Creatine is one of the most used and researched nutritional supplements available, mostly associated with short-term gains for athletes.

But the latest research — much of which is led by Dr. Darren Candow, a Professor and Scientific Advisor with over 120 peer-refereed journal manuscripts — outlines benefits far greater than just athletic performance...

Especially for middle-aged adults (and up), and plant-based eaters who aren't getting creatine through their diet.

Complement co-founder, Matt Tullman, recently had the honor of interviewing Dr. Candow, where he shared a full newbie's guide to everything you need to know about creatine, including:

• How creatine research has shifted over the years (2:16)
• The groundbreaking benefits of creatine supplementation for plant-forward eaters (7:20)
• The effects of creatine on longevity and non-athletes
• Healthy supplementation (exactly how much to take) (11:55)
• The positive long-term effects of creatine supplementation for women (38:42)
• Bone density and the impacts of aging (41:40)
• Who should be supplementing with creatine

And a whole lot more.

Watch the full interview, here:

Matt Tullman:

Darren Candow, thank you so much for joining us on Nome Athlete Radio. I'm so excited to dig in with you. I think you are the smartest person on creatine on the planet. You've been making the rounds onto some really big podcasts and we're so grateful that you've made some time for us to dig into all things creatine and also other lifestyle interventions. I'll give you a little background, but I'll just start by saying thank you for making time for us today.

Darren Candow:

Yeah, no, thanks for having me. Excited. And I would say I don't think I'm the smartest. Maybe I'm just a good messenger of the research out there. We'll go with that.

Matt Tullman:

Well, I don't know. And I'll say why I think that you are a PhD, a clinical exercise physiologist, a professor and director of the Aging Muscle and Bone Health Laboratory at the University of Regina in Canada as well, and very impressive. You've done 130 peer reviewed manuscripts, supervised 20 masters and PhD students, and received research funding from quite a few health institutes, so really impressive. But even more so on editorial review boards for the Journal of International Society of Sports Nutrition, nutrients, frontiers, advanced Exercise and Health Sciences. So you are about as immersed in this stuff as you can get. So I am really excited to dive in and I should just mention that your research program focuses on the development of effective lifestyle interventions, something we're really big on, particularly creatine monohydrate for nutrition and physical activity IE resistance training for the practical and clinical benefits that we see in muscle bone, brain heart health. So I mean, look, those are all the topics that we spend a lot of time on for good reason. So I'm so excited to dig in with you and that's why I say you're probably the smartest person on creatine.

Darren Candow:

Well, thank you so much. You're too kind, but really looking forward to our discussion today. And yeah, thanks again for having me

Matt Tullman:

After all these years. If you could sum it up, and this may be a really unfair question, but I think creatine is unfairly maligned for reasons that maybe you can help us understand. But at a minimum, it is often thought of as sort of that nutrient that the muscly guys that are doing a lot of short-term damage to their body in order to achieve some sort of superficial benefit, IE the musculature, the body composition, but it's at the expense of the long term. I think something that we are starting to appreciate is that at least when it comes to creatine as a supplementation protocol, it may not actually sacrifice the long term. It may even advance some of our goals related to longevity. So I, I'm curious if you could sum it up, why should we be thinking creatine and maybe just paint the picture for where we are today relative to this shift that I think has happened just in the last few years?

Darren Candow:

Yeah, yeah, it's an excellent segue because I think there was validity to that original premise where creatine just seemed to be for athletes, primarily males wanting to get bigger, stronger, faster. And the excellent pioneering research came out with a loading phase, which is about 20 grams a day for seven days, and it was very effective for saturating muscle and leading to a huge increase in muscle performance. The downfall with the loading phase, it can lead to weight gain. So that eliminated a lot of people who did not want to gain weight and weren't willing to even increase weight in the short term. And so young females, for example, older adults would never consider this because we originally thought it was just for individuals in high performance sport. And then in the last probably two decades, it's been a huge explosion and evolution where creatine, we'll talk about where it's produced in the body, but from a supplement perspective, if we take in a little bit more than what we're getting in our diet for most individuals, it started to show amazing health benefits.

It showed improvements in bone density. It showed improvements in muscle not only for younger individuals, but both males and females, and again, older adults. And the older population is so important because as we get older, we're losing muscle and bone mass and that's leading to functional impairments. And then just recently we're starting to see the emergence potentially of this molecule that's found in our body, found in some food products that has huge implications for brain health. And I think that's really come into light, especially after covid where instances of depression and anxiety and sleep deprivation have really gone up and super excited to talk about why it's evolved. And was it a secret before? I don't know. I just think we didn't have enough research to get it out to everybody.

Matt Tullman:

I'm already taking notes and had to unmute myself where to go from there. Let's go's start at the basics, then we'll get into the biochemical and then we'll get into hopefully something for endurance athletes, something for folks who have anabolic objectives, some folks who just want the longevity. And I want to particularly spend a moment on women because I think so often as you noted, they get left out of this conversation and there maybe are particular benefits, particularly women who are postmenopausal. So that's kind of the arc. But let's go to the very, very basics. You mentioned the loading phase. There's weight gain. I think a lot of us at the most, again, superficial complaints you might hear is one, if I take creatine, it's going to do damage to my kidneys or liver perhaps. And two, there's no point of taking creatine because it's just pulling a bunch of water weight into your muscles and it's making you look puffy.

