Aliquot #131: The Muscle and Bone Benefits of Creatine

Creatine is one of the most widely studied and commonly used supplements in sports nutrition. As a naturally occurring molecule in the body, creatine plays a central role in cellular energy metabolism, especially in tissues that demand rapid energy turnover like skeletal muscle and the brain. In recent years, scientists have begun to explore how creatine supplementation might support health and function across the lifespan, not just in athletes, but also in older adults, clinical populations, and anyone hoping to maintain health with age. The research is growing, and so is our understanding of creatine's potential benefits outside the weight room.

In this episode, creatine expert Dr. Darren Candow and I take a closer look at creatine through the lens of 2 critical systems, muscle and bone, and we'll unpack how creatine supplementation affects muscle quality, physical function, and even skeletal health, particularly in older adults. Let's start by looking at creatine's effect on muscle. When most people think of creatine, they think of weightlifters and massive muscle gains, and that reputation isn't undeserved. Creatine is one of the most well-supported supplements for improving high-intensity performance and muscle hypertrophy, but its benefits might be much more far-reaching than you think.

In this segment, Dr. Kando and I explore how creatine affects muscle training capacity and recovery, not just in athletes, but in anyone looking to maintain muscle function with age. Today I'm joined by Dr. Darren Candow, who is a leading researcher in the creatine field and muscle aging. He's published over 140 papers on nutrition and exercise performance, how it affects muscle, muscle health, muscle aging. Uh, Darin, I'm super excited to have you here today to have this conversation with you, to go deep into the science of creatine. Yeah, no, thanks for having me. I'm really excited as well. Absolutely. I've read several of your studies. I'm a huge fan. A lot of really important and interesting research to talk about. Okay. Maybe we could start— start where it's most popular.

I mean, a lot of people think about creatine in its role in exercise performance. However, there's been a lot of emerging research in other areas. Maybe you could give people just a quick snapshot. And yeah, like it's really evolved over the last 40 years. It's gone from athletes getting bigger, stronger, faster. Now we're looking at potential benefits on bone health, brain health, cardiovascular health, even in children and during pregnancy. So it's evolved from just the young male athlete to pretty much anybody on the planet is now considering creatine either in their diet or supplementation. So for the next few hours, super excited to talk about all aspects of creatine and the evidence-based research behind it.

Well, let's talk about the resistance training and improving performance, muscle health. I mean, Why, why are people— why is it so popular? Well, because it works from a muscle performance perspective. So it really— it basically increases the ability to produce ATP or maintain it during an exercise session. So, for example, when you're doing, you know, a squat or leg press or even running, you're doing muscle contractions and phosphocreatine, which is what we're going to be talking about today from creatine supplementation. It really maintains ATP or adenosine diphosphate. So if you have more ATP longer, you can exercise at a higher capacity, a higher intensity, and that delays the utilization of other energy systems that might be a bit slower.

So anybody involved in high-explosive anaerobic type of sports, weightlifting, high-intensity interval training, for example, probably would experience some benefits from creatine supplementation. And how is it going to benefit you? Is it going to improve your training volume? Is it going to make you stronger? All the above. So it definitely seems to increase training volume. So that's either the load by the reps, by the set, or exercise capacity from a cardiovascular perspective. It definitely— if you were to choose one thing why creatine has been so effective, it's improving muscle strength. You could also encompass that with endurance and power. It also improves lean body mass. So here's a big discrepancy that a lot of the viewers might not know.

When we measure lean body mass in the labs, we're technically measuring blood, connective tissue, soft tissue. So we're not directly measuring muscle mass. We need to do a lot more research on that. But in general, about 50% of the value of lean body mass we consider muscle. So it has some small favorable effects. There's been some studies with QCT as well as ultrasound. But you can get an increase in lean body mass, regional muscle thickness, muscle performance. But probably the area that most people don't realize is the recovery. recovery aspects. It really seems to have some anti-catabolic effects, potentially anti-inflammatory effects. And that's interesting because it's from the aerobic community.

