Proteomics 101 - Amino Acid Testing for Building a Healthy Immune Response

Hello everybody, and welcome to Proteomics 101. I am Dr. Dan Kalish, and we're going to talk about amino acid testing for building a healthy immune response. Probably not the first thing that you would think of when you think of the immune response, but hopefully, we can convince you that this is the first place to start when you're building a healthy immune response.

Now, I should just do a quick sound check, make sure you guys can hear me. If someone could raise their hand, and then I will, thank you. I will relax. Okay, now I can relax. So, um, [Music] I thought I would start off with telling you the punchline of this whole thing. So, in case something happens and you need to go check your email or leave, even in the next five minutes, you'll get the main point of the talk. So, I'm going to start off with the most important thing rather than building up to the most important thing and telling you at the end.

So, the most important thing here is that when our immune system is activated, when our immune system is activated, and we get inflamed, and we make a whole ton of cytokines, and we have a cytokine storm, or maybe even just a cytokine drizzle, right? Then what happens is that we deplete amino acids. In order to do that, there's one really important amino acid that is how you make, uh, many of these cytokines. This is called tryptophan. And so, if you have a lot of, uh, inflammation, if you have a lot of tissue damage, and you're fighting an infection actively, then it could be any kind of infection. It could be a viral infection, it could be a parasitic infection, it could be a bacterial infection. It doesn't really matter, right? You're going to have this depletion of tryptophan, and that's going to limit, severely limit, your ability to synthesize proteins because proteins require 20 amino acids in order to be synthesized. And the rate-limiting step in the synthesis of all proteins in the body, except for collagen, is tryptophan. It's the amino acid that we have in the smallest amount in every single protein. So, if you looked at every single protein in the human body, you would see there's approximately the same amount by percentage of tryptophan in every one of those proteins, and it's the smallest amount of an amino acid in any human protein. So, it's susceptible to problems. And this explains so many different things in functional medicine about why people get one problem, at least, sixteen hundred other problems, because it really does matter. So, the whole rest of the hour, we're gonna talk about the background behind this, but that's really the punchline. And, um, [Music] we'll also look at cases towards the end. If you want to stick around for that, you are welcome to do that as well.

And so, who am I? For those of you that are new to me, um, Dan Kalish. I founded the Kalish Institute for Functional Medicine a long time ago, 2005, actually. I've trained thousands of doctors in how to do lab interpretation, how to set up practices. We have courses on business development. We have courses primarily on lab interpretation. I've worked with the Mayo Clinic, I'm doing some research. I've worked with Richard Lord, who's one of the original scientists that developed much of the work that we do in our field. And, a matter of fact, I had a two-hour talk with Richard today and a little pep talk for what we're doing right now. Anyways, and I've been IFM certified and have been seeing patients for a really long time. And, uh, 25 years of clinical experience. I'm, it's almost 30. This got to the age where I kind of try to downplay my age, a number of years I've been in practice, not inflate it, you know. So, um, getting kind of old. I'm almost 60, you know. I may look like a spry young person to you, but time has marched on.

And so, what are we doing here? We've got on March the 9th, a lab interpretation boot camp. These are our most popular classes that we offer on amino acids and vitamins. If you think this talk is interesting and you really want to learn how to, you know, interpret labs, these boot camps that I teach have a very similar format to what we're doing today. There's a lecture, and then there's lab review, lab review, lab review, then there's a lecture, and then there's lab review, lab review, because I really want people to learn how to interpret the labs. That's the whole point of, uh, the Kalish Institute, to understand how to interpret labs. So, if you're interested, you can register now. It starts on March 9th. You get 200 bucks off if you have that secret code GDAA22. That stands for Genova Diagnostics Amino Acids 19, you know, 2022. So, anyways, if you're interested in that class, go check it out. It's, uh, 12 weeks of amino acids, and it's like everything you ever wanted to know about how to do this stuff.

Okay, to the point at hand. This is the process we are observing. I already said this once, we say it again because this is the main point. You get an infection, it triggers inflammation, that depletes your glutathione. Okay, we're following that, right? And then it damages the mitochondria. Why? Because the glutathione are protecting the mitochondria. That's one of the main things that glutathione does. And then this is all happening. Your oxidative stress levels go way, way, way, way up. Okay? And you don't have the antioxidants, i.e., glutathione, et cetera, to protect you. So, then the gut lining can get damaged. We're not really talking about that, but just pointing that out. We're not forgetting about the microbiome. For those of you that are really into the microbiome, this is a, you know, for sure a microbiome relevant, you know, subject area too. So, you have to do GI testing independent of what we're talking about today.

And then the body then relies upon these adequate levels of amino acids to make antibodies. Antibodies are proteins. Antibodies are made up of 20 amino acids. If you're missing even one of those 20, your antibody production will suffer. Proteomics 101 says that in order to synthesize human proteins, all proteins in the human body, except for collagen, you have to have all 20 amino acids present. Okay? You also need amino acids, ironically, to make glutathione, and we'll look at that in detail. You need amino acids to support your anti-inflammatory process. That's our pioneering pathway and the whole tryptophan thing. And in order to make cytokines, and we'll look at that in detail too.

So, any acute infection can cause a problem. And in some cases, you can have an acute infection, and then the effects of that ripple out for years or months afterwards. Or you can have a chronic low-grade infection that generates a negative response over a long period of time. Similar process, really. One's a little more, uh, exaggerated, and one's a little more gradual. The weakest of weak links, you know. And I think that if there was like a complaint department, and you could file complaints about like how you felt about the design of the human body, I mean, I'd be first in line, and I'd be writing this one down first. I'd be like, "Guys, why, why did you make tryptophan so important and give us so little of it?" Just seems like a design flaw, major design flaw. Tryptophan depletion.

