Weight Loss Resistance: Lab Based Treatment Strategies

Hi, and welcome, welcome, welcome! I am Dr. Dan Kalish, and I am here today to talk to you about weight loss resistance and lab-based treatment strategies for all that good stuff. And so, um, today's webinar is born out of a decade or two of frustration with dealing with this problem in clinical practice and just like, what the heck is going on here? Trying to figure out how we can actually get a little deeper into these treatments. And I hope, uh, this is going to be super helpful for you and your practice.

So, we'll talk a little bit about, uh, what's going on at The Kalish Institute, a little bit about myself as an introduction, and then we'll jump right into the topic. And then towards the end of the class, I'll review a couple of example labs so you can see how this actually is applied in the real world with real lab tests. And then we'll have some time at the very end for questions.

Right, so I, I'm Dan Kalish. I am the founder of The Kalish Institute and I've done a lot of different work in the industry. About 10 or 12 years ago, we had a group of five doctors from the Mayo Clinic take my mentorship training program, which evolved into a research study that we did on adrenal and GI programs. I've worked with Dr. Richard Lord now for the last 10 years, who's the scientist that developed organic acids testing, amino acids, fatty acids, the GI Effects test. That was all out of his lab and his brain. And he and I have worked together really closely for a decade now, which is one of the great privileges of my career. Um, I'm, if I'm certified, I've been in practice for 30 years. I actually do this work still with patients, so I'm in the trenches. And most of my time is spent teaching, uh, practitioners how to do this work through the different classes that we have.

Speaking of which, we have a new class coming up I've never taught before. I'm very excited and I want to thank Genova for their partnership in all this work and tonight's webinar as well as in the upcoming boot camp that we're doing. So if you have the privilege of being a Genova practitioner, Genova client, you can get 20% off our next webinar. And I mean our next boot camp, which is starting May 11th. So again, this is a brand new course. I spent quite a few months putting this together for you guys. It's a very broad introduction to how to interpret the NutraVal. Today's class, we're just looking at two markers on this test. There's a lot of markers on this test. It's a, it's a beast of a test to really start to understand. So, um, this class, this boot camp is really to try to introduce you to the whole spectrum of the lab and and get a sense for how you can start to use it right away with patients and then the things that you may want to study in the future, too. So again, we've never taught this class before. It's starting May 11th. You get 20% off if you use this Genova Diagnostics code, discount code. And hope a bunch of you will join that class. I'm excited about it.

Okay, so now for tonight's talk. You know, the big, there's a couple of big picture themes that I would just hope you walk away with. One is what I like to call this "Labs to Lifestyle" thing, which is that we're going to identify a pathway for tonight. It's beta oxidation. We're going to see what the lab markers are that identify that that pathway has a problem. We're going to see how you can support that pathway with nutrients. But then the kicker, this is what makes it functional medicine, not just like lab interpretation medicine. Then you're going to activate that pathway with a lifestyle change. So I wanted to show you tonight the whole process for this one pathway because in the past, it's usually been taught by myself and most people in an isolated way. Like, you learn about the exercise thing somewhere, and you learn about carnitine somewhere. But I'd like to try to put that together.

And then the next concept that's probably equally important is that if you're going to open the floodgates of energy production by giving someone carnitine and riboflavin, a bunch of other B vitamins to fix beta oxidation, you better be prepared for the downstream effects of that on the other parts of the pathway. So you have to support the entire pathway as much as you clear up that one particular roadblock. That's super, super important because the roadblock in one place leads to an open space later, right? And if you're going to all of a sudden flood the system, uh, by fixing one thing, you have to anticipate what the effects are there. And I'll show you what I mean on all this when we get into the protocols. But I just want to present that as an idea. Stimulate the pathway with the supplements, kick that into gear with the lifestyle, and then that comes together in a way which is really unstoppable, and you will be getting results that you haven't seen before.

So for the specific pathway for today, we're going to talk about fat burning, a little bit about fat production in the human body, and learn about the biochemistry behind what is this, behind like the most important diseases of our time. Like the number one killer is still on the planet is heart disease. And if you can't burn fat well, you're gonna store it. And that's not a good thing for your heart, your cardiovascular system. If you are producing fat inappropriately, like making too much fat from carbon, eating too much carbohydrate, again, that's going to put you at risk for metabolic syndrome, heart disease, obesity, all kinds of problems that are really plaguing the planet right now. So this is a large issue. It's a little bit more than just somebody losing a few pounds or somebody wanting to slim down. This is, you know, kind of ground central for what's affecting human beings right now. And then you also get these other sort of run-of-the-mill complaints: fatigue, weight gain, poor sleep, that are going to be a result of a disturbed metabolism.

I like these diagrams that are like, you know, everything in one shot. So let's take a look at this one and try to figure out what the heck they're saying here. The center of lipid metabolism. And you can just Google this, the website will pop up. It's a really cute little website. Um, but here, acetyl-CoA is in the middle. And wouldn't you just like that to be there if you're a biochemist? That's kind of how biochemists think about this. Now, I just have to mention the CoA part of acetyl-CoA. The CoA part of acetyl-CoA, and this is going to come to be important in a minute. So try to remember this is what vitamin? I don't know. I'll ask it as a question. Does anybody know? Type in what, what is divided when they say CoA? What vitamin are they talking about? Anybody know? You should all know this one. There should be like 100 answers already here. Let's see if anyone got it right. Yes, okay. Thank you, Robert. B5. Okay. Uh, now that's going to become important in a minute. Again, I mean, it's important enough right here.

