Biochemist Explains: Most People Don't Know They're Glycine Deficient (And It's Harming Them)

Glycine is your body's natural blood thinner. That's probably the easiest way to put it.

The normal diet gives you 2 or 3,000 milligrams a day of glycine, but guess what? It's not enough. I got zero inflammation because I was taking 10 g a day of glycine. In order to have a heart attack, you probably need to be glycine deficient. It's normal to have minor micro injuries to your arteries, even your coronary arteries all the time. But if you're glycine deficient, you then get inflammation following from injury. One of the most significant results I've ever seen, just people who have CPS-1 deficiency, men don't get heart attacks. The worst processing is cutting the meat off the bone and throwing the bones away. That's the worst kind of meat processing that we do. Glycine is maybe the most or the second most abundant amino acid in the body, but yet most people are deficient in it. I had to pinch myself a few times years ago when I first made these discoveries. It was like, is this real? Could it be this simple? And people to this day still tell me, "Ah, it can't be that simple."

Hi everyone. We've got an episode all about the link between glycine and heart disease. Keeping our heart healthy. Can glycine be a part of it? We have statins. We have surgery. We have blood pressure medications. And heart disease is our number one killer. But Dr. Brend over here, a biochemist who studied immunology and nutrition actually and glycine extensively, Yale-trained, as credible as it comes. And we're going to talk about, we're going to break it down for you because he believes glycine is a missing piece of this puzzle. And glycine is also something many of us are deficient in because of the way that we're eating today. All the muscle meats, none of the connective tissues and the bones and the other parts of the animal that actually contain the balancing glycine. So, welcome to the show, Dr. Bren. Um, I'm really excited to dive in.

>> Yes. Thanks very much. And and we eat too much of everything.

>> Oh, yes.

>> Me too. That also has to do with glycine. Glycine has to do with with obesity, with diabetes, and all and all of those are related to heart disease, as everybody knows. And they're all related to chronic inflammation, as everybody knows. But they seem to not know about how glycine fits in, which fits in so perfectly in that jigsaw puzzle of human physiology and health and disease, you know, and it's somehow it's still not well-known. So that's what I'm here for, trying to make it better known.

>> Yeah. Dr. Brend's on a mission to help people understand that glycine deficiency is a real thing. This is part of a series. So we're breaking down, we've done many extensive conversations. If you haven't seen those, I'll link to them in the description, but we've broken it down to blood sugar and cancer and methylation. And today we're going to talk about the link between heart disease and glycine. So, Dr. Brain, tell everyone how did you get into this work and why should people trying to prevent heart disease be concerned?

>> I got into this work because I was with a group that was studying longevity. They were studying aging and so they were looking at rats and trying to, you know, do whatever they could to their food or whatever to make them live longer. And they came upon something called methionine restriction. That methionine is the great universal methylator, which is an essential amino acid. And if you actually restrict the amount of methionine the animals could eat by putting a little, they could still eat as much as they wanted, still ad lib feeding, but you restricted the amount that's in their food so that they would just barely have enough to subsist. They were still active and happy and all of that, you know, not neurotic little rats running around, but they were they didn't grow to normal size. It did inhibit their normal growth, but they lived 30 or 40% longer. Instead of living for two and a half years, they would live for four, you know, and stuff like that. That was a big deal. That was back in 1993. They published their first paper. And other groups published, they did it in mice. They did, you know, and so by the early 2000s, it was recognized in their research, the aging research field, as a real thing, methionine restriction as something distinct from caloric restriction, which you might have heard about, just eating less altogether. So, it was different. As a consultant to this foundation, you know, I work, I've been working with them for many years. They said, "Well, what, you know, can you explain it?" So, I did some research and I began to look at the literature and realized that, because what I was trying to do then is what can we feed people that's going to deplete methionine? Can we do something? Because the first thing that occurred to the group was to do a methionine-restricted diet. Well, a methionine-restricted diet is the most ghastly, awful diet you can imagine. Everything that tastes good has methionine in it. You know?

>> Give us examples.

>> Muscle meat, right?

>> Muscle meats. Yes. Muscle meats. Chicken and beef and pork and, you know, bacon and all that stuff is loaded with methionine. Dairy is loaded with methionine. So, it's like it would be the strictest kind of a vegan diet. The only thing you might have that's not loaded with methionine for dairy is to have cream in your coffee instead of milk. That'll give you less methionine.

>> If you restrict methionine, do you also restrict growth?

>> Yes. Well, yes, that's right. Absolutely. But, you know, but this was, you know, longevity was the thing. And so this is what we're looking at at animal models, the good kind of animal research where you take care of the animals, you know, to the text, you take care of the animals. These animals are like pets, the rats and mice, you know, and they look forward to their feedings. They even stick their paws out to have their blood sampled, you know, stuff like that. Oh, sure. You know, because they're pets. What do they know?

>> They don't know the difference between a pet and a work animal or an experimental subject if they're treated well. It's like a like a horse, you know, a horse is a work animal, you know, but you know, you could say, "Oh, you're enslaving horses." Excuse me.

