Transcription
Hi everyone, Dan Kalish here to talk today about genetics. Oh, it's so exciting! This is like my favorite subject in the whole world. Oh, and I spent like five hours today, literally five hours, just today talking about genetics. Oh my god, we could go on for years, but let's, um, let me maybe do, uh, kind of a little orientation to the subject area, and then we can get into probably the most popular SNP these days. A little strange, considering there's like 20,000 different proteins in the body that can get screwed up, but we've all settled on MTHFR as being the one to talk about. The other 19,999 proteins just have to kind of wait their time, I guess. You know, it's, anyways, uh, it's kind of funny, but that's the way it is.
And then, um, thinking about, is folate even matter with methylation? Does it matter? I don't know. Maybe not. Maybe it doesn't matter at all. That's a controversial thing. That's just to get you kind of a little pissed off and engaged. Put your phone down, stop checking your email for a second, and think, what's this Kalish guy saying? Folate's not the key to methylation. It's absolutely not the key to methylation at all. It's one of the, I don't know, any more than, you know, picking up your mail in the morning is a key to a happy life. I mean, is that essential? Do I pick up my mail every morning? Yeah, I do. And is that kind of important? Yeah, it is. Like, you don't want to not pick up your mail every day, but, you know, is that like the only thing about life? No. So folate is a key thing. It's important, but it's not the only thing with methylation. We're going to talk about all that biochemistry, okay?
But then, before we even get there, just talk a little bit about genomics in general, and functional genomics versus genomic testing. And now, this is one of those cases where you can have both. It's like the Reese's Peanut Butter Cup. You can have your chocolate and your peanut butter at the same time if you want. Just go buy a Reese's. It's my favorite candy bar, in case you're wondering. Um, and, you know, there's no reason you can't have both. So you can run genetic profiles, and you should, you know, if you're really into this stuff. But then you should be able to run and interpret functional genomic tests, meaning we're doing functional medicine tests to see if there are genetic issues present, such as MTHFR. And what I want to do today is try to cover the, the bulk of the markers that you should be considering on a functional medicine test if you are concerned about an MTHFR problem, okay? And then maybe take one step back and talk a little bit about the history behind all this stuff, right?
So my teacher, Dr. Richard Lord, whose work this is all based upon, was a young graduate student in the late 1960s at the University of Texas at Austin. And while he was at UT, he was teamed up with the Clayton Institute and some of the more famous nutritional researchers of, of all time, to be honest. And one of the things Richard was thinking about, and I was talking about this to him this afternoon, was he was thinking about as a 20-something-year-old guy, "Well, they're just discovering all these vitamins. That's interesting. B12, folate, pantothenic acid. They didn't know these things existed until this time, right?" He's like, "Wow, that's so cool. We're finding all these vitamins." And then all these researchers knew that there was wide genetic variation in the need for these different B vitamins that were just being discovered. And then Richard's thinking, "Hmm, well, we know in some children, if they're missing certain genetic functions, you know, certain genes are mutated and not working well, we know they die right after birth. We know that's a very bad thing. I wonder if there's a spectrum of disorder for these genetic mutations. I wonder if there's an adult-onset version of these different genetic issues." He was thinking about this in the 1960s, okay?
And lo and behold, here we are today, realizing there are two general categories of genetic problems. There are genetic mutations, they're called inborn errors of metabolism. These are fatal to newborn babies, so we take them very seriously because if a baby dies, it's a horrible thing, and everyone on the planet can agree on that. Very few things we can all agree on. Everyone agrees if a newborn baby dies or has damage to their central nervous system or is suffering horribly, it's, it's not acceptable at all, right? And so we've put a lot of energy into, as a culture, into figuring out these inborn errors of metabolism. But what Richard thought of back in the '60s, and then now has been endorsed by scientists worldwide, is that these inborn errors of metabolism that happen in newborns can manifest in adulthood, okay? And so you can have the new terminology for this is inherited metabolic diseases, IMD, inherited metabolic diseases in adults. These are adult-onset disorders. Are they any different than what happened to the babies? No, they're the exact same problem that happened to babies, but they are milder. They don't appear until adulthood, and they're usually not fatal, okay? They usually don't kill people, but they can be pretty severe. And so there's a spectrum of potentially fatal genetic disorders to disorders that can appear in adulthood.
And my sort of premise is that in the field of functional medicine, in the, the 30 years that I've been involved, and if I go back to my teacher's teachers, like Timmins and Frieder, they started doing this kind of natural medicine work in the '70s. So I have a perspective that goes back maybe to the late '60s, early '70s. What's that? I don't know, 50 years or something like that. So for the last 50 years, natural medicine practices have been like a magnet for people with genetic disorders. Not the childhood kind. Those kids are handled in the hospital by pediatric geneticists. I'm talking about the adult-onset genetic disorders. Just flock to functional medicine practices because no one understands them, and they have these whack-a-doodle problems that don't make any sense. They don't respond well to medication because they have what? Adult-onset inherited metabolic diseases. And that's what we're trying to talk about, right? There's a spectrum here. And so MTHFR is an example of a problem where it's a genetic disorder, right? It's a genetic problem, but it's not a mutation. It's not life-threatening, okay?
