0:00 One of the big mistakes made by the in the dietary field is to think of glycine as non-essential. Well, glycine is your body's natural anti-inflammatory. It's That's a very interesting story treating dental implants to keep them clean from gum infection. They actually have micronized glycine powder. If it's making a mess in your gums and teeth, we may be doing the same thing with blood circulation. Glycine is your body's natural blood thinner. Sir, what we think we need isn't based on the full potential of glycine as we'll get into Well what's enough? Glycine, deglycine, forms of glycine. What do you think about that? No, I think about as that that's you know, that's what happens when a little bit of ignorance comes in. You know. I don't know,
0:45 some of the answers, you know, we'll still find them out with future research, but it it is It's just amazing how universal and fundamental glycine is as a nutrient. And it's not necessarily just inflammation, just to let you go to sleep at night, right? Yeah, oh same yes, it's the same glycine receptor. So allergies, autoimmune disease, asthma. What are some of the big inflammatory conditions that you've seen um maybe improve with glycine supplementation. Oh well I learned a lot. Welcome everyone. This is gonna be an amazing podcast with a world-renowned biochemist and expert, Dr. Joel Brind. This is part two to a glycine podcast that we did before. Glycine is this amazing amino acid that many of us, I would say almost all of us are deficient
1:33 in because the rates are what we think we need isn't based on the full potential of glycine, as we'll get into. So you could be aging more quickly. You could have out-of-control inflammation. You might not be sleeping as well. Your risk for cardiovascular disease and metabolic issues might be higher than they need to be. So today we're gonna break down at least 10 different reasons you might want to start paying attention to your glycine intake. how to do it, where you can get it. And then we're also going to answer some of your very insightful questions from the previous podcast. So welcome Dr. Brind. Thank you for joining me for this part two. I'm really excited. Thanks for the follow-up. Great to be here with you again. Thanks. Okay, so tell everybody, just a quick intro to you, Dr. Brind, how did you get so interested in glycine? I learned about your work when I had your book The Glycine Miracle, which I told them before
2:22 I read twice. It was one of the best books I've ever read, one of the most understandable books, and I think one of the most impactful health books you can read. So What led you to writing that book? I was I was doing research as I've been doing I just to tell you I've been a professional researcher for something like 53 years. And uh I at the time I was working as a consultant, consulting biochemist to a research foundation who was doing work on longevity. And they came upon a finding of uh if of if they fed laboratory rodents, rats and mice, a diet that was almost deficient in the amino acid methionine, not talking about glycine yet, methionine. People may know that from methylators and so on. Methionine is known to be a an essential amino acid. But if
3:12 you feed just barely enough for these rats and mice to survive, they will actually live 30 to 40% longer. So this was a very big deal. This was back in the nineties, nineteen nineties. And uh it was reproduced by many other labs. It's now quote a thing, that there's something called a methionine restriction, which is not still totally understood. Which if you restrict the amount of methionine, let the animals just eat as much as they want, the food just has a barely enough methionine in it to sustain their normal function And they will live longer. One of the things I was asked to do is to figure out why. So my what I was trying to do was actually come up with some kind of dietary formula to mimic. methionine restriction. What can
3:58 we put in that's actually going to help get rid of excess methionine? And it turns out that the amino acid glycine is the body's way of getting rid of excess methionine. Now wait a minute, rewind. What do you mean excess methionine? This is an essential amino acid. Yes, it's essential. And because it's essential, your body has so many ways of recycling it, regenerating it, reusing it that it really needs very little. So methione of all the amino acids, which are bulk nutrients, you need so many grams per day. For methionine, you only need maybe half a gram. 500 milligrams, you've got plenty. Maybe 300 milligrams is better, right? We try to get the diet so that it'll look like you have 300. Well, it turns out other people, other researchers in the 90s had just
4:44 established that the body uh when it gets rid of ex when you have excess methionine, it gets rid of it through a particular pathway that uses up glycine. It's actually a It's an enzyme called glycine and methyltransferase, which is in fact the most abundant protein in human liver. It's a protein that utilizes glycine to get rid of excess methionine, because methionine is so essential to methylations, DNA methylations, neurotransmitter methylations. Many people who know something about nutrition know that methionine is a very key nutrient. And your body has particular ways of dealing with it, and every biochemist student learns about the methionine cycle, how this is recharged, how methionine is recharged. In fact These days in the modern United States of America
5:34 where you're going to McDonald's or you're going to some other place where you're eating those cheeseburgers every day and you're eating meat, fish, and poultry day in and day out three times a day. It's those muscle meats which are loaded with methionine. So in fact, our methionine cycle is usually not working right after we eat. In the hour or two after we eat that cheeseburger, our liver is busy getting rid of the methionine. And guess what? When it gets rid of the methionine, it uses up glycine. In fact, it needs two molecules of glycine to get rid of every excess molecule of methionine that you eat. So now Here we have the modern American diet. Compare that to our forebears, whether they came from another country or they were in the U. S. some generations
6:20 ago when people didn't have that much to eat. And they didn't waste anything. So they used to throw the bones in the soup. Now we throw the bones in the trash. So we eat the muscle meat. We cut the muscle off the bone, we eat the muscle meat. We throw the trash in the soup. Not only Are we eating more and more methionine, which we have to get rid of? But the glycine is in the bones because every third amino acid in collagen, which is the protein component of bone or connective tissues also, is uh is glycine. So there that's about by weight it comes out about 25% by weight of collagen is glycine. So we're doing a double whammy where not only are we eating more muscle
7:05 meats, more methionine, But we also are getting rid of that amino acid that we get otherwise from the bones and connective tissues that we use to get rid of it. So these days. We have a an amino acid which was thought to be non-essential, which is really conditionally essential. And the condition, the general condition is that it's really essential, because in not only two ways, but three ways, because you know what? We eat more, so we have more methionine, but we throw away the glycine we need to get rid of it. And because we eat so much. We're all getting fat, right? So we get overweight. And guess what happens? When you get overweight, your liver makes less glycine. Yeah. So it's a triple whammy that the glycine levels, even though
7:53 they're quote, normal is a statistical term, it just means what everybody's got. So what's normal is not necessarily healthy. And proglycine, it's certainly generally not the case in this day and age in this country. So we have an epidemic of what? All manner of chronic disease that's blamed on chronic inflammation. Yes. We have arthritis and diabetes and cancer and heart disease and all of these things that you see commercials for expensive medicines for, things that are based in chronic inflammation. And then on top of all that, people ask their own question about inflammation. They say, oh, inflammation, why do we have chronic inflammation? Inflammation is the body's first
8:41 response. The cells that do inflammation, they're called macrophages. They're the body's first responders to infection or injury. So they come right around whenever there's infection or injury, which means cell death. And they clean up the mess and and then they uh importantly they have to secrete all kinds of poisons in order to be able to kill whatever microbe got into you before it kills you in the case of infection. And it turns out that these first responders don't always come out with guns blazing. They and with guns blazing inflammation. The cells that do inflammation, when they're out there just cleaning up after injury, cleaning up the mess, getting the tissue rebuilt.
