189. Creatine as Medicine: Brain Health, Bone, & Longevity | Darren Candow, PhD

Welcome to Medicine Redefined. I'm Dr. Altamasharaja, and I'm Dr. Darsh Show. Let's put the help back in the health care. Our guest today is Dr. Darren Kandau, professor and director of the aging muscle and bone health laboratory at the University of Regina, Canada. He is one of the world's leading researchers on creatine supplementation and has published more than 150 peer-reviewed papers, more than anyone globally in this space. He has secured over $2 million in research funding, and has spent his career studying how nutrition and resistance training can meaningfully improve muscle, bone, and brain health across a lifespan. His work has shaped much of what we know about creatine for aging, performance, and functional health. In today's conversation, we are going to go deep than the usual creatine talk. Dr. Kandau breaks down what the research actually shows about his impact on muscle, bone, and brain health, especially as we age, and how creatine fits into real-world training, clinical care, and long-term health. We also explore emerging areas of research he's excited about, and discuss why creatine may be far more relevant to everyday medicine than most people realize. If you've ever wondered what creatine can do beyond the gym, then this episode will give you an entirely new perspective. Enjoy. Before we dive into today's conversation, I have an exciting update. My new practice, Refining Health and Performance, is officially launching Sue. It's a practice built around health, longevity, and performance. The Medicine 3.0 approach we talk about every week here on this podcast. And here's the best part, it's a telemedicine clinic, so you can work with me from the comfort of your whole. Our founding member, Roma is now live, so if you'd like to learn more or join the wait list, visit refininghealthrx.com. All right, let's go to the episode. Dr. Darren Kandau, welcome to the show. Thank you so much for having me. I'm so excited as we were just talking about to get right into it. And my hope is that what I'll just say is, I think people, listeners of this show, recognize that Bo Darshan, I've been talking about creatine for a long time. And I think for those of us in the know, particularly with the exercise, science, ex-fizz background, we've probably crowned creatine as the undisputed champion when it comes to supplements, from a muscle physiology, performance, strength, power, standpoint, right, with respect to safety, and efficacy, not of all supplements, maybe caffeine if we're counting that as one, two. However, my hope is that by the end of this conversation, people will start thinking about creatine as getting it out of the gym bag and into the medicine cabinet. Right. So with that, I'd like to kind of start with getting a little bit about your background in terms of how does someone devote their pretty much their entire career to one molecule? How do you even get into that? By accident. So this is a unique story. And I think a lot of our researchers are in the same boat. So I did my master's degree looking at glutamine. And at the time, glutamine was touted, and this was in 1999, 2000 when I started. At the time, glutamine was the newest thing on the block, so to speak. A lot of endurance athletes were using it. You know, for any cannibal like a sex set, we're coming out at animal models and sepsis and cancer. And, you know, it's an unessential amino acid. But if we give a flooding dose, could it actually have some beneficial effects as the most abundant amino acid than we have? And, you know, you do all the work leading into your masses as you guys know, and then you write your thesis distance. And then you recruit subjects and you give a really high dose. And at the time, I think it was about 45 grams a day, very expensive, because we wanted to see the effect. And you do Dexifer body composition and strength, the power in young individuals and comparable sea. But it had no effect. It was essentially worthless. It had no greater effect on lean body mass, muscle performance, or a measure of protein breakdown. And at the same time, by doing that, my colleague, Dr. Niren Burke, who was in industry right now, was looking at creatine monohydrate. And to keep in mind, 1992 was when Roger Harris published the big paper on creatine and air cult with him in 1996. So just a few years later, my colleague and mentor, Dr. Phil Chilaback, were getting interested in creatine monohydrate. And we started to know, or see that individuals independent of what they were taking, were getting bigger, stronger, faster. And when you find the results of unblind dates, let those on creatines substantially improve lean mass, measures of muscle cross sectional area, and performance more than placebo. So I started to pivot and sort of help out in those studies. So I was quite fascinated that this naturally occurring compound that's been discovered since 1832. It was actually discovered before ATP sacrifice is a self to help maintain the energy currency. And it's sort of exploded ever since. So the last two decades of this primarily focused on creatine supplementation, not just for young athletes. The evolution now for aging population. So my dissertation was on the aging population. And it's quite interesting how it's evolved from just skeletal muscle. Now we have interest in bone cardiovascular system and of course the brain. So I like your knowledge at the beginning, just getting away from the gym bag. It's something that's sort of taken the world, if you will, by storm. I think we need to tone down some of the expectations or results. I think they're getting a little bit blown out of proportion, especially around the brain. There's a lot of nuances when it comes to females. There's no such thing as female creatine. I'm not convinced females respond better or worse off than males when you look closely at the cellular data. So we can talk about all these nuances out there. And hopefully I can provide a evidence based research approach to it. Let's start right there because in prep for this, you know, as I had looked at some of your other work, I actually took 20 grams right before I started this right here, right? Because I wanted to be fired up on all cylinders. So what is it that that we need to maybe turn the dial down? And maybe people have gotten a little bit too excited to hyperbolic. And what's this female creatine that you're talking about? Let's start with this. I think one of the biggest concerns right now. I mean, we can talk about mis-misconception. But the studies have seemed to be evolving around the brain or suggesting that a super high dose or much higher than what most people are used to, except for those that have tried the loading phase. So a creating loading phase is 20 grams a day for about five to seven days. That's way too long to saturate your muscle, but it's often used in research studies. And after that, you can reduce it as little as two grams a day to maintain skeletal muscle source. Keep in mind, there's about 80% already full capacity of your muscle. So supplementation only has about 20% to work with. The brain is unique. It has a blood-brain barrier. It also makes its own creatinates. So when days that you're not stressed, if you're getting adequate sleep, proper hydration, you know, you don't have any big metabolic stressors. I hate to burst everybody's bubble, but taking a supplement is not going to have any noticeable effect. Your brain's already making enough cells. A lot of people think, oh, when they hear me or others, we talk about what we consider acute studies of metabolic stressors. So to piggyback, if you are in an unstressed population for extended periods of time laying on the beach in Mexico for a vacation comes to mind, you're not going to get any cognitive benefits from creating. However, during acute metabolic stressors or disease, that's the best lines of evidence where I hire those is likely needed to get through the blood-brain barrier and then over compensate for what you're indulgously making. So for example, your brain is already making about a few grams of creatin. Is that enough when you're sleep deprived? If you suffer a concussion, stroke, Alzheimer's disease, likely not because a common denominator in the pathophysiology of those both diseases or head trauma. Is a reduction in brain creatin. So maybe then the brain says I need help from circulation. It will allow more creatinine or accumulate more. The best lines of evidence for creatin and cognition seem to be a higher dosage. 