Dynamic Dialogue with Danny Matranga - 311: Creatine Masterclass II (with Dr. Darren Candow)

Episode Date: August 10, 2023

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Hey there, everyone. Welcome in to another episode of the Dynamic Dialogue podcast. As always, I'm your host, Danny Matrenga. And in this episode, I will be interviewing Dr. Darren Kandao. He is a researcher from the University of Regina up in Canada, and one of the world's best researchers, experts, enthusiasts when it comes to creatine supplementation. You've heard me talk about creatine a lot. I believe it to be safe. I take 5 to 10 grams every single day, and I encourage it often. But I am not a researcher. I am not a scientist. I am just giving you my best interpretation of the data. And Dr. Kandow is much better at this than I am. So today we're

discussing creatine, what it is, how to supplement with it, supplementation in infants, supplementation in pregnant populations, supplementation in older populations, creatine and muscle, creatine and bone, creatine and brain, creatine and blood lipids, creatine and blood sugar, creatine and blood pressure, creatine and depression, creatine and hair loss. You name it, we're talking about it. Hopefully by the end of this podcast, all of your fears about creatine and questions will be answered. Thanks so much for listening and enjoy. This podcast has some awesome partners and one of my favorite, of course, is Legion Athletics. Legion is my go-to supplement manufacturer for what I like to call my big rock supplements. This would be my protein powder, my pre-training formula, my post-training formula,

and creatine, and my kind of ancillary vitamins and micronutrient protection. So why do I like Legion so much? What sets them apart? It's quite simple. Legion uses all natural ingredients. All the formulas include natural coloring and natural sweeteners. No artificial sweeteners, just stevia. And every single formulation, be it a pre-workout or a vitamin, contains clinically effective dosages of ingredients shown to work in humans in clinical research supported by robust trials. No filler, just legit ingredients in each and every formulation proven to work. The whey protein isolate is so light. It's fantastic. It mixes in water. It tastes amazing. And I drink it every day, even as somebody who's

lactose intolerant. That's just how high quality this whey protein is. And it's sourced from Irish dairy cows that are raised well, eat their natural diet, and packaged in climate-friendly packaging. I love their plant protein too, for those of you who like something that's a little on the thicker side and you aren't a fan of animal products. Also, I love Legion's pre-workout, but specifically the pre-workout that does not contain caffeine. That would be their Stim-Free Pulse. I'm a huge, huge fan of beta alanine and L-citrulline, but I don't like taking in wildly high amounts of caffeine. So if you are somebody who likes pre-workout with caffeine, you can try pulse. Or if you like it without caffeine, because you maybe

want to enjoy your morning coffee or monitor your caffeine consumption, try the pulse stim-free. My favorite flavors there for sure are the new grape and the amazing, amazing tropical punch. As for my creatine, I get that from Legion's Recharge, five grams each and every day. I take it on the days I train as well as the days I do not because Recharge also contains L-carnitine, which can help with promoting muscle recovery and decreasing soreness, as well as some ingredients to help with creatine utilization. And of course, my favorite supplements for my ancillary micronutrient health are Legion's multivitamin and Legion's greens powder. Not only do these two products contain a ton of high quality vitamins and minerals,

they also contain unique adaptogens like KSM 66 ashwagandha and reishi mushroom, which I like to take each and every day to promote my health. If you want to cover all your bases with a high quality protein creatine post-workout or the ancillary micronutrient health stuff like greens, powders, and multivitamin, I encourage you to go over to legionathletics.com and check out using the promo code Danny. That'll save you 20% on your first order and you'll rack up points that you can use the same way as cash every time you use the code and you'll also be supporting the show. Dr. Kanda, how you doing, my friend? Excellent. How are you?

I'm doing quite well. For those of you who are listening, again, this will be my second episode with Dr. Kanda. with Dr. Kandao. I've been a creatine proponent for quite some time looking for the Mount Rushmore of creatine researchers, if you will. And Darren is on that. He is one of the world's foremost researchers on the subject of creatine, creatine supplementation, how it can benefit the body, how it can benefit the brain. So you're in for a real treat today. But for people who have not yet listened to the first episode, and maybe who do not understand what a researcher does, what an academic does, how does one become the go-to PhD for all things creatine? Well, you're too kind. I think I'm a good creatine messenger of the research.

There's some really excellent researchers around the world, but I'll take the compliment and run with it. But I actually got into creatine research kind of by accident. We were doing amino acid research and we were investigating glutamine and lo and behold, glutamine kind of didn't do anything for a healthy body. We gave a massive dose and it was kind of didn't do anything for a healthy body we gave a massive dose and and it was kind of interesting to see uh evidence sort of refute what was a myth or misconception about a non-essential amino acid and right about the time in the late 1990s early 2000s creatine research really got a lot of momentum based on some really landmark studies and a lot of athletes limper

christie at the 96 olympics uh was admitted to taking creatine and uh so it sort of blossomed for the last 20-25 years uh investigating the efficacy uh safety and some emerging areas with creatine which i'm sure we'll talk about today so uh it went from amino acid uh research into creatine and it's been the focus of my research probably for the last two decades. Gotcha. And so when you are researching a supplement, just so people can understand what is the day-to-day lab work, the data acquisition? What do you have to do to run a study about how creatine works for all the different things we know it works for? Yeah, it's an excellent question. It's a very slow, monotonous, daunting process. The first thing is anytime you're going to give a

compound to a human, and even sometimes in an animal, you have to get ethics approval from your institution. And that's comprised of individuals from different faculties or medicine to make sure basically that the compound or whatever you're adding or asking to be given to a human is safe. And so you have to provide a lot of research on that. And then once the ethics is approved, then the real work kind of starts, you have to come up with a formulation of your methodological plan, how you're going to recruit subjects. What's your inclusion exclusion criteria? Then you have to run the study. And if it's a training study, I'll give people an example. If it's a six week training study, when you read the article, it probably took a year to finish to occur.

