Transcribed using AI transcription; errors may occur. contact Mikki for clarification
00:04
Hey everyone, it's Mikki here. You're listening to Mikkipedia. And this week on the podcast, I speak to returning guest, Dr. Darren Candow. So I spoke to Darren back in March, 2022. So I was super stoked to bring him back and chat about the advances in the creatine space, which have largely not been performance related, but much more in the lines of health and longevity, which

00:33
you guys know I'm super passionate about as you are too. So Darren and I talk about dosing creatine for different effects, i.e. what you might do for performance versus, say, cognition or sleep deprivation, where the research lies with respect to the brain, healthy aging, the best time to take creatine and what to take it with to enhance its potential effects.

00:58
sex differences in creatine usage and we chat about what we see in literature versus anecdotally what is often reported with creatine and a whole lot more. Darren as you know is the go-to expert in this space and not only does he research it but he lives by some of the principles that we talk about and that's what makes him such a resource to be able to pick his brain in these issues so I was so appreciative that

01:25
Darren was happy to come back on Mikkipedia to chat to me about this. So for those of you who haven't listened to the first episode with Darren, I've got a link to that in the show notes, it's episode 71. Dr Darren Kando is a full professor and associate dean of graduate studies and research in the Faculty of Kinesiology and Health Studies, University of Regina. Dr Kando supervises the Aging Muscle and Bone Health Laboratory and serves on the editorial

01:54
for the Journal of Aging and Physical Activity, Journal of the International Society of Sports Nutrition, and Bio-gerontology. Dr. Darren Kando has received over $1.5 million in research funding from various funding organizations, both public and private health, and has published over 100 journal and knowledge dissemination articles involving exercise and nutrition. He also serves as the Chief Scientific Officer

02:22
for TDF Sports and I have also popped a link to his profile at the university in the show notes. So before we crack on into this conversation I would just like to remind you that the best way to support this podcast is to hit the subscribe button on your favourite podcast listening platform. That increases the visibility of Micopedia and amongst literally thousands of other podcasts that are out there. So more people get to hear.

02:51
updates in the research field from experts like Dr Darren Kando. Alright team, enjoy this conversation.

03:01
Darren, thanks so much for taking the time to speak to me this morning about round two on creatine. It really does feel like there has over the last couple of years just been this explosion of research, not necessarily in the performance realm, but more in that health and longevity space. And certainly a lot of people are talking a lot more about it and it's much more mainstream. Is that just me or are you seeing that as well?

03:29
No, you're totally correct. It's a huge explosion. We kind of thought we knew everything about creating from an athletic performance perspective. But I would say in the last at least decade, conservatively, it's been a huge push on the health aspects, everything from bone health for females to cognition and potentially brain health. We're actually seeing benefits for pregnancy by Stacey Alleri out of Australia. So it's actually starting to have

03:54
more of a health aspect, and I'm really proud and happy that there's a lot more focus on female health as well. Yeah, nice one. And I think what's super interesting is, you know, you do have these, you have supplements and they appear to have like isolated benefits for one particular thing. And what I would say is sometimes people are a little bit more suspicious when you say, oh, this is this one supplement, and it has these multiple sort of benefits.

04:23
of the role that creatine plays in the body, right, and in different organs. Can you just remind us of sort of the primary, I suppose the primary, I guess, mechanism with which we use creatine or it's in the body, just the real basics? Yeah, that's an excellent segue. It's a nitrogen-containing compound, very similar to an amino acid, but basically we have it in our cells to help maintain adenosine triphosphate or ATP, and that's the energy currency of our cells.

04:52
Of course creatine got a lot of its fame and promise for skeletal muscle because if you have more creatine in your muscle what was happening is when people were performing exercise, primarily weight training, they were able to do more repetitions, get stronger and over time they got bigger, stronger, faster. So that's one of the main mechanisms. Creatine is an anaerobic compound per se. It helps maintain adenosine triphosphate in our cells.

05:15
But keep in mind our bone cells as well as brain cells use creatine for energy as well and maybe that's helping explain some of the profound benefits that it's emerging. But there's a lot of other cellular aspects of creatine which we'll get to. The other cool thing about creatine is we naturally produce it in the liver and brain, but we can also get it through our diet. So when you eat red meat or seafood or even smaller amounts of poultry, you're getting about maybe one to two grams on average of creatine per day.

