224 ‒ Dietary protein: amount needed, ideal timing, quality, and more | Don Layman, Ph.D.

1. 0:00 – 0:08

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to "The Drive" podcast. I'm your host, Peter Attia. [upbeat music]

2. 0:08 – 4:39

   Don’s background: from growing up on a farm to studying nutritional biochemistry

   1. PAPeter Attia0:09

      Hey, Don. Thank you so much for making time to sit down today. Um, I've heard a lot about you over the past couple of years from our mutual friend Layne Norton, who suggested that, you know, we sit down and go even deeper down this nutrition pathway. Uh, what you may not know about me is nutrition is my least favorite subject, but I think I, I say that only because I, I, I, I'm so tired of sort of the, uh, religious aspect of nutrition. Um, so I'm, I enjoy talking about nutrition through the lens of biochemistry, but thereafter, my, my patience for it has, has dwindled over the past decade. So, uh, I have a feeling we'll get along just fine because your entire background [chuckles] is based on nutritional biochemistry as opposed to nutrition religion. [smacks lips] Um, but-

   2. DLDon Layman0:55

      Well, first of all, it's great to, uh, meet you, Peter, and, uh, even electronically. And, and, uh, my, my interest was a little sort of the opposite. I was interested in biochemistry first, and studying organic chemistry just seemed so boring and esoteric that nutrition I could actually apply my biochemistry to things people were interested in. So I kinda like that split, but I, I totally get your aspect of the zealot ends of the spectrum. [chuckles]

   3. PAPeter Attia1:24

      Did, did ... You know, you grew up on a farm, if I'm not mistaken, correct? In Illinois.

   4. DLDon Layman1:29

      Yes, that's correct.

   5. PAPeter Attia1:29

      And, uh, before we started recording this, you mentioned to me that your parents, your dad lived to 97, your mom to 102. So you're, you're at the midpoint of your life right now essentially based on your-

   6. DLDon Layman1:41

      [chuckles]

   7. PAPeter Attia1:41

      ... good genes. Um, but what was it like growing up on a farm, you know, 70 years ago?

   8. DLDon Layman1:48

      It was a great experience. Um, uh, you know, back in the '50s when I [chuckles] was born, uh, agriculture was very poor in the United States, and so you sort of grew up in that background. But I think some of the things I learned was I learned about animal growth, I learned about reproduction, I learned about growing corn and soybeans. I learned about life cycle, and I just got an interest in food. W- uh, you know, we were, we were growing it. We were... had it there on the farm and, and so it just made me interested in it. And then, you know, combined with that, I always had an interest in science and sort of evolved to be a kind of a natural marriage, I guess. [chuckles]

   9. PAPeter Attia2:31

      So when you're going to college, did you study biochemistry and organic chemistry first? That was your undergrad?

   10. DLDon Layman2:38

       Yeah, the, the, the background, uh, the serendipity of how I got into nutrition, it certainly wasn't anything I knew about. I was in a small town. Uh, went to a school that had, like, 400 people in it, and, and so it certainly wasn't anything I knew about. But I knew I liked science, so I went to first u- uh, Illinois State University to study chemistry, and I pretty quickly realized I had no aptitude for inorganic chemistry. But [chuckles] I sort of understood biochemistry pretty well. Uh, I got to the end of it, and it was actually during the Vietnam War, uh, and I was s- scheduled to go into the military. Uh, and so I was totally unemployable. And the university said, "Hey, you're doing really good at this chemistry stuff. We'll give you a graduate assistantship, and you go when you go." And all of a sudden I ended up with a deferment getting a master's degree in biochemistry. [chuckles] And my mentor at that time says, "You really have a knack for this nutrition part of it. Why don't you do a PhD?" And I sorta said, "Oh, really?" [chuckles] And so I ended up at University of Minnesota doing a PhD in nutritional biochemistry and fell in love with all of it. So it certainly was no grand plan, but it kinda fit my background of agriculture, food, sports nutrition. I fell into a group that was doing muscle metabolism, and it just kind of all fell together for me.

   11. PAPeter Attia4:05

       Now, was Ancel Keys at the University of Minnesota at that time?

   12. DLDon Layman4:09

       He was not. He had left, but his legacy was there with George Blackburn, uh, and, uh, Ivan Frantz and some of those individuals. So I certainly got that background while I was there and, and certainly invested a lot of how my n- early thinking of nutrition and, you know, I think Layne Norton, who you've talked with before, is, uh, has talked about how our thinking of nutrition evolves. My certainly has evolved.

3. 4:39 – 18:10

   Don’s philosophy on nutrition, muscle, and metabolism

   1. DLDon Layman4:39

      [chuckles]

   2. PAPeter Attia4:39

      Well, tell me a little bit about what, at least as far as you can remember, what was your, what was your underlying philosophy of nutrition circa, you know, 1975, you know, which is probably when you were doing your PhD, I'm guessing.

   3. DLDon Layman4:55

      Yeah. I, I think sort of one of my earliest sort of thinking about nutrition, again, it sort of dates to my interest in animal growth and, but also sports nutrition. Um, I very early developed the philosophy that nutrition was really about two tissues, two tissues: the brain and skeletal muscle. If those two tissues were healthy, you were gonna live a pretty good life. Everything else is regulatory: the liver, the heart, uh, the kidney, the gut. Everything else adapts to your environment, but you have to focus on those two. And I think if you tailor your nutritional requirements around that thinking, you end up with a much more sensible approach. And I, I sort of coined the concept that, uh, my colleague Dr. Gabrielle Lyon and I always use of muscle-centric nutrition.

   4. PAPeter Attia5:51

      Mm.

   5. DLDon Layman5:51

      Uh, and you know, if you keep muscle healthy, you've got a good shot at avoiding obesity, avoiding diabetes, avoiding cancer, et cetera, et cetera.

   6. PAPeter Attia6:01

      Well, let's go into that a little bit. I mean, I want to get into some weeds on a whole bunch of other really nuanced-

   7. DLDon Layman6:05

      Sure

   8. PAPeter Attia6:05

      ... stuff, but let's-

   9. DLDon Layman6:06

      [laughs]

   10. PAPeter Attia6:06

       ... let's, let's follow this thread for a moment. So when you say that, I assume you're at least in part referring to the, the following two facts. One, muscle is the largest sink for glucose. Uh, so, you know, 75 to 80% of our glucose storage capacity exists within skeletal muscle. And then there's another factor of muscle, which is it's a very early depot for excess adipose tissue. So once we start to let little droplets of fat accumulate within muscle cells, it leads to this process of insulin resistance that then creates a problem for the first point that I made, which is you now make it harder for your carbohydrate storage unit to accept carbohydrates, and of course, that leads to hyperglycemia and ultimately diabetes. Is that part of why, uh, that formulated your thesis, or is there more to it?

   11. DLDon Layman7:02

       More to it. I, I, I mean, I think what you stated is, is correct, but I do think about it differently. I think about, um, muscle really serves two functions. One, the obvious one is mobility. Uh, most people, uh, get to the age of 65, uh, beyond that, most people actually die from some form of immobility, falls, breaking something, hospitalization. So functional mobility is critical. But the other aspect is metabolism, and muscle is a primary site for insulin activity. Uh, you mentioned glucose storage. Uh, I look at it more as an issue of glucose utilization, uh, uh, and also fat utilization. So basically, your blood glucose and your blood lipids are heavily... I mean, obviously the amount you eat makes a difference, but the actual level is heavily dependent on your muscle metabolism. And you sort of commented about insulin resistance being associated with fat. Actually, insulin causes insulin resistance. So if you chronically elevate insulin too long, uh, that is the definition of type d- two diabetes, is that basically insulin causes insulin resistance.

   12. PAPeter Attia8:26

       Well, s- say more about that. I mean, I... It- it's hard to untangle some of the causality here, right? I mean, uh, you know-

   13. DLDon Layman8:32

       Yeah. Sure

   14. PAPeter Attia8:32

       ... I spoke with Jerry Shulman, God, probably it's been two years ago, and y- you know, in, in his paradigm, right, you have the accumulation of diacylglycerides within the actual, uh, myocyte. So not in- not, not interstitially, right, or not between them, but it's the, it's the actual accumulation of lipid within... And it's funny, I'm blanking on which enzyme now that inhibits, but it's basically down the PI3K pathway, the PI3 kinase pathway-

   15. DLDon Layman9:03

       Right

   16. PAPeter Attia9:03

       ... where you basically render the muscle cell less sensitive to the signal of insulin telling the GLUT4 transporter to come up. And so-

   17. DLDon Layman9:14

       Yeah

   18. PAPeter Attia9:14

       ... th- this hyperinsulinemia is, is effectively the first way that you can externally measure insulin resistance. Is that sort of in line with what you're saying?

   19. DLDon Layman9:25

       Yes and no. So, um, Jerry Shulman's great. Uh, I definitely followed his research a, a lot. Um, and the, the thing to understand about the biochemistry is you can create the models to give you a negative feedback. So he's absolutely correct that, um, that, uh, diacylglycerol or ceramides will feed back to the insulin receptor, the GLUT4 transport and the insulin receptor and cause insulin resistance. Uh, so that's, that's true. So that, that is a philosophy of fat centric-

   20. PAPeter Attia10:06

       Mm

   21. DLDon Layman10:06

       ... that fat causes all the problems. On the other hand, you can do the exact same thing with glucose. Too much glucose will also inhibit the insulin receptor, uh, and cause that same exact feedback. It doesn't accumulate the ceramides or the, uh, the diacylglycerol. I did some research with diacylglycerol, and w- if you sort of do it in the, in the issues of high carb, low carb, you won't find those effects.

   22. PAPeter Attia10:34

       Hmm.

   23. DLDon Layman10:34

       So the question then becomes which one's more likely to be physiological-

   24. PAPeter Attia10:39

       Hmm

   25. DLDon Layman10:39

       ... because people are eating, um, 350 grams of carbs per day, or because they're eating 90 grams of fat per day, which one's likely to cause it? Uh, Bob Wolfe, there's a th- philosophy called the Randle hypothesis.

   26. PAPeter Attia10:56

       Mm-hmm.

   27. DLDon Layman10:56

       I don't know if you've heard of it.

   28. PAPeter Attia10:57

       Yep.

   29. DLDon Layman10:57

       But basically, the philosophy is, uh, the Randle hypothesis was that fatty acids, the diacylglycerol cause all the problems. And what Bob Wolfe did was basically run that experiment with sa- stable isotopes, and he showed it's actually the reverse, that fatty acids are not inherently toxic, but glucose is. It has its own disease. We call it diabetes. And so when you eat excess carbs, you ha- must get rid of them. You absolutely have to dispose of them in the next two hours, where fat basically can hang around for much longer. It's just simply not that toxic to the body. In fact, the body, the b- the body always wants a certain level of free fatty acids in the blood 'cause that's the fuel for the heart, okay? So it's always high.

   30. PAPeter Attia11:45

       Now, what, what about the idea that the excess-
4. 18:10 – 26:30

   The controversial relationship between saturated fat and atherosclerosis

   1. PAPeter Attia18:10

      all that kind of stuff. We're gonna, we're gonna go deep on that. But let's go pick it up back in University of Minnesota. You've got the legacy.

   2. DLDon Layman18:16

      Mm-hmm.

   3. PAPeter Attia18:16

      And I'm guessing at the time You know, Keys is really famous for two things in the mid-'70s, right? I think by that point he's probably already published his Seven Countries study and the-

   4. DLDon Layman18:25

      Right

   5. PAPeter Attia18:26

      ... the hypothesis now is a very fat-centric view of, you know, the, the negative consequences of dietary fat, specifically dietary saturated fat in the American diet, especially as it pertains to ASCVD. And then I suspect the second thing that he's probably still famous for is the starvation experiments, um, that were, I'm guessing, done in the 1950s. I mean, these were done on conscientious objectors, so they're probably in the '40s or '50s, right?

   6. DLDon Layman18:54

      Yeah. I, I can't exactly date that, but you're exactly right. So those were... I mean, we learned a lot about starvation at that point [chuckles] for obvious reasons. We can't do experiments like that before, but we learned a lot about body composition and how the body starves. So those were good. But certainly the legacy was there, and when I got to Minnesota, you know, I sort of bought into the cholesterol and the saturated fat and total fat and, you know, I, I sort of s- okay, this is what everybody's teaching and, you know, that's what they... I was forced to learn. That's what they were teaching. Uh, and so I bought into it. But, you know, as I slowly started doing experiments and early in my career we did a lot of fasting type of experiments with animals to look at composition changes, and I did malnutrition work in, in Northern Africa, and I sort of got into all of that and I, I, I started realizing, you know, I don't really believe that. And one seminar I will always remember at Minnesota was individual by their name of Fred Kummerow came to Minnesota and gave a seminar about the dangers of cooking oils, and specifically trans fats.

