The Creatine Episode

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I mean, to your earlier point there, I'd say there was a time, like maybe two years to 18 months ago, when all the podcasts, all the health and wellness podcasts, the ones that are sponsored by Athletic Greens, you know which ones they are. They all had a creatine series or show, and it was as far back as that that I remember you and I saying we wanted to cover something on creatine. And then, like, gradually people saying, you know, should I be taking creatine? I have friends who constantly ask, should I be taking this supplement? The problem is, like, I listened to all those podcasts at the time, and not one of those people struck me as credible because they all come across like a little bit too persuaded of their own merits and the merits of the research. And the big tell for me is they oversimplify. And so when you ask them questions like, what should I take? They say, you must do this. When should I take it? It has to be at this time. How should I consume it? The only way to do it is the best way to do it is the following, you know? And those things are a big put off for me. So the big problem is not unique to creatine. I think it's true of all supplements, is that the whole supplement industry has been a victim of its own rampant ambitions to sell us stuff. And I find it extremely off-putting. So it really did take 18 months to find someone who we felt would be measured and calm and analytical enough because you need someone who's a scientist and a credible one, a good communicator, someone who's also got experience and not merely theoretical, but also practical and is able to understand like what that is going to happen in the real world. And I, hopefully we delivered that with Eric. I think to some extent, when we look at the stuff that we've done on this podcast over the last few years, is that we always encourage our listeners and people who are looking at supplements and those type of things to be quite cynical about it and to do your due diligence when it comes to those type of things. And in a way that kind of almost contradicts what we're talking about here, where we're talking about the benefits or known benefits. You'll hear some of the detail from Eric Rawson now, but I think we're all quite cynical. I am very cynical when I've been listening to talks about creatine. I've always wanted to really say, well, I don't know how credible this is. I don't know whether if I'm taking this, it's going to do some damage to me, all those type of things. And I think that's why it was so important because he answers a lot of questions that I had about creatine use. And I think that's why we needed to get him on the pod. So yeah, here he is, Dr. Eric Rawson. Eric, so welcome to our Science of Sport podcast and a big thank you because we know that between you and Ross, you've had a bit of a back and forth because you've been traveling a lot and Ross and I have been discussing doing a podcast on creatine for quite some time. And the reason why it's become such a big thing for us is that trying to find the most credible voice in this creatine world when there's so much noise around this sort of space is quite difficult. But it seems to me, given the fact that we've introduced you now, that this is something that's been a big part of your life, the creatine story over the last two decades. I appreciate the invitation. I'm thrilled to be here to have this conversation. And yes, somehow I stumbled into the world of creatine research, which matched well with my own personal interests. And it's been quite a ride for about 30 years now. I mean, give us an idea of when you sort of first came to this topic and what kind of, how did you get involved in this particular topic? Because it's obviously a very focused subject that's gone in and out of popularity in the last two decades. Yeah, well, I mean, I never had any intention of getting exactly here, metabolically speaking, and certainly never even into the world of research. I simply didn't know what it was. You know, I, I guess I would say as a child, without knowing it, I was fascinated by human performance. And I had my, you know, late 60s, early 1970s inspirations, people like Alexiev in, in weightlifting, of course, Arnold Schwarzenegger in bodybuilding. But there were some, some health and fitness gurus too, like, like Jack LaLanne. And everything these people said just made incredible sense to me. And I found myself really pulled towards individual sports, loved team sports, but I really loved individual sports. And although I will watch and enjoy, you know, the tour, so in, you know, cycling, I'll watch and enjoy marathoning. It, it's always been the strength and power and sprinting type activities that, that really, really fascinated me. And I, I just didn't know what to do with it, except go to the gym, train, try to get bigger, faster, stronger. And at some point in time, I was out in the working world and was a bit bored. And I said, you know, there's a lot of science out there and, and I have this rare opportunity. I'm not currently married. I don't have kids. I don't have a dog. I don't own a home. Why don't I just drop everything and go back to graduate school and learn everything about sprinting and hypertrophy and resistance exercise. And, and for me, it was always 50% nutrition and 50% training. You know, my brain couldn't separate them. And right before I went back to graduate school, a few years before, I became aware of the hot new dietary supplement, you know, based on very little research. And that was creatine. So I walked into graduate school, not having any idea what research was. And I said, I want to study things that make me bigger, faster, and stronger. And I want to start with this stuff, creatine. I mean, what was your interest in that you're saying that you, it was relevant to your journey. Were you a power lifter or what were you into any sort of strength training specifically or? Yeah, I, I guess I'm, I'm one of those rare people who started in bodybuilding and then dabbled in other things. Bodybuilding is typically filled with ex-wrestlers and ex-football players and so forth. And, and, you know, from my, you know, childhood love of, of superheroes, I eventually stumbled across the old advertisements in the back of comic books, the Charles Atlas advertisements that, that offered me a, a special type of training that would make me look a certain way. And then I, I think I probably saw Arnold on Wide World of Sports. And what was a real, um, real moment for me was, um, my oldest brother had a, an introductory weight training book by a man named Bruce Randall. And there's a picture in the book that I, I often show in my presentations. And it's a picture of, of two men. And on one side of the, the, the screen, it's a 400 pound man and he is close to 600 pounds on a barbell on his back. And on the other side of the screen, it's a, a very lean, very muscular bodybuilder at the Mr. Universe. So one 400 pounder and one 220 pounder. And it, it, when I looked at the book as a child, it turned out they were the same man. And I thought you could do both of these things. Both of them, literal superheroes to me. You could do that with diet. You could do that with exercise. And, and I was just hooked. Uh, and bodybuilding became the pathway. And then I would step out of bodybuilding and, and do something else, sprinting or combat sports. But, um, every time I did, I would lose muscle so fast that I would say, you know, this, this isn't really conducive to what I really want to do. And I would get pulled back to, to bodybuilding. Uh, so it's, it's always been about the high intensity sports to me, whether it was thinking about, um, you know, getting bigger, faster, stronger, or at this age, you know, successful aging. It all ties together. And were you competitive as a bodybuilder? Did you enter competitions and things like that? Yeah, competed a few times, uh, and, um, you know, retired as a young man right before the decision to go back to graduate school, which, uh, as you know, the, the, the graduate school process, the PhD process is, is so consuming. I thought, you know, to do this well, um But, you know, at