For the longest time, we never thought creatine was for endurance or aerobic-type athletes. And the best lines of evidence from a recovery aspect come from long-duration aerobic exercise— a marathon, ultramarathon, a triathlon. It seems to reduce cytokines. So those are markers of inflammation. So, there's a whole gamut of mechanisms. There's about 10 what we consider anabolic factors, and then there's probably just as many as an anti-catabolic effect. So, it has a plethora of benefits, which I'm sure we'll talk more about in detail today. Yeah. So, you— okay, to go back, you just gave a total information dump, which is awesome. Let's go back first to the explosive power you were talking about.

It seems to really help benefit in that explosive power, like you're talking about doing a squat. Yes. I don't know, maybe the first few seconds of an interval, something where you're going, you know, using all that power. Yeah. Is, is it— is creatine benefiting? Benefiting? Is that how it's benefiting, increasing the training volume, or is there something else that's happening? Yeah, in 2 ways. So it really seems to maximize either the recruitment or the ability of type 2 muscle fibers. And when we talk about aging, unfortunately, those are the ones we're losing as we get older. But it really seems to work in the 2nd, 3rd, and 4th sets.

So for example, if you were to do 4 sets of leg press compared to placebo, you may not notice any difference in the first set because we think we have enough ATP or phosphocreatine stores in our muscle. But when it comes to set 2, 3, and 4, that's where creatine really comes to the rescue. The individual or group can do more repetitions and then over time they can actually do a greater volume. We think with weeks of training, if you're doing more volume, you can actually get greater physiological adaptations. So when we look at all the meta-analysis, when you compare creatine and weight training to creatine placebo and weight training, there is a greater increase in lean body mass, muscle size, as well as muscle performance.

So creatine, there is something there from a mechanistic standpoint to allow that. And we think muscle fiber recruitment, primarily type 2 muscle fibers, is one of the main reasons. Does it affect the recovery time in between sets? Excellent question. It does. It really speeds it up. So on average, if you were to totally wipe out your normal creatine stores, it takes about 3 to 5 minutes for your mitochondria to recover that. However, creatine really, really speeds up that recovery, which is great for the average person. They don't have a lot of time to work out. They can't wait around for 3 to 5 minutes in between a really intense set. So, it really speeds up the recovery. Not only does it speed up the recovery after every set, but in between contractions as well.

So, over time, the individual could probably have a really intense great workout in less time total and get actually more favorable effects. And, I think this is really important. We're talking about here, I mean, we were talking about squats, these explosive types of power types of training. Right. And this is a really important field because, you know, you often hear about people talking about the loss of muscle mass as we age. You talked about losing type 2 types of muscle fibers more readily than the type 1. So, these are the types of muscle fibers involved in that explosive type of power type of exercise.

And, you know, people don't think about how power decreases with age, how strength decreases with age, and how that affects our quality of life, how it affects our physical independence, our fall risk. Right, right. And so, I think just focusing on this type of training, I mean, the creatine is the icing on the cake, right? Yeah. But just focusing on doing these types of multi-joint compound types of lifts, which is something that I, in the past, I would say, year, a good year now, a solid year of doing CrossFit type of training where I'm doing strength training, I'm doing resistance training, strength training, and high-intensible interval training that's including you know, the types of stuff that I'm used to doing, biking and rowing, but also adding in, you know, doing, doing some drop sets with, with, you know, front squats with the barbell and things like that.

It's super important. So there's velocity or power training or variety training. First, we got to get people to move and then allowing them to give some type of benefit to their training program. So creatine is probably the one that will be number one when people select it, even probably more than caffeine nowadays from an exercise training capacity. So, it should be considered. It can have a lot of substantial beneficial effects. And, as we get older, after about the 4th decade, unfortunately, we start to lose these type 2 muscle fibers. And so, exercise has to be foundational. And, if anything else can be beneficial, protein, creatine, I'm all for it. And, I think most people hopefully will be as well. Yeah.