   7. PAPeter Attia20:08

      Mm.

   8. DLDon Layman20:08

      And Blackburn and Franz just ridiculed him. Basically said, "This is the craziest thing we've ever heard. All these plant oils are great." Uh, and basically f- you know, 20 years later, we banned trans fats from foods literally m- as the most dangerous fat that you can encounter. So I, I always remember that just sort of thinking, well, you know, people who ha- have bought into this dogma aren't necessarily right, and we need to keep questioning it. [chuckles]

   9. PAPeter Attia20:38

      Speaking of Franz, um, obviously in 1973 he completes a study, the Minne- Minnesota Coronary Experiment. Um, I, I actually find this to be one of the most difficult studies to interpret, not so much the one that he published 16 years later, by the way, in 1989.

   10. DLDon Layman21:02

       Yeah.

   11. PAPeter Attia21:02

       But the one that-

   12. DLDon Layman21:02

       Yeah

   13. PAPeter Attia21:02

       ... Chris Ramsden republished just a couple of years ago based on all of the data from Franz's study plus data he never published. This to me is one of the most complicated stories, and I, uh, I will tell you, I have posed this question to every friend of mine who is more steeped in nutrition than I am, and, um, I still don't have a great sense of how to explain these results. So I'll, I'll explain it for the, for the listener and the viewer, and I, I'm curious to your thoughts. So the experiment was done, um, in basically institutionalized patients. So again, maybe not a study that could be done easily again today for ethical reasons, but had the advantage of being so well controlled. You, you basically had patients that were randomized into two groups. Their total energy was identical. Their total split of macronutrients was identical. The only thing that differed was that in one group it was high saturated fat, and in the other group it was high polyunsaturated fat. The hypothesis being tested was is saturated fat intake leading to increased major adverse cardiac events, heart attacks and strokes? The experiment that completed in... I think it ran... I, I can't remember exactly. I think it ran about five years. In 1973 showed no difference. There was no difference in cardiac events, despite the fact that the group that was on the higher polyunsaturated fat group did indeed have much lower cholesterol levels. Now this was... This predated the subfractionation, so they weren't measuring LDL and HDL. They were just measuring total cholesterol, and at the time there was some correlation between cardiovascular disease and total cholesterol levels. At the extremes that was certainly true. Again, because I didn't think we'd be talking about this, I don't have the numbers all in my mind, but we'll link to it all. But directionally I believe that the higher PUFA group relative to the saturated fat group was about 30 milligrams per deciliter lower in total cholesterol, and based on everything we know today, we would assume that much of that was in LDL cholesterol indeed being lower and non-HDL cholesterol. And yet there was no difference in events, and of course it's become a very famous and unfortunate story in nutrition research in that Franz chose not to publish it because he didn't like the results. It didn't match his hypothesis, which was that the group on lower saturated fat would have fewer events. Ramsden went and published all of these data plus a whole bunch of subdata, as I said, just a few years ago, I believe in The British Medical Journal, and actually found something that was... that threw a wrench in my initial hypothesis. My initial view of the Minnesota Coronary Experiment was it probably wasn't a long enough intervention. It might be that five years was not long enough to appreciate a difference. And so it was underpowered or too short in a duration to see a benefit if there was a benefit. But in Ramsden's analysis you actually saw the opposite, 'cause he now looked at some subgroups, and you actually saw a higher incidence of coronary events in some of the people that were consuming the high polyunsaturated fat diet. And I can't remember what the dominant oil was. I'm blanking on it. I don't remember if it was canola or safflower. I think it was safflower So how much of that do you remember, Don, from your time there? And can you, can you shed any light on this or do you have any thoughts on, you know, how to interpret that experiment?

   14. DLDon Layman24:38

       Well, first of all, I am definitely not a lipid expert, so [laughs] um, I, I... You know, I sort of remember the study, but I can't put any more numbers to it than you did. I actually did some research with Ivan Frantz and Penny Kris-Etherton when I was at Minnesota, so I, you know, I sort of was in the loop at the time, but that's been a couple of years ago. Um, yeah, I think if one really looks at the literature on saturated fat and is fair about all of those studies, you find a very mixed bag. You... The Women's Health Initiative and all of those kinds of things. Uh, and unfortunately, the people who believe the hypothesis have either delayed publishing it or said, "Well, it couldn't have been wrong," and tried to... You know, it could've been wrong, and they tried to find all kinds of excuses as opposed to just believing it. Um, you know, there's an old theory in science that, you know, if the theory's correct, it'll get stronger over time, and if it's not, it gets weaker. And I think one would have to realize that, A, the cholesterol theory, the total cholesterol theory has definitely gotten weaker, and the saturated fat hasn't s- held up very well. Um, you know, we still believe it, but your comment a f- a little bit ago, it's first and foremost calories. If you put excess saturated fat on top of too many calories, that's probably a problem, but if you're at or below your calorie needs, I don't see any data that suggests it is. So, you know, my c- sort of joke or comment all the time is that if you're committed to being obese, you probably ought to pay attention to the quality of your fats, but if your goal, if your goal is to be lean and healthy, calories is what you're paying attention to, and the macro distribution i- is sort of your personal

5. 26:30 – 33:46

   The basics of protein and amino acids

   1. DLDon Layman26:30

      preference.

   2. PAPeter Attia26:31

      So let's talk a little bit now about how your interest in protein came about because, you know, of all macronutrients, this is the one I have to pay the most attention to. Um, and it's honestly the one where I feel like I fall the shortest. You know, I, I feel like I have some days when I nail it, and I have too many days when I come up short. I never go overboard. I never go to bed at night thinking, "God, I ate too much protein today." But I do go to bed sometimes thinking, "I don't think I ate enough," um, for my goals, right?

   3. DLDon Layman27:04

      Yeah.

   4. PAPeter Attia27:04

      My goals are to sort of maximize muscle protein synthesis. My goals are to preserve lean tissue as long as I can, and frankly, that's the goal for my patients. So, um, how did, how did this become a, a strong interest of yours?

   5. DLDon Layman27:17

      Well, the real interest started in my master's degree 'cause I got interested in studying protein turnover, protein synthesis, and I was working with Arlen Richardson, who was a expert in aging, and we were studying age-related changes in protein synthesis. And we actually discovered, uh, the changes in mRNA over time, that the poly-A tails on mRNA get shorter, uh, your ability to put ribosomes on the message goes down, and you have lower synthesis. So that efficiency of change of protein synthesis over time is a theme that runs through all of my research, and we'll get into efficiency in adults and things like that. So that was sort of the beginning. When I went to Minnesota, then I sort of got a muscle s- focus on it, and, and one of the first things I learned in graduate school is we don't really have a protein requirement. We have a requirement for nine essential amino acids and organic nitrogen, organic amines, which all translates into the fact that we can make 11 of it- se- of amino acids, and nine we have to have in the diet. And one of my favorite, uh, quips I use when I'm talking in, to groups on stage is that, you know, protein we should think of as a vitamin pill. We don't have a daily requirement for a vitamin pill. We have a requirement for 12 vitamins inside the pill. We don't actually have a daily requirement for protein. We have a requirement for 9 or 20 amino acids inside of it, and so s- talking about a protein requirement just reflects ignorance. We have a specific requirements for nine essential amino acids, and that gets into the complexity then because these amino acids are essential for building blocks for new protein, but every one of them has a metabolic role, like leucine and mTOR or arginine and nitric oxide or lysine and carnitine or cysteine and glutathione, and all of those roles are vastly above the minimum that is detected for nitrogen balance for the RDA. And so that's where people fall apart is that we, we think about vitamin C and we know there's a minimum RDA to prevent scurvy, but people will take 5 or 10 times that during COVID for immune response. But we resist thinking that way about amino acids, and it's exactly the same.

   6. PAPeter Attia29:47

      You know, that's a great point, Don. Maybe we should spend a minute helping people understand what an amino acid is because, you know, I took biochemistry. I have my little cue cards. I can draw every one of the amino acids.

   7. DLDon Layman29:59

      [laughs]

   8. PAPeter Attia30:00

      Not anymore, by the way.

   9. DLDon Layman30:01

      I can't.

   10. PAPeter Attia30:01

       Yeah, I was gonna say not anymore.

   11. DLDon Layman30:02

       Yeah. [laughs]

   12. PAPeter Attia30:03

       But, but there was a day when I could draw all nine of them, but, but let's help people-

   13. DLDon Layman30:06

       Yeah

   14. PAPeter Attia30:06

       ... understand. I think most people understand what glucose looks like. If you've listened to this podcast, you're no stranger to the idea that glucose is a six-carbon ring, and each one has a hy- couple hydrogens on them, and one of them's got an oxygen and a hydrogen on it as well. I think most people who have listened to this podcast have a decent sense of what a fatty acid looks like. Long stretch of carbons. If it's saturated, there's no double bonds, so it's just littered with either two or three hydrogens, depending on where it sits in the chain. And then, of course, you store them by putting three of those onto a nice little three-carbon glycerol backbone. But I actually think most people, uh, understandably have less clarity around what an amino acid is, and you've already alluded to the fact that there are 20 of them, and 9 of them we can't even make. I mean, we're-- if we were deprived of these things, we'd be dead, so we gotta eat them. But, um, can you give folks a sense of the nomenclature? What, what, what is an amino acid? What do these things look like?

   15. DLDon Layman31:10

       Yeah. So, um, a little bit like a fatty acid, uh, an amino acid has a carboxy end, uh, connected with a carbon, and then it has a nitrogen end. And when the body is making... So when we eat protein, we get these amino acids in some sort of a string, but we totally digest them down to probably individual amino acids, maybe di or tripeptides, and we absorb them that way. They get to the blood, uh, as single amino acids for the most part, and then the body begins to reconnect them based, like, i- on the messenger RNAs. Our DNA tells us how to reconnect them. And so we connect a carbon to a nitrogen, and we string them together. Of these 20 amino acids, though, they all have that car-- that acid and nitrogen part, but they also have a side chain ranging from a very simple one like glycine with just a hydrogen to ones like tryptophan that have a big aromatic part to them. And so all of these are different, and they go into proteins in different structures. The n- the DNA tells us how we put them together. And proteins can be simple like insulin with 51 amino acids, or they could be like myosin with thousands. Uh, and so they're als- And then every protein in the body has a different turnover rate. Some of them, like insulin, might last 15 minutes, and some of them, like myosin or let's say collagen, might last 250 days. [laughs] And so they turn over at different rates. So that's sort of what they are. Um, but beyond that building block structure, then every amino acid has other kinds of structures. Uh, it might be like lysine, where part of it becomes the molecule known as, uh, uh, ca- uh, carnitine, which is for fatty acid metabolism, or it might be the nitrogen off, off, uh, arginine that goes to nitric oxide for vasorestriction, or it might be cysteine, which goes to part of, of creatinine or glutathione. So we can get the leucine, which is sort of my favorite, which is a signal, uh, which really got me interested in protein and metabolism, is a signal for muscle protein synthesis. So again, they all have this building block structure. They get strung together, uh, in different links. Uh, but they also have other metabolic functions, and that's what people don't recognize when they're talking about protein requirements.

6. 33:46 – 43:44

   Origin and limitations of the current recommended dietary allowance (RDA) for protein intake

   1. PAPeter Attia33:46

      So let's talk about that RDA, right? Because [clears throat] when we look at our patients and evaluate them from a nutritional standpoint, um, almost without exception, we come to the conclusion that they are not getting enough amino acids based on how much protein they're consuming. Now, I don't know how much of that is the nature by which food is prepared these days, the nature by which, you know, protein makes up a certain amount of the caloric, uh, uh, intake based on various types of, you know, prepared foods and things like that, and how much of that just base- is based on a belief system of what people need, perhaps coming back to the RDA. So, um, h- how-- what-- So first of all, let's tell people what the actual RDA is and, and how it came to be.

