, to which fat accumulating with the liver. You have problems with the muscles not working properly. And then you have problems obviously with excess lipids. Triglycerides are high, cholesterol is high, all that. So, when we look at the lab markers, and we're only looking at two: lactate or lactic acid, pyruvate or pyruvic acid. When we're going to look at those markers, they're reflecting the function of enzymes. The two enzymes we're going to look at: lactate dehydrogenase and the pyruvate dehydrogenase complex. When Richard first taught me about the pyruvate dehydrogenase complex, and he spent like a whole, like literally two or three hours trying to describe this thing to me, I was like, "Well, we've really crossed over to the point where this is stuff that I don't need to know." You know, like, and now, eight, nine years later, I mean, this is like mission-critical stuff for clinical practice. So, I promise, everything that I'm teaching you, I not only learned from Richard, but then I applied it in my practice for a long time and realized, "Oh, gosh, he was right. You need to know this in order to appropriately treat patients in general."
So, you need to know what an enzyme is and a coenzyme. I don't like the term coenzyme because it reminds me a little bit about the term like co-pilots. Like, if you get on an airplane, which I'm about to do in a few days, you get on an airplane, you walk on a plane, and there's a pilot and a co-pilot. You clearly immediately think that the pilot is the critical part of this plane getting somewhere, and the co-pilot is there in case something really bad happens to the pilot. But you, if you are ranking things, and if somebody said, "Look, we got to kick one of these people off the plane," you would for sure say, "Oh, that co-pilot is not as important. Get the co-pilot off. Let's keep the pilot here." So, a coenzyme makes the term, makes it sound like it's less important than the enzyme. But it's not. It's not like the pilot-co-pilot situation. The enzyme can't work at all unless the coenzyme is present. Okay? So, the, the coenzyme is the only thing, or only in the presence of the coenzyme can the enzyme actually function properly. Another way to think about it is that they're the non-protein portion of the enzyme. The enzyme can't work without this other thing. So, you have cofactors like magnesium and calcium. We're really much talk pretty much today only talking about B vitamins as the coenzyme. But it's the part of the enzyme that's required to make it work. So, we're going to look at enzymes for a minute, and then we're going to look at coenzymes, and then we're going to look at how that manifests on the lab.
In order to make an enzyme, you, it's their proteins. They're all proteins. So, you have amino acids that are strung together into these different structures, alpha helices, and all these different chains and things. And then eventually it folds itself up into a protein. But to, important point to remember is that all these proteins, all these enzymes that we're talking about, are simply strings of amino acids. So, immediately your mind should go to amino acid testing, which we're not talking about tonight. But if you're low in amino acids, this whole process doesn't go very well. Or if you have a snip, if you have a genetic defect in the strings of amino acids aren't laid out properly, then the enzyme is not going to work very well. And that becomes extra, extra important because a lot of our patients have variations based on genetics in their biological requirements for B vitamins. Roger Williams is a scientist, was a scientist, died a long time ago, who wrote a book about this called Biochemical Individuality. Roger Williams, Biochemical Individuality. He wrote that book in the 1950s talking about how different people had different genetic needs or genetic requirements for B vitamins and how the lack of these B vitamins in certain people could cause depression, anxiety, fatigue, all these different problems. And Roger Williams has some street credentials. He discovered two of the B vitamins himself in his lab. So, he wasn't just like pontificating. He wasn't like a blogger that was reading a research study and then regurgitating it. He's actually the scientist that discovered a couple of the B vitamins. I love that. And he was Richard Lord's graduate, what do you call it, you know, dissertation advisor. He's one of his, uh, professors when Richard was in graduate school.
