The Peter Attia Drive - #299 ‒ Optimizing muscle protein synthesis： the crucial impact of protein quality and quantity, and the key role of resistance training

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

00:00:16.540 my website, and my weekly newsletter all focus on the goal of translating the science of longevity

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00:00:53.200 of the subscription. If you want to learn more about the benefits of our premium membership,

00:00:58.020 head over to peteratiyahmd.com forward slash subscribe. My guest this week is Professor

00:01:05.980 Luke Van Loon. Luke is a professor of physiology and exercise and the head of the M3 research unit,

00:01:13.660 which is a part of the Department of Human Biology at the Faculty of Health Medicine and Life Sciences

00:01:19.480 at Maastricht University. He is internationally renowned for his research that is focused on

00:01:24.500 skeletal muscle metabolism in humans, and he is focused on four main fields of interest,

00:01:31.000 which include skeletal muscle metabolism, exercise metabolism, sports and clinical nutrition,

00:01:36.680 and aging. I first came across Luke when I saw a video from a lecture he gave many years ago,

00:01:43.200 and it's not common that I'm watching a video of somebody talking about protein,

00:01:47.440 where I'm actually stopping and watching it for great lengths because I'm actually learning

00:01:52.740 something. So I immediately became hooked, became more and more familiar with his work,

00:01:57.000 and ultimately wanted to have him on the podcast. Luke received his PhD from Maastricht University

00:02:01.160 in the Department of Human Biology. Subsequently, he did an internship at the Department of Kinesiology

00:02:05.840 and Health Education right here in Texas at the University of Austin, though long before I got here.

00:02:10.860 And then he did a couple of postdoctoral fellowships, one in Australia and one back at Maastricht University.

00:02:17.020 He is also the associate editor of the International Journal of Sports and Exercise Metabolism and is

00:02:21.920 on the editorial board of the European Journal of Sports Science. In this episode, we talk about

00:02:26.440 the role of insulin and glucose for endurance exercising. We talk about the role of protein

00:02:32.040 in all of this. We speak about how different types of proteins in different forms will foster muscle

00:02:38.540 protein synthesis in different rates. So we talk specifically, of course, about the absorbability,

00:02:44.120 digestibility, amino acid quality, and other features there. Of course, we talk again

00:02:49.180 in length about some of the different types of protein. First of all, the difference between animal

00:02:54.300 sources and plant sources. But using probably more helpful designations than that, we get into

00:02:59.720 even specific types of protein. So for example, even if you're talking about milk-based protein,

00:03:04.560 what are the differences between whey and casein? And we also talk about the use case,

00:03:08.960 if at all, for collagen protein. Talk about how protein digestion is impacted not just by the

00:03:15.220 type of food, but even by the preparation of the food. And we cover the relationship between activity,

00:03:19.600 lean mass, building muscle and protein from resistance training, and the role that protein

00:03:23.660 specifically plays in that in terms of timing and type of protein. So without further delay,

00:03:29.200 please enjoy my conversation with Luke Van Loon.

00:03:37.300 Luke, thank you so much for being here. I know it's evening time for you. And as we were talking

00:03:41.260 a moment ago, I think there's a decent chance we're not going to get through all of this. You laughed

00:03:45.820 when you saw my agenda of topics. So maybe we will have a little Austin reunion. We'll do the next one

00:03:52.140 in person here in Austin. But let's give folks a little bit of a bit of your background. You have quite

00:03:57.180 a storied resume. Can you give us a little bit of the highlight?

00:04:00.280 Yeah. As many people, I didn't know where to go to college. As most of us exercise physiologists,

00:04:05.840 we're all field athletes. So we want to know how our genetics can be actually just compensated for

00:04:13.440 by science. And so I wanted to do movement sciences. So I studied movement sciences here

00:04:18.960 in Maastricht, the Netherlands. After that, I went to Austin, Texas for my master internship to work with

00:04:25.120 Jack Wilmore, who people in exercise physiology will obviously know at UT. After that, I finished

00:04:31.600 did my PhD in Maastricht again. Then after that, I went to Melbourne to work with Mark Hargraves,

00:04:38.020 also well known to most people in this field, spent some time in Melbourne, and then came back and

00:04:43.140 actually did the rest of my career here in the Netherlands. So from assistant prof to associate and

00:04:48.760 to prof here. And that's already been like, I don't know, 13, 14, 15 years ago.

00:04:53.180 Today, we're going to not talk so much about the movement stuff, although that would be obviously

00:04:57.220 very interesting. And our audience, I think, would appreciate that as much as what we're about to

00:05:00.860 talk about. But we're going to talk more on the nutrition side of things. We're going to talk

00:05:05.540 specifically and in great detail about protein. But that's, if I'm reading your CV correctly,

00:05:10.540 not necessarily the first foray into nutrition that you took, correct?

00:05:15.460 No, that's correct. So my main interest was in the beginning, and also my PhD was in fuel selection.

00:05:21.240 So substrate selection during exercise. And of course, most of that stuff is done during endurance

00:05:26.820 type exercise. And if you're thinking about substrates, you of course are not thinking about

00:05:31.460 protein, which is from a quantitative point of view is not a very good substrate. So it's

00:05:35.920 carbohydrate fat metabolism. And most important or most interesting thing for me at that time was that

00:05:42.280 they had set up a stable isotope research facility here. So you could track metabolites.

00:05:48.440 The first things that that lab did is actually measuring carbohydrate oxidation rates.

00:05:54.820 So you would simply throw in some stable isotope labeled carbohydrates in your drink.

00:05:59.940 And by simply the oxidation of those carbohydrates, and you would actually expire, exhale 13 CO2.

00:06:07.660 Because then if it's labeled with 13C, you get 13 CO2 after you oxidize it. And by simply

00:06:13.340 acquiring your expired breath, you can actually calculate how much of your energy came from a

00:06:18.980 sports drink. Now, that was so cool for me at that time.

00:06:21.580 Just to be clear, you would also need to know the amount of oxygen consumption to be sure

00:06:27.160 that that CO2 came from glucose and not from fat, correct?

00:06:31.260 Yes. So it's a combination of indirect kilometry. So that's total oxygen uptake, total carbon dioxide

00:06:37.600 production combined gives you total energy expenditure and also total oxidation of

00:06:42.540 carbohydrates and fats. And then because you know what percentage of the carbohydrate derived CO2 was

00:06:50.420 expired by 13 CO2, you could calculate back how much of the carbohydrate is coming from your drink.

00:06:56.300 And that is cool because then you'll see how much of the drink are you actually using.

00:07:00.280 Now, it's interesting, Luke, that there's a method obviously that uses deuterated water and C13,

00:07:05.840 doubly labeled water, to measure energy expenditure in a free living environment over a long period of time.

00:07:11.320 Is the method you're referring to only using labeled carbon and therefore only suitable for a short period of

00:07:18.100 time to evaluate glucose oxidation? Or do you also label oxygen and potentially get energy expenditure

00:07:25.420 over a long period of time?

00:07:27.040 If you use doubly labeled water, you can actually do that over several days. You need several days in

00:07:32.580 order to do that. So this is really a way of you're getting carbohydrates in, you start oxidizing them,

00:07:38.700 that CO2 is also mixed in your blood. So it takes a while before the expiration of labeled carbon is also

00:07:45.640 a good proxy for the amount of carbohydrates that you're oxidizing. So it takes about two hours,

00:07:51.840 they are in a nice steady state. That's why we're measuring endurance athletes, of course.

00:07:55.920 And then for one or two hours, you can measure the oxidation rate. So that's only for exercise trials,

00:08:00.640 for example.

00:08:01.700 And did this tend to be more accurate than the estimate you would get of carbohydrate,

00:08:08.780 oxidation rate, just using the indirect calorimetry and the Weir equation? Or was the point here

00:08:14.940 to determine not total carbohydrate metabolism, but specifically how much is coming from the drink?

00:08:19.940 Exactly. Exactly. So the basis is still in the red calorimetry. So respiratory exchange ratio,

00:08:25.800 and then from the carbohydrate oxidation, you can see how much of that carbohydrate is coming from

00:08:31.300 your drink.

00:08:32.040 Got it. Versus glycogen, for example.

00:08:34.400 Exactly. So you have your glycogen coming from your liver. You have your glycogen coming from your

00:08:39.660 muscle. You can actually detect that with an intravenous glucose tracer with a different label.

00:08:43.820 And then you have your 13C label in your drink. So you can actually see all three substrates.

00:08:49.520 So you can see what is coming from the drink, what is coming from your muscle glycogen,

00:08:54.680 and what is total coming from your plasma glucose, which includes, of course, the drink,

00:08:58.940 but you can subtract that from total. And then you have all three different sources.

00:09:03.400 And of course, that was not enough for us. So we also wanted to know what fatty acids are being

00:09:08.840 used from your intermuscular triglycerides, so the fat inside your muscle fibers, and what is coming

00:09:14.780 actually from the fat tissue that is releasing fatty acids, and then transported to the circulation

00:09:20.400 and taken up in the muscle. Because that is also an important topic for athletes, but as we will

00:09:25.320 probably touch upon later, also, for example, diabetes patients.

00:09:29.660 Well, it's not going to be possible for me to just leave that one alone, Luke, and jump into protein,

00:09:34.440 because I got to understand, especially for my own selfish needs, as I'm preparing for kind of a

00:09:41.500 long distance endurance thing. I thought my long endurance days were behind me, but I do have one

00:09:46.120 more very long endurance event that's going to take about 20 hours coming up in a few months. And it's

00:09:51.540 been so long since I've thought about how to prepare energetically for something like this. And I really

00:09:57.940 believe, at least based on my history, that nutrition can make or break you in these 20-hour

00:10:03.840 marathon events. So tell me some of the things that you learned in studying, even though I know you

00:10:10.640 are only studying it only, you know, over two hours. But what did you learn about, for example,

00:10:16.220 the rate of carbohydrate metabolism, muscle glycogen, liver glycogen in the steady state?

00:10:23.360 So I thought we already had quite a list, but I think-

00:10:25.900 Just added something to it.

00:10:28.820 No, so one of the most important things is basically all the glucose that is extra coming in

00:10:33.460 your circulation will be used for oxidation during exercise. So a continuous supply of glucose coming

00:10:40.880 from your gut is a good idea to save your liver glycogen, to keep your liver glycogen intact, or at

00:10:46.920 least not to deplete it too fast. And so if you can maximize that, and of course, we know that with

00:10:52.660 glucose or glucose polymers, that is about at a rate of 1 to 1.1 grams per minute, so about 60 to 70

00:11:00.220 grams per hour. However, it can be a little bit higher if you actually add some fructose,

00:11:05.860 because fructose requires a different transporter. So if you combine both glucose or glucose polymers

00:11:11.980 with fructose, you actually can get a little bit higher, but that's only for really the high-end

00:11:18.300 athletes that can actually gain that high energy expenditure. Then you can maybe go to 1.3,

00:11:23.820 1.4 grams per minute. And so that would be the ideal from the carbohydrate point of things.

00:11:29.240 But of course, if you're doing a 20-hour endurance event and you're well-trained,

00:11:34.000 you'll actually be using quite a lot of fat because that's what you're training for.

00:11:38.400 And in that case, you require your fat stores in your muscle, as well as in your, yeah, I mean,

00:11:43.880 you already have enough fat stores in your fat tissue, of course, because theoretically,

00:11:47.880 if you're a 70-kilogram weighing lean man, you can run for almost, I think so, what would it be,

00:11:55.460 probably three days or something like that, 24 hours? Of course, that is only theoretical.

00:12:00.560 But it's obvious that the amount of fat inside your skeletal muscle tissue is also very relevant

00:12:06.100 because, I mean, you know, you appreciate that your muscle glycogen storage increases as you become

00:12:13.200 a better endurance athlete or a better athlete on itself. The same goes for intermuscular triglycerides.

00:12:19.780 Just to clarify one thing, Luke, because people who listen to this podcast may remember,

00:12:24.880 gosh, it was a couple of years ago, I had Gerald Schulman on from Yale. Jerry's one of the world's

00:12:29.860 experts on insulin resistance. And we spoke there about the mechanism by which intracellular fat,

00:12:36.900 or it was actually diacylglyceride, not triacylglyceride, within the cell was one of the

00:12:42.840 hallmarks of insulin resistance. But I think you're talking about something different here.

00:12:47.580 Are you talking about triglyceride between the muscle cells and not in?

00:12:52.900 No, this is actually, I mean, you will actually appreciate that as a physician as well.

00:12:57.500 So a lot of the clinical work is done by clinicians and people that focus on the clinical work. The

00:13:04.220 exercise physiologists focus on the exercise work and sports or sports supplements. You do notice that

00:13:10.380 a lot of work that has been done in the two fields does not get used by either side. So when I was

00:13:17.280 doing substrate metabolism muscle and the selection and how that is organized and regulated, first,

00:13:22.680 I was interested, of course, in carbohydrates, because during moderate to high intensity exercise,

00:13:27.300 from a quantitative point of view, that's the most important substrate source.

00:13:30.800 And so as exercise intensity increases, you depend more on your endogenous carbohydrate stores.

00:13:37.380 But what you can see is during moderate intensity exercise and lower, much of the fat is actually

00:13:42.620 being used by athletes. And that increases also during higher intensity exercise as you become a

00:13:47.680 better athlete. So as a good athlete, you get the same exercise intensity, even the same relative

00:13:53.000 exercise intensity, you can oxidize more fat. And that is the benefit because you need less of your

00:13:58.920 limited stores of carbohydrates. Now, the body of an athlete or the muscle of an athlete adapts to

00:14:06.040 store more glycogen. But it also adapts to store more fat inside muscle fibers. And that's

00:14:12.440 intramicellar lipids. So that's really inside the cell lipid droplets that you see in a muscle fiber. So

00:14:18.160 in these days, I was actually cutting muscle biopsies up, looking under the microscope. And if you actually

00:14:23.860 see them, you see those individual fibers, a lot of lipid droplets. It looks like you're looking at a

00:14:28.580 soup from the top, and you see those little droplets floating around. Now, that is a storage

00:14:34.160 that is ample use by athletes. And Hans Hoppler in those days was one of the first to do electron

00:14:41.300 microscopy pictures of that. And if you then look inside one of those lipid droplets, you see that

00:14:47.040 on most of those lipid droplets, there's a mitochondrion attached to it. It's like a backpack.

00:14:51.960 It's like the mitochondria is the backpack of a big lipid droplet. And so we started, and I think we

00:14:58.440 were running the first, to start measuring how much of that lipid inside the muscle, inside

00:15:04.020 the muscle fibers, is being used during exercise. And we did that using those stable isotopes

00:15:11.160 indirectly, but also by taking muscle biopsies before and after exercise, and looking at the

00:15:17.320 number and the size of these small lipid droplets. And that goes down. So athletes use a lot of the

00:15:23.720 intramylocellular lipid for their energy provision, and particularly in the beginning of exercise.

00:15:29.880 And then you think like, hey, this makes sense. When you start exercising, all your lipolysis in

00:15:35.680 your fat tissue takes time to get that process going. Perfusion, lipolysis.

00:15:41.180 Yeah, this is almost immediate access, prime the pump.

00:15:44.480 Exactly. Yeah. So just to be clear, I was never aware of this, that you could actually see

00:15:50.300 mitochondria on the fat droplets within the cell of the muscle. Would this be a fundamental

00:15:57.180 distinguishing feature between the muscle cell of an athlete and the muscle cell of somebody

00:16:01.720 with type 2 diabetes, which will also have fat within the muscle? Will it simply not have the

00:16:07.320 mitochondria and therefore not be turning to it as an energy source out of the gate?

00:16:11.220 Very likely. I've never seen electron microscope pictures of that because it's difficult to

00:16:15.860 quantitate that because there's so many lipid droplets, so you can't make it quantitatively.

00:16:20.180 But we actually, and exactly what you said, there were also other people in our university and our

00:16:25.540 department looking at diabetics. And then I started to be interested in, hey, what's the difference?

00:16:31.920 Because if you compare an endurance train athlete and a diabetic, they both have huge

00:16:36.820 intermicellar lipids. And the difference is, the athlete uses it, depletes it, builds it up again,

00:16:45.080 but the diabetic doesn't. And if we actually exercise the diabetics, they were not really using

00:16:50.400 that intermicellar lipid. And that makes perfect sense because why? Because their blood is full

00:16:56.320 with free fatty acids. So the muscle is not going to use those limited stores in the muscle

00:17:01.600 because it's constantly getting free fatty acids from the circulation. So in the diabetics,

00:17:06.580 it's a permanent storage with very little turnover, while in the athletes, it's a substrate source that

00:17:13.420 is constantly being used. And so the use, the turnover of that substrate is the important factor

00:17:19.340 driving towards insulin resistance or actually insulin sensitivity.

00:17:23.600 Yeah. I remember reading a paper 12 years ago that very erroneously came to the conclusion

00:17:32.360 that athletes on a ketogenic diet who had high amounts of intramyocellular lipids were insulin

00:17:41.200 resistant. And I was shocked because I couldn't believe they could fail to look at turnover rate

00:17:47.080 and actually differentiate a static from a dynamic process. This is obviously a more important

00:17:53.340 example and a more relevant example. Yeah. One of the fun things that we actually did is we saw that

00:17:58.460 athletes in the beginning use a lot of intramyocellular lipids, but in the second stage of their

00:18:03.460 endurance exercise, they stopped using them. And then we thought like, strange, why is that?

00:18:07.920 But it actually happens when your free fatty acids in the circulation go up. And it makes a sense,

00:18:12.860 of course, by the time that your adipose tissue is constantly actually feeding free fatty acids,

00:18:18.560 you're not using that storage depot anymore in the muscle. So as soon as free fatty acids went up,

00:18:24.260 the use of intramyocellular lipids went down. And then we thought like, hey, what would happen

00:18:28.980 if we reduce the free fatty acids in diabetics during exercise? And we actually gave them a sippamox.

00:18:36.040 So it's something that blocks adipose tissue lipolysis. So in the diabetics,

00:18:41.580 the free fatty acids would not go up anymore, they would actually go down. And they suddenly

00:18:46.200 started using the intramyocellulipids. And that improved post-exercise insulin sensitivity.

00:18:51.940 So it's a very nice way to stimulate the turnover of the intramyocellulipids. And it's probably one

00:18:58.280 of the mechanisms that makes insulin sensitivity improve after exercise.

00:19:03.840 What role does insulin play in accessing the intramyocellular fat store? So obviously,

00:19:10.660 insulin plays, along with maybe hormone-sensitive lipase, the most important role in determining

00:19:16.820 the rate of esterification versus lipolysis in the fat cell. And obviously, we know the role

00:19:22.360 insulin plays for glucose into the muscle cell. Obviously, there is also a non-insulin-dependent

00:19:29.560 glucose uptake. But where does insulin, if at all, factor into both the athlete and the diabetic

00:19:35.540 with respect to how fat is getting into and out of the muscle or into the muscle and then oxidized?

00:19:42.900 So insulin, of course, also stimulates fatty acid uptake. But if we're talking in an exercise

00:19:47.300 setting, insulin doesn't play a whole important role anymore during and immediately after exercise

00:19:52.600 because the stimulation of your AMPK pathway also stimulates glucose uptake. As you know,

00:19:58.540 the GLUT4 transporters are actually translocating to the outer membrane.

00:20:01.740 Insulin-dependent or exercise-dependent, two separate pathways. For fatty acids, it's even

00:20:07.600 a lot more difficult because the free fatty acids, a lot of it is actually facilitated diffusion.

00:20:13.300 Yeah, I was about to say, because the membrane is fat-soluble, I was going to ask you how

00:20:17.740 I assumed it was just going to diffuse through with a gradient?

00:20:21.520 A very chance finding. We were just a lucky finding on the side of the study.

00:20:25.060 When we were measuring depletion of intramyacel lipids in the leg in a non-invasive way using

00:20:31.300 MRS, magnetic resonance spectroscopy, we did that in the leg. But just for fun, we also measured the

00:20:37.420 arm. And of course, you're not cycling with your arm. So we did an MRI before and after exercise.

00:20:44.100 And of course, the fat in the muscle went down in the legs, but it actually increased in the arm.

00:20:48.640 So simply, the greater turnover, the greater flux of free fatty acids in inactive muscle,

00:20:54.040 it actually increased the amount of intramyacel lipids. A lot of it is not regulated.

00:20:58.660 Yeah.

00:20:59.340 The muscle is not that intelligent. The muscle just takes what it can get. It's very opportunistic.

00:21:04.480 Yeah. This is incredibly fascinating. What do we know about the endurance athlete's capacity

00:21:10.040 to consume fat and during a steady state exercise? So for example, if a person is doing,

00:21:17.280 again, I'll just be selfish and use my own example, right? If I'm doing a 20-hour activity and let's

00:21:24.040 just say energy needs are going to be relatively low because the energy expenditure is, let's just

00:21:28.840 say we're requiring 500 kcal per hour. So we could almost meet that through ingested glucose. That

00:21:37.500 would be 1.25 grams per hour. But truthfully, that would be sort of punishing on a GI system for 20

00:21:44.080 hours. So you'd want to sort of potentially maybe limit that to 30 grams per hour of carbohydrate,

00:21:51.000 which would meet about half those needs. Would you say, look, you're very likely going to need

00:21:58.040 nothing else because the remainder of that will be met through endogenous fat stores and a little

00:22:03.080 bit of endogenous glycogen? Or would you say, no, you could prime that with a little bit of

00:22:07.800 additional substrate that is presumably fatty acid?

00:22:10.780 Yeah. I mean, that's a difficult question, of course, because nobody's done a lot of work in

00:22:15.340 long-term, I mean, that long-term endurance type activities. But after I've done, and this is

00:22:21.400 always fun if you do nutrition research, first you start with carbohydrate-related research because I

00:22:26.000 thought the be-all and end-all of everything is liver and muscle glycogen. But then you start looking

00:22:31.620 at, oh, the intramuscular triglycerides are an important substrate source as well. What happens if you

00:22:36.780 deplete them after a few hours of exercise? And how fast do you replete them? Because if you were

00:22:42.180 to do a next session with depleted intramuscular triglycerides, you wouldn't have that prime that

00:22:47.540 you're referring to. So repleting, that is also important. And then we realize that only carbohydrates

00:22:53.300 is not enough. You also need fat. And of course, now that I'm actually doing a lot of research in

00:22:59.820 protein, we now know that we also need protein. And then we're back to food. But that's another

00:23:05.340 discussion. Let's talk about that. Let's talk about your transition. I could sit here and pick

00:23:10.020 your brain all day on the carb and fat issue. But how did your own interests transition you

00:23:16.220 towards protein metabolism? So just going slightly back to your last question,

00:23:21.340 because I think you're asking also a practical question for yourself. So when we saw that fat was

00:23:26.460 important in the muscle, we started also looking at post-exercise fat repletion. So you have enough fat

00:23:32.660 to provide enough fatty acids during that long, the 20-hour endurance event. But I think you should

00:23:37.820 not start doing that with too low of an intramuscular fat level. And when we started talking with ultra

00:23:43.540 endurance athletes, they were actually proving me right. But even though there's no data,

00:23:48.700 they were saying like, look, I can't really perform in several day events, so multi-day events,

00:23:53.780 if I don't eat enough fat. And that's maybe because of the intramuscular lipid storage that you want to

00:24:01.160 replete between several days. And it takes one or two days to replete it. So if you do more of these

00:24:07.920 20-day events back to back, then the fat repletion is important. For a single event, I would think it

00:24:13.760 wouldn't be that important. Do you have a sense we do tend to quantify glycogen capacity? We would

00:24:20.180 say maybe a healthy, athletic, reasonably sized male would have 100 grams of glycogen storage capacity

00:24:27.260 in the liver, three to 350 grams in the muscle. I'm sure there are athletes even higher. Do you

00:24:32.360 have a sense of what those numbers are like in the muscle for how many grams of fat could be stored

00:24:37.880 in the muscle of a healthy athlete? No, it's way less than that. I think there were estimates and

00:24:43.600 now I have to really think because I'm going back 20 years. I think it was also around like 100,

00:24:49.640 200 grams. But that's still a lot because of the caloric density of fat being higher. I mean,

00:24:55.820 that's functionally as many calories as you would have from glycogen.

