Mentorship Miniseries - Mitochondria and Cellular Energy: Chronic Fatigue and Depression

Hello everyone, and welcome to our mentorship mini-series. I hope you all are surviving out there and doing well. We have a lot to talk about, so I will start with a little introduction for those that are new. This is a series of classes, so if this is your first one, you can attend the others. I guess we send out what you call links to the recordings.

Today, we're going to focus on mitochondria and cellular energy, chronic fatigue, and depression in a very big, big picture sense, as big a picture as we could go, really. And let's see here. There you go. That's me. I'm Dan Kalish. I've been teaching for IFM for a little while, doing their practice implementation courses. I've done research with the Mayo Clinic, which is kind of cool. That was a good project. And right now, I'm working very intensively, one might say, with Dr. Richard Lord. A matter of fact, I spent a couple hours with Richard just earlier today. When we're going to talk about what he was talking about in a moment. I've been in practice for a really long time, and I teach these courses where we show doctors how to interpret labs, set up programs, protocols, and get practices going. The courses that I teach are kind of half oriented around clinical and half around business skills. You know, what we're going to be talking about today is focusing on oxidative stress in the brain and how all that kind of comes together, or doesn't, in terms of your mitochondria and why a lot of these patients we work with are so tired and depressed. And then we're going to look at some supplement programs. The second part of today, after the talking part, will be, you know, some looking at looking at some labs.

We have events coming up at the Kalish Institute. We have, in the big picture of all this, we have a series of boot camps coming out this year. The first one we'll be doing in April is on amino acids and vitamins, very relevant to what we're talking about today, amino acids and vitamins. Um, you're welcome to sign up for that. You get a 20% discount. If you're listening to this and you see that discount code, you can grab it, enter it in, and you'll save 20%. And that is a two-month deep dive intensive on amino acids and vitamins. Richard Lord teaches half of it in his lectures, I teach half of it. These are lectures no one's ever heard before. It's the real deal, right? So those who don't know Dr. Lord, he is the founding scientist of our whole industry, right? He's the scientist that started organic acids testing, fatty acid testing, amino acid testing. He developed the GI Effects test, which Genova uses now. The microbiome analysis was all his idea. He's the guy, you know, he's been retired for a long time. I talk to him twice a week, and he tells me what to tell you guys. That's basically what's happening now. Why I've become his, anyways, it's great. It's a great thing for you, it's a great thing for all of us, it's a great thing for him too, because he's the, you know, the best teacher in our industry for sure. And it's great for you all to be able to hear his words, even though they may be through, you know, interpreted through me a little bit. And then in June, we'll be having a genomics boot camp. That's the first time we've done that too, looking at how you can find snips, how you can identify snips on these functional tests that we all look at all the time. That's kind of an innovative class that hasn't been done. You can also get 20% off on that.

And we have a mentorship class starting at the end of this month. A few of you will sign up, I would hope. That's a one-year version of this, where there's day after day and hour after hour and month after month of lab analysis and business discussions and just making it all work so you guys can have super successful practices. It's a really great class. We have a large group of doctors in it now, and it is just getting better and better every year, really, thanks to Dr. Lord and all the stuff that he's teaching me. So I teach all those courses. They're weekly live classes where we interact and go over your cases, and then there's all these pre-recorded lectures that get into the clinical side of all this. And you can get a thousand dollars off on that class if you register using that code, right?

So now, for our topic at hand, you know, just some background on on what we're really going for here. The big story, the big picture, is the major source of oxidative stress in the human body is generated by the human body from our mitochondria making energy. And so if you have an excess of oxidative stress from mitochondria and from outside sources as well, right, this is considered generally to be an extremely bad thing. And that causes severe problems with everything that you can imagine, including, very importantly, the brain. And in fact, if you have too much oxidative stress, it can kill the neurons in the brain. And this is the name for that, right? Apoptosis. Apoptosis, or programmed cell death. The cell just goes, "Uh, enough's enough. You know, it's too much oxidative stress. You know, I'll live another day. I'm going to go to the next life." And poof, the cell is gone. And you basically don't want brain cells killing themselves, right? That's generally a negative thing. Glutathione is what stands between your brain cell and this oxidative stress by reactive oxygen species, okay?

So we all kind of know that, but where it gets interesting is that moment to moment, day to day, second to second, millisecond to millisecond, glutathione is competing with methylation. The process of methylation. Glutathione is competing with the process of methylation. And why is that so important? Well, because these are the two most important processes in your body. Glutathione as a master antioxidant, and methylation, which does everything. And you all have studied methylation, and we all know MTHFR, right? This is, but what's kind of underappreciated, I think, is the extent to which methylation's impact is impacted by these other processes in the body. And that's what we're going to talk about today, right?

And so, well, let's just look at a few diagrams in a second. B vitamins are part of this story. And B6, folate, B12, you know, we have to have B1, B3, B5. All these B vitamins are required for us to be alive from moment to moment. And a lot of the patients that we work with have genetic issues. That means, basically, it translates into the fact that they need a lot more B vitamins than the average person you might think would need. And so one of the most common things in practice is to be able to identify these people, pick them out, and give them the right B vitamins so that they can get better. And again, B vitamins are what make everything in your body actually work. There's not an option for having B vitamins. And by the very nature of the name, vitamin B, vitamin, right, we know that you can't get them internally. I mean, you can make a little bit of niacin, I guess, from tryptophan, but in general, for most of the B vitamins, you have to either, you get them from an outside source, you have to eat them. A lot of people don't eat enough B vitamins.

