KoopCast

Collagen Supplementation for Ultrarunning with Luc van Loon, PhD and Keith Baar PhD #206

November 30, 2023 Jason Koop/Luc van Loon/Keith Baar Season 3 Episode 206
Collagen Supplementation for Ultrarunning with Luc van Loon, PhD and Keith Baar PhD #206
KoopCast
More Info
KoopCast
Collagen Supplementation for Ultrarunning with Luc van Loon, PhD and Keith Baar PhD #206
Nov 30, 2023 Season 3 Episode 206
Jason Koop/Luc van Loon/Keith Baar

View all show notes and timestamps on the KoopCast website.

Episode overview:

Luc van Loon 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. Luc has an international research standing in the area of skeletal muscle metabolism and has published well over 475 peer-reviewed articles. Current research in his laboratory focuses on the skeletal muscle adaptive response to physical activity, and the impact of nutritional and pharmacological interventions to modulate metabolism in both health and disease.

Episode highlights:

(22:50) Results of collagen research: collagen stimulates neither connective nor contractile proteins in muscle, potential explanations, the benefits of collagen are not confirmed, areas for future research

(42:35) Dietary protein intake: athletes who exercise more consume more food, thus their protein and amino acid intake per kg body mass is already high, recap

(45:57) Sources of collagen: collagen from skin sources are superior, dangers of concentrating heavy metals in bone broth, example of athlete consuming arsenic from salt

Additional resources:

SUBSCRIBE to Research Essentials for Ultrarunning
Buy Training Essentials for Ultrarunning on Amazon or Audible.
Information on coaching-https://www.trainright.com
Koop’s Social Media: Twitter/Instagram- @jasonkoop

Show Notes Transcript Chapter Markers

View all show notes and timestamps on the KoopCast website.

Episode overview:

Luc van Loon 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. Luc has an international research standing in the area of skeletal muscle metabolism and has published well over 475 peer-reviewed articles. Current research in his laboratory focuses on the skeletal muscle adaptive response to physical activity, and the impact of nutritional and pharmacological interventions to modulate metabolism in both health and disease.

Episode highlights:

(22:50) Results of collagen research: collagen stimulates neither connective nor contractile proteins in muscle, potential explanations, the benefits of collagen are not confirmed, areas for future research

(42:35) Dietary protein intake: athletes who exercise more consume more food, thus their protein and amino acid intake per kg body mass is already high, recap

(45:57) Sources of collagen: collagen from skin sources are superior, dangers of concentrating heavy metals in bone broth, example of athlete consuming arsenic from salt

Additional resources:

SUBSCRIBE to Research Essentials for Ultrarunning
Buy Training Essentials for Ultrarunning on Amazon or Audible.
Information on coaching-https://www.trainright.com
Koop’s Social Media: Twitter/Instagram- @jasonkoop

Speaker 1:

Trail and Ultra Runners. What is going on? What's happening? Welcome to another episode of the Coupecast.

Speaker 1:

As always, I am your humble host, Coach Jason Koop, and this episode of the podcast is all about Collagen, which is a supplement that is ubiquitous in the sports performance marketplace. The promise of Collagen to help strengthen, repair or rebuild tendons and ligaments has permeated sports culture today. In order to illustrate this point, let's just look at some of the market statistics. Collagen alone represents a whole 2% of the entirety of the sports supplement marketplace. When you look at all the sports supplements that are out there, collagen is a whopping 2% of that entire marketplace. Now, despite Collagen's promise and presence, much is still unknown on if it actually works as it's purported to. So enter into the equation Luke VanLoon, who is our guest today on the podcast. Luke 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. He is one of the foremost experts in the area of skeletal muscle metabolism, having published well over 475 peer reviewed articles. The current research in his laboratory focuses on skeletal muscle adaptive response to physical activity and the impact of nutritional and pharmacological interventions to modulate metabolism in both health and disease states.

Speaker 1:

Now there's a bit of a further background that's important for this particular podcast. I have been attempting to wrangle a podcast on Collagen for about 5 months now and originally Professor Keith Barr had agreed to come on the podcast to help us unwind this topic. Between Keith and Luke. You would have two of the most foremost experts in the entire world on this subject and, for whatever reason, although Keith agreed to come on to this podcast, he and I could never finalize a date and really lock it down. So I turned to Luke to help fill the gap. Now, as it turns out, and unbeknownst to me, keith was in the middle of a move to Luke's lab, literally two offices down from him, and in the middle of this podcast, keith graciously agreed to partake in some of the back and forth.

Speaker 1:

I hope you guys enjoy the banter and the knowledge on this one. It is a great one. All right, with that as a bit of a backdrop, I am stepping right out of the way. Here is my conversation with Luke VanLoon and Keith Barr, all about collagen supplementation. I'm really stoked for today's discussion because it's, as you are very well aware of. What we're going to talk about in terms of collagen is a really hot topic in nutrition science and especially in supplementation. But before we kind of get into that and just so the listeners can kind of learn a little bit more about you and what you guys do in your lab you guys have a fantastic set up there and you guys have done a lot of great work over the years Can you give the listeners a little bit of a perspective on the type of research that you do and really all the things that you kind of have access to in your lab as well, because I think that's another unique thing that we can kind of start to bring to the forefront.

Speaker 3:

I'm maybe to start off with. I'm responsible for a research group that is about 30-35 people changes over time, of course, but that's always been that kind of size. What we do is we do research on the interplay between nutrition and exercise, but that is actually on a very broad scope. It goes from sports nutrition and athletes all the way down to nutrition in the intensive care unit patients. We look at the interaction between nutrition and exercise when there's a lot of exercise, like sports nutrition, but also on the other end, when there's a lack of sufficient physical activity, immobilization, disuse, bed rest, intensive care unit stuff like that and how nutrition and exercise is placed around in muscle loss, for example, as well as the muscle gain or performance gain or stuff like that.