00:24:59.640 Yes, but I think the calories are not important. The most important, but the priming dose to actually

00:25:05.600 cover from activating the adipose tissue towards having enough free fatty acids in the circulation.

00:25:12.680 And that takes about half an hour, 45 minutes. And that's where it's important.

00:25:18.260 Last question on this topic. I know I said we would leave it, but this just reminded me of something

00:25:22.160 else, which is what does the window of time look like in which an athlete has the greatest opportunity

00:25:29.900 to replenish intramuscular fat stores and intramuscular glycogen? Presumably it's a window

00:25:36.920 following exercise. How long does that window remain open?

00:25:40.980 First, I mean, they don't know exactly, but within about the first four or five hours,

00:25:45.340 we see that insulin, that glucose uptake is less or almost not insulin dependent.

00:25:52.100 So basically the more carbohydrates you ingest, the more it goes into the muscle. But then as your

00:25:57.960 glycogen levels increase, then you get a break on glycogen deposition. So glycogen storage is

00:26:05.740 inhibited simply by its content. So it's a self-limiting process, which is great because if you don't,

00:26:11.680 you actually have a muscle disease. So the first few hours, all the GLUT4 transporters are in the

00:26:17.960 sacral emma. So all the glucose that comes into circulation gets sucked into the muscle.

00:26:23.080 Meaning just the contraction of the muscle alone during exercise is getting that GLUT4 transporter

00:26:28.520 into the membrane without the need of insulin and it's open field running for glucose coming into the

00:26:36.380 cell. Exactly. And that's one of the reasons why exercise is so good for maintaining glucose

00:26:43.460 homeostasis. It's not only the total amount of muscle, but especially the way you use the muscle.

00:26:49.760 I mean, the easiest way to actually cruise through your glucose tolerance test is before you go to

00:26:54.560 your GP, you actually run for two hours because then you'll have the lowest OGTT that you'll ever see.

00:27:00.200 Yeah, I did that actually once just as a test. I wanted to see how insulin sensitive I could make

00:27:07.300 my muscles before a two-hour OGTT. And I don't remember the exact results, but it was astonishing.

00:27:15.540 Glucose at the start is maybe 80 milligrams per deciliter, 30 minutes in an hour and two hours later,

00:27:21.060 it never went above a hundred milligrams per deciliter in glucose. But also to your point about the

00:27:26.740 insulin independence, I don't think my insulin went above 11. Even a fasting insulin above 11 is not

00:27:33.700 uncommon. So yeah, that's a very interesting experiment. What about the fat window? Is that

00:27:38.300 also about a four-hour window? For those of you interested in that insulin effect, I mean,

00:27:43.180 that goes up to 24 to even people have shown 48 hours after. And that is the reason why nowadays

00:27:49.160 for exercise for diabetics, they say 150 minutes of exercise throughout the week, I would think that's a

00:27:55.760 minimum. That's the advice, but at least every other day. And at least every other day is because

00:28:01.920 every session improves your glucose homeostasis for up to 24 hours. So if that exercise is actually

00:28:08.300 every other day, you maximize benefits from the exercise with each and every meal that you ingest

00:28:13.700 afterwards. For fatty acids, it's actually less difficult because it doesn't seem to be tightly

00:28:18.140 regulated because of the facilitated diffusion of your fatty acids. But of course, if you're an athlete

00:28:23.000 and you're consuming a huge load of carbohydrates, especially also during exercise, of course,

00:28:28.400 you're going to limit your lipolysis. And then you have less fatty acids. So the only thing that we

00:28:34.500 really did, that doesn't seem to be a short frame. It's just constantly going. It seemed like up to

00:28:40.820 about 48 hours, the fatty acids, the intermicellal lipid was almost at the same level again.

00:28:47.200 And just to be clear, are you saying that most of the filling of the muscle with fat

00:28:54.460 will come from endogenous fat stores via lipolysis? Or is there a role for exogenous,

00:29:02.280 i.e. dietary fat in the post-exercise phase to boost that further? And I understand your point,

00:29:08.240 but I want to make sure the listener understands that the relationship between carbohydrate ingestion

00:29:13.020 and lipolysis is very clear. The more carbohydrate you ingest and the higher insulin goes, the more

00:29:18.260 you inhibit lipolysis, which is the breakdown of fat from the stored fat cell. But with that

00:29:23.640 explanation out of the way, does my question make sense for you about the source of the fat?

00:29:28.740 Yes. So in a well-trained athlete, about 50% of the fat oxidation during exercise

00:29:33.700 comes from your intramuscular triglycerides. And the other 50% comes from free fatty acids released

00:29:39.800 from your adipose tissue transported to your blood taken up. Now, the only studies that we've done

00:29:45.380 here was with fat supplements during exercise, because there's not much reason to take fatty

00:29:50.300 acids because there's enough fatty acids being released from your adipose tissue. We did play

00:29:54.460 around, and that was Oscar Juerkender actually playing around, with medium-chain triglycerides.

00:29:59.860 So medium-chain triglycerides are actually smaller fatty acids. The tail is less long,

00:30:05.720 and they can be actually transported directly into the mitochondria. So they don't need the

00:30:10.920 CPT1 facility of transport. So we thought that was nice to get a faster oxidation labeled substrates.

00:30:19.400 They show that the medium-chain triglycerides, even during high-intensity exercise, are really

00:30:25.840 oxidized. And the idea was that could save carbohydrate use, so that you can maximize fat

00:30:32.420 use during high-intensity exercise, and therefore spare glycogen and improve performance. Now,

00:30:38.540 basically, it worked with MCTs, but then we tried to see whether we could make it quantitatively

00:30:43.780 interesting, and then almost everybody got diarrhea. Yeah, I was about to say, the big challenge with

00:30:50.260 getting sufficient enough MCT volume is the gastrointestinal distress. And I think for most people,

00:30:57.780 at least if consuming it in a pure oil form, 30cc is really pushing it. I mean, when I was hard on MCT oil

00:31:08.680 back in the day, this is 12 years ago, I could do two tablespoons of MCT. So whatever, how many

00:31:16.280 ever milliliters that is. That said, and I haven't done this, but I do see other products out there that

00:31:22.140 are somehow lawfulizing the MCT. They're almost putting it into a powder form. Have you seen any

00:31:28.300 of these things? Yeah, I've seen suggestions that there's a lot of MCTs or MCT-like products that

00:31:34.360 presumably have less issues on the gastrointestinal tract. Yeah, I haven't used them, and I haven't

00:31:40.200 used them in research. Still, I would contemplate, like, in what amounts do they actually contribute

00:31:46.360 substantially so that it improves performance? And I think as long as you can actually reach your goals

00:31:51.960 with carbohydrates, why would you play around? But yeah. Is there a role for MCT oil immediately

00:31:57.580 following exercise as a very quick, rapid source of fatty acid in the muscle? Or are you saying no,

00:32:04.580 because right after exercise, your insulin is so low, just let the lipolysis fill the tank? Why

00:32:09.360 would you bother adding? We all want to lose a little bit of adipose tissue anyway, right?

00:32:13.920 Yeah, I think so. I agree. I'm a nerd, of course. So I love to see what is happening,

00:32:18.200 but I don't think it has any relevance in practice. Okay. So with that very interesting

00:32:23.620 detour out of the way, let's talk about how your professional interests pivoted from this

00:32:29.740 obviously interesting and relevant field to another. I think one of the interesting things

00:32:34.060 was when I saw, they called that the athlete's paradox, high intermicella fatty acids in high

00:32:39.700 intermicella lipid stores in diabetic and obese people, and also in athletes. So what is the

00:32:45.720 difference between them? So I started doing some diabetes related research and exercise work in

00:32:51.140 diabetics to improve insulin sensitivity and improve substrate metabolism. And then we were

00:32:56.100 taking muscle biopsies. My mentor back then, Dr. Hans Kaiser, he was actually teaching me how to take

00:33:01.380 muscle biopsies. And he's a physician, so he was taking biopsies. And what we often saw is that when

00:33:07.800 you took a biopsy from an athlete, it's like a chunk of muscle sitting there, like a piece of good steak.

00:33:14.240 But then if we took biopsies from the diabetics, often sedentary people, it was like a blob.

00:33:22.000 It wasn't standing up. It didn't have any structure. It was just like liquid. And then we always saw that

00:33:28.320 and we were discussing that. And it was obvious that diabetes or a more sedentary lifestyle comes with

00:33:34.380 changes in muscle quality. And of course, if you start thinking about muscle quality, you start thinking

00:33:40.760 about protein synthesis and protein metabolism. And because I was working with older people,

00:33:46.640 because the diabetics were older than my athletes, this is much more interesting than the athletes,

00:33:52.500 what is happening with that muscle? And then you automatically go from only substrate to protein

00:33:57.940 metabolism. And yeah, that's where I got stuck and still haven't figured everything out. Or actually,

00:34:02.980 I have more questions than I ever had before.

00:34:05.040 Well, I think that's the mark of a really fun place to be truthfully. Let's give folks some

00:34:10.660 basic background. Let's not say any more about carbs and fats for the moment, because we could

00:34:14.760 spend hours just defining them. But I do think people at a high level clearly understand that

00:34:19.980 if you include ethanol, there are four major macronutrients. But let's talk about this one

00:34:25.060 called protein. What is protein? What are the building blocks? What's it's made up of? What defines a

00:34:31.600 protein? Which ones can we make? Which ones can we not? I'll let you run with that in any way you see

00:34:36.020 fit. Protein is one of the three macronutrients. Protein consists of amino acids. Amino acids are

00:34:42.180 the building blocks of protein. And so they're also the building blocks of our cells, because all our

00:34:48.360 tissues is mainly protein, of course. We have, say, about 20 or depends how you define it, 20 or 22

00:34:55.980 amino acids, of which nine are essential. The rest is non-essential. The definition of essential is

00:35:02.920 always confusing to my students, because essential means we can't make ourselves, so there's no

00:35:08.860 endogenous synthesis in our bodies, in humans. Whereas the non-essential, you can actually, to some

00:35:15.060 extent, synthesize. Now I'm probably mucking it up for everybody, because what I always say to the

00:35:21.140 students, that doesn't mean that your non-essential amino acids are not essential in your diet.

00:35:27.220 And then they never differentiate between them anymore. Because as far as I know, I reckon that

00:35:33.380 it's almost impossible to synthesize those non-essentials. That is something that is still

00:35:38.240 a topic that I would like to address, but that's difficult to humans, of course, because you can't

00:35:42.860 simply just throw away all the protein and start feeding amino acids. And maybe we'll just also,

00:35:47.960 just so people kind of get a sense of these things, they're called amino acids because they have a

00:35:54.460 very clear structure. And I have to be honest with you, my biochemistry is so rusty, but I sort of

00:35:59.680 remember them having, was it, did they have a carboxyl head and a nitrous tail with a carbon in

00:36:05.700 between? And then each- An organic acid. Yeah, yeah. So it's an organic acid with this nitrous tail. So

00:36:10.120 nitrogen is the big piece here that we don't see in carbohydrates and fat. Carbohydrates and fat

00:36:15.780 are basically carbon, hydrogen, oxygen. Here, you have carbon, hydrogen, oxygen, but you also have

00:36:22.420 this big piece of nitrogen. So I'm sure we will talk about nitrogen balance. And then you have other

00:36:26.740 things thrown in there. Methionine has a little sulfur in it and things like that as well. But I

00:36:31.220 guess the point is, biochemically, they all have a similar backbone, but what differentiates the 20 or

00:36:36.880 22 of them is kind of the what's in the middle. That's the special sauce for each one. And that's what

00:36:41.320 differentiates them. That's what differentiates them. Yeah, that also defines their individual

00:36:46.380 characteristics. Now, we see that amino acids are important as our own building blocks, of course.

00:36:53.540 And so that's why we need to consume protein because they provide us with those building blocks.

00:36:58.860 But what is interesting, and we'll come to that later, is that those amino acids are more than

00:37:02.640 building blocks. They're also signaling molecules that directly stimulate muscle protein synthesis.

00:37:08.960 So they directly activate the mTOR pathway driving muscle protein synthesis. And so it's interesting,

00:37:17.700 and I always explain it to first-year students, you have a building site where you actually have

00:37:23.060 bricks being delivered. And the bricks themselves pick up the phone and call the bricklayers to come

00:37:27.820 over. So it's really amazing how that works. So simply eating, and I'll come to that later,

00:37:33.260 stimulates your muscle protein synthesis. Now, of course, I'm a muscle physiologist. So

00:37:38.640 most of my work is on muscle. We've been starting to work also on different organs because this is of

00:37:44.180 interest and there's not a lot of data there available. But what we do need to know is that

00:37:48.860 you're synthesizing about 300 grams of protein on a daily basis. That includes tissues, that includes

00:37:55.900 hormones, that includes enzymes, blood proteins, everything together. It's about average estimate

00:38:01.540 about 300 grams. As most of the listeners will consider is that they are consuming about, say,

00:38:08.800 70 to up to 100 grams of protein per day. That means that for 70 grams, for one gram a day,

00:38:15.260 for a 70-kilogram weighing man, that would be you're recycling 230 grams. And this is something that

00:38:22.440 people don't realize. So yes, we consume foods and we need those building blocks, but you're also

00:38:28.380 constantly using amino acids that are being released from the breakdown of tissues. And then you use

00:38:35.140 them again. You're making 300 grams. You're only ingesting 70 grams. So that means on a 24-hour basis,

00:38:42.060 you're recycling 230 grams of amino acids from your own body. So you're very sustainable.

00:38:47.840 Let's talk a little bit about the use case for it, right? So 300 grams being utilized per day.

00:38:55.220 Let's talk about how that differs in an active person, a person who's strength training, a person

00:39:00.480 who's doing steady state cardio training, a person who's not training. Let's just use those three

00:39:06.140 examples. I don't think anybody would have data on that because this is on the whole body level.

00:39:11.380 So organs, tissues, the guts, everything. And I think if we're asking these questions,

00:39:16.100 we have to just move back to a muscle-centric perspective.

00:39:19.460 There's a question I want to ask before all of this, which is a technical question

00:39:24.020 that explains to people the methods that you use to actually do these types of measurements.

00:39:30.320 You already talked a little bit about one isotope method with respect to carbohydrate metabolism.

00:39:35.800 Can you explain the technical tools that permit this type of study for amino acids?

00:39:41.400 I'll keep it very simple. You have stable isotopes. So everybody knows from high school,

00:39:47.480 or most of you will know from high school, that in chemistry, you have carbon 12 or carbon

00:39:52.040 is weight of 12. In nature, there's also carbon 13. And carbon 13 means it has an extra nutrient

00:39:57.880 in its core. It's stable, doesn't fall apart. You also have 14 carbon that's unstable, falls apart,

00:40:04.040 and you add radioactivity. And that's why it's a radioactive isotope.

00:40:06.920 Now, you can actually purchase carbon 13 labeled metabolites. And so you can also buy carbon 13C,

00:40:16.260 carbon 13 labeled phenylalanine, for example. Nowadays, we often use phenylalanine as the tracer

00:40:22.000 because it's an essential amino acid that is hardly metabolized in muscle or not metabolized in muscle.

00:40:28.560 And it's not as volatile as, for example, leucine. And leucine, of course, has a lot of other effects.

00:40:33.620 So you want to have a nice, stable amino acid that is a good representation of other essential amino acids.

00:40:40.220 So if you actually buy 13C labeled phenylalanine, you can dilute it in a bag of saline, infuse it in the body,

00:40:49.220 and then you actually have like 5% of all your phenylalanine floating around in your circulation.

00:40:55.200 And then you take a muscle biopsy. Then you take the muscle out of the biopsy.

00:40:59.700 You take the protein out of the biopsy. You can even separate mitochondrial protein or myofibular protein.

00:41:06.400 So that's actin and myosine, for example. And then hydrolyze that protein back to its free amino acids.

00:41:12.320 And then use mass spectrometry to look at how many of those amino acids in the muscle protein

00:41:18.140 are coming from the carbon 13C labeled phenylalanine.

00:41:22.000 Now, a few hours later, you take a new biopsy,

00:41:24.560 and you see how much more of that 13C phenylalanine is built into the muscle proteins.

00:41:29.700 If you divide that by the availability in the circulation and the time between the two biopsies,

00:41:34.500 you have a fractional synthetic rate, generally expressed in percent per hour.

00:41:39.320 Now, on a daily basis, that's about 1% to 2% per day.

00:41:43.740 So it's always confusing. It's always magic to me.

00:41:47.320 That means if all the proteins in your muscle are generic, which they aren't, of course,

00:41:51.520 but assume an average, then they are actually completely refurbished in 50 to 100 days.

00:41:58.020 So I always ask people to look at their own arm and realize that in 50 to 100 days,

00:42:04.080 they have a new arm. It's completely refurbished.

00:42:07.100 That is amazing.

00:42:08.260 So the individual proteins in the muscle are broken down and build up again.

00:42:13.740 And we can measure that by infusing those labeled amino acids and simply measuring their synthesis rates.

00:42:20.260 First of all, that is an absolutely amazing idea that is, of course, self-evident based on the nature of what we know about protein turnover.

00:42:31.980 But when phrased that way, it is simply remarkable, right?

00:42:36.220 In other words, we don't take it as so earth-shattering that every three months,

00:42:42.000 our entire hematopoietic system turns over.

00:42:45.240 I mean, we know this. We know that every 90 days, a red blood cell is gone and it's replaced with a new one.

00:42:51.000 Effectively, the entire red blood cell architecture in my body today is completely new from what it was three months ago.

00:42:58.240 But when you talk about it through the lens of muscle, it's much more complicated.

00:43:04.220 I mean, it's just much more difficult to wrap your mind around.

00:43:07.880 Obviously, one of the questions is, but I don't notice any difference.

00:43:11.280 What preserves the architecture?

00:43:14.240 This gets to what is being replaced and what is technically not being replaced.

00:43:19.680 How does the shape change so that we don't look different, so that we're not a constantly morphing creature?

00:43:26.740 So you have more questions than I can ever answer, but that is also, and we'll come back to that later, I hope.

00:43:32.340 So we started also measuring turnover rates of tissues other than muscle.

00:43:36.080 And then it gets even more freaky.

00:43:39.400 And then you start really thinking, like, how is this regulated?

00:43:42.660 Let's not do this because it will be confusing, but we've also measured protein turnover in the brain, in the human brain.

00:43:48.940 And then if you see those turnover rates, then you have different questions.

00:43:51.960 But let's not go there. Let's take it to the muscle for now.

00:43:54.140 So it means that in order to keep the muscle and maintain muscle mass, you need to stimulate it because the breakdown will continue.

00:44:04.760 And so in order to maintain your muscle as it is, you actually have anabolic stimuli that stimulate the synthesis.

00:44:11.600 And then we come back to nutrition and exercise because it's food intake and particularly, of course, protein intake and exercise that stimulate muscle protein synthesis.

00:44:21.420 How these two stimuli know which proteins to build and in what structure, oh, man, that is just an enigma.

00:44:29.760 I always show a picture of Lance Armstrong and, I don't know, who am I showing as bodybuilder?

00:44:35.500 Actually, that changes every so many years, one of the Mr. Universes.

00:44:39.500 And so I showed them that these two guys have huge protein synthesis after an exercise session, but the phenotypic response is completely different.

00:44:46.900 And so with resistance type exercise, you build a lot of myofibular protein, while the endurance athlete will build a lot of mitochondrial proteins.

00:44:55.540 So how the body knows by the recruitment of your fibers, which proteins should be synthesized?

00:45:02.280 I mean, we know a lot of molecular pathways, of course, but how it's directly regulated.

00:45:06.800 I mean, first, we thought we had everything by measuring mRNAs.

00:45:11.500 Then we thought we had everything by measuring Western blots, protein content, and then protein phosphorylation.

00:45:16.640 And then we went to transcriptomics.

00:45:18.760 And then we suddenly knew that we had post-translational modification.

00:45:22.440 And then we had mRNA splicing.

00:45:24.480 It's getting complex and complex and complex and complex.

00:45:26.940 Let's use that example, right?

00:45:28.400 So we'll put up a world-class endurance athlete against a world-class bodybuilder.

00:45:34.300 And let's even simplify the equation and take drugs out of it.

00:45:38.280 So let's even suggest, let's talk about not the best bodybuilder, because obviously they are using high amounts of anabolic steroids,

00:45:45.180 but a world-class natural bodybuilder who still, by any metric, is enormous, and a world-class endurance athlete.

00:45:52.880 The question, of course, is how does the body know, in the case of the bodybuilder, to build myofibrilar protein,

00:46:01.160 meaning to disproportionately build that, whereas in the endurance athlete, you're disproportionately building mitochondrial protein.

00:46:06.700 Now, the obvious answer to me seems to be the training stimulus.

00:46:10.100 The bodybuilder is pushing enormous amounts of weight repeatedly within the confines of certain reps and certain sets.

00:46:18.560 And the endurance athlete is never, ever stressing the muscle at a single rep.

00:46:23.760 If you think about it, an endurance cyclist might be 80 to 100, 80 to 100 cadence, and they'll do that.

00:46:29.800 They'll do hundreds of thousands of those repetitions, but none of them are as hard as the reps that the bodybuilder is doing for 6 to 12 reps.

00:46:39.000 So that's an obvious difference.

00:46:41.120 Is the question that we don't understand how that is translating a signal into the MPS?

00:46:47.320 Yes, I mean, we don't know.

00:46:49.960 And if I would actually pose this question to a second- or third-year student, they would actually just move away from the real answer by going towards saying, like, hey, it's different fibers.

00:47:01.220 And, of course, that's part of the answer because a resistance-type athlete will more likely recruit the type 2 fibers.

00:47:08.180 The type 2 fibers are more likely to build in mass.

00:47:11.080 If we see people doing resistance training, it's mainly the type 2 fibers that get bigger.

00:47:14.920 We see that with the bodybuilders as well, huge type 2 fibers.

00:47:18.320 The opposite happens when we get older.

00:47:20.000 You get smaller type 2 fibers, actually, and that is where most of the muscle loss with aging actually comes from.

00:47:25.680 While the endurance athlete, we don't see much happening with the size of the fibers.

00:47:29.560 We just see greater capillary density.

00:47:31.680 We see more mitochondria, higher density of mitochondria, subsarcalameal mitochondria.

00:47:36.980 So the adaptive response is completely different.

00:47:39.820 And part of it is because of which fibers you recruit.

00:47:43.000 But it's not the complete answer because if you do, for example, you probably noticed the discussion about high reps, low reps, low weight, high weight.

00:47:53.260 There's now very nice studies that show if you do high reps with a low weight, if you do the 2 exhaustion, you also start using the type 2 fibers.

00:48:03.200 And you also get hypertrophy.

00:48:04.820 And that's a nice way, especially in rehabilitation, that you can actually drive those type 2 fibers without putting too much effort on the just operated the hip or the leg or whatever just operated on.

00:48:15.660 So it's not the complete answer.

00:48:18.520 There's more going.

00:48:19.480 But what is exactly the signal, the molecular signal from the tension on the muscle towards the synthesis of the specific sets of proteins?

00:48:29.300 There's enormous amounts of pathways involved.

00:48:32.620 And I'm not sure whether we'll ever completely know what is happening now and where that selection is going to be.

00:48:38.900 And that's actually all.

00:48:39.780 It's just so fascinating that we can't understand the cascade that goes from stimulus to muscle protein synthesis.

00:48:48.020 Would it be reasonable to assume that the bodybuilder has more upregulation of mTOR than the endurance athlete?

00:48:56.200 Or is that even a stretch in terms of an assumption, given that it's difficult to measure that?