that level of meat consumption, this was an athlete who was probably modifying his muscle creatine levels. So we have this research from 200 years ago. We have supplements in the 1800s. And creatine was really all the rage. You know, there's a textbook published in the early 1900s, which, it has over 500 references in it. So creatine and creatinine research was, for 100 years, just incredibly popular, and what is really quite fascinating to me is all of this research predates the discovery of a phosphocreatine, predates the discovery of ATP, it predates the discovery of the creatine kinase reaction. So these people were doing all of this work missing, you know, the fundamental pieces of energy metabolism. And, you know, there's even human supplementation trials, one of them in the 1920s, pre-muscle biopsy. So they measured creatine ingestion and they measured creatine that came out in the urine, and some of the creatine magically disappeared. And they said, well, where did the creatine go? How and where and why is the body retaining this nutrient? So, you know, 100 years of supplementation research and 200 years worth of metabolic research. And I think things really changed in, you know, most of your listeners are familiar with Jonas Bergstrom and Eric Hultman when they refined the muscle biopsy technique in the 60s. And, you know, their early research on glycogen and liver glycogen, muscle glycogen, dietary manipulations and exercise performance, those were followed by research on high-energy phosphates and the creatine content of muscles with people like Roger Harris and Kent Soalan leading the way. And that was the real turning point when we could look inside skeletal muscle. And there's this gap between identifying how important creatine was in energy metabolism in the 70s and the 1992 paper that showed supplementation was effective at increasing muscle levels. And we've talked to Roger Harris about where that, you know, what was the explanation for that gap? And in the 1970s, Roger Harris with Eric Hultman and Jonas Bergstrom, they were deep into the process of supplementing creatine. And they did some pilot work where they fed creatine to two athletes and they unknowingly supplied creatine to two athletes who had very high natural levels of body creatine, so they didn't respond to the supplement. And they said that the experiment is a failure. Let's move on. And they moved on to carnosine and beta-alanine and some other things, and creatine died until, you know, the late 1980s, early 1990s when Roger Harris was working with horses. And, excuse me, as the story goes, I have my automatic light on here. As the story goes, someone inadvertently sent him a bottle of creatine and he tried to feed it to a racehorse. And because creatine is rather insoluble, he tried to dissolve a massive amount of creatine in a small amount of water and the syringe jammed and he couldn't feed it to the horse. So instead of giving up, he ate it himself. He supplemented himself with creatine. He dissolved it in warm water and had someone take blood samples and noticed this massive increase in blood creatine. And he said, we should really rethink this again. And the comedy is that if he didn't have a problem with his methods and he actually got the horse to eat the creatine, it would have shown nothing because horses don't respond to creatine. So he would have failed twice, once with the swimmers with the high muscle creatine levels, once with horses who don't absorb creatine, and it never would have happened. So actually, it was almost a bit of luck. Yeah, it was just luck. And Roger, behind the scenes, was working with some athletic groups and they published that first biopsy study in 1992 in Clinical Science that showed you could indeed increase your muscle creatine levels with supplementation. And that was the Olympics year, and several Olympians, notably Linford Christie, came out and said, you know, I attribute my medal to, in part, to this supplement upon some interviews with some reporters. And, you know, I was in the gym. I wasn't in graduate school yet. I was unaware of Roger Harris or the journal Clinical Science. And we were just doing this by feel. And we knew this was an effective supplement. The differences in your resistance training performance were just striking. And that's kind of where the modern era started with all of that craziness up until Roger's paper in 1992. How did they synthesize creatine a hundred years, a hundred and fifty years ago? Because as you say, it comes from meat. How do you create creatine from very basic levels to something that you can take? Yeah, so I think they were doing some purification, you know, research, you know, a hundred, two hundred years ago that was very time consuming and probably there was contamination with creatinine and the creatine. It's just some, you know, there's a couple of simple reactions that you can now standardize and synthesize creatine easily and from a manufacturing standpoint. But that didn't happen until Rogers work with, he was working, you know, he was a lab guy and a wonderful scientist, but he was bright enough to contact athletics and contact industry. And then someone, you know, took the bull by the horns, so to speak, and, you know, refined the manufacturing process and brought it to the market. And then suddenly it was just everywhere. So in the late 80s, 90s, you were using it. In the early 90s, I think there is, I recall some creatine phosphate supplements that were available. But it was right around the time of Rogers paper that it seemed to become more widely available. And then it just became available everywhere and very heavily marketed towards the strength and conditioning and the bodybuilding communities. So it was a bunch of things happening behind the scenes at the same time with science and manufacturing. And bear in mind, Rogers paper was a descriptive study. It just said biopsy and blood data, you know, and it was seminal. You know, from that paper, we learned that indeed, because most supplements just get destroyed during digestion, right? This entered the blood and it increased in the muscle. We also learned that exercise increased muscle creatine uptake as well, which was really important. And that's it. This was not a performance study. We had to wait another year for someone to publish a muscle fatigue during high intensity exercise type of study. And then there was kind of a trickle, 1993, 1994, 1995. And then it just exploded. And, you know, there was other things happening, you know, Nikolai Volkov in the former Soviet Union, whose name pops up in all different types of performance enhancement discussions, was very likely feeding athletes creatine in the late 70s and the early 80s in the former Soviet Union. You know, they have a small amount of research that was published many years after the fact, but, you know, the lore is that this was happening a lot earlier than people thought, just based on the metabolic pathways in the textbooks. Welcome back. You are listening to the Science of Sport podcast. I remember very clearly I was in my early 20s in the 90s, and I remember being a member of the local gym and creatine was all the rage for, you know, I mean, it doesn't look like now, but back then I was a very skinny chap. And it was everybody was suggesting that I take creatine. And that was, that was the muscle that if you were a skinny teenager, early 20s, that's what you would take to build your muscle. And it was the, and it was the legal safe way to do it, which was also quite a critical component because obviously there was a lot of illegal stuff happening back then. Absolutely. And what was interesting is that, you know, the bodybuilding world has just been plagued with dietary supplement after dietary supplement that, you know, you're targeting a somewhat vulnerable population and 99% of this stuff just doesn't work. You know, the athletes figured out that protein was necessary to some extent, essential amino acids, but a lot of the products that appeared that were testosterone boosters and guaranteed, you know, hypertrophy products, they just didn't do anything and creatine clearly did. So for, for, you know, the first time you could take something