Speaker 3:

So we try to basically be active in both the sides, both the clinical as well as the non-clinical side of things. That is particularly relevant because we work at the Maastricht University Medical Center here in the Netherlands and that means it's a hospital and a university at the same time. So actually we have pretty good access to most clinicians. We just have to walk down the hallway and we are in the surgical rooms so we can work with orthopedic surgeons, brain surgeons, diabetes and oncologists, so that is really an option that we can see also in other patients and that makes it a lot more interesting to see the broad scope from health, from pathology to physiology.

Speaker 1:

And a lot of times those things have this like overlap, where we take things that we learn from a clinical perspective, or maybe even in a diseased population, into sport and then sometimes all the way over into elite sport. And you're nodding your head right now for the people that are on the YouTube version. Why don't you explain that a little bit better to the audience, because it is a fascinating area?

Speaker 3:

I always make a joke out of this that most of the clinical work ends up in elite sports.

Speaker 1:

One time or another.

Speaker 3:

And a lot of the nutrition work that we learn in sports needs to be employed in the hospital for patients, and of course it goes back and forth both ways. But, for example, I like to apply generally all the sports related stuff I apply as physiology, health, I see the athlete in most conditions as the healthy situation and I see everything else as either the prevention of disease or the high risk of developing disease, like most of us not being not exercising enough. Not for the most listeners on this podcast, but most other podcast people are not necessarily that healthy and not that active, and then, of course, apply it somewhere else. Where it becomes interesting is that exercise is, of course, medicine and that's one part, so we can use exercise to prevent disease and even treat disease and basically recover from disease, and I always like I mean, I wish there was no disease, but being sick is like playing professional sports. I think that's a statement that you can make and unfortunately we don't treat it that way.

Speaker 1:

I'm reminded of a previous guest on this podcast that you're probably familiar with, but I don't know if you knew that he was on our podcast, enigo San Milan, who kind of has a little bit of this duality role where he's looking at people in the cancer world cancer patients and things like that, and then also, obviously, world class cyclists all the way up to Tour de France champions, and he would always remark that the way that we should study disease population is through the lens of these highly competitive and elite athletes, because they largely show an absence of disease. And, just to your point, we can apply a lot of those principles all the way towards the other side of the spectrum.

Speaker 3:

And most of the interventions are the same. I mean, if you're trying to make an Olympic weightlifter get his gold medal, it's not that much different from an elderly lady who is only like 47 kilograms and is not allowed to live at home anymore because she can't stand up from the toilet anymore and she doesn't have enough strength in her upper legs. So the interventions that we do with both these subjects is basically the same.

Speaker 1:

We're just scaling the weight down a lot.

Speaker 3:

It's the point where we start off is completely different. But it's the same. The interventions are typically the same. It's recruitment, it's optimal recruitment, it's nutritional support, etc.

Speaker 1:

Well, I think a little bit of that perspective is going to come through in the conversation that we talk about, which is going to primarily revolve around collagen, maybe exclusively revolve around collagen. We're recording this on a Thursday and the people who listen to this podcast will recognize I host, ask Me Anything on Wednesdays and by far the two supplements that I get the most questions on are collagen and creatin, and it is a leap between those and anything else. Even all of the fancier things that have come out now exogenous it's ketone esters and things like that. Collagen and creatin kind of come to the very top and I did a previous podcast with Scott Forbes on creatin, which was received really well. Now we're going to tackle the second one.

Speaker 1:

But I like to use that as a little bit of a litmus test because you know that it's a supplement that's in front of people. They see it. It's extremely pervasive and we're going to get into why that is so pervasive in just a second. I pulled up some stats from the nutrition industry, but before we get into that, let's just do a collagen primer. Fundamentally, what is it? So the listeners can kind of understand when they see it on the shelf in their grocery store, supermarket. What are they actually taking in what? Fundamentally, what is a collagen supplement?

Speaker 3:

So one I think we should start off with is just talking about protein, and then we can move towards the collagen, because otherwise you don't understand the hype and the interesting collagen. So all your tissues, all your living tissues, are constantly being rebuilt and broken down. That is just ongoing. That is what we call turnover. And so muscle is also a tissue that is constantly broken down and built up again. So muscle protein, and we call that muscle turnover, and that occurs at a rate of 1-2% per day. So basically, in three months you have completely refurbished your muscle.

Speaker 3:

And now you ask yourself, like, why would the body do this? Because that takes a lot of energy, of course, but it makes sense. Because this muscle plasticity that's what we call it makes you allows you to look like a bodybuilder in months or years, or to look like an ultramarathon runner, and I think most people listening to this will actually know that their phenotype is different than from a bodybuilder. So it's quite different. So your body adapts to different types of exercise and that is made possible because of this turnover.

Speaker 3:

Now there's two reasons why the muscle does it. Why the muscle actually maintains or can change, it needs stimuli, and those stimuli come from two sources. One is physical activity muscle contraction and the other one is from food intake, mainly protein, because protein provides you with amino acids and those amino acids are also the building blocks of your own muscle tissue. You also re-synthesize muscle based on building blocks amino acids that are coming from the breakdown of your own tissues. Because you ingest about 70 grams of protein on a daily basis, but your body produces about 300 grams of protein on a daily basis, which, if you're in balance, can only mean that you're actually recycling 230 grams. So that's already amazing, if you think of this. You're constantly recycling, you're constantly building and rebuilding.

Speaker 3:

It's a very good math problem, yeah and that gives you the adaptability to exercise. Now the big question is what protein stimulates muscle protein to the greatest extent, and that has been a question that the last 20 years everybody has been looking for. And we now know that the capacity of a protein to stimulate muscle protein synthesis depends on the rate of digestion and absorption. The faster it gets digested and absorbed, the more strongly it stimulates muscle protein synthesis. But it's not the be all and end all. It's also the amino acid composition, and we know that the essential amino acids are particularly good in stimulating muscle protein synthesis, but especially the amino acid leucine, and everybody's heard about this because I assume you also heard that about supplements that leucine is a very potent anabolic signal. Of all of the amino acids, it has the strongest anabolic signaling properties. So, in general, proteins that are easily digested and have a high essential amino acid content, and particularly high leucine content, can actually stimulate muscle protein synthesis to a greater extent than an equivalent amount of other proteins. And what is that protein? Whey protein, and everybody heard about that. That is now whey protein and that's why everybody shouts I want whey protein, which is basically 20% of milk protein. Now the differences are, of course, very small and we can go into details on plant based proteins, a lot of proteins. That probably takes too much time for this possible podcast. Happy to come back, but that is the reason why everybody just talks about whey protein.