00:49:00.940 I mean, we now also know that a lot of the hypertrophy is actually mTOR.

00:49:04.300 The stimulation of muscle protein synthesis can be mTOR-independent.

00:49:07.700 There's so many parallel pathways that are driving responses.

00:49:11.460 And like I said, for example, if you ingest protein, you stimulate mTOR signaling, you stimulate mRNA translation initiation, and you get greater protein synthesis.

00:49:22.180 But it actually is not continuously stimulated if you do not provide all the building blocks.

00:49:27.840 So if we, for example, after exercise or even at rest, we provide people with the brine-chain amino acids, so mainly leucine, is driving that anabolic response.

00:49:37.900 It's the signaling response.

00:49:39.100 So here you stimulate muscle protein synthesis.

00:49:41.500 And for up to two hours.

00:49:42.840 But if we give the same amount of leucine, or in this case, brine-chain amino acids, in a similar amount of milk protein, so containing the same amount of brine-chain amino acids plus all the other amino acids, we see that response is actually sustained over a more prolonged period of time.

00:49:56.920 So it's not only the stimulation, it's the stimulation in combination with the right amount of building blocks at the right amount of time.

00:50:05.460 How I always tell it to the students, you have a parking lot where you want to park as many cars as possible.

00:50:10.580 You can put the light on green to drive in, but if there's no cars, nothing's going to happen.

00:50:15.420 And so it's a combination of the right signaling responses plus the availability of your substrate.

00:50:22.060 I want to come back to this in detail because it's very relevant.

00:50:25.000 It's also, there was a recent study that came out that I believe you were an author on, if I'm not mistaken.

00:50:30.420 Maybe I am mistaken.

00:50:31.320 But the study looked at the duration of muscle protein synthesis following the digestion of different types of amino acids.

00:50:37.920 So we come to that.

00:50:38.880 But let's take a step back for a moment and make sure we at least cover the basics of how protein is even digested.

00:50:44.280 And I want to talk about three types.

00:50:47.620 So one, I want to talk about a whole meal.

00:50:50.200 So a meal of protein that often comes with fat.

00:50:53.540 So let's talk about eating a steak.

00:50:55.000 And they want to ask how that differs from two different types of milk-based proteins, whey protein and casein.

00:51:03.920 So I want to understand what is actually happening from a digestive standpoint and how the thing that you actually consume and put in your mouth turns into building blocks that presumably are being absorbed somewhere in the ileum or jejunum.

00:51:21.560 So I'll just first take protein and then go to the specific protein sources or meals.

00:51:27.700 So protein is basically ingested, goes to your stomach, acid is added to it.

00:51:34.420 So you have the first basically start of the digestion.

00:51:38.300 You actually can get clotting of your protein due to the acid.

00:51:41.620 We'll come to that later if we compare casein versus whey.

00:51:45.000 Then it goes to the duodenum.

00:51:47.100 Then you'll have all your enzymes being unloaded on your protein.

00:51:50.820 If they can get access to it, you actually get the free amino acids.

00:51:55.540 A lot of people have suggestions that are also oligopeptides, di- and tripeptides.

00:52:00.080 So small proteins composed of a few amino acids.

00:52:03.360 There are transporters in the gut that would allow them to actually enter the intestinal wall or the intestinal cells.

00:52:10.080 We think from a quantitative point of view, it's hardly relevant, but it's possible.

00:52:15.120 The amino acids are then, part of them are actually incorporated into intestinal protein because the gut also has a very rapid protein, much faster than muscle.

00:52:24.700 So part of it actually remains in the intestinal tissues as protein.

00:52:29.180 Some of it is released on the other side of the intestine in the portal vein.

00:52:33.220 The portal vein transports it to the liver.

00:52:35.500 The liver can do something with the amino acids if it wants to make proteins, but most of it is actually released in the circulation.

00:52:43.200 And there it can basically perfund it to all those different tissues, taken up and used for muscle protein synthesis.

00:52:50.600 We don't have a real storage depot.

00:52:53.260 There's a small free amino acid pool.

00:52:55.400 If you compare it with the intact protein pool, they always say it's very small in muscle, but acutely after a meal, it can actually vary a lot.

00:53:04.060 So it's a buffer, a temporary buffer, but we don't really have real storage sites for amino acids.

00:53:10.500 So that's the whole pathway.

00:53:12.580 Let's finish one thing there, actually, Luke, because that's an important point you raise, which is unlike fat, which can be stored in unlimited quantities, and glucose, which can initially be stored in glycogen, although that's a relatively finite store,

00:53:28.280 and then eventually can be stored as fat through de novo lipogenesis, what exactly happens to excess protein if we consume it?

00:53:38.000 And let's just use an extreme example, right?

00:53:39.580 Like I sit you down and give you a 200 gram protein meal, make it whatever number you want, such that the point is you clearly have excess amino acids once fully digested.

00:53:50.380 What does your body do with those?

00:53:53.620 Yeah, so first, the amino acids, you said that we have no storage, like the glucose is stored as glycogen, the fatty acids are stored as fat, but the amino acids are stored as protein.

00:54:04.060 But is it a real storage depot?

00:54:05.880 Now, if you ask me and yourself, we hope we're not losing muscle, so we say we don't have a storage depot.

00:54:11.300 But if we end up in a concentration camp, then we're actually quite happy that we have a storage depot of amino acids in the form of muscle.

00:54:18.880 So it is a storage depot, but we hope that we're not using it.

00:54:22.340 So if we get excess protein, we thought, I mean, in the literature, a lot say that everything that you can't immediately process is being oxidized.

00:54:30.060 Now, that study by Jorn Trommeler that you just referred to that we published a few weeks ago, we showed that with 100 gram oxidation, at least in the first 12 hours after ingestion, is very overestimated.

00:54:43.300 But, I mean, over the long run, if you keep continuing eating more protein, and in a setting of over calories, you simply store the protein as fat.

00:54:53.360 What's the pathway that that happens?

00:54:56.000 Because it's so funny, when I think back to biochemistry classes more than 25 years ago, what I vaguely remember was amino acids could undergo gluconeogenesis to become glucose, and then either glycogen or fat.

00:55:10.040 Is that what you're referring to?

00:55:11.880 Yes.

00:55:12.420 Okay.

00:55:12.640 And then it's different for different amino acids.

00:55:15.580 And, of course, it's a very inefficient way.

00:55:18.360 So that is also one of the reasons why people tend to get less fat accumulation if they overeat in a form of protein, besides the satiety effect.

00:55:29.700 Right.

00:55:29.840 Because there's a thermogenic and thermodynamic loss or use of energy just in the metabolism of protein that itself is obviously beneficial if your goal is to store less energy.

00:55:42.280 Correct.

00:55:42.880 Now, I have to say something about the techniques that we use, because we were interested.

00:55:49.120 I mean, we've done protein synthesis measurements all the time.

00:55:53.340 But at some point, exactly what you were saying, I wanted to know more about the digestion and the absorption prior to stimulating muscle protein synthesis.

00:56:00.840 And in order to understand that, you need those stable isotope traces, not only in an infusate, but you would like to have those labeled amino acids in the food as protein.

00:56:12.800 Now, you can't purchase those.

00:56:15.040 So about 15 to 20 years ago, we worked with Yves-Barry in France because they already made intrinsically labeled protein.

00:56:23.800 So what they did, they infused a cow with those labeled amino acids.

00:56:30.420 And so the cow integrates those labeled amino acids in the milk.

00:56:34.300 And then you can actually use the milk in clinical experiments.

00:56:37.460 Now, we wanted to take it one step further because we wanted to have the number of labeled amino acids in the milk so high, which is very expensive, to actually see the digestion and absorption, but even the incorporation in the muscle.

00:56:51.740 So we spent more than 50,000 years of tracer.

00:56:54.960 And the first time, that's pretty challenging because you actually put it in a cow.

00:56:58.460 You infuse it in a cow and you just hope you're ever going to see that money back.

00:57:02.020 We put labeled phenylalanine in a cow.

00:57:05.820 The cow made milk.

00:57:07.280 We extracted the milk.

00:57:08.900 We got the protein powder and we used it in clinical experiments to assess digestion, absorption, release, extraction over the leg, and incorporation in the muscle.

00:57:20.200 Now, if you see this, I mean, we can now go into the quantitative measure because we actually did this to see the difference between casein and whey.

00:57:28.300 We'll come to that later.

00:57:29.260 But simply that I bought tracers, isotopes in the U.S., they send it over.

00:57:36.280 I had it in a small jar on my desk.

00:57:39.380 Then I went to Wageningen, or first in France, actually.

00:57:43.260 And we've done it a few times since.

00:57:46.280 You actually infuse it in a cow.

00:57:49.520 You actually get the milk.

00:57:51.280 You bring the milk to a factory to extract the milk protein.

00:57:53.880 About a year later, that same phenylalanine is now integrated in milk protein on my desk.

00:58:01.100 The same whole molecule that came from the U.S. to my desk.

00:58:05.660 From the U.S. to France in a cow.

00:58:08.600 Then from the cow's milk on my desk again.

00:58:11.760 Then it went into an older subject.

00:58:14.180 In a study, we took a muscle biopsy.

00:58:17.100 Now, a year later, I have a muscle biopsy on my desk that has that same full amino acid integrated in the muscle.

00:58:24.880 And I actually dissolve it, bring it to the mass spec analysis, and I have that same amino acid in my hand again.

00:58:32.700 That amino acid has been around for four years and went from a lab in the U.S.

00:58:39.160 through a cow, through a cow's blood protein, through the milk protein, to my desk, back into somebody else's leg.

00:58:47.520 That's amazing.

00:58:48.300 And just give me a sense of yield.

00:58:50.880 When you made the casein or the whey protein from the cow's milk, what fraction of the phenylalanine was actually labeled with the isotope?

00:59:01.100 We got 25% of the trace that we found back in the milk.

00:59:05.780 And so you can imagine, as a Dutch person, I'm supposed to be cheap.

00:59:10.080 So losing 75% of that money in a cow is not something that you can sleep on.

00:59:17.080 So we butchered the cow.

00:59:19.720 How much of the phenylalanine did you find in the meat of the cow then?

00:59:23.680 Exactly.

00:59:24.400 So this was really funny because we actually butchered the cow.

00:59:27.540 So we got, of course, it gets difficult because you have to multiply it by total amount of meat.

00:59:32.160 And if you butcher a cow, you don't get all the meat.

00:59:34.220 But we sampled all the organs.

00:59:35.820 And that was a starting point for us to start measuring turnover of other organs in humans.

00:59:40.160 But what was interesting is that different muscles had different enrichment, but it was all ballparked the same.

00:59:45.480 We never calculated whether we actually came back to 75%, but it must have been very close.

00:59:51.880 But we use that meat, and that will come back to your other question, to see whether there's a difference in the digestion and absorption when you ingest meat as a steak.

01:00:00.720 Or if that same steak was first put in a meat grinder, and you had basically minced meat.

01:00:07.000 Huge difference.

01:00:08.340 With minced meat, you get more rapid digestion and absorption, which should also expedite your muscle protein synthesis.

01:00:15.200 Because the more rapid absorption, the greater and faster the release of leucine, the greater the stimulation of muscle protein synthesis.

01:00:23.400 Now, that was a fun study for us to do.

01:00:25.840 And when we were writing it down, I was trying to find in the literature some suggestion that the minced meat versus steak,

01:00:32.980 there was some data to suggest that it improves, accelerates digestion and absorption, potentially improves anabolic responses.

01:00:38.800 We came up with a study that was done in the 60s that showed that this was epidemiology and has its limitations,

01:00:46.040 that people that have their older people that still have their own teeth generally also have their muscle still intact.

01:00:52.880 So that was a nice link to say that your mom has been right on a lot of things.

01:00:58.620 Because, I mean, I spent probably like 30 million euros of research money in the last 30 years

01:01:03.260 to provide clinical proof that my mom was right on a lot of things.

01:01:06.420 Meaning when she said, chew your food.

01:01:08.840 Chew your food, but even something as simple as sitting upright.

01:01:12.540 Huge effect on digestion and absorption.

01:01:15.120 So all of these things come back.

01:01:16.860 So chewing is a factor that drives the anabolic response to feeding.

01:01:21.560 And so it's really funny then if you go to mixed meals, what you just said,

01:01:25.420 if there's macronutrients coming together, a lot of energy will actually reduce gastric emptying or slow down gastric emptying.

01:01:33.820 That is one factor.

01:01:34.740 But the matrix of food, the chewing of the food, all of these, whether you cook it or not, even that is an important one.

01:01:42.940 We'll come to that later as well.

01:01:44.300 I mean, there's so many topics here.

01:01:45.840 We did a study with eating eggs that were raw or cooked.

01:01:49.720 Huge effect on digestion and absorption.

01:01:52.800 I actually tried to have Sylvester Stallone on that paper, but he never responded, unfortunately.

01:01:58.260 Rocky's protein shakes.

01:01:59.460 We basically said, was Rocky right or wrong?

01:02:01.900 Because in the first movie, we actually used part of his script.

01:02:05.660 He's ingesting those raw eggs.

01:02:08.380 Wouldn't it not be better to actually cook those eggs because you have more rapid digestion and absorption?

01:02:13.000 I think of how many raw eggs I consumed as a child because I watched Rocky.

01:02:18.860 It's insane.

01:02:19.660 How I didn't get salmonella, it's a miracle.

01:02:22.160 Anyway, so it was.

01:02:24.260 Let's go back to the example of the steak versus the ground beef.

01:02:30.300 So ISO quantities, so 50 grams of protein in a steak that obviously will have some fat with it.

01:02:38.700 In fact, let's make them not just isocaloric and isoprotein, but everything about them is the same.

01:02:43.820 So same amount of fat, same amount of whatever.

01:02:45.920 One is ground, one is not.

01:02:47.720 Talk me through the kinetics of those two in an individual.

01:02:52.080 Yeah, so I think the most important factor is, of course, that all the enzymes that are being released in the duodenum and also part of it, also the gastric emptying, of course, is accelerated with your minced meat, with your ground beef.

01:03:03.140 So you have more rapid gastric emptying.

01:03:05.400 The acid has already had more space to actually have its effect.

01:03:09.420 Faster gastric emptying, then it gets into the duodenum.

01:03:12.020 You don't have those big chunks of meat, but you actually have those enzymes that can actually attach everywhere much easier, so you get more rapid digestion and absorption.

01:03:21.620 It's a little bit similar to, for example, casein and whey.

01:03:25.540 Everybody knows now, I mean, all the athletes that say we need whey protein, but that's because micellar casein, the other 80% in milk, 20% whey, 80% casein.

01:03:36.740 That was actually the first study.

01:03:38.020 That's actually the study why we did the intrinsically labeled protein.

01:03:41.760 We got the milk, processed the milk down to micellar casein and down to whey because for all those years, specialty companies was telling me that predigested protein, the hydrolyzed protein, is more rapidly digested and absorbed.

01:03:56.100 And I said, where's the proof?

01:03:57.840 And they said, like, yes, this in vitro essay shows.

01:04:00.500 I said, in vitro essay doesn't mean anything to me.

01:04:02.720 In vitro assays, you have all these tubes and glass things, and then they screened for digestion and absorption.

01:04:09.360 But to me, the human in vivo system is much more complex because all those tubes and glass cylinders are actually alive in a human.

01:04:18.080 So I want to assess this in a human in vivo setting.

01:04:21.200 And then they asked me, like, how would you want to do it?

01:04:23.660 And then I said, like, yeah, I would infuse a cow and this and that.

01:04:26.720 And then they looked at me like I was completely crazy.

01:04:29.100 It took me seven years until they funded it.

01:04:32.360 And then we got the milk, processed micellar casein and whey, and we also got the micellar casein and we pre-digested it with enzymes.

01:04:43.640 So you get a casein hydrolysate.

01:04:45.580 Now, we've all checked them for digestion and absorption.

01:04:49.280 And then you see that the hydrolyzed casein and also the whey protein are much more rapidly digested and absorbed than the micellar casein because the micellar casein in the acidity of the gut starts coagulating like spoiled milk or something like that.

01:05:06.100 And so the gastric emptying is probably reduced or slowed down, but also the capacity of the enzymes to basically start digesting the foods.

01:05:16.360 And so that's how we now know that rapidly digestible protein is more likely to stimulate muscle protein synthesis to a greater extent.

01:05:26.460 So there's two characteristics of a protein.

01:05:28.780 That is the digestion of it and the rate of digestion.

01:05:32.260 But then you would expect that a pre-digested casein would do exactly the same as a whey protein, but it doesn't.

01:05:39.180 Just as rapidly digested and absorbed, but whey protein still has a greater anabolic response.

01:05:45.320 And of course, that might have something to do with the amino acid composition.

01:05:50.280 And we know that whey protein has a higher leucine content.

01:05:53.620 And so if we add, for example, free leucine to casein, we get a greater anabolic response.

01:05:59.020 So obviously, the amount of leucine is an important factor.

01:06:03.120 So in a nutshell, two characteristics of a protein and their capacity to stimulate muscle protein synthesis is digestibility, the rate of digestion, and the amino acid composition with particularly the amount of leucine in the protein.

01:06:17.900 And anything that slows down the gastric emptying or the release of leucine in circulation will likely also slow down the anabolic response.

01:06:25.360 So let's unpack that a bit because there's a lot there.

01:06:28.900 We're kind of collapsing digestibility and rate of digestion into one feature.

01:06:34.520 Although, can't they be disentangled a little bit?

01:06:38.020 Because the example of the whole meat versus the mince meat, presumably they have similar digestibility.

01:06:46.480 They have just as much sinew.

01:06:48.620 They have just as much fat.

01:06:49.880 But one has been effectively broken down, and it would have a higher rate of digestibility, correct?

01:06:54.900 No, I think with cooked meat, the digestibility is the same.

01:07:00.400 It will take a little bit longer for the steak than for the mince.

01:07:03.760 Sorry, I mean, the rate of digestion, wouldn't that be quicker?

01:07:06.680 Yes.

01:07:07.060 Yes.

01:07:07.440 Yes, yes, yes, exactly.

01:07:09.200 I mean, if you're ever in for a sabbatical and you want to do a few years of research at Maastricht,

01:07:13.520 please come over because these are all the same questions that I had, and there's so many more.

01:07:18.520 I mean, we as nutrition scientists, we love to work with a single ingredient,

01:07:23.860 because otherwise we don't know what is going on.

01:07:26.300 So most of the work that we've done in the past is actually comparing protein X with protein Y.

01:07:31.640 And then with protein, I mean protein isolate or protein concentrate, so protein powders.

01:07:38.600 And that's why a lot of people in the public media just, of course, read or like to see our studies,

01:07:44.220 because it's about the powders they eat.

01:07:46.880 But, of course, normal people don't eat protein powders.

01:07:50.380 Protein isolates are concentrates.

01:07:52.160 We eat foods.

01:07:53.340 Now, if you go back to the literature and looking at how many studies have assessed the anabolic response to eating foods,

01:07:59.460 that is very slim.

01:08:00.900 Because, I mean, nobody's interested in foods.

01:08:04.020 I mean, it's often like, is protein X versus this?

01:08:06.500 Because if you start having meals, everything comes together.

01:08:10.060 Plant-based proteins, animal-based proteins, the processing of the protein,

01:08:15.180 whether it's heated or not heated, whether it's cut fine, minced, not minced, chewing well, not,

01:08:21.360 whether it's combined, how much on the plate, how many fibers,

01:08:24.900 all of these things together actually determine the anabolic response to feeding.

01:08:30.900 And then the digestibility becomes most important.

01:08:34.520 I think 99% of our studies, the digestibility is not an issue because we use extracted proteins.

01:08:40.460 Also, when we go to plant-based proteins, and that's, I guess, also a topic that you want to discuss,

01:08:46.380 most of the plant-based proteins that we have assessed are plant-based proteins,

01:08:51.300 and I prefer to call them plant-derived proteins, that have been extracted from the whole foods.

01:08:56.760 And then the digestibility, it's often still a little less than animal-derived proteins,

01:09:02.520 but it's not a major issue anymore.

01:09:05.380 It's a major issue if it comes in the form of whole foods.

01:09:09.320 All right.

01:09:09.640 Let's go through this in some detail because this is super fascinating.

01:09:13.140 But before we do, I want to really ask the question of how much does it clinically matter

01:09:19.960 the rate at which muscle protein synthesis is stimulated?

01:09:24.340 Because what I'm hearing so far, and I want to try to summarize this for both myself and the listener,

01:09:29.420 is that you really have three factors that are going to determine

01:09:33.200 the rate at which muscle protein synthesis takes place.

01:09:37.740 You have the digestibility of the thing that you are ingesting.

01:09:42.840 And this could be the difference between a plant-derived protein and an animal-derived protein.

01:09:49.600 This could be the difference between a cooked protein versus a not-cooked protein.

01:09:55.280 And this could be the difference between two different types of proteins, period.

01:10:00.060 You then have the rate at which this protein is digested.

01:10:04.560 You can picture a curve with the x-axis being time and the y-axis being digestion.

01:10:10.160 The rate of digestion will speak to the shape of that curve.

01:10:13.500 And again, I think there are probably many things that impact that.

01:10:17.020 But the obvious examples you've given here would be how the food is cut.

01:10:22.280 And it could be ground beef versus whole beef.

01:10:24.840 How well the person chews.

01:10:26.760 All of those things impact the rate.

01:10:29.240 And then the third factor is the composition of the amino acids itself.

01:10:34.600 You've alluded to leucine many times.

01:10:37.520 We talk a lot about leucine on this podcast because, of course, it is the number one and

01:10:43.100 the most potent mTOR stimulator.

01:10:45.700 But obviously, there are other proteins as well.

01:10:47.440 Lysine, methionine.

01:10:48.960 These are probably more pro-anabolic.

01:10:51.280 And therefore, the concentration or distribution of amino acids plays a role.

01:10:55.380 Now, let's go back to the macro question, which is,

01:10:58.140 A person is looking to maximize, optimize, maintain, increase lean body mass.

01:11:07.160 This should be a goal of everybody, right?

01:11:09.660 It doesn't matter if you're a 75-year-old woman or a 25-year-old man.

01:11:15.040 The maintenance of lean body mass, if not the increase in lean body mass,

01:11:20.160 is a very important pillar of living a long, healthy life.

01:11:25.260 So, if that is true, then presumably anything we can do nutritionally,

01:11:30.840 we'll talk about training later, but anything we can do nutritionally

01:11:34.120 to maximize or increase muscle protein synthesis should be good.

01:11:38.980 But the one thing that we're missing is the window over which that happens.

01:11:44.240 So, is the goal always to maximize that for the highest peak independent of the base?

01:11:51.680 Or do we want more of a time-released effect where we say,

01:11:56.400 Look, we'll take a lower rate or a lower peak muscle protein synthesis,

01:12:00.280 but I'd like to sustain that for many, many hours.

01:12:03.360 You're laughing, so I've touched a nerve,

01:12:05.740 which means I'm probably asking a question you are asking,

01:12:08.680 but I'll let you go from there.

01:12:10.260 This is awesome.

01:12:11.060 I mean, these are all the questions that the field has and that we all have.

01:12:14.680 So, it becomes much more difficult because one factor we didn't discuss is the amount of protein.

01:12:21.480 Because the amount of protein also has an effect, of course, on the curve.

01:12:25.820 And you can compensate with the amount.

01:12:28.820 We'll probably come back to that as well.

01:12:30.360 But yeah, there's estimations up to two to three grams of leucine in a meal

01:12:34.920 will actually induce a rapid increase in circulating leucine,

01:12:39.680 and that will stimulate muscle protein synthesis.

01:12:41.860 And if you have enough building blocks available,

01:12:44.700 you have an anabolic response for at least up to five hours.

01:12:49.460 So, this has led most of us in the field to believe that it's best to ingest,

01:12:54.900 at least now we're talking about healthy people.

