Creatine: The Underrated Powerhouse for Muscle and Brain Health

Creatine might be the most underappreciated nutritional powerhouse in our health toolkit. While many associate it exclusively with weightlifters and athletes, the science reveals a molecule with profound benefits reaching far beyond the gym.

Mark Pettus MD and John Bagnulo PhD,MPH dive into creatine's fundamental role in human physiology as part of our body's most immediate energy production system – the ATP-PCR pathway. They unpack how this simple compound supports not just muscle strength and lean body mass, but potentially shields against age-related decline in both physical and cognitive function.

The conversation dismantles persistent myths around creatine safety, clarifying why concerns about kidney damage and steroid-like effects are scientifically unfounded. Both hosts share their personal experiences and professional insights about optimal dosing (3-5 grams daily), sourcing (creatine monohydrate remains the gold standard), and why dietary sources alone (mostly red meat and small fish) often fall short of providing optimal levels – especially as we age and our natural creatine synthesis declines.

Perhaps most fascinating is the emerging research around creatine's role in brain health. Lower brain creatine levels correlate with neurodegenerative conditions like Alzheimer's, Parkinson's and ALS, suggesting that maintaining adequate creatine stores might help protect against cognitive decline through multiple mechanisms – from basic energy provision to antioxidant effects and enhanced dopamine recovery.

Whether you're an athlete seeking performance gains, someone focused on healthy aging, or simply exploring evidence-based supplements with remarkable safety profiles, this episode offers valuable insights into why creatine deserves consideration as part of your daily health regimen. Listen now to understand how this simple molecule might be working silently to protect your most metabolically active tissues – muscle and brain – throughout your lifetime.

Research studies referenced can be found at https://www,thehealthedgepodcast.com

Transcript

Introduction to Metabolic Health and Lean Mass

Speaker 1 0:03

Well welcome to the Health Edge. Translating the Science of Self-Care, I'm Mark Pettis, and with my friend and colleague John Bagnullo John, good morning buddy.

Speaker 2 0:10

Hey, good morning Mark. It's great to see you.

Speaker 1 0:13

Great to see you. As always, we have, in our last few podcasts, john looked at the really important relationship between muscle mass, lean body mass and strength. Metabolic health and how lean body mass is one of the time-proven predictors of longevity and quality of life and, as we've talked about in many, many podcasts, metabolic health as characterized by normal blood sugars, normal insulin levels, normal blood pressure levels, a lean waistline, low triglycerides and high HDL. The connection between all of those attributes of metabolic health and lean body mass and strength is powerfully strong, and so today we are going to look at creatine as a supplement and some of the evidence that has supported creatine and that really dovetails nicely with this concept of muscle mass and metabolic health.

Understanding Creatine and Energy Systems

Speaker 2 1:31

Yeah, I mean I would say creatine is probably one of the more underappreciated micronutrients. Nutrients, however you want to classify it, but it's really underappreciated. Nutrients however you want to classify it, but it's it's really underappreciated, and I think it, uh, it has benefits that most people are unaware of, mark, in terms of how far reaching they are in different areas of our physiology. I mean, certainly it plays a huge role in in strength and in a person's ability to uh, you know, to gain lean body mass, which, as you just said, is so protective. But wow, I mean, you know some of the body mass which, as you just said, is so protective. But wow, I mean you know some of the other influences that creatine has on our health are really remarkable, especially, you know, brain health, neurological health, and it's very, very difficult for people to get the amount of creatine that they probably need on a daily basis for a variety of reasons. So I think it's an awesome topic and it's one of my favorites.

Speaker 1 2:30

Yeah, and we'll come back to this connection between creatine and brain health, cognitive health, degenerative neurologic disease risk, which is a really hot area of research right now and rapidly evolving. So great that you brought that up, john, because this is a much bigger story than just than muscle mass and strength. How would you, for someone sort of new to this topic, john, how would you help them understand what creatine is, where you you know? Where do you find the body? What does its role seem to to be?