Speaker 3:

Now collagen is another protein. Collagen comes from also animals and it's made from skin and bones and stuff like that, so that collagen that is also protein, is a different amino acid composition From an amino acid composition. It's not a very high quality protein, it's a very poor quality protein because half of the protein, half of collagen, is mainly composed of glycine and protein to other amino acids. Now is basically the story. Hey, your muscle doesn't contain a lot of collagen. It does contain collagen because it's important to transfer the force that the contractile units have. So the contraction of the muscle has to be regulated all the way down to your tendons, your ligaments, your bones, otherwise you don't have any benefit of your contraction. So all those tissues, structural tissues, need to be firm and capable of transferring force to your bones, otherwise you can't run, you can't do anything. So it's an important factor and it actually is. Also adapts to exercise. If you perform exercise, the collagen in your muscle with also your tendons, everything adapts as well, seems to be a little bit more sluggish, but it also adapts.

Speaker 3:

Now, your collagen in your muscle, but especially your collagen in your tendons and your ligaments because there's a lot more collagen in there and in your bone and your cartilage that is also composed of your own collagen, and that collagen contains, again, a lot of glycine and protein. Now then you can easily make the story. You suggest that if you have a lot of glycine and protein in your collagen, in your body, then maybe it's also good to eat a lot of proteins with glycine and protein. Now, that makes sense, of course, but the best question that you have to ask is my body, does it already have enough glycine and protein in my normal nutrition? That's what you always have to ask, because the basis is your normal nutrition and on top of that, you might actually want to take supplements. Now the big question is there enough glycine and protein in your nutrition to maximize adaptability? Now, that is a question I think is not solved yet. But that is the story, the big story about collagen.

Speaker 1:

I feel like we just wove together a sport supplement history lesson with physiology, because a lot of the listeners that were doing endurance sports kind of in the early 2000s will remember this leucine revolution is what I'm going to term it where once we identified that leucine was one of the key regulators in muscle anabolism, a lot of the recovery drinks started to include and promote the fact that they had leucine in them. They're taking advantage of the research that was coming around the time. There were some hype around it and things like that. The way that I've always described this to athletes and the coaches that I work with is that some of the nutrition marketing that has been coming out has come out with more of an anatomical, with more anatomical content to it.

Speaker 1:

Take this and this protein or amino acid is going to selectively target this type of this part of your anatomy muscle, tendon, collagen kind of whatever it is. You said something that I think is extremely interesting. It makes sense, like logically, when you think about it. Oh, of course I want to take in the substance that's going to selectively target this tissue, but then the remaining question is does it actually matter? You've reframed it into. Do we have enough of it already for the supplement to actually make a difference. That's some of the things that you've been exploring with your college and research. Am I encapsulating that in a fair way?

Speaker 3:

Now and then. Lee, it's not that much different from the Romans saying you have to eat the heart of a lion in order to be brave. It makes sense that you think like, hey, if it's something that my body needs, I'll get it. But the question is does your body need it? That's the real question. Of course, it's the same with leucine. It stimulates muscle protein synthesis, but you can't build muscle when you don't have all the building blocks. So if only leucine, you can't do a thing. So you make it simple, but the reality is, of course, much more complex.

Speaker 1:

Yeah, 100%. So I pulled together some industry stats in advance of this to try to set up a, mainly why I was honestly trying to figure out why I get so many questions on it and it'd be very easy for me to just like chalk it up and be cynical and say, oh well, all the Instagram influencers are promoting it and some other sort of marketing phenomenon. But actually kind of went to the data and I found some interesting things. There's some estimates out there that put the collagen market at 2% of all of the sports supplement marketplace, which I think that's actually kind of remarkable. Like 2% to most people might seem like a really small number, but if you back out and you think about all of the sports, all of the sports supplements not just the things that we see in endurance, sports, right, carbohydrate, caffeine, recovery drinks and things like that all of the sports supplements you walk into your GNC, you can go online and buy all this stuff. If this one thing that we're going to talk about takes up 2% of that, that calculates to a 1.5 billion, with a B segment of the marketplace and people who, when we kind of move outside of the social media world, people might not recognize the entirety of that scope, but they realize how pervasive it is, because here in the US you can go into any grocery store and find it in the vitamin aisle any single one, in all different forms gummies and powders, and you name it.

Speaker 1:

I guess what I'm saying is it's pervasive. So, with that as a little bit of a backdrop and a little bit of the history lesson that you just kind of went through, what? How does that match up with some of the research that you've actually seen in the area, mainly starting, you know, 20 or so years ago, where we're starting to kind of identify this? How does that actually match up in terms of the supplement itself and actually being something that is promoted as being so efficacious, right, I guess what I'm trying to articulate is does the research actually indicate that it should be as pervasive as it is?

Speaker 3:

Yeah. So I think that's also a question that I had and that's why. Because I'm not. I mean, I'm a muscle physiologist and I'm interested in nutrition and I started with doing a lot of carbohydrate metabolism studies. Then I went onwards towards more fat metabolism and then, like yeah, made mostly since the last two decades it's mostly protein metabolism and of course you always look for novel things and at some point there was more and more interest in in, in in college and also I mean people probably also know the name keep bar yeah, as a keeper I was actually.