20 grams are more seem to be ideal or you could take four to five grams a day, but it needs to be on for several months to accumulate both studies come from clinical depression and long COVID. But for the healthy individual, 20 grams a day at least seven days if not longer to compensate in the brain. So I use the analogy of me if I fly to Europe, I'm very susceptible to jet lag and sleep deprivation. That's where a high ghost might come to the rescue. Your viewers will say, well, how do I know if I'm going to suffer a metabolic stressor the next day you go? So I kind of look at it as a preventative strategy. We can talk with the world and mouse model for concussion. But I think you're taking slightly higher amounts than what's recommended. Kind acts as like a safety barrier for when you do have to go through those stressors. Your dog got up in the middle of the night jet lag, sleep deprivation, got to admit if you suffer trauma. So I think during times of metabolic stressors, that's when brain creatin may benefit from supplementation. But every other time it's likely not there. Do you mind breaking down exactly what type of physiologic effect a metabolic stressor has? It's our listeners and I know that creatine helps with energy production right in the gym before doing a big bench press. How is it working physiologically in the brain? What exactly mechanistically is happening? Holy so let's start with skeletal muscle. You go to the gym, you'll flate weights the next 36 hours. You typically can feel some type of strain or muscle soreness. So that's usually accepted. We typically don't feel that exact same amount in the brain, but it's very similar. So creatine supplementation increases also creatine which enables more ATP to be used or recycled. Not only in skeletal muscle, but very active in the brain. A lot of people know that the brain is highly metabolically active. It's more active when you're stressed. So that is a common denominator, just like still the muscle and increases brain bioenergetics, but elegant work out of the rodent model has now shall chew classic mechanisms why we think creating acts as a fire extinguisher to decrease the flames of the brain when it's stressed. Think of creating acting as a fire extinguisher putting out the smoke. It decreases reactive oxidative species as three of us know and everybody totally watching highly involved in an aging pathologies of the biological process of aging. It also acts as an anti-inflammatory. So it not only improves mitochondrial health or function, it seems to have some anti-inflammatory effects there. So the net result is yes, it can help maintain brain bioenergetics, but it sort of rescues or decreases the inflammatory response allowing the tissue to recover more. So if you have a slightly elevated amount in reserve in the brain, when you go through those stressors, maybe you will be able to recover more. So that's been what. We show in the mouse and rodent model where they consume creatine for three, five and 40 days before they went through head trauma and concussion and they had 50% reduction in cortical damage. Can a professional athlete in the NFL NHL take creatine before head trauma? That begs the question with that speed up recovery or decrease the symptoms. That's the area that I'm really fascinated with. Can creatine be sort of like a prophylactic for UFC boxing, Sydney Crosby on the penguins when they suffer head trauma, can they speed up? What about children, you know, when they're falling off their bike or an older individual falling at home and they hit their head, diagnosis of concussion is very difficult to do. Could this metabolite taken in slightly higher amounts than what we're naturally producing have any beneficial effects. We certainly hope so more research needs to be done, but I'm not seeing any detrimental effects. There's never been a study to suggest that a higher amount has any brain adverse effects. They still need to be looked at, but I would be, you know, we're only talking about 10, 20 grams. If we were talking about protein, we'd be talking about hundreds of grams. So again, it's a small amount. But I think in certain populations, you should at least consider it. I personally just take 10 or slightly more. So that's a bit different. 3 to 5 is great for muscle. 8 to 10, 8 to 12 is good for ball. I think the sweet spot is 10 for the whole body because I do believe 10 can get into the brain and potentially if you're taking on a daily basis, accumulate to cause those benefits. If you're a university student listening and you're like, oh my god, finally exams are coming up. I have three finals on Friday. I'm not going to sleep all night and you're up for over 24 hours. Classic study last show to Germany said that 30 grams taken before 21 hours of sleep deprivation. Alibated brain creatine was the first study ever to get into the brain in one dose, but offset the detrimental effects of memory. So I think these are unique populations where you know if it's coming, you can slightly prepare yourself. 30 grams a day be taken consistently. I don't think so. I think you would run into some GI issues or some other complications from consistency. But if I'm flying to Germany next week and I know I got to drive to the airport, wait at the airport, fly overnight, which I can't sleep. Then you get off in Paris and maybe you're going to Italy, you're up for 24, 36 hours. That brain fog is detrimental. And that's where I think creativity can come to the rescue there. So there's lots of examples. If you're healthy, not you're going to experience anything. If you're stressed, that's where I think it can out. In this study that your reference right there with sleep deprivation, that was an acute sleep right one night or night of sleep deprivation. And now they've also looked at it for 36 hours, 20 grams a day a lot more. It didn't have the same beneficial effects as this one. And again, these two studies are the one jury that did 21 hours. They're using MRI and MRS. So super expense, elegant, the technology to sort of measure differences in brain creating. The big downfall with brain creaking research right now is not a lot of labs have that. So they're subjectively measuring memory and cognition. But you really need to measure brain creating and then how does that associate with changes? Yeah. Yeah, when I first read that a couple of years ago, I guess when it first came out, I was super excited. And you know, my initial thought was, okay, well, what about residents medical residents who are going through stressful time where you're pretty much lead deprived for three to five or seven years if you're a surgical residency. And I've talked to Darsha about this offline. It's like, or new parents, right, especially if your kid is not a great sleeper. It's like on call and never coming off recall. And then, you know, at that point, I would wonder at 25 grams or 30 grams, can you take that for years on end? We just don't have that data. And it also gives me a little bit of pause at that point. We've had we have studies in Parkinson's are up to five years on high goals. But the good news to your analogy is two studies with clinical depression. You know, the Utah, the world's leader in psychiatry research with creatine supplementation, these individuals want to run SSRIs or did CPT therapy. And only five grams was significant for eight weeks. So there's a key lower goals, what you need to take