The Peter Attia Drive - #224 ‒ Dietary protein： amount needed, ideal timing, quality, and more ｜ Don Layman, Ph.D.

00:00:00.000 Hey everyone, welcome to the drive podcast. I'm your host, Peter Atiyah. This podcast,

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00:00:41.700 head over to peteratiyahmd.com forward slash subscribe. Now, without further delay,

00:00:47.740 here's today's episode. I guess this week is Don Lehman. Don is a professor emeritus of food science

00:00:54.120 and human nutrition at the University of Illinois, Urbana, Champaign, where he served as a member

00:00:59.140 of the faculty, as well as the chair of foods and nutrition, the director of human ecology and the

00:01:04.140 associate dean of agriculture. He earned his bachelor's and master's degree in chemistry at

00:01:08.880 Illinois State University and his doctorate in human nutrition and biochemistry at the University

00:01:12.580 of Minnesota. His research has focused on muscle development, protein and amino acid metabolism,

00:01:17.640 and nutrition in the context of athletic performance, obesity, diabetes, and cardiometabolic

00:01:21.520 health. Don currently consults for many food industry companies, including Kraft,

00:01:26.180 Nestle, Hershey, the Dairy Council, the Egg Board, the Beef Board, among others.

00:01:29.900 This episode and discussion with Don really focus around the concept of what he calls a muscle-centric

00:01:35.080 nutrition view, which is how should we think about nutrition, protein, and various amino acids if our

00:01:40.480 goal is to maintain or maximize and build muscle, especially as we age. In this episode, we talk about

00:01:46.440 Don's background, his interest in protein, muscle, insulin, anabolic factors in general.

00:01:50.880 We explain what the RDA for protein is, how it came about, how it's clearly being misunderstood by

00:01:58.360 people as a recommended amount of protein versus a barely minimum protein amount for survival.

00:02:05.600 Talk about the nuances of animal versus plant protein. We talk about the difference in protein

00:02:10.660 requirements between children and adults, even normalized to mass, of course, and we talk about

00:02:15.440 what happens to children who are protein deficient early in life. And then we look specifically at

00:02:20.460 protein needs under various circumstances. So for example, what's the maximum amount of protein

00:02:24.420 that can be consumed and used in one sitting, meaning the most amount of protein that you can

00:02:29.440 consume in one sitting, which still contributes to muscle protein synthesis. Talk about the ideal

00:02:34.020 timing of consuming protein throughout the day and around exercise. We talk about the importance of

00:02:38.240 protein quality when looking at how much or how little a person consumes. And then we talk about

00:02:42.780 how these things change as you age. So without further delay, please enjoy my conversation with Don later.

00:02:54.160 Hey Don, thank you so much for making time to sit down today. I've heard a lot about you over

00:02:59.000 the past couple of years from our mutual friend, Lane Norton, who suggested that we sit down and go

00:03:04.260 even deeper down this nutrition pathway. What you may not know about me is nutrition is my least

00:03:08.860 favorite subject. I say that only because I'm so tired of the religious aspect of nutrition.

00:03:15.080 I enjoy talking about nutrition through the lens of biochemistry, but thereafter my patience for it

00:03:21.300 has dwindled over the past decade. I have a feeling we'll get along just fine because your entire

00:03:26.200 background is based on nutritional biochemistry as opposed to nutrition religion. Well, first of all,

00:03:31.920 it's great to meet you, Peter, even electronically. And my interest was a little sort of the opposite.

00:03:39.140 I was interested in biochemistry first and studying organic chemistry just seemed so boring and

00:03:45.180 esoteric that nutrition, I could actually apply my biochemistry to things people were interested in.

00:03:51.260 I kind of like that split, but I totally get your aspect of the zealot ends of the spectrum.

00:03:57.380 You know, you grew up on a farm, if I'm not mistaken, correct? In Illinois.

00:03:59.920 Yes, that's correct. And before we started recording this, you mentioned to me that your

00:04:05.180 parents, your dad lived to 97, your mom to 102. So you're at the midpoint of your life right now,

00:04:10.780 essentially, based on your good genes. But what was it like growing up on a farm 70 years ago?

00:04:16.280 It was a great experience back in the 50s when I was born. Agriculture was very poor in the United

00:04:24.400 States. And so you sort of grew up in that background. But I think I learned about animal

00:04:29.720 growth. I learned about reproduction. I learned about growing corn and soybeans. I learned about

00:04:35.620 life cycle. And I just got an interest in food. We were growing it. We had it there on the farm. And

00:04:42.660 so it just made me interested in it. And then combined with that, I always had an interest in science and

00:04:48.580 evolved to be a kind of a natural marriage, I guess.

00:04:52.840 When you're going to college, did you study biochemistry and organic chemistry first? That

00:04:58.060 was your undergrad?

00:04:58.620 Yeah. The serendipity of how I got into nutrition, it certainly wasn't anything I knew about. I was in

00:05:04.280 a small town. I went to a school that had like 400 people in it. And so it certainly wasn't anything I

00:05:10.960 knew about. But I knew I liked science. So I went to first Illinois State University to study chemistry.

00:05:17.900 And I pretty quickly realized I had no aptitude for inorganic chemistry. But I sort of understood

00:05:24.360 biochemistry pretty well. I got to the end of it. And it was actually during the Vietnam War.

00:05:31.060 And I was scheduled to go into the military. So I was totally unemployable. And the university said,

00:05:37.880 hey, you're doing really good at this chemistry stuff. We'll give you a graduate assistantship. And

00:05:42.040 you go when you go. And all of a sudden, I ended up with a deferment getting a master's degree in

00:05:47.800 biochemistry. And my mentor at that time said, you really have a knack for this nutrition part of

00:05:53.080 it. Why don't you do a PhD? And I sort of said, oh, really? And so I ended up at University of

00:05:59.300 Minnesota doing a PhD in nutritional biochemistry and fell in love with all of it. Certainly was no

00:06:04.880 grand plan. But it fit my background of agriculture, food, sports nutrition. I fell into a group that was

00:06:12.800 doing muscle metabolism. And it just kind of all fell together for me.

00:06:17.240 Was Ansel Keys at the University of Minnesota at that time?

00:06:20.520 He was not. He had left. But his legacy was there with George Blackburn, Ivan France, and some of those

00:06:28.740 individuals. So I certainly got that background while I was there and certainly invested a lot of

00:06:35.780 my early thinking of nutrition. And Blaine Norton, who you've talked with before, has talked about how

00:06:42.720 our thinking of nutrition evolves. My certainly has evolved.

00:06:47.240 Tell me a little bit about, at least as far as you can remember, what was your underlying philosophy of

00:06:52.600 nutrition circa 1975, which is probably when you were doing your PhD, I'm guessing?

00:06:58.440 One of my earliest thinking about nutrition, again, it sort of dates to my interest in

00:07:04.840 animal growth, but also sports nutrition. I very early developed the philosophy that nutrition was

00:07:13.320 really about two tissues, the brain and skeletal muscle. If those two tissues were healthy, you were

00:07:20.660 going to live a pretty good life. Everything else is regulatory, the liver, the heart, the kidney,

00:07:27.160 the gut. Everything else adapts to your environment, but you have to focus on those two. And I think if

00:07:34.020 you tailor your nutritional requirements around that thinking, you end up with a much more sensible

00:07:39.380 approach. I sort of coined the concept that my colleague, Dr. Gabrielle Lyon and I always use,

00:07:45.440 of muscle-centric nutrition. If you keep muscle healthy, you've got a good shot at avoiding obesity,

00:07:51.680 avoiding diabetes, avoiding cancer, et cetera, et cetera.

00:07:54.840 Let's go into that a little bit. I mean, I want to get into some weeds on a whole bunch of other

00:07:58.820 really nuanced stuff, but let's follow this thread for a moment. So when you say that,

00:08:03.900 I assume you're at least in part referring to the following two facts. One, muscle is the largest

00:08:10.700 sink for glucose. 75 to 80% of our glucose storage capacity exists within skeletal muscle.

00:08:18.280 And then there's another factor of muscle, which is, it's a very early depot for excess adipose

00:08:24.840 tissue. So once we start to let little droplets of fat accumulate within muscle cells, it leads to

00:08:30.600 this process of insulin resistance that then creates a problem for the first point that I made, which is

00:08:36.200 you now make it harder for your carbohydrate storage unit to accept carbohydrates. And of course,

00:08:42.140 that leads to hyperglycemia and ultimately diabetes. Is that part of why that formulated your thesis or

00:08:49.160 is there more to it?

00:08:50.480 More to it. I think what you stated is correct, but I do think about it differently. I think about muscle

00:08:57.840 really serves two functions. One, the obvious one is mobility. Most people get to the age of 65.

00:09:04.980 Beyond that, most people actually die from some form of immobility, falls, breaking something,

00:09:12.820 hospitalization. So functional mobility is critical. But the other aspect is metabolism.

00:09:19.720 And muscle is a primary site for insulin activity. You mentioned glucose storage. I look at it more as

00:09:28.560 an issue of glucose utilization and also fat utilization. So basically your blood glucose

00:09:35.320 and your blood lipids are heavily, obviously the amount you eat makes a difference, but the actual

00:09:41.760 level is heavily dependent on your muscle metabolism. And you sort of commented about insulin resistance

00:09:49.720 being associated with fat, actually insulin causes insulin resistance. So if you chronically elevate

00:09:56.820 insulin too long, that is the definition of type 2 diabetes, is that basically insulin causes insulin

00:10:03.800 resistance.

00:10:05.420 Say more about that. It's hard to untangle some of the causality here. I spoke with Jerry Shulman,

00:10:10.840 God, probably it's been two years ago. And in his paradigm, you have the accumulation of diacylglycerides

00:10:18.660 within the actual myocytes. So not interstitially, right, or not between them, but it's the actual

00:10:24.480 accumulation of lipid within. And it's funny, I'm blanking on which enzyme now that inhibits,

00:10:30.360 but it's basically down the PI3K pathway, the PI3 kinase pathway, where you basically render the

00:10:38.260 muscle cell less sensitive to the signal of insulin telling the GLUT4 transporter to come up.

00:10:45.080 And so this hyperinsulinemia is effectively the first way that you can externally measure insulin

00:10:52.320 resistance. Is that in line with what you're saying?

00:10:55.180 Yes and no. So Jerry Shulman's great. I definitely followed his research a lot. The thing to understand

00:11:02.580 about the biochemistry is you can create the models to give you a negative feedback. So he's absolutely

00:11:09.900 correct that diacylglycerol or ceramides will feed back to the insulin receptor, the GLUT4

00:11:16.740 transport and the insulin receptor and cause insulin resistance. That's true. That is a philosophy of

00:11:25.900 fat centric, that fat causes all the problems. On the other hand, you can do the exact same thing

00:11:32.620 with glucose. Too much glucose will also inhibit the insulin receptor and cause that same exact feedback.

00:11:40.860 It doesn't accumulate the ceramides or the diacylglycerol. I did some research with diacylglycerol and if you

00:11:48.540 do it in the issues of high carb, low carb, you won't find those effects. So the question then becomes

00:11:55.660 which one's more likely to be physiological because people are eating 350 grams of carbs per day or

00:12:04.920 because they're eating 90 grams of fat per day, which one's likely to cause it? Bob Wolf, there's a

00:12:11.040 philosophy called the Randall hypothesis. I don't know if you've heard of it, but basically the philosophy

00:12:17.060 is the Randall hypothesis was that fatty acids, diacylglycerol, cause all the problems. And what

00:12:24.400 Bob Wolf did was basically run that experiment with stable isotopes and he showed it's actually the

00:12:30.380 reverse that fatty acids are not inherently toxic, but glucose is. It has its own disease. We call it

00:12:38.200 diabetes. And so when you eat excess carbs, you must get rid of them. You absolutely have to

00:12:44.620 dispose of them in the next two hours or fat basically can hang around for much longer. It's

00:12:50.000 just simply not that toxic to the body. In fact, the body always wants a certain level of free fatty

00:12:55.680 acids in the blood because that's the fuel for the heart. Okay. So it's always high.

00:13:00.820 What about the ability to turn that excess glucose into fatty acid via de novo lipogenesis? Are you

00:13:05.860 saying that doesn't happen quickly enough to alleviate some of the toxicity of acute hyperglycemia?

00:13:13.420 It doesn't happen super quick. I mean, that's a great question. There's a lot of people who argue

00:13:18.560 how much de novo lipogenesis actually occurs, but basically when you get into requiring high

00:13:27.680 amounts of de novo lipogenesis, now we start talking about fatty liver. And so now you start

00:13:34.120 seeing triglyceride problems. People who are actually doing a lot of de novo lipogenesis typically

00:13:41.360 have elevated triglycerides. So that's one of the first signs that you're disrupting that flow.

00:13:47.260 So triglycerides in general are there to recycle free fatty acids. So the adipose is always dumping

00:13:54.900 free fatty acids out for the heart and other tissues. The problem comes in is when you start

00:14:00.580 blending that with too many carbs and too many fats. So first and foremost, calories are always

00:14:06.040 the problem. But when you have excess calories and then you start rebalancing these macronutrients

00:14:11.320 is when you get into trouble. You're obviously intimately familiar with this. Maybe even some of the

00:14:15.580 listeners are, but there's a very famous paper by Mark Hellerstein circa mid-90s, 94, 95, that

00:14:22.000 demonstrated really a very small amount of de novo lipogenesis taking place with carbohydrate feeding.

00:14:27.700 I absolutely believe the results of the paper, but I also think it's a very narrow context and it's not

00:14:33.040 necessarily the context of an overfed individual. Therefore, I think our capacity for de novo lipogenesis

00:14:38.760 depends heavily on total energy content or total energy balance. And therefore, I think there is a

00:14:44.360 scenario where in the Hellerstein paper, you can feed a high carbohydrate diet, but within the overall

00:14:50.260 composition of a low energy diet or a balanced energy diet, and DNL is actually quite low.

