FoundMyFitness - #100 The Optimal Creatine Protocol for Strength, Brain, and Longevity | Darren Candow, PhD

Episode Date: March 31, 2025

Download my "How to Train According to the Experts" guide Discover my premium podcast, The Aliquot Creatine is renowned for enhancing strength, but its benefits extend far beyond muscle power. In this episode, Dr. Darren Candow, a leading researcher with over 140 peer-reviewed publications, explores creatine's diverse physiological impacts, from bolstering cognitive resilience under stress to mitigating symptoms of depression and protecting against cognitive decline caused by sleep deprivation. He explains why the conventional dosage of 5 grams per day might be insufficient, and how higher doses (10–25 grams) could unlock additional therapeutic effects. Timestamps: (00:00) Introduction (04:34) What makes creatine effective for exercise performance? (08:01) The loss of explosive power with aging (09:36) How creatine speeds up recovery between sets (12:13) Two ways creatine boosts muscle strength (14:12) Why creatine might not speed typical weight-training recovery (16:38) Anti-catabolic effects (17:16) Why do men and women respond differently? (18:50) Dietary creatine vs. supplementation (19:36) Is creatine supplementation necessary—or optional? (21:05) Why plant-based may benefit most (22:15) Should creatine dosage change with age? (23:01) Loading vs. daily dosing (25:57) Why 5 grams might not be enough—other tissues (27:48) Can creatine prevent bone loss—even without weight training? (28:10) How creatine supports osteoblast activity (29:51) Preventing hip fractures with creatine (32:33) Creatine vs. bisphosphonates (36:21) Why creatine isn't just for weightlifters (38:52) Why stressed brains benefit most (40:57) Why brain aging accelerates demand (43:54) Why 10g per day might be the optimal dose (45:45) Why creatine counteracts sleep deprivation (48:53) Before vs. after concussion (51:17) Should dosage be adjusted by weight? (52:39) Does creatine improve sleep on training days? (55:34) Creatine for Alzheimer's and Parkinson's—does the science hold up? (57:08) Can creatine help with depression and anxiety? (1:00:24) The role of creatine and glutamine in preventing respiratory illness (1:02:40) Why creatine may enhance endothelial health and circulation (1:04:04) Creatine's role in cardiometabolic health (1:05:45) When does loading actually make sense? (1:06:51) Creatine's dual role—preserving muscle and enhancing recovery after injury (1:09:46) Is creatine effective without exercise? (1:12:01) Why creatine might improve male fertility (1:13:57) Is it safe for children? (1:17:21) Creatine supplementation during pregnancy (1:18:54) Could creatine boost motor skills in kids? (1:19:34) Creatine monohydrate vs. the rest (1:24:15) How to avoid digestive issues with creatine supplementation (1:26:56) Does timing matter—and should you cycle it? (1:28:32) Should you take creatine every day—or only workout days? (1:29:17) Why caffeine might blunt the effects (1:32:21) Does creatine increase body fat—or is that a myth? (1:33:08) Preventing cramps (the hydration myth) (1:34:33) Understanding the creatinine confusion—why creatine won't damage your kidneys (1:36:59) Why creatine is linked (wrongly?) to baldness (1:40:22) Debunking myths—sleep, cancer, urination (1:43:39) How creatine affects homocysteine levels (1:46:32) Creatine and protein—the ideal post-workout pair? (1:49:26) How to pick the best creatine supplement (1:51:46) What to know about micronized creatine Watch this episode on YouTube Show notes are available by clicking here

Welcome back to the podcast. Today we're doing a deep dive into one of the most well-research and widely used supplements, creatine. And joining me is Dr. Darren Kandau, one of the world's leading experts on creatine, muscle physiology, and aging. Dr. Kandau is a professor and director of the Aging Muscle and Bone Health Laboratory at the University of Regina in Canada. He's also the director of research for the Athlete Health and Performance Initiative and has published over 140 peer-reviewed papers, on how nutrition, particularly creatine and resistance training, impact muscle, bone, and brain health. Most people associate creatine with strength and power, but its effects extend far beyond that. In fact, in this episode, Darren and I discuss how research now suggests creatine supplementation may play a role in cognitive function, particularly under stress or sleep deprivation, muscle and bone health, especially in aging populations, endurance performance, and hit adaptations. It reduces inflammation and improves recovery. We talk about metabolic and cardiovascular health with potential benefits for cholesterol, triglycerides, and even vascular function.

We even discuss mental health conditions like depression. We also get into a lot of specifics regarding creatine supplementation, including how creatine supplementation works. The best ways to take creatine should you cycle it is timing important. Does it work better if you take carbohydrates? We talk about dosing strategies. Standard recommendations are three to five. grams per day, but the question is, should some people take higher doses? We discuss creatine and whether or not we need a loading phase for it or you can just start with a daily dose.

We also talk about different forms of creatine. Monohydrate is the gold standard, but what about HCL or other formulations? And we also discuss a lot of different common concerns. Does creatine cause bloating, GI distress? Does it interact with caffeine? Does it cause baldness? Is it bad for the kidneys? and many other concerns. We also dive deep into the emerging research on creatine and sleep, including whether creatine actually improves sleep or if it's just helping the negative effects of poor sleep. So by the end of this episode,

you'll have a comprehensive understanding of creatine, how it works, how to use it, and whether it makes sense for you. If you haven't yet downloaded our free guide, how to train according to the experts, you can get it at how to train guide.com. We just uploaded it to include new creatine protocols. This guide distills insights from top experts featured on the podcast into one actionable resource.

It covers protocols to build muscle mass and strength efficiently. Training strategies to improve cardiorespiratory fitness, which is a key biomarker for longevity, evidence-based approaches for enhancing metabolic and brain health, and also options tailored for highly time-constrained individuals. Again, it's completely free and available at how to train. guide.com. If you're interested in exploring creatine even further, we've compiled a comprehensive set of resources for you. Head over to foundmyfitness.com forward slash topics where you'll find a deep dive into all the current evidence-based research on creatine. Just scroll through the alphabetical

listing until you'll find the letter C. It's also a part of my mission and sincere commitment to deliver high-quality evidence-based science and practical health tools to everyone entirely free without advertisements. To make that possible, we rely directly on support from you, our listeners. If you appreciate the depth, the rigor, the objectivity we bring to every episode, please consider becoming a Found My Fitness premium member. Premium membership is the best way to directly support our work, and it also grants you access to exclusive perks like the Aliquot, which is our members-only podcast, monthly

live Q&A's with me, and our curated Science Digest. Your support directly enables us to continue providing trustworthy, actionable information on health, fitness, and aging. You can sign up for that at foundmyfitness.com forward slash premium. Again, that's foundmyfitness.com forward slash premium. And now on to the podcast with Dr. Darren Kandau on all things, creatine. Darren, I'm super excited to have you here today to have this conversation with you to go deep into the science of creatine. No, thanks for having me. I'm really excited as well. Absolutely. I've read several of your studies. I'm a huge fan. A lot of really important and interesting research to talk about. Okay. Maybe we could start where it's most popular. I mean, a lot of people think about creatine in its role in exercise performance. However, there's been a lot of emerging research in other areas. Maybe you could give people just a quick snapshot. Yeah, like it's really evolved over the last 40 years. It's gone. from athletes getting bigger, stronger, faster.

Now we're looking at potential benefits on bone health, brain health, cardiovascular health, even in children and during pregnancy. So it's evolved from just the young male athlete to pretty much anybody on the planet is now considering creatine either in their diet or supplementation. So for the next few hours, super excited to talk about all aspects of creatine and the evidence-based research behind it. Well, let's talk about the resistance training and improving performance, muscle health. I mean, why are people, why is it so popular?

Well, because it works from a muscle performance perspective. So really it basically increases the ability to produce ATP or maintain it during an exercise session. So for example, when you're doing, you know, squat or leg press or even running, you're doing muscle contractions and phosphol creatine, which is what we're going to be talking about today from creatine supplementation. It really maintains ATP or adenosine dye trifosate. So if you have more ATP longer, you can exercise at a higher capacity, a higher intensity. And that delays the utilization of other energy systems. That might be a bit slower.

So anybody involved in high explosive an aerobic type of sports weightlifting, high-intensity interval training, for example, probably would experience some benefits from creating supplementation. And how is it going to benefit you? Is it going to improve your training volume? Is it going to make you stronger? All the above. So it definitely seems to increase training volume. So that's either the load by the reps by the set or exercise capacity from a cardiovascular perspective. It definitely, if you were to choose one thing why creatine has been so effective, it's improving muscle strength.

You could also encompass that with endurance and power. It also improves lean body mass. So here's a big discrepancy that a lot of the viewers might not know. When we measure lean body mass in the labs, we're technically measuring blood connective tissue. soft tissue. So we're not directly measuring muscle mass. We need to do a lot more research on that. But in general, about 50% of the value of lean body mass, we consider muscle.

So it has some small favorable effects. There's been some studies with QCT as well as ultrasound. But you can get an increase in lean body mass, regional muscle thickness, muscle performance. But probably the area that most people don't realize is the recovery aspects. It really seems to have some anti-cadabolic effects. potentially anti-inflammatory effects. And that's interesting because it's from the aerobic community. For the longest time, we never thought creatine was for endurance or aerobic type athletes.

And the best lines of evidence from a recovery aspect come from long duration of aerobic exercise, a marathon, a marathon, a triathlon. It seems to reduce cytokines. So those are markers of inflammation. So there's a whole gamut of mechanisms. There's about 10, what we consider, anabolic factors. and then there's probably just as many as an anti-cadabolic effect. So it has a plethora of benefits, which I'm sure we'll talk more about in detail today.

So, okay, to go back, you just gave it total information dump, which is awesome. Let's go back first to the explosive power you were talking about. It seems to really help benefit in that explosive power, like you're talking about doing a squat. Yes. Or, I don't know, maybe the first few seconds of an interval, something where you're going, you know, using all that power. Is creatine benefiting, is that how it's benefiting increasing the training volume? Or is there something else that's happening?

Yeah, in two ways. So it really seems to maximize either the recruitment or the ability of type 2 muscle fibers. And when we talk about aging, unfortunately, those are the ones we're losing as we get older. But it really seems to work in the second, third, and fourth set. So for example, if you were to do four sets of leg press, compared to a placebo, you may not notice any difference in the first set, because we think we have enough ATP or fossil creatine stores in our muscle. But when it comes to set two, three and four,

that's where creatine really comes to the rescue. The individual or group can do more repetitions, and then over time, they can actually do a greater volume. We think with weeks of training, if you're doing more volume, you can actually get greater physiological adaptations. So when we look at all the meta-analysis, when you compare creatine and weight training to creatine placebo and weight training,

there is a greater increase in lean body mass, muscle size, as well as muscle performance. So creatine, there is something there from a mechanistic standpoint to allow that. And we think muscle fiber recruitment primarily type 2 muscle fibers is one of the main reasons. Does it affect the recovery time in between sets? Excellent question. It does. It really speeds it up. So on average, if you were to totally wipe out your normal creatine stores, it takes about three to five minutes for your mitochondria to recover. that. However, creating really, really speeds up that recovery, which is great for the average

person. They don't have a lot of time to work out. They can't wait around for three to five minutes in between a really intense set. So it really speeds up the recovery. Not only does it speed up the recovery after every set, but in between contractions as well. So over time, the individual could probably have a really intense, great workout in less time total and get actually more favorable effects. And I think this is really important. We're talking about here, I mean, we were talking about squats, you know, these explosive types of power, types of training. And this is a really important field because, you know, you often hear about people talking about the loss of muscle mass. As we age, you talked about losing type two types of muscle fibers more readily than the type one.

So these are the types of muscle fibers involved in that explosive type of power type, you know, exercise. And, you know, people don't think about how power. decreases with age, how strength decreases with age, and how that affects our quality of life, how it affects our physical independence, our fall risk. Right, right. And so I think just focusing on this type of training, I mean, the creatine is the icing on the cake, right? Yeah.