So we're going to look at how glucose turns into pyruvate and then potentially into lactate on its way to acetyl-CoA so you can make energy. And then we're primarily going to focus on fatty acids because that's the main fuel supply for the human body and how fatty acids are converted into acetyl-CoA. So if I look back at the last 30 years and I think, what is the one thing I should have learned like 29 years ago? It's what I'm talking about tonight, which is that fatty acids, when human beings are under, you know, under, when you're resting, you're not exercising, you didn't just eat a meal, but the majority of our lives, fatty acids are fueling 80 to 90% of our ATP needs. It's almost all fat that we're burning. So if this mechanism is not working well, there's some pretty stiff penalties to that, you know, in terms of how people feel. So again, acetyl-CoA, the CoA part is vitamin B5. We're talking about how fatty acids come in here, but we're also going to touch a little bit on how glucose converts into pyruvate. And there's test markers for all of this stuff that we're talking about. Every single pathway that we're talking about has a lab test that you can look at, a lab marker on the NutraVal or metabolomics test that Genova has. So you're not guessing about this. You're like, you have a pyruvate problem, you have a carnitine problem, you have an adipic acid problem. It's all on the labs. It just helps to see the biochemistry first. I think then the lab makes sense. It's like hard to learn it the other way around. Like I was taught this work looking at the lab and then reverse engineering the pathway. I'm trying to teach it the other way around. Learn the pathway and then the lab makes total sense. You're like, oh, I totally, that's whatever it's a lab report. I can see what that means because I understand the biochemical pathways. So I'm trying to reverse the way that this is taught.

Understandings, general understandings that you should be following. Beta oxidation is a mechanism by which we burn fat. It's also called fatty acid metabolism. Sometimes at rest, between meals, it's generating the bulk of our energy. The key nutrients here: carnitine, riboflavin, which is B2, pantothenic acid, which is B5, and niacin, which is B3. So all you need to remember really is carnitine and B vitamins because the B vitamins are generally given all together. Most people don't prescribe them separately. And that you can correct all this with a lab-based program. This is not like some mystical problem that people have.

So most fats in the body, most fat in the body is made by your liver, which is kind of strange. You would think it would come from your diet, but it doesn't. Your liver is making most of the fat. And if the human being eats too many simple carbs, too much sugar, too many refined grains, the liver is going to take those extra calories and convert them into fat. So that's why fat production makes a big difference here. What we want is for the body to take a modest amount of carbs and a modest amount of sugar and turn that into fuel and spend the most of its time burning fat, not storing fat. If you eat a lot of carbs, that's going to raise insulin and that's going to block the fat burning mechanism. If you eat too many carbs, you're also going to have excess of cholesterol. And all of these things can accumulate and end up causing problems.

So cholesterol is considered in general bad from a biochemical standpoint. There's actually websites out there. There's websites for everything. There's like pro-cholesterol websites that are written by biochemists who are like, "Hey, cholesterol is not bad." This is not vilified. Just because it can be dangerous at high levels, it's also like an absolutely essential component to making every single steroid hormone in your body. I mean, if you're against cholesterol, then you're effectively against testosterone, progesterone, estrogen, cortisol, and DHEA. Cholesterol is also absolutely essential for maintaining cell membrane integrity. And so it's when it goes too high that it's a problem. And that is what we're talking about now. How can you make that not happen? If we can burn fat instead of for storing fat, if we can keep glycolysis or the burning of glucose under control so we're not storing a bunch of fats, triglycerides stay moderate, cholesterol stays moderate, then we can use the glucose that we do have for energy and then support that primarily with the fatty acids that we're going to be talking about tonight.

Now, this is a strong component of this is exercise. And so when people want to lose weight with exercise, they tend to think that if they just do high-intensity exercise non-stop every day, they're going to start to burn fat. And that's absolutely not true. We'll go through some detail on that. Similarly, if they're eating too many carbs, they're not going to burn fat because they're going to be having this high insulin state. So the right kind of exercise, which is called Zone 2 exercise, is essential to get beta oxidation to work. So when you run these labs and you see somebody has a fat burning problem, if you get them on Zone 2 exercises and give them the right supplements, and that's going to come together as a package. If they're doing Zone 2 exercise to burn fat, but they don't have enough carnitine in their system, it's not going to work. And they're going to be telling you, "I don't know what's happening, Dr. Kalish. I'm on the treadmill every day." And I'm like, "Well, you're overdoing it." "No, I'm doing Zone 2. I'm not doing Zone 5. I'm doing the right kind of exercise, but I haven't lost a pound. In fact, I'm getting fatter every month." You need to have the shuttle to be able to burn fat in terms of nutrition and how all that works with carnitine and those pathways. And then you also need to do the Zone 2.

So the reverse is true also. If someone's just thinking they're going to take carnitine and they're going to lose weight without exercise, that's delusional. You got to bring these two things together. But if, in general, people don't, in general, people are looking at it from one perspective or the other. And my hope is that we can start to look at every pathway in the body as a dysfunctional pathway that has a nutritional basis and then a lifestyle change that can back that up.

Okay, so let's talk a little bit about lipids. Lipids are important for myelin, for cell membranes, for energy storage, steroid hormones, fatty acids. There's different kinds. We're going to primarily talk about palmitic today, although there's all these other fatty acids that you can study that are pretty interesting. We're going to talk a little bit about cell membranes, which are made up of phospholipids, phosphorus and lipids together. And then a little bit about cholesterol and triglycerides, but not too much. And as a group, the different roles of lipids include making carcinoids, dealing with membranes. All the membranes in your body are made up of fats, right? They help with, uh, acetylation of proteins. That's how proteins are able to work within the cell membranes. The fatty acids are important across the board for a lot of different things, but we're going to kind of hone in and just focus on the fat burning part. But just to say that this is not to minimize the importance of fats.

Okay, so here is the kicker slide. And, uh, let me just focus here for a sec. All right, so now take this in. Take a deep breath because this is where it gets kind of intense. So we're not going to worry about medium-chain fatty acids because they sneak right into the mitochondria. That's not complicated. In fact, there's no carrier because they're small. They just go, either they go right into the mitochondrial membrane. So here's our mitochondria and a membrane has an inner and outer membrane. There's two membranes. And medium-chain fatty acids just go right in. Where we have a problem is with what are called long-chain fatty acids. And why they call that? Because they're long. They're longer than the medium ones. They're short ones and there's long ones. So they're long. And because they're long, they're big. They can't get through the membrane by themselves. So you have your palmitic sitting out here, your fatty acid, and you need to take it into the mitochondria to make energy. But it can't get in. It can't just diffuse across the membrane because the membrane is made up of fat too, and it's too big of a fat to go through there. So which is probably a good thing. If you could, if, if palmitic or if the long-chain fatty acids could get into your mitochondria, it'd probably just be a total mess. I'm sure it would be. Just then your mitochondria will get fat, you know, it'll be bad. So our body keeps them out. And it, what does it do with them? It throws them over to cholesterol and triglycerides and it does other stuff with them. But at least it doesn't let them into the mitochondria except for one at a time. And how does that happen? Step one is your body takes that fat and it crams a carnitine molecule on it. And that carnitine molecule escorts the fat across the membrane where it can get broken up. That's the key. If you don't have the carnitine shuttle working well, then this won't happen. And then you've lost your fuel supply for 80 to 90% of your ATP. I mean, you could eat a bunch of medium-chain fatty acids. Good luck trying to live on that. That's not going to do it, right?