01:12:56.700 If you become older, you become less resistant to the anabolic properties of amino acids,

01:13:00.500 anabolic resistance, probably also something that we'll come back to later.

01:13:03.920 But if you're a healthy, active male or female,

01:13:06.980 20 grams of protein is assumed to be the optimal amount to maximize muscle protein synthesis

01:13:13.540 for up to four to five hours after a meal.

01:13:16.860 And this is the reason why in so many packages, you now see 20 grams.

01:13:21.240 Everywhere you see 20 grams.

01:13:23.240 Now, that comes from studies showing that ingestion of 40 grams of protein

01:13:27.120 does not result in greater muscle protein synthesis rates than 20 grams of protein.

01:13:31.800 So, it's assumed that 20 gram is the optimal amount in healthy people.

01:13:36.800 And of course, we always have those discussions.

01:13:39.140 If you're 120 kilogram, you probably need more.

01:13:41.480 If you're 50 kilogram, you probably need less.

01:13:43.740 Yes, but you can't do a study with every individual in the world.

01:13:46.660 But 20 grams.

01:13:48.360 Now, if you assume that you would have an anabolic response to each main meal,

01:13:53.200 then the advice is there to ingest 20 grams of protein with each main meal.

01:13:57.660 Now, if you're becoming older, there are suggestions you need more to compensate for that.

01:14:03.740 But let's stick now with healthy people.

01:14:05.880 That's 20, 20, 20, possibly also an evening protein snack, 20.

01:14:10.440 And then you already have 80 grams of protein,

01:14:12.580 which for most people is already more than one to 1.1 grams protein per day.

01:14:17.500 Now, we are people that believe that you actually could use more protein,

01:14:21.320 which automatically happens when you become active.

01:14:23.560 Because when you become active, you eat more, and then you easily eat more than 1.1.

01:14:28.540 So it's a non-discussion.

01:14:30.140 But so the idea is distribution of protein, that every meal is an anabolic response.

01:14:35.840 Just one question before you go further.

01:14:38.000 This 20 grams is the maximum amount of protein you need to get maximum protein synthesis,

01:14:46.660 muscle protein synthesis, was based on what type of protein?

01:14:50.860 That was based on milk and eggs.

01:14:52.500 So there was a study on milk, and there was a study on an egg.

01:14:55.780 Okay, so it's whole food.

01:14:57.220 It's not using just whey or just casein.

01:15:00.760 No, it's not whole foods.

01:15:01.860 This is in protein concentrates.

01:15:03.280 So egg protein concentrates and milk protein concentrates.

01:15:05.620 So that's a very important point, because as I said,

01:15:09.420 if your digestibility is not 100%, which in a meal is never, of course,

01:15:14.160 and you have a delay in digestion and absorption,

01:15:16.320 then 20 grams could be suggested to be a minimum.

01:15:20.200 Yeah, so in other words, what I'm hearing here is,

01:15:22.500 for people like me who don't really like shakes that much,

01:15:26.820 I prefer to eat food as opposed to drink shakes.

01:15:29.060 I do drink them because sometimes it's convenient.

01:15:31.660 But if you're going to try to get this through food,

01:15:34.460 by definition, you're going to be working with an inferior protein

01:15:38.240 from the standpoint of speed in terms of digestibility and rate of digestion.

01:15:43.820 So you might need a protein meal that's 30 grams or more.

01:15:47.540 And then if you're 90 kilos, you're probably on the bigger end of that.

01:15:51.640 Anyway, you might be 40 grams that you need per meal of real food.

01:15:54.780 Is that kind of how you would think about that?

01:15:56.880 Yes.

01:15:57.440 And so automatically you also get to that,

01:15:59.540 because we always have those discussions, of course.

01:16:02.000 Because if I say that you need more protein,

01:16:04.140 you ingest more protein,

01:16:05.260 and they look at me like I'm advocating a high protein diet.

01:16:07.620 But these discussions are, of course, always a little bit weird.

01:16:11.180 If you have a 65 kilogram weighing Tour de France cyclist,

01:16:15.240 and he only consumes a very little amount of protein

01:16:17.980 in the form of only 10% of his energy intake,

01:16:20.640 he's still ingesting probably more than two and a half grams

01:16:23.100 of protein per kilogram body mass per day,

01:16:24.980 even though he absolutely doesn't need it

01:16:26.740 for his limited amount of muscle.

01:16:28.740 The more active you become and the more healthy you are,

01:16:31.940 the more protein you consume.

01:16:33.940 We always have, I mean, World Health Organization

01:16:35.800 says 0.8 grams per kilogram body mass per day.

01:16:38.600 But yes, maybe you can survive on that.

01:16:41.200 That's fine.

01:16:42.000 But it's certainly, in my beliefs, not optimal.

01:16:44.960 But whether it's optimal or not, it's a non-discussion.

01:16:47.760 Every healthy, relatively sedentary person,

01:16:50.740 I mean, whether it's here or in England or the US,

01:16:53.180 healthy people, nothing strange,

01:16:55.220 they're not a complete recreational athlete,

01:16:57.640 already consume between 1.1 and 1.3 grams

01:17:00.900 of protein per kilogram body mass per day.

01:17:02.800 And they're not even trying to consume more protein.

01:17:04.720 We're typically pushing our patients much higher than that.

01:17:08.500 We're asking patients to be closer to 1.6 grams per kilo per day.

01:17:13.720 And truthfully, if we're really trying to put muscle on people

01:17:16.580 and their training volume is high,

01:17:18.540 we're closer to two grams per kilo.

01:17:21.040 It's great if you can reach that.

01:17:23.740 I mean, here in the hospital, I mean, we're doing a lot

01:17:26.220 because I do a lot of clinical work.

01:17:28.420 So we evaluated protein intake in the elective hip

01:17:32.860 and knee surgery patients.

01:17:34.320 So the older population, but these are not sick.

01:17:36.900 They're coming in for a new knee or new hip.

01:17:39.320 So this is a new generation of patients that we get, of course,

01:17:42.780 because in the past that was associated with a lot of pain.

01:17:45.820 But these are patients that want to go skiing

01:17:47.940 with the grandchildren again.

01:17:49.880 So they want a new hip or new knee.

01:17:51.480 So they come in, they're very healthy.

01:17:53.520 But in the four days that they're in the hospital,

01:17:56.760 to go back to the advice,

01:17:57.800 ESPN guidelines, for example,

01:17:59.440 between 1.2 and 1.5 grams of protein per kilogram body mass per day.

01:18:03.740 That's the clinical advice for recovering patients.

01:18:06.300 You know what they actually, so in our hospital,

01:18:08.920 so what they actually get,

01:18:10.440 what they're being delivered is 0.8 grams.

01:18:14.240 How much lean mass do they lose in four days of inactivity?

01:18:17.400 We'll come back to that.

01:18:18.520 So they get 0.8 and you would say like,

01:18:21.780 oh, give them more.

01:18:22.860 They consume 0.5.

01:18:25.320 So the healthy patients in the hospital here,

01:18:28.520 the healthy patients go for elective surgery.

01:18:30.800 In those four days, they consume 0.5 grams,

01:18:33.740 which is one third of the clinical guidelines

01:18:36.860 for the advised amount.

01:18:38.620 And they lose about 1.4 kilograms.

01:18:41.480 Wow.

01:18:42.260 So they'll lose more than three pounds of lean mass in four days.

01:18:48.200 And I've talked about this extensively on the podcast

01:18:50.440 about the asymmetry in how quickly you lose

01:18:54.140 versus how long it takes to get back.

01:18:56.640 And of course, we talk about this a lot

01:18:58.200 in the context of falls that result in fractures,

01:19:00.780 because here it's an even more vulnerable population

01:19:03.820 for many reasons.

01:19:04.960 First, unlike the elective hip replacement

01:19:07.300 and the elective knee replacement,

01:19:09.160 whose patients are generally very healthy

01:19:11.080 and able to get back to PT quite quickly,

01:19:14.520 especially in the hips,

01:19:15.680 the people who are falling and fracturing femur and neck,

01:19:19.140 neck of femur and hip,

01:19:20.460 they're typically not as healthy

01:19:21.680 and they're much longer to get back to recovery.

01:19:24.700 And they're potentially bedridden

01:19:26.400 for much longer periods of time.

01:19:28.140 And oftentimes they never make it back

01:19:30.360 to the level of muscle mass,

01:19:32.860 strength and function prior to,

01:19:35.280 in fact, I'm not sure if you're aware of this statistic.

01:19:37.040 You probably are,

01:19:38.020 but Adam Cohen on this podcast mentioned that,

01:19:40.580 you know, we talk a lot about the 15 to 30% of people

01:19:43.980 over 65 who will die within a year of a hip fracture.

01:19:47.740 What we don't talk a lot about,

01:19:48.980 of the people who don't die,

01:19:50.980 call it the 70 to 85% who don't die within a year,

01:19:54.140 50% of them never regained their same function pre-fall.

01:19:59.940 In many ways, I find that statistic even more profound.

01:20:03.880 I was giving lectures for a group of older people,

01:20:06.100 general public here,

01:20:07.100 and I basically mentioned those numbers,

01:20:08.900 not thinking about basically what I was saying.

01:20:11.760 So half the audience turned white when I said that,

01:20:14.500 because of course there were a lot of people

01:20:15.900 that actually broke their hip.

01:20:17.780 But we took biopsies from patients coming in

01:20:20.620 with a hip fracture after falling.

01:20:22.780 And we compared that muscle with aged,

01:20:25.560 matched people that didn't have a hip fracture

01:20:28.300 or didn't have a fall.

01:20:29.680 And we compared it with young women.

01:20:31.680 Most women are the ones with hip fractures

01:20:33.300 because the men have already passed away.

01:20:35.680 But you actually saw that the size of the type 2 fibers

01:20:38.220 was tremendously smaller in the women with the hip fracture

01:20:43.340 than the ones that didn't have the hip fracture,

01:20:45.360 even though we matched for almost everything,

01:20:47.100 lifestyle and everything.

01:20:48.460 Well, it's very interesting there

01:20:49.720 is the causality could be in reverse.

01:20:51.600 I think you could also make a very compelling case

01:20:54.340 that having smaller type 2 fibers,

01:20:58.020 which means having less power,

01:21:01.160 having less force generating capacity,

01:21:03.700 would make you more susceptible to a fall.

01:21:06.700 In fact, I wouldn't be surprised

01:21:07.980 if there's a bidirectional association.

01:21:11.720 So lower type 2 muscle fiber size and density,

01:21:15.040 much more predisposition to a fall.

01:21:17.220 Once you are inactive,

01:21:18.260 you now experience even greater atrophy,

01:21:20.940 which as you pointed out earlier,

01:21:22.740 atrophy of the type 2A muscle fiber is,

01:21:25.920 I would argue it should be described

01:21:27.600 as one of the hallmarks of aging,

01:21:29.160 right up there with decreased mitochondrial functioning,

01:21:32.640 increased senescent cells,

01:21:34.000 all of the things we typically think of with aging,

01:21:36.040 we should really be adding atrophy of type 2 fibers.

01:21:38.620 And that's why maintaining muscle,

01:21:41.900 there is more than maintaining muscle.

01:21:43.680 It's also especially maintaining the type 2 fiber size,

01:21:47.360 because what we now often see with patients getting back,

01:21:50.560 and especially now with COVID,

01:21:52.360 we are sending people home much more fast

01:21:54.620 because we don't want them to get a bacteria or anything like that,

01:21:57.760 and we don't want them to attract COVID.

01:21:59.500 So we send them home earlier.

01:22:01.300 Now, what happens when a lot of older people go home,

01:22:04.000 and even if it's not a hip fracture,

01:22:05.740 but an elective knee or hip surgery,

01:22:07.740 everybody means well.

01:22:08.920 So children, grandchildren,

01:22:10.680 relax.

01:22:11.020 The first thing that they will do while you're in the hospital,

01:22:13.180 they'll put your bed downstairs into the living room.

01:22:15.640 So those people will never walk stairs again.

01:22:18.580 First of all, they're afraid of walking stairs.

01:22:20.800 They won't walk stairs again anymore

01:22:22.680 because everything is put down.

01:22:24.840 So they never recruit their type 2 fibers anymore.

01:22:27.760 They might go for walks,

01:22:29.080 but you don't recruit those type 2 fibers.

01:22:31.640 So you need to stand up from the toilet

01:22:33.360 several times in a row.

01:22:35.200 You need to do, or if possible, resistance training.

01:22:38.220 You need to have somebody do resistance training

01:22:40.760 with your walking stairs.

01:22:42.420 You need to recruit those type 2 fibers

01:22:44.540 because otherwise it just goes down.

01:22:47.300 I mean, we now believe that age-related muscle loss,

01:22:50.440 I mean, it's a demographic,

01:22:51.840 but it's not a physiological process

01:22:54.100 of a slow decline in muscle.

01:22:55.700 We now believe it's short successive periods

01:22:58.780 of reduced physical activity

01:23:00.920 that are actually experienced

01:23:02.760 after which they don't fully regain their muscle.

01:23:06.960 And that adds up in the last two decades of life.

01:23:10.100 And that seems to be contributing

01:23:11.620 to the muscle loss that we see in those demographics.

01:23:15.440 Let's talk about that again

01:23:17.180 because I think that is such an important point

01:23:19.900 that I want to make sure

01:23:21.680 not a single person listening to us

01:23:24.680 missed that point.

01:23:26.380 Let me restate it, and I want you to clarify.

01:23:31.500 We have long looked at data.

01:23:34.800 These are all sorts of data.

01:23:36.980 These are anthropometric data.

01:23:38.880 These are functional data

01:23:40.320 where we put activity monitors on people.

01:23:43.180 And there is an unambiguous and clear decline

01:23:47.520 in spontaneous activity, deliberate activity,

01:23:51.320 and lean mass in the aging individual.

01:23:55.500 And the decline starts somewhat slowly

01:23:59.620 and by about the seventh decade starts to accelerate.

01:24:05.320 By the eighth decade,

01:24:06.760 when a person is in their 70s,

01:24:09.560 the decline is so rapid

01:24:12.000 that it appears almost irreversible.

01:24:15.100 We would typically talk about this

01:24:17.000 as an inevitability of aging.

01:24:19.020 Hey, that's just the physiology

01:24:20.720 of what happens to the muscle.

01:24:23.020 But a minute ago,

01:24:24.480 you said something entirely different,

01:24:26.360 which suggests that it is not inevitable

01:24:28.800 and that it is not a continuous slope of decline

01:24:33.040 that reflects some physiologic process

01:24:37.120 within the atrophying muscle.

01:24:38.580 But instead,

01:24:39.460 it's a series of discrete declines,

01:24:43.020 each one precipitated by a period of inactivity.

01:24:47.260 Some of them perhaps deliberate,

01:24:50.680 meaning,

01:24:51.480 hey, I'm going on vacation for a week

01:24:53.540 and I'm just going to sit on the beach and do nothing.

01:24:55.620 Some of them forced upon us by injury or illness.

01:24:59.180 First of all, did I get it right?

01:25:00.720 Is that what you basically said?

01:25:02.800 Yes.

01:25:03.040 And I think everybody has that observation.

01:25:05.380 Think of parents or grandparents

01:25:07.020 that you saw in the last,

01:25:09.060 say, 10 years before they died.

01:25:10.400 Everybody will say it started with that urethra infection.

01:25:15.460 It started with that surgery on the hip.

01:25:18.580 And then you actually have all these little episodes

01:25:20.880 and then you saw that happening.

01:25:23.100 And that's exactly what is happening.

01:25:24.540 But this is, of course, muscle centric.

01:25:26.920 So I'm talking about muscle loss.

01:25:28.760 Of course, if we're talking about

01:25:30.220 cardiovascular disease and progression,

01:25:32.200 that's a different story.

01:25:33.760 But for the muscle loss,

01:25:35.520 it's not something we don't believe anymore

01:25:37.760 that it's in an individual,

01:25:39.920 there's not a gradual loss over time.

01:25:42.440 Because in the individual level,

01:25:43.920 it can be completely different.

01:25:45.480 The demographics show this

01:25:46.720 because as we age,

01:25:48.240 there are more people in that situation

01:25:50.540 where they have short successive periods

01:25:53.080 of reduced physical activity.

01:25:55.840 And I think one of the first period people

01:25:57.480 to actually publish this

01:25:58.660 was Douglas Penn Jones,

01:25:59.860 who unfortunately passed away himself

01:26:01.740 at a way too young age.

01:26:03.720 But he called it the catabolic crisis model.

01:26:05.600 What I find interesting about that is

01:26:08.380 you mentioned that maybe this doesn't apply

01:26:10.920 to a decline in cardiorespiratory fitness

01:26:13.400 or cardiovascular functional,

01:26:15.220 those other things.

01:26:16.200 Maybe, but I would argue

01:26:17.700 that a muscle centric view

01:26:20.400 could potentially be the most important view.

01:26:23.600 Because when your movement stops,

01:26:27.040 everything else deteriorates with it.

01:26:30.120 People say, well,

01:26:31.100 what would that have to do

01:26:32.040 with heart health or brain health?

01:26:33.320 I would argue it has everything to do

01:26:35.260 with heart health or brain health.

01:26:36.820 When a person becomes sedentary,

01:26:39.000 everything deteriorates in its wake.

01:26:42.060 Of course, your cardiovascular system

01:26:43.920 will deteriorate at an accelerated rate.

01:26:46.580 Of course, we know unequivocally

01:26:49.100 your brain will erode at an accelerated rate

01:26:52.500 when you become inactive.

01:26:54.760 And of course, we know that the quality of your life,

01:26:57.520 your happiness, your well-being

01:26:59.000 will deteriorate as you become inactive.

01:27:02.300 And so you could make a very compelling case,

01:27:05.940 I believe,

01:27:06.660 that a muscle centric view

01:27:08.480 might be the most important view.

01:27:10.800 I agree.

01:27:11.720 And that sometimes it's like talking to a mirror

01:27:13.520 when you respond.

01:27:16.020 We've done bed rest studies in healthy people

01:27:18.120 because we often use healthy young people

01:27:20.020 as a model to see what inactivity does.

01:27:22.980 And besides that 1.4 kilograms of muscle

01:27:25.560 that we see disappear in a week,

01:27:27.100 or if we immobilize a leg,

01:27:29.660 almost 220 grams of muscle

01:27:31.660 that is lost in a week,

01:27:33.040 we also see a massive decline

01:27:34.860 in oxidative capacity.

01:27:36.680 We see a decline in insulin sensitivity.

01:27:39.700 So all of these markers

01:27:40.940 that we have for cardiovascular

01:27:42.300 and metabolic health

01:27:43.360 go down in a single week of inactivity.

01:27:47.040 So it's completely right.

01:27:49.200 But of course,

01:27:50.100 in one person,

01:27:50.960 it might be the cardiovascular decline

01:27:52.480 that is driving the muscle loss,

01:27:53.860 while in the other person,

01:27:55.180 it's the muscle loss

01:27:55.840 that's driving the cardiovascular decline.

01:27:57.940 Yeah.

01:27:58.940 I'll make another shameless plug

01:28:00.360 for an idea

01:28:01.060 that we talk about a lot on this podcast,

01:28:03.080 which is this idea

01:28:04.080 of the centenarian decathlon,

01:28:05.660 this idea that

01:28:06.580 the best way to avoid this fate

01:28:09.220 when you're in your middle age,

01:28:11.120 when you're young,

01:28:11.720 whenever,

01:28:12.360 is to be very deliberate

01:28:14.100 and specific about the type of training

01:28:15.840 and of course nutrition

01:28:16.940 that is necessary

01:28:18.400 to have the most physically robust

01:28:20.940 final decade of life,

01:28:22.280 what we call the marginal decade.

01:28:24.540 And so if you train

01:28:25.560 with great specificity

01:28:26.880 to be very active

01:28:28.780 and very independent

01:28:30.520 and free of pain

01:28:32.220 and all of those things

01:28:32.940 in the last decade of your life,

01:28:34.680 by definition,

01:28:35.460 you're going to be doing

01:28:36.480 a lot of varied forms of exercise

01:28:38.800 and you're going to have to be

01:28:40.800 supporting that nutritionally

01:28:42.200 to get there.

01:28:43.000 I want to go back

01:28:44.040 to kind of one last housekeeping issue

01:28:46.700 on the protein side,

01:28:48.500 which was the difference

01:28:50.680 between whey

01:28:52.180 and casein protein

01:28:53.740 in identical amounts

01:28:56.460 relative to the parameters

01:28:58.480 you've spoken about.

01:29:00.160 Digestibility,

01:29:01.220 speed of digestion

01:29:02.200 and amino acid composition.

01:29:04.460 What are the differences

01:29:05.300 and where do you see

01:29:07.220 the use cases

01:29:08.240 clinically between them?

01:29:09.600 So the digestibility

01:29:11.320 is the same.

01:29:12.160 It's 100%.

01:29:13.000 So there's no differences there.

01:29:15.460 But if you ingest

01:29:16.400 casein versus,

01:29:17.980 and that's micellar casein

01:29:19.240 versus whey protein,

01:29:20.820 the whey protein

01:29:21.500 is much more rapidly digested

01:29:23.200 and absorbed.

01:29:24.300 You see a greater spike

01:29:26.060 in your essential amino acid

01:29:27.820 concentrations in your blood,

01:29:29.140 including leucine,

01:29:30.720 and you get a greater stimulation

01:29:32.760 of muscle protein synthesis

01:29:34.000 as a result.

01:29:35.620 However,

01:29:36.140 the longer you measure,

01:29:37.320 the more the casein

01:29:38.260 catches up in the whey.

01:29:39.380 That's also something

01:29:40.120 that you have to realize.

01:29:42.060 Yeah.

01:29:42.240 Tell us about that study

01:29:43.240 that just came out

01:29:44.080 a few weeks ago,

01:29:45.180 which seemed to challenge

01:29:47.620 a lot of the conventional thinking

01:29:50.140 around the amount

01:29:52.300 of usable substrate

01:29:53.740 that one could ingest.

01:29:54.880 So traditional thinking

01:29:55.740 had been,

01:29:57.300 boy,

01:29:57.560 it's awfully hard

01:29:58.860 to use more than

01:30:01.660 40 to 50 grams

01:30:03.460 of protein

01:30:04.320 in a meal

01:30:05.140 for muscle protein synthesis.

01:30:07.160 And if I recall,

01:30:08.660 you had three groups

01:30:10.100 in this study,

01:30:10.900 a group that was given

01:30:11.880 zero protein,

01:30:13.160 25 grams of protein,

01:30:14.400 and 100 grams of protein.

01:30:16.220 That was all casein,

01:30:17.700 correct?

01:30:18.540 That was milk protein

01:30:19.380 concentrates.

01:30:20.320 It was a milk concentrate.

01:30:21.540 So that means

01:30:22.180 equal parts casein

01:30:23.360 and whey,

01:30:23.760 or what was the breakdown?

01:30:25.100 80-20.

01:30:26.160 80-20 in favor of which?

01:30:27.940 Casein is always 80

01:30:28.960 and whey is 20 in milk.

01:30:30.680 Okay.

01:30:31.040 So if you have milk,

01:30:31.880 about 80% is casein,

01:30:33.200 20% is whey.

01:30:34.200 Got it.

01:30:34.860 And then tell us

01:30:35.540 what you saw in that study

01:30:36.740 over a long enough

01:30:37.580 period of time.

01:30:38.680 So this was a study

01:30:39.820 where we used

01:30:40.840 that intrinsically labeled

01:30:41.740 protein combined

01:30:43.100 with intravenous infusions

01:30:44.580 of amino acids.

01:30:46.040 And that allows us

01:30:46.600 not only to measure

01:30:47.280 muscle protein synthesis,

01:30:48.340 but also

01:30:50.040 how much protein

01:30:51.280 is actually released

01:30:52.180 in the circulation

01:30:53.000 from what you ingest.

01:30:54.980 And so we could make

01:30:55.940 a full quantitative assessment

01:30:57.380 of what is happening.