Okay, so here's the enzyme structure. It's made up of strings of amino acids. They get folded up into these shapes based on all the ways that the amino acids themselves are shaped. And then the enzyme part is the structure we just saw. The coenzyme, it's always represented like this, where you have an enzyme and it's kind of like a lock and a key, or, you know, like this diagram here, where the coenzyme fits into the enzyme, and that's what makes it work. Now, when we're looking at the electron transport chain, citric acid cycle, glycolysis, we're looking at how energy is produced in the body and how we burn up energy. Each one of these steps involves an enzyme. So, converting pyruvate into acetyl-CoA requires an enzyme called pyruvate dehydrogenase. Converting citrate into cis-conitate requires another enzyme. So, there's enzymes for each one of these steps. And where we're going to focus on now is up here in the conversion of pyruvate to acetyl-CoA. If you can do that successfully, the acetyl-CoA then goes into the citric acid cycle and you start to make energy, which is pretty cool. You make from one molecule of glucose, two pyruvates, and then around 30, 32, 34 units of ATP. That's what should happen if glycolysis is working. Glucose goes to pyruvate, pyruvate goes inside the mitochondria, and you net out 30-some units of ATP. If that process is not working great, and there's a break right here, pyruvate goes over this way to something called lactate or lactic acid. And if pyruvate goes to lactic acid instead of our movement going to acetyl-CoA, how many units of energy do you get? How many ATP do you get? If anyone gets this right, I'll be like super impressed. It's two. So, if you're going through anaerobic energy production, there's not enough oxygen, you're converting, converting the pyruvate to lactate, or maybe the enzymes busted up, not working right, you get two units of energy. If you do it properly, you get 30-some, 32, 34 is like that, three, five, depending on how you want to look at it. So, obviously, if your lactic acid is high or your pyruvic acid is high, your energy systems are not working very well, and you're going to be what? Pretty darn tired. If one molecule of glucose netted two ATP for someone next to me, and it got me like 32 ATP, obviously I'm going to have a lot more energy. So, this is directly relevant to fatigue and fat burning and all these other kinds of mechanisms.
Now, another thing I'll just point out here on this diagram is, you know, why if you're thinking like, "Oh, I don't really know about B vitamins, it seems like B vitamins are just kind of yesterday's news. Who really cares about B vitamins?" Well, there's a B vitamin that's responsible for that step. There's a B vitamin that's responsible for that step. There's B vitamins responsible for that step. You see? Well, the Bs are everywhere. Everywhere you see a B, it's a B vitamin. So, how well do you think this thing's going to work if you don't have B vitamins? It's not going to work even a little bit. Even the electron transport chain requires B vitamins. All of this. Which ones? We just list them off. Thiamin. All this. And I'll show you some diagrams of them. You got to have B vitamins for all this. But you don't want to just give everybody B vitamins just because you think that it's a good idea. You got to test for it. That's the whole point. So, again, this ties together the previous talk and today's talk.
Here's glucose, a six-carbon molecule. It gets split in half into pyruvate. And then the pyruvate sneaks into the mitochondria. So, out here is in the cytosol. Down in here is inside the mitochondria. That pyruvate sneaks into the mitochondria, it loses another carbon, becomes acetyl-CoA, and then we make energy out of it. When you're doing beta oxidation, you take a fat, fatty acid, you, you tack this fatty acyl-CoA thing onto it that I talked about that a lot in the last talk. You can go back and listen. And then that sneaks through the mitochondrial membrane. You go through beta oxidation. But you end up in the same place with acetyl-CoA. All roads lead to acetyl-CoA. I remember my favorite B vitamin, B5, acetyl-CoA, the CoA part, it's vitamin B5. So, if you don't have enough vitamin B5, this is not going to work very well, uh, at all.