If you want to get more and more of this stuff, just a quick little advertisement here. In June, we're doing a lab interpretation bootcamp. First time I've ever taught this subject, functional genomics. Where's that information coming from? Well, my last four years of working with Richard Lord. It's my attempt to analyze and categorize and teach that information. We do have tons of hours of Richard speaking, Dr. Lord speaking, in his eloquent and scientific way. And then we'll have me talking about the different cases and case workups. Case-based learning is the idea. And then we also have Nathan Morris speaking about SNPs specifically. So there's a couple of different speakers. I'm the main one, but you'll have a couple of other folks to listen to. If you guys are interested in understanding how to interpret functional medicine labs from a genetic perspective, you get 20% off. If you have, remember that little code there. If you forget the code, you know, you could email the office. I'm sure they'll give it to you.
And then in the summer, in August, we have what's been our most popular bootcamp so far, which is our telehealth business essentials camp. You guys want to get into the whole practice building, uh, that kind of stuff? You're welcome to join that course as well. Again, you get 20% off. You use that code, okay? That's what's coming up soon. Uh, this is me. I forgot to introduce myself for those of you that are new. So I'm Dan Kalish. I've been doing a lot of stuff in the last 20 or 30 years. One of the things I did recently was on the faculty of the Institute for Functional Medicine. I headed up their practice implementation, implementation program for a couple of years. I've worked with researchers at Mayo Clinic on analyzing the work that we teach in my mentorship class. We published a study with Mayo Clinic on the Kalish method, so to speak. We've, the last four years working with Richard Lord, my IFM certified. I've been doing this for a long time, and I'm just sort of, um, what am I saying? Uh, just sort of, um, coming into my own as a practitioner now. It took 29 years, but I feel like it's finally, finally starting to happen, okay?
So this is what we're really confronted with, this diagram here, and this is what we want to settle into and think about for a little while, okay? So let me grab a pointer here and start pointing away at things now. And I want to try to do this, that so I'm going to talk for a little while, try to keep it short. Um, then I'm going to stop and pause and take a little break, and then we'll look at some cases. If you guys are interested in hanging around for the second part, it'd be great. You can listen to some cases, and, uh, if you don't have time, you can take off after the lecture is done. So let me see here. There we go. So now let's start off with some basic facts, and I will pose these as questions, uh, because that's the way that Dr. Lord's been training me for four years, so I'm just used to this now. All right. And you can raise your hand or type into the chat box if you know the, the answer to this question, all right?
So we're talking about a process called methylation. What does your body spend 50 to 60% of its methylating on? What is your body making? Methylation is about making things, right? Methylation is all about making things. This is how I explain to patients. What is methylation for? Is for making things. It's for making hormones, making neurotransmitters, for making your detox pathways work. What's the number one product of the methylation process? All right, okay. Now, there's a lot of guesses coming in, and I don't want to like ridicule or make fun of you because that's not a good technique because I want you to take my classes. But no one's even close. No, you guys aren't even close. And the reason why I'm asking this question is because Dr. Lord asked me this question three or four years ago, and I would have put money on everything that you guys are saying. So Sammy, building carnitine. Sammy, again, homocysteine. You guys aren't even, you guys are off by like a factor of 10, okay? So, ah, someone got it. Creatinine or creatine, okay? Your body spends almost all of its methylation time and energy making creatine, which gets converted into creatinine. Creatine. What is creatine for? Do you guys remember? This is way back in school, everyone. You probably forgot. It's for muscle energy. So methylation, primarily by volume, is designed to produce energy for muscles, okay? That's the main reason why we methylate. Is that the most important thing? I don't know. But it's the thing that you do the most when you methylate.
What's number two? I'm not going to talk to you guys, I'm just going to tell you. Number two is making cell membranes through choline. So if you add those two together, the creatinine or creatine production and the cell membrane or choline production, that's like 80% of your methylation energy going in that direction. That's crazy, right? You don't, no one even thought of that because the way that we learn about methylation is for these very important but very small factors that methylation is responsible for, right? So I just want to throw that out there so that you can start to think, "Wow, if my patient is not methylating, it means they're not going to be making enough creatine or creatinine. They're not going to have enough energy for their muscles. They're not going to be doing really well with their with their cell membranes either." That's a big problem. And then you can get into the more typical stuff that we think about: neurotransmitters, detox pathways, hormone production, etc., okay? So again, methylation is primarily a process, primarily a process of building things, primarily a process of building things.
And so how do you like structure this building? Well, first of all, you need to get single carbons together into what is called the single carbon, or sometimes it's referred to as the one-carbon pool. And you can see the color there, it's sort of light blue, looks a little bit like a swimming pool, right? So you can remember the one-carbon pool. It's like a pool, it's like a swimming pool. And what is that? Well, it's a whole bunch of carbons. And where did those carbons come from? It's another trick question. Does anyone know that? No. None of us ever learned this stuff. No one ever teaches this stuff. That's why none of us know it, right? That carbon comes from serine, glycine, histidine, tryptophan, and glutamate or glutamine. There's five amino acids. The same again: serine, histidine, glycine, glutamine, and tryptophan, from which we pull carbon into the single-carbon pool. And why do we do that? Because then, using, and finally, we can talk about folate, using folate, right? We then can convert those carbons over here into, or not convert them, but bring them into this cycle, okay? And it's a very simple cycle. This is the destination of the single carbons. And this cycle is converting homocysteine to methionine and methionine to homocysteine. And the key nutrients that do that are serine, glycine, histidine, glutamine, and tryptophan to provide the carbons. Single-carbon pool, you need the folate, 5-methyltetrahydrofolate. You need the methyl B12. You need the B12. And of course, you need B6. And you have to have enough methionine present in order for this all to work.