9:26 starting all of those signals for building new tissue for tissue repair, that's not inflammation, but it's mistaken for inflammation. Why? Because inflammation always happens. Why? Because it turns out glycine is the body's own natural regulator of inflammation, and we don't have enough of it. So we get inflamed, or parts of our body get inflamed. when there's no infection. And that was probably, I would say, in all of the whole glycine story. And you read the book, The Glycine Miracle, right? You can get it on Amazon that I wrote. And the real, what's the real discovery? The real aha discovery, this is the nugget of what's really crucially important is that inflammation
10:12 is not a national response to injury. When I get injured, if there's no infection, I don't get inflammation. I found it out with self-experimentation, the hard way, literally. Yeah. And you've told me like in the first podcast you told your stories of like burned by the sun, but not having the subsequent inflammation from the sunburn or having the disability and pain from having a fall onto my tailbone onto a concrete floor. And the concussion. And you told me about your CRP levels through your life. Which is the same thing. CRP is the general measure for inflammation. It's a it's a more modern version of an old blood test that used to be called the CED rate, the erythrocyte sedimentation rate. You take some of your blood in a tube and where they
10:58 where it can't clot and the red cells will slowly settle. If you're really healthy, they'll settle so slowly it almost never settles. Your blood is really stable. If you're ill, if you have any sort of level of inflammation, they settle, they really go down like a rock. They sediment very quickly because of a protein that your liver secretes called the C-reactive protein. And CRP levels, when you measure my CRP levels, they're a standard part of an ordinary lab test metabolic profile. My CRP levels are always the very bottom. Because I'm not glycine deficient. Yeah, and you've been how many how much have you been taking for how long? And then because you're the biochemist, before we get into the other applications, tell us How does it do this with the macrophages? How does
11:43 it keep these macrophages quiet? And how does it prevent the end stage of inflammation? Give us that story too so that they can. Oh, okay. The whole story of inflammation inflammation is a It's a whole defensive response like it's a war. When the body starts an inflammatory response, it's war. So in war you have all kinds of different levels of activation and You have level different kinds of armaments and different kinds of bullets and different kinds of missiles and ships and tanks and all of that. The same thing is true with the body. There are all kinds of cytokines, you may remember. From the COVID pandemic, the cytokine storm that was killing everybody. Oh, everybody's dying from a cytokine storm that is happening in the lungs with this COVID pneumonia. And uh what is the cytokines store? Cytokines are these chemicals, proteins mainly, and peptides,
12:36 smaller, smaller molecules that are secreted in some of them, things like hydrogen peroxide that are secreted. by these macrophages in order to kill whatever is coming in that's going to kill you. And if you have too much of it, it will ultimately kill you. The ultimate response against an infection Now really the people who get really serious infections and ultimately succumb to it, they typically will have something called a toxic shock. Toxic shock syndrome where the where all of these armaments are they go nuclear. They blow up and just fill the place with inside the body with these very toxic materials. And that's needed in cases of really bad infectious agents like anthrax. Right, which is fatal in a lot of cases. So the immune system's response to anthrax is like
13:24 nuclear. It can kill you. Ebola, this kind of thing. So the so what is it that starts the inflammatory cascade? It's a cascade of different materials that build up and have different kinds of cells that they target and so on. And what is it that limits it? So what normally happens? First of all, these macrophages get activated into what I call rend mo, rend v versus mend. Rend is really to tear things up to start shooting up the place. And they will do that if they're provoked because they detect the signature of some kind of bacterium. Could be anthrax or something else, just e typically They use I forget there's something used experimentally with the cell wall, cell wall polysaccharides, the lipopolysaccharides that are characteristic of bacteria If you put
14:15 those in the presence of macrophages, the macrophages will react to them. They will go into rend mode. Technically it's called M1, macrophage 1 mode, as opposed to macrophage 2, which is clean up the mess mode. And in that M1 mode they will shoot up the place. They will actually develop something that looks like an artillery cannon and a shell that will literally explode and the cell will the final Thing of the nuclear reaction is like the cell will explode, releasing all of these toxins all over the place, and you get that in toxic shock, which is largely fatal. So the first reaction to put these cells into the rend mode requires a an activation. That is inhibited by glycine. That is, it's naturally regulated by glycine. How does that
15:02 work? It's like an electrical switch? If you know anything about electricity, so you have a switch on the wall for the light in the room, right? And There's two wires connected to the switch, right? So one of them is hot and the other one is it's not connected, it's cold. So that means there's a voltage between the two poles of the switch When it's not closed when the light isn't on, that's 120 volts, right? In the US, in the walls 120 volts. When you close the switch, you turn the light on, what happens to the voltage? Now the poles are connected. The voltage between them is zero. Now the switch is on, so the switch has become depolarized. The voltage has gone from 120 to zero. In the case of your cells, they dwarf that way too Not with 120 volts, without
15:48 all electric eels or anything, or even higher than that. But with about 70 millivolts, 0. 07 volts. So there is every cell that normally exists has a resting potential. Usually around not only your nerve cells, but other cells too. They have a resting potential, a resting voltage of around 70 millivolts. And that's a resting voltage. If the cell is turned on, if something happens to turn the cell on, it becomes depolarized, the voltage becomes zero, and the cell gets activated. So what happens to do that? And first of all, what maintains that potential? You have more negative charges on the inside of a cell. and more positive charges on the outside. That's just the way the cells are naturally balanced. More negative inside, more balanced on the outside.