So here's what I like this slide because it's, this is, by the way, from the long-chain fatty acid disorder group. There's actually a long-chain fatty acid disorder group, believe it or not. You could just Google that and see these slides on your own if you want. But I like how they made this one black because this is the bad part. So carnitine can get blocked here. Beta oxidation can also be blocked over here. This enzyme, there's a bunch of different places that it can go wrong. We won't maybe get too into the details on that. It's kind of interesting, but it's probably not that important because then change what you're going to do. But this part is important here. So I want to dwell on this slide for a few minutes.

Okay, now, uh, first, let's get oriented here. Here's the cytosol. Here's the outer membrane of the mitochondria and the inner membrane of the mitochondria. And here's the inside of the mitochondria over here. Okay, so blue is cell. All the way on the right is inside the mitochondria. So the mission here is to get your palmitate or palmitic acid, by the way, you can measure palmitate or palmitic acid on these labs too. It's one of the fatty acids they measure. You got to get that, the main fatty acids, got to get way the heck over here so you can turn it into energy. And I can't just sneak across the membrane because it's too bloody long. And I'm just going to show you how big this thing really is. You see the palmitoyl-CoA? That's, oh, and there's our CoA again, by the way. Remember I said that was going to become important later? So this is your palmitic acid combined with a CoA. Look how big that sucker is. It's huge. That can't get across the membrane. But you see the palmitoyl carnitine? That is, that can get across. This is the whole problem. Your body has to take the palmitoyl-CoA, knock that CoA off, cram on a carnitine so we can get through the membrane. It's just a size problem. That's it.

So let's go back over to this one now. So now, once you understand the biochemistry here, it just makes so much sense. Here we have our palmitic acid or palmitate. It's now converted into palmitoyl-CoA. But your body's like, "Yeah, I don't think so, guys. It's too big." See that? It's too big. You cannot get across this membrane. No, no way. It's just too big. So palmitoyl carnitine is formed. You rip off the CoA, you cram on a carnitine, and that palmitoyl carnitine slips right through that membrane using that particular, uh, transfer enzyme thing. Goes right through this translocase protein. It's like a, like one of those, um, little shoots you see on like a water park or something. It goes into there and all of a sudden, yahoo! You got your car, you got your fatty acid into the inner part of the membrane. Now, what happens if I say, "Okay, well, that was a lot of work. I'm gonna get my carnitine back out." Carnitine goes back out to grab another fatty acid. And then here's our palmitoyl-CoA. You cram the CoA back on and then you start to make the fat. Do you see how complicated that is? I mean, it took me like two minutes to just explain that. So every one of these steps, something can happen. There can be a snip or an enzyme defect in any one of these steps, which is going to mess this thing up. Or you can just have a garden variety carnitine deficiency. Could be genetic, could be a nutritional problem that makes this mechanism not work. And now you can't burn fat. Any, any mistakes in this system, you can't burn fat. There's no like backup system. There's no other form of carnitine. It's either carnitine or not. And just think about the amount of work this involves. It's complex. And it's a lot of steps. And you have to bring a lot of fatty acids over here just to stand up and move around and breathe and live your day.

Okay, so that's the central problem. I've got other diagrams here. It's just the same thing but different viewpoints so you can get a visual on this in case that other diagram annoys you for some reason. Here's our long-chain fatty acid going into the mitochondria and then being broken down. Here's our medium-chain, goes straight in, doesn't need the carnitine. The long-chain needs the carnitine. And the short one doesn't. Then it's getting oxidized. And then here's again the same basic diagram, but I'll just show you how carnitine is recycled. So again, we have the cytosol here, the mitochondrial matrix there. We have our, see the carrier there? The carnitine is dragging the stuff here. Then it's coming back out and going back out. So as soon as you see in the back and forth and back and forth, you just use the carnitine over and over again. By the way, it's a random factoid, thought of the day: carnitine is made from the amino acid lysine. So you just keep that in the back of your mind somewhere.

Then eventually, if all this is going well, then we shovel the energy down towards, uh, the citric acid cycle and the electron transport chain. And then, you know, we've got energy happening. The problem, if I was going to complain about anything, the problem with this system is that it's highly susceptible to environmental toxin damage. Which is kind of a bummer because there's a lot of environmental toxins out there. And so if you read and listen to one of the leading naturopaths, really one of the leaders in our entire field since it was formed, Dr. Joe Pizzorno. If you don't know about Dr. Pizzorno's books and lectures and writings, you should look him up for sure. P-I-Z-Z-O-R-N-O. Joseph Pizzorno. He founded Bastyr University. I think of him as one of the top five or ten luminaries in our field since the day it was founded. So, you know, his current research focuses on environmental toxins and exposure and how that is affecting metabolism. And it shows that environmental toxin exposure, I have to say this slowly because it's kind of devastating. Environmental tox and exposure is more responsible for the obesity epidemic than diet, than poor diet and lack of exercise. He's got the research to back that up. Let me say that one more time. Environmental toxin exposure, damage to the mitochondria, damage to the mitochondria from chemicals and heavy metals is more responsible for the obesity epidemic than poor diet or lack of exercise. And that's a heavy statement. That's a risky and heavy statement to make in public. And he's got the research to back it up. So you can look up his stuff and and read and see if you agree with him or not. I do. Why do I agree with him? Because he's right. And he's got all the scientists, he's got teams of science people working on this for a long time to figure this out. So one of the reasons why this is happening is environmental toxin exposure. And so we'll do another webinar someday on how to get rid of the environmental toxins because that's an important part of repairing metabolism. But for today, we're just kind of focused in on, uh, the beta oxidation part. But just to give you a little context, there's also the role of environmental toxins in creating this big mess in the first place.