And then you could argue on the other side of this, then, "Okay, maybe the design department would go back, 'Well, yeah, but why did you guys design antidepressants?' Because antidepressants deplete tryptophan, and that was your idea, wasn't it?" So, we have a lot of reasons why people are susceptible to having reactions to chronic infections, or react, or long-term reactions to acute infections. And a lot of it centers around amino acids. And this is the weakest of the weak links. And it's not one that you think of in regards to immune function, even a little bit, right? You wouldn't wake up in the morning and think, "Oh, yeah, I'm gonna give this patient tryptophan because they have an immune problem." It would never even occur to you to do that. But when we go back to the basic biochemistry of all these pathways, you're going to realize, "Oh, gosh, this is actually kind of important."

So, infection triggers the inflammation that raises the cytokines that reduces the available tryptophan. Infection triggers inflammation, raises cytokines, that reduces the available tryptophan. And there's not much of it around anyways, right? Because it's the amino acid that we have in the smallest amount. Now, your serotonin is in jeopardy, okay? So, you're a little depressed, can't sleep well, that's one problem. Maybe you're overeating ice cream at night or whatever, you know, from low serotonin. However, it's protein synthesis that's even more of a big issue. Because you can have these localized issues that have to do with the serotonin being low, depression, mood problems, like that. But with the protein synthesis being on the rocks, you have global issues. And which proteins? We're talking about all proteins. All proteins.

I just put this as a summary thing. We're not going to be able to talk about this, but I just wanted to have like a summary slide so you can just kind of see where we're going. These are the supplements that you should know how to use in order to fix what we're talking about today. You should know how to dose these. You should know how to find who needs these and who doesn't. You should, it's just as important to me, find out who doesn't need something as who needs something, right? For example, if someone's, like, really low in omega-6s, and you don't know that, and you give them omega-3s, you're going to make them worse, right? So, you want to, you want to sort through these. But these are the main issues here as a summary. I don't even need to read them off, right? You can see them all. And we're going to kind of touch on each of these in the talk, but I just wanted you to get a little eyes-on kind of view of this so you can see where we're headed with all this.

So, the key understandings here are that amino acids have a role in protein synthesis. So, that would be making insulin, making hemoglobin, making antibodies, et cetera, right? And then amino acids also have a role in enzymes. All enzymes are proteins. So, it could be a cytochrome P450 enzyme that's for detox. It could be pyruvate dehydrogenase, that's an enzyme we use to regulate carbohydrate metabolism. It could be lactic acid related, lactate dehydrogenase. It could be a complex two or mitochondrial related, succinate dehydrogenase. So, if you have a problem with one amino acid, let's say tryptophan, it could be glutamine too, it could be any of these, could be any of the 20, but we're just kind of picking on tryptophan, so it's easy for you to remember. If you have a problem with tryptophan, you're not going to be able to assemble succinate dehydrogenase as an enzyme sufficiently to run your citric acid cycle, and that's what we call a mitochondrial problem. At the same time, you're not going to be able to make enough pyruvate dehydrogenase. That's a blood sugar instability problem. That's basically what we call insulin resistance. And your cytochrome P450 problems are going to pop up, and you're not going to clear toxins very well, okay? So, all that happens if you're missing one amino acid that's critical.

What we usually think, or at least I usually used to think about amino acids, was in their non-protein roles. So, if you're not a biochemist, but you're a practitioner, I would guess you're like I was for 25 years, which is that you thought about amino acids almost exclusively in their non-protein roles, because that's how we learn them. Glutathione production, you need glycine, glutamine, and cysteine. The inflammatory response, you need tryptophan for methylation. You need these five that I'll show you in a minute in the single carbon pool. So, we usually think about amino acids in their non-protein role. But it's important to think of them both ways. If you want to say which one is more important, any clinician would say the non-protein roles. Any biochemist, any person who studies human physiology would see the pro, would say it's the protein synthesis part that's way more important. So, it's just something to think about, throwing it out there.

They play roles in the neuroendocrine system and the GI tract, which we're not talking about today, but it's really important in detox pathways, right? You need all kinds of amino acids for all kinds of purposes. You need tyrosine and 5-HTP and glycine to make brain chemicals. You need amino acids to run the citric acid cycle. You need amino acids to heal and repair and turn over the gut lining. Glutamine is the most important one there. You need amino acids like taurine and N-acetylcysteine and and glycine for detoxification pathways. You even need tons of amino acids for methylation, and more than just methionine, I'll show you that in a minute, okay? So, they play a role across all these different factors, all these different body systems.

And then when I'm thinking about patients, I'm always thinking about this human aspect of the work, right? We're mostly, this is, oh, I think I have like one human slide here. Everything else is about the pathways. But, you know, we have a human being in front of us who's got symptoms, and they're not happy, or they wouldn't be seeing you. No one ever comes in and says, "Gosh, it's so great to see you, Dr. Kalish. I have depression, anxiety, and weight gain, and it's just really, uh, you know, great to be here." No, they're unhappy. They've got problems. They've got symptoms. And then we're trying to figure out the underlying cause. Is there an infection? Is there a toxin? Is it epigenetics or genetics? Is there a structural problem, an injury? Is it full of, you know, mercury, or full of Lyme disease, or who knows what they're going through? The underlying causes. And then we have to kind of bridge this gap. And so, the way that I always think about this work is, how am I going to explain this to a patient? And so, if you learn new concepts and then practice explaining them to patients, then you can kind of embody the work, I think, at a much more profound level. And then people will do what you want because you're a good communicator. So, I think the hardest part of the job for me, at least when I first started doing it, and I don't struggle, I'm pretty good at it now, I was going to say I still struggle with it, but I'm pretty good at it now, but that took 30 years to figure out, is just how do you communicate all this to another human being who's suffering so that they get motivated to do all the things that we want them to do? And so, I like to have models like this so I can show patients, "You're over here on the symptom side. I'm over here on the underlying cause side. Let's meet somewhere in between so we can get you feeling better, but also figure out really what's going on." So, you get people understanding about what your model is. And, you know, I'm sure each of you have different models that you use, but you want to write them down and show them to patients. And also, this doctor-patient equilibrium where I have my agenda, they have their agenda, and making sure that we're, we're working in concert together so you don't end up solving the wrong problem, and then the patient's not really happy. That doesn't really make a lot of sense.