So now, oh no, this is like a big picture view. The biggest picture view of what we're doing here. So let me just try to expand this a little bit so you can see it better. Now, on the on the left side of your screen is folate, the folate cycle, and a single carbon pool, okay? And then on the right side is all the stuff that has to do with oxidative stress. So I'm just giving you the short version of this. The short version is that when we're, um, methylating, right, what we're doing is we're running this cycle up here, and we're converting methionine and homocysteine, and methionine to homocysteine, and homocysteine to methionine, right? The cycle goes back and forth. And we're doing that by relying upon what's called a single carbon pool, which are all, which is the origin of which is these amino acids over here, like serine, and glycine, and histidine, and tryptophan. So your body takes these amino acids, it breaks them down a little bit, and creates this ability then to, you know, thanks to folate, only different types of folate, to to make this methylation process work. And so the famous one of the, you know, problems here is MTHFR. So you can have problems with folate, or B6, or B12. And the B vitamins being messed up from a genetic issue or whatever it may be, is going to mean that you're not going to methylate well. But you can also have a lack of glycine, serine, or histidine that causes the exact same kind of, you know, problem with methylation. So methylation is a pretty broad, broad area, and a lot of things can screw it up, a lot more than just the B vitamins. Deficiencies of amino acids or genetic defects related to amino acids can cause a problem as well.

And then where I really want to look at here tonight is here. And this is way too small. So let me, let me just blow this up because, and then we'll, uh, we'll have to exit presenter mode for a second. Okay, just bear with me while I do this. We'll come back to presenter mode in a moment, but I just want you to see this because it's so important. And we want to look at this for a few minutes, and then we can get a regular scheduled programming here. Here's the image. So methylation and glutathione are in direct competition. You can do one, or you can do the other. And your body's trying to do them both at the same time. So let's look at this really big picture here. Hopefully, you guys can see that now. So at the top of this diagram, you see it says oxidative stress. So when there's a lot of oxidative stress, right, when there's excess oxidative stress, methylation is decreased because we have to increase the ability to make glutathione. So there's a whole bunch of antioxidants in your body, right? There's vitamins like vitamin E and vitamin C, but we can't make those under sudden demand. If you're all of a sudden exposed to oxidative stress, of course, you use the other antioxidants to protect yourself. But glutathione is the main regulatory system that can instantly be expanded, millisecond to millisecond. You can make huge amounts of glutathione. But every time you make a molecule of glutathione, you're going to be pulling from your ability to run methylation. Now, before you think that's a bad idea, the reason why your body does this is because your cells don't want to die. And if you get too much oxidative stress on the cell, then it's going to go through this whole cell death problem. And so when your body's, you know, down getting down to the nitty-gritty here, and it's like, "Okay, am I going to do some methylation or am I going to make glutathione?" You're going to make glutathione every single time. So if you have a lot of oxidative stress, glutathione levels are going to go up. And every little bit of glutathione you make is going to decrease the amount that you can methylate. So you're not going to be able to methylate your DNA, you're not going to be able to produce hormones, you're not going to be able to do all the stuff for the brain that methylation does when you have a lot of oxidative stress because your body is going to be distracted and be directing all the resources towards making glutathione. That's the crux of this whole discussion, okay? And so if there's a lot of oxidative stress, your glutathione levels go up, your methylation function drops, and that makes people depressed. That's kind of the nitty-gritty part of this all, right?

So let's go back here to our regular slides. Now, what that means is that moment to moment, as your body is trying to figure out what to do, it has to assess, "How much glutathione do I need to make right now? And how much can I use these same resources to methylate?" And a lot of these decisions are coming down to what's going on with your mitochondria. And so what are the mitochondria? The mitochondria consume about 90% of the oxygen that we, you, you know, breathe. It's pretty important, you know. And if you think, and I do this in talks when I'm talking to patients, you know, um, if you're wondering how important your mitochondria are, let's just take a deep breath in, everybody can do this. Yeah, I can't see you guys, but you have to do this, right? Take a deep breath in, and then blow it out, and then hold your breath out, and see how long you can do that. And the reason why it's difficult to do this, and the reason why you can't do this very long, is because you really need oxygen to run your mitochondria to make ATP. Again, again, again. Glutathione protects the brain, but it's competing with methylation. So that's our concern here.

So in terms of the labs, you can test for all these different things. You can test for things like lipid peroxides. That, if it's high, if lipid peroxides are high, that means that the lipids are being oxidized, damaged. That means that, you know, the membranes. Mitochondria are made up of membranes, remember that. They have the inner membrane, the outer membrane. There's a lot of membranes. The mitochondria, and they're made up of these fats. And if you're getting a lot of lipid peroxidation, then you're going to have damage to the mitochondria. You can also measure CoQ10. Look at tests in the second half of the talk. You can measure magnesium. You can measure all these mechanisms with these pretty simple labs. You can look at organic acids to actually measure mitochondrial function specifically. You can even measure the detox capacity and see how much these toxins are building up that are leading to the extra oxidative stress that's new kingdom mitochondria, right? So these are all options with our testing. You can measure oxidative stress itself, and it just goes on and on, okay?