All right, so now I just have to mention this because it's one of those things that you learned in school and I learned in school, but then we just kind of forgot, which is that you make fat or fatty acids in your liver. The liver cells are making tons of fat. Mostly they're making it from carbohydrates, the dietary carbohydrates that are excessive. So if you eat carbs, you have a few extra carbs lying around from whatever meal you ate. Your body's gonna go, "Okay, what are we gonna do with this energy source? Well, it's excess energy. Well, we'll just turn it into fat." Then what are we going to do with it? Well, we don't need to burn it because we got plenty of fat already. Uh, I guess we'll just store it in the form of triglycerides or maybe we'll just make some cholesterol for kicks. So just to, it's not all about diet, right? It's not all about dietary fat. It's dietary carbohydrate plays a huge role in in what we're talking about because if you eat too many carbs, you're going to make fat in your liver. Number one, here's our palmitic. See that? It's kind of small. If you squint, you can see it. You're going to make fats in the liver. And then number two, the high insulin is going to block this whole mechanism that we're talking about. High insulin levels block. Remember those enzymes I just showed you over here? Let me go back to those. If you eat too many carbs, the high insulin output blocks these enzymes and this whole thing falls apart. It's messed up. This is like, it's like a bike chain with a bunch of links in it, and then something just comes in and goes, snip, and breaks it. And that's why people can get fat when they're eating too many carbs.

Okay, so now we'll look at some labs in a minute. And the markers for beta oxidation are adipic acid and suberic acid. And there's a couple of letters, but those are the two main ones. And then we're also going to look at some markers for glycolysis, which are pyruvate or pyruvic acid and lactate or lactic acid. So just keep those in the back of your mind. Those are the four that we want to look at. And, um, because this is all kind of related in a way. So when we start to look at the exercise component, like how can you get someone to exercise properly to stimulate beta oxidation, or how can you get someone to exercise in such a way that the person can burn fat more effectively? You want to train your mitochondria. If this was, if you're, if you're, you know, if this was like a university course, you'd want to say, "Okay, this is like a 10-week class: Mitochondria." And we're just going to focus on how you burn fat. We want you at the end of this class to be the best fat burners out there. That's the training. It's like an intensive training program. It's like a Green Beret boot camp kind of training program. How does that happen? The instant response would be to think, "Oh, well, if I just go and do CrossFit three times a day, and I work out high intensity on my bike and my rowing machine, and I just, the harder that I work, the more I'm gonna get my mitochondria." Unless that doesn't work like that. Bummer. It's Zone 2 exercise. It's Zone 2 exercise that heightens the mitochondria's ability to burn fat. And I'll show you what these zones are in a second. It's Zone 2 exercise that really matters. You need a little bit of high intensity, of course, and that's a good thing to stress your system. But the primary way that you burn fat is with Zone 2 exercise. There are slow-twitch muscle fibers that are developed with Zone 2. Zone 2 is like you're, you know, on an easy jog, you're on an easy bike ride, you're doing a swim, you're rowing, you're breathing hard, but you're breathing such that you could have a conversation or sing a line of a song. So you're not breathing so hard that you couldn't talk. You're out there saying, "Hey, how's it going on the bike?" You know, you could say that or you could sing a tune for a second. So if you can't sing a tune or you can't say, "Oh, hey, how's it going over there?" then you're not in Zone 2. You're going up to Zones 3, 4, or 5.

So Zone 2 exercise, it's moderate exercise. And there's fancy ways you can measure it more specifically. You can look that up if you want. But when you're doing Zone 2, one of the things that happens is that you develop slow-twitch muscle fibers, which makes sense. When you're doing high-intensity exercise, like always super hard CrossFit workout, or you're rowing as hard as you can, you're developing fast-twitch muscle fibers, appropriately named, right? Slow-twitch for your first lower activities, fast-twitch for your faster. The thing about slow-twitch muscle fibers is that they soak up lactic acid super fast. So if you train in Zone 2 a lot, when you do get to a high-intensity workout, those slow-twitch fibers that you spend most of the week developing soak up the lactic acid to make your high-intensity workout much more successful. So a lot of professional cyclists and marathon runners, people like that, are using this whole Zone 2, Zone 5 thing because it's a way to actually train yourself to be healthier, to be, you know, what you call it, a better athlete. For our purposes, we're not usually training athletes. We just want people to be healthy. So this would be the ultimate sort of longevity strategy or the ultimate strategy for your patients to have chronic fatigue type problems and such that you want to eventually be able to move them over from sitting on the couch all the time and barely being able to get up the stairs to be able to do Zone 2. So you're training their mitochondria as you're giving them the nutrients they need to run beta oxidation. That's super important.

So Zones 1, 2, 3, 4, 5. Most people just talk about Zone 2 and Zone 5. Zone 2, as I said, is the "I'm exercising hard, but I could still have a conversation." Zone 5 is you're pretty close to your max and you're breathing so hard you could speak. Right? And you can look at heart rate, and there's ways you can calculate this all by heart rate. But for our purposes right now, we are thinking slow-twitch developed by Zone 2, fast-twitch developed by much harder exercise. We want to develop slow-twitch muscle fibers that handle lactic acid really well. And we want to develop a little bit the fast-twitch. Generally, if it's a longevity sort of weight loss kind of program, three to five hours a week of Zone 2 and one or two sessions a week of Zone 5. That's the general recommendation. And the Zone 5 doesn't have to be very long. It can be just like anywhere from 10 to 12 minutes of high intensity. Some people say as much as 30 to 40 minutes with a warm-up.