So, um, standard treatment sequences also, you know, we do a lot of these different, um, uh, just sort of examples in my mentorship class that I teach, and we're just kind of pulling a piece of this out and talking about today. But I just want you to understand that, you know, I always look at these things in a context of all these different body systems and not just this one thing like we're doing today, amino acids. So, um, and a simple example, you could have a malabsorption problem. I had two patients yesterday with malabsorption, two in a row. And that could be their whole amino acid problems because their gut's not working, okay? So, it doesn't have to be, you know, limited to amino acids are the only problem, you know, it could be coming from the gut.

So, essential questions that we want to think about. The main roles of amino acids. We've talked about that. Protein synthesis. If someone ever comes up to you on the street and they look at you and they say, "This has never happened to me, but it could happen, right? What are the main roles of amino acids?" And you should not hesitate. You should just immediately say, "Protein synthesis." You have to practice that in case it ever happens. Protein synthesis, protein synthesis. The non-protein functions, we're going to get into in a minute. But I'm trying to emphasize the protein part because we're all as clinicians always on this other side. And we're going to talk about methylation, glutathione, a little bit on GI, and then maybe if we have time, a little bit on my. Methylation has to do with glutathione.

Now, I also like to group things just for clinical purposes, which would probably be upsetting to any of you that have a degree in biochemistry. But anyways, this is just how I think about them when you're actually doing treatments. There, you should scan the lab test and look for the three amino acids that are required to make glutathione: glycine, glutamine, cysteine. If they're not adequate, you got a problem, right? You should be able to scan the lab and look at the five that are related to methylation in a single carbon pool so that you know what those are. You should be able to scan and look for arginine and citrulline for nitric oxide production. You should be able to, gut lining repair is pretty easy because it's mostly glutamine. So, it's this one. And then cytokine production, mostly we're talking about tryptophan, okay? And so, as you look at these labs that we're going to do when we get to the second part of the class here, you're you're wanting to categorize, categorize each amino acid deficiency and try to throw it into a clinical sort of subheading or topic. Because when you add them all up at the end of the lab, then you're like, "Oh, well, that makes sense. This person has inflammation of the microvasculature." Which is kind of one of the few things that I've seen most of the long-haul COVID experts agree on is that patients have inflammation of their small, small, small blood vessels. Wouldn't that relate to nitric oxide? It's got to, you know? And say, "Oh, a person has low glutathione and a heavy toxic burden, wouldn't that relate to your ability to make glutathione?" So, these bigger picture, you know, things here. And I, whenever I look at any one of these labs, I want to check all five of these things. These are like top-line items that you just need to know: glutathione, methylation, nitric oxide, gut lining repair, and cytokine production. And when we're thinking about immune function, it just doesn't get more important than these things here. So many other things you can look at. We can't look at everything.

And what we're measuring then is the inflow and outflow of amino acids. Most of the time, this is done with blood tests. Here are the 20 amino acids that I talked about for a while, and you can see tryptophan at the very bottom there because it's the one that's the smallest by percentage. And then the non-protein functions, which we've already harped on. And they can see this is a nice little trait. I'll just show you real quick. So, we're kind of relaxing now. We're not thinking about proteins anymore. We're thinking about arginine and its relation to nitric oxide, methionine and cysteine and their relation to glutathione production. Here's a good one: glycine and its relationship to making bile acids, your gallbladder. So, you know, the list goes on and on. You can study this quite, you know, for years, you know, still keep learning things about how these work.

The protein functions of amino acids is where most people don't really pay attention at all, you know. I certainly didn't for 20, 25 years of my career until I met Richard Lord. And in 2015, this is one of the first things that he asked me about, and he clearly understood that I didn't understand. And so he took two or three years out of his life to convince me that proteins matter, basically, and that amino acids are critical. Any low amino acid is going to interfere with the production of proteins. And here are just some examples of what that could screw up: digestive enzyme production, the transport proteins like hemoglobin and albumin, structural proteins, hold us together, right? Hormones like insulin, defense, which is really probably what's on everyone's mind these days, which means immunoglobulins, et cetera. And then contractile proteins, so things that have to do with muscles. So, if you can't make proteins, your insulin levels are going to be challenged, right? You're going to not be able to make it as adequately as you might otherwise. If you can't make proteins, immunoglobulin production will suffer, and so your immune response will not be what it should be. And if you want to make a lot of antibodies, you need a lot of amino acids to do that.