year yeah finished to occur uh we just finished a two-year training study in post-proposal women which took all an entire decade to publish oh wow um and it takes a lot of money when you're running these imaging uh piece of equipment and training and supervising uh it takes a lot of work and and i think a lot of people especially on social media will see a little post or someone talk about a paper that came out. And behind the scenes, it probably took hundreds of hours of research time. If it's a graduate student thesis, that graduate student easily put in hundreds of hours of researching all the data. And then you come up with formulating the results. And sometimes it doesn't work.

And how do you sort of report that to the scientific community and i think reporting null data is just as important if not more important than sometimes the beneficial effects because i think what's happened is there's so many products that are being marketed that do not have evidence-based research behind it i think we need to be very cautious about the safety profile of a lot of things marketed. In our lab, we use third party tested creatine monohydrate. No other ingredients are in the compound. And so we're very confident that whatever we're assessing is very viable. But I think a lot of consumers should be really cautious. At the end of the day, there's maybe a handful of things that might work.

Yeah, on that list, I would say for every five things that could have some small beneficial effect, there's probably 500 other things out there market that don't have any effect and could harm someone. I probably talked about that today as well. I totally agree. I think, you know, when you're looking to supplement to improve performance, longevity, or aesthetics, there the most robustly researched ergogenic aid, maybe outside of like caffeine is probably creatine. And so, you know, I'm at this point, everybody knows it's an amino acid derivative. It's non-hormonal. So it's, it is safe for men and women. So safe, in fact, that they've studied it in some pretty interesting populations is this big question I've been wanting to ask you, like, what are some of the populations that creatine has been shown to be safe for that many people might assume? I can't take it.

I'm a woman. I can't take it. I'm an older adult. Okay. You know, who is creatine for other than dudes who want to be better at football or lifting weights? So let's start at the bottom. So there's some excellent researchers, Andrew Yoggam and Chad Gersick in the United States who look at children. And that's a big area of caution and concern. And right off the bat, I'll preface this that the existing data suggests that creatine is totally safe for children and adolescents.

However, the one thing that we haven't assessed yet, and it's in the works, is the blood biomarkers. So when I say it's safe, that means they haven't reported any nausea, GI tract irritation, some things that are anecdotal. To conclude, it's completely safe. We need to do blood biomarkers. And so that's in the works now and then when you sort of move up into a young adulthood and to middle age uh we're seeing no adverse effects from recommended to even high dosages even at the the loading phase 20 grams a day wow you may get a little bit of gi track irritation or a little bit of water retention but at the end of the day compared to placebo placebo, they're pretty much null. But I use our most recent study as kind of the

Bible, if you will, when it comes to safety. So the study I alluded to was in postmenopausal women. And it was one of the rare creatine studies that was adequately powered. So when we talk about that, a lot of issues with sport nutrition research, protein, caffeine, it's very difficult to get the people to volunteer who are taking the supplement or at least willing to try it. And when you need 80% statistical power, usually you need a large sample size. And again, it's very difficult to do. The study I'm referring to costs in Canada over half a million dollars to run. Wow.

But we did get over 200 postmenopausal females. And this is an interesting fact. We gave over 10 grams of creatine every single day for two straight years. And we measure blood and kidney enzymes and function every year for two straight years. And there was no greater adverse effects compared to placebo. Wow. So in other words, when people say is creatine safe, I usually like to use this study and say we gave 10 grams, which when you compare to the average recommended dosage, double the amount. Yep.

double the amount yep in a population that is typically already having predisposed issues with kidney and liver function because as we get older sometimes organ sure functionality can go down they had no adverse effects wow and i know this is going to come up but not a single female came to me and said my hair is thinning or i'm bald. I know that's going to come up a little bit later. Sure. And when we look at all the other studies around the world, great researchers in Brazil, they've looked at many markers of kidney and liver function at even higher dosages. Creatine is very, very safe. The safety profile is there.

It has generally recognized safety profile in the United States. So overall, I would agree it's probably one of the safest, most effective dietary compounds. And again, the list is very small that a human can consume. And when we say effectiveness, it is effective, but the magnitude of effectiveness is still small as well. You got exercise, and maybe this will give you a small beneficial effect. And I think that's fair. When you hear concern around creatine, I'm sure a lot of it is misinformed, maybe sensationalized, misunderstanding of what it is and how it works.