So when you're looking at labs and you want to see, "Okay, how screwed up is my patient's methylation?" You can look at folate markers, and we'll review these at the end of the class, okay? You can look at B12 markers. There's two enzymes that B12 is required for, and only two enzymes in the whole human body. Isn't that wild? So like, if you look at the enzymes, like I think niacin has like 300 enzymes it's in control of. B12 only regulates two enzymes, and they're both sitting right here, super important, okay? You could have low serine, glycine, histidine, glutamine, tryptophan, or methionine, and that could interfere with methylation, right? If the serine, glycine, histidine, glutamine, and tryptophan are low, you're not going to have enough single carbons in your little swimming pool. And if your methionine is low, then this whole thing's not going to work at the top here, okay? So you could have problems with any of these nutrients, and then this is not going to work as one would want. And then you're not going to make your DNA, you're not going to make your creatine, you're not going to make your cell membranes, you're not, and they've got a list of here too, Dr. Lord put together. You're not going to make your methylated nucleic acids, you're not going to make your methylated proteins, your phosphatidylcholine. All these things are going to start to fall apart, okay, if you don't have this process in place.
So when you're looking at a lab, you want to think globally: Is there enough methionine? Is homocysteine high or low? Is there enough B12, B6? What's happening with these amino acids? Not just methionine, but the other five. What are they? Serine, glycine, histidine, glutamine, and tryptophan. If those are low, you're not going to have the single carbons, and you can't sling these carbons around, which is what methylation is. You can't move these carbons around if you don't have the carbons, right? You need to get them from somewhere. All right.
So now, that's kind of like the introduction, and then I'm skipping around, I know, but I want to make this other point here first, okay? So now, you ready for this? We've got methylation. Most of the time, it's producing creatine. We're helping with cell membranes as a side job. It's helping making our DNA. It's helping with hormone production, detox, all these super important things, okay? But if you take a step back from that for a second, there's something that is so much more important, so much more important than methylation, that your body will prioritize it over methylating, okay? So your body, on a second-to-second, millisecond-to-millisecond, moment-to-moment basis, has a choice. It can direct your resources to methylation, which we just said is super important, or it can direct your resources to what's the second one here? Well, it's kind of, it's not a very hard question because it's a slide that's up: glutathione production, okay?
Now, this turns out to be so important that it's more important than methylation. Glutathione. So let's look at this. I'm not criticizing anyone or anything, but whoever designed this was kind of messed up, you know, kind of messed up in their head. Because the design team here decided, "Okay, the most important thing for this body that we are designing, this human being, well, besides emotional development, spiritual development, loving other people, besides all that stuff on the science side, the team that put that together, I don't know, they did okay. They could have eliminated hate and anger and murder, maybe. But anyways, forget about the, like, the spiritual side. But on the biochemical side, this design team was thinking, 'Okay, we got to keep cells alive. If cells are dying, then the game is over. So we're going to make this one thing the most important thing in the whole body, and that's going to be glutathione.' But we got to make stuff. Like, this person's got to move around, they got to have cell membranes, they got to have hormones, or they're not going to have sex, they're not going to reproduce. So we're going to give them methylation too, okay? But we're acknowledging that no matter what, producing glutathione is always going to be more important because if the cells die and the person dies, it really doesn't matter if they get methylated or not, right?"
So there is a mechanism here, and it's again, kind of messed up, and you can see it right in this pathway here from Dr. Lord's diagram. Homocysteine will convert to cysteine, cystine, cystathionine. You can see all these down here through this transsulfuration pathway. If your glutathione levels are in trouble, if you don't have enough glutathione, you're going to make more glutathione. And every time you make more glutathione, you're going to have less available methylation. So if you have a problem with glutathione, by definition, the person's not having a normal methylation process. So, in other words, you could get everything perfectly set. You could get enough folate, you could get enough B6, you could get all those single-carbon pool amino acids lined up, you could dial in their SAMe and give them methionine and get all that working just right, and none of it's going to help with methylation if their glutathione levels are low, because the body's going to just shift all that stuff down to glutathione production because it's more important for the cells to stay alive than it is for us to make stuff, okay?