   2. DLDon Layman34:38

      So the RDA is a recommended dietary allowance. So it's n- some people think it's daily, but it's a dietary allowance, so it's sort of a generic number. And the argument is that for all RDAs, uh, we sort of test a population and come up with an average number. And then for a safety factor, which average would be 50% would be deficient, and so we add a safety factor of two standard deviations, which supposedly 97.5% of the people would be adequate to prevent any, any signs of inadequacy at that point. But that also means 2.5% of the people are actually deficient at that point. [laughs] So that, that's sort of the definition. Um, where does the RDA come from? I think it's useful to go back in history just a little bit then on protein. Um, how did we begin to evaluate protein needs? Well, it all came out of animal sciences. Uh, back in the early 1900s, before we even knew the essential ami- all the essential amino acids, uh, farmers were trying to say, "How do I get animals to grow best?" You know, and different kinds of proteins and things like that. And they developed protein quality scores and things like that. So, uh, how much growth did I get for what I fed? Uh, how much nitrogen did I deposit for how much I fed? So these were all rapidly growing animals, and we developed this concept really of nitrogen retention. Um, that basically, uh, we've now translated into what's called nitrogen balance, and that's how we determine the protein requirement. Basically, what's important in all of that discussion, that long-winded explanation, is that all of the concepts were developed for growth Where nitrogen balance was positive. You could measure a change over time. And as we've now tried to start applying that to non-growing adults, it gets a lot more vague. Um, so it's important to recognize that what we think about protein requirements is, A, developed from nitrogen balance, where you measure all of the nitrogen you're eating, which you can do pretty good, but then you have to measure all of the nitrogen you're losing, which we're really bad at [laughs] . And we call that nitrogen balance.

   3. PAPeter Attia37:00

      Can you explain how that's done, Don? That's... This is... I think we're gonna talk so much about it that I, I think it's, it's worth getting into the details of how nitrogen balance is calculated. Le- and let's do it in a human.

   4. DLDon Layman37:10

      Yeah.

   5. PAPeter Attia37:10

      So if, if I came into-

   6. DLDon Layman37:12

      Yeah

   7. PAPeter Attia37:12

      ... your lab-

   8. DLDon Layman37:12

      So yeah

   9. PAPeter Attia37:12

      ... how would you do this?

   10. DLDon Layman37:13

       Uh-huh. So, so let's start with the front end. Let's start with n- nitrogen in. So that's basically you just take a, a bunch of food and you do an chemical analysis and you measure the nitrogen, and you multiply it by a factor of 6.25. So A, you're measuring nitrogen. It's not really protein. It could be nucleic acids. It could be anything with nitrogen. You're calling it protein. And then you're multiplying it by 6.25, which says, "I believe that protein contains 16% nitrogen," which also isn't always true. So now we've got this error on the front end [laughs] . And now on the back end, we're gonna try and measure losses. So the primary loss of, of nitrogen in the body is in the urine, urea. So that's pretty easy to measure. You collect that. Second would be the stool. Uh, so you can collect that. But then you get into things like sweat and skin loss and hair loss and respiratory nitrogen, ammonia in the breath, and those are all incredibly vague. So everyone who knows nitrogen balance says that nitrogen balance underestimates requirement. Everybody, uniformly [laughs] . But that is where the RDA comes from. And it, it... When you do short-term studies, what you find is most people, young adult- And again, all these studies were done with college-age students, so they're kind of right at the end of their growth. Uh, and basically, in a short-term seven-day study, they looked okay. So that's sort of where we're at. Uh, in the last 20 years, those of us who study protein have gone beyond that and said, "Well, nitrogen balance is one outcome, but it..." Like the vitamin C argument, there are other outcomes based on amino acid metabolism that may be more important than minimum nitrogen balance. And, and we now know that protein handling goes down, the efficiency goes down as we get older, so now we have much higher requirements that we, that most of us talk about for adults.

   11. PAPeter Attia39:22

       So just to be clear, Don, going back to something you said, the reason we all agree that that standard nitrogen balance underestimates the requirement is it's easier to measure the sum of the ins than the sum of the outs.

   12. DLDon Layman39:36

       Yeah, exactly. And, and, and the chances are y- you're significantly underestimating the outs.

   13. PAPeter Attia39:44

       Yeah. Especially if you do... I mean, when I was a s- surgical resident, there were times we did nitrogen balance on patients who were on long-term TPN, total parenteral nutrition, in the ICU. These were patients that, um, it wasn't clear how long it would take for their guts to start working again, so they had to be fed all of their nutrition through a central line, which is very complicated feeding to do.

   14. DLDon Layman40:13

       Yeah.

   15. PAPeter Attia40:13

       And when we would have the nutrition team come and do a consult and do a nitrogen balance, I mean, they literally had to put a tent over that patient to-

   16. DLDon Layman40:22

       Right

   17. PAPeter Attia40:22

       ... uh, that was... You know, they were doing the best that they could in the ICU to basically create a laboratory environment to calculate-

   18. DLDon Layman40:29

       Yeah

   19. PAPeter Attia40:29

       ... nitrogen balance, which turns out is, you're not surprised, very important for a critically ill patient, right?

   20. DLDon Layman40:36

       Right.

   21. PAPeter Attia40:36

       I mean, that is a hyper, hypercatabolic state. And if you're trying to create an anabolic state in that person to keep them alive, it's imperative that you understand how much nitrogen they have, uh, or how much nitrogen that they require.

   22. DLDon Layman40:51

       Yeah.

   23. PAPeter Attia40:51

       So, um, the, the simple idea of I'm just gonna tell you how much protein you're eating, and I'm gonna measure the nitrogen in, that's coming out in your urea, that's, that's just not gonna cut it. That's just too simple. Yeah.

   24. DLDon Layman41:05

       And currently, a lot of those studies are simply done with a factor. So they don't put them in tents-

   25. PAPeter Attia41:09

       Yeah

   26. DLDon Layman41:10

       ... or buildings or whatever. They just measure urea in the urine, and everything else is just sort of-

   27. PAPeter Attia41:16

       It's like 1.3 of that

   28. DLDon Layman41:16

       ... well, we think it's a one point-

   29. PAPeter Attia41:18

       Yeah. Yeah.

   30. DLDon Layman41:18

       Yeah, exactly. [laughs]
7. 43:44 – 51:35

   Protein sources: determining quality, absorption rates, and how to track intake

   1. PAPeter Attia43:44

      So now let's talk about that measurement of what's actually happening with those amino acids. Actually, only... There's a question I wanna ask you even before that. Let's think about the normal... When people think of protein, they think of meat, right? That's gonna be a great source of protein. Obviously, there's mo- there's protein in most foods have some protein in them. But, um, if you, if you were eating a, a piece of steak, how many of those 20 amino acids are in there? Are they virtually all in there?

   2. DLDon Layman44:13

      If you're looking at animal-sourced proteins, whether it's meat or eggs or milk, uh, basically all of the amino acids that a human would need are in those because they're basically, you know, obviously a chicken's not a mammal, but the others are mammals and basically we have the same amino acids, the same proteins. So they're, they're all there. Uh, meat is a good example 'cause they're all pretty much in the right balances. But every protein has a little different balance of essential amino acids. Um, w- you know, you can look at dairy proteins, and dairy proteins are something we can fractionate 'cause they're all water soluble. So we know a lot about alpha-lactalbumin versus lactoferrin and lactoglobulin, et cetera, et cetera. [laughs] So we know that, you know, a lot of differences about amino acid compositions of individual proteins.

   3. PAPeter Attia45:10

      And so going back to what you just said then, animal protein we typically think of as sort of meat, mammals, right? You know, beef, pig, stuff like that. And then of course you've got sort of bird protein, mostly chicken for folks, and then fish protein, and then you have eggs, dairy.

   4. DLDon Layman45:26

      Yeah.

   5. PAPeter Attia45:26

      We're saying basic-

   6. DLDon Layman45:27

      So of the first three-

   7. PAPeter Attia45:28

      Yeah

   8. DLDon Layman45:28

      ... the first three are exactly the same for a protein.

   9. PAPeter Attia45:31

      Okay.

   10. DLDon Layman45:32

       So whether it comes from a cow or a pig or a chicken or a fish, muscle protein is still muscle protein.

   11. PAPeter Attia45:41

       And how do we think objectively about the quality of a protein? This is a topic that, uh, you, you've, you've talked about extensively but, but... And, and there's a, there's a, there's a way, there's a numerical way to talk about that. Isn't there an efficiency of, of that protein versus, you know, tofu versus, you know, soybean-

   12. DLDon Layman46:03

       Yeah

   13. PAPeter Attia46:03

       ... versus rice? You know, that, all the way down to-

   14. DLDon Layman46:06

       Yeah

   15. PAPeter Attia46:06

       ... sort of lower and lower protein density foods.

   16. DLDon Layman46:10

       Yeah. Protein quality is something that I think a lot about, and I'm actually w- w- working with a group now to sort of reinvent how we think about that. But I think you're referring to protein quality in a sense of PDCAAS or DIAAS or something like that. Basically, we realize that when you look at a protein, there are two, there are two factors. One is what's the composition of the ess- those nine essential amino acids, and the other is what's its bioavailability? How well do we digest it and absorb it? Um, with animal proteins, uh, and most isolated proteins, you know, even, uh, soy protein isolates, uh, the digestion absorption's pretty close to 100. It's usually 95% or higher, uh, for all animal proteins. For plant proteins though, it gets into, uh... You, you need to realize that in a plant, the, the protein is there for the purpose of the plant. [laughs] And so a lot of it is attached to fibers. It's to structures, you know. We, uh, the plants have proteins attached to the leaves and the stems and the roots and the flowers and, and, uh, the seeds and it... You know, when you start to isolate that, uh, if you just eat it in a raw form, uh, it may only be 60, 70% available, uh, because we can't digest the fiber. So those are the two factors. We can put those two together and get a protein quality score, and we can, uh, determine that a whey protein isolate, because of its essential amino acids, is 20% better than a soy protein isolate just because of the amino acids. Or we can compare, uh, a wheat protein, uh, you know, a, a wheat bran, and we realize that it's only 40% available, you know? So if you look at wheat bran on a cereal box, and say it was a wheat flour, uh, and it says there's four grams per serving, there's actually less than two that you can actually absorb. And so, you know, that, that's how we look at it. Um, in my opinion, uh, the, some of the problems with those right now is it's hard to compare across foods and it's hard to build a meal that way. We can say that whey is better than soy, and so if you're only eating those two things, that's okay. But what happens when you start putting them together? And so we... I am working on a grou- with a group trying to build a protein quality score that really based on three amino acids, uh, lysine, methionine, and leucine, which in my opinion are the key markers for adult health. Uh, and so we're trying to rescore it differently, but, you know, that- Again, long-winded story about protein quality, but that's how it's measured

   17. PAPeter Attia48:59

       No, that's, that's very interesting, Don. So what you're saying is, if I'm understanding you correctly, you could brute force your way through life by looking at every single thing you eat and trying to figure out the DIAAS score for its protein. So, okay, I'm about to have a rib eye. That's gonna be about a 96% DIAAS. Uh, I'm gonna have my, you know, soybeans over here. That's about an 80% DIAAS. I'm gonna have my whey isolate. That's 100% DIAAS. I'm gonna have my shredded wheats. That's a 40% DIAAS. That's a tough way to go through life, because you can't just add up the pro-

   18. DLDon Layman49:33

       Yeah, and, and, and they're not truly addi-

   19. PAPeter Attia49:34

       Yeah

   20. DLDon Layman49:34

       ... yeah, they're not truly additive. You can't really figure that out.

   21. PAPeter Attia49:37

       That's right.

   22. DLDon Layman49:37

       And the, and the average person doesn't even have that data. I mean, if you go into the USDA database with, whatever, 7,000 foods, uh, there are 4,000 that actually have amino acid scores, and of those, there's probably less than 300 that have DIAAS scores. And so you can't put it together. Uh, there's no way. And so we're trying to develop a system that allows people to get better than that. If you, if you look on a label on a package and you see, again, a wheat cereal that says it has four grams of protein, well again, that's a nitrogen analysis times 6.25 for all the problems I've said. And then if you look over at another column, it'll say daily values.

   23. PAPeter Attia50:24

       Yeah, exactly.

   24. DLDon Layman50:25

       And there are almost no, almost no label have daily values for protein because they don't... That would require a PDCAAS or DIAAS score, and nobody has them. And so that four grams really would translate into less than two, but nobody's being told that.