01:30:58.880 Now,

01:30:59.260 previously,

01:30:59.880 like I said,

01:31:00.980 most of our studies,

01:31:02.640 people like to work

01:31:03.560 on office hours.

01:31:05.060 So you have

01:31:05.780 two hours

01:31:06.380 of a run-in period,

01:31:07.840 maybe an hour

01:31:08.620 of an intervention,

01:31:09.560 and then four to six hours

01:31:11.480 of postprandial.

01:31:12.500 So after a meal,

01:31:13.800 measuring of muscle protein synthesis.

01:31:15.600 Those are long days.

01:31:16.480 So most of the studies

01:31:18.240 so far show

01:31:19.100 that 20 grams of protein

01:31:20.460 does not do better

01:31:21.400 than 40 grams of protein

01:31:22.740 to stimulate protein synthesis

01:31:24.420 for up to four to six hours.

01:31:26.600 Because that's typically

01:31:27.380 what we do.

01:31:28.320 Why do we always measure

01:31:29.300 a four to six hours?

01:31:30.240 That's all the labs

01:31:30.900 doing this kind of work

01:31:31.760 is because that's the time

01:31:33.160 between two meals.

01:31:34.340 So that makes sense.

01:31:36.260 So the 40 grams always,

01:31:39.320 if you see the studies

01:31:40.360 and a lot of other labs,

01:31:41.700 it looks like a greater response

01:31:43.300 than the 20 grams,

01:31:44.080 but it's not significantly different.

01:31:46.320 And what we saw

01:31:47.220 with the intrinsic label protein

01:31:48.500 that a lot of the protein

01:31:49.520 is not digested yet,

01:31:50.780 or at least not released

01:31:51.840 in the circulation.

01:31:53.040 And the longer you measure,

01:31:54.660 the more of that protein

01:31:55.660 still coming in.

01:31:56.840 Same with what I said,

01:31:57.920 the casein is catching up

01:31:59.160 on the way

01:31:59.620 because a lot of the casein

01:32:01.160 is not absorbed yet.

01:32:02.900 So what Jorn wanted to do,

01:32:04.580 and this was crazy

01:32:05.380 because he wanted to ingest

01:32:06.660 100 grams of protein.

01:32:08.100 To be honest,

01:32:08.600 he's so crazy,

01:32:09.320 he actually wanted to have

01:32:10.100 more treatments.

01:32:10.840 And I said,

01:32:11.300 it's not going to happen

01:32:11.920 because that's way too expensive.

01:32:13.600 And this was already

01:32:14.440 very expensive.

01:32:15.500 So we did a zero,

01:32:16.980 25 is what is being advised,

01:32:18.880 give or take.

01:32:19.740 And then the 100 gram

01:32:20.720 as an absolutely

01:32:21.720 unpractical amount.

01:32:23.700 And so we actually measured,

01:32:25.740 if I'm correct,

01:32:26.500 at four, eight,

01:32:27.340 and 12 hours

01:32:28.100 after the ingestion.

01:32:30.360 And so what you saw

01:32:31.760 is that if you measure

01:32:32.760 for an extended period of time,

01:32:34.940 that 100 gram

01:32:35.860 is still increasing

01:32:37.420 muscle protein synthesis

01:32:38.640 for a longer period of time,

01:32:41.120 resulting in a greater response

01:32:42.560 over time.

01:32:43.600 So the suggestion

01:32:44.760 that you can't get

01:32:45.760 a greater response

01:32:46.600 with more protein

01:32:47.560 is biased.

01:32:49.000 It's biased because

01:32:50.000 you don't measure long enough.

01:32:52.020 Now, the problem is,

01:32:53.800 this is a study

01:32:54.520 that everybody,

01:32:55.340 at least in my field,

01:32:56.300 needed to see

01:32:57.000 so to better understand

01:32:58.700 what is happening.

01:32:59.820 But it doesn't necessarily

01:33:01.320 translate.

01:33:02.340 And of course,

01:33:02.980 that's the problem now

01:33:03.820 with papers.

01:33:04.500 People start calling me,

01:33:05.640 like interview this,

01:33:06.800 interview that,

01:33:07.520 like,

01:33:07.940 should I eat one meal a day?

01:33:09.900 No,

01:33:10.420 that's not what we're saying.

01:33:11.940 I still think

01:33:12.800 that it's good

01:33:13.340 to have a distribution

01:33:14.280 of protein throughout the day

01:33:15.600 that every meal

01:33:16.620 has an anabolic response.

01:33:18.300 But it doesn't mean

01:33:19.520 if you have small meals

01:33:21.340 that you're going to

01:33:22.220 disappear in three weeks.

01:33:23.900 So the body adapts.

01:33:25.460 And if the body

01:33:26.120 has a huge meal,

01:33:27.140 it's still being used.

01:33:28.640 Makes sense

01:33:29.280 because if you have a,

01:33:30.240 we also wrote that

01:33:30.960 in the discussion,

01:33:31.840 if you have a snake

01:33:33.020 or a crocodile

01:33:34.120 that once in so many days

01:33:36.360 devours a goat

01:33:37.960 or a chicken

01:33:38.900 or whatever,

01:33:39.600 then it can actually see

01:33:40.600 that animal actually

01:33:41.440 stuck in the gut

01:33:42.200 for weeks

01:33:43.180 and it's actually

01:33:43.920 consuming it.

01:33:45.080 Now,

01:33:45.620 to some extent,

01:33:46.640 humans can also do that.

01:33:48.680 So it just shows you

01:33:49.820 that the response,

01:33:51.060 there's no limitation

01:33:52.160 in the response

01:33:52.880 and it can actually

01:33:53.760 range longer

01:33:54.880 than what is

01:33:55.520 previously expected.

01:33:57.560 Do you think

01:33:57.920 if you did that experiment,

01:33:59.840 but instead of using

01:34:00.960 a milk concentrate,

01:34:02.620 which was majority casein,

01:34:04.640 you used a pure whey isolate,

01:34:06.600 do you believe

01:34:08.060 that you would have

01:34:08.780 still seen

01:34:09.540 muscle protein synthesis

01:34:10.960 at the 12-hour mark

01:34:12.320 or do you think

01:34:13.080 that the rapid

01:34:14.520 digestibility of whey

01:34:16.080 would have changed

01:34:17.060 the kinetics significantly

01:34:18.600 and you would have been

01:34:19.640 largely done

01:34:20.520 at the 4-6-hour mark?

01:34:22.540 I think the difference

01:34:23.460 between the 25

01:34:24.420 and the 100 grams

01:34:26.080 might have been smaller,

01:34:28.000 but it would still

01:34:28.660 be evident

01:34:29.300 because then

01:34:30.800 the duration

01:34:31.440 of the extension

01:34:32.320 is smaller,

01:34:33.100 of course,

01:34:33.460 with the whey

01:34:34.060 than with micellar casein.

01:34:35.660 But the comparison

01:34:36.680 with milk

01:34:37.340 is very small

01:34:38.220 because,

01:34:39.220 I mean,

01:34:39.740 milk still

01:34:40.360 is very rapid.

01:34:41.440 I mean,

01:34:41.680 it's always funny

01:34:42.480 that people say

01:34:43.080 like this is slow

01:34:44.140 or this is fast.

01:34:45.540 It's all relative.

01:34:46.600 Yeah.

01:34:46.980 It's all very fast.

01:34:48.280 It's all concentrated proteins.

01:34:50.220 If you compare it

01:34:51.220 with full meals,

01:34:52.400 you get a completely

01:34:53.480 different picture.

01:34:55.100 And that's what

01:34:55.600 Philippe Pinkerts

01:34:56.400 in our group did.

01:34:57.360 He compared

01:34:58.040 the real meal,

01:34:59.460 a vegan meal

01:35:00.260 versus a typical Dutch,

01:35:01.960 I don't even know

01:35:02.700 whether I'm still

01:35:03.240 allowed to say that,

01:35:04.220 typical meal,

01:35:04.920 was actually

01:35:05.900 in Holland,

01:35:06.500 vegetables,

01:35:07.240 potatoes,

01:35:07.600 and a piece of meat.

01:35:09.260 Now,

01:35:09.880 we made those two plates

01:35:11.320 having exactly

01:35:12.920 the same energy

01:35:13.660 and exactly

01:35:14.500 the same amount

01:35:15.200 of protein.

01:35:16.380 But now,

01:35:17.380 we also have

01:35:18.100 that digestibility

01:35:19.000 factor in there

01:35:19.800 because we weren't

01:35:20.940 using powders

01:35:21.720 in a drink.

01:35:22.700 We actually have

01:35:23.260 a full meal,

01:35:24.440 a plate

01:35:24.980 with all vegan

01:35:26.380 whole foods

01:35:27.280 and a plate

01:35:28.880 with a piece

01:35:29.660 of meat

01:35:30.080 and potatoes

01:35:30.900 and some veggies.

01:35:31.780 And was the

01:35:32.860 vegan plate

01:35:33.780 cooked protein

01:35:34.700 or was it raw?

01:35:35.640 Yes,

01:35:35.960 it was cooked protein.

01:35:37.400 But it has

01:35:37.900 a little bit more fiber.

01:35:39.360 The plate is also

01:35:40.060 a little bit bigger

01:35:41.380 because the energy

01:35:42.840 density is,

01:35:43.560 of course,

01:35:43.780 smaller.

01:35:44.420 And then everything

01:35:45.140 comes together

01:35:45.720 also with the

01:35:46.360 digestibility.

01:35:47.760 And then you

01:35:48.260 actually saw

01:35:49.020 no measurable

01:35:50.920 anabolic response

01:35:51.840 with the vegan meal

01:35:52.620 and you saw

01:35:53.920 a massive

01:35:54.760 anabolic response,

01:35:55.920 muscle protein

01:35:56.400 synthetic response

01:35:57.240 with the

01:35:58.160 omnivorous meal.

01:35:59.140 And that shows

01:36:00.360 you that,

01:36:00.840 I mean,

01:36:01.140 and that doesn't

01:36:02.220 mean before

01:36:02.800 everybody just

01:36:03.420 staggles again

01:36:04.060 that I say

01:36:05.000 that you shouldn't

01:36:05.600 be eating vegan.

01:36:06.880 But the point

01:36:08.060 is that an

01:36:08.880 omnivorous meal

01:36:09.780 with animal

01:36:10.700 derived proteins

01:36:11.560 has a greater

01:36:12.380 response when

01:36:13.440 you compare it

01:36:14.120 in an amount,

01:36:15.520 the same amount

01:36:16.240 matter,

01:36:16.560 the same amount

01:36:17.160 of protein.

01:36:18.240 So quality

01:36:18.940 counts.

01:36:20.400 Yeah.

01:36:20.740 Let's go back

01:36:21.420 to what you

01:36:21.800 talked about

01:36:22.280 with respect to,

01:36:23.280 we completely

01:36:23.840 talk about the

01:36:24.400 relative speed

01:36:25.900 between whey

01:36:26.880 and casein.

01:36:28.100 But let's put

01:36:28.720 those in the

01:36:29.380 context of

01:36:30.580 a meal.

01:36:31.600 So what does

01:36:32.560 the kinetics

01:36:33.280 curve for

01:36:34.420 a casein

01:36:35.260 shake look

01:36:36.260 like compared

01:36:37.060 to ground

01:36:37.580 beef or

01:36:38.060 whole steak?

01:36:38.800 Is it

01:36:39.120 significantly

01:36:39.760 faster?

01:36:40.980 No,

01:36:41.180 that's similar.

01:36:41.780 Cooked beef

01:36:42.280 is still

01:36:42.880 very fast.

01:36:43.560 So if you

01:36:43.920 have cooked

01:36:44.540 meat or

01:36:45.760 concentrated

01:36:46.580 protein isolate

01:36:47.480 from an

01:36:48.240 animal source,

01:36:48.880 it's all

01:36:49.260 very rapidly

01:36:49.920 digested and

01:36:50.600 absorbed with

01:36:51.540 peak amino acid

01:36:52.480 levels,

01:36:53.020 I think between

01:36:53.920 30 and say

01:36:55.580 75 minutes.

01:36:57.140 if you

01:36:58.240 have a

01:36:58.920 full meal

01:36:59.520 with potatoes,

01:37:01.060 veggies,

01:37:01.440 fibers in it,

01:37:02.340 it will take

01:37:02.940 two to three

01:37:03.380 hours longer.

01:37:04.820 From a very

01:37:05.180 selfish standpoint,

01:37:06.020 I want to ask

01:37:06.580 you a question.

01:37:07.300 So I always

01:37:08.620 do my strength

01:37:09.340 training in the

01:37:09.980 morning.

01:37:10.840 Many days,

01:37:11.660 I just don't,

01:37:13.000 maybe they're

01:37:13.260 not that hungry

01:37:14.000 or I kind

01:37:15.320 of run out

01:37:15.840 of time

01:37:16.460 before I need

01:37:17.220 to jump

01:37:17.680 into stuff

01:37:18.400 and I'm

01:37:19.500 not always

01:37:20.480 diligent about

01:37:21.440 eating or

01:37:22.620 consuming protein

01:37:23.680 right after that

01:37:24.520 workout.

01:37:25.000 Now truthfully,

01:37:26.600 in part,

01:37:27.180 it's because,

01:37:28.220 well,

01:37:28.580 I want to ask

01:37:29.100 you this

01:37:29.300 question.

01:37:30.080 Let's just

01:37:30.560 assume two

01:37:31.120 scenarios.

01:37:31.760 Scenario one

01:37:32.400 is finish

01:37:33.520 exercising,

01:37:34.240 finish strength

01:37:34.640 training,

01:37:35.620 consume nothing

01:37:36.280 but water,

01:37:36.980 coffee for

01:37:37.980 another three

01:37:38.560 or four hours

01:37:39.380 before consuming

01:37:40.400 a high protein

01:37:41.220 meal versus

01:37:42.940 finish exercising

01:37:44.520 and immediately

01:37:45.460 consume 25 grams

01:37:47.000 of whey protein

01:37:47.720 in a shake

01:37:48.340 with nothing else

01:37:49.420 in it,

01:37:49.660 just whey protein

01:37:50.460 in water,

01:37:51.340 you're getting

01:37:51.740 100 calories,

01:37:53.020 chug it down

01:37:53.720 and then eat

01:37:54.680 that protein

01:37:55.820 rich meal

01:37:56.340 of 40 grams

01:37:57.200 four hours

01:37:58.180 later.

01:37:59.040 Significant

01:37:59.540 difference in

01:38:00.140 muscle protein

01:38:00.660 synthesis

01:38:01.060 between these

01:38:01.620 two over

01:38:02.360 the course

01:38:02.900 of days

01:38:03.560 or does it

01:38:04.380 all come

01:38:04.720 out in the

01:38:05.120 wash where

01:38:06.340 assuming you

01:38:07.260 get iso

01:38:08.020 amounts of

01:38:08.720 protein

01:38:09.100 throughout the

01:38:09.600 day,

01:38:10.060 does it

01:38:10.580 matter?

01:38:11.540 On 24

01:38:12.160 hours,

01:38:12.660 definitely

01:38:13.080 there's a

01:38:14.060 difference.

01:38:14.960 For example,

01:38:15.900 if you ingest

01:38:16.980 protein immediately

01:38:17.780 after exercise,

01:38:19.560 you get at

01:38:20.180 least for the

01:38:20.620 first five

01:38:21.100 hours,

01:38:21.520 you definitely

01:38:21.980 have a much

01:38:22.520 greater response

01:38:23.260 because exercise

01:38:24.700 makes the

01:38:25.380 muscle more

01:38:25.880 sensitive to

01:38:26.620 the anabolic

01:38:27.040 response to

01:38:27.660 food intake.

01:38:28.680 However,

01:38:29.060 what people

01:38:29.480 forget is

01:38:30.920 that your

01:38:31.700 response to

01:38:32.740 breakfast the

01:38:33.420 next day is

01:38:34.260 still increased

01:38:34.940 and probably

01:38:36.100 also your

01:38:36.760 lunch and

01:38:37.340 dinner the

01:38:37.720 next day.

01:38:38.720 So if you

01:38:39.060 do an

01:38:39.320 exercise session

01:38:40.160 today and

01:38:41.180 you get all

01:38:41.720 freaked out that

01:38:42.560 you didn't get

01:38:43.100 a milkshake

01:38:43.800 after your

01:38:44.480 session,

01:38:45.520 don't worry

01:38:46.080 because the

01:38:46.940 next day all

01:38:47.860 your three

01:38:48.300 meals are going

01:38:49.080 to be greater

01:38:49.640 responses because

01:38:51.020 of the exercise.

01:38:51.880 so I get

01:38:53.080 so many

01:38:53.500 times the

01:38:53.960 question like

01:38:54.560 how important

01:38:55.040 is the meal

01:38:55.500 before or

01:38:56.580 after the

01:38:57.180 exercise and

01:38:58.620 I say if you

01:38:59.220 do a consistent

01:39:00.240 training,

01:39:01.280 then there's

01:39:01.580 always three

01:39:02.060 meals before

01:39:03.080 your session

01:39:03.680 and after

01:39:04.380 your session

01:39:04.920 because you

01:39:05.660 train every

01:39:06.180 day.

01:39:06.480 So then every

01:39:07.580 meal is still

01:39:08.280 responding to

01:39:09.020 the previous

01:39:09.460 exercise session.

01:39:11.160 Now, is there

01:39:11.920 a benefit of

01:39:13.040 immediately after

01:39:13.980 exercise versus

01:39:14.740 a few hours

01:39:15.300 later?

01:39:15.920 We've done

01:39:16.500 that study,

01:39:17.840 so not sure

01:39:18.920 whether we

01:39:19.240 touched the

01:39:19.800 topic as

01:39:20.300 well,

01:39:20.860 pre-sleep

01:39:21.260 protein

01:39:21.680 feeding,

01:39:22.160 that's a

01:39:22.440 topic that

01:39:22.800 we've been

01:39:23.080 working a lot

01:39:23.620 on also

01:39:23.980 on patients.

01:39:25.180 So we

01:39:25.860 gave people,

01:39:27.120 I think it

01:39:27.520 was even

01:39:28.100 60 gram,

01:39:28.800 really proof

01:39:29.220 of principle

01:39:29.560 study,

01:39:30.440 exercise in

01:39:31.180 the evening

01:39:31.520 and then

01:39:32.600 40 or

01:39:33.120 60,

01:39:33.500 I don't

01:39:33.740 remember,

01:39:34.680 we gave

01:39:35.000 protein then

01:39:35.480 and then we

01:39:35.880 measured the

01:39:36.460 response the

01:39:37.260 next morning

01:39:37.840 after breakfast,

01:39:39.240 after 20

01:39:39.880 grams of

01:39:40.280 protein in

01:39:40.680 the morning.

01:39:41.980 So what I

01:39:42.660 was thinking

01:39:43.140 like if there

01:39:43.940 is a window

01:39:44.400 of opportunity,

01:39:45.760 then if you

01:39:46.320 give 60

01:39:47.320 grams of

01:39:47.780 protein immediately

01:39:48.440 after exercise,

01:39:49.800 maybe you

01:39:50.380 shorten the

01:39:50.940 window of

01:39:51.320 opportunity.

01:39:52.360 So if you

01:39:52.760 already provided

01:39:53.460 the exercise

01:39:54.000 after the

01:39:54.660 session,

01:39:55.220 you don't

01:39:55.740 respond as

01:39:56.360 well to the

01:39:57.000 next dinner

01:39:57.620 the next

01:39:58.000 morning.

01:39:58.700 What I'm

01:39:59.240 basically hearing

01:40:00.020 you say is

01:40:00.780 if you have

01:40:01.760 100 units of

01:40:02.920 response in

01:40:04.000 you,

01:40:05.160 the timing of

01:40:06.200 your meal

01:40:06.800 might not

01:40:08.100 impact the

01:40:09.780 total amount

01:40:10.460 of response,

01:40:11.120 it just

01:40:11.540 determines when

01:40:12.340 that response

01:40:12.940 occurs.

01:40:13.300 if I slug

01:40:14.380 that 25

01:40:15.220 grams of

01:40:15.840 whey protein

01:40:16.500 as I'm

01:40:17.500 walking out

01:40:18.020 of the

01:40:18.280 gym,

01:40:18.720 I will

01:40:19.200 get more

01:40:19.700 of my

01:40:19.980 100 units

01:40:20.620 of response

01:40:21.260 then,

01:40:21.880 but I

01:40:22.260 will get

01:40:22.680 less of

01:40:23.280 it four

01:40:23.780 or five

01:40:24.140 hours later

01:40:24.600 when I

01:40:24.860 have a

01:40:25.480 big protein

01:40:26.040 lunch.

01:40:27.060 I think

01:40:27.380 that's a

01:40:27.700 much clearer

01:40:28.120 explanation

01:40:28.720 then.

01:40:29.360 So that

01:40:29.700 was basically

01:40:30.180 the design

01:40:30.640 of the

01:40:30.860 study.

01:40:31.540 And it

01:40:31.800 fits with

01:40:32.380 what I've

01:40:32.940 learned,

01:40:33.420 of course,

01:40:33.740 for glycogen.

01:40:34.680 Because you

01:40:35.380 ingest

01:40:35.760 carbohydrates

01:40:36.320 immediately

01:40:36.720 after exercise,

01:40:37.760 so you

01:40:38.120 expedite,

01:40:39.160 accelerate glycogen

01:40:39.940 resynthesis.

01:40:40.440 But if you

01:40:41.660 don't have

01:40:42.160 to exercise

01:40:42.900 until two

01:40:43.540 days later,

01:40:44.400 it doesn't

01:40:44.840 make a

01:40:45.140 difference because

01:40:45.800 then you

01:40:46.160 have a

01:40:46.480 full 100%

01:40:47.300 recovery of

01:40:48.200 your glycogen.

01:40:49.460 Which again

01:40:49.720 is very

01:40:50.360 different from

01:40:51.080 the way I

01:40:51.580 grew up.

01:40:52.420 I mean,

01:40:52.580 when I

01:40:52.820 grew up

01:40:53.260 as an

01:40:54.020 endurance

01:40:54.380 athlete,

01:40:55.120 it could

01:40:55.300 all be

01:40:55.500 wives'

01:40:55.940 tales,

01:40:56.240 but the

01:40:56.480 traditional

01:40:56.800 thinking

01:40:57.180 was you

01:40:58.220 need to

01:40:58.600 be

01:40:58.800 mainlining

01:40:59.760 carbohydrates

01:41:00.920 the second

01:41:01.660 you get

01:41:02.080 off the

01:41:02.460 bike or

01:41:02.960 out of

01:41:03.220 the water

01:41:03.660 or whatever

01:41:04.220 because you

01:41:05.240 have this

01:41:05.560 very small

01:41:06.480 glycogen

01:41:07.020 window where

01:41:08.260 for an

01:41:08.760 hour you're

01:41:09.600 going to

01:41:09.800 maximally

01:41:10.280 assimilate.

01:41:11.580 And it

01:41:12.220 might be

01:41:12.580 the case

01:41:12.980 that,

01:41:13.460 well,

01:41:13.720 it's true,

01:41:14.300 your maximum

01:41:14.960 assimilation

01:41:15.620 would occur

01:41:16.180 in that

01:41:16.500 window,

01:41:17.340 but you

01:41:17.640 will still

01:41:18.120 incorporate

01:41:18.780 carbohydrate

01:41:19.440 into glycogen

01:41:20.060 later.

01:41:20.520 It just

01:41:20.740 might not

01:41:21.080 occur at

01:41:21.400 as high a

01:41:21.780 rate.

01:41:21.980 Is that

01:41:22.220 kind of

01:41:22.640 the same

01:41:22.940 situation?

01:41:23.920 If you're

01:41:24.140 exercising

01:41:24.620 every

01:41:24.960 Saturday,

01:41:26.000 it doesn't

01:41:26.420 make a

01:41:26.700 difference.

