Dietary Protein, Muscle Growth, Resistance Training, Amino Acids, Plant vs. Animal Protein Sources, Anabolic Growth | Luc van Loon | #148

About the guest: Luc van Loon, PhD is a Professor of Physiology of Exercise and Nutrition and Head of the M3-research group at the Department of Human Biology at Maastricht University. His lab focuses on the skeletal muscle adaptive response to physical (in)activity, the impact of nutrition on metabolism, and related topics.Episode summary: Nick and Dr. van Loon discuss: amino acid biology; branched chain amino acids like leucine; atypical amino acids like taurine; muscle growth & muscle biology; dietary protein and plant vs. animal protein sources; resistance training and anabolic growth; the limits of dietary protein on muscle growth; and more.*This content is never meant to serve as medical advice.

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* Episode transcript below.

Full AI-generated transcript below. Beware of typos & mistranslations!

Luc van Loon 3:25

Oh, I think that's the publication's actually, it's, it's as normal, but I think this one got a lot of attention by worksheets. And it seems that we're publishing more. I think I've always been publishing but mostly we do not mean I don't I do not tend to send it to high impact journals. Because I generally prefer to send it either to the exercise people or the nutrition people. So they often come up in lower impact journals, which doesn't mean the quality is anything less of that. But you want to formula was the lead author of this really wanted to send it off at a high impact journal. He's young and ambitious, I've already lost that stage. doing that. That's why a lot of attention.

Nick Jikomes 4:09

Do you feel like you actually get better reviews, higher quality reviews when you send it to more like specialty journals rather than, you know, the top to your sexy big name journals?

Luc van Loon 4:22

I think a lot of the the higher impact journals is a lot of who knows who. And also a lot of combination studies where for example, human and animal work and a lot of cell work are combined. And sometimes that makes sense for some studies. For some studies, it's absolutely doesn't make sense. Because sometimes those three models are not they don't mean they do not necessarily align.

Nick Jikomes 4:50

Yeah, I guess I mean, yeah, there's probably a lot of ways that you know, a mouse mouse has metabolism works very differently than a human's. And if you try and compare them you're you're trying to fit a square, you know, a square peg into a round hole. Yeah, one

Luc van Loon 5:04

major problem that you have, for example, we got this, this this question a lot that, for example, we show for example, protein synthesis, or amino acid uptake or perfusion or, or anything that is directly measurable as a dynamic measure, like muscle protein synthesis over the last few hours, blood glucose uptake or release from the liver, stuff like that, that we do with stable isotopes, that gives you a real physiological signal of a process that is ongoing. And then often we get responses like, Oh, you haven't shown a mechanism. And then I say, I'm just thinking like, we've just show you showing you the mechanism, because that is the effect that has on glucose uptake, blood perfusion press, protein synthesis, whatever. And then what they want to see is, for example, a whole scholar of mRNAs, or western blots or phosphorylation of specific proteins. And to be honest, I'm not very in favor of that, because it only gives you snapshots of what happens at a certain point in time, because that's only one biopsy. One time point that shows you light, x is on light, y is off, that doesn't give me any mechanism and gives me only an insight that there are a few proteins that might be relevant, or really have a relationship and a process that I was looking for. So I'm always a little bit pissed off when I hear somebody saying, like, you have to do molecular signaling in order to get a mechanism. That's that's absolutely not what I think.

Nick Jikomes 6:32

Yeah, I mean, what what you're speaking to, I think, is, it's a pretty deep problem in that, what you're really saying is the language scientists use, we often use language in different ways. So you know, when a molecular biologist says mechanism, and they have a background in transcription, they want to see gene expression patterns. When someone like use this mechanism you have you have something different in mind. And people often sort of, frankly, when people ask for mechanism, oftentimes not always, certainly, but oftentimes, it's kind of just a lazy lazy assessment, saying, yeah, just show me what I'm familiar with. Yeah. And

Luc van Loon 7:09

so the the main thing that we do, and that's not because we're preaching for our own ministry, but we use a lot of stabilized setups, and why, because we can see the dynamics in a process and nothing in the body is regulated, on a simple concentration, everything is regulated on changes in uptake, release, stuff like that. And that's why we love to use, stabilize the traces and measure the dynamics of muscle physiology or whole body physiology. And what is always funny is, then you still have to think because one of the nice examples that we have is, for example, that I always try to teach the students is for example, if you ingest glucose, like an oral glucose tolerance test, your glucose concentration goes up, and then it goes down again. And always give people the example what happens now, if you add fiber, non digestible, no matter blah, icicle fiber to the glucose, then everybody naturally will say, Okay, you get less of an increase in glucose concentration, it attenuates, and then actually goes down again, so you get a little more blunted glucose response degree. So what is your conclusion that if you see a study and you see a blunted glucose response, with fiber added to glucose, what is your conclusion of this experiment? Probably