Speaker 3:

I was in a professor in our lab temporarily. He does his, he's on his sabbatical here, so he's actually two officers further on. So we work together to see how we can align the work that he's done with the work that we do. So because we both want to figure out what is the reality about collagen and so there is some in vitro and in vivo work that suggests that it does a lot, especially for ligaments health, for regaining strength and performance recovery after after injury. I'm a muscle physiologist, so mainly what I do is I look at how the muscle changes and adapts to exercise and what a nutrition gigging is an extra benefit. So we'll come back to that other work. But what we have done so far is to see whether we could actually show that the collagen in the muscle which is used to transfer force is sensitive to nutrition. So the first thing we've done is just look whether your collagen in your muscle responds to exercise, and it does so.

Speaker 3:

If you perform exercise, it's not only the contractile protein in your muscle that actually gets more synthesized, but also the connective protein fraction. We can take those two fractions out and then look at those fractions and we see that also that part of the muscle adapts. So if you perform exercise, also the connective network in your muscle adapts and we can see greater protein synthesis over hours after exercise. Now if you provide protein during recovery from exercise and I'm not even defining what kind of protein you see that the muscle generally responds by even greater muscle protein synthesis, and that is, of course, the basis of protein. During recovery, you further increase the stimulation of muscle protein synthesis which theoretically would help you recover faster or improve further, improve your adaptability and get more bang for your buck, if you want to say it that way. So greater response to your training session.

Speaker 3:

Now, we don't see that for collagen structures in the muscle. But we do see it for contractile protein. So we see myofibrilin, that's the contractile protein response to protein intake. But if we ingest the similar amounts of the same protein, we don't see it happening on the connective muscle protein in muscle. Now, that's possible because it's not the ideal protein because, for example, most of the studies are done in dairy protein. Dairy protein doesn't contain a lot of glycine and protein and if we give dairy protein after exercise, we actually see a decline in the availability of these amino acids, which might suggest that there's not enough in the acute phase during recovery from exercise.

Speaker 3:

So for me that sounded a little bit like the stuff that you read or that you see in the media, like there could be something there. So and then we pick it up and then we start doing research, of course, because a lot of the hypes in the media often are not backed up with science. We always follow behind, because it takes a lot of time to do studies, you have to get funding for studies, etc. So we've looked at collagen now and the collagen. If we provide collagen, we don't see an increase in muscle protein synthesis, but also not in connective protein synthesis in muscle. So so far we've done a few studies where we failed to find an effect, both acutely as well as during one week of training, using in both cases different types of tracer methodologies to see whether we see an increase in connective tissue protein in muscle. So so far we have been disappointed. So we don't see a magical effect on muscle connective protein synthesis rates.

Speaker 3:

Now, is that because there's so little collagen in muscle that we can't pick it up? Is it because the collagen doesn't have a lot of essential amino acids and not a lot of leucine, so it's still doesn't stimulate collagen protein synthesis? Or the connective tissue protein in muscle doesn't respond in a six hour period, but needs is more sluggish. Now there's all data that suggests that these things might happen, so we're not out of there yet. So we I don't have any clear answers here, excuse me to all the listeners so far we have not confirmed the benefits of collagen on muscle connected protein synthesis. Are we already finished now? Do we think like that's just a hoax? No, it's possible that we can't pick it up and still relevant over a more longer time frame. And the other thing is, of course we're looking at muscle where there's not a lot of collagen.

Speaker 3:

What about the ligaments, the tendons, the bone, the cartilage? Because these structures have a lot more collagen of course. Those are almost 80 percent collagen. So possibly, if you hurt or destroy these tissues, that there is a lack of sufficient glycine and protein. There are some people that have also done some calculations that there's not enough of these amino acids in our diet because our diet doesn't contain much collagen anymore because we have all these processed foods. That's possible. It's also a great story. There's people suggesting that hydrolyzed collagen have bioactive peptides that have capacity to stimulate all these kinds of processes, maybe in vitro. I haven't seen any data to show that in vivo in humans. So a lot of stuff still that needs to be done, but it is at the moment, of course, a supplement that is being sold and used a lot.

Speaker 1:

Okay, you just walked through the entirety of everything that I just wanted to talk about, so we're going to try to kind of go into each one of those areas a little bit deeper. That was a fantastic summary, by the way. The way that you have drawn out this storyline is that muscle and connective tissue respond to two different stimuli exercise and the nutrition and then kind of the interplay between those two kind of fundamentally is, I think, something that they both respond to exercise, but they do not both.

Speaker 3:

They do not seem to respond both to nutrition. Correct, yeah, at least not in a short time frame.

Speaker 1:

And so the first thing I want to explore specifically with collagen and I think this kind of this will set up the nutrition side a little bit better. That's why I want to dive into it first is if we know collagen responds to exercise, does it respond differently to different types of exercise? So endurance, high repetition exercise versus high force and or high velocity exercise, Can you explain that interplay a little bit better and then we'll start to move to the nutrition side.

Speaker 3:

Yeah, so if you perform resistance type exercise, you actually get my fibula more my fibula protein is being expressed. If you do endurance type exercise, you get more mitochondrial proteins being expressed. That explains why Jay Cutler, the bodybuilder, or Lance Armstrong both have very high muscle protein synthesis rates after an exercise session, but their phenotypic response is quite different. So high protein synthesis does not necessarily mean a lot of muscle. But if you do resistance exercise, you get more mass. So my fibula proteins.

Speaker 3:

If you are an ultra mountain runner, you actually focus more on other proteins, such as mitochondrial proteins, to allow you to oxidize a lot of fat. So the first dissociation I have to give is that different types of exercise lead to a different stimulation of different sets of proteins that lead to the adaptability that you're seeking. Now, to what extent the nutrition factor plays into that process, that is far from elucidated, but it's likely that, for example, more force, more eccentric force, more weight dependent exercise has more effect on your ligaments, your bones and your tendons. That's not a lot of in vivo studies that have shown that, because you have to actually sample these tissues in vivo. Now, with muscle tissue that's relatively simple. You just take in a biopsy needle and you take muscle biopsies. But of course, taking repeated biopsies out of tendons, ligaments, bones of cartilage in a just outside situation during exercise, that is not as easy and maybe not even at the core. So that's why we don't have much data there. But we don't expect it to be that much different from what you expect from muscle.

