Transcription
function, and I'm super excited to be talking about this. The first time I've actually given this particular talk, and I have a lot of things that I want to throw at you all.
So for those of you that are new to the Chaos Institute, I am heavily involved in IFM. I was for the past two or three years at all the IFM events and may have met some of you there doing their practice implementation program. We took a break from that this year. A few years ago, back in '16, 2016, I worked with Mayo Clinic doing a bunch of research on adrenal and GI programs. Right now, the last four years, I've been working very closely with Richard Lord, who, those of you that are in the older range, over 50, let's say, know Richard as one of the really the founding scientists for our field and the creator of organic acids testing. You know, had his hand in amino acids and fatty acid testing, was very involved in all this work early on. And, um, we're going to talk about his work interpreted through me today. I've been in practice for a long time, still have an active phone practice that I work on quite a bit, and then I teach a lot. And we have a couple of things coming up that are directly sort of derivatives of what we're talking about today. So if this is interesting to you after tonight's talk, then you may be interested in signing up for either our Lab Interpretation Boot Camp on Amino Acids and Vitamins, which is a very deep dive into that subject that we're going to skim over today, or our Genomics Boot Camp, which is coming up in June.
Okay, and these are all new materials. I've been working on these for about four years now. I'm pretty excited. Both of them are eight-week intensives getting into how to interpret labs. It's all about labs, labs, labs, enzymes, enzymes, enzymes, how to do protocols, how to really design things properly. And we're going to talk a little bit about these bigger subjects today, okay? So you get an introduction to what we're trying to go for.
And so I want to figure out how can you key in, based on labs, on the ideal metabolic pathways that you want to correct? And how can you really understand, from a biochemical standpoint, what these pathways are all about? Okay? And once you see the pathways and you understand the science behind it, then the prescribing and the treatment part just comes naturally. Also, I have found that if you really understand the pathways, when things go bad and patients react in ways you can't understand initially, you'll be able to assess it through by understanding the dynamics of the supplements and how you're changing things.
And you also want to be able to explain the value of these tests to new patients. Every single new patient that you're working with should be running a neutral valve or an organic acid test. Just that should be, I don't know, it's like buying a bicycle that has wheels on it. You know, you would you buy a bicycle without wheels? Probably not, because it would just like lie on the floor and you can't even roll it around, right? Let alone ride it. So seeing a patient without a neutral valve to me would be like buying a bicycle without wheels. Like, I just wouldn't even think about it. Like you wouldn't, like it's never been done before. You would never, ever in a million years see a bike shop that would sell a bike without wheels on it. Like, have to buy the wheel separate if you feel like you can afford them or something. Like, if you want to ride it. No. So, like a neutral valve is an essential workup for every single patient that we see, not just for certain special people.
And once you understand the basics of what we're talking about, the B vitamins, the carbohydrate metabolism markers, CoQ10, how magnesium works, how oxygen works, we're going to cover today as well, then, you know, you should have some enthusiasm about, you know, making sure everyone does these tests. So we want to keep it simple and have an overview of why B vitamins are important, what they actually do in carbohydrate metabolism, and then for the citric acid cycle and energy production in those pathways. The three things that you just want to memorize and just know when someone says mitochondria, you should just think CoQ10, magnesium, and oxygen. So I say mitochondria, you think CoQ10, magnesium, and oxygen. Like mitochondrial problems, I'm tired all the time, I can't lose weight. CoQ10, magnesium, and oxygen. And be able to look at the labs and understand which, or or all, of those things the person may need.
And then as the biggest picture understanding, and if you're in a rush tonight, you've got something else to do, or you want to watch like a good TV show on Netflix or something, you could basically just read this slide, kind of extra carefully, and then slink away. If you leave your computer running, I won't even know that you left a conference and just go do something else for a little while, okay? The key point here is that amino acids have two roles. And this is just something you want to just take a few minutes to take to just sort of begin to wrap your mind around, because this is one of these big picture concepts that's so big and so important that it's easy to miss. Okay? It's so big and so important that it's easy to miss. It's so big and so important that people don't talk about it, like, ever. All right? So I'm going to talk about it now.
In the very first part of this talk, ready for this? So amino acids have several, many, many roles, but let's just boil it down to two. They have a role in protein synthesis, which proteins, all proteins in the human body require the same 20 amino acids in roughly the same percentages. Insulin, hemoglobin, every antibody, collagen. Collagen is the big exception, collagen is this whole weird thing. But besides collagen, all the proteins in the human body require the same amino acids in roughly the same percentages. If you're missing one of those 20 amino acids, you cannot assemble proteins. Which proteins? All proteins except for collagen require the exact same ratios of the same amino acids. Okay? Why are the proteins so different? Why is insulin different than hemoglobin, different than an immunoglobulin? Because of the way that your DNA strings together the amino acids into these different sequences. The enzymes that we're going to focus on tonight, and there's a whole bunch of them that have complicated but interesting names like pyruvate dehydrogenase, lactate dehydrogenase, my favorite, succinate dehydrogenase, which is part of complex two, part of the electron transport chain. Those are enzymes. Those are made from amino acids. They are proteins. So now, that's the most important role of amino acids.
Secondarily to that, secondary to that, there's the non-protein functions of amino acids. This is how we usually think about amino acids. It's just based on their non-protein functions. Okay? Which is not that important, right? I mean, it's pretty important, but not that important. When the body has a choice, it's going to prioritize the production of proteins over the production of these non-protein functions. What would be the most classic non-protein function? Should be something like tryptophan to make serotonin. Can you live with low serotonin levels? Yeah, you're going to live for a long time, you're just going to be depressed. Can you live not making proteins? No, you can't. Okay? So the non-protein functions of amino acids get all the attention and all the focus and all the excitement in our industry. And yet, the protein functions of amino acids are far more important. And if you understand that, then you realize that the enzymes that we're talking about tonight are proteins, then you can put this together. You're like, wait a minute, you mean that you can't run your metabolism without these enzymes, and these enzymes are made from amino acids, which are forming into proteins? That is the gist of the whole talk. And in order to get that enzyme that's been created from amino acids to work properly again, you need to use B vitamins, which is the second part of the talk. And we're going to talk a little bit about protein folding and misfolding and how all this actually works.