Nick Jikomes 8:28

less glucose was absorbed or less insulin was secreted, the fiber sort of getting in the way, fiber

Luc van Loon 8:34

delays glucose uptake into the body? Yeah, so can actually find hundreds of studies in the literature. Now I do the same thing. But then I do the following give an amount of glucose concentration goes up goes down again. Now I perform one hour of exercise before I ingest glucose. I got again, a blunted glucose response. What is your conclusion, then? Hmm,

Nick Jikomes 9:00

so So you're saying you can get the same dynamic pattern, but the body is obviously doing something very different with the glucose in each case, you you have

Luc van Loon 9:07

the outcome, that is exactly the same, but your explanation conclusion is 180 degrees, the opposite one of them, you're gonna delays the digestion and absorption and therefore the rate of appearance of glucose coming into the circulation. And exercise accelerates the uptake of glucose from the circulation. So the rate of disappearance from the circulation is increased. It's a complete different mechanism, completely different physiological process, but the endpoint in concentrations is the same. And that's where tracers come in handy because they, you know, whether it's the rate of appearance of glucose into the circulation that is attenuated, or whether it's the uptake of glucose from the circulation that has increased. That's why we like to study these things. Yeah,

Nick Jikomes 9:53

yeah. See, I mean, you guys have done a lot of work with these tracers. So you can see not only the temporal dynamics of things links as they change when you take blood samples and things, but you can also end up seeing like, Where Where do the things go in the body, are they actually being taken up more or what released

Luc van Loon 10:11

more are taken up more. And then preferably, if we also managed to sample the different organs or tissues, we can also say where it's going. And that gives you much more insights in what is really happening in the body. And so I like the other example, if your glucose level of my glucose level hopefully is about six meatballs, believe in now. If we start cycling, now, our glucose flux in the body increases several faults, but our glucose concentrations hopefully stay exactly the same. So your concentrations in the blood don't tell you anything, what is happening, and certainly not where it is happening.

Nick Jikomes 10:50

And so a lot of today's discussion is going to send around the center around what the body does with protein, what it does with amino acids. When we eat high protein diets, different amounts of protein, after exercise, a lot of it will center on a paper that we'll eventually talk about. But I want to talk about some basic background stuff to get started. So when we talk about eating protein, traditionally, speaking, for a normal, healthy person, what would be considered like a high protein meal or an average protein meal in terms of how many grams of protein you might just at lunch, or at dinner or something like that,

Luc van Loon 11:29

a modest meal will be about 20 grams of protein, if you have an evening dinner with some meat, you easily go up to 40 grams. So somewhere in between foreign for an average meal of an average meal adult of about 70 to 80 kilograms.

Nick Jikomes 11:43

So roughly speaking in that range, that would be the amount of protein very roughly speaking, that someone normal person is eating to sort of just maintain their body composition, how might that compare to someone who is intentionally trying to build muscle and is doing a lot of resistance training and is eating, quote, unquote, a lot of protein on purpose? How much might they be targeting?

Luc van Loon 12:05

Yeah, so if we talk not about a meal, but about daily protein intake, then of course, the World Health Organization says that we need to consume point eight grams of protein per kilogram body mass per day, most of us consume one to 1.2 grams of protein per kilogram body mass per day, normal people, everyday people that you see on the streets, if you are very active, and you're exercising a lot, even if you're not particularly interested in protein, you consume more food. If you consume more food, and generally 10 to 15% of your energy that you consume comes from protein, then you easily go up to 1.3 1.4. And of course, if you're an athlete with a very high activity level, and or you also consume protein supplements, they often go from 1.4 to even well above two. That's not said that it's required. That's the last thing now, I would say. And

Nick Jikomes 12:59

what has traditionally been the different ways of thinking about how much protein is enough? And how much is too much. What are some of the parameters here that people think about when they think about healthy amounts of protein to eat?

Luc van Loon 13:13

Yeah, so So normally, on a daily basis, it's somewhere between 10 to 15 Energy percent coming from protein is sufficient. But if, as I said, if you're physically active, and you eat it consume a lot more energy, you automatically consume an excessive amount of protein. So the minimal amount, which I do not say it's the optimal amount would be the point eight or point seven, eight grams of protein per kilogram body mass per day, as the World Health Organization advises. But of course, I think more ideal would be around one to 1.2. Now, one of the reasons is, what we now think, or what the literature has shown in the past, is that you get an anabolic response following the ingestion of about 20 grams of protein, high quality protein, when you're unhealthy adults. And so the assumption is that with every main meal, you get an anabolic response that basically balances the overnight negative response. And then you can be in net or balance net protein balance throughout 24 hours. And so if you have three main meals, or four main meals, depending, you basically have three or four times, say 25 grams of protein, which is around 75 grams of protein, which is about one gram per kilogram body mass per day. So every meal, preferably consuming about 25 grams of protein.