Now, I'll just mention one other thing because this is kind of important in a minute with pyruvate. Here, we're measuring it. Pyruvate and pyruvic acid are the same thing. We're going about to see a couple of labs where we're measuring pyruvate. If pyruvate is high, what tends to happen then is the energy is not coming down into acetyl-CoA. That carbon chain is not coming to acetyl-CoA. So, this, the citric acid cycle is not working as well. If pyruvate is high, it implies that pyruvate is not going into the mitochondria. This is a mitochondrial problem. You're not getting the substrate from glucose broken down into pyruvate into the mitochondria. So, if pyruvate is high, it means it's not getting into the mitochondria. Everything below this line is the mitochondria. These are the mitochondrial membranes here and here. And if pyruvate builds up high enough, it starts to convert into lactic acid or lactate. And the reason why your body does that is because if you're generating a lot of pyruvate and you can't make it go down into here successfully, perhaps because you're exercising super hard and you can't get enough oxygen to make this work because this is all oxygen-dependent down here, then that pyruvate is going to convert over to lactate. And the only difference between pyruvate and lactate are lactic acid is a hydrogen. Your body takes a pyruvate, there's all this extra hydrogen floating around because you're starting to get acidic from all the exercise, and it attacks that hydrogen onto pyruvate and it turns it into lactate. And then the lactate, or otherwise known as lactic acid, starts to build up. And that can become problematic. If you're an athlete, high lactic acid, it's going to lead to muscle burning and eventually to muscle fatigue. You won't be able to run as far or lift as much weight once that lactic acid gets high enough up. You know, your body can't keep performing. And that is anaerobic metabolism. Pyruvate to lactate. It does get you a little bit of energy, remember. It gets you like around 2 ATP, which is enough if you have to sprint for a minute or two, but not enough if, you know, you're working in an office for 10 hours. Many of the patients that we have are not professional athletes, but their pyruvate and lactate are high, and they're going to get muscle pain and stiffness and all these signs of the acidity that you would get if you're an athlete that just worked out super high, except for they're not working out. They just have these enzymes that are not working properly. But anyways, the point is that the whole reason for this system is for us to make cellular energy. So, high insulin and low oxygen equals lactic acid high and pyruvate high. We get that. So, if there's a lot of oxygen, then you're going to go through the citric acid cycle and make energy. If there's not enough oxygen present, then lactic acid builds up because that's the anaerobic pathway. That's the pathway we use when there's not enough oxygen.
So, most of the time, people think about this like with an athlete. So, if an athlete is riding their bike in the Tour de France, or they're just riding up a big hill or whatever they're doing, they're breathing so hard because they need more oxygen to make the mitochondria work. And then eventually, you can't, you know, if you're sprinting, for example, there's no way you can get enough oxygen in your system to make this aerobic system work. So, you click over to this glycolytic system, you start to burn glucose into pyruvate into lactate. And if you've ever, you know, sprinted up a hill or run up a flight of stairs or five flights of stairs, you feel that burning. That's your body becoming more acidic because you're in anaerobic, you know, energy production. And that's fine if you're sprinting up some stairs once in a while. But if you're in, if these enzymes aren't working, you end up with the same mechanism kicking in: high pyruvate and high lactate. But it's not because you just worked out. It's because your body's screwed up. High levels of insulin are going to stimulate this process that I'm talking about, stimulates glycolysis that's messed up, that's going to make your pyruvate go up and make your lactate go up, not because you're worked out and you're like exercising and you're healthy, because your insulin is high. That's a big problem. Low tissue oxygen can contribute to lactate problems also. Why would that happen? Well, remember, if you're running up a flight of stairs super fast, eventually your tissues don't have enough oxygen to make all that energy. Even if you're breathing really hard, that's where lactate kicks in for an athlete. But if you're sick, like you have a viral infection, I don't know, nobody gets viruses, right? Nobody? Oh my gosh, can you believe like this whole planet just got this virus? That's unbelievable. Anyways, you get a viral infection that lowers your tissue oxygen. The same mechanisms kick in. You don't have enough oxygen, so you start to get these wonky things with your, with your blood sugar. And if you're already sort of metabolically damaged and you get a virus that reduces your oxygen levels, then you're in extra, extra bad trouble.
So, this is an image right out of Richard Lord's book. Carbohydrate metabolism deficiencies of B1, B3, chromium, lipoate. That's a fancy way of saying lipoic acid or CoQ10. So, the, the central, I'll just read this quote. "The operation of the central energy pathway of glycolysis, the breaking down of glucose, generates large dynamic pools of lactate and pyruvate." Love that. Uh, yeah, well, you could say a little bit more here too. Uh, yeah, that's all right. That's enough.
Now, here is your second quiz question for the day. What's that? It's big. It's complicated. I'll give it away. It's got three dimers. This is pyruvate dehydrogenase. That's the enzyme. That's what it looks like. The ribbony structure on the left. And then the other way they visualize these enzymes. Hundreds and hundreds of amino acids. There's a lot of ways this thing could be built wrong. If you get one amino acid out of sequence, it's not going to fold quite right. That's what we call a snip. And then that little docking station model that we just looked at doesn't work. So, if the actual enzyme is misfolded a little bit because of a snip, a single nucleotide polymorphism, some kind of genetic defect, not a life-altering defect, just a little snippy snip thing. There's a little snippy snip thing. Then this thing doesn't quite fold right. And then the B vitamin can't slot in quite, quite right. So, guess what? The regular amount of B vitamins that most people need will not be sufficient for some people to get this enzyme to work. So, there's a lot of genetic variance in what people need in terms of B vitamins. Again, this is, uh, looks like biochemistry, but it's not. This is like a supplement ad.