What are the things that... Hair loss is one that we indicated, kidney and liver health. What are some of the things you've heard from maybe it's study participants, maybe it's friends, colleagues, family members about why they might be concerned about creatine? What are you hearing? The two biggest things that come up is GI tract irritation, usually during the loading phase. So for those listening, the loading phase is just typically 20 grams a day for five to seven days now to put it in perspective we're only producing in the liver and the brain about one to three grams of creatine per day okay for those on a vegan based diet you're consuming no creatine but those on an omnivore diet maybe eating red meat or seafood a couple times a week you're probably taking in one to three grams as

well okay when you do the basic math we're probably in that five grams of creatine range sure oh if you're taking four times that amount there may be some chance that some individuals may experience some adverse effects the most common is gi tract irritation or water retention yeah typically only occurs during the first one to two weeks um and it's one of the biggest reasons that creatine research in young females is so underrepresented uh it's very difficult to get young females to do the creatine loading phase yeah in our lab we don't usually recommend the creatine loading phase unless it's for an aging population and you can simply take a lower dose uh based on the size of the individual,

or you can do an absolute amount. And I say just divide it up into more frequent dosages throughout the day. You may want to take it with food. And that seems to work very well from decreasing the GI tract irritation and or water retention. So if you take three meals a day or four, a little bit of creatine mixed in your yogurt or in your orange juice or whichever is a very viable way to get it into you. And without having a bowl of stoles dragging a lot more water than more frequent, smaller dosages, that's something I would recommend. And I do that myself, actually. Sure. I like that. I've had good luck with that with clients. Just if you are either currently dealing with GI distress and adding

creatine is concerning, space it out, have it with food, don't take it all at once, even if it's five grams. Speaking of loading, before I forget to ask you this, do you need to load creatine or can you take a maintenance dose and be, I guess, patient waiting for saturation to occur? I think the existing body of evidence says you can do whatever you want. Now I'll put it into sort of two options. The loading phase is the most effective and rapid way to saturate your muscle. The premise here is we're talking about muscle.

We haven't talked about bone or brain or anything like that yet. But for most people taking creatine are interested. They're looking at it from a muscle perspective. They want to get bigger, stronger, faster. So bloating is the most rapid, effective way. And if it's the most rapid and effective way, there's excellent research to suggest an association. If your creatine stores are saturated,

that can lead to exercise and muscle performance improvements. However, there is that potential of GI tract irritation and or financial costs of creatine. People say, I just don't want to take that much. Excellent research from the late 1990s also showed three grams a day, every day will get you to the same level. It's just going to take you about 30 days to saturate the muscle compared to the loading phase which you can probably saturate it to be honest after two days but we usually recommend five to seven it's really up to the person if they want to take a small amount every

day uh till they're blue in the face and you know exercise and be happy great um again this is from a muscle perspective we don't know the effects on bone or brain yet sure but those are two viable strategies our lab kind of goes in the middle we like to to do it based on the weight of the person so that's a relative load and so we simply put people on the scale and if they're 70 kilograms we give them 0.1 gram per kilogram per day if they're a young healthy individual if they're older we give them 0.1 gram per kilogram per day. If they're a young, healthy individual, if they're older, we give them 0.15. So that averages out to about seven to 10 grams of creatine a day. Wow. Typically give that in two or three dosages throughout the day.

And that's a very viable strategy. All three are effective and all three are very safe. Gotcha. Okay. Before we move on again, the words saturation come up a lot and water retention come up a lot. When we are retaining water through creatine supplementation, where are we retaining it? And would this be a reason to avoid this supplement if your goal was body fat reduction or weight loss? It's perfect timing. So the water retention is intracellular. So sort of picture your muscles ballooning up.

I think most people, males and females, want an increase in muscle size. in muscle size yeah and when the water is dragged into the muscle in a in alignment with sodium it sort of stimulates a whole bunch of things under the the i guess the membrane of your muscle to work and people have heard of growth factors and satellite cells and and things like that and and so creatine doesn't directly increase the rates of protein synthesis like protein does but it does turn on a lot of other things in the cell. And it's also provides an anti-catabolic, almost an anti-inflammatory response. So the majority of creatine that does increase water translocation moves into the muscle. So I would argue it's totally viable for a bodybuilder going on stage ufc whichever because

it's inside the muscle uh and we've now shown in older adults at least that creatine and resistance training uh it does not increase body fat and we have a new paper coming out in young adults uh showing that creatine does not increase measures of body fat as well. So I think that's a myth or misconception. If anything, creatine super hydrates the muscle. So it's a good chance it also decreases the risk of cramping, especially in hot environments. Interesting. That could be a good use case. A lot of people suffer from cramps, idiopathic cramps.

I don't know what it is. I think I'm drinking enough water. Maybe they are, maybe they aren't. Maybe it's an electrolyte imbalance. But if you have been one of those lifetime persistent crampers, potentially another thing to try here. Speaking specifically about that postmenopausal population that you've studied, a really good segue to talk about brain and bone. Yes. You know, like that's the research that most interests me. I've been taking creatine as a bro creatine user for a decade. And so, you know,