>> Everybody works for a living one way or another. It's what you call it and how it's how you treat people that counts. And so you don't treat horses the way you treat people, but you treat them nicely. You treat you treat everything humanely. So it's this kind of animal research I like and it's very, very useful. So they found that if you feed a methionine-restricted diet, they'd live longer. But why? But why? But why? So doing the research on the methionine cycle, all the biochemistry of methionine, that one which which takes, delivers one-carbon methyl groups to different molecules like DNA, like neurotransmitters, like hormones to modify them in ways to make them active or inactive, you know, that sort of thing. Very universal kind of service, molecular service done for the body's overall biochemistry is done by methionine. So, in fact, graduate school and in even in undergraduate in biochemistry, everybody learns about the methionine cycle because methionine is an amino acid which is essential. In fact, it's the one you need the least of. Well, why do you need the least of it? It's essential because it's essential. Your body has many ways of recycling it and regenerating it. That's why 10 to 20% of the population is low methylators. Hey, how come they're not dead? How come you have low methylators in the population at a very high percentage? Because your body has a lot of redundancy and a lot of ways to work around that low methylation. And dietarily, there are other ways we can help work around it so that your physiology becomes really more normal so that you can go 5 hours from meal to meal instead of desperately needing a snack after an hour or two, that kind of thing. So the reason why a defect in the methionine cycle, which is what these low methylators are, it's an enzyme that helps to recycle methionine. The reason why these things are not fatal defects is because there is a lot of redundancy. And so when you have a lot of methionine in your diet, that methionine cycle that we all learned how the body conserves this precious little essential amino acid methionine, it ain't so precious. In this society, we have tons of it. We got 10 times more than we need because the methionine requirements, the daily requirement for methionine is about 3 to 500 milligrams. This is a bulk nutrient. This is an amino acid. So, for example, glycine, the normal diet gives you two or three grams, 2 or 3,000 milligrams a day of glycine. But guess what? It's not enough. You need 10,000 milligrams because that's what you need more of. And I can explain why and it will shortly. But that's how I got into this. And so it was my job to try and find something that would help to get rid of excess methionine. Well, some research had come out in the 1990s about methionine clearance. There's the most abundant enzyme in human liver, at least in America where we eat so much methionine. The most abundant enzyme in human liver is an enzyme called glycine N-methyltransferase. It is the enzyme which is the main, the only initial clearance enzyme for methionine to get rid of methionine. Glycine N-methyltransferase. Glycine means a methyl group is transferred from activated methionine, which is called SAM. People probably understand that it's transferred to glycine in order to get rid of that methionine, to get rid of that extra methyl group. And in fact, you need two molecules of glycine. One to take that methyl group as glycine and methyltransferase. That's called transmethylation. And the other half of the clearance cycle for methionine is called transsulfuration. And there the glycine is needed in order to make glutathione.

>> I'm not going to talk about glutathione much today because we could talk for years about that. That's a very big topic. Suffice it to say that making glutathione is the is one of the two ways that every molecule of methionine gets cleared. So you need to waste two molecules of glycine to get rid of every excess molecule of methionine because your liver gets rid of the excess. So you're not doing that methionine cycle an hour after you've eaten that cheeseburger. Your liver is busy getting rid of it as fast as it can.

>> Right?

>> So, so that was my hypothesis then is let's try and see if we can feed glycine if that can help to accelerate the clearance of methionine and thereby increase lifespan. So guess what? We did that. Published an abstract in San Diego in 2011 and published a paper with the National Institute on Aging with mice in 2018 when it was finally published. I'm not sure around there. That was the National Institute on Aging, their interventions testing program, ITP program. And, um, we got the mice or the rats in my initial study in 2011, they lived longer. They didn't live that much longer. Not as it wasn't as strong as methionine, but they also didn't decrease in size. But importantly, it did not affect the amount of methionine in their blood. Not one bit. So an excess of glycine does not help to clear it. There's always enough glycine around because remember glycine, even when you're deficient, that's another thing that's confusing about it. Glycine is maybe the most or the second most abundant amino acid in the body, but yet most people are deficient in it. Cuz that's not enough because glycine has other jobs. When we get to inflammation, I'll talk about the other jobs of glycine. But that's what we found was that it extended lifespan anyway. Why? And we're not sure exactly why it did in these mice, for example. It looks like the main reason it extended life was in slowing the growth of lung cancer because most of them die of lung cancer. They die because the cancer grows and grows and grows and finally it gets so big they can't breathe anymore so they die. But glycine inhibits solid tumor growth. That's been demonstrated certainly in animals and that's how it increased lifespan there. But I believe that it generally will increase and certainly improve the quality, if not the quantity of life because we know that it has a tremendous effect on decreasing inflammation and everybody's dying one way or another from chronic inflammation. So glycine fights that in many ways. But that's how I got into it and then realized, yes, glycine does increase longevity or increase lifespan or decrease whatever it is that's decreasing lifespan. So you, the animals live longer. But it wasn't doing methionine restriction. It was not affecting the amount of methionine. It was doing something else. And what it was doing was it was basically, I think, doing everything else that glycine does, especially stopping chronic inflammation or inappropriate inflammation, but it had nothing to do with glycine and methylation. But that's how I got into it into that this particular corner of the biochemistry universe. Then I started taking it myself because glycine's harmless, harmless, non-essential amino acid. You know, you eat grams of it every day. So I sampled a little like the old-time scientists. I'm old school, right? They used to do. I said, "Oh, can so I said to our, you know, people in the lab, you got a bottle of glycine?" "Yeah, here's the glycine." You know, this is your scientific glycine. Open up the bottle and, you know, don't do this at home. I mean, I I, you know, I do experiments on myself and I don't necessarily advise everybody to do that, but, um, everybody...

>> Medical advice.

>> ...selves. It's just you got to be you got to know what you're doing. Anyway, so I tasted this glycine. You know, it could have been a bottle of cyanide. I wouldn't do that, but it was glycine. And I tasted it and I realized it's sweet. That's why it's called glycine. Glycine means sweet amine. That's why I made a product. I called it sweet amine, you know.

>> Yes.

>> That's what glycine means. It has a bad aftertaste. So, you got to you got to kind of cut it with a couple of other things, you know, to make it taste more like sugar, but it's it's easy enough to do. You can cut it with sugar if you want. That's how I got into it. And so, I I I did an experiment and I started just taking 10 grams a day to see what...

>> 10 grams a day is way more than you're going to get usually from food or...

>> Yeah. Of ordinary food, you get two or three grams. So, let me take another 10 because if I unless if I took an extra gram or two, I don't think I would notice a difference. But it seemed to me that this was something that would be important to do that with. It's like the scientific method is really, you have a question and then you get a hypothesis. Where'd you get your hypothesis? Rubbing two neurotransmitters together, you know, just...