And then if you take a step back and you think about the ramifications of that, it's that when we see patients, which is almost all the patients that I see, probably you too, that have multiple problems. They're tired, they have an autoimmune disease, they're depressed, they are in pain, physical pain, they can't sleep really well, and they have rashes or something like that, right? And it's not that they have completely different reasons for each of those problems to have occurred. In general, we want to say in functional medicine that there's an underlying cause. And whether that's genetically based, or related to an environmental toxin, or related to what their diet's been like, or whatever it may be, there's also just at the biochemical level of the cell, the concept that there can be nutritional deficiencies that affect all body systems. Maybe that's a way to think about it. You can have a nutritional deficiency like an amino acid deficiency or a B vitamin deficiency that's going to affect every single body system because they're affecting how all the enzymes and all the proteins work. And that's where you get into single solutions that solve multiple problems. And I see this every day in my practice, like literally every day in my practice. I don't practice every day, but I see it every day at my practice. I practice two days a week, so I see it two days a week, which is that. And this just happened this just happened yesterday. It happened, it happens every day, okay? So, I give a patient arginine and glycine because that's what the labs say is or the nutrients that are low. And then they come back in a month and say, "My sleep is better, my energy is better, my skin rash went away, and my joints don't hurt as much." So, and then in the old days, I would have thought, "Well, that's a little strange." But now I just think, "Oh, I guess that they were having a problem synthesizing proteins, and I just fixed that. That's a good thing." Okay? So, you can have a single solution like an amino acid treatment based on a lab test. And you can't guess about this, at least I can't. I don't know anyone who has the intuitive wisdom to look at someone and say, "Arginine, not glycine," or to say, "Oh, I'm pretty sure it's tyrosine, not phenylalanine." You have to do the testing. And the testing just immediately reveals all the things that we're talking about.

Okay, so then I've talked a lot about protein synthesis, kind of got that point. Now we're going to think a little bit about non-protein functions of amino acids and a couple of examples here. If the person is full of toxins, maybe they have a bunch of mercury in their mouth, or they drink a ton of coffee and drink a ton of alcohol, then they could deplete an amino acid like glycine. That's going to then not only impact their detox capacity, but it's going to impact their ability to make proteins. And what we're really taught, and so then that one deficient amino acid, glycine or tryptophan or whatever it is, could over time interfere and cause problems with hormones, problems with insulin, problems with neurotransmitters, problems with the gut lining, problems with the joints, and so on and so on. That's why these nutrients are so central because once the process gets in place and the deficiencies developed, the ramifications can be quite profound, systems-wide, across systems. And we kind of, kind of said that already.

So, I want to get into a little bit more detail. We're going to look at some pathways, and then we'll have time to review labs, okay? So, oh, and here's, this is the article I pulled this from. "Redox Imbalance Links COVID-19 and Chronic Fatigue Syndrome." But they have a nice little blurb here, which is a sort of functional medicine ask, so I thought I'd quote it here. You can see, uh, "In this review, we summarize the evidence that people with acute COVID-19 and with chronic fatigue syndrome have biological abnormalities, including redox imbalance, systemic inflammation, neuroinflammation, and impaired ability to generate energy, right, cellular energy, and a general hypometabolic state." That is like a summary of what we primarily look for in functional medicine. And some people who have acquired COVID and have recovered from it, either a severe or a mild case of COVID, have these long-lasting reactions. And why is that happening? And how can we assess overall human health to try to prevent that process from occurring in the first place, or to reverse it if it has occurred? And this to me is what functional medicine has been waiting for. We've been spending, we've all been spending 50, you know, my teachers go back two generations since the 1970s, you know, plus maybe 60s, even 50 or 60 years of understanding how inflammation works and how to stop it, understanding how chronic infections affect the body and how to reverse the damage of infections, understanding cytokines, measuring these pathways, looking deep, deep, deep into the mitochondria to figure all these things out. And now we have our moment to really share this with the world who needs it more desperately than ever before.

So, here we have viral replication leading to inflammatory cytokines. And you'll see in a different slide that tryptophan is right here. Tryptophan's what's helping this process along. So, the more inflammatory cytokines that you make because of viral replication, the more you deplete your tryptophan. And remember, there's only a little bit of it anyways, and you need to have it to make every single protein. Eventually, this is going to have a problem, you know. You're going to also have problems with inflammation and oxidative stress altering mitochondrial function. And then that leads to a whole host of other problems: problems with the blood vessels, problems with the brain.

There's another slide from that same study. And just again, mechanism. So, if you want, some of you, it just helps to see it right here. We have mitochondrial dysfunction related to viral replication. There also are studies coming out that showed that a person could have a past infection that was perhaps squelched for the most part, that flares up when their immune system gets weak in relation to COVID. Then you can have sort of these secondary responses. It may not actually be the COVID virus anymore that's involved in this whole thing, but there's some other low-level infection that was just sitting there, not causing problems, that's now been activated. I mean, eventually people will sort that out. For the current moment, it doesn't really matter because we're going to do the labs and fix what we see on the labs, regardless of what the actual source of it was, right? There's going to be oxidative stress. So, of course, we want to measure oxidative stress and correct for it. And one of the main, most important antioxidants is sitting right here, glutathione. Of course, you can also use vitamin C and vitamin E, etc. And important to note that the mitochondria, they don't really have a diagram in this one, but the mitochondria, the things, if you're hypoxic, if you don't have enough oxygen, that's going to impact the mitochondria and decrease mitochondrial activity. If you don't have enough glutathione or magnesium or CoQ10, it's going to decrease mitochondrial functioning, okay? And that's going to make people really, really tired.