Once again, three keys for energy production. The three kind of must-haves, right, are magnesium, CoQ10, and oxygen. In order to make any of these things work, you have to have those three present. Okay? Magnesium is involved in every aspect of ATP production, including that final connection with ATP to make the ATP come alive and biologically active. You have to have magnesium, right? And for the electrons to do their thing in the electron transport chain, you got to have CoQ10. I'll show you some pictures about that. And then obviously, oxygen's critical. In order to just emphasize how critical oxygen is, I like to do a short little thing, which you guys can please participate in, which is you take a deep breath. Then everybody do this. You just stand up, take a deep breath in, and blow it all the way out, and hold your breath out. And see how long you can hold your breath out for. If you're not feeling very comfortable, you're starting to think about how important oxygen actually is, right? And you can breathe again. All right? So now, if you don't have oxygen, you're not going to make it for very long. Oxygen getting to the mitochondria to make all this energy production stuff work is mission critical. So CoQ10, magnesium, and oxygen, we want to investigate those and the relationship between the B vitamins. Once this all starts to crystallize in your mind, then you're going to have it made, right?
Now, in order to demonstrate this, I maybe is the word, I'm going to just show you a whole bunch of images, all right? A whole bunch of different images. And the hope here is that one of these will kind of click, you know, and make sense for you, and that'll be a good thing. All right? So let me just see here. Hang on a second. Yeah, my computer is acting so wiggy, but you guys can see the slides, right? No, you can't see the slides. Hang on a second. How is that? Yeah, you can. Okay, good. So all right, ready? This is again, like a big picture concept that may take you months or years to really fully wrap your mind around. It's certainly taken me like 27, 28 years to wrap my mind around. When we're under stress and we're catabolic, by definition, what's happening is we're depleting amino acids and we're depleting B vitamins. That's what catabolic or stress physiology is. So if these amino acid levels are dropping and or these B vitamin levels are dropping, how does that impact what the body does? That's the big question.
And so to address that, you have to think through the other aspects of basic care, right? What's the underlying cause of the problem? We're not even really talking about that today necessarily. What's the physiological damage going on? What are the symptoms a patient has? What are the GI problems and associated hormone issues, right? And there's this bigger picture when you're setting up treatment programs where you're looking at everything from their spiritual life and emotional life and their history of abuse to their catabolic physiology to how well their liver is working to the fact that they're depressed and constipated. So there's this spectrum of things that we're doing. But I think that the more that you can understand these physiological mechanisms, the more that you can pull together successful patient programs. So you understand the pain that the patient's feeling, right? You talk to and figure out what's the gain for them? What do they want to change? Maybe they don't want to change some things that are painful to them, but maybe there's some others that they want to do. You got to figure that out. Then ultimately, what are their life goals? What are they even on this planet for? And why are they seeing you? And what's their big picture? Okay? And then figuring out treatment options and treatment sequences. We're talking about a narrow area today. We just want to emphasize that there's, you know, other things that we're doing also in the background with these more complete programs.
So the, the mechanism of action here in the mitochondria is that we take all this fuel or energy from our food, we crank it through these various cycles, and we end up generating ATP in the process of doing that. A lot of free radicals are generated as well. The more energy that you make, the more free radicals that you make. So this is kind of a balance going on there. And then again, ultimately, we use fats, carbohydrates, and amino acids or proteins to put them into this citric acid cycle and end up at the end of the day with a huge amount of ATP. Now, the very interesting thing about this is that you can measure each one of these steps with great precision and know exactly what part of what pathway is not working. You can measure these markers here to see if fatty acids are being turned into fuel properly or not. You can measure pyruvate and lactate quite precisely to see if carbohydrates or glucose is getting converted into acetyl-CoA for energy or not. You can measure citrate, succinate, fumarate, and these things really, really matter a lot for a patient who's tired, gained weight, their brain isn't working quite well, et cetera, et cetera. And it's all in the effort to produce our ATP down here. You see the CoQ10 again, okay? So I'm going to keep showing different angles of the same process here so you can start to conceptualize this more clearly.
And what we're doing then with our patients is figuring out where this process is broken and how we're going to repair it. And I'm telling you, if you learn how to do this well, you can fix all kinds of crazy neuropathies. We've had in the last few months of my training program, the mentorship program alone, we've had doctors correcting problems from seizures to depression to kids who have major developmental problems. If you really get into the mechanisms of action of all these different enzymes, you can do some pretty amazing work that most people can't do because they haven't really learned how to interpret the labs, right?
So now, one of the things that we want to focus on, because this is a common problem, is when you see elevations on the test of either lactate or pyruvate. And there's a bunch of enzymes in there that really matter. And if lactate and pyruvate are being produced properly, then the pathways go right down to acetyl-CoA, you can see that, and then entering into the citric acid cycle, energy is made. So if there's a backup and there's high lactate or high pyruvate, you've got a major problem with the ability to get glucose broken down and crammed into the mitochondria where you can start to turn it into energy. And if lactic acid is building up or pyruvate is building up, the person's going to become very unhealthy. Their brain is not going to do well. The excess of lactic acid, the excess of pyruvate causes some major health problems. It's very important that there's a flow that goes through here and that glycolysis is working properly, allowing citric acid cycle functions to work, and then ultimately the electron transport chain to work, okay? And there's potential snags in all of these potential areas, all these areas here. So let's look at this, and it really matters where the break is. So there can be a problem up here with lactate or pyruvate, right off the bat. They can't make energy from glucose. Clearly, that's a problem right there. There can be a problem right here with the citric acid cycle itself, or there can be a problem in the electron transport chain. And these are all treated in very, very different ways. And if you can specify, and we had a patient this morning in class, oh man, what was the, oh, it was a neuropathy. It was maybe even the doctor is on this call, I don't know. Was one of the students in the mentorship? Patient's main complaint was a neuropathy. The main problem was with one of the B vitamins, right? And like, for example, thiamine deficiencies are going to cause problems up here. And if these chemicals like lactate and pyruvate build up, you're going to have neurological problems for sure. That's what happens. And so if you look at your patient and you see these neuropathies and you look up what does, you know, thiamine deficiencies cause, or what does high lactic acid cause, or high pyruvate cause, you'll be like, whoa, those are the same problems. And all I need to do is give them thiamine and riboflavin, and they get better.