00:14:56.960 Conversely, you can feed a high carbohydrate diet in the context of a high energy diet. And I think we

00:15:02.100 would probably see a much greater amount of DNL. Totally. You're exactly right. I think the context

00:15:06.820 matters. And I do think that the first, if we were describing this as a polynomial, right? Like the

00:15:12.460 first order term is energy. The first order term is how many calories are coming in. And that probably

00:15:18.220 matters more than the ratio of carb to fat. Go back to that Randall hypothesis or Wolf discussion.

00:15:25.740 You always want to think about it as that carbohydrates, excess glucose is toxic. If the

00:15:31.460 blood level is high, you'll damage basically every tissue from your eyes to your toes.

00:15:37.900 And so you have to dispose of the glucose. So Hellerstein's, what he showed was that if you have

00:15:44.220 a diet, say the American diet, 50% carbs, 35% fat, and you take in 1000 calorie meal, or 800 calorie meal,

00:15:55.580 which one are you going to put into fat quickest? You're going to put in the easiest one,

00:15:59.840 the one that's already fat. And so the carbohydrate is going to get burned and the fat's going to go to

00:16:05.620 fat. It's just simply the body is selecting the easiest pathway. But if you switch that and Jules

00:16:12.180 Hirsch did it, and then Jeff Volek did it later, if you switch that to a 80% carb 10%, then you'll see

00:16:19.960 that de novo liposynthesis. And one of the interesting things out of it is when the body makes fat,

00:16:26.100 the only thing it can make is saturated fat. So we have a lot of saturated fat in the blood that

00:16:32.640 actually doesn't come from eating fat, it comes from eating carbs.

00:16:36.720 Again, in the context of how much we're eating, right?

00:16:39.060 Yeah, exactly. It's important for people to realize we burn around 100 calories per hour,

00:16:44.880 that would be 2400 calories per day. So 100 calories per hour, in a two hour period,

00:16:50.920 you're only burning 200 calories. So everything else has to be stored. Average American meal is 400

00:16:57.280 to 1000 calories, that means you have to store all of that.

00:17:01.320 Is that an argument, you think, for spreading out calories more over the course of the day?

00:17:06.220 That takes us into a protein discussion, and I would say absolutely not.

00:17:11.440 Two angles to that. One was there was a theory back when I was early in my career,

00:17:17.220 back in the mid 80s by Gil Lavelle. And he was arguing that lots of small meals was good for

00:17:25.360 less fat deposition. And it was an artifact of how he did the study. He did it with animals and

00:17:32.280 basically showed that when you made the adaptation to lots of small meals, the animals didn't gain as

00:17:38.500 much as if you adapted them to like two meals per day. But the artifact was when you adapt an animal to

00:17:45.540 two meals per day, they go through a starvation period, because they'd have to learn to do it.

00:17:50.480 And when you come out of a starvation period, you're making more fat.

00:17:54.320 So we redid it with a longer adaptation period. And what we found was that reducing the number of

00:18:00.980 meals per day actually is thermogenically advantageous, you actually waste more calories.

00:18:06.680 So we actually redid that and published it. The other aspect we can get into is protein.

00:18:11.320 Protein needs to be distributed at specific meals. The distribution needs to be high.

00:18:16.740 And eating lots of small meals is a really bad choice for a lot of reasons. And we can get into

00:18:22.700 that. Yeah. And I definitely want to get into that because if there's one area I really want to double

00:18:27.300 click on today, it's everything from protein timing, protein type, animal versus plant, protein

00:18:33.900 efficiency, amino acid variability, all that kind of stuff. We're going to go deep on that. But let's go pick

00:18:39.080 it up back in University of Minnesota. You've got the legacy. And I'm guessing at the time,

00:18:44.020 Keyes is really famous for two things in the mid-70s. I think by that point, he's probably

00:18:48.260 already published his seven-country study. And the hypothesis now is a very fat-centric view of

00:18:56.640 the negative consequences of dietary fat, specifically dietary saturated fat in the American diet,

00:19:02.160 especially as it pertains to ASCVD. And then I suspect the second thing that he's probably still famous

00:19:07.180 for is the starvation experiments, I'm guessing done in the 1950s. I mean, these were done on

00:19:12.360 conscientious objectors. So they're probably in the forties or fifties, right?

00:19:15.600 I can't exactly date that, but you're exactly right. I mean, we learned a lot about starvation at

00:19:21.140 that point for obvious reasons. We can't do experiments like that before, but we learned a

00:19:26.560 lot about body composition and how the body starved. So those were good, but certainly the legacy was

00:19:32.380 there. And when I got to Minnesota, I sort of bought into the cholesterol and the saturated fat

00:19:38.520 and total fat and, okay, this is what everybody's teaching. And, you know, that's what I was forced

00:19:43.560 to learn. That's what they were teaching. And so I bought into it. But as I slowly started doing

00:19:49.160 experiments and early in my career, we did a lot of fasting type of experiments with animals to look

00:19:56.080 at composition changes. And I did malnutrition work in Northern Africa. And I sort of got into all of

00:20:03.220 that. And I started realizing, you know, I don't really believe that. And one seminar I will always

00:20:09.440 remember at Minnesota was individual by their name of Fred Kummerow came to Minnesota and gave a seminar

00:20:17.460 about the dangers of cooking oils and specifically trans fats. And Blackburn and France just ridiculed him.

00:20:26.080 Basically said, this is the craziest thing we've ever heard. All these plant oils are great.

00:20:31.300 20 years later, we banned trans fats from foods, literally, as the most dangerous fat that you can

00:20:38.120 encounter. I always remember that just sort of thinking, wow, people who have bought into this

00:20:43.640 dogma aren't necessarily right. And we need to keep questioning it.

00:20:47.680 Speaking of France, obviously, in 1973, he completes a study, the Minnesota coronary experiment. I actually

00:20:57.160 find this to be one of the most difficult studies to interpret, not so much the one that he published

00:21:02.780 16 years later, by the way, in 1989, but the one that Chris Ramsden republished just a couple of years

00:21:11.200 ago, based on all of the data from Franz's study, plus data he never published. This to me is one of

00:21:17.940 the most complicated stories. I will tell you, I have posed this question to every friend of mine who

00:21:24.140 is more steeped in nutrition than I am. And I still don't have a great sense of how to explain these

00:21:29.520 results. So I'll explain it for the listener and the viewer. And I'm curious to your thoughts. So the

00:21:33.960 experiment was done in basically institutionalized patients. So again, maybe not a study that could

00:21:40.700 be done easily again today for ethical reasons, but had the advantage of being so well-controlled.

00:21:45.420 You basically had patients that were randomized into two groups. Their total energy was identical.

00:21:51.940 Their total split of macronutrients was identical. The only thing that differed was that in one group,

00:21:58.360 it was high saturated fat. And in the other group, it was high polyunsaturated fat. The hypothesis being

00:22:05.300 tested was, is saturated fat intake leading to increased major adverse cardiac events, heart

00:22:12.540 attacks, and strokes. The experiment, I can't remember exactly, I think it ran about five years,

00:22:17.480 in 1973 showed no difference. There was no difference in cardiac events, despite the fact

00:22:23.960 that the group that was on the higher polyunsaturated fat group did indeed have much

00:22:29.060 lower cholesterol levels. This predated the sub-fractionation. So they weren't measuring

00:22:34.040 LDL and HDL. They were just measuring total cholesterol. And at the time, there was some

00:22:39.000 correlation between cardiovascular disease and total cholesterol levels. At the extremes,

00:22:43.120 that was certainly true. Again, because I didn't think we'd be talking about this, I don't have the

00:22:47.020 numbers all in my mind, but we'll link to it all. But directionally, I believe that the higher

00:22:52.040 PUFA group relative to the saturated fat group was about 30 milligrams per deciliter lower in

00:22:57.800 total cholesterol. And based on everything we know today, we would assume that much of that was in

00:23:02.960 LDL cholesterol indeed being lower and non-HDL cholesterol. And yet there was no difference

00:23:07.840 in events. And of course, it's become a very famous and unfortunate story in nutrition research and

00:23:13.920 that Franz chose not to publish it because he didn't like the results. It didn't match his hypothesis,

00:23:19.020 which was that the group on lower saturated fat would have fewer events. Ramsden went and published

00:23:25.140 all of these data plus a whole bunch of sub-data, as I said, just a few years ago, I believe in the

00:23:29.680 British Medical Journal, and actually found something that threw a wrench in my initial

00:23:33.620 hypothesis. My initial view of the Minnesota coronary experiment was it probably wasn't a long

00:23:39.260 enough intervention. It might be that five years was not long enough to appreciate a difference.

00:23:44.800 And so it was underpowered or too short in a duration to see a benefit if there was a benefit.

00:23:52.260 But in Ramsden's analysis, you actually saw the opposite because he now looked at some subgroups

00:23:56.420 and you actually saw a higher incidence of coronary events in some of the people that were consuming

00:24:02.500 the high polyunsaturated fat diet. And I can't remember what the dominant oil was. I'm blanking on

00:24:08.100 it. I don't remember if it was canola or safflower. I think it was safflower. So how much of that do you

00:24:13.860 remember, Don, from your time there? And can you shed any light on this? Or do you have any thoughts

00:24:18.660 on how to interpret that experiment?

00:24:22.180 Well, first of all, I am definitely not a lipid expert. So I sort of remember the study,

00:24:27.760 but I can't put any more numbers to it than you did. I actually did some research with Ivan France

00:24:33.600 and Penny Chris Etherton when I was at Minnesota. So I sort of was in the loop at the time, but that's

00:24:40.340 been a couple of years ago. I think if one really looks at the literature on saturated fat and is

00:24:47.540 fair about all of those studies, you find a very mixed bag. The Women's Health Initiative and all

00:24:53.520 of those kinds of things. And unfortunately, the people who believe the hypothesis have either

00:24:58.820 delayed publishing it or said, well, it could have been wrong. And they tried to find all kinds of

00:25:04.040 excuses as opposed to just believing it. You know, there's an old theory in science that

00:25:09.800 the theory is correct. It'll get stronger over time. And if it's not, it gets weaker. And I think

00:25:15.420 one would have to realize that A, the cholesterol theory, the total cholesterol theory has definitely

00:25:21.820 gotten weaker. And the saturated fat hasn't held up very well. We still believe it. But your comment

00:25:28.460 a little bit ago, it's first and foremost calories. If you put excess saturated fat on top of too many

00:25:35.440 calories, that's probably a problem. But if you're at or below your calorie needs, I don't see any data

00:25:41.680 that suggests it is. So my sort of joke or comment all the time is that if you're committed to being

00:25:47.500 obese, you probably ought to pay attention to the quality of your fats. If your goal is to be lean and

00:25:53.340 healthy, calories is what you're paying attention to. And the macro distribution is sort of your

00:25:59.080 personal preference. So let's talk a little bit now about how your interest in protein came about

00:26:05.100 because of all macronutrients, this is the one I have to pay the most attention to. And it's honestly

00:26:11.640 the one where I feel like I fall the shortest. I feel like I have some days when I nail it and I have

00:26:18.040 too many days when I come up short. I never go overboard. I never go to bed at night thinking,

00:26:22.480 God, I ate too much protein today. But I do go to bed sometimes thinking I don't think I ate enough

00:26:27.160 for my goals. My goals are to maximize muscle protein synthesis. My goals are to preserve lean

00:26:32.320 tissue as long as I can. And frankly, that's the goal for my patients. So how did this become a strong

00:26:38.100 interest of yours? Well, the real interest started in my master's degree because I got interested in

00:26:43.600 studying protein turnover, protein synthesis. And I was working with Arlen Richardson, who was an expert

00:26:50.340 in aging. And we were studying age-related changes in protein synthesis. And we actually discovered

00:26:56.420 the changes in mRNA over time, that the poly-A tails on mRNA get shorter, your ability to put ribosomes on

00:27:06.080 the message goes down, and you have lower synthesis. So that efficiency of change of protein synthesis over

00:27:13.360 time is a theme that runs through all of my research. And we'll get into efficiency in adults and

00:27:19.460 things like that. So that was sort of the beginning. When I went to Minnesota, then I sort of got a

00:27:24.460 muscle focus on it. And one of the first things I learned in graduate school is we don't really have

00:27:30.600 a protein requirement. We have a requirement for nine essential amino acids and organic nitrogen,

00:27:38.640 organic amines, which all translates into the fact that we can make 11 amino acids and nine we have to

00:27:45.360 have in the diet. And one of my favorite quips I use when I'm talking to groups on stage is that

00:27:52.480 protein we should think of as a vitamin pill. We don't have a daily requirement for a vitamin pill.

00:27:58.200 We have a requirement for 12 vitamins inside the pill. We don't actually have a daily requirement for

00:28:04.120 protein. We have a requirement for nine or 20 amino acids inside of it. And so it's talking about a

00:28:11.620 protein requirement just to reflect ignorance. We have a specific requirements for nine essential

00:28:17.320 amino acids. And that gets into the complexity then because these amino acids are essential for

00:28:24.040 building blocks for new protein. But every one of them has a metabolic role like leucine and mTOR or

00:28:31.420 arginine and nitric oxide or lysine and carnitine or cysteine and glutathione. And all of those roles are

00:28:39.900 vastly above the minimum that is detected for nitrogen balance for the RDA. And so that's where

00:28:46.480 people fall apart is that we think about vitamin C and we know there's a minimum RDA to prevent scurvy,

00:28:53.160 but people will take five or 10 times that during COVID for immune response. But we resist thinking

00:28:59.760 that way about amino acids and it's exactly the same. You know, that's a great point, Don. Maybe we

00:29:05.640 should spend a minute helping people understand what an amino acid is because, you know, I took

00:29:10.440 biochemistry. I have my little cue cards. I can draw every one of the amino acids. Not anymore,

00:29:16.200 by the way. I can't. Yeah, not anymore. But there was a day when I could draw all nine of them. But

00:29:21.020 let's help people understand. I think most people understand what glucose looks like. If you've listened

00:29:27.020 to this podcast, you're no stranger to the idea that glucose is a six-carbon ring and each one

00:29:32.820 has a couple hydrogens on them. And one of them's got an oxygen and a hydrogen on it as well.