And so it's like it looks like you've gained muscle mass, but in fact when you stop creatine supplementation, all of that goes away and you go back to your normal size. So my understanding, and I'll just then turn it back over to you, is even if that's true because of maybe the benefits in terms of energy management and total output, as long as you're training and it helps you in training, perhaps you're gaining muscle or perhaps you're gaining anaerobic capacity with the help of creatine. And so you got to do the work. I think we're all clear on that you got to do the work. It's not a miracle drug, but help us kind of wade through some of those really common misconceptions perhaps or maybe there's some validity to them.

Darren Candow:

Yeah, I think the best way to start is what it is and essentially a nitrogen containing compound that is naturally produced in all our bodies in the kidneys and liver and brain, but we can also consume it through food products such as red meat, seafood and poultry. And of course if you're plant-based or vegan, that limits that ability. And that's why I think the safety profile of creating is so high because our body will naturally recognize this product. But what happens if you take the loading phase? So really we are only producing about one to three grams every day, and then some individuals may be consuming anywhere between zero grams if you're a vegan all the way up to about three grams if you're a carnivore. So if you add those two together, the lowest dose that has been shown to accumulate beneficial effects from a muscle perspective is another three grams add up.

All that is about 10 grams in total. We do excrete some down the toilet and that's why we get false positives when we go to our doctor. So for those who are watching, if you ever are taking creatine when you go for your annual blood work, make sure you tell your doctor you're on it because it's going to come up with a high creatinine and that's going to alarm the doctor saying that you've killed your kidneys. And we now know study after study, that's not the case. But by taking the loading phase 20 grams a day, that's a tenfold increase of what we're probably synthesizing or consuming. And yes, creatine is osmotic. So you go all the way back to high school biology. Osmosis is translation basically a fluid from an area of high concentration to low concentration. So creatine will take water from your bloodstream into your muscle, and by doing that, the muscle will swell.

And of course that turns on the magic of creatine from a muscle performance. But when you take a little bit of water from plasma or the blood into the muscle, you can get an increase in intracellular water retention. And that's why a lot of individuals, primarily male will feel a little bit more muscular, their shirts will feel a little bit tighter. But females on the other hand, when we've asked them, they say they don't want that because the number on the scale could go up. So there's many things we'll probably talk about today, ways to get around that weight gain, but that's kind of the premise of why the loading phase was popular, but we don't really use that very often. I think unless you're an athlete, the loading phase is not necessary. It can cause some GI tract irritation and we seem that a low dose taken daily for the rest of your life can be very effective without causing that weight gain or potential adverse effects. So I think the loading phase, and that's a good place to start, is primarily just for those athletes. Paralympics coming up. I'm sure there's a lot of high performance athletes really needing a burst, but if you're the average gym goer and you're looking at it from a muscle performance perspective, you could probably go as low as three grams a day, that's a half a teaspoon, put it in your food, away you go, and you'll probably get benefits over time.

Matt Tullman:

And as you pointed out, this is a compound that does not exist in plants. So for those of us who eat a fully plant-based diet, this is something that we may want to consider. I have started taking creatine. I'm a big fan actually across our team. We've all been playing around with it and most of us have really liked it. And so I solicited a long list of questions from all of them because we all have these curiosities. One of 'em was that loading phase. So help me tease through what are the pros and cons. You mentioned gi, I track irritation, but we live in this maximalist society where you're like, well, if it's good for the athlete, even as a casual gym goer, maybe there's something I can benefit. Is it worth that loading phase? I can tell you I've never done a loading phase. I'm a minimalist in that sense. Somewhere between two and five has been, and I've noticed a tremendous difference both in cardiovascular and also resistance training. So I'll stop there. Loading phase, is it worth it for let's say casual gym goer, but someone who cares about the performance in the gym? And if you're going to take creatine, what's happening there and why would you choose to do a loading

Darren Candow:

Phase? Yeah, so the loading phase is super effective. It's the most effective strategy that we currently understand, and that's where you're taking five grams a day, or sorry, five grams four times a day for about seven days that will fully saturate the muscle or think of your living room completely full of creatine. There's nowhere else to go. And then after that, you can reduce it down to about two grams a day to maintain what's naturally in the muscle. So super effective, really rapid. If you're looking for a really quick boost to weightlifting performance, whichever it is, that's the best way to go. The downfall is you will gain weight, you will experience likely some GI track irritation. The weight gain can average anywhere between one to three kilograms and it does subside after a while. Some people feel a little bit of cramping and sort of GI track irritation during it because you're taking so much water from the blood into the muscle, you got to make sure you're drinking a lot of water during the loading phase.