Speaker 1:

And you described some of the classic studies that have already tried to be done, where you have a group of subjects they go through predominantly what would be a resistance training exercise.

Speaker 1:

They then supplement with collagen or some form of collagen plus vitamin C and there's all these different permutations of that, and then we measure some biological artifacts within the blood and other in other tissue samples to try to see if the collagen supplementation plus the exercise, which is the, you know, the condition that we're studying has actually had an effect. And I'm gonna leave it to you to kind of summarize the basket of all those, because you wrote a really nice narrative review on a lot of this. When athletes are doing this which is the common, I would say, that's the common thing that they have in their head I'm gonna go strength train or do some sort of plyometric training and then I'm gonna take a collagen supplement and somehow that's going to affect the tensile strength or the force that I can produce within within connective tissues. What does the research say on how that interplay actually gets teased out at the end of the day?

Speaker 3:

Yeah. So the question is, to what extent does the, the collagen supplementation have an effect on that process? Because it's not about what your supplement is doing. If you do that over a longer period of time, it is your diet, it is your habitual physical activity, it is your exercise, physical, related physical activity, and all those things come together. So it's impossible, or nearly impossible with research, to figure out which factors is affecting which factor, because then everything comes together. And that's exactly what I said is is collagen an effect there, an effect of that directly stimulates any of the collagen synthesis in all these different tissues?

Speaker 3:

That's one, or is it simply a provision, a source of building blocks that you require From for the added adaptability of these tissues? But of course, those building blocks are also coming from your bread, meat, fish, milk, dairy, whatever. So you also get them from other sources. Then your supplement and that is what it makes always makes it difficult. For example, people say, hey, in this study we didn't see an effect of protein supplementation on strength gain or endurance gain. Yeah, it all depends on what your supplement above. What I mean. If you have a diet that contains everything and you have a high energy expenditure and you also consume my energy diet, which is healthy and balanced. You generally also consume enough of all nutrients that you need to maximize adaptability, but the question is in what cases it's not, and that's the difficult thing to find out.

Speaker 1:

So is it? The researchers always hate it when I ask them to postulate on something, but I'm still gonna do it. Would it be reasonable to postulate that collagen supplementation would be more effective in an individual who has inadequate overall protein intake?

Speaker 3:

If overall in protein intake means yes, I think, then yes, but then I still don't know how much protein you require or how much of the individual amino acids you require to maintain or Increase your collagen networks in your muscle bone, the cartilage, ligaments and I don't know. But overall you can imagine, if you don't have enough amino acids then your turnover will cannot be made, cannot be maintained, so that would have a negative effect in the long run.

Speaker 1:

What you mentioned. Like you mentioned, keith Barr is just a couple of offices away. I did not know that before recording this podcast, so that's novel information for me. He has produced a lot of the research that would indicate that collagen actually is an effective supplement for to remodel Connective tissue, and I'm wondering if you can kind of, you know, peel back the curtain a little bit, since now he's a, you know, kind of a direct colleague of yours of when, like how you try to kind of reconcile this. How do you reconcile some of the research that indicates that there's no effect and some of His research that indicates that there actually is an effect?

Speaker 3:

So I'm not sure what he's still here because it's now Vitamin. I can double check. I mean we are fighting each other and we're just saying like, like we want to know what is real, because a lot of the work the key does. Of course he sees benefits like practical benefits and functional performance and stuff like that in plasma proxy markers that might be used to estimate collagen turnover, collagen synthesis in the body, and he looks at, for example, engineered ligaments ex vivo, in vitro, what they actually do, and he sees a lot of positive effects.

Speaker 3:

But then we look at the muscle. So we haven't really looked at those other tissues yet. We look at the muscle bulk in the legs. We don't see direct impact on the connective tissue protein synthesis. But again, I on the line the connective tissue protein out of the muscle that we get is only a very small amount of that as collagen, and so Can we pick up that, the effect that might be there and is it relevant? That was already your question. So the big question is tendon ligaments. But then we have to. The only way that we can harvest tendons and ligaments in vivo humans is when they get surgery. So we want to do a lot of interventions prior to surgery to see whether the intervention have an effect during the time before we harvest the ligaments and the tendons.

Speaker 1:

But you can imagine these studies are much more difficult to plan because we can't just simply stick a needle in there and get a piece of tissue and so, outside of that, are we really going to be stuck at looking at some of the plasma markers, some of the bio markers, as surrogates to postulate if, in fact, connective tissue is being remodeled or synthesized?

Speaker 3:

Yes, I mean that would be nice, but of course you can also imagine I mean, you have a lot of collagen in your body, you have a lot of bones, you have a lot of. So if you see an increase in that marker, is that because of collagen turn over? Is it because of bone turnover? Is it related to the legs that you just have been been been using during your run or your eccentric run or whatever your downhill run? Or is it because your skull is remodeling? I mean, what does that plasma sample mean of the tissue or the place of the limp that you're interested in?

Speaker 1:

That is the difficulty he always in some, in some of the peachy dish models, they've studied different aspects of how collagen supplementation might work, so tendon size, thickness, stiffness, the rate of force that it that it can apply. Can you summarize it if collagen supplementation or exposure to collagen Affects any one of those properties to a larger extent than any of the other ones, like does it make it bigger without the force application or do you just see more force application without the, without the increase in size? Does there seem to be a phenomenon in any of those rounds?

Speaker 3:

I don't know whether you do guest guest appearances, but I mean it will be cool to actually see If you ask you to come on the podcast several months ago, so maybe you can bother him and you can come back.

Speaker 1:

I'm going to try it. We'll try. This will be a first.

Speaker 3:

And so the listeners can think about this question Does the ligaments do the ligaments, or does the tendon ever see collagen? Yeah, there we go in the human body. That is the question. Think about, while I see, what I okay.