00:29:38.100 I think most people who have listened to this podcast have a decent sense of what a fatty acid

00:29:42.540 looks like. Long stretch of carbons. If it's saturated, there's no double bonds. So it's just

00:29:49.140 littered with either two or three hydrogens, depending on where it sits in the chain. And

00:29:53.880 then, of course, you store them by putting three of those onto a nice little three-carbon glycerol

00:29:58.880 backbone. But I actually think most people, understandably, have less clarity around what

00:30:04.240 an amino acid is. And you've already alluded to the fact that there were 20 of them and nine of

00:30:09.640 them we can't even make. If we were deprived of these things, we'd be dead. So we've got to eat

00:30:13.720 them. But can you give folks a sense of the nomenclature? What is an amino acid? What do these

00:30:18.240 things look like? A little bit like a fatty acid. An amino acid has a carboxy end connected with a

00:30:24.640 carbon. And then it has a nitrogen end. So when we eat protein, we get these amino acids in some

00:30:31.940 sort of a string. But we totally digest them down to probably individual amino acids, maybe

00:30:37.880 di or tripeptides. And we absorb them that way. They get to the blood as single amino acids for the

00:30:44.300 most part. And then the body begins to reconnect them based on the messenger RNAs. Our DNA tells us how

00:30:50.640 to reconnect them. And so we connect a carbon to a nitrogen and we string them together. Of these 20

00:30:56.940 amino acids, though, they all have that acid and nitrogen part. But they also have a side chain,

00:31:03.780 ranging from very simple one like glycine with just a hydrogen, to ones like tryptophan that have a big

00:31:10.880 aromatic part to them. And so all of these are different. And they go into proteins in different

00:31:17.140 structures. The DNA tells us how we put them together. And proteins can be simple like insulin

00:31:23.400 with 51 amino acids, or they could be like myosin with thousands. And then every protein in the body

00:31:29.880 has a different turnover rate. Some of them like insulin might last 15 minutes. And some of them like

00:31:36.740 myosin, or let's take collagen, might last 250 days. And so they turn over at different rates. So

00:31:45.600 that's sort of what they are. But beyond that building block structure, then every amino acid

00:31:50.660 has other kinds of structures. It might be like lysine, where part of it becomes the molecule

00:31:56.780 known as carnitine, which is for fatty acid metabolism. Or it might be the nitrogen off

00:32:03.220 arginine that goes to nitric oxide for vaso restriction. Or it might be cysteine, which goes to

00:32:10.520 part of creatinine or glutathione. So we can get the leucine, which is sort of my favorite,

00:32:16.640 which is a signal, which really got me interested in protein and metabolism is a signal for muscle

00:32:23.020 protein synthesis. So again, they all have this building block structure, they get strung together

00:32:29.560 in different links, but they also have other metabolic functions. And that's what people don't

00:32:35.000 recognize when they're talking about protein requirements. So let's talk about that RDA,

00:32:40.880 because when we look at our patients and evaluate them from a nutritional standpoint,

00:32:45.800 almost without exception, we come to the conclusion that they are not getting enough amino acids based

00:32:53.200 on how much protein they're consuming. Now, I don't know how much of that is the nature by which food

00:33:00.140 is prepared these days, the nature by which protein makes up a certain amount of the caloric intake

00:33:06.460 based on various types of prepared foods and things like that. And how much of that just is based on a

00:33:10.960 belief system of what people need, perhaps coming back to the RDA. So first of all, let's tell people

00:33:16.560 what the actual RDA is and how it came to be.

00:33:20.100 So the RDA is a recommended dietary allowance. Some people think it's a daily, but it's a dietary

00:33:27.260 allowance. So it's sort of a generic number. And the argument is that for all RDAs, we sort of test

00:33:34.340 the population and come up with an average number. And then for a safety factor, which average would be

00:33:40.580 50% would be deficient. And so we add a safety factor of two standard deviations, which supposedly 97.5%

00:33:49.480 of the people would be adequate to prevent any signs of inadequacy at that point. But that also

00:33:55.420 means 2.5% of the people are actually deficient at that point. That's sort of the definition.

00:34:01.240 Where does the RDA come from? I think it's useful to go back in history just a little bit then on

00:34:06.460 protein. How did we begin to evaluate protein needs? Well, it all came out of animal sciences.

00:34:12.760 Back in the early 1900s, before we even knew all the essential amino acids, farmers were trying to say,

00:34:19.480 how do I get animals to grow best, you know, and different kinds of proteins and things like

00:34:24.600 that. And they develop protein quality scores and things like that. How much growth did I get for

00:34:30.780 what I fed? How much nitrogen did I deposit for how much I fed? So these were all rapidly growing

00:34:38.200 animals. And we developed this concept really of nitrogen retention. That basically, we've now

00:34:45.080 translated into what's called nitrogen balance. And that's how we determine the protein requirement.

00:34:52.920 Basically, what's important in all of that discussion, that long-winded explanation is that

00:34:58.920 all of the concepts were developed for growth, where nitrogen balance was positive, you could measure a

00:35:05.480 change over time. And as we've now tried to start applying that to non-growing adults,

00:35:11.920 it gets a lot more vague. So it's important to recognize that what we think about protein

00:35:17.920 requirements is A, develop from nitrogen balance, where you measure all of the nitrogen you're

00:35:23.120 eating, which you can do pretty good. But then you have to measure all of the nitrogen you're losing,

00:35:28.440 which we're really bad at. And we call that nitrogen balance.

00:35:32.620 Can you explain how that's done? We're going to talk so much about it. I think it's worth getting

00:35:36.420 into the details of how nitrogen balance is calculated. And let's do it in a human. 0.76

00:35:40.800 If I came into your lab, how would you do this?

00:35:44.080 So let's start with the front end. Let's start with nitrogen in. So that's basically,

00:35:48.240 you just take a bunch of food and you do a chemical analysis and you measure the nitrogen

00:35:52.880 and you multiply it by a factor of 6.25. So A, you're measuring nitrogen. It's not really protein.

00:36:00.800 It could be nucleic acids. It could be anything with nitrogen. You're calling it protein.

00:36:05.400 And then you're multiplying it by 6.25, which says, I believe that protein contains 16% nitrogen,

00:36:12.840 which also isn't always true. So now we've got this error on the front end. And now on the back

00:36:18.780 end, we're going to try and measure losses. So the primary loss of nitrogen in the body is in the urine,

00:36:25.640 urea. So that's pretty easy to measure. You can collect that. Second would be the stool.

00:36:31.320 So you can collect that. But then you get into things like sweat, skin loss and hair loss and

00:36:38.600 respiratory nitrogen, ammonia in the breath. And those are all incredibly vague. So everyone who

00:36:46.180 knows nitrogen balance says that nitrogen balance underestimates requirement. Everybody, uniformly.

00:36:53.220 But that is where the RDA comes from. When you do short-term studies, what you find is most people,

00:37:01.820 and again, all these studies were done with college-age students. So they're kind of right

00:37:06.220 at the end of their growth. Basically, in a short-term seven-day study, they look okay. So that's where

00:37:14.080 we're at. In the last 20 years, those of us who study protein have gone beyond that and said,

00:37:20.760 well, nitrogen balance is one outcome. But like the vitamin C argument, there are other outcomes

00:37:26.760 based on amino acid metabolism that may be more important than minimum nitrogen balance.

00:37:32.940 And we now know that protein handling, the efficiency goes down as we get older. So now we

00:37:39.120 have much higher requirements that most of us talk about for adults.

00:37:43.620 So just to be clear, Don, going back to something you said, the reason we all agree that standard

00:37:48.760 nitrogen balance underestimates the requirement is it's easier to measure the sum of the ins than

00:37:54.420 the sum of the outs. Yeah, exactly. And the chances are you're significantly underestimating the outs.

00:38:03.140 Especially if you do, I mean, when I was a surgical resident, there were times we did nitrogen balance

00:38:09.720 on patients who were on long-term TPN, total parenteral nutrition. In the ICU, these were

00:38:16.600 patients that it wasn't clear how long it would take for their guts to start working again. So they

00:38:21.820 had to be fed all of their nutrition through a central line, which is very complicated feeding

00:38:27.780 to do. And when we would have the nutrition team come and do a consult and do a nitrogen balance, 0.72

00:38:33.880 I mean, they literally had to put a tent over that patient. You know, they were doing the best

00:38:37.600 that they could in the ICU to basically create a laboratory environment to calculate nitrogen

00:38:43.140 balance, which turns out, you're not surprised, very important for a critically ill patient.

00:38:48.640 That is a hyper, hyper catabolic state. And if you're trying to create an anabolic state

00:38:54.900 in that person to keep them alive, it's imperative that you understand how much nitrogen they have

00:39:00.400 or how much nitrogen that they require. So the simple idea of, I'm just going to tell you how much

00:39:06.040 protein you're eating, and I'm going to measure the nitrogen that's coming out in your urea,

00:39:10.920 that's just not going to cut it. That's just too simple.

00:39:13.540 Yeah. And currently, a lot of those studies are simply done with a factor. So they don't put them

00:39:18.320 in tents or buildings or whatever. They just measure urea in the urine and everything else is just sort

00:39:25.120 of, well, we think it's a one point. Yeah, exactly. Exactly. And so obviously,

00:39:30.400 we're perpetuating an error based on ignorance.

00:39:35.060 So then let's go one step further, Don. How do you use isotopes to now really get into what's

00:39:42.400 happening, not just on the boundaries, but how that nitrogen? And by the way, I think there's

00:39:48.020 one point we should make for the listener who might be still lost as to why we're talking about

00:39:51.680 nitrogen. Proteins have nitrogen. Amino acids all have nitrogen. Carbs and fats don't.

00:39:58.480 So this is where we can really speak to the source of the nitrogen. And now, as you mentioned,

00:40:04.680 anything with a nucleic acid is going to have nitrogen as well, but the majority of the nucleic

00:40:09.680 acids come in proteins. Come in protein foods.

00:40:13.140 Yeah, would be found in protein-based foods. You're exactly right. I mean, fats and for the most part,

00:40:20.000 annoying essential fatty acids, carbs and fats are basically energy sources. They're carbon-carbon

00:40:25.520 bonds that provide energy, where amino acids have a very different purpose and structure.

00:40:31.500 And that nitrogen is part of what makes them different.

00:40:35.260 In other words, we consume carbohydrates virtually exclusively for their energy content,

00:40:42.100 fat mostly for its energy content. There is some structural importance that comes with fat and

00:40:47.460 cholesterol. But really, you don't want to be consuming protein for energy.

00:40:51.240 Right. The only caveat I would say to that is that there might be reasons that people are

00:40:58.580 hypersensitive to carbohydrates, where taking in more protein beyond what you might actually need

00:41:05.700 for protein metabolism might be a substitution for carb calories. We can get into that conversion and

00:41:12.760 things like that. But I talk with people and they say, how much protein? What's your high end? And I

00:41:17.580 sort of give them one number and I say, but the caveat is you might want to take more if you're

00:41:23.220 really trying to struggle with a carbohydrate issue.

00:41:26.080 So now let's talk about that measurement of what's actually happening with those amino acids. Actually,

00:41:31.640 there's a question I want to ask you even before that. When people think of protein, they think of

00:41:34.620 meat. That's going to be a great source of protein. Obviously, there's protein in most foods have some

00:41:40.000 protein in them. But if you're eating a piece of steak, how many of those 20 amino acids are in

00:41:46.280 there? Are they virtually all in there? If you're looking at animal source proteins, whether it's

00:41:51.960 meat or eggs or milk, basically, all of the amino acids that a human would need are in those because

00:41:59.720 they're basically, obviously, a chicken's not a mammal, but the others are mammals. And basically,

00:42:06.040 we have the same amino acids, the same protein. They're all there. Meat is a good example because

00:42:11.880 they're all pretty much in the right balances. But every protein has a little different balance

00:42:17.720 of essential amino acids. You can look at dairy proteins and dairy proteins are something we can

00:42:24.360 fractionate because they're all water soluble. So we know a lot about alpha-lactalbumin versus

00:42:30.120 lactoferrin and lactoglobulin, et cetera, et cetera. We know that a lot of differences about amino acid

00:42:36.500 compositions of individual proteins. Going back to what you just said then, animal protein,

00:42:41.380 we typically think of as meat, mammals, beef, pig, stuff like that. And then, of course,

00:42:46.420 you've got sort of bird protein, mostly chicken for folks, and then fish protein. And then you have

00:42:51.460 eggs, dairy. The first three are exactly the same for protein. So whether it comes from a cow or a pig

00:42:59.400 or a chicken or a fish, muscle protein is still muscle protein. And how do we think objectively

00:43:07.320 about the quality of a protein? This is a topic that you've talked about extensively, but there's

00:43:15.000 a way, there's a numerical way to talk about that. Isn't there an efficiency of that protein versus

00:43:19.960 tofu versus soybean versus rice, all the way down to lower and lower protein density foods?

00:43:27.640 Yeah, protein quality is something that I think a lot about. And I'm actually working with a group

00:43:33.760 now to sort of reinvent how we think about that. But I think you're referring to protein quality in

00:43:39.560 a sense of PD-CAS or DIAZ or something like that. Basically, we realize that when you look at a protein,

00:43:46.460 there are two factors. One is what's the composition of those nine essential amino acids? And the other

00:43:52.560 is what's its bioavailability? How well do we digest it and absorb it? With animal proteins and most

00:44:01.360 isolated proteins, even soy protein isolates, the digestion absorption is pretty close to 100. It's

00:44:08.160 usually 95% or higher for all animal proteins. For plant proteins, though, it gets into, you need to

00:44:16.180 realize that in a plant, the protein is there for the purpose of the plant. And so a lot of it is

00:44:22.800 attached to fibers, to structures. Plants have proteins attached to the leaves and the stems and

00:44:28.720 the roots and the flowers and the seeds. And when you start to isolate that, if you just eat it in a raw

00:44:35.220 form, it may only be 60-70% available because we can't digest the fiber. So those are the two factors.