So I would probably only recommend it for the athletes or individuals rehabilitating from an injury where they need a lot more creatine in the body or the muscle to overcome the catastrophic effects of injury. When I did the loading phase, I gained eight pounds in seven days. Now for me, it didn't really matter because I understood the kinetics, but to some individuals, they're like, whoa, whatever you're giving me. Unfortunately they think it's body fat and we put out paper after paper now showing that creatine does not increase body fat, it's probably an indication of net water retention in the body, but it does subside. But sadly, a lot of people withdraw or stop taking creatine within the first week if they take the loading phase. So again, we don't really use that. We use a relative dose. If you go on the scale and you're 70 kilograms, we use 0.1 all the way up to 0.15 grams if you're older per kilogram.

So just say if you're 70 kilograms, that's seven to 10 grams a day. You don't have to take it in a bolus. You can divide that up into smaller dosages. And if you take it with food, it really decreases some of the anecdotal effects of bloating. But from a vegan vegetarian perspective, they respond the best on the planet. And the reason is, as you mentioned, they're not getting any dietary creatine, so their muscle or just think of your living room is only half full. They got a really high capacity to go. And we did a seminal study in 2003 with muscle biopsies and vegans and vegetarians compared to omnivores, and they responded exceptionally well. And I often hear this from vegans and vegetarians when they take creatine, they're like, wow, I did more repetitions. I recovered quicker. I put on lean mass. I got faster both males and females.

So it's very nice to see that both biological sex are considering this and we're having a lot more evidence coming out now. I still think the research females young and post-menopausal is well underrepresented. I would love to do more work there, but it will come, I think. So again, going back to your question about the loading phase, I think it's for the athletes for those rehabilitating from an injury, a broken leg, whichever it is, we can talk about probably a better dosage, which might be more consistent, maybe a greater adherence to a program and probably easier to do during the day.

Matt Tullman:

Well just, so for those not as easily translating kilograms in their head, I typed it in 70 kilograms, 150 pounds, 80 kilograms, 176, that's probably going to cover, I'm guessing 90 kilograms, you're probably closer to 200 pounds. You said 0.01 was the recommended dose.

Darren Candow:

Yes. So that's important, not 1.0, it's 0.1 to 0.15 for individuals older or after the age of 50. So 0.1 70 kilograms, that's only seven grams. They take that daily. They do not do the loading phase when we do the relative. And the reason for this is we theorize that the larger you are, you have more doorways to your muscles to allow creatine in. So if you're a hundred kilogram linebacker, you're probably going to be able to utilize more creatine than someone who's 50 kilograms, very similar to caffeine. The dose is really dictated by the size of the person. So that's kind of why we base it off that. And we've shown this relative dose to be extremely safe and effective from various populations.

Matt Tullman:

So if we're talking about a woman who's just 110 pounds, that's 50 kilograms, you're talking about five grams a day all the way up to a much larger person at 90 kilograms, that's 200 pounds, we're talking about nine grams a day. So in the five to nine grams plus or minus, depending on your weight is where you guys are seeing the most benefits. Let's touch on longevity, then we'll move our way out of sports performance and into longevity and all the other benefits. But recovery, you just mentioned a broken leg or something. Give us the download on why this creates help with recovery particularly. I mean, I would've been surprised if you told me. Well, I wouldn't have been surprised if you told me it helps recovery for muscles, but if I tore a ligament, if I broke a leg, I wouldn't have thought that. I think of it much more as like you said, getting those extra reps. Right. So tell us how does it help with recovery?

Darren Candow:

Yeah, so specifically there's only been a few studies we've shown with mobilization with the plaster cast that when the cast has taken off that muscle strength and muscle mass was better preserved than placebo. And then there's been a few studies from Europe showing that some cellular signals, if you will, are sort of turned on quicker in the presence of creatine. So the theory is that creatine during immobilization and of course right after for rehabilitation, somehow it unlocks some of the potentials from a cellular perspective to sort of stimulate muscle growth or strength maintenance better. So for the pro athletes, for the individuals that have hurt themselves, I think it's something they can consider which could speed up recovery, and that is a viable strategy for athletes. And of course, everybody who's injured a limb or fractured a limb, it could be something there. We don't think it will preserve bone, but that hasn't been looked at, and it's a very important area when you take the plaster cast off, the limb is usually half the size of the healthy one. We know muscle goes down, we know bone will go down, but could creatine offset the rate of bone loss that may have massive implications for hip replacement surgery, individuals with a limb fracture pro athletes that hasn't been looked at, and we definitely need to see that down the road.

Matt Tullman:

Awesome. Fascinating. You also mentioned, sorry, so we'll jump over to another myth as long as we're sticking at the superficial trying to address all the things that people think about. I think I've actually seen a study that suggested that you may be more likely to injure yourself if you are supplementing on creatine. I know a lot of people have that kind of misconception. Maybe it has to do with being able to push yourself harder, and so you are lifting things that maybe you weren't used to or over exercising because you have more energy. Tell us where does that come from and is it substantiated by the preponderance of evidence?

Darren Candow:

Yeah, so research certainly does not support that. If anything, it goes the other way. So it probably stemmed from the increase in muscle cramping. Some people would expect during the loading phase and people thought, oh, it causes cramping, but I was like, you know what? It actually hyper hydrates the muscle, so it actually decreases the rate of cramping. So this has important implications for exercising in the hotter summer months. But there's, as you're right, if it does increase a little bit of soft tissue doms or muscle soreness, it's probably because it increased training volume. So that's what could happen over time. But there's no greater increase in fracture, soft tissue injuries, micro tears, anything like that. That's a total myth. Yeah,

Matt Tullman:

Yeah. As is any sort of impact to kidneys, we covered that. And what is the longest study duration just to give people a peace of mind?