So in terms of the genomics aspect of all this, and the genetic aspect of all this, the, the short history of conventional medicine's use of organic acids is that, you know, they were developed and used for newborn babies, right? And for looking for, you know, relatively rare genetic disorders. And when Dr. Lord was in graduate school, he had this moment of thought where he realized, "Oh gosh, well, if you're using organic acids testing for detection of inborn errors of metabolism that can kill a newborn baby, I wonder if there's some application for adult onset problems?" Okay, the adult onset problems that are related to the same exact issues. And so one of, in the '60s, when Richard was in graduate school at the University of Texas in Austin, his main professor was a man named Roger Williams. And I love that he almost made it to a hundred years of age, right? He was born in 1893. Dr. Williams discovered folate, pantothenic acid, B6, and lipoic acid. And I just had this vision of Richard Lord being this young, 20-something-year-old grad student sitting in some, you know, lab at the University of Texas, and Roger really, I'm sticking his head out of his office down this, you know, down at the end of the hall, going, "Hey guys, guys, come down here! I just found B5!" You know, this is like cool stuff. This is like the origins of nutritional science. Um, he got his PhD in 1919, Dr. Williams did. That was a long time ago, okay? There was a pandemic going on when he got his PhD. How ironic is that? Anyways, and if that's not enough, Roger's brother, Robert, found thiamine. What a crazy family. Anyways, it's interesting, kind of history here.

And what Williams said way back in the 1950s, 1950s, he was an old man though, right? What he said in the '50s was that in his book, if you haven't read his book, you have to get his book. It's called Biochemical Individuality. It's a must-read. You have to read it. Biochemical Individuality, Roger Williams. What he said in the 1950s was that as he was discovering these B vitamins, was that he realized then that there was a huge genetic variation in the amount of B vitamins that different people needed. And he attributed these B vitamin genetic disorders to adult onset mental health problems. In the 1950s, he had that figured out, all right? So what we're talking about is not really a new idea. And in fact, the research has gone on since then, right? And we know that mitochondrial dysfunction is a key player in the manifestation of depression. There's a nice review article from, um, a neuroscience journal. And I just thought I'd bring this quote out here because I thought it's kind of cool from that paper, right? Is that alterations of mitochondrial functions and membrane polarity, which increase oxidative stress, which we're just talking about, right? Increase oxidative stress and apoptosis, cell death, may precede the development of depressive symptoms. And then this one-liner down here is great because the brain has high aerobic activity, requiring 20 times more energy than the rest of the body by weight. It's highly vulnerable to conditions stemming from impaired energy production. So it means that the mitochondria are extra important for your brain. A resting cortical neuron, a resting brain cell, consumes 4.7 billion, with a B, ATP molecules every second. So in the time it took me to read that, I just chewed through tens of billions of units of ATP in one neuron. And one would hope, at least I would hope, that I've got more than one resting cortical neuron right now. I've got gazillions of neurons in my brain consuming billions of ATP molecules. So you can see there's the flow through the system is massive. We're making huge amounts of this stuff. So you get a little error in a system that's running that hot, you got a really, really major problem. If you're driving a 1985 Honda Civic down the freeway and, you know, the cylinders are slightly misfiring, you probably wouldn't even notice. If you're driving a 2020 Formula One race car and there's a little glitch with the motor, it could blow up and you could die, right? So when you're cramming that much substrate through a system, little errors make a really big difference. And that's why this mitochondrial system is so susceptible to having problems, why we see problems with it all the time. I mean, I see this problem, these kinds of problems, in my practice like literally every day that I'm in practice, okay?

So with amino acids, I'm sorry, with organic acids, we can find a whole lot of information out. We'll look at some labs in the second half of this little class today. And high levels of organic acids can mean that there's problems with certain nutrient levels. Low levels of organic acids can mean a chronic lack of mitochondrial populations, right? There's just not enough mitochondria present to even register a reaction, okay? And if you joined us late, we have a couple of boot camps coming up. If you like this stuff, I created these short eight-week courses, kind of a deep dive into proteins, amino acids, and vitamins is the first one starting in April. And in June, we have one on genetics and how you can look at functional medicine lab tests and start to understand snips from that. It's kind of reverse engineering things. We also are going to have a special guest in that class who talks about snips. And there'll be lectures from Richard Lord in both of these courses, 10, 15 hours of Richard talking at a very high science level, and then me reviewing cases and going through all the clinical application stuff, okay? You get 20% off of each of these if you sign up using these codes. And these are the first time that we've done either of these courses. And I guarantee you're just going to enjoy them. And we price them really reasonably, so it's not a huge amount of money for you to worry about. We have the mentorship coming up at the end of the month as well. For those of you that are interested, you can set up a call with one of me, one of me, one of me, with me or my staff, and we can talk to you about that class, all right? It's great. The mentorship, we just do what I'm doing today, but it's like week after week, and it goes on forever, okay? You learn everything that you need to know.

So the key nutrients for correcting mitochondrial problems: CoQ10, magnesium, B vitamins, and carnitine. So these are the four that I use every day in practice. You should know how to dose these. If you underdose them, it doesn't work. So, you know, we'll talk about that when we look at some of the labs. Talked a lot about free radicals and oxidative stress already. That's what we're worried about, you know? And we're essentially concerned about free radicals damaging the mitochondria. And then when we look at the brain specifically, you can see this diagram shows a healthy mitochondria, and then as it gets damaged more and more, how that has a very negative impact on the brain, and a very negative impact on your DNA, and a whole bunch of other things, right? So the mitochondria, as we're saying, are very, very important. And there's all kinds of research that goes back many years, and a lot of research happening right now about how depression, how the aging process, how the reason why our cells die, and why we die, is tied back to the health and functioning of mitochondria. And it's cutting-edge stuff, right? There's research universities all throughout the world right now that are trying to crack the code on mitochondria so they can solve this depression problem, right? And also so they can solve the issue of us getting older and dying. That's maybe even more important. I mean, people care a little bit about depression, but people care a lot about dying. And so it's a pretty hot topic right now. And I think there's a shift in the scientific community to look at mitochondria and a little bit of a pulling away from looking at neurotransmitters as the sole reason for depression, okay?