00:44:43.120 We can put those two together and get a protein quality score. And we can determine that a whey

00:44:49.500 protein isolate because of its essential amino acids is 20% better than a soy protein isolate

00:44:56.000 just because of the amino acids. Or we can compare a wheat protein, a wheat bran, and we realize that

00:45:03.580 it's only 40% available. So if you look at wheat bran on a cereal box and say it was a wheat flour,

00:45:10.440 and it says there's four grams per serving, there's actually less than two that you can actually

00:45:15.740 absorb. That's how we look at it. In my opinion, some of the problems with those right now is it's

00:45:22.660 hard to compare across foods and it's hard to build a meal that way. We can say that whey's better than

00:45:28.220 soy. And so if you're only eating those two things, that's okay. But what happens when you start putting

00:45:32.900 them together? And so I am working with a group trying to build a protein quality score that really

00:45:38.800 based on three amino acids, lysine, methionine, and leucine, which in my opinion are the key markers

00:45:46.520 for adult health. And so we're trying to rescore it differently. Again, long-winded story about

00:45:52.140 protein quality, but that's how it's measured. No, that's very interesting, Don. So what you're

00:45:56.240 saying is, if I'm understanding you correctly, you could brute force your way through life by looking

00:46:00.780 at every single thing you eat and trying to figure out the dias score for its protein. Okay,

00:46:06.360 I'm about to have a ribeye. That's going to be about a 96% dias. I'm going to have my soybeans over 1.00

00:46:12.580 here. That's about an 80% dias. I'm going to have my whey isolate. That's 100% dias. I'm going to have

00:46:18.800 my shredded wheats. That's a 40% dias. That's a tough way to go through life because you can't just 1.00

00:46:24.540 add up the protein. Yeah, they're not truly additive. You can't really figure that out. And the average

00:46:29.560 person doesn't even have that data. I mean, if you go into the USDA database with whatever,

00:46:37.720 7,000 foods, there are 4,000 that actually have amino acid scores. And of those, there's probably

00:46:44.960 less than 300 that have dias scores. And so you can't put it together. There's no way. And so we're

00:46:52.100 trying to develop a system that allows people to get better than that. If you look on a label,

00:46:57.800 on a package, and you see, again, a wheat cereal that says it has four grams of protein, well,

00:47:04.100 again, that's a nitrogen analysis times 6.25 for all the problems I've said. And then if you look

00:47:10.220 over at another column, it'll say daily values. Almost no label have daily values for protein

00:47:16.520 because that would require a PD-CAS or dias score and nobody has them. And so that four grams really

00:47:23.200 would translate into less than two, but nobody's being told that. And by the way, just for folks

00:47:28.420 who are hearing us use the term dias, that's digestible, indispensable amino acid score,

00:47:33.540 correct? Right. And I have a big problem. The digestibility is where a lot of people have been

00:47:38.760 focusing, but I have a big problem with the amino acid scores because they're incredibly low.

00:47:44.400 They're way too low. They're established by the World Health Organization, by the FAO,

00:47:50.340 which is really designed to prevent malnutrition in Africa, where we know from our Institute of

00:47:56.360 Medicine that the essential amino acid scores are much higher than that should be. You mentioned

00:48:02.220 stable isotopes a little bit ago or tracers. We know from stable isotope studies that all those FAO

00:48:09.520 amino acid scores are too low. And so that's part of the equation that we're not telling people either.

00:48:15.460 I want to come right back to that, but I'll finish this one point, which is what you're offering as

00:48:19.960 an alternative to people living in spreadsheets to calculate how much actual indispensable amino acid

00:48:26.260 they're getting is, hey, what if we make this easier and you focus on the actual content of three

00:48:33.000 amino acids? So we're going to take a subset of essential amino acids. And if I recall,

00:48:38.100 I remember leucine was clearly one of them. Lysine was one of them. Was methionine the other one?

00:48:43.120 Methionine's the other one. Yeah.

00:48:44.460 So we're going to take methionine, leucine, lysine, and we just want you, Peter, to walk around

00:48:49.640 and make sure you get enough of those with each meal. If you do that, the rest will take care of

00:48:54.840 itself. Is that effectively what you're saying?

00:48:57.400 That's exactly what I'm saying. If you look at Diaz scores right now, the amino acids scoring,

00:49:03.740 A, I've already said it's too low. But if you look at how they're scored, they're not scoring

00:49:08.580 apples and apples. They're scoring apples and oranges. So if you look at the soy deficiency,

00:49:14.220 all legumes like soy or pea are limiting or deficient in methionine. And you score that against

00:49:21.560 whey, what you end up is the limiting amino acid in whey is considered histidine. And no one has ever

00:49:28.420 shown histidine to actually be a limiting amino acid in an adult. It's a limiting amino acid in

00:49:34.420 children and babies. So now we're comparing apples and oranges. They're not fair. So if you compare

00:49:39.920 methionine to methionine, it's not 20% higher, it's 250% better comparing soy and whey. We need to

00:49:48.840 compare apples and apples. We need to compare them across the three essential amino acids that are

00:49:54.120 actually likely to be limiting. Where histidine, phenylalanine, to my knowledge, no one has ever

00:49:59.840 shown those to be limiting in an adult. So why do we consider them limiting?

00:50:04.040 So you've already mentioned the importance of leucine and listeners of this podcast are no stranger

00:50:09.060 to leucine because we've had David Sabatini on, we've had Matt Kaberlein on. I mean, we've gone deep

00:50:15.040 in the weeds on mTOR. In fact, it was one of David's postdocs that actually discovered the leucine

00:50:20.740 sensor on mTOR. So we know now pretty unambiguously, leucine is an amazing trigger for mTOR. Of course,

00:50:28.840 there's going to be a subset of people listening to this who are confused, but wait a minute,

00:50:32.160 Peter, if rapamycin is good and rapamycin inhibits mTOR, how can leucine be good if leucine turns it on?

00:50:38.440 And of course, they're forgetting the chronicity of the state. Sometimes you want it on, sometimes you

00:50:42.240 want it off. But when we're talking about eating, we want it on, right? We want to be able to turn

00:50:46.740 mTOR on for muscle protein synthesis. So let's circle back to our earlier comment about how often

00:50:53.640 you eat. So now we've got an issue of mTOR and whether it needs to cycle on and off. And not only

00:51:00.220 does leucine turn it on, but so does insulin. Probably the worst case scenario, and you can use

00:51:06.000 a lot of animal studies to back this up, would be people who eat a lot of small carbohydrate meals

00:51:11.820 that continuously activate mTOR. What we want to do is use specific meals with the right amount of

00:51:19.460 insulin to activate muscle-centric mTOR. mTOR is in every tissue. And what you don't want to do is

00:51:26.440 continuously activate it in liver or some other tissue. And so that's where the confusion gets

00:51:32.160 into it is people ignore the fact that insulin is just a biggest trigger in other tissues where

00:51:38.740 leucine is a very unique trigger in muscle. Let's go back to the practical application of

00:51:43.600 this. So we know why leucine matters. Can you say a bit more about methionine and lysine and why

00:51:48.140 raising them to the level of leucine becomes a great proxy for overall protein load?

00:51:55.080 If you look at limiting amino acids actually in food, lysine is always limiting in grains.

00:52:03.220 And that has been shown in animal science over the years. That's a major limitation

00:52:08.460 in how you feed, what the minimum amount. So that one is probably limiting for protein synthesis. 0.78

00:52:15.840 It's also in carnitine and some other things, but lysine is probably mostly for protein synthesis.

00:52:22.860 Methionine, if we look at the amounts we need, we need about 3.4 grams of lysine per day.

00:52:29.260 We need probably a little less than one gram of methionine. So they're not in the same proportion

00:52:34.180 either. But the methionine is what we call part of the one carbon pool. And so basically for the body

00:52:41.360 to make and repair DNA, to make and repair RNA, to make taurine downstream, to make non-essential

00:52:49.020 amino acid cysteine, to make glutathione the oxidant, methionine is the key to all of those pathways.

00:52:56.420 Methionine is one of the most limiting and it's limiting in all legumes. So we think of soy and pea

00:53:03.020 and lentils and things of that nature is higher quality protein. They are, but they're still

00:53:09.000 limiting in methionine.

00:53:10.400 What are some of the natural sources of food that are high in methionine?

00:53:14.320 The classic one of, quote, sulfur amino acids is eggs. Eggs are quite high in the sulfur amino acids,

00:53:21.900 which are methionine and cysteine. But all animal products are adequate in them. And basically all

00:53:29.720 plant products are pretty low in them. You grew up on a farm.

00:53:33.000 Yes.

00:53:33.540 We look at animals like cows, which are quite muscular, eating basically just hay and grass.

00:53:40.460 For them to be able to be as catabolic as they are and produce so much muscle, does that just speak

00:53:47.080 to the incredible volume of that plant that they have to chew to make sure they're getting enough

00:53:52.540 methionine, enough lysine, and enough leucine?

00:53:55.340 I think you meant anabolic, not catabolic.

00:53:57.440 Sorry, anabolic. Yeah, yeah, yeah. In such an anabolic state, I mean, what volume of total protein

00:54:04.500 in the form of grass and hay and things like that do they need to get a sufficient amount of

00:54:09.520 those muscle-building amino acids?

00:54:12.200 That sort of wanders us into a sustainability argument, which I really love to wade into. But

00:54:17.960 cattle, ruminant animals, are a very important part of the food chain because of their stomach,

00:54:24.740 which is full of bacteria, one of the things to think about for essential amino acids is really

00:54:31.300 the only place they come from in life is bacteria. Nothing else can make them. Our primary source of

00:54:39.020 them in nature is the bacteria on roots of plants. So the bacteria on the roots will take the nitrogen.

00:54:47.800 Why do we fertilize our garden is nitrogen? The bacteria will take that inorganic nitrogen and 1.00

00:54:54.400 form organic amines with it. And those organic amines then can be made into proteins in the plants.

00:55:01.340 But as I said earlier, the problem with plants is that they don't have the same balance as we need.

00:55:07.500 They have the plants to make roots and flowers and things like that. The beauty of a ruminant is they

00:55:13.860 can take that plant and they can digest it and the bacteria then will rebalance all of the amino acids. 0.93

00:55:21.780 They'll capture inorganic nitrogen and they make the essential amino acids that mammals need and

00:55:29.020 they concentrate it for us. So basically humans, one of the arguments is humans evolved by being able to

00:55:35.900 use more concentrated protein. If we just ate plants, it's hard to get enough. But if the ruminant 0.90

00:55:43.300 animal can actually digest all of that, form it into appropriate amino acids. So basically for every

00:55:51.160 60 grams of protein an animal eat, they'll make 100 grams of essential amino acid balanced protein.

00:56:00.640 Wait a minute, say that again.

00:56:01.820 So for every 60 grams of plant-based proteins and nitrogen that they'll take in, they can upcycle

00:56:09.200 that to 100 grams of amino acid balanced protein. So ruminants are called upcyclers. So whether it's

00:56:16.280 in dairy or meats or goats and sheep and deer, all of those ruminant animals upcycle by eating grasses,

00:56:24.360 they produce great quality protein. No other animal can do that.

00:56:28.880 And just to make sure I understand the mass balance of that, the bacteria are obviously the engine of

00:56:34.280 that upcycle, but you can't make nitrogen out of nothing. So you're saying...

00:56:38.620 They're making protein out of nitrogen.

00:56:40.600 That's right. That's what I was going to say. So they're getting the nitrogen from the fertilizer

00:56:43.820 that went into the grass.

00:56:46.100 Not quite. They're getting nitrogen that's inorganic in the plants, but it's not actually in protein forms.

00:56:52.820 Okay.

00:56:53.060 And so it's in the fibers and other kinds of things. So they're able to upcycle that.

00:56:57.780 They're able to increase the value of non-amino acid nitrogen. Plus they capture all of those

00:57:05.880 other nitrogens.

00:57:07.620 So first of all, I had no idea that was happening. I'd never heard of that phenomenon. So that's

00:57:12.340 incredibly fascinating. Secondly, are they also disproportionately creating amino acids

00:57:19.020 that weren't necessarily there in the plant? So in other words, if you use the example you gave

00:57:22.300 earlier, which is you eat a hundred grams of cow protein, you're going to probably get

00:57:29.300 quite an amount of methionine, lysine, and leucine. Is it true that that amount of amino acid was not

00:57:35.560 even present in the 60 grams of grass protein that they consumed?

00:57:40.500 That's exactly what's happening. So the bacteria, if you look at the flora in the cow,

00:57:45.900 they have certain bacteria that will produce methionine or a lysine. So they can basically

00:57:53.200 take an amine nitrogen, or they can take glycine, a non-essential amino acid, and they can make it

00:57:59.540 into amino acids. One of the supplements that you can actually feed a cow is urea, a human waste

00:58:07.140 product type of thing. We excrete nitrogen waste as urea in the urine. You can actually feed urea,

00:58:14.160 a nitrogen source to a cow, and they can make it into methionine or leucine or lysine.

00:58:20.860 Unbelievable. So it's an interesting argument. Now we're venturing from nutrition into religion

00:58:25.040 because there's certainly a group of people who would argue that we should not be eating any animal

00:58:29.680 protein whatsoever. We shouldn't eat meat, we shouldn't eat eggs, we shouldn't eat dairy, etc.

00:58:34.000 A counter argument to that would be it's awfully difficult without these animals to get adequate

00:58:40.020 amino acids, especially if you stop thinking of it in terms of an RDA and start thinking of it in

00:58:46.540 terms of essential amino acids. I try and stay away from the religious argument of it. That's a

00:58:52.300 personal preference. As you said, I grew up on a farm where we raised cattle and pigs, we raised corn and

00:58:58.540 soybeans, and so I saw it as a life cycle type of thing. I think of it as a biochemist, and there's just

00:59:05.800 no question that ruminant animals play a very important role in our food system, and one we

00:59:11.960 can't really replace. We can't just idle millions of acres of grassland and pretend that we can grow

00:59:20.160 avocados on them or broccoli. Cattle basically spend a year of their life on basically nothing but grass.

00:59:28.800 Sheep and goats the same, but those are amazing contributions to our food system.