05:44
But those emphasizing a carnivore diet are getting a lot more. And of course, on the flip side is what about the vegans and vegetarians? Will they respond to creatine? And if they do, do they respond better? Current body of evidence suggests they do. And it's likely because, obviously, they have a reduction coming through their diet. Yeah. And on that, Darren, I often get asked a question about creatine, should I supplement, and where can I get it from my diet? And you've just said, one to three grams we may get if we have an omnivore.

06:13
style approach. So in your work and in the research that you and your lab have conducted, but also what you see with your colleagues, is it enough just to rely on our diet alone, or do you think that those health and longevity benefits actually are conferred more when you supplement? Yeah, that's an excellent question. So let's, I guess, if you back back into the question, is it absolutely essential to take creating supplementation? The answer is no, because vegans and vegetarians can respond exceptionally well without the

06:43
taking a supplementation. However, when you do increase the amount in addition to diet or natural synthesis, i.e. through supplementation, there's over a thousand peer-referred articles now clearly showing that a small greater amount or accumulation can lead to a profound benefits primarily muscle performance. So in as little as three grams a day can accumulate in about a month and then you can get beneficial effects on performance and lean tissue mass.

07:10
The dose might be a bit different for cognition or the brain, but we've done muscle biopsy studies of vegetarians and they only have about half the amount of creatine in their muscle and when you give them a supplement, they respond exceptionally well and it's likely because they only had half the amount compared to an omnivore or obviously a carnivore starting out with. And obviously you mentioned how creatine sort of acts in the body at that level of the ATP. Does creatine then help?

07:38
the mitochondrial health. There's a lot of talk about mitochondria, everywhere in the types of supplements, CoQ10, urolithin A, et cetera. What kind of integration or link do we know occurs with creatine in our mitochondria? Yeah, it's actually highly linked. So although creatine is an anaerobic or is theorized to be anaerobic, the mitochondria plays a crucial role in its recovery. So when ATP is synthesized in the mitochondria, the creatine kinase reaction sort of shuttles it.

08:05
and then we use that. So after exercise or even your sets or post exercise recovery, that's when accelerated rates of creatine seem to occur. So that's why it may have beneficial effects for some of the aerobic athletes. But to that point, the mitochondria sort of engulfs reactive oxidative species or inflammation. And that's why creatine seems to have some of these anti-inflammatory effects, not only in muscle, but also the brain as well. So interesting because...

08:33
So many people talk about it at the absolute cellular level that dysfunctional mitochondria is one of those sort of hallmarks of, I guess, chronic, outside of the performance benefit, but like disease. Yeah, and so creatine will kind of decrease the amount of work that the mitochondria has to do to fight off, obviously, reactive oxidative species or VO2 kinetics. But there's been some preliminary data in roads where creatine may help stimulate mitochondrial biogenesis.

09:03
We now know we get that plentiful with exercise, primarily aerobic, but creating might be there to help adjunct that. Not shown in humans yet, but it's there to have some potential problems for the mitochondria for sure. Super interesting. Darren, you mentioned that sort of optimal dose potentially for musculoskeletal health around that sort of three grams. And also that we may require high doses for brain bone health. So what does the research suggest there?

09:31
Yes, so from a skeletal muscle perspective, we're very confident three to five grams is a very viable daily amount to take. But bone is a little bit different now. There's not a lot of research on bone health. The majority is focused on postmenopausal females. So keep in mind the cessation of estrogen might be playing a greater role here. But the lowest dose that we've shown in combination with exercise to be effective is about eight grams. The better results came a little bit higher, about 11 grams.

09:59
But please note, they were taking that daily for at least a year. So bone takes a long time to turn over from a magnitude of treatment effect. But we don't think young females would get any beneficial effect, or younger females at lower dosages. We just don't know that. There's been great sites out of Brazil where they've given one to three grams of creatine without exercise, and they had no effect whatsoever. And then from a brain perspective, it's a bit more tricky. The brain has the blood-brain barrier.

10:28
It doesn't like to allow a lot of things in and it's very limited or apprehensive to circulating creatine through supplementation. Creatine supplementation can slowly accumulate in the brain, but we only start to see and accumulate in areas of traumatic or metabolic stress such as depression, anxiety, maybe concussion. A common denominator there is that their baseline creatine stores are reduced. So maybe the brain is more sensitive and requires or...

10:57
maybe relies more on supplementation. But please note, if you're a healthy young individual, adequate sleep, great diet, no abnormalities, creatine from a cognitive perspective is not gonna have any noticeable effects. It only seems to have some effects if you're sleep deprived or have metabolic stressors. And you've probably just described half of the people listening to this podcast. Yes, everybody in the world pretty much. Yeah, yeah.