And then here are the symptoms that they're talking about with the long haul, right? Extreme persisting fatigue, impaired cognitive function and brain fog, pain, can't exert, can't exercise, having headaches, lightheadedness, dysautonomia. And I think this one's super important: endothelial dysfunction. That's where nitric oxide comes in, okay? All these things kind of going together. Enough oxidative stress, cells start to die, people get inflamed, and all this bad stuff starts to happen. And so, in terms of interventions, we want to test for and correct mitochondrial function. We want to measure oxidative stress down to the level of which antioxidants are problematic. Is it C? Is it E? Is it glutathione? Fix it. You want to be able to use anti-inflammatories, the things, the curcumins of the world, you know, those types of products, SPMs, and all that good stuff. And you really, really, really, really want to understand endothelial dysfunction in these patients. How are those blood vessels working? And what can you do to repair them? Nitric oxide, nitric oxide, right? Very simple way to repair endothelial damage. And you can test for the nutrients that make nitric oxide, which are primarily arginine and citrulline, two of the amino acids. But actually, like Biotics, and the amino acid company are so, so into this stuff. And now, I know it sounds a little crazy, maybe, but this stuff really works. I see it every day. And it's so frustrating to see practitioners that don't know this. And it's such a simple thing to learn, you know? It really can change your practice if you get on board with this. It really can. It's, you know, I didn't learn any of this stuff until 2015. I'd been in practice since 1992. I'm seven years into this on a 29-year career, or whatever, you know? So, I'm kind of, was late to the party to figure this out. Maybe that's why I'm so kind of enthusiastic about it, because I hate to think of people waiting for 22 years to figure this out. And then, if I had known, if I had known the things that I am explaining today in my first year of practice, would have changed the trajectory of thousands of my patients' lives, you know? I don't even want to think about it. I want to go, that's a negative thought, but, you know, anyways, it's a motivating thought to get you guys to learn all this stuff if you can, if you're interested.

All right, so infection setup. Just the same exact thing. But now we're throwing in here's the pro-inflammatory cytokines, the IDO, remember that? Everyone studied that. And then here's our tryptophan, very susceptible, little innocent tryptophan, just sitting there. And if these pathways get activated, okay, you're going to make all these anti-inflammatory things. Your immune system is cranking up. But you can measure kynurenine, quinolinate, decolonate, you can measure tryptophan, you can measure neural inflammation on these labs. And that is kind of profound. You can see this, and then you can correct whatever is wrong. "Altered tryptophan absorption and metabolism could underlie underlying long-term symptoms in survivors of COVID-19." And, lo, just a quick quote here for you: "Low serum and muscle tryptophan levels, as well as elevated kynurenine levels, may be to blame for COVID-19's most common long-term symptoms such as depression, sleep disturbances, and fatigue." Makes biochemical sense.

Now, in terms of protecting ourselves against this cytokine storm or recovering from it, we have to think about glutathione. And then when you think glutathione, I don't know, do you think amino acids? Not really. I mean, you'd probably think N-acetylcysteine, but you don't think like globally. So, there's NAC, or cysteine, that's required. But we also need glycine and glutamine to make glutathione. And then, strangely enough, glutathione is in constant competition with the process of methylation, such that if we need to make glutathione, we will do that by sacrificing our methylation processes. So, if you need to make a lot of glutathione, you're not going to methylate very well. And these pathways, they're not just interlinked, they're co-dependent. That's big. That sounds negative. They're interdependent, completely. If you crank up the faucet on making glutathione, your methylation capacity will drop. That's the way your body's set up. And your body always prioritizes glutathione production over methylation because it's literally a matter of life and death to the cells. So, it doesn't get more important than glutathione in human physiology.

And, um, in fact, there's a great blog post and article that Mark Hyman wrote that I always quote because I read it, I was like, "Wow, that is so cool. He's such a smart guy." And it was, um, you can Google it later, Mark Hyman Glutathione and Methylation. And he's in there talking about the two most important processes in the human body for cells to survive, for us to survive: glutathione and methylation. We'll talk about them both. Now, glutathione is made from cysteine, glycine, and glutamine. If you're missing one of those, it's going to be harder to make your glutathione. So, these amino acids are important. And the glutathione is what is standing between you and a cytokine storm. It's protecting your mitochondria. It's protecting your body against these inflammatory reactions. It's protecting your body against a negative long-term outcome from an infection. And if you later on want to Google, please don't do it right now, but maybe right when I'm done talking, you can Google glutathione and COVID, and you'll see all these researchers throughout the world who are studying this right now. It's a hot topic, super hot topic for obvious reasons. And we can measure this stuff. Don't have to guess. Don't have to guess.

Talked a little bit about the single carbon pool. These are the amino acids that are required for methylation: serine, glycine, histidine, glutamine, tryptophan. You have to memorize that. You just look at it on a chart or something, okay? But remember that there's this overlap between methylation and glutathione. So, these two things are linked. And here's how that process works. There's a single carbon pool here, and you can see that this is how we methylate. But we have to pull those carbons from somewhere. I don't know, I always just think methylation was just about like folate and maybe B6, B12. And on a good day, I would think about methionine and choline and homocysteine. But never really occurred to me, where's all this stuff coming from? Well, it's coming from serine, glycine, histidine, glutamine, and tryptophan. Those amino acids are what contribute carbons to the carbon pool, a single carbon pool. And then the single carbon pool is what the methylation process is doing is moving around these carbons. So, anyways, you don't have the amino acids, it's not going to work.

Similarly, glutamine and the gut lining. Tons of research on this right now. You can look this up later. But in SARS-CoV-2 infections, there is a strong link between how people respond to COVID and whether their gut microbiome is in good shape or not. There's also a strong link between people who get SARS-CoV-2 and having gut problems afterwards. So, in other words, if your gut is not in good shape and you get COVID, the outcomes are not so great. If you get COVID, the outcomes for your gut are not so great. It can work either way. And of course, glutamine is the one that we're primarily thinking of there in terms of gut lining repair for the intestinal barrier. And a lot of patients that I've been seeing in my practice lately are suffering from either new gut problems that they never had, or old gut problems that have come back since they acquired COVID.

So, these are the pathways that I would look at if you guys want to kind of geek out on this a little bit later on: glutathione biosynthesis, cytokine production and tryptophan, methylation and the single carbon pool, the GI tract and glutamine. You're probably all pretty familiar with. And then just the concept of protein synthesis. So, you just kind of do a little refresher on it. And I certainly did when I first started to work with Richard. I mean, it's kind of interesting, you know, um, spend, go to the Khan Academy or some free website or somewhere. And lots of universities have websites that have tons of information on protein synthesis. And so, it's a fascinating subject. It's directly related to all the work that we do day in and day out, you know? So, it's not like, um, an abstract kind of thing, you know, it's, it's more like front and center.