Darren Candow:

So we just published probably one of the longest that have at this, and it was in postmenopausal females. And I really like this because that's a population that organs start to deteriorate just like muscle as we get older. But we gave 11 grams a day. I didn't make a mistake there. We gave 11 grams a day for two straight years and we measured all their liver and kidney enzymes on an annual basis and it resulted in no greater adverse effects compared to placebo. And this was a really important study because it was adequately powered. We had over 200 individuals in the study. It took a decade to finish. So we're very confident now that even a higher dose, if you don't have any preexisting kidney or liver impairments at the end of the day, any excess would probably be filtered down the toilet or hopefully it trickles into your bone and brain because the majority is taken up by muscle. But at the end of the day, we didn't see any greater adverse effects on liver or kidney function, and that's been repeated worldwide. So we're very confident it is probably one of the safest, most effective dietary compounds because it has over a thousand publications on creatine and we're just not seeing any reason why it would cause any alarms. For a healthy individual,

Matt Tullman:

It is likely the most researched compound ever. I can say that for sure. So you offered 0.1 grams per kilogram body weight as a general recommendation. Does that change at all based on your goal? So for my mom who's in her seventies and maybe she's thinking about her heart and her brain and longevity a little bit more versus someone who's an endurance athlete versus someone who's in the gym trying to do resistance training with an anabolic objective, just paint the picture. How does that recommendation maybe change?

Darren Candow:

Yeah, and that's very important. So we've already talked about the loading phase. Now let's talk about two other ones that are very popular and I think very of interest to the individuals you mentioned. So we do the loading phase as we mentioned, because usually our studies are shorter term and we're looking to find some results. So again, 0.1 gram all the way up to 0.15. Do you have to do that dose? You don't. It is safe and effective, but here's something to also consider if you're just looking from a healthy muscle perspective, if you want to get a bit stronger, maybe put on lean tissue mass, I'm very confident based on other really good research that you could take as little as three grams a day probably till the day you die, it would eventually accumulate and cause beneficial effects. It gets a little different though when you say, Hey, what about bone?

Well, the lowest dose of creatine ever been shown to have bone beneficial effects is eight gram. And then the neck up is really more unique where we have the blood-brain barrier, you kind of want to go two ways based on current research. You either want to take about four to five grams a day for several months, or you want to take the bloating phase for at least a week. So now you have three options. I got muscle, bone, brain, I collapse the data and I personally take 10 grams a day, divided it up into two five gram dosages every day that look at it from a whole body perspective. But you might get some people say, I don't care about bone or brain, I'm just looking for muscle strength on the bench press. As little as three grams a day could be viable. But if you get an individual saying as your mother a little bit older, maybe prone to osteoporosis, we're starting to see some bone benefits again with combination of exercise around eight grams and then everybody on the planet is interested in cognition, memory, offsetting, whatever it is. We're not sure the dose yet, but the two camps are the loading phase, but that might cause some GI tract irritation or take a smaller dose and just take it for a long period of time. So at the end of the day, I usually recommend a social media 10 grams a day every day as long as you want,

Matt Tullman:

That has a nice ring to it, 10 grams for all the benefits you need. Do you recommend any sort of cycling? I mean it sounds like you could take three grams a day or maybe 10 grams a day forever, but do you reach a point of saturation that you intend but then maybe a point of sort of a customization where you don't get certain benefits?

Darren Candow:

So this is a delicate answer. So let's pretend we're just talking about muscle, your bicep and tricep. There is logic. If you're taking a higher dose, now remember I said you can go as low as three grams, which is probably viable. I'm taking 10 for the whole body, but for those individuals saying, I just want it for muscle, I think you could run into some issues if you're taking a high dose just for muscle, because remember the living room will get full really quick if you're taking a whole bunch more, you're going to extre it down the toilet or you're going to sort of desensitize those doorways to your muscle. It's kind of like a type two diabetic continually taking in sugar. You get insulin resistance, but then you might say, Hey, what about for bone and brain? We don't know if you need to cycle it.

My thought is if you're taking about five to 10 grams a day, if 95% go to your muscle, and if your muscle says, whoa, we're really full, why don't you go to bone and brain? Hopefully some of that creatine will trickle into those precious tissues besides going to your kidney. So there is a potential danger taking a high dose just from muscle, and I certainly don't think you need to go much more than 10 grams if you do at all for a long period of time. There's never been a study to your point that has looked at continuous daily dose versus cycling. And the reason for that is when you take creatine for about 30 days, at least when it saturates your muscle or taking the loading phase, it takes about a month to come out. So you'd have to ask research participants to saturate the muscle, wait around for 30 days, come back in, do it again. So it's a very tough study to do the theories there, but again, we've given it for every day for two straight years and not seen any negative effects. I will point out creatine does not downregulate or stop your natural synthesis in humans. So by taking it every day, be confident that the mRNA or the protein expression is not turned off. And that's why we've actually seen a study in Parkinson's disease for five years. It didn't have a great beneficial effect, but again, no negative side effects.