16:38 But through the ordinary business. of going around like an amoeba or like a macrophage in the clean up the mess mode, phagocetizing, right? Amoeba like amoeba-like gobbling up damaged bits of cells and cells that are past their prime and all of that to clean up the damage from whatever injury has taken place. naturally ions which carry these charges will leak in and leak out. So mostly in the inside of the cell it's a lot of potassium ions, all the positive ions, and on the outside of the cell it's sodium ions. And because of the imbalance between the size and the charge, there is this net negative charge on the inside. So if that depolarization happens, if as because the leakage naturally happens. And they're ordinarily pumps going. If you think about
17:27 a uh like a boat on the sea, right? If you have a you got a yourself a sea going yacht And what do you got in the basement basement of the other basement? In the bottom of the hull, you have a bilge pump, right? That's order ordinarily always on to pump out water. Why? Because it's Because the ship is going around on the sea and it's getting toss tossed and turned and it's water is gonna be splashing in all the time. And so you need to have a bilge pump going to always pump out the water. Well, the same is true with the cell, except it's not well, there is always water inside and outside, but what's different are the ions. So you naturally are going to have sodium ions coming in. and potassium ions leaking out. So you have pumps going all the time in the cell membrane
18:13 that pump potassium in and sodium out, which keeps to maintain this gradient, this difference between the ions inside and outside. One of the things that keeps the ionic balance right is to allow chloride ions, which have a minus charge, to come in Because chloride is naturally very low on the inside and very high on the outside. So if you open up a little channel, guess what? Chloride will flow in. You don't have to pump it. It flows right in through these channels. And when chloride flows in, it increases the negative charge on the inside, which keeps the membrane polarized. It turns keeps the switch off. It's a trigger lock. It keeps the trigger from turning on, keeps the switch from going on. Well it turns out that these chloride channels are regulated
19:00 by glycine. They're called glycine-gated chloride channels. They're gated regulated by glycine And they're also called the glycine receptor or the classical glycine receptor. It's the same one it's important in the central nervous system, which is why another one of these reasons why glycine is so important in terms of sleep, calming your nervous system. But it's the same one that's in these macrophages of the immune system that will do inflammation if they become depolarized. So that's so when there's enough glycine around, it keeps the chloride channels open. for enough chloride to come in so that the cell doesn't get depolarized and inappropriately activated. What's enough Yeah, what's enough? That's what I was just gonna say. I've seen it's
19:49 normal. It's two hundred micromolar. Guess what? That's not enough. So would most people range Yeah. The normal range is like a hundred and fifty to four hundred micromolar. No, you need at least five hundred five hundred to a thousand micromolar. It's fine. If it's more, it doesn't hurt you. It's almost open-ended at the top. So you know glycine has to be at least around 500, otherwise your macrophages will get activated in the case of merely cellular injury and not infection. And then you will get inflammation. And why is it chronic? First of all, it's not appropriate. That's the thing to recognize, as I said before. the big discovery is that most of this chronic inflammation as a result of injury is not appropriate at all. And when I say injury You
20:37 get micro injuries just from circulating blood, just from running on a treadmill, even low-impact stuff. You're over just blood circulation is going to give you micro injuries, especially around branch points Ovulation. High pressure. But blood's a very arterial circulation is a very high pressure. fluid system and wherever there are branch points, high pressure branch points, you get turbulence. And wherever you get turbulence, you're going to get micro injuries. So what? If they just heal, that's normal, right? Yes, no problem. But if you're glycine deficient You get inflammation. And how? Inflammation plaque formation at arterial branch points, leading to heart attacks, strokes, embolisms, all of these problems, which glycine actually prevents. Yeah.
21:28 And we're gonna get to that in a second. I want you to tell us though, how would someone test for this? I know before you told us that you don't have enough glycine if you're becoming inflamed because you're injured, but if someone wanted to go about testing it, How would they do it? You can go to a lab, you can get a regular lab test for glycine. It's called an ELISA. Okay. Lab tests are funny. They're called the the lab tests for a lot of things are called ELIZAs. They're immunoassays. They use the antibodies. And ELISA stands for enzyme-linked immunosorbent assay. And it was they developed an ELISA because they used to use radioactivity to measure these things way back in the day, but now radioactive, the word radioactive has become radioactive. So the old
22:13 test that used to work this way was called IRMA, immunoradiometric assay. So we dumped Irma for Eliza because Irma was radioactive. I like to tell that store in college. The kids understand it. And now you've been taking eight grams of glycine for I don't know maybe eight years. Some experimentation, but steadily especially my own formulation, sweetamine. I've been taking for about 15 years. And how do your levels measure? Have you had them tested? I no, I don't I I tested them way back when I worked in a lab and that was easy to do. And so my levels were maintained at around 700 plus. Okay. Micro. Okay, perfect. And now I want to get into the conditions, but 60%
22:59 of Americans have at least one chronic disease, many of them tied to inflammation. So allergies, autoimmune disease, asthma, what are some of the big inflammatory conditions that you've seen maybe improve with glycine supplementation? Oh well, I learned a lot Yeah. Yeah, I learned from my own self-experimentation, obviously, from injury, but I learned a lot just from starting the business. selling sweetamine and having customers post testimonials and say, wow. I was hoping this was gonna help me with my aches and pains and it really did help with my ape S But I don't have migraines anymore. I wasn't even taking it for that. Yeah. You see, there are testimonials like that. Oh yeah. Surprise. You were feeling a lot of effects of inflammation. And the these and people say you should be very cautious with glycine and because you don't want to take too
23:46 much right away. And it's true if you take too much and for some reason you don't agree with the free amino acid formulation of straight glycine, you might get a headache. you might get diarrhea even. Very rare. But then it goes away, so you stop it. It doesn't hurt anybody. It's not, you know, give a Snickers bar to somebody with a peanut allergy, it'll kill them. And I think I'd read about studies, yeah, and and that's another thing we're gonna get into in a second, but I've read studies where they actually put glycine straight into the bloodstream. Oh they do that actually. This is done the if you really want to see the toxicity of glycine, people say oh you've fed rats or you've fed people so much and so much. Nobody ever gets fed as much as they get fed. There is a very common condition, benign prostatic hypertrophy or benign prostatic