And let's take a look here about how this works. This is a nice little graph. It's from this study right here, "Beyond the Calorie Paradigm." So I, I like this because it contrasts the two. As your exercise intensity gets greater, going to the right here, you can see the blue line, which is beta oxidation or they call it lipid oxidation, same thing. Beta oxidation decreases as your intensity of exercise goes up. So in other words, if you want to burn fat, you want to be in the less intense exercise point. As exercise intensity goes up, the amount of carbohydrate that you burn goes up. That's the red line. Okay? We're trying to burn fat, so we want to be in this low-intensity workout place. Except for maybe once a week, you can do high intensity because it's important to get that glycolytic system fired up and working really well. In my case, what do I do? I ride my bike. The place that I live, I can ride my bike up a really gradual hill for like an hour. That's my Zone 2. And then it's not very creative, I turn around and I come down. That's about my, that's my Zone 2 workout. But it's really steady. It goes up. And then when I get, you know, once or twice a week and I want to do high intensity, I have a rowing machine. I love the rowing machine. I can't do it very long. So I'll get on that thing and I'll do like, I'll try to hold it around a two-minute, if you guys have done any ERG stuff, that's kind of hard, at least for an old guy like me, hold the, you know, time to like two minutes, um, uh, you know, per 500 meters and then rest a little bit and then do another one of those and do intervals basically on the rowing machine. Um, and that's, that's it.

So now this is just kind of a nice little quote here. Glycolysis occurs in both aerobic and anaerobic states. So aerobic, the more intense you're getting with the exercise, the more anaerobic you're getting. The less oxygen that you're able, well, the more oxygen that you need, right? And it gets to the point where you can completely come out of aerobic, it can go into anaerobic states because you're making so much energy, you can't get the oxygen in and out of your lungs fast enough to make it work. So in aerobic conditions, pyruvate enters the citric acid cycle. We're going to look at that in a minute, and you get a net production of 32 ATP. In anaerobic conditions, pyruvate converts to lactate and you get two ATP. Okay, so with oxygen, 32 units of energy. Without oxygen, two units of energy. A lot of our chronic fatigue type patients, or people that are tired all the time, you're going to see on the labs, they have high pyruvate and high lactate. And they're running basically like a glycolytic system that's dysfunctional. Of course, they're tired. They're, you know, not able to burn fat. They're not able to burn carbs properly. And they're stuck in the same kind of physiology that an exercise person would be stuck in.

So I mentioned this already, the environmental toxin problem. Now there's something new that's come along. I don't know if you've heard. So, um, it was called COVID, or is called COVID. And it turned out that one of the commonalities in COVID was that, of course, it was this viral infection that maybe came in through the nasal passageways or through the lungs. But one of the things that happened to everyone with COVID was there a certain amount of vascular inflammation. Now, for a lot of people, it wasn't a big deal. They recovered, they were fine. But for around 20 million Americans, they estimate there's lingering symptoms of having had COVID that we call long-haul COVID. And one of the common things amongst all those people is that there's some level of vascular inflammation still. And that is similar to what we're talking about with cardiovascular disease because obviously with cardiovascular disease, you have this problem with lipids and with the inflammation in blood vessels leading to plaquing and the problems that you would associate with having a heart attack or having high blood pressure or those kinds of things. So we're seeing a whole another reason, in addition to diet, exercise, and environmental toxins, for people to have a damaged metabolism and damaged mitochondria, which is long-haul COVID. So these things are kind of all in the same rubric in a way. And so it's because the point of that is, it's, you just, it's going to be even more important to learn how to test and track mitochondria in the next five, ten years than it was before. I mean, it's pretty bad before. But the last study I read was, well, there's one study that came out a few years ago, 88% of Americans had a damaged metabolism or metabolic syndrome of some sort. Now it's like up to 93%. Almost everyone in the United States has this problem. And then you layer in the whole COVID response, it's just a bloody nightmare.

Okay, so this is one of my favorite scientists, Robert Naviaux. He's written a lot about the cell danger response. And this is one of his earlier papers from 2014 in the journal Mitochondrion. And what he calls the cell danger response is related to what we're talking about. So when your body is attacked, and it could be anything. It could be like, you don't like your mother-in-law and you're really stressed out because she's visiting. It could be because you, um, have an environmental toxin exposure. It could be because you have a gut infection. It could be because you have a vaccine reaction. It could be because you had COVID. Any of these things, there's a universal response that cells go through. And as soon as there's an affront, I think the easiest way to think about it is with a virus getting in. So as soon as a virus gets into the cell, but again, this is a universal response. It could be an emotional stress, it could be environmental toxin, it could be any of these things. So there's a big enough stress that the cell perceives. The mitochondria do a couple of things that seem a little wacky. Number one, the mitochondria start to generate inflammatory fatty acids. Your mitochondria start to generate inflammatory fatty acids and they cram these fatty acids into the membrane. The next thing the mitochondria do is they take all that oxygen that they were using to make energy and they make reactive oxygen species. They start to create oxidative stress. So this is a way of your cell protecting itself by trying to destroy whatever got in or to destroy itself so other cells don't get bothered by the problem. The net net of all this is that the mitochondria are on the ropes and they're not performing their normal functions. And all the things that we're talking about now kind of come into play, especially because membranes are starting to get damaged. And again, this is from Naviaux's work, the cell danger response. And I'll just go through the first part of this because it's relevant.

So here we have containment and innate immunity. So here's the, the new information. This is the bad thing, right? Stress, injury, toxin, infection, heavy metal, some kind of pollutant turns on the cell danger response. Your body cranks up this ATP. It shoves the ATP out. ATP starts to work as a signaling molecule instead of making energy with it. Your body spews it out. It's kind of cool. And so all your other cells are looking around going, "Holy moly, what's happening to Matt over there?" You know, Matt is a made-up cell I just made up. And you're like, "Oh, I don't know. Matt's spewing out ATP. He must be in trouble." Okay, so not a good thing. Obviously, people are getting tired when this is happening. Their cell loss, there's all these things going on. And this is part of your, your immune response. And it's also, this is the thing is, the cell danger response is the same response to, it could be that you got stabbed with a pitchfork or something. You're still going to have the same kind of response. And what we're worried about is when people don't go through the rest of the cell danger response, they don't repair, they don't get their system, their system back on track. And we're going to see that on these labs.