Matt Tullman:

Got it. That's really fascinating that your body or your muscles will retain it for about 30 days. Sometimes I think about that. I go on a two day trick and I forgot it, and it's probably psychosomatic that I feel like I don't have the power that I did in the gym, but I do. So in terms of the daily regimen, when you start to see a desaturating instantly, but it's a very, very slow off ramp, is that what I'm understanding?

Darren Candow:

It's super slow. And here's a couple strategies. So creatine is primarily found in these type two muscle fibers or the large ones we typically do during high intense activities. So if you're going to say, Hey, I am going to Mexico for a month or traveling to Europe, whatever, and I'm not taking my creatine with me, I would suggest if you're going to be able to work out exercise at a high intensity, exercising at a high intensity will help maintain the creatine in the muscle. It's not going to increase it above normal levels, but it's going to help maintain it. That's one thing. The second comes down to diet. Now for those who do consume red meat, poultry, seafood, it's a viable strategy of when you're vacationing to try to increase that amount in your diet because for every five, for every kilogram of I guess meat, you get about five grams.

So that could be a focal point when you're on vacation for someone like yourself or other vegans and vegetarians, you're not going to have that. So again, intense exercise is going to help maintain it, but you still have at least 30 days, even if you just laid on the beach and did nothing before it comes back. If you're fortunate to go on vacation for an entire month and be inactive, and that's okay, that's great, but most people who are taking creatine are usually active. Any activity will help. The more intense you perform, exercise a little bit heavier weight, a little bit more reps, that's a very viable strategy to help maintain it. Atlas in our muscle about four weeks, we think in the brain it's even slower. And people say, why does it stay in there? Creatine is trapped when it gets into the muscle or brain, the compound gets a little too big to just leak out.

So that's why it takes a slow time to sort of transform into this byproduct called creatinine. And for those watching, they're like, oh, I've heard about this. This is why my doctor gets mad at me. They use creatinine as a measure of kidney function, and again, to repeat myself for those going to the doctor, make sure you tell your nephrologist or GP that you're taking creatine. Creatine produces creatinine in the blood. It's a byproduct, and that's what they measure in the kidney. So usually what happens is the doctor says, oh my God, what are you taking? Your kidneys are destroyed. No, you stop the creatine. They go back to normal in most cases. I'm not a medical doctor, but that's usually what happens. So just make sure you tell your doctor that you're taking creatine.

Matt Tullman:

It's important to have a candid conversation with your doctor about anything you're taking. Correct. I have heard from so many people where they didn't realize you're taking X or Y and all of a sudden they see this and it's like, well, they're actually just eating a lot of citrus fruit and it has this effect. So if you're playing with your diet in any way that's out that normal kind of bell curve, if you will, you could get some weird test results and really freak out your doctor, so have that conversation. So a lot of times you hear that you should be taking creatine with some sort of carbohydrate, maybe even a simple carbohydrate to help with the uptake of that creatine. You are more so describing it as a long-term, kind of saturate the muscle game in any given day, assuming that you're taking creatine, not in a fasted state, but maybe you are, right. Is there any consideration that you would pay to combining creatine with certain macronutrients?

Darren Candow:

So there's really good evidence that carbohydrates, high glycemic sugars can spike insulin to a high degree and really increase creatine uptake into the muscle. I think that's probably something to consider for the high performance sport. I will point out the dose of carbohydrate needed is probably not even going to be considered by the average person because of everybody's phobia with high glycemic carbohydrates. The nice interesting thing is that protein, it's very gluconeogenic. It will spike insulin as well, and you get way greater health benefits from plant animal-based proteins. So if you had to choose the one, I would always recommend protein because you get so many health benefits from protein. But it is interesting, in 1992, they clearly showed that exercise was extremely beneficial for increasing uptake into the muscle. And if you're like, well, I like the exercise and I take creatine and makes sense to take creatine probably before, during, or after you work out when blood flow and those doorways are open.

So I always look at creatine by itself. I never really worry about what I'm putting it in. I drink five grams with water during my workout and I'll put it in my breakfast. At the end of the day, muscle contractions seem to be a very viable strategy to sort of unlock its potential. I'd stay away from the simple sugars unless you're an Olympic athlete or someone that's really needing it because there's a lot of concerns around high glycemic processed carbohydrates, low glycemic fruits and vegetables will have a minimal effect. So at the end of the day, I would say exercise first, protein second, and I probably wouldn't even consider carbohydrates as a viable source because the dose just needs to be so high. That's like a bag of candy or half a liter of orange juice. Today's society, I think with diabetes and things like that, I would probably just say protein, but exercise is probably the best viable option.

Matt Tullman:

And because it sounds like it's a long-term saturation game anyway. I mean drinking like you say, a half liter of orange juice every day just to increase the uptake by a certain percentage doesn't really make sense. At some point you're really just trying to saturate the muscle over a long period of time. And you mentioned for you, you add it to your breakfast, you sip it during the workout, so really is kind of pre-workout, right within the 15 minutes because you want to have your blood pumping. That's kind of the number one strategy.