Okay, so pyruvate needs to get to acetyl-CoA. This is outside the mitochondria. This is inside the mitochondria. If this happens properly, your heart is in good shape. Your brain is in good shape. You won't have diabetes, atherosclerosis, high blood pressure. All these things won't happen. If this is not working properly, if pyruvate can't go here, then pyruvate goes in bad directions. You have a buildup of triglycerides, cholesterol, lactic acid, insulin resistance, all these bad things happen. And here's what, what separates the good from the bad here is this pyruvate dehydrogenase complex. That's the enzyme I just showed you on the previous page. And what makes that thing run? CoA. We already know what that is. That's B5. That's vitamin B5. NAD, niacin. Lipoate, that's a fancy name for lipoic acid. FAD, that's a fancy name for riboflavin. It's the B vitamins and lipoic acid that make this enzyme work. So, if this marker is high, pyruvic acid is high, it means this enzyme is not working. And how do you get it working again? B1, B3, B5, lipoic acid. Maybe toss in some chromium if you're in a good mood. Back to this list here. B1, B3, chromium, lipoic acid, and CoQ10. You can put that on the hit list too, if you want. You can put magnesium in there if you really would twist your own. There's the enzyme. If it's not working quite right, then you give the B vitamins to force that reaction to go forward properly. This is kind of like more of the same thing, biochemistry-wise. Here's another view of the same thing. The pyruvate dehydrogenase complex. B1, lipoic acid, B2, B3, B5. You got it.
Here's lactate dehydrogenase. I think that looks like a Christmas tree ornament or something. I don't know why they do it like that. But this is, this turns out to be super important. This is the lifestyle part that's important. So, here we have our glucose. If it goes to pyruvate and then to acetyl-CoA, then we're all good. You're breathing, the oxygen is making energy, I'm in water, and all that's good stuff happening. If that doesn't work because this enzyme, pyruvate dehydrogenase, is busted up, not working right, there's a block there, then lactate goes high. Okay? That happens if you exercise super hard and you become anaerobic. It can also happen if you have some kind of damage to this enzyme here. What are the major ways that these enzymes get damaged? Oxidative stress and environmental toxin exposure. In fact, someone who I trust implicitly, Joe Pisorino, Dr. Joseph Pisorino, one of the leaders of our field, if not the leader in our field right now. For those that don't know Pisorino, you should Google him later. You should get all his books. He's like, you've got to read all of his books. It's just kind of what you have to do. Um, so he's one of the thought leaders in our industry. And, uh, um, I mean, this is not a direct quote, but this is what he has said many times at talks I've been to, is that, uh, the, how can I say, I didn't want to say it in an offensive way, but that environmental toxin exposure is a more important variable for the advent of the increase in diabetes and then metabolic syndrome and all these problems that we're talking about tonight, then either diet or exercise. Environmental toxin exposure is more responsible for the obesity epidemic and the diabetes epidemic than diet or exercise. And that's a very, very strong and controversial statement to come from a scientist such as himself. And he has all the data to back that up. In other words, environmental toxins damage these enzymes, lactate dehydrogenase, pyruvate dehydrogenase, and then you, you can't burn blood sugar. In fact, you can't burn glucose effectively. So, it might not even be primarily a diet or exercise problem. It could be that these enzymes that we're talking about are being damaged from environmental toxin exposure.