Okay, so again, some conceptual framework here. We're going to look at a few markers in one second. I just want to set up for the last part here, which is that insulin resistance changes the way that we deal with fats. I already mentioned that. And here I want to show you this one pathway and then we're going to look at labs. So here's our glucose converting into pyruvate. And a condition where there's a lot of oxygen and a lot of relaxation, a lot of happiness in your life, and you're in Tuscany and you're sitting at a picnic table and you're eating a good meal and your family's around you and everything's good, then that pyruvate goes into the mitochondria and we make energy out of it. In a not so good situation, if there's not enough oxygen present, there's some other kind of stressor, one of these enzymes is not working right, that pyruvate is going to go over to lactate or lactic acid. And you're going to see high lactic acid. Now, if you're healthy and you have good muscle tissue, remember the slow-twitch muscle fibers, they're going to soak up that lactic acid. If you're not healthy and you don't have a lot of muscle tissue, you're going to have high lactate. You can potentially also have high pyruvate. And what you don't have is glucose or energy going into the citric acid cycle. That's a really big problem. And frequently, this enzyme here, pyruvate dehydrogenase, can be dysfunctional too. So again, that causes the same thing. There's a block right here. Now, when we look at labs, this is going to be super important. And I'll show you why.

Oh, and before I get there, for those of you that are late, you are excused for being late. And I couldn't see you sneak in the room. And for those of you that have already left, I can't see you sneak out of the room. It's kind of one of the advantages of being on a webinar. I know when I go to conferences, I either sit in the very front because I want to be engaged and listen and I want to like raise my hand and stuff, or I sit in the very back because I'm thinking I might want to get up and stretch and get a glass of water or go to the bathroom. But anyways, for today, if you're late, we have a new class coming up. I've never taught before. I'm pretty excited about it. I put a lot of time into this. It's a general overview of Genova's NutraVal test. General overview, including mostly about the organic acids, but also a little bit about amino acids and fatty acids too. Starting on May 11th. If you're a Genova client, you get a 20% discount. And I want to thank Genova profusely. They're a wonderful group to work with. We love them over there and want to support the lab as much as possible. They're really one of the foundational labs in our industry. They've been around as long as I've been around, and I've been doing this 30 years. They've been around probably a little bit longer than me. And so anyways, great company, a real institution in our industry. And starting to focus more on teaching you all how to wrap your minds around these labs conceptually. But this class is also about actionable protocols you can use right away. I was in practice for over 20 years. Then I met Richard Lord. I've had 10 years of working with Richard intensively on each one of these markers, drilling me. I mean, like he'll drill me on him literally, like, "What does this one do? What does that one do? Do you know about this?" And this is like an intensive area of study for me for decades. And I want you guys, even with this first class on the NutraVal, to have access to protocols that are clinically effective, even before you understand everything in the world about benzoic acid and its relation to hippuric acid and how your liver worries about it, all that kind of stuff. So that's the goal of this course is to get you clinically competent at a, I don't want to say superficial, but at an introductory level, even if you're brand new to this, I want to get you able to interpret these labs and be able to do programs, design programs that are going to make a difference for patients, right?

Okay, so let's take a look at some labs. All right, uh, and, you know, I'm totally biased. If you say, ask me, you know, which lab is the best for organic acids, because I'm, my mentor and teacher for a decade is Richard Lord, and he's like, I mean, he's like more than a father to me. I don't know what he is to me. He's like a very important figure in my life. Um, and, you know, uh, so I'm a very strong proponent of this particular test. There are other good tests out there, uh, but this is the one that I'm really endorsing for you guys. And let's see, here's our test, NutraVal. This is a NutraVal. Yeah, you can also order the metabolomics. That's a, um, similar to a NutraVal, but there's no blood draw. It's a little less expensive. So Genova has a metabolomics or a NutraVal. Either one is fine. They're not exactly interchangeable, but if you're in the very beginning of doing this, metabolomics is fine. It's a little cheaper, so it's a little easier to get your patients to do it. Uh, and let me just show you one of these reports too. I didn't pull up samples for this class purposes, but let me just show you what one looks like so you can see the name of it, everything. And most of the students in the, my mentorship class now are doing metabolomics.

I think it's a good place to start if you really are gung-ho. The neutral valve is fine. I don't know, do you want a BMW 3 Series or a 7 Series? You know what I mean? It's like they're both nice cars. So this isn't, you know, easier to do a little less expensive metabolomics and you'll see it's very similar. Many of the markers are similar for everything that we're talking about today. These two tests would be interchangeable. So either metabolomics or, um, sorry, hit the wrong button there. Metabolomics or Neutrival. I just happen to pull up neutral valves here. So what I'm trying to do is get us beyond this summary page. So let's not even look at it. Let's just go into the weeds here where you can really start to learn how this stuff works.

So now here is a very good summary of everything that we just talked about. And let me look at this for a moment. And then the cool thing about this is that you can see the lab markers at the same time. Okay, so that should be on your screen in a pretty clear way. So number one, we talked about beta oxidation a lot. That's the burning of fats. Adipic acid and subaric acid, those are the markers. If either one of those is high, it means beta oxidation isn't working very well. Either of these markers high means beta oxidation is not working very well. Then you can give carnitine, B vitamins, and magnesium. Now, B vitamins and magnesium are required for everything on this page. Carbohydrate metabolism, B vitamins and magnesium. Citric acid cycle, B vitamins, the magnesium. Okay, so you need that's generic across all these. All and you can see in the fine print here, B vitamins, these are B vitamins all down in here. So any one of these markers off in this page, give them a B complex and magnesium. One B complex a day, a strong one. Magnesium 200 milligrams twice a day, plus a multivitamin. And then whatever individual nutrient you want. In the case of what we're talking about today, you're going to want to load them up on carnitine. Therapeutic doses. It's therapeutic dosages of carnitine start at around 2,000 milligrams. 500 milligrams isn't going to do anything. If you're going to use carnitine, use it, you know, 2,000 to 3,000, maybe 2,500 somewhere in that range. It causes diarrhea if you give too much too quickly. So just taper the person onto it. Maybe give them a thousand milligrams for three or four days and then bump it up to two thousand. But don't just give them like a 500 milligram pillow because it's just going to waste everybody's time.