Again, another view of the same thing, right? We're taking glucose and pulling it into these energy-releasing pathways so we can make these nutrients. So let's take a moment and just take a, you know, like a celebratory moment here for B vitamins. And I have like a personal problem with how we treat B vitamins as an industry, okay? Is that first of all, they're either called coenzymes or cofactors, and that just enrages me. So you think about like, if you get on an airplane and you walk on the plane, you know, we used to fly all the time. I used to fly like 20 times a year for seminars back in the pre-COVID days. So you get on the plane and you know, there's always a couple people milling about at the very front of the plane, and they have hats and white shirts on, and sometimes like some little tie or something, and they're pilots. And there's one, quote, there's one pilot, and then there's always one co-pilot. And you're really thinking, like, who's the main pilot here? Who's the pilot that matters? Like, if the co-pilot has a heart attack, are you going to be worried? You know, a little bit, but not really that worried. If the pilot has a heart attack, are you going to be thinking, yeah, that could be a problem. Because that co-pilot is probably not as good, or, you know, there would be a pilot, you know. Not so. Just using the term cofactor or coenzyme immediately degrades the B vitamins down. Think about like a co-star in a movie, it's the same thing, right? They're not the star, they're the co-star. So our, this matters, right? Because in our psychological framework, we use these terms and we denigrate the B vitamins. They seem like they're not that important, which is why it flips people out when they give a high therapeutic dose of thiamine and they watch neuropathies go away in someone that's been sick for 25 years. Like, yeah, well, it's not just a cofactor, it's a factor. It's a, it's a major constituent. It's a part of the enzyme. The enzymes that we're going to look at, okay?
So think of it this way. There's the enzyme, which is made out of protein, and I'll show you the amino acid sequences in a minute. And then there's the cofactors or coenzymes, which in the, for our example today, are the B vitamins. The enzyme cannot work without the vitamin. It's completely just going to sit there and do nothing, okay? Or almost nothing. You can also have cofactors that are minerals, but we're talking about vitamins for now. So think about the B vitamin as the non-protein portion of the enzyme. It's not the co-pilot, it's like you have two pilots. Okay? The B vitamins are as important as the enzymes themselves in order for this whole thing to work. They're part of the same package. And then you will realize that one of the most powerful tools that you have clinically are B vitamins. I'm telling you, thiamine, riboflavin, niacin, pantothenic acid, folate, B12. It doesn't get more powerful than that.
When my teacher Richard Lord was quizzing me, and every, we work together twice a week, you know, and he likes to quiz me. I don't know why he's an old man, but he just likes to get me going, you know? So, and he always, he often asks me impossible questions that he knows I don't know the answer to. And so this happened like six months ago, and he's like, "Okay, Dan." And you gotta imagine this elderly gentleman with a very, very, you know, deep voice with a Georgia accent, which I won't try to imitate, but he's like, "Okay, Dan, what is the one nutrient that would eliminate human life immediately, the most urgently, the most quickly, the most dramatically, if it was absent?" I'm thinking, oh man, that's a hard question. I'm thinking, I don't know. What do you think? Glutathione? Or I don't know, B12? I don't know. Maybe, who knows? My tryptophan? I really didn't know the answer. And then he just let me stew over it for a while. And then he then he expanded the question. He's like, "Not just human life, all life on this planet, except for maybe a few bacteria." All life. B1. Okay? If you don't have B1, all life would just cease immediately. Okay? Not just human life, but animal life and other life. Okay? These are very, very important nutrients. They're not peripheral, they're central to this whole system working.
And I think there's no B vitamin lobby. The B vitamins aren't very expensive. They're not very sexy. You don't really see B vitamin conferences. You don't hear, like, you know, some supplement companies say, "Oh, this is the year of the B vitamin, and we're going to focus on marketing B vitamins this year." All right? They just don't. Because there's no money in it. Because they cost like 10 or 20 bucks for a bottle. And I mean, there haven't been a lot of new B vitamins lately, right? So it's not very interesting, honestly, to our industry. But it's really, really important for clinicians because you learn how to use these, you can change people's lives really quickly.
So typically, again, I'm against this. We think of the B vitamins as like these coenzymes, and there's an enzyme, and then it fits in there, and then everything happens. But forget about that. We're going to look in a minute at what really happens. So to understand some of these markers, it helps to see where things are coming from. So they're these alpha-ketos that we measure. When these markers go high, it indicates B vitamins are low because these B vitamins are used in certain metabolic processes to do with amino acids, okay? So high markers generally on these tests mean that there's B vitamin levels are low. In the citric acid cycle itself, or Krebs cycle, you have B5 that gets it started. If you don't have B5, you can't make acetyl-CoA. So right off the bat, everything's over. So B5, super important. You need B3 for a certain step. B1 and 2 and 3 for that step. We're going to talk a lot about B2 as an example in a few minutes, okay? And a little bit about B3. So these B, and then B12 is in there as well. So you need these, uh, you need these vitamins at certain key points in order to make this cycle work. And here's another example of it, but that's kind of complicated. Let's get that one. Let's look at this.
