Transcription
Up. You're having a good evening or morning, depending on where you are living. So, I wanted to do something a little bit different and do a sort of advanced laboratory interpretation for an hour, or maybe half an hour, whatever amount of time you go in and hang in there for. And then, welcome to ask questions at the end, as this is pretty complicated necessarily.
So, um, quick little update. So, for the last two and a half years, I've had the great privilege of working with Richard Lord. Dr. Richard Lord, those who either don't know, wrote a book a decade or two ago called "Laboratory Evaluations in Integrative and Punctual Medicine." He's the scientist that originally developed the first organic acids test, which we now call the Nutri-Eval or the Organix or Ion Panel. He was the first scientist that developed fatty acid testing in our industry, the first one that did amino acid testing. He's really the scientific mind behind much of the work that we all do today. He's the scientist that developed the GI Effects test. If you ever order a GI Effects, that was Richard Lord's work. And so, you know, he and I have been working together really closely for two-and-a-half years. He's written several books now since he and I started to work on this, you know, training relationship where he's training me. Those books are now available on iBooks. If you're interested, you can look up Richard Lord at iTunes or iBooks. You'll see his new work. And, you know, one of the things that he's been drilling me on for a long time is these organic acids ion panels, Nutri-Eval, whatever you want to call them. And so, it is kind of testing a special relation to the brain, and I want to talk about tonight. I have been focusing on this one subject area for, you know, maybe 15 years. I just started to understand the deeper points of this like about a week ago. So, I thought I'd do a class on it because I really get it now. It's taken so long. This is, I would call it advanced lab interpretation. If you don't totally follow this the first time, that is probably good. That means that you're looking about it. And if you totally understand every ramification of this, then your IQ is probably a hundred points higher than mine. More power to you. Great. I'm not trying to do this to confuse people. I just feel like the way that Dr. Lord taught me, he just drilled me on this, and then a few months later, it again. And after two and a half years, bingo, the lights went on, and I totally understand this whole pathway now. And so, I want to try to explain it. And it's directly relevant to many of the complex cases that we work with. This is not just like an abstract scientific concept. This is like rubber meets the road when you're working with depression, anxiety, you know, really, you know, severe memory problems, anything to do with the brain. Could be kid, could be an older adult, could be anybody. And so, there's a couple of big picture concepts, I guess. There's maybe three of them. But this, let me just look at some slides. Oh, can I get through? But I want to talk about the essential fatty acids, and I want to talk about the kynurenine pathways, okay? And how you can interpret your patients' labs to get a really deep understanding about what's going on with your brain.
So, right off the bat, let's take a look at this here for a second, because everyone always wants to know what to do. And so, I thought I'd put the "what to do" slide first, basically, instead of less. So, if you're like my father was in academia, and I grew up in an academic environment in Berkeley, California, and academics are very predictable way of doing things, right? They write a paper, could be 50 pages or 5,000 pages, and they'll use, you know, ideas and ideas, and then there's a conclusion at the very end. And, you know, for clinicians, we always, that's really frustrating to go based on that, because clinicians want to know what to do. So, I'm going to start with the "what to do" part, and what supplements you can use to fix this. So, you have a couple options, and we're going to get to the "why" part in a minute, okay? We're doing this backwards. So, tryptophan is available from any of the companies that we work with, and you have 5-hydroxytryptophan, or 5-HTP. And you're going to need to use them both in different circumstances for what we're about to talk about. And so, tryptophan is great because it is the rate-limiting step in the synthesis of all proteins except for collagen. Okay? That's what direct Richard Lord quote. Richard told that to me two and a half years ago, and I was like, "Dude, there's no way." I didn't say this. I was just thinking, "Dude, there's no way that that is possible. I would have known if tryptophan was a rate-limiting step in the synthesis of all proteins to separate ecology." And like, someone would have told me that 20 years ago. I looked it up. It's true. You shouldn't believe me, you should look it up, too. That's a profound statement. Don't say it one more time. Tryptophan is the rate-limiting step in the synthesis of all protein. Okay? That's a big statement. And in regards to what we're talking about now, that's going to be relevant for mitochondrial function, be relevant for neurotransmitter function, and a whole bunch of other things, right? So, if you have a patient who has neurotransmitter problems, and you know they have a mitochondrial issue, and you want to rebuild their mitochondria, tryptophan is a good choice to use as a supplement. However, tryptophan has a fatal flaw. And so, you can't always use tryptophan. And once in a while, you need to use 5-HTP. 5-HTP is not the rate-limiting step in the synthesis of all proteins except for collagen. 5-HTP converts to serotonin in an unlimited fashion. And so, by that, I mean, with tryptophan, there's an enzyme here, you see tryptophan hydroxylase, and when serotonin levels get to a certain point, there's a mechanism that shuts off the conversion over. Oops, sorry, I changed the page by mistake. There. There's a, there's a mechanism that will shut down a conversion, okay? So, what'll end up happening is you won't have, you have a limited amount of serotonin that you can produce from tryptophan, okay? Because that, that ends the, shuts things off. Sorry, my computer is acting up on me here. Okay. So, 5-HTP is one enzymatic pathway further down the road, there, right? 5-HTP will convert to tryptophan to serotonin in an unlimited fashion. There's no limit on that. All right. So, 5-HTP is better for patients who are really low in serotonin. You have to dump in a lot of the precursor to get the serotonin up because there's no rate-limiting step. The more 5-HTP you give, the more serotonin they're going to make. And tryptophan is better in situations where you want to work with the mitochondria, okay? So, they each have their place. I use them both every day in my practice. And if you kind of keep that in mind, if you want to work, and sometimes one will work better with a patient than the other, too, you know, especially for things like sleep. So, you should just have them both around. Anybody use them both? Okay. Not, it's like one is better than the other. And, you know, the worst-case scenario is you try one of them, doesn't work, then you try the other.