00:59:33.500 I was completely unaware of this capacity to concentrate and almost up-produce both in

00:59:41.940 quantity and quality of amino acid. That's a very interesting finding. Where were we before we

00:59:47.520 went down that path? Because I was just trying to understand how it happened. I also didn't

00:59:51.040 appreciate the role of the bacteria. Oh, I know where we can go back to. You mentioned that you have

00:59:55.460 spent some time studying the difference between, call it 20-year-olds and 60-year-olds in terms of the

01:00:02.640 efficiency of muscle protein synthesis. This is where you probably have to get into the isotopes.

01:00:08.160 Now you're getting into sort of nuanced stuff. What do we know about a 20-year-old versus a 60-year-old

01:00:15.980 who puts their muscle under a progressive overload? They're doing resistance training.

01:00:20.200 They're being provided with adequate amino acids. Let's assume they're being provided with not just

01:00:24.420 the right quantity, but the right quality of amino acid. What do we know about the assimilation of

01:00:30.600 that amino acid into new muscle tissue across? Pick any age you want. I just use 20 and 60.

01:00:35.960 I know you've studied this at very specific age points.

01:00:38.580 Piece of background before we get into that, it's important to recognize that whether you're 16 or 65,

01:00:46.100 your body needs to make nearly 300 grams of new protein per day. There's a protein turnover. Every

01:00:53.940 tissue in the body is turning over. Some as fast as liver enzymes where you replace every hour,

01:01:00.600 muscle proteins where you replace with half-lives of around 15 to 16 days. So every 30 days,

01:01:08.120 collagen turns over at about half-life of 100 days, which is why if you hurt your knee,

01:01:13.380 it takes so long to repair it. But basically, if you put that into thinking, the body replaces literally

01:01:20.400 every protein in it about four times a year. That's a pretty remarkable number. And then if you think

01:01:26.500 we have to make 300 grams of new protein per day, the average American intake is around 80 grams or less,

01:01:34.480 women 70, men 90. That means that there's a recycling thing going on. So of every new protein that's

01:01:43.340 getting made in the body, about six out of seven amino acids are getting recycled. All of that sort of

01:01:50.540 feeds into this process of protein synthesis, protein turnover. And remember, I said what I was

01:01:57.380 doing with my master's degree. We were studying the age-related changes. What we now know is that

01:02:03.240 as you get older, the efficiency of that protein turnover goes down. So where a 16-year-old, you give

01:02:10.500 them a certain amount of protein, they'll have a very good response. A 65-year-old will have maybe no

01:02:17.020 response at all, or 10% or something. But what we have learned with the study of leucine and

01:02:24.900 initiation factors and all of that, is that if you give an enriched source of essential amino acids

01:02:31.940 more protein, you can actually make the adult look just like the 16-year-old. So what we know is that

01:02:39.300 the efficiency goes down, but the capacity to respond doesn't. And so what we're now thinking is that

01:02:46.720 what we now know is that if you have a requirement, it's about twice the minimum RDA. So instead of

01:02:53.160 0.8, it's 1.6 grams per kg, we can get the adult, the 65-year-old to respond just the same as the 20-year-old

01:03:02.200 as far as muscle protein synthesis. You know, a moment ago, Don, we talked about how it's a slippery

01:03:07.080 slope if you just focus on total protein. So when you say 1.6 grams per kilogram, does this assume

01:03:14.640 it's from a whey-like product and an animal-based product? And if that person says,

01:03:21.620 hey, I'm 65 years old and I'm on a plant-based diet, are you going to say that number is going

01:03:25.500 to need to be higher? That's a great question and a great way to ask it. What we know is that

01:03:31.720 most people who go to a plant-based diet, a vegetarian diet, decrease both the quantity

01:03:36.600 and the quality. So your point is exactly right. If you're on a plant-based diet, you'll need more

01:03:44.060 protein and that means you'll have to have more calories. But what's the threshold for that?

01:03:49.920 What we would probably argue is that if you have 100, 120 grams of protein per day,

01:03:56.380 it probably doesn't matter the distribution between animal and plant because you probably

01:04:02.320 have enough to cover it. If you're only eating 50 grams of protein per day, then it makes a big

01:04:09.960 difference. You'll never catch up to your essential amino acid needs. So somewhere between 50 and 120,

01:04:16.740 it depends on what you choose. If you're going to be plant-based, have 125 grams of protein per day

01:04:23.160 and you're probably fine. But if you're going to be vegetarian and you think you're going to get

01:04:27.740 wrong with 56 grams per day, you're going to get in trouble. Going back to this difference earlier

01:04:33.420 about the, call it anabolic resistance between the 65-year-old and the 16-year-old, the obvious

01:04:39.220 thing that comes to mind is there's a huge difference in androgen level between those two.

01:04:44.720 What are the other things that might explain this anabolic resistance that, by the way, I think it's

01:04:49.660 very interesting that you can overcome that by a higher amount of protein. But prior to that work

01:04:54.960 around, what else do you think explains anabolic resistance? Clearly the hormone issues are first

01:05:01.280 and foremost. So I always make the comment that when you're growing, hormones are your friend. They're

01:05:06.820 sort of driving it. And you look at malnutrition in Africa and children will grow on really lousy diets.

01:05:15.600 They may not grow as healthy. They may not live as long, but there's a survival reproduction nature to

01:05:22.660 that. Now we switch to talking about healthy aging and I want to live to where my parents,

01:05:28.680 I want to get to that century mark. Now we talk about healthy aging and now we change the criteria

01:05:34.800 that we're looking for. Let's just think about mTOR for a second and try and put that in framework.

01:05:40.460 There are four different signals that regulate mTOR. We've mentioned leucine. We also mentioned

01:05:47.000 insulin, an enzyme, a factor known as AMP kinase, which is carbohydrate sensitive, is energy sensitive.

01:05:54.860 And then another molecule known as red one, which is stress sensitive, particularly resistance exercise.

01:06:01.800 So there are four different things, the individual balances. When you're young and growing insulin and

01:06:07.640 IGF-1 dominates that. And insulin first and foremost is a growth hormone. And when you stop growing at 25,

01:06:15.800 it ceases to have an effect on protein synthesis and muscle. And so now the shift, the whole thing

01:06:21.460 shifts to protein quality. Protein quality is not nearly as important when the system's dominated by

01:06:27.300 hormones. And so now what we know is as we get older, we can buffer that loss of the hormones by

01:06:34.460 higher quality protein, mostly leucine and resistance exercise. Those two factors will balance out

01:06:42.780 the growth issue that young people have the benefit of the growth part. So that's the way you have to

01:06:48.700 think about the change in efficiency with aging. Speaking of aging at the front end of what you just

01:06:54.000 said, I want to go into that a little bit more. And I think most people will recognize that this is an

01:06:58.500 enormous problem in the developed world. And we should talk about it through that lens because I 0.97

01:07:02.580 think that's where it's most stark. But I'm curious as to whether or not you think this could become a

01:07:07.480 problem or even plays a role in childhood obesity rate. So let's talk about what happens to a child

01:07:13.380 that is protein deficient at the beginning of their life. What is the implication of that later in life?

01:07:20.220 So when I got into protein, John Waterlow and Joel Millward and Peter Garlick and Vernon Young were the

01:07:27.720 godfathers out there that I learned from. And I got involved with some international malnutrition

01:07:33.920 with the U.S. International Agency for International Development, USAID Project in Morocco. And so we

01:07:40.820 looked at that and that led us to doing some animal studies. And basically, we used the animals to look

01:07:47.980 at malnutrition and recovery. And what we found was that malnutrition, starvation insults early in life

01:07:56.120 would stunt muscle development, basically limited the DNA development, limited the cellular development,

01:08:02.360 and basically stunted lean mass in the children and in the animals. And if that was stunted,

01:08:09.200 basically, what happened is the individual as an adult was always predestined to have low lean body

01:08:16.480 mass and high body fat, obesity. And that was really the origins of how we started thinking about

01:08:23.400 muscle centric health. If muscle didn't develop right, if it wasn't metabolically correct,

01:08:29.640 you were predestined to some of these other things. And I mentioned Gabrielle a lot, Dr. Gabrielle

01:08:34.740 Lyon. That's sort of how we put that concept together is muscle centric health. We've got to

01:08:40.240 have the correct development and we have to have the correct protection as adults, because that's kind

01:08:45.480 of where both your mobility and your metabolic health start. Don, what's the mechanism? Do we have

01:08:51.220 a sense of why, you know, for example, maybe people are aware of this, but when you look at children

01:08:56.120 in places like Africa who are really malnourished, at first glance, you almost pause and think, well, 1.00

01:09:02.620 why are their bellies so big if they're malnourished? And yet they don't realize that's an actual,

01:09:07.140 that's an extreme, and I don't even remember, it was kwashiorkor, was that the name of it?

01:09:11.160 Exactly.

01:09:11.740 Yeah. And what's the pathophysiology of that? Why is the extreme malnourishment lead to that

01:09:16.660 protruded abdomen and things like that? So there's sort of two terms, two directions that

01:09:23.260 childhood malnutrition goes. One is called merasmus, which is sort of the skin and bones

01:09:28.280 look, and the other is kwashiorkor, which is that inflated belly looking. The belief of those two 0.84

01:09:34.720 differences is that in kwashiorkor, there's disproportionately poor protein, and that leads

01:09:42.160 to changes in water balance and edema. People have argued, is it cortisol-based, you know,

01:09:48.320 is it stress-based? It appears to be an imbalance in the protein to energy relationship, where in

01:09:55.260 merasmus, they're just short of total calories and total protein and everything. But in kwashiorkor,

01:10:01.580 it appears that the quality of the protein, they're eating these starchy porridges and things like that,

01:10:07.540 totally deficient, probably in lysine and methionine, and that leads to water imbalances

01:10:13.860 and other things. And what is it about this critical window of development where this protein

01:10:21.140 deficiency makes it very difficult for them to put on lean mass later in life and creates a propensity

01:10:28.520 for adiposity? We actually did some of that original research stuff we did way back in the

01:10:35.700 late 70s, early 80s. Muscle is a very unique cell structure. We have what are called muscle fibers.

01:10:43.080 And unlike a liver cell, which has a DNA, a nucleus in each cell, muscle cells are multinucleated.

01:10:51.540 They have what are called satellite cells around them. And so as the original fiber begins to develop,

01:10:58.700 the satellite cells will put DNA, these nuclei into it. And what we determined was that

01:11:05.940 each DNA has a certain amount of protein it can handle. And so what the DNA ultimately determines

01:11:13.260 how big your muscle can get. And so what we determined was that late in pregnancy, early in

01:11:18.940 lactation, if the insult occurs during that, you stunt these satellite cells and you don't develop

01:11:25.500 enough DNA. So the muscle is always limited in its potential size. Wow. I was aware of the

01:11:32.900 propensity for adiposity later, was not aware of the limitation in lean growth. So this is really

01:11:38.400 the double whammy. It's effectively lifetime sarc obesity. Yeah. So basically you're decreasing your

01:11:44.120 lean mass, you're decreasing your metabolically active tissue. And so you're sort of stuck with

01:11:49.520 minimal calories, will deposit fat. In the U.S., it would be hard to imagine a child developing

01:11:55.300 kwashiorkor, but clearly there are kids in the United States that are disadvantaged enough that

01:12:00.640 they're not going to be exposed to high enough protein in either quality or quantity. Do you think

01:12:06.000 that there's, to a lesser extent, some of this problem that's going to happen in developed nations

01:12:10.400 like the U.S.? I think it's possible. Frankly, these are the kinds of things I worry about with the

01:12:17.340 advocates of plant-based diets. We're starting to see New York City taking animal proteins out of

01:12:23.920 school lunch. I mean, what is that really going to do? We're conducting a public health experiment

01:12:28.920 without actually having any knowledge of that. I think that's frightening. The issue is public

01:12:35.500 school lunches, nursing homes, daycares. These are all under these federal guidelines where we're

01:12:41.680 diluting out the quantity and quality of protein at the same time with no knowledge of what that's

01:12:47.120 really going to mean. I think that's pretty frightening to be doing that kind of public

01:12:51.660 health experiment without knowledge of it. I hadn't even considered it through that lens,

01:12:56.500 actually. Let's talk about something else that we alluded to briefly, but now I want to get back to,

01:13:01.760 which is maximum protein usability or assimilation in a given sitting. I'll tell you where I come at this.

01:13:10.860 One of the challenges that I've observed in taking care of patients is when they get into a very heavy

01:13:18.660 regimen of time-restricted feeding. You're probably aware of this, Don, but there are ideas that say,

01:13:23.840 look, if you can just limit the amount of time that you eat but not place any limits on what you eat or

01:13:29.440 how much you eat or what you're eating from into this sort of intermittent fasting window,

01:13:33.820 it produces some health benefits. It's certainly an effective way to reduce calories. If the goal of the

01:13:39.760 exercise is to reduce total energy expenditure and you create a narrow enough window, you will indeed

01:13:46.120 do that. But what we've seen repeatedly is people who, after say six months of adopting a very narrow

01:13:54.000 feeding window, say one meal a day, will lose weight but disproportionately will lose lean tissue.

01:14:00.780 The diagnosis here is pretty straightforward. They clearly reduced energy intake,

01:14:04.760 but they probably reduced protein intake too much. Body composition actually got worse despite the

01:14:11.680 fact that weight went down, which then gets to a point which is, well, can't you just eat all of

01:14:16.080 your protein in one meal? If a person says, I'm just going to eat one meal a day, let's just say this

01:14:20.900 is a very active person, right? They're going to eat 3,000 calories in one sitting, which I will raise

01:14:25.760 my hand to saying I can do that quite easily. I'm quite a glutton. Even if I was able to eat

01:14:31.360 150 grams of protein in one sitting, is it clear that my body will get the benefit from that,

01:14:38.180 that it would if I ate 50 grams three times a day? Yeah, it's quite clear that you won't get a

01:14:44.960 benefit, that there is a limit. So now we need to think about the body as muscle versus everything

01:14:51.760 else. We're going back to the muscle-centric view that I like. You're probably sensing a theme with

01:14:56.640 me at this point. The muscle, there's a lot of data now that muscle can handle protein meals for

01:15:04.160 an optimum anabolic response between about 25 and maybe 60 grams. Then you start getting into

01:15:12.180 distribution. If you're going to have 150 grams per day, how should you distribute it? One of my

01:15:18.620 pet peeves in nutrition, I'm slightly getting off track here, is people refer to protein as a percentage

01:15:26.220 of calories. Protein is not a percentage of calories. Protein is an absolute number. You need to decide

01:15:32.980 on what you're going to build your diet around. So right now we're building it on 150. The issue with

01:15:39.040 protein is being an absolute number. If your calories go down, say you're now a 75-year-old woman and your

01:15:46.080 calories per day is now 1,200 calories, you still have 100 gram per day protein requirement.