   25. PAPeter Attia50:40

       That's right. And, and by the way, just for folks, uh, who are hearing us use the term DIAAS, that's digestible indispensable amino acid score, correct? Yeah.

   26. DLDon Layman50:49

       Right. Right.

   27. PAPeter Attia50:50

       Okay, so-

   28. DLDon Layman50:50

       And I have a big problem. The d- the, the digestibility is where a lot of people have been focusing, but I have a big problem with amino acid scores 'cause they're incredibly low. They're way too low. And so we ha- they're established by the World Health Organization, by the FAO, which is really designed to prevent malnutrition in Africa, where we know from our Institute of Medicine that the essential amino acid scores are much higher than that, should be. Uh, you mentioned stable isotopes a little bit ago, or tracers. We know from stable isotope studies that all those FA- FAO amino acid scores are too low. And so that's part of the equation that we're not telling people either.

8. 51:35 – 57:35

   Leucine, lysine, and methionine: three important essential amino acids

   1. PAPeter Attia51:35

      I want to come right back to that, but I'll finish this one point, which is what, uh, what you're offering as an alternative to people living in spreadsheets to calculate how much actual indispensable amino acid they're getting is, hey, what if we make this easier and you focus on the actual content of three amino acids? So we're gonna take a subset of essential amino acids, and if I recall, I remember leucine was clearly one of them. Lysine was one of them. Was methionine the other one?

   2. DLDon Layman52:03

      M- methionine is the other one.

   3. PAPeter Attia52:05

      Yeah.

   4. DLDon Layman52:05

      Yeah.

   5. PAPeter Attia52:05

      So we're gonna take methionine, leucine, lysine, and we just want you, Peter, to walk around and make sure you get enough of those with each meal, and if you do that, the rest will take care of itself. Is that effectively what you're saying?

   6. DLDon Layman52:18

      That's, that's exactly what I'm saying. If you look at DIAAS scores right now, um, the amino acid scoring, A, I've already said is too low, but if you look at how they're scored, they're not scoring apples and apples. They're scoring apples and oranges. [laughs] So if you look at the soy deficiency, all, all legumes like soy or pea are limiting or deficient in methionine, and you score that against whey, what you end up is the limiting amino acid in whey is considered histidine.

   7. PAPeter Attia52:50

      Mm.

   8. DLDon Layman52:50

      And no one has ever shown histidine to actually be a limiting amino acid in an adult. It's a limiting amino acid in children, in babies, but nobody... So now we're comparing apples and oranges. They're not fair. So if you compare methionine to methionine, it's not 20% higher, it's 250% better in soy, comparing soy-

   9. PAPeter Attia53:13

      Soy to whey

   10. DLDon Layman53:13

       ... and whey.

   11. PAPeter Attia53:14

       Yeah.

   12. DLDon Layman53:14

       So, so we, we need to compare apples and apples. We need to compare them across the three essential amino acids that are actually likely to be limiting, where histidine, meth- uh, phenylalanine, to my knowledge, no one has ever shown those to be limiting in an adult. So why do we consider them limiting?

   13. PAPeter Attia53:31

       All right. So you've already mentioned the importance of leucine, and, and listeners of this podcast are no stranger to leucine because, you know, we've had David Sabatini on. We've had Matt Kaeberlein on. I mean, we've gone deep in the weeds on mTOR, and in fact, it was one of David's post-docs that actually discovered the leucine sensor on mTOR. So we know-

   14. DLDon Layman53:52

       Yep

   15. PAPeter Attia53:52

       ... now pretty unambiguously leucine is an amazing trigger for mTOR. Of course, there's gonna be a subset of people listening to this who are confused. "But wait a minute, Peter, if rapamycin is good and rapamycin inhibits mTOR, how can leucine be good if leucine turns it on?" And of course, they're forgetting the chronicity of the state. Sometimes you need mTOR off. Sometimes you want mTOR off. Uh, sometimes you want it on, sometimes you want it off. But when we're talking about eating, we want it on, right? We want to be able to turn mTOR on for muscle protein synthesis, right?

   16. DLDon Layman54:22

       So let's circle back to our earlier com- comment about how often you eat.

   17. PAPeter Attia54:28

       Yeah.

   18. DLDon Layman54:29

       Uh, so now we've got an issue of mTOR and whether it needs to cycle on and off.

   19. PAPeter Attia54:35

       Mm-hmm.

   20. DLDon Layman54:35

       And not only does leucine turn it on, but so does insulin.

   21. PAPeter Attia54:38

       Yep.

   22. DLDon Layman54:39

       And so probably the worst case scenario, and you can use a lot of animal studies to back this up, would be people who eat a lot of m- small carbohydrate meals that continuously activate mTOR. Uh, what we want to do is use specific meals with the right amount of insulin to activate muscle-centric r- uh, mTOR. mTOR is in every tissue, and what you don't want to do is continuously activate it in liver or some other tissue. And so that's where the confusion gets into it-

   23. PAPeter Attia55:10

       Absolutely

   24. DLDon Layman55:11

       ... is people ignore the fact that insulin is just a biggest trigger in other tissues, where leucine's a very unique trigger in muscle

   25. PAPeter Attia55:20

       Yep. Um, so now let, let's go back to the practical application of this. So we talk ... So we know why leucine matters. Can you say a bit more about methionine and lysine and why, um, using ... You know, raising them to the level of, of, um, of, of leucine becomes a great proxy for overall protein load?

   26. DLDon Layman55:40

       So if you look at, if you look at limiting amino acids actually in food, lysine is always limiting in grains, and that has been shown in animal science over the years. That's a, that's a major limitation in how you feed, what the minimum amount. Uh, so that one is probably limiting for protein synthesis. Uh, it's also in carnitine and some other things, but w- lysine is probably mostly for protein synthesis. Methionine is one of the least ... Uh, so if we look at the amounts we need, uh, we need about 3.4 grams of lysine per day. We need probably a little less than one gram of methionine.

   27. PAPeter Attia56:24

       Hmm.

   28. DLDon Layman56:24

       So they're not in the same proportion either. Uh, but the methionine is what we call part of the one-carbon pool, and so basically for the body to make and repair DNA, to make and repair RNA, to make taurine downstream, to make the a- non-essential amino acid cysteine, to make glutathione, the oxidant, methionine's the key to all of those pathways. And so, uh, we ha- Methionine is one of the most limiting, and it's limiting in all legumes. So when we think of soy and pea and a lot of, you know, and, and lentils and things of that nature as higher quality protein, they are, but they're still limiting in methionine.

   29. PAPeter Attia57:08

       What are some of the natural sources of food the, that are, that are high in methionine?

   30. DLDon Layman57:13

       The classic one of quote, "sulfur amino acids" is eggs.
9. 57:35 – 1:04:55

   The vital role of ruminant animals in the production of quality protein

   1. PAPeter Attia57:35

      Don, how ... W- you know, you grew up on a farm, right? So y- you, you know-

   2. DLDon Layman57:39

      Yes

   3. PAPeter Attia57:39

      ... we look at animals like cows, which are quite muscular-

   4. DLDon Layman57:42

      Yeah

   5. PAPeter Attia57:43

      ... eating-

   6. DLDon Layman57:43

      Yeah

   7. PAPeter Attia57:43

      ... basically just hay and grass.

   8. DLDon Layman57:47

      Right.

   9. PAPeter Attia57:47

      For them to be able to be as catabolic as they are and produce so much muscle, does that just speak to the incredible volume of that plant that they have to chew to make sure they're getting enough methionine, enough lysine, and enough leucine?

   10. DLDon Layman58:02

       I think you meant anabolic, not catabolic. [laughs]

   11. PAPeter Attia58:03

       Yeah, sorry, sorry, anabolic, yeah.

   12. DLDon Layman58:05

       Yeah.

   13. PAPeter Attia58:06

       In, in-

   14. DLDon Layman58:06

       Yeah

   15. PAPeter Attia58:06

       ... in such an anabolic state, I mean, what volume-

   16. DLDon Layman58:09

       Yeah

   17. PAPeter Attia58:09

       ... of total protein in the form of grass and hay and things like that do they need to get a sufficient amount of those muscle-building amino acids?

   18. DLDon Layman58:19

       That sort of wanders us into a sustainability argument, which I really love to w- wade into, but cattle, ruminant animals, are a very important part of the food chain because of their stomach, which is full of bacteria. One of the things to think about for, for, um, essential amino acids is really the only place they come from in life is bacteria.

   19. PAPeter Attia58:45

       Hmm.

   20. DLDon Layman58:46

       Nothing else can make them. Uh, and so our primary source of them in nature is the bacteria on roots of plants. So the bacteria on the roots will take the nitrogen. Why do we fertilize our gardens? Is nitrogen. The, the bacteria will take that inorganic nitrogen and form organic amines with it. But ... And those organic amines then can be made into plant, into proteins in the plants. But as I said earlier, the problem with plants is that they don't have the same balance as we need. They have the plants to make roots and tree, you know, limbs and roots and flowers and things like that. The beauty of a ruminant is they can take that plant and they can digest it, and the bacteria then will rebalance all of the amino acids. They'll capture inorganic nitrogen, and they make the essential amino acids that mammals need, and they concentrate it for us. So basically humans, one of the arguments is humans evolved by being able to use more concentrated protein. You know, if we just ate, you know, if we just ate plants, it's hard to get enough. But if the, uh, the, the ruminant animal can actually digest all of that, form it into a, into, uh, into, uh, appropriate amino acids. So basically for, for every 60 grams of, of protein an animal eat, they'll make 100 grams of, of essential amino acid, you know, balanced protein.

   21. PAPeter Attia1:00:24

       Wait a minute. Say, say that again.

   22. DLDon Layman1:00:25

       So they're basically upcycled.

   23. PAPeter Attia1:00:26

       S- yeah, say that again.

   24. DLDon Layman1:00:26

       So for, f- so for every 60 grams of plant-based proteins, uh, a- and nitrogen that they'll take in, they can upcycle that to 100 grams of amino acid balanced protein. So ruminants are called upcyclers. So whether it's in dairy or meats or, you know, also, you know, goats and, and sheep and, and, and deer, all of those ruminant animals upcycle. By eating grasses, they produce great quality protein. No other animal, no other animal can do that.

   25. PAPeter Attia1:00:59

       And just to make sure I understand the mass balance of that, the bacteria are obviously the engine of that upcycle, but you can't make nitrogen out of nothing. So you're saying-

   26. DLDon Layman1:01:10

       Right

   27. PAPeter Attia1:01:10

       ... the other four-

   28. DLDon Layman1:01:11

       But they're making, they're making protein out of nitrogen.

   29. PAPeter Attia1:01:13

       That's right. That's what I was gonna say.

   30. DLDon Layman1:01:14

       So they're-
10. 1:04:55 – 1:12:50

    The differing needs and impacts of dietary protein for a 16-year old compared to a 65-year old

    1. PAPeter Attia1:04:55

       Um, so where were we before we went down that path? 'Cause I was just trying to understand-

    2. DLDon Layman1:04:59

       [laughs]

    3. PAPeter Attia1:04:59

       ... how it happened. So, so also didn't appreciate the role of the bacteria. Um, I think we were about to get into... Oh, I know where we can go back to. You mentioned that you have spent some time studying the difference between, call it 20-year-olds and 60-year-olds, in terms of the efficiency of muscle protein synthesis. So... And this is where you probably have to get into the isotopes, right? Now you're getting into sort of the nuanced-

    4. DLDon Layman1:05:26

       Yeah

    5. PAPeter Attia1:05:26

       ... stuff. But what do we know about a 20-year-old versus a 60-year-old who's under, uh, who puts their muscle under a progressive overload? So they're, they're now asking, you know, they're, they're, they're doing resistance training. Um, they're being provided with adequate amino acids, and let's assume they're being provided with not just the right, uh, quantity but the right quality of amino acid. Um, what do we know about the assimilation of that amino acid into new muscle tissue across... And, and pick any age you want. I, I just used 20 and 60, but I, I know you've studied this at very specific age points.