So this is how, now remember, we're talking about there's two aspects here. There's the enzyme, which is an amino acid string that's put together and folded up into a protein. And then there's a B vitamin that interacts with that enzyme called the coenzyme. But we don't really like that term, but we have to use it because that's what they call it. And these two come together. There's the protein portion of the enzyme, the non-protein portion of the enzyme, the B vitamin. They come together to make things happen. So how does the protein portion of it work? Well, if you remember back in school, your body takes amino acids and strings them together like beads on a necklace or something. And then those amino acids, depending on their sequence or order, start to fold up into these things called alpha-helices and beta-sheets. And then based on charges that each of these amino acid side groups have and how basically arranging themselves in space, right? They make this tertiary structure. And then finally, they make the final structure, which is the actual protein itself. All this is dependent on the amino acids being present and being in the right order.
Now, here's your first quiz question for the day. What do they call it? What do they call it when one of these amino acids is out of sequence? What's that called? Does anyone know? You can type in the answer, and I'll give you maybe 10 seconds to ponder that. What's it called when one of the amino acids is out of order or you're missing one? Anybody know? Yeah, it's a SNP. Thank you, Carrie. It's a SNP. That's what a SNP is. So what happens when an amino acid, one amino acid is out of sequence? The thing doesn't fold right. It's a structural problem because now everything's going to be a little bit off. Everything's going to be a little bit off because that amino acid is out of sequence. So now when you look at these kinds of structures, like here's one of the enzymes that we're talking about, pyruvate dehydrogenase. There's a lot of amino acids in there. There's hundreds and hundreds and hundreds of amino acids strung together, curling around each other to form this beautiful shape. Both of these images are of pyruvate dehydrogenase. One is sort of, you know, literal with the ribbons going, and the other is a little more pictorial, okay? But the same exact enzyme here depicted two different ways. You can imagine how likely it would be that there would be an amino acid that was out of order that would make this thing a little bit off.
And if you're thinking about how much do we use these enzymes? This is hard to believe, but I just read this like a week ago, I'm pretty sure it's true. One cortical neuron, one brain cell, one single brain cell in your cortex at rest. I love these scientists, they're like very specific. Single cortical neuron at rest. So it wasn't a sick person, it wasn't a stressed person, it was just a normal, probably college student or something, at rest. Generates one cell in the brain generates 4.7 billion with a B, billion units of ATP every hour. No, every second. Every one second. So one brain cell that's just sitting there, not really doing anything, creates 4.7 billion units of ATP every second. So think about the throughput on these enzymes. They're good, they're making a lot of stuff, right? Oh, there's a, it's not like, you know, they're grabbing one little thing and an hour later they grab another thing. No, there's like billions and billions of these reactions happening per second per cell. So if that enzyme's a little bit off, it's not going to work right. And do you think that's pretty common? Absolutely, yes.
So when, when Richard Lord was in graduate school, this is in the late 1960s. My teacher Richard was like, packed up his bags, left Georgia. I think he was the first person in his family to go to college. Wentz going to graduate school at the University, University of Texas in Austin. And he got into really what was at the time, the world's premier nutritional program, working under, many of you probably know his name, a biochemist named Roger Williams. And Williams, can you imagine Richard Lord at 25 or something like that? It's kind of hard to imagine him being a kid. But anyways, this Georgia boy shows up. And Williams is literally discovering B vitamins, like he's finding pantothenic acid. This was like the heyday of metabolic understanding, right? Scientists discovering these nutrients and these enzymes that we're looking at today. And so Richard, back in those days, thought, well, you know, it's interesting, yet there's so much genetic variation in between these enzymes. Maybe there's a way that we could someday test for this. And that's what organic acids testing is. It's an attempt to understand, are these enzymes working properly or not? If pyruvate dehydrogenase enzyme is not working, what do you think happens? Pyruvate's gonna build up. It's gonna go high, right? And if you see high pyruvate on the test, there's something wrong with this enzyme. It may be that the B vitamins are insufficient. It may be that the enzyme's not folded right. It may be that the person's eating a horrible diet, they don't have the B vitamins. Doesn't have to be a genetic issue, right? It could be that they're an athlete and they're just burning through so much ATP that the enzymes just like burned out and it's not working great, okay? So every time you see a high marker, you got to look and see, okay, what is the enzyme that's causing that? And why is it a genetic issue? Is it a protein folding problem? Is it a B vitamin issue? Is it a genetic issue? Is it a dietary issue? What's driving that potential, potential problem? And if you can figure that stuff out, you can solve cases left and right that might be sort of mystifying to you now.
So here's a breakdown of pyruvate itself. So you see pyruvate is in the cytosol, it's the, you know, outside part of the cell, and then it's going into the mitochondria. You see the yellowy part, that's the mitochondria. It's literally going, being transported into the mitochondria where then it's turned into acetyl-CoA and then it goes into the citric acid cycle, okay? That's the mechanism that we're looking at here. And here's another enzyme. Remember we talked about pyruvate and lactate? Lactate dehydrogenase. Look at that. Way that is a big complicated enzyme with hundreds and hundreds and hundreds, I don't know, I think it's like 1200 or 1500, something amino acids. Hundreds of them strung together in order to make this enzyme. How many amino acids do you need? You need all 20. If you're missing one, will it work? No. In order to make this enzyme, how many amino acids do you need? You got to have all 20. If you're missing one, will it work? No. So you could have a problem with a SNP, whether or not, whether your body has decided to go on strike a little bit and not assemble these amino acids properly, in which case it's misfolded and it doesn't work that great. Or you could be missing a single amino acid and it's not going to fold properly either. If you're low in glycine or something, it's not going to work, okay? Remember, so now you see the power of a single amino acid. So like, for example, tryptophan, it's really important to make serotonin. But remember, depressed people are still alive. If you can't make lactate dehydrogenase or you can't make pyruvate dehydrogenase, you're not going to be alive. You're not going to live the rest of that minute. You'd be dead, okay? So your body prioritizes this a little bit. But if you're low in tryptophan, the ability to fold these, to fold these proteins properly is going to be compromised, and you're going to have an enzyme that doesn't work that great.