>> You get you get struck by an idea, by a hypothesis in your mind. So, you know, I mean, this is it's inspiration. Let's just call it inspiration. That's I was inspired to take 10 grams a day. And so I did that starting in like 2008 and I didn't notice anything. I felt fine. Everything was good. No, no change. I kept taking it. I what I did is I formulated like a Jell-O dessert kind of thing where I added I started with gelatin because gelatin has a lot of glycine in it. It's about 25% glycine by weight. So a 4 oz serving of a gelatin dessert without any flavoring at all or just with the juice flavoring has half a gram of glycine in it. So, I figured, okay, let me start with that. And I added another 8 and a half grams per serving. You know, when you make Jell-O, you know, you you heat up the water and you put in the gelatin and then you you dissolve the gelatin and you just add glycine. It's water-soluble. And then you make your Jell-O. And that's how I had 10 grams a day. In fact, before I decided to go into business and sell it to anybody, I figured, well, I better make sure it's really safe. So, I I had 40 grams a day for a month, and I still felt fine. But I not only felt fine but...

>> Any additional benefit or just fine? You just didn't know?

>> I just felt fine. But well, benefits retro. So, for example, when I say feeling fine, when I was, you know, in my 30s and 40s and 50s and it would snow, you know, in the in I was in the Northeast in Upstate New York and we would get snow just about every year several times and I would do shoveling. So I'd go out and I'd shovel the snow for for snow blowing, but there are a lot of paths and pieces that you have to shovel by hand. So between the snowblower and hand shoveling, I'd be out there for an hour in a typical snowstorm shoveling the snow. And then the next day, my back would be sore, but I knew it would go away eventually. It was just sore for a day. So you say, but that's that was part of my feeling fine. Once I discovered the glycine miracle, as the book says,

>> Yeah.

>> and started taking 10 grams of glycine a day, I no longer had those pains. So now in my 60s, now in my 70s, but in my 60s and 70s, I go out and shovel snow for an hour and I wouldn't even get sore. I felt better than I did when I was in my 30s. So it was so it was helping there, but nothing I noticed because it was normal to me and nothing seemed to change. But then a couple things happened. And I fell 40 onto a concrete floor directly onto my tailbone at the Home Depot one day. And although you'd think I'd have to go to the emergency room, I managed to get up and finish loading up the sheetrock I was buying and cutting. And that night my wife and I had tickets to a dinner dance. We actually went dancing. It didn't bother me. And the next morning I felt absolutely normal. Not even a pain in my rear end. Nothing where I had fallen. Just a huge bruise, you know, as evidence that I had fallen. But there was no pain. Then the same year I got a severe sunburn. And when I realized that I had had this sunburn because I was at a ball game. I wasn't at the beach, you know, but it was full sun. It was near the solstice. There new stadium, no no obstructions. And around the fifth inning, you know, of this ball game, I started to feel a little warm on my thighs. And I looked down and I was like a boiled lobster. And I hadn't done this to myself since I was in my early 20s. Certainly, you know, back in my reckless youth, right? So I knew that I was going to be I was 100% certain, right? I'm not going to have excruciating pain just dressing, undressing, bathing for the next couple of days. Life would be hell. But guess what? Once I got in the shade, it just started to fade.

>> Went away. And then I realized, you know, because I had done research on the skin and my in my graduate studies, I was with the dermatology department at NYU School of Medicine and that's where I did my thesis work. So we do a lot of work on skin. So I knew about skin and inflammation in the skin and so forth and you know started to put two and two together and realized that this is inflammation that between the fall which should have created massive inflammation and the sunburn which should have created massive inflammation I got zero inflammation because I was taking 10 grams a day of glycine. These are some of the most dramatic results I've ever had in any experiment I've ever done on myself or on any other lab equipment. I don't usually do experiments on animals, you know, except these feeding things I was talking about. But I had never gotten such dramatic results in anything. That was, you know, Eureka moments that it was it was really about inflammation. And then I started reading the literature more about glycine and inflammation. And there was an enormous amount of work, a great body of work that was done in University of North Carolina during the 1990s by a fellow named Ron Thurman who was a toxicologist. And they did great work. Unfortunately, he actually died suddenly of a heart attack at the age of like 61, I think, in 2001. And I I think because even though he did this great work on glycine, he didn't try it on himself.

>> Do you know that for a fact?

>> If he had decided to try experimenting with 10 grams of glycine a day, he wouldn't have had a heart attack.

>> Do you know that as for a fact that he didn't use glycine?

>> Yeah, I would say yes because he had a heart attack. I would say that as a doctor would say, I would say that's diagnostic for a heart attack is is...

>> In order to have a heart attack, you probably need to be glycine deficient unless there's some other really extraordinary event going on like maybe, you know, a skiing accident, you can get a fat embolism which can get into your heart, stuff like that.

>> Okay, so can I say you that's a very strong statement right there. I want that seems like a nice entry point because I've read in the literature higher levels of glycine potentially lower risk for cardiovascular disease. So tell us what are the mechanisms?

>> Well, yes, and that may be and also when I say in order to have a heart attack, I mean you have to be glycine deficient over over the long haul.

>> Okay. Yes. So give us some context for that statement and then talk about the various mechanisms. I know blood pressure. I think glycine works on many different mechanisms.