Nick Jikomes 14:38

And you said high quality protein there. What exactly do you mean by high quality protein? And how do we think about protein quality? Yeah, so

Luc van Loon 14:46

that's, that's, that's a discussion that we would have if we would start talking about plant based proteins, of course. So that's, that's I can actually make that into a two hour lecture. So we don't have time but protein quality is you can actually define it in three different ways. levels one is digestibility availability of the protein for the human body. So that depends largely on how the protein is packaged, not packaged in a factory, but by nature. So if you have, for example, plant based proteins, a lot of the protein does not become available because it's more difficult for the human body to extract by protein digestion and absorption. So first factor is digestibility. Now, much of the research that I and my colleagues do is often with plant based proteins that are derived from plant based foods. So that's protein isolates, and concentrates think protein powders, then the digestibility is already very high, then you have the rate of digestion and absorption. proteins that are more rapidly digested and absorbed, allow more of the amino acids to be released in circulation. And they tend to have a higher anabolic response, because you have a faster increase in circulating essential amino acids, which drive the anabolic response to feeding. And the third one is the amino acid composition. A lot of the lower quality proteins have either a lower essential amino acid contents, and often they are deficient in one or more specific amino acids. Notorious is that very, very, a lot of the plant based proteins can be deficient in thymine, or lysine. And often they're also very low in leucine. But of course, it's not for every plant based proteins, because there's a lot of different ones. But those are the three things that define the quality of a protein. And then of course, if you ask different people, quality is a depends on functionality. Of course, if you ask an immunologist what he thinks of quality, that is something else, then you ask, for example, a muscle physiologist who studies muscle muscle protein synthesis, but from a protein synthesis point of view, it's digestibility rate of digestion and amino acid absorption kinetics, and the amino acid composition. And

Nick Jikomes 17:05

I want to spend a little time talking about some of the different types of amino acids. So as many listeners will know, amino acids are the building blocks of proteins. One of the distinctions to be made between the different types is essential versus non essential. So the essential amino acids we need to acquire from diet because we can't produce them endogenously. But there are other differences, too. One that I'm interested in hearing about is branched chain amino acids. What are those? And how are they sort of unique or special. So

Luc van Loon 17:36

two branched chain amino acids is those are three amino acids, leucine, isoleucine, and valine. And of course, I think Leucine is the most the most well known to most people listening is that Leucine is one of the strongest amino acids that signal towards the anabolic pathway, the mTOR pathway. So we believe nowadays that Leucine is one of the most important components that drives the increase in muscle protein synthesis. When you ingest protein. Of course, it's probably not only leucine, it's also the interaction with other amino acids. And what people should never forget is that it's only the signaling response. So if you ingest the protein, you see an increase in circulating essential amino acids and non essential amino acids in the blood, they actually trigger the muscle to activate anabolic pathways such as the mTOR pathway. leucine plays an important role in that. But it's likely that there's also an interaction with other amino acids. But even if you stimulate that whole signaling pathway, you still need all the signal all the amino acids as building blocks to be available to support a higher muscle protein synthesis. And that is something that we don't know everything about, because to what extent is a certain amino acid limiting the postprandial in after a meal increase in muscle protein synthesis?

Nick Jikomes 19:03

I see. So some amino acids. So all of these amino acids that we typically talk about leucine and others, they're used as building blocks of proteins, but some of them are additionally signaling molecules, meaning that they're binding to receptors changing gene expression and the behavior of cells the cells are actually doing with the materials that we feed them. Yep. And

Luc van Loon 19:24

then they also have an interaction with directly on the betta cells in your pancreas in stimulating insulin, but insulin is in the acute postprandial muscle protein synthetic response to feeling sorry for that long sentence. Insulin is a permissive hormone, and other stimulatory but it's still part of the process.

Nick Jikomes 19:42

I see. So you can actually you can. Glucose is not the only way to stimulate insulin. We've

Luc van Loon 19:47

done studies in the past was really cool is to show that for example, in diabetics, you can still get a very strong insulin response, even though their response to glucose is attenuated. So if you Your glucose is hardly an insulin response anymore. But you give them glucose together with amino acids, and you still have quite a normal response. So a lot of the issues with signaling in the pancreas, or in the betta cell is triggered by not only glucose, but also amino acids, and also the interaction between the two.

Nick Jikomes 20:19

What about I hear sometimes about atypical amino acids? So things like taurine, which aren't used as building blocks for proteins, but are still amino acids?