    6. DLDon Layman1:06:05

       Piece of background before we get into that. It's important to recognize that whether you're 16 or 65, your body needs to make nearly 300 grams of new protein per day. So there's a protein turnover. Every, every tissue in the body is turning over, uh, some as fast as liver enzymes we replace every hour. Muscle proteins we replace with half-lives of around 15 to 16 days, so every 30 days. Collagen turns over at about half-life of 100 days, which is why if you hurt your knee, it takes so long to repair it. But basically, if you put that into thinking, the body replaces literally every protein in it about four times a year. That's a pretty remarkable number. Uh, and then if you think of we have to make 300 grams of new protein per day, the average American intake is around 80 grams or less, women 70, men 90. Um, that means that there's a recycling thing going on. So of every new protein that's getting made in the body, about six out of seven amino acids are getting recycled. All of that sort of feeds into this process of protein synthesis, protein turnover. And what... Remember I said what I was doing with my master's degree, we were studying the age-related changes. What we now know is that as you get older, the efficiency of that protein turnover goes down So where a 16-year-old, uh, you give them a certain amount of protein, they'll have a very good response. A 65-year-old will have maybe no response at all or, you know, 10% or something. But what we have learned sort of with the study of leucine and initiation factors and all of that, is that if you give an enriched source of essential amino acids, more protein, uh, you can actually make the adult look just like the 16-year-old. So what we know is that the efficiency goes down, but the capacity to respond doesn't. And so what we're now thinking is that, what we now know is that if you have a requirement that's about twice the minimum RDA, so instead of .8 it's 1.6 grams per kg, uh, we can get the adult, the 65-year-old, to respond just the same as the 20-year-old as far as muscle protein synthesis.

    7. PAPeter Attia1:08:39

       Now, you know, a moment ago, Don, we talked about how it's a slippery slope if you just focus on total protein. So when you say 1.6 grams per kilogram, does this assume it's from a whey-like product and an animal-based product? And if, if that person says, "Hey, I'm 65 years old and I'm on a plant-based diet," are you gonna say that number is gonna need to be higher?

    8. DLDon Layman1:09:03

       So, uh, that's a great question and a great way to ask it. Um, what we know is that most people who go to a plant-based diet, a vegetarian diet, decrease both the quantity and the quality. So your point is exactly right. If you're on a plant-based diet, you'll need more protein, and that means you'll have to have more calories. Uh, but what's the threshold for that? What we would probably argue is that if you have 100, 120 grams of protein per day, it probably doesn't matter the distribution between animal and plant because you probably have enough to cover it. Okay? Uh, if you're only eating 50 grams of protein per day, then it makes a big difference.

    9. PAPeter Attia1:09:51

       Mm-hmm.

    10. DLDon Layman1:09:51

        You'll never catch up to your essential amino acid needs. So somewhere between 50 and 120, it depends on what you choose. You know? So, you know, if you're gonna be plant-based, you know, have 125 grams of protein per day and you're probably fine. But if you're gonna be vegetarian and you think you're gonna get along with 56 grams per day, you're gonna get in trouble.

    11. PAPeter Attia1:10:14

        Going back to this difference earlier about the th- you know, call it anabolic resistance, right? Between the 65-year-old-

    12. DLDon Layman1:10:21

        Yeah

    13. PAPeter Attia1:10:21

        ... and the 16-year-old. The obvious thing that comes to mind is there's a huge difference in androgen level between those two.

    14. DLDon Layman1:10:30

        Right.

    15. PAPeter Attia1:10:31

        What are the other things that might explain this anabolic resistance that I think, by the way, I think it's in- very interesting that you can overcome that by a higher amount of protein. But prior to that workaround, what else do you think explains anabolic resistance?

    16. DLDon Layman1:10:45

        Clearly, the hormone issues are, are, are s- first and foremost. So, you know, I, I m- I always make the comment that, uh, when you're growing, hormones are your friend. They're sort of driving it, and you look at malnutrition in Africa, and children will grow on really lousy diets. They may not grow as healthy, they may not live as long, but there's a survival reproduction nature to that. Um, now we switch to talking about healthy aging, and I want to live to where my parents, you know [laughs] I want to get to that century mark. Now we talk about healthy aging, and now we sort of change the, uh, we change the criteria that we're looking for. Um, let's just think about mTOR for a second and try and put that in framework. Uh, there are four different signals that regulate mTOR. Uh, we've mentioned leucine. W- we also mentioned insulin. Uh, uh, uh, an enzyme, or a factor known as AMP kinase, which is carbohydrate sens- is energy sensitive, and then another molecule known as REDD1, which is stress sensitive, uh, particularly resistance exercise. So there are four different things the, the individual balances. When you're young and growing, insulin and IGF-1 dominates that, and insulin first and foremost is a growth hormone. And when you stop growing at 25, it ceases to have an effect on protein synthesis and muscle. And so now the shift, the whole thing shifts to protein quality. Protein quality is not nearly as important when the system's dominated by hormones. And so now what we know is a- as we get older, we can buffer that loss of the hormones by higher quality protein, mostly leucine and resistance exercise. Those two factors will balance out the growth issue that young people ha- the benefit of the growth part. So that's, uh, the way you, you have to think about the change in efficiency with

11. 1:12:50 – 1:19:50

    Consequences of protein deficiency in childhood

    1. DLDon Layman1:12:50

       aging.

    2. PAPeter Attia1:12:51

       Speaking of aging, at the front end of what you just said, I wanna, I wanna go into that a little bit more and, um, I think most people will recognize that this is an enormous problem in the developed world, and we should talk about it through that lens 'cause I think that's where it's most stark. But I'm curious as to whether or not you think this could become a problem or even plays a role in childhood obesity rates. So let's talk about what happens to a child that is protein deficient at the beginning of their life. What, what is the implication of that later in life?

    3. DLDon Layman1:13:23

       So when I got into protein, um, uh, w- John Waterlow and Joe Millward and Peter Garlake and Vernon Young were sort of the godfathers out there that I learned from. Uh, and I got involved with some international malnutrition with the U.S. International Agency for International Development, USAID project in Morocco. And so we l- looked at that, and that, that led us to doing some animal studies. And basically We look-- used the animals to look at malnutrition and recovery, and what we found was that s- malnutrition, starvation insults early in life would stunt muscle development. Basically limited the DNA development, limited the cellular development, and basically stunted lean mass in, in the children and in the animals. And if that was stunted, basically, uh, what happened is the, the indi- the individual as an adult was always predestined to have low lean body mass and high body fat, obesity. And that was really the origins of how we started thinking about, uh, muscle-centric health. If muscle didn't develop right, if it wasn't metabolically correct, you were predestined to some of these other things. And, uh, I mentioned Gabrielle L- Dr. Gabrielle Lyon, and I-- That's sort of how we put that concept together, is muscle-centric health, we've got to have the correct development, and we have to have the correct protection as adults because that's kind of where both your mobility and your metabolic health start.

    4. PAPeter Attia1:15:03

       Don, what's the mechanism? Do we-- Do we have a sense of why... You know, for example, may- maybe people are aware of this, but when you look at children in places like Africa who are really malnourished, um, at first glance, you almost pause and think, "Well, why are their bellies so big if they're malnourished," right? Well, you know, pe- a- and yet they don't realize that's an actual-- that's an extreme... And I don't even remember. Wa- was kwashiorkor? Was that the name of the-

    5. DLDon Layman1:15:30

       Exactly.

    6. PAPeter Attia1:15:30

       Yeah.

    7. DLDon Layman1:15:30

       Yeah. Exactly.

    8. PAPeter Attia1:15:31

       And, and what's the pathophysiology of that? Why is the extreme malnourishment lead to that protruded abdomen and things like that?

    9. DLDon Layman1:15:38

       So there's sort of two funct- two terms, two directions that childhood malnutrition goes. One is called marasmus-

    10. PAPeter Attia1:15:46

        Yep

    11. DLDon Layman1:15:47

        ... which is sort of the skin and bones look, and the other is kwashiorkor, which is that kind of a, a inflated belly looking. Um, the, the, the belief, the belief of those two differences is that in kwashiorkor, there's disproportionately poor protein.

    12. PAPeter Attia1:16:05

        Mm.

    13. DLDon Layman1:16:05

        And that leads to changes in water balance and edema. Uh, people have argued is it cortisol based, you know, is it stress based? But it, it appears to be an imbalance in the protein to energy relationship. Where in, uh, marasmus, they're just short of total calories and total protein and everything.

    14. PAPeter Attia1:16:26

        Mm.

    15. DLDon Layman1:16:26

        But in, in-

    16. PAPeter Attia1:16:27

        Yeah

    17. DLDon Layman1:16:27

        ... in, uh, uh, in kwashiorkor, it appears that the quality of the protein, they're eating these starchy porridges and things like that, totally deficient probably in lysine and methionine, uh, and that leads to water imbalances and other things.

    18. PAPeter Attia1:16:45

        And what is it about this critical window of development where this protein deficiency makes it very difficult for them to put on lean mass later in life and creates a propensity for adiposity?

    19. DLDon Layman1:17:03

        So again, w- we actually did some of that original research, uh, and this was stuff we did way back in the late '70s, early '80s. Uh, muscle, muscle is a very unique cell structure. We have what are called muscle fibers, and unlike a liver cell, which has a, a DNA, a nucleus in each cell, muscle cells are multinucleated. They have what are called satellite cells around them. And so as the original fiber begins to develop, the satellite cells will put DNA, these nuclei into it, and what we determined was that each DNA has a certain amount of protein it can handle. And so what the DNA ultimately determines how big your muscle can get. And so what we determined was that late in pregnancy, early in lactation, if the insult occurs during that, you stunt these satellite cells, and you don't develop enough DNA, so the muscle is always limited in its potential size.

    20. PAPeter Attia1:18:07

        Wow. Um, I was aware of the propensity for adiposity later, was not aware of the, uh, the limitation in lean growth. So this is really the double whammy, right? You, you... It's effectively lifetime sarcobesity.

    21. DLDon Layman1:18:20

        Right. Yeah. So, so basically you're decreasing your lean mass, you're decreasing your metabolically active tissue, uh, and, and, and so you're sort of stuck with minimal calories with deposit fat.

    22. PAPeter Attia1:18:33

        Now look, uh, uh, in the US it would be hard to imagine a child developing kwashiorkor, but clearly there are kids in the United States that, uh, are disadvantaged enough that they're not gonna be exposed to high enough protein in either quality or quantity. Do you think that this-- that there's, to a lesser extent, some of this problem that's gonna happen in, in developed nations like the US?

    23. DLDon Layman1:18:56

        I think it's possible. Um, frankly, these are the kinds of things I worry about with the advocates of plant-based diets. You know, we're starting to see New York City taking, uh, animal proteins out of school lunch. Um, I mean, what is that really gonna do? We're, we're conducting a public health experiment without actually having any knowledge of that. Uh, I think that's frightening. And the, the issue is public school lunches, uh, nursing homes, daycares, these are all under these federal guidelines where we're diluting out the quantity and quality of protein at the same time with no knowledge of what that's really gonna mean. So I think that's, you know, I think that's pretty frightening to be doing that kind of public health experiment without knowledge of it.

    24. PAPeter Attia1:19:46

        Yeah. I hadn't even considered it through that lens actually. Um,

12. 1:19:50 – 1:27:51

    Muscle protein synthesis: ideal timing, small meals vs. big meals, and more

    1. PAPeter Attia1:19:51

       let's talk about something else that we alluded to briefly, but now I want to get back to, which is, um, maximum protein Uh, usability or assimilation in a given sitting. So, um, I, I'll, I'll tell you where I come at this. So, so one of the challenges that I've observed in taking care of patients is when they get into a very heavy regimen of time-restricted feeding. So you're probably aware of this, Don, but, you know, there are ideas that say, look, if you can just limit the amount of time that you eat but not place any limits on what you eat or how much you eat or what you're eating from, um, into this sort of intermittent fasting window, uh, it produces some health benefits. And, uh, it's certainly an effective way to reduce calories. So if the goal of the exercise is to reduce total energy expenditure and you create a narrow enough window, you will indeed do that. But what we've seen repeatedly is people who, after, say, six months of adopting a very narrow feeding window, say one meal a day, will lose weight but disproportionately will lose lean tissue. And, um, so, so the, the diagnosis here is pretty straightforward, right? They, they clearly reduced energy intake, but they probably reduced protein intake too much. And so body composition actually got worse despite the fact that weight went down. Which then gets to a point which is, well, can't you just eat all of your protein in one meal? So if a person says, "I'm just gonna eat one meal a day," and let's just say this is a very active person, right? So they're gonna eat 3,000 calories in one sitting, which I will raise my hand to saying I can do that quite easily. I'm quite a glutton.