So now let's try to go outward a little bit here. I hope you guys are not watching on your phone because you probably can't see this because I'm making it kind of small. But here, tink tink tink, we're going to give our carnitine because these markers, here's our pyruvic acid and lactic acid. Now, along with our carnitine, we're going to recommend Zone 2 exercise because that's when you force the mitochondria to burn fat. Why would you want to give somebody a ton of carnitine and then have them do glycolytic exercise where they're burning carbs? This doesn't make any sense. If you want the mitochondria to work better doing beta oxidation, make it do beta oxidation. It's like if you want to learn how to play the piano, you should practice the piano. If you're trying to learn how to play the piano and you're practicing drums, that's not going to help your piano playing very much. I'm not against drumming, but if you want to do piano, do piano. So do the exercise to meet the problem, and then you'll have this synergistic effect. It's quite profound.

Now here's the citric acid cycle, which we're really not talking about now except for something I mentioned in the very beginning. And there's, you got to put your thinking caps on for one second here. Okay, so let's say your patient has high adipic acid and sebaric acid, and you give them carnitine. Now, all of a sudden, beta oxidation is working, and you're doing three hours a week of Zone 2 exercise. So it's really starting to go well. What's going to happen next? Acetyl COA is going to go up. What's going to happen next? It's going to feed into the citric acid cycle. What's going to happen to all these enzymes here? They're all going to start to work really hard. Imagine if you had like a flood or like a dam. Let's say you had a river and it had a big dam, and then you opened up the dam like it was a World War II movie or something and they bombed the dam, you know? Now all the water is pouring out. Everything downstream is going to get activated. So all of this stuff's going to start to work a lot harder. So you got to anticipate that where the program's not going to work. So you give the carnitine. How much? Start with a thousand, go up to 2,000 a day, spread out, you know, like 1,000 in the morning, 1,000 at night, something like that. Um, and then, and then be sure to give him a combination product that has a little bit of everything you need for these lower pathways. So magnesium, B complex, and carnitine. And then every one of the companies, the professional brands, will have a mitochondrial product. It'll be mitochondrial boost or mitochondrial oomph or mitochondrial whatever, and it's going to have a whole list of all the stuff you need for all these other enzymes to work properly. So just make sure you cover that. You could also potentially cover these downstream effects just with the B complex, magnesium. You'd have to add in some CoQ10. So either use a comp, either use a, what do you call it, combination product or, uh, here, let me show you here. I'll show you the different ways to do it. So B complex and just give that with breakfast. If they don't eat breakfast, just give it with a large meal. And then we want magnesium. I usually use a glycinate form, but there's other kinds of magnesium. That's not the only kind. Uh, say it's 100 milligram capsule. It's very typical. Two in the morning, two later. Then you're getting your L-Carnitine. Don't use the acetyl carnitine stuff. That's for the brain. That's a different purpose. So you got a 500 milligram. So you're doing two there, two there. Now you could use a Mido combo product that's kind of easier, or you could just add in some CoQ10 if you wanted and a multi, you know? So you have a couple of different options there. I think it's easier to use a mitochondrial combination products because they have a little bit of everything that the mitochondria need.

So now let's look at the markers themselves. Here we go. Cellular energy and mitochondrial markers. Couldn't be more clear than that. Adipic acid is at a 6.2. Subaric acid is at a 1.8. The reference range here is around a two. So this one's quite high. Sebaric acid should be well, the high end of the reference range is 2.1. 1.8 gets you into the yellow zone, which is still a problem, but, you know, it could be worse, I guess. Now we look at pyruvic acid and lactic acid, and they're both normal. So this person has normal glycolysis or normal carbohydrate metabolism. We're forgetting about these for now. These are Ketone body things. We're going to, we're ignoring these for now. Sorry, just pretend that those are their. So that, uh, sorry, I should have done that before. So pyruvic acid, lactic acid are normal. So we're not going to mess with that so much. Really, we're going to work with beta oxidation.

Okay, let's look at another one. Nutrival or metabolomics, either one will work. We're skipping the summary page because we're being more sophisticated than that. We're not against the summary page, but we're like, I think we could do better than that. Oh, so now we see adipic acid is high and pyruvic acid is off. So let's scoot down here and see. So now we have some potential problems with carb metabolism, but a primary problem again with, uh, with the part with carotene. And let's look here. It's another example. I'm sorry, I'm scooting the wrong way here. Pyruvic acid, lactic acid, adipic acid, suparic acid. They're all heading in the low, low ranges. And let me find you one more here. Well, I'll just make one up. Let's just pretend, okay, because it's a, uh, I'm gonna have to hunt down another example. But let's just pretend for a moment, use your imagination. Let's pretend that pyruvate and lactate are high here because you're going to see that frequently. Pyruvate and lactate are high. And let's say a subaric acid is high too. Let's make them all four high. How about they're all four high? It was going to see that a lot. All four of these markers are high because I just want to be able to design a program for you that has that example. So now we know that with the beta oxidation markers being high, we're going to use carnitine. How much? 500 milligrams. Start with it once a day, bring it up to twice a day. So 2,000 total. We're going to always use magnesium glycinate or some other form for every one of these metabolic patterns. We're always going to use B complex. You can use individual B vitamins, but that's unnecessary. I was going to say unnecessarily complicated, but that's not funny because B complex complicated ways. That's not even a funny joke. When I, when I make jokes like that, my kids, they look at me and they, at least they acknowledge I made a joke. They'll say, that wasn't even funny, and they won't laugh, but only, okay, it wasn't very funny.