Luc van Loon 20:30

Yeah. So I mean, sometimes there's no there was an interesting paper suggesting that taurine is a very important factor or a relevant factor that is a sort of biological marker for H. Now, I'm pretty, I'm pretty critical about that. I don't believe it. But I mean, we are now actually. So normally, when we do a full amino acid assay and bloods we actually don't even look at story. But nowadays, we actually put it in our screening as well to see whether we see any evidence of that. But that will be the next few years that we collect data and actually look at, also look at very interesting.

Nick Jikomes 21:07

So I think you're referring to so this is actually work that I've covered on the podcast before. So touring isn't a typical amino acid. It's founded in certain foods. It's not used as a building block for proteins, but people have correlated it with aging, meaning it tends to go down with age in all different animals that you look at. And when people the basic result that that has been shown not so long ago, was that they were able to supplement animal diets, worms, flies, monkeys, or, you know, rodents, at least, they were supplementing animals with taurine, and basically seeing a life extension effect. You're saying that there might be more to the puzzle than that.

Luc van Loon 21:48

There's no better, there's more what I actually often need, there's less to the puzzle. So we see a lot of these bit of a lot of these studies that we can't reproduce. But I mean, time is on our side, let's just see what happens. And I would like to see, for example, in the older populations that we have, whether we see a change, for example, in touring, when we mobilize all the people, and they become more trained. I mean, we've done that in the past, we have different omics techniques, to show that from a transcriptomics perspective, you can actually differentiate between an old muscle and a young muscle or a muscle piece of muscle from an older person for as a younger person, but then the difference is quite clear. But then if you start exercising these older people, suddenly, the profile isn't longer is no longer differential, you can't actually see the difference anymore. So a lot of the differences that we see between young and old and in protein synthesis and anabolic resistance, and in transcriptomic profiling, the muscle is often lifestyle related.

Nick Jikomes 22:54

I see. So it can be an artifact of lifestyle rather than an aging related thing, per se. Yes,

Luc van Loon 22:59

I mean, for example, you know that in muscle, you have type one and type two fibers. Now in younger people, especially if they also ask to do some resistance exercise, that type two fiber is always bigger than the type one fiber. Now, if you become older, we know that especially the type two fibers get smaller. So even if the muscle fibers are exactly the same, and you take a biopsy from an older and the younger person, then because of the type two fibers are smaller, you will actually have relatively more type one fiber in the older adults than in the younger adults. So that would already induce a response or difference. So this is one of the reasons why aging research is often easier. Humans are sorry, in animals, because you can't compare only age per se. Young older people, you compare lifestyle comorbidities, go medication, comorbidities, all of these other things and also changes in the muscle that occur.

Nick Jikomes 24:02

Yeah, that makes that makes sense. I mean, you're naturally gonna have a different lifestyle as you age, sometimes for aging related reasons, but sometimes for other reasons. And I mean, as you were just saying, if the tissue composition itself changes, and you're not controlling for those changes, then you've got a compound there that you may not be taking, taking into account. When we think about protein, like I want to give people a sense for like what happens to protein as we eat it, and then it gets incorporated into our bodies. So let's just say you know, sit down for a meal, I eat some steak, something with high protein content that has a good amino acid profile, good digestibility Can you give people a bird's eye view for what is happening in the breakdown process going from the stomach into the GI tract and ultimately getting incorporated into your tissues?

Luc van Loon 24:55

And that's that's that's great to just that question because that's the the main thing that I'm interested in, and that's the reason why we actually started infusing cow's with labeled amino acids, etc. We'll come to that later probably, so that we can actually follow that process from beginning to end. So if you ingest a simple meal, it generally contains about 20 grams of protein, those 20 grams of protein will be drugged, broken down into smaller pieces from your from your gastric and your guts to your intestine, then you will actually get dye and try paps and only go peptide. So smaller chains of amino acids, they will be further dissect it into smaller amino acids, most of the amino acids will be absorbed by the intestinal lumen in the form of free amino acids, a lot of them will actually be retained in the intestinal tissues also for the turnover of the gut about depending on whether you have rapidly digestible protein or slowly digestible protein between 50 and 80% of the amino acids will actually go through the portal vein after the gastrointestinal tract, through the liver, into the circulation. And there are they actually flowing around your meal also has an effect on your insulin release. So your pancreas releases some insulin, what insulin does is it opens up the vascular beds, so your all your blood vessels, at least in the insulin sensitive tissues, which include muscle. So those amino acids that have just entered the circulation will flow to the muscle, the muscle will see those amino acids will be taking those amino acids up somewhere in that process, all those signaling pathways are switched on stimulating mRNA translation, protein synthesis is increased. And if lucky, you have all the available building blocks to build the protein that you want. Depending on what you've done. The last say 24 hours before that meal, you will actually synthesize proteins. If you've done the resistance exercise, you'll build actin and myosin to become like, say a bodybuilder type. If you've done for example, a lot of endurance type exercise, you might be building all components of mitochondria that allow you to oxidize a lot of a lot of fats. So a lot of people always that's a big mistake in the literature that people pick protein synthesis as muscle building. No, it's reconditioning it's conditioning of your muscle refurbishing of your muscle towards where you want it to be. It's not necessarily muscle accretion.