    2. DLDon Layman1:21:39

       [laughs]

    3. PAPeter Attia1:21:40

       Um, even if I was able to eat 150 grams of protein in one sitting, is it clear that my body will get the benefit from that that it would if I ate 50 grams three times a day?

    4. DLDon Layman1:21:56

       Yeah. It's quite clear that you won't get a benefit, you know, that there is a limit. Um, so, so now we need to think about the body as muscle versus everything else. Um, so-

    5. PAPeter Attia1:22:09

       So we're, we're going back to the muscle-centric view that I like.

    6. DLDon Layman1:22:11

       Yeah. [laughs] Yeah. Uh, you're probably sensing a theme with me at this point. [laughs] The, uh, the muscle, there's a lot of data now that muscle can handle protein meals for an optimum anabolic response between about 25 and maybe 60 grams.

    7. PAPeter Attia1:22:31

       Mm.

    8. DLDon Layman1:22:31

       Okay? So then you start getting into distribution. If you think you're ... If you're gonna have 150 grams per day, how should you distribute it? Um, one, one of my pet peeves in nutrition, uh, I'm slightly getting off track here, is people refer to protein as a percentage of calories.

    9. PAPeter Attia1:22:54

       Mm.

    10. DLDon Layman1:22:54

        Protein is not a percentage of calories. Protein's an absolute number. You need to decide on what you're gonna build your diet around. So right now we're building it on 150. Uh, the o- the, the issue with protein is being an absolute number, if your calories go down, say you're now a 75-year-old woman and your calories per day is now, um, 1,200 calories, you still have 100 gram per day protein requirement. So now your protein needs are 35 to 40% of your calories. Uh, if people are doing weight loss, it's an absolute number. So people should never talk about percentage of calories. Uh, that's, that's basically people who don't think protein's important say, well, fat should be 30%, carbohydrates should be 50%, and that leaves 15%. I mean, you don't ... You have to think about protein first. So, so that was the issue. Um, as far as distribution, um, from my research, one of the things that we believe is that the most critical meal of the day is the first meal of the day. When you have had an overnight fast-

    11. PAPeter Attia1:24:05

        Mm-hmm

    12. DLDon Layman1:24:05

        ... your protein synthesis is down and that mTOR signal molecule is down-regulated. It's inhibited. And until you have enough leucine, around 3 grams which translates to about 30 grams of protein for most people, until you have a, a meal that has 30 or more grams of protein, your muscle stays catabolic. So you're continually breaking down protein. We think that's a significant a- aspect of aging, that people have lower and lower protein, they don't eat protein at breakfast, and that, and we know the efficiency's going down in the first place, so we want a front load protein in the day. So we want at least two meals that are well above 30 grams of protein. So I always have people shooting for 40, 45 at the first meal, another 45, 45 at their last meal, and then in between, um, you know, a- again, if we're, if we're talking with people who are, um, m- let's say an elderly woman trying to maintain minimal muscle, I'll concentrate on those two meals. If I'm talking with somebody who's trying to do weight loss, I'll concentrate on three because I don't want them getting hungry. If I'm talking with someone who's trying to be hypertrophy, a muscle builder, I'll concentrate on four. So how many meals per day do I make anabolic and muscle? And by anabolic I'm thinking 35 grams or more. And the data that we know for absolute certain is the first and last meal are absolutely important. The middle meal, I'd be hard-pressed to tell, show you a single study that where anybody's ever sho- looked at lunch. [laughs]

    13. PAPeter Attia1:25:53

        And so the reason that you're saying for the anabolic person we need four meals is we just simply need, we know it, we know we need it for positive nitrogen balance. We're just gonna have to get the amou- yeah.

    14. DLDon Layman1:26:02

        Right. So there's two, there's two aspect. There's one is mTOR signaling muscle protein synthesis Leucine effects, and the other is total protein per day. So those two lead say, "Well, if I need more protein and I max out at 50 grams, I need another meal." [laughs]

    15. PAPeter Attia1:26:19

        And what about timing? Um, so let's just talk about someone who's doing their strength training in the morning. So let's say someone's gonna do strength training from 8:00 AM to 10:00 AM. Do you want them having that first bolus of protein before the workout?

    16. DLDon Layman1:26:37

        There's some debate about that. Um, you'll find some people and trainers who believe that. We did some studies, and most of them were with animals, where we looked at different timing, and we find that e- exhaustive exercise is catabolic no matter what. So having protein ahead of it doesn't make... So we, we find the benefit is after the exercise, when the system is now finely tuned, we've stimulated red w- w- actually, we've inhibited red one, the system mTOR is ready to go. So we find the benefit is after exercise, not before.

    17. PAPeter Attia1:27:15

        And just to be clear, y- y- what you're saying is, look, you can take all those amino acids before, but it's not going to prevent you from becoming catabolic during exercise. Because-

    18. DLDon Layman1:27:27

        Yeah

    19. PAPeter Attia1:27:27

        ... again, exhaustive exercise is a catabolic activity. So you are gonna be breaking down-

    20. DLDon Layman1:27:33

        Yeah

    21. PAPeter Attia1:27:33

        ... muscle no matter how many amino acids are on board while lifting. It's more important-

    22. DLDon Layman1:27:38

        Yeah

    23. PAPeter Attia1:27:39

        ... after the lift that you have a good meal.

    24. DLDon Layman1:27:42

        You'll find some disagreement in that in the literature, but I strongly believe that what you just said is correct, and my research supports

13. 1:27:51 – 1:33:07

    Protein needs of children

    1. DLDon Layman1:27:51

       that.

    2. PAPeter Attia1:27:52

       And talk about the efficiency or the window in time post a workout in which you want to make sure you're getting that first big meal of protein. Is it one of those things... We, we, we... I'll tell you a funny story. So my, my youngest son, who's now five, but when he was, like, three, I mean, I don't know, for whatever reason, he just fixated on protein, probably because we kept telling him to eat this and eat that because there was protein in it. "Hey, eat your salmon. It's got protein. Eat this 'cause it's got protein." And basically, he has become the protein police of the preschool.

    3. DLDon Layman1:28:27

       [laughs]

    4. PAPeter Attia1:28:28

       So he just, he walks around and he looks at kids' snacks and he's like, "That doesn't have protein. That granola bar does not have protein. That has protein." [laughs] And you can imagine what these people who work at the preschool say to my wife when she drops him off and picks him up. She's like, "Uh, are you a nutritionist?" And she says, "No." "Oh, okay. It's just, you know, your, your son really fixates on everybody's protein consumption."

    5. DLDon Layman1:28:53

       Yeah.

    6. PAPeter Attia1:28:54

       Um, so we joke about how he's gonna be like that, like one of those bro protein guys who's just gonna be all obsessed with his protein and when he's eating it and stuff like that, so.

    7. DLDon Layman1:29:05

       I've lost our train of thought here for a minute, but just to s- focus on the children for a moment, so we're talking about adult protein needs, and I don't want everybody to walk away thinking, "Gee, I need to get 50 grams of protein in my kid."

    8. PAPeter Attia1:29:18

       Yeah.

    9. DLDon Layman1:29:19

       Um, children, children will be very efficient at maintaining growth with small snacks of e- you know, 8 to 10 grams of protein, where that will have virtually no impact for an older adult. So, you know, a, a, a protein bar that had, um, 10 grams of protein is a perfectly legitimate snack for a child, where essentially the only thing it would do is probably increase liver enzymes in a 70-year-old. So don't want all the mothers think that they're doing a bad thing by giving their child a 10-gram protein snack. [laughs]

    10. PAPeter Attia1:29:52

        Okay, I want to go into... I remember what we were gonna come back to, so I'll take us back there.

    11. DLDon Layman1:29:55

        [laughs] Okay.

    12. PAPeter Attia1:29:55

        But let, let's talk about that a bit more.

    13. DLDon Layman1:29:57

        Yeah.

    14. PAPeter Attia1:29:57

        So, um, 'cause that's actually news to me. I didn't realize that there was minimal benefit in smaller quantities of protein. So this is another argument for don't dribble out your protein. Commit to it.

    15. DLDon Layman1:30:10

        So, so-

    16. PAPeter Attia1:30:11

        It's binary.

    17. DLDon Layman1:30:11

        Yeah.

    18. PAPeter Attia1:30:12

        You eat it when you eat it-

    19. DLDon Layman1:30:12

        So-

    20. PAPeter Attia1:30:12

        ... and then you don't when you don't.

    21. DLDon Layman1:30:15

        Yeah. So again, children versus adults.

    22. PAPeter Attia1:30:17

        And adults, yeah, yeah.

    23. DLDon Layman1:30:17

        In the adult, if, if, if we have, if we have, uh, every meal of the day, uh, let's say we have 100 grams of protein, but we take it in in very small meals, 15 grams-

    24. PAPeter Attia1:30:30

        Yeah

    25. DLDon Layman1:30:30

        ... trickled in all day long, you will never stimulate muscle protein synthesis. But your liver will be perfectly fine. Your gut will respond to that amount of protein. Your gut, your liver, your heart, your kidney, all of those organs will respond to the no- the net protein per day no matter when you ate it, but muscle doesn't. Muscle is specific. Uh, muscle is such an energy d- a- as you mentioned earlier, there's so much mass to muscle. Muscle isn't triggered unless the diet is exactly right, and we could get into teleological arguments about leucine at this point, branched chain amino acid. Why does the muscle sense that? But basically, the muscle senses energy, insulin, protein before it triggers, and if all of those aren't balanced, it won't trigger, but your liver will.

    26. PAPeter Attia1:31:23

        Yeah. I mean, I guess to your point, teleologically, you might make the case that the liver has more concern for the brain than the skeletal muscle, and m- maybe it gets priority over being happy-

    27. DLDon Layman1:31:34

        Yeah

    28. PAPeter Attia1:31:34

        ... because it has to maintain glucose homeostasis.

    29. DLDon Layman1:31:37

        Yeah.

    30. PAPeter Attia1:31:37

        And without glucose homeostasis-
14. 1:33:07 – 1:37:27

    How important is timing protein intake around training?

    1. DLDon Layman1:33:07

       anyway.

    2. PAPeter Attia1:33:07

       Okay. So I'll take you back to where we were before I sidetracked us. It was now asking about how big a window you have-

    3. DLDon Layman1:33:15

       Oh, yeah

    4. PAPeter Attia1:33:16

       ... to refeed-

    5. DLDon Layman1:33:17

       Right

    6. PAPeter Attia1:33:17

       ... to maximize muscle growth.

    7. DLDon Layman1:33:21

       So, so we actually did that first experiment i- in rats. So Josh Anthony and Tracy Anthony were in my lab, uh, that was just before Lane came, uh, and what we were looking at was exhaustive exercise, again in rodents. We were looking at this catabolic state. We were trying to look at how to muscle regulated recovery. And so we were looking at what were called initiation factors, and we discovered the link between leucine and an initiation factor called EIF4. And that is sort of the downstream effect of mTOR. mTOR is a regulator and it stimulates EIF4 and S6 and other initiation factors. And so what we found was that when you came out of an exhaustive exercise, muscle is catabolic until you took in enough leucine to reverse it. And so we started looking at feeding right after exercise.

    8. PAPeter Attia1:34:19

       Mm.

    9. DLDon Layman1:34:19

       And Stu Phillips and a number, you know, Doug Pat Jones and L- Luke Van, a lot of people sort of picked up on that. Um, okay, so now the caveats. Um, the biggest effect of feeding right afterwards is about a two-hour window, but that's in untrained individuals. Um, if you begin to look longer, you can have a bout of resistance exercise and you'll detect a difference. You'll begin to make them... You'll start regulating that red one protein factor, and you'll see an anabolic effect the next day, 24 hours, 36 hours later. So when does your protein effect? Well, it makes it more effective all the time. Um, the more trained you get, the less you're gonna see a post-exercise effect. So if you're beginning training, you're in the first four weeks, post-exercise protein probably makes sense.

    10. PAPeter Attia1:35:16

        Mm.

    11. DLDon Layman1:35:16

        If you're well trained, you're basically training the same way and you've been doing it for six months, I don't see any effect difference between having protein within two hours after exercise versus just having your three or four meals per day. You won't see any difference in either mass or strength.