11:24
Creeteen, are there any sort of carriers that can help creatine sort of cross that blood-brain barrier a little bit easier? And I mean, I don't know much about this area, but I have heard people talk about different things. Yeah. So from a brain perspective, the only thing that we're starting to see from a reliability, that means study after study, is a common called GAA. It's guanidino acetoacetate. It's the precursor for creatine. And when you combine the two, it seems to allow more creatine.

11:52
regulation or uptake into the brain. It's theorized to open more doorways, so to speak. But from a muscle perspective, protein, carbohydrates can allow that as well. But one of the best things is prior muscle contractions, also known as exercise. So Roger Harris's study in 1992 clearly showed that when you exercise and then take creatine, you get an increased uptake into the muscle. So when people say, what's the best way to take creatine, they say, make sure you exercise. And the response will last hours and hours after the session.

12:21
It's nice that the timing of creatine is kind of irrelevant, but please make sure the listeners exercise because that's the foundation for how unlocking the potential. Yeah, nice one. And with creatine's potential role, obviously, in the brain, obviously, there's, I'm thinking about athletes, but also anyone who are in contact sports and they are at greater risk of traumatic brain injury. Is creatine part of a protocol?

12:49
that you might recommend or sports physicians recommend that they take? Yeah, it's interesting. It is emerging. I'm getting a lot of questions from coaches, athletes and even governing bodies. We think it's still in its infancy and we know a little bit about some protocols. So the protocols are either the loading phase, which is about 20 grams a day, or about 4 to 5 grams for several months. That has been shown to accumulate into the brain.

13:16
We don't know the optimal dosing pattern and we don't know the areas of the brain it really targets, white matter, gray matter or something else. So it's still in its infancy. I would say the next 20 or 30 years will really unlock its potential. But what we're starting to come to a consensus is that the dose needed to accumulate significantly in the brain is probably more than muscle. So now you get to a conundrum. What if you're taking a dose for muscle, bone, and then brain?

13:45
which is best. We have a new paper coming out where we make the case that each tissue might require more, but to cover all bases, I take 10 grams of monohydrate a day and I take two five gram dosages to sort of look at, okay, I'm checking off the box for muscle, bone, and then cognitive effects as well. So I personally take 10, but I wouldn't recommend maybe to start that if someone's just interested in taking it, you can start in a smaller dose. No studies ever shown 10 is the best.

14:14
But based on the totality of research, I've sort of did the math and come up with an average recommendation for myself. If people take creatine, are they going to notice an appreciable difference? Is there more sort of like putting pennies in your bank? Like you sort of know that it's gonna be good for later. Yeah, the thing we often see is when you are engaging in exercise and take creatine, your recovery and or performance from a muscle performance perspective or exercise performance will go up.

14:41
The thing that we see the most is either more repetitions can be performed or your increase in strength. Those are the performance measures that seem to go up first. Lean tissue mass will go up eventually. We're actually seeing a small decrease in fat mass or no effect over time. But you'll never notice an increase in bone density because obviously you can't see that. We do start to see some cognitive effects in those that are having sleep deprivation or jet lag. People say they don't experience as much fogginess.

15:08
And in a recent study we put out with a colleague in Norway with long COVID, it decreased the incidence of headaches. So it seems to have some promise for sort of speeding up recovery in the brain. But from a muscle perspective, those are the most immediate results. Yeah, nice. And with the jet lag and the long COVID, like, were the doses up at about that sort of, did you say 8 to 11 grams? Yeah, they varied. Some did the loading phase.

15:35
the long COVID was about four grams a day for six months. So again, you either got to take a lower dose for a longer period of time. So, you know, when people say, can I take three to five grams? I'm like, absolutely. I would say after several months, maybe half a year, it will start to accumulate in other areas. But in those tissues that are more metabolically stressed, that's where creatine seems to have some favorable effects. So for example, if someone was considering a creatine supplementation and they're on three months, their muscles are probably full.

16:04
maybe the beneficial effects of bone were there, maybe it's starting to accumulate in the brain if they need it. But at the end of the day, is it required for supplementation? No, you can get it through the diet. But during times of metabolically stressed incidences, that's what creatine seems to have some promise. Do we know anything, Darren, about the heart? And is there any research in the heart and yeah.

16:29
Yeah, there's minimal research, but it has shown problems for cardiac rehab. So after an individual will suffer some type of cardiovascular strain or a bandage seems to have some beneficial effects on some of the smooth muscle properties as well as cardiac muscle. We actually did a very nice study a few years ago on stroke rehabilitation. And what we saw was in stroke survivors that actually creatine and resistance training improved gait speed.