01:41:27.120 Louise Burke

01:41:27.580 has clearly

01:41:27.980 shown within

01:41:28.480 24 hours

01:41:29.140 your glycogen

01:41:29.560 are back

01:41:29.880 to normal.

01:41:30.660 If you

01:41:31.200 are in

01:41:31.780 the Tour de

01:41:32.140 France

01:41:32.440 and you

01:41:32.800 have to

01:41:33.400 excel

01:41:33.820 every day,

01:41:34.960 you're

01:41:35.280 going to

01:41:35.740 miss the

01:41:36.440 third day

01:41:36.860 of the

01:41:37.100 Tour if

01:41:37.900 you don't

01:41:38.240 start taking

01:41:39.060 in carbohydrates

01:41:39.660 after the

01:41:40.240 session.

01:41:41.100 Now,

01:41:41.500 going back

01:41:42.020 to that

01:41:42.880 study.

01:41:43.540 Protein

01:41:43.840 ingestion

01:41:44.320 after an

01:41:44.960 exercise session

01:41:45.560 performed in

01:41:46.040 the evening,

01:41:46.880 does that

01:41:47.540 impact your

01:41:48.420 response to

01:41:49.000 morning?

01:41:50.260 And so,

01:41:50.760 the other

01:41:51.060 trial was no

01:41:51.940 protein after

01:41:52.640 the exercise

01:41:53.300 and doing

01:41:53.880 the same

01:41:54.240 thing in

01:41:54.480 the morning.

01:41:55.460 I thought

01:41:56.120 that the

01:41:57.360 response to

01:41:58.040 breakfast would

01:41:58.660 be reduced

01:41:59.320 if you

01:41:59.860 already

01:42:00.160 ingested

01:42:00.720 60 grams

01:42:01.600 of protein

01:42:02.100 in the

01:42:02.400 evening.

01:42:03.100 It

01:42:03.280 didn't.

01:42:03.660 The

01:42:04.460 responses

01:42:04.960 were exactly

01:42:05.860 the same

01:42:06.300 to my

01:42:06.660 surprise.

01:42:07.800 So,

01:42:07.980 the

01:42:08.060 responses

01:42:08.580 to

01:42:08.860 breakfast

01:42:09.240 exactly

01:42:09.920 the

01:42:10.180 same.

01:42:11.060 So,

01:42:11.800 net,

01:42:12.400 I must

01:42:12.820 say,

01:42:13.580 that the

01:42:13.900 people ingested

01:42:14.560 the 60

01:42:15.020 grams prior

01:42:15.940 to sleep

01:42:16.440 had a

01:42:17.040 benefit in

01:42:17.980 that time

01:42:18.340 frame.

01:42:19.060 Whether it's

01:42:19.680 caught up

01:42:20.220 later on

01:42:20.980 24,

01:42:21.780 48,

01:42:22.360 72 hours,

01:42:23.680 I don't

01:42:23.980 know.

01:42:24.200 In other

01:42:24.420 words,

01:42:24.640 I was going

01:42:24.960 to ask

01:42:25.200 you that.

01:42:25.460 You only

01:42:25.840 did this

01:42:26.260 for one

01:42:26.820 dinner,

01:42:27.200 breakfast,

01:42:27.740 and sleep

01:42:28.480 session.

01:42:29.040 Yeah,

01:42:29.320 so,

01:42:29.560 so,

01:42:29.820 these

01:42:30.080 studies,

01:42:30.660 so,

01:42:30.980 studies with

01:42:31.780 infusion of

01:42:32.620 tracers are

01:42:33.860 almost always

01:42:34.640 limited to

01:42:35.340 about 12

01:42:35.860 to 24

01:42:36.380 hours.

01:42:37.340 Why?

01:42:38.020 Because you

01:42:38.600 have these

01:42:38.960 turnover of

01:42:39.660 the tissues.

01:42:40.840 So,

01:42:41.040 at some

01:42:41.300 point,

01:42:41.980 your tracer

01:42:42.560 will become

01:42:43.040 available from

01:42:43.860 the breakdown,

01:42:45.060 and then you're

01:42:45.760 measuring tracer

01:42:46.520 recycling.

01:42:47.680 It's different

01:42:48.360 techniques,

01:42:48.960 and we can

01:42:49.320 go into that

01:42:49.960 with D2O.

01:42:51.060 There's different

01:42:51.600 techniques to

01:42:52.280 counter that,

01:42:52.860 but if there's

01:42:53.400 acute tracer

01:42:54.120 infusion studies,

01:42:55.300 you're limited

01:42:55.760 to 12 to

01:42:56.840 up to 24

01:42:57.560 hours.

01:42:58.540 But so far,

01:42:59.300 long-term

01:42:59.660 training studies

01:43:00.400 basically have

01:43:01.040 shown that

01:43:01.560 protein

01:43:02.020 supplementation

01:43:02.900 can further

01:43:03.920 increase

01:43:04.460 gains in

01:43:05.380 muscle mass

01:43:05.960 and muscle

01:43:06.320 strength.

01:43:07.080 That evidence

01:43:07.640 is there.

01:43:08.700 The evidence

01:43:09.180 becomes smaller

01:43:09.940 when people

01:43:10.420 eat more

01:43:10.940 protein,

01:43:11.760 and it

01:43:12.580 gets stronger

01:43:13.220 if you look

01:43:13.860 at people

01:43:14.340 that do

01:43:14.840 not consume

01:43:15.400 enough

01:43:15.660 protein.

01:43:16.600 I mean,

01:43:16.900 we had a

01:43:17.340 black-and-white

01:43:17.880 response to

01:43:18.620 frail elderly,

01:43:19.960 six months

01:43:20.420 of training.

01:43:21.260 If we didn't

01:43:22.060 provide them

01:43:22.580 additional protein,

01:43:23.840 they didn't

01:43:24.420 gain more

01:43:24.820 muscle.

01:43:26.000 So,

01:43:26.520 the more

01:43:26.980 frail people

01:43:27.640 are,

01:43:28.100 the more

01:43:28.380 important the

01:43:29.060 amount of

01:43:29.380 protein gets,

01:43:30.040 but it's also

01:43:30.500 because they're

01:43:30.960 not consuming

01:43:31.500 a lot.

01:43:32.720 I want to

01:43:32.960 actually come

01:43:33.320 back to the

01:43:33.740 elderly in

01:43:34.820 some detail,

01:43:35.420 but I do

01:43:35.740 want to put

01:43:36.200 a bow on

01:43:36.680 this topic

01:43:37.180 here,

01:43:37.640 which is,

01:43:38.340 we don't

01:43:39.600 really know

01:43:41.020 over the

01:43:41.880 long-term,

01:43:42.900 meaning over

01:43:43.340 months and

01:43:43.920 years,

01:43:44.400 if there is

01:43:45.720 a benefit

01:43:46.260 to consuming

01:43:48.180 a very

01:43:49.340 highly digestible,

01:43:51.300 rapidly

01:43:51.780 absorbed,

01:43:53.180 good quality

01:43:54.500 amino acid

01:43:55.380 composition

01:43:56.340 protein in

01:43:57.740 the immediate

01:43:58.240 aftermath following

01:43:59.120 exercise.

01:43:59.600 It sounds

01:44:00.220 like it's

01:44:00.920 still unclear

01:44:01.680 if there

01:44:02.520 could be

01:44:02.780 a net

01:44:03.020 benefit.

01:44:03.940 So,

01:44:04.100 if a person

01:44:04.440 listening to

01:44:04.920 this says,

01:44:05.360 look,

01:44:05.540 I want

01:44:05.940 everything

01:44:06.580 in my

01:44:07.700 favor to

01:44:08.500 maximize my

01:44:09.280 odds of

01:44:10.580 optimization and

01:44:11.940 maximization of

01:44:12.640 muscle mass,

01:44:13.220 I'm going to

01:44:14.200 consume 25

01:44:15.160 grams of

01:44:15.720 whey protein

01:44:16.320 following every

01:44:17.140 workout.

01:44:18.060 Again,

01:44:18.420 from a caloric

01:44:19.160 perspective,

01:44:19.980 it's irrelevant.

01:44:20.900 It's 100

01:44:21.480 calories,

01:44:22.560 right?

01:44:22.820 It's like

01:44:23.360 less than 5%

01:44:24.500 of your daily

01:44:25.200 intake,

01:44:25.720 but it

01:44:26.640 would arguably

01:44:27.680 be the most

01:44:28.540 efficient way

01:44:29.460 to deliver

01:44:29.980 amino acids.

01:44:31.280 Is there any

01:44:31.940 reason not to

01:44:32.640 do that?

01:44:33.160 Let's just

01:44:33.520 start with that.

01:44:34.100 Is there any

01:44:34.420 downside of

01:44:35.320 doing that

01:44:35.920 as opposed to

01:44:36.760 going through

01:44:37.140 the hassle

01:44:37.520 of consuming

01:44:38.020 a meal

01:44:38.660 when you

01:44:39.200 finish your

01:44:40.180 training?

01:44:41.480 No,

01:44:41.660 on the

01:44:41.840 individual,

01:44:42.400 absolutely

01:44:42.740 not.

01:44:43.600 The only

01:44:43.900 problem that

01:44:44.580 I do

01:44:44.960 have is

01:44:45.740 that if

01:44:46.400 you advocate

01:44:47.200 too much

01:44:47.800 to use

01:44:48.340 protein

01:44:48.900 supplements

01:44:49.380 and stuff

01:44:49.740 like that,

01:44:50.080 people stop

01:44:50.640 thinking about

01:44:51.420 their food.

01:44:52.620 So,

01:44:52.980 we've had

01:44:53.300 people coming

01:44:53.920 in here

01:44:54.320 saying like,

01:44:54.940 oh,

01:44:55.460 I put a

01:44:55.940 lot of

01:44:56.140 interest in

01:44:56.620 my nutrition

01:44:57.220 and my

01:44:57.540 diet.

01:44:58.240 And then

01:44:58.720 I asked

01:44:59.060 them,

01:44:59.400 so how

01:44:59.740 do you

01:44:59.900 do it?

01:45:00.580 Yeah,

01:45:00.780 I take

01:45:01.100 29

01:45:01.520 supplements.

01:45:02.880 Just first

01:45:03.640 think about

01:45:04.180 your nutrition

01:45:04.740 and if

01:45:05.500 every meal

01:45:06.220 contains

01:45:07.060 good solid

01:45:07.840 foods

01:45:08.300 and with

01:45:09.180 ample

01:45:09.560 protein,

01:45:10.780 if you

01:45:11.100 then on

01:45:11.400 top of

01:45:11.720 that decide

01:45:12.280 that it's

01:45:12.680 easier and

01:45:13.200 more practical

01:45:13.680 to take

01:45:14.140 a whey protein

01:45:14.720 supplements

01:45:15.180 after a

01:45:15.680 training session,

01:45:16.540 be my

01:45:16.900 guest.

01:45:17.660 But if

01:45:18.280 all the

01:45:18.740 rest is

01:45:19.120 crap,

01:45:20.160 then please

01:45:21.120 do not

01:45:21.540 even consider

01:45:22.200 those whey

01:45:22.920 protein

01:45:23.220 supplements

01:45:23.660 because first

01:45:24.400 think about

01:45:24.880 your nutrition.

01:45:26.140 So I had a

01:45:26.820 lot of

01:45:27.100 people in

01:45:27.480 my life

01:45:27.860 asking me

01:45:28.440 how important

01:45:30.100 is it whether

01:45:30.660 I take my

01:45:31.220 protein shake

01:45:31.820 before or

01:45:32.880 after the

01:45:33.380 training session?

01:45:34.620 But I had

01:45:35.000 never somebody

01:45:35.740 that came up

01:45:36.200 to me like,

01:45:36.980 Luke,

01:45:37.180 how important

01:45:37.720 is it if I

01:45:38.340 skip one

01:45:38.920 training session

01:45:39.640 or I miss

01:45:40.980 one training

01:45:41.480 session?

01:45:42.260 Consistent

01:45:42.700 training is

01:45:44.060 the benefit.

01:45:45.300 Consistent

01:45:45.740 training so

01:45:46.440 that every

01:45:46.900 meal is a

01:45:47.620 greater impact

01:45:48.340 on your

01:45:48.580 muscle protein

01:45:49.120 synthesis.

01:45:50.540 It's the

01:45:50.980 same,

01:45:51.260 the questions I

01:45:51.860 always get

01:45:52.460 interviewers

01:45:53.240 on the

01:45:53.440 radio and

01:45:53.840 they say,

01:45:54.560 Luke,

01:45:55.280 what should

01:45:55.780 we eat

01:45:56.280 in order

01:45:56.580 to lose

01:45:57.040 weight?

01:45:58.180 And I

01:45:58.520 have only

01:45:58.820 one response,

01:45:59.560 it's less.

01:46:02.520 Yeah,

01:46:03.100 exactly.

01:46:04.060 But that's

01:46:04.420 people.

01:46:05.020 It's easier

01:46:05.580 to drink a

01:46:06.380 whey protein

01:46:06.800 supplement than

01:46:07.820 actually just

01:46:08.700 leave the house

01:46:09.660 at six o'clock

01:46:10.220 in the morning

01:46:10.540 and do an

01:46:10.900 extra session

01:46:11.440 of training.

01:46:12.340 Yeah.

01:46:12.800 Let's talk a

01:46:13.480 little bit about

01:46:13.980 eating less

01:46:14.660 because again,

01:46:15.760 people who

01:46:16.600 listen to this

01:46:17.080 podcast are

01:46:17.620 very familiar

01:46:18.180 with the way

01:46:18.680 I think

01:46:19.200 about this

01:46:19.540 but I'll

01:46:19.800 just sort

01:46:20.180 of explain

01:46:20.700 it to you

01:46:20.980 very,

01:46:21.240 very quickly.

01:46:22.180 I sort

01:46:22.480 of break

01:46:23.060 it down

01:46:23.400 into three

01:46:23.980 strategies to

01:46:25.060 go about

01:46:25.460 eating less.

01:46:26.100 So strategy

01:46:26.520 one is a

01:46:27.240 very deliberate

01:46:28.100 strategy called

01:46:29.520 caloric restriction.

01:46:30.620 So it's the

01:46:31.080 only way that

01:46:31.720 you directly

01:46:32.440 go about

01:46:33.040 eating less

01:46:33.660 which is

01:46:34.540 clearly what

01:46:35.140 bodybuilders

01:46:35.820 do where

01:46:36.240 they're tracking

01:46:36.900 every macronutrient,

01:46:38.960 every calorie,

01:46:40.360 they are

01:46:40.820 counting them

01:46:41.620 and they are

01:46:42.620 shrinking that

01:46:43.640 volume of

01:46:44.520 calories lower

01:46:45.500 and lower

01:46:45.920 and lower

01:46:46.320 to reach an

01:46:47.320 energy imbalance

01:46:48.440 that is

01:46:49.280 sufficient for

01:46:50.120 the amount

01:46:50.740 of fat loss

01:46:51.260 that they're

01:46:51.500 trying to

01:46:52.100 produce.

01:46:52.960 Again,

01:46:53.360 you could argue

01:46:54.280 that this is

01:46:54.760 the most

01:46:55.040 flexible way

01:46:55.840 to go about

01:46:56.340 weight loss

01:46:56.860 because it

01:46:57.620 is agnostic

01:46:58.420 to when you

01:46:59.300 eat or what

01:47:00.320 the actual

01:47:01.040 constitutive elements

01:47:02.480 are of the

01:47:02.940 diet.

01:47:03.400 It's really

01:47:04.140 just paying

01:47:04.760 attention to

01:47:05.280 the energy

01:47:05.720 balance or

01:47:06.280 imbalance.

01:47:07.380 The second

01:47:07.760 way that you

01:47:08.400 can go about

01:47:08.900 doing this

01:47:09.420 is indirectly

01:47:10.380 through dietary

01:47:11.160 restriction.

01:47:12.220 You talked

01:47:12.560 about a

01:47:12.840 vegan diet.

01:47:13.620 Hey,

01:47:13.800 you're taking

01:47:14.200 a lot of

01:47:14.880 things out

01:47:15.380 of the diet

01:47:15.900 and many of

01:47:16.780 them are

01:47:17.000 energy dense

01:47:17.840 so there's

01:47:18.680 a very good

01:47:19.000 chance you're

01:47:19.420 going to lose

01:47:20.220 weight just

01:47:20.920 on the basis

01:47:21.480 of the

01:47:21.960 restriction.

01:47:22.920 Similarly,

01:47:23.520 with a ketogenic

01:47:24.120 diet or something

01:47:24.880 of that nature,

01:47:25.740 you're going to

01:47:26.400 really generally

01:47:27.480 eat a lot

01:47:28.220 less and it's

01:47:29.300 that effect

01:47:30.320 of the diet

01:47:31.140 on perhaps

01:47:32.220 your appetite

01:47:32.760 and food

01:47:33.280 choices that's

01:47:33.960 going to result

01:47:34.480 in lower

01:47:35.180 energy intake

01:47:36.100 and therefore

01:47:36.900 energy imbalance.

01:47:38.500 The third

01:47:39.020 technique,

01:47:40.120 also indirect,

01:47:41.260 is time

01:47:41.620 restriction,

01:47:42.540 which people

01:47:42.960 call intermittent

01:47:43.500 fasting.

01:47:43.900 here you're

01:47:44.740 going to

01:47:45.400 make a

01:47:46.580 larger and

01:47:47.440 larger window

01:47:48.340 of non-eating

01:47:49.500 and by extension

01:47:50.800 a smaller and

01:47:51.600 smaller window

01:47:52.180 of eating

01:47:52.660 that eventually

01:47:53.820 results in a

01:47:55.000 caloric deficit.

01:47:55.940 Now,

01:47:56.640 we have

01:47:57.380 historically,

01:47:58.580 meaning in our

01:47:59.080 practice,

01:48:00.300 cautioned people

01:48:01.400 about excessive

01:48:02.640 use of time

01:48:03.560 restriction

01:48:04.120 if people

01:48:06.000 fit a certain

01:48:06.860 demographic

01:48:07.500 and that is

01:48:09.020 you are

01:48:10.020 obviously

01:48:10.480 overnourished,

01:48:11.520 which is our

01:48:12.520 way of describing

01:48:13.280 you have excess

01:48:14.260 adiposity,

01:48:15.460 you have high

01:48:16.180 visceral fat,

01:48:16.900 all of these

01:48:17.300 things,

01:48:17.560 you're metabolically

01:48:18.120 unhealthy,

01:48:18.480 so you're

01:48:18.840 overnourished.

01:48:19.580 We need to

01:48:20.580 make you

01:48:21.300 less nourished,

01:48:22.160 but if you're

01:48:23.180 also under

01:48:24.060 muscled,

01:48:25.100 I get very

01:48:25.880 worried about

01:48:26.720 excessive time

01:48:27.580 restriction

01:48:28.040 because with

01:48:29.340 calorie restriction

01:48:30.600 comes protein

01:48:31.480 restriction and

01:48:32.200 with protein

01:48:32.800 restriction

01:48:33.240 comes not

01:48:34.660 just a

01:48:35.000 reduction in

01:48:35.680 mass,

01:48:36.260 which on

01:48:36.960 some level

01:48:37.480 is the goal,

01:48:38.660 but a

01:48:38.940 disproportionate

01:48:39.800 loss of lean

01:48:40.580 mass.

01:48:41.380 So I want to

01:48:42.060 pause there.

01:48:42.540 Does this

01:48:43.180 resonate with

01:48:43.700 you,

01:48:44.080 all of these

01:48:44.640 trade-offs?

01:48:45.960 I fully agree

01:48:46.280 on that.

01:48:46.720 The third one

01:48:47.480 is of course

01:48:48.160 the time

01:48:48.840 restricted

01:48:49.240 feeding or

01:48:49.840 intermittent

01:48:50.200 fasting.

01:48:51.160 It works

01:48:52.100 for people,

01:48:52.780 but it

01:48:53.920 doesn't work

01:48:54.800 in a

01:48:55.280 scientific

01:48:55.660 setting because

01:48:56.540 now there's

01:48:57.020 a lot of

01:48:57.280 studies coming

01:48:57.740 out.

01:48:58.020 We've also

01:48:58.400 done a

01:48:58.700 study on

01:48:59.060 that.

01:48:59.740 So if

01:49:00.360 you

01:49:00.600 standardize

01:49:01.420 the

01:49:01.540 nutrition,

01:49:02.260 so the

01:49:02.660 caloric

01:49:03.040 content of

01:49:03.720 the diet,

01:49:04.840 you actually

01:49:05.320 see exactly

01:49:06.180 the same

01:49:06.860 fat loss

01:49:07.740 or weight

01:49:08.080 loss with

01:49:09.180 the

01:49:09.520 intermittent

01:49:10.100 or the

01:49:10.480 time

01:49:10.680 restricted

01:49:11.060 feeding

01:49:11.460 versus the

01:49:12.520 same

01:49:12.780 feeding but

01:49:13.360 then X

01:49:14.380 percent of

01:49:15.080 less caloric

01:49:15.640 intake doesn't

01:49:16.820 make any

01:49:17.480 difference.

01:49:18.420 But let's just

01:49:18.720 make sure people

01:49:19.160 understand what

01:49:19.700 you just said

01:49:20.240 and I want to

01:49:20.560 make sure I

01:49:20.880 understand what

01:49:21.200 you just

01:49:21.420 said.

01:49:22.100 You're saying

01:49:22.880 that if you

01:49:24.540 normalize for

01:49:25.480 calories across

01:49:26.660 the course of

01:49:27.260 the day versus

01:49:28.140 in a shrunk

01:49:28.900 window, if it's the

01:49:29.740 same number of

01:49:30.300 calories, there's no

01:49:30.980 weight loss.

01:49:31.900 Exactly.

01:49:32.520 There's less

01:49:32.980 weight loss.

01:49:33.520 So if you have

01:49:33.840 25% energy

01:49:35.040 restriction,

01:49:35.920 independent of the

01:49:36.860 time frame,

01:49:37.880 you're going to

01:49:38.320 lose the same

01:49:38.800 amount of fat

01:49:39.660 mass.

01:49:39.940 Now, for

01:49:40.960 me, intermittent

01:49:42.020 feeding or

01:49:42.800 time-restricted

01:49:43.460 feeding works

01:49:44.080 because I go

01:49:46.220 to the

01:49:46.480 university, spend

01:49:47.300 most of my

01:49:47.800 day here, have

01:49:48.920 no time to

01:49:49.540 eat, running

01:49:50.140 back and

01:49:50.780 forth, and

01:49:51.620 then I come

01:49:52.060 home, I sit

01:49:53.040 behind a

01:49:53.460 computer doing

01:49:54.300 all my emails

01:49:55.060 and revisions

01:49:55.960 of manuscripts,

01:49:56.500 and I start

01:49:57.700 eating way too

01:49:59.180 much and also

01:49:59.920 crap food.

01:50:01.300 So I think

01:50:01.820 more than 70%

01:50:02.780 of my food

01:50:03.420 intake, energy

01:50:04.080 intake, is

01:50:04.700 between 7 or

01:50:06.260 8 and 12

01:50:07.300 o'clock at

01:50:07.800 night.

01:50:08.040 If I do

01:50:09.520 time-restricted

01:50:10.260 feeding from

01:50:11.460 say 10 to

01:50:12.200 6, I will

01:50:13.080 lose weight

01:50:13.640 because I

01:50:14.960 wouldn't have

01:50:15.320 time to eat

01:50:15.960 that amount

01:50:16.400 of calories in

01:50:17.260 that time frame.

01:50:18.400 And that's

01:50:18.880 good for a lot

01:50:19.480 of people because

01:50:20.520 they actually

01:50:21.280 change their

01:50:22.140 homeostasis and

01:50:23.120 for a few

01:50:23.520 weeks they

01:50:24.000 lose a lot

01:50:24.480 of fat

01:50:25.140 mass and

01:50:25.940 then they

01:50:26.240 start eating

01:50:26.760 differently and

01:50:27.420 then they

01:50:27.700 gain weight

01:50:28.140 again.

