Mentorship Miniseries - Understanding Fatigue and Mitochondrial Energy Production

Hey everyone, and welcome back to our uh mini-series. This time, we're going to talk about fatigue and mitochondrial energy production, specifically the electron transport chain, kind of breaking it down to where all the action happens. And then how you can prescribe CoQ10 and magnesium to make that whole system work better.

So, we are going to jump right in. I'm going to talk for a little while with some slides, and then I will show you some labs for a little while, some really interesting ones actually I found. And then we'll have some questions at the end. So, if you have questions, you can type them into your little box there. I'll look down at the end. And, um, yeah, I'm assuming my sound is working, you can see the screen. Last time we had some technical problems, but I, I think I've sorted myself out.

So anyways, if this is the first one of these that you've been to, my name is Dan Kalish. I've been doing practicing functional medicine since 1992, which is a long time. I've been training people since, I don't know, '95, '96, kind of early on. Started working with Dr. Timmins, Bill Timmons, and training practitioners in the early part of my career. But some really great teachers, and fortunate to have been running this training program dedicated basically to teaching lab analysis skills. That's kind of always been the thing from the very beginning. I've done some research with Mayo Clinic, we're working with Richard Lord. Been in practice for a long time. We like to do these mini-series to educate doctors. And then we have tiers of classes, right? So we have these free mini-series like you guys are listening to now. We have these boot camps that are kind of, you know, moderately, mildly priced, affordable, uh, classes, kind of low emotional commitment. They're only two months long, eight weeks. You could do anything for eight weeks, right? And we have two of those coming up: Telehealth Business Essentials Boot Camp in August, the uh, Cardio Metabolic Health Boot Camp in September. You get some discount of 20% there if you use those codes for listening to this. And then we have my full year-long mentorship, which a few of you, I'm sure, will sign up for. That'll be starting in the fall as well. If you're really committed, you want to put a year into learning how to do this stuff, that's really what the mentorship is for.

All right. And so this is a little complicated, but we have a lot of slides to kind of make sense of it. And I guess I would just start off by framing kind of like the biggest picture view of this. What we're going to try to figure out today is how electrons move and bounce around, and how they're eventually captured, grabbed, literally grabbed by the electrons are grabbed and the little orbits are grabbed by CoQ10 and then shuttle through this amazing thing called the electron transport chain. So the electron transport chain is named for what it does. It's transporting electrons. Like you might call a highway a car transport chain, right? It's transporting cars. It's pretty cool how this works. And, um, a lot of times it doesn't work right. And, and the most common complaint, I'm sure all of us have in our practices, is fatigue and weight gain. And that's kind of what we're talking about, right? This is like a core, kind of central component of metabolism. And, um, I don't know, you can fix it, you can test for it, and you can fix it.

And so we learned all these things in high school, maybe in college, maybe in medical or naturopathic or chiropractic or acupuncture school. You took some physiology courses. So we're going to review some of the basic physiology because it actually matters in this situation. And then I can think of this almost as like applied biochemistry or applied physiology, really. Um, and then there's just these are just like notes of things that you should just remember and and and know. And if you don't know, then you kind of remember from when you were in school. And and then this is not like, you know, kind of school information just because it's interesting. This is cool information because if you know this clinically, then you can really help people, right?

So number one, the electron transport chain takes place within the mitochondrial membrane. That is like, we could just stop right there. You guys could just think about that and and take that into your practices. So let's say it again: The electron transport chain, where is it happening? It's physically happening within a membrane, okay? And these membranes are all fatty acid derived, right? And these membranes are fat made of fat. And so fat-soluble antioxidants really matter in terms of protecting the structure that houses and sort of uh, provides a place to be for the electron transport chain.

So the other thing, this is like confusing because there were big things about glucose, carbohydrate. The citric acid cycle primarily is burning fat. And then this is this like a, just to kind of make you think hard, mitochondria make fatty acids as well as burn fatty acids, which is trippy. And that's kind of a new research finding. That doesn't matter too much other than except for that when there's not enough mitochondria present, when there's not enough mitochondria present, their contribution in terms of making fatty acids can make a really big difference for some people, okay, in terms of energy. And then the energy made from fat in a fat-friendly place, right, right. So we're making energy from fat in a fat-friendly place, the membrane that relies on the fat-friendliest molecule in the body, CoQ10. So CoQ10 is like more of a fat than most fats are. It's 50 carbons long, which means it's incredibly fatty-ish. And when you see it in the fatty membrane, you realize, okay, this is all fat-based. We're burning fat, we're using fat. And so patients that are on really low-fat diets could get into a little trouble if, if they're not too careful.

And then we just start right off with like, how do you fix this stuff? What we want to use is CoQ10, magnesium, and oxygen. Oxygen is breathing exercises. So that's the lifestyle change. And then we're going to get into detail on the CoQ10 and magnesium. And sometimes you can't just supplement magnesium. And we're going to talk about magnesium's relationship with glutathione, okay? Because in people who are low in magnesium, have been taking magnesium for years, it's never really helped them, they almost always have a glutathione problem. So magnesium and glutathione are tied together. And magnesium won't work for our purposes today in terms of improving energy production if glutathione levels are low. So as soon as you see or suspect a magnesium problem, you go right to the glutathione markers and figure that out. And then CoQ10 has many ways to figure out how, you know, if, if you need to supplement with it or not. I'll show you all those. But then the other bigger picture thing then is that the, the very, um, act of making energy generates oxidative stress. And so we have to take that into account with all these programs as well.