So, when I was talking about tonight is figuring out how the combination of the assessment of essential fatty acid levels and the kynurenine pathways reveals these new patterns in treatment-resistant depression. I've had several cases of this. I want to show you a couple of them tonight. The kynurenine pathway assessment, including kynurenine and picolinate, can appear to be normal or low in these cases, along with a really specific essential fatty acid pattern that I'll show you, which is going to be low omega-6s. And this concept is then of under inflammation. So, I want to talk about this under inflammation, or when the brain is under-stimulated. And then we're also going to get into more detail on the kynurenine pathway as well. So, this idea that the under inflammation could even happen is just outrageous, and I wouldn't have believed it myself if I hadn't seen it a couple times this year, oh, in patients. And we also wanted to differentiate between omega-3 and omega-6 issues, okay? And why some people may be resistant to the typical treatments we might use, antidepressants or essential or amino acids. This slide is in there because I want to do a talk on the urea cycle, but we don't have time tonight. But just maybe this is like a preview of maybe next time we can talk about this, because this is really important too, and I just learned about this. We can talk about it, but it's about, it's a really great way to help people detoxify, but we don't have time for that, okay? I just threw that in as a reminder. Maybe we'll talk about if we have a few minutes at the end, okay?
So, arachidonic acid. Everyone's familiar with this. Everybody, you know, when you first start studying clinical nutrition, you learn about arachidonic acid, prostaglandin production, and how when people get not enough omega-3s and too many omega-6s, they get inflamed, bad things happen, right? And arachidonic acid is like mission-critical for its production of prostaglandins, right? All these immune-related things that are happening, the economy needs all this kind of stuff. Super, super, super important in nutritional science. It doesn't get more important than arachidonic, right? So, on the right-hand side, you see the omega-3s. On the left-hand side, the omega-6s. And you can see the arachidonic. And in general, in the integrative medicine and clinical nutrition world, we think about high, or what's a relatively low levels of omega-3s and an inflammatory problem happening, an inflamed patient that's got too much of this arachidonic acid, too much of these, right? You know, pro-inflammatory things moving. Yeah. With anything in the body, when there can be something in excess, there can be something that happens in the reverse, when there's a deficiency. And that's what I want to talk.
Oh, and then we're also doing a plug here from a class. So, have a really great mentorship training program now. We're going to be starting a new group in January. If you're interested in signing up, you can save a thousand bucks by remembering that code VIP January 2019. The mentorship includes hundreds and hundreds of hours of information, like the one hour we're doing tonight, but it's all organized in a really great way. So, if you're interested in doing the class, it keeps getting better. It's going to be a good year in 2019, and it'd be lovely to have you join us. We have a really great group of doctors that are coming in every class. If you've been on the fence for a while, just take it. You know, just sign up for it. If you don't like it, I'll give you your money back. If you've been on the fence for a while and you're just thinking, "I don't know if it's really worth it. This Kalish guy seems a little strange." Just sign up for the class. You know, if for some reason you don't like it, we'll just give you a refund after the first 30 days or something like that, okay?
So, that's, let's look. Let me pull up some of these labs here. Let me show you. The rest of the time, we're just going to look at labs now. It's just sort of a setup so you can see what we're trying to talk about here. So, here we go. Papa dog. Sorry, I'm going to get out of here because we're not going to eat the PowerPoint anymore. And that I have a new computer, and I'm battling with it still. I don't really, we're not really getting along fully yet. It's going to be maybe a little bit longer though, didn't Peter and I kind of make peace with one another. All right, there we go. Thank you, computer. So, let me show you what we're talking about here now. This isn't an Ion Panel. You'll see very similar results on organic acids testing from Genova. You'll see very similar markers on the Nutri-Eval from Genova, the basic test that a lot of us use. You know, I would say this is like one of the most fundamental functional medicine tests. And what we're looking for here, in terms of the markers, and most of these names are probably familiar to you all, is I'm, you see kynurenine marker 25, quinolinic marker number 26, and then picolinate marker number 27, okay? Those two for covers, that's really what we're starting to think about here, okay?
