- When you think of creatine, you probably think of gym bros, lifting weights and putting on muscle. But what if this naturally occurring compound found in everyday foods like meat and fish and commonly used as a supplement holds a far more surprising secret? A recent research paper has uncovered a fascinating connection between how much dietary creatine intake we have and something more serious, our risk of developing cancer. Join us today as we dive into this intriguing study and explore the unexpected association that's making people talk about creatine for something other than muscles. Let's get started. Welcome back to the Building Life on Gothic Podcast. Thanks so much for stopping by. I really appreciate it. We haven't met yet. My name is Jordan Renneke. I'm a dual board certified physician in sports and family medicine and the goal of this podcast is to keep you active and healthy for life through actual evidence-formed education. And today we're talking about a study that's looking at creatine and cancer risks. So let's dive into it right now. All right, so first we're gonna start with a little overview on creatine, right? So the most common association is muscle growth, right? People take this to get bigger muscles. People use it in the gym. That's what it's thought about. And that's predominantly what it has been used for, but more and more studies have been coming out saying it may be used for other things. But the most common use is for muscle growth. And in reality though, if we step back, it's not necessarily muscle growth. It is crucial for energy metabolism in the body. It's a big thing. There's a schematic on this slide here for the video version people are watching. Audio we'll explain through, but essentially explaining creatine metabolism. So creatine is naturally found in foods we eat and the body, and it's a big component of ourselves. And it's huge for metabolism in the body, energy expenditure. So creatine reacts with ATP or adenosine triphosphate. Everyone talks about ATP. ATP is important for releasing energy and stuff. It reacts with it in the liver, kidney, and pancreas to form phosphocreatine. So this phosphocreatine is then stored in the muscles. This is the big thing here. So, and when you need rapid energy, like you need a sprint or a one rep max or something explosive, when you need rapid energy, and when it's required, phosphocreatine decomposes quickly, releasing a phosphate group and regenerated ATP. This newly formed ATP then can immediately be utilized by the muscles to support muscle contraction and other demanding biological processes. So pretty much what's happening is we have ATP and creatine making phosphocreatine. And phosphocreatine is like the first fuel used up. Like when you need to do something fast, now it's a go and it will release that, right? It releases the phosphate group. We have ATP, you can use ATP for energy, but this is stored in the muscle. So creatine, the idea is like you take more so you can make more of this phosphocreatine. So you have more stores, so essentially you can work harder. And that's the big thing. Predominantly, this is used, creatine is for like short term exercise, right? This is not like endurance runners, like, "Yeah, I'm just loading up on creatine all the time 'cause it's not gonna help their performance, right?" Like they're not running through this phosphocreatine energetic pathway, usually that's more aerobic. But for people who need to do explosive things, sprints, heavy lifting, things that you get lots of rest for and do very quickly once and then rest a little bit, that's like what creatine is for specifically. And it's found predominantly in the muscles, but also it's found in the brain. And that's what people are talking about more and more. And the body does produce it naturally. And dietary sources include things like fish and meat specifically. And a lot of people are talking about using it as a supplement, specifically usually. Creatine monohydrate, about five milligrams per day, that's like the normal dose. And yeah, so that's kind of where we see the creatine here. A lot of people take it as a supplement. You do get some eating it, but a lot of people are talking about supplementing it. And in this study though, they talk more about dietary creatine. So that's just at least worth mentioning there. So next study overview. This is coming from the National Health and Nutrition Examination Survey, so NHANES, where everyone gets all their data on all the studies. A very large dataset, over 25,000 US adults were in this dataset. And this is a retrospective analysis, right? So they're just looking at data after they analyze without a specific question, right? So they kind of, what they do here in these ones, this NHANES data collects an enormous amount of data. And then these researchers are saying, "Okay, what angle can we take? Let's do creatine and cancer." That's literally what it comes down to essentially, which is a cool, interesting idea. But in no way, shape, or form was this study, like the NHANES dataset, done with the idea of, "Hey, we're gonna use this to look at creatine and cancer." No, so we're just essentially looking back saying, "Okay, let's look at it and see what happens." So essentially, kind of just throwing stuff at the wall and seeing what sticks, but that's neither here nor there. And in this NHANES data, they use data in here from dietary interviews. So essentially they had a 24 hour recall over two days. So what they're saying, how they measured the food intake was, "Hey, over the last two days, what did you eat?" Which comes with the enormous amount of problems, right? Who remembers what they ate is specifically over the last two days. You know, I think most people have a decent idea of