In terms of what magnesium does, it regulates hundreds and hundreds of enzymes. In fact, Dr. Lord and I were just doing a recording today on magnesium. And he, a direct quote from his talk this morning: Calcium and magnesium are the body's central regulators, period. Calcium and magnesium regulate muscle contraction, nerve function. They're, they're just absolutely critical. And it's very common for people to be deficient in magnesium. So that's going to destabilize all these different systems from the brain to the DNA to the energy production, all these different things. And so I know when I was working with the naturopaths and being trained in the '90s, I mean, Dr. Glenn, he just gave everybody magnesium. Now he's just basically walking that it was just a matter of what form of magnesium he gave. Almost every patient, magnesium. And Glenn's one of the best doctors I ever met. Didn't do any lab testing. He just figured out what was wrong with people, you know, in his own, with his own methods. But, um, magnesium and B6, that was just like what we sold just about everybody. And now I can appreciate why, because you can fix 300 different things with one supplement, 300 different enzymes that could be messed up, you can fix it all with magnesium, okay?

So if magnesium is not working, again, we're thinking about the magnesium-glutathione dyad. Okay? The major source of oxidative stress, reactive oxygen species in the body, is from mitochondrial energy production. I'll say that again. So most of the oxidative stress in the body comes from us making energy. So you get too much of this stuff, it's bad for your blood vessels, it's bad for your DNA, it's bad for everything, right? And then if you get too much of these, you know, uh, too much oxidative stress, you can have LDLs getting oxidized and you get plaque development. And glutathione, you know, some similar things happen to DNA, right? Too, if you get oxygen, too much oxidation, DNA gets physically structurally damaged. You get what they call DNA adducts. And then the DNA doesn't lead to, you get abnormal cell replication, which is what we call cancer, right? So these are these are major issues, right? Heart disease, cancer. And glutathione is standing between your body and the death of the cell. The, what prevents cells from dying from oxidative stress, from too much oxidative stress, is glutathione. There's other antioxidants, obviously, but glutathione is the really big important one that matters the most.

So the short version of this story, and you can read about this in Dr. Lord's book in much more detail, okay, if you want. His book is Laboratory Guides to Health, Laboratory Guides to Health, Richard Lord. You can buy Dr. Lord's book from wherever you buy your iBooks or iTunes or those kind of things. It's a book you can read on a computer, okay? And basically, if you have a person who's low in magnesium, and you give them magnesium, but they're also low in glutathione, the magnesium will not be able to increase cellular energy production because the body knows that there's not enough glutathione present. And so it limits energy production because it doesn't want the cells to die. If there's a choice between cells dying and making energy, your body will choose to not make energy to preserve the health of the cells, okay? So that means that if you have low glutathione, magnesium won't have its intended effect. And all the research on this is in Richard's book, if you want to study the study the study the studies behind all this, okay? But the short answer from the clinical version of the of the problem is that if you give magnesium and it's not working, you have to check glutathione and fix glutathione. If you give glutathione support and it's not working, you have to check magnesium. You have to use these two in concert, or the programs don't work. So magnesium requires glutathione to work. Glutathione requires magnesium to work. They have to be done together.

And this is just a nifty little diagram on how you make glutathione, right? So you take glutamine, cysteine, and glycine. Those three amino acids come together in a really happy place and you make glutathione from them. And that's kind of a miracle that that even occurs. But that's the production of glutathione. And you got to kind of memorize this, okay? So let's say that again: glutamine, cysteine, glycine. Those are the three amino acids which you need to make glutathione. Because glutathione takes on such a central role, if you ever see a lab marker that indicates low glycine, low cysteine, or low glutamine, then you should panic a little bit and think, oh gosh, this person probably can't make enough glutathione, okay? So glutamine, cysteine, glycine. I use usually cysteine is supplemented in the form of NAC or N-acetylcysteine. Very few people prescribe actual cysteine. It's almost always NAC, right? So I prescribe NAC, L-cysteine, glycine, and glutamine. At least half of my patients, maybe more. At least half. You see this problem so often that maybe three quarters of my patients get one or all three of those amino acids, okay? It's super common to have problems with that.

Now, again, I just said that's already. I say one more time: primary source of oxidative stress is the mitochondria. At the same time, excessive oxidative stress damages the mitochondria. You know, it's a questionably designed system. It's a little delicate, it's a little sophisticated. And what we don't want is excessive free radicals. And you can measure all these oxidative stress things when we look at the labs. We can, I can point those out. But you can measure whether DNA is getting damaged. You can either measure fat-soluble antioxidants, water-soluble antioxidants, you can measure ATP, you can measure oxidative stress up and down in a dozen different ways on these labs. You can see it, okay?

And then just to keep this in mind too, that we talked about magnesium and glutathione, but there's also this combination of glutathione and methylation. So the body has this other competitive system going, right? Where you're either going to methylate or make glutathione. Every second of your day, of your life, your body's prioritizing: Am I going to methylate? Am I going to make glutathione? Am I going to methylate? Am I going to make glutathione? If, and the body, when it needs to choose one of these, always would choose the production of glutathione over methylation, okay? So let's say that again: You always are going to preferentially make glutathione, and you will do that at the sacrifice of methylation. So if you see a glutathione problem and glutathione levels are low on the lab, you by definition have long past the point where methylation was a problem, right? Methylation has been dragged into this for sure, for sure, for sure, because your body is going to prioritize and make glutathione and sacrifice the process of methylation. And what dictates that is oxidative stress. So if there's a normal amount of oxidative stress, your body methylates away and it makes plenty of glutathione, and everybody and everything is happy. If there's too much oxidative stress, your body is going to need to make glutathione, and it's going to sacrifice the whole process of methylation. It doesn't matter if you're MTHFR, what your genes are doing, okay? You could have the whole genetic component with methylation or not. It doesn't really matter. If your glutathione levels are low, methylation is going to shut down, okay? And it's not a genetic problem, right? That's just an oxidative stress problem. So that's super important. Magnesium, glutathione, glutathione, methylation, those are all tied together.