So, again, 25 kynurenine, 26 quinolinic, and 27 picolinate. So, the standard way that we understand this, right, is that when kynurenine goes up, there's inflammation. I'll show you the image of that. When kynurenine goes up, there's inflammation in the body, right? And that inflammation is driving, you know, being driven by some, you know, she's, oftentimes a gut irritation or gut, you know, some kind of toxin or whatever it is that's, you know, causing the body to react with an inflammatory response. We make a lot of this interferon, right? And that interferon-gamma drives it up kynurenine. And kynurenine goes up high enough, then quinolinic goes up, then the brain gets agitated, and then all of a sudden, we have an inflamed brain. And that sort of concept, I think that's been really familiar in functional medicine circles for quite a few years now. And so, and let's talk about this standard way that we look at it. They've all look at this first, and then we can talk about maybe the exception that, that we're going to look at as well. So, let me, again, I mean, let me kind of follow this for you, in case you're, this is a little new to you. Let me just trace it out with him, a little spotlight feature here, and see how this works. So, the body is inflamed, right? There's the inflammation. There, interferon gamma goes up, the immune system is getting involved. We make more kynurenine from tryptophan. Does your tryptophan? This is I do enzyme. We convert the tryptophan into kynurenine. Now, the brain isn't inflamed. Did some flames? We make quinolinic. And then we have this effect. The quinolinic has on the glutamate system, the major excitatory neurotransmitter system of the brain. And if there's enough kynurenine and quinolinic goes up high enough, then these brain cells get agitated. It's like a water balloon getting shaken, shaking, shaking, poof, and it pops, right? And then the brain cell is roasted, and it's not good. And so, we can, as you can see here, magnesium to help calm things down and whatnot. But the more inflamed you are, the higher your kynurenine goes, the higher your quinolinic goes, and the more potential you have for depression, or anxiety, or memory problems. And this is the whole model of the brain being inflamed, right?
Now, if you look at the top here, you'll see tryptophan is also converting into kynurenine in your liver. And in your liver, that kynurenine eventually, then due to B6, gets converted into quinolinic and then eventually into B vitamins, okay? So, tryptophan gets converted to kynurenine in your liver. Tryptophan gets converted to kynurenine inside your brain. And when we're looking at these tests, you can tell from the lab whether the conversion is happening in the liver or the brain. And why does that matter? Because one means that your brain is inflamed, the other is that you have a significant vitamin B6 deficiency. And when we were joking about this on Monday with a group of doctors, but when I was in my very first year of practice, like my first month of practice, I walk into this naturopathic clinic. I'm working with this guy, Dr. Freda, and he's literally unloading cases of magnesium and B6, like, you know, cases by the twelve, and just handing them to patients. And he would give almost every patient B6 and magnesium. And then I'm thinking, "Well, this is a little Looney Tunes. Why is this happening?" And then patients were coming back a month later saying, "Oh my gosh, you cured my neurological problem," or "My fatigue is gone," or "No miracle cases happening left and right, just from using B6 and magnesium." This is why here we're looking at it. One of the major reasons why, because B6 is essential for neurotransmitter production, for detoxification capacity, for so many, for the use of every amino acid, right? Every amino acid is broken down in your system, and it will, that breakdown of every amino acid, you know, requires B6. So, to utilize any amino acid in the body, you have to have vitamin B6 present. That's just one of the most essential nutrients in clinical nutrition. And then here's our magnesium, right over here. It's on the same exact system, right? When your brain is really inflamed and agitated, magnesium calms things down and protects the cells. So, we really need magnesium. We really need B6. And when we look at these labs in a minute, you're going to learn how to differentiate what is an outright B6 deficiency versus what is an inflamed brain. And remember, kynurenine goes up in each case. In what situation? It's going up in the liver due to B6 deficiency. In the other case, kynurenine is going up in the brain because the brain is well-claimed. And then, once we go through that whole rigmarole, we're going to talk about something which, and this is the radical part about tonight, is it possible that your kynurenine could be too low? Is it possible that your quinolinic could drop too low? And, you know, here I am talking to Richard Lord for two years, saying this the whole time. And he's, but he said it again on Monday. It's like, you know, if I've always wondered, down for the last decade or so, I wonder, you got to imagine an older gentleman with a southern accent. He's a very fine gentleman from Georgia. You know, I've always wondered, Dan, what does it mean when these markers are low? There's no literature on this. No one really knows. But for every other marker, for vitamin D, for homocysteine, for cholesterol, for any of these markers, even for blood pressure, we know that too high is bad, and too low can be bad as well. So, what happens if this quinolinic system, kynurenine, quinolinic, is too low? There's not enough stimulation to the brain, and that glutamate system then would be flat, okay? And that's exactly what we see in some of these patients. It's not in the literature anywhere, but I've seen it in my practice now a couple times, and you'll see it on these labs, and it'll, and it'll start to become, I think, more obvious, okay? So, we want to talk first of all about the high kynurenine system, and how you can diagnose those situations. And then we can get a little radical and talk about, is it even possible, or what does it mean if it's low? All right. All right.