it longer. But I think five grams is very feasible. Take that on a daily basis. I did elevate brain creating source and it also approved or decreased symptoms of depression and anxiety. For those with long COVID surge, I showed that four grams a day for three and six months was enough to accumulate into the brain. The common denominator when you talk to the authors is that maybe in those cases, the brain is begging for help, you know, long COVID chronic fatigue syndrome depression. And of course, the individuals in the studies on depression were on their medication. So creatine has never been shown by itself to have any antiprecipus effects by itself. I'm sure those studies are coming, but for those listening and you fall into the metabolic stressor category, if you say, you know what, I just want to go with three to five grams an egg. I think you'll eventually get there. They may not come to the rescue as fast as you want. But if you know you got a big thing coming up, there is evidence to suggest at least you could consider. Yeah, what part of the brain is it made in? Well, it's great. It is made in various functions. The one we think is the prefrontal cortex seems to be the area where fossil creatine seems to accumulate, which is great for memory. The sororium and thalamus in Paul Deschentent, and probably the most overlooked study of all the ones published in 1999. It was the first to show in Germany that a single dose of creatine 20 grams elevated not only total brain creatine, but in different regions of the brain, but you need a four weeks at 20 grams and a healthy population to accumulate. So that goes back to my idea healthy population. It'll eventually accumulate. But if you're stressed, it seems to suck it in a little bit more. Yeah, the reason I question is it's been bugging me a little bit is because when I think about, you know, not dramatic brain injury and I'll put anybody who might had a brain tumor in resection. I guess if you've had surgery, I would consider that still trauma. But if somebody's had a criniectomy or a criniotomy of some sort and then a certain part of their brain has been removed or they've had a large enough infarct where the neurons are dead there and you know are certain parts of the brain that are responsible for making it. Are those individuals something that you should just can, you know, just consider long term. Yeah, we have any thoughts to that or. Well, it's interesting. The oligodendrocytes, glial cells and neurons and even astrocytes will express creatine, but the astrocytonic feet don't. So that's why it's so blunt that coming in, but you raise a good point. The only times we see our individuals born with creatine synthesis deficiencies that were agat or the other enzyme involved in synthesis. It's not causing a synthesis over time and that's where supplementation really seems to come to play. So that's an interesting thought. If someone goes to a brain tumor surgery, whichever, and some of the really healthy cells are removed, maybe creatine can all separately speed up the recovery. That's a phenomenal question and an area that certainly has not been looked at. The one thing that actually has them talking about this is I guess if you've had a history of a brain tumor, is that an area where you would want to and this is how we're just discussing and not medical advice anybody listening please don't take it as such. But is that area would you would you want to supply something that could potentially give those cells, you know, if you have a tumor that's been resected. And again, this is pure speculation, but from the anti cancer possibilities of creating which are emerging, the theory is there. Yeah, maybe a higher dose could not because sort of act as a non-fermological from chemotherapy to other types of radiation could that have any extra any inflammatory effects to the cell. When we look at the anti cancer properties, we're not seeing any growth from normal dosages in humans. Mark Ternopolsky is written an elegant section in one of our recent papers on the potential anti cancer properties for creating. We're starting to look at that in South Carolina with breast cancer, prostate cancer, but from a malignancy growth, we're not seeing any evidence from a recommended healthy dose, human populations. Got it. So you mentioned obviously a lot of overhyped when it comes to brain injury. What is something that would change your mind on that? What are you looking for with the outcome research? I know you mentioned that there's a paper that you're going to be submitting soon. Tell us a little bit more. Well, first off is when the lab actually measures brain creatine with MRIs, they need to determine the medical detectable change against our normal synthesis. They also need to determine is creatine supplementation decreasing our natural production or augmenting it. And the third thing is how does creatine supplementation get into the brain quicker compared to our natural recovery? So for example, it is so difficult to design this study except for the study that came out last year because what happens is you want to randomize two populations that get head trauma to a placebo or creatine. And then measure the symptoms of cacushion after problem is we used to think it would take a long time for creating to get into the blood and accumulate to the brain until the study came out last year in Germany of 30 grams. That was a high enough dose to get in. So can someone go through head trauma as a prophylactic or that a supplement take a super high dose? They can they need to be medically monitored, but I think the big change is does create an increased brain creating stores and what's the correlation between improved symptoms of cacushion? Gotcha. And then in regards to sleep deprivation, do we know when that dose has to be taken that 20 grams is it right at bed or should be split up for saturation? The studies that looked at it was in a short proximity before. So again, and it was, you know, we don't know when we're going to hit her hand or go through sleep deprivation. Can you take it late at night? You can. However, antidotely, I've heard from numerous people. I mean, I would venture against 50 different people who see when they take creating in the e's name, they have insomnia, they're waking up all night. And so you speculate is it because they're drinking a lot of water and they're going to the bathroom, but I will say from a biochemical perspective. Creatine is the biggest methyl scavenger in the body. So if you take a high dose of creatine on an empty stomach or late at night, it's possible that the high dose is bluntening the methyl scavenging, allowing more methyl groups to be there for what we call neurotransmitters and epinephrine. So sometimes people take a high dose of creatine on an empty stomach, for example, and they feel a little jittery. That could be from a number of reasons, but if you look at it from a sleep, it's interesting the theory. I'm not ruling it out totally that if you look at the methyl group scavenger, maybe some of that is influencing some people that they have intermittent sleep. On the contrary, we published a paper two years ago in menstruating young females who resist the strain. When they consume creatine on the days they worked out, they actually slept an hour longer. So right now, we just don't know the effects on sleep. We're starting to have evidence on sleep deprivation. So 10 milligrams at baseline, at least that's kind of what you do. 20 milligrams in times of acute stressors. Sorry, that's weird. 