01:15:52.560 So now your protein needs are 35 to 40% of your calories. If people are doing weight loss,

01:16:00.000 it's an absolute number. So people should never talk about percentage of calories. That's basically

01:16:06.160 people who don't think protein is important and say, well, fat should be 30%, carbohydrates should

01:16:12.140 be 50%, and that's at least 15%. You have to think about protein first. So that was the issue.

01:16:17.980 As far as distribution, from my research, one of the things that we believe is the most critical

01:16:24.640 meal of the day is the first meal of the day. When you have had an overnight fast, your protein

01:16:31.320 synthesis is down and that mTOR signal molecule is downregulated. It's inhibited. And until you have

01:16:39.240 enough leucine, around three grams, which translates to about 30 grams of protein for most people,

01:16:46.440 until you have a meal that has 30 or more grams of protein, your muscle stays catabolic. So you're

01:16:53.780 continually breaking down protein. We think that's a significant aspect of aging, that people have

01:17:00.760 lower and lower protein, they don't eat protein at breakfast, and we know the efficiency is going down

01:17:06.380 in the first place. So we want a front load protein in the day. So we want at least two meals that are well

01:17:14.160 above 30 grams of protein. So I always have people shooting for 40-45 at the first meal,

01:17:21.480 another 45-45 at their last meal. And then in between, if we're talking with people who are,

01:17:28.780 say, an elderly woman trying to maintain minimal muscle, I'll concentrate on those two meals. 1.00

01:17:34.980 If I'm talking with somebody who's trying to do weight loss, I'll concentrate on three,

01:17:39.560 because I don't want them getting hungry. If I'm talking with someone who's trying to be

01:17:44.520 hypertrophy, a muscle builder, I'll concentrate on four. So how many meals per day do I make anabolic

01:17:51.260 and muscle? And by anabolic, I'm thinking 35 grams or more. And the data that we know for absolute

01:17:58.440 certain is the first and last meal are absolutely important. The middle meal, I'd be hard-pressed to show

01:18:06.060 you a single study where anybody's ever looked at lunch. And so the reason that you're saying for

01:18:11.080 the anabolic person, we need four meals is we know we need it for positive nitrogen balance. 0.99

01:18:15.900 We're just going to have to get the amount. Two aspects. There's one is mTOR signaling,

01:18:20.040 muscle protein synthesis, leucine effects, and the other is total protein per day. So those two

01:18:25.880 lead say, well, if I need more protein and I max out at 50 grams, I need another meal.

01:18:31.700 And what about timing? Let's just talk about someone who's doing their strength training

01:18:36.500 in the morning. So let's say someone's going to do strength training from 8am to 10am. Do you want

01:18:42.780 them having that first bolus of protein before the workout? There's some debate about that. You'll find

01:18:49.540 some people and trainers who believe that. We did some studies and most of them were with animals where

01:18:56.100 we looked at different timing and we find that exhaustive exercise is catabolic no matter what.

01:19:03.920 So having protein ahead of it doesn't make it. We find the benefit is after the exercise when the

01:19:10.080 system is now finely tuned, we've inhibited red one, the system mTOR is ready to go. So we find the

01:19:17.960 benefit is after exercise, not before. And just to be clear, what you're saying is, look,

01:19:23.280 you can take all those amino acids before, but it's not going to prevent you from becoming catabolic

01:19:29.360 during exercise. Because again, exhaustive exercise is a catabolic activity. So you are

01:19:36.880 going to be breaking down muscle no matter how many amino acids are on board while lifting. It's more

01:19:43.120 important after the lift that you have a good meal. You'll find some disagreement in that in the

01:19:49.180 literature. But I strongly believe that what you just said is correct. And my research supports that.

01:19:55.640 And talk about the efficiency or the window in time post a workout in which you want to make sure

01:20:02.480 you're getting that first big meal of protein. I'll tell you a funny story. My youngest son,

01:20:08.980 who's now five, but when he was like three, for whatever reason, he just fixated on protein.

01:20:13.940 Probably because we kept telling him to eat this and eat that because there was protein in it. Hey,

01:20:19.000 eat your salmon. It's got protein. Eat this because it's got protein. And basically he has become the

01:20:24.100 protein police of the preschool. He walks around and he looks at kids' snacks and he's like,

01:20:29.640 that doesn't have protein. That granola bar does not have protein. That has protein.

01:20:35.420 And you can imagine what these people who work at the preschool say to my wife when she drops him off

01:20:41.020 and picks him up. She's like, are you a nutritionist? And she says, no. Oh, okay. It's

01:20:46.160 just your son really fixates on everybody's protein consumption. So we joke about how he's going to be

01:20:51.820 like one of those bro protein guys who's just going to be all obsessed with his protein and when he's

01:20:57.580 eating it and stuff like that. I've lost our train of thought here for a minute, but just to focus on

01:21:02.400 the children for a moment. So we're talking about adult protein needs and I don't want everybody to walk

01:21:07.980 away thinking, gee, I need to get 50 grams of protein in my kid. Children will be very efficient 0.89

01:21:14.160 at maintaining growth with small snacks of eight to 10 grams of protein where that will have virtually

01:21:20.440 no impact for an older adult. So a protein bar that had 10 grams of protein is a perfectly legitimate

01:21:27.740 snack for a child where essentially the only thing it would do is probably increase liver enzymes in a

01:21:34.020 70 year old. So don't want all the mothers think they're doing a bad thing by giving their child a

01:21:39.320 10 gram protein snack. I remember what we were going to come back to. So I'll take us back there,

01:21:43.940 but let's talk about that a bit more because that's actually news to me. I didn't realize that there was

01:21:48.240 minimal benefit in smaller quantities of protein. So this is another argument for don't dribble out

01:21:55.720 your protein. Commit to it. It's binary. You eat it when you eat it and then you don't when you don't.

01:22:00.420 Yeah. So again, children versus adults. And the adult, if we have every meal of the day,

01:22:07.760 let's say we have 100 grams of protein, but we take it in in very small meals, 15 grams

01:22:13.600 trickled in all day long, you will never stimulate muscle protein synthesis, but your liver will be

01:22:20.020 perfectly fine. Your gut will respond to that amount of protein. Your gut, your liver, your heart,

01:22:26.320 your kidney, all of those organs will respond to the net protein per day, no matter when you ate it.

01:22:33.060 But muscle doesn't. Muscle is specific. Muscle is such an energy. You mentioned earlier, there's so

01:22:39.140 much mass to muscle. Muscle isn't triggered unless the diet is exactly right. And we could get into

01:22:46.420 teleological arguments about leucine at this point, branch chain amino acid. Why does the muscle sense

01:22:52.580 that? But basically, the muscle senses energy, insulin, protein before it triggers. And if all

01:23:00.860 of those aren't balanced, it won't trigger, but your liver will. To your point, teleologically,

01:23:05.780 you might make the case that the liver has more concern for the brain than the skeletal muscle.

01:23:11.820 And maybe it gets priority over being happy because it has to maintain glucose homeostasis.

01:23:16.280 And without glucose homeostasis, the brain would literally die within 20 minutes.

01:23:21.380 Your liver, your heart, those have to function. Middle of the night, your liver still has to be

01:23:26.500 making protein, but your muscle doesn't. While you're laying there in bed, your muscle is catabolic

01:23:32.260 and it's supplying amino acids. So all those other organs work. So while I argue about muscle-centric

01:23:39.480 health, the reality is moment to moment, it's organ-based. But long-term, your overall health

01:23:47.800 is determined on keeping the muscle healthy because it keeps everything else healthy.

01:23:52.140 Just because I want to keep talking about this before we go back to where we were before I

01:23:55.160 distracted us. Is the reason that it's okay for kids to be eating much smaller amounts of protein,

01:24:01.120 is it simply just the mass? My youngest weighs 25 kilograms.

01:24:04.860 Is it basically just saying, look, he probably doesn't need more than 40 grams of protein a day.

01:24:11.340 So for him to have a 10 gram serving is 25% of his protein. That's like me having 40 grams.

01:24:18.180 And plus his protein synthesis, as we mentioned earlier, is driven by hormones where yours isn't.

01:24:23.320 So his growth is highly efficient. It's driven by hormones and he will accommodate it in small doses.

01:24:29.960 And you're right. He probably only needs 45 for the day anyway.

01:24:33.380 So I'll take you back to where we were before I sidetracked us. It was now asking about

01:24:38.140 how big a window you have to refeed to maximize muscle growth.

01:24:45.980 So we actually did that first experiment in rats. So Josh Anthony and Tracy Anthony were in my lab

01:24:53.580 just before Lane came. And what we were looking at was exhaustive exercise, again, in rodents.

01:24:59.680 We were looking at this catabolic state. We were trying to look at how to muscle regulated

01:25:06.260 recovery. And so we were looking at what were called initiation factors. And we discovered the

01:25:12.900 link between leucine and an initiation factor called EIF4. That is sort of the downstream effect

01:25:20.600 of mTOR. mTOR is a regulator and it stimulates EIF4 and S6 and other initiation factors.

01:25:28.180 And so what we found was that when you came out of an exhaustive exercise, muscle is catabolic

01:25:34.340 until you took in enough leucine to reverse it. And so we started looking at feeding right

01:25:40.820 after exercise. And Stu Phillips, Doug Patton Jones, and Luke Van Lee, a lot of people sort of

01:25:46.540 picked up on that. Okay, so now the caveats. The biggest effect of feeding right afterwards

01:25:53.080 is about a two-hour window. But that's in untrained individuals. If you begin to look longer, you can

01:26:01.580 have a bout of resistance exercise and you'll detect the difference. You'll start regulating that red one 1.00

01:26:07.980 protein factor and you'll see an anabolic effect the next day, 24 hours, 36 hours later.

01:26:15.080 So when does your protein affect? Well, it makes it more effective all the time.

01:26:19.020 The more trained you get, the less you're going to see a post-exercise effect. So if you're beginning

01:26:25.560 training near the first four weeks, post-exercise protein probably makes sense. If you're well-trained,

01:26:33.460 you're basically training the same way and you've been doing it for six months, I don't see any effect

01:26:38.700 difference between having protein within two hours after exercise versus just having your three or four

01:26:45.240 meals per day. You won't see any difference in either mass or strength.

01:26:49.700 I remember having this discussion with Lane as well and being very surprised by that, being

01:26:53.660 pleasantly surprised, by the way, because it says, hey, look, once you get to a point where you're well

01:26:58.240 trained enough, you don't have to be so maniacal about meal timing. You can just focus on the big

01:27:04.320 picture, which is total protein, protein quality, and spreading it out such that you don't exceed

01:27:11.020 the metabolizable fraction of it at any one sitting.

01:27:14.700 Exactly. You'll hear trainers take that last statement, metabolizable energy, and you'll hear

01:27:19.760 trainers say, well, you can't use more than 30 grams at a meal. You won't digest it or whatever.

01:27:24.680 That's not true. I mean, you'll digest and absorb 100 grams of protein at a meal,

01:27:29.360 but muscle in particular only has a window of around 25 to 60, depending on protein quality,

01:27:36.240 where it can use it. The liver will use all of it. I mean, it doesn't matter.

01:27:40.120 We have what is known as first pass metabolism of protein, which confuses the issue even more.

01:27:47.460 When you eat a meal of protein, approximately 50% of the protein is degraded to nitrogen and carbon

01:27:54.460 before it ever gets to the blood. Almost 50%. The exception to that are the branch chain amino acids,

01:28:01.100 leucine, isoleucine, valine, and almost 75, 80% of those get into the blood. And we're back to that

01:28:08.180 teleological argument. Why did muscle learn to sense that? Because that basically shows up in

01:28:14.040 the blood in direct proportion to the meal. And the muscle learned to sense that as a meal quality.

01:28:19.860 It says, oh, wow, this meal has adequate quality for me to trigger this very expensive process of

01:28:26.300 protein synthesis, protein turnover. And until it sees that signal, it won't do it.

01:28:31.660 While we're on the topic of muscle, Don, another thing I've learned somewhat recently that surprised

01:28:37.460 me was the importance of leucine in fatty acid oxidation by the muscle. One of the things that

01:28:43.960 is such an important pillar of our practice is low-end aerobic training. We call it zone two. So zone two

01:28:52.580 mitochondrial efficiency. So this is basically pushing your muscles to the maximum point at which you can

01:29:00.980 keep lactate below two millimole. And in a very fit individual, you can generate a lot of power

01:29:07.140 while still keeping lactate below two millimole. I mean, the best in the world can produce more than

01:29:12.320 four watts per kilo while still keeping lactate below two millimole. And they're doing so virtually

01:29:18.740 exclusively with fatty acid. So we will pair this type of analysis with CPET testing, and we will look at

01:29:25.900 fat oxidation rates. And again, you will see the fittest of the fit have insanely high fat oxidation

01:29:32.040 rates. They're over a gram, roughly a gram per minute. Point of that is, look, a really good muscle

01:29:38.060 doesn't just rely on glucose. A really good muscle can oxidize fats very effectively. What role does

01:29:44.780 leucine play in that? That's a great question. And I don't think it's been researched well enough.