So, let's take a look here. I've got some other things pulled up for you. I hope I'm not, if you're totally confused, you can raise your hand or something. See, see, but we'll do questions at the end, all right? Okay. So, here's the actual marker. So, you see the kynurenine sitting there, right? That's number 25. And then you see quinolinic and picolinate. We're going to focus on those. There's other markers on here that we're ignoring, just for today. And then I want you to go up here, you look a little higher up on the lab, and you'll see that there's another marker that is super important. And again, if you're ordering Nutri-Eval, you just have to kind of extrapolate. They have these similar markers on the Nutri-Eval, but the names are a little slightly different. I think it's like kynurenic acid or something like that, instead of kynurenine, but it's the same basic marker. And so, the B6 marker here is called xanthurenate. And let's put up here, sigh, oh, and it's under the B section, okay? Now, my computer is really, apologies, if this is something not working here, I might have too many windows open here. You go, come on. It's number 18, xanthurenate, okay? So, if xanthurenate is high, this is the easy part. If xanthurenate, that's high, it means your B6 levels are low. That's the only thing you remember from tonight. I promise you will help a couple dozen people on the next month. So, means to say it a few times. If your xanthurenate levels are high, just number 18, if xanthurenate levels are high, that person needs vitamin B6, okay? Xanthurenate builds up when B6 levels are deficient. And you can give 50 or 100, even 200 milligrams of B6 to someone who's deficient. Oftentimes, the higher levels are required. I usually start with either a hundred or 200 milligrams of B6. I know that's a lot, but if xanthurenate levels are high, it's warranted. Now, obviously, this case, they're not high. We're just kind of talking theoretically here, okay? So, again, if xanthurenate is high, give them a hundred or even 200 milligrams of vitamin B6. Have them come back in a week or two, and you're going to start to see some changes, assuming you're doing some other basics with clinical nutrition, well, okay? So, that's easy. That's the B6 marker.
Now, the question then comes, well, what does it mean when the kynurenine levels are high? Let me blow up another example. I think you have one right here. There we go. So, look at me ahead, it already for you. Look at that. I'm not usually this organized. Okay. So, let's look at kynurenine again. You see number 25, kynurenine is high. So, kynurenine is high. That can mean one of two things. Remember, kynurenine can go up in the liver if there's a B6 deficiency, or kynurenine can be high. It could mean that the brain is inflamed, or it could be both. Again, it's ticking over two years to understand the full implications of what I'm talking about tonight. So, in this case, the kynurenine is high. So, the first thing we do is look at the xanthurenate and see if it's high. Then we know there's a B6 problem. This one's borderline elevated, so it could be a B6 problem, okay? And then we're also looking to see what's happening with the other brain inflammation markers, the quinolinic and picolinate. And in this case, it's kind of borderline, but the kynurenine is clearly high. The quinolinic and picolinate are in the high end of normal, okay? What should happen in an inflamed brain? Is a kynurenine, quinolinic, picolinate should all be elevated. That's what's supposed to happen when the brain is in, in bad shape, right? In this case, it's a little borderline. I would say though, it's a judgment call, but certainly the pattern is there. Quinolinic and picolinate are hot, or in the height, you know, one short, one quintile short of the highest. In fact, if you look at picolinate, it's 7.8, and the cutoff is 8. You know, I would call those borderline. And so, that makes sense. This is looking like an inflamed brain, right? Because they're all either high or borderline high. The three inflammatory markers, kynurenine, quinolinic, picolinate. So, this person probably has a B6 problem and a problem with and then plain brain.
Now, let's look at these other examples here, just so you can see what else can happen. And again, what we're, we're thinking of in the typical situation is that the brain is inflamed. Kynurenine, picolinate, and quinolinic are either elevated or borderline elevated as a group, right? They're all three up. That's what you would expect to see in a brain that's inflamed. Just look at one more example here, and then the big question becomes, well, what happens if those inflammatory markers are low? Is it automatically assumed that the person's fine? And the answer is, absolutely not. That's the tricky part. So, let's just look at one more set here, and this is a judgment call. So, I'm not saying this is an easy thing to calculate or figure out. That's why it took me two and a half years to even understand it. So, now, in this example, sorry, there we go. In this example, you can see the kynurenine, quinolinic, and picolinate are all in the normal ranges. All right. The kynurenine, quinolinic, picolinate are all in the normal ranges. And that's the normal lab. Where it gets difficult is to assess when these markers are too low. You'll see in very rare cases, kynurenine, quinolinic, and picolinate, all three being low. That's a pretty easy one, because then you know there's a pattern where they're all three low. There's going to be something wrong. But what I wanted to show you that's kind of unique, that's pretty amazing, is this pattern here. So, remember what we're working under this assumption that when the brain is inflamed, we're going to give tryptophan or 5-HTP, and we're going to, you know, treat the inflammation and figure out what's going on with a person's gut and do all these other things, obviously, as well. But though, you know, one of the main things that we want to do is get a, let me get this out of here. One of the main things that we want to do is, you know, control for the inflammation. We're not, I'm, well, we're talking about tonight, it's just their brain-related treatments. There's obviously other stuff that you can do to make these situations better.