Now, if you do end up with a problem with lactate and you, or pyruvate, and you start to fix it with chromium, lipoic acid, and the B vitamins, then you also want to accentuate this pathway and get the person to exercise properly so they can burn up their glucose. So, it's not just a matter of throwing the nutrients at them. You want to make a reason for the body to take that pyruvate into acetyl-CoA. You need to give the mitochondria a reason to make energy. And that basically is called exercise. Oh my gosh, that looks too complicated. I don't know. I pulled these slides out and I think, "Oh, this is so important. I gotta talk about this." It's just pyruvate going to lactate. So, just remember, pyruvate comes from glucose. You split that glucose molecule in half. It goes from six carbons to three carbons. Pyruvate is, to lactate, it's just taking a pyruvate and cramming a hydrogen on there. That's the only difference. You can see the little hydrogen here. See that? That's it. That's the only difference. And the key point is that if pyruvate is working properly, the mitochondria get the energy. If pyruvate is going high and it goes over to lactate, then you're in insulin resistance. All these bad things are happening. Lactate itself isn't bad. Lactate is just a pyruvate with a hydrogen on it. It's not trying to hurt anyone. In fact, lactate is a preferred fuel source for some places in the body, like your brain. Your brain loves lactate because it grabs the lactate and it's like, "Oh, well, this is cool. All I have to do is take the hydrogen off and guess what? I have pyruvate." That's what I want for energy anyways. So, lactate is a preferred fuel source for a lot of tissues. If you're exercising really hard, you're building up a ton of lactate. That lactate is going to go to other muscles. Let's say you're, I don't know, running up a hill. You know, the lactate can go to your arm muscles or something like that, not your legs, but your arm muscles, and be used as a fuel source. So, lactate is not bad. It has its role. But again, this is under anaerobic conditions that we're talking about. And the Cori cycle is the reuse of lactate. Just to show that we're not trying to vilify lactate here. Lactate can convert back into pyruvate and even back into glucose. That's what your body, that's what we call the Cori cycle. And then when I put this lactate and induces insulin resistance in skeletal muscle, too much lactate is where we get into trouble. You want to be able to disperse the lactate very effectively. High levels of insulin are going to stimulate glycolysis. The effects of, here we go, insulin influences acidosis by promoting glycolysis. The thing is, once the system gets jammed up, you have multiple, multiple problems. So, high lactate or pyruvate, you have to use the B vitamins, lipoic acid, chromium, CoQ10, and magnesium. You also want you to think a little more advanced in terms of thinking downstream. And I'll show you what I mean by that. If you're going to make more energy, then you also want to think about what's the ramification of making that energy. And I'll show you that when we look at the labs here in a moment.
All right, so I'm going to review a couple of labs and design a program or two, and then I'll open it up for questions, uh, that you guys can ask. And let's look at some labs. Oh, and before, for those of you that joined us late, we are doing a boot camp on this exact topic of the Nutrival. But we're going through the whole test tonight. We're just going through two markers. Going through the whole test. It's a pretty intense class. You get a discount of 20% off of it through Genova if you use this special code. It starts next week. If you really want to understand the broader implications of the Nutrival and be able to apply that in your practice, then that's really what this boot camp is for. All right, and I hope a bunch of you'll sign up for it. We have two or three spots available as of an hour ago. And let's see, let's pull up some labs.
So, now here's a Nutrival. Now, you could easily do a metabolomics also. Fine to do the metabolomics from Genova or the Nutrival. For the purposes of tonight, they're basically interchangeable. So, um, I'm going to skip down to the graphic images here where it gets more interesting. There we go. So, that should pop up on your screen. And let's just review what we're looking at here for a moment, and then we'll design some programs. So, last week's talk was about beta oxidation and fatty acids. If either of these markers, adipic acid or suberic acid, are high, means beta oxidation is not working very well. You got to fix that. Today's talk is about pyruvic acid and lactic acid. So, now, can you just see that enzyme sitting right here? And also, just to draw this, let me just draw this for you. My grandfather, Max Kalish, was a very famous artist in the 1920s and '30s. And I did not inherit any of his drawing or sculpting skills, which is sad because I can't draw anything. But I'm trying to draw a straight line there. That red line. Everything above it is the cytosol. Everything below is the mitochondria. So, beta oxidation happens in the mitochondria. Pyruvic acid enters the mitochondria and turns into acetyl-CoA, right? If pyruvic acid or lactic acid are high, it means your glucose or carbohydrate metabolism, carbo, it's, I like it when they name things for what they are. Carbo, or carbon hydrate, it's hydrated. It's got a water molecule crammed on it. Carbohydrates are glucose are not converting into energy well. If pyruvic acid or lactic acid, it's high, that implies the beginning of insulin resistance. And it implies, well, the beginning of all these things that we're talking about: metabolic syndrome, atherosclerosis, high triglycerides, high cholesterol, fatigue, depression, all these different things. It's the beginnings of that. There are obviously a ton of dietary things you can do. We're not talking about that at all. This is lab review. But obviously, you could eat your way out of this problem too. If you eat properly, you can change this with intermittent fasting and all that. Okay? So, then, well, I don't think we have to review any of that. We're not really talking about that. So, let's just look at the actual lab report here.