So on a moment-to-moment basis, depending on how much oxidative stress is present, you're either going to be able to methylate and build things or produce glutathione, but you can't do both at the same time, okay? You're going to have to prioritize one or the other. Now, if you have a really healthy diet and not very much oxidative stress, and you're drinking your broccoli juice every day, you're doing all the things you can to keep all these, you know, compounds normal, then you have enough available substrate to methylate. You have enough available substrate to make glutathione when you need it, and things work out. But if the glutathione levels drop, the whole thing falls apart. And then what would happen? Let's just make up a situation that I see literally every day with like 80% of my patients. Let's make this up, okay? Low glutathione patient walks in the door. They have low glutathione. And they come in, and this happened to me like twice this week already, I'm telling you, it's been a long week. They come in and they say, "I don't know, Dr. Kalish, but I thought I read all this stuff and I watched this blog and I listened to this podcast, and I'm like a paleo hacker, self-treating kind of person." Okay, that sounds like a great plan, doesn't it? How's that working out for you? And then they come in, they say, "Well, you know, every time I take some folate or B12 or folate, I get a lot worse." Well, what would happen in your body if you were low in glutathione and then you took a whole boatload of folate and you forced your body to methylate more against its will? It's going to make an even bigger problem for your glutathione, and then people get worse. So you have to consider both sides of these equations when you're working with methylation. You have to consider restoring glutathione status as you give them methionine, folate, B6, B12, and get the methylation working. These two have to work in concert, and the body will always prioritize the production of glutathione over the production of, over the ability to methylate, okay?
And then you can test for all this stuff. It's not a random thing. So when you're testing for glutathione, you can test pyroglutamate, sulfate. You can test amino acids that help you make glutathione. The most famous one is cysteine. You can also test glycine and glutamine, which also help you make glutathione, right? You can test all those. And you can also test alpha-hydroxybutyrate. So there's a whole, there's like, I don't know, six or eight different tests you can do to see what someone's glutathione status is like. And then with methylation, you want to test homocysteine, B6, B6, B12, and folate. And I'll show you those markers in a minute. And very importantly, methionine, okay? Because if the person is low in methionine, then the cycle is going to be thrown off. And it's an integrated cycle between methylation and glutathione production. If you just tweak one aspect of it, not really good things happen.
When I was in co-, no, when I was in college, I was in my second or third year of college. I was living in New Hampshire, and then the White Mountains of New Hampshire, working with this psychiatric community. I wasn't committed, I was not one of the patients, I was a student intern, sorry. Um, anyways, and it was R.D. Laing, and so you may be old enough to remember R.D. Laing, very famous psychiatrist in the '60s and '70s. And I had a job that I did on the side to make a little cash, and it was at a newspaper plant where we would assemble the Sunday newspaper. And so there was a, what do you call it, like a belt, you know, that was had all the different sections of the paper, and you had to like assemble the different sections in time. And if you didn't do it quite right, then everything would get screwed up because this conveyor belt would keep delivering stuff, right? So you have to be really fast, or, you know, problems would happen. It's kind of like that with methylation, right? If you're not assembling all these different component parts properly, this thing doesn't work. You can't just do one thing really well within a complex cycle, right? Because you're going to speed up one part of it, and then if you're not attending to the other parts, then the person could potentially get worse. So if you have someone come in and they're stimulating one part of this and it's making them worse, just look at the labs, and you'll see, you know, all these different aspects of the problem laid out in lab work itself.
So I have a couple of quotes in here just because, I don't know, because this is like the important stuff. So, um, let me see, a couple of quotes just to look at. "Biochemical reactions involving the transfer of methyl of methyl and related single carbon units necessary for synthesis, regulation, and clearance of DNA. Can't imagine anything more important than that." Okay. "However, the large majority, 80%, of total methyl transfer activity is directed at the production of creatine and choline." Those two together make up about 80%. I don't know, there's a whole bunch of studies on this if you want to Google it and read about it, it's pretty interesting. "Tetrahydrofolate, it's the active form of folate. It's accepting the single carbons. It's accepting the single carbons. That's its job. If it doesn't have the single carbons to accept, then it's not going to work really well, okay?" What are those single carbons? Remember over here, they come from serine, glycine, histidine, glutamine, and tryptophan. So if those amino acids are low, you don't have enough single carbons, you can have a problem. All right.
And then just a quick refresher, then we can look at some labs. I think we're right on time. Methionine circulating to homocysteine and back, okay? That's what we're talking about. You can see the B12 working on the other side there, okay? Coming together, and then you see that arrow down to cysteine. That's the one that would go down to, um, if you drew that arrow from cysteine lower, it would go down to glutathione. And if you have high homocysteine levels, you could have problems with B6 or B12 or folate or methionine. So high homocysteine is a giveaway. Is low homocysteine good? That's a trick question. Well, normal homocysteine is good. High homocysteine is bad. And extremely low homocysteine is bad too, because it's a cycle. If the homocysteine is too low, then the cycle is not working right. Um, okay. And that's, and here are the different markers that we're about to look at: folate, FIGLU, and here, oh, here's a nice little diagram too. Then we'll, we'll just do one more, one or two more slides, and we'll look at the, at the lab.