24:31 hyperplasia the benign prostatic disease, which is the prostate swells up, it impairs uh urinary function. So a standard The therapy for this is a surgical procedure called a TERP, a transurethral prostatectomy, which is like a rotor router kind of thing. It's a very crude procedure, you'd think it's and what they do is while they're doing this very crude surgery. When I say crude, this surgery was perfected a hundred years ago. They still do it. It still works. And so work gets rid of the excess tissue and then it heals up very quickly. And they wonder why you wonder why it heals quickly because what they use to irrigate is You can't irrigate with water because that's not the same ionic strength as blood. You've got to have the right ionic strength of dissolved salts
25:21 in it as blood. But you don't want to put it in salt water, that really stings. So they what they some years ago, some decades ago, they settled on using two percent glycine. Because it has the same osmotic strength as blood serum or plasma, but it doesn't sting. And so they use that. And you wonder why people get along so well. Because what what get get along after this surgery so well, recover so well, is because they actually irrigate the surgical site with two percent glycine, it floods the circulatory system with glycine, sometimes up to a hundred times. the normal value. You may instead of one one one millimolar, a thousand micromolar, you might get
26:06 a hundred thousand micromolar. 100 times normal that. And it still doesn't do any permanent harm to anyone. You just let it wash out. It washes out of your system very quickly. So it's I would say when people say how much is too much? What's a toxic amount that is really poisonous? Actually, I don't think you can eat enough glycine and actually absorb enough glycine by eating it. to cause yourself any real harm. That's how safe it is. People they will cite things in the literature, oh glycines, it's a risk, it's risky. And then you look at the literature and you see they injected IP into the chest cavity of rats they injected ten grams per kilogram of glycine or something and they managed to kill a few rats. It's really Unbelievably safe. That's why I feel I've been in business now for 17 years and I'm I don't worry about legal problems or anything like
26:55 that because I might worry about legal problems if I was selling peanuts. Yeah. Yeah. With peanut allergies and so on. But this there's nothing in sweetamine, my product there, that you could actually get allergic to. It's you may not agree with you to take glycine as the free amino acid. I mentioned before, right? Collagen. So you can take it as gelatin or collagen peptides. If you take uh an enriched source of glycine in that way, bone broth, any of those very good 25% glycine, those require digestion, which means they don't get into your bloodstream right away. And for those people, some occasionally people will get headaches or they'll get diarrhea or some kind of digestive system. Symptoms you can read this in WebMD, it's say glycine, one of the side effects
27:42 They're all just transient. If for some reason you are intolerant, that is to say, taking the free amino acid straight up disagrees with you. And there's some people that it does, maybe one or two percent of people. Yeah, that's great. But yeah, go to food sources, lower the dose. There's lots of ways. We're gonna talk about all the ways. Divide the doses, do whatever you want. So I tell people something, they say, I can't take your product because I don't like it sweet. Can you remove the sweetener? I say no glycine. is naturally sweet. Yeah. It just has a bad aftertaste. So we just we we modify a little, not chemically modify it, but we add just enough and formulate it just so it tastes a little more like sugar, all natural, but but it's still gonna be naturally sweet. We can't I say we can't take the sweetness out of it. So you either have to take
28:28 capsules, which is very impractical, or just take it in a form that requires digestion. So take it as gelatin. or collagen peptides, which is really the the same nutrient. Or nowadays everybody's big on magnesium, you know, that they're selling your magnesium glycinate. Yes, I've that all over the place. Magnesium glycinate. Yeah, you have to do that. Best sorts of magnesium, so absorbable. And but do you know that and they say take these two big pills and you get your 300 milligram daily requirement of magnesium? And those Two big horse pills that you have to take to get your 300 milligrams of magnesium. Guess what? You're getting two grams of glycine because magnesium glycinate is 86% glycine Okay, so everyone's gonna be able to do that. Is that consistent, two grams
29:17 pretty much in every formulation? Is that kind of stable? One and a half to two, depending on whether they say they're g providing two hundred milligrams or three hundred milligrams. Okay. They say that's the minimum requirement for magnesium is 200 to 300 milligrams, and depending on what brand you get. They'll say our serving size will give you 200 milligrams or 300 milligrams. The 200 milligrams will give you a gram and a half of glycine, and the 300 milligram will give you two grams of glycine. Perfect. Thank you for the game. Bone broth gives you for every gram you get a quarter gram of glycine. Yeah, we have a bone broth too, like you said, or you can make yours own at home and then I wanted to be clear about this too. Essential aminos. Like if you're taking an essential amino acid supplement, that doesn't always mean that you're going to be getting glycine. Oh yes. See classically. Yeah One of the big mistakes made by
30:07 the in the dietary field is to think of glycine as non-essential. They call it non-essential because your body can make it from scratch. Yeah. That is the when I say scratch, I mean your body can make glycine from carbon dioxide, ammonia, and formaldehyde. Your liver mates it from that every day. So it's very fundamental material. You don't even you can get natural, you say is it glycine natural organic? You can get natural glycine that's not organic because Glycine is actually made in the inorganic environment. You can find it on meteors and comets and asteroids. Yeah. It's so fundamental. It's been around here for so much longer than living things have been around. It's a really almost like a soul. I consider glycine. a bridge substance. It's inorganic and organic. It's organic, sure. It's a one of the building blocks of proteins. It's
30:56 an as it's a an essential amino acid. But on the other hand, it's made inorganically all the time, just in the environment. And anyway, that that's I just wanted to say I have this amino acid. Yeah We were talking about what's this what do we mean by essential. No, in fact classically, yeah, classically to make a very long winded story short it in the classical lexicon of what is or what is essential and what is non essential, and they say that glycine is non essential, if you take a formula that says gives you one hundred percent perfect balance, of your essential amino acids, it won't have any glycine in it. Because they don't think of it as essential. In fact, if you