Now, this is not that hard. If you see adipic acid or suberic acid high, it's a beta oxidation problem. If you see pyruvic acid or lactic acid high, it's a glycolysis problem. And there we go. High lactic acid. High lactic acid. That is a problem. That's exactly what we've been talking about. It's complicated, but I'll just point out sometimes they're both high, pyruvic acid and lactic acid are both high. Sometimes it's just pyruvic acid, and sometimes it's just lactic acid. Probably don't have time to get into why, but you have to trust me on that. Sometimes one is high, sometimes both is high. In any case, it's a problem with glycolysis. Whatever combination of highs in this particular patient, we just have the lactic acid high.
Now, just for fun, let's look at the toxin markers and see what's going on there. Because remember, we said that Joseph Pisorino, the leader of our field, has declared through his intensive research, his team's research, his people working from, they look at those stuff, the number one reason why we're facing this obesity and diabetes epidemic is not diet. It's not exercise. It's environmental toxic exposure. Those environmental toxins damage your metabolism. There's a virus which many people have gotten recently called COVID, which is very well known for damaging your mitochondria. So, we had an environmental toxin crisis already with rates of diabetes and metabolic syndrome, all these problems skyrocketing. And then we just layered on to that, it would be like taking a rocket that.
was shooting up towards the moon and traveling pretty well and just stopping it for a minute and then putting on like a booster to make it go faster.
Covid's like a metabolic destruction booster on top of the environmental toxin thing. I mean, you can't even comprehend the level of problem that we're facing here. So pyroglutamic acid going high means that there's some kind of problem with detoxification pathways, and that's going to feed into and perhaps even cause your high lactic acid. Why? Because the environmental toxins that are indicated based on pyrolutamic acid being high, it's a glutathione indicator. Whoosh, they come over and they hit the enzymes and mess up the enzymes that are responsible for metabolism. These enzymes are damaged, they're oxidized, they're attacked, basically.
And then I don't know, we can look at some other markers on here and see. Probably don't have time to do that. I don't know. Do we not really? Okay. So let me just design a program so you can see how this actually plays out. Bingo. Here you go. So now the lactic acid marker was high, so we know that there's a problem with, remember, let me just let the nutrients B1, B2, B3, B5, lipoic acid, and CoQ10. So the B vitamins generally are covered with a B complex. Either giving one or two of those a day typically is enough. Lipoic acid, all the supplement companies have that. It's usually sold in like a 300 milligram tablet, so you want to give at least two of those a day. That's minimum 600 a day. It's low level, okay? More is okay. CoQ10 usually comes in like 100 milligram. It's expensive, I know, but you're worth it. You know, a couple hundred milligrams twice a day. And then you need some kind of a multi-pack or multivitamin. If you want to be a little extra fancy, depending on how much magnesium is in the multi-pack, you may want to use some magnesium glycinate or some other form of magnesium. You may have your favorite kind of magnesium, but try to get at least three or four hundred milligrams a day in total of magnesium for for these programs right now. Oh, and just for fun, we saw the pyroglutamic acid was high, so you would also give NAC. That'll come in a 900 milligram capsule and you could give that. So the NAC will bring up the glutathione levels to protect the mitochondria and the enzymes inside the cell. The B complex feeds, remember, it's the coenzyme. The B's are the coenzymes, they're what make those enzymes work. So if the markers are high, you give the B's. Lipoic acid, remember pyruvate dehydrogenase complex, it's required for that. CoQ10, we didn't really talk about, that's complicated. Magnesium is important for all of metabolism, and NAC is related to the glutathione. Okay, so that's a basic program. How long would you do it for? I don't know. Depends on how sick the person is, I guess. It could be like a six-month program. And then at the end of the six months, what do you do? Retest, retest, retest. And on the retest, you should see pyroglutamic acid dropping down, lactic acid dropping down. It should get better. That's the whole point of doing this. And then you can adjust the program based on the new lab.