So now we're going to look at B vitamins and and think about their importance. They act as coenzymes. I don't like that term because when we use that term coenzyme, it immediately sort of dumbs down the B vitamins. So I think of it like this, like, um, when you get on an airplane, which we're all going to be doing again soon, hopefully, and you, you walk in, and you know, you look over to your left, and you see there's a pilot and a co-pilot. And you automatically know that the pilot is just the better person to be flying that plane, and that the co-pilot is there kind of as like a backup, right? They're there because something might happen to the pilot, in which case, you know, they don't want to like put, say to the passengers, "Oh, someone put their hands up if they can fly a Boeing 747." They got the co-pilot there, yeah. But the co-pilot is in a diminished role. And there's only one pilot. There's not like two pilots, okay? There's a pilot and a co-pilot. So we use this term coenzyme, and I've used this term, we all have, right, since we learned nutrition. You immediately think it's not that important. You're like, "Yeah, the enzymes are really important, but the coenzyme is like the co-pilot, not really that important." And that is not true. Cofactors are actually the non-protein part of the enzyme. In some of these enzymes, right, they're covalently bonded. In other enzymes, they're just like super important electrically attracted things. They're not actually physically part of the enzyme. But cofactors, whether it's minerals like magnesium or calcium, whether it's the B vitamins we're talking about now, the cofactors are absolutely essential for the enzymes that we're talking about to work. So we can make energy, so your mitochondria can function. You could fly the plane without the co-pilot, right? If the co-pilot died of a heart attack, I don't know, how worried would you be? You'd be a little worried, but you wouldn't be super worried, right? But in the case of enzymes, if the cofactor is not there, or the coenzyme is not there, it doesn't work at all. That would be like if the pilot and the co-pilot died, and you're in some serious trouble, okay? So this is super, super important to understand that the B vitamins are not a peripheral thing. They're a central, key role of exactly everything that we're talking about, okay?

So every little step that we use to make energy requires something happening with a B vitamin, and something happening with magnesium, and CoQ10 is in the mix as well. And if you're missing any of these nutrients, you're going to have a really big problem. So I decided I'd show one example where you can see the inner mitochondrial membrane there. So remember that's made up of fatty acids. So you have to have your omega-3s and omega-6s for this whole thing to work. If you look at the bottom of the diagram, you can see succinate going to fumarate. When we look at the labs, just remember that because we're measuring that with an organic acids test, we're measuring how well complex II works in the electron transport chain, okay? We're getting very specific and very granular about the functioning of mitochondria. And typically, enzymes are are presented like this, right? Where you've got this little key unlock thing, and the thing fits in there, and then it works. But what's really happening is quite a bit more complicated. What's really happening is we're stringing together all these amino acids to make proteins, and then what's going on is those proteins are starting to fold up, right? Those amino acid strings are starting to fold into different shapes. And something like complex II, this is an image of complex II here. It's concerned, complex II, succinate dehydrogenase enzyme, it's part of complex II from the electron transport chain. It's this thing that we're looking at right here, right? Complex II, the enzyme called succinate dehydrogenase, is embedded in the actual, um, what you call it, this thing here, is embedded in the mitochondrial membrane, okay? Now, here's another diagram of the same thing. That's the enzyme itself. That's a bunch of proteins folded up, right? I'm sorry, a bunch of amino acids folded up. And then here it is, embedded in the actual, uh, little collection of fats that are together that form up the membrane. So here's the enzyme. There it is, embedded in the membrane. Here's another image of the same thing. That's more graphically oriented, right? Not a literal image. And that's what we're talking about, is this thing working or not? And here's another thing again, another image again, succinate dehydrogenase, same enzyme. And you can see FADH, right? That's a B vitamin coming in. So succinate converting to fumarate will only happen in the presence of that B vitamin. If you don't have the B vitamin, that's not going to happen. And this entire thing is going to be dysfunctional. The all the energy your body put into making this enzyme, all the energy your body took into building the mitochondria, none of that matters if you don't have the B vitamins sitting there to tie this whole thing together, okay? So these are not like optional. The ability to use amino acids and B vitamins and string them together and get the vitamins to work, right, are essential for us to have normal functioning. And if you have mitochondria that are damaged from oxidative stress, then they're not going to work very well, and that ATP production is going to suffer. And if that starts to happen, then one of the first parts of the body that's going to feel the impact of that is your brain, okay? And then you're going to get patients that have fatigue and weight gain and depression because of this lack of ability to make all that happen, all right?

So let's look at, I'm going to show you some. We're going to take, we're right at the half-hour mark. I feel good about that because we're right on time. So I'm going to take a break for about 30 seconds. We're going to come back, and we're going to talk about, if you want to stick around, if you have to run and make dinner for your kids or whatever, go for it. If you have a minute to stick around, we're going to review labs right after the break, okay? All right.