So, the improvements in the muscle strength presumably are coming because you're Increasing your training volume, right? Is that— or is there a direct effect on strength? Yeah, there's actually a neurophysiological recruitment. So now creatine has been touted as a new neurotransmitter. So this is quite interesting. It actually seems to release a lot of things from a neuromuscular perspective. But the biggest thing is the ability to recruit not only type 1 but these type 2 muscle fibers as well. And then of course, if we're having greater muscle or motor unit recruitment, we can potentially lift longer, heavier, and over time get sort of more of an increase in strength.

The other big thing from a cellular perspective is that creatine causes calcium to come back in a little vesicle in our muscles. If you've taken high school biology or university, this will be your nightmare. But I remember everybody talking about the sarcoplasmic reticulum, and it's an area that just releases calcium to allow our muscles to contract. And creatine speeds up the uptake of calcium. So some of the evidence out of Europe has shown that it increases relaxation time or the ability of the, the proteins in your muscle to grab hold of each other to contract. So there's a cellular aspect there explaining why we think we get an increase in muscle performance. I say strength, but endurance and power are all lumped in there as well.

So endurance is the ability to perform repetitions to fatigue or power, move an object as fast as you can. They're all vitally important, but we think strength is overall, from a global perspective, number one. It's probably the main reason a lot of older adults are placed in long-term care facilities. If they have a reduction in strength, they can't live independently. So, that's why, again, resistance training or weight-bearing exercise, as you mentioned, CrossFit, whichever it is, foundational. I'm from Canada, so shoveling the driveway in the winter counts because anything that's a load against you is really beneficial to the body. I think people underestimate the benefits of moving. And then, if anything can be taken in in this form, creatine, it'd be very, very beneficial. Yeah.

You mentioned some of the Anti-inflammatory effects of creatine, particularly in the context of more endurance type of training, people that are perhaps running marathons or just clocking in a lot of hours of running or cycling per week. Right. Is that— so I think that, that goes into some respect in the recovery sort of bin, right? And I'm wondering if that also plays a role in recovering from doing your resistance training, strength training, like on a recovery day. So I mean, do you think it plays a role just broadly in recovery? Yeah, it does.

Now, this is interesting, and I probably would have been the most surprised when we wrote the paper on this, that we don't think traditional weight training, where you're doing a set, you're resting maybe a minute to 2, it seems like it's not catabolic or intense enough. Now, most people will say, shake their heads, say, hey, when I'm in the gym, I'm really putting a lot of effort in. I think from a mechanistic standpoint, When you're doing running or long-distance continuous muscle contractions, it causes this large catabolic effect to the body. So that really heightens the inflammatory response. Weight training is acute: 10 seconds of work, 3 minutes of rest; 10 seconds of work, 3 minutes of rest, or whichever it is.

And we just don't see creatine having a lot of superior effects from a resistance training recovery aspect, probably because the rest intervals for the average person are there. But from a long-distance event, you're running hours, you're swimming, whichever it is. The best lines of the come from triathlon and marathon running where the increase in these markers called cytokines were elevated, but creatine sort of attenuated that rise. Could allow the individual to recover and get back on the track or whichever it is quicker. But, I've talked to some good colleagues in Canada and it just seems like weight training is too intermittent. Now, when you mentioned CrossFit, that's different.

I'm thinking of the 3 sets of 10, you move from machine to machine, you rest, you have— but CrossFit or something that's really continuous would probably fall in line here of the necessity for creatine. So that would be a very good study to look at the effects of creatine on the recovery aspects of something like high-intensity interval training or CrossFit, for example, or military type of training that's really endurance and resistance training. So you just gave me another idea to run with, but it's logical. The more intense, the more demanding. I think that's where creatine's anti-inflammatory properties would come into play. So when people hear catabolic, or, you know, they'll think, they'll think of muscle breakdown, right?