    12. PAPeter Attia1:35:35

        Yeah, I remember having this discussion with Lane as well and, and being very surprised by that, right? Being... But pleasantly surprised, by the way, because it says, hey look, once you get to a point where you're well trained enough, you don't have to be so maniacal about meal timing. You can just focus-

    13. DLDon Layman1:35:50

        Exactly

    14. PAPeter Attia1:35:50

        ... on the big picture, which is total protein, protein quality, and spreading it out such that you don't exceed the metabolizable fraction of it at any one sitting.

    15. DLDon Layman1:36:01

        Right, exactly. And people... You'll hear trainers take that last statement, metabolizable energy, and you'll hear trainers say, "Well, you can't use more than 30 grams at a meal. You won't digest it or whatever." That's not true. I mean, you'll digest and absorb 100 grams of protein at a meal, but muscle in particular only has a window of around 20, 25 to 60, uh, depending on protein quality, where it can use it. The liver will use all of it.

    16. PAPeter Attia1:36:27

        Mm-hmm.

    17. DLDon Layman1:36:29

        I mean, it doesn't matter.

    18. PAPeter Attia1:36:30

        Yeah.

    19. DLDon Layman1:36:31

        We have what is known as first pass metabolism of protein, which confuses the issue even more. When you eat a meal of protein, approximately 50% of the protein is, is di- is, is degraded to nitrogen and carbon before it ever gets to the blood. Almost 50%. The one exceptions, the exception to that are the branched-chain amino acids, leucine, isoleucine, valine, and over almost 75, 80% of those get into the blood, and we're back to that teleological argument. Why did muscle learn to sense that? 'Cause that basically shows up in the blood in direct proportion to the meal, and the muscle learned to sense that as a meal quality. It says, "Oh wow, this meal has adequate quality for me to, to trigger this very expensive process of protein synthesis, protein turnover," and until it sees that signal, it won't do it.

15. 1:37:27 – 1:41:07

    The role of leucine in fatty acid oxidation by muscle

    1. PAPeter Attia1:37:28

       While we're on the topic of muscle, Don, another thing I've learned somewhat recently that surprised me, um, was the importance of leucine in, um, fatty acid oxidation by the muscle. So, you know, one of the things that is such an important pillar of our practice is, um, kind of low-end aerobic training. We call it zone two. So zone two mitochondrial efficiency. So this is basically pushing your muscles to the maximum point at which you can keep lactate below two millimole. And in a very fit individual-

    2. DLDon Layman1:38:06

       Exactly

    3. PAPeter Attia1:38:07

       ... that, you can generate a lot of power while still keeping lactate-

    4. DLDon Layman1:38:10

       Yeah

    5. PAPeter Attia1:38:10

       ... below two millimole. I mean, the, the best in the world can produce more than four watts per kilo while still keeping lactate below two millimole, and they're doing so virtually exclusively with fatty acid. So we will pair this type of analysis with CPET testing and we will look at fat oxidation rates. And again, you will see the fittest of the fit have insanely high fat oxidation rates. They're over a gram or, you know, roughly a gram per minute. Um, so tell me, uh, so, so another point of that is, look, the, a really good muscle doesn't just rely on glucose. A really good muscle can oxidize fats very effectively. What role does leucine play in that?

    6. DLDon Layman1:38:56

       That's a great question and I don't think it's been researched well enough but, uh, there's no question. So leucine, I, I mentioned earlier when we were talking about amino acids and every amino acid has a different side chain. Well, leucine is one that's referred to as a branch chained amino acid and its side chain is purely carbons. It's a carbon chain that looks a lot like a fatty acid. And so leucine is one of really two amino acids that are ketogenic. It is metabolized as a fatty acid. And what we know is that leucine will also activate the CPT1 enzyme, the carnitine palmitoyltransferase enzyme, which is the link of bringing fatty acids into the mitochondria for oxidation. So there's a benefit there. Um, it gets, uh, even more complicated in that when you have higher leucine it also begins to inhibit pyruvate from going into the, um, into the mitochondria. So when you oxidize a leucine, the nitrogen that comes off of it is put onto pyruvate generating an alanine and so the body begins to recycle glucose. So it becomes kind of steady state on glucose and emphasizes fat oxidation. So back when you were talking about Shulman's studies early, if you overload all of that, basically you can make the leucine inhibit carbohydrate oxidation. So if you have huge amounts of carbs coming in and then you overload the system with leucine, you'll inhibit pyruvate oxidation and so that could look like insulin resistance. But if you look at the physiology of how it's supposed to work under conditions where you'd be burning fat like you just described, leucine actually stimulates fat oxidation and spares glucose for the brain and other tissues. So again, you really have to think about how the experiment's set up and what it's put-- you know, what, what's getting inhibited and what's getting pushed.

16. 1:41:07 – 1:55:24

    High protein diets for fat loss: Results from Don’s clinical trials

    1. PAPeter Attia1:41:07

       Now you've recently, um, actually taken an interest in weight loss, right? So the dietary interventions that can be efficacious for, for weight loss and, and treating things like metabolic syndrome. So-

    2. DLDon Layman1:41:19

       Yeah

    3. PAPeter Attia1:41:19

       ... let's build off this idea a little bit but how do you incorporate, um, the strategy around reducing energy intake, right? 'Cause, 'cause that's-- this is sort of how I think about weight loss-

    4. DLDon Layman1:41:31

       Yeah

    5. PAPeter Attia1:41:31

       ... right? Like you got to reduce the intake but I think of-

    6. DLDon Layman1:41:34

       Right

    7. PAPeter Attia1:41:34

       ... three broad ways that you can approach that. So three strategies, right? One is you just reduce calories and that becomes the only focus, so you, you, you pay attention to the total energy content of food without thinking about the timing of food or the macro distribution of food. The next approach is you spend less time thinking about the total number of calories, spend more time thinking about the macronutrients. Create... I, I describe it as sort of create a boogeyman in the diet, some things that you avoid and-

    8. DLDon Layman1:42:04

       Yeah

    9. PAPeter Attia1:42:04

       ... the restriction of certain things becomes a roundabout way to restrict total energy.

    10. DLDon Layman1:42:10

        Right.

    11. PAPeter Attia1:42:10

        And then we talked about time restriction as well as another strategy. Um, so it-- h-how do you, how do you think about manipulating that middle bucket of-

    12. DLDon Layman1:42:20

        Yeah

    13. PAPeter Attia1:42:20

        ... you know, changing macros to achieve-

    14. DLDon Layman1:42:24

        Yeah

    15. PAPeter Attia1:42:24

        ... energy deficit?

    16. DLDon Layman1:42:25

        So I totally agree. Weight management is a calorie issue and it's not the same for every individual. Everybody's got a little different efficiency so, you know, we understand it's not-- you can't be an accountant and expect to just count calories all the time. [laughs] But, um, let me build it as a story of how we thought about it. Uh, back in the late '90s, uh, the keto, you know, Atkins and the keto diet were out there and Barry Sears and, uh, protein, you know, the Zone Diet and Michael Eades and the Protein Power. And I was looking at all of those things and we were doing those leucine experiments and we had discovered this effect of leucine on muscle protein turnover and some of these metabolic things with, you know, fat metabolism and I basically took the leap of faith and said, "You know, I think the underpinning of all of these diets is really the protein carb ratio and how can we manipulate that?" And so I started thinking, "Well, you know, if we're going to create diets, one we know that from a satiety standpoint protein is probably the most satiating." You know, l-lowers, fat would be next, carbohydrate the least. Uh, we were concerned about big insulin swings, so we wanted to sort of balance out our carbs per meal. We know that if people are overweight they tend to have big post-carbo-- post-meal carbohydrate and insulin swings where they get two hours later they'll have insulin low, uh, carbohydrate lows. And so we started trying to think about that and we said, "Okay, so we think the first meal after an overnight fast is critical." So we're going to correct that. So we basically started saying, "How much protein do you need?" Thirty, 40 grams of protein, uh, to get both satiety, protein synthesis effects. Um, we knew that protein had a higher thermogenic effect Burns more calories, more heat than either carb or fat. So we wanted to front load that effect. People have argued that, well, that's because protein or the nitrogen, it's harder to digest and absorb. We don't think that's true at all. We think the thermogenic effect is stimulating muscle protein synthesis.

    17. PAPeter Attia1:44:44

        Mm.

    18. DLDon Layman1:44:44

        We know that that is a massive ATP expenditure, and so what we want to do is maximize that at every meal. So our first meal, we want it to be 40 grams of protein. We wanted to have a carb level that would not overstimulate insulin, so we kept that under around 30 grams for what we created a carbohydrate threshold concept, uh, we could go into, and then fat sort of to round out the calories. And we basically developed three meals a day to distribute like that. Um, we basically increased the protein to about 1.6 grams per kg, and we ran the study comparing it to the food guide pyramid with 0.8. So as far as we could tell, we did three different studies. One a total feeding study where we fed everyone, a second study with diet and exercise that was four months, and a third study was multi-centered with 120 subjects that lasted 16 months. And so we did three studies, and what we saw-

    19. PAPeter Attia1:45:46

        The, the, and the last, the last two were free living where they were res-

    20. DLDon Layman1:45:50

        Total. Total

    21. PAPeter Attia1:45:50

        ... they were, they were responsible for the food. But the first one they were fed?

    22. DLDon Layman1:45:55

        The first one we fed them in the lab so we knew exactly what they were eating.

    23. PAPeter Attia1:45:58

        Yeah.

    24. DLDon Layman1:45:58

        The second one, we actually fed them for their first two weeks for a few meals so they really saw what it would look like.

    25. PAPeter Attia1:46:06

        Yeah.

    26. DLDon Layman1:46:06

        And the last one was totally free living based on the diets and manuals that we developed.

    27. PAPeter Attia1:46:13

        And, and each of these was two arms where the only difference was the protein?

    28. DLDon Layman1:46:19

        So in the first one it was two arms, uh, food guide pyramid, high carb/low protein versus higher protein and low carb. The second one was two by two, so we basically had the diet treatment, and then we had a resistance exercise treatment.

    29. PAPeter Attia1:46:35

        Mm-hmm.

    30. DLDon Layman1:46:36

        So high protein, low exercise.
17. 1:55:24 – 2:01:26

    Influence of industry funding on nutrition studies

    1. PAPeter Attia1:55:24

       So Don, this kind of brings me to, to sort of, uh, y- you know, something we've talked about before, which is, you know, so much of this research that you've done has been funded by industry. And a lot of people are gonna say, "Well, we're gonna discount everything Don just said because..."

    2. DLDon Layman1:55:40

       [laughs]

    3. PAPeter Attia1:55:40

       You know? So, so, so give us the names of some of the organizations that have, have funded your work over the last four decades.

    4. DLDon Layman1:55:48

       So, so let me backdrop that for you. Um, so I had the leucine concept that leucine was gonna be key to protein synthesis in muscle. We ran a study in the early '80s where we realized it was initiation st- effect. And so we then started to realize, we started looking for what those initiation factors were gonna be, and it's EIF4. So we sent that as a proposal to NIH, National Institute of Health, for 10 years and basically it was continuously turned down and they said, "Well, we only study disease, and we don't know of any deficiencies of protein, so it's not a priority to us." And so basically I was left with What turned out to be a revolutionary idea of reinventing protein that NIH wouldn't fund. And basically, I finally went to Kraft Foods, the National Cattlemen's Beef Association, the National Dairy Association, uh, the American Egg Board, um, and, uh, some of the other groups who were inherently interested in protein, and they fun- and w- we had some from the USDA from... I lo- I was at a land-grant university. So those were the funding sources that basically unlocked all of this knowledge about protein, uh, for adults, leucine, mTOR, uh, muscle-centric health. All of that was unlocked simply because we could get funding from Kraft and Beef. And, you know, am I biased? Well, you know, everybody who eats is biased in some way. And, you know, if you, if you look at research, and I think maybe Lane said this with you, I never believe research when I read it until I see it in three more labs. So I don't mind if people look at my research and say, "I don't believe it," but my research has been out there, very clear theories for 20 years now, and every test makes it stronger. And so that's how you believe it. The fact that Kraft or Beef funded it is irrelevant. The issue is everybody who's ever run the study after me shows the exactly same thing.

    5. PAPeter Attia1:58:04

       And do you think NIH has... Or have you seen... I know you've been, you know, semi-retired now. You're kind of s- not really retired, but you're, you're, you're retired from the grant cycle. Um-

    6. DLDon Layman1:58:15

       Exactly

    7. PAPeter Attia1:58:15

       ... but, but d- do you have colleagues that are still in it, or do you see any evidence that NIH has taken a broader purview to health? Uh, if nothing else, they should be able to look at the fact that two-thirds of Americans are, you know, have metabolic syndrome.