Speaker 1:

Okay, it's at this point where Luke goes and grabs Keith from just a couple of offices down, brings him into the office for the final part of this banter up. You guys enjoy this Conversation where we're finishing it up with both Keith Barr and Luke Van Loom. Hello, so my name is Jason Keith we, you and I have corresponded a little bit via email and I think it's probably dropped off and all of your moves and things like that. But we're talking about all things collagen and I did not know before Recording this podcast that you were literally a couple of offices down from Luke. So in all of this we'd be, since we were talking about your research, we'd be remiss not to take a few minutes and kind of pull you back into the room Without rehashing all of the history that Luke just gave us.

Speaker 1:

He just gave us an entire timeline of both the research as it relates to Collagen and how and how collagen supplementation actually affects athletes, as well as kind of a 101 Physiology and anatomy led a lesson within that particular silo. We're not going to rehash that, but one of the things we did start to talk about is some of the work that that you see in terms of how collagen actually might specifically affect tendons across different properties of those tendons. So size, race at rate of force, race rate of force, development the thickness and things like that. And so you can just jump in here right into the deep end and explain. Do we see some of this differentiation in the research here?

Speaker 2:

So so I think the like Luke will tell you for what he's spent you know the last, what 20 years doing on his losing protein component. That's exactly what I thought. You can take all the losing rich protein and you can have the most perfect losing rich protein. If you're not gonna exercise, you're not gonna move, it's not gonna do anything for you. So when with collagen is probably very similar. So what we're seeing is it is, is it? We can see increases in collagen production by cell and we measure pro collagen peptides. We can measure pro collagen synthesis in cells. We it goes up with exercise and there's probably a nutritional effect there as well. But, just like with losing rich protein and scale the muscle, the effect of the nutrition is smaller than the effect size of the exercise.

Speaker 2:

The exercise and you know Luke and I both do this, we'll give an hour-long lecture on this is what exercise does for you. Oh, and you could also eat these things and everybody's like, oh, eat stuff instead of exercise. Yeah, sure, I can eat stuff, I can eat collagen and that'll do everything. The reality is, if you want to get it into your tenants and ligaments, you can't just be laying on your bed or in on your couch and taking collagen. That's going to affect your skin probably. So I think you're gonna have, just like I said there, the. It's more about load management than anything else, and so understanding what are the stimuli they are going to be important for collagen synthesis is really important.

Speaker 2:

So and this is so, camille Herron, who's who's, as you guys you'll know, is one of the is probably the greatest Ultra endurance runner right now At least, for on the women's side, she's done an incredible work. She's also did a master's degree in bone mechanobiology and what she learned there was that bone response to short periods of exercise and In the interest. So she actually trains in two periods. Tenants and ligaments are the same way. College cartilage is the same way. That's far more important for an ultra marathoner. If you take the same amount of load that you're gonna do over a week and instead of doing it in big single sessions, do it in two Smaller sessions, that's gonna have a better effect on tenants, ligaments, cartilage and bone.

Speaker 2:

Then taking a nutritional supplement. The nutritional supplement may modulate. It may help you, especially in an ultra athlete where you could get what we call conditionally essential amino acids, where if you're getting enough load, you're getting enough tissue breakdown you're getting enough of what we call mechanical fatigue that you need more glycine to repair those structures. Then glycine could become a conditionally essential amino acid. In that situation then supplement with dietary college and move, be good. But again that's going to be special to the ultra endurance athlete, because in most athletes we're not going to exercise it that low.

Speaker 1:

Well, and the debate around a two a day session versus a one a day session is multi. I have to put my coaching hat on for just a second, because we're talking about things that are very specific to the two tendons and ligaments, and when we're coaching an athlete, we have to think about everything that's going on and how, where their weak links are, and how we're going to improve their cardiopulmonary system, and on and on that's. We're not going to adjudicate that in this particular podcast. The fundamental question still remains. I understand where you're coming at from a mechanical standpoint.

Speaker 1:

Let me rephrase the question, and I think something the audience will really, really kind of recognize is in those situations where we understand that the exercise is going to be the bigger hammer as compared to nutrition, in terms of all of these adaptive responses really and we're talking about connective tissue specifically here would supplementation with collagen enhance that adaptive response, either in a strength training session and or an endurance session? Because fundamentally that's what people are trying to get at At the very beginning of this podcast. I can walk 200 meters over to my grocery store and find five different forms of collagen. It's very pervasive kind of everywhere around the world and particularly here in the US and what the people who are active, who are listening to this podcast they're running 60 miles, 100 kilometers a week, something like that. They're active athletes and they're going to want to know is this supplement going to enhance the adaptive process that they are already going to get through exercise.

Speaker 2:

Yeah, and the data there is still too young to say. There's only enough data on older people with osteoarthritis. There's a meta analysis that shows that dietary collagen decreases symptoms and improves cartilage in those individuals. As far as young exercising adaptive people, the data is too young to know.

Speaker 2:

There are suggestions that, yes, we can see at that adaptations like rate of force development in strength athletes and in our football players in the US at UC Davis when they took collagen, the rate of force development and they lifted heavy weights the rate of force development got better and we saw performance changes that were better than when they took placebo. But Luke has shown that with a bunch of different types of exercise he doesn't see an increase in collagen turnover in the tissue in the muscle and maybe the same thing is going to be true in the tendon. But again, that's one or two studies there, one or two studies from England, one or two studies from us. It's not like there's a body of literature that there is for, say again, losing your protein for muscle or for other types of things that can improve adaptation.

Speaker 3:

But what you should never forget I mean exercise leads to greater turnover of your tissues. Now if you suggest that the greater turnover which makes sense because you only have, you can only recycle so much is that it also leads to a greater requirement of the nutrients in those tissues that have a higher turnover. So theoretically you could say, if you have a lot of load on your tendons and ligaments, you need more glycine and protein, but of course that is covered by a greater food intake because you also have a high energy intake. I mean sometimes and many of your listeners probably will say, my relatives can't understand how I can be this thin and eat so much, because they're actually expanding a shitload of energy and that is only possible by eating a lot. So that also means you eat a lot of protein and people don't look like they're eating a lot of protein.