Speaker 2 3:09

yeah, well, sure, um, I mean, I think the the most basic and important place to start is to help. You know, everyone understand that we've got three. We've got three energy systems or three different ways that the body can generate ATP or can use ATP for energy. Most people are aware of things like glycolysis or the Krebs cycle, which generate ATP from the food in our diet, but then you have this very, very immediate and the most rapid source of energy in the body, which is the ATP-PCR system. So, you know, creatine and more specifically, phosphocreatine, can be bound to ATP and it provides the body with a very, very quick source of energy that is being used all the time. It's not as though we only use it when we're doing something like high intensity, like a sprint or, you know, doing some type of resistance training. No, we're, we're going to use the ATP, atp PCR system. This adenosine triphosphate and phosphocreatine molecule is going to be split and ATP is going to be generated from that, all the time, around the clock, and our brains actually use that for a much larger percentage of their energy than probably any other tissue in our body. So it's an energy. You know, creatine is really intricately and critically involved in this most immediate energy system and the more creatine that we have available to the body, then the typically the better our phosphocreatine ATP stores are going to be. So you know it starts there, mark, and and if you have, you know limitations and how much dietary creatine that you, that you get, the body can make it from. The body can make creatine from amino acids, um, but it's you know it's not a really a an incredibly efficient system and there are limitations to that in terms of how much we make, and there's some evidence that we make less as we get older, even if we do have all the amino acids necessary to do that. So it's an endogenously produced molecule. It's not as though we have an rda for it or anything like that, because you can make it endogenously in the body.

Dietary Sources and Age-Related Changes

Speaker 2 5:26

But it certainly helps to get more of this creatine already already made ready to go from our diet, and the richest sources, of course, are red meat and then after that animal protein. You'd get into things like small fish, like create. You know creatine is found in really high levels in mackerel and in sardines. Those are some of the highest richest sources of creatine after you get out of the red meat world, but it's found to a lesser extent in things like poultry and other fish. Eggs have very small amounts, dairy products small amounts. Red meat is far and away the greatest source and obviously a lot of people don't want to eat red meat every day, mark, for different reasons, and a lot of people don't eat small oily fish on a regular basis or things like, you know, shrimp and shellfish. So your richest sources of creatine are quite often limited in the diet, and so that's where people, if they're not making creatine endogenously in their body, from having adequate dietary protein, the right amino acids, then they, you know, sometimes are limited by the small amounts that do come into their diet.

Speaker 2 6:34

So it can be a rate limiting factor to a person being as strong, carrying the lean body mass that they ultimately should or need for high quality of life.

Speaker 2 6:44

And, as we'll talk, like you said a little later, you know, brain health, it plays plays a big role there as well.

Speaker 2 6:50

So it's really a it's a fascinating molecule, given the fact that we can reduce it in our body if we have all the amino acids necessary to do that. But as we get older, that time kind of drops off right, and so then we're left at a place of almost deficiency, and if we don't have enough coming in from our diet, then it's. You know, it's one of those things we can assume we're going to you're going to have some, some consequences, and one of those will be we might not be as strong as we, as we could, we might not carry as much lean body mass as we should for optimal health and, you know, at the at the front of the brain, we may not have everything clicking there on all cylinders Like it could be if we had a little more creatine. So I, you know, I think Mark and I'll end on this we're at a place now in terms of our understanding with creatine. That it's. It would be one of the more important nutrients to supplement with, especially if we want to improve the aging process.

Speaker 1 7:50

Great overview, john. And as we connect the dots, creatine as a really important energy reserve, energy source. Not surprisingly, most of it is found in muscle Ninety, ninety, five percent. The rest is predominantly in the brain, right. So we know these to be very metabolically active tissues with very high energy demand. And demand, while it may be high at a, at a, at a basal level, frequently, will require these condition-specific increases, and so it's not surprising that red meat would be such a rich source.

Safety Profile and Common Misconceptions

Speaker 1 8:43

And I'm always struck, john, just as a biologist, how we always talk about, you know, one of the challenges in nutritional science is we look at very specific ingredients, a micronutrient, a macronutrient, and there's a tendency in that reductionist worldview to miss sort of the big picture, this amazing orchestration of molecules that nature packages. So isn't it interesting that red meat we talk a lot about red meat in addition to having this amazingly full complement of amino acids which are ideal from the perspective of protein muscle synthesis, that it's also your greatest source of creatine, which obviously is an important molecule in enhancing how those amino acids are used to develop lean and maintain lean body mass. And then there's this sort of a bit more subtle issue of the mitochondria, right, we know these are mitochondria rich tissues because they are so energy demanding and, uh, you know when we in know, when we in a moment, when we start looking a little bit at cognition, the mitochondria have really become kind of a central area of research and basic science and clinical research. And when you begin to consider the fact that creatine, creatine phosphate and that metabolic pathway that you described could be a really important system, biochemical system for mitochondria in those energy-rich tissues, so much of what we know drives chronic, complex disease and degenerative neurologic diseases can be traced in some way to disruption of mitochondrial function. So I love the way these things sort of that dosing level that seems to optimally promote these health benefits Many people just are going to fall short and I couldn't agree with you more, john.