and feel it, you know, a natural product, a nutrient. And that really, that really changed things both in the scientific communities and in the gym communities, because there was just a lot of wishful thinking and a lot of predators, a lot of predatory supplements sales. And finally, there was something here that people could say, this really works, even though the research was a few years behind. So how do we define creatine? Is it a supplement, a vitamin, a drug? How would you define it? Kind of in a class by itself, right? It's, it's a nutrient because you, if you are not a vegan vegetarian, you consume creatine in your diet. It is a metabolite stored inside your muscles and used to make energy during times of, of high demand. And it's a dietary supplement. You can buy it on the, on the shelf. Amino acids are involved in the synthesis, but it's not an amino acid, although it does contain nitrogen. You know, it, it's kind of in a special class based on its chemical structure, but it's a metabolite and nutrient and a supplement. Yeah. And, and the process, I mean, give us a bit of a breakdown as to the process as to why it works and why is it, why does the muscle take it up? Sure. I'd be willing to bet that there are small changes in uptake, perhaps, that we couldn't even measure. This is an issue that comes up in a different way. People often ask me, you know, should I cycle my creatine? And, you know, what happens if I stay on creatine? Things like that. But the body is fantastic when there are small perturbations in intake, you know. If you were to say, well, if you were to eat too much sodium, your body would excrete extra sodium. If you were to eat, you know, too little iron, not enough to become deficient, but if you eat too little iron, your body will increase iron absorption, right? There's all of these compensatory reactions all of the time. So it makes sense that if you're a vegetarian, your body would compensate by over-synthesizing creatine, but we know the creatine, we know that vegetarians have lower blood creatine and we know they have lower muscle creatine. So it doesn't seem to react like that with this particular nutrient. You know, it's interesting, there are some acute studies where they placed people on vegetarian diets and within three weeks, their muscle creatine levels get rather low. So it seems to be a fast reaction and it seems to be a sustained reaction. But again, how do we look at a non-essential nutrient? You know, a deficiency in calcium that leads to a bone disease is clear and that's the way we've been looking at, you know, deficiency diseases and nutrient, adequate nutrient intake for hundreds of years. But with creatine, because we manufacture it, what do we do with those people who have low blood, low muscle creatine levels? Is this a segment of the population that should be, you know, more interested or more encouraged to supplement with creatine? What about the opposite case? Someone who takes a lot of creatine, do they just stop manufacturing their own? Yeah, and that's why I get asked that question so often. And when I hear people use words like cycle, you know, should I cycle my creatine intake? I have some concerns that their mind is focused on performance enhancing drugs. With the athletes I talk to and the students I talk to, and unfortunately, you know, the masses who are being very influenced by Instagram today, I can kind of tell where the questions come from. And with something like a medication, something like testosterone, you know, that has the ability to really suppress endogenous production for weeks or months after treatment, this is a nutrient, right? When people frame it like a drug, I think when people frame something like a drug, they expect drug-like effects, beneficial effects, and they also expect drug-like side effects. And I think that kind of fed into the hysteria about creatine that I've had to deal with for the past 30 years. So it's a fair scientific question, is there a compensatory reaction? Does your body stop synthesizing or decrease endogenous synthesis? And my answer is, I hope so, right? If you over-consume iron, I hope your body down-regulates absorption. If you over-consume calcium, I hope your body absorbs less. If you under-eat calcium, I hope your body absorbs more. So if you're taking large amounts of creatine as a supplement or probably more difficult through food, I hope your body down-regulates synthesis a little bit. And then because this is a nutrient and not a drug that overwhelms the system, I've not seen any evidence of suppression or long-term suppression or any need to cycle, there's that word, the supplement. When people ask me that question, should I cycle my creatine, I ask them if they cycle their multivitamins, and I usually get a strange look, but you know, with a little bit of conversation, they realize that they're holding creatine to a different standard. You know, do you cycle your calcium supplements because you have some concern about, you know, some long-term chronic effect? Do you supplement any other, do you cycle any other nutrient or is it just this one? Can I just take a step back just so I can, so that for all of us, I mean, for the non-scientists, I've got a lot of questions about how this works. So just give us an idea of what creatine actually does because you talk about it being in part of the energy process, but how does it work? It's not a glucose molecule or anything like that. So what does it do and how does it work with the body? That's a great question. And I love the gas tank analysis here, you know, and also the analogy to carbohydrate metabolism. So if I were to say, you know, your muscles are filled with carbohydrate, filled with glycogen, glycogen is involved in energy production, ATP production, that supports muscle contraction. And, you know, endurance type activities rely heavily on carbohydrate metabolism. So if you followed a high carbohydrate diet or if you carbohydrate loaded and you increased the amount of carbohydrate in your muscles, we would expect an improvement in some type of endurance exercise performance. Same idea here, except with high intensity brief activity, maximal activity. So your muscles are filled with creatine. If you follow a diet that's high in creatine, in this case, it's not as simple as with carbohydrate, right? So the supplement would probably be needed here, but your muscles are filled with creatine. If you could get a little bit more in the tank, your muscles, then because creatine inside your muscle supports maximal intensity, we would expect sprinting type maximal intensity exercise performance to be improved. So, you know, your muscles use ATP to contract and we store very little ATP in our muscles. We also store very little creatine and phosphocreatine, but we store more than ATP. So your muscles right now are filled with creatine and phosphocreatine. And when you begin exercising, so if you were to, you know, take off your headphones and take off in a sprint, you know, to prevent that drop in ATP levels, the first line of defense is muscle creatine and phosphocreatine to donate the phosphate from phosphocreatine to adenosine diphosphate, two phosphates to convert it back to adenosine triphosphate, three phosphates to sustain muscle contraction. So this is normal, this is how it works. But if we think of a gas tank, you know, if you have a 10 gallon tank and you fill your tank of gas, you can always squeeze in a little bit more and top off the tank. And then you should be able to last a little bit longer. And it's really that simple. And the same thing we have with, for instance, carbohydrate loading. The tank is full, but I bet you can top off the tank with some dietary or supplemental manipulation here. And then with creatine, if you're doing high intensity exercise, whether it's a sport or whether it's something in the weight room, we would expect you to be able to last a little bit longer. And indeed, that's been the case. I would say that most of the effects are energy production, fuel. So adding more fuel to the tank. Secondary effects are going to be an increase in phosphocreatine resynthesis. So here's where energy metabolism between carbohydrate and creatine are different. Your