10 grams. Sorry, grams. I apologize. Yeah, 10 grams. Now we know the muscle is really greedy, right? You've talked about that. Now, does the split of the dosing matter? Does it have to be 10 or 20 as a bolus for their brain to get it? If that's the tissue that you're targeting, or can you get five and four? Is there any art to that? That is the magic question. And we're still surprised that it hasn't been done. So I'll sort of give you what we think. The dose that a Germany gave a bolus dose all at once, 30 grand shots. The problem with that is some of that will be residing or causing issues in the GI tract if you did that over time. A study of Utah looked at two, four, and 10 grams. It had some small beneficial effects, but they were statistically significant. So the question is, can you take smaller and more frequent dose of dose compared to a large bolus dose? Do they have any different effects in the brain? We don't technically know yet. I will say a study we did last year in healthy university students in Northern Iowa, who took 10 grams a day or 20 grams a day for several weeks. There was no difference on measures of cognition. So right now all the evidence is unknown. We still need to do dosing strategies to come up to the optimal dose, not only for the brain, but the rest of the body. Now it's impossible to do that. So that's why I'm suggesting 10 grams seems to be an average. Again, it's never been shown, but 10 grams seems to be a dose that definitely will check off the box or skull and muscle. If there is any benefits to the bone, it's likely around that 10 gram dose. And then 10 grams sure, accumulating the brain when you look at 4 gram all the way up to the high dose. So it's never been shown, great question. And hopefully some research comes up with that all the time. Love it. So you mentioned bone health. Let's let's get into that. So from my understanding and maybe this is new now is bone health, bone density. Once you hit the age of 30, 35 is actually very difficult to kind of put on. Right. So they talk a lot about getting young athletes into work away lifting to really start building that density. Creatine, of course, now has an effect on bone health or learning. Tell us a little bit more about how that works. Yeah. So it's interesting when you look at the bone remodeling process, you know, osteoblast, osteoplast. The theory was that maybe creatine would serve as fuel for the osteoblast cells. And there were some in vitro studies to show that those osteoblast cells sort of use creatine for fuel. They become more energized. So the hope was, wow, maybe they could lay down more full-space solstice and calcium matrix. And then on the other hand, creatine seems to have a better effect from an anti-resorctus, that's likely to bispostinate. So a few studies have shown that markers of collagen breakdown in the urine were reduced when you take creatine with exercise. So you combine an improvement, hopefully an osteoblast activity and an increase or decrease in osteoplast activity. Maybe an individual prone to bone related diseases would benefit from supplementation. Unfortunately, there's only a few clinical studies combining resistance training and walking for one year or two years that have shown any beneficial effects on bone, primarily in postmenopausal females. There was a very small reduction in bone mineral density loss in the hip. Both males and females over the age of 50 didn't improve bone area below the knee. And then some measures of bone strength were maintained or improved. But keep in mind, that was only after one and or two years of exercise at a high dose of 8 to 12 grams a day. The downfall here is the vast majority of other studies do not show any bone benefits, including meta-analysis reviews. So at the end of the day, we conclude that if creatine does have any bone benefits, they are small, but they're not to be ignored. I think in the populations such as postmenopausal females, at best we might conclude there's some evidence to suggest it might have an anti-resourced effect, and that could be important for someone who's prone to osteophenia falls or fractures later on in life. It certainly does not increase bone density. At best we think there's a preservation effect there. Creatine by itself will have no effect. Great studies out of Brazil showed one in three grams a day for two years and a nullified exercise needs to be there to be to stimulus. And at the end of the day, would I take creatine for substantial bone health? No. But I think at the end of it, it's an added bonus that you do get any benefits. I've heard you talk elsewhere about bone geometry, and that's a term that I wasn't familiar with. Can you talk a little bit about that and in relation to this conversation, but also why is that important for us to be aware of? We call bulgeometry or architecture. Now when you look at 3D imaging like CT stands, we're starting to get intrepectular and cortical bones. The delve all with bone related studies with creatine we measure dexas. So again, we're looking at aerial composition of the bones. But with CT and high resolution, we can get inside. And it's the first time we introduce bulgeometry or strength. So if you picture your pan, you don't want it to crack. So the bone is actually stronger. And it's really important for the WHO's perspective that an improvement of bone strength now is being really important for offsetting the rates of falls, fractures and or frailty. So improving or maintaining strength, i.e. geometry is an important factor. Okay, very cool. So with respect to the other things like so we've talked a lot about, you know, I guess the most exciting thing in terms of the evidence if I had to summarize it for folks with bone health seems like it's very preliminary. If there is maybe mild with with cognitive brain health that's a little bit stronger. And if we could actually specifics to come back to the brain health, I know we kind of put a bone on it, but when they're getting these outcome measurements, we're talking. Is it recall memory recall is what is what is the term cognition? What are the true metrics that actually that are improved with creating supplementation for brain? It's a very wide variety. I'm talking like stroke tests. It's something to test you can do online with a computer. They're looking at puzzles, memory cognition, word recall. So when you look at all the studies, there's a wide gamut. They sort of combine this into an overarching area called cognitive or memory benefits. Reaction time falls in that category against. It's kind of like the wall wall west is very open. There's no specific one. One of the most unique studies is when they did stroke tests. And if you're not familiar with it, you can Google it and try it. And I only last four words where you read the different colors of the words, which actually are in air. And they asked these individuals to do it for 90 minutes. I didn't even imagine the mental fatigue that these poor people had. And creating seem to improve memory cognition after they did such a drastic mentally fatigue. So it's a wall wall west when it comes to these types of measures. But at the crux is what we want is an improvement in brain creatine levels. The best studies was skull a muscle measure muscle biopsies are use mrs to measure the amount of creating getting into itself. And then of course that's correlated with the form. And so those are the really elegant desires you want to focus on. I love it. So shifting gears a little bit. You know, the other thing that's actually really having its moment, right? So I think creatine like you talked about menopause appropriately so. And then of course the whole field of longevity. And in darshan eye for the actress for those who listening as we were talking about. And I would say we're probably the originally longevity experts because we look at people with their quality of life and function, especially as they age and how healthy they can be. We recognize that obesity is certainly a big problem. But so is sarcopenia and being sedentary in muscle law. So how or what has your research been and what have you looked at in terms of when you look at the literature in its effects and. Reducing muscle laws and just I suppose more graceful aging. Yeah. It's the biggest focal area of my research. So we're really focused on sarcopenia. And then of course the contributing diseases after so many organizations classify sarcopenia based on three things