>> Glycine works on many different levels. As far as cardiovascular disease is concerned, the important level is that of inflammation. And when you think about the cardiovascular system, especially the arterial tree, that's a high-pressure fluid system. It's like, you know, when you turn on the sink or the tub or the shower, you know, that's high pressure in those skinny little pipes that comes in to the basin. And a fat slow-moving water pipe is the drain pipe. So those are your veins. Your arteries supply that high-pressure fluid. And the drain pipes, the veins and also the lymphatic system are the drains that drain it out. So when you have high-pressure fluids circulating like that, especially at branch points, especially especially at the highest pressure branch points like where the carotids branch off from the brachiocephalic artery from the systemic aorta, where the, especially where the coronaries break off or branch off from the coronary artery, that's virtually right there before they even get out of the heart, before they even get out of the sort of circumference of the heart, even though they're beyond the valve. That's where the coronaries branch off. So at that point where you have like a 90° branch point off a very high-pressure fluid system, the highest it ever is in the body, you're going to get turbulence. And where you get turbulence, the engineers will understand this, wherever you get turbulence in a biological system like this, you're going to get damage. So just from, you know, these stories about these wonderfully fit jogging people, and jogging is very good exercise. But did you notice that some of the key proponents of jogging, how did they meet their end? They died while they were jogging. Because if you have underlying cardiovascular disease, anything that's going to really make your blood pump harder because your blood is hypercoagulable may induce a clot. Well, the reason why your arteries become clogged up is because if that that injury is normal, normal when you do exercise like that and it's good for you and it's normal to have minor micro injuries to your arteries, even your coronary arteries all the time because your body is designed to just repair them. No big deal. But if you're glycine deficient, you then get inflammation following from injury. See, nowadays, if you look up any source of information, whether it's WebMD or Wikipedia or any scientific journal or medical journal you like, you just look up inflammation, and it tells you inflammation is the immune system's first response to infection or injury. And that's a half-truth. It is not a normal response to injury. That's what I found out with my self-experimentation with severe injury, no inflammation. How's that happen? No infection. No need for the immune system to start secreting poisons to kill something that isn't there. So why does that always happen? Good question. It always happens because there is a nutritional deficiency that we don't recognize, and that's a deficiency in glycine. That's why it happens because I know for a fact it doesn't happen. I had a very interesting conversation with a colleague about a year or two ago and she was from, I think she was from your part of the country, like Colorado, someplace, you know, nice sunny mountainous place. She had a nice tan and I was talking to her about glycine and everything about how I had that sunburn and she says, "Oh, I don't have that problem." And I said, "Well, you have pretty fair skin." I said, "You are you have like a bone broth fanatic?" She said, "Well, yeah, I am. I have bone broth every day." I said, "Oh, well, that's why you're not glycine deficient. One of the very, very few." So, she doesn't get sunburns. She, you know, a little redness, but it goes away. And you might think, oh, you know, that's my genetics. I don't burn. I tan, you know, and there is a component to genetics, but I mean with her, it was it was very clear, you know, she gets gets enough glycine and not many people do. If you take a glycine supplement like Sweet, I put in eight grams, right? If you'd ordinarily eating two or three, that gives you the other eight, you get your 10 plus a day of glycine, you have enough so that your body does not do inflammation as a result of injury, only infection where it's appropriate and where it may save your life because that's what it's for. But not in the case of injury. In the case of injury, inflammation only does more harm. In the case of chronic micro injuries like from blood circulation, heart attacks. In the case of chronic micro injuries from ovulation in the ovaries, ovarian cancer, that's these have been epidemiologically demonstrated that when you have repeated injuries or cases of massive cell death, what do you have? You know, breast cancer, what a scourge. Well, what happens every month when you're not pregnant in a non-conceptive cycle? The third week of every cycle, your breasts grow because it's getting ready to feed a baby if there is one to come along in nine months. Well, it starts to grow for about a week and then when there is no conception taking place, what happens? The cells die off. The hormones disappear. The estrogen and progesterone that are making those cells multiply like crazy, they disappear. And so, what happens? The cells die off. What happens when they die off? They get reabsorbed. No big deal unless you're glycine deficient. So in most women, they can find that there is signs of inflammation in that third week at the end of the third week of a cycle when you're, you know, the premenstrual time, you know, PMS or that premenstrual period, there's inflammation in the breast, low-grade inflammation. You might not feel any pain or swelling or anything. You might feel some pain and swelling in the early part of the menstrual cycle because that's when the breasts are growing. So you feel that breast tenderness, but in the you don't feel it in the third week of the cycle because that's where they are regressing, but there's a low-grade inflammation month after month, year after year. The more menstrual cycles you've had, the greater your risk of breast cancer. No surprise, shouldn't be, once you understand, you know, the big picture of what's going on in the body with the hormones and the, you know, all these physiological whether there's exercise injury or micro injuries that happen due to physiologically normal events, even programmed events like ovulation and, you know, menstrual cycle. All of these things in a glycine deficient body will chronically produce these conditions which give rise to things like cancer and heart disease. Now they're blaming everything on inflammation. Well, they're right. Why is another question, you know, and it's not that these are the only things. Remember I said we we fed these mice glycine. They all died of cancer, right? So it's not like, oh, you know, Britain says if I take glycine, I'll never get...

>> And remember this is, you know, first of all, I'm not a physician, so I'm not giving medical advice. I'm a scientist and a professor.

>> Right.

>> Emeritus, anyway. But I, I don't, I don't give medical advice. Number one. And number two, you know, these things are not absolute. You know, it's a this is a nutrient. We all have finite lifespans on earth. You know, we're going to die of something. And it's going to be, and it used to be that cancer was one of the ways that old people died. Did he die of old age? One of the thing he died of old age. Well, what exactly did he die of? Oh, maybe he had lung cancer. You know, something like prostate cancer or lung cancer or I say prostate cancer because, you know, they've done studies where if you do an autopsy on men who die, centenarians, you know, very, everybody wants to know if you live to be over 100, what was the secret? So, they've done studies where they do autopsies on centenarian men and they find out that every one of them has prostate cancer.

>> It just didn't grow, you know. So cancer used to be one of the ways that old people would die. Now you get people in their 30s and 40s and 50s and even younger, they get cancer. Childhood cancer is another kettle of fish. But but but now cancer has become a bigger and bigger and bigger scourge. And we wonder why because that should not happen to younger people, to middle-aged people. And one of the big reasons is diet. And you see what's happened with our diet. We get a triple whammy of glycine deficiency. Unlike our forebears, and I don't care what ethnicity you come from. Your grandma did not throw the bones in the trash of whatever animal it was that she cut up for the for the meal. It was it went into the soup, not the trash. Because in the soup, you actually through boiling the bones, leech out the collagen, the gelatin. You notice you you take the bone broth, you put it in the refrigerator, it gels. That's gelatin. And gelatin is 25% glycine by weight. So, it's a lot of glycine. So, we didn't used to throw that out. So, now we throw it out. Now it's all you get your fried chicken or you get your hamburger or all of these things are muscle meats. We cut the... So we talk about processed meats. Yes, processed meats are not great for you. But the worst processing is cutting the meat off the bone and throwing the bones away. That's the worst kind of meat processing that we do.