I have plenty of anecdata and I scream from the rooftops all the time. Like if you're going to take one thing, I really think this could be the thing. And I'm open to being wrong about it. I don't have nearly the same skin in the game as you do. But when I see research emerging that this is uniquely beneficial for multiple types of tissue now, we've left the muscle tissue. We're now talking about the bone. We're now talking about the brain. What are we seeing with creatine let's start with perhaps the skeletal system is it beneficial because i've heard a lot of people say about protein and about creatine about supplements it makes your bones weaker you know it leeches from your bones a lot

of this again is misinformation what are we seeing in the research between bone and creatine and how they interact yes so it's interesting that when you put bone cells osteoblasts and osteoclasts in the presence of creatine they seem to become energized and when you look at the pathophysiology of bone turnover which is very slow these cells use creatine for energy just like kind of our cells use it to create and maintain energy in our muscles uh so there's only been a few studies less than 10 uh and it's been very interesting and clear so unlike muscle creatine supplementation when regards to bone has to be a lot higher than a typical dose for muscle and it typically has to be combined with exercise so good researchers from brazil have looked at really low dosages one and three grams per day for two straight years without

exercise and that had no bone benefits whatsoever our labs in collaboration with dr phil chilebeck who's one of the world's best clinical researchers we've shown numerous times that with resistance exercise and walking a higher dose of creatine can have some not all but some favorable effects and this is primarily in older adults we've shown in older males healthy older males 15 above that creatine and resistance training can decrease a marker of bone breakdown so it's kind of like a bisphosphonate if it preserves the bone it may make it a little bit more resistant to fracture but in the postmenopausal female population which we've targeted because they are at a higher or greater risk for osteoporosis creatine has been shown to decrease the rate of bone mineral density loss and also increase bone

strength so we speculate that creatine in combination with weight training and walking is creating some metabolic stimuli that might help preserve the bone. What we don't know is it can decrease fracture incident later on in life. Sure, which would be extremely valuable for menopausal women. Which would be extremely valuable for menopausal women. But it does not appear to be the case that any of the misconceptions around creatine having a negative effect on skeletal health, there's not a lot of credence there. No. And you would also argue, well, we're looking at populations who are already age-related

predisposed to bone loss, and we're not seeing any detrimental effect. Now, the next logical question would be what about young population, and there's good evidence or correlation, if we can increase bone at a younger age, maybe that'll decrease the rates of osteopenia, osteoporosis, and frailty a little bit later on. The theory here, I guess, is that creatine and resistance training, hopefully, if it increases muscle, the muscle will pull on your bone when you're doing activities of daily living, and that might help preserve the skeleton as well. So we're really happy with some of the results. Again, it's not the be all end all, it'll never replace a pharmacological intervention. At the end of the

day, exercise and creatine may have a small, favorable preservation effect on the skeleton as we get older. low-risk supplement compounds that are quite... As far as supplements go, folks, creatine is very affordable. You can find designer forms of creatine and creatine products that can be expensive. We might talk about those. But actual creatine monohydrate is fairly affordable for supplementation. And without seeing any negatives and seeing all these positives or ways in which it works synergistically with other lifestyle behaviors, I see it as a major enhancer for athletic capability, for bone tissue, for muscle tissue. And the one that is the absolute most exciting to me is the brain. My dad has Parkinson's disease, pretty advanced Parkinson's disease. He got it in his 40s. So he's now almost 70. He's had the illness since I was 10. So he's had the unfortunate opportunity of living with this illness for longer than most people do.

Most people get it later. So you don't see how advanced and progressive it can be. And I remember reading creatine literature and coming across a link between creatine and Parkinson's, which then led me to this kind of larger meta link between creatine and the brain. And you mentioned the liver and the brain make between one and three grams of creatine. What benefit to human evolution would there be for the brain making creatine or using creatine? Let's start there first. Yeah.

So the brain is very similar to our muscle that it actually is very metabolically demanding. I think we can all attest to that when we're sleep deprived or jet lag or whatever. We're very foggy and we just wish that coffee would kick in quicker and make us you know get on throughout the day and uh the brain as you know from the pathophysiology of understanding it the brain is unique uh the brain will actually synthesize its own creatine unlike muscle which doesn't so muscle likes to suck in a lot of creatine about 95 percent whereas the brain will make a little bit of wow and then of course the the brain has the blood brain barrier it doesn't like a lot of things

getting in it doesn't want to so the theory here is it's very easy to see a response in skeletal muscle from creatine supplementation sure what we're seeing is the brain is resistant so we probably need higher way longer supplementation protocols to elevate brain creatine stores and to do this there's only a few universities in the world that have this magnet which can actually measure brain creatine concentration and when you look at the small body of research and this is where a lot of caution needs to come into play sure and that's in a limited number of studies across a variety of populations both sex different age groups and including some individuals on depressive medication creatine has the potential and there is evidence that creatine

can increase brain creatine stores so if you increase brain creatine stores just like our muscle you need creatine to maintain at ATP and or reduce inflammation and oxidative stress. But the dose is way higher than what we're seeing for muscle and even bone. Sure. When you look at all the studies, on average, the best studies are showing that 20 grams a day for multiple maybe needed. There's a few studies that have shown about five to ten grams can have some effect so here we are in a conundrum we got three to five grams or a loading phase for muscle it's probably about eight to ten where we see some benefits and i would argue probably ten or more is probably needed for bone and people say why is it different well 95 of what you ingest

or synthesize is stored in your muscle yeah only a trickle amount going to your bone and brain so it kind of makes sense to take more yes you may excrete more down the toilet but some will eventually accumulate in those areas sure and this is a really important distinction. We do see an increase in brain creatine levels. It's way lower than what we get in muscle, probably half or less. And it seems to only be effective when the brain is stressed. Interesting. This is very interesting. If you're a healthy person, you're sleeping well, no metabolic deficiencies. I don't know if creatine is going to give you any extra brain