01:29:50.140 I mentioned earlier, we're talking about amino acids, and every amino acid has a different side

01:29:55.200 chain. Well, leucine is one that's referred to as a branch chain amino acid, and its side chain is

01:30:01.940 purely carbons. It's a carbon chain that looks a lot like a fatty acid. And so leucine is one of really

01:30:08.900 two amino acids that are ketogenic. It is metabolized as a fatty acid. And what we know

01:30:16.680 is that leucine will also activate the CPT1 enzyme, the carnitial palmitone transferase enzyme,

01:30:25.120 which is the link of bringing fatty acids into the mitochondria for oxidation. So there's a benefit

01:30:31.080 there. It gets even more complicated in that when you have higher leucine, it also begins to inhibit

01:30:38.440 pyruvate from going into the mitochondria. So when you oxidize a leucine, the nitrogen that

01:30:46.600 comes off of it is put onto pyruvate, generating an alanine. And so the body begins to recycle

01:30:53.740 glucose. So it becomes kind of steady state on glucose and emphasizes fat oxidation. So back when

01:31:01.140 you were talking about Schulman studies early, if you overload all of that, basically, you can make

01:31:07.700 the leucine inhibit carbohydrate oxidation. So if you have huge amounts of carbs coming in,

01:31:13.480 and then you overload the system with leucine, you'll inhibit pyruvate oxidation. And so that

01:31:19.480 could look like insulin resistance. But if you look at the physiology of how it's supposed to work

01:31:24.840 under conditions where you'd be burning fat, like you just described, leucine actually stimulates fat

01:31:32.280 oxidation and spares glucose for the brain and other tissues. So again, you really have to think about

01:31:38.920 how the experiment's set up, what's getting inhibited and what's getting pushed.

01:31:44.020 You've recently taken an interest in weight loss, right? So the dietary interventions that can be

01:31:48.920 efficacious for weight loss and treating things like metabolic syndrome. So let's build off this

01:31:53.560 idea a little bit. How do you incorporate the strategy around reducing energy intake? This is sort

01:31:59.840 of how I think about weight loss. You got to reduce the intake, but I think of three broad ways that you

01:32:05.160 can approach that. So three strategies, right? One is you just reduce calories and that becomes the only

01:32:10.600 focus. So you pay attention to the total energy content of food without thinking about the timing of

01:32:16.360 food or the macro distribution of food. The next approach is you spend less time thinking about the

01:32:21.380 total number of calories, spend more time thinking about the macronutrients. I describe it as sort of

01:32:25.440 create a boogeyman in the diet, some things that you avoid. And the restriction of certain things

01:32:30.880 becomes a roundabout way to restrict total energy. And then we talked about time restriction as well

01:32:36.320 as another strategy. How do you think about manipulating that middle bucket of changing macros

01:32:42.220 to achieve energy deficit? I totally agree. Weight management is a calorie issue and it's not the same

01:32:49.320 for every individual. Everybody's got a little different efficiency. So we understand you can't be an

01:32:54.260 accountant and expect to just count calories all the time. But let me build it as a story of

01:33:00.800 how we thought about it. Back in the late 90s, Atkins and the keto diet were out there and Barry

01:33:07.340 Sears and, you know, the zone diet and Michael Eads and the protein power. And I was looking at all of

01:33:14.340 those things and we were doing those leucine experiments and we had discovered this effect of

01:33:20.560 leucine on muscle protein turnover and some of these metabolic things with fat metabolism. And I

01:33:27.780 basically took the leap of faith and said, you know, I think the underpinning of all of these diets is

01:33:34.040 really the protein carb ratio. And how can we manipulate that? And so I started thinking, well,

01:33:40.080 we're going to create diets. One, we know that from a satiety standpoint, protein is probably the most

01:33:46.660 satiating. Lors, fat would be next, carbohydrate the least. We were concerned about big insulin swings.

01:33:53.920 So we wanted to sort of balance out our carbs per meal. We know that if people are overweight,

01:34:00.020 they tend to have big post meal carbohydrate and insulin swings where they get two hours later,

01:34:06.120 they'll have carbohydrate lows. And so we started trying to think about that. And we said, okay,

01:34:11.400 so we think the first meal after an overnight fast is critical. So we're going to correct that. So we

01:34:17.420 basically started saying, how much protein do you need, 30, 40 grams of protein to get both satiety,

01:34:24.780 protein synthesis effects. We knew that protein had a higher thermogenic effect, burns more calories,

01:34:32.020 more heat than either carb or fat. So we wanted to front load that effect. People have argued that,

01:34:37.480 well, that's because protein or the nitrogen, it's harder to digest and absorb. We don't think that's

01:34:42.460 true at all. We think the thermogenic effect is stimulating muscle protein synthesis. We know that

01:34:48.080 that is a massive ATP expenditure. And so what we want to do is maximize that at every meal. So our

01:34:55.780 first meal, we wanted to be 40 grams of protein. We wanted to have a carb level that would not

01:35:01.300 overstimulate insulin. So we kept that under around 30 grams for what we created a carbohydrate threshold

01:35:07.700 concept we can go into. And then fat sort of to round out the calories. And we basically developed

01:35:14.180 three meals a day to distribute like that. We basically increased the protein to about 1.6 grams

01:35:21.900 per kg. And we ran the study comparing it to the food guide pyramid with 0.8. So as far as we could tell,

01:35:29.160 we did three different studies, one, a total feeding study where we fed everyone, a second study with diet

01:35:35.500 an exercise that was four months. And a third study was multi-centered with 120 subjects that lasted 16

01:35:43.380 months. And so we did three studies. And the last two were free living where they were responsible for

01:35:49.180 the food, but the first one they were fed? The first one we fed them in the lab. So we knew exactly what

01:35:54.280 they were eating. The second one, we actually fed them for their first two weeks for a few meals. So they

01:36:00.880 really saw what it would look like. And the last one was totally free living based on the diets and manuals that

01:36:07.880 we developed.

01:36:09.620 And each of these was two arms where the only difference was protein?

01:36:14.240 So in the first one, it was two arms, food guide pyramid, high carb, low protein versus higher protein, low carb.

01:36:21.120 The second one was two by two. So we basically had the diet treatment, and then we had a resistance exercise

01:36:28.200 treatment. So high protein, low exercise, high protein, et cetera. And then the last one was diet

01:36:35.620 with a generic recommendation for exercise, but just a two treatment fact.

01:36:40.900 So what did the first experiment show, the really well-controlled one?

01:36:44.100 The well-controlled one, what we found was that with the higher protein, and as far as we could measure

01:36:50.080 exactly the same calorie intake, the people on the higher protein, low carb, lost more total weight,

01:36:57.060 more total fat and less lean, and that stabilized their insulin and glycemic regulations and lowered

01:37:05.260 their triglycerides across the board.

01:37:08.140 Do you remember what the difference was in weight and fat mass? And was it all explained by the

01:37:13.020 thermodynamics of the difference in protein?

01:37:16.000 It was close. We found that if you assume that body fat, you know, 3,500 calories, and you can make

01:37:23.720 that calculation, you figured out that the people on the higher protein diet were getting a benefit of a,

01:37:31.480 I think it was around 170 calories a day eating the same calories. So that could be about the

01:37:38.240 thermodynamic effect.

01:37:40.060 So in other words, that amount spread out over the duration of the study explained the difference in weight loss.

01:37:44.720 Right. So both groups lost weight. They were both on weight loss diets, but the protein people lost,

01:37:50.280 I didn't look those numbers up, but they lost around eight pounds more and something like

01:37:57.680 six and a half of it was fat.

01:37:59.860 And did they also complain less of hunger or was there a difference subjectively between the groups?

01:38:04.760 We did a satiety check using an analog scale. We just asked them to rate how they felt and stuff.

01:38:12.260 And one of the things that the dietitians who were running the study always came back is

01:38:16.180 they said that the protein people were never talking about food and snacks, but the people

01:38:22.340 on the high carb diet were always talking about being hungry and snacking. There's definitely

01:38:27.080 a different satiety and compliance issue to it.

01:38:31.080 I assume the fat was constant in that study.

01:38:33.500 First study, which was only 12 weeks, basically all subjects in both groups finished the study.

01:38:38.900 And the longer studies would got into four months and longer. We found much higher dropout rates in the

01:38:45.020 high carb group too.

01:38:46.880 So did the results of all three studies point in the same direction, which was that a higher

01:38:51.620 protein weight loss, so a protein sparing weight loss diet, which gets back to your point earlier,

01:38:57.000 stop thinking about protein as a percent of total calories. Protein should always be absolute.

01:39:03.800 And if you want to think about it that way, as you reduce calories, protein should increase the

01:39:07.680 total fraction of calories. Is going to preserve lean tissue better, maintain satiety better,

01:39:12.820 and plus there's potentially this bonus of the thermogenic effect of protein.

01:39:17.020 Right. It definitely partitions the weight loss toward fat, protects muscle,

01:39:22.060 lean tissue, definitely has higher satiety. One of the things we know, in fact, for a long time,

01:39:28.680 there was a lot of debate whether people over 60 should ever practice weight loss because they

01:39:33.700 would lose too much lean mass and they can't gain it back. Doug Patton-Jones had the theory that

01:39:39.680 sarcopenic aging isn't a gradual decline. It's a series of acute effects that you injure yourself,

01:39:47.760 you're in bed, you have a surgery, whatever. You acutely lose lean mass and you can never gain it

01:39:53.060 back. So we were concerned about that. We want weight loss, but we don't want people to lose

01:39:57.960 any lean mass, especially if they're adults. If you're a 20-year-old, it probably doesn't matter so

01:40:03.080 much. But if you're older, you're beyond 40, it does matter.

01:40:06.660 It's a scary thought, Don, if you think about it, right? 40 is not that old. And yet I recently

01:40:11.900 had shoulder surgery. The time that we're recording this, I'm probably about five months

01:40:15.480 out from that shoulder surgery. And I still have not gained back all of the muscle mass. Now,

01:40:20.700 I think I will gain it back, but I look at how difficult it has been and how acutely I lost it.

01:40:27.980 Within three weeks, I was 10 pounds lighter. I lost 10 pounds of body weight. And it's obviously

01:40:37.540 not just from the shoulder. It's when you don't have an arm, you can't squat, you can't deadlift,

01:40:43.040 you can't do all of these other things. So obviously some of that was water weight, but

01:40:47.560 I think seven of those 10 pounds was lean tissue that I lost in a span of three weeks.

01:40:51.920 There's some tremendous research by my colleague, Doug Patton Jones, who unfortunately passed away

01:40:57.380 this last year, who did a lot of that kind of bed rest sort of study and looking at older adults

01:41:03.360 versus younger. And in the same period of time, an older adult in bed rest will lose four times as

01:41:09.940 much muscle as a younger adult. It's frightening how fast you can lose it. And to your point,

01:41:16.060 if you're diligent and do weight training, you can begin to gain it back, but it's hard to ever get

01:41:21.640 back to ground zero if you lose it and aging. And people will ask me, well, all this leucine stuff,

01:41:28.020 when does it really come into play? It's not as important for a 20 year old as it is for 60,

01:41:33.120 but where's the middle ground? You know, where does it change? And I think it's a little like bone

01:41:37.800 health. Once you're 40, you're sort of on the back end of that and you need to be much more careful.

01:41:43.280 Doug and I ran a study, which everybody quotes now, where we took 90 grams of protein and looked

01:41:50.140 at it distributed as three meals per day, 30, 30, 30 versus 10, 20, 60. And we found that with the

01:41:58.040 same amount of protein, the same overall diet, you would have higher net protein synthesis with the

01:42:04.500 distribution to breakfast. So that's kind of where all the distribution data came from was that study.

01:42:10.060 We ran that study in 37 year olds. The average age was 37. So we think that by mid 30s, you can

01:42:18.200 detect the distribution effects. And just to be clear, Don, do you think that the reason 30, 30,

01:42:23.940 30 was better than 10, 20, 60, because you started the day at 30 or because you had three meals where you

01:42:32.500 cleared the hepatic threshold? That's a great question. And one that I wish the Twitter world would

01:42:37.900 understand, I think the effect is moving at the breakfast, the first meal. I think that frankly,

01:42:45.000 we'd have been better off. You should have done it 60, 20, 10 as the other arm, right?

01:42:49.700 No, I think it should have been 40. What's the math? 40, 10, 40. I think the first and last meals are the

01:42:56.460 key. And I'll give you the reason for that. We've done a number of studies in animals. Other people,

01:43:02.460 Mike Rennie and Phil Atherton have done it in humans. But when you trigger mTOR at that first

01:43:08.900 meal, we know that it's still stimulated five hours later. So why do you need leucine for mTOR at

01:43:16.480 lunch if it's still stimulated? You don't. So there's nobody has actually studied that at this

01:43:21.320 point. Unless you're the person who just is so big. Like if you're laying and you're 200 pounds and

01:43:27.380 you're a bodybuilder. But the key to what you just said is now you're talking total protein per day,

01:43:32.680 not a leucine effect. It's not a leucine TOR effect. There's not this threshold to it.

01:43:38.300 Total substrate. It's total substrate. It's okay. Lane needs 250 grams of protein per day. 0.99

01:43:43.600 He'd be better off putting that in four or five meals than putting it in two. So that's the difference

01:43:49.340 that people need to understand is that distributing across all the meals, if it's for weight loss and

01:43:55.180 appetite, that's great. But it's not an mTOR effect. So Don, this kind of brings me to something we've

01:44:01.040 talked about before, which is so much of this research that you've done has been funded by

01:44:05.520 industry. And a lot of people are going to say, well, we're going to discount everything Don just

01:44:10.660 said. So give us the names of some of the organizations that have funded your work over

01:44:16.160 the last four decades. So let me backdrop that for you. So I had the leucine concept that leucine was

01:44:23.160 going to be key to protein synthesis and muscle. We ran a study in the early eighties where we

01:44:29.680 realized it was initiations effect. We started looking for what those initiation factors were

01:44:35.740 going to be and it's EIF four. So we sent that as a proposal to NIH, National Institute of Health

01:44:42.300 for 10 years. It was continuously turned down and they said, well, we only study disease and we don't

01:44:49.960 know of any deficiencies of protein. So it's not a priority to us. And so basically, I was left with

01:44:57.500 what turned out to be a revolutionary idea of reinventing protein that NIH wouldn't fund.

01:45:04.600 I finally went to Kraft Foods, the National Cattlemen's Beef Association, the National Dairy

01:45:11.400 Association, American Egg Board, and some of the other groups who were inherently interested in protein.