>> I love you. So it's not the red meat so much that's killing you. It's the red meat not in balance with what it's normally attached to. You know, the bones and the connective tissues that attach it because that's all collagen. So, that's one way that we're getting a lot less glycine. The other thing is we're not only eating that meat, the muscle meat, more exclusively, but we're also eating more of it. It turns out when you eat more of it, what happens? Everybody's overweight. Not everybody. I was overweight. I lost about 25 pounds recently. I mean, it was it was an effort, but worth the effort. I had to because I was tripping into diabetes. And I I would will tell you about diabetes. I I was in impaired glucose tolerance back in 2007. My mentor at the time who, you know, I told you about, he was the one who was the dermatologist and cellologist. We used to have a blood club. We used to draw each other's blood every week and, you know, look at our and we so we had these longitudinal measurements of everything in our blood and we'd go first thing in the morning, you know, before you'd eat. And so it came my my blood sugar came up 129, which is now considered diabetic. He says, you know, I think you ought to maybe try and take metformin. You know, and I said, I, you know, I can I can regulate this with with diet. I'll I'll be okay. Don't worry about it. So what happened? Well, that was 2007 and a couple of times it was bouncing 125, 127, 129 fasting glucose. Before that, it had been 95, 105, 110, 115, something like that. But then that soon thereafter is when I started my experiments on glycine. So guess what? With glycine, I never went into diabetes. I stayed in impaired glucose tolerance until 2024. So, it's about 16 years. For 15 years, keeping my glycine up high kept me out of diabetes and just in impaired glucose tolerance. So, now I'm back in impaired glucose tolerance because I lo finally I lost the weight. Study I like to quote is that diabetes can go away without losing the weight if you're glycine deficient to begin with. But that's another story. We're talking more about heart disease today, right? So, but anyway, just in terms of how you can be glycine deficient. So, that's two ways then. And if you're gaining more weight, which puts you in vulnerability to diabetes, more often than not, you get diabetes if you're overweight. A lot of people are very overweight or obese. And what happens? A recent research from the Mayo Clinic in Minnesota and also they have a branch in Jacksonville, Florida, and they have a children's hospital there. There was some very good research done in like 2023, 2024 where they, I love these doctors who are really good at doing research. A lot of scientists are want to be doctors and doctors are want to be scientists. I'm just a scientist. But there's a this is a doctor who is a really good science. Some doctors are good scientists. Some are very good at both. His hypothesis was, hmm, you know, we have a lot of children. It's a children's hospital and what most of the children in the hospital for? Well, most of them are obese. A lot of them, you know, 8, 10, 12, 14-year-olds, they're all obese. And so they have these medical problems and they need to be hospitalized for this, that, and the other thing. So they did a study where they took a look at these obese kids versus normal kids and they looked for markers of heart disease, the typical markers like CRP and other other markers they were looking at. They looked at the whole metabolic profile to see what's different about these kids. Do they look like the same kind of blood profile that you find in older people, middle-aged and older people who have heart disease? They're too young to get the heart disease, but are they headed for heart disease? Can we tell by what the markers are in their blood? And guess what they found among other things? Glycine. And they studied that a little further and found that there are several pathways to synthesize glycine because they say it's non-essential because your body can make it, but it can't make enough. One of the main pathways for synthesizing glycine, guess what? Is inhibited in obesity. So your body is now making less glycine. So you eat all the muscle meats and now you're eating too much food altogether. So eating all the muscle meats that depletes glycine. You're eating too much food altogether, you get overweight. That depletes glycine. It's that way also. And then what are the even the muscle meats that we're eating are depleted in collagen. Usually you have some coll, you know, like you have grass-fed beef, they have, you know, their muscles are, you know, are tougher. You know, you need to cook them longer and so forth. Why? Because they have more collagen in them, so they're actually more nutritious. Anyway, there's there's a lot of things, at least three things that are going into being glycine deficient. It's the quality of the muscle meat, the fact that we're not eating the bones, and also the fact that our body is making less. That all contributes to making us glycine deficient. So, obesity and what I'd like to point this out with COVID, even though we're not talking about that, remember the comorbidities with COVID that made people die of COVID if they had cancer, if they had heart disease, if they were obese, even if they weren't diabetic, if they were obese. They were all conditions in which people are deficient in glycine. There have been studies showing that those conditions which are the comorbidities of COVID mortality are also the comorbidities also characterized by glycine deficiency. So there's a lot of things, you know, that way.

>> We're going to do an episode about that one next. But I want to bring you back for a second. So inflammation, right? I think everyone's waking up to the fact that if we just measure our serum cholesterol, it doesn't necessarily tell us as much as many people would believe. You have to look at the bigger picture, inflammatory conditions, right? Do you have elevated inflammation? But also, we know that diabetes can be a precursor and increase the risk of heart disease. And we know that glycine, like you were saying, can keep you out of that diabetic territory. But there's also elevated homocysteine and elevated blood pressure and this anti-platelet aggregation impact of glycine.

>> Yeah, that's that's that's the other mechanism for keeping your coagulation down. Can you talk about that?

>> However, I'm going to I'm going to push back a little bit because I'm not a fan of the idea of homocysteine and toxicity. I'm not sure I'm not sure that that's really a thing because when that came out first, it was it was a research paper on a genetic variant of people who had a deficiency in an enzyme called cystathionine synthase. Homocysteine combines with serine to make another amino acid called cystathionine. So it's cystathionine synthase is the first enzyme and there are people who are deficient in cystathionine synthase and so they had elevated homocysteine and so they also were at higher risk of heart attacks and so they said, "Oh, we can fix that." They gave him methylfolate and they lowered that homocysteine right back to normal and the heart attack rate did not change. They still had the same rate of cardiovascular disease even though they lowered the homocysteine to normal. So I still unless I've seen something recently that's that's changed my mind, I haven't seen anything yet. It's not homocysteine that's the culprit.