Then we think about, you know, oxygen. And this is an easy message to talk to patients about because everybody understands that it's important to breathe. People usually don't think of oxygen as a nutrient, but it is, right? So the three major nutrients we're talking about today: oxygen, magnesium, and CoQ10. And they're all essential to life. And the mitochondria are so important, they're consuming almost all the oxygen that we consume. So the reason why we're breathing, to a large extent, is to get the oxygen down into the mitochondria. And that's the final step of the electron transport chain is oxygen, okay? That's the final step. So these electrons are bouncing around as we metabolize our food, and then they're ending up binding to oxygen. And this is the reverse of what happens in plants, right? Plants generally are outside living their little plant lives, right? And they're taking in sunlight and water and stuff from the soil, and they're creating energy, right? Through the process of photosynthesis. Then we eat the plant, or if you eat animals, which I do personally, I try not to eat animals, but I really like animals, so I eat hamburgers and carnitas and fish and stuff. But if you eat animals, the animals got their energy from eating plants in general, right? So either way, it's originally the energy's coming in from photosynthesis. It's going into plants, or going into animals from plants. And then we're freeing up that energy that the plant created or that the animal absorbed from the plant. So we're breaking that energy down. The plants are building it up, right? And it's all about electrons. So we're like literally eating like sun rays, right? And then breaking those sun rays down to make this energy that we're talking about.

And then here is where it all happens. And and here are the things that you kind of want to know to make sure this works. And there's earlier talks that we've done on glucose and glycolysis and how you take carbohydrate and make acetyl-CoA. And then also, you know, fatty acids and how you take fatty acids through beta-oxidation and make acetyl-CoA. A couple of side notes: one-third of the fat that we burn, that we have, is made, uh, is is from dietary fat. Two-thirds of the fat in the body that we're using is produced in the liver by the liver, okay? So just to point out that fatty acid functions, metabolism have a lot to do with liver function. Hence, when this goes bad, is what we call fatty liver, right? The fat builds up in the liver. That's not a good thing, okay? And then acetyl-CoA is ultimately what we're concentrating everything on in order to make our energy. And all during this process, things are flying around, the NADHs of the world and the NADs and the FADs, right? And electrons are bouncing around. And eventually, what happens is we get the energy into the citric acid cycle, and this thing spins around, okay? And then we get up to here, the electron transport chain. And now, where are we? We're in the mitochondrial inner membrane. So this is the membrane, see that? What I'm circling there, that's the membrane. What is that made out of? Fatty acids, okay? And embedded in those fatty acids, embedded in that membrane, is the electron transport chain. Remember this from school: Complex 1, 2, 3, 4. And then Complex 5 is a super cool one. It has like this rotor thing on it, like a windmill, right? And so the process is such that we're breaking down all these electrons, things are flying around, we're pumping up protons up here, okay? You can see the protons up here, H+. And then eventually, there's so many protons up there that the protons rush back down through Complex 5. They're H's, right? They bind with oxygen and make H2O or water and ATP, okay? So the electrons are driving the protons up here. The protons are swinging back on down through Complex 5, binding up with oxygen to make water, and then ATP, okay?

Now, this is all the story of electrons, right? From the moment that the photosynthesis thing hits the plant leaf, or you eat the animal, or whatever, we're all just talking about the flow of electrons. And what carries the electrons through the transport chain is CoQ10. It's represented here just as Q. Kind of cool, like it reminds me of the James Bond movies, isn't that guy named Q? The guy who was always giving James Bond like the secret watch and the, "Oh, by the way, this is a new watch I have. It was a gift for my birthday. It's, it's a very nice watch. I'm in love with my new watch." But they, it gives like, you know, the secret pens and watches and stuff. The guy's name is Q. So anyways, Q means CoQ10, okay? And Q, shall we call it Q just for fun, is shuttling electrons. And it's the only thing that does. There's not like some other thing that can shuttle electrons. So the electron transport chain is all about Q or CoQ10 pulling electrons from one of these complexes to the other. And this is so crazy, it grabs them one at a time. How do you even imagine that? Can you imagine the speed at which this is happening? It's like billions of times a second, okay? So your CoQ10 is like vibrating at some crazy rate, grabbing electrons and throwing them on to the next complex. If that doesn't happen, then you don't make ATP. So in my mind, oxygen is extremely important. And we can all tell that if we just take a breath and hold your breath for a while, you realize oxygen is really important. But CoQ10 is equally important. And so is magnesium, because magnesium makes this whole thing work, okay? So if patients are wondering, how important is it that I take my magnesium supplement? Well, it's about as important as breathing if you want to make energy, okay? These are not, you know, just supplements, right? These are the nutrients that are used to make energy inside the human body.

Now, here's another blow-up of the electron transport chain. And this one is nice because you can see really clearly that there's a membrane, okay? So here's our mitochondria, the outer membrane and the inner membrane. And the electron transport chain embedded in the inner membrane, okay? And again, there's Complex 1, 2, 3, 4, 5, et cetera, et cetera. And eventually, we're making ATP. So again, we just want to think about membranes. And this becomes really important because membranes are made out of fat. And membranes can be damaged if you don't, if from oxidative stress. And you use, what use fat-soluble antioxidants to protect yourself from that damage? And it's going to be come in handy when we look at the labs. You want to remember that how do we protect these membranes? The membranes that house the electron transport chain, we protect them with fat-soluble antioxidants.

So here's another example of the same thing. Oxidative phosphorylation, okay, is a fancy way of saying it. And here we have our protons, our H+s, in that inner membrane space, intermembrane space between the inner and outer membrane. So here's the cell cytoplasm, here's the outer membrane, here's the inner membrane, and here's the electron transport chain. Where is it? It's embedded in the membrane. What's the membrane made out of? Fatty acids. What protects fatty acids from oxidative stress? Fat-soluble antioxidants. And this is cool because you can see the electrons going along here, right? And then the protons building up over here. And then eventually the protons build up so much of a concentration gradient, there's so many of them, see the high concentration gradient, that they flow down here, they spin this little water wheel looking thing, and then you make ATP, okay?