Nick Jikomes 27:38

When we eat that protein we break down to the amino acids or body absorbs all that. How much of the protein synthesis that's happening? How much of the muscle reconditioning and the refurbishing? How much of that is coming from the amino acids that we ate in our last meal? Versus? Are there amino acids stored for later use? Like, like, how much can we have in the bank and not be dependent on diet? Probably

Luc van Loon 28:06

one of the reasons why I was happy to come back on the podcast, because you're asking these questions that that makes sense. So the interesting thing is, is that if you imagine that on a daily basis, all of us synthesize about 300 grams of protein. And that is muscle that is brain that is kidney that is enzymes, that is hormones, anything, acute phase proteins, 300 grams of protein. Now we just discussed the amount of protein that we consume on a daily basis, say, one gram of kilo per kilogram body mass per day. So when you're 7075, to 75 grams, say 75 grams. So we take 300 grams, and we ingest only 75 grams to stay in balance. That means we are recycling 225 grams of protein on a daily basis. So a lot of the response after a meal is actually taking part of the amino acids from what you ingest it, but also a lot of the amino acids that were actually released from tissues breaking down. So it's really cool to see that we're constantly refurbishing our tissues. And what is an amino acid now in your brain might be one in your left toe, in an hour from now or tomorrow morning. It's really amazing how that works. And you can actually see that online, basically, if you take these tissues, I see.

Nick Jikomes 29:30

So you know, when we think of, you know, oftentimes when we think about protein and diet and exercise, we think of getting progressively bigger muscles. And it's probably natural for a lot of people to think of like, you know, you have your muscle that you have right now. It's built out of the amino acids that are in there. And we're going to sort of stack things on top of that. What you're saying is it's actually constantly all of it is constantly turning over and it's much more dynamic.

Luc van Loon 29:54

And that's why it's so so I mean, I still find it magical to see that if you ingest 20 grams of protein that you see muscle protein synthesis being increased. Because in the total now we come back to tracers, in the total dynamics of the system, that 25 grams is nothing, because there's actually fivefold more amino acids being released into the circulation. And about 80% of amino acids released in the circulation is not coming from your gut. So it's only that little extra 20% spark in amino acids coming from the gut, that it actually setting up that whole response to a meal. But there's a lot of other amino acids constantly being released into the circulation. So

Nick Jikomes 30:37

So So if, you know, if someone's eating 75 grams of protein a day on average, typical person, but you have, you know, 300 grams per day of turnover. And a lot of that just comes from recycling the protein that's already inside of you. How does how does that relate to the idea of excess dietary amino acids and, and consuming too much amino acids? How do you start to think about that?

Luc van Loon 31:04

Yeah, so at some point, you will, if you, if you ingest too much protein or more than you need, you will start oxidizing it. There might be some futile protein, synthetic Seikaly, we don't really know where that is what that is, we also always for for Mir, to make things easier, we tell ourselves that the muscle tissue or the tissue free amino acid pool is stable and very small. We always say that I've never seen really critically a proof of that. So temporarily, you can actually get much of an increase in in amino acids in the free pool in the different tissues. But from a regulatory point of view, that can't be too long, because then it's the regulating the whole metabolism. So most of them, at some point, there'll be oxidized.

Nick Jikomes 31:58

And I don't know much about this area. But I know that there, there's a lot, there's a lot to learn here. oxidized amino acids? Are they bad for you? Do they want to minimize the amount of oxidized amino acids? How does that work?

Luc van Loon 32:15

No, I mean, if you if you actually ingest a large amount of protein, you will you can oxidize it, just as well as that you can oxidize carbohydrates and fats. The only reason is that it's actually very costly to convert them and oxidize them. So that is one of the reasons why besides the fact that proteins in the diet are also say the eating is that this high protein diet often helps in losing weight, both by restricting food intake, and also because of the conversion to fat is actually more energy demanding.