Now, here's a side-by-side, two different. And we can look at these markers side-by-side. So, on the left-hand side, you'll see the amino acids broken down. And this is what we've been talking about, right? What's happening with tyrosine, tryptophan, whether to the brain. And if you see a pattern where many of the amino acids are high, it's a B6 deficiency. B6 helps us break down and process amino acids. So, if amino acid levels are high in the blood, there's a B6 deficiency. If you see a problem where the amino acids are low, it means a person is low in amino acids, and it could be a variety of reasons why that's happening. It could be because of diet, they don't eat enough protein. Well, that's pretty rare, I think. It could be related to the edge of cork acid insufficiency, they're not digesting their protein very well. It could be related to digestive tract infection. Any of those things could trigger it, right? So, again, patterns of high amino acids, like you see on the left, mean that there's a B6 deficiency. B6 is used to break down the amino acids. Patterns of low amino acids, more like you see on the right, mean that the person needs them, you know, needs the amino acids. And again, you're going to figure out why they're not absorbing them, or to diet, or whatever it may be. So, high levels, you treat with B6. Low levels, you treat with free-form amino acids themselves.
And then I want to show you what was really quite stunning for me. And you can see that woman on the left has potassium and magnesium problems. And, you know, they're different in some ways here. One of them has arsenic and mercury toxicity, the other one doesn't. But the really interesting part is on the next page here. This is a real "aha" moment. So, now we're looking at essential fatty acids. So, if you're getting into, like, you know, the top 5 or 6 nutrients that are just mission-critical, B6, magnesium, essential fatty acids, omega-3s, you know, would probably be almost people's list. If you look at the woman on the left, got a problem with low omega-3s. And so, that is obviously, if we all know, you know, directly related to depression, anxiety, cognitive problems. Thousands and thousands of research studies on that. Anyone's pretty aware of that. Even the conventional medical community, I think, is kind of accepted there's a role of fish oils and all this. But what we're interested in more now, or they may get sixes. And it's a very unusual pattern in this particular patient. You'll see her omega-6 levels are low, and her arachidonic on the left is low at a 128, okay? If you look at the woman on the right, you'll see her arachidonic, that's number nine, is in the lowest quintile. And you'll see for both of these patients, there's a pattern within the omega-6s of low levels. It's not just a single low. And in fact, they follow a pretty similar pattern. If you want to look at it, and I'm going to have to talk about some of the fine points of this test for a moment to, to clarify that. So, you know, like three years ago, I was 51. I thought I had been doing this 20 years. I kind of know what I'm gonna know, and I'm gonna like, kind of ride out, like, career, you know, teaching and doing these things. And then I ran into Richard Lord, and I have learned more in the last two years from Richard than the cumulative 20 years prior to that. And every Monday, I get to sit down and talk with him for several hours. And it's like, it's like literally talking to a textbook that has, you know, not only did he create these labs, but, you know, when he worked at Metagenics for 30 years, he saw literally hundreds of thousands of these tests. I mean, he developed them, but he watched them. This is his baby, really. And he's a very sharp scientist. He works till seven days a week, reading research studies. He's at his office every morning at 9:00, and seven days a week, this guy is still hammering away at the science. It's just phenomenal, you know? And the highest compliment I've ever gotten in my career happened about two weeks ago, because I had the one patient that we're talking about on the left, and we're reviewing this other lab on the right, but it was no, like a year later, right? And we're going through the lab, and then I just thought, "Holy moly, I have seen this pattern before." And I looked it up, and what I'm about to show you, I was like, "Richard, look, they both have the exact same pattern." And he's like, I was kind of quiet for a while. He didn't say, "Good job, Dan," or "You're such a great doctor." It's just not his style. He's very kind of, I don't know, he's very, well, I don't know, modest or whatever he is. But he said, "Dan, we're gonna have to write this up as a paper. This is going to be like your first research paper." And I was like, "Okay, that's the way I'm saying, hey, kid, you figured out something here." It's really the highest compliment you could get. In case you're, you ready for this? Look at the omega-6s on the left. The first one is fine. We know right away this woman is getting omega-6s in her diet because linoleic is the first in the pathway, right? Woman on the right, the linoleic, which is the first in the pathway, is fine. It's not a dietary insufficiency. She's getting the omega-6s. They both are. But look what happens with gamma-linolenic, low. Look what happens with eicosadienoic, a-kai, even primarily pronounced that one, low. Look what happens with each one. It's going down the line here, right? Low. And then here, we get to our primary guy, the arachidonic, and it's low as well. All right, you see that pattern there? Although, and then look on the other side. Normal to start with. So, they're getting in her system. It's not a lack of omega-6s there. There. But as the conversions happen, drops out, and now it's just outright low. And you get all the way down to arachidonic, and it's low, okay?