So then CoQ10 is moving the electrons along. Magnesium is making this whole thing work. You can't even really lecture on magnesium because it's doing 300 things. I'm trying to figure out a way to talk about it still. It's just that magnesium is doing everything, okay? 300 different things here. So it's hard to put together slides on that. It'd be like 300 different slides just on magnesium. But just, you got to imagine magnesium is doing everything all throughout these systems. CoQ10 is clearing electrons. Oxygen is turning into water, right? Because these hydrogens are all floating around. That's kind of the process that we're talking about.

So then you can test for lipid peroxides. That's damage to the membrane, right? Because if we're looking at oxidative stress to lipids, easy thing you can see isn't, is this membrane getting damaged or not? That's important, right? You can measure CoQ10 in a whole bunch of different ways. I'll show you when we look at the labs. And you can measure magnesium, at least, I don't know, I just counted six different ways quickly, so we'll show you those too, okay? Many, many data breaks. You can use mitochondrial function testing with organic acids. You can see the toxins building up causing oxidative stress. You can see the oxidative stress markers. Everything we're talking about can be measured on a lab. This should be basic standard medicine. Every doctor in the world should know about this. This is basic human physiology. This is not even really integrative medicine. This is just like human physiology 101, right? We should all know about this stuff and be able to fix these problems.

Here's the same example, the same thing. You've probably seen that one enough now. So all these complexes that are embedded in the membrane are proteins. And all proteins are made from strings of amino acids. So it turns out amino acids are really important. And here's, I don't know, this is one of my favorite enzymes. I don't know why. I just think it looks really amazing. So these are all, you know, when you're making an enzyme, you should string together amino acids into these alpha helices and beta sheets, and then the thing folds. It's incredible. It just folds on itself based on all the charges and which amino acids are where, right? You want to know something really strange? Is that all human proteins, except for collagen, forget about collagen, but all human proteins contain the same ratios of the same 20 amino acids. I'm going to say that again: All human proteins, except for collagen, like a protein that makes your heart, a protein that is, I don't know, like hemoglobin is a protein, thyroid hormones are proteins, last time I checked, right? Muscle protein. All human proteins, except for collagen, are made of the same amino acids in about the same ratios. Some create, I always imagine that there's different combinations, I mean, there's different sequences, but about the same ratios. That becomes clinically important because the amino acids that are present in large amounts, you want to supplement large amounts of, right? The amino acids that are present in small amounts are very, um, easy to be disrupted. Tryptophan is the amino acid that has the smallest sort of contribution to human proteins by, um, by, I don't know if you say it, by weight or by number, by percentage, okay? So anyways, this is a protein here. It's made up of 20 amino acids. Tryptophan makes up this protein. And if you're low in tryptophan, you can't make this thing. If you're low in glycine, you can't make this thing. If you're low in tyrosine, you can't make this thing, okay? And this, I picked this enzyme because it's really cool, it looks cool, and it has this complex role, right? Oh, that was kind of a pun, but I didn't intend it. It's a, it's Complex 2, succinate dehydrogenase. This is part of the electron transport gene and it needs vitamin B2 to work, okay? If you don't have B2, this thing doesn't work. And there it is, the enzyme embedded in where? The inner mitochondrial membrane. The inner mitochondrial membrane. Can you see how this little ribbony part of it here? You can see how it's constructed. It's really kind of a beautiful site. See this part here? Okay, that part here. See how just how long that is there? The length of that. Check it out. Why is it that just that length? And why is that thing bobbing on top? Look, because that's the part of the enzyme that sticks itself into the membrane. See this? There it is. It's in the membrane there. See that? Those are the ribbony things. And then the other part sticks up, okay? So this is Complex 2. It is also controlling succinate converting to fumarate. And that is something that is dependent on vitamin B2. In fact, when I'm circling right here now, that is vitamin B2 wedged into the protein portion of the enzyme, okay? And that vitamin getting in here is what allows your body to convert succinate to fumarate. And then you can see the little electrons here going down. There's the electrons going down. Where are they going to? Well, they're going to eventually get grabbed by ubiquinol. That's our CoQ10, or shall we just call it Q, right? Q is grabbing the electrons from Complex 2 and bringing them over to Complex 3. Amazing. And if you don't have the right vitamins in and nutrients like CoQ10, and this whole thing just falls apart.

Here's another example, that's the same enzyme. But now you can see it embedded in the electron transport chain. And this one is always a little confusing, but we measure this stuff, so you got to know this. Here's the, here's a citric acid cycle up top, right? You're familiar with this. Acetyl-CoA, citrate, isocitrate. This is a citric acid cycle. Complex 2, or the succinate dehydrogenase, this enzyme, right, is is involved in converting succinate to fumarate. So it's involved in the citric acid cycle. It's also involved in electron transport chain at the same time. That was so confusing to me for so long because I kept seeing this thing show up in two different places. It's the same enzyme, okay? And it's con, and this mechanism up here is controlled by vitamin B2. But down here, you need the Q to make it work, right? Q grabs the electrons from Complex 2 and throws them over to Complex 3. The rate at which this is happening is truly astounding. We calculated it the other day, Dr. Lord and I did. It's, it's billions of times a second. You're doing this. CoQ10 is moving billions of electrons, it's per second, it's incredible.