boost. But the best data seems to be improving symptoms or measures of cognition. Yep. And memory. Yep. Potentially in older adults or those going sleep deprivation or hypoxia. Interesting. When you look at all those areas, it's when the brain is really stressed could creatine provide some effect and if it does uh we have to be very cautious here it's going to be small it's not going to save the day from jet lag or sleep deprivation but there is evidence to suggest it can alleviate symptoms and the most promising is post-concussion in children i was going to ask you that question this is an area we can spend a few minutes on this, but from the neck up, we came up with a huge paper a few months ago, summarizing all the data. So there is potential. Sadly, though, to your point, when it comes to Huntington's and Parkinson's and MS, we don't really see good,

viable, adequately powered research to suggest it has beneficial effects. It does in muscular dystrophy. Sure. I think what needs to happen is larger long term scales studies need to be done. Yeah. Or we can be concluded. So I would venture the next 20 or 30 years of creating research will probably focus on the neck up. Taking a break from this episode to tell you a little bit about my coaching company, Core Coaching Method. More specifically, our app-based training. We partnered with Train Heroic to bring app-based training to you using the best technology and best user interface possible.

You can join either my Home Heroes team, or you can train from home with bands and dumbbells or elite physique, which is a female bodybuilding focused program where you can train at the gym with equipments designed specifically to help you develop strength as well as the glutes, hamstrings, quads, and back. I have more teams coming planned for a variety of different fitness levels. But what's cool about this is when you join these programs, you get programming that's updated every single week, the sets to do, the reps to do, exercise tutorials filmed by me with me and my team. So you'll get my exact coaching expertise as to how to perform the movement, whether you're training at home or you're training in the gym. And again, these teams are somewhat specific. So you'll find

other members of those communities looking to pursue similar goals at similar fitness levels. You can chat, ask questions, upload form for form review, ask for substitutions. It's a really cool training community and you can try it completely free for seven days. Just click the link in the podcast description below. Can't wait to see you in the core coaching collective, my app-based training community. Back to the show. I think so. And that's the trend that I'm getting just from the researchers that I follow. I think with Parkinson's, just using that as an example, there's only so many things you can do to improve a neurological condition like that. And even medication is limited. But if you think about a supplement that has a safety profile and efficacy and affordability for the average person, and we know we're going to get

a net positive effect on muscle, that's positive for movement disorders. You know that you're not going to see any negative effects, maybe a small net positive for bone and brain, that to me would make it worthy of supplementation, even if we knew, look, this isn't going to have a pharmacological effect, because many of these brain disorders, these age-related neurological changes, have downstream effects. They affect how much we move, how much we engage, how much we interact. People tend to metabolize protein more poorly as they age. They need more. I've found, I don't know if you've found this to be the case, many women as they age, they tend to enjoy meat-based protein less. I find many of my clients after they go through menopause,

they're just not into eating as much meat. So those are populations that would benefit, even if we can't say, look, it's going to fix your Parkinson's. That's not a fair ask. But I'm going to buy it if it can give me even the smallest extra benefit to perform activity, easy living or whichever. And you made a really good point here when it comes to dietary changes, probably in the last decade. So we were fortunate to look at vegetarians all the way back in 2003, and they respond exceptionally well. And people say, well, why do vegans and vegetarians respond different to people who consume meat and i'm like well it kind of makes sense creatine is naturally found in red meat and seafood for those who don't consume those products and most people are now emphasizing plant-based proteins they're probably going to get a response and sure enough they got an increase in intramuscular creatine which correlated with increases in performance and they said i said, I can recover faster, I might put on more muscle mass and strength. And from the brain perspective,

Carolyn Ray did one of the best studies in the infancy of creatine research when it came to the brain. And sure enough, vegetarians seem to have a greater cognitive response. But that was just one study, really elegant study from my colleagues in brazil have compared vegetarians and people on an omnivore diet and diet didn't influence what was in the brain but it certainly influenced what was in the muscle so when you look at the small body of literature i think vegans vegetarians and those maybe decreasing the amount of red meat and seafood in their diet um may actually have a greater or favorable effect from those on a very carnivore-based diet. So it is interesting how this shift in the environment or

food source or preference has implications for creatine as well. I want to talk about a couple other unique medical conditions or let's call them biomarker irregularities. I mean, you see these a lot in Canada. We see these a ton in the United States, probably more here than anywhere else. Dysregulated blood lipids and dysregulated blood sugar. And again, I'm not a creatine researcher. I'm a creatine enthusiast. I do not have the scientific literacy capacity or wherewithal to dive too deeply into these things. But a lot of people want to know, can I take a supplement? Or what

and how will this supplement affect me if I have high blood pressure, high blood sugar, or high blood lipids? Are there contraindications? And if not, are there benefits? Because I'm of the opinion based on what I've seen, that there might even be a positive effect, but it might be related to the activity of the individuals who supplement with these things. So the blood pressure one is a bit interesting, and it may come down to the dosage. So some of my colleagues in the United States have looked at the effects of creatine on cardiovascular and vascular health. And if you're trapping in a lot of water that could increase blood pressure so for people with hypertension maybe the creatine