Now, just to explain something. Number 10 is high. Why is that? Well, because it's not a very accurate, that particular marker. Number 10. The way you can tell it's not very accurate is to see how the hash marks here are divided up equally on all these other markers. You see how on marker number 10, there's this long stretch there where the low quint, the lowest or first quintile takes up almost the entire graph? That means that it's not a very specific test. That means when the numbers fall anywhere within that range, they can't tell where the numbers are, okay? So, what, when Richard, when Richard was originally setting this lab report up, he was trying to tell you, of course, no one really got the memo on this, that the markers that have the even hash marks, and there's five marks, you can see the quintile markings are very precise. And when the machine, when the mass spec machines puts out a number, they know exactly where it was, where it is. But when number 10 comes out of the machine, the mass spec machine, there's this huge area, like 80, 80 percent, they just can't tell where the number is. They're still testing for it because they, you know, are trying to find something. But so, this one marker that's high here is not very accurate. And you just carry through with the entire organic acids profile. Whenever you see a first quintile marker that takes up the entire length of the graph, it means that that marker is not very accurate. Yes, there were winning. Hey, there's a black box, the area here. We just don't know how to find it. So, just toss that one out. In this case, it's not part of the low pattern. And similarly, when you're reading these tests, if you ever see one of these where the hash mark is just so wide like that, don't take it too seriously. They're trying to tell you these other markers are much more accurate. This one, not so much. I was looking at these labs for over 20 years until I learned that little fact. It's really helpful because labs telling you, "Super accurate, super accurate, we got the hash marks." Not accurate. So, we're going to toss out number 10. If you toss out number 10, you see both these women are okay on the first marker, and then the whole rest of their omega-6 system just is falling apart, arachidonic on down. All right.
So, what does that mean? Well, I don't know. It means that they need omega-6. And in this case, I used a GLA product. And the GLA, I think that I use is 200, 40 milligrams per capsule. And rather than giving them two a day, as I usually do for just like a hot flashes or night sweat situation, for each of these women, I gave them six capsules a day because I know that there is a frank deficiency happening, and we really want to move the numbers. Now, if you're wondering, well, why is this happening? And this is something that's just, I don't, I personally find like, actually literally exciting is what you're seeing. And I don't remember the name of the enzyme. You didn't write down. One of you could. Oh, you know it's something like six delta desaturase. I think it's delta-6 desaturase. That's raised. But don't quote me on that. But there's an enzyme, okay, that is responsible for converting linoleic into gamma-linolenic, okay? And then other enzymes that are responsible for these further conversions, right? So, there's clearly, and some more obvious on this one, on them over on the right, it's clearly a break right here. And that, again, that enzyme, which I think is six delta desaturase or delta-6 desaturase, forget the name of it, that enzyme is clearly missing. It doesn't, not missing, but there's not enough of that enzyme to make that reaction go forward. So, these women are getting enough GLA in their diet, but they're not able to convert it down through to arachidonic. So, the genetic problem, and I'm sure if you ran all their snips, you would see it on a genetic test, 100% guarantee you, it's a genetic issue, okay?
So, now we're seeing omega-6 deficiencies. We're going to give to GLA three times a day. We're in both of these cases, we had a complete reversal of the anxiety and depression in about two weeks. Both of these women, one in their 20s, one in their 50s, had lifelong anxiety and depression. But now, here's where the, here's where it gets like doubly interesting. Now we're going to cut back to their brain markers, and we're thinking, hmm, they're low in omega-6, they're low in arachidonic, they're low in the fatty acids that we think of as being pro-inflammatory. Usually, we're worried about too much inflammation. And in fact, my entire career, and yours probably too, has been spent working with people who were inflamed, overly inflamed. If there's a buzzword in functional medicine, inflammation causes depression, and gut inflammation, and oxidative. I mean, inflammation is just, you know, a huge part of what we do, huge. But look at these patterns. The kynurenine was low, and the quinolinic and picolinate even lower. Here, we have the kynurenine was normal, and the quinolinic and picolinate were both low, okay? So, remember what we said, where, when quinolinic is high, we know it's a problem, and there's inflammation driving this agitation, and that glutamate system is not doing very well. But what happens when quinolinic is too low? I mean, it's an open question. And again, you know, Richard and I have been talking about this for two years. There is no research on that. It's just assumed that low quinolinic is okay, and that low picolinate is okay. But now we can tie in, at least for these two women, and I'll bet I'm, you know, just since I gave this talk to my students last week, we've already had two other cases from students. Why, oh, wait a minute, come on. So, I would feel, it's one of the ways of how we learn in functional medicine. But probably not going to get a pharmaceutical company to do a research study on this. But if we all pull our resources, start to look at your labs and see if you see this pattern too, that's how we learn from each other in functional medicine, right? How I learned all the stuff that I know from other clinicians. And you probably will see some patterns where the kynurenine, quinolinic, and picolinate, well, the kynurenine is either normal or low, and the quinolinic and picolinate both are quite low, okay? And that would be an under-inflamed brain. And in this case, these two cases, plus with two others that we've already gathered in the last few days, we're looking at, you know, a B6, I'm sorry, omega-6 deficiency, and then under-inflamed brain. It's quite a miracle to to work with people. And I've worked with both these women for maybe two years prior to figuring this out, meaning that I did all these other treatments with them and had some benefit, or they wouldn't have stayed with me. But to see somebody that you've been working with for several years completely eliminate their anxiety and depression that was present since they were four or five years old, you know, just from taking a bunch of omega-6. Oh, it's really quite dramatic. Now, what's going to be interesting, and I haven't done this yet, is when we retest all of them, or both of them, and we see, I don't know if these markers are going to come up or not. But I'm pretty convinced that there's a genetic block with the production of the omega-6s, and that that is somehow impacting this kynurenine system.