Speaker 3:

But also another homework for your listeners If you have two of the France athletes who are only like some are 60, 65 kilograms, they have like 25 megajoules of energy on a day in the Tour de France and even if they eat less than 10% of their energy and protein, they are still close to three grams of protein, bikini and body mass, which is possibly three to four times as much as they would typically need as a sedentary adult or normal adult. So in other words, they already have four times as much of most of the amino acids. So is then glycine and protein still limiting? I don't know, but I would think not.

Speaker 1:

That's the second great math problem that you've given us today, Luke, by the way. So let me try to synopsize this. We have a bio plausible mechanism of action to which collagen could potentially enhance the adaptive response. There is limited research on both sides to say that it could in fact be adaptive to that or enhance that adaptive response underneath exercise conditions, as well as a small body of literature to say that. You know what? It probably doesn't make a difference. Fair synopsis Yep, yep.

Speaker 3:

But then it doesn't necessarily mean that we I mean, we're still human and we're scientists, but we're still also human a little bit. So when my ex-girlfriend broke her hip running downhill, I actually put her on collagen and protein, even though I don't have any evidence that it works, but I think for recovery out of complete broken hip when she got severe surgery I thought it was a good choice to do it because it couldn't harm a lot. She's now running again, while the doctor said don't run. Is this only an NS1? Is this science? No, this is not science. But so I think there is a basis to it. But I think the basis is only relevant when you think that you require a lot of turnover of a lot of tissues that have a lot of glycein and protein, and then it all depends on your diet how much is in there and is it sufficient or not?

Speaker 1:

So certainly not magic. There's another summary. There requires Nothing is magic. Yeah, nothing is magic. I think we need to kind of consistently drill that message home.

Speaker 3:

If magic to understand that you have a new arm and a new leg in two to three months and that you're turning over these tissues. You don't realize that, how fast all these living tissues constantly refurbish themselves. I think that is magic. I still can't comprehend how that works.

Speaker 1:

You guys bring up one final point that I want to drive home to the listeners and I'll let you guys go. Actually, I've got a cheeky question at the end of this if you both stick around. But is there any negative? Because a lot of times we talk about supplements and I'm kind of removing the elite athletes that can potentially and just contaminated supplements and they get flagged for a doping offense. Let's kind of leave that aside. But is there any negative to collagen supplementation? Because once again, it's so pervasive? There are a fair amount of actors within that space that will include like fillers within their supplements, or what's on the label is not what is actually contained within the supplements. Can you give specifically within collagen in the commercial space? Can you give just an overview of that landscape?

Speaker 2:

There's absolutely issues, and the biggest issue is that if you is the source of collagen, it's not because you want type one versus type two. That really doesn't matter. What matters is when you're getting your collagen from fish skin or from poor sign skin or from bovine skin. So the skin sources. That's going to be a better source of collagen, because all big animals store their heavy metals in their bones. So what you find in bone broth, in things where you're isolating collagen from the bones, is you're also bringing out lead and you're bringing out other heavy metals that those animals and you're concentrating them. And so really, what you're looking to do like I normally live in California you have to have a special label on your gelatin or your hydrolyzed collagen because you have to abide by the California regulations that something within this is known to cause cancer and it's not the collagen, it's actually the heavy metal, and so what you're really looking for is you're looking for a skin-based source, and so the companies are starting to put where they're sourcing the collagen from, because you don't want to be.

Speaker 2:

We had one athlete who was oh, I'm taking this great, this hydration supplement. He was an ultra athlete. He was taking this. It was like a salt-based thing that was from the Great Salt Lake. It had like so much arsenic in it he couldn't understand why he was not feeling the energetic. Okay, yes, you're gonna concentrate, you're gonna get salt, but you're also gonna get everything else that's in there. And so when we're looking at collagen, we want that collagen to come from the skin-based sources, because you're not gonna get heavy metals in that way.

Speaker 1:

Excellent, that's the main component, excellent.

Speaker 1:

So I'm gonna leave you guys with this. I pulled up this quote for you, luke, in particular. But, keith, now that you're here, we can pull it up in a cheeky way, because I wanna know like how much you guys really, you know, go to Battle Royale and have arm wrestling contests over this stuff. The quote that I'm gonna read you guys are both fit dudes. I'm sure it'd be an epic arm wrestling match if you guys end up doing it. It's, luke, it's from your recent narrative review and it states that there are no data to our knowledge to support the claim that the ingestion of collagen drive peptides may stimulate connective tissue protein synthesis rates. And now that you guys are colleagues, I've just just from a social standpoint, you guys can agree to disagree. You guys can have like different viewpoints on things.

Speaker 3:

No, I was fully pleased with that, but then you should not. So that doesn't mean that the amino acids in the collagen are not building blocks for the collagen in your body, because we've actually shown that you ingest protein, that those amino acids end up in your collagen, in your tissue. So they are precursors, but there's no additional, because that's the difference. Is it stimulating or is it used as a building block? Yes, they're being used as building blocks. I'm confident on that, but whether they have a certain benefit and there's no evidence on that yet.

Speaker 2:

Yeah, so what we know for the leucine and the leucine-rich protein is we can identify a mechanism where that activates protein synthesis within muscle cells. We have yet to do that in connective tissue cells, and so that's the difference that Luke is saying here. Leucine-rich protein all of the amino acids from that, are going to be used to build muscle. The amino acids that are in collagen is not a complete protein, but those amino acids will be used to make collagen, but it'll also be used to make muscle and other things within the body. The question that Luke, the statement that Luke is making, is that we don't have a way that says that when you eat that hydrolyzed collagen, it's going to go in and activate your cells in the same way that leucine activates a muscle cell.

Speaker 1:

Is it like anatomically selective? We talked about that earlier in the podcast, right?

Speaker 2:

Yeah, yeah, and there might be. We've got a potential mechanism where it could, and that's one of the things that we're really interested in studying, but to date there's nothing that says that there is a stimulating effect of hydrolyzed collagen or any form of dietary collagen on connective tissue cells.