loading phase could be something to stay away from but if it also improves cardiovascular function and elasticity of the arteries and veins that could have a rebound effect where reduces blood pressure so there's not blood pressure is never really measured but there's there's potential to have some beneficial effects there as well regarding blood glucose the only way this really would work uh again if you independent of type 2 diabetes creatine has been shown in a few studies to improve glucose disposal in the muscle or open more doorways. These things called GLUT4. But that's been isolated to more clinical populations. So the theory would be if you put on more muscle mass,

you may be able to suck in more glucose at a greater rate because you're moving. And therefore, it's not going to accumulate in the blood and eventually lead to adipose tissue. But we don't really see hardly any effect of creatine on any measure of lipolysis, hormone sensitive lipase or blood lipids. It doesn't have any influence on cholesterol per se. In humans, there's some data in mice and rats. But to extrapolate that to humans is very difficult. But I think if creatine can give anybody the incentive to move, the key here is the movement is probably going to improve your blood lipids and blood glucose. If creatine gives you some potential or thought to move more often, I think exercise is the key. And I always argue the founding youth is exercise, no pill or powder or supplement.

I always argue the founding youth is exercise, no pill or powder or supplement. And if you combine everyone on the planet, it's going to have any close effect to exercise. Aerobic and resistance training is so powerful. When you're depressed or you have no energy, just go work out. And when you ask people how they feel, they say, I feel way better. And I'm like, no pill or powder, not even the biggest coffee you can find. They'll do that. pill or powder or not even the biggest coffee you can find. They'll do that. But I just think I'm buying anything backed by evidence that can motivate anybody in our population to move. You just get so many health benefits from it. 100%. No pills, powders, or potions will ever

trump lifestyle change. You mentioned depression. I think it's worth discussing. change. You mentioned depression. I think it's worth discussing. I'll say this as a caveat for anyone listening. I'm not a depression expert. I know that all depression, it's multifactorial. It would be foolish for us to walk away from this podcast having anyone believe that creatine is the cure for depression. Certainly listen to, you know, the feedback you're getting from your general practitioner, your psychiatrist, if you're managing depression, don't just start creatine and stop doing what you're doing. But I've seen some research about creatine and depression that was very encouraging to me that made me think, well, Hey, you know, it could totally be related to what you

just said. When you take creatine, then you move. And when you move, it's much harder to be depressed. But is there a positive association between creatine supplementation and relieving symptoms of mild depression? Yeah. And right now there is, there's some emerging areas. So there was a couple really good review articles from clinical populations. Now, this is important to mention that those studies that were primarily done in the early ages, these individuals were still under the pressure of medication. So we're adding creatine to that. And that seemed to have some small beneficial effects. No study has ever looked at people with depression or anxiety or PTSD without medication. And we're definitely not or PTSD without medication. And we're

definitely not saying stop your medication. We're just saying that's what needs to be done before a consensus can be made. But there was also a couple of good papers that came out and looked at NHANES data, which is sort of questionnaire data from the United States. And they looked at the association between dietary creatine intake, so for red meat or seafood. association between dietary creatine intake so for red meat or seafood and lo and behold the more you ate in the diet the less depression symptoms and anxiety that you had so there was a theory here that maybe lifestyle if you can afford red meat or seafood or people choose those good quality proteins totally and keep in mind red meat and seafood they do have essential fatty acids seafood with the omega-3 which has been linked to brain also isolating it down to creatine you got to be very cautious here

but there is potential and i think that's something to consider um moving forward same thing with anxiety and there's a couple theories around ptsd the one common link though that is out there uh and when you look in the fine details of the articles but depression and anxiety has been correlated with reduced brain creatine stores so the theory here is maybe creatine is overcoming some of the detrimental effects of those issues and just hoping to countermeasure what's happening naturally in the brain and and there's justification potentially for that because in healthy, non-depressive individuals, you're probably not going to get any beneficial effect. So again, it's antisympathy. The research

is very minimal, but there is some potential. Gotcha. Okay. So we've kind of covered muscle, we've covered bone, we've covered the brain, we've covered of covered muscle. We've covered bone. We've covered the brain. We've covered some special populations. There is a population that this might be taboo to ask, but like infants, has creatine been studied in infants? And I do not ask this so that I can one day put my, you know, one week old child on creatine. I ask this because I think it provides a good lens into the safety profile for people who might be on the fence, for people who might be like, I'm really a purist when it comes to what I put in my body. How do I know that it's safe? And for me, a good litmus test is if it's safe enough for a baby, it's probably safe

enough for you. And I've even wondered if people who are... This is the number one question I got when I asked, hey, I'm going to be talking with Dr. Kandow. What would you guys like to know? Creatine for babies and creatine for women who are currently in the process of producing a baby. So do we have data on infants? Do we have data on pregnant women? And can we make any inferences, maybe not prescriptions, but inferences with that data? Yeah. So when I heard about this, probably about 10 years ago, I was like, well, hang on, we're getting a little crazy. And then two exceptional researchers in Australia, Haley Dickinson and Stacey Ellery. And Hayley's gone more into industry, but Stacey is the foremost leader when it comes to creatine and reproduction and pregnancy. And Abby Smith-Ryan in the United States is right there with her.