31:44 just take a mixture of essential amino acids and nothing else, it's actually going to strip glycine from your body. And you need to take more of it. Why? Methionine. Remember the excess methionine? That you need glycine, two molecules of glycine to get rid of every one molecule of methionine. That's taken in excess. That's what your liver actually does. And so that's so we found that out actually doing some longevity experiments with it. I was looking first thing I tried to do We ran some experiments with rats and then with mice to try and simulate methionine restriction by feeding glycine. We give these if we give the animals lots of glycine, that will help them clear their methionine and they'll live longer. Yes and no. Yes, it helped them live longer, but no, it didn't help them clear methionine because guess what? Their methionine levels didn't change one
32:33 bit. But they live longer. Something else is going on. Yes, the something else that's going on is That methionine restriction is actually removing a source the excess methionine is actually poisoning you by robbing you of glycine That's how that's happening. So it's the glycine. It wasn't really so much the methionine. If you have excess methionine, your liver is going to get rid of it. There will always be enough glycine to get rid of excess methionine. And why do I say that? That gets into s some of the different ways that glycine works are not all about its biochemistry. So glycine, oh biochemical, yes, it's important in making DNA and it's It's important as a building block for proteins and it's important in synthesizing other amino acids. But actually, when
33:22 it works to stop inflammation, It's not acting in a biochemical way at all. As I said, it's a gate to this chloride channel. It's just a ligand almost like a hormone, but something that operates that way. It operates a switch. It keeps the switch closed. Keeps the switch open, which means off, right? Keeps the switch open so that you don't get excess or inappropriate inflammation. So it's in that sense. It needs to be, we talked about blood levels, and what my blood level was about 700. We talked about micromolar, which is a met a way of measuring things by the piece rather than by the gram So so it's about half millimolar glycine or five hundred micromolar glycine. Now
34:10 in order to make all the proteins that your body needs to make, and it needs glycine to make all of them because there's some glycine in every protein. And glycine is about the most abundant protein, most abundant amino acid that you have. If you have even 100 micromolar glycine, you have enough to make protein. So you see, It really is non-essential as a as a biochemical, as an amino acid, in terms of its biochemical building block function You can't run out of glycine, your body's gonna make enough, but it's not gonna make enough for its function which needs bulk amounts of glycine. to be in the solution to act as a trigger lock to keep things from going haywire. And it's not necessarily just inflammation, just to let you go to sleep at night, right? Yeah, old. Same yes,
35:00 it's the same glycine receptor. Yeah. We're gonna give you a game. Yeah, I love that. We're gonna go there and I wanna close this section really quick and then we're gonna go to those distinct like sleep and cardiovascular. But I just wanted to say you can get glycine in plant products. It was something many of you mentioned, but the amounts are just a lot smaller. And so you, for instance, you could have a gram in a cup of soybeans or half a gram in a cup of lentils or chickpeas. You're just going to have to eat a ton to get to that eight grams. That's what I'm saying. Soybeans is about as high as it gets in the plant kingdom. Yeah. Which is why the botanical name for soybeans is Glycine Max. Glycine Max. Yeah, glycine max. That's the max glycine you're gonna get out of a
35:45 plant is from glycine max. Soybeans. And you said that vegetarians, vegans typically have higher levels of glycine because they're not eating so many muscle meats. Do you think that's optimal? Or do you think we should be getting the meat-based nutrients and having meat but also balancing it with glycine. It's all about the amino acids. And people say the amino acid mix in animal foods is Not as healthy. And animal meat eaters, they get more cancer, more heart disease, they die younger. Vegans live longer, they get less cancer, they get less heart disease. Wait a minute now. The trouble with this measure of animal protein is usually we throw away the glycine. Yeah. Because the collagen is not included. I would say you can eat a healthy and adequate diet if you are a vegan,
36:30 and you can eat a healthy and adequate diet if you are an omnivore, our body's designed to be We're designed to be omnivores where we can eat everything, a good mix of things. And your body will do fine with any of them as long as you get the right mix. So if you're a vegan and you don't get enough glycine, you're not going to be optimally healthy. If you're a meat eater and you keep throwing the bones into the trash and not the soup. and eating that the glycine that you need, you're not going to be healthy. So it's a matter of getting complete proteins, which is the right balance of essential amino acids, but you can't forget the glycine, which is not ordinarily included in that mix. Perfect. And then this last supplement I want to talk about, Glynac. I know you have some big thoughts on this. Like Glynac Two recent trials have shown that it
37:17 can improve many parameters of hallmarks of aging, gate speed. Strength, you mitochondrial function, all on and on. And it's a buzzword these days. So glynec, glycine, cysteine, tell us. Okay, well scientists. A couple of scientists, Doctors Kumar and Sekar, who are at Baylor University in Texas, who have been promoting this idea of Gleinac. They call it the power of three because The big three there is a little tripeptide called glutathione, which is another buzzword, right? Glutathione, it's your body's key antioxidant. You know, that if you don't have enough glutathione, a lot of things can go haywire, and that's true. And glutathione is an interesting, it's a tripeptide. It's a little molecule made of just three amino acids. Uh glutamine, no glutamic acid,
38:07 cysteine, and glycine. The glutamic acid part is non-essential and there's always an excess of that. the limiting ones, the ones that you might not have enough of are cysteine and glycine. So they say if you take these two that are the limiting ones glycine and cysteine. NAC is, by the way, an abbreviation for N-acetylcysteine, which is just the dietary form. It's cysteine. Okay, so it's Glynac is glycine and cysteine in supplement four one one to one ratio. So if you take those two limiting components of glutathione, You'll have lots of glutathione and that they call this the power of three because glycine has great benefits. Glutathione has great benefits, and cysteine has benefits because that's the key part that makes glutathione the antioxidant.