Darren Candow:

Yeah, it's blood and these doorways get activated. Obviously when you're contracting your muscle, it's no different than allowing glucose in when you're exercising. So I usually have it with a high protein breakfast and then I work out in the afternoon, so that'd be about five or six hours later, and then I just drink it after and then I'll have a meal. So hopefully we're letting people know it's a very convenient, the timing of creatine is irrelevant. It's not like caffeine. And so people can take it when they want, if they want to take it right before bed or as soon as they wake up. It is one of these things. And again, you don't have to take it in one bolus or one amount. You can divide it up and for those watching that say, Hey, I've tried it, but I've gotten a little bit of water retention or some GI track irritation, my guess is you're just drinking it. Put your creatine with food. As long as the temperature is not really, really high or acidic, that digestive processes can help absorb it. So I have a lot of females taking three grams of breakfast, lunch, dinner, nine grams from a whole body perspective, and they've said it's very viable. It doesn't taste like anything. There's candies out there now and there's a whole bunch of new evolution with creatine. So I think it's something that individuals can consider.

Matt Tullman:

Awesome. I want to get a little bit more specific now, but one last question. For a general population, what is your preferred type of creatine? I think we often hear about monohydrate. Maybe you can, I think there's hydrochloride, there's probably gluconate. What are the pros cons or if you have a preference, what would that be?

Darren Candow:

Yeah, so monohydrate is the only one that's actually been assessed repeatedly to shown to be safe and effective. All the other forms or marketed or purported forms of creatine, we're not even actually sure if it is creatine have been shown to be effective that way. And the reason for that

Matt Tullman:

Is marketing out there. That may or may not be accurate, and I can't believe that

Darren Candow:

The name gives it away. Monohydrate, creatine linked the water. When you ingest it, you simply diffuse the water in the GI tract, the hydrochloric acid in your stomach will take that away. The cool thing with creatine is it really dissipates at a higher pH than your stomach. So it remains intact, it goes through the stomach, goes through the small intestine, and when it enters the blood, it's identical to what's being produced by the brain and liver. So that's why the body recognizes monohydrate is safe and effective. And the bioavailability or meaning how much creatine gets through your digestive tract into the demanding tissue is near a hundred percent. So I always question, why would you go out and spend way more money on another purported product that we don't know is safe and effective compared to the old boring, the only one we use in our lab, it's third party tested, and I say if it's a hundred percent it's safe and effective, why mess with a good thing? But I guess it's been around since 1832. It's kind of boring. People say, we know about it, we got to flash it up, but we only use monohydrate.

Matt Tullman:

Water's been around for a while, but they figured out how to sparkle it thing. How about kids? At what age would you consider it? Is there any studies around this for kids? That's about the small ones.

Darren Candow:

So is there always an area of caution around pregnancy and children and adolescents? Just because it's evolving and two of the leaders in this area, Andrew Jao and Chad Gersa in the US have clearly shown subjectively that creatine is very safe and effective for sports performance. And some of the health measures in children and adolescents, they're currently measuring blood, which will be the first time we now look at kidney and liver and blood biomarkers in children to make sure it's safe. Stacey ery in Australia has shown even during pregnancy and for fetal development, it can be safe. And people say, how is that possible? We'll go back to what we've talked about. It's naturally produced in the body. The body recognizes it, and if you take a low dose, it's no different than eating a salmon steak or a red meat steak. The body will process it, and that's probably why it is safe and effective at lower dosages. So some caution obviously needs to be there. We're just not seeing any reason at recommended dosages why it would have any detrimental effects. But a loading phase two, a child would probably cause some of those adverse effects two to three a day. I can't see why it would, but again, we need to do those big, long-term clinical trials.

Matt Tullman:

Cool. Let's talk about women. You mentioned maybe some of the benefits for postmenopausal women. Let's start there, and I guess maybe because you just mentioned pregnant or breastfeeding women, if there's any more comments on that, I'll let you take it away.

Darren Candow:

So we'll start with the pregnancy. And again, they primarily use animal model, and we don't know if creatine gets transferred to breastfeeding, so that's an area of potential research focus. But during pregnancy, it seems to increase the energy status for the developing a fetus and or mother. So there's a theory. Could some children's rate of prevalence with inborn creatine deficiencies or some of those complications be offset? That's an area of interest for sure, but a lot more research needs to be done in humans for sure. As we progress, there's not a lot of research in perimenopausal or premenopausal females. When we look at younger females, they definitely improve strength, endurance power, and lean tissue mass. But the big focal point has been on the menopausal transition into post menopause. And the theory here is when the ovaries are having cessation of estrogen, you're simply left with the adrenal cortex or a little area of your kidney to produce estrogen.