Now, the vast majority of time, we're doing it right. So, let's look at the opposite, because this is an unusual situation, but I just wanted to explain it so we can all ponder it, and hopefully, you'll come with, come up with some conclusions on your own. The more common situation, let's talk about that for a few minutes. We have a few minutes yet. Still have a few minutes. All right, another five or ten minutes, and I'll open it up for questions. The more common situation is going to be this one here, where the kynurenine is high, with quinolinic and picolinate either borderline high or high. This is an inflamed brain, okay? So, in this situation, I'll show you what you can do for treatment. Well, well, first of all, the bigger picture treatment is always in functional medicine, find out where the inflammation is coming from and treat it. We focus on the gut a lot, as you know. You might do anti-inflammatories like curcumin or the fish oils or whatever it may be that you're doing to calm things down. But when someone has a high kynurenine and quinolinic, picolinate are not too far behind, you know, that you want to work with the inflamed brain. And assuming that you've looked at the B6 deficiency problem that we talked about earlier, okay? So, I want to show you the pathways for that. And I always get asked this question, and so I might as well go or. And the question is, well, well, if these pathways are active, am I going to make the patient worse if I give them 5-HTP or tyrosine or tryptophan? And I've never seen that happen. I understand a concern and why you might be worried about that, but I don't think that is gonna, at least I've never seen it in my practice or with any of the people that I've coached and worked with. So, I don't think you're going to run into trouble. And I'll show you why that concern is present. I mean, I've got a few slides on that here. So, the concern is, is understandable. So, there's two, there's two versions of this we look at here. So, this one, you can see quinolinic and picolinate on the bottom. And the idea being that when the brain is inflamed, we call an eight, quinolinic, as well as kynurenine, are going to go up, right? And if we dump in tyrosine or 5-HTP, is that going to go down through these inflammatory pathways and make the person worse? I've never seen it happen ever. And you know, been giving a lot of people a lot of these amino acids for a really long time. I think it's a theoretical concern. The way that I think about it is, if you're, if you're driving a car, and your gas tank had a bunch of leaks in it, is it bad to put more gasoline in there? No. I mean, I mean, we're not fixing the inflammatory problem, but I don't think you're going to trigger or make the inflammatory problem worse by giving someone tyrosine. In fact, you're just supplying them with a nutrient that they're burning through at a high rate. So, with high kynurenine, quinolinic, picolinate, you can absolutely use 5-HTP, tryptophan, tyrosine, any of those. So, you see the pathways here. Tyrosine comes down to dopamine, then down to picolinate, quinolinic. So, tyrosine is fair game. And then the more common pathway that we think about a little more often is here. You see tryptophan, the upper left, going down to kynurenine, okay? And then eventually, you see that xanthurenate and the bottom quinolinic. So, all these markers, and as the kynurenine goes up, you can see how there'd be a draw or a pull or depletion of the, of the serotonin, right?
I'm just going to turn off my webcam because this is running so slow now. Treatment-wise, you can use tryptophan. We talked about that. That converts to serotonin. It also helps with mitochondria. Or if you want to get the levels higher, you can use 5-HTP. You won't get that benefit for the mitochondria, but you'll get more of a push on serotonin. And then we're always wanting to make sure that we, you know, control for the inflammation and do all the other functional meds and things that we do, okay? So, dosage-wise, I usually start people on 300 milligrams of 5-HTP a day, either a hundred breakfast, lunch, and dinner, or 300 at night to help them sleep. I usually start people at 3,000 milligrams of tyrosine a day, usually a thousand breakfast, lunch, and dinner. I boost up 5-HTP to as high as 600 milligrams often in people that have a lot of brain-related problems. I boost up the tyrosine up to as much as 6,000 milligrams often for people that have a lot of brain-related problems. We start low and then titrate up so we don't get into trouble. Generally, you find that people will respond within a week or not. So, if they're on these amino acids for more than a week and they're not responding, you can change the dose, usually, you know, increase it. If it's tryptophan, I usually start with around 1,500 milligrams a day, a thousand to 1,500, usually at night. And if you're made of both tyrosine and 5-HTP, you can give them both together during the day. 5-HTP tends to make people drowsy. Tyrosine is low stimulating. So, you can give a hundred milligrams of 5-HTP and a thousand milligrams of tyrosine three times a day if you want to get them both in. And you can see there's pathways, right? The quinolinic, picolinate is related to tyrosine. Also, it's related to the tryptophan and serotonin systems. So, you can use the tryptophan and tyrosine together, or use the 5-HTP and tyrosine together quite effectively.
And fact, oftentimes you need to to really get a more complete solution, so you don't just have to use a single amino acid.