And certainly, you know, there's, there's a big component to sarcopenia, inflammation in sarcopenia, which is age-related muscle breakdown. Is there, is there a role for creatine in, in preventing the breakdown of muscle? There is. It's very mixed. So we don't have a lot of data. First off, creatine doesn't directly increase protein synthesis, which might be a surprise for a lot of our viewers. Sort of works in, in a magical other way, which we can talk about. But from a muscle breakdown perspective, it seems to reduce something called leucine oxidation, primarily in young males. And that's an indicator of whole body breakdown. We've also shown in our lab it reduces 3-methylhistidine, which is another indicator of whole body breakdown. But nothing is directly shown in the muscle itself.

And for some reason, females don't experience this. We've looked at it in young and older females. We don't see the same effect. The only logical explanation is it could have something to do with progesterone or estrogen. We just don't know that. And from an anti-catabolic effect, decreasing some of these tissue repair mechanisms, there's not a lot of research out there. But unfortunately, we're not seeing any evidence that creatine increases protein synthesis. So unlike protein, which it does, creatine seems to help increase muscle size in other ways. Satellite cells, growth factors, things like that. But it does decrease protein breakdown, primarily though in males. And we still don't know exactly why, but we think estrogen or the other sex hormones might be involved.

Does creatine have a general anti-inflammatory effect in both males and females? It does in young and older individuals. But here's an important distinction. The more stressed the body is, it seems to come to the rescue more. So if you're a young individual, adequate sleep, proper nutrition, you're probably not going to notice any anti- inflammatory effects. It's when the body is under times of extensive exercise or trauma, hypoxia. I'm sure we'll talk about the brain and sleep deprivation. So whenever the body is more stressed or under more attack, that's when creatine seems to come to the rescue. Creatine's role in muscle health is pretty well established, but what if it could do more, like help preserve bone?

That's the surprising possibility researchers are beginning to explore, especially in the context of aging and bone disease. In this segment, Dr. Kandow explains how creatine might support bone health in 2 key ways and why it likely won't work without weight-bearing exercise. We also discuss the difference between preserving bone and building it, why postmenopausal women may benefit the most, and what dosage might matter for long-term skeletal strength. Listen to Dr. Kandow explain. Well, let's talk about bone. So one of the best things you can do for bone health is weight-bearing exercise, these compound Lifts, the things that we were talking about with improving your, your explosive power and your strength. Right, right. How is creatine adding to that? By 2 ways, a direct and indirect.

So let's go with the boring direct. It sort of increases osteoblast cells. These are the cells that sort of create or the formation of our bone cells. So in rodents, osteoblast cells have been energized in the presence of creatine. So it was logical to think In humans, maybe our osteoblast cells, the cells that are responsible for increasing bone size and strength, might have more fuel. And these cells do use creatine just like our muscles do for fuel, um, and potentially increase bone density. And if that's true, we've just cured osteoporosis, basically. Um, the other line of thinking, which is surprising, going back to this anti-catabolic, uh, phenomenon, is the best lines of evidence with bone are from an anti-catabolic perspective. It seems to resemble a bisphosphonate.

So a lot of reviewers are maybe taking a bisphosphonate, it sort of preserves your skeleton. I know my mom is taking that as well. So creatine reduces something called the osteoclast activity or bone resorption. So for some reason, it really inhibits these osteoclasts from sort of chopping down our bone and increasing blood calcium levels when not needed. And then of course, if it sort of increases osteoblast potential, maybe the recycling of bone gets stronger. It's kind of like laying a foundation of a house. The bricks are stronger. You're sort of putting the bricks together a little bit faster and then inclement weather is not chopping away the bricks or the cement. So that's how we theorize it was working.