So, now, um, I know that was a lot of information, but I want to kind of try to ground the whole thing now by showing you some lab examples so you can see how this plays out in real life. This is a NutraVal from Genova. And I want to thank Genova for helping put this workshop on very much. They have a great team, and I so enjoy working with them and supporting their cause as well. And let's see here. Oh, I gotta do one more thing before I do this. Sorry, sorry, hang on here. I have to do the final slide. I always forget the final slide. Okay. So, if you joined us late, Kalish Institute, we have an amino acid and vitamins boot camp coming up. It starts on March 9th. It's 12 weeks of talks by me about how to do this work, of case study after case study after case study after case study of how to apply this. I took all the common situations that I've seen in the last 20 plus years, the things that I see every day, put them into this class as case studies. You can learn all the things you have to, how do you deal with depression? How you deal with athletes? How you deal with chronic fatigue? How you deal with mental blocks, diseases, all the things that I just see day in and day out, all the things that I didn't know and which I know now, I put into the case studies. And we also have a whole series of lectures in here by Dr. Richard Lord himself. Who, if you have a strong, you know, biochemistry background, you will love. Um, even if you don't have a strong biochemistry background, you may not understand what he says, but it's really, really interesting, you know? And so, it's a great class. And if you want to join us, you get $200 off just for knowing about Genova Diagnostics and hearing this workshop. So, $200 discount, and the code is GDAA22. And we start that in about a week, and it's a 12-week course. There's six live calls where we interact and go over cases, and then there's all this case studies and lectures by Richard and I in there so that you, at the end of that, feel confident with starting to order these tests and interpret them. All right, okay, so back to our regularly scheduled programming here. All right, NutraVal. This, this first page, the summary page, kind of takes a lot of challenges out of the interpretation because you've got like a really, you know, bird's-eye view of everything that's happening. Green is me, not so great. Yellow is bad. Red is like, not good at all. So, the guy is color-coded for us too. And let's just look and see with this particular patient. Now, for patients who have had chronic infections that are being reactivated, that's one category. I'm just thinking of the category of people I'm seeing in the last six months. Patients that had chronic, that had old infections that I fixed, that have been reactivated for some reason, COVID, right? Patients who had problems that they never had had before after they acquired COVID, or patients who want to prevent problems from happening and they're just worried about it because they can read the newspapers and they see what's going on. So, you can use these protocols and labs for prevention of any of these problems happening in the first place. You can use these to help with people who have old problems that are coming back now, which I'm sure you guys are all seeing in your practice like I am, or you can use these for people who have new problems directly, directly related to newer infections. Again, it could be viral, bacterial, parasitic, any, any kind of bug that we're talking about. It just happens to be a lot of people have this virus right now.

So, antioxidants. Just, I mean, the easiest thing to do with these labs is just look at the most important stuff first and don't worry about the more trivial things. So, if it's red, it's bad. So, this person has a really clear problem with oxidative stress, which fits in with everything that we were just saying. Now, you're thinking, "My lead treatment, my number one treatment is going to be antioxidants." And then you're thinking, "I wonder which ones?" Well, then you look at it down there. You can see, "Oh, well, glutathione is low." So, I'm going to want to support glutathione either by giving them glutathione or giving them N-acetylcysteine and glycine, maybe even glutamine. You also can see their lipid peroxides are high. So, that means that the lipids are being oxidized or damaged. So, you want to include some fat-soluble antioxidants. Fat-soluble antioxidants. Glutathione is the master antioxidant and super, super important. But the best of the best fat-soluble antioxidants would be CoQ10. People might argue vitamin E or vitamin A or beta-carotene, but I personally would just say CoQ10. That's a personal preference. I mean, that's like asking someone, "What's the best German car?" And one person says Mercedes, the other person says Porsche, and then the other person says Lexus, but that's not a German car, right? So, you know, so that's a personal opinion. But I, I would use CoQ10 if I see a fat-soluble thing because it does so many other things, especially because we see right next door, this person also has mitochondrial problems, and the CoQ10 will help cover that.

So, one of the, it's not really a trick, but one of the things that you learned over the years, and I was talking with one of my students about this, one of the mentorship students, and he's like, maybe two years into the course, and he, he brought this up spontaneously. I was just so happy. Uh, uh, he's like, "Oh, you know, Dr. Kalish, I've been working on, I've been working on products that can do more than one thing at the same time." Like, "You got it, dude. This is like where it's at." So, for example, if you have lipid peroxides that are high, and you know you need to deal with that, but then you also have problems with the mitochondria, then you're thinking about, you know, maybe I could use one product to solve a couple different problems, okay?

Now, we can break this down, and you can look more specifically at, you know, the details of the test here. I'll show you here. Make that smaller, maybe you can see that better here. So, you can see specific pathways that are thrown off. And the general assumption is, if the mitochondria are under assault, something is assaulting them, right? And so, if there's problems with the mitochondria, like you're seeing here, there's something that's damaging them. Maybe there's not enough oxidative, you know, protection against oxidative stress. Maybe there's a neurotoxin. Maybe, in our case that we're talking about today, maybe there's some kind of an infection going on. And then you just want to kind of pick on the areas where you see the biggest problems. And let me show you here. They also have a nice breakdown later on in the test where you can see individual markers in more detail, right? So, let's hone in on the ones that we're talking about today because it's, it's too much of a test to cover everything, uh, here. Amino acids. So, isoleucine, leucine, lysine, methionine, you know, alanine's borderline low, threonine is low, valine. Those are all deficient. More amino acids here. Alanine is low. Cysteine, borderline low. Protein, a little low. So, we're certainly seeing our fair share of low amino acids.