So then, um, let's see. Then a combo product is to be easy. Combo Mido product. Think of that as like a Mida mitochondrial multivitamin. Every company will have one of those depending on your favorite brand. And then we had high pyruvate and high lactate in our example. So guess what? You gotta add lipoic acid. This is like the secret sauce. Sometimes it's called alpha lipoic acid. Usually it comes in a 300 milligram. You can get it a little stronger. And so for glycolysis, you need B vitamins plus lipoic acid. And then you also need CoQ10. You can see there's overlap with these programs. So this would be a program for someone with a problem with both beta oxidation and glycolysis. You add the lipoic acid, and you're kind of forced to add the CoQ10 because you need the CoQ10 for the glycolysis part also. And in fact, a lot of this stuff is actually right here. I'll show you in the, in the parentheses. They show you these things, you know? Let me blow this up so you can see it better. You can see the mg for magnesium, B2 for riboflavin, lipo weight for lipoic acid. So they got a lot of clues throughout here. Down here, you'll see CoQ10, um, depending on the pathways here. Okay, so that indicates that. And then in other parts of the test, I just want to show you other parts of the lab for a moment here, and then we'll, I'll go to questions right after that. Okay, um, there's B vitamin markers, which is relevant to what we're talking about. So that's an important section to look at also. Then, oh, and some future time, we'll talk about toxins because one of the major reasons why you would have damage to the mitochondria, damage to your carnitine shuttle, would be because of environmental toxin exposure. So you want to look at that detox section and fix that. In other words, your liver needs to burn the fat. If your liver is full of environmental toxins, no fat burning is going to happen. You have to clear the environmental toxins out so the liver can burn fat. Your liver will not want to burn fat when there's a lot of environmental toxins in storage because we store the environmental toxins in fat. And if you burn the fat, you would get really sick. So your body holds on to fat when there's environmental toxins present. You got to get the toxins out, then you can burn the fat. So just keep that in mind. If what I'm talking about today doesn't work very well, that's probably what's going on. And then glutathione, very important antioxidant. It's one of the major ways that we protect our mitochondria. So that's directly relevant. And oh my gosh, let's not get into the amino acids because that's too complicated. But let me just show you how I would beef out the program. So based on what we just saw, we would also give glutathione. 100 milligrams of liposomal glutathione two times a day. That's going to protect the mitochondria, get those glutathione levels back up. The person also had this environmental toxicity problem. So I would additionally give NAC and glycine to clear out the toxins. And those would be, I don't know, let's be conservative, 1,500 milligrams of each daily. And then you need some kind of binding agent if you're going to clear out environmental toxins. That could be any kind of fiber or something like that. So with an expanded program now, we've got carnitine, magnesium, and B complex and the combo product for beta oxidation. We've got the additional lipoic acid and CoQ10 for glycolysis. And then this particular lab had low glutathione. We're using glutathione to protect the mitochondria. They had environmental toxin markers were up. So we're using NAC and glycine to clear those toxins out. And then some kind of a binding agent. So that's a more complete program. I give you an idea how you can expand this. So then this would be, I would call this, uh, a six month, what would you call it? How would we call it? Metabolic repair program. I just made that up. You could call it whatever you want. Metabolic repair. That sounds good though. Or you could call it like fat burning stimulating program. Fat burning fix. That sounds like a book. I like that. But that is a bookstore. A fat burning fix. Whatever you want to be more glib about it. And then with [Music] um, liver detox support and, uh, support or the most important nutrient in the body, glutathione. Spelled wrong. So I just want you to get a cl, see how you can take a single lab and start to expand out with the program. And this is still doable. I don't think this would be overwhelming for somebody. It's not that many pills. You know, I think most people could handle that. And you can get the NAC and glycine in a liquid. I mean, sorry, in a powder. The glutathione comes in a liquid. So you're not really in the, the fiber is obviously in a powder. So really, you're only talking about one, two, three, four, five, six, six or seven pills in the morning, six or seven pills at night, and some, and a drink. You know, I think that's doable for most people.

All right, so now we're right at time. Let me just mention that we have a boot camp coming up on the neutral valve or metabolomics. It's the same test essentially at its core. Starting May 11th. You get a 20% discount if you use this code from Genova. And again, I want to thank Genova for helping us put this conference on right now today, our webinar on today. And I'm gonna stop the official lecture and go to questions. So if you need to run, pick up your kids at school or something, you can take off. Okay, and let's go for questions. So, uh, there are contraindications for recommending carnitine. One of them is thyroid medications. You got to look that stuff up. I'm assuming you guys are responsible. You gotta look that up. Um, and Gordana and Robert got the B5 question right. I'm just saying that giving them credit after the fact here. So, um, Catherine's asking about companies in general. I like Quicksilver as a company. I think they're really good. I trust their brand in general. Uh, I'm not interested in prescriptions for weight loss. I think that's, you know, I'm, yeah, I'm against that. I think there's better things that we could do here. Uh, I think we already talked about dosages. We got that covered. So intermittent fasting throws you into a state of beta oxidation, doesn't it? Now, as you said that earlier, if you've just eaten a meal or if you're exercising really hard, you're going to be burning glucose of some kind. But if you haven't, the longer that you haven't eaten, the more your body goes to fat burning. So intermittent fasting is a way of stimulating mitochondrial repair and beta oxidation. And if you exercise while you're fasted, that's even better. However, this is a big however. You got to earn that. A lot of the patients that we work with in the mentorship program, a lot of people in my class, on my practice, not just my practice, but the doctors I work with every week, those patients can't handle intermittent fasting because they've got major blood sugar problems. They've got major adrenal or thyroid or mitochondrial problems, and they're just not healthy enough yet to do intermittent fasting. So there's a lot of patients that are going to crash if you do intermittent fasting too early. That's what I'm trying to say. But once a person is reasonably healthy, intermittent fasting can be a really great thing. Um, so phospholipids, there's some special phospholipid products that you can use. Each company will have one. So whatever favorite brand you have, I don't think that they're that different, to be honest. Um, yeah, there are some issues with carnitine and TMAO. In that case, I think people use the acetyl carnitine that I said don't use. So there's a way around that problem. You can look that up. I think that was Joseph that asked that question. I'm pretty sure you can use acetyl-l-carnitine. It's quite a bit more expensive, but I think it gets you around that TMAO problem. Let's see, uh, see, I was just getting the questions right here. I'm gonna over a little bit over time. I'm gonna have to stop in one second. I think if I'm out of time here. Okay, anyways, great questions. I'm sorry I couldn't get to all of them. I hope you guys join us for a future one of these. And I hope a bunch of you sign up for, um, this lab interpretation boot camp. With this particular class, you'll be able to submit your own labs. We'll review them in class, as well as having a pretty extensive curriculum to go over. So hopefully that's going to help you all. Okay, take care, everyone.