Now, here's another diagram, the same thing. You guys kind of got the point here. Here's a cell membrane with CoQ10 in it, okay? And it works sideways. It's not going up and down, it's working sideways. And this is just a reminder for me to think about because I knew at this point in the talk, I'd be really kind of, what do you call it, pigeonholing things and getting into this little niche thing. But just a reminder that we're not just looking at mitochondria, we're not just looking at CoQ10. We're talking about adrenal hormones, a neurotransmitter function, and sex hormone levels. And we're always focused on the gut, kind of pathologically focused on the gut. And then we're always thinking about detox capacity and getting the heavy metals and chemicals out, right? So just a reminder that this is all about systems medicine. We're just kind of honing into this one narrow area now. And that it also always includes a patient, for better or worse, right? It's a human being on the other end of this that you're trying to get better, trying to meet their life goals and get them better physically. And just, um, and that there's sequences for all these overall treatments that we teach, or I teach in the various classes, okay? So just to contextualize this a little bit. Now we're back to the regularly scheduled program here.

So one or two more things about CoQ10, and then we can look at labs, and then we can have questions, okay? So remember, how is it made? That's a hard question. Does anyone know what's the original starting point for the production of CoQ10? You know, and if no one, I'm going to give you guys like maybe, dude, like a few seconds to think that one over. Let's see if Robert's got it. Oh, that's so close. Robert said cholesterol. That's a very legitimate and very close guess. All right, let me show you guys. Hang on. I'm gonna skip slides here. Here it is. This is the origin story. My wife's cousin, who's a good friend of mine, always says it's origin stories, like when you're watching Marvel superhero shows and stuff. What's the origin story there? Acetyl-CoA turns into CoQ10. Acetyl-CoA turns into CoQ10. Where does acetyl-CoA come in? That was the very first slide, right? It comes from fatty acids and from carbohydrates, okay? So if you eat too much, you, you know, drink sodas or have too much sugar, you're going to have excess acetyl-CoA, which is going to lead to excess cholesterol. And so there's medications that are widely used, HMG-CoA reductase blockers, right? Their statins block the conversion of acetyl-CoA to cholesterol. But in the process of doing that, they also block the production of CoQ10. And they block the concept, or the mechanism, we might say, of protein prenylation, okay? Because the medications work up here. So what is protein prenylation? Protein prenylation involves this funny stuff called geranylgeranyl. And it is basically the system by which your body locates uh, proteins into cell membranes or mitochondrial membranes, for that matter, right? So your body makes the protein, and it has to then get it transported to the membrane, right? Protein prenylation is a transport mechanism for that. So that mechanism is disrupted if you disrupt, uh, acetyl-CoA, right? And then of course, CoQ10 being produced is going to be sacrificed as well. So that's just kind of an interesting little factoid.

And then here we are again. Acetyl-CoA, CoQ10. It's a really long molecule, right? 50 carbons long. Five of these carbon isoprene units, and each of them is 10 carbons long. So it's 50 carbons long. All these fatty acids that we're talking about that make up the membrane are like, what, you know, like 16 or 18 carbons long. This thing is like three times longer than a fatty acid. That's it. That's why I was saying in the funny, in the beginning, kind of funny way, it's more of a fat than the fatty acids are. It's this massive string of carbon, and it's jittering back and forth, slinging electrons around, right? Our good old Q here. Oh, and this is a whole other series of things. I don't know if we have time for this. Um, I don't know. I've had to quickly summarize it so we don't run out of time. But, yeah, and that's okay. We can skip. This is about coenzyme A. You don't really need to know that acetyl-CoA. But anyways, we should say, what is acetyl-CoA? So acetyl-CoA is an acetyl group or an acetate group with CoA, right? Coenzyme A. What's coenzyme A? Otherwise known as vitamin B5, or pantothenic acid, okay? And so it turns out that that's incredibly important. Pantothenic acid is this whole process working, right, right? So, um, just never, I always forget about pantothenic acid because it doesn't show up on the testing very clearly. So you just always want to keep in mind, pantothenic acid is super important. It's the CoA in acetyl-CoA, right?

So then mitochondria. This is the summary before we look at some labs. So mitochondria sustain damage from a variety of sources. Could be making energy, could be a lack of oxygen. Is there a worldwide pandemic going on right now where millions and millions of people are going to suddenly not have enough oxygen? Yeah, a little bit. So, you know, there's nutrient deficiencies, like a lack of magnesium would cause mitochondrial damage. Lack of oxygen from a respiratory infection would cause mitochondrial damage. Lack of CoQ10 from bad diet would cause mitochondrial damage. Oxidative stress from the gut, oxidative stress from deep, you know, toxins, environmental toxins, heavy metals, chemicals. Once the mitochondria are damaged, they can't make enough ATP. Patients come in, it's impacting their brain, their heart, their muscle tissues. They're just not feeling, you know, like they should. We run these tests, we can correct these metabolic disturbances, we can reverse the fatigue and weight gain and depression and all these other symptoms that, you know, you might not think were reversible. You know, and I, I've, I've been doing this 29 years, but I'd have to tell you guys, every day in practice, not every patient, that would be lying, but every day in practice, I'll have at least one case where I am not saying this, but I'm just thinking, I can't believe this worked this well. You know, I am still consistently shocked by how effective these lab-based programs are on a daily basis. In the old days, it was like every patient, I'd be, you know, blown away by it. But now, a lot of things I know, I kind of expect you to get better. That was easy, you know? But every day, there's at least one patient where I'm thinking, man, I can't believe that works so well. So I just want to encourage you to get more and more into lab interpretation because it never ends. The excitement here doesn't end. I have, I'm more giddy and excited about it now than I was 15, 20 years ago, because you just get better at it over time, okay?