But just focusing on doing these types of multi-joint compound types of lips, which is something that I, in the past, I would say, a good year now, a solid year of doing CrossFit type of training where I'm doing strength training, I'm doing resistance training, strength training, and high-intensive internal training that's including, you know, the types of stuff that I'm used to doing, biking and rowing, but also adding in, you know, doing some drop sets with, you know, front squats with the barbell and things like that. It's super important. So there's philosophy or power training or a variety training. First, we've got to get people to move and then allowing them to give some type of benefit to their training program.

So creeteen is probably the one that will be number one when people, selected, even probably more than caffeine nowadays, from an exercise training capacity. So it should be considered. It can have a lot of substantial beneficial effects. And as we get older, after about the fourth decade, unfortunately, we start to lose these type 2 muscle fibers. And so exercise has to be foundational. And if anything else can be beneficial, protein, creatine, I'm all for it.

And I think most people hopefully will be as well, yeah. So the improvements in the muscle strength, presumably are coming because you're increasing your training volume, right? Is that, or is there a direct effect on strength? Yeah, there's actually a neurophysiological recruitment. So now creatine has been touted as a new neurotransmitter. So this is quite interesting. It actually seems to release a lot of things from a neuromuscular perspective.

But the biggest thing is the ability to recruit not only type 1, but these type 2 muscle fibers as well. And then, of course, if we're having greater muscle or motor unit recruitment, and we can potentially lift longer, heavier, and over time get sort of an increase in strength. The other big thing from a cellular perspective is that creatine causes calcium that come back in a little vesicle in our muscles. If you take in high school biology or university, this will be your nightmare, but I remember everybody talking about the sarcoplasma reticulum. And it's an area that just releases calcium to allow our muscles to contract. And creatine speeds up, the uptake of calcium.

So some of the evidence out of Europe has shown that it increased. this relaxation time or the ability of the proteins in your muscle to grab hold of each other to contract. So there's a cellular aspect there explaining why we think we get an increase in muscle performance. I say strength, but endurance and power are all lumped in there as well. So endurance is the ability to perform repetitions to fatigue or power move an object as fast as you can. They're all vitally important. But we think strength is overall from a global perspective, number one. It's probably the main reason a lot of older adults are placing long-term care facilities. If they have a reduction in strength, they can't live independently. So that's why,

again, resistance training or weight-bearing exercise, as you mentioned, CrossFit, whichever it is, foundational from Canada. So shoveling the driveway in the winter counts because anything that's a load against you is really beneficial to the body. I think people underestimate the benefits of moving. And then if anything can be taken in in this form, creatine, it would be very, very beneficial. You mentioned some of the anti-inflammatory effects of creatine, particularly in the context of more endurance type of training, people that are perhaps running marathons or just clocking in a lot of hours of running or cycling per week. Is that, so I think that that goes to some respect in the recovery sort of been, right? And I'm wondering if that also plays a role in recovering from doing your resistance training or strength training like on a recovery day. So, I mean, do you think it plays a role just broadly in recovery?

Yeah, it does. Now, this is interesting, and I probably would have been the most surprised when we wrote the paper on this, that we don't think traditional weight training, where you're doing a set, you're resting maybe a minute to two. It seems like it's not catabolic or intense enough. Now, most people will all say, shake their heads, say, hey, when I'm in the gym, I'm really putting a lot of effort in. I think from a mechanistic standpoint, when you're doing running or long distance, continue. muscle contractions. It causes this large catabolic effect to the body. So that really heightens the inflammatory response.

Weight training is acute. 10 seconds of work, three minutes of rest. 10 seconds of work, three minutes of rest for whichever it is. And we just don't see creatine having a lot of superior effects from a resistance training and recovery aspect. Probably because the rest intervals for the average person are there. But from a long distance event, you're running hours, you're swimming, whichever it is. The best lines of the fence come from triathlon and marathon running, where the increase in these markers called cytokines were elevated.

The creatine sort of attenuated that rise could allow the individual to recover and get back on the track or whichever it is quicker. But I've talked to some good colleagues in Canada, and it just seems like weight training is too intermittent. Now, when you mention CrossFit, that's different. I'm thinking of the three sets of 10, you move from machine to machine, you rest, you have a CrossFit or something that's really. continuous would probably fall in line here of the necessity for creatine. So that would be a very good study to look at the effects of creatine on the recovery aspects of something like high-intensity interval training or CrossFit, for example, our military type of training that's really endurance and resistance training.

So you just gave me another idea to run with, but it's logical. The more intense, the more demanding, I think that's where creatine's anti-inflammatory properties would come into play. So when people hear catabolic or, you know, they'll think, they'll think of muscle breakdown. Right, right. And certainly, you know, there's a big component to circophenia, inflammation in circophenia, which is age-related muscle breakdown. Is there a role for creatine in preventing the breakdown of muscle? There is.

It's very mixed. So we don't have a lot of data. First off, creatine doesn't directly increase protein synthesis, which might be a surprise for a lot of reviewers. It sort of works in a magical other way, which we can talk about. But from a muscle breakdown perspective, it seems to reduce something called leucine oxidation, primarily in young males. And that's an indicator of whole body breakdown. We've also shown in our lab, it reduces three methyl histinine, which is another indicator of whole body breakdown. But nothing is directly shown in the muscle itself. And for some reason, females don't experience

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

But it does decrease protein breakdown, primarily though, in males. And we still don't know exactly why, but we think estrogen or the other sex hormones might be involved. Does creatine have a general anti-inflammatory effect in both males and females? It does in young and older individuals. But here's an important distinction. The more stress the body is, it seems to come to the rescue more. So if you're a young individual adequately sleep, proper nutrition, you're probably not going to notice any anti-inflammatory effect. it's when the body is under times of extensive exercise or trauma, hypoxia.

I'm sure we'll talk about the brain and sleep deprivation. So whenever the body is more stressed or under more attack, that's when creatine seems to come to the rescue. And getting, struggling back to, you know, people that are supplementing with creatine and it improves their training volume and improves their strength. Why do people have to supplement with creatine? Well, they don't actually. So a little bit of clarity. So we naturally are producing creatine in two main areas in the liver and in the brain. And on average, we're producing about one to two grams. Then we're also consuming in the diet anywhere between one to three grams or none. So a vegan is not getting any dietary creatine. Those that are on a carnivore diet might be all the way up to about three grams. And we excrete through the urine product called creatin and about two. So when you do the math, We're in a net surplus anywhere between 1 to 2 grams a day. And we know it's not essential because vegans can live a long, healthy, successful life. But we consider it conditionally essential because when we see all the evidence, I think there's over 1,000 peer-review papers.

When we take in a little bit more, there is some substantial beneficial effects across the whole board, not just muscle. We're now looking at bone, brain, and the immune system. So from a perspective of a vegan who is not getting. any almost amount of dietary creatine. They're relying on their liver to make it. What's going on in their brain? You mentioned the brain makes creatine. Yeah, it's very interesting.

So on average, vegans have substantially less muscle creatine compared to an omnivore or carnivore diet. But an elegant study out of Brazil about four years ago, they used sort of an MRI for the brain. And they showed that vegans and omnivores had the same amount of brain creatine stores. So that's really substantiating that the brain-making. its own creatine. It probably makes enough for the non-stressed individual, but during times

in metabolic stress, the question is, will vegans or omnivores need more? And it's likely that that's true. Yeah. During development, is the developing brain making its own creatine like... It is, yeah. Just like our liver is making its own creatine. It's using, and it's probably an accelerator rate for brain development, cognitive development. Again, our brain is small, but it uses 20% of our daily energy. And, of course, during development, that's when it's very, very precious as well, yeah. So, creatine is mostly found in animal foods, meats, poultry, fish. Yes.

None in plants at all. Trace amounts. You'd have to eat the entire orchard of whatever plant you're thinking. And same with milk. You'd have to drink all the milk from a Jersey cow to get any significant amount. So that's why it's unrealistic, you know. So if we're having, if we're producing between, you know, one, to two grams? At best. At best. Just in our liver. Correct. And that presumably then is being

transported to muscle. That's the whole 95%. We can't forget about the bone and brain are the main areas. Yep. Okay. And then if let's say you're getting, I think I was reading some N. Haynes study where on average people get younger adults, not older adults, get anywhere between one to two grams a day from their diet. Right. But older adults are getting on that lower end, not even necessarily even at one gram. So older adults are getting even less. Yes. But then, you know, is there more to be consumed by the muscle or does it get spread around?

Yeah, that's an excellent question. So the thought is as we get older, we have reduced fossil creatine stores in our body, so they might need more. And the hope is about 95% is housed in our skeletal muscle. But now with the emergence of research, the rest is in bone and brain specifically. So the hope is if we take in more, our muscles will be full, which is great. But now, hopefully, we're going to have some trickling into our bone, which is even just as important. And I think most people would argue from the neck up, that's really important from a global perspective with all the neurological diseases, depression, anxiety. So I'm one of the big proponents of taking a lot more than probably what's recommended based on the evidence.

based research to sort of disperse throughout the whole body, not just skeletal muscle. Well, let's talk a little bit about that. So in some of these, you know, the strength training, resistance training studies, what's the common dose that's taken? And maybe we can talk a little bit about, I mean, there's the loading phase, which I've never done. So I actually take five grams a day. And although I might start taking more after this podcast.

So I'd love to know, like, what is the average dose that's taken to improve, you know, your strength training, your resistance training, your training, your training volume, and then we can go from there. Yeah. So, I mean, in 1992, Roger Harris came out with the seminal protocol, where, as you just mentioned, this loading phase, it's the most viable, rapid way to really saturate your skeletal muscle. This has nothing to do with the bone or the brain. And so that's 20 grams a day for about seven days is usually what's recommended.

A bit of new information, you only need to do that for two days, and then your muscles are saturated. So the loading phase was designed for athletes to really rapidly sort of fill up the room, if you will, from a skeletal muscle perspective. After that, you can reduce it as little as two grams a day. So again, that's a half a salmon steak. That would be half a chicken breast or whichever. So it's very viable. They call that the maintenance phase. The only problem with the loading phase is it's so rapid. It does cause water to enter a lot of ourselves. And a lot of individuals do not like this potential net water retention or GI tract irritation. We don't usually use that in our labs for that reason. But for the athletes, the World Championship coming up, the loading phase followed by a maintenance phase is a very viable rapid way. Young females hate it because of that water retention and weight gain. The good news is you can take as little as two to three grams a day, no loading phase, and take that on a daily basis probably for the rest of your life.

And that will definitely accumulate and fill up your muscles in about 30 days. We don't know if that low dose will get. into the bone or brain on a long period of time. What we've done is look at a relative dose, so that means everybody has a certain weight. We put them on scale, and we use 0.1 gram all the way up to 0.14 grams per kilogram. So, for example, if you're 70 kilograms,

you're taking 7 grams a day, all the way up to about 9 grams a day. You can take that in one bolus dose or split it up into smaller dosages throughout the day. I wouldn't go any less than 1 gram. One gram doesn't seem to get in the blood as rapidly as we need. So that's something for your viewers, if they're microdosing, no less than one gram. But you can split it up two and a half grams, five grams, whichever you want.

I take a lot more than that based on our new clinical data. I'm 48 years of age. I know the effects of aging and from a bone and brain perspective. But really all this dosing came from muscle. And we have all these new areas. That's why I think the emergence of new dosing strategies is really come to light. I definitely want to get into some of these, you know, potentially negative effects of the high, high dose. Right, right. But let's talk a little bit about your new emerging data on bone health.