reduction in muscle strength primarily lean mass or muscle mass loss and then functional ability. So let's start with strength. I think one of the most robust lines of evidence of someone asked me what's one of the main reasons you would consider creating in addition to your exercise program. I say it's an improvement in strength primarily the upper body. So the best lines of evidence suggests yes you get them proven in muscle performance. There's better evidence in the upper body versus lower and we could talk about that from an aging also creating perspective. What hasn't been shown and this might be ironic to the viewers is when we say muscle what we really are meaning from studies is lean mass. The problem of measuring lean mass is 50% is usually skeletal muscle 50% is water connective tissue organs things like that. So at the end of the day, creating in combination with weight training is only been shown to increase lean mass by the one and a half kilograms. So at best we're putting on maybe 700 800 grams of muscle now to a young individual they're like what that's not very much. Keep in mind at the age of 40 you start to lose skeletal muscle and then not only can creatine resistant training maybe hold that. I think it will or at all say I'm buying that if you can give me 500 grams more muscle that can improve functionality in the performance of activities of daily living. And those two improvements are correlated with meta analysis showing that creatine and exercise improve sip of stand at six minute walk. So I think overall creatine sort of got its press in the older populations if you will by improving all three facets there. It also has some small effects on limb muscle thickness by measuring ultrasound or PQCT in the upper and lower lambs there. So overall I think of an older adult 15 above was thinking of taking creatine. Those are some small beneficial effects they should at least experience in addition to exercise alone. I think the key to always exercise as a driving force. There's only been a handful of studies of creating without exercise that many beneficial effects in clinical or older populations. Those are primarily coming from disuse atrophy and mobilization. But what about bad rest what about older populations in the hospital post surgery these are all areas of research I definitely need to be looked at. I suppose you know I'm thinking about power right powers the other reason in terms of people start aging and powers one of the main reasons that you know in terms of not being able to catch yourself from a fall or or miss a step when you're going. I suppose if it's strength times velocity in force production with that respect it would help but has creatine been shown to or mitigate the reduction in power over time as well. Not specifically from a functional task but when it comes to it isolated a type of equipment like an isokinetic dinaminer yes it has so Jeff Stokes on a few studies in the inception of creatine research looking at that as well. Our lab fails to find a decrease or an improvement in power we typically use vertical jump or a medicine ball throw and measure the distance there so these are subjective measure so I think it comes down to the measure or how elegant it is that you're assessing. But there is some evidence to suggest that only maintains power but it can't approve it's we don't see that in our lab but it might be based on the type of assessments we're going. So given we're talking about the aging population how does anabolic resistance coming to play here. So it's a it's a very interesting fact and it's debatable but we do know that as we get older we have a blood to response to two things resistance training and dietary protein so that's where this aging anabolic resistance comes to play. There's researchers out of Texas who would argue that if you maintain exercise your entire life you do not get aging anabolic resistance so it's not inevitable so anybody listening if you're young please exercise and eat high quality protein as often as you can. But the theory here and then we bring in creating is there is some evidence especially in the lower limbs that the larger muscles of the quadriceps have reduced muscle creatine kinetics or stores and those are the muscles you typically use you know during leg press sprinting squats. The lower limb muscles of the gastrox seem to be preserved compared to the young individuals those are used walking in minimal activities at daily living so. Is anabolic resistance contributing to creatine or vice versa we don't know why I think it likely means that older adults might require a small bit more compared to a younger individual. And that's why some of our best lines of evidence of use a higher dose of creating and showing more favorable effects as we get older it makes sense you know as muscle is deteriorating especially type two muscle fibers that's where creating a store maybe older adults need more to compensate for those losses. Do you think with anything like the six minute test a lot of that is also just the improvement from the cognitive standpoint. I'm just thinking out loud here especially when you're talking about the upper body having more of pronounced effect compared to lower body. It can the other thing that comes to mind us a good point is a cardiovascular improvements were starting to see now with creating supplementation but. You're right I always envision you know the cognitive effects near the end of a stressful spin class whichever could have come into play we don't know yet but I'm envisioning you know at the world cup in five minutes to go for the world cup championship. Bulls those individuals are so fatigued could create Tina of help I don't know if you watch the rider cup this year in New York but macaroid looks so exhausted on Sunday and he's kind of probably say he takes 20 grams a day could that situation where he was so mentally fatigued cause an individual to take him maybe 20 or 30 grams to cause him to play batter against chef flora on Sunday to win we don't know but you could tell he just look so tired and this is a professional goal for making hundreds of millions of dollars a year. So it goes to show all the money in the world can't overcompensate some of the detrimental effects of the tea. He's listening maybe he's going to take more next time for the rider cup I don't know but I envision certainly big events I think of the Boston marathon or something that's mostly so daunting cognitive late could creating at least be one small tool in the toolbox the look at those effects and I'm very excited and curious to see where this is going to go on the future. I'm thinking about what you mentioned earlier in terms of those who are avid exercises throughout the entirety of their life tend to have less of those issues for metabolic resistance but I'm thinking about you know some people might be avid exercises but maybe they're just runners and they're not as much into resistance training as opposed to me who I he doing long distance steady state cardiovascular exercise but I love just train training. And we know that you know with respect to the former you're going to have more type one muscle fiber so for the that type of person as they are aging should they be taking even more given that maybe type two is where more of the saturation is going to be happening or is this me getting a little too much into the weeds here no it's 100% valid that's where the best evidence is pointing so let's look at the evidence a long duration cardiovascular exercise which is extremely catapult for those listening resistance training is not actually not that catapult to the self because there are the money is sold. But if you go and learn four hours straight the detrimentally catapult to the body so you're going to be in a negative protein balance and a few studies have shown for an iron man or ultra a marathon taking creatine five days before substantially reducing planetary cytokines so creatine have this anti inflammatory effect potentially