And then let's think about the ramifications for this. There's two levels of ramifications. One is that, and the first one you should think of is that any one of these 20 amino acids that are low that are required for protein synthesis are going to interfere with protein synthesis. And for our topic today, meaning, um, antibody production. But also, if you were a diabetes specialist, you could say insulin production. Or if you were a thyroid specialist, you could say thyroid hormone production. But we're talking about immune functions today, so we're thinking about, okay, any of these being low can interfere, or will interfere, with antibody production. It doesn't matter which one it is. Like, the most innocent one on here is threonine. Like, honestly, have any of you even said the word threonine in the last year? Probably a handful of you are putting up your hands right now. We could do a poll later if you want, but probably not. Have you, any of you sold a bottle of threonine in the last year? It's not something that you just think about, like, ever. However, if it's low, you can't make proteins in the context of what.

We're talking about today, it means antibody production is going to suffer. That's a really big problem. So, in some ways, for protein synthesis, threonine is just as important as methionine. And yet, we all know methionine. You use SAMe, you think about homocysteine, you think about all kinds of things about methionine. But when it comes to protein synthesis, this guy is just as important as this guy. Okay, so all of these amino acids, then you would want to supply for protein synthesis. And usually, people do that when there's multiples like this with a free-form amino acid powder. Usually, it's dosed to enter like a teaspoon a couple times a day, you know, between meals. If people have gut problems, they're going to have reactions to it. So, if they have reactions to the amino acids, you know, do a gut test. You should do a gut test anyways, probably.

Now, separate from that, we could think about the non-protein functions of some of these amino acids and how they would relate to what we're talking about. So, right off the bat, arginine is low, and arginine is required for nitric oxide production, which is required for repairing endothelial cells, right, the endothelium. And so, if arginine is low and you're suffering from any kind of microvascular problem, then it's not really going to go away until you bring your arginine up, bring up the nitric oxide levels, and then the blood vessels will become smooth and healed and soft and pliable and happy once again. So, right off the bat, arginine makes a huge difference. Similarly, I'm picking on the ones that we're talking about. Oh, methionine. Methionine is required for methylation. So that's pretty important because if you can't methylate, you're going to have problems with glutathione. I think we already saw earlier in the lab that this person has a glutathione problem. Let's see. Uh, that was, that was a different part of the test, but I think we already saw that. Let me just go back up there. As you can see, they rate that, uh, where'd it go? It's up here, and the diagram thing here. There it is, glutathione. Okay, so we already knew they had a problem with glutathione. So, you can look at this in a couple of different ways. You can look at the individual markers, you can look at the sort of summary markers. There's a whole bunch of different ways that you can try to manipulate this. Okay.

So, let's look at one or two more labs and then we'll open it up for questions. Let's see. You know, once you've done five, six, eight, ten thousand of these, it's not that hard. I'm joking, not joking. I'm not joking. That's serious, actually. But it's kind of funny because these are really, really hard if you've, when you've done, if you've reviewed 10,000 of these with 10,000 patients, I promise you, you will be happy that you spent all that time. And I hit the 10,000 patient lab review mark, I don't know, maybe 10 or 12 years ago, maybe longer, maybe like 15 years ago. And I was like, oh, glad that first 10,000 is over. Now I can kind of get down to work here. But I'm saying that, you know, half jokingly. But so, if you're, if you haven't done 10,000 of these labs yet, don't worry if you're a little overwhelmed. It's a normal part of the process until you get to around 10,000 labs. And if you read one of those Malcolm Gladwell books, he talks about this is 10,000 hours of anything is required to really get good at it. Like the Beatles had 10,000 gigs that they played before they made it big. And Bill Gates had 10,000 hours in front of a computer from when he was a little kid before he made it big. So, you need 10,000 X's to really get good at something. So, don't freak out if you don't feel like you understand it fully. You know, you can rely on courses like mine and the lab folks and all the support they have at the lab company and the lab reports themselves can help support, you know. But you don't, I want to encourage you all to pursue this because it's really important to learn this. You can help a lot of people. And if you're a little nervous about ordering labs because you're not sure about interpreting them, then, um, just do it anyways, you know. And then find somebody who can help you interpret it if it's not me. All right.

So again, glutathione is a little low. Taurine is low. We didn't talk a lot about that. ITOHDG is up. That means there's a lot of oxidative stress. So we can really, for this purpose, maybe just look at, um, these relationships here, just on this home page. So let me just try to explain this. So, and this goes right back to the very first part of the conversation. When we get an infection, we have a lot of oxidative stress and inflammation. Those two go together. And so, as a result of that, lipids can get oxidized. That's what the high lipid peroxides is showing. ADOHDG can go up. That shows a lack of antioxidant protection. And glutathione, the master antioxidant, can go down. Taurine can drop too. So, part of that whole picture. So, as this oxidative stress slash inflammation is getting worse and worse and worse, you lose your ability to protect the mitochondria. So now they're a target. In addition to that, if you're hypoxic, you don't have enough oxygen, if you don't have enough magnesium, if you don't have enough CoQ10, if you don't have enough of any of the 20 amino acids, you can't build mitochondria. You can't build the enzymes that the mitochondria run on. In addition, if you have toxins, they will damage the mitochondria. So, oxidative stress damages the mitochondria. Infections that generate inflammation damage the mitochondria. And then the result of all this is low glutathione, low magnesium. You can see a bunch of these citric acid cycle markers are high. So now you've got a huge amount of oxidative stress. There's inflammation that's driving all this. You run a gut test, you probably see even more inflammation on that. And then now you've got the mitochondria that are completely getting shredded. And you got to fix that to get the fatigue and brain fog and energy levels to come back. Absolutely. Just have to fix that.