38:57 That's the antioxidant part of glutathione. So there's a a big literature that goes back far before these researches, that goes back decades. a very big following in of glutathione and how important that was. Interestingly, with the group that I was working with who established the methionine restriction as a way of increasing lifespan We found that the model the animals who were methionine restricted, not only did they live long longer, but their levels of glutathione were lower than the controls. So this made everything go tilt in the reasoning. And what I've concluded is that basically, yes, glutathione is important and it is a key antioxidant. And You the more the
39:43 more of this muscle meat that you eat, the more you're stressing your mitochondria, making them run hotter, that kind of thing. the more you know like reactive oxygen species you have, the more antioxidation you need, the more glutathione you make. Because in fact When your liver is processing that excess methionine and using up glycine, it's also going to be as a byproduct. It's amazing how everything is so perfectly balanced as a byproduct. your liver is going to make more glutathione. So the more oxidative stress there is, if everything is still working right, the more glutathione your liver is going to make Glutathione is important, yes, if you're it has to be understood in that way, that it's not always the absolute amount that you need.
40:31 The other thing about glutathione Is that yes, the cysteine is just as important and it's limiting, but muscle meats have lots of cysteine. Cysteine is a sulfur container amino sulfur-containing amino acid. It's made from methionine. And it's the antioxidant part, as I said. So when your liver gets rid of excess methionine, it's also generating more cysteine and more glutathione. So why would you necessarily need to take glynac as a supplement if you have a diet that is providing an excess of muscle meats, an excess of cysteine? So that's not likely to be limiting. So that's one question I have. The question I have scientifically about it is that in all of this
41:20 research that I've been able to find about Glynac, They never test gly. They test glutathione, all three of them. They test cysteine. They test glynac, but they've never shown supplementation studies with just glycine. Why do you think that is? I don't know. I m I think my punch is that in some way people are they're stuck on glutathione. The other thing is They do find that peop people do take NAC and it does have benefits. And another thing may also be The whole tile roll business which made the news lately about somebody saying if Trump says tile roll's bad for you, I'm gonna take a whole bottle and then they end up dying from it. You can't overdose You can overdose very easily on something like Tylenol because because it's a acetaminophen,
42:07 also known as paracetamol. And acetaminophen is known to be toxic to the liver. How is it toxic to the liver? It specifically degrades glutathione. Specifically defuses the gly the knack part, the the cysteine part of glutathione is oxidized by paracetamol by Tylenol. So when you take Tylenol you are naturally degrading glutathione. You're specifically targeting and poisoning your glutathione. So that may be one reason why people often are deficient in cysteine and they would need to take neck. So what I say is if you like pa if you like Tylenol as a pain reliever, always take neck with it. I love that advice. And I'm wondering if you were gonna design the experiment
42:55 to really parse out whether glycine alone. could be as effective. What would you do? And then why do you think this hasn't been done in human clinical trials? Because there's a lot of animal evidence around glycine and some human, but why do you think that there hasn't been this development? I don't know. Yeah. I would if uh your first I like your first question. If I were to do it, how would I do it? I have tested just glycine. People might ask me, why don't you test next? I'm not in a position to do that. I was working with the National Institute on Aging and we I had an occasion where I could test glycine on mice and we had a very good result. A nice paper came out of that about five years more than that now. Time passes. Was it 2015 or 2016? I don't know. Within the last ten years anyway, we had a a very nice paper came out in aging cell about glycine
43:46 extending, significantly extending the lifespan in mice. And that was done in three separate study centers simultaneously. The result is solid. And so that's what we uh what we did, but I don't have the the occasion, the opportunity to test them. I suppose if I had a laboratory now I would certainly want to reproduce the test with GlyNAC and compare them to glycine alone, NAC alone, and also glutathione. You try to you you do all the different parameters. It's just odd that this one parameter of glycine alone was missing. And who knows? There's always things to be discovered. And the last thing I'm going to do is say anything bad about Glynax supplementation because that's very good for you. If you don't need the NAC, well, it's not gonna hurt you. Yeah. With a simple amino
44:34 acid. And it's something I oh sorry, go ahead. Yeah, that's uh it's not gonna hurt you, so I I wouldn't object to that. It's just scientifically I wonder why they didn't didn't test everything individually. Yeah, that's interesting. And maybe a daily intake of adequate glycine. could prevent the need for it. I did try it out this week and I did sleep well, but I also eat a lot of glycac. I don't I can't read what's in the It's Glynac. I tried it. Oh that's Glynac, okay. Glynac, I tried it out this week and I slept a lot longer than usual. I don't usually take supplemental glycine, I usually drink it and eat it. So That could be why. But it was interesting. I just love your thoughts on that and I love how balanced you are. And I hope that study is eventually done. There was a study, a a recent study in, I think Obesity around glycine. Do you want to start do
45:21 you remember that study? Oh the International Journal of Obesity. Yeah, yeah. Tell us about that study. The last time I published in that journal was 1991. Good journal. I just haven't been publishing in that area. The uh that was about obese when you are obese your liver actually makes less glycine. They're actually documented that. I think I mentioned that just in passing and earlier on in this discussion. You did. That it's one of those double, triple, quadruple whammies where you're short on glycine and short on glycine and short on glycine. There was a group it was a mayo clinic group. And that was working at a mail clinic in Minnesota and also in Jacksonville, Florida. They're working with kids. who are obese kids because that's an ep epidemic now
46:07 in kids too. And of course heart disease in a is an epidemic, but it's not an or epidemic in little kids. You don't find ten, eight, ten, twelve, fourteen year old kids getting dying of heart attacks. So the doctors, these uh yes, they were mayo clinic doctors. What they were testing was a very interesting hypothesis. We have markers for heart disease among middle-aged and older people. LDL cholesterol and various other markers for art disease. If we and we're kids, we're a children's hospital. They were a children's hospital in that that one in Jacksonville. They said so we want to see if they have markers for heart disease. These obese kids, do they have markers for heart disease? And if they have markers for heart disease, maybe that would be predictive, right?