allowing the body to recover quickly and then when you look at the aging population they're already having elevated amounts of oxidative species inflammation or low grade inflammation causing sarcopenius. Maybe taking smaller amount will allow their body to at least recover quicker from that type of exercise so you have her health and of course other aspects of beneficial effects weight trades so I think there is enough logic to suggest that creatine can be elevated insert populations and when we look at the safety profile it's exceptional so at the end of the day I think having a little bit more is advantageous. So we've touched on brain bone muscle yeah right and let's let's talk heart yeah how does it play with the cardiovascular system that's the heart makes its own as well is my understanding correct. It's exactly the same now the heart is a little bit different because unlike skeletal muscle the cardiovascular system is not so it's going to be taken it up through circulation so the lip basically the liver and the brain are the only two and dodges is working making it the rest would you need. There's not been a lot of research on the cardiovascular system because you know creatine was not the part of the anaerobic a lack of system why would someone utilize in the cardiovascular system use it when they can rely on glycogen and and add a post tissue and protein but. But recent research is suggesting from a cardiac rehab perspective where heightened elevations of inflammation that creatine can improve into field function basil dilation and maybe have some hard health benefits so that is an interesting area I think it's emerging for those that are involved in cardiac rehab to look at the pathophysiology or help creatine can be added to a rehabilitation program for some individual so it's not a lot of research out there but the evidence that I've seen is very positive. So I guess it necessarily wouldn't be improving contractility or anything in that sense with muscle like power or like because it's not necessarily strengthen that but you're saying it's more visa dilation so you're just getting better blood flow almost like. Nitric oxide will work as supplementation yeah and that's where our journey one of the main three mean on the right of it comes with now I will say that some of the men analysis suggests that creatine supplementation in young populations it has no effect or actually decreases absolute VO2 max so I don't think you're going to be taking creatine to improve your maximal ability to use oxygen. We did a study during hit training and creatine failed to find a beneficial effect there as well so I'd like to see more research in this area looking at the mechanisms of different types of cardiovascular size but the best lines of evidence come from long duration but in theory you would think spin class and hit class would be right up creatine's alley using the anaerobic a lack the system multiple sprints but right now it doesn't seem to have any effect of anything at sales at both systems the more research would happen to be done in the field. It's interesting. Awesome. Dare can we get into dietary preferences so myself I'm a vegetarian I've been taking creatine for a long time now one of the most common questions that get asked is how do you have muscle? I don't know maybe it's genetic it's for your teen who knows what it is. Like what do we know based off how much creatine people are consuming based off a omnivore diet and if they get meat versus obviously those that are not eating meat. Well first off vegans probably respond the best in the world the second best in the world to creating supplementation those born with an inborn synthesis to fish you first those on a carnivore diet would likely experience the least benefits. So from a vegan perspective just think of your muscles half full of creatine and the only reason I say that is the only area putting creatine in there because you're not eating it is the liver. So you're producing maybe one to two grams a day from three amino acids originate glycine in the diet. Now those eating a carnivore diet where they're eating a lot of creatine through red meat or seafood they're going to be taking a lot more don't think that suppresses the liver from making it. We don't know if it suppresses the brain from making it but at the end of the day if it does would come back to baseline once you stop either through diet or supplementation. So newer studies have shown vegans respond exceptionally well to supplementation you're kind of having more room in the in the muscle to get a benefit we don't know the effects of creating for with vegans on bowl. And there's a few studies showing that vegans respond very well the creatine supplementation Carolyn raised on that. But the best study and this is kind of interesting was done at Brazil a few years ago that vegans and omnivores have the exact same creatine levels in the brain. So that validates that the brain is making its all creating it doesn't need to rely on what's through circulation from muscle totally different. I think vegans would respond exceptionally well the people who likely wouldn't is rather making a lot in dodgesly through genetic factors they have either preference from the diet of taking in a lot of red meat or seafood. The issue with always you would have to eat almost a kilogram of seafood or red meat to get about three to five grams. So financially ethical treatment of animals whatever your preference it can be very difficult to do we've been talking about five 10 20 grams. That's why I think supplementation so viable and attractive for some people but that's an important distinction. Creatine technically is not essential if you're naturally making it is not essentially an essential in the last. So the nice thing here is that do not need supplementation but if you do take a little bit more that's where some of the benefits seem to come into play. Is there is there creating in any dairy products because I just wanted to distinguish vegetarian vegan as well. So vegetarians are getting a little bit more creatine just through trace amounts you would have to eat or drink all the milk from a Jersey cow to get any significant amounts. Pultury and in the poultry would have the lowest concentration that your fish has the highest concentration. And then after that would be red meat. Sorry got so steady fish beef will be right up there as well that hearing macro a funny salmon natural will have the highest concentrations per serving. So you know a salmon steak and a half would give you maybe three to five grams of creatine at best. A large steak would as well a couple chicken breasts might have an accumulation there as well. So it's not impossible but if you're thinking I need 10 20 grams. It's difficult. Yeah. We typically say supplementation in addition to diet. No study has ever looked at okay what are you eating then we'll just make up the difference with supplementation. And I think that's a very interesting question there as well. Sure. Interesting. Yeah because I guess none of these studies are actually checking endogenous right where we're just checking. That's right. So you'd have to measure your baseline intramuscular stores but we don't measure what the brain and liver are making. Sure. And then we can't measure the suppression. So again it's you're sort of juggling what we're eating what we're making what we're supplementing and just seeing the effect prepared. We'll see about. Are there any any test people could do in terms of genetic markers or look at specific snips that would suggest that you are a. Honestly hyper responder maybe actually even a hyper responder creatine but also are you. And over like over producer with respect to endogenous creatine production or if you have suppression I know you mentioned there are specific genes. That people will have those enzyme deficiencies that that I'm sure you can check for. But nowadays people have access to their 23 and me and data and all these things are