And more times than not, it's not enough. So a lot of females will take hormone or estrogen replacement or other therapies, but creatine has actually been shown to improve muscle and have huge benefits potentially for bone health. We've shown in these clinical trials that the rate of bone mineral density loss is attenuated or decreased in post-menopausal females, they get an increase in bone strength as well as a preservation of the skeleton primarily around the hip. So post-menopausal females have been a focal point in our lab, and it's been shown that exercise and creatine is a one two combination for not only improving lean tissue mass and strength, but bone I will point out you will not get any bone benefits without exercise. So creatine alone is not going to give you any bone benefits. Exercise has to be there. Exercise pretty much has to be there for all the potential benefits of creatine except for probably the neck up.

But again, those individuals are performing exercise or activities of daily living, but very clear that the dose for bone right now is about eight grams or more. We don't know if a lower dose is as effective. Bone takes about six months to a full year to turn over from a statistical perspective. That's why a lot of researchers refrain from bone because it's so expensive to do these studies and you also need really good imaging. But as it stands right now, there's about 10 studies published. We're fortunate to publish the majority, and all we can say is that creatine and exercise seems to preserve the aging skeleton, but it doesn't increase bone mineral density at anything. It just will help preserve. But that can have implications for offsetting fracture or falls later on in life.

Matt Tullman:

I want to go deep on two things. You mentioned bone turns over in about a year. I know what that means, but it's a wild concept. So please extrapolate that we are not static beings. What is actually happening as that bone turns over and becomes totally anew every year?

Darren Candow:

Yeah, actually bone is more metabolically active than our muscle. We just don't see bone, right? We look in the mirror and we're like, oh, we see our muscle and body fat, but underneath, when muscle is pulling on bone, we have this bone remodeling process. We have cells called osteoclasts that break down a little bit of calcium when we're not eating a lot of calcium in our diet and maybe we have a metabolic disease or inflammation, it basically means when our blood requires or our muscle or heart requires calcium, where's the biggest storage area? It's our bone. So calcium is used by our heart, our brain, our muscles. So calcium is an essential nutrient, and we store calcium in our bone, but when we need it, these little cells sort of shave away some calcium, it gets into our blood and when all the other areas of our body are satisfied, we also have bone building cells, osteoblasts that take that calcium and repackage it into bone.

So in other words, we're always sort of remolding our skeleton on a daily basis, but it takes a long time before you get to notice an effect. From an imaging perspective, usually we can see some change in about 12 weeks, but on average it's probably about six months or more. So you need a DEXA scan or a CT scan to really notice an effect that's a measurable. So it's an area we never consider, but it's a hot topic area for osteoporosis or caia or frailty. And we'd really like to focus on the old, old age, maybe 80 and above. Those individuals are really prone to metabolic diseases and we think exercise and maybe creatine can help somewhat.

Matt Tullman:

Yeah, which brings you to the second point. You mentioned exercise. You got to keep repeating that there is no such thing as a perfect pill to solve all of our problems, got to put in the work, but what does the work mean? And let's particularly again, focus on longevity, focus on bone health, right? Because falling is a major is highly correlated to broader issues as your years go on, and obviously all cause mortality, right? If you break a hip and you're immobile, your quality of life goes down precipitously and then the prognosis for your life long term. So it's really, really important to maintain that physical activity, but also to maintain the structural integrity. What does exercise mean in that context? Because I know just standing gravity pushing on your bones and muscles and that connective tissue and that alone has been shown to improve bone density, just standing, walking, but what do you see clinically?

Darren Candow:

Yeah, so the best form of exercise from a bone perspective is weightbearing or low bearing. So just think of weight training or plyometrics or things like that. But is that viable for a lot of clinical populations? You could argue maybe or maybe not. To me, it's always nonsensical when people say, oh, just do cardio, just do weights. I say, you should be doing both for a number of whole body perspectives. And when you do both, you improve balance agility. So when you slip on a little bit of ice, maybe you can withstand that. Strength will obviously come from resistance training, and that's the number one cause of sarcopenia. And of course we want to live longer, so our telomeres at the end of our chromosomes really respond to both exercise, but primarily aerobics. So from a lifelong perspective, you should be doing both. We recommend 150 minutes of aerobic exercise a week, two or more sessions of resistance training.

And I think a viable strategy is to separate those two. For a lot of people. Maybe you do your weight training Monday, Wednesday, Friday in your cardiovascular exercise Tuesday, Thursday, Sunday, or whichever it is, whatever's the most viable for you. But I think both are effective. If you had to choose one though, I would lean towards resistance training because resistance training will give you the vast majority of the benefits from cardio, but it also gives you the beneficial effects to bone, muscle and strength, which for the most part, cardiovascular exercise won't do. I think of cardiovascular exercise as beneficial for fat burning, longevity, cognition, heart health, diabetes, things like that. But I really promote both anytime we can from a health perspective, both modalities are very important.

Matt Tullman:

Got it. Thinking about females for a little longer, are any specific benefits to women at any point in age in terms of hormonal responses to creatine?

Darren Candow:

There's not much evidence to suggest that reine influences hormones directly. There's been a couple studies and we've done one that has shown an insulin-like growth factor. That's kind of an anabolic type of hormone, but it can disrupt estrogen, but we don't know why that is. So overall, there's minimal to no evidence that creatine can influence anabolic or catabolic hormones. So for the average person concerned with that, the evidence is not there and it's not supporting any big issue whatsoever.