16:55
So it has some preliminary data there to show maybe creating an exercise might be a therapeutic intervention post-traumatic events such as cardiovascular disease or stroke. Yeah. And what kind of doses as we've seen in this like emerging research? Yeah. It was about 0.1 gram per kilogram, so about seven to eight grams per day. So a little bit slightly higher than what we recommend for skeletal muscle, but it was more from a rehabilitation perspective. Yeah. Do you get pushback, Darren, from doctors who look...

17:23
at markers of kidney health and then are like, hey, you've got to come off your creatine or like what, can you just describe to us, or are there any contraindications with that? Cause in fact, I had an inquiry about that, I believe last week even. Yeah, it probably happens multiple times a day, 365 days a year. So.

17:43
Creatine is not creatinine, so there's a little disconnect. So when you go to your GP or nephrologist and you get an annual blood work done, whichever, you know, you're measuring your blood glucose and cholesterol, they usually check off a box that has EGFR, so that's estimated kilometer filtration rate, right beside it is creatinine. Now creatinine is the metabolic byproduct of creatine. So when you're contracting your muscle and doing exercise, creatine is used, but it gets broken down to a waste product called creatinine.

18:13
and then it's filtered through the filter of your body, which is the kidneys. The issue by going on creatine supplementation is that you've elevated your creatine and therefore when you exercise or use more of that creatine, your creatinine stores go up and then when your doctor sees that, they're like, oh my God, your kidneys are not working properly because you have elevated creatinine. For those thinking of supplementation, please tell your doctor you're on creatine supplementation. It's likely that your creatinine will be elevated. Your estimated...

18:41
filtration rates will be poor and that doesn't necessarily mean that your kidneys are in failure and I'm not a medical doctor but what happens is when they go to their doctor and they come off creatine those values go back to normals clearly showing that it wasn't your kidneys in failure it was just the metabolic byproduct of a supplement so that happens all the time. From a safety profile perspective we've done a number of studies now looking at kidney and

19:11
But the best study is the two year one where we gave 11 grams of monohydrate a day for two straight years. And we did measure liver and kidney enzymes annually and there was no difference compared to placebo. And that was at a super high dose. If you have pre-existing kidney or liver abnormalities, please check with your doctor or at least consult with them. But at the end of the day, recommend a smaller dose of creatine should not cause any adverse effects. Okay. And then if people are concerned with what they're seeing, I guess that the

19:40
the solution would be to come off the supplementation and then recheck their kidney function or liver enzymes to just assess their normalcy? That's correct. A lot of people, before they take supplementation, will go get their values checked, then go on the supplement and then check that again. And if they're elevated, they simply go off creatine for four weeks and then go back to see their doctor. And more times than not, those values come back to baseline. And it's just a simple metabolic, the biochemistry of the molecule is broken down to a...

20:09
a marker because a lot of labs don't want to do the pure filtration rate. They do an estimate and they use creatinine for that. Yeah, okay. I always wonder with things like updates in our knowledge about how the body metabolizes supplements and things that when that all sort of filter into, I don't know, medical school or something, often it doesn't appear to. And if you exercise, you're on a high protein diet, you're creating kinase, the enzyme is going to be elevated potentially because you're exercising more.

20:36
So there's a lot of things to understand before we get these false positives, which happen almost on a daily basis, yeah. Yeah, yeah. Darren, obviously, I mean, do we understand the sex differences and how sort of creatine impacts? And I mean, I sent a question through and I believe I even, I text you on Instagram actually, and you were very nice about getting back to me, but so many of my female clients.

21:02
say that they experience more water retention during their luteal phase or an increase in those vasomotor symptoms if they're in that perimenopausal phase, which I haven't seen that in the literature. Do you have any sort of reports anecdotally or? Yeah, so let's start with the first part, the bloating or water retention. We typically only see this in males. We don't see a lot of this in females.

21:27
However, if they do experience it, it's probably because the dose is too high to start with. So if you do a loading phase, a lot of studies say 20 grams a day for seven days, and then we'll do a maintenance phase. That's where we typically see the GI tract irritation, water retention, or bloating. For those susceptible to that, please don't do the loading phase. I would simply start with three grams a day, but here's an important distinction. You can take the three grams, which is about a half a teaspoon at once.