So this is again, Dr. Lord taking the time to put together biomarkers of methylation-related factors. Thank you, Richard. And for those of you that never met him, I mean, I'm, I don't know, I spend so much time with Richard now, you know, twice a week I get to speak with him, and it's just the most, he's just the most intelligent person I've ever met. And he's also, you know, just written so many great books. You guys should buy his books. They're all available through iTunes. And, you know, he's just a profound thinker, and he's really dedicated his life to, you know, unveiling the science to clinicians like ourselves, you know? But anyways, here's his list: methionine, homocysteine, glycine, histidine, dimethylglycine, betaine, choline. These are the things you should be thinking about with methylation, right? And then here again, glutathione status biomarkers. Well, why does glutathione matter? Well, it does, right? Because if glutathione levels are low, your body is going to pull on methylation, deplete methylation, reduce methylation to make glutathione, okay? Again, biomarkers: 8-OHDG, or 8-hydroxy-2'-deoxyguanosine, pyroglutamate, alpha-hydroxybutyrate, sulfate. These are all glutathione markers, but they're directly related to methylation. And then you can look at vitamin deficiency markers for aminoglutamate, for folate, methylmalonate, very famous for B12, and xanthurenate for B6. You just need to learn how to interpret these labs, okay? You just need to learn how to interpret these labs.
Again, let me show you in a picture. Well, I want to show you on the labs. We're at the half-hour mark, okay? I covered all the slides. I'm going to take a deep breath. You guys can go get a glass of water or something. I'm going to take a short break here and pull up some labs too. Oh, I hit the wrong button. Wonder that didn't work. There you go. All right, now we're talking. Okay, okay. So before we go there, let me say what we're here for. Oh, what's going on? Kalish Institute in June, we have a lab interpretation bootcamp. Eight weeks on genomics, not regular genomics, but functional genomics. How to interpret functional medicine lab tests, understanding the genomics at play that are happening in front of you, okay? So when you have a genetic test that's positive, let's say the person has MTHFR, does that mean that that gene is expressing? No, it just means that they have the gene. How do you know it's expressing? You look at the functional test for what? For B6, B12, folate, methionine, homocysteine, right? The functional tests show you what genes are expressing. So you need to be able to read and interpret it and understand the genomic testing and then see whether that's expressing on a functional test or not. And that's what that bootcamp is about. It's not everything about that subject area. It's a very wonderful introduction to the ideas behind that. I've been looking at this stuff for 29 years. I've been actively studying the genomics for four years. I put in every Monday and Thursday into this for four years. I'm barely scratching the surface of this myself, so, you know, to be an expert at this takes decades. I'm just setting expectations there, okay? It's a two-month class. You're not going to become an expert, but at least it'll open your eyes. And I guarantee you, if you take that class, you'll be able to find five or ten patients in the next year and you're gonna be like, "Damn it, they have a genetic disorder. I know you do. I can see it. I can see it on the lab." And that is a very rewarding experience. It's very exciting. And then what happens in students in the mentorship class? It's like, "Oh, they get it." And I've seen that happen with so many people at the Kalish Institute now. They get their first case. This kid has got, you know, autism. It's an eight-year-old, and they see this lactate and pyruvate level that's just like a thousand times normal, and they're just like, "Oh my god, that's what's causing the neurological issues." I'm like, "Yeah, just go for it. Give them the B vitamins they need. Let's get this done with, okay?" So it's a very exciting kind of work. You get 20% off.
And then we have the telehealth business essentials bootcamp. For some reason, our most popular bootcamp is in the summer. It's all about the business stuff. If you want to learn how to financial planning, business planning, operations. I hate all that stuff, but I've been forced to become good at it, and so I teach it. If you're not very good at financial planning, business planning, sales, operations, marketing, you can take that class. You suffer through it with me, you know, it's just what we have to do to stay in practice, right? It's just one of those reality things you got to deal with, okay?
So now let's look here at the labs, and we'll blow this up a little bit now, and we, I kind of laid out the general premise. Now we're looking at an Ion panel. You can also do Neutral Vowels, they're very similar, almost identical tests. And here we are, right on the page, and it's not too hard to see. You can see in the header, it says "Methylation Cofactor Markers: B12 and Folate." Okay? So I'm going to show you, you know, the basics of these. Is that if your methylmalonate is high, that marker is super high, it means that you're low in folate. I'm sorry, it's low in B12. If formiminoglutamate or FIGLU is high, it means you're low in folate. So these are functional markers for B12 and folate. This person doesn't happen to have those problems, but you get the idea, right? And then we'll just keep going through here, and we'll find all the different markers because there are many. Oh, let's go to the beginning, just so you can see. Uh, remember the single-carbon pool? Kind of a shocker that amino acids matter with methylation, but that's where the carbons are coming from. And you can measure each one of these amino acids. It's very convenient that we can even do this. It's almost, I would say, like a miracle, practically, that we can do this stuff. And so there's your methionine. You'd want to measure that. If methionine was low, you would have a problem with methylation because, remember, methionine is going to homocysteine and back and forth. And then we can lay out here, remember the other ones? Histidine, serine, glycine, glutamine, tryptophan. They're all measured right here. It's not very complicated. If tryptophan's low, you give tryptophan. If, uh, histidine is low, you give histidine. You give the glycine's low, you give glycine. You give the amino acids that are missing, then that's going to help them with a single-carbon pool, which is what they need for methylation. And then we don't really talk about that much for this. Let's see. Oh, don't need any of that stuff. Oh, yeah, here, here's our 8-OHDG, remember that one? That's a glutathione marker. Marker seven there, 8-hydroxy-2'-deoxyguanosine. Okay, that's a marker that's required. If that marker is high, it means you're potentially low in glutathione. And let's see, then we also need to learn the B6 marker. It's marker number 18 on this lab, xanthurenate. If that's high, person is low in B6. So B6, B12, folate, methionine, obviously. If homocysteine is extremely high or extremely low, either way, it's a problem. And then here's the glutathione markers also, because now we're kind of dragging glutathione into the argument here. And you'll see there's three markers here that help you look at glutathione levels, and they are sulfate, pyroglutamate, and hydroxy-alpha-hydroxybutyrate. Those three, 33, 34, and 35. Those are all a referendum on glutathione.