    8. DLDon Layman1:58:32

       Yeah.

    9. PAPeter Attia1:58:32

       And that should at least give pause to think we might need to revisit the way we're approaching-

    10. DLDon Layman1:58:38

        Yeah

    11. PAPeter Attia1:58:38

        ... nutrition and, and therefore-

    12. DLDon Layman1:58:40

        Yeah

    13. PAPeter Attia1:58:40

        ... maybe we should be funding, quote-unquote, "non-diseased research" in nutrition.

    14. DLDon Layman1:58:46

        I, I think they definitely have. Um, Chris Lynch, who's director of nutrition at NIH now, uh, that position didn't even exist back when we-

    15. PAPeter Attia1:58:54

        And where... Is that within NIDDK? Where does that sit?

    16. DLDon Layman1:58:57

        That's a great question. I think it's across multiple institutes.

    17. PAPeter Attia1:59:02

        Okay.

    18. DLDon Layman1:59:02

        So which one actually funds the most? I think NIDDK might be-

    19. PAPeter Attia1:59:06

        Mm-hmm

    20. DLDon Layman1:59:06

        ... the one. Um, the Cancer Institute. I, I think it... I think his unit actually bro- goes across multiple-

    21. PAPeter Attia1:59:15

        Okay

    22. DLDon Layman1:59:15

        ... uh, institutes. But again, that didn't e- exist back in the late '80s, early '90s. Um, so, you know, I think it may be a little broader, but there is a general philosophy still at NIH that, uh, NIH does not do applied food research, that industry should fund it, so that becomes a catch-22.

    23. PAPeter Attia1:59:40

        Yeah. [laughs]

    24. DLDon Layman1:59:40

        You know, there... You know, if we're gonna study the difference between whey and soy, unless you can say, "Well, that's gonna cure heart disease," they're not gonna sun- fund it. Um, and so you have to then go to the Dairy Council and say, "I wanna do this study." And then people say, "Well, you were funded by the Dairy Council," or I go to the Soy Board or whatever. Um, so it's a catch-22, but basically the alternative is we put our head in the sand and we don't do the research. So basically, I look at people in nutrition right now, um, and literally, I don't know anybody in nutrition who doesn't get industry funding. That's just simply how you have to get funded.

    25. PAPeter Attia2:00:24

        Yeah.

    26. DLDon Layman2:00:26

        One of the things I would also point out in this whole issue of bias, it's important to recognize that the animal commodities are all under the USDA supervision because they are, uh, animal commodities and they're, they have checkoff boards. So that means everything they say in advertising has to be screened, where the grain industry has big companies like Kellogg's and Pillsbury and Coke and Pepsi, and they can literally go out and say anything they want. And so you'll see a product out there that pretends to be, uh, an egg, and they'll claim that they're better than eggs, but egg can't come back and, and refute it. They can't say... So you've got two different playing fields: one that's highly restricted and, and supervised, and the other which is fair game. You know, fir- you know, First Amendment, I can say anything I

18. 2:01:26 – 2:10:05

    Don’s thoughts on plant-based and synthetic “meats”

    1. DLDon Layman2:01:26

       want. [laughs]

    2. PAPeter Attia2:01:27

       On that topic, Don, w- how, how closely have you paid attention to kind of, uh, both the plant-based meat and the synthetic meats? I've, I've, I've paid a little bit of attention 'cause obviously there's two companies that are, uh, pretty-

    3. DLDon Layman2:01:40

       Yeah

    4. PAPeter Attia2:01:40

       ... popular. I can never remember their names. I think it's Beyond Meat and Impossible Meat or something like that.

    5. DLDon Layman2:01:45

       Exactly. Got it.

    6. PAPeter Attia2:01:46

       And, and they're plant-based meats, right? So they're making-

    7. DLDon Layman2:01:49

       Right

    8. PAPeter Attia2:01:49

       ... meat out of plant. And then you have a whole host of companies, none of whom I can remember the names of, that are actually trying to make synthetic meat. Um-

    9. DLDon Layman2:01:57

       Yeah

    10. PAPeter Attia2:01:57

        ... the little bit that I've read about that, which really amounts to reading, like, two scientific articles-

    11. DLDon Layman2:02:02

        Yeah

    12. PAPeter Attia2:02:02

        ... uh, left me with the impression that that will not be technically feasible, um, that, that just from an energetics cost, mass balance, um-

    13. DLDon Layman2:02:13

        Right

    14. PAPeter Attia2:02:13

        ... sanitation, GMP standpoint, that's not gonna happen.

    15. DLDon Layman2:02:16

        Right.

    16. PAPeter Attia2:02:17

        So it's, um-

    17. DLDon Layman2:02:18

        Yeah

    18. PAPeter Attia2:02:18

        ... uh, that, that's my way of saying either I'll be proven wrong or that will turn out to be one of the biggest boondoggles, um-

    19. DLDon Layman2:02:24

        Yeah

    20. PAPeter Attia2:02:24

        ... of industry in some time. Um, do, do you have thoughts on either of those two, uh, i- including kind of nutritional composition and, and how it feeds into-

    21. DLDon Layman2:02:34

        Yeah

    22. PAPeter Attia2:02:34

        ... an amino acid perspective?

    23. DLDon Layman2:02:36

        First as an overview, I think that as the world continues to expand in population, we're probably gonna need additional protein sources. Um, we may be near our capacity for animal-based proteins. I mean, we may not be able... You know, I, I don't think we can double it again.

    24. PAPeter Attia2:02:55

        Mm-hmm.

    25. DLDon Layman2:02:56

        So we may be near. So we're gonna need other sources. So you know, I, I accept that plant-based proteins are important to us. Uh, I totally agree with your comment about synthetic proteins. I don't think that will ever be economically or environmentally feasible. I don't think that's true. Uh, then we get into sort of the, the, the popular versions of plant-based, you know, Beyond Burgers and things like that, and the reality is it looks like a flash in the pan. I mean, people tried it, uh, and basically if you go to a Burger King and look, basically they had a good sales for a few months, and basically, and you tracked that, it was all people who don't normally go to Burger King. It was people who were interested in the plant-based burger. They went and tried it once and never came back. [laughs] Um, so basically we know the stock has fallen through the bottom now. We know that nobody's using it. Um, the problem with it is, um, let's take Beyond, uh, you know, Beyond Burger. Uh, basically it's a pea protein that's produced in Canada. It's shipped to in China 'cause we can't process it in the United States. There's no processing for the most part. They're beginning to develop it, but when it came out, there was none. Shipped to China, China processes protein, ships it back to the US. Uh, we know transportation is the number one cause of greenhouse gas in the world. Uh, and so now we've shipped it all over the country, comes back to the US, and they process it into something, uh, with, like, 25 ingredients. Probably five or six of them are not FDA-approved, uh, and so now you have s-

    26. PAPeter Attia2:04:38

        What, what... I was, I wasn't aware of that. What... Why, why, why so many?

    27. DLDon Layman2:04:40

        They have multiple products. They have multiple components and synthetics that have never really been studied, and they're not FDA-approved, so they're basically relying on safety, uh, without ever proving it. Um, you know, will that ever come back to haunt them? I don't know. But, you know, in the, in the spirit of having natural foods, there's certainly not anything natural about them. Um, so anyway, I, you know, I think that plant-based proteins have been around a long time. Um, I think trying to pretend that it's meat, um, or, you know, calling, calling, uh, soy drink milk or almond drink milk, I think those are travesties. I think those are standards of identity. Uh, almond milk has, uh, what, one gram of protein per eight ounces, where m- cow's milk has eight? Calling that milk is, is pure deception. Uh-

    28. PAPeter Attia2:05:38

        You know what? My wife-

    29. DLDon Layman2:05:39

        And that's why there are laws-

    30. PAPeter Attia2:05:39

        My, my wife, uh... I love cashew milk, by the way. That's how I make all my smoothies-
19. 2:10:05 – 2:14:11

    Problems with epidemiological studies of dietary protein

    1. PAPeter Attia2:10:05

       Well, Don, this has been really interesting. I'm, I'm so glad that we were introduced and, um, uh, I can talk about protein all day because it's an eternal interest of mine personally, but also in terms of helping as many of my patients as I can. I think this is, uh, perhaps the, you know... It's not the macronutrient that gets the most debated on Twitter. That's reserved for carbs and fat. But this is, this is the one that I think we need to be paying more attention to. So, uh, I'm grateful for the work you've done and for, uh, the attention you've brought to it today in our discussion.

    2. DLDon Layman2:10:38

       Yeah. I appreciate the opportunity to do that, and I, you know, I maybe one th- thought I'd leave you with that we haven't touched on is people talk about high protein, uh, and I think it's important to try and come to grips with what that means.

    3. PAPeter Attia2:10:52

       Mm.

    4. DLDon Layman2:10:52

       If you look at all of the epidemiology, which I think is pretty bad science, the definition of high protein is about 1.2 grams per kg, and low protein is actually below 0.8. And so a lot of them will express it as percentage of calories, and they'll say less than 10%. And so when you look at the epidemiology, you need to realize they're talking about very narrow ranges of protein intake. Uh, and, and it really isn't the protein that's making a difference, it's the calories and the other things that are going with it. And I'll just, one last thought. When I was, for four years, I was director of research for the American Egg Board, so I funded all of the research that basically got the cholesterol, uh, uh, direction, uh, eliminated from our guidelines. Uh, one of the things we funded though was there was a lot of research suggesting that eggs had a high correlation with obesity and diabetes and heart disease. And so we funded some research with, with, uh, uh, Theresa Nichols and Vic Vurgon, who are experts in the NHANES data, and what they looked at was that in the epidemiology, the difference between the first quartile and the last quartile for egg consumption was three to three and a half. So they were basically saying that a half an egg per week, or per week, yeah, per day, uh, I'm sorry, per week, half an egg per week was the difference in causing obesity, heart disease, and diabetes. And so what they did was they went into the NHANES data and they factored out all of the eggs that were eaten at fast food versus the eggs that were just eaten at home in a, quote, "good nutrition setting." And what they found is in every case, eggs now became a positive.

    5. PAPeter Attia2:12:40

       Yeah.

    6. DLDon Layman2:12:40

       They reduced obesity, they reduced... So basically, it's not the egg, it's the egg and the company it keeps, and you can make anything a bad diet.

    7. PAPeter Attia2:12:49

       Yeah, and I think to your point, it's when we talk about epidemiology pointing at high protein being, uh, a problem, you realize anybody who's tried to actually consume high protein realizes it ain't high protein, it's high calorie-

    8. DLDon Layman2:13:05

       Yeah

    9. PAPeter Attia2:13:05

       ... that's the problem.

    10. DLDon Layman2:13:06

        Yeah. Exactly.

    11. PAPeter Attia2:13:06

        And the protein is along for the ride because again, 1.2-

    12. DLDon Layman2:13:10

        Yeah

    13. PAPeter Attia2:13:10

        ... uh, grams per kilo is actually kinda low protein in the-

    14. DLDon Layman2:13:14

        Yeah

    15. PAPeter Attia2:13:14

        ... context of a high-calorie diet.

    16. DLDon Layman2:13:17

        If you do, if you look at epidemiology and you do any food surveys, what you realize right away is that the data for protein is pretty good. If I ask you how many eggs you ate yesterday, you'd give me the number. If I ask you how many ounces of milk or how many grams of pro- of meat, you'd give, 'cause we sell those by ounces and weights. But if I ask most people how many carbs they ate yesterday, they'd miss it by 200 grams. [laughs]

    17. PAPeter Attia2:13:46

        [laughs]

    18. DLDon Layman2:13:46

        And, and so that's the problem with epidemiology is that the errors are, are not homogeneous.

    19. PAPeter Attia2:13:53

        They're, they're not spread out. Yeah.

    20. DLDon Layman2:13:54

        They're-

    21. PAPeter Attia2:13:54

        Yeah

    22. DLDon Layman2:13:54

        ... they're not equal. So anyway, I ramble on, but a great pleasure to chat with you, Peter.

    23. PAPeter Attia2:13:59

        Thank you, Don. This was fantastic. [upbeat music]

Episode duration: 2:14:11