Now, if you're into the biochemical pathways, again, we're talking about the same thing over and over because I just want to just reinforce it, and maybe one of these slides will click for you, you know, and I never know what slide might click for what person's brain. But again, uh, let me grab my little thing here. Here we go. So now we have glucose going to pyruvate. If there's enough oxygen, then it goes down this way, which is a good thing. If there's not a lot of oxygen, then it can go this way and lactate goes up, which can be good or bad depending on if you're exercising or you have chronic fatigue, you know? So if, again, lactate is high, it means this lactate dehydrogenase enzyme is not working. If pyruvate is high, it means pyruvate dehydrogenase as an enzyme is not working. So right off the bat, if either these problems is going on, the person is, you know, just completely screwed right away. It doesn't matter what's happening with CoQ10 because right off the bat, you're not, it's not working right. And to make matters worse, if pyruvate builds up or lactate builds up, they cause their own problems just because their levels get high, and it makes people a little wonky with their nervous system, okay? So we just looked at lactate dehydrogenase. Remember, it's made up of amino acids that have to be properly folded. We just looked at pyruvate dehydrogenase, very complex structures, a lot of things can go wrong with these. So it shouldn't surprise you if you take some time later today to Google lactate dehydrogenase genetic issues, you will see that lactic acid urease, where there's a lactic acid buildup, are some of the more common genetic issues that are known to science. In young children, they can be very bad, right, life-threatening. And so of course, we diagnose and treat kids the day they're born if they have these genetic issues. However, you can have an adult-onset, very mild version of a defective lactate, lactate dehydrogenase enzyme, and not learn about it until you're 47 and you collapse when you're trying to do a marathon and you realize that, you know, your body's just not working like it used to. And you go see some functional medicine doctor and they run a test and they see that your lactate is like super high. Like, wow, this looks really high. I think you have a problem with B vitamins and with this enzyme. We're going to fix that, okay? Thiamine. And then we're going to talk for a moment in a moment too about acetyl-CoA and the citric acid cycle. Not going to forget about that. Mitochondrial complex II. Mitochondrial complex II.
Before we get to that, I'm going to give you a short commercial break. For those of you that joined late, first of all, we have a Lab Interpretation Boot Camp coming up in a couple of weeks, April 12th. First time I've taught this. It is a massive extension of what we're talking about tonight, but it's eight weeks long. There's tons of material. It's Richard Lord giving a whole series of incredibly complicated lectures, and there's me giving a whole series of incredibly simple lectures to try to really get you to understand how to prescribe amino acids and vitamins in a clinically effective way. We're giving a 20% discount for Genova folks, whom you all are. And if you enter a GD21, you get 20% off. And it's around a thousand bucks or something, $1200 if you get the discount. I think it's $1500 as a regular price. So it's a little bit over a thousand bucks. And then we have a June 1st Boot Camp on Functional Genomics, which is getting into the most commonly observed SNPs that we see and how you can start to do combinations or integrations of a SNP test and a functional medicine test and realize, wow, maybe they've got a methylation defect, and I can see that on both sides, and now I'm going to fix that as well. Again, 20% off this Genova discount, GD21. If you guys want to join us for those classes, um, you can do one or both. We're kind of independent depending on what you're listening, what you're most interested in, okay? And those are coming up, and those are based on the last four years of my work with Richard Lord. Pretty excited about them. All right, back to our regularly scheduled programming.
So mitochondrial complex II is really, really important. You know, I have to get my glasses on to even read this slide. I don't know how I got to be 56 years old, but but here I'm going to read it out because you guys can't probably read either, right? "Dysfunction of succinate dehydrogenase leads to accumulation of succinate, which is categorized as an oncometabolite and signaling molecule. It is a major player in mitochondrial reactive oxygen species generation and contributes to ROS either directly or indirectly. Genetic mutations as well as epigenetic regulation of the complex genes are associated with several pathological conditions." That's bad, right? Similarly, both metabolic and epigenetic malfunctions have emerged as the underlying molecular mechanisms of the pathologies. So you can read a lot about this. I think it's really interesting. Complex II, in various aspects of cell biology, is the crossroads of oxidative phosphorylation and the TCA cycle. So let's look at it. There's a bunch of science people saying that this is super important. Complex II, succinate dehydrogenase, is an enzyme. So right away, what do you know? Those ribbons that you're looking at are amino acids strung together. If there's an amino acid missing, because I don't know, because a person has a bad diet, or because the DNA didn't assemble it properly, then the protein might be a little misfolded, in which case it's not going to work really well, not going to work perfectly. If there's not enough B vitamins, B vitamins in this case, it's riboflavin, then that's the coenzyme, right? But it's essential for the enzyme to work. So again, look at the structure and kind of memorize what that looks like. You can see the little ribbony things at the bottom and the fluffy little thing at the top. There's a reason why those little ribbony things are there. And that's another quiz question for you. Like, how long are those little ribbony things? How long are they? Just long enough to fit into the inner mitochondrial membrane. This is the same molecule, okay? So remember, little ribbony things that we saw about 10 seconds ago? Look at them. They're just long enough to fit into the inner mitochondrial membrane. That's them right there, okay? How cool is that? This enzyme just went into the membrane. This is all fatty acids here, you know, and then here's your succinate, which we can measure. Here's your fumarate, which we can measure. In order for succinate to move over to fumarate, you have to have a B vitamin present. Which B vitamin? B2. If B2 is not there, none of this works. None of this works, not even a little bit, okay? And I'm just going to zoom in on this image so you can see a close-up of B2. Um, so remember how complicated this enzyme is? We saw this is individual amino acids strung together in ways that are, you know, hard to even imagine. I'm going to zoom in now so you can see the B vitamin. You see the B vitamin there? Now, is it starting to show up? Okay, see the FADH2? That's the B vitamin. So you imagine if this protein is misfolded, that B vitamin's not going to slot in quite properly, and then it's not going to work. So what, what do you need to do to fix that? Get on it with the amino acids and fix that part of it, if it's necessary. You can't fix the SNP, obviously. But then you can give the person B vitamins in a higher amount so the enzyme starts to work properly. And that's what we're doing therapeutically with these labs, okay?