there's certain snips that you could look at. The two well not steps will you definitely look at the two enzymes and then you would measure the amount being naturally producing the liver. The brain you have to do an MRS study for that and see the effects and you have to do it long to tunely to see the effects over time. We can estimate what you're getting through the diet but really you would put people in a metabolic wards feed them a creatine free diet. See the effect there so you'd have to do a lot of work that would be a randomized control clinical trial and a medical work. It's tough to do. That's tough to do. So I want to talk about creatinine kids. I need to thank Darish for pointing me into these delicious gummies that I use from time to time. And my daughter will ask me for these gummies that I have. I'll give it to her but my wife will look at me like what are you doing? How dare you like you know she's going to be four in a couple days. Okay. And to my knowledge and my reading of the literature there's really no problem. Especially because we've talked about everybody's making it. So what can you educate the listeners on respect to creatine supplementation in kids? And I mean actual children. Yeah. Yeah. There's a handful of individual studies and a few great review articles by checker sick and Andrea agon of the United States. And based on all the data there's no adverse effects currently with creatine supplementation of recommended dosages and actually children. Just like adolescents get improvements in a geology balance. Proism body composition. Surgeon has even took taking a step further and look at it needs data. And if you're getting one gram of creatine or less that can have some detrimental effects for childhood development from bone speech as well as muscle. So the minimal threshold seems to be about a gram per day in the diet. That's kind of easy to do unless the child is very picky of an eater or you can get through supplementation. So right now we're not seeing any adverse effects. No reason why a child can't take small amounts that you could do 0.1 gram per kilogram of their size. If the child's a picky eater, you know that to be difficult to to get enough creatine. But right now we're not seeing any adverse effects. If anything, there's beneficial effects. And again, obviously as a parent, you want to talk either to your GP or look at the evidence based research here. I'll take you back this a little bit further that we're starting to see an evolution now that there's benefits for creatine during pregnancy. Transfer of my breath until the feed is now that was primarily been shown in in the mouse and sheet model. A staciolubri is the leader here from Australia. And if you're interested in pregnancy and creatine just search her name. She's got some really good review articles out there. I'm not a medical doctor. If you're thinking of pregnancy or anything like that, please talk to your medical practitioner. But again, there is some potential benefits. And she's doing the first randomized control 12 right now in females looking at the effects of creatine. You know, we used to just look at creatine on young biological males. Now it's gone all the way left the females pregnancy all the way up to the elderly populations. So from an age perspective, we're starting to see evidence in all aspects. I'm curious about the formulation of creatine right? I'll talk about gummies. I'm basically listening to Rhonda Patrick and Peter Tia talk about gummies. Do we know if those can be standardized? Are we actually getting five grams in those gummy formulations? Yeah, we don't specifically know for a peer of refereed publication yet. I know there's been some talk on social media. But I will preface this and I'm sure those studies are coming out. But in 2003 Roger Harris, Lee Roger Harris did a really classic study where he looked at meat versus creatine in solution versus creatine in candy. And when he looked at all of those three sources, creatine did get into the bloodstream. They were at different rates, but all three were very bioavailable. The area I'd have conserved with this creatine in an acidic environment for a long period of time. Because I think the pH will interfere with creatine stability. You'll probably get broken down to creatinine over time. But until those studies come out, we're still circulating. I would venture a guess where creatine and gummy is a solid form. I don't see any reason why it wouldn't be a bioavailable source based on Roger Harris's work. But I'm very eager to see those studies coming. God, you're very cool. Okay. And then most people take a powdered form. I mean, that's what I do. We've always heard monohydrate now is the best to take. There's also something called creapure. Can you explain what that is? I know it's out of Germany, but people may see that on the model. Yeah. So it's the world's most elegant type of creatine monohydrate. So creapure has grass status. It's the only type of of creatine that is primarily found in most reputable companies. A creatine monohydrate is this form of creatine that is the safest, most effective. Creapure is a form of creatine monohydrate that undergoes rigorous testing. There's two areas of the world that primarily produces Germany. And as well as China, but Creapure is the one that's in purified from a safety and efficacy standpoint, using a lot of randomized control trials. Amazing. There are any other areas that we haven't explored that you're excited about. The respect to clinical stuff outside of that was tried and true. Yeah. So the area is that I'm super excited for more work on the brain. You know, a great study came out on Alzheimer's disease this year. It was a ground breaker showing 20 grams a day, three weeks, improved symptoms of Alzheimer's. We're now sort of look at diagnosed dementia. One of the females across the lifespan. We don't really have much work in the perimenopausal area. It's so often overlooked, but what about young females? So premenopausal, perimenopausal, and then post. We got to look at those areas as well. The anti-cancer properties is a main area of interest for me. I'm partnering with a great colleague in self-care line. I love breasts as well as prostate cancer can't create his anti-inflammatory effects. Be important there. So those are three of the big areas. I think the one that we can talk a little bit about is any of the other myths that your viewers come to. You know, if you look at me, I don't know if people have seen it. This creatine caused bulldozer when I was seeing any evidence or that I was going bald before. I think as you guys being medical practitioners, you probably still get the creatine and kidney dysfunction question all the time. And I think a lot of viewers say I take this blood requisition form. My doctor checks off creatinine. They don't care. They'll creatine and right below it is EGFR and low and behold it. I forgot to tell him I was taking creatine supplementation. And when creatine enters the bloodstream, it gets locked into the muscle and when it's metabolized, it doesn't leave as creatine. It leaves as creatinine. And so if you have elevated amounts in the blood, it's a false indication of kidney function. So anybody listening to your thinking of increasing diet or supplementation, make sure you tell your doctor that you're on creatine supplementation. It's likely going to elevate your creatinine levels a little bit more. What about caffeine? We can come to use with creatine because what thing I stopped doing was actually taking creatine with that pre-workout. But then actually learned that it was probably a myth. Yeah, so it's an area of controversy. We still don't know. So I'll sort of give you two avenues. The best studies that show there's an interference effect of calcium being released from the circle plasma reticulum for those listening to go all the way back to high school biology. But caffeine likes to release calcium to your opponent and then your muscles can contract. But