01:50:28.940 So sometimes

01:50:29.860 it's easy to

01:50:30.660 change your

01:50:31.140 routine and

01:50:32.280 your bad

01:50:33.500 nutritional

01:50:34.140 habits, but

01:50:35.320 the time of

01:50:35.940 feeding is not

01:50:36.840 a metabolic

01:50:37.280 effect to

01:50:37.960 lose more

01:50:38.360 weight.

01:50:39.100 Yeah, so

01:50:39.520 what we like

01:50:41.140 to do to

01:50:41.620 try to get

01:50:42.200 around the

01:50:43.060 effect of

01:50:43.860 people losing

01:50:45.440 too much

01:50:46.060 lean mass,

01:50:47.200 and again, I

01:50:48.100 find this to

01:50:48.740 be particularly

01:50:50.120 important in

01:50:51.040 women who

01:50:52.220 want to lose

01:50:53.140 weight using a

01:50:54.200 time-restricted

01:50:54.780 feeding approach,

01:50:55.600 but who frankly

01:50:56.660 already have an

01:50:57.620 ALMI or an

01:50:58.600 FFMI that's in

01:50:59.660 the bottom 20%.

01:51:01.280 Just for folks

01:51:02.220 listening, these

01:51:03.220 are two different

01:51:03.920 ways that we

01:51:04.920 measure and

01:51:06.040 quantify lean

01:51:06.960 mass on

01:51:07.500 people, so

01:51:08.060 this is people

01:51:08.940 that are coming

01:51:09.360 in with, they're

01:51:10.360 under-muscled as

01:51:11.160 we describe them.

01:51:12.500 We will say,

01:51:13.220 look, if you

01:51:13.680 want to eat

01:51:14.280 between 2pm

01:51:16.320 and 7pm, that's

01:51:18.500 your feeding

01:51:18.940 window, you have

01:51:19.540 a five-hour

01:51:20.380 window to eat,

01:51:21.780 so 19 hours of

01:51:23.060 not eating, five

01:51:24.480 hours of eating,

01:51:25.680 we find that

01:51:26.500 women can't, and

01:51:27.460 again, I say this

01:51:28.120 because it is

01:51:28.920 mostly women that

01:51:29.760 experience this, but

01:51:30.380 I think it could be

01:51:31.080 true for anybody,

01:51:32.080 it's very difficult

01:51:33.240 to consume your

01:51:34.780 total amount of

01:51:35.660 protein if we're

01:51:36.340 trying to get

01:51:36.880 you to 1.6 or

01:51:38.360 1.8 grams per

01:51:39.720 kilogram in a

01:51:40.880 five-hour period.

01:51:42.400 Furthermore, you

01:51:43.440 have that 19-hour

01:51:44.680 window where you're

01:51:45.800 missing one of the

01:51:47.020 major inputs to

01:51:48.100 muscle protein

01:51:48.740 synthesis.

01:51:50.240 So a workaround

01:51:52.020 is, hey, during

01:51:53.780 that period of

01:51:54.200 time, you're going

01:51:54.660 to have two

01:51:55.500 shakes that are

01:51:57.240 virtually no

01:51:58.060 calories, but are

01:51:59.560 going to give you

01:51:59.980 50 grams of

01:52:00.880 protein, a 25-gram

01:52:02.300 whey protein shake,

01:52:04.620 again, just mixed

01:52:05.240 with water, at

01:52:06.140 8 o'clock in the

01:52:06.800 morning, and again

01:52:07.780 at 11 o'clock in

01:52:08.600 the morning, and

01:52:09.220 then at 2 o'clock

01:52:10.020 you're going to

01:52:10.400 eat a meal, and

01:52:11.560 at 7 o'clock you're

01:52:12.440 going to eat a

01:52:12.840 meal.

01:52:13.200 So you're going to

01:52:13.860 get your total

01:52:14.620 amount of protein,

01:52:15.920 and yeah, you've

01:52:16.780 sort of cheated on

01:52:17.940 your time-restricted

01:52:18.700 feeding because you've

01:52:19.500 had 200 calories

01:52:20.680 outside of it, but

01:52:21.960 let's be honest, the

01:52:23.100 purpose of this is

01:52:23.860 caloric restriction.

01:52:25.020 That 200 is

01:52:26.080 relatively small

01:52:27.060 compared to what

01:52:27.720 you would have

01:52:28.280 consumed throughout

01:52:29.660 the day.

01:52:30.520 So, again, long

01:52:31.920 question, I

01:52:32.520 apologize.

01:52:33.020 It's as much

01:52:33.840 for the listener

01:52:34.360 as it is for

01:52:35.020 you.

01:52:36.040 Would you take

01:52:36.860 that approach as

01:52:38.160 a better way to

01:52:39.620 tackle two

01:52:40.600 simultaneous goals?

01:52:42.280 Lose fat mass,

01:52:44.140 preserve or gain

01:52:45.120 lean mass

01:52:45.740 simultaneously?

01:52:47.080 That would be the

01:52:47.900 main goal, and I

01:52:48.600 would completely

01:52:49.220 agree, but I

01:52:49.880 missed one factor.

01:52:51.220 I'm 100% sure that

01:52:53.080 you actually added

01:52:53.720 the effect.

01:52:54.280 Of course, the

01:52:54.740 training effect,

01:52:55.540 yes.

01:52:56.040 The resistance

01:52:56.640 training.

01:52:57.500 So, even if you

01:52:58.420 have, I mean,

01:52:58.920 old studies show

01:52:59.820 that if you have a

01:53:00.980 caloric restriction,

01:53:02.300 you lose fat-free

01:53:03.160 mass, you lose

01:53:03.800 muscle mass.

01:53:05.020 But if you do

01:53:05.780 twice a week a

01:53:07.180 resistance training

01:53:07.860 session, even in a

01:53:09.480 caloric deficit, you

01:53:10.700 don't lose muscle

01:53:11.860 mass.

01:53:12.680 So, you can prevent

01:53:13.780 the muscle mass with

01:53:15.180 simply two sessions of

01:53:16.840 resistance type

01:53:17.500 exercise a week,

01:53:18.900 preferably more, but

01:53:19.820 of course, that's the

01:53:20.580 minimal.

01:53:21.300 So, besides that

01:53:22.600 protein, it's the

01:53:23.580 exercise that makes

01:53:24.980 you respond way more

01:53:26.600 to the same or less

01:53:27.800 amount of protein

01:53:28.380 that you ingest.

01:53:29.000 And in the scenario

01:53:30.800 I described, where

01:53:32.060 you're going to have

01:53:32.980 that person have a

01:53:33.740 protein shake at 8

01:53:35.360 o'clock in the

01:53:35.860 morning and 11 o'clock

01:53:37.600 in the morning, and

01:53:38.280 then eat two meals

01:53:39.500 between, say, 2 and

01:53:40.500 7, it's probably not

01:53:42.140 that important where

01:53:43.020 the training session

01:53:43.880 goes within that day

01:53:45.520 at this point.

01:53:46.220 I mean, I think for

01:53:46.960 many people, it's just

01:53:47.680 convenient to do the

01:53:48.740 exercise in the

01:53:49.780 morning, and I agree,

01:53:51.140 of course, that that's

01:53:51.980 half the battle, is you

01:53:52.840 have to have the

01:53:53.420 training stimulus to

01:53:54.640 produce the effect.

01:53:56.280 I mean, that's why

01:53:56.920 people always ask us,

01:53:57.980 like, should we

01:53:58.400 ingest the protein

01:53:59.160 immediately after, or

01:54:00.020 an hour after exercise

01:54:00.920 doesn't make a

01:54:01.480 difference.

01:54:02.280 No, not really,

01:54:03.100 because every meal

01:54:04.980 following your

01:54:05.740 training session will

01:54:06.800 have a greater

01:54:07.320 response.

01:54:08.580 And so, also, before

01:54:10.380 the next session, there

01:54:11.380 will, again, three

01:54:12.260 meals or four meals.

01:54:13.720 So, it's a

01:54:14.440 continuous, consistent

01:54:15.720 effect of training to

01:54:17.340 make you respond better

01:54:18.880 to the same amount of

01:54:19.840 protein.

01:54:20.800 And also, in the

01:54:21.460 hospital, this is

01:54:22.220 essential.

01:54:23.560 Simply feeding people

01:54:24.680 more protein because

01:54:25.720 they're deficient and

01:54:26.540 losing muscle is not the

01:54:28.080 only solution.

01:54:29.600 Actually, if you make

01:54:30.620 them a little bit more

01:54:31.940 active between meals,

01:54:33.400 every meal has more

01:54:34.500 effect.

01:54:35.580 If we do a little bit

01:54:36.540 of exercise, more of

01:54:38.020 the meal will actually

01:54:39.000 be converted to muscle.

01:54:41.160 So, using that

01:54:42.080 intrinsic label

01:54:42.700 protein, I always have

01:54:43.940 three different

01:54:45.160 settings in my

01:54:46.480 lectures.

01:54:47.020 The first one is,

01:54:48.560 this intrinsically

01:54:49.260 protein shows you,

01:54:50.600 beyond any

01:54:51.520 discussion, you are

01:54:53.280 what you eat.

01:54:54.420 In fact, you are what

01:54:55.520 you just ate.

01:54:57.180 Now, funny enough, if

01:54:58.440 you eat that same

01:54:59.260 protein after you've

01:55:00.380 done a little exercise,

01:55:01.800 more of that protein is

01:55:03.120 converted to muscle.

01:55:04.460 So, if you're physically

01:55:05.440 active, you are more of

01:55:07.300 what you just ate.

01:55:08.800 Now, every athlete is

01:55:10.200 using this and every

01:55:11.060 coach knows this, but we

01:55:12.700 hardly use it in medical

01:55:13.900 care.

01:55:15.000 And so, it gets worse

01:55:16.560 because then you come to

01:55:17.620 the third part of the

01:55:18.940 lecture where I show you

01:55:20.620 that with physical

01:55:21.480 inactivity, you become

01:55:23.360 anabolically resistant.

01:55:24.440 So, if you become

01:55:25.960 physically less active,

01:55:28.120 you are less of what

01:55:29.260 you just ate.

01:55:30.760 Now, the problem is,

01:55:31.920 when you become sick

01:55:32.960 or ill or you get

01:55:34.080 surgery, you have

01:55:35.560 two issues.

01:55:36.800 You exercise less or

01:55:38.560 you become less

01:55:39.460 physically active, but

01:55:41.120 you also eat less.

01:55:42.640 So, it's a double

01:55:43.440 whammy downwards.

01:55:45.020 And that's what makes

01:55:46.000 us so susceptible and

01:55:47.880 vulnerable to a short

01:55:49.400 period of inactivity or

01:55:50.600 sickness.

01:55:50.900 The term anabolic

01:55:52.680 resistance is intuitive

01:55:53.960 because obviously people

01:55:55.120 understand what insulin

01:55:56.060 resistance is.

01:55:57.080 But with insulin

01:55:58.220 resistance, we can

01:55:59.040 actually really explain

01:56:00.320 mechanistically what's

01:56:01.260 happening.

01:56:01.680 I referred to Jerry

01:56:02.520 Shulman.

01:56:03.020 He provided a very,

01:56:04.360 very elegant explanation

01:56:06.240 of what's happening

01:56:07.240 intracellularly, what the

01:56:09.000 triglyceride or

01:56:10.160 diacylglyceride, if I'm

01:56:11.220 not mistaken, is doing

01:56:12.180 in the cell and how

01:56:13.860 it's impeding the

01:56:16.000 signal transduction to

01:56:17.260 move the GLUT4

01:56:18.040 transporter up to the

01:56:19.320 translocated site to

01:56:20.560 bring more glucose in,

01:56:21.560 et cetera.

01:56:22.540 I haven't followed that

01:56:23.740 discussion, but I mean,

01:56:25.000 it's still a discussion

01:56:26.500 which fatty acid

01:56:27.640 intermediate is actually

01:56:29.240 causing the whole

01:56:30.240 signaling.

01:56:31.040 Is it the storage of

01:56:32.180 the fat?

01:56:32.600 Is the inflammation that

01:56:33.720 you get from the

01:56:34.320 storage of fat?

01:56:35.300 Is it diacylglycerol?

01:56:36.840 Is it, are the

01:56:37.760 ceramides, the

01:56:38.600 fattyacyl-CoA?

01:56:39.980 I mean, yes, but it's

01:56:41.260 at least the inability

01:56:42.780 to process that fat in

01:56:44.500 the muscle is inducing

01:56:45.400 the insulin resistance.

01:56:46.720 So, the question now is,

01:56:47.960 do we have the same

01:56:49.040 level of detail around

01:56:50.920 what is actually inducing

01:56:52.460 anabolic resistance, which

01:56:53.840 is a topic that I don't

01:56:55.220 think people are as

01:56:56.300 familiar with, but

01:56:57.160 unfortunately need to be

01:56:58.980 as familiar with, given

01:57:00.760 its prevalence under two

01:57:02.960 conditions, inactivity and

01:57:05.520 aging?

01:57:05.900 I think that's the million

01:57:07.680 dollar question.

01:57:09.040 I think the first time that

01:57:10.740 anabolic resistance was

01:57:12.060 published, as a name was

01:57:13.140 coined, was by the people

01:57:14.780 in Dundee, Mike Rennie, the

01:57:16.800 late Mike Rennie.

01:57:17.640 So, he did a study where he

01:57:18.840 provided essential amino

01:57:20.220 acids to people, young and

01:57:21.700 elderly, and when they

01:57:23.760 provided a greater amount of

01:57:25.820 essential amino acids, you

01:57:27.140 saw in the young people a

01:57:28.860 greater muscle protein

01:57:29.880 synthetic response.

01:57:30.940 As we discussed before, he

01:57:32.820 got the greatest response, the

01:57:34.260 highest muscle protein

01:57:35.180 synthesis following the

01:57:36.440 provision of 10 grams of

01:57:37.820 essential amino acids, which

01:57:39.640 is perfect because 10 grams

01:57:41.120 of essential amino acid

01:57:42.280 translates to about 20

01:57:43.760 grams of protein, so it

01:57:45.140 nicely fits with those

01:57:46.360 other studies.

01:57:47.680 If he gave 20 grams of

01:57:49.400 essential amino acids, there

01:57:50.600 was no significant further

01:57:51.960 increase over the next few

01:57:53.520 hours.

01:57:54.500 So, that was normal response

01:57:56.880 and in line with everything

01:57:57.860 that we discussed before.

01:57:59.460 If he did the same thing with

01:58:00.800 the older population, he saw

01:58:03.020 that that increase in muscle

01:58:04.200 protein synthesis,

01:58:05.180 was less steep, and also

01:58:07.320 leveled off more rapidly.

01:58:09.320 So, that's how he coined

01:58:11.240 anabolic resistance, and that

01:58:13.180 was, I think, 2005.

01:58:15.180 Now, it took our lab almost 10

01:58:19.120 years to verify or to confirm

01:58:21.060 those data because we wanted to

01:58:23.100 show the same thing with a less

01:58:25.340 lab-based approach, not essential,

01:58:28.180 with that 20 grams of intrinsically

01:58:30.600 labeled protein.

01:58:32.040 And when we actually finally managed

01:58:34.120 to do that study over a long

01:58:35.420 period of time, we saw that

01:58:37.240 basal protein synthesis is not

01:58:39.600 different between young and

01:58:40.580 elderly.

01:58:41.500 So, if they're relatively active,

01:58:43.380 basal protein synthesis, if

01:58:44.640 there's a difference, it's

01:58:46.080 actually higher in elderly than

01:58:47.460 the young.

01:58:48.400 But the response to the 20 grams

01:58:50.160 of protein is less in the older

01:58:52.760 population.

01:58:53.340 So, the same amount of protein

01:58:55.580 that was ingested did not lead to

01:58:58.780 the same amount of protein

01:59:00.060 synthesis.

01:59:01.200 And with the intrinsically

01:59:01.980 labeled protein, we could show

01:59:03.020 that less of the ingested protein

01:59:04.500 was converted to muscle.

01:59:06.060 So, that is also anabolic

01:59:07.580 resistance in a more single meal

01:59:09.480 like type of approach.

01:59:11.000 Now, the big question is, and this

01:59:13.880 is now a lot of people are focusing

01:59:15.680 on anabolic resistance, what is

01:59:17.740 causing anabolic resistance?

01:59:20.040 That could be digestion.

01:59:22.060 That could be absorption.

01:59:24.660 That could be, and that's what they

01:59:26.060 call splenic sequestration, the

01:59:28.340 uptake of amino acids and what

01:59:30.260 happens between taking up in the

01:59:32.000 gut and releasing in the

01:59:33.580 circulation.

01:59:34.940 And, of course, if scientists use

01:59:36.520 difficult names, always beware.

01:59:38.700 It generally means that they don't

01:59:40.260 know what they're talking about.

01:59:41.900 So, when we say splenic

01:59:43.500 sequestration, everybody says

01:59:44.700 like, okay, but it just simply

01:59:46.360 means we don't know to what

01:59:48.560 extent the amino acids that were

01:59:50.240 actually going to the portal vein

01:59:52.080 or actually being absorbed in the

01:59:53.980 intestinal tissues and not being

01:59:56.340 released in the circulation.

01:59:57.640 That's splenic sequestration.

01:59:59.720 Where is it?

02:00:00.180 Is it in the liver?

02:00:01.080 Is it still in the intestine?

02:00:02.400 Is it taken to other tissues in

02:00:04.000 between the portal vein, like

02:00:05.380 lymphatic system?

02:00:06.500 We don't know exactly.

02:00:07.360 And then the release in the

02:00:08.940 circulation.

02:00:10.060 But then insulin also plays a

02:00:11.620 role because if there's not

02:00:13.560 enough insulin, and insulin is

02:00:15.520 not stimulatory but permissive, is

02:00:18.020 how much of the tissues are being

02:00:19.780 perfunded.

02:00:20.840 So, they get blood.

02:00:22.260 Because if the blood doesn't

02:00:23.380 perfuse the muscle, those free

02:00:25.360 amino acids are never going to be

02:00:26.620 seen by the muscle.

02:00:28.100 Then we have the uptake in the

02:00:29.700 muscle.

02:00:30.500 And then you have those signaling

02:00:32.340 responses, emphal pathway in the

02:00:34.060 muscle.

02:00:34.280 On all these levels, anabolic

02:00:36.680 resistance can reside.

02:00:38.420 So, it's impossible to find it.

02:00:40.540 And so, a lot of people are

02:00:41.520 focusing on all these different

02:00:42.620 areas.

02:00:44.220 And then the problem is, and this

02:00:46.240 is the problem with every study in

02:00:48.420 where we actually look at aging, we

02:00:50.900 compare young and older people.

02:00:53.040 We don't follow the same person for

02:00:55.020 40 or 50 years because that doesn't

02:00:58.160 work for studies.

02:00:58.980 And it takes too long.

02:01:00.100 That's why we use all those animal

02:01:01.600 species or any organisms like the C.

02:01:04.240 elegans or whatever.

02:01:05.700 If we compare young and old, we're

02:01:07.380 not comparing the same person.

02:01:10.400 We're actually comparing lifestyle,

02:01:12.240 comorbidity, pharmacological

02:01:14.240 interventions that they have, food

02:01:16.080 intake, all of these things.

02:01:18.680 But I just said that physical

02:01:20.640 activity makes the muscle more

02:01:22.140 sensitive to the anabolic properties

02:01:23.780 of amino acids.

02:01:25.200 Does it make perfect sense to say

02:01:26.880 that less physical activity makes the

02:01:29.800 muscle less sensitive to amino

02:01:32.260 acids?

02:01:33.280 So, the only way to study this, and

02:01:34.800 this is what we do, is we

02:01:36.260 immobilize young people.

02:01:38.180 So, we put one leg in the cost for

02:01:40.160 a week.

02:01:41.340 And then if you didn't believe the

02:01:42.460 story about 1% to 2% turnover of

02:01:44.480 muscle, you know, because even after

02:01:46.820 a week when the cost comes off, you

02:01:48.880 don't need an MRI scan to see which

02:01:50.620 leg had been in the cost because you

02:01:52.820 actually see the loss of muscle in

02:01:55.220 that leg.

02:01:56.260 How much do you have to pay a young

02:01:57.720 person to subject themselves to a week

02:01:59.780 in a cast?

02:02:01.260 Oh, to be honest, that is actually,

02:02:02.780 so one week is, I mean, six weeks

02:02:04.320 would be difficult, especially here

02:02:05.840 with health sciences and medicine.

02:02:07.580 A lot of the students, I mean, are

02:02:08.700 active, but one week, they actually

02:02:10.700 love the experiments.

02:02:12.340 I mean, now they can choose the color

02:02:13.920 of the cost as well.

02:02:15.580 So.

02:02:16.360 I think of some of the crazy

02:02:18.100 experiments I got paid to do while I

02:02:20.660 was in medical school.

02:02:22.100 At the time, what I would do for $1,000

02:02:24.180 was, I won't admit it publicly.

02:02:26.680 Have you been able to study this

02:02:28.640 longitudinally in a mouse, for example?

02:02:30.880 No, no.

02:02:31.260 So we only do animal stuff, human

02:02:33.480 studies in vivo.

02:02:34.780 I hardly do any, I mean, I do some

02:02:36.240 animal work with collaborators.

02:02:38.060 Is anybody studying this?

02:02:39.520 Because again, you raise a good

02:02:40.580 point, which is without a

02:02:41.880 longitudinal assessment, which would

02:02:43.500 not be possible in humans, we really

02:02:45.940 are stuck without understanding the

02:02:49.360 nuances.

02:02:49.860 Of course, in humans, you can do a

02:02:51.000 crossover between active and inactive,

02:02:52.880 and that might provide an answer to

02:02:54.740 the question.

02:02:55.220 But as I listened to this list of

02:02:57.500 differences in absorption, circulation,

02:02:59.800 the splanchnic sequestration, which is

02:03:01.320 a, I've never considered that.

02:03:03.380 The perfusion related makes total

02:03:05.160 sense, uptake in the muscle, lower

02:03:07.160 mTOR activity.

02:03:07.940 We know mTOR activity is lower in the

02:03:10.340 elderly.

02:03:10.960 I mean, it could be any of the above.

02:03:12.780 It could be all of the above.

02:03:15.100 And what do I think that they're really

02:03:16.620 important?

02:03:17.360 I don't think so.

02:03:18.440 Yeah.

02:03:18.660 At the end of the day, we know what you

02:03:19.860 need to do, control what you can

02:03:21.160 control, be more active, consume more

02:03:23.520 protein.

02:03:24.360 But so if we take that previously

02:03:26.880 immobilized leg and we give that

02:03:29.620 person an amount of protein, I see a

02:03:32.580 35% difference between the leg that was

02:03:36.200 previously immobilized and the leg that

02:03:38.340 was not immobilized.

02:03:39.700 So there's a 35% anabolic resistance

02:03:43.100 after one week of inactivity.

02:03:46.480 That is much more than we see as a

02:03:49.160 difference between the young and the

02:03:50.780 older.

02:03:51.800 So with one week of inactivity, I can

02:03:54.400 make a young leg or a young muscle

02:03:57.540 respond completely like a senescent

02:04:00.160 muscle.

02:04:01.340 And now the fun thing, if I actually

02:04:03.600 take an older person and I do some

02:04:05.320 exercise and I give him protein, I see

02:04:07.760 a completely normal response.

02:04:09.840 If I take a biopsy of an older person, I

02:04:12.160 see smaller type 2 fibers.

02:04:13.900 If I train that person for three months,

02:04:16.680 the type 2 fiber is bigger than the

02:04:18.060 type 1 fiber.

02:04:19.000 And I don't see any difference in the

02:04:20.840 response to a younger person.

02:04:22.520 And I can say the same thing about

02:04:24.000 satellite cells.