And so you're talking about, so I mentioned five grams a day. And well, maybe before we get to that, how long does, if I'm taking, if someone's taking five grams a day and, you know, how long does it take to get your muscle stores saturated? And then, let's say, your resistance training, right? So you're working, let's say your resistance training and endurance training. I mean, you're working out five to six hours a week. I'm just talking about my schedule here. Yeah. Okay. And then, and I'm doing five grams a day, right? Is, am I just constantly saturating my stores, even though I'm, you know, pulling down from them as I'm working out? Or how does that work? Perfect. Because five is the average global recommendation. And that's a fantastic dose overall, we think, to start, especially from a muscle perspective. So it'll take you 21 days to fully saturate your skeletal muscles. So after that, you're going to have some being excreted in your

urine, or let's pray here, hopefully some is now being uptaken into your bone, because the muscle is pulling on bone. Your bone is a very metabolically active tissue, which no one actually sees in the mirror, and then hopefully some is trickling more into your brain. So the thought is, okay, five grams is very viable, easily 21 days, your muscles will be full, taking five grams a day thereafter. Some would probably go into form of creatin, but hopefully, and we don't know this, maybe some is going into your bone being used by your immune system, your GI track, your gut health, and your brain. So five is a great dose.

I'd like it to be higher just because of some of the new data to suggest every day we get out of bed, we're a day older. There's some good evidence to suggest bone needs a bit more. And of course, the brain, we still don't know. But I have some lines of thinking about when we're really metabolically stressed how much to take. But if you're taking five, rest assured, you're doing exceptionally well, yeah. Well, let's talk about bone.

So one of the best things you can do for bone health is weight-bearing exercise, these compound lifts, the things that we were talking about with improving your explosive power and your strength, right? Right. How is creatine adding to that? By two ways, a direct and indirect. So let's go with the boring direct. It sort of increases osteoblast cells. These are the cells to sort of create or the formation of our bone cells. So in rodents, osteoblast cells have been energized in the presence of creatine.

So it was logical to the thing in humans, maybe our osteoblast cells, the cells that are responsible for increasing bone size and strength might have more fuel. And these cells do use creatine just like our muscles do for fuel and potentially increase bone density. And if that's true, we've just cured osteoporosis, basically. The other line of thinking, which is surprising, going back to this anti-cadabolic phenomenon, is the best. lines of evidence with bone are from an anti-cadabolic perspective. It seems to resemble a bisphosphonate. So a lot of reviewers are maybe taking a bisphosphonate. It sort of preserves your skeleton. I know my mom is taking that as well. So creatine reduces something called the osteoclast activity or bone resorption. So for some reason, it really inhibits these osteoclasts from sort of chopping down our bone and increasing blood calcium levels when not needed. And then, of course, if it sort of increases osteoblasts, potential, maybe the recycling of bone gets stronger. It's kind of like laying a foundation of a house. The bricks are stronger. You're sort of putting the bricks together a little bit faster. And then inclement weather is not chopping away the bricks or the cement.

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

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

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

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

But if I was to take eight grams, would I tell my parents to take eight grams and not work out? If I did, I don't think they'd expect anything on the bone. The bone is really stubborn. It's just like our brain and creatine. It's really really stubborn. I think the main force is the driver of weight training out. What about someone who is, let's say a postmenopausal woman who's, who's experiencing some perhaps osteopenia.

Yes. Do you think before trying some of these other standard of care treatments, like bisphosphates, for example, you mentioned, doing the weight-bearing training and the creatine, perhaps 8 grams or 10 grams a day, would be a good first line of defense to try before trying some of these other drugs that do have negative side effects? So if you're in line for a bisphosphonate, there's no way that creatine or weight training will come close. So a drug effect will always be superior. The effects we're seeing even from a significant perspective with creatine are so small.

We don't even get to a clinical perspective. But let's talk about weight training. I 100% agree. If I had to choose one for bone, it's weight training or pliometrics or anything that you feel to the body. And then consider creatine in your treatment program. Creatine would never replace a pharmaceutical intervention from a bone perspective. And the effects we're seeing are so small, even over two years. At best, it's preserving.

Now, this begs the question, maybe the adults we chose were too healthy. None had diagnosed osteoporosis or osteopinate or frailty. What if we took a population with severe osteoporosis, maybe creatine could come to the rescue there? That's another thing we're starting to hopefully get governmental funding for down the road. But a lot of young females, a lot of young males, and of course older females, even postmenopausal, their skeleton is still very beneficial and strong. They may not have incidences of osteopenia or fracture risk. But until we do a study and diagnose osteoporotic males and females, we just don't know if it's the disease or maybe they were just healthy enough. Well, prevention is obviously, I think, the key, right?

If we can encourage people before they're experiencing massive breakdown on their bone or osteoporosis, osteopinia, to, you know, engage in resistance training and not the single joint exercise where you're making your biceps bigger, right? I mean, like, you need to, you need to be doing these multi-joint compound lips, rows, you know, presses, anything that's multi-joint. And then perhaps in combination with creatine, if it's really, if it's preserving bone, that does really suggest. a preventative role, right? Yeah, and that's 100% correct. Like, the movement is got to be there. And I think most people are aware of the benefits of exercise. And then if creatine or protein or whatever it is your eating can give you a small

beneficial effect, I'm all for it. And I think a lot of people would be there as well. So creatine definitely has the potential. It kind of has a lot of potential for a lot of things. But without protein, you know, those two need to be there. We don't think creatine can rescue a hypokolaric diet, especially low in protein, but we just don't know. I argue that creatine falls in line with protein with his aging anabolic resistance. As we get older, my guess is where we have lower creatine in some of our muscles as we get older.

We need more. So now there's a young versus older stereotype, just like protein. Younger individuals may respond from 20 to 25 grams all the way up to older adults. So I think creatine is definitely a part of my day. And I try to promote the evidence-based research, especially from an older adult population. If anything we can do to offset chronic disease or getting chronic disease, that's beneficial. And we're starting to really focus on young females. Exercise is so important, adequate protein.

And then creatine, it's not just for males. We're seeing a plethora of benefits for young biological females, which is really important. It is. You know, when you hear the word creatine, you think about, like, the genie. Jimbrough, right? Like, I mean, it's like you're taking the creatine, trying to get, you know, their muscles bigger. And the reality is, is that, you know, women, women are also very susceptible to, I mean, they're susceptible to, you know, losing muscle mass and strength. But bone is a big one.

It is, yeah. And when we look at all the data, females get an improvement in muscle performance, primarily strength. That's the population. We've seen the best bone benefits. Now they were post-menopausal, but reduction in bone mineral density, bone strength. And then we're seeing from a sports perspective, agility balance. So for the females watching, don't shy away from creatine. It's extremely potentially beneficial in combination with exercise.

And if you're worried about weight gain or whichever, do not do the loading phase. It's not needed. You can start as little as two to three grams a day. Divide that up even. So I'll tell a lot of our clients or participants, you can take one and a half grams in the morning, wait until the evening to take one and a half grams. that really decreases the chance of water retention. But if you're eating red meat or seafood, you're getting a little bit amount.

For the vegans watching, keep in mind you're not getting any. And that's why supplementation, third-party tested, they are vegan-based, could be considered. I mean, it seems like it would be very important for that population of people in particular. Yeah, we've done some really fascinating studies with vegans and vegetarians, and they respond exceptionally well because we're doubling the amount of creatine, which is the high-energy compound in our muscle. so those individuals can do more repetitions, higher volume, quicker recovery. So it really has favorable effects for male and female vegans and vegetarians. And again, those emphasizing a plant-based diet with everything going on in the world nowadays, a lot of people are looking to more plant-based diets for health reasons or whichever,

and then they might need to consider a supplement. So usually we're not in the market of talking about supplements, but this one is the one that seems to come to mind where it might be difficult to get the amount needed in your diet. from financial costs, ethical treatment animals, whatever your own habitual preference is, and if they're third-party tested, it's the safest most effect of ergogenic aid out there right now. The safety profile is exceptional,

especially at the dosages we're talking about. When we talk about protein, we're talking hundreds of grams. At most, we're talking maybe 10, 20 grams for the athletes, which is basically two teaspoons in the run of a day. So it's not a lot, but there is a lot of evidence-based research behind it. Yeah, and we'll definitely dive a little more to the supplementation, but I'm interested in the brain, and we've gone from the role of

creatine. It seems to have multiple roles, anti-inflammatory, anti-cadabolic. It's obviously important for producing ATP, you know, regenerating the ATP. What about the brain? Super exciting. Like, this is such an emerging area. So from the neck up, I think the next 20 to 30 years will be focused almost entirely on this. So our liver produces creatine and our brain actually is unique. It also produces creatine. But the brain is very resistant. We have the blood brain barrier for a really important reason. And the brain says, you know what? Circulation, we don't need creatine in the blood. We're making our own. So an individual getting adequate sleep, no chronic disease, no metabolic diseases, no neurodegenerative diseases is producing adequate

amounts of brain creatine. It could be as little as one to three grams. Now, our brain is small from stature, but it uses 20% of our daily energy. And of course, as we all know, when you're really tired, sleep deprivation, running around chasing your children, most people that I know are really metabolically stressed primarily from a cognition perspective. And that's where creatine seems to have the best lines of evidence. Sleep deprivation, hypoxia, I jet lag. I was up at 3 o'clock this morning and flew down. So I'll be taking a really high dose today to hopefully offset the chance of inflammation or cognitive decline. So when we look at the totality of emerging evidence, it's split. Some studies don't see any effect, but the ones that do is in a population where

they're either mentally fatigued, sleep deprivation, or during times of aging, and that's where memory comes into play. And the common denominator seems to be the more that the brain is stress, the more creatine seems to come to the rescue. Same analogy from a muscle and bone perspective. So we can talk for hours just on the brain, and it's a very exciting area for sure. So the brain is stress. So brain aging. Older adult.

Yeah. That's aging is a stress on the brain. It is. So supplementing with how much creatine can improve cognition in, let's say, older adults. Yeah. As little as about five grams has been shown to have some potential, but this is interesting. I just, you know, 20 minutes ago said that the loading phase wasn't needed for muscle. The best studies for the brain look at 20 grams a day for at least a week. So now you're in a conundrum. I'm looking at muscle, bone, and brain. And the theory here is that since the

blood-brain barrier is very resistant to creatine, and unfortunately, we have this really important glial cell called astrocytes, which are the most, the biggest in our central nervous system. It sort of acts as a filter from our blood into our cells, and it really determines what gets in and it says, hey, foreign pathogens, no, you're not getting into the neuron or the cell. So unfortunately, they don't have the creatine transporter or doorway. So that's why uptake into the brain is very blunted. So the thought is to get an improvement in brain creatine stores, you need longer duration of supplementation or higher dosages.

So the best lines of evidence using MRS have shown that higher 20 grams a day seem to be the most viable. There's been a single study looking at about four grams a day, but it took three three months to accumulate in the brain. Unlike our muscle, which acts as like a vacuum, it sucks in all the creatine from our blood. Our brain says, no, no, no, I'm only going to take what's in our blood, i.e. supplementation, when need be. So that's why sleep deprivation seems to have the best lines of evidence or mental fatiguing challenges.

Yeah. Okay. So let's, if you're someone like myself who's been supplementing with five grams a day for a year. Okay. That's enough time for it to eventually accumulate. into the brain, presumably? Yeah, like that low dose, remember, you need about two to three grams now. I'm not sure about your diet, but you're going to need that just to maintain your muscle.

And then comes down to your genetics. What's more in jeopardy? Is it your bones or brain? So again, the 5% that's remaining throughout the body is in your testes, heart, bone, and brain. So for me, as a biological male, it's going to different areas compared to you as a biological female. But my hope is, wait a minute, let's go a bit higher. so we're sort of sort of checking off all the boxes. My guess is five grams.