We are back, and we've got a couple of classes coming up, as I mentioned. The lab interpretation boot camp, where we're going to do a deep dive on this, priced pretty low. You can check it out with a discount, totally affordable. And then genomics boot camp coming up as well. And we have a new mentorship course starting. What we're trying to do in the bigger picture of things here, and what I'm trying to do educationally, is tie together these boot camps as basic, kind of introductory level things that you just should know, things like amino acids, vitamins, um, fatty acids, we'll do later. We're going to do, you know, the basics of genetics right now, getting that stuff down. And then for those who that really want to start a practice and start to make a serious, you know, income doing this, then we have the mentorship, okay? We're trying to offer things that are at different levels. So not everybody's ready to do the mentorship. Took me a long time to figure that out. So I'm going to review some cases in part two of our evening right now, and then we'll open it up for questions at the very end. So, and these are just random cases. Hopefully, they're going to work out. These are not, I sometimes, to be honest, sometimes I use like fake cases, you know, that are ones that I put together to prove a point. But these are just random ones that I picked, okay?

So what do we say? The most important. So when I say, when I say mitochondria, what, what's the immediate first thought that you have? CoQ10, magnesium, oxygen. Those are the three things. CoQ10, magnesium, oxygen. Just got to memorize that. Someone says mitochondria, you think CoQ10, magnesium, oxygen. Oxygen means the capacity to breathe, right? And a lot of our patients don't breathe well. So the lifestyle change for mitochondria is to coach patients on breathing, holding your breath, deep breath, belly breathing, whatever kind of breathing you want to do, exercise to get them breathing, right? That's the key. And then for the nutrients, we're looking at magnesium and CoQ10.

So here is a test panel. It's called an Ion Panel from Genova. They also have a test called, uh, Neutroval, which is very similar. I prefer the Ion Panels because I'm old. Anyone who's under the age of 50 or 60 likes the Neutrovals because the younger crowd does those. They're basically the same test, they're interchangeable. Um, whenever I meet someone that really is into Ion Panels and I look at them, I'm like, "Okay, you got a lot of gray hair." I don't have much hair at all, you know? But anyways, it's kind of cool. It's sort of like a, a bonding thing for the older doctors because we used to always use these. In bloody blood, anyways, the Neutrovals are equivalent, all right, from, uh, from Genova. So low magnesium, right off the bat, you know, hey, if you're low in magnesium, there's no way your mitochondria can function properly. So we know this person has a problem right off the bat. And that's not an easy, not a difficult diagnostic thing to determine, okay? Oh, this was a good one. Again, I picked this one randomly. CoQ10 levels are low. Two reasons why there's no way this person could have good mitochondrial function. The two main ingredients out of three, magnesium and CoQ10, are both testing low. What do you need to do? Give them magnesium and give them CoQ10. And not just a little bit. Magnesium causes diarrhea if you give too much, so be careful. But you want to give at least 200 milligrams of magnesium two or three times a day to start to get those levels up. And it's going to take six months, you know, at least maybe a year to get magnesium back to normal. And then CoQ10, you want to give at least 200 milligrams a day. Anywhere from 200, some of the docs that I work with, you know, use a thousand to 1200 milligrams of CoQ10 a day, okay? It gets really expensive. This main prohibition, prohibiting factor there, but at least 200 milligrams of CoQ10, if not more. If the patient's extremely tired and depressed, 400 or 600 is warranted. Again, it's an expensive product, but it's worth it. Um, this person has low omega-3s. So now we know what the cell membranes are not working well. The mitochondrial membranes don't have the right fats. So there's another compromise there. And if the membranes aren't the right thickness, then none of this stuff works, okay? So remember, I showed you that enzyme that's embedded in the membrane. It's really important. And then now we're looking at the actual organic acids markers here. And we can look here, uh, you can zone in or zoom in on energy production. Citric acid cycle. Doesn't get any more clear than that, okay? Now, remember I showed you that enzyme a minute ago? We can look at it again if you're confused. And we saw that enzyme and complex II, remember that? The pyruvate dehydrogenase enzyme. It converts succinate to fumarate. Remember, remember, you needed a B vitamin to make that happen. And the B vitamin wasn't there, it wouldn't happen. So if you get a backup with that enzyme, you would see succinate be very high. That means that that enzyme's not working. What does that mean practically? That you're not pushing that electron transport chain forward. You're not carrying those electrons down. And so you're not making ATP in the normal way. Now, this particular lab has some different examples. And of course, there's different enzymes for each step, right? We don't have time to go through all of them. But you can see the high markers here indicate that that enzyme is not working at its proper capacity. So that person needs more what? B vitamins, magnesium, and CoQ10 to force that reaction, that chemical reaction, to to move along properly. And then that's going to have, you know, direct impact and improvement. Uh, will it help improve how that person's brain works? So again, succinate and fumarate, we're looking at that. Now, it's going to bring you back, just real quick here, to the images that we were looking at, so you can see how that works. I'm not saying this is easy. This is why we have like a year-long class, okay? Because you can't just figure this out in an hour here. But at least you can see if this is of interest to you. And if it is, you should take my other classes because I want to teach you guys how to do this properly. Remember now, complex II, you see succinate going to fumarate. That's what we're looking at on the lab. CFADH, FADH2, okay? That's a B vitamin sitting there. That's the B vitamin that's making this work or not work, okay? And it's acting as a coenzyme. But you know, it's not a co-pilot. It's a, if it's not there, the enzyme can't work. And the enzyme is made up of amino acids, remember? Here's what the, I mean, what the actual succinate dehydrogenase enzyme looks like. That's a whole bunch of amino acids strung together. They got folded up. And here's that same enzyme buried in the lining of the mitochondria, right? The membrane of the mitochondria. And then here's that same enzyme. You see succinate to fumarate requires a B vitamin. If you don't have that B vitamin, then this whole thing falls apart. And this entire enzyme is just going to sit there and it won't do anything, okay? Succinate, this doesn't convert to fumarate for fun. You have to have the B vitamin triggering this enzyme to make this reaction go through. That's the key point. And you can see that working or not working on the test. I mean, how cool is that? So this person has three markers that are high under citric acid cycle functioning. So you know the mitochondria, right off the bat, aren't working well. We already said that they had low CoQ10, low magnesium. And then we're going to look at their B vitamin markers, which are all very low. That's a complicated subject. We probably don't have time for. But anyways, so you get the idea, right? And you can see there's also some brain problems with other things going on here as well.