Speaker 1 11:05

There are over 500 peer-reviewed articles in creatine as supplements go and that sort of wild west of uncertainty around quality of the research, creatine really sort of rises to the top in terms of the quality of the research that supports its use, its benefits and, as we'll touch on, really a remarkable safety profile. This is a very, very safe molecule and I thought maybe we could briefly touch on what I often hear as misperceptions about creatine, one of which, john, just to start on that path. As a kidney specialist, I was frequently asked about the potential for adverse effects of creatine on the kidney, and many people might know or might not know that when we assess kidney function, we do that with a blood test that looks at that, essentially that level. You know your creatinine is the blood test and creatine is a precursor to creatinine in the kidney. So that connection often leaves people leery that taking too much creatine might overwhelm the kidney and create some toxicity, and so that how do you address someone that approaches you with that potential concern, john?

Speaker 2 12:48

Well, I mean, I have a really interesting story. I won't take too much time with it, but when I, you know, I got a before my PhD, I got a master's in public health and, um, one of the things you have to do with, you know, depending on the program, you just kind of go up in the community and you may also work on other fronts. I would go speak to high school um student athlete. You know, groups, organizations might be made up of parents at, you know, the beginning of a season so you might have an auditorium with. You know, I don't know, depending on the high school, you might have a couple hundred parents in there that want to hear a little bit about the upcoming season and what's really important for their, you know, for their student, in terms of their health. And you know there'd be a couple of different speakers there.

Speaker 2 13:30

I would do that and sometimes I'd go to universities and talk to their athletic departments about different aspects of sports nutrition. And this is going back there, like we're, in 1990, 1996, 1997, right, and creatine had been around at that point for around three or four years. It came, you know, creatine really became available in like the early nineties and I was. I had the good fortune at the university of North Carolina because I was minoring in exercise physiology that I actually was part of a study that was conducted there on creatine. As a graduate student I enrolled in the study. I saw immediate personal benefits to using creatine, so I became a believer early on, mark this is, like you know, again, mid 90s. And then when I you know again as towards the end of my MPH program, I would go out and I'd speak and I was amazed, mark. I was amazed at the number of parents, the number of athletic directors at different places that that told their student athletes they were not allowed to take creatine.

Speaker 2 14:30

Now, again you speak, I think, so wonderfully, about the safety and the overwhelming body of evidence that demonstrates the safety of creatine in comparison to so many other things that people eat and take that have very, very shady, right, shady research, to say the least. So you know what's fascinating is that it's an incredibly safe molecule and yet today, 30 years later, there are still people to your point, mark that think it has adverse effects on renal health, that it will cause, you know, undesirable skeletal muscular changes like excessive cramping, dehydration, and really I'm going to say that in most cases it's the opposite. That's true. I actually consider it for even a young student athlete to be one of the most protective supplements that they can take. I recommend it for all of the pitchers that I work with in my coaching baseball coaching because it makes the body hang on to more water and that's really beneficial, uh, for connective tissue, for skeletal muscle, especially if you have, you know, potential for repetition, you know use injuries. I think it's one of the most protected things and I I just find it again fascinating that a lot of these parents who might send their kids to school with a certain lunch made up of certain things, they don't question, but they really turn the spotlight on creatine. It's probably one of the best things their kids could be taking. So, as you know, mark, and you and I joke about this all the time things get turned upside down in terms of what people are concerned about. A little knowledge is sometimes a really dangerous thing, and that's the case with, I think, with creatine. Again, I think you covered it really well.

Speaker 2 16:15

This is a molecule that most people don't get enough of. Um it's got a really specific role to play in different physiological pathways and when it comes to muscle health. Um, you know it's, it's indispensable. You got to have it or you're going to have a higher risk of injury. You're going to have less lean body mass at any stage in life. Um, so I think it's been well studied, going back to the early nineties and to your point. Everything really checks out, um, whether you're an athlete, whether you're a 70 year old that's looking to have a higher quality of life. Um, you look, it's got benefits. It doesn't have any downsides.