You'd have a small increase in brain creatine content. But if you have a really non-stressful life, the brain says, no, go to the bone or we'll excrete it down the toilet. But if you're metabolically stressed, it's begging for more. I'd like you to be probably higher than five, but I think it'd be interesting to look at some pre-post MRS scans. And it's viable. It could be there.

The study that did four grams was in long COVID. These individuals, brain fog, fatigue, headaches, things like that. So the brain was really begging for recovery. Okay. So you just mentioned the best studies showing any improvement in. And when we're talking about improvement, we're talking about cognition. We're talking about like memory. Memory.

Okay. You said 20 grams, right? Which is definitely what I don't want, the swelling part of that, which happens around 20 grams. Yes. So have there been studies looking at 10 grams? Is that like a sweet spot? The seminal study was out of Germany, and they did two versus four versus 10.

And this is where I personally take at least 10. And they use MRS studies. And they only showed that about 10, doubled the percent increase in brain creatine content. But they also measured it in the gray matter, the white matter. And I believe the thalamus, and it all improved by about 10 percent. Now, it was a small sample size because they run on MRS is. super expensive. So statistically it wasn't there, but the percent improvements were a lot higher. And when you look at all the other data, 10 grams seems to be a very viable dose to not only check

off the box, definitely for muscle. We're now checking off the box for brain and now we're, or sorry, bone, and then we're also checking off the box for brain as well. So I personally take about 10 grams a day on average, but during times of metabolic stress, sleep deprivation, or jet lag, I'll increase it to 20. So today I will take 20 grams because I flew down from Canada. I'll take 20 grams again tomorrow. But when I get back home, I'll decrease it back down to 10. If any is being excreted down the toilet, I'm totally fine with that. Creatine is very cost effective, but I want to make sure I'm maximizing all my abilities. And the immune system, especially in Canadian winters, is really heightened and activate it. And I really have found in the last few years,

I'm not getting flu-like symptoms. Hopefully that's from exercise. or die, but who knows, maybe creatine is helping because there is some anti-inflammatory effects. You went to another area that I definitely want to talk about, but like before that, so 20 grams, then, you're saying acutely when you're in the sleep deprived state, jet lag, you know, let's say fill in the blank type of, you know, extreme stress. Is that immediate? So let's say like you miss, you're like up late. You're up late one night and you have something to do the next morning or the next day.

You have to be like on your game. If you take that 20 grams either at night, would you take it at night before you go to sleep or in the morning or does it matter? And will it have an effect immediately? Yeah, and I love learning. And this is just so 20 grams might be too low. It's surprisingly to your viewer. So another study came out of Germany. They did as very elegant design.

It was a crossover. And they gave 0.35 grams per kilogram. So even if you're only 70 kilograms, that's 25 grams in a bolus dose. And they measured it for 21 hours of sleep deprivation. and it really improved memory, cognition, and it increased brain-creating content. So that high a dose, not only does it get into your plasma or blood really quickly, probably in about three hours it's peaking. When your brain is stressed, it's being taken in quite readily.

So during times of metabolic stress, it seems to work now. The argument is, how do I know I'm going to be stressed tomorrow? How do I know I'm going to have a bad night's sleep? You don't. So that's why I think taking a higher daily dose might be a safety, but the days you're like, oh, I didn't sleep at all, and I have a big presentation later. Or me as a professor teaching four classes of term, I've really increased the amount. I would say I might be the most saturated person on the planet because I've been taking creatine for decades.

There's no reason to stop. We can talk about cycling or continuous. But I'm even taking more in hope that it's getting into my brain. Again, 20 years ago, it was just muscle. Then we've evolved into the bone and now we're getting into the brain. And I think a university student's midterm week at final exam, staying up all night cramming. Maybe creatine could really improve their ability to score better on tests.

And when you look at the mental fatiguing studies, that's when creatine seems to work. After you've done a whole bunch of fatiguing exercises, or sorry, taking creatine before, it really speeds up your ability to maintain memory and cognition. And we can talk about neural filament things in the brain or BDNF, and that's some of the mechanisms primarily in Rodin. So there is some mechanisms showing that creatine is decreasing oxidative stress. or really having some potential for neuronal health, which now you think of Alzheimer's, dementia, neurogenital diseases.

So I'm super excited to see where this is going for the next 20 or 30 years. I wonder if there's any effect just because it's sort of a triaging of like it's helping with the energy. And so it's like freeing up other energy, you know, for like other, you know, taking care of oxidation. And that's probably the best overall segue. So it increases brain bioenergetics. And if it can, one of the common to numbers with depression or concussion is that they have reduced brain creatine stores and bioenergetics compared to a healthy control on average. And so maybe creatine is bringing those values up or even slightly more.

And now the brain has more energy capacity to do and deal with all the daily stressors of society. Yeah, absolutely. So TBI, I mean, traumatic brain injury, the way I think of it is like real-time brain aging. Yes. It's just, it's like all of a sudden you just get an, an. knocked your head and it's like accelerated aging. So what would be a protocol for someone that, you know, let's say they take a blow to the head or they get hit with the ball, soccer ball, or, you know, whatever the football,

whatever sport that they're doing, would it be like they should be taking high dose immediately? Yeah. So I'm now in the camp and I think a lot of other researchers and a lot of the words coming from here in the United States. But if you're in contact sports, creatine should be taken on a daily basis because, unfortunately if you do get hit in the rodent model when because you can't do this as in humans but when they've

actually forced concussion in rodents taking creatine beforehand the recovery symptoms are really accelerated and in the only single human study was in children as soon as these people in Scotland got head trauma they put them on 0.4 grams of creatine per kilogram so about 20 grand these are just children

immediately and over six months these children that were taking creatine had substantial improvements in self-care and efficacy no blood biomark were taken, but at least it showed the improvement in recovery. So instead of waiting until you get hit, why not take the preventative role? And that's why, again, I think for me, and again, it's opinion, but we've seen some data to suggest that 10 grams might be a good viable dose, more or even a little bit less,

depending on why you're taking it. But I personally take it from a whole body perspective. I don't play any contact sports now, but who knows? I could go out and skate and fall and hit my head or skiing or, we'll. whichever, and maybe that would help accelerate recovery. I'm taking it just for any chance to have some potential brain benefits, but the big areas, it does increase the recovery aspects of concussion. So NFL, NCAA, especially down here in the United States, trillion dollar industry,

I got to believe these players are taking creatine in anticipation. I know the quarterback for the dolphins, I think he's had three concussions this year. So his brain is so compromised right now, massive inflammation. and hopefully his medical team is at least considering high dose with his other treatment program to get there. And they should be taking it for the benefits on muscle, you know, and explosive power. Exactly. Yeah. Those, you know, high intensity moments.

You mentioned earlier about 0.1 grams per kilogram body weight. So how would you adjust, let's say, you know, you're taking 10 grams of creatine per day? And you're wanting the effects, the benefits of muscle, bone, brain, as do I. Right. However, I do not weigh as much as you. Right. So would you, is there a scalable amount per kilogram body weight you think would be something that, or is it hard? That's an excellent question.

And the answer would probably be no, because when we go on the scale, we don't consider the head. Even when we do dexas scans is headless. So, you know, if I'm 80 kilograms, I'm taking about, there's the sweet spot about, you know, nine to 10 grams a day. taking it from a weight perspective to correlate to the brain, it is almost impossible because we need to measure the weight. Where it's a hard tissue, it's a little bit of soft, but it's usually hard tissue. I think overall body weight, very similar to how people do protein based on lean mass or total body structure.

So you can take creatine based on lean body mass, but it's very difficult. You would have to have some type of imaging apparatus. So we just usually recommend it on body mass. They hit all the aspect. That makes sense. And it really does seem like there's this sort of. triaging where it's like, okay, the muscles consuming it. It's like the greedy one and then whatever's left over, maybe the bone. But if the brain's stressed, well, maybe the, you know,

it's funny how the body can figure that out. Like, you know, the brain needs it. So, you know, there was another, there's some interesting research that you also published kind of in the, in the brain area is sleep, right? And I'd love for you to talk about that study. I thought it was so interesting, these resistance training females, and you gave them creatine, and it really seemed to help improve their sleep on training days. Yeah, it was colleagues at University of Idaho, and Brown, and C.J. Prush. And they looked at young, healthy individuals, biological females. And we gave a pretty high dose here, five grams, plus we add a five grams of placebo. So 10 grams a day versus a 10 gram placebo. And this was done for six weeks. And they resistance train with a tonal home gym for two days a week. And the interesting thing is total sleep duration on the days they trained was substantially higher. I think it was about almost an hour compared to placebo. And again, these are young university age students that were taking, creating about five grams a day.

The nice thing is it also improved strength. There was no big fluctuations in weight gain, which was very, very interesting, no adverse effects. Now, there was no mechanisms assessed, but the logic was that on the days these individuals are training, maybe they put in more effort. So creatine helped recover the body a little bit more, allowed that body to be in repair mechanism a little bit more, and they slept more for about an hour on average more. We still don't know the exact reason,

but it is interesting that it improves sleep duration. And it's almost kind of the opposite of what we were just talking about. We were talking about if you're in this context where you're jet lagged, you're sleep deprived, and you take the creatine, and it kind of helps you get over that brain fog that like... Right. You know, you're just, you're not quite, you know, on your game.

Yeah. It goes against most of the comments I get where when people take high-dose creatine, some people say they feel like insomnia or intermittent sleep. And the theory there from a rodent model out of Belgium is that maybe the brain is recovering quicker, that it doesn't need to sleep as long. So we still need a lot of work to do. We need to look at different stages of sleep. I'd really like to look at some blood biomarkers,

indication of what's happening from an inflammation perspective. So there's a lot of work in that area. to go, yeah. You know, the other thing I was thinking about, Darren, was, I mean, so adenosine. Yes. Mm-hmm. Is there, is there a role? Because, I mean, it's downstream of ATP, right?

So I'm wondering if there's any role, because adenosine is something that does make you sleepy. Yeah, yeah. I always think of caffeine, the adenosine intake. Right, right, right. Yeah, no, it's possibly there. There's been a lot of speculation they thought also glycine is implicated and where glycine is involved in the, in the synthesis of creatine. So there's a lot there.

I think we'll talk maybe about homocysteine a little bit later in the methyl. So, God, there's a lot of areas to look at. And I think we thought we knew everything about creatine. And now it's taken on a new life its own. And again, I'll have a job for maybe 20 or 30 more years looking at this. Oh, yeah. Well, let's go back to the brain and talk about another. So we talked about brain aging, you know, traumatic brain injury, which is stressed.

We talked about lack of sleep, you know, and things that's stressing the brain. I guess, you know, neurodegenerative disease is a very stressful thing on the brain as well. be interesting to see if creatine can help in that regards. Although, again, prevention is always, it's always better, right? If you can help. Yeah, we've looked at the totality of limited evidence, and we're not seeing a lot of effects yet. There's benefits on young boys with muscular dystrophy, but that's a little bit different.

But when we look at ALS, Parkinson's, Huntington's, multiple sclerosis, all those dimensioned Alzheimer's, we're not seeing a lot of problems. There's been a few small-scale studies that show benefits. But when you look at a properly sample-sized study, it was a big one, five years in Germany, didn't see any greater effects. So again, maybe the dose was two. When I look at the dose, they use it very small compared to now our body of evidence suggesting higher dose, big sample size. And then, of course, what about the effects of the disease? Can Creighting really rescue the effects to give a significant effect?

We don't know preventing would be the number one thing. But we're starting to do a study in Northern Iowa to look at the effects of creating. 18 now in individuals with cognitive decline. And I believe there's a study out of Kansas that are actually looking at people with diagnosed Alzheimer's. So super excited to see these results if it can have any effect, even help one person, even regardless of a statistical effect, if it can have individual results. I think it's something we need to consider. Yeah. Okay. Well, what I was going to get to was the other part of, you know, brain disorders, you have neuropsychiatric disorders. You have depression, anxiety.