muscles are filled with glycogen, but when you burn through that glycogen, it's gone. You need to eat to replace it by and large. With phosphocreatine, if you were to sprint maximally, your levels would go down to zero. But then when you sit down, you resynthesize the phosphocreatine over the course of several minutes. That recovery, that phosphocreatine resynthesis is faster when your muscles are loaded with creatine. So there's, you're starting out with more fuel, there's that effect, but in between bouts of high intensity exercise, you're recovering faster and that could be in between sets of squats in the weight room, or it could be in between plays or downs or something in a given sport. You know, even in sports like what I call soccer and football, there are periods of standing still, walking, jogging, sprinting. And during those low intensity activity periods, you're resynthesizing phosphocreatine. So there's opportunities to enhance performance of the sprints, even when it's embedded in a team sport. It doesn't just have to be in between sets of squats. So it's mostly you're starting fuel level, but it's also phosphocreatine resynthesis. There's some other studies to show you that, this is gonna be silly the way I phrase this, but a muscle cell that's loaded with creatine is a happier muscle cell. So creatine is an adaptive nutrient in that there are changes in gene expression, changes in satellite cell activity, and there is water sucked into the muscle cells. All of this creates kind of a happier intramuscular environment that's more conducive to adapting to exercise training. So creatine as an adaptive nutrient is very real, not as powerful as protein as an adaptive nutrient, right? So if you just have a glass of milk after you lift weights, that's a very powerful additional stimulus to the training. I think having creatine loaded muscles is also a powerful stimulus for the adaptive response, which might be particularly important for clinical and patient populations. But when we're talking about sports science, it's fuel and it's recovery during high intensity bouts. So basically, if I'm thinking about this now, you're exercising, running, cycling, lifting, whatever it is, throwing. Your muscle is consuming ATP and forming ADP, and creatine phosphate is its most immediately accessible means by which to recreate the ATP to keep that high intensity exercise going. Is the use of creatine phosphate driven almost entirely exclusively by the flux or the demand? Or is it kind of apportioned even over longer duration? Because I've often wondered, an 800 meter runner whose event lasts 1. And then a study would come out that would show improved performance for 30 seconds and then 60 seconds and then two minutes. And then some of the biopsy work showed that when you creatine load and combine it with carbohydrate loading, you actually force more carbohydrate into the muscle. So there's a secondary advantage there that people weren't even detecting. You know, the first study that came out that showed improved performance with creatine supplementation in longer than a minute or so, and I scratched my head and said, I'm not sure what to make of this. And then the biopsy data came out and then people really started to focus in on combined carbohydrate and creatine ingestion and, you know, you're metabolically enhanced in two different energy systems. Lots of overlap. Yeah, because my next question was going to be based on that research that you're suggesting that it's all to do with, you know, if you're a powerlifter, it's instant, it's sprinting. But as you're saying now that the supplement, we're going to call it creatine because it's got its own area, that helps carbohydrates, therefore it does, in fact, improve endurance performance then at the longer you go because it's enhancing the absorption of carbohydrates. Is that a fair summary? Absolutely. And, you know, the research started with the exercise performance research, started with, you know, 30 seconds or less. So Wingate tests and 10-second cycling sprinting tests and, you know, 10-second tests to try to get at the repeated, you know, high-intensity type of sprinting format. But there's a few other things that were going on there. There is some studies with cycling where, you know, I often tell people when they ask if this is useful for endurance athletes, I say, well, how does every single cycling race end? And they say, well, with a sprint. I say, okay, well, that's been addressed. There are several cycling studies where they showed that creatine supplementation enhances not the endurance performance, but the performance of the sprint if it's embedded in the endurance ride or if it's at the end of the endurance ride. And then people started to say, oh, it's not just for 100-meter sprinters, it's also for endurance athletes. And, you know, sport performance is so difficult to study, right? There's so many variables that are not metabolic, right? There's field conditions, there's weather, there's your competition, you know, all of these different things. But I think the most consistent finding in this literature is not sport performance, it's laboratory sport performance. So cycling, treadmill running, jumping, you know, repeated jumping. And even more impressive is the research when you combine resistance exercise with creatine supplements. So resistance exercise is essentially repeated bouts of high-intensity exercise. And if your sport would not benefit from creatine at all, and I'm not sure what sport that would be, you know, it's 2026. What athletes don't do strength and conditioning? Golfers, tennis, swimming, you know, so if I'm enhancing the quality of your strength and conditioning workouts, if you believe in strength and conditioning, then we have to assume that this translates onto the playing field or onto the pitch or into the pool. So at worst, this is a training aid that enhances strength and conditioning performance. Now, if we look at sport performance, you know, and we go back to that example of soccer or football, absolutely. You know, periods of standing still, walking, jogging, and then sprints. If I can enhance that sprint, that's the difference between a goal or no goal, you know, if you're a striker. Same thing with gridiron football, the same thing with rugby. There is a reason this is the most consumed sports supplement in the world. You know, athletes have been wrong about some things, but they trusted their instinct on this one, and they're benefiting in the weight room and they're benefiting on the playing field because most sports are a mix of high intensity, moderate intensity, and low intensity exercise, except for golf. And lawn bowl. Yes. That's a good. Give us an idea of the magnitude of these changes. And actually, in doing so, can we also just talk a little bit about the quality of some of the studies? Because I imagine like with many supplement studies, especially in the early days, I would imagine there was a lot of really bad stuff that was done where they didn't adequately control for diets, training, training history, sex, potentially. Plus there would have been some studies that didn't have a good enough control group and so on. So my broadest question to you is, do we now have very high confidence in the quality of the research? I know that's been an issue for sports sciences in general, but is this field, can this field stand and say, we believe it's good enough? And then what does that research actually show in terms of the size? Are we talking 2% or is it 7%, 8%, 9%? Yeah, those are great questions. And I think the first one's much easier to answer than the second question. You know, sports science has suffered with some low quality research, but you know, I would say that the second hardest type of research to do is a training intervention in humans. And number one would be a training intervention with a nutritional intervention on top of it in humans. It's, you know, it's rough working with even untrained individuals and athletes are, of course, very complicated. So with creatine, there was so much excitement because this was effective, right? That there's, you know, when you study these dietary supplements and you try to publish your paper