this, but like how much you're eating of it, who knows? That's a big thing. That's dietary epidemiology. It's a big issue, but that is one thing. But despite these limitations, it is possible to use this and have it be helpful. And so they also looked at things like demographics, health status, age, sex, race, education, BMI, lifestyle, whether someone smoked, drank alcohol, activity levels, and different biomarkers as well. But those are the big things, kind of lots of demographics. And the purpose of the, sorry, excuse me, extra data, they were trying to control for different compounding factors. They use these other things like health status, age, sex, BMI, lifestyle, they're trying to control for confounding figures. And so they're trying to separate the effects of creatine from other healthy habits. That's the big thing. And what they looked at there specifically, they're trying to say, "Hey, like, can we tease out just creatine, is creatine just doing this or something else?" Spoiler, they won't be able to do that 'cause it's not designed to do that. But that's the intent of why you run these analyses to try to separate them. So kind of cool to think about. And main findings, overall, the main findings that higher dietary creatine intake was associated with a lower risk of cancer. And on the video version here, we have a slide kind of showing stuff. And you can see the picture shows a marked decrease in the fourth or biggest quartile of creatine intake. So they kind of broke them up into four quartiles, meaning low, middle low, middle high, and highest. And they found that the biggest and only statistical difference they really found was in that biggest quartile, people eating the most amount of creatine. And for each standard deviation increase in creatine intake, the risk of cancer decreased by about 5%. And that's what they saw. At first, they saw something called the J-shape association, where a J-shape would means that with, yeah, you'd have increased cancer at low and high amounts, meaning like, oh, at the start, if you have a low amount of creatine, you have cancer, then it'd go down. And high again, it kind of went back up. But that was eliminated after adjusting for various factors so they didn't see that. So overall, they did find that the more you ate, the lower the risk for cancer you had with creatine. And yeah, overall, it was described as pretty significant in the findings. I mean, statistically, that one was there, but they thought it was worthwhile. And the association of this, of increased creatine, still remain even after accounting for age, sex, BMI, which controlling for those confounding factors again is something we try to do. So overall, there was an association with cancer and creatine, but it's kind of in the opposite direction that most people, from a scare tactic perspective, you hear creatine and cancer, and you're like, oh my gosh, but actually decreased that. So that was kind of interesting. Moving on to the mechanism of, well, why would that be the case? Well, the answer is really unclear. And any guesses are purely mechanistic speculation, which I don't really care for. I think this is one thing we see all the time, all the time in pop sci media, in terms of the Instagram world and YouTube, I get it, I play that game. But a lot of people will take a study, of a mechanistic study, which saying, hey, like this little Petri dish finding that I found or something in rats, this could extrapolate to this, and this is why it is. Like that's just taking too many leaps, I'm not here for it. So overall, anything I tell you here is just literally speculation, but it's at least fun to think about. I think that's intellectually stimulating, so we're gonna talk about it. Cancer, as we know, is linked to chronic inflammation, oxidative stress, and immune dysfunction. And creatine may play a role in all those things. It may have some anti-inflammatory and antioxidant properties. It may actually play a role in immune modulation, affecting the immune system, things like T cells and macrophages. It may be actually boost the activity of other cells lines as well, like B cells, which are part of the immune system, and it could enhance activity of, once again, T cells and macrophages, which all those together, if they're not doing well, that can lead to cancer. And creatine might overall be making the immune system more effective. That's what we think about. And is it making it? We don't know. More research has to be done. That's entirely speculation. But overall, I thought it was just kind of cool to think about why it could be, and there's just some explanations they offered. I'm not a creatine expert in terms of the physiology behind it, and so I think it's kind of cool to think about we're learning a lot more. But in the study, that's what they mentioned. And this is a correlative study, right? Not a clinical trial. So we definitely can't say that creatine prevents cancer. This is only an association and a weak one at that. There definitely needs to be lots and lots of more research done on this. And looking at the quartiles, I just wanted to dive a little bit deeper in this chart that we saw before. So when we divide these participants into four groups based on daily creatine intake, right? So lowest to highest on the right picture there, we'll see what happens. The lowest cancer risk is in the highest quartile, and it's statistically significant difference between the highest and lower quartile. So that when you see the lowest to highest, there seems to be a difference. Second and third quartiles have lower rates than the lowest intake, which is the first quartile, but it's not statistically significant. So when I step back, what does that mean is, we found statistically significant