All right, let's look at one more here. Let's see. We'd have right on time. Look at me now. If you were in the mentorship class, all right, you would be doing this every week with your own cases. I'm just saying that's what we do in class. We just look at lab after lab after lab. And those of you that are in class, there's probably a few of you listening to us that are actually in the class, you're probably chuckling and saying, "Okay, let's get over yourself." You know, but let's see. Okay, amino acids. Remember we started off the talk, we talked about methylation, okay? So if you don't have enough methionine, you're not going to be able to methylate. If you don't have enough tryptophan, you're not going to be able to methylate. If you don't have enough glycine or serine, you can't methylate. Methylation is not just about B vitamins. You got to have that single carbon pool, which comes from amino acids. And similarly, in people who don't methylate well, you're going to typically have problems with homocysteine because, as we saw, there's a direct, you know, that's what's happening in methylation. In fact, I had two patients this week, high homocysteine, low methionine, obviously not methylating very well, okay? And why is that important? Because it ties directly to what we're talking about because glutathione, as an antioxidant that's protecting the brain, is going to be preferentially produced by all those compounds that could also help you methylate. So the more oxidative stress you have, the more damage that's going on with the mitochondria, the worse off your methylation is. Those two are the, those are the two most important body processes, right? Glutathione and methylation. And they're linked. There's a wonderful blog post from Dr. Mark, Mark Hyman, from a bunch of years ago. If you Google Mark Hyman glutathione, and he just lays it out. He's so good at saying things in plain English. He just lays out what are the two most important things in the body: methylation and glutathione. I'm just trying to show you the sciency part of it, okay? So you can interpret these labs, you can figure out what's going on, all right?

So this particular patient, again, we're looking at their citric acid cycle, and there's only one marker that's high, number 14, hydroxyl methyl. That specifically is a marker for CoQ10. So this person has a functional need for CoQ10. And the rest of that stuff wasn't that bad. Now, again, you see on this new, there's a different test, a different patient. You see glycine is low. Does that matter? A little bit. Why does that matter? Because we use glycine to help methylate. We also use glycine. See how low glycine is there? We also use glycine to make what? Who knows? Somebody tap into the little question box if you know what is glycine the most famous for in terms of what it helps you make? Does anyone know that? Glycine. Let me see if anyone's got it. Oh boy, that's great. Okay, Constance. No. Daniel Hartman, 10 points. If I had a gold star, I would hand it out to Daniel Hartman. Glutathione. So glycine. But there's a lot of answers that are right for glycine. But glutathione is made from glycine, cysteine, and glutamine. So if you're low in glycine, you see this marker here, pyroglutamate is high. That's one of the key markers for glutathione. If pyroglutamate is high, your glutathione is low. If your glycine is low, you can't make glutathione. Does that matter? Yeah, because that's what's protecting the mitochondria. You know, you're, as we're just sitting here today, your body right now has about 30 grams, 30 grams, not milligrams, 30 grams of glutathione just floating through your bloodstream. Just think about how much that is. I mean, if you ever bought a gram of cocaine, if you've ever taken, that was a joke, by the way. If you've ever, um, if you've ever, like, if you take a 500 milligram pill, right? Imagine 500 milligrams of any capsule that we sell. Imagine 60 of those. That's 30 grams, right? That's how much glutathione is floating through your bloodstream right now. And your body burns through three grams of glutathione every day. And that's a healthy person. The sick patients we work with, who knows how much glutathione they burn through? So eventually, it burns out, and you get high pyroglutamate. That means there's not enough glutathione left. The glycine levels are low in this patient. They can't make glutathione anymore, okay? So it's gone from, "I can't methylate, I'm making glutathione" to "I can't even make glutathione." That's as bad as it can get for the human body because if it gets bad enough, cells start to die. And that's what's happening in our patients' brains who have these problems. That's why environmental toxins are so dangerous and so bad, okay?