So, I'll just show you like a sample of what a program would look like. And, you know, you know, doing this thing now, like, I think, you know, this is one of the advantages of getting really old is that you just kind of think about things in a different way. So, there's like basic programs you can do. There's intermediate programs that you can do. And then there's advanced programs that you can do. And, you know, what's really interesting to me is that the really advanced doctors, the ones that are senior to me, that have been in practice, let's say, 45 or 50 years, do really basic programs. Not interesting. And the younger ones, like, let's say, the doctors, man, between the age, they've been in practice, like between 10 and 30 years, I'm kind of in that range, they do the really complicated program. But once people get extremely good at this and get super advanced, they go back and do basic stuff. So, if you're new to this and you're doing basic programs, you're doing the same programs as people have been doing this for 50 years. Have that's why you can be confident in ordering these tests. You have to worry about, oh, I don't know enough to do this, because you learn, you learn, you learn. You get intermediate, you get advanced. 30 years go by, you go right back to doing the basic stuff. Antioxidants. This is all basic stuff. Just get the dosages up. You know, find a good brand and don't hold back. Give them some glutathione. What the heck? Just find a liposomal glutathione. Give them a couple hundred milligrams twice a day, three times a day. I don't know. Give them NAC also. What the heck? Life is hard. People need help. Just load them up with all these things, right? This is like a really, it's all the basic stuff that we talked about. Oh, remember the lipid peroxides were high, so give them the CoQ10. And then always, always, always include B vitamins, some kind of B complex, maybe once a day, twice a day if you want to get aggressive. And then a really good multi-pack. All the companies have these things. And there you got a program that's direct. Oh, you know, you want to be, if you want to be fancy pants about it, I've been doing this a lot lately, um, you could use lipoic acid too. Give a lot of it though. I don't know. Give a little. Let's not be crazy. This is a basic program. Like that, something like that would start to address something like this, okay? And it doesn't have to be more than that to get clinical results if you include the lifestyle changes with it. All right.

So, I want to pause for a moment. I want to thank Genova again before we get to questions. We're hitting the one-hour mark. So, um, I'm still going to do questions, but we're going over time. I know some of you may need to leave. If you're interested in the amino acid boot camp, check it out, sign up. If you have some extra time, you can, let's stay around, listen to the questions, or you can run away now. Maybe come back, listen to the recording. And I'm going to take a pause for a moment and then look at questions, okay? All right. Let's see what happened here. My thing got all formatted weird, huh? That's strange. Okay. Um, so if the person is low in tryptophan and giving Tryptophan gives them a headache, that could be a lot of different things. But just give them a combination free-form amino acid product that has tryptophan in it, and that should solve the problem. Okay. Um, do I suggest Genova's Cardio Ion panel? Absolutely. That's a really wonderful test, very well thought out. Let me see. I'm not sure why this is not working. Hand second. I'm going to lower technical, but there we go. All right. Um, let's see. What time does the amino acid class meet on Wednesdays? I think it's around 4 p.m. It's either 4 or 5 p.m. Pacific time. Oh, cysteine is also listed as cystine, C-Y-S-T-I-N-E. They're interchangeable. Some labs report cysteine, some cystine. They're interchangeable. If they're vegans, some of my best friends are vegans. That's not a joke. I am an aspiring vegan. I'm not a vegan. I had carnitas burrito last night. Um, but if you're a vegan, just do the lab and see. Healthy vegan. I mean, I think the vegan vegan diets are great. And just run the lab and see. You never know. You might be low on carnitine. If you're vegan, you might be low in amino acids. So, we do both blends and comp and single products. Both blends and single products. The amino acid course is not covered in the mentorship. It's kind of held out separate, separate content. Yep. Gut lining. So, if you have patients who have had COVID and have unusual food cravings or gut problems, you definitely want to run the GI testing plus the neutral valves. Um, low amino acids because of vegetarian diets. I mean, I would say more malabsorption. You know, if they have parasitic infection or something else going on that's interfering with their absorption. Um, it could be vegan diet, but I've never seen, well, some, most of the vegans I've worked with have been pretty healthy. I don't think a vegan diet necessarily causes, unless they're really just only eating carbs and not eating any beans or potatoes or anything like that. Let's see. I'm just going to see how I get to use all these. Um, yeah, the neutral valve is becoming like the go-to test in this space, I think for sure. Tryptophan is one of the 20 amino acids. 5-HTP is much more solely focused on serotonin and melatonin. So, if you primarily have serotonin and melatonin problems, 5-HTP can work better. If you have more of a broad amino acid problem, then tryptophan can work better. Let's see. How do amino acids, amino acids and people that have major gut problems can cause a lot of gas and bloating. They have big bacterial overgrowth issues. You know, they can go bad on people. Let's see here. I'm just scanning through the questions. Oh, yeah. So, if CoQ10 tests high, it's almost always because they're supplementing with it already. Okay. There's just one case I showed that the patient had high CoQ10, but they had high lipid peroxide. So, it's probably because they're supplemented with CoQ10 prior to doing the test. Supplement low methionine, just get methionine, 3,000 milligrams of methionine. Let's see. Adrenal treatments. Amino acids and adrenal treatments are kind of separate. You could do them together or separate. Let's see. I think I'm running out of time here. Okay. I'm going to stop. All right, you guys. I know I didn't get to all your questions. I'm sorry about that. Hopefully, I'll join you all, especially those of you that had a lot of questions, join us for the amino acids boot camp. We can have three months of this rather than just an hour. And I look forward to talking to you guys at the next one of these. Okay, bye for now. You.