difference between the lowest intake group and the highest. We saw a trend towards improvement when we compare the lowest intake group and the next highest intakes, but it wasn't statistically significant. So the only one time we saw statistical significance was between the biggest and the smallest intake. So that's kind of cool to think about, but and helpful. And it's important to remind her that, once again, this is about dietary creatine and not supplements. So we cannot extrapolate findings of supplements. So what you will see, I guarantee it, look after you listen to this podcast, go look around you. I guarantee you will see videos of people saying, creatine decreases your cancer risk. And they will say that, they will say that, because one, they're either just trying to get clicks, which, hey, gotta get clicks, I understand that, but I'd like to do it in an honest way. Or they're doing it 'cause they don't understand. They don't understand that this is, you can't do that. You can't say that dietary intake is what we saw in the study and that equates to supplement intake. May that be the case? If this is indeed true and pans out, is that the case? Well, how we get there? Well, you literally have to do these studies, first of all, hitting mechanistic plausibility and randomized controlled trial, proving that it's creatine in diet first. That's what you do. And that's how you could say it happens. Or you'd have to do a different study of supplemental creatine and a randomized controlled trial, once again, and seeing if that decreases cancer. And so that's what you'd have to do to prove it. And so if someone says, you see on social media, tag me, tag me, or tag this video to them and say, hey, you're kind of misleading there a little bit, but you will see that I guarantee you, because it sounds like an awesome headline, right? Like, oh my gosh, creatine decreases cancer. Well, the answer is maybe, we're not sure. And by no way, shape, or form, we can confidently say that. So, but let me know if you see that, 'cause it's gonna be out there. There are some other subgroup analyses that they did as well that I wanna mention on, specifically gender differences. And interestingly enough, the link was much stronger in men than women, which doesn't make a whole lot of sense to me or anyone. There's a possible theory that men generally have more muscle mass and various hormone levels related to testosterone. Maybe there's some interaction between creatine and that, and that's what happens, and you know, 'cause creatine's predominantly stored in the muscle with the phosphocreatine. I don't know. It was pretty much grabbing for straws, but it was kind of interesting. And they also looked at BMI as well. And in overweight individuals, overweight individuals saw a significant benefit from higher creatine intake. Maybe, yeah, maybe potentially this is mitigating increased cancer risk with obesity, right? We know people who have obesity tend to have high risks of cancer, so maybe this is mitigating some of that. Whereas in underweight individuals, higher creatine intake was associated with a higher risk of cancer, which is kind of surprising. So in overweight, it seemed to help more. In underweight, it did not seem to help as much. And so overall, there does seem to be a relationship between creatine body composition and cancer risk, but it's complex and nuanced. And in no way, shape, or form am I gonna say, "Hey, I understand this is what it is. I just thought it was kind of cool to see." And one other thing as well is aging. This one is age is a major risk factor for cancer. The study confirmed that. Again, on the chart here, you can see, if you're looking on the video version, you see as you get older, your risk of cancer just goes up. And we've known that, right? We know that cancer is typically a disease elderly. Tragically, it's not all the time, and we're getting earlier and earlier. And is that to do with our increased, how terribly unhealthy we are? Maybe, who knows? But regardless, we know that age is a risk factor. And yeah, they did find that individuals over 66 had a 18.3 times higher cancer risk than those 20 to 36. And so, yeah, just as you go up, huge risk. And reiterating once again that aging significantly affects cancer risk. So what they found in the studies that you shouldn't ever get older, I saw that in a breakdown. This is why I laughed at that thing. Yeah, study shows don't get older. It's a risk factor for everything. But it's worth mentioning as well that we know. We talked about body composition and gender differences and age. So those all play a risk factor as well. So what are the implications here? Well, these are exciting findings 'cause it's cool, right? Opens up a new way to think about creatine potentially. Maybe it's not just this bro supplement anymore. But that being said, there's been a lot of research coming out about creatine and cognition, which I can do a podcast about that if people are interested. So creatine's getting more mainstream, right? This is becoming part of people's stack and this is like a normal thing. And here's just another thing to talk about, which is cool. And so it might just be another way that we have benefits beyond just the muscle benefits, which is really cool. And what does this do in terms of adding to the existing evidence? Well, the study supports the growing evidence of creatine's diverse benefits, specifically brain health, cognitive function, neurogenesis, those are the things that people are studying. This doesn't touch on those, but it's kind of broadening, which is kind of cool. But I do want to emphasize, this really can't tell us anything, like at all. And people once again will take this and say, "This is why creatine is so good. "We