And then a quick little advertisement, then we'll look at some labs. So if you want to improve your business, you want to make more money, you want to work less hours, you want to do something different with your career, or you're just starting a practice, Telehealth Business Essentials Boot Camp. It's if you want to start a telehealth practice, that's relevant, but it's also, it's relevant for any kind of practice building. It's just a business class, basically, financial planning, business planning. It's two months long, kind of forces you to deal with your business, okay? But it doesn't have to be telehealth oriented. And then the Cardio Metabolic Boot Camp is going to be starting at the end of September. And that's probably the thing I've been the most excited about. Richard Lord and I have been working on this actively for several years. I've got a tremendous amount of material from him that you guys can hear if you join that class. And it's going to be really cool. And you get a 20% discount if you use those codes, okay?

All right. So now let's look at some labs and try to remember these things. We can cut back and forth if you need to. All right. So let's look at this guy first here. So this is an Ion Panel from Genova. Use many other labs to do this. A lot of people also use the Neutral Vowel, which is almost identical to this test. I just prefer this format, but you could use Neutral Vowel if you want to give the same data, almost identical. There's a few markers that are different. Um, let's just, let's just skim through here and we can kind of riff on things that I mentioned. Now, I briefly mentioned, and this is like quiz time, just to refresh your memory, that glycine is one of the three amino acids from which you make glutathione. So glycine being low, that doesn't seem like a great way to start, you know, the first page of the lab test. And there's not any other amino acids that are low around it, right? Just glycine. Of all the amino acids to be low in, that's not a good one. Because right away, you're thinking, hmm, I wonder what's happened to this person's glutathione. And maybe it hasn't affected it, maybe it has. We don't know yet because we haven't gotten that part of the lab yet. All right, these are all my patients, by the way, that we're looking at. So let's, let's just scoot on down to the portions of the lab that matter. Oh, wait a minute, wait a minute. I'm just scanning for things that I just talked about. You guys see that glutamine low? Now that's not good either, is it? Because that's one of the amino acids that you make glutathione from. Now, there's lots of other things that glutamine does, but we're just trying to focus on this one subject tonight. So glutamine and glycine are both low. That's two out of three. That's not boding so well, right? And then I missed it, but let's look back now that we're kind of stuck on this for a second. Um, what happened to the cysteine here? Oh, cysteine was normal. So there's nothing there. But glutamine and glycine are low. That's kind of our first set of information. I'm just going to skip through the parts that we didn't really talk about tonight. And then here we go. Magnesium. Magnesium is low, okay? So now you're thinking, hmm, I could give them magnesium. But wait a minute, the latest research shows there's a magnesium-glutathione dyad. If I'm going to give magnesium and get it to work to help their cardiovascular system, to help their muscle spasms from not happening, to relieve their migraine headaches, whatever you want to use your magnesium for, does 300 different things, right? You're going to only be effective or be maximally effective in the use of magnesium if you support the glutathione. How are you going to support the glutathione? Well, we just saw they need glycine and glutamine. And then we get to CoQ10, and that doesn't look very good either. So how would you feel if you were missing magnesium? So 300 of your enzymes are subpar, and you didn't have enough CoQ10? So that little billions of times a second electron shuttle thing ain't happening. You just feel like crap. You would have to, there's no way you could feel good with those two nutrients low. It'd be impossible. You'd have to be crazy to have that happening and still feel good. Now, this is a rather dramatic example, but it's a good example. And I just, my staff just randomly sends me these, right? So I just say, send me some tests. And all five of the fat-soluble antioxidants that are measured are low. So how would you feel if you were a cell membrane, right? You're just trying to live your life. You're like a cell membrane, maybe you're a mitochondrial inner membrane, and you're trying to take care of your electron transport. You're like, okay, guys, go for it. Let's make energy. Now, and then you have no protection, no vitamin E, no vitamin A, no beta-carotene. All the fat-soluble antioxidants just disappeared on you, and you're just taking oxidative stress hits constantly. Your membrane is just getting shredded, right? That's what is happening to this person. Not enough fat-soluble antioxidants to protect the fats. Lipids. Lipid peroxides is a direct measure of, are the lipids being damaged or not? And this marker is high. So the answer is absolutely yes. Low fat-soluble antioxidants, lots of lipid damage. That bodes poorly for anything that's related to a cell membrane or a mitochondrial inner or outer membrane, which is what we're talking about now, right? We kind of skip some of this other stuff we're not talking about. And then I said I would talk about, there's all kinds of other ways you can measure or test for CoQ10 in addition to measuring CoQ10. So here's another couple of ways. If you see high pyruvate, that's, or or high lactate, even more so, that's a sign that you're low in CoQ10. If you see problems with the energy production markers or citric acid cycle markers, especially hydroxymethylglutarate, that's a problem with CoQ10, okay? So there's literally a half a dozen different ways you can see CoQ10. And remember, magnesium is involved in all these different steps, especially within the citric acid cycle. So here's your magnesium right there, right? So if there's problems with this section here under citric acid cycle, you're also thinking about magnesium. And then there's a couple, three glutathione markers: alpha-hydroxybutyrate, pyroglutamate, and sulfate are all markers for glutathione. In this patient's case, alpha-hydroxybutyrate is high, okay? So that's a problem with a lack of glutathione, lack of glutathione.