>> It's it's really it really has to do with the methionine and glycine balance. If you have cystathionine synthase, it has to do with glutathione, for example. But there's more even more about glutathione that I don't think it's quite everything that everyone thinks it's cracked up to be. It's important. It's an essential component. But glycine, glycine is one of those things that's so fundamental that it's so important in so many pathways that if you don't have enough of it, a lot of things can go wrong. However, your body knows that and makes enough of it to do almost everything it can with glycine. And the reason why it stops inflammation is because it is there almost like a salt. It it does not have in inflammation. Its function is not biochemical. That's another thing that kind of throws the research off. It doesn't have a biochemical function. What it is is a gatekeeper. It's a gatekeeper for channels that allow chloride ions to flow into the cell in order to balance it electrochemically so that these immune cells, these macrophages, the first responders of the immune system, don't start shooting the place up with their poisons because they've activated because they've lost their polarization, their electrical polarization at the surface membrane. So it allows these so-called glycine-gated chloride channels, otherwise known as glycine receptors, need glycine is the big hand that opens it up and holds it open. If it's not open, the glycine deteriorates, the voltage at the surface deteriorates and the cell can be activated unnecessarily. So you get excessive reactions to infectious organisms. That's what the first series of papers by the Thurman group at UNC showed is they show they took these, I remember it was, they took rat alveolar macrophages, the things that go crazy and cause the cytokine storm in COVID, alveolar macrophages, and showed them in the absence of glycine or with very little glycine, you would see this tremendous electrical spike when the cell would get activated. When you put in lots of glycine, as much glycine as you could get when you supplement as much as you can, you got you it it did not prevent inflammation. It did not prevent the activation in the presence of bacteria which tell it, yes, now it's time to get activated because these Staphylococcus organisms don't belong here and we better kill them before they kill us. That's appropriate inflammation. And even with a lot of glycine, you get a nice sinusoidal spike, very nice spike when you got a challenge with the bacterial lipopolysaccharide with a lot of glycine, but you, but the spike was not crazy high. So you get an excessive reaction if you don't have enough glycine or you get a reaction, you get these cells activated when they shouldn't be activated at all, as with just with injury and no infectious agent present, no microbe. So that was all some of the wonderful research that was done in the 1990s by the Thurman group at UNC. So it's its role is in stopping inflammation is doing just that. It's it's stopping the activation of the cell by holding those valves, if you will, those chloride channels at the surface of the cell open to allow the influx of this negatively charged chloride ion. And that's what keeps the cells normal and quiescent. Well, to do that, you need levels that are something in the neighborhood of north of 500 millimolar. Well, what does that mean? Well, that you don't have to know much about it except that's the way we measure glycine is in millimolar units or, I'm sorry, micromolar units, which is a thousandth of millimolar units. How many micromoles per liter? Is that a lot? Well, that's actually a lot for an amino acid. In fact, the normal range for glycine concentration according to, you know, Quest Diagnostics or any of the other labs is about 150 to 400, 350 to 400 micromolar. That's considered the normal range. So, north of 500 is north of the normal range. But actually, if you're less than 500, you're glycine deficient.

>> Because it has to be that high because again, glycine for all of its biochemical uses, you don't need that much. There's plenty of glycine around whether it's making cancer cells grow or normal cells grow or any other function. There's always going to be plenty of glycine around in a normal body, in a normally glycine deficient body. But for this purpose, for the stabilization of macrophages so that you don't get inflammation, you need a lot more there. So there are all kinds of things about glycine that have kind of thrown off ordinary, you know, research trends and trains of thought, including the fact that it's not non-essential after all. It really is essential, but not really for biochemical function. It's essential for a cellular physiological function that has to do with the activation of the cells that cause inflammation. I had to pinch myself a few times years ago when I when I first, you know, discovered made these discoveries. It was like, is this real? Could it be this simple? You know, people to this day still tell me, "Ah, it can't be that simple."

>> You're not presenting it as like the only factor. It is just a big factor.

>> Right. Not only that, but and yes, and it is the crit, it's the critical factor. It is the if you have chicken soup or bone broth, that's really what it is. If you could strip glycine out of bone broth, you're not going to get all those benefits of bone broth. So, that is the factor, but that's a scientific principle called Occam's Razor. It's the simplest explanation. That's another thing doctors, especially. You'll see that in my book, The Glycine Miracle. I point out in a number of cases where doctors will do this wonderful research and then they get into the discussion section where they discuss what the research means and they'll talk about, well, you know, this situation is very it's complex. And when they say that, they usually mean they don't understand it.

You say that this situation or this, this, um, this process is complex, is usually a scientist's way of saying, "I don't know anything about it." Saying, "I don't know." And they're really kind of covering their rear ends, if you will. But it leads you to the wrong conclusions of saying, "Nah, it can't be that simple." But in fact, a truly scientific approach says the simplest approach. This is Occam's Razor. It's the simplest hypothesis that fits is usually the one that is acting. So you don't reject hypotheses because they're too simple. You reject hypotheses because they're too complex.

"I love it."

Like, you know, you know, what is it? Tommy said the all the planets and the sun revolved around the earth in these complex epicycles until, you know, Copernicus blew them out of the water, you know, and no, they just all go around the sun in simple elliptical orbits. There you had your simple explanation. The complex explanation was thrown out because it was, it didn't, it was unscientific. It had to be following the scientific method. Had to be discarded.

"Yeah, and last thing before because we're got to, we're going to tell people exactly how they can get enough. But, but I love this anti-platelet. I feel like this anti-platelet effect. So tell us about that and then let's talk about."