And there's been about 15 studies now showing that it has a lot of anti-resorptive effects. So think of anti-catabolic to the bone. We have not shown in a single study an increased bone mineral density. So this is really crucial. We are not saying that creatine and weight training increases bone mineral density, but it certainly decreases bone mineral density loss, and really specifically around the hip region. which is crucially important for a lot of older adults because when they fall, if they, if they land on their hip, they could be more susceptible to fracture. So there's a lot of anti-catabolic effects. And we've just shown in a long-term clinical trial that improved bone strength. So picture a pen or pencil. You can't crack it as much there.

I think weight training is the main driver when it comes to bone. The more muscle you have from an indirect perspective, there's more muscle pulling on bone. So that's very beneficial. Look at gymnasts. They have phenomenal bone mineral density and muscle mass there. So there's a lot of potential Yeah. There, um, it's not, uh, overwhelmingly convincing, I think, because bone takes a long time to turn over. But this is interesting, the lowest dose ever been shown to be effective is 8 grams of monohydrate a day. Now, as we just talked about, 3 to 5 grams is great for muscle, but now you're getting into bone. What needs to happen is a dosing study. Could 5 grams over maybe 2 years be equivalent to 8 grams over 2 years or even higher? Uh, that is very expensive to do.

Um, and, but it's been in the back of my mind. I would just speculate that 5 grams over time will still benefit your skeleton, but you need such a large sample size to get these small effects, either from a DEXA or CT scan. And that's probably why we haven't seen it yet. But in all our clinical trials, 8 grams. But the Brazilian group have looked at 1 to 3 grams for 2 straight years and not a single improvement. So weight training is there, and I think that's the big driver for many of the muscle bone perspectives. Yeah. So you think just supplementing with creatine by itself, even if you're doing 8 grams, isn't really going to necessarily affect your bone health if you're not doing any weight-bearing exercise?

Even considering the, you know, preventing the breakdown— I mean, preventing the activation of these osteoclasts that are breaking down the bone? I would be very surprised. I think you need that mechanical loading from weight training or weight-bearing exercise, plyometrics, that cause the bone to turn over, and then maybe creatine doesn't increase the resorptive, or it increases osteoblasts a little bit more. The cool thing with osteoblasts, it releases a cytokine called osteoprotegerin, which acts as a decoy, and that's been shown in in vitro studies there. So, there is some cellular data, which is a bit surprising when it comes to the skeleton, not just imaging. But, if I was to take 8 grams, would I tell my parents to take 8 grams and not work out?

If I did, I don't think they'd expect anything on the bone. The bone is really stubborn. It's just like our brain and creatine. It's really, really stubborn. I think the main force is the driver of weight training. Yeah. What about someone who is, let's say, a postmenopausal woman who, who's experiencing some perhaps osteopenia? Yes. Do you think before trying some of these other standard of care treatments like bisphosphonates, for example, you mentioned Doing the weight-bearing training and the creatine, perhaps 8 grams or 10 grams a day, would be a good first line of defense to try before trying some of these other drugs that do have negative side effects. So, if there's— if you're in line for a bisphosphonate, there's no way that creatine or weight training will come close.

So, a drug effect will always be superior. The effects we're seeing even from a significant perspective with creatine are so small, we don't even get to a clinical perspective. But let's talk about weight training. I 100% agree. If I had to choose one for bone, it's weight training or plyometrics or anything that you feel to the body. And then consider creatine in your treatment program. Creatine would never replace a pharmaceutical intervention from a bone perspective. And the effects we're seeing are so small, or even over 2 years, at best it's preserving. Now, this begs the question, Maybe the adults we chose were too healthy. None had diagnosed osteoporosis or osteopenia or frailty. What if we took a population with severe osteoporosis? Maybe creatine could come to the rescue there.

That's another thing we're starting to hopefully get governmental funding for down the road. But a lot of young females, a lot of young males, and of course older females, even postmenopausal, their skeleton is still very beneficial and strong. They may not have incidences of osteopenia or fracture risk. Right. But until we do a study and diagnose osteoporotic males and females, we just don't know if it's the disease or maybe they were just healthy enough. Yeah. Well, prevention is obviously, I think, the key, right? If we can encourage people before they're experiencing massive breakdown of their bone or osteoporosis, osteopenia, to, you know, engage in resistance training and not, and not the single joint exercises where you're making, making biceps bigger, right?