So now let's just say that this patient has chronic fatigue, or they're depressed, or they had a cardiovascular event, you know, they had a scare with a heart attack, or they had some chest pain, or something happened to their cardiovascular system, not, not doing so well. Let's just do a quick little program design here, okay? Okay, we're right on time. So you would take this lab and you would think, okay, what are we going to do? What are we going to do? What are we going to do? Well, we want to boost up glutathione. And we could get kind of fancy about it, right? Because we could give glycine, 500 milligram capsules, perhaps. You want to get it up to three grams a day minimum. So three and three. You can give glutamine, 500 milligram capsules. You can also use them in a powder form, which would be a heck of a lot easier. And they both taste kind of sweet. So you might want to use them in powders. Why glycine and glutamine? That's how we're going to get our glutathione up because both of them were low. And they are two of the three amino acids you need to make glutathione. You could use glutathione too if you wanted. Then you're going to want to use magnesium. Some kind of chelated magnesium. Usually, they're around 100 milligrams a capsule. And give at least a couple, 300, 400 milligrams of that stuff. Now we got our magnesium covered, our acetylcysteine, I'm going to see our glutathione covered. And then, uh, oh, CoQ10. This person was low in CoQ10. Usually, that's like 100 milligrams, something like that. They were also low in vitamin E. Remember that fat-soluble antioxidants? That's usually 400 IU. So I give a couple of those. They're also low in vitamin A. I have a disaster here. I use the drops for that. Usually use around three to five drops. And then they're low and beta-carotene. And to say you do. And then always, always, always want to use a multi and extra B vitamins to make all this work, okay? So that would be this person's program. Getting the glutathione levels up here, getting magnesium back, restoring CoQ10, getting the fat-soluble antioxidants to protect those cell membranes, and a multi and some extra Bs. And this could be a patient that has a, you know, neurological condition with this kind of, you know, mitochondrial and fatty acid type damage. It could be a person who has, um, just depression, you know, a variety of things. And you probably would also want to give, and we didn't really talk about this, but some omega-3s. We'll put a question mark by that. Often times you'd use omega-3s, so you're getting the fatty acids up too, okay? So that's again, an example of a simple program you can design.

I want to show you one more thing just for a minute. Some of you may have seen this if you're students in the program. If not, you may have not seen this. So we have a wonderful, wonderful medical doctor who's in the class, and she submitted this for us this week at the Tuesday mentorship call. And so she developed COVID in 2020. And the lab on the left was done right after she had the COVID infection. She then entered into a many month.

period of not feeling well after the covid. When the first lab was done, a month or so after she was diagnosed with covid, she started a supplement program. Six months went by. The new lab on the right was just done recently, and it is, you know, after six months of treatment. And so I just think this is interesting because, you know, most of you probably haven't seen pre-imposed testing on a covid patient yet. And so she recovered from the covid acute infection, right, but had a lot of chronic symptoms. And at that first test, her homocysteine was high. It's normal after six months. On that first test, her magnesium was low. It's normal after six months. On that first test, her zinc was low. It's normal after six months. Okay? Just so you can see this stuff really works. This isn't like, you know, something I'm just making up. You guys can waste an hour of your time that you could be watching Netflix. Or, by the way, if you're looking for a great TV show, "Recreation" um, or even if you're not, you're just kind of stuck. If you don't watch TV, good for you. But if you do watch TV and you haven't seen "Goliath" yet, my partner and I are watching it. It is the best show. We both like it. So it's apparently a show that, you know, men and women can both get into. It's Billy Bob Thornton. It's just a great TV show, "Goliath," that's on Amazon. Okay?

So again, right after covid, CoQ10 levels, you can see where abysmal. And then what happened after six months of treatment with CoQ10? They came up. It went from the lowest quintile to the fourth quintile. Vitamin A was low. Low and behold, she took some vitamin A. It came back up. Very important vitamin A, right? For all kinds of things, not just for your eyes, for mucosal membrane tissues, all kinds of things. And let's look here at, we don't have time to go over the whole test, but I just want to show you maybe the markers that we're talking about tonight. So, and this doesn't take a rocket scientist to see on the left-hand side, there were a ton of high markers a month after covid. After six months of supplements on the right-hand side, massively improved, right? So mitochondrial function improved, beta oxidation improved, carb metabolism improved, energy production improved. Just, just wonderful changes here. I'm just pretty excited about. Okay. All right.

So now let's look at questions that have come in. All right, I'm going back up to the beginning. So the name of Richard's book is "Laboratory Guides to Health." "Laboratory Guides to Health." It's expensive. It's like three or four hundred bucks. It is 1200 pages. It is 30 years of work of the top scientists. Each one of those pages of the 1200-page book will take you days or weeks to read. It's very densely written, very densely written. It's not the kind of book you can just sit down and read at all. It's more of a reference book for when you really need it. Um, and there's so much information in there. "Laboratory Guides to Health." Now, I have been telling people you can only get it from, from iTunes stuff, but I guess it's available on, as a Google book too. Here, "Laboratory Guides to Health," Richard S. Lord. Anyways, you can search around for it, you can find it. Okay?

And then, yeah, so I, I'm very old-fashioned in terms of things, and I do use glutathione in my practice. But here's the thing is that you can use fancier, more complicated things. This is from Carol's question from earlier. You can use fancier, more complicated antioxidants to reduce oxidative stress. But if the person's low in glycine or low in glutamine, they have to have those amino acids in order to make proteins. What proteins? All proteins in the human body are require glycine and glutamine. All proteins in the human body require glycine and glutamine. So if you're using glycine, glutamine to improve mitochondrial function or make glutathione levels better, you're also going to be improving gallbladder function and toenail function. You're going to be improving function throughout the whole body because you need glycine and glutamine to make all proteins. Now, that doesn't mean that you should avoid other fancier antioxidants. It's just that the glycine and glutamine, if they're low, are primary. You can add extra stuff on top of that. But you can't give a fancy antioxidant like, for example, you can't give someone glutathione if they're low in glycine and glutamine as the main treatment. You have to give the glycine and glutamine. If you want to add the glutathione, you can do that. Why can't you? Because the main roles of glycine and glutamine are protein synthesis, not glutathione production, right? The main roles of glycine and glutamine are to make proteins. Which proteins? All proteins in the human body. So you're getting a global correction on proteins, protein synthesis when you give glycine and glutamine. If you want to add glutathione to that or add Protandim to that, you can. But you can't substitute, right? The fat-soluble antioxidants are E, A, beta-carotene, CoQ10, excuse, excuse me, that list that we just saw. And you can use N-acetylcysteine. It is my go-to supplement for raising glutathione. So you can absolutely use N-acetylcysteine. Okay? If you don't respond to supplemental glutathione, then you want to do, you know, one of these more complex tests. And remember about all these other variables, you know, there could also be an underlying stressor, an underlying reason why glutathione is being used up, chemical toxicity, heavy metals, things like that. Um, sorry, a little noisy here for a second. Um, if someone is on intermittent fasting, I wouldn't give them supplements on an empty stomach except for the amino acids, but not other things. They're going to cause an upset stomach. You can use cod liver oil for vitamin A for all kinds of other things as well.