Speaker 2 16:56

So and again, as with anything, I think it can be abused. If you started taking 20 grams of this stuff a day, then I think that there is the potential for it to maybe work against a person in different areas. But even that is, you know, is less clear. But I think you talk about three to five grams a day. Look, I think the research clearly supports it from not only a not only from a performance or an improvement in health basis, but definitely from a safety standpoint. So it's, you know it really checks all the boxes that we like to look at. And, yeah, I, I just think that it's. It's amazing, as I just said, how people question this but don't question a lot of the things that are truly undermining either their own health or their kids' health are shaped and so often held as an absolute truth when in fact not grounded at all in truth.

Brain Health and Neurological Benefits

Speaker 1 17:59

And creatine and sort of that historical perspective is one that definitely falls into that category, john. The three to five grams a day is clearly a well-established sweet spot, if you will 3,000 to 5,000 milligrams a day. And people often talk about or maybe even debate the different forms of creatine. But at the end of the day, creatine monohydrate is what has been looked at in most of the studies and creatine monohydrate is, you know, the gold standard form of creatine. There are other forms but they're not in any way proven to be better, more effective, more advantageous than creatine monohydrate. And I liked what you said, john, about. You know, historically often there was this tendency to want to load creatine really high doses, up to 20 milligrams a day, maybe for five to seven days, to build those levels up. I think the research is pretty clear today that there's no great advantage to loading and that, starting on a maintenance dose of three to five grams a day I take five grams a day. I think you very subtly and significantly raised the point, john, that for most of us, as we age, we do tend to have more anabolic resistance, do tend to have to be more careful to create conditions that allow that muscle hypertrophy to optimize itself, and so I lean toward that higher dosing at least for you know, my age and my health goals and it, you know it's, as we've talked about, extremely well tolerated.

Speaker 1 19:55

On occasion I may hear somebody talk about a gastrointestinal side effect and you know, sometimes I'll tell folks if they're sensitive to it. Maybe they have irritable bowel, they have some GI issue, that that five gram a day. They might try splitting that into two and a half grams twice a day instead of a one five gram dose. But rarely will a person find that sweet spot to be intolerable from a side effect standpoint. So that's, like I think, really important. And then some of the other sort of anecdotal things that might come up that I'll hear about. John is, I think and this kind of falls into the same sort of myth of the creatine kidney issue is creatine as sort of an anabolic steroid. I think you know, anytime you talk about something that might help develop and maintain lean body mass, that it must be something like a steroid which raises red flags. So how would you help mitigate those fears, john, for someone who is concerned that creatine is a steroid.

Speaker 2 21:13

Well, I mean just molecularly. It's a pretty simple molecule. You know it's not a hormone, it's not involved in any of those endocrine pathways. It's basically molecularly. It's just something that again increases an energy system, or the capacity to produce energy, from this really most basic ATP PCR system. So it starts there and because of that it enables muscles to again hang on to a little more water, which is protective. So it increases what we call cell turgor, the amount of water held inside a muscle cell, very important for muscle health and preventing soft tissue injury. So it's got that big benefit. And then it's because you have more energy available to a muscle, a muscle is going to be able to contract with a little more force and then because of that you're going to get, you know, slightly more of these little tiny microfibril tears which have to when they recover. When a muscle cell repairs from that comes back a little bigger and a little stronger.

Speaker 2 22:17

So really basic structural changes, not endocrine. There's no hormonal component to this. So it's pretty far, far removed from the steroid type effects on health, from the steroid type effects on health. And again, it's found in food in the same form that you're talking about here in terms of creatine monohydrate. It's just a really simple molecule that allows muscles to function better, more efficiently, more effectively, and then when they recover from that bout of exercise, they come back bigger and stronger, which is obviously that's your, that's your goal with strength training. So really basic stuff here. And doesn't you know? Creatine has never been shown to affect lipid levels or have any influence on testosterone and things like that. So it's just, it's just completely removed from the whole androgen testosterone anabolic steroid discussion.

Speaker 1 23:21

Yeah, so good points of clarification there, John, and I will upload a lot of the studies and reviews for people to look at, but in general they're very consistent in their outcomes of improved body composition with respect to lean body mass, measurements of strength, power, the velocity with which one can exert a force, and that research is consistent across the board. Some studies that we can begin to add, some of the early data on cognitive and neurologic benefits, would make this an ideal consideration for men and women and, as you point out, John, the research that has looked at younger adults and adolescents show it to be equally effective and very safe. So this has a really broad use case, use consideration across both sexes, across the age continuum and, again, just predominantly upside. And so I think a good place to sort of bring this home, John, is to reflect a little bit on this emerging area of cognition.