Let me see. We've got time for maybe one more case, and then we'll do some questions. Let's see. We've got one more here. These are all Ion Panels. These are all from Genova. You can do the Neutrovals, they're basically the same. So if you were in a class, then you would be looking at these cases every week, right? So doctors submit cases like this. 64-year-old, divorced, blah, blah, blah, like to lose 10 pounds, healthy lifestyle. What's going on? This one's depressed and has arthritis. And then we do, you know, we do more than just these tests, obviously. We do gut testing. Oh, there's a gut test right there. We do gut testing and look for infections in the gut and all these other things. But here's the portion of lab we want to look at, okay? So amino acids are looking pretty good. That's nice. Some of them are high. That's for another day. We talk about that. Oh, wait a minute. Homocysteine is high. Pretty high, 14. That's not good, right? Magnesium levels are normal. I'm not worried about that. CoQ10 levels are high. Taking CoQ10, obviously, a little too much. The omega-3s are low. So now we know membranes are not working well. Why does that matter? Well, remember back to our little diagram here, that enzyme. Last time I checked, that enzyme that helps you make energy. How much energy? 4.7 billion units of ATP in one second in one brain cell. These enzymes are working hard, okay? Really hard. That enzyme's sitting in that cell membrane. You don't have the threes and sixes, the omega-3s and sixes. That is sitting in a messed up membrane. It's not going to work right, okay? So that's pretty important. Some membranes are pretty important. And then we're just kind of scanning through the test for our purposes of the class here. And we're looking at the citric acid cycle. Oh, perfect. Look how high succinate is. So what does that mean? The succinate dehydrogenase enzyme ain't working. You're not taking that succinate and converting it to fumarate. And look how low fumarate is. It's undetectable. There's a perfect example. I should save this one. Succinate is high, fumarate is low. Not only is it low, they couldn't even measure it, okay? So what does that mean? It means that this enzyme is not working right. And remember that B vitamin, that FADH, moving the electrons down, that whole thing's not working. The, the membrane is not working right. There's not enough for the B vitamin to grab succinate and make fumarate. So what's going to happen? You're going to stall out energy production right there. No matter how much you breathe, or how much you give someone CoQ10, or how much magnesium you give, if you don't give them that B vitamin, I think it's just going to be stuck forever. And when people have really bad versions of these things, like succinate dehydrogenase enzyme problems, they get pretty sick. They get neurological symptoms. They're going to, we have this one person in class, they have seizures, they have, you know, pins and needles and paresthesias. They can have all kinds of pretty severe problems. It's not just depression and fatigue, you know. This can go on and be much more dramatic than that, okay? And then we're also looking at, uh, let's see. We have time for one more. Let's do one more. I believe in volume of testing too, you know, just looking at one lab is like not enough for most people. So here's another case. Again, these are out of old case cases from old classes that I taught. But just, you know, when you're in class, when you're in the mentorship, you submit the case, but then you also tell us like, what treatments did you try? What problems are going on? So you can really do a workup that's helpful for you and your patient, okay? So now we look at the amino acids. Not so bad. They all look pretty good there. And then we're kind of hunting for mitochondrial problems here, right? So let's see. Um, okay, glutamine is low. So remember, what do we make glutathione from? Glutamine, cysteine, and glycine.

So if that's low, we just got a question mark about glutathione. Magnesium is low, so right away you know the mitochondria are not doing that great. CoQ10 is normal, not worried about that. And then we're going to look at the fatty acids are not so great. They need some omega-3s to make their cell membranes stronger, right, and work better. And then we can look at the citric acid cycle. That's not bad, it's actually normal. Okay, so they still need magnesium, but the citric acid cycle part looks pretty good. And who knows, maybe this person is doing something right. Maybe they're eating really healthy food or they're doing something.

But here's, and I'm going to end on this one, then we're going to do questions. Okay, this is the most important marker on the entire lab, according to who. It's not my personal opinion. If I were you guys, I wouldn't trust my personal opinion at all because I don't know. What do I know? I'm just some guy that grew up in Berkeley, California, and likes to ride bikes. But Dr. Richard Lord invented this test, and he has told me on multiple occasions and forced me to memorize the fact that sulfate is the single most important marker on this entire test. If sulfate is low, it's the worst thing that could happen. It's the first marker I look for anytime I get one of these tests. And why is it? Because sulfate or sulfur is the key indicator for low glutathione. If sulfate is low, glutathione is low. Why does that matter? Because glutathione is a master antioxidant. It protects your body. It's more important to your body than methylation is, and methylation is pretty darn important. And according to Dr. Everybody, right, to Dr. Lord, or Dr. Hyman, to everybody, methylation and glutathione are the two key processes that keep us alive. If sulfate is low, glutathione is low. It's the worst thing that can happen to a human being.

So what do you give? Well, you look at the lab. In this case, they need glutamine, but probably more importantly, N-acetyl cysteine or NAC to get the sulfate up. You may even give a little glycine. Three grams to six grams of NAC, three grams to six grams of glycine, a little bit of glutamine in this case because the glutamine levels were low. Usually, glutamine is not as important. The main nutrient that you use to restore glutathione is NAC or NAC. You could also use glutathione if you want to get fancy, but N-acetyl cysteine has some real advantages. And you want to get that into the mid-range. It usually takes about six months to get it up one quintile to the right. So this person's probably looking at 12 months of three to six grams a day of N-acetylcysteine with some glycine and maybe a little glutamine to do what? To get their glutathione back on track. Does that matter? Yeah, super important. It's a master antioxidant, right? Is that going to help their methylation? Absolutely. It's going to help all these different body processes that we've been talking about.

Okay, so now we're right on schedule. I'm going to mention, uh, I'm going to go to questions. There's two boot camps coming up: Amino Acids and Vitamins, Functional Genomics. We've got a mentorship class starting. You guys can just plug away and sign up for everything that makes sense to you. And we're going to take a couple minutes and go over questions. So best way to take liposomal glutathione? You know, twice a day. Most people can take it, half in the morning, half at night. You can also use N-acetylcysteine and glycine. They have some really profound benefits. They boost glutathione also, but they have a wider range of effects. You know, because they can also help with what? Methylation. Remember, they're the precursors to the single carbon pool, so they'll help you with methylation as well as a bunch of other things.