Again, here's the actual enzyme. Here it is, embedded in the membrane. And here's another view of the exact same thing. Pyruvate dehydrogenase. Oh, sorry, that's the wrong one. That's the wrong slide. Sorry. Here it is again. The electron transport chain now, okay? It's the same enzyme, complex II. They call it. It's part of the electron transport chain. I know we all learned this in school. I know we all forgot this. Like, who, you know, you don't just walk around thinking about stuff like this day to day. But here's our succinate, which we can measure. Here's our fumarate, which we can measure. If succinate is going high, it means this enzyme is not working. Why is that matter? Because it's part of complex II, which is chugging along these electrons until they finally get dumped over here, you know, with the ATP production thing happening, okay? So if this enzyme doesn't have enough B2, it's not going to work. You're not going to make energy. You also need, importantly, as we said, think about the mitochondria. Think CoQ10 and magnesium and oxygen, right? So it's not just the B vitamins. CoQ10 and magnesium and oxygen are required. Magnesium, arguably the most important, because it's involved in every step of energy production. CoQ10, pretty darn important, because it's involved at the end there. And here's another image of CoQ10, okay? Again, with the same complex, same exact thing. But we don't have the fancy little enzyme picture. Now you can see the riboflavin there churning away. These are the things we're measuring: succinate, fumarate, malate, citrate. That's what organic acid testing is. Pyruvate at the top there. And then at the end, you can see oxygen, right? The final electron acceptor in the electron transport chain. So anyway, this is a, this slide is like, CoQ10 is important too, okay? That's that point of that slide. Sorry, forgot to say that. And the point of this slide is you don't even want to think about how important magnesium is, because you would just lose your mind. In fact, very good friend of mine, when I was first starting in practice, a medical doctor named Dr. Jay Cohen, he was a wonderful man. He's really kind to me. It was literally my first month in practice. And Jay came in, he's a medical doctor, he became my patient. What's this guy doing here? And he had this horrible painful condition of his legs, polymyalgia rheumatica or something like that. And anyways, we, he kind of, he kind of adopted me. I don't know what was going on there. But he was quite a bit older, he's probably like 40 years older than me. He's just really a nice old guy. And I was like, interesting guy. Anyways, he ended up devoting the second part of his career to studying magnesium full-time, okay? That's like the full-time job. So we just have one slide on this. This is a slide like, okay, science people spend a long time why magnesium is important because it's involved in every step. It's involved in so many things, like we don't even have enough time to talk about why magnesium is important. So I put this slide up as a reminder to just talk about it. But like, you know, really, you could be a full-time researcher and just barely scratch the surface of why magnesium matters. So you have to just trust me on that. So CoQ10, magnesium, and then the third and final one that we're talking about on a nutrient level is oxygen.
So how does oxygen get around? Well, oxygen gets around with on hemoglobin. That's how the whole thing works. And so what is hemoglobin made of? Well, heme is made of porphyrins. This is a porphyrin ring. How do we make porphyrins? We use glycine. Interesting, right? So your body takes glycine, assembles porphyrins, and then that's the basis of heme. And here's what the pathway looks like. You can look this up, it's kind of interesting. Basically, it's glycine going to heme is what we're talking about here. And then this is what it looks like when hemoglobin all folds itself together with the heme part and the globin part, right? And then the oxygen part and all that. There's also myoglobin, which is important for oxygen delivery as well, right? Is transporting oxygen? Is stored on my, oxygen. Myoglobin is storing it. And then here's what the heme molecule actually looks like, kind of stuck in. Now you're getting familiar. Those ribbony things are the amino acids strung together, okay? So you can imagine there could be problems with this not working so great. It's a rather complex structure. So bottom line here is though, is you can't make the porphyrin rings if you don't have glycine. That means you can't transport the oxygen. So again, we're right back to the same kind of core nutrient deficits that can trigger problems throughout the body. You could have a glycine deficiency, not be able to make hemoglobin. This is common. I see this every day. I see this like literally every day, if not with one of my patients, then in class. We see this every day. A glycine deficiency, you can't make hemoglobin, you're not transporting oxygen that great. So what are the mitochondria going to do? Are they going to celebrate the fact that your my, your hemoglobin's like messed up and they're not getting oxygen? No. They're going to like go on strike. Your lecture on transport chain is just going to be like, really? This is the best you can do? This is the best you can do? You're bringing me like second-grade oxygen levels because your glycine is low and you can't make hemoglobin, right? Well, let's guess what I'm going to do. I'm not really going to participate in this whole energy production thing anymore. And that's what we call a hypometabolic state or mitochondrial retraction. A lack of oxygen or hypoxia, lack of magnesium, which is common, and most of the American population is low in magnesium, a lack of CoQ10. Any one of these nutrients that's deficient, oxygen, magnesium, CoQ10, the mitochondria are just like, yeah, you know, maybe some other time, you know? And then the levels of mitochondrial populations start to drop, and then people get chronic fatigue and depression, all these problems. So when we're looking at the labs, we want to be able to assess all this, right? Assess the amino acids, assess the B vitamins, understand what proteins are working and what proteins are not working in terms of the folding, the enzymes, are they working? Are they not working? And start to pull all this together into actual protocols that we can use to treat people.