of no, it didn't work. This is a negative finding. This is a non-finding. Or, you know, some of these products had no theoretical basis whatsoever. And suddenly we had a product that had a sound theoretical basis. It was clearly bioavailable. And, you know, the early studies showed improved performance. Then everyone was studying creatine. And the first flaw in the research became that not everybody has the capability to do muscle biopsies. So, you know, I encourage my students, you know, the study you want to pay the most attention to has an exercise performance outcome and is a functional outcome. And it has a biological outcome like muscle creatine, muscle glycogen, some sort of biological measurement that can support the changes that we see functionally. But not everyone can do muscle biopsies. And the creatine research, I think, exploded in part because of Roger's, the duration, the length of Roger's study. Once we found out that you could, in as little as five days, have a, you know, a measurable effect of performance, then everyone was doing five-day studies. Right, and some of them were of a lower quality. Many of them were of a very high quality. At this point in time, we have so many systematic reviews, so many meta-analyses. You know, we're talking about close to 700 studies. And the research holds up. And I think some of the weaker studies get washed out. And, you know, some of the weaker studies showed an effect. Some didn't show an effect. But, you know, we're pushing 700 studies here of the effects of creatine on muscle outcomes, sprinting or resistance exercise outcomes. So I think we can say without a doubt that under the right circumstances, this is going to be effective and effective provided you can increase your muscle creatine levels. Yeah, just on that, are we confident that there's not 650 studies sitting in someone's filing cabinet or computer that didn't ever make it because it showed nothing? I'm never confident of that. But, you know, I look at it very globally. Again, Louise Burke has spoken of saying to me, the plural of anecdote is not anecdata. And so I shouldn't include coaching observations and athlete behaviors in with my rigorous meta-analyses and systematic reviews. But there is a reason that creatine use is 100% in a lot of different sports. There's a reason it's used in the pros and for my Olympians and, you know, across all age groups. And that's because there's a measurable effect. Despite the limitations of our research and the peer review process, you know, the majority of studies are showing a positive effect. You know, if you pull out the one study of someone running, you know, a 5K and creatine didn't enhance performance, well, that doesn't even make metabolic sense that it would. You know, there is, there are, there's quality control issues all over our field. And I know people are working hard to improve them, but I think with creatine, we have enough good data at this point in this population to come to the logical conclusion, plus population data and, you know, anecd data. Okay, so how large an effect are we talking here? And I know that's a very difficult question because it depends on our famous, if we have a coffee mug on the show, it's going to say it depends on it. So I'm like, how can I lie to say it depends, even though that's the answer. What sort of margins are we talking here? Like I found some systematic reviews that talk about like sort of mid single digit percentages. Is that what you? I would agree with that interpretation. You know, this problem is not unique to the sprinting and the high intensity world. You know, I've seen values in, you know, time to exhaustion tests that report 30 and 40% improvements in endurance performance. I think those numbers are very dangerous to release into the wild. You know, if you're talking about caffeine or carbohydrate and, you know, a 40% improvement in performance, be very, very careful. I think really for the, you know, there's that small group of nutrients and supplements and compounds that we described in the IOC dietary supplement consensus statement, meaning caffeine, excuse me, dietary nitrate, buffers creatine levels remain the same. So there's no effect of sprint training. You can look at the placebo group from all of these creatine supplementation studies, and you can see that the sprint training or the resistance training didn't alter people's muscle creatine and phosphocreatine energy levels. So this seems like it's alone from the buffers and dietary nitrate as a physiological system that doesn't respond to exercise training. Detraining is a different discussion, but training, it seems to be like if it were me or if it was the world's number one sprinter, we stand to receive the same benefit based on whether our tank is naturally half full or naturally three quarters full. Interesting thing about creatine is everyone is a responder. You're just a low, medium, or high responder based on your starting level when it comes to skeletal muscle, not brain. Well, let's move on to some of the, I mean, it is one of those topics that I think is interesting because I think for the general population, there's a lot of misunderstanding around creatine. I remember back in the day, there was always this discussion about whether or not it was doping. Is it illegal or what? Why isn't it doping? Well, I think Ross could speak better on this than I ever could. You know, there's, you know, do no harm, and it's a nutrient, a naturally occurring nutrient. It's part of your diet. Theoretically, you could eat, you know, 10 pounds of meat a day and alter your muscle creatine levels. I don't think many people will do that, but, you know, theoretically you could do this with diet. And, you know, it puts it in the category with really smart carbohydrate ingestion and small amounts of caffeine and things like that. So it was never doping to me. I'll say that, you know, I detect, and this is my opinion and my experience, it's not fact or research, but I always detect a bias in anything that comes from the muscle building community in terms of that fear, right? If you're expecting drug-like effects, you're expecting drug-like side effects, and then people start to morally attack it and say it's cheating. And I've never seen anyone go after a dietary supplement like with creatine without any scientific foundation, just wild speculation about a whole host of systems in your body potentially being destroyed. And then the doping things, you know, meanwhile, athletes are using caffeine, they're using bicarbonate, but somehow the nutrient creatine, which we've been studying for 200 years, is doping. So I always saw a real bias there for the population who was really benefiting from or against the population that was really benefiting from creatine in elite sport. So what's implied in your answer is that there's no evidence of harm. And incidentally, WADA has three criteria, right? It's, is it performance enhancing? You've made the case for it to be yes. The second one is, actually, it's the third one, but we'll do that one first, against the spirit of the sport. Now, that's a really slippery one. I mean, how do you know? But the third one is no evidence or it's banned because there's evidence of harm. So are we saying here very strongly and convincingly that there is no evidence of harm? Because like Mike, I remember when I was still a teenager in school, we had a show in this country, it's like our version of 60 minutes, it was called Carte Blanche. And they had this whole expose on the harms that young schoolboys were causing themselves by taking creatine. And we were warned about kidney issues and the fact that you're going to overload and have to excrete this excess and so forth. Muscle cramps were said to be caused by creatine. There was all kinds of stuff going around. Was that just part of the fad and the hype as it died down? And is there evidence to positively refute it now? Yes, there was no research to support any adverse effects. I guess I'll start at the end and say that last year, Rick Cryer published the largest safety trial. And Rick's study, I think there's 685 studies where people ingested creatine to the tune of about 13,000 research volunteers, and