01:45:18.460 We had some from the USDA. I was at a land grant university. So those were the funding sources

01:45:24.680 that basically unlocked all of this knowledge about protein for adults, leucine, mTOR, muscle-centric

01:45:33.660 health. All of that was unlocked simply because we could get funding from Kraft and beef. Am I biased?

01:45:40.540 You know, everybody who eats is biased in some way. If you look at research, and I think maybe

01:45:46.520 Lane said this with you, I never believe research when I read it until I see it in three more labs.

01:45:53.040 So I don't mind if people look at my research and say, I don't believe it. But my research has been

01:45:59.040 out there, very clear theories for 20 years now, and every test makes it stronger. And so that's how

01:46:05.800 you believe it. The fact that Kraft or beef funded, it's irrelevant. The issue is everybody who's ever run

01:46:12.000 the study after me shows the exactly same thing. Do you think NIH has, I know you've been semi-retired

01:46:19.040 now. You're kind of not really retired, but you're retired from the grant cycle.

01:46:23.100 Exactly.

01:46:23.820 But do you have colleagues that are still in it, or do you see any evidence that NIH has taken a broader

01:46:28.720 purview to health? If nothing else, they should be able to look at the fact that two-thirds of

01:46:35.640 Americans have metabolic syndrome. And that should at least give pause to think we might need to revisit 0.99

01:46:41.520 the way we're approaching nutrition. And therefore, maybe we should be funding

01:46:46.440 quote-unquote non-diseased research in nutrition.

01:46:50.500 I think they definitely have. Chris Lynch, who's director of nutrition at NIH now,

01:46:55.640 that position didn't even exist.

01:46:57.740 Is that within NIDDK? Where does that sit?

01:46:59.940 I think it's across multiple institutes. So which one actually funds the most? I think NIDDK might be

01:47:07.180 the one. The Cancer Institute. I think his unit actually goes across multiple institutes. But

01:47:15.100 again, that didn't exist back in the late 80s, early 90s. You know, I think it may be a little broader,

01:47:22.080 but there is a general philosophy still at NIH that NIH does not do applied food research,

01:47:30.860 that industry should fund it. So that becomes a catch-22. You know, if we're going to study the

01:47:36.700 difference between whey and soy, unless you can say, well, that's going to cure heart disease,

01:47:42.900 they're not going to fund it. And so you have to then go to the Dairy Council and say, I want to do

01:47:48.420 this study. And then people say, well, you were funded by the Dairy Council, or I'd go to the soy

01:47:53.760 board or whatever. It's a catch-22. But basically, the alternative is we put our head in the sand and

01:48:00.460 we don't do the research. I look at people in nutrition right now. And literally, I don't know

01:48:06.640 anybody in nutrition who doesn't get industry funding. It's just simply how you have to get funded.

01:48:11.900 One of the things I would also point out in this whole issue of bias, it's important to recognize

01:48:18.680 that the animal commodities are all under the USDA supervision because they are animal commodities

01:48:26.480 and they have checkoff boards. So that means everything they say in advertising has to be

01:48:32.040 screened. Where the grain industry has big companies like Kellogg's and Pillsbury and Coke and

01:48:39.320 Pepsi. And they can literally go out and say anything they want. And so you'll see a product

01:48:45.000 out there that pretends to be an egg and they'll claim that there's better than eggs, but egg can't

01:48:52.820 come back and refute it. So you've got two different playing fields, one that's highly restricted and

01:48:59.600 supervised and the other, which is fair game, you know, First Amendment, I can say anything I want.

01:49:04.320 On that topic, Don, how closely have you paid attention to both the plant-based meat and the

01:49:09.720 synthetic meats? I've paid a little bit of attention because obviously there's two companies

01:49:13.980 that are pretty popular. I can never remember their names. I think it's Beyond Meat and Impossible

01:49:18.420 Meat or something like that.

01:49:19.900 Exactly. Got it.

01:49:21.040 And they're plant-based meats. So they're making meat out of plant. And then you have a whole host of

01:49:25.860 companies, none of whom I can remember the names of, that are actually trying to make synthetic

01:49:29.260 meat. The little bit that I've read about that, which really amounts to reading like

01:49:33.000 two scientific articles, left me with the impression that that will not be technically

01:49:37.860 feasible. Just from an energetics, cost, mass balance, sanitation, GMP standpoint, that's not

01:49:45.420 going to happen. That's my way of saying either I'll be proven wrong or that will turn out to be one

01:49:49.520 of the biggest boondoggles of industry in some time. Do you have thoughts on either of those two,

01:49:54.660 including nutritional composition and how it feeds into an amino acid perspective?

01:49:59.140 First as an overview, I think that as the world continues to expand in population, we're probably

01:50:06.880 going to need additional protein sources. We may be near our capacity for animal-based protein. I don't

01:50:15.000 think we can double it again. So we may be near. So we're going to need other sources. So I accept that

01:50:20.560 plant-based proteins are important to us. I totally agree with your comment about synthetic proteins. I don't

01:50:27.280 think that will ever be economically or environmentally feasible. I don't think that's true. Then we get

01:50:34.160 into the popular versions of plant-based beyond burgers and things like that. And the reality is

01:50:41.280 it looks like a flash in the pan. People tried it. And basically, if you go to a Burger King and look,

01:50:47.540 they had a good sales for a few months and you track that it was all people who don't normally go to

01:50:53.280 Burger King. There was people who were interested in a plant-based burger. They went and tried it once

01:50:57.500 and never came back. So basically, we know the stock has fallen through the bottom now. We know that

01:51:03.680 nobody's using it. The problem with it is, let's take Beyond Burger. Basically, it's a pea protein

01:51:10.160 that's produced in Canada. It's shipped to China because we can't process it in the United States.

01:51:16.520 There's no processing for the most part. They're beginning to develop it. But when it came out,

01:51:20.820 there was none. Shipped to China. China processes protein, ships us back to the U.S. We know

01:51:27.140 transportation is the number one cause of greenhouse gas in the world. And so now we've shipped it all

01:51:32.480 over the country. Comes back to the U.S. and they process it into something with like 25 ingredients,

01:51:40.180 probably five or six of them are not FDA approved. And so now you have...

01:51:45.540 I wasn't aware of that.

01:51:46.420 They have multiple products. They have multiple components and synthetics that have never

01:51:50.700 really been studied and they're not FDA approved. So they're basically relying on safety without

01:51:57.060 ever proving it. Will that ever come back to haunt them? I don't know. In the spirit of having natural

01:52:03.040 foods, there's certainly not anything natural about them. Anyway, I think that plant-based proteins have

01:52:10.260 been around a long time. I think trying to pretend that it's meat, calling soy drink milk or almond drink

01:52:19.800 milk. I think those are travesties. I think those are standards of identity. Almond milk has,

01:52:26.160 what, one gram of protein per eight ounces, where cow's milk has eight. Calling that milk is pure

01:52:32.760 deception. And that's why there are lots... I love cashew milk, by the way. That's how I make

01:52:36.580 all my smoothies and stuff. My wife calls it nut juice. I do too.

01:52:40.240 You're going to have some of your nut juice?

01:52:42.240 Yeah. You know, I'm not against using them, but I think the consumer should...

01:52:46.200 I just think the nomenclature needs to be correct.

01:52:48.560 One of the examples I like to use is that if you look at a wheat cereal, pick any,

01:52:55.320 but take a wheat cereal that has four grams of protein per serving. We always said that's only

01:53:00.920 two probably. On the label, it says you mix it with three-fourths of a cup of milk. So now we have

01:53:07.100 10 grams. And if you look at the lysine balance of that, it's exactly balanced. But if you go to soy

01:53:13.660 milk, A, soy milk only has six grams per eight ounce per cup instead of eight, so now you already

01:53:21.220 have less protein. And it's also deficient in lysine. So it takes almost a quart of milk,

01:53:27.480 takes almost 30 ounces of milk to balance that cereal. So if you're a mother feeding this to your 0.99

01:53:33.400 child and thinking, well, I'm doing a plant-based thing, and I'm feeding them a totally deficient diet

01:53:39.520 diet with six ounces of soy milk for breakfast, I'm feeding them a totally deficient diet. How

01:53:45.640 many mothers know that? 0.94

01:53:47.160 Look, if I don't know that, I'm guessing a lot of mothers don't know that.

01:53:50.440 And so those are the kinds of things that we think need to come out about protein quality.

01:53:55.020 We want a system where we can show people an additive value and that at the end of it,

01:54:01.040 and I put that meal together, this is a company called WiseCode that I'm working with.

01:54:05.700 We think that we can show with using QR codes and your phone will simply add them up and you

01:54:11.820 can tell what your total meal looks like. Yeah, that would be incredibly helpful. As I alluded

01:54:16.700 to earlier, still something I have trouble with is doing it, especially on days when I don't have

01:54:21.840 access to as much meat. What it comes down to for me is just how much did I have from leftovers the

01:54:26.220 night before. So I've got a meat-based meal, which is my dinner. Wild game is sort of our routine,

01:54:32.620 right? So elk and venison and stuff like that. And if I'm smart enough and thoughtful enough to

01:54:37.240 make a lot extra, I can basically have it for breakfast and lunch the next day. But sometimes

01:54:41.720 I'm not. And then I'm making protein shakes. I'm eating a venison bar here and there, but it gets

01:54:46.580 a lot harder. And I'm having a hard enough time just making sure I hit the total grams per day of

01:54:51.640 protein. There's no attention on my end going into, hey, how much methionine is here? How much

01:54:57.440 leucine is here? How much lysine is here? If you've got 125 grams of protein in your diet per

01:55:03.400 day, chances are you'll hit those numbers. Where leucine is a meal-to-meal number, lysine is a daily

01:55:09.900 number. It doesn't matter meal-to-meal. It's a total. Yes, for me, that's probably okay. But then I think

01:55:15.840 about it for my wife or my female patients where it's hard to get them up to 120 grams per day. 0.95

01:55:22.880 We struggled with all of the adult women we had in our studies. We had whatever, 300, 400. It's a 0.99

01:55:30.220 real struggle to keep a female at 100 grams of protein per day. It's just a struggle. Then quality 1.00

01:55:36.560 becomes an issue. That's my concern with the whole plant-based movement is that do people have the

01:55:43.280 resources? Can you make that healthy? Sure you can. But you, A, need a lot of knowledge. You need a lot

01:55:50.080 of food skills and you're going to have to eat synthetic products because you can't get it from

01:55:55.600 eating, you know, lentils and rice. You just can't eat enough of them. And so you're going to have to

01:56:01.560 have shakes or supplements or something to get to that kind of level. Otherwise, the track record says

01:56:08.680 that vegetarians will end up somewhere in the 60s for their protein per day. And quality does make a

01:56:14.580 difference at that level. Well, Don, this has been really interesting. I'm so glad that we were

01:56:19.540 introduced. I can talk about protein all day because it's an eternal interest of mine personally,

01:56:24.540 but also in terms of helping as many of my patients as I can. It's not the macronutrient that gets the

01:56:29.820 most debated on Twitter. That's reserved for carbs and fat. But this is the one that I think we need to

01:56:34.720 be paying more attention to. So I'm grateful for the work you've done and for the attention you brought

01:56:39.400 to it today in our discussion. I appreciate the opportunity to do that. One thought I'd leave you

01:56:45.180 with that we haven't touched on is people talk about high protein. And I think it's important to

01:56:50.500 try and come to grips with what that means. If you look at all of the epidemiology, which I think is

01:56:55.800 pretty bad science, the definition of high protein is about 1.2 grams per kg and low protein is actually

01:57:04.580 below 0.8. And so a lot of them will express it as percentage of calories and they'll say less than

01:57:10.820 10%. And so when you look at the epidemiology, you need to realize they're talking about very

01:57:16.640 narrow ranges of protein intake. And it really isn't the protein that's making a difference. It's the

01:57:22.340 calories and the other things that are going with it. One last thought for four years, I was director

01:57:28.560 of research for the American Egg Board. So I funded all of the research that basically got the

01:57:34.200 cholesterol direction eliminated from our guidelines. One of the things we funded though, was there was

01:57:41.480 a lot of research suggesting that eggs had a high correlation with obesity and diabetes and heart

01:57:47.440 disease. And so we funded some research with Teresa Nichols and Vic Vergoni, who are experts in the NHANES

01:57:54.780 data. And what they looked at was that in the epidemiology, the difference between the first

01:58:00.340 quartile and the last quartile for egg consumption was three to three and a half. So they were basically

01:58:06.260 saying that a half an egg per week was a difference in causing obesity, heart disease, and diabetes.

01:58:12.520 And so what they did was they went into the NHANES data, and they factored out all of the eggs that were

01:58:17.660 eaten at fast food, versus the eggs that were just eaten at home in a quote, good nutrition setting.

01:58:23.500 And what they found is in every case, eggs now became a positive. They reduced obesity,

01:58:28.820 they reduced. So basically, it's not the egg, it's the egg in the company it keeps. And you can make

01:58:34.920 anything a bad diet.

01:58:36.720 To your point, when we talk about epidemiology pointing at high protein being a problem,

01:58:43.360 you realize anybody who's tried to actually consume high protein realizes it ain't high protein,

01:58:49.140 it's high calorie, that's the problem. And the protein is along for the ride. Because again,

01:58:54.540 1.2 grams per kilo is actually kind of low protein in the context of a high calorie diet.

01:59:01.860 If you look at epidemiology, and you do any food surveys, what you realize right away is that the

01:59:08.620 data for protein is pretty good. If I ask you how many eggs you ate yesterday, you'd give me the

01:59:14.120 number. If I ask you how many ounces of milk, or how many grams of meat you'd give because we sell

01:59:19.640 those by ounces and weights. But if I ask most people how many carbs they ate yesterday, they'd

01:59:25.760 miss it by 200 grams. And so that's the problem with epidemiology is that the errors are not

01:59:34.520 homogeneous. They're not equal. So anyway, I ramble on but a great pleasure to chat with you, Peter.

01:59:41.120 Thank you, Don. This was fantastic. Thank you for listening to this week's episode of The Drive.

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The Peter Attia Drive - September 26, 2022

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

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