All right, so now I'm gonna, um, do a quick summary and then I'm gonna spend a minute or two looking at some lab examples so you can see how this works on testing and then we'll open it up for questions.
Okay, okay. So then, let me show you here. So, all that information. Now, let's, let's look at a test and apply it. It's like applied physiology. And I know if you haven't done this a lot, this may seem a little sketchy. I know when I first ran into organic acids, I was like, I didn't really understand why they were important. I mean, I kind of knew they're important because all the smart people, you know, just seemed to do them, but I didn't really understand them. Honestly, for the first 10 or 15 years of practice, I didn't understand any of this stuff. And so, if you guys can even understand 10% of what I'm trying to say tonight, you'll be further ahead than I was, you know, at year 15. It's all right in front of us on these labs.
So, here's a sample. This is a Neutroval test from Genova, and they are very kind to spend a long time redoing these formats in much clearer, better colors. I love the graphics, they're easier to read, you know, and they have like a cheat sheet thing in the very beginning, which is kind of nice when you're first learning how to do this stuff. So, like right off the bat, they give you, and you may not have seen these yet, these are pretty new, um, Neutroval again from Genova. And here's the first page of the reworked one. Can again, they summarize, you know, mitochondria, inflammation, toxins, methylation. Where's the main issue? So, these are great just as a patient education tool, orientation tool for yourself, so you can kind of go hunt down the areas that you want.
And now we're going to look at mitochondria, obviously, because that's what the class is like, what the class is about today. But let's just look at these markers for a moment without even looking at the test. You can see. So, now, number one, we talked a lot about lactate and pyruvate, okay? They're measured here, okay? Right here, lactic acid and pyruvic acid. It's really straightforward. We talked a lot about CoQ10, it's measured there. We talked a lot about magnesium, it's measured here. If these markers are off, you know exactly what to do. And then we talked about the succinate dehydrogenase enzyme, right there it is, succinic acid. If that's high, that enzyme's messed up, okay? If this is high, then the pyruvate dehydrogenase enzyme is messed up, and you know that you need to give the B vitamins and figure out the amino acid snip slash protein folding part of that, okay?
When you actually get down to treatments, most of what we're talking about today is either B vitamins or amino acids. It's not particularly complex treatment-wise. But where I think you'll stumble the most, because this is where I have struggled for years, is in getting the dosing right. And this is not like a 50 milligrams of B vitamins kind of situation, right? That's not going to, I mean, if the person, you're just never going to get people like that. They could just go to the health food store and buy a B complex. They can get better if their problem is dietary or their problem is 50 milligrams of B here, this or there. They probably would have figured it out before they started to pay doctors to help them, okay? So, we're usually talking about needing to dose people quite a bit higher in order to get these enzymes to work. But remember, if the enzyme's not folded right and the amino acid sequence isn't right, or they're low in amino acids, things are not going to work. You need to give it an extra little kick in the pants.
And back to Richard Lord, Roger Williams in the 1950s wrote books about this. And the seminal book on this, which is still relevant today, even though it was written like 60 years ago, is called Biochemical Individuality. If you haven't read it, you got to buy this and read it. Biochemical Individuality by Roger Williams. This is my teacher's teacher, right? The guy that discovered a lot of these B vitamins. And in the 1950s, he sat down and wrote a book about the genetic variation in psychiatric patients with schizophrenia, bipolar disorder, and manic depression. And this depression and that depression, who had genetic issues with B vitamins, okay? It's, you know, was re, you know, re-released in 1998, but I think this thing was written in like '53 or '58 or something like that. This is a really old book. These people figured this out like two generations ago, okay? Now we have the technology to test for all this stuff. That's the cool part.
Here are the B vitamin tests, right here. You can't get more plain than that. Riboflavin, B2. The marker is high, they need riboflavin. I'm going to take a little issue with the 50 milligram thing, okay? You could start there, but probably they're going to need 100 or 200 or 300 milligrams. Probably 50 is not going to cut it, okay? If there's ill niacin, it's just sitting right there. That marker is in the red. You know the person needs B3. Now, you know, if you give someone, think about it this way, if you give somebody B2 because this test marker is high, you're affecting that succinate dehydrogenase enzyme that we just looked at. That's part of Complex II. You are changing the electron transport chain when you give them a high dose of vitamin B2. It doesn't get more profound than that in terms of how you can alter human physiology, you know? It doesn't, I mean, and you can retest them in six months, retest them, and if that number's down, guess what? You just fixed a massive metabolic disorder for that human being. And then when they come back in and say, "Oh yeah, doc, I don't know what's in that stuff, but I bought an extra 16 bottles for me and the whole family because my neuropathies are gone and my depression's completely gone and my wife said she feels better too," you know, you're not going to be surprised. You're going to be like, "Gosh, you know what? That's what the succinate dehydrogenase enzyme can do if it works right."
Let me show you some pictures, Carl, and tell you about why this is better now. And we should probably test your whole family because there could be a genetic component here. Let's get everyone in, the kids too. Oh yeah, yeah, we should for sure test your kids, especially the ones that have ADD, before this gets to be something out of hand like it did with you and your depression, right? That's how deep this stuff is, okay? Now, again, CoQ10, like if it's low, it's low, you give it, right? That's pretty simple. Um, thiamin, there's a breakdown here, riboflavin, and it really, oh, magnesium, right? That's that covers the bulk of what we talked about.
Now, for oxygen, remember, you want to think a little bit outside the box, okay? You give breathing exercises to make sure they're well-oxygenated. A lot of people don't breathe very well, so that's the lifestyle change. And at the same time, just to provoke some here, remember how do we transport oxygen? How does it get to the mitochondria? Then how does it get stored inside the mitochondria? Hemoglobin and myoglobin. What is it made of? Porphyrin rings. How do you make porphyrin rings? Turns out it's made from, they're made from glycine. Is glycine on here? Yeah, last time I checked, it was. Find it. So, if glycine levels are low on this test, of course, now I can't find it. It's in here somewhere. There it is. If glycine levels are low in this test, they might have an oxygen transport problem. It's that simple. So, you got to pay attention to amino acids and B vitamins, and all things will work out, okay?