One other thing I would mention is there's kind of a heavy hitter in here, which I use literally every day with patients. Probably my favorite supplement of all time. Well, my favorite supplement all the time is probably pregnenolone because I'm still, you know, a loyal adrenal HPA axis kind of guy. But my second favorite supplement would be mucuna. Mucuna pruriens, which is a herbal form of l-dopa, and that is just a beautiful, beautiful supplement to use for people that have low dopamine. So it's just another thing to keep in mind. You can use these here and make sure you don't forget about the b6. And I'll show you the mucuna here on this particular pathway. Let's see. You see where there's tyrosine that goes to dopa, then dopamine. So dopa or l-dopa, you can get in a, you know, you can give to patients in a non-prescription form. It's called mucuna. Most of the companies have a product with mucuna in it, and it converts beautifully down into dopamine, norepinephrine, and epinephrine. That's very effective. Again, it's probably my second favorite supplement of all time, and I use it quite a bit.
All right, so let's just wrap up here. Let me show you. Hopefully, this would just get you thinking. Remember a couple variables. One is that you want to check the kynurenine. Typically, if they're high, the brain is inflamed, and you can, you know, do the treatments that we just talked about. If the xanthurenate is high, they have a B6 problem. Don't be shy. 100, 200 milligrams of B6, totally fine. You won't hurt anyone with that. If they have the omega-6s low, and there may be an underinflamed brain, so always, you know, keep an eye out for that. That's what any possibility. And don't be shy with the GLA dose. You just, if they do need the omega-6s, you know, you can dose them on, again, triple what the typical dose would be. Two 250 milligram capsules, you could bring it up to six. Whenever you see, remember we saw that enzyme defect. Whenever you see a genetic defect or outright low level on these labs, you know, you can generally treat with a pretty high dose. And I was gonna say get away with it, but not get away with it, but, you know, make a big difference. And I think one of the biggest problems that I see in our profession is that people are using the right products, but they're dosing way, way too low, way too conservative. And so one more time, we can look at the pathways here, talking about omega-6s, that linoleic. Remember that person had enough of the initial omega-6, but they didn't have enough of all the other ones, except for that one marker that was kind of the inaccurate marker. So omega-6s to get a little more inflammation in these unusual cases, right? And then in the more, excuse me, in the more typical cases, we're using the 5-HTP, tryptophan, or tyrosine to deal with the situation.
We have a class starting next month if you're interested in joining. The way that the mentorship is structured, I have a whole year-long curriculum you go through. We have a very active community that has thousands of hours of case studies and special interviews with different practitioners. It's a very expansive program. You get access to everything for a year. We have a live weekly call once a week, kind of like this, where we review labs, but you're the one sending in the labs, and we look at your labs in the class. There'll be a new group starting January 18th. You get a thousand bucks off if you have that code. And if you have any interest in joining, I'd be happy to talk to you, or you can talk to one of our sales people like Mark, kind of get you oriented.
All right, now I'm going to open it up. We have a couple of minutes. If there are any questions, you can raise your hand or just ask a question in the little box thing there. Let me see any questions coming in. You guys all kind of fully grew up eating all this? Oh, wait a minute. There's Dave. Dave has his hand. Let me grab David. I'm Renee. Renee, are you there? Trying to unmute you over there already. Yeah, they're already there. I gotcha. I muted. Yeah, I'll read Renee's questions and because there may be, um, I assume that estrogen dominance and insulin resistance will also drive. Yeah, absolutely. We didn't talk about that. Drivers of this, anything that's pro-inflammatory. So insulin is classic, right? In terms of pro-inflammatory. Let's see if I can. My computer is just not really working on it. Let me see. Michael's there. You had a question. Let me see if I can unmute Michael. Michael, you there? Nope. All right, let me see. We got another question here from Patrick. See, the unmuting feature is not working very well. However, you guys can still hear me. Here on the Krebs cycle, why do I always find succinate low? I don't know. I don't see that on my tests. Should it be low all too often? No, what lab company you're using, but if you're using the or Genova Organic Acids, Organic profile, I haven't seen that to be a problem. Sometimes these labs go through like a little crisis where the reagents are not calibrated well, and you might have a few months where things are a little bit off. But I don't think that's happened at, you know, lately. But no, every lab has its little glitches once in a while. And let me see here. For some reason, I can't really unmute anyone. I don't know. Maybe because my computer's a little off. So I might have to wrap it up for tonight. If you guys do have any burning questions, feel free to send them in and go over them. Otherwise, B6. Yeah, so the B6, I would start with at least 100 milligrams a day. You can get it in 50 milligram capsules. Give 50 breakfast, 50 lunch. And don't be afraid to go up to 200 a day if the person seems like they need a little bit more of a boost. Again, a lot of times with these B6 deficiencies or omega-6 deficiencies, we're seeing a genetic flaw, and so the person just needs a much heftier dosing. You might think and analyze, titrate them up. You know, you really won't get into trouble with the B6. Will it increase dream recall? What you warn people about with B6 is if they have excessive, excessively vivid dreams, have them cut the dosage back. Okay? That would be the sign that they're taking too much of it.
All right, everyone. Sorry for the technical problems tonight. Hopefully, we got through most of this okay. And we'll have another talk like this in the new, in the new year. And I hope you have a great holiday season. Okay, bye for now. [Music]