46:53 This is a big deal in scientific research if you can find something in the blood that's gonna say, you know what, in 20 years you're gonna drop dead from a heart attack or likely to because you have too much of this. Therefore you should change your diet or take this medicine or do whatever you need to do to normalize it. So they noticed in these kids that they have all the markers, a lot of the markers for typical cardiovascular disease that they see in middle-aged and older people. And they don't have the disease, but they have the markers. And so they looked at the markers, and what are the markers? One of the key markers turns out to be glycine. that the glycine is low. Why is the glycine low? Is it diet not so much diet in terms of not enough glycine in the diet, probably just too much food altogether in the diet, because the kids are obese. And obese kids, their liver makes
47:46 less glycine. So now they're hypoglycinemic growing up, which feeds into all the the intravascular the in inflammation inside the blood vessels leading to atherosclerosis and plaques and by the time they're in their thirties A lot of them do die of heart disease or get significant heart disease. So that's that's how they looked at some of the markers, the molecular markers, the genetic markers. using a tool called the genomics to see what what genes are actually expressed in the uh in the blood of these kids. So they've done some very good research. In uh at this group this is Mayo Clinic again with the I forget which children's hospital it is in Jacksonville, Florida, but I like the work they do. Very uh foresightful, I guess. Very good. Looking at some very interesting questions which are of great benefit. And we'll be of great benefit,
48:35 I think, to to people's health. And underscoring the importance of glycine is one of the things that's come out of that. Yeah, and in our last podcast, you said you were starting to be able to influence the cardiologists in your life or family. And are the mechanisms the same, like in our blood vessels? Is glycine working to turn down that inflammation in the yes. And not only that, glycine works in several ways. Inflammation, you have an increase in one of your Clotting factors that's made by the liver, I think factor seven. So that blood is more clottable that way. Glycine is also anticoagulant. There are some things now it's a big deal to say different things. Make your platelets aggregate. Actually glycine Is your body's natural blood thinner? Well.
49:21 Because it just on platelets, it's I'm not gonna I'm not gonna give any medical advice and say, oh, your doctor put you on clopidogrel, so you don't need that, just take glycine. Theoretically Theoretically it might work, but you you can't medically predict these things, especially in individuals. But I would say that glycine, yes, is your body's natural blood thinner. It has the same glycine receptors on platelets. And instead of being a trigger lock to prevent them from causing inflammation, what it does to the platelets, it prevents aggregation, because the aggregation of platelets. into a plug is one of the mechanisms by which your circulatory system plugs up holes and keeps you from bleeding to death from ordinary ordinary insults of daily living. It does that.
50:08 So it it it inhibits platelet aggregation, keeps this naturally thin, your blood's natural blood, your body's natural blood thinner. It it inhibits the uh the uh secretion, I think, by the liver of factor seven. I think that's the one. And also another particular one that's big in inflammation is that there is another another protein that is secreted by platelets called pi 1, P A I 1 pl Plot platelet aggregation in no not platelet. It's it's secreted by plates. It's called plasminogen activator inhibitor one. See when your blood clots When something happens, right, when the there's a cut in one of your blood vessels, it secretes a little substance
50:53 is released from the injured tissue, which starts what's called the coagulation cascade. The cascade because one enzyme activates another that activates another that activates another in order to amplify the response. So that from a few little molecules, you can actually get milligram quantities of a platelet of a fibered plug that can plug up the hole, keep you from bleeding to death. You get seriously injured, that sort of thing. But at the same time, if there were just a coagulation cascade, every time you got a little cut Your whole circulatory system might clock, right? Now you have this cascading system, what's gonna stop it? But the same time that the coagulation system is activated An anticoagulation system is also activated in the same spot. It's
51:42 called the fibrinolytic cascade. And fibrin is clotted the substance that uh make turns your blood into jello, right? So it can't flow and plugs up a hole. There is also a fibrinolytic cascade which ends up in dissolving clots. So you may have heard of in heart attacks and strokes, they now use something called these clot busting drugs. Plasminogen, I forget now what the name of it is, but these are kinases. Oh, kind of. Enzymes that work in that way, that yeah, the clot busting drugs that will act as fibrinolytic agents, which will dissolve clots. They will literally break them apart enzymatically. That is automatically activated whenever the climbing cascade is activated, so that you end up with the only place where the plug actually stays
52:29 is in the hole in the wall. That's called fibrin stabilization factor. That stabilizes the clot, but you don't want a clot inside your circulatory system where the blood is supposed to be flowing So the anticoagulation cascade, the ultimate enzyme there, which dissolves the clot, is called plasminogen. And I'm sorry, it's called plasmin And plasminogen is the substance that's turned into plasmin right before it. So plasmin, the the activator of plasminogen. Plasminogen activates plasmin, but there is a plasminogen activator inhibitor which will inhibit the dissolving of
53:19 the clots And that is a part of this very complex system, but it is increased in inflammation. When you have systemic inflammation, not only does your C-reactive protein go up, which is what we talked about earlier. That's a clinical test for whether there's a lot of inflammation. But one of the hallmarks of inflammation is that your pi 1, your plasminogen activator inhibitor goes up, which means your blood ultimately between that and factor 7 and the platelets, if you have systemic inflammation, your blood is more claudable So people end up with heart attacks and strokes and what do they do? They put them on drugs like Clopidogril and the name names escape me at the moment of some of them. But if you people are familiar with these blood thinners, the blood thinners typically Warfin, is that one? What's that? Warfarin. Yeah,
54:08 warfarin is another one of those. Warfarin is a it's a good rat poison. Do you know that's where that comes from? That was a rat poison. The way the way it works is rat poison is they warfarin, they put it in the bait trap. And the rats eat it. And they start to bleed internally because it inhibits coagulation. So they go outside looking for water and die. Oh. I think so it's a blor I don't know if you want to include that in the podcast, but that's that's just a little story about yeah, warfarin. In a medically supervised proper dose, it actually extends lives for many years for people who otherwise have blood which is hypercoagulable. How do you know their blood is hypercoagulable? You had a heart attack. You had a stroke. That was inappropriate coagulation.