at the same time, creatine likes to take it back in so it can be recycled quicker. So we think caffeine and creatine might act as tug of war. But there's only some muscle contractile property of principles. Excellent studies out of the UK as well as I believe Germany has clearly showed a 350 milligrams or more of caffeine powder interferes with some of those effects of creatine. But most beverages, teas, coffees, even energy drinks do not have 300 million of caffeine. So I'm confident that if you mix it in your tea, cola, whichever that's fine. If you're starting to notice that you've been doing that for a long period of time and you're not noticing any beneficial effects, rather from the caffeine or creatine, you may want to split those up. I don't think caffeine and creatine interfere with each other from a formal kinetic perspective. We definitely don't know. And when I say caffeine, that's the powder. We certainly don't know if it interferes with coffee. And we're actually doing that study now at different dosages there. So if you like to throw it in your coffee or tea, go ahead if you're getting results. Great. Well, Darren, this has been amazing, man. Thank you so much. Like I said, I think that not too long ago myself and a couple of students, we actually send a survey out to a lot of the primary care colleagues in this area. I just don't understand their perceptions on creatine. And you're right. They still have this idea that creatine is going to be problematic for the kidneys. And that's the main one. In fact, I'll say this. I think I remember you talking about us talking to nephrology and some of the things. And when I was in intern, so this was circa 2017. Remember talking to a nephrologist about why are we not using cystatin C as a marker for kidney function, particularly in individuals who have high amounts of muscle mass are using creatine or just active because we know that creatinine is it's going to be an indicator for muscle mass and just muscle turnover, not necessarily just creating supplementation. And you're always going to have falsely elevated GFR. And oftentimes, myself included, it looks like I'm in stage two, stage three kidney disease, depending on where I am. If I go to GFR. And, you know, he gave me some non-sensical explanation that man actually made no sense. And I think these things are really, really hard to break with the tradition, particularly in the States. And on Canada has a slightly different system. So my hope is that we're going to be able to share this to some of our medical colleagues. You're doing some amazing work. You're constantly publishing here at the forefront of research and really pushing the boundaries of the respect to our approach to how this, I guess, gym supplement is now being talked amongst individuals and from a medical sense like we did today. So where can our listeners connect with you? Where can they stay in touch with you? Can they reach out to you if they have questions or anything like that? Yeah, I think the common ones on Instagram is the most popular at Dr. Derek Handel. Same handle for Twitter and LinkedIn. But Instagram seems to be the area most people come to me for questions or publications. We have a lot going on. We're going to be looking at creating and concussion. We're looking at creating and hit fracture. And then we're looking at different dosages. Smaller, more frequent dosages throughout the day have any different effects on bolus dosages. So there's lots going on. We currently have seven studies ongoing in the lab and we're always trying to publish quite a bit. So yeah, maybe I'll come back in a year and we can do an update and see what's up there. Actually, Dr. Derek, real quick, actually the concussion piece. Yeah, this is a selfish question. So what's interesting is that, you know, I mentioned we did sports medicine. I think for most folks training in sports medicine, we trained a lot of sports related concussion. Creating is actually one of the things that will recommend somebody immediately in the acute stages after concussion. The part that I almost always certainly mandated, I use that term very loosely, is when I see these post-concussive syndromes, right? So there are persistent concussive syndromes a year out, two years out. The one thing that I struggle with before this, I was always recommending five grams. And my question is like, are there any specific studies looking at those prolonged, miserable minority type symptoms? And if so, how long can somebody supplement for? We're still looking at six months or is that data still coming from that parking stuff that you talked about? Yeah, the only data we have a long term is in retired NFL players. And unfortunately, we have a decrease in bringing creating levels of correlation with head trauma. So the thought here is I agree. I now think anybody involved in head contact sports should at least be educated on some of the beneficial effects of creating thing that before. And then of course, immediately after. We don't know any of the long term effects there as well, but these are large scale clinical trials which need to happen. Hopefully, we're going to start one very soon and also look at populations that have symptoms. Maybe, you know, it's never too late. Maybe you get you start doing studies where you get people to volunteer one or two years in if they're still having symptoms. That's what we've done with long COVID and see can create teams provide any benefits even longer term on the road. So I don't know if it's ever too late to start just like exercise, but I do know that the animal model is definitely suggesting that if you take it before head trauma, it will decrease cortical damage. Can that improve symptoms of concussion? And in the only study looking at traumatic brain injury was in children. And when these children suffered head trauma, they took 0.4 grams per kilogram. So very high dose on a daily basis for three and six months. They didn't measure brain creatine. These children had improvements in speech, self care, a decrease in fatigue and headaches. So I think we're starting to see some evidence to at least consider this. They're susceptible to head trauma or God forbid. If you do suffer it, at least talk to your doctor and say, Hey, I think there's something with this creatine. It's not going to have any detrimental effects of anything. The upside is there. What was the courage? What was the average age range in that study that you went from one all the way up to believe 18 years of age? Well, it was quite a wide range. Yeah, big right. Okay. Cool. Well, there there's two things I'm thinking about right now. The first is how do we get Roy McElroy to be a lister of the show? You mentioned it. But the, but the second thing I'm thinking about, man, is everything we talk about today. I mean, every single one of my patients is a class example of everything you talk about. It's our opinion of brain health, brain injury, stroke, you know, and just waiting for that day where we can actually hold it in our hospitals and, you know, treat our patients with it. So that would be fantastic to see. You're obviously in Canada. We're here in the US, but irrespected by me. There are healthcare atrocities, if I could say, across the world. So the last question we ask everyone is how do we put the health back in healthcare? All of that's an excellent question. I think the biggest thing is awareness. I think there's a lot of statements you guys mentioned. It was hard to even get doctors to understand that the evidence-based research on creativity and you're all trained in a certain pathology and pathophysiology. But I think the awareness is getting health back there and understand that there's alternative forms. I think exercise and proper nutrition are two of the areas that we all often overlook. But those are the areas I think we can at least do better with, especially in my area. Amazing. Thank you, Diane. Absolutely. Okay. Let's see it next year. Absolutely. Here. Thank you. Thank you.