"Right. Yes. So platelets, yeah, platelets are part of the clotting mechanism. There are a couple of different clotting mechanisms. One of them is platelets, which are these little plugs which plug up the holes physically. And then there are a lot of biochemicals that are involved. But some of them are made by platelets. So there's a couple of ways platelets are involved. So one of the ways that platelets are involved is that when platelets are activated in order to do their thing, they get sticky. So one platelet sticks to another platelet, and they stick, they stick, they stick to the surface where the tissue is damaged, you know, where there's a cut in the blood vessel, and they form a plug. So that's part of the clotting process. Well, they have glycine receptors, glycine-gated chloride channels. That was demonstrated by again, the Thurman group showed that back in the '90s. Shemer is the first article of that one. Anyway, Peter Shemer. What happens is if you don't have enough glycine, your platelets are more sticky. And if you have enough glycine, they're not. So they will not form a clot abnormally. And we all know what happens when you have a clot that's abnormal. You can get an embolism. You can get a clot somewhere in the middle of a perfectly otherwise good vein or artery. It can get stuck in your lungs, you have a pulmonary embolism. Or if it gets stuck in your coronary arteries, you get a heart attack. If it gets stuck in your carotid arteries, you get a stroke. Dangerous things to happen when they're not supposed to happen. That's why it's a very complex series of interconnecting system to make a blood clot and also to make the blood unclot. Because when you have a clot form and all of a sudden that cascade of events which is necessary to amplify the biochemistry so that something that happens at a molecular level, a little little cut, a little insult at a molecular level or a little bit bigger, can all of a sudden generate a clot that may be milligrams in size, can generate a fibrin plug that can plug things up. You need a lot of amplification. In order to amplify it, you need this what's called an enzyme cascade. Enzyme A activates enzyme B, enzyme B activates enzyme C, enzyme C, and so on. You've got about seven steps till you finally get to thrombin, which, uh, takes fibrinogen and turns it into fibrin, which is the insoluble clotting material. Well, in order to do that, how are you going to do that without now making all of a sudden your whole circulatory system clot up? Is you have to have an unclotting cascade that's activated at the same time as the clotting cascade, which breaks up all the clots as they're forming before they are stabilized by an enzyme that sits where, just outside the right where the breach is in the blood vessel. Right where the blood vessel is cut, you have your Factor 13, fibrin stabilizing factor, which cross-links those fibrin fibers and makes that plug permanent and instead of being broken up by plasmin, which is the unclotting enzyme. The activation of plasmin, the formation of plasmin, which breaks up a clot, is activated by another enzyme called plasminogen activator. And you may have heard of like tissue plasminogen activator, which was revolutionary to save people in heart attacks and strokes, and they still do it. That's the clot-busting enzyme."

"Tissue plasminogen activator. So that stops the unclotting, so allows the blood to flow freely. That's how clotting happens. And platelets are less sticky to make their own clots. But platelets also make some soluble factors which participate in the blood clotting cascade. And one of them is PAI-1, PAI-1, that's called plasminogen activator inhibitor-1. If you, instead of plasminogen activator, there is also a plasminogen inhibitor or what inhibits the plasminogen activator, which is more conducive to forming clots. So when you have inflammation, your platelets are more sticky, just even directly because they're not enough glycine around. But you also have inflammation now, and the platelets are activated. So the platelets also secrete more PAI-1. So if you have more PAI-1, it inactivates the inhibitor of plasminogen and helps to stabilize clots even where they shouldn't be. And then on top of that, you have inflammation also increases the liver synthesis of Factor 7, which is one of the important, one of the critical participants in that coagulation cascade of enzymes. So directly on the platelets and also indirectly through being in inflammatory when you are, you know, people who have heart disease, people who have cancer, people of people who have blood that is in a well, people who need blood thinners, right? Your doctor would know. He'll put you on a blood thinner, right? People who need blood thinners have blood that is hypercoagulable, and glycine is your body's natural blood thinner. That's probably the easiest way to put it. And then people say, 'Oh, can I just take glycine instead of Plavix?' Well, you know, once you're involved in medication, you can't, you got to trust the one who knows how to manipulate medication because you're now beyond the normal parameters of what your body's used to doing. And you have, you got to be supervised by a doctor. And I'm not a doctor, anyway. Not only I'm not, I'm not a doctor. I'm not that kind of doctor. And I'm not your doctor. So don't ask me about medical questions."

"So not medical advice."

"I never give medical advice."

"About that."

"I will tell you how the process works that may be relevant to your condition. I will tell you what the research shows about it, and I'll tell you to ask your doctor if you want to know what you should do about it. But, uh, you know, that's, that's all I can do."

"Yeah, that's perfect. And can you tell us, is there, what is the state of the research here? Are there a lot of good trials looking at glycine supplementation and heart disease, either mortality parameters?"

"Well, yeah. There's some. There was some that was done by the Cleveland Clinic some years ago where they were studying because the Cleveland Clinic is a very big place, you know, so they had hundreds of thousands of patients over the years or millions of patients. So they had lots and lots and lots and lots of blood samples and genetic records and things like that. So they did a very interesting study where they had another one of these genetic variants was a genetic variant for, um, CPS, an enzyme called CPS. CPS is the first step in the urea cycle. So, um, what is that? Well, urea is the way we excrete excess ammonia. Most of it that we get from amino acids. Amino acids have that amino part, that nitrogen, that ammonia nitrogen, and you, you have to get rid of it. So we can't excrete ammonia, you know, that's, you can't have it in high enough concentrations in your blood to excrete it without it being toxic. Ammonia is toxic. And it's a little bit of ammonia. That's another thing with nomenclature. They say ammonia, oh, a toxin. A toxin. Yeah. In the wrong concentrations, it's toxic. In low concentrations, it's normal. Remember, I was talking about glycine being at least 500 micromolar. Ammonia, five or six micromolar, right? A lot less, you know, one-fiftieth or one-hundredth the amount of glycine you should have as ammonia, but you do have some ammonia. Well, in any case, most of the ammonia is converted to urea. And the first step of converting ammonia to urea is CPS, carbamoyl phosphate synthetase. There's a, you know, genetic, uh, variant of that. And it was enough for the Cleveland Clinic to have enough samples to be able to look at disease. And they looked at, so they looked at MACE, major adverse cardiac events, among, uh, people with this CPS-1 deficiency because what is the, a consequence of the CPS-1 deficiency is, guess what? Glycine. As I said, it's like the most or the second most, I'm not sure which, abundant amino acid in the blood. You have a lot of it, even if you're deficient in it. So that's the major source of ammonia, which is the major source of urea. So if you get a backup in that pathway that makes urea because your CPS-1 is only half of what it should be because you have one bad gene for doing it, then guess what? You're going to get a backup in glycine."

"Yeah."