Those are also, unfortunately, very common nowadays, even in younger adults and adolescents. So there's been some interesting research with creatine and depression. Yes, there has. It's an emerging area, primarily to Utah. There's a great psychiatry group there. And as a caveat, no study has ever looked at creatine without antidepressant medications. So they're always as adjunct. So we're not saying creatine could ever replace anxiety or antidepressive medications.

But in these subpopulations, primarily females with clinical depression, it's really starting to have some speed up recovery and decrease some of the symptoms. The mechanisms are starting to emerge. It's starting to have a role primarily from Roans, and this is implicated in depression where they have reduced brain creatine stores. So maybe creatine supplementation can bring those levels up. There's potential to increase BD and F. So that has been implicated there as well. And there's another thing called neurofilament, our life. light chain. It's an indication of neuronal damage. And one gram of creatine in your diet has been

shown to reduce that. So there's potential there. But the overarching thing with antidepression is it increases brain bioenergetics, as you mentioned, and decreases again. Here we go. Mitochondrial health decreases reactive oxidative species. All these are implicated in all the brain and cognitive decline and primarily depression. So I'm really excited in that area. A big RCT needs to be done, though, because it's always being added to either cognitive behavior therapy or SSR eyes, yeah, for sure. And there's also a big inflammatory component in depression. There's the inflammation. In fact, there have been studies just in healthy young individuals where they induce inflammation. So, like, LPS, it can cause depressive symptoms. Yeah, yeah, and 100%. So the anti-inflammatory role

comes back there as well. So you'll start to hear these two words, anti-catholic and anti-inflammatory. People think of Advil or Tylenol from an anti-inflammatory, but creating seems to work. Some very similar in the Cox inhibitors as well, but it seems to decrease cytokines. So it could be something there to consider. Well, what's interesting is, you know, activated lymphocytes, T cells, consume just enormous amounts of energy, you know, and to basically become active and fight off pathogens. Right. And so I'm wondering if creatine is taken up by, you know, these immune cells and it maybe helps in some way. I mean, you're saying it reduces cytokines.

I mean, a lot of these T cells are, you know, producing cytokines to fight off things. But who knows if they have, if they have that energetic boost? Yes. How that could affect, you know, just, I would say, like, the broader, like, not having this huge kind of war going on, right? Yeah. Yeah, there's been some cellular data around the immune system cells, around creatine, specifically around T cells or macrophages. That's where the anti-cancer idea came in from creatine, specifically, like, I don't know. regarding lymphoma, leukemia.

So that's more in vitro. There's a lot of work needs to be done. But there's a lot of studies now to look at the anti-cancer potential of creatines, primarily from the anti-or-the-heightened immune system response. I wonder if there's any, has anyone ever looked at, you know, creatine's role in helping prevent infectious, you know, disease or respiratory illness, fighting off pathogens.

Like, just anecdotally, I supplement with glutamine. Okay. grams of, it's about 5.6 grams of glutamine I take a day and with creatine, five grams of creatine. And it has made a insanely big difference in my susceptibility to respiratory illness, which I have a, I have a little seven-year-old who brings home everything. Everything, okay, yeah. Yeah, it's like a vector. Yeah. And it's made a really big difference. And glutamine also is just, it's consumed by activated T cells. Right. Right. Right. Yeah. Use for cancer. Yeah. And treatment, sepsis and things like that. Yeah. So it would be interesting to see if there's any effect of both of those, but even just

looking at creatine as well. I know glutamine's been shown in endurance athletes, like, who are very prone to respiratory illness, like these marathon runners. It's really like they're really just getting to that catabolic state, right? Yeah. It's interesting because I was the first to do glutamine very high dose in weight training based on the premise that, you know, if it did have anti-cannabolic effects for cancer long duration and that was my master's thesis and we didn't see any effect, probably going back to our initial start, where resistance may not be stressful or catabolic enough in continuous duration compared to long duration events. So that's very interesting. Are you familiar with any of that workup of the long distance runners and glutamine?

There's like a few studies showing that these marathoners and stuff, they don't get as much, as many respiratory illnesses if they're taking glutamine. Yeah, no, I'm very familiar. I had to do the whole literature search. And it was a higher dose. And they also looked at it for sepsis, but the immune system response T4 and T8, I don't think, were nearly as high. And that was from long duration. And a young, healthy individual, they probably might not notice any effect. But again, that was the idea of the premise behind it was more of an anti-cadabolic. And why it didn't work for me, it was a non-essential amino acid. And of course, for protein synthesis, you need all the essential.

So it was a trying moment when I was doing my master's, but it works out in understanding it. Well, there certainly doesn't seem to be any shortage of interesting the things to study with creatine and it's like, you know, the field is exploding. So maybe someone out there will be looking at that at some point. Another really interesting area is the vascular health. And, I mean, there's just like, we were just chatting about a recent study coming out. Indothelial cells have transporters for creatine. They do right next to the astrocytes, which don't. So the endocel cells at the blood-brain barrier especially, but around all the smooth muscle, they do have the transporter. So that was one of the theories. Mike Ornsby just put out a study in Eric Rosson just

recently in older adults. And that makes sense because you look in a population that might get some benefits. And they show some very small favorable effects from creatine supplementation, either a week long or for up to four weeks, I believe. It was a loading phase and then down to about five grams a day. So it has some favorable effects for end of field, I think it was macro and microvascular function. So that might have potential down the role for cardiac rehab or individuals with cardiovascular disease or even subsets of that like type 2 diabetes or metabolic syndrome so that's an area to stay tuned for as well as emerging um and um same with type 2 diabetes there's potential there as well potentially improving glucose disposal again if there's more

muscle activation you have more glute four doorways maybe more glucose gets in so the Brazilian group is leading the way there so it's gone from just athletes to now looking at the health aspects for a lot of different conditions and interesting chronic disease has come to the forefront, which is very exciting. I've also come across some other like cardiometabolic health benefits, so glucose, but also triglycerides. With cholesterol in there too, can you talk about that? Is that maybe some mixed data? I'm not sure if everything is showing the same. It's totally mixed. Some show decrease in triglycerides, LDL, and then others don't see the effect. And again, I think it comes back when you look at those studies with the population.

If they're compromised as we get older, they're probably going to be more of an effect. And then the question is, was it dietary change that did it or was it the creatine itself? So that's one of the big issues when we give a creatine supplement. If you don't consider what they're already consuming or now they've initiated exercise compared to a true placebo, there is potential. The mechanism seemed to be from a triglyceride perspective. it seems to increase energy expenditure, some thermogenic potentially effect

that might explain why creatine decreases body fat in individuals 18 and above. But from the cholesterol perspective, we don't really know the mechanism there. And that's an area I'm sure that'll be exploding down the road. So creatine decreases body fat in combination with resistance training

compared to resistance training alone. Correct, yeah. Now small, about 1% or about 0.5 kilograms, there's some potential mechanisms there, but the thought is maybe increase in lean tissue mass, increase energy expenditure. So a lot of people are very cautious. They don't want to take creatine because they think it's going to increase fat mass. What the research is suggesting is increasing lean body mass, potentially decreasing fat mass. So usually the number on the scale barely changes after you do an intervention, yeah.

Well, going back to this loading phase and this higher dose, I mean, when I say higher, I mean, 20 grams. All these studies doing that, I mean, barring the brain stuff, is it really just to like kind of get their store saturated quickly because the study is you're not going to wait 30 days? So it's really, you know, all these other people trying to do this loading stuff, just kind of following the studies, but really they don't have to do that unless they're like tomorrow when I hit the gym and have that explosive power benefit. Yeah, if you need a really quick effect, like rehabilitation from an injury, ACL surgery, something where you're, you. you need to rehabilitate the muscle quickly or you're an athlete. The loading phase, to me, is not needed from a muscle perspective. Now, because we've talked about bone and brain might need a bit more. So now maybe the new daily loading phase is maybe, you know, five, 10 grams a day or a little bit more.

But that athlete, 20 grams a day for seven days followed by the maintenance, that is only ever been shown to have beneficial effects to muscle. There's been a few studies that have looked at it now from a brain, but again, that's from a different perspective. You just brought up a point that I was thinking of, and that is surgery or injury. How does create, because that's a stressful situation. We're talking about, you know, really creatine shining in that background of some sort of stress, whether it's training or, you know, sleep deprivation, but also, you know, you can have something like an injury or a surgery where you're planning a stressful event. Yeah, it's multifactorial. The studies that have looked at it from a rehabilitation perspective. perspective, creatine seemed to increase these thing called myogenic transcription factors.

So what are boring your audience, these are little guys that sort of tell DNA to sort of increase proteins in a quicker way. So these myogenic regulatory factors went up during rehabilitation. And then we did a study when we got individuals to put on a cast volunteer and creatine seem to maintain strength. Going back to the mechanism, it probably has to do that reduction in protein breakdown or the anti-cadabolic anti-inflammatory effect. Again, we don't think it has anything from a synthetic perspective because creatine doesn't,

but it has been shown to increase satellite cells, which are native for recovery and rehabilitation, growth factors, IGF1, and decreases myel statin, the one that increases protein breakdown. So all of these factors come into play. It's like the caramel secret. There's a whole bunch of things that go into that chocolate bar. Creatine seems to work in a very variety of ways. And then again, on the other side, it's certainly been shown to decrease react-aboxative species. So it seems to have more of a preservation to the cell effect.

But from an injury perspective, it seems to speed up recovery. Do we know would it speed up recovery if you took it before surgery? The jury's out on that. We'd have to do ACL surgery or studies on that long-term clinical trials. We see a bit of promise in osteoarthritis, but not a lot of other ones. And because basically the studies haven't been done. And what's the dose on some of those? These are usually the loading phase with a slight maintenance phase,

or if they're looking at it from a cellular perspective, it's usually just the loading phase, seven days pre-post, they'll do biopsies or cellular data. So the 20-gram a day loading phase, and then the maintenance phase being about five? Yeah. Okay. And if someone's already taking, let's say,

five or 10 grams a day, and then they're going to have a surgery, do they still need to do the loading, or should they just continue on? I would just continue on, or even slightly a bit more, because when the tissue is under trauma, you get heightened inflammation,

reactive oxidative species or stress, and then protein breakdown. So maybe it could help speed up your ability to recover quicker. We don't know any of the effects of creatine on cross-education where if someone has an immobilized limb and they train the opposite limb, we don't think there's any effect. It's a great study to do. And that could have huge applications for professional athletes or individuals that have or waiting for ACL surgery. Instead of sitting around all day, go to the gym and train the healthy limb. And maybe creatine could potentially increase more drive there.

It's a study I've always wanted to do. We just haven't done it yet. Okay, so it sounds like, you know, in most cases, you know, the creatine plus the training, resistance training or endurance training, is the key. But in some situations when there's just a massive amount of stress from, you know, perhaps an injury or surgery or sleep deprivation, and creatine can shine on its own. Is that correct? Yeah, there's actually a small body of research in healthy individuals young and old that say creatine without exercise actually improves muscle performance.

So those that I think of disuse, bed rest, immobilization, sedentary individuals, maybe they have functional mobility issues or people that don't know or have access to weight training. Creating by itself has been shown to improve muscle performance, improve strength, endurance, their ability to perform repetitions to fatigue. Primarily in older adults, but there's been studies in younger individuals. And that's sort of where creating research blossom. All the initial studies were very acute. seven days, the loading phase, and then we saw improvements over time on muscle performance. And that sort of paved the way to lifelong interventions, which include exercise, is the main thing, yeah, for sure.

Yeah, exercise is definitely the most important thing. But I know I'm going to ask you to speculate a little bit here, but let's say you do have an older adult who is sedentary and, you know, just getting up out of a chair is hard. It can be challenging. Do you think that even supplementing with creatine in that regard maybe help them a little bit more? Two meta-analysis has been performed, both in Canada. We were fortunate to do one, Stu Phillips. I know it's been a guest, I think, for you.