02:04:25.560 So muscle on itself is actually doesn't

02:04:29.500 seem to get that old.

02:04:31.340 It actually still responds completely

02:04:33.380 normal and I can normalize for age by

02:04:35.840 physical activity.

02:04:37.520 Yeah, I was about to say the two

02:04:38.960 examples you gave there completely

02:04:41.240 changed the discussion.

02:04:42.780 Again, I think it's worth restating

02:04:44.660 them because you're saying so many

02:04:46.500 important things.

02:04:47.160 I just want to make sure people are

02:04:48.740 not missing these, right?

02:04:50.100 So you took a group of young, healthy

02:04:52.440 people who presumably have lots of

02:04:54.920 anabolic capacity.

02:04:56.260 You put them in a cast for a week and

02:04:58.880 you immediately demonstrate upon

02:05:00.320 removing the cast that the leg that

02:05:03.500 has been immobile for a week is 35%

02:05:07.560 less responsive to protein assimilation

02:05:11.480 than the other leg.

02:05:13.400 That's an anabolic resistance factor of

02:05:15.240 35%, which you also pointed out is far

02:05:18.700 greater than what you see in an aged

02:05:20.480 individual.

02:05:21.460 It depends whether that age is an active

02:05:23.680 older or a normal or if that older person

02:05:25.940 is lying in bed for three weeks with

02:05:27.540 COVID, we're talking about another

02:05:29.080 situation, but yeah.

02:05:30.420 But then the other thing you said was

02:05:31.380 you can take an aged individual who

02:05:33.320 might have, again, 20 or 30% less

02:05:36.780 anabolic response to protein than a young

02:05:39.300 person, but if you exercise them, you can

02:05:42.640 bring them up to the same level as a

02:05:44.860 younger person.

02:05:46.100 These two factors suggest that activity

02:05:49.740 might be the main determinant of anabolic

02:05:52.400 resistance and an aging individual or age

02:05:56.540 within an individual is simply a proxy for

02:05:58.820 activity.

02:05:59.780 And so it's more difficult for older

02:06:02.040 people to maybe do the same training

02:06:03.980 loads, but the muscle itself is still

02:06:07.760 responsive.

02:06:08.540 So the good news is you don't have to

02:06:11.040 start exercising when you're 40 to

02:06:13.280 actually have good muscle when you're 80.

02:06:15.580 You can still do it at 70.

02:06:17.100 Now it's better to do it at 40 as well,

02:06:19.360 but at any age, and that's also 100 plus,

02:06:23.360 the muscle is still very responsive to

02:06:26.860 physical activity and it has nothing to

02:06:30.040 do with hormones.

02:06:31.080 And that is also something that I get so

02:06:33.260 fed up with.

02:06:34.300 We've just finished a study with prostate

02:06:37.100 cancer patients.

02:06:38.280 Now, you know what happens when they get

02:06:39.820 endogen deficiency therapy?

02:06:41.640 They lose a lot of muscle mass.

02:06:43.560 They gain a lot of fat mass.

02:06:44.940 They have an increased risk of becoming

02:06:46.440 diabetes, developing cardiovascular

02:06:48.520 disease.

02:06:49.280 Besides the effects that they become a

02:06:50.740 little bit lethargic, we did training

02:06:52.980 with them, resistance training, two to

02:06:55.080 three times a week.

02:06:57.100 The ADT had no effect on their muscle mass.

02:07:00.380 They actually gained muscle mass.

02:07:02.180 So despite the fact that they had no

02:07:04.620 testosterone, they were basically chemically

02:07:06.740 castrated, two to three times per week

02:07:09.160 resistance training, increased muscle mass,

02:07:11.760 increased muscle strength, and attenuated

02:07:14.360 fat mass gain.

02:07:15.840 It's that easy.

02:07:17.280 It's ridiculous that people go on ADT and

02:07:19.860 are not immediately getting resistance

02:07:21.360 training in addition to it because it

02:07:23.820 prevents all the negative side effects.

02:07:26.320 You've now hit on the second point that I

02:07:28.880 think is really frustrating and difficult

02:07:30.880 to hear and I really hope that there are

02:07:32.580 people out there in a position to do

02:07:35.120 something about this, right?

02:07:36.080 Which is, look, there's such a disconnect

02:07:38.240 in medicine when it comes from doing really

02:07:42.400 wonderful things to then missing the boat on

02:07:46.220 the support system that's needed.

02:07:48.200 So the two examples here is the one you just

02:07:50.460 gave.

02:07:51.400 You know, does it make sense to put a man on

02:07:53.160 androgen deprivation therapy?

02:07:54.540 Yes, it does under certain circumstances.

02:07:56.960 If a man has metastatic or inoperable high

02:07:59.600 grade prostate cancer, he needs to be on

02:08:01.680 androgen deprivation therapy.

02:08:03.760 And as you pointed out, yeah, as you pointed

02:08:05.600 out, he is being chemically castrated and I

02:08:07.980 have seen many of these men and they are quite

02:08:10.600 miserable because they are losing lots of

02:08:14.140 muscle mass, they are gaining lots of fat, and

02:08:17.120 they are becoming metabolically profoundly

02:08:20.120 unhealthy.

02:08:20.700 And yet you would think that for every oncologist

02:08:25.100 that puts a patient or every urologist who manages a

02:08:28.920 patient through androgen deprivation therapy, it

02:08:32.660 should be as important that prescribed alongside that

02:08:37.840 androgen deprivation therapy is a resistance training

02:08:41.100 program and a proper diet around high protein intake.

02:08:45.120 And I would say, look, you should be resistance training four

02:08:47.860 or five times a week.

02:08:48.880 I mean, this is the most potent thing you have to

02:08:51.900 counterbalance that.

02:08:53.140 And the other example you gave that's just infuriating is to

02:08:55.480 think of all of these sedentary hospitalized patients who are

02:08:59.000 basically being protein restricted.

02:09:00.720 Again, we talk so much in the United States, and I'm sure it's true in

02:09:06.920 Europe about the cost of health care and the burden of health care and

02:09:10.620 the burden of the sick individual and how so many dollars of a person's

02:09:15.380 health care allotment are spent at the end of life when the quality is

02:09:18.540 so low.

02:09:19.220 And yet the system itself is broken in that it doesn't even understand the

02:09:24.100 basic fundamentals of exercise and nutrition.

02:09:26.920 And the funny thing about this that isn't really funny is this is what I

02:09:31.740 think gives much of the population a total lack of trust in the medical

02:09:35.840 establishment because they see, hey, you guys don't know about exercise and

02:09:41.760 nutrition.

02:09:42.420 So why should I believe you on these other things where you actually do have

02:09:46.140 an authority?

02:09:46.680 And I feel like I've seen an acceleration of this over the past few years.

02:09:50.460 COVID clearly didn't help.

02:09:51.940 We don't have to talk about why I think COVID policy eroded a lot of trust.

02:09:56.580 But I think there's something even deeper than that, which is just a general

02:10:00.060 belief that the medical system doesn't communicate through a strong position of

02:10:05.960 knowledge when it comes to the real way to use exercise and nutrition as medical

02:10:11.560 interventions.

02:10:12.340 I think everybody knows that lifestyle is important, but they sometimes just do not

02:10:16.720 realize how relatively easy it is to do it.

02:10:20.080 And so we should have scientists and clinicians talk more.

02:10:23.400 And it's changing, but it's going very slow.

02:10:27.100 Give you a nice example.

02:10:28.460 I mean, when you're in the hospital, you get your last meal at around five or six o'clock

02:10:32.760 if you're lucky.

02:10:33.880 And then the next morning at, say, eight o'clock or nine o'clock in the morning.

02:10:38.460 So you spend almost nine and six or 15 hours of fasting, 15 hours of fasting when you're

02:10:46.340 at the risk of losing muscle.

02:10:48.060 And you're not eating in those 15 hours.

02:10:50.100 That's stupid.

02:10:50.600 But not a single athlete in the world will do that.

02:10:53.460 So we were wondering, like, if you provide protein prior to sleep, does your gut actually

02:10:59.040 process it while you sleep?

02:11:01.500 Now, that sounds easier said than done.

02:11:04.040 So we called some of our subjects.

02:11:06.180 And actually, they call us, especially the elderly.

02:11:08.380 They're really great to work with.

02:11:09.640 It's amazing.

02:11:10.720 So they call us and say, like, look, I haven't been to your lab in the last two years.

02:11:13.960 Don't you have a study running that I can participate in?

02:11:16.560 I would say, like, oh, must the answer come over?

02:11:20.100 What we'll do is we'll take a muscle biopsy.

02:11:22.680 Then we'll take a nasogastric tube, put a tube down your nose into your gut.

02:11:26.960 We'll make you sleep in the hospital overnight.

02:11:29.640 At two o'clock in the morning, we will tiptoe into the lab, push 40 grams of preheated intrinsic

02:11:35.300 label protein in your gut without waking you up.

02:11:37.940 And in the morning, I will wake you up with a muscle biopsy.

02:11:40.500 And then they say, where can I sign up?

02:11:43.420 These guys are really amazing.

02:11:45.380 But we did this.

02:11:46.580 And what happens if while they're sleeping and you provide the protein in the guts, it's

02:11:51.460 rapidly digested and absorbed just as easily as in the morning.

02:11:55.140 So there's no restriction there.

02:11:56.880 And they actually synthesize muscle protein at night.

02:12:00.040 Next morning, we see the incorporation in the muscle.

02:12:02.820 So when we published that study, it was really weird.

02:12:05.640 I got phone calls from coaches all over the world asking me where they could buy those

02:12:10.360 nasogastric tubes.

02:12:12.200 And then I had to explain.

02:12:14.140 I said, this is a proof of principle study to show you that the gut functions while we

02:12:19.100 sleep.

02:12:19.720 But if you want to do something, just give people a protein-rich snack between dinner

02:12:25.020 and going to bed because that will expedite reconditioning, help you with your recovery

02:12:30.140 from training.

02:12:30.820 And more importantly, it might help older people or people in the hospital to attenuate

02:12:37.040 muscle loss while in the hospital.

02:12:39.280 Now, that's part one.

02:12:40.960 Second part is you should actually start doing that with a small protein snack in the evening.

02:12:45.860 Done that as well.

02:12:47.280 Then the next step is, does it actually work in hospital?

02:12:50.680 Because if you provide a protein-rich snack, do people still eat the same the next morning?

02:12:56.600 Now, that's already difficult because then in the hospital, this is actually not the

02:13:00.720 invasive work that we do.

02:13:02.140 I just wanted to have people bring around cheese cubes in the evening in the hospital

02:13:07.360 and see how it affected 24-hour food intake in patients.

02:13:11.700 It went up by 20%.

02:13:13.260 So that is stuff that we don't even manage with supplements because people don't eat them.

02:13:19.240 They get a supplement of the meal.

02:13:21.100 It's just thrown away.

02:13:22.720 So bring people a nice protein-rich snack in the evening.

02:13:26.440 They increase protein intake by 20%.

02:13:28.480 It's that easy.

02:13:29.940 I want to talk a little bit more about protein supplements.

02:13:33.480 We've talked extensively about the milk protein isolates, whey, and casein.

02:13:37.940 I get asked questions all the time about this.

02:13:39.740 And unlike you, I don't know the answer.

02:13:41.340 So I'm kind of like, you know, my answer is I don't think that matters.

02:13:44.560 But for example, my wife's friends always ask me about collagen.

02:13:49.940 Hey, should I be consuming this collagen or that collagen or this collagen?

02:13:53.980 And my response is I don't think that matters.

02:13:56.160 I frankly think you're just better off consuming a high-quality protein that has a balance of all of the amino acids.

02:14:03.900 But tell folks, first of all, what collagen is and then maybe answer my question about whether or not there's a unique benefit to consuming collagen as a supplement.

02:14:12.940 I'm almost thinking like I should do less research.

02:14:16.080 I don't get all these questions.

02:14:17.340 So collagen is a protein that is pretty prevalent in your body because it's the main protein that is a structural protein.

02:14:28.120 So collagen is in your cartilage, your bone, your tendons, your ligaments, and all of that.

02:14:33.780 And it's also in muscle, a very small amount relatively.

02:14:35.800 And it's important to transfer the force of your muscle towards your tendons.

02:14:41.760 So even in the muscle, all of your contractile proteins need to be linked to collagen in order or connective tissue proteins in order to transfer the force.

02:14:53.380 Now, a lot of people in the market you see now ingest collagen supplements because it helps you with strength, force, skin, bone, ligaments, and stuff like that.

02:15:04.880 Now, we're interested in because it's a very nice source of glycine and proline.

02:15:10.760 About 50% of your collagen is glycine and proline.

02:15:13.780 So it's a poor protein from a total perspective.

02:15:16.400 It's not as balanced as an animal-derived meat protein or milk protein.

02:15:20.480 But it contains a lot of glycine and proline.

02:15:23.400 So what you could say is that, hey, your ligaments, your cartilage, your bone also contains a lot of glycine and proline.

02:15:31.120 And so it's a good source of these two amino acids.

02:15:33.440 Makes perfect sense.

02:15:34.880 So the story makes sense.

02:15:36.280 But it's a little bit like if you eat something that you need, it's going to be better for you.

02:15:40.920 But the question is, do we already get enough glycine and proline in our diet and is additional via collagen of additional value?

02:15:50.040 Now, that is something that we don't know.

02:15:52.320 We have been starting to look at this.

02:15:54.520 And so we've been ingesting collagen and whey protein after exercise.

02:15:59.540 And then we look at myofibular protein synthesis, but also muscle connective protein synthesis.

02:16:07.380 And I hope that doesn't go too fast.

02:16:10.000 Exercise stimulates both myofibular as well as muscle connective protein synthesis.

02:16:15.320 So the adaptive response in muscle is both connective proteins as well as myofibular proteins.

02:16:20.900 Now, if you ingest protein, it further increases the response to exercise and you see greater myofibular protein synthesis.

02:16:30.380 However, the ingestion of dairy protein does not seem to increase muscle connective protein synthesis rates.

02:16:39.440 So, so far, at least for up to six hours after exercise, your contractile muscle response to protein in addition to exercise, but your muscle connective does not.

02:16:52.000 Now, we've tried that also with collagen and we do not see a greater increase in connective tissue protein synthesis rates in muscle.

02:17:02.460 So either it is not happening in the first five hours and the exercise is already a stimulus enough.

02:17:08.740 And the response is later on, or there's enough glycine and proline in dairy protein.

02:17:16.160 How much are you seeing in the muscle connective tissue response to dairy?

02:17:20.880 I was under the impression, based on what you said, that it was virtually none.

02:17:23.880 Is it some, but just pales in comparison to the exercise?

02:17:27.600 It pales in comparison to the exercise, exactly.

02:17:30.020 Okay.

02:17:30.880 No significant increase in muscle connective protein synthesis in addition to the exercise effect.

02:17:36.420 Have you done this activity or this experiment without exercise?

02:17:40.260 Because obviously exercise is such a potent stimulus that, as you said, it might be dwarfing what we see.

02:17:45.580 Have you done that experiment?

02:17:47.180 Yes.

02:17:47.540 We also done it without exercise and it does not seem to be responsive to nutrition.

02:17:52.500 But I have to make an exception in that study by Jorn, that huge amount of protein, that 100 grams, we suddenly see it.

02:18:00.140 Interesting.

02:18:00.740 Interesting.

02:18:01.380 So in that study where you gave the massive dose of protein and those were not exercising patients.

02:18:07.460 Over a longer period of time.

02:18:08.720 Yeah.

02:18:09.320 But that was exercise as well.

02:18:10.900 I see.

02:18:11.220 So it seems that based on those data, there is no benefit in both myofibular or muscle connective tissue protein synthesis using collagen versus using whey or casein.

02:18:24.820 So if a person is taking a collagen protein because they believe that it will disproportionately help them increase the strength of their connective tissue, the data would say that that is not correct, at least in the presence of an exercising individual.

02:18:42.160 Yes.

02:18:42.880 Over five hours, I guess, to be fully complete.

02:18:45.320 Yes.

02:18:45.680 Okay.

02:18:45.900 So from a practice translation, I still hold an option open for ligaments, tendons, bone, cartilage, because when I look at muscle connective protein, the fraction that we actually take out of the muscle contains only a few percent of collagen.

02:19:02.880 So the muscle doesn't contain a lot of collagen.

02:19:05.940 So the question is, is it not more important for tendons, ligaments, bone, and cartilage?

02:19:11.300 I wouldn't say that it's not working there.

02:19:14.020 So, again, we are also athletes, we're also patients, and we're also scientists.

02:19:19.840 So as a scientist, I haven't seen evidence that it actually leads to greater connective tissue protein synthesis rates.

02:19:27.040 But if I would actually break my hip or I would actually have a major issue with my knee and I'm recovering and rehabilitating, I think I would take both a protein supplement that also has a little bit of collagen in order to be sure that I get enough glycine and protein.

02:19:43.120 The other point to consider is, if there are people listening to this who are just using collagen as their supplemental protein source, they're undoubtedly compromising myofibrillar muscle protein synthesis.

02:19:55.580 Because as you said, they're basically just getting a lot of proline and glycine, and they're probably really missing out on leucine, lysine, methionine, and the other amino acids that are far more potent.

02:20:07.600 It's a very low-quality protein from the perspective of amino acid balance, yes.

02:20:12.780 But it's a nice source of glycine and proline.

02:20:15.060 But if you take enough protein, probably the glycine and proline is already sufficiently available in your diet.

02:20:20.940 However, if you have major issues with ligaments, tendons, or other almost purely collagen-based structures, it might be a benefit.

02:20:29.340 I'm not throwing that away.

02:20:30.800 That is something that we still want to look at for the next few years.

02:20:33.220 But the jury is still out on that.

02:20:35.900 Yeah.

02:20:36.560 Let's talk a little bit about something you said earlier, which was what some targets might be for a meal.

02:20:42.780 So you mentioned two to three grams of leucine in a meal.

02:20:47.160 If you really, really want to kick muscle protein synthesis into overdrive.

02:20:51.980 Do you have any other rules of thumb around specific amino acids?

02:20:55.980 One of the things we do try to talk to our patients about, especially patients who are plant-based, is rather than just have them worry about the different bioavailability of this protein versus that protein, is just sort of focus on how much leucine, lysine, methionine you're getting across the course of a day or even in the course of a meal.

02:21:15.580 But I'd like to hear your guidelines around that.

02:21:17.300 So many of the plant-derived proteins are low in lysine and or methionine.

02:21:23.080 So that is always a discussion, of course.

02:21:25.980 Now, if you eat a lot of meat alternatives, often these meat alternatives lack or have a low amount of lysine or methionine.

02:21:35.140 So a lot of these projects are spiked or fortified with those individual amino acids.

02:21:40.180 However, if you eat a well-balanced meal, you typically have different plant-based proteins in your meal that often compensate low lysine or low methionine.

02:21:51.660 For example, one protein has a high lysine and the other one has relatively high methionine.

02:21:56.760 So they compensate.

02:21:57.880 So that's why also your mom would say, have a diet that is balanced with a lot of different sources.

02:22:03.400 Then the problems become smaller and you don't have to expect huge issues.

02:22:08.320 Certainly not if you're consuming enough protein because you can compensate for lesser quality by greater quantity.

02:22:16.280 And that's also the confusion with, for example, the Game Changers documentary that everybody seems to have seen.

02:22:21.600 If you have a huge football player and he's consuming a massive amount of food, I couldn't even care less where the protein comes from.

02:22:29.600 Because simply by the mass of protein, he or she already compensates for lesser quality by the simple mass, the large amount of protein.

02:22:37.660 I mean, the hype is also here.

02:22:40.080 I got a phone call from somebody in the hospital saying like, look, what do you think?

02:22:43.500 Should we actually get only plant-based foods for our patients?

02:22:48.040 And I'm thinking like, oh no, because quality becomes important when you actually have low quantity of food.

02:22:56.840 So people that due to cancer or pain eat less, don't give them a high plant-based foods.

02:23:03.360 It sounds like you're doing a good thing, but you're not helping them at that stage in life.

02:23:08.440 Yeah, that's very interesting, right?

02:23:09.920 You would think that the most vulnerable people, the smallest people, the people eating the least, the people who are in this case,

02:23:17.780 greatest at risk for loss of lean mass need to disproportionately focus on the highest quality sources of protein.

02:23:24.340 Everybody means well, and especially that's also the communication between clinical care and science that often you think like, oh, a plant-based diet is healthier.

02:23:34.620 Yes, it's healthier if you're over-consuming energy.

02:23:37.980 And so if you need a more plant-based diet, it will allow you to eat less energy, become less obese or less overweight.

02:23:44.120 But it doesn't mean it's good for everybody necessarily.

02:23:48.040 Luke, I want to sort of, before we wrap up, ask you one more question to think about until we meet again, hopefully in person here in Austin.

02:23:55.240 Over the next 12 to 24 months, what is the single most interesting question you would like to explore in your lab?

02:24:03.920 I don't think I'm going to answer it in a year.

02:24:07.680 I'll give this as a kickoff.

02:24:08.980 We'll start over with that one.

02:24:10.300 We measured protein synthesis in brain tissue in humans.

02:24:15.760 So people that have severe epilepsy, they get surgery in the brain, so the skull is lifted.

02:24:21.160 These people were great.

02:24:22.360 They actually wanted to participate in research.

02:24:25.180 So we infused labeled amino acid tracer, and we actually got part of their neocortex.

02:24:31.900 And we measured the synthesis rate of these amino acids incorporation in the human brain throughout surgery.

02:24:37.920 Turnover rate of the human brain is almost three times as high as muscle.

02:24:43.780 And of course, there's slowly turning over proteins and fast turning proteins in your brain.

02:24:48.720 But generically, on an average level, you can actually translate that into you have a new brain in about three weeks.

02:24:57.420 Why do you still think you're you?

02:24:59.460 I mean, that's insane.

02:25:00.520 That's an interesting question.

02:25:01.560 Yeah.

02:25:01.800 Do all amino acids cross the blood-brain barrier?

02:25:06.180 To be honest, I think so.

02:25:07.780 But there might be differences on the large neutral amino acid transporters, basically, for all amino acids.

02:25:12.980 Do you have any sense of which amino acids are disproportionately used by the cortex?

02:25:21.300 No.

02:25:22.080 So you're asking now, I mean, I'm not a brain physiologist.

02:25:25.120 So we did measure.

02:25:26.260 I mean, we published this in Brain, I think, about two years ago.

02:25:28.960 So I think the amino acid composition, if I remember correctly, of the brain was not that much different from muscle.

02:25:36.200 Wow.

02:25:36.880 But the turnover of your brain, and of course, we know this, the brain has plasticity as well, just as your liver, just as now we're also looking at tumors.

02:25:44.540 So everything is growing and breaking down at an immense rate.

02:25:49.960 And I can't grasp my head around it because it means that everything is just doing this.

02:25:55.840 And you don't notice it.

02:25:56.660 Everything seems solid, but it's constantly broken down and built up again.

02:26:00.300 The amino acids in your brain now might be in your toe tomorrow morning.

02:26:04.140 How does the body do this?

02:26:06.480 And how do all these organs communicate?

02:26:08.400 It's really amazing.

02:26:10.540 Well, I think it is safe to say we won't have an answer to that question the next time we meet.

02:26:16.500 But I think what we will have are some more questions and a deeper dive on this.

02:26:21.860 So Luke, thanks very much for staying up late to talk with us this evening.

02:26:25.180 Your time.

02:26:25.680 Look forward to hopefully seeing you in person, and maybe you'll wear some orange for me next time in support of your amazing countryman, Max Verstappen.

02:26:36.640 I will do so.

02:26:37.720 Thanks for having me.

02:26:38.760 It was fun talking.

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The Peter Attia Drive - April 22, 2024

#299 ‒ Optimizing muscle protein synthesis： the crucial impact of protein quality and quantity, and the key role of resistance training ｜ Luc van Loon, Ph.D.

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