Nick Jikomes 32:49

I see. So. So gram per gram, if you're eating a high protein diet, compared to a lower protein diet, you're basically making your body do more metabolic work. So it becomes easier to burn calories. Yep. Interesting. And is there any? Is there any? I mean, at some point, you know, is there a clear line? Or do people have different opinions? About You know, what excess actually means we're talking about excess amino acids is too much actually becoming clearly unhealthy at some point in terms of promoting aging or promoting excess growth beyond what the body actually needs? Yeah, it's this,

Luc van Loon 33:31

this is always a little bit of a of an issue, I always get the so we're talking about all the people, for example, and often they do not consume enough protein. And then we suggest that they should consume more protein and everybody gets worried than saying like, hey, my dad actually induce some risks. For example, kidney damage and stuff like that. There's no evidence for that at all. But the big the biggest thing is do realize that sometimes you hear people talking about high protein expressed from a relative point of view. And sometimes you hear people talking about high protein from an absolute point of view. So imagine, for example, a Tour de France cyclist, he might consume on a on a busy day, 25 mega joules of energy up to even more than 30 mega joules of energy on a daily basis. They don't consume your huge amounts of protein rich foods, because a lot of it is carbohydrate, as you know. So if they can show they probably consume well below that 10% of their diet from protein, but then, just calculate yourself this the homework for the viewers and the listeners 30 mega joules of energy, he does use. So 10% is protein, how much protein that actually is. So they consume a diet that is low in protein, but the absolute protein intake is more than two and a half grams per kilogram body mass per day and So differentiate between high protein in an absolute demand and high protein and a relative amounts. Now I don't see any problems with a high protein diet in a relative amount. And on an absolute amount, it depends on your energy intake and energy expenditure. And if people are in energy balance, I don't see big issues there

Nick Jikomes 35:23

at all, I say. So if you're an energy balance, you're eating an appropriate amount of food for how much physical activity you're engaged in. You said you don't see a problem with the relative amount of protein, meaning, you know, if you're eating a high percentage of your calories as protein, as opposed to a higher percentage as another type of nutrient, but

Luc van Loon 35:42

didn't within the normal limits, of course, were foods, I mean, and then you also work like select, say, between five and 25. Is

Nick Jikomes 35:49

this like a controversial area because I feel like I hear a lot and some of its from science people, and some of its from other types of people commenting on the science. So I don't know how much truth gets lost along the way, there do seem to be quite a lot of people out there saying you should really limit protein intake, it can have detrimental effects if it gets too high, even in relative terms.

Luc van Loon 36:14

Yeah, so and I hear I see and hear these things all the time. For also fats, and also for carbohydrates. And also in the relationship or, for example, mechanisms to induce insulin resistance. Sometimes you hear that amino acids can induce insulin resistance, fatty acids can reduce insulin resistance, and glucose can also induce insulin resistance. I always explained to the students basically saying that if the milkman comes by with two bottles of milk every day and you only drink one, then it's not going to take a week before you start calling him to bring you only one bottle. That's insulin resistance. So if you actually infuse any micronutrients, or glucose free fatty acids, or amino acids in the circulation, and the tissues can't actually process that anymore, then they will probably say I don't want more. That's insulin resistance. That's not necessarily part of pathology. So yes, amino acids can induce insulin resistance. But yes, glucose as well and fatty acid as well. So every excess of nutrients can induce insulin resistance, and therefore anabolic resistance, etc, etc. So much of it is simply energy balance. As long as we own energy balance, things cannot can hardly go wrong. It's the problem when we get excess foods, and then the body has difficulty handling it, then you get ectopic lipid deposition you you develop insulin resistance, etc. And those are all ways of the body to adapt to this balance in your energy intake and energy expenditure.

Nick Jikomes 37:55

And how do we so So do we think about excess at the level of calories or at the level of different macronutrients? Because I know a lot of people emphasize that, you know, you can still get insulin resistance, you can still get obesity, even if even if you're not in positive energy balance. So So in other words, you know, I've had people on the podcast emphasize that, you know, to people consume the same amount of calories, but get very different metabolic outcomes or levels of fat deposition or insulin resistance, because some specific nutrients are having an outsize effect on the insulin piece of this or the fat synthesis piece of this, etc.

Luc van Loon 38:36

Yes, but I've never seen a study that convinced me that if you ingest foods in energy balanced, makes you obese. I don't think that's possible, simply. So, so

Nick Jikomes 38:48

being being a positive energy balance is necessary for that. No,

Luc van Loon 38:53

I mean, yes, for it to be obese, you have to be in a positive energy balance. I mean, this is the same thing. Like, I've heard so many, quite, I've actually been asked a question about food intake, restriction and, or full time, time, time, restricted feeding, or intermittent fasting, all those different popular terms. Now, a lot of people in not in science, and I mean, even myself, if I apply intermittent fasting, I lose a lot of fat. What I basically do, I mean, I don't live to too healthy. So I basically consumed probably about 70% of all my energy after seven o'clock in the evening, because in the morning, I went to the lab, I spend most of the time at work, not having time to eat or not thinking about eating. And in the evening, I'm sitting to revise papers and trying to think about stuff and being stressed out about grant applications and stuff like that, and then they start eating behind my computer. So, if I do intermittent fast asking, and I decide only to eat between eight o'clock in the morning and four o'clock in the afternoon, then I will still eat very little. But then if I don't eat between six o'clock in the evening and 12 o'clock going to bed, it means that I actually restrict more than 70% of my of my energy intake, of course, I'm going to lose a lot of weights. Plus, I also going to admit, not eating a lot of unhealthy foods. But we've also done studies where we compare intermittent fasting, when we consume exactly the same foods in in the standardized, balanced way, at different time points, then we don't see any difference, we see exactly the same. If it's in a hypocaloric diet, we see exactly the same weight loss.