Um, let's see. Oh, the, the boot camp. Someone asked about how much the boot camps cost. That's a very good question. Thank you for asking it. Now, you guys, if you know, don't tell everybody about this, but you guys get a discount on these for listening to this class. And if you go to the Canvas Institute homepage, click on classes, you will see Lab Interpretation Bootcamp, $749 a month for two months. So basically, it's $1500 bucks, and you get 20% off. So that's like knocks it down by $300. So it's $1200. It took me four years to put that class together. Can I just say that it's not an unreasonable price? Kind of underpriced a little bit.

A best time to keep CoQ10? Usually in the morning and at lunch because sometimes it energizes people a little bit. Um, let's see. Yeah, NAC plus glycine and glutamine is glutathione. And yes, we often see low CoQ10 in people on statins. That's a very common effect of the statin. And these low GGT, an indication of low glutathione? Well, certainly could be because glutathione's, you know, the supreme king of all those pathways. So I don't know specifically about that, but I wouldn't be surprised. I'm more of a specialist in the functional test, so I don't really correlate them with the blood work very much. So if someone has low methylation and low glutathione, then the whole point is to figure out why. Where's the oxidative stress coming from? Is it their gut? Is it environmental toxins? You have to, you know, do all the lifestyle changes and all those other things. And if your sulfate is low, you're going to use N-acetylcysteine to replace it, right, and bring the glutathione back up. You guys will all get a replay of this. Yep. I repeat the test every six or eight months typically. I don't feel like you need to do it too much sooner than that, you know. And I'll show you why you can use glutathione for all these things, uh, but I'll show you why cysteine is really good. Um, so I don't use glutathione very often. You can, not against using it. Um, yeah, if you do these tests while someone's pregnant, the interpretations are quite different because high levels of hormones are going to change all these markers. Okay. Yeah, so the boot camp is eight weeks. There's a live call every two weeks. That's why there's only four calls on there. Okay. And in between the two weeks, you have these homework assignments to listen to all the lectures and do all the reading. Yeah, so organic acids test is one of the most important tests for fatigue and depression, for sure. I put it in the top three. All right. Um, see, I'm trying to get to all the questions here. For the supplements discussed, let's see, six to twelve months. Yeah, so labs again are done, repeated every six to eight months. All right, let's see. And then I do work with patients on the phone. If you're a patient, you're listening to this, you can do a phone consult with my staff and get started. Let me show you here real quick before we wrap up. We've got a couple more minutes. I have the diagram back here at the beginning that's going to answer a bunch of these questions here. It is. So let me, let me make this bigger so you can see that I'm talking about. Hang on one sec. There we go. This guy here. Bigger. Okay, there we go. So there's your glutathione. It's going from being reduced glutathione to oxidized, right? That's where it's grabbing these electrons, right? The whole point is it's negating the oxidative stress by reducing the bad guys. But here's your cysteine right here in the center. So cysteine has the ability to improve your glutathione levels. Cysteine is critical for methylation. Cysteine is critical for every, you know, so many things, right? It's a very central and very critical. It's a mucolytic. It's, you, they're using it now in emergency rooms for COVID patients in various parts of the world. There's research going on for that. It's a really important central nutrient here. You can also use glutathione if you want. And here are the markers that we were just looking at on the test. Sulfate right here, goes high and then low. If you have a glutathione problem, pyroglutamate also goes high and then low if you have a glutathione problem. And you can also measure alpha-hydroxybutyrate. It goes high if you have a glutathione problem. So with this one test called the Ion Panel or Organic Acids, you can measure hydroxybutyrate, sulfate, and pyruvate glutamate and give it a very good indication what's going on with your glutathione. You can also measure then, right, cysteine, glycine, and glutamine. It also measures homocysteine and methionine and all the B vitamins. So you get a very accurate sense of what's going on. And if that's not enough, it measures oxidative stress in a variety of ways we didn't talk about. So you can see exactly what's happening in this picture for a patient and get a really comprehensive program put together.

But I'm going to wrap it up now. But the take-home message here, right, is where we started, which is that there's this process called methylation, and that's really, really important. This is a process called the production of glutathione, which is even more important. It's the most single most important thing that happens in your body to prevent your cells from dying. Is if oxidative stress gets too high, the cells die, including the brain cells. In order to prevent that from happening, your body has a very flexible moment-to-moment, millisecond-to-millisecond ability to crank up glutathione. It can't just crank up vitamin C because you got exposed to oxidative stress three seconds ago, but it can crank up glutathione. As you make more and more glutathione, you're able to make less and less. You're able to methylate less and less. Okay, these processes are competing. So you're either going to transmethylate here, okay, and do the methylation things, or you're going to pull down to transsulfuration and you're going to do the sulfur compound thing down here. You can't do both at the same time fully, right? So when there's a lot of oxidative stress, the thion is going to go up, eventually it's going to crash. If sulfate is low, it means you've already gone through high levels of glutathione and it's low now. It means a long time ago you stopped methylating really well, okay, and now you've got some serious, serious problems, right, with the brain. So anyways, that's kind of the take-home message. You can measure all this stuff. You guys are interested, you can sign up for some courses with us. And otherwise, we'll be doing more of these mini-series coming up in the near future. Okay, take care everyone. Talk soon.