Speaker 1:

But you guys still have hope because you're doing future research on this and maybe we can bring you back a year or two down the line when something does come out and might shed a little bit of a different light on it.

Speaker 3:

Exactly. Yeah, so we're I mean always, I mean we're not necessarily people that want to show a benefit of a certain supplement Often that is the question, but we want to understand how it works. So even if a supplement works, we're still thinking about to what extent does this nutrient already is provided the normal nutrition, and of course, using supplements can make your basic research interesting, because then you have a high volume of that nutrient so you can see what it does. But that's like I said a supplement is, for definition, on top of something, and so a supplement can only work where your optimal nutrition is not optimal yet.

Speaker 2:

And the only other thing I'll add to that is that we're we've been doing a basically a high throughput study with human pen and cells and ligament cells to say are there things that actually can stimulate collagen synthesis? And we have found those in natural products. So whether you combine something that does stimulate the cell to make more collagen with the amino acids that are in college and whether you're going to have something that's going to be better, we don't know that yet, but that's what our the next step is going to be is to find, because in in the animal proteins for muscle protein synthesis the loosing is high. That's why they're really good Can we find that loosing equivalent that is going to then combine with the amino acids that we have in the protein is now going to give us that bigger stimulatory effect? That's really the next question.

Speaker 1:

And that's always the dialogue, right? We see this work. This is how it works. What's the analog and another tissue? Right? We know this mechanism. We know we can kind of select for this mechanism with this particular component, right? Whether it's nutritional component or whatever, how do we move that into another tissue within the body using that same framework? I think that's a great way to put it. Thank you guys. Luke, thanks for Kajole and Keith to come on the podcast.

Speaker 3:

I feel like I got to tune so you don't have to beg anymore. I know I don't have to beg anymore.

Speaker 1:

I know sometimes it's oh, it's okay.

Speaker 1:

I know sometimes it's like herding cats to to to. You guys are very busy people. I'm I'm busy as well, and I lose podcasts and interview requests in my inbox all the time, so I completely get it. I'm very appreciative of your time and I'm extremely appreciative of the work that you do, because things that you got, that both of you do and both of the both of you have done for years, helped me make sense out of the entirety of the content that I have to pay attention to, which is both in the research world and in the lay world and the questions that I get from athletes. And as I opened up this podcast with, collagen is one of the top two collagen and creatin the top two supplements that I get questions on a weekly basis. It's pervasive within the dialogue of endurance athletes everywhere and the work that you guys have done has helped me kind of articulate what it could potentially mean for athletes, so I'm very grateful for that.

Speaker 2:

Welcome. You're welcome, and it's really important for you to realize that most of the research we do is on on recreationally active people. So when you're talking about ultramarathoners, that's a different thing entirely, and so a lot of what we find for somebody who exercises three hours a week that's not what your population is. So in those situations you're much more extreme. There might be very different effects of nutritional supplements in that population.

Speaker 1:

There is special lot, that's for sure. Since both of you guys are now in the same place at the same time, I'll leave some links in the show notes to find where they can find you guys. But how can they go about finding more about you in the work that you guys do?

Speaker 3:

I mean, you have our website like wwm3researchnl, that basically he has all the work that we do and all the links to all the publications, and there's also a website in a keeps lab, yeah, but I'm not as good about keeping up the data is Lucas.

Speaker 2:

So the minds? I don't even think that I own it anymore, so I do when new stuff comes out. I don't go on Twitter anymore because it's gone very bad, but when new stuff does come out, I put it up there, and I'm starting to do that with both research gate, with also starting to do that on Instagram, which I don't really understand how it works, but I'm trying. I have a 16 year old daughter. She should be able to teach me, so there we go, we'll help.

Speaker 3:

We'll help you get some more followers and complicated all the work that we do now is probably also going in on our website, because that's collaborative work. So hopefully we end up not fighting too much and we actually agree on something at some point. There we go Awesome.

Speaker 2:

It's really important always is that we publish everything as open access so everybody can see the published work, and that's the best way to find it. If there's anything that's older, that's not open access. If you just email either one of us, we're happy to send our stuff because basically the rule of thumb is that the average number of research articles are read by one person, so that's the average across the board.

Speaker 2:

So when we get requests that say, oh, I'm really interested in this, so that's just like hey good, there's a second person who's going to read this, so we're happy to send our papers out to people. So awesome.

Speaker 1:

Well, I'll include links in the show notes to all of that, as well as your Instagram handle. Hopefully you can pick up a few more followers, keith, and we can propagate that social media channel. Once again, I appreciate you guys coming on the podcast today. All right, folks, there you have it, there you go. Much thanks to Luke VanLoon for coming on the podcast and Keith for serendipitously joining us in the middle of that. I had no idea that was going to happen. I had no idea that's what was going on in the background, but I'm really grateful for that very fortunate event where we bring both of those experts in the room and talk about everything.

Speaker 1:

Collagen. I hope you guys are better informed about this really unique, ubiquitous and maybe important supplement in the world today. Time will tell, as if the claims end up matching what the supplement can actually do. If you enjoyed this podcast, please feel free to share it with your friends and your training partners, or maybe your coach, or maybe, if you are a coach, your athletes, because I know we get a lot of questions on how or if collagen can actually improve all these tissues that it is claiming to actually improve. Don't forget to check out my research newsletter, research Essentials for Ultrarunning. There will be a link in the show notes to that. If you want to keep up on the latest ultramarathon related research, there is no better resource than Research Essentials for Ultrarunning. Y'all go and be sure to check that out as well. As always, I appreciate the heck out of each and every one of you listeners out there. As always, we will see you out on the trails.

Collagen in Sports Performance
Collagen's Role in Muscle Protein Turnover
Collagen and Muscle Protein Synthesis
Exercise, Nutrition, and Collagen's Effects
Collagen's Impact on Tendons and Ligaments
Collagen in Commercial Space
Experts Discuss the Benefits of Collagen