Practical Recommendations and Conclusion

Speaker 1 25:10

Some of the research that we've looked at, where one can actually measure creatine levels in the brain, show clear we call them correlations people with degenerative neurologic diagnoses, Alzheimer's, ALS, Parkinson's when they're included in research that looks at creatine levels in the brain, you will see diminished tissue levels and this sort of goes along, John, with this energy deficit, this challenge of the mitochondria optimizing energy production in people with these degenerative neurologic challenges.

Speaker 1 25:53

And so when one gets more creatine and can demonstrate increases at the level of the tissue, the end organ of increases in those levels in parts of the brain where it is measured, you do tend to see improvements in measures of cognition. And again, I think that this is very early in its in this research. But it's an exciting area because again I think it adds to this mounting evidence of degenerative neurologic diseases, not as as necessarily separate, right Genetically influenced, but metabolic disruptions, fundamentally at the level of energy and bioenergetics. And creatine becomes a very unique and and and and a pretty much a of a of a easy consideration when one is looking for some additional things to consider along the lines of prevention or management of those issues.

Speaker 2 27:05

Yeah, you know I love the description of an energy crisis for the brain. I mean, we know that that's implicated in not only, as you mentioned, als, parkinson's and general cognitive decline or dementia, but it's certainly part of Alzheimer's as well. When the brain goes into this energy crisis, then two things happen it can't function properly and it can't certainly maintain the structural hierarchy and all the pathways that are necessary for optimal function. It's that third law of the energy. Everything goes towards maximum entropy, right. So that disorder that's always something we're fighting, especially as we get older has to be maintained with adequate energy stores in the brain. The only way you're going to hold on to ATP is with having enough creatine to bind onto it so you can have those stores present.

Speaker 2 27:55

But you touched on some other things that are really important. So I think it's very multifactorial. You mentioned the mitochondria. Creatine has antioxidant properties. We know that it protects the brain and neurons against oxidative stress, so that's a part of this story as well. You talked about Parkinson's. The dopamine recovery is enhanced with higher levels of creatine, so it's got just so many different layers to it that go maybe a little further than just having a better energy state. That's certainly, I think the most fundamental thing to understand some other benefits to having higher levels of creatine stores in the brain that kind of really spill over into some of these other conditions or diseases that you know we really can appreciate other pathways in. You know, oxidative stress really is very destructive to the aging brain, as is, you know, not recovering as much dopamine as we could ideally. So it's got a lot going for it, mark, and it doesn't really have any downsides. So I, yeah, I hope our listeners, you know, really consider adopting a modest dose of creatine as part of their daily regimen.

Speaker 1 29:15

That's a great summary and conclusion and I will, on our website, thehealthedgepodcastcom, upload some of these review articles for anyone who's interested.

Speaker 1 29:29

This recording can be found on our website.

Speaker 1 29:33

It can also be found on YouTube found on our website, it can also be found on YouTube, and certainly our podcast, the Health Edge, is on all of the media channels.

Speaker 1 29:45

So great to be getting into this particular topic, john, and I was thinking, you know, we just had daylight savings time, where we're getting into the season of light, and we'll come back maybe with our next recording of a topic that's near and dear to both our hearts and that's the importance of light, um, of of nature, vitamin n and circadian rhythms, right, all the all these things. You know, when you, when you add a creatine three to three to five grams a day to a whole food diet, one that's very restrictive of high glycemic processed carbohydrates, one that maybe overcomes some of the fear of animal protein, add that to some resistance exercise, as you would say, time under the load, getting a little more time outdoors, this is a great time of year to begin to put those pieces together and in biology, the beauty of that is the amplification of one plus one plus one where, suddenly, you're looking at 10, 20. And this is a great time of year to be reinvigorating those systems that are alive and well in us but need the right conditions to be optimized.

Speaker 2 31:06

I like that, Mark. I think this is a time of year for great synergy Definitely. That sounds awesome. That might be a two or three part series on light.

Speaker 1 31:16

Yeah, I think so we could run quite a ways with that. Well, john, as always it's, it's really great to see you and to and to learn from you and to share in this, in this discussion, and we hope, we hope, people find some value in these conversations and we thank those of you for listening and tuning in. Be well, stay well and peace.

Speaker 2 31:41

Same to you, mark. Thanks so much. Love you man.