should be on it," and all that stuff. And here I'm talking about, right? So I think it's cool and important, but it's more of like a, "Hey, gee whiz, "this is kind of neat." Not like, "Oh my gosh, this is practice changing." In no way, shape, or form when I read this or look at the study and be like, "Well, shoot, I need to start taking creatine "'cause it's gonna help me avoid cancer." Like that's never my brain. If I take creatine, it's 'cause I have other things that I want to do and I have take creatine at various times I take it. It is something I would take for performance or muscle reasons, but certainly not for this. This might be like, "Hey, maybe there's benefit." But you just can't take anything from the study 'cause it's just an observational study looking at it, but it's cool to see. And yeah, it's just really kind of fun to look at. So that's really what it is. And I do want to talk about the limitations though. Every time I talk about a study, I want to talk about limitations just a little bit, just 'cause there's always gonna be limitations. And first thing was that there was reliance on self-reported dietary data, right? So potential for recall bias and inaccurate reporting. So people are historically really poor at getting accurate records of what they eat. It's just like, we're not good at it, it's tough. And so we also might run into recall bias, which means people unintentionally misreport what they eat, either what they eat or how much they eat of a certain food. A lot of times bias where it's like, "Oh yeah, like I ate this many servings of vegetables," when in reality, they didn't eat any of that. And so trying to feel better and they feel, they know they're getting their answers recorded so it can be there. So that's one thing. Another thing is they didn't isolate for meat intake or consumption of energy total. So they didn't actually distinguish how much meat you're eating, how many calories, which as you know, can be a huge factor. There's also lack of differentiation in creatine sources. So they didn't distinguish between creatine from different foods, meat, poultry, fish. Yeah, and that's kind of interesting 'cause these other components in these foods may play a role, right? Like maybe the people who ate more fish and more omega-3s and stuff and had even decreased risk. So there could be components in the food that affect the outcome that we don't quite know. And so also are there people who are just more health conscious and they tend to eat more of a certain food or more foods with creatine in general? So people are trying to increase their protein, they're working out, all that stuff. It's just impossible to separate the food from creatine in this study. And that's why this study is nothing more than just a, "Oh, that's cool, that's interesting, we'll see." As I mentioned before, it's a cross-sectional design, meaning this is only a snapshot in time and we cannot determine any sort of cause and effect, only a little bit of correlation. And this study population as well is limited to the United States adults. So findings may not be generalizable to other populations and there's a lack of long-term data on this. And so, yeah, didn't examine the effects of creatine over years. So cool, cool study, but lots of limitations as always. And as I said, how do we make sense of this? It's a cool study, but that's just it, it's just one study. It doesn't really say much else and it kind of gets the wheels spinning for future research, that's kind of where I see this. And this is not practice changing it. I'm not taking creatine, as I mentioned before, for this reason and you shouldn't either. If you read this, yeah, if you change your practice and the things you do and the way you live your life and the things you put in your body based on one study using food frequency questionnaires and food recalls, then you need to pump breaks. That's really what it comes down to. You need to calm down and just like wait for someone to tell you what's up, 'cause yeah, we will see this all the time where people read something else and they change and they flip back and forth. Don't worry about that yet, calm down. It's kind of cool, but it's another reason to show that creatine may be something worth considering, but certainly don't hop on, yeah, on that train yet. But I'm happy to see these results the way they are and not the other way around, right? So if they did find increased intake of creatine and increased cancer risks, that's gonna be a lot harder to explain away. People are gonna be like, "Oh, stop taking your creatine," or I'm just glad I didn't say that so I can say, "Yeah, you can take creatine, it's fine. It seems like it's safe. Maybe you get some other benefits outside of the muscle and performance stuff." But yeah, I'm just glad I don't have to explain away why you shouldn't be terrified of creatine, 'cause that would be another easy one to say on social media and say, "Oh, stay away from it." But it's kind of cool and yeah, I just wanted to jump ahead of this and kind of talk about this, I've seen it making its way around social media. So I wanna take my, you know, put my opinion on it and kind of my interpretation of it as well. So, but that is gonna be it for today. Thanks so much for stopping by. If you liked it, it would mean the world to me. If you either liked the video on YouTube, subscribe to the podcast on your podcast platform or choice, or go on the YouTube channel and subscribe, that would mean a lot. And if you did enjoy it, if you shared it, that'd be the biggest compliment ever. That really means a lot and helps spread the word, which I appreciate it. But thanks for stopping by, I really appreciate it. Now get off your phone, get outside, and we'll see you next time.