Let's look at some more labs. I'm into, you know, one of my theories, I don't know if this plays out for you guys, but it seems to for most people, is just to do volume of lab testing, you know, just to do a lot of tests because some of this just happens, you know, with repetition. You know, you just see it over and over, and then it becomes almost like you're just looking for, like you can magically find it. I'm going to talk for another five minutes or so, and then we'll open up for questions, okay? So let's see what we can find on this one. Methylmalonate and formiminoglutamate are both low. That's good. Oh, this one's all normal. Well, that's not very helpful, sorry. There are normal, healthy people out there. It's kind of not what we always expect to see, but let's see here. Coach, that doesn't look very good, does it? Let's see, we gotta find the right problems here. It's not gonna make sense. Now, this one, oh, yeah, okay. This is a good example of something else. Let me just show you this here though. Let's just, let me just blow this up so you can see it one more time. So you want to check maybe six or eight things. The first thing that you would do is go right to marker number 21, that's for formiminoglutamate, also known as FIGLU. If that marker is high, then the person has low folate, right off the bat, you know there's a problem. Methylmalonate would be the next one I'd look at, which is the marker for B12, okay? If that's high, then B12 levels are low. And you get B12. And then xanthurenate is the next one, marker 18. If that's high, you get B6. So that's half the battle right there, right? That's B6, B12, and folate. The general way you prescribe those is you give a B complex and then an additional amount of the individual B that's low. So if they're low in folate, you give a B complex and some additional folate. At the low on B12, you give a B complex and some additional B12. If the low on B6, you give a B complex and some additional B6. General rule of thumb I've always been taught by everybody that taught me is never give a single B vitamin by itself because they work in concert together, and it's not going to do a great service to them to just give one B vitamin in a high dose by itself. And then don't underdose people. Don't overdose them either, but, you know, don't underdose people because then it doesn't really work very well. Uh, let's see. And then just a quick refresher here on, let me find one more test. And one sec here. How about we pull up, let me pull up one from a recent class? So what happens in the mentorship, and we do this in the bootcamps too, is we have, um, in the bootcamps, we have four one-hour sessions where we review the cases that are part of the class. So I have these cases from my practice that I put into the class, and we review them, which seems to help people quite a bit. And the way the class is structured is, you know, I present the cases in the coursework, you get to analyze them, write up programs, and you can come to class and see the programs that I've designed. And then in the mentorship course, um, we actually do real labs that doctors are sending in of their own, you know, so they're, "I got this patient today, and here's the lab. What do I do about it?" Kind of thing. And let me just show you an example of that. We can pull up some labs from the last week or two of class. And it's a really good group of doctors. We have a kind of beginning group, we have a more advanced group. Let's see here. We go. Let's try this. This is just random, kind of keep me on my toes here. That didn't really work, did it? Let's try that again. Sorry. Uh, I'm clicking on it, but it's not opening. There we go. There we go. Thank you. Thank you, computer. All right, so let's take a look at this. And then, yeah, we'll have time for questions. You can type your questions into the little box. Let's see how many I can get to. Okay, so clinical rounds. This is from a few weeks ago. This is Aaron sent in a test. Let's look. What was wrong with this person? Weight gain of 40 pounds since March. That's not good. So that's not exactly what we're supposed to be talking about here, but let's just look at the lab and see what's going on. Anything that jumps out? We can kind of talk about it, but let's go and look at the B vitamin markers first. So now you guys are learning. Oh, there you go. C marker 18, xanthurenate is high. That means this person needs B6. But methylmalonate and FIGLU are normal, so they don't need B12 or folate. But you're going to give B complex that has all the B's and then extra B6, usually 100 or 200 extra milligrams of B6. B6 is something you want to dose generously, usually, just to keep the person going. And then we can look at the oxidative stress markers for glutathione. Those all look pretty good, okay? And then what happens in class is in the mentorship, then people submit their program that they designed, and we talk about it in class. Here's another lab from Stephanie. Body is painful to tender pressure all over soft tissue. Let's look and see the methylation markers again. There we go. Methylmalonate high. You nailed it. B12. Xanthurenate borderline high, a little bit of a need for B6. FIGLU not high. So this person's potentially not methylating because they're low in B12. What do you do? You know, B complex, all the B vitamins together with some extra B12. Titrate the dose up to get a clinical effect. Let me just keep scrolling. We're going to do one more. Um, let's find a full-on Ion panel that has all the amino acids. So as part of, and do not ignore this, like everybody, you want to screen for the gut problems too, okay? So we're not ignoring gut problems, we're just not talking about tonight, but everyone should do a gut test, especially if they have a methylation defect. Um, that's sort of for a different day, but we're not ignoring that, we're just not talking about tonight. And a large part of the success in the practice, right, is the integration of all these different things, being able to interpret the amino acids and fatty acids and methylation pathways and being able to interpret a gut test. It's an overwhelming amount of information, to be honest. There's hundreds and hundreds of markers you need to understand and memorize, okay?