I mean, like, Like, you need to, you need to be doing these multi-joint compound lifts, rows, you know, presses, anything that's multi-joint. And then perhaps in combination with creatine, if it's really— if it's preserving bone, that does really suggest a preventative role, right? Yeah. And that's 100% correct. Like, the movement has got to be there. And I think most people are aware of the benefits of exercise. And then if creatine or protein or whatever it is you're eating can give you a small beneficial effect, I'm all for it, and I think a lot of people would be there as well. So creatine definitely has the potential. It kind of has a lot of potential for a lot of things, but without protein, you know, those two need to be there.

We don't think creatine can rescue a hypocaloric diet, especially low in protein, but we just don't know. I argue that creatine falls in line with protein with this aging anabolic resistance. As we get older, my guess is where we have lower creatine in some of our muscles as we get older, we need more. So now there's a young versus older stereotype, just like protein. Younger individuals may respond from 20 to 25 grams all the way up to older adults. So I think creatine is definitely a part of my day, and I try to promote the evidence-based research, especially from an older adult population. If anything we can do to offset chronic disease or getting chronic disease, that's beneficial. And we're starting to really focus on young females. Exercise is so important.

Adequate Protein and then creatine is not just for males. We're seeing a plethora of benefits for young biological females, which is really important. It is. You know, when you, when you hear the word creatine, you think about like the gym bro, right? Like, I mean, it's like you're taking the creatine trying to get, you know, their muscles bigger. And the reality is, is that, you know, women, women are also very susceptible to— I mean, they're susceptible to, you know, losing muscle mass and strength, but bone is a big one. It is. Yeah. And when we look at all the data, females get an improvement in muscle performance performance, primarily strength. That's the population we've seen the best bone benefits. Now, they were postmenopausal, but reduction in bone mineral density, bone strength.

And then we're seeing from a sports perspective, agility, balance. So, for the females watching, don't shy away from creatine. It's extremely potentially beneficial in combination with exercise. And if you're worried about weight gain or whichever, do not do the loading phase. It's not needed. You can start as little as 2 to 3 grams a day, Divide that up even. So I'll tell a lot of our clients or participants, you can take 1.5 grams in the morning, wait till the evening to take 1.5 grams. That really decreases the chance of water retention. But if you're eating red meat or seafood, you're getting a little bit amount. For the vegans watching, keep in mind you're not getting any. And that's why supplementation, third-party tested, they are vegan-based, could be considered. Yeah.

I mean, it seems like it'd be very important for that population of people in particular. Yeah. We've done some really fascinating studies with vegans and vegetarians, and they respond Exceptionally well because we're doubling the amount of creatine, which is the high-energy compound in our muscle. So they— those individuals can do more repetitions, higher volume, quicker recovery. So it really has favorable effects for male and female vegans and vegetarians. And again, those emphasizing a plant-based diet— with everything going on in the world nowadays, a lot of people are looking to more plant-based diets for health reasons or whichever, and then they might need to consider a supplement.

So usually we're not in the market of of talking about supplements, but this one is the one that seems to come to mind where it might be difficult to get the amount needed in your diet, um, from financial costs, ethical treatment of animals, whatever your own habitual preference is. Uh, and if they're third-party tested, it's the safest, most effective ergogenic aid out there right now. The, the safety profile is exceptional, especially at the dosages we're talking about. Like, when we talk about protein, we're talking hundreds of grams. At most, we're talking maybe 10, 20 grams for the athletes, which is basically 2 teaspoons in, in the run of a day. So it's It's not a lot, but there is a lot of evidence-based research behind it. Yeah. I hope you enjoyed part 1 of this creatine-focused aliquot. Look for parts 2 and 3 soon.