But they've come out with some exceptionally detailed animal studies as well as the potential in humans. well as the potential in humans and when you talk to these individuals and look at their papers yes it has a lot of potential for fetal development wow we don't know what creatine being metabolized to creatinine in breastfeeding or breast milk but there's a lot of potential and when you look at fetal development and the mother going through pregnancy, metabolic demand is very high. And sure enough, there's a few really good papers. They've looked at creatine in sheep of all things, but they're using that as a model for pregnancy and fetal development. And Stacey's shown that it has a lot of potential.

Again, there's hardly any research in viable humans um but the potential is there and the safety profile for the pregnant pregnant female was very high as well so that's an area that's coming i can totally concur with a lot of people saying whoa hang on here we we don't want to be taking anything but you know when you look at the metabolism if our liver is producing it in our brain it's probably natural and this is where I think this is the important part to come in. We're only talking when I say creatine about creatine monohydrate. There's a lot of other marketed ones out there, but monohydrate simply means creatine molecule with a water molecule attached to it. And when you consume it from food or being produced in the liver or through a supplement,

the water molecule dissolves in the stomach. And what's left is exactly what our body's producing. So it kind of makes sense. It's no different than protein or carbohydrates. Our body's used to it. It recognizes it. And creatine can only get in our cells through a specific doorway. And that's probably why the safety profile is exceptional.

Love that. Let me ask you a question then about practicality. A big one, we've hit on this a lot, just the digestive distress and GI distress that people have a tendency to report. And I'll say this, it's like 10%. I find that the clients that I work with that report GI distress with creatine are usually smaller females taking a five gram dose. And a lot of this can be worked around with splitting the dosage up and spreading it out. But are there secondary compounds that work synergistically with creatine to enhance absorption and maybe decrease GI distress. I've heard of people taking it with juice to increase the proliferation of GLUT4 on the muscle. Hey, let's get more of those pathways, as you said, open so that we can suck this thing up.

What are things that people can do if they're already taking creatine or they want to take creatine to enhance the bio availability, to increase the absorption. You know, so many people, they already have an A, but they want an A plus, you know, what, what can they learn from you about maxing out creatine availability? Yeah. So the availability or the absorption of creatine monohydrate is almost a hundred percent. There's some traces. That's cool. So that gets into the blood and then of course we all say let's accelerate blood flow to the muscle yeah yeah the only thing

that has been shown by research is protein and or a very high dose of carbohydrates now when you look at the dose of carbohydrates that is needed to augment greater than creatine alone no one on this planet is probably going to want it anymore with her. But protein is very gluconeogenic and it can have the same effect. So people say, Hey, can I put my creatine in my smoothie? Or I was like, of course, why wouldn't you? Greek yogurt in the morning, a hundred percent. It may actually help.

It's going to give you a, maybe a small greater, uh, uptake, but keep in mind once the muscle is full it's got nowhere to go you're probably going to excrete it so at the end of the day it can give a small effect i argue you know what's the best thing to upregulate creatine intake in the muscle it's exercise i was gonna say training prior muscle contractions stimulate blood flow transport kinetics they open up the doorways in the muscle and creatine sucked in the muscle really, really well. We don't know if that's the same effect for the brain and bone. And that's an area for future research. So when people say I really want to maximize every little advantage, how can I maximize creatine uptake? I'll say, well,

most research suggests taking in close proximity to exercise, or there's the key word, you need to exercise to get the effects of this. You can take creatine in the face, you may get a little bit of brain health benefits, but you're not going to hardly get any muscle or bone benefits unless you're exercising. And the primary form of exercise is weight training. Gotcha. Okay, I would I take my creatine after I train. It's just part of the ritual. It works really well for me. I also did this because I take caffeine before I train. And I have heard, if you don't know, is that competition or that lack of synergy between these two compounds that a lot of people talk about. Is that legit?

Is that worth worrying about? If I'm an athlete, if I am a regular fitness junkie and I go downstairs, I walk into the kitchen, I have a whole cabinet for my supplements. And I've got the protein, I've got the casein, the whey, the vitamins, the fish oils, but everybody has the pre-workout. And that's become so popular that I think a lot of people think, oh, I'm going to take Casey in the way, the vitamins, the fish oils, but everybody has the pre-workout. And that's become so popular that I think a lot of people think, I'm going to take my pre-workout right now.

And so I don't forget, I'm going to throw my creatine in there. Are those people maybe missing out on either of those compounds when we look at caffeine and creatine interaction? So it's probably the biggest question next to baldness that I get is because everybody loves caffeine and everybody loves creatine for the most part. So the best cellular research does have evidence to suggest that caffeine and creatine oppose one another like tug of war at an area in the cell that's really important for muscle contraction. And then when you look at the studies that have looked at creatine supplementation for more than one day, if they do that caffeine seems

to interfere with some of the effectiveness of that. So a couple schools of thought, I agree with you pre exercise caffeine, checkmark, post exercise or intro workout creatine is another checkmark. For those who are taking pre-workouts i highly doubt the only two compounds in that workout are caffeine and creatine they're called alanine and sodium bicarbonate and leucine and all this stuff so you'll never be able to tell what's causing you to have an effect um but there is good evidence to suggest that caffeine and creatine together can cause GI tract issues and or oppose one another at the cell membrane. And we did a small study last year clearly showing