So now let's look here. Methionine is okay. But if it was low, you would give methionine. That would help them methylate as much or more than anything, right? We see glycine is low and serine are low. Those are two of the amino acids that supply the single-carbon pool. So you'd want to give those to help with methylation, okay? And then we can look at, let's see, homocysteine. Homocysteine is high. By definition, they're not methylating well. B6, B12, and folate to lower that down. And then let's look at the B vitamin markers themselves. So again, this person, if they were low in methionine, methionine is critical. Low in glycine, glycine is critical. Use the amino acids along with whatever markers are showing to be problematic on the B vitamin section. And let's see here. If they're methylation, oh, look, oh, this is perfect. FIGLU, formiminoglutamate. Finally, we found one. But we didn't see this. This took me like, I don't know, like 16 minutes of scrolling through labs to find you one test with a functionally low folate. Let me say that again. It took me 16 minutes scrolling through a half a dozen lab tests to find you a single example of a FIGLU, formiminoglutamate, that's high, which means a functional deficiency of folate. Does this happen a lot? Well, yeah. Does it happen with everybody? Absolutely not. It took me 16, now 17 minutes to find this, okay? Not everybody that has a methylation problem has a folate problem. Not everybody that has the MTHFR gene is going to express that as a folate problem. You got to do the functional test. So you don't know. Every one of these cases could have been an MTHFR case. I'm just, just pretend maybe one is low in methionine, that's what they need. Maybe one's high in homocysteine, that's what they need to correct. Maybe one's low in the five-carbon pool guys, right? The tryptophan, glycine, serine, glutamine, and, um, histidine, right? Maybe, maybe that's what's going on. Maybe it's folate, but not that often. Not every time, at least, okay? That's the whole point of, of thinking through this. And if you see that bigger picture, then you might even think, "Well, wait a minute, their pyroglutamate is low. Maybe that's why they're not methylating well, because they're putting all their methylation substrate products to glutathione production." That's going to screw up methylation. Remember, low, low pyroglutamate means low glutamine. All right, I'm sorry, I'm really, I'm rambling now. I'm not rambling, but I'm like, you know, kind of on the soapbox. When I, when I lived in London in college, I was at the University of London for a while. I don't know why I was there. I was doing this sleep study thing with like psychology people. And I remember walking through Hyde Park in London. It was like 20 years old, and there was actually a guy actually standing on a literal soapbox yelling at people. I was like, "Whoa, never seen that before." That's what these Brits do. They're actually like standing yelling on something. That's where they got that expression from, okay?
I'm going to end with a question that you guys won't know the answer to, just to mess with you. So when you see all these B vitamin markers low, does that mean everything's okay? That's just a messed-up question. Let's see. Let me show you a good example. If you see all these B vitamin markers low, undetectable, is that good? Does that mean the person's super healthy or not? Let's see. All right, so let's get to questions. Um, all right, here a second. Uh, there we go. All right, so let me try to get to as many questions as I can, and we have about 10 minutes left. So let us see here. I'm trying to scroll through the questions here. Oh, that's a good question. Does the carbon pool need all five amino acids? No, you can contribute if you have enough of, you know, one. Can the lack of one make up for the other, right? So, um, that's what your body does. It's just kind of accommodates. What do you think about giving NAC instead of glutathione itself? Okay, so that's a great question from Nicole. I'm going to answer it with a diagram. Now, I'm not against glutathione. Some of my best friends take glutathione. That's not a joke. My fiance has a refrigerator full of glutathione that I bought for her. So I'm, I mean, it is in my refrigerator at home right now, as we speak. And the person I love most in this world takes glutathione, okay? So I'm not against glutathione. So don't think that this is an anti-glutathione thing. But the question is, do you want to take glutathione? And yes, you can. But what about N-acetylcysteine? Would that help? Maybe, because maybe N-acetylcysteine or cysteine helps with methylation, glutathione production, dopamine production. It's an amino acid, one of the 20, that's responsible for all protein synthesis. So if you give someone cysteine or N-acetylcysteine, it helps with protein synthesis throughout the entire human body. Every single protein will benefit from.
That so cysteine for some patients can be a superior form of support to raise glutathione than glutathione itself. And you can even use both. You can use cysteine to help with all these different things that I just mentioned, including protein synthesis throughout the whole body. And then separately, you can use glutathione to specifically help with glutathione.
Okay, see other questions. What do you, what do you do when glutathione makes someone nauseated? Yeah, so I always start with N-acetyl cysteine. If that's not working or not enough, then I add glutathione to it. Okay, so there's nothing wrong with using glutathione, but it's my backup plan, not my initial plan.