they find nothing, absolutely nothing. So, you know, for years, I would say, you know, as it grew, I would say, Ross, go read this one paper on creatine in the kidney. And then eventually I would say, Ross, go read these five papers on creatine in the kidney. And then it was read the, you know, read the review on creatine in the kidney. And now we're at the point where there's so much data that we can drop it into a giant review article. And there's just nothing there. So there's, you know, narrative reviews, systematic reviews on creatine not having adverse effects on thermal regulation, maybe even small benefits, not having adverse effects on kidney function, not having adverse effects on muscle function, for instance, cramps and strains and tears. And there's actually a fair bit of data that shows that creatine reduces the risk of muscle injury, reduces the risk of muscle cramps, reduces the risk of muscle damage or enhances recovery. So it's either you break even or you might even be getting a small gain in these areas that we're, you know, we were all supposed to die from. But it's, you know, it's me back in the 1970s and 1980s and people with a drink in one hand and a cigarette in the other hand telling me that I'm going to die from eating too much protein. That was never based on anything. And somehow a milk protein supplement was more dangerous than milk. And that was never based on anything, you know. And that's still going today when I'm in, you know, a sporting event, particularly youth sports. My goodness, the things that come out of people's mouths and often what they've been told by their physician. I'll always take a moment to make fun of physicians having no nutritional or exercise training whatsoever. I still hear this nonsense, you know, creatine and cramps, no evidence. Creatine and kidney, no evidence. Just because your kidneys excrete a larger concentration of something, that doesn't mean there's disease or a strain or stress. Imagine if every time you had a salty food that, you know, the increase in urinary sodium was life-threatening. This is not, the human body is smarter than that and much more resilient. So, I think at this point we can say there's just no signal there. And there are, you know, full disclosure, there's a half a dozen or so case studies and most of these people were taking ridiculous doses of creatine. I could never figure out how they would have the time to take 200 grams of creatine per day. And, you know, these are retrospective case studies and these people had a lot of other issues going on, a number of confounding factors. But, you know, for the most widely consumed supplement in the world, probably outside of caffeine and protein, to have no signal whatsoever in safety. But I still get the questions every lecture I do. I was going to ask you, there must be a theoretical line at which it could become excessive overload. And like I think, you can correct me if I'm wrong, maybe it's changed. You often see they say 0.3 kilograms per kilogram of body weight. So, someone who weighs 80 kilograms, that's, let's call it 30. So, you're saying there are studies where people have exceeded what's recommended like by 700% or sevenfold and then you might get problems. But as long as you're sensible, no issue, right? Well, yeah, absolutely. If you follow manufacturer recommendations, there's no evidence of adverse effects. Some of these case studies and, you know, we teach our students that retrospective case studies are the weakest form of science there is. You don't throw them away. You don't disregard them. But they're weak and they're often missing pieces of the puzzle. But some of them, there's, you know, a recent case study of creatine supplementation, you know, plus cocaine. And clearly, they were blaming the creatine in the article title. There's, you know, creatine supplementation plus large amounts of anabolic steroids. And clearly, creatine was included in the title for, you know, a reason. And that's what got it noticed and that's what got the notoriety. But these case studies just have so many confounding factors. It's, you know, it's good to put them all in a PowerPoint and use it as a research methods lecture some days. Is it fair to say that the only area where there isn't any evidence is long-term sustained creatine usage? Yeah, and that's addressed in Rick's safety study. We have data going out years, so beyond five years of, you know, creatine supplementation. And that's just about as good as you can get with a dietary supplement. You know, the manufacturers of any dietary supplement, in the United States especially, because of the laws, there's really no incentive for them to fund high-quality research. So people like me have to somehow convince organizations like the NIH to fund research on a dietary supplement for some reason when the manufacturers or the distributors, you know, they're just unlikely to do so. So I think long-term data going out several years is available and has been for some time, again showing no signal for adverse effects. But, gosh, that's hard to come by in the whole dietary supplement world. Yeah, for sure. Everything. Yeah, fair enough. Well, I suppose, I think the time has come for us to discuss now the current excitement around creatine. And we'll talk about, you've touched on some of the talk about the elderly and the frail and that sort of thing. Let's just kind of try and figure out how it sort of came back into fashion again. What was the trigger that brought creatine back into the, well, let's say the internet burst because that's kind of How is the stimulus to help the creatine do its thing? You don't have to actually lay training on top of it. Yeah, that's a great question. I think optimal would be resistance training plus creatine. Again, all older adults should probably be lifting weights unless there's a medical contraindication, and the creatine would enhance that process. If they're unable to do resistance exercise, perhaps their fitness is too low, then maybe it's activities of daily living plus creatine. Certainly, if we look at the kids with muscular dystrophy, they can't do intense exercise. They can't do resistance exercise, and they have a really robust increase in muscle strength. So there's a benefit there for really delicate, really frail muscles just from the creatine alone. Optimal, creatine plus training, without a doubt, young, old, anything. But if we can't work the exercise in, then I think there's value to the creatine as well. And I'll go back to that comment from earlier about the adaptive response. Improved gene expression, increased intracellular or intramuscular water, increased satellite cell activity, these are all important benefits to someone who's in some sort of a frail or vulnerable state. And there's obviously also talk about that it's assisting people with dementia and Alzheimer's. What evidence have you seen on that? Yeah, I mean, this is someplace I never thought I would be because I'm a neck-down muscle person. I avoid the brain at all costs. All respect, I know the brain's telling my muscles what to do, but skeletal muscle is just the coolest stuff in the world to study. And there was a paper in the late 90s from Deschen and colleagues, and they showed that, again, methods matter here, right? You can't biopsy people's brains. So they fed people creatine, and they used MRI, you know, magnetic resonance spectroscopy, to get a concentration of brain creatine. And they showed that you could increase brain creatine with creatine supplementation. And we read this paper and we thought, so? I mean, it's almost entirely in your skeletal muscle where it maintains ATP during intense exercise. What are we supposed to do with this paper? And then subsequently a paper came out that showed improved cognitive processing. And we went, oh, energy production and cognitive function has some parallels between energy production and muscle function. And then, you know, I had to spend the past decade learning how to get things in and out of the brain, what brain energy metabolism looks like, and how to even measure brain performance, which is not my original area of interest and certainly not my training. Right now, you know, there's, I'll say, a