And we've done two meta-analysis. And then when you look at creatine in older adults with resistance training, though, it did improve tasks of functionality, sit-to-stand. So getting out of the bed, off the toilet, getting out of a chair. Again, that was with exercise. Without exercise, nothing has been there. So I would love to say yes. But again, the movement of exercise. But the nice thing is for those willing to do, you know, is it resistance bands?

Anything that you feel mechanical stress, creatine will give you a slightly greater benefit. But for those that are in jeopardy of chronic disease, I think you should consider it. Absolutely. So another question of mine, you were talking about where creatine. transporters are where it's synthesized. You mentioned it's created in the liver and the brain. But you mentioned it goes to the testes. There's a little bit down to the testes.

So any organ that only has the enzymes to make it, so since it's made in the liver and brain, it'll be dispersed to other areas. So the interesting thing is the area that it's created, it goes through circulation to different transporters. So male fertility has become a big issue. And there was a thought that, oh, creatine, since sperm relies, it's a flagella.

So since sperm are relying, movement on creating so much. Maybe it's down-regulating sperm production and my good colleague out of Norway, Sir Joshiuk, who's one of the world's best creating researchers, has looked at this in many forms and not showing any effect of anything. It improves the vitality and mobility of sperm. So that could have huge implications for male fertility. So yeah, it's an area that you probably would never think of, but it's an area that has shown some evidence-based research behind it. And that's, that was going to be my question. Is it affecting fertility? Yeah. It's going it's going to testes. It's so again, that could have applications for

individuals trying to start a family or male fertility issues. We don't see any down regulation. There's a thought of taking in supplementation. Maybe that'll give your brain and liver a bit of a break. And there's evidence to suggest that maybe if you're taking creatine on a daily basis, those organs don't need to make as much because you're offsetting that. But again, when you stop supplementation, it goes back to baseline or it doesn't disrupt any of that. And the good thing is from a fertility perspective, there's no evidence to suggest it downregulates sperm motility health. We can talk about hair follicle loss and thinning, the same idea if the viewers were looking at me. But that was the same idea. Maybe creatine

was causing baldness. So maybe it must be doing the same thing to sperm. It must be killing off the cell. And we just don't see any of that research, yeah. Well, good. Yeah. Well, let's get into those myths. Before we get into those, I kind of wanted to, we've talked a lot about adult. We've talked about older adults, the effect of creatine on many different tissues in those populations. But at the start of this podcast, you said something that caught my attention. And that was, you said children and you see pregnancy. And, you know, I'm a mother of a seven-year-old who's quite active, you know, plays soccer and tennis. And I often wondered, you know, can children take creatine? I mean, obviously weight adjusted. But is there any, has there been any, you know,

evidence in children? Has anyone looked at children? besides the TBI study. No, there has. Chad Gersick and, and Yagam at the Mayo Clinic here in the United States are the two most profound researches in that area. And they've looked at study after study in children, young children, adolescents,

and there's no adverse effects. And why would there be? If our body doesn't like it, we just excrete in it. There's a big push right now in some states trying to ban creatine and younger individuals, and they're just not looking at the evidence-based research. So overall, there's no adverse effects. We still need to do a little bit of blood work,

but it improves health, agility, coordination, muscle mass. There's no reason. And so that's why I'm one of the big proponents. I argue, including the fetus, why someone couldn't take creatine, if we're already producing it, it's not like caffeine a drug effect, or we're already producing it. That's like telling people you can't take protein in your food or supplement. That's just nonsensical.

So I'm one of the big people who say anybody can take creatine. Even if you have chronic kidney disease, there's some benefits It's because it'll help the kidneys absorb creatine. And so right now there's potential benefits for children. For pregnancy, Stacey Oliver in Australia, is the leading researcher there in Abby Smith-Rine in UNC. And so they're actually looking at fetal development, having more brain bioenergetics for the female. We now know that the transporter from breast milk is there. And then when you look at habitual diet, again, Sir Dawson has looked at Anne's data.

And for those children taking less than one gram, it leads to, to a lot of potential detriments later on cognition impairments, lean body mass, bone mineral. So, I mean, a serving a salmon is about three to four grams of creatine. A hamburger would even have that. So, again, in habitual diet, unless the child is vegan, they're probably getting a little bit of a amount. And the dose, two to three grams, or you can even do 0.1 gram because they're so much

smaller. So if I had a child, I just have animals, a dog. I would give my children, creatine, for sure, as early as possible, because I'm looking at brain development, bone development, muscle, immune system. It has all those benefits. And keep in mind,

if our body didn't like it, we just make expensive urine. Like, we just excrete it. People see this when they go for their blood requisition. They see creatinin on this blood requisition form, and that's all it is a byproduct. So it's very safe. The safety profile is exceptional.

Wow. I mean, so a few things here. So with respect to the dose with children, so you said 2 to 3 grams or 0.1 gram per kilogram body weight, or is that applicable to the children as well? I mean, if you want to do 5 grams or more, I don't see any reason why not. Do they need to be taking the 10 and 20 grams? We just don't have the data to support that. But a low dose, 2 to 3, 5 grams is totally viable.

And vegan kids, probably even more so, right? And then pregnancy, has there actually been any human data? looking at women supplementing with creatine being safe? Just subjective questionnaires, how they're feeling, things like that. It's too dangerous in a sense because we just don't know yet. And to get an ethics board approval at a research institution is very difficult, even for teenagers and adults under the age of 18. So I know Stacey is in our big myth's paper is concluded that we need more randomized control trials.

A big trial because we definitely want to get this one right and make sure it's 100% safe, not just for the unborn child, but also for the mother. So there's going to be a lot more data to come out. But overall, there's no reason to suggest there's any issues whatsoever. Yeah. And again, coming back to the vegans, that comes to mind, because you're talking about women who are pregnant, who are only relying on their liver ability to make creatine, right?

So that would be phenomenal to get a study like that done. But do you think it'll be approved? I think down the road, when they look at the hypoxic environment of fetal growth, I think it probably will get approved, but we're going to need a lot more clinical data to suggest it's safe and maybe a pilot study in that. The issues with pilot studies are usually low sample size, so then from a feasibility perspective, it might be have, it actually, I can see it in a multi-country to get a lot of people in different countries to come together and make the sample size that high. So that's something to look forward to as well, especially in addition to the neurodictory. neurodegenerative diseases, you know. I know I'm jumping all over the place here, but going back to the kids, you mentioned, the creatine supplementation was shown to improve agility. Now, why is that? Is that because of the type 2 muscle fire? Or the motor unit recruitment or maybe muscle activation. So there's a whole plethora of ideas from a balanced agility, a coordination perspective. It could be that they're able to exercise at a higher capacity, sort of almost hyper-accelerate muscle development. Those are all the things that are. in its infancy to look at. Again, there hasn't been a study to look at blood biomarkers for, like, liver and kidney

enzymes, but I would be very surprised if a low-dose study was done and there was any issues, yeah. Okay. Well, getting into some of the supplementation, you know, questions, and I think we've kind of touched on quite a few, but I want to kind of dive a little bit deeper. You first mentioned, of course, I think a lot of people that are familiar with the creatine-filled know creatine-minohydrate. Creatine-minohydrate.

Is that still the... gold standard for supplementing with creatine. If so, why? Yeah, it's the only standard. So when I say creatine today, it's monohydrate. And the reason being is based on its safety and efficacy. So monohydrate means that creatine is linked to water. So when it comes to your GI tract, the water diffuses in the hydrochloric acid of your stomach. So that molecule, it's very unique. It can actually get through our small intestine intact, unlike protein, which gets degraded. Creatine is very unique. It's because the acidity of our stomach is actually two acidic. It doesn't like it so much.

So it gets through. And then when it gets in our blood, the creatine that you're taken from supplementation monohydrate is identical to what's being synthesized in the liver. So that's likely why the safety profile is so exceptional. Now, there's probably 50 different other market of forms of creatine out there. First, it has to be creatine when it gets into your blood. So whatever market of form you want to try, make sure it is creatine getting into the blood or it's useless. Second, no other creatine has ever got. into the cell and had superior effects. There has been a few studies to look at creatine hydrochloride and with the ester bond

to get sort of through the phospholipid bi layer of your cells quicker, but no study has ever showed it to be safer or more effective. So I know monohydrate has been boring. It's been around since the 1990s. But in my opinion, why mess with a good thing? And probably because the efficacy and safety behind it. Well, why do people turn to these other forms? Is it because of GI distress?

that can be experienced with monohydrate. Is it, is, it seems as though, like, I get mixed reviews. I'll talk to, like, almost like 50% of people say, hey, like, I get GI, like, stomach distress, GI problems if I take creatine monohydrate. Some people have to go to another form or they have to lower their dose. Right. Why does that happen? Are there any ways around that?

Is there, like, any tricks to improving, you know, the ability of your stomach to digest it? I think 99% of it is marketing. I think people get conned into buying something that's more expensive or flashy. And maybe they're making some errors with the monohydrate. They're taking it probably from the loading phase. So creatine monohydrate has been shown to increase intracellular water. So it's based on the doorway. It sort of brings water with it.

And some people get GI track irritation or some weight gain and other forms of creatine are marketed to not do that. I argue if it doesn't do that, it's probably not. creatine. In other words, creatine is osmotic. If you're taking a form of creatine that doesn't increase intracellular water a little bit, I would question the validity of that type of creatine. So I'm in the camp of 100% monohydrate based on the mechanisms, the structure of the molecule, and the efficacy behind it. Do you need to spend more on a fancy type of creatine? If it works for you, I'm all for it, but at the end of it, I don't think you need to. Well, the question is, like getting back to what you said, if it's not increasing intracellular water, then it may not be doing what it's supposed to do. And ultimately, that's the whole point. So, you know, the question is if you're taking creatine HCL or, you know, there's liposomal, liposomal creatine or there's a GNC brand that's like it's an AMP creatine, HCL. So it's like, you know, at the end of the day, the bulk of the research is done using monohydrate.

And 99% of all the thousands of papers. And the one I hear a lot is there's a better bioavailable form than monohydrate. And I'm like, wait a minute. Creatine monohydrates bioavailability is near 100%. There might be a little bit extracted from the gut. So how can you get more than 100%? And then if it even got into the cell, I've never seen a study to show that it increased protein synthesis or had any of the effect on satellite cells or whichever. I'm only aware that it increased creatine content.

So the good thing there is in those cells, I think it was hydrochloride. That means it is a form of creatine, but did it lead to performance benefits better than monohydrate? I've never seen it. So I just caution people, just don't get con in a lot of these marketing forms, really expensive forms when monohydrate is the one true. And it says, I'm going to Germany and we're going to be talking for four straight days in two weeks, a monohydrate.

Why? Because that's what all the evidence-based researchers need. need to talk about because it's the only form that seems to be very viable. Well, aside from the marketing, I think some people, I know some people personally that even taking like a five gram dose of creatine minohydrate experience like stomach issues. Yeah. So what can those individuals do? Yeah.

So I recommend these people, and it happens quite often, the sort of microdose. So I would say if you're taking five grams, take about two and a half grams in the morning, wait at least six hours and two and a half grams later. Also take it with food. So I put, I have, for breakfast, I'm sort of boring, but I take Greek yogurt, collagen protein, weight protein, blueberries, and I usually put 10 grams of creatine in my yogurt, but some people can't. So if you want, you want to put two and a half grams, but if you want to start as low as three grams, one and a half in the morning, one and a half in the evening, or you could do one and a half in the morning, another one and a half with lunch. With food seems to increase the absorption because of the insulin from carbohydrates and or some of the effects of fat. most times is when people just drink it with water.