All right, so now let's look at one more test here. Uh, here's your amino acids as well as your fatty acids. Oh, those are important too. There's so much to talk about. You know, when I was designing the boot camp, which you guys are all going to sign up for, right? When I was designing this boot camp, I mean, the hardest thing was cutting the PowerPoints down. There's so much information on this test. But the hard part, I think for clinicians, if you're new to this, new to this means your first 10 years of doing interpreting these labs. So new to me is with, you know, your first 10 years. If you're new to this, I think it helps to have a model or a structure that you can look at these kinds of tests with. So that you can, even before you understand every single marker on the test, you can still design super effective clinical programs. And where I see people get tripped up the most is they try to use too many supplements at the same time because they don't have a sense of a model of prioritization or sequencing. And then the dosages are just like whack-a-doodle. You know, someone will give like, I don't know, I see the stupidest things like, um, well, I don't know, like they'll give like 50 milligrams of CoQ10. You gotta start with 200, 400 is better. And it's not like 50 milligrams of CoQ10 is going to work if you just do it for a couple years. You have to get to a therapeutic level of these products so that you make these enzymes work properly. So if the enzyme's damaged and you need an X amount of B1, giving half of that is not going to make the enzyme work. It's never going to come together. You have to get the right dose, the clinically effective dose. And everybody in our industry is underdosing people now, and it just doesn't work. Frustrating, frustrating for all.
Here's another nutrival. Oh, no, sorry, this is a metabolomic. So you can't even tell. I didn't do that on purpose, but, um, they're almost identical. The nutrival involves a blood draw, the metabolomics doesn't. But for what we're testing for now, this is, um, exactly the same. And I'm all for the metabolomics and skipping the blood draw. If you guys don't want the hassle or the cost of a blood draw, do have metabolomics. If you can deal with the blood draw, your patients can deal with it, obviously, the nutrival is better, it's more information.
So now here's the next patient's. Look at pyruvic acid and we've got one or two more minutes of this and all these questions. Okay, pyruvic acid and lactic acid. Pyruvic acid is high, lactic acid is not. Remember in the last case, it was the opposite. It doesn't matter. One of them is high, both are high, doesn't matter because your body can convert pyruvic acid to lactic acid. They can go back and forth. If one of them is high or they're both high, it means there's a problem. So here, let's blow that up so you can see it. So now in this case, lactic acid normal, pyruvic acid high. So that pyruvate dehydrogenase enzyme isn't working well. So what do you have to do? Remember the PDC complex, you got to get here. You have to, in order to get the enzyme to work, that's the enzyme, that's what it looks like, it's big, it's complicated. In order to get it to work properly, you need to give this list of things right here: B5, niacin, lipoic acid, riboflavin, right? All these have to be in there to make this complex work. And not just a little bit, a therapeutic amount to make that enzyme work properly. Once it works properly, it's going to push that pyruvate over into the mitochondria where you make energy. Okay, so high pyruvic acid and let's see, uh, anything else stands out on here? Nothing really. So let's just look at that as a program. Oops, sorry, I hit the wrong button there. I should have hit that button. So now in this case, it's high pyruvic acid and the last one it was lactic acid. So in general, this is a little nitpicky. You don't need to use CoQ10 as much with this particular pattern. So you could probably take the CoQ10 out. Um, what else would change? That's about it, probably. Yeah, that's about it. Otherwise, oh, and there should be, um, in the multi-pack or the multivitamin, you should have something that has chromium in it. And the other blood sugar support products come assuming that it's a big assumption, chromium plus other blood sugar support that could be in the multi-pack or you could use a separate product for that.