54:55 That's how we know Nice. But again, then those are blamed on chronic inflammation that leads to those conditions. Yes. Lysine works against that. That's nobody's saying glycine, oh, it's a cure all it's just an essential nutrient. You have to have lots of different nutrients. Glycine's one of them that tends to be overlooked and it's very key It doesn't mean it's gonna absolutely prevent anything. No, and this is yeah, not medical advice, but just like you say, and that's right, but it it will help to keep Things normal doesn't I love that. And I wanna go through a few more because if you have time because I there's so many different applications. One one that I thought was particularly interesting along these lines that it can be an antidote to the overconsumption of sugar and liver protective in that way. So do are you familiar with that?
55:43 Well, I don't know about Not sure about the sugar part in the i i in terms of diabetes. If you talk about becoming diabetic, which we t tend to can tend to blame on the overconsumption of sugar, which has a lot to do with it, because you see your body is really designed to deal with famine, not feast. Yeah. It's designed to manage to keep itself alive in the most meager circumstances where it can barely get enough of anything to to rub two molecules together to generate energy or reproduce a cell So your cell your body is designed really to withstand famine, but not to withstand feast. For example, with sugar, the insulin pathway, insulin is a way of getting rid
56:28 of sugar, burning it, storing it, turning it into fat, whatever you have to do with it. It's really just that insulin pathway. It's really just the only pathway there is. Whereas uh if you so that's what if you have too much of it. If you have too little of it, you have seven ways till Sunday to regenerate sugar. Your body can make sugar. M and what we got no sugar. Wait a minute. We need some sugar to run on. The brain can run on ketone bodies and the muscles can run on fatty acids and And we still need some sugar. You still gotta have some sugar, but you don't need to eat any. You can have a carbohydrate-free diet because it's non-essential. Your body can make sugar from almost anything. Any amino acid, your body can make sugar, including glycine, your body can make sugar from it if it has to. It can make sugar from fat, a little of it, not that much,
57:16 but it can make ketone bodies and it can make a little sugar. So in order to withstand starvation, your body has a lot of alternative pathways, a lot of redundancies built in. But not to get rid of it when you have too much. Same thing with methionine, muscle meats that we we have so much of these days. There's really only one way to get rid of excess methionine, and that uses up glycine. There's no other pathway for it. But if you're short of methionine, oh, there's so many ways to regenerate it and recycle it and reuse it. And there's lots of different ways, which is why, even though essential, you need so little of it. Because your body can do a lot with it. Do you get into these I know people a lot of people talk about methylation, below methylators, for example. That's a very interesting story. Yeah, tell us about that because I do hear a
58:07 lot about glycine and methylation and you wonder because you people I think somebody even commented after the last podcast they said They said, well, isn't glycine bad if you're a low methylator? You know, you need because glycine gets rid of methionine. Methionine is the key methylator. It's activated to form SAME, which is the active form of Methionine, that's the methylator. You need methylators because DNA bases need to be methylated variously to turn them on and to turn them off. Neurotransmitters need to have methyl groups added. These one carbon units are added universally by something called acidenosyl methionine, which is the activated form of methionine, the essential amino acid. So you gotta have it. Your body has lots of ways to re
58:52 And what does methylation do? Just tell us what you're doing. What does methylation do like at a very basic level for someone who might be new to the concept? It's uh methylation is just if you think of little ball and stick models of atoms and molecules, it's just a little p a little like a a little stick that's It's it's like a cog and a wheel. So it's it's a signal. So if your DNA is trans transcribing and translating, making all these proteins and making more DNA and going on about its business and doing that which genes are getting turned on, which genes are getting turned off. So you it goes through so a part of the DNA there'll be f this particular base will have a Methyl groups sticking on out at one particular place that gets bypassed. We don't make that
59:38 protein. So methylation is one of the ways that the genome operates in order to uh using it as a switch to to turn on or turn off or bypass certain genes the translation of transaction translation of certain genes transcription, I guess, at that level DNA. So that so that's what a methyl group does. It's a physical it's a physical other little stick, a little cog in the in the machinery. that that changes the shape of the molecule in order to exert a particular function informationally. It's interesting, like just like glycine at the cell surface. It comes down to being a switch. So this has a lot to do with switching in the copying of information in DNA. So the addition or subtraction of methyl groups. That's just one way methyl groups are important. They're just they're
1:00:26 important to make So many different things, hormones, neurotransmitters, because a methyl group is a one carbon unit. And if we're playing with our little sticks and blocks and everything like that, there's a one One carbon unit. And so it's important. So methionine is very important. And so there's only so here's what happens. The methionine cycle, what it does is it regenerates the methionine. That's the main pathway for regenerating methionine when there's not enough around, when you're not eating it. So you eat this cheeseburger, which is loaded with methionine. And then over the next hour or two, your liver is busy getting rid of almost all of it. Now that's okay, because now you have this regenerating machinery to remethylate your methionine Except there's
1:01:13 very common mutations. One is called C C677T mutation of MTHFR. People who have it and who studied it know what I'm talking about. It's a lot in the popular literature. It's called methionine tetrahydrofolate reductase, which is it's a key step in the re-methylation of methionine. And if you have this particular mutant version, when I say a particular version, depending on where you come from in the world, 10% to 20% of the population may have a particular mutation in this gene. So the enzyme doesn't work well. So you're not very good at regenerating methionine. If you take glycine, glycine, remember glycine Suppose it is used to get rid of
1:02:02 excess methionine, but if you add more glycine, it doesn't help you get rid of methionine. It doesn't do that. You always have enough glycine to get rid of all the excess methionine your liver has. The trouble is in between meals, and a lot of people like this, they know they need high protein snacks in between meals because they need to have more methionine. Why? Because your methionine clearance system works just fine and you have enough glycine to keep that working
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