that creatine improved one measure of muscle size, but the group who took caffeine powder and creatine powder together did not. So it was indirect evidence that they may blunt each other during a resistance training program. Interesting. Okay. I'm going to ask you this question because I think you're an expert on both of these topics and we've hinted at it a lot. Creatine and baldness. Yeah. That's, that's my question. You've gotten into studying creatine for a living and you also happen to have no hair and, and, you know, most of that can be driven by genetics, you know, any, any, you know, there's a ton of content on the internet about, uh, male pattern baldness now, because, you know, more people are looking for options and there are drugs and compounds and topicals and,

and ways to regrow hair. And I think people also look to avoid things that might cause hair loss. So can we put the people at ease a little bit when it comes to creatine and hair loss? Yeah. And I've only recently changed my stance on this, how I paint the picture of this. So before I said, there's no evidence on the entire planet to show that creatine causes hair loss, and I just kept it at that. And then I sort of was thinking about this. Well, from a scientific perspective, we need to back up a little bit. The only study ever in the world, and this is shocking, there's been over 1000 peer referee studies on creatine. The only study was the

famous rugby study from Australia, where young individuals like ourselves were put on a high dose of creatine. They did use the loading phase, but they did a crossover design, which is kind of cool, where these individuals were randomized to take seven days of creatine, about 20 grams a day for five to seven days. And then they measured a whole bunch of hormones in the body. And the hormone that was implicated or became famous was DHT, a derivative of testosterone. And when you look at the biology and genetic literature, DHT is correlated, not caused, but associated with hair thinning and hair follicle loss. So immediately people said, well, if this hormone went up, these individuals must be losing their hair and going bald. And a couple of really important things from that study, resistance training alone will cause DHT levels to go up. Just because a hormone goes up does not lead to a phenotypical change.

I think we all know that from testosterone and estrogen and growth hormone. And another big thing is the DHT did go up more on the creatine supplement compared to placebo but it was still within the physiological normal range and people say what do you mean by that i'm like well next time you go to your doctor you're probably going to get your cholesterol measure and he's going to say your hdl falls within normal range so there's a lot of variation between sex and age and geographical location. So at the end of the day, if you stop at that study, there's no direct evidence that creatine causes hair loss. They did not measure hair cross-sectional area or thinning.

But then I also say, well, hang on a sec, though. There's never been a study in the world to show it doesn't. Right? So we got to be careful here. Just because it's never been shown, it doesn't mean it's never been world to show it doesn't right so we got to be careful here just because it's never been shown it doesn't be it never been shown to do it but i will say this i've assessed over a thousand research subjects with high dose creatine even the post-menopausal female study for two straight years and not a single study or sorry not a single person has ever come to me and said darren my hair is standing or falling out now that kind of says it all we don't have any evidence to suggest

it does i really am praying that a study finally says you know what we're going to work with the dermatology department and we're going to actually measure cross-sectional area and hair thinning. I get this question on social media. I could literally say creatine caused or decreased cancer. And they're like, I don't care about that. Does it cause baldness? It's amazing how people are focused on it. And there's a few of us researchers in creatine world that are bald. So we're not really good messengers when it comes to that.

But we have to be cautious here from a scientific perspective. There's no evidence to suggest it does. It's never been shown it doesn't. But again, we have to base that on scientific evidence. Sure. I'll provide anecdotes, anecdata of my own. Three or four months ago, I had a alopecia flare up. And for people who aren't aware, alopecia is you lose a chunk of your hair. It could be caused by stress. And I was concerned about getting this hair to grow back. And even knowing everything that I know, I felt this little voice in the back of my head saying, hey, maybe you should stop the creatine. And I told myself, you know what? I'd rather be small and bald, or I'd rather be big and bald and muscular and bald and get these benefits to be

bald. So I did not stop supplementing with creatine during the entire protocol by which I went about regrowing this hair, which involved a combination of topical essential oils and regular visits to the dermatologist. The hair grew back and the gentleman physician dermatologist said, very rarely do I see hair grow back this rapidly. So that is not evidence beyond my own anecdote, That is not evidence beyond my own anecdote, but if one can regrow hair while supplementing with five to 10 grams a day, and we don't have any reason to really believe that this is causing balding, I would say to anyone listening, creatine and the health-promoting behaviors that you're likely to do in conjunction with your supplementation is going to be more likely to cause hair growth than it probably is a loss in hair overall.

But yeah, Dr. Kandout, thank you so very much for following up with the latest and greatest research. Anything people should keep an eye out for, any emerging research that you're excited about and where can they find you? Yeah, I think the couple studies we have in our lab, we're going to be looking at creatine again with resistance bands at home post pandemic and look at the effects in older adults. And then we're still trying to finally answer is the timing of creatine an issue or even consider. So those are some big areas. And we're starting to move now on cognitive measures, even consider. So those are some big areas and we're starting to move now on cognitive measures, depression, anxiety, and things like that. And the easiest place is on Instagram at Dr. Darren Kando. I try to promote as much research, not just creatine, but other things that come out.

And yeah, that's probably the easiest place to find me. Well, and guys, I try to share all of Dr. Kandow's research. I'm pretty bad at it, but I will keep you up to date on all things creatine. And I'll try to provide you with as many experts as I can. And I think we got one of the world's best today, man. Thanks a ton for your time. No, thanks for having me. It was great. Appreciate it. you