21:54
But you could even divide that up into two 1.5 gram dosages and maybe do that in the morning and evening with food. You'll probably notice hardly anything. And if you wanna work up to five or six grams, you can take multiple three gram dosages or whichever you like. But taking a bowl as they're intermittent is fine. We don't know if one is better than the other. We're actually doing that in our lab right now to see if there's an advantageous effect.

22:19
Regarding the differences in the luteal phase, Abby Smith-Ryne in North Carolina has shown that there's not really any fluctuation in those, but it's so hard to control from an experimental perspective. You could start in the luteal phase and then your post-testing's in the follicular. We tried to manage, it's extremely difficult to do. Then you also have to look at environmental temperature, hydration status, things like that. At the end of it, we don't think it plays a major role, or sorry, a minor role, if any, so not even a major role.

22:47
But there needs to be more long-term clinical trials on that. And then what about the stage of lifespan? Like what if we take premenopausal young females versus perimenopausal, and of course compare it to post without the cessation, or sorry, the cessation of estrogen and the menstrual cycle, then we would have a better idea. But this is an area that I think will be really a big focal point for the next few decades. But again, for those that do not, the bloating or GI tract irritation.

23:15
Do not do the loading phase. I think that's the area that gets a lot of people. And then they stop taking it because they said, I gained two or three pounds, just take a smaller dose and that should be fine. Yeah, and you know, as you sort of described, splitting even a small dose, that's quite good, reassuring. And what about the idea of just cycling creatine off in your luteal phase? I mean, obviously it'll accrue just a little bit slower over time, but that's not a bad strategy.

23:44
Yeah, so the theory with cycling is very valid. It's never been shown if cycling is better than continuous. But if you want to take cycling, so for example, once your muscles and brain cells are full, it takes about four to five weeks before those levels come back to baseline. We put out a study a few years ago that's showing that creating just some of the days you work out was very advantageous. But my answer to this is change with the brain effects.

24:10
So now I suggest take creatine every day for a couple of reasons. You're gonna have that nice consistency and then on the days you may not be working out specifically like walking and activities of daily living, that's fine. But that's when the extra creatine may accumulate in bone cells or the brain. So I think creatine is kind of like a vitamin. If you take it every day, great, you'll probably get better benefits. But if you just take it on the days you work out, we've shown at least from a muscle perspective, you get beneficial effects there as well.

24:40
And you mentioned about bone health and postmenopausal woman and the potential benefit because we lose estrogen. Yes. Can we chat about that Darren and the relationship between creatine and the bone? What does it do and what do we know? So there's two categories of bone cells. One is called osteoblast.

25:00
And these are the cells that are involved in forming bone as we're growing and developing. So they kind of take calcium and phosphate salts just like cement and package together into our skeleton. And when you put osteoblasts or these bone building cells at a pituitary just with creatine, they get energized. So the theory was these cells, just like our muscle cells or fibers, use creatine and creatine kinase for energy. And at the same time, we show now that these indicators of osteoclast or bone breakdown are blunted.

25:29
So now we're starting to put the piece of the puzzle together. Maybe creatine has some slight anabolic effects to bone building cells, and it also decreases bone breakdown. So at the end of the day, you might have more deposition of bone over time. And that might explain some of the benefits we see in post-menopausal females for having an increase in bone strength and offsetting bone mineral density loss over time. And are the studies been done in sort of sedentary individuals or

25:56
Or like, is there a protective role there? Or like bed rest, for example, which is obviously like you can lose bone either very slowly over time or sorry, or muscle mass as well, I suppose, or quite quickly. Yeah, the vast majority of the populations were untrained because we tried to target a segment of the population that were causing a lot of healthcare issues or are trying to improve these individuals to work out.

26:22
So that's the main population. We never looked at young athletes. And at the end of it, it would probably have no effect if their bone is already healthy and strong. But the next logical area, as you mentioned, bedrest, so mobilization, what about frailty or individuals with osteoporosis? I think those are the populations that might even get a greater benefit because the bone might be more sensitive to use the supplement and translate that in the bone beneficial effects. Yeah, and does there any, I mean, you mentioned protein

26:52
being a vehicle for helping creatine with muscular health, but is it bone health as well? Yeah, the small body of evidence where we looked at creatine with protein has not really looked at bone. And if it has, there's been no effects. The problem with bone is it takes at least six months of training before it starts to turn over. And we usually need to do a year, two or three years, and they're very expensive to do. And unfortunately, the body of research is very small, so we can't really conclude if it would have any greater effects.