"So they found that men, it wasn't true in women, probably because sex differences in the kidney function and in the expression of this function. But among the men who had CPS-1 deficiency, the incidence of major adverse cardiac events was drastically reduced. But the most, one of the most significant results I've ever seen, just tremendously, tremendously. It's like people who have CPS-1 deficiency, men don't get heart attacks. It's like, you know, they just don't. And so they, they wondered why and they explored why and they said, 'What, you know, what is it about CPS-1 deficiency?' And they found out it was because glycine was high. And they did their other epidemiological adjustments. So you say, 'Well, you know, they have more glycine, but is it because of the glycine or is it something else?' So they say, 'What if we adjust for this and what if we adjust for that?' And they ended up, no, it's the glycine. Unfortunately, some of the subsequent work that this group at the Cleveland Clinic did, they didn't follow up on the glycine thing after they had established in 2015 that glycine, low glycine was a risk factor for heart disease. This happens all the time. Discoveries are made and they don't follow up, you know."

"And what do they consider low glycine? And was there like a threshold, like with above a level that seemed protective? Like, you know what I mean? Like was there a kind of level?"

"This is, did I ever, I know you had requested some papers for me. If you, if you, uh, anyway, the first author of this paper is Hartiala, H-A-R-T-I-A-L-A, Hartiala, 2015, I think. And I can send you a copy. Yeah."

"But that's, that was from the Cleveland Clinic where they have a lot of patients in it. And as I say, they didn't follow up on what it was, what they didn't follow up with what was it about the glycine that decreased the incidence of major adverse cardiac events. If they had found out, if they had just looked a little, that paper that you know, that Shemer paper from the Thurman group that showed that glycine receptors are present in platelets and platelets respond, their aggregation, aggregability response to glycine concentration changes, they would have found that paper because that paper was already in the literature. So the good work on the part of the, uh, Cleveland Clinic people, but not so good work on following it up and actually exploring the mechanism for why that, uh, genetic variant actually dramatically decreases the risk of major adverse cardiac events in male, in men. That's fascinating."

"So I don't remember the details of the levels."

"I have to buy it. So that's okay. That's okay if you don't remember. I'm just wondering what the goal is though, and you've done a lot of research that we get ourselves above that 500 micromolar."

"Yeah. And people say, 'Can we measure glycine?' So I don't, I haven't measured my glycine levels. Remember I said we used to have a blood club. So in those days, my glycine was leveled a lot. We measured a lot. And I remember in the times that I was supplementing actively glycine, my level went up to about 720, 730, whereas ordinarily it was down to like 300 something."

"And I'll have to test mine someday because I had the same thing as you. Like I actually just realized I fell the other day, and I, it didn't like bother me, and I didn't wake up and, but I when I saw the bruise, I was like, whoa. But like, it didn't stop me in my everyday life because there isn't a lot of pain. I had to see it visually. And so I'd love, I need to test mine one day. Because, and we're gonna talk right now about how you get enough. And like he's been hinting at bone broth daily. I do two to three cups, gelatin daily, collagenous cuts, grass-fed meats, connective tissue. Now I eat glycine, but Dr. Burn has also formulated something. So tell us about Sweetamine, but also why is Sweetamine different? I've been getting questions. Why is it different than any other glycine supplement on the market?"

"Well, the, the only thing that's materially different is that it has taurine in it. I also add, uh, a little, little less than a gram of taurine, 800 milligrams of taurine in it. Otherwise,"

"It's more designed to be added to food, right? And like you make your, like, lysine lemonade in the morning where you put like a lemon and water and Sweetamine. So it's less like a, 'I got to take it.' It's more like something you can enjoy."

"It's food, you know? I mean, it's not. Yeah, it's food. It's not. It's not made to give you some superhero amount of glycine in your blood. It's made to give you a healthy amount, which most people just don't have. But, um, but otherwise, the main thing is it's just taste. I mean, you know, I tweak it a little bit with natural sweeteners to make it a little bit more like sugar. But, uh, it really has almost no calories. It's got like 24 calories. And it's, the main thing is is that it's, it's convenient and portable. So you can carry it with you on the plane. You can take a box of it with you and pack it in your carry-ons. They'll open your carry-on to see what you got if you got 10 or 12 boxes in there, as I sometimes do. And then they'll test it and say, 'Oh, it's okay.' But it's, um, it's portability and convenience. And some people say, 'Oh, I can buy glycine a lot less cheaper. Just buy glycine powder.' And I say, 'Yes, you can.' Because whenever you formulate anything into a, a prepared product, even, even a capsule as opposed to a pill, even a capsule or a packet of anything, you know, half the cost or more is in the packaging. So, you know, you, you can, you know, if you don't want to, if you can't afford, and it's not, it's a, most of my customers pay because I run sales and they buy like months' supplies at a time, several months at a time. Most of my customers pay about or less than a dollar a day. And that's not a whole lot. You say, 'Oh, I can get all the glycine I need and buy it in bulk and do it for 25 cents a day.' Yes, you can. You can also go to Starbucks or Dunkin Donuts and buy your coffee. You can make it for one-tenth the price in your own kitchen."

"Yeah."

"You know, it's a matter of, it's a matter of taste and convenience and all of that. And it, it, the point is many times or a few times more expensive than buying bulk glycine powder, but it's still very, very cheap because, you know, many times a very low number is still a very low number. So for less than a dollar a day or about a dollar a day, give or take, depending on how much you buy at a time, it's not, you know, it's, it, it's really, it's really a convenience. So, you know, and if you don't, you don't have to use my Sweetamine. I mean, you can buy glycine from anybody else if you want to get just glycine. If you want to get just organic stuff because it's, you know, for bone broth, you know, then, then one way or another, just get it. I don't care who you buy."

"Exact. Yes, that's exactly right. We're just here to raise awareness around the deficiency of glycine, uh, and what how it links to the other conditions. And like you said, we're not just trying to sell you. So, make your own bone broth at home. That's probably the cheapest way if you have the time and the desire."

"If you're paying nothing for the bones. Yeah. But, you know,"

"If you're paying nothing for the bone. Yeah. Bones are expensive though."

"They can be expensive. Yeah, that, that is true. So, yeah, we've given you so many different options. Thank you, Dr. Burn, for your passion and your research and, um, for spending time with me again. I, I really, I thoroughly enjoyed our conversations and, um, know about your comments."

"I'm a professor, so I don't have a classroom every day to talk in front of. So, I'm, you know, I got to get my, I got to get my fix of talking."

"We are very excited to be in your classroom. And let us know if you guys have any topics or questions, um, for us to delve into in future episodes."