smaller amount of studies that actually measure brain creatine than muscle creatine. Because even though not everyone can do muscle biopsies and wants to study creatine, even fewer people measure brain creatine and want to study creatine supplements. Right, so there's brain researchers out there who measure a lot of, you know, brain chemistry, but they don't care about creatine supplements. So now we're down to a very small group of researchers in the world. And for a while, the people who could measure brain creatine in response to creatine supplementation were not the people who measured cognitive processing in response to creatine supplementation. So we grew two bodies of literature. One, does brain creatine increase with creatine supplements? And we would say yes. And the other, does brain, does creatine supplements improve cognitive processing without any biological measurements to back it up? And we would say yes. And at this point in time, we have about two dozen studies. So pales in comparison to 700 creatine supplementation, you know, muscle type studies. We have about two dozen studies where people were given recommended, you know, reasonable doses of creatine and cognitive processing was measured before and after the supplementation protocol. Now these studies are very, very difficult to compare because they use different supplementation doses, different supplementation durations. They use different populations, old people, young people, vegetarians, stressed people, people who were stressed with physical activity, people who were acutely stressed with mental activity, sleep deprived people. And throughout those two dozen studies, there's a statistically significant signal that you see in the individual studies and you see in the narrative reviews. And now we have, I think, three metas, three systematic reviews and metas that show an improvement in the common measurements between those studies, which is usually memory. Now, my opinion at the moment is that the stronger studies are going to be when the brain is somehow challenged. There's an acute need that's created where brain creatine levels drop or are inadequate and supplementation works. I guess we should, we should start with the physiology here. And that is to say that the brain manufactures its own creatine. Unlike muscle, where muscle is ready to take up exogenous creatine, the brain manufactures its own creatine and it seems a bit resistant to exogenous creatine. So if you challenge the brain with something like sleep deprivation or a mentally fatiguing task, it has a higher energy need. And in that instance, what we've been saying for a few years is it appears that those are the studies that are the most clear that there's an improvement in cognitive processing when you're under some type of duress. And that could be acute sleep deprivation or it could be chronic, like aging. What about concussion? That's where we are now. So with healthy people and brain or Alzheimer's patients with brain, we've leapt into brain injury. And this is perhaps the area that makes the most sense to me. And, you know, if you chart out the neuro metabolic cascade of a concussion, you know, what happens when you get hit in the head? There's this massive wave of membrane depolarization. There's this increased energy need. There's ATP depletion. There's increased lactic acid. There's reactive oxygen species, mitochondrial dysfunction. If you diagram out all of the areas of the brain where something happens during a concussion and then overlap it with creatine biology, you will find that there is a considerable amount of overlap. Right, so when you get hit in the head, your brain creatine levels drop and then there's an increased ATP demand. There's calcium rushing in that can't be pumped out because of the lack of energy. It just on paper looks like a perfect fit. And a lot of things in physiology stop right there with the arrows and the metabolic pathway, right? But at least we had a theoretical basis. There's some really good animal work here. And I never, ever talk about animal work when there's human work available because it's just so often doesn't translate. But the animal work is compelling, you know, because they can sacrifice the animals and quantify the damage. So they give these poor animals a traumatic brain injury. And if they preload them with creatine, rats and mice, the reduction in tissue damage is up to 50% less damage, plus less reactive oxygen species, better mitochondrial function. All the things that look good on paper that they can measure in animals when you preload a laboratory animal with creatine, all of these things light up for less damage and a healthier brain. And you know, this is the point of the conversation where people say, yeah, Eric, but those are rats and mice. All right, that's a biochemical pathway. And there's some human data, right? There's a couple of clinical studies, so open-label hospital studies, not randomized controlled trials, but open-label hospital studies where there were children who had a severe brain injury. So this is not a rugby player with a concussion. These are children with severe brain injuries. And they were supplemented with creatine in these two studies. And the children given creatine had remarkable improvements in all of the things we associate with concussion. So memory, mood, personality, cognitive processing. And then all of these other variables that hospitals measure that we wouldn't measure in our research, but like days in the ICU, you know, length of intubation, things like that. And the creatine group responded much better than the group that didn't get the supplement. And you know, the evidence, although circumstantial, it's starting to add up. You know, so we have theoretical. We have animal. We have some patient populations. We are missing the randomized controlled trials in athletes who have concussions. But there are some other research studies that I think are really enlightening. A nice cross-sectional study recently out of Dave Howell's lab in Colorado. Simple cross-sectional observational brain creatine levels in teenagers and adolescents who've had a concussion. And the brain creatine levels strongly inversely, you know, indirectly correlate with their concussion symptomology. And this is about a week and a half after a concussion. And it makes metabolic sense. It's just cross-sectional, right? And there's one really impressive study from Alosco and colleagues, and it shows the same type of correlation. But what impresses me, this study is in National Football League retired players. So these are people who had multiple, you know, head impacts in their career. They are years into retirement, and they still have a relationship between their symptomology and their brain creatine levels, meaning the lower your brain creatine, the worse you are. So we have some nice cross-sectional data in humans. We have the animal data. We have the patient population data. We have the theoretical pathways. You know, if you forced me, you know, I would say without the randomized controlled trials, this is largely circumstantial. But, you know, all over the world in elite sport, if someone has a concussion, they're immediately put into kind of a creatine protocol. Now, there are some other nutrients that are of interest there too, but creatine is the big one right now where people are saying, you know, we have all of these data on improved muscle function and we have an excellent safety profile. It's widely available. It's inexpensive. If there is a benefit to your brain at this particular point in time, then why would we hold back? So it's circumstantial, but it's When do you have the time to take this? When will your adherence be the best? If you work out in the evening, are you going to take your creatine when you get home? You know, questions like that are important in nutrition. For me, I don't think hard about this at all. The easiest delivery system for me is Greek yogurt. I use the powder, I take a five-gram scoop, I drop it in my yogurt, and that's it. You know, and we can go into details of the studies that show that carbohydrate-protein combinations increase uptake. Well, what I usually consume after my workout is some