Matt Tullman:

Gotcha. And one last very important question, water retention strategies. You talked about the intracellular, well, I'll just ask you because as you said, there's so many benefits. And then I want to talk a little bit about the, and heart health just as we wrap up. But for those women who are hesitant or they start the process and they see themselves bigger, I see myself in the mirror and I like the larger size, but I can see why that may not be the goal. What strategies are there?

Darren Candow:

Yeah, I think, and again, this is from the healthy individual perspective, let's start with three grams a day, but I want you to divide that up into two 1.5 dosages in the morning and evening that's going to have a minimal osmotic effect to the muscle Start and do that for maybe seven to 14 days. See how you're tolerating it. If you don't notice any fluctuations on the scale, then move up to five grams. But I still want you to divide that up into 2.5 dosages, so the same strategy, just a little bit more in the morning and evening. And then if you notice, hey, I did that for two more weeks after that, you can move it up to maybe if you want to do the 10 grams from a whole body perspective, 3, 3, 3 or a little bit more at supper, I think dividing it up or more frequent smaller dosages, it won't cause as much drag per session. You'll still accumulate in the muscle and that hopefully will trickle to the bone and brain. And I think that's a very viable strategy. What we've seen in the past is if you take the dose that's too high all at once, that can cause some of the disruptions. But by taking smaller, more frequent dosages, we speculate and we've heard from a lot of people, it's very tolerable and no adverse effects.

Matt Tullman:

Cool. I know we're going to run out of time, but I want to make sure we spend a little bit of time. You mentioned the Parkinson's study. There wasn't a great deal of benefits there, but I remember, well, I'll let you riff on the same direction you want, but people don't consider the fact that the brain and the heart are muscles and the brain in particular consumes. I mean, you probably know the statistic, I've forgotten it, but a tremendous percentage of our total metabolic burn is our brain. It is incredibly energy intensive, and at the end of the day, creatine is very much related to energy management. Tell us what are the benefits that we can see in the clinical data around heart and brain health over the long term?

Darren Candow:

Yeah, so you're absolutely right. The brain is only about 2% of our body weight, but uses up 20% of our energy per day. And that's just normal. If you're metabolically stressed, sleep deprivation, working overnight, you have children running around, you're up. So the brain is always stressed and the brain, just like muscle, uses creatine to maintain the energy status of ourselves. And when the brain is stressed all through those examples, even during covid, that can really cause some, what we think, some brain disruption. So when you look at some of the metabolic diseases, depression, anxiety, concussion, those neurophysiological diseases, they typically have a common denominator. Their brain creatine stores are reduced compared to a healthy control. So one of the theories is if you supplement the diet with creatine, it will get through the blood-brain barrier. It's very slow. It's about half the amount is in the muscle, but it can accumulate, and that may help explain why we're starting to see some beneficial effects in certain conditions or populations where the brain is stressed.

Older adults, hypoxia, sleep deprivation come to mind. But when the brain is not stressed, if you take a young university student sleeping well, they're not going to see any noticeable benefits from creatine. We see the best evidence when the brain is stressed, and that's also referred to as the heart. There's been some really good studies out now showing that there's no detrimental effects to cardiovascular function. We've shown that it can improve stroke rehabilitation, and then from the heart being a cardiac muscle, it has acton, mycin, all these cellular things just like our biceps do, but it can use creatine to maintain the energy status of the heart as well. And it could have huge rehabilitation application for heart failure or individuals that have suffered angina or are cardiac arrhythmias. So there's a lot of potential, but the brain seems to be the area of focus right now.

And we put it with that big paper heads up on creatine. We speculate why we're not seeing a lot of benefits for Alzheimer's. There's actually never been a study in humans because you need such a large sample size, and it's very difficult to get those individuals from depression and anxiety. There's some promising effects, but only when in combination with a medication, creatine has never been shown and never will probably be shown to offset the effects of no medication for those diseases or conditions. So that's why I think exercise, creatine medically supervised, you're going to probably see a lot more coming out in the next 20 or 30 years.

Matt Tullman:

I'll advocate for you to be the first to try to prove that mental health without any sort of pharmaceutical intervention could be solved through exercise and some reine. I'm a big fan of the thinking that exercise and sunshine may well be the best antidepressants in the world, and they're the cheapest, but awesome. Well, Darren, thank you so much for giving us this deep dive. I'm so excited about your work and your efforts to dispel some of the myths around creatine. Is there anything that I didn't ask, any call to action, any way we can support your work? And I guess last but not least, where can folks find you if they want to follow some of your work more closely?

Darren Candow:

Yeah, no, and again, thank you for having me. It was great. We have a bunch of studies that are upcoming in aging individuals in long-term care facilities and the timing of CRE team, we're really going to sort of answer that. But if they want to follow me, probably on Instagram at Dr. Darren hand is the best way to do it. I try to post a lot of research, not just on creatine, but there to help improve healthy aging and longevity. So at Dr. Darren Candle is probably the best way. Yeah.

Matt Tullman:

Awesome. Well, thank you so much again, Dan. Really, really appreciate it and look forward to following you there.

Darren Candow:

Great. Thanks so much.