And so, oh, how is she feeling after six months? So the doctor that I just showed you is feeling fantastic. I wish she could have heard her on the call. Yeah, so that program worked to bring her energy back and make her feel quite a bit better. Oh, Robert's asking a good question. Why do her lipid peroxides go up after improvement of fat-soluble antioxidants? All right, you guys. Oh, man, that's a good question, Robert. All right. Hey, I'm saying I know the answer to it. That's why it's a good question. I'm only reading the questions I know the answer to. That's a joke. I'm not, I'm trying to read them all. But let me show you guys here. So Robert's question is a really great one because he noticed something that I didn't talk about because he's smart and he's paying attention. He's thinking about this stuff. Let me show you the answer. And this is actually a really important clinical finding thing you should know. You've got to know this one, or you're going to get screwed up on these labs. So Rob's question here is, why did her lipid peroxides go up after improvement of fat-soluble antioxidant function? So let me show you the answer to that. This is super, super important. You guys should try to remember this forever. Okay?

So now look at the first test, Robert. See her fatty, her fats were low. See the saturated fats are low, and they came up. And you'll see also here, look how low the omega-6s were. And you see how the omega-6s came up. So here, here's the big picture thing you got to remember. This is so important because you're going to see this a lot. If the initial test shows low fatty acids, the initial test shows low fatty acids, low overall fats, then lipid peroxide, see how this one looked normal here, can look normal even when you have a lack of fat-soluble antioxidants. Why? Because there's not a lot of lipids around. Remember, those saturated, those polyunsaturated fats were all low on the first test. So that lipid peroxides on the first test is a false normal. When her lipids came up into the normal range, we're seeing a more, what do you call it, realistic or more accurate view of what's really happening. So, in other words, if you see low fat-soluble antioxidants and low lipid peroxides, you should just flip to that next page and be thinking, I wonder if she's super low in omega-3 or omega-6 fatty acids. Okay? So again, there's not a lot of fatty acids present to get oxidized on the first test. So that first lipid peroxide number looks okay, but it's not okay. As soon as you got the fatty acids up, then you can see the true picture. That's a really cool one. I'm glad Robert caught that. That's an important concept. You could totally misinterpret these labs if you don't know all these little tricks. That's why Richard's been trying to cram this stuff into my brain the last five years. Um, just to make this stuff work. All right, let me see if I can get a few more questions in. We got one more minute. Okay. Um, oh, Barbara said the book is worth the money and a great deal. I totally agree with that. Yeah. Um, it, it is absolutely like a go-to reference. You can, if you're doing functional medicine, you have to have that book. It's the lab book, um, of all lab books. How do you know which kind of magnesium? I usually use a multi-chelated magnesium or I use magnesium glycinate because it's less likely, it's less likely to cause diarrhea for people. You know, so persistent. Recommend specific recommendations for persistent post-covid brain fog? Yeah, do the labs and then just follow what the labs say. Totally worked for that doctor that we're talking about, right? Her energy levels were back to the point where she's almost giddy with energy. But it's all lab-based, right? Because you don't know how the oxidative stress or the damage or the lack of oxygen or the parasite infection is going to damage people, right? Whether it's covid or it's Lyme disease or mold or parasite, we just don't know what the damage is going to be until you do the labs. So if a patient is being treated for a cholesterol with a cholesterol-lowering medication, do you take them off it? Um, no, absolutely not. You know, I understand that a lot of primary care doctors are required by law, really, to prescribe by the rules that they follow to prescribe statins. So I think our job really is, through my job really is, to do the test and if the person is on a statin and would be very arrogant meaning to take them off it. You know, you say, okay, if you're going to take this statin, here's what your labs look like. So let's just correct for that with the CoQ10 that you need and the nutrients that you need. And obviously try to change your diet. But we're not, I'm not on a campaign to get people off of every medication. You know, I think that that can really backfire, you know, for a lot of people. A lot of people. Um, okay, so if you use NAC, do you also have to supply glutamine and glycine? No, not necessarily. But go based on the labs. You know, if the glutamine and glycine are normal, you can use N-acetylcysteine by itself and that can work really well. What about the mucolytic effect of NAC in the gut? Terrible for the gut long-term. Yeah. So if you're worried about that, just use the NAC for three months or six months, or you can give pure glutathione in and of itself. You know, that's totally an option. Best amino acid powder supplement? So I use Pure Encapsulations Amino Replete and I use Designs for Health Amino Acid Synergy. Those two, honestly, depending on which one is in stock because since COVID, to happen, the back orders are intense because the companies can't get, you know, raw ingredients. They're trying to make things as fast as they can. They just can't get stuff shipped to them. So I interchangeably use those depending on what's in stock at Fullscript. You know, do you need to wait to treat? No, you can treat these cases immediately as soon as you want. You know, you don't have to wait. How can you find a doctor that works with these things? You know, you can contact Kalishwellness.com and talk to our health coach Ariel if you want to find a doctor referral. Yeah, so this, the Ion Panel includes serum and urine. So it's organic acids combined with from Genova combined with blood work, right? All right, okay. I'm going to wrap it up. I think I got to most of your questions. We're right on time. Take care, everyone. And I hope you join us at one of these boot camps or I'll see you on one of these mini-series in the future. All right, bye for now. You.