Nick Jikomes 40:48

I see. So if you actually control so this gets to a point, you know, I've heard others make, which is that if you're doing so what you're saying, if I'm if I'm hearing you correctly, tell me if this is a good translation. And in other words, if someone loses weight, because they're doing daily intermittent fasting, it's not the time core, it's not the time restriction, per se, it's that doing that time restriction has helped them actually consume fewer overall calories. Yes,

Luc van Loon 41:17

in combination with also maybe stimulating them to exercise more to be more active. It's also very nice studies from Boss showing that if you skip breakfast, you tend to be less active throughout the day. So there's also an interaction between eating, having eaten and being physically active from an habitual point of view.

Nick Jikomes 41:36

I see. Besides the calorie side of this, just the catabolic sort of the calories in and turning that into fat piece of this the obesity piece. Is there any benefit to time restricted feeding in terms of inflammation markers, or other aspects of physiology?

Luc van Loon 41:57

Oh, temporarily, I think it's good. I mean, but in the long run, I don't think it makes that much of a difference. I mean, you can use it to, I mean, you know that athletes, for example, like to do long endurance type exercise sessions in the morning, before breakfast in order to maximize fat oxidation. So that is the way how with diet, you can play around with optimizing adaptive responses to exercise. For example, if you want to do into intermittent high intensity exercise, you're not going to do that in the morning in an overnight fasted state, because then you won't actually reach that normal exercise intensity. So yes, you can, you can work with diet and physical activity to moderate acute physiology and acute metabolism. And that can help you benefit from different medical depends on your aim, shoot targets and what you want to achieve.

Nick Jikomes 42:53

And when we think about when we think about muscle, and building muscle, we can think about a bodybuilder we can think about a different type of athlete, I imagine based on what you've told me, and what's out there in the literature, people have probably had lots of different opinions about how much protein is a good amount, the time course that you eat it on, should you be eating it spread out three meals a day, should you be eating it right before a workout and things like that. Can you give us sort of a bird's eye view of the different ways of thinking about that, that sort of set us up to discuss your recent study? Yep.

Luc van Loon 43:27

So people have shown that they started living fusing amino acids, then they started with ingesting free amino acids. And after that, more studies were doing ingestion of certain amounts of protein. And they showed you that you get an increase in muscle protein synthesis for up to about five hours after ingesting a single bolus of protein or free amino acids. And that has led us to believe that every main meal with sufficient protein stimulates muscle protein synthesis for say, up to four to six hours. And that if you do that three times a day, you're basically balanced out a negative if overnights protein balance, and then you're in balance or in maintenance over 24 hours. So that's the reason why nowadays people are being advised to ingest about 20 grams of more protein with each main the main meal, the spirits nicely over the day. And for example, for more active athletes going up to four or five meals a day, also nicely distributed throughout today. That is the basis on the individual studies that showed is that a single meal leads to an anabolic response.

Nick Jikomes 44:38

So if that was sound, in other words, if you were a bodybuilder and you had the choice between eating for 25 gram protein meals versus 100 grams protein meal, most people up until recently would have said spread it out.

Luc van Loon 44:53

Yes, because the suggestion was that if you ingest more than that 25 grams then most of it will be oxidized.

Nick Jikomes 45:02

Got it? And so what? What was this recent study that you guys did? What was the basic setup?