All right, so let me just do a quick synopsis here about what we're trying to talk about. So the most important concept here is that you can look at the lab, you can figure out exactly what's wrong in terms of lactate or pyruvate, lactic acid, pyruvic acid. You can get the person on the right supplements. And then in order to stimulate these pathways, you want to get them exercising. And that depends on their level of fitness. So if they're really unfit, walking a half an hour a day, maybe like revelatory. If they're already reasonably fit, then you want them to do high intensity exercise. Why? Because when you get high intensity exercise, you become anaerobic. Anaerobic energy production kicks in, which is the glycolytic pathway. You want to work that pathway out so that becomes embedded in your physiology. You don't have to do the high intensity training more than twice a week. It doesn't have to be more than anywhere from a few minutes to maybe a half an hour. Usually people do intervals. It doesn't have to be very long. But once or twice a week of high intensity training will get that glycolytic pathway working properly. And you combine the supplements with that, then it really comes together. So exercise is really the key to making these programs work. But most of the patients that we work with don't have the energy to exercise in the beginning. So you have to do the labs, the supplements, and then get the lifestyle component kicked in. If you're doing the beta oxidation programs, we talked about that last class, then the exercise is more focused on zone two and working in mitochondrial efficiency and developing slow twitch muscle fibers. Glycolytic is fast twitch, zone two beta oxidation and slow twitch. And obviously we need them both in order to be super healthy. Okay, so I'm going to wrap it up there. If you guys want to stay on a little late, um, we can answer some questions. Otherwise, I hope to see some of you in this class coming up next week and have a good night.
All right, so question time. I'm going to get to as many of these as I can. I'm just giving Gerald credit for getting the heart question right. So did Cindy, which is good. A bunch of you got the heart. Carla got the heart question right. Now, that was pretty impressive. I didn't think anyone would get that right. John got it right too. All right, so let's see. Um, let's see. Oh, oh, for testing snips, um, there's a couple of different options. You have Pure Encapsulations has a very good, uh, program for that. You can check out Pure Encapsulations website. They have a good genetic screening tool there that's free if you're as a customer. There's, uh, yeah, I'm all for using genetic testing. You, you can layer that on top of what we're talking about here. A few more advanced. That's a really good thing. If pyruvic acid is high and lactic acid is not high, they remember they convert back and forth to one another. So, or maybe I didn't talk about that. So sometimes pyruvic acid will build up a lot and it won't be converting to lactic acid yet. Sometimes it'll convert to lactic acid and go back to pyruvate. So that can vary depending on which mechanisms are kicked in. Let's see. Um, what role does one's biochemistry play in tissue oxygenation? This is all about tissue oxygen. The, I can't say that about tissue oxygen levels. Everything that we're talking about tonight is impacted by tissue oxygen. So if your tissue oxygen drops at all, even a little bit, there's sensors in there, in there in your mitochondria, in the cells that tell, uh oh, this is not good. Oxygen is dropping. We're going to shut this ATP production thing through aerobic glycolysis down. You have to do that because imagine if you were low, if you were low in oxygen and you didn't shut down the citric acid cycle, guess what would happen? Really bad things because you'd have like part of the cycle running and generating all kinds of metabolites that would be dangerous for your body. Um, see, yeah, and so most of the companies that we work with have a metabolic combo product. I'm all for doing those. It'll have chromium, lipoic acid, maybe some biotin in it. So I'm all for using that depending on what company you guys prefer, you know. Uh, let's see. And the day before they do the test, I would not, I would have a person do their normal exercise routine. Um, but if they do CrossFit like once a week, I wouldn't have them do CrossFit like right before the test. So you probably want to, that might influence things a little bit. Uh, yeah, so you can use, but basically with any of these programs, the reality is you end up using some CoQ10, magnesium, carnitine. Uh, I'm forgetting probably one or two other things. There's, there's maybe four or five products that you end up using. I'm trying to keep it simple tonight, but for sure I would always use CoQ10, carnitine, magnesium as like a base for any of these mitochondrial support programs, but the dosing is going to vary depending on the labs. Let's see here. I'm thinking I'm going to run out of time now. So in terms of addressing the toxic and the toxicants, the toxins that cause problems, heavy metals, chemicals, you can test for all these different things. You can test the detox pathways. That becomes a big part of the correction. Lipoic acid is favored more with the lactic acid buildup, but in fact, it's used with both, but maybe the dosages would be a little higher with lactic acid. Uh, and in the boot camp, I'm going through each section of the test. It's a survey class. There's so many markers on there. It would take, well, I don't know, I could tell you probably two or three years to really cover each marker in detail. The idea of this boot camp is that it's a survey of the entire test so you can get started and apply it quickly. Okay. All right, I'm going to wrap up for now. We're at a time. Take care everyone. I hope to see you in another class soon. All right, bye for now.