I find that's where they get the GI track irritation just because it's going through the GI track quickly, taking water with it. But with food, whenever we tell people that, they say it all went away, yeah. So that would be an interesting experiment for someone to try that's experienced GI problems to try taking it with food,

and carbohydrates seems like it might be really good. Really good. Okay. So, and then the other thing is, you're talking about like lower dose, microdosing and spreading it out. does that, is that something you'd have to do like forever or is that like to kind of get your gut used to it? Or is it? Kind of both.

It's almost from a consistency perspective. But there was a study done in 2003 where they showed a smaller, more frequent dosages were better than a super large 20 gram bolus dose. So it's almost like this retention idea. But taking, you know, multiple 1.5 gram dosages or wherever it might not be feasible on a daily basis. But, you know, a quarter of a teaspoon, two and a half grams, whichever, that would get your body. used to it, then slowly titrate up. So the best way I usually tell people is start with three grams, one and a half, morning and evening, then move it up to five, two and a half, then move it up to nine, but then I say three, three and three, and then eventually you're sort of getting tolerated. It's

like caffeine, starting with a small coffee and working up to a large. Your body gets used to it, and then there's more in circulation, yeah. Well, you said these smaller doses were more effective at what? The idea was that it would get into the blood, maintain peak or plateauing plasm. levels and hopefully you can retain more than some being excreted as creatin. The thought was a super mega bolus dose, so maybe 20 grams. Now there's new evidence that can get into brain, but there's logic like some of that would be cleared from the kidneys and because the muscle may not be able to take that in all at once, you know.

Okay. So dosing studies need to be really done, yeah. Well, this kind of goes to another question I had, which was we talk, we've been talking a lot about dose. Right. But it's also about, you know, if. If you're taking the cycling of it. So, you know, some people like to slam their protein shake right after a workout.

Is there any reason to worry about that with creatine? Because you're talking about repudent, like saturating the stores. It seems like it's a, okay, well, you're trying to saturate the stores. I don't know that cycling around that's going to do anything. So that's a two-part answer, I think, from a timing perspective and cycling. So from a timing perspective, unlike caffeine, we don't think the timing really. plays a major role. There is one area that I would just recommend. It's post-exercise or pre-exercise. And the reason for that is that we think blood flow or transport kinetics is turned on with muscle

contraction. So if you want to take creatine within an hour before you work out, or I drink five grams during my workout, or right after, that seems like a very viable time. But for the viewers, the timing seems to be irrelevant. But that begs the question, what about cycling? So if you've been taking creatine for maybe two months, three months, it's very likely your muscle stores are sulf saturated that when you're consuming the extra creatine, that you would just be excreting it. So some people say, hey, I don't want to do that. I don't want to waste my money. I'm going to cycle it. I now argue you should take it on a daily basis because of the emergence of like, okay, I'm okay with the muscle being full. If someone's going down the toilet in urination, that's

okay. But now I'm hoping our bone is taken in some. Our brain is taken in some. So we used to be in the camp where you just need creatine on the days you work out. Now I say take it every day and hope some is going to go to your brain and muscle, or sorry, bone, because on the days you're not working out, your muscle is not sucking it in as fast. Maybe those other tissues are getting replenished. So do you think it's better to take creatine, like you're taking it in the morning if you're going to work out in the morning, but what if you work out in the evening? Do you want to take it in the evening?

Yeah, I would take it. Any in close proximity to exercise, I would take it. So if you work out twice a day, you're taking creatine twice. today. But if you take it in the morning and then work out later in the night, that's totally fine. We're not seeing any big differences. But I'm a big advantageous proponent of taking in close proximity to exercise. And that's within an hour pre-imposed. Okay. So some of the other questions are interaction with other supplements, other compounds. for a very, very, very, very long time.

I put creatine in my coffee. I put everything in my coffee because it just masks everything. I just didn't do it in one. I've never really had any GI problems with creatine supplementation myself. But I'm not sure that I'm supposed to be doing that. Yes, so I'm one of the rare people, and most people argue against me, I don't do it either. So there's two ways to look at this. The thermokinetics of creatine and caffeine do not oppose each other, but from a cellular perspective, they certainly do.

So remember when I talked about the circoplasm reticulum, caffeine likes to release calcium, but creatine likes to take it in. And some really good research of Europe have shown that the two molecules oppose each other from a muscle relaxation time. But the dose of caffeine seems to be the most important factor. If the dose is over 250 milligrams or even higher, that's when it seems to have the interference effect. If the dose is lower, it doesn't seem to have an interference effect. So the average large black coffee from Starbucks might be 3, 400 milligrams of caffeine. So if you were to put your scoop of creatine in there and sip on it for hours, you probably won't notice an interference effect in a few times. But if you did that every day for months, you might notice a blunting effect.

If you did it a one-time shot, you were doing an experimental trial, you might not notice it. So I never combine the two. I always have coffee early in the morning. I love coffee. And then I wait at least two hours before I take my first thing at creatine in anticipation of those cellular interference. But other people, other big-time creatine researchers say, no, they take it together. If it works for you, great. But there's something there that makes me a little cautious.

And we've done the only training study. It was underpowered. but they did interfere with each other. Yeah. Okay. Is creatine heat sensitive? It is. It denatures a little bit.

So if you warm up the solution, some people don't like the grittiness. So when the temperature rises, it will decrease the, or increase the solubility, if you will. It will not degrade it to creatin unless it's super heat it for a long period of time. So if you are putting it in your coffee. The heat is not the act. It seems like the caffeine molecule might be the one that might interfere with it. Okay. So you don't have to worry so much.

much about it being in like a hot liquid like tea or but if you had like a normal k cup is 80 milligrams there should be no interference effect you could have two of those but if you get up to it like a large coffee so a normal cup of coffee here in the united states maybe 80 to 100 milligrams should be totally fine yeah yeah okay um well this is all really good information i think addressing some of these the the myths and you know questions the misconceptions i mean all those because you've published a couple of meta-analysis or review articles, I guess, or review articles on this. And so you talked about, let's talk about the fat gain, right? So that was kind of when you touched on a little bit. I mean, especially women, women. And is it really just because of the lean mass increase?

Yeah, there has been some cellular animal data to show that increases thermogenesis. But overall, the decrease in body fat is there, but it's very low. So don't run out and buy creatine. I think you're going to lose 20 or 30 pounds. We're seeing at best about a 1% decrease in body fat and about 0.5 kilogram reduction over time in combination with weight training. Now, that could have implications for obesity, type 2 diabetes or chronic diseases down the road. But the nice thing is a lot of people had a myth at creating increased body fat. We don't see any evidence to that. Okay.

So it's doing the opposite. The hydration myth. So what about you hear, I've heard some people talk about cramps. It's causing cramps or dehydration. It's opposite. It's superhydrates the muscle. So it could be from the sodium potassium pump or disruption from dehydration. But if you're metabolically dehydrated, creatine is not the cause.

If anything, creatine is trapping water into the cell. It also has been shown to increase extracellular water and total body water in some studies. So from a cramping or dehydration perspective, it's actually opposite. So for those exercising upcoming summer months, NFL football players, two-day practices, in July, creatine might actually help hydrate the muscle and decrease the chance of muscle cramping or dehydration. Oh, that's super important. Interesting.

Has anyone directly looked at that? I think Rick Kreider's done some studies with that when he looked at NCAA players, but a lot of people don't take the myth was that it was dehydrating and we just don't see that. Where did that myth come from? I think what happened was in the inception of creatine research, a lot of people were not drinking water or going through some practices like wrestling, wearing rubber, suits, extreme hydration. They happen to be taking creatine, and then they said, well, I'm on creatine.

Since it traps water, therefore my cells must be exploding or muscles, and therefore it was causing cramping. And we just don't see any evidence behind that, yeah. Okay, so it was like a correlation thing. Yeah, it was the opposite, and it sort of went with you. Okay, we've talked a lot about the kidneys and you're talking about creatin, and I'd love to talk about. That's, that's one that I hear a lot, that it can, it's bad for the kidneys, it's bad for the liver.

Can you address that? It's probably the biggest concern. So we've looked at study after study and rest assured from a clinical perspective, creatine does not adversely affect renal liver or cardiovascular cells. And we've given 11 grams a day in postmenopausal females to a population where their organs are under a little bit more stress and no adverse effects. The theory here was that when creatine enters your muscle, when it gets metabolized, it's non-enzymatically metastomatically. metabolizes something called creatin. And those watching say, oh, wait a minute, I just saw that my doctor checked that off.

And the reason they do that is creatin is a byproduct. It's supposed to be filtered by the kidneys. So if you have high blood creatinin, that means your filtration rate in the kidneys is not working properly. Think of your Britta water filter. It's clogged up. So unfortunately, when a lot of people go to their doctor, they don't say, hey, to the nephrologist or GPM on creatine supplements, because it's logical that if you're taking creatine, your creatin might be acutely raised, and then that causes a false positive if your estimated filtration rate is low.

So your doctor says whatever you're taking, stop, it's killing your kidneys. We know that's not the case because when they do stop, their kidney function just comes back. So it's just the metabolism of the molecule. Okay, well, this is really important. I've had a few people reach out to me and tell me that their creatin was elevated, and I don't think they told their GP that they were taking creatine or creatine. And so the idea here is that it's the metabolism of the creatine to creatin that's being excreted through urine. That's right.

So creatine and fossil creatine don't leave the muscle. It gets left in the muscle as creatin. Creatin can also be raised with a very, very high protein diet, excessive exercise, or dehydration. But make sure if you're on creatine supplementation, tell your doctor, because it's logical that your creatin in the blood will be elevated. that's just from the metabolism of the supplement. Now, if your liver enzymes are through the roof, that could be an infection. So again, make sure you go and get medical screening and guidance. But every time we hear this, it's usually a false positive.

I see. False positive. Okay, so it's really good to talk to your physician about that. Baldness. That's one. That's one. It was that rugby? Was it rugby players?

Yeah, yeah, yeah. I was going bald way before I started taking creatine. So a lot of people say, oh, well, obviously. And it's interesting. It was a great study in a sense that they looked at a novel concept. So they had elite rugby players do a crossover design. And a crossover design is really powerful. That means the group gets both placebo and creatine.

So it really controls for diet, genetics, hormones, things like that. And when they took 20 grams a day, it might have been even 25 grams a day for seven days during the creatine supplementation phase, they increased the hormone, dihydroxy, testosterone, or dhhty. and most people say, oh, I think I've seen commercials about this. It's a surrogate of testosterone, but it's been highly linked to hair follicle loss and thinning from a cellular perspective. They measured it in the blood, so the correlation, you know, it's just a surrogate. But when they went up, I think it went up by about 57%, but it was still within the physiological range. And what I mean by that is when you go to your doctor and they measure your blood glucose and it comes back and the doctor says, no, it's within the normal range.

cholesterol is in the normal range. Even increasing by 57%, I think that was the number. It was still within the normal range. When they were on placebo, it increased by about 40%. So everybody says, whoa, hormone went up. Correlation, causation, everybody was freaking out that this hormone went up. They did not measure hair follicle loss, thinning, cross-sectional area, no dermatologist was involved. But a lot of people have run with this.

And to this day, they cite this single study that even didn't look at free test testosterone, there was no increase. So just because D.HT went up a little bit, and they started lower, so there was more room to improve, people think it causes baldness. I've assessed easily over 1,000 people. Males and females, not a single person who said, hey, whatever you're giving to me, double blind is causing my hair to fall out. And I got to believe a participant would say, I'm not taking this anymore.

My hair's falling out. And I do know, I can't talk about it because I'm not sure, but I do know that there's been a paper submitted. that have looked directly at hair follicle loss and thinning with creatine supplementation. And that was going to be my next question. I mean, first of all, has anyone replicated this study? It sounds like no. No.