Luc van Loon 45:12

So where do we start? So, we like to measure not only muscle protein synthesis, but also the digestion of protein, the absorption of the amino acids, the release and the circulation, so that we can also see what happens with the food that you ingest. Completely. Going back to the question, you asked, how many of the amino acids that have been incorporated into protein after a meal are actually coming from the last meal, you ingested, that other stuff that we want to know. And in order to do that, we do not only infuse labeled amino acid traces into circulation, but we also ingest labeled amino acids that are incorporated into milk protein, and you can't commercially buy that stuff. So the only way of doing that is actually making it yourself. Not making it making it ourselves is not completely true, because we have the help of a cow. So we infuse a cow with labeled amino acid traces. And we've done that now several times over the last 20 years. The cow incorporates those labeled amino acids in the milk, we extract the milk by simply milking the cow, we extract that protein, we end up with milk powder, or whey or casein, whatever we want to do with it. And then we use it in clinical experiments to see how much of 20 grams protein is actually digested, absorbed over time, and used to stimulate muscle protein synthesis. And because we use traces both intravenously, in in a vein, as well as in the protein, we can actually differentiate between protein synthesis, and what happens with the protein that you ingest. Now, that's a long explanation for the point that we wanted to make is to what extent is all the protein that you ingest absorbed within the timeframe that we're measuring muscle protein synthesis. And most of the times people, there's only two or three studies that that did a dose response effect, or muscle protein synthesis. And both those studies show that 20 grams of protein have a high quality protein, either egg or milk protein, stimulates muscle protein synthesis for up to four to six hours. And after that, there is no further increase if you ingest 40 grams. And that has been the basis that everybody says 20 grams is sufficient to maximize muscle protein synthesis after a meal. Now, what we see is that if you give larger amounts, probably not everything is digested and absorbed within those four to six hours, depending on how much time you take. So you're in trouble. And he gets the credit for all of this. He was a nagging me for at least two or three years to do his study with 100 grams of protein. And I said, like, like you're on. I mean, I'm interested from a conceptual point of view, but nobody's interested because we're never going to advise people to ingest 100 grams of protein. Now, we ended up still doing the study, because the conceptual studies are, of course, much more fun than the more practical, practical, applicable studies. So we provided zero 20, and was 2525 and 100 grams of protein. And what we see within a few hours, those 100 grams is by far not digested and absorbed. And if we continue to measure muscle protein synthesis, we see that the anabolic response is much greater if you measure over a longer period of time. And then the 100 grams does give a greater response than the 25 grams. So

Nick Jikomes 48:49

when you say greater anabolic response, meaning you've got people longer

Luc van Loon 48:54

increase in muscle protein synthesis over a more prolonged period of time, ending up of more protein being synthesized over that timeframe. So

Nick Jikomes 49:02

all things being equal to different people. Same resistance exercising protocol, they eat 25 versus 100 grams, the person eating 100 grams will see more anabolic response. Yes. And so there's there's more anabolic response for consuming more protein. But how much you know, we talked about oxidized amino acids before? How much are you still wasting most of that extra 75 grams? Or is most of it actually getting used? No,

Luc van Loon 49:38

we actually did not see a massive increase that we that could have been hypothesized by some people, that you get a disproportionate increase in protein oxidation. We didn't see that.

Nick Jikomes 49:54

And can you remind us so what type of people were you? What kind of subjects did you have in the study? Were they healthy, normal individuals that were they bodybuilders what kind of people are these?

Luc van Loon 50:06

No? Are we typically don't do better bodybuilders because you have no idea what they what they got taking? Of course, yeah, but what they are doing. So these are all healthy adults. Let me double check what their age was. I think in the range of I

think we do too many studies.

Nick Jikomes 50:37

Okay, but like not normal healthy adults that there were there wasn't anything. It's not some very special pool of people. No. And so when you give them 100 grams of protein at a time it like, is that did you say this was like a protein powder? Or are they drinking like a milkshake here? How exactly are they consuming that?

Luc van Loon 51:00

Yeah, that's that's just milk protein. And then there's often the same amount of volume of water. So it's actually a huge amount of protein.

Nick Jikomes 51:09

And so, using this tracers, you can measure the amino acids in their body at multiple time points for a number of hours after they ingest this. What was what was the resistance training? They did? When did they do it relative to the samples that you took, and and how intensive was it?

Luc van Loon 51:30

Lots of questions there. So we had 36, healthy recreationally active young men. So these are basically students, or healthy. They are used of doing exercise, but not necessarily being like gym rats being in the being in the gym every day, we made them do some whole body exercise, but the focus lies lies on leg exercise. So leg press leg extension, but we also did chest press and lat pull downs. So we like to activate the full body. But of course, as we're measuring muscle protein synthesis in the legs, we always just focus most of it on the legs. And I think what we normally do is like like three to six sets, or something like that. I think let's see here for every exercise 10 tenths of maximal repetitions for familiarization. And then three to six repetitions are that's the one that's the one around, so I think about four or five sets in for every exercise. So it's about half an hour to 45 minutes of resistance exercise. And then we ingest the protein, or we take a biopsy first. And then we ingest a protein, I think it was about 800 mils of water. So that's basically cycling bottle one and a half. And then we have muscle biopsies at and it's actually quite a lot of them at 02 and 44 and 80 and 720 minutes. So that's 12, even up to 12 hours after. And so that allows us to do the acute in gestion, digestion absorption. And that is over the four hour period, so to sit 240 minutes, and then we go to double that amount. So that's eight hours for one and 80 minutes, then basically the 25 grams is completely digested and absorbed. And then we go all th