So N-acetyl cysteine and glycine, you got to dose it right. So NAC should be between 3,000 and 6,000 milligrams a day. 500 milligrams of N-acetylcysteine is not enough to do anything unless your patient is like a chipmunk or a squirrel or something. Okay, so human beings have 30 grams of glutathione in their body. Human beings burn through 3,000 milligrams of glutathione every day. Like it's by the gram, you guys, that we burn through this stuff. So if someone's low, and that's a healthy person, right? Healthy people burn through 3,000 milligrams a day. So if you give someone 500 milligrams and they're not, they not only need 3,000 a day just to be normal, right, but they're deficient. Nothing's going to happen. So 3,000 is an absolute minimum up to 6,000 of NAC per day. Don't make people sick. Don't give them like 6,000 on the first day, but start off with 3,000 and if they need to go up, go up.
Glycine similarly can be used. How much? 3,000 milligrams to start. You can go up to as much as six without any trouble. You make 3,000 milligrams of glutathione every day when you're healthy. So these are not high dosages. These are just replacement dosages for a person who's messed up.
I had a patient today, no, yesterday. Yesterday, she's, I don't know, somewhere in Europe. Anyways, it doesn't matter. She's like, "But Dr. Kalish, my glutathione levels are testing low. You say I need N-acetylcysteine, but I've been taking it." I said, "How much?" She said, "600 milligrams." I said, "Well, you need, you know, like literally 10 times that much." She was like, "Oh, okay." Same thing with the B vitamins. I'm not making this up. She was taking five milligrams of vitamin B2 a day. I'm like, "Okay, we're gonna start you with a hundred and then we're gonna see, you know, like, and maybe we're gonna have to bring it up." Okay.
Um, let's see. I think I did that already. Oh, I'll show you here. Um, for William, about tests for glutathione status. Let me just highlight them on here so you can see the pathways and everything. So you can, to check glutathione status, pyroglutamate is one. Pyroglutamate sulfate is a wonderful test, and alpha-hydroxybutyrate. So alpha-hydroxybutyrate sulfate and pyroglutamate all indicate low glutathione. Depending if they're high or low, it's kind of complicated. They can go high, that means one thing. They can go low, that means another thing. It's kind of complicated to interpret that. Probably take an hour to describe all the variation there.
And if low cystine is present, or low taurine is present, low glycine, or low glutamine, then you also would suspect low glutathione because you make glutathione from cysteine, glycine, and glutamine. And taurine is involved, but it's not like what you make it from, but it's involved because it's a sulfur amino acid. Okay.
Okay, let's see. So if someone's low in amino acids on a test and they're getting enough protein, then you would use free-form amino acid powders to bring that up, usually at least one teaspoon twice a day. Sometimes it makes sense to use more, but eating more protein is not going to necessarily correct the low amino acid. There are very few people that are deficient in amino acids because they're not eating enough protein. That's pretty rare. Sometimes they might have a digestive problem and they're not breaking the protein down, but that goes back to the gut testing.
The tests that we're looking at today are from Genova. Yeah. So should you support phase 2 liver detox when giving methylation vitamins, or only if the detox pathway is problematic? Yeah, I think it's the second. Myra, I think it's only if the detox pathways are problematic. I don't think you always have to do that. I mean, if they start to get kind of sick, you would want to add it in.
But so figlu undetected, but folic acid not tolerated. So when figlu is high, that means that they need folate. Okay. If figlu is low, it's complicated, and we're not, we're talking about that maybe some different talk when we talk about hypometabolic states. That's a different phenomena. So when there, each one of these markers has a different meaning when it's high or low. There's no universal rule. You just got to learn it marker by marker. That's why I'm, you know, standing here, we're sitting here talking about this.
Metabolomics is a great test. It doesn't involve a blood sample. You can just finger prick, so it's easier. Okay, so you can use the metabolomics, the Nutrival, or the Ion panels. Let's see, trying to get through all the questions here. Yeah, so you want patients to stop taking supplements for three days or longer prior to doing the test, unless it's something they're highly dependent on. Okay.
Yeah, so you have to be careful. If you're using like 6,000 milligrams a day of NAC, you got to think that through and look at other variables because you're going to be stimulating all kinds of stuff, right? So you're going to be stimulating all these different pathways and then some. So be careful when you get those dosages that high. You've got to monitor people and kind of know what you're doing. You know, if 8-OH is high, then you can use antioxidants of any stripe. You could use glutathione, NAC, cysteine, CoQ10, vitamin A, vitamin E. You have a whole sort of range of different nutrients you can use in that situation. All right.
And so let's see here. Sometimes this test doesn't work right. Uh, there you go. It's funny because my computer kind of gets started at the end of the day, and I almost think it's me going insane or something, but I really think it does. Okay, so we're going to wrap it up. If you guys want tons more of this, you can join one of our boot camps in June. We have the Lab Interpretation Bootcamp on Functional Genomics, which you're welcome to attend. You get a 20% discount off the full price, and that's where we're going to spend two months doing a deep dive into interpreting these labs from a genomic perspective. And then in the summer, in August, we're going to have a Telehealth Business Bootcamp. I think we started doing these twice a year. They've been our most popular ones. We talk about financial planning, business planning, how to build a practice. Both of them are two months long. Both of them, you get a discount if you do that code. And I look forward to talking with you again at the next one of these. Bye for now. You.