And has, second, has anyone, you know, directly looked at hair follicle? It's in review right now. But if I had to have a magical guess, it doesn't affect hair follicle loss or thinning. So if people are watching me, they're like, oh, and then they look at other creatine researchers, I can blame my parents and primarily my mother for that for the maternal DNA. But then there's other people with false heads of hair, so it can't be a cure. It's like carbohydrates cause obesity. That's nonsensical.

It's everybody's different. But I still get this on a daily basis, both from males and females. They don't want to take it or their hair is thinning. And I'm really glad that this study is coming out because the way we should have answered this is we don't know. Until a study emphatically says, no, we didn't see any of the effects. we would have to say we don't have any evidence to suggest it does and we don't have any evidence to suggest it doesn't. And even when this study gets published, we'll probably have to do multiple. But it just has never been done.

And no rodent studies? No rodent studies? Nothing. I think it's an area that people said no one cared about and then all of a sudden everybody cared about it. So is there any other really, I think, prevalent misconceptions or myths that you want to talk about or know about? There's so many. I think the big one that. The big one we're getting a lot is does it increase hypertension or blood pressure?

Because if it increases water into the body, could that have any effects? And we're not seeing any adverse effects there. The other one is we do not see any evidence that disrupts sleep. Although we talked about the study earlier, it doesn't have any negative effects there. And then cancer. So this is an area that is difficult to answer or talk about because we just don't have a lot of human cellular data. From the in vitro data, we're not seeing any in humans, at least, from recommended dosages, any malignant growth or any cancer promotion.

If anything, we're seeing anti-cancer properties from improving anti-inflammatory responses there. And in our latest paper, The Miss and Misconceptions Part 2, one of the world's best creatine researchers and medical doctor, Mark Turnipolsky, read really good section on that. So if anybody's interested, read that, and it seems to have some potential for cancer rehabilitation. When you're looking at tissue loss, caxia, it seems to have some beneficial effects there. and I'm collaborating with Kieran Fairman in University of South Carolina looking at prostate and breast cancer rehabilitation. So I think you're going to start to see some medical applications growing more than just young healthy individuals.

Again, the common denominator is all these are sort of asking something for help. It's either rehabilitation or prevention. And that's where I think creatine has really changed. It used to be for just young individuals who are healthy. And now it seems to have some of these health aspects. So very exciting times to be talking about it. Yeah. Are you familiar with any of the research of Dr. Carey Kurnier?

Out of Universe Alberta. Yeah. So cancer there. I don't think he's ever looked at creatine, but he does a lot of community base yet. Yeah, I just had him on the podcast. And he was, you know, he does a lot of exercise, the role of exercise in cancer treatment. And, you know, not just aerobic, but resistance training. So that would be interesting for you guys to have a discussion.

The other thing that came to my mind that I now remember, I've, I've, heard a lot of people talk about is creatine supplementation increasing their urination, particularly during sleep, like having to go urinate frequently. I just answered this question on Instagram. So an individual, because I said I take a pre-sleep sometimes and that'll keep me out peeing all night and I said, oh, actually, that's interesting. So in this misconception paper as well, there's a section there that the creatine molecule, whichever, does not increase urinary output.

But people thought since it's creating creatin and you need to filter it, we think it's the increase in fluid ingestion that you're probably taken either with exercise or what is usually recommended with creatine. That's actually a myth as well. You don't need to increase tons of water consumption. But the molecule doesn't cause an increase in urination. It's not a diuretic or it doesn't increase urinary flow that way. I do hear that a lot. My logical guess is you're probably putting the creatine in eight ounces of water and you're probably drinking more water or exercising. And that's one of the things.

But there's no evidence to suggest the molecule itself stimulates urination. Okay. Well, that's good to know. I think we've covered a lot. There's one area I did want to talk about. And we talked about kind of saving at the end because there's more speculation here. And this is just an interest of mine. I remember several years ago, a former colleague in mine, Mark Shiginaga, was talking to me about, you know, creatine production in the liver being one of the biggest.

biggest sort of sinks for methylation. And that's because you need, you need methyl groups to produce it. Yes. And as a byproduct, you also make homocysteine. And so he was talking about some, at the time, I think it was pretty preliminary, but some evidence showing that if you did supplement with creatine, that the enzymes and the liver that do produce creatine were, there was a feedback. And they sensed that.

and they didn't use so much of the methyl groups were being shunted to other methylation pathways. And so I'm just wondering if you've come across any evidence looking at creatine supplementation and homocysteine levels, for example. Yeah, the most studies don't support it. And that's where we got to the point where, oh, if it doesn't decrease homocysteine levels, then maybe exogenous creatine doesn't reduce our natural creatine synthesis. the studies that show it does are in animals, and I believe there was one human trial, but the majority shows it doesn't have any effect. Now, that could be the dose there, but you're totally right. Methynein is donating, I think it's 40% of our methyl groups to creatine synthesis.

So if I'm taking more dietary creatine or supplementation, why use that? Why not decrease the amount being synthesized? Because that has huge implications on anethyl health and cardiovascular health. But ironically, it's not even equivocal. The majority suggests it doesn't decrease. Maybe the studies are not long enough, or maybe they're not in populations that need it as much. Right. So the question is, like, maybe you need to start with a population that has elevated homocysteine.

Correct. Yeah. Yeah, yeah, yeah, yeah. Because it's hard to detect small changes when you already have. And it's easy to do. You just look at some of these blood biomarkers, but there's not a lot of studies. There's probably less than 10. Majority in rodents, you and human.

And I think last time I checked, it was probably seventh against three supported it. So there's a lot of methodology issues there. Well, maybe someone will look at it. Yeah, absolutely. Especially as we start to get into the vascular health, for sure. That's a huge area. So I would be shocked if more studies don't come out in vascularity health or angiogenesis or anything like that, potentially looking at homocysteine as a surrogate marker for potentially explaining some of the effects.

Yeah. Because if homocysticine comes down, you would speculate endothel health would go up. in some of those things, yeah. Right. Well, if you talk to any researchers doing vascular health research with creatine, that'd be great. So I think we've covered pretty much just a lot of ground, really interesting stuff. Did we miss anything? There's anything that you wanted to discuss?

Geez. No, you hit the caffeine one. I knew that was an important one for people. Are there any other interactions with other? You know, let's go back to the carbohydrate one because I think people hear this. The best way to augment creatine into the muscle is with muscle contraction, which is great. But the dose of carbohydrate is shown to sort of increase it is almost over 75 grams. And I think most people are not going to consume that.

Protein is a great one to add creatine too because it's insulinogenic as well. So combining creatine and protein will probably give you a superior effect. There's been two studies that show you get a greater increase in muscle performance and lean body mass when you combine creatine with protein. In this protein case, it was weigh protein. It was only about 30 grams. So now when you're looking at your post-exercise meal, pre-exercise meal, I think creatine and protein are good friends. Consider them as something that you may want to consider,

especially in your post-exercise meal or like I take at least 50 grams of protein with breakfast. I put my creatine in there. I don't need to worry about it until later on, and then I usually drink it or have it with a meal. Most creatine is tasteless. You can put it in food. That's fine. You can, you know, the heat would denatured a little bit, but it's something to consider it. I'm glad you brought this up because to clarify, maybe some people were confused when we were talking about this earlier, the timing of the creatine around exercise.

It was to improve the uptake of creatine into muscle, and that can be done before or after, like, in close proximity to the exercise. Yeah, and if you don't want to work out, keep in mind, it still accumulates, maybe just not as quick. So the study in 1999-2 was very elegant. they had one leg exercise and that increased creatine uptake by about 37%. And in the other leg that didn't exercise is still improved by 25%. So at the end of the day, the person at home watching TV, taking creatine, whatever, for some time, they're still accumulating, but exercise unlocks a lot of the doorway, so to speak, that's sort of get it in there more.

So it might give you a little bit extra benefit. And that's why I say approximate exercise is a very viable time to take it. But if you're looking for the benefit in terms of improving or increasing your training volume, in, you know, the explosive power, the strength, that it doesn't necessarily have to be timed around the exercise. Just take it. Just take it. Like, if you don't want to take it all at once, take it in small dosages. I think consistency. I now recommend take it every day. Just get it like a multivitamin, whatever you're doing, but just keep in mind. It's giving you not only exercise benefits, but I'm really. really happy to see the emergence of the health benefits. And I think in today's society,

we could all use a little bit of help. Yeah. It sounds like there's no reason not to take it. I mean, there's a lot of benefits that the muscle, the bone, the brain, very, very convincing. Third-party testing, you can look for companies that have been vetted that are, that are, you know, reliable brands. And that's always like a good, too. Yeah, that's a big thing that we didn't talk about. So if you are considering supplementation, again, you don't necessarily need it if you're getting it through your diet. but make sure third-party tested, I would really focus on monohydrate based on the evidence-based research. Monohydrate has grass status. Creepure is from Germany.

It's the most scrutinized. It has less purities. That's an excellent form of creatine monohydrate. Make sure it's pharmaceutical grade. So all these things that you would do by putting something in your body, just do a little bit of homework. But if you're not seeing certified safe or third-party tested, that's something to be a little cautious. And the other thing is, when you're buying a compound or ingredient, with a whole bunch of ingredients in there.

We don't know if the creatine is going to be effective or not in these pre-workouts, things like that. There's no reason to suggest not. But when I've been talking about creatine in our experimental studies, we're giving 100% pure creatine. We're not giving it with 10 or 12 other compounds that you've got at a grocery store, things like that. But again, so there's a little bit more work that needs to be done if you're considering a multi-ingredient compound. Yeah, and that's a good point because we were talking about taking, you know, 10 grams a day, which is your sort of go-to and now soon will be mine. Okay.

You don't want to take 10 grams a day of some mixture of things, right? You want it to be just creatine. Yeah. Now, you mentioned creatine pure. Creia pure. Creia pure. Monohydrate, yep. That's very pure.

It's very pure from Germany. It's third-party tested. Now, as a disclosure, I'm on the advisory board for Crea-pure, so full disclosure. And that's helped sponsoring the creatine conference in Germany in a few weeks. But it has grass status. And when you look at the independent lab results, it's, 100% pure. There has been some issues out of Asia with transportation and not being third-party tested.

So I think the consumer just needs to do a little bit of work. Most companies nowadays, if you're on the shelves of a product, are very reputable. And again, if it has third-party tests, it's safe. Just look at the ingredients. It should say monohydrate or if you're entertaining another form of creatine. That should be the only ingredient or at least the most important ingredient on the product. What about micro-ionize? Yeah, that's a new form to get away from someone.

the things you mentioned on GI track irritation. So that's just being continually processed. It's very fluffy. I've noticed some of the new products. It dissolves exceptionally well, get away from that crittiness that the creatine can cause in a solution. So these are just coming up with new alternative forms to help please a lot of individuals, make it more attractive. But it's another form that can just sort of be sort of solubility is very high. Is there any reason to believe it wouldn't work. It's because it's monohydrate, right? So it should do the same thing. 100%. It's just a different way to get it into your body. If you like it, really, really micronized. So it's pure fine. I just take normal, and if there's a little bit of grittiness

at the bottom, that doesn't bother me. But some people, they do. Okay. Well, excellent. We've just covered so much wonderful information. And thank you so much for taking time to talk about all this research with me today. And thank you for doing all this research. I mean, really, You've just done an amazing job covering so much important ground in terms of the effects of creatine on human health. Thank you so much for having me. Had a great time. Thank you. Me too.

Thanks. Thanks. Thank you to Dr. Daring Kandau for coming on the podcast. After this episode was recorded, a new study was published suggesting that creatine supplementation was not effective for increasing muscle mass. But that study is not what most people think it is. Dr. Kandau, who was actually one of the co-authors of the paper, joined me to break down what the study actually showed, what the data support, what they don't, and how to interpret the findings in context. You can watch that full breakdown on the Found My Fitness Clips YouTube channel.

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