So, let me, um, close up these things and open it up for some questions. Let's see. Oh, and don't forget, if you're late, have a boot camp where we're going to do like a couple months of this. I got a lot. This boot camp is so overbuilt, you guys. It's Richard Lord actually giving these lectures. It's really cool, and it's me too. I'm going to, you know, I'm doing all the case reviews and everything, but you get a chance to listen to Richard. And, um, I spent four years creating these talks. They're really good. They'll blow your mind. Each one of these hour and a half talks he gives, you're going to just sit down for two or three weeks and think, "Wow, I got to listen to that again. What did that guy just say?" It's really deep. He's a very profound teacher and he's changed my life probably more than anyone else in my, you know, professional life. And so, I'm really trying to represent his work as best I can here. And then we have another boot camp, then that also features Richard's lectures and talks that he and I have been going through in the last four years. It's sort of like the best of, you know, I have hundreds of hours of his material and I tried to pull together for you all like the best lectures, uh, that he's given. And then I have all my material in there. And you get a big discount if you're a Genova person, okay?
All right, so we're going to take a break. I know some of you may need to leave because we're at the hour, but I'm going to stick around for a few minutes and answer questions. Um, this is all recorded, so if you need to leave, you can listen to the recording later if you want to get questions. Okay, and let me just start from the top here and see. A lot of questions came in. I'm trying to get to as many as I can. I actually have to teach my mentorship class in a few minutes, so I don't have too much time. But let's see, let's see. I have a very, very difficult personal relationship with my laptop, and I try to be kind to it on a really regular basis, but, you know, it's not working for me anymore. And I think, just between you and me, I think I'm going to get a new laptop. There we go. Now I'm scrolling, right? Because it's not scrolling down, and it knows that there's like 170 doctors waiting here. Uh, so have you ever done any of that? Yeah, this is a good question. Everyone always asks this. Does a single OAT test replicate? Absolutely. You think they didn't look at this? Yeah, they did. There's actually, so each individual organic acid marker had slightly different variation week to week and sample to sample. And this has actually been looked at very carefully. Some of them are really tight, meaning like you get almost the exact same number. If you test the same group of human beings every Tuesday morning at nine, you'll see, you know, sulfate. It's just like, boom, boom, boom, boom, same number, same number, same number. Some of them have wider variation for various and interesting reasons. So you got to learn that on a marker by marker basis. But absolutely, the one that flux, just to give you an example, pyroglutamate fluctuates a lot based on females and where they are at in their menstrual cycle, and males doesn't really move around that much. So there's a lot of variation, but you can understand it. It's not to do with the accuracy of the testing, it's a description of what's going on biochemically in that particular patient, right? Which is, it adds a whole other level of interest to this testing, to be honest.
Um, let's see. Yeah, so we will have recordings of this available. We'll send out a link to the recordings, um, probably tomorrow, since this is kind of late. Probably won't do it today. I'm going to, let me see. I'm going to stop my camera because I think that's screwing up my bandwidth here. Let's see. Stop. And let's see if we can get one or two more questions in. Oh, yeah. So for the classes, how do you sign up for them? You just go to KalishInstitute.com. Let me show you that here. KalishInstitute.com. And we'll probably send out links also, but if you want to sign up sooner than that, you go to KalishInstitute.com and click on the classes button, and it'll take you right to the classes. And yeah, you can, anyone can take these. I mean, mostly it's medical doctors, chiropractors, naturopaths, acupuncturists, physical therapists, you know, but, you know, you don't have to be licensed to take one of these if you just kind of want to do it for your own personal interest, that's fine too. We have a nurse that just signed up. We have a couple of pharmacists in the group right now. Um, oh, selecting dosing levels for B complex. So you always want to start low. And when you, let's say you target an individual B vitamin like B2, we talked a lot about, you always need to give the B complex first, one or two B complex a day, and then stack on top of that the additional B2 or stack on top of that the additional, you know, thiamin or whatever it is that you want to beef up, okay? That's the general rule of B vitamins. Never give a single B vitamin by itself because that can cause some problems for people.
Um, yeah, prior to doing the testing, I usually have people stop all their supplements for like a week before. And yeah, we'll have recordings going out again. And so a strong multi, to answer Alan's question, is like the foundation for all these problems. If you want to keep it simple, you can do that as a simple way of converting things. And then a couple people asking about the Great Plains test. That's a great company. I don't use them, so I can't really teach their lab because it's quite a different structured test. But a very old and very, uh, wonderful doctor, not old doctor, but old friend of mine from way back in the day, Dr. Kurt Wohler, teaches over at Great Plains, and he's one of the hands down, one of the best doctors that I've ever met. So if you guys want to get into Great Plains, that's an option too. But I'm very loyal to Genova because Richard Lord is the one that, you know, is in this vein of, um, so I pretty much only do the Genova testing, only teach the Genova testing, just based on my relationship with Richard. But I'm not anti-other lab, right? There's all these other labs have a place in the world. And in terms of brands of vitamins, so I emphasize in my practice pretty much two brands only. I use Pure Encapsulations and Designs for Health, and I find I can get pretty much all the products I need between those two brands. And then the dosages for glycine, we'll wrap up with that last question, is three to six grams a day. Three to six grams a day for glycine.
All right, okay gang. Thanks for hanging in there for a long talk. I hope it was helpful and kind of stimulated some thoughts for you. If you're interested in more, come back and we'll be doing these boot camps, uh, coming up in April and June, okay? Take care everyone. Have a good evening.