type of high-protein, you know, moderate carbohydrate type of food. And, you know, if it's late at night, it's usually a Greek yogurt. When I get sick of Greek yogurt and I switch to protein shakes, then my creatine goes in the protein shake. And it's usually post-exercise because that's when I have that type of meal. But, you know, people don't need to be titrating doses of dextrose and measuring all of these, you know, precise, you know, macronutrients. Throw it in your yogurt, throw it in your cottage cheese, throw it in a protein shake. You know, it's a bit insoluble, and, you know, I could throw it in an electrolyte fluid replacement type of drink, but I tend to drink those slowly, and eventually it settles at the bottom. And I don't like that. So for me, that doesn't work. For other people, that might be fine. Some people have smoothies. Throw it in the smoothie. But it's monohydrate, and it's importantly to me is at your convenience at the time you're most likely to show good adherence. Is it five grams? You just said that's the amount you use because, like, in the beginning, people said you need a loading phase, and then you already addressed why you don't need to cycle it. But are we going five every day and that's how you go? Or is it more initially? Yeah, so it's – I tend to lose the absolute values. So if you want to load 20 grams per day will cover most athletes and most individuals. Unless you're a very, very small person or a very enormous 300-pound, you know, plus athlete, 140-kilogram plus athlete, you know. 20 grams per day should cover it. If you want, if you're in a hurry and you want super-saturated muscle creatine levels in five days, then 20 grams per day for five days. If you're not in a hurry, then five grams per day for a month will get you to the exact same ceiling, the exact same muscle saturation level. And I think for most people to have five grams four times per day is annoying and will decrease adherence. So the scoop is five grams. If the scoop is full, great. If it's half full, that's okay too, right? Anything in a three to five-gram range will cover the majority of the population, and it's soluble enough in a protein shake or a smoothie or, you know, a yogurt that people tend not to get turned off from it. So I use the little scoop once per day. And, you know, it's important to remember that the washout period for creatine is weeks, right? We published data some years ago about a high responder and a month off creatine, and his muscle creatine levels were still like 25% elevated. So if you take your five grams per day and then you decide, you know, I'm going to go away for the weekend. I kind of don't want to take my creatine with me or I don't want to fly with white powder. Don't. You know, you can buy single-serving packets. I have those. But if you don't take your creatine for two days, the loss of creatine from your muscles will be very tiny. It's going to take four to six weeks to get down to baseline levels, you know, without the supplements. So don't beat yourself up. Try to take it seven days per week. If you miss a day, you're okay. You know, take it the next day. No need to reload or do anything silly. Just, you know, if you've the same as any other nutrient, if you forgot your calcium pill today, you're okay. Just get back on track tomorrow. You know, I don't want to labor this point because, like, when I listen to other experts talk about this, and I don't think some of them are experts, they'll say, the studies say 0.3 to 0.5 grams per kilogram per day. So, again, that 80-kilogram male, 40 grams. And these people will tell you that actually overshoot that. Do more. So they're saying 50 grams a day. You're saying you can get away with one-tenth of that, and one month from now, I'll be at the same place as that person at 50 because they're just excreting the equivalent of 45 a day over the course of a month. That's what's happening? So I don't like the 0.5 number. The 0.3 number is okay with me because that's, for an 80-kilogram me, that's 24 grams per day, right? Yeah. That's not outrageous. You know, the old urine values show you by day 3, 10 to 15 grams per day is coming out in your urine. And we've published some low-dose data, as some other people, showing that, you know, you don't need 20 and you certainly don't need 50. You know, you need to kind of overwhelm the transporter and create this effect where your muscles are, you know, really inviting the creatine in, so to speak. But I think we're overcomplicating things. And I think part of this is the brain data. My guess is that we might wind up with tissue-specific recommendations in a couple of years, but I'm really disappointed with other podcasters saying, you know, oh, I didn't get enough sleep last night, so I took 30 grams of creatine per day to fix it. I don't think that's how human physiology works. I think that's an oversimplification, and I'm seeing these escalating doses again, which, you know, are foolish and a bit worrisome to me. I think if you've got to do it relative to body weight, maybe 0.3 will be sensible, but, you know, what are we to do with our extremely large and extremely small athletes? You know, nutrition, the same thing with protein dosing, you know, per kg, you know, per meal, per day. These come from a conversation with our athletes and with our patients, and we have to individualize these types of things. You know, this is why I prefer just the one scoop a day because it's more easier for people to be compliant, and, you know, Eric Altman's original seminal study was the one that showed that just the one scoop per day for a month gets you to complete muscle saturation. And then what can someone expect? You mentioned something earlier that within five days that that first study had shown something. Is that something that people listening to this can expect? They start creatine on Monday. Can they expect that by the weekend they notice something different? What is that something? Yeah, I suppose it depends on, on either I said depends. I know I'm not supposed to say depends. Go ahead. I would say it's different per population. For someone like me who spends a lot of time in the weight room, clearly I'm getting extra repetitions. It's within a few days, you know, and you just have that, if you were to go for a run or a ride and some days you go, I feel fantastic. I feel effortless. I'm beating my best time with less effort. You know, people, a lot of people have felt that before. That's, you know, kind of what being properly hydrated and full of carbohydrate feels like. And that's what being full of creatine feels like too. Is you say, wow, I'm really having a great day. I'm going to push it a little further. But it's, it's, you always feel like you're having a great day because your muscle creatine levels, you know, up, it's elevated, it's supersaturated as long as you keep taking your one scoop per day. Some people, you know, with a lot of muscle, they'll feel rounder, more full, which, you know, athletes report from carbohydrate loading. Um, and, and for some people, that's a good feeling, you know, but especially in the weight room, I think it's, you know, it's going to be sports specific. You know, if you're a sprinter and hundreds of a second matter, you will notice this in a few days that, you know, you have a little bit left at the, you know, at the end of your event. If you're a team sport athlete, my guess is if you have to sprint near the end of like full time and in soccer or football, you'll say, wow, I, I still had a kick there after 90 minutes. and it's, it just has to do with having your muscles full of creatine, having them supersaturated. So that could be in five days at 20 grams per day, or it could be in a month at three to five grams per day. Yeah. If you notice that roundness or size, volume, that's not muscle mass in the first while, right? That's fluid retention. Is there a chance of bloating and gastrointestinal discomfort early on? Yeah. So there is the GI issues. You know, the way I answer this is if you tell me creatine upsets your stomach, I will believe you. If you ask me what the research shows, I'll say there's, there's no data on gastrointestinal upset, but it makes sense that we have