27:21
people who are interested in preserving their bone health and resiliency, like let's say you're my age, it would be beneficial to be on creatine now to help with that sort of preservation. Is that what we think? Yeah, well first is exercise. If there's no stimulus from exercise, nothing will happen. And then the effects from creatine again, 50 and above have been small, but yet favorable.

27:47
So I think for the viewers, please note, you're not gonna experience these magical wonders that a bisphosphonate or other, a pharmacological intervention may occur. They can have some preservation effects, but I think a lot of people are interested in at least preserving what they have. If anything, they might get some small effects. We certainly have not shown any detrimental effects. In other words, when these females took creatine, they did not get an accelerated reduction in bone strength or health. So that's very beneficial to look at.

28:12
And I guess the same would apply for a sedentary individual on their muscle health as well. They're not going to have any negative effects from taking creatine. Yeah, that's a great segue. We've never seen it backwards like, oh, we gave you creatine, you got worse. That's never happened. So at the end of it, the worst case scenario is you get the benefits of exercise and maybe creatine's effects were small, we just couldn't detect it. But in a group mean setting, we usually do see some beneficial effects. Yeah, nice one. What do you think is, what do we know is happening?

28:42
with the brain, Darren, I know I seem to be tangiting a lot into my little areas, but I'm super interested, like with the traumatic brain stress, like you mentioned, you did mention sort of like mental stress, and I've heard you talk about sort of work stress and things like that, like what determines that mental stress for someone to actually benefit from creating? Yeah. So the brain is small, but it uses about 20% of our energy per day.

29:10
and when you're more cognitively stressed, that increase will go up. So a common denominator, sleep deprivation, working overnight, jet lag, clinical depression, anxiety, a common denominator is that their creatine levels are reduced compared to a nice, young, healthy control. So the thought is if we gave you additional creatine in the body, maybe that will accumulate and sort of compensate in the brain to bring those levels up to the baseline. So when you do feel another stressor, you have adequate amounts to offset or fight that off.

29:40
And the main mechanisms primarily in the rodent model, but we're starting to have more information in humans is that it reduces oxidative stress or inflammation, just like muscle. So the theory is that maybe the brain can recover quicker under times of metabolic stressors, or may not need as much time to sort of maintain those activities of daily living. So some recent data has come out with clinical depression. And when these individuals still on medication, of course, took creatine, their outlook,

30:09
performance measures and subjective recovery measures did improve. We started also see that in anxiety and other forms of like PTSD. So a common denominator of all those as well is that it seems that creating supplementation may be an adjunct to either medication or lifestyle interventions to improve some benefits in certain populations. There's clear evidence in young, healthy individuals, you're not gonna get any greater effects.

30:35
So please note, if you're watching and you're getting adequate sleep, you have a good diet, no huge stressors in your life, you're probably not gonna notice any of the effects. There's been a meta-analysis on memory in older adults and that has improved, but the best evidence is when we take people and sleep deprive them and when we say we want you to do a bunch of memory or cognitive tests, their ability to perform those is elevated. So again, there is evidence to suggest there's something there.

31:01
we need probably 10 more years of research before we know the concrete mechanisms and the populations. Right, but I guess we could just hedge our bets and be thankful we're taking it now, I suppose. That's right. Yeah, yeah. It'll never prevent a concussion. I think that's globally, or head trauma, but it has been shown to improve symptoms of recovery from head trauma. So again, the mechanism we think is around that inflammation, oxidative stress. Yeah, nice.

31:30
And you mentioned that there was some research on sort of memory recall in an older sort of population. Do we think that it has the ability to, or could we suppose that it could help with that preservation of memory over time, like help reduce cognitive decline? Yeah, that would be globally impactful. So we have a study planned in the fall to look at the effects on dementia.

31:55
There's a current study I'm aware of on Alzheimer's, and if it has any benefit on dementia or Alzheimer's, that's a game changer from a global perspective. You can almost throw everything else away. I mean, if that could solve or have any impacts on neurophysiological and sort of those cognitive effects on those disease state populations, that would be massively important. So those are coming. We don't see currently any big benefits on Parkinson's, Huntington's, or multiple sclerosis. The issue there with those studies that have been done, they've been small scale.

32:24
the dose has been questionable or the intervention that they did as well. So we need these long-term large-scale studies. The issue with all human research is very difficult to get the number of people required to have what we call statistical significance or adequate power. And it's gotten worse ever since COVID. It's very difficult to get people to volunteer. So we are struggling, but we're still trying to maintain the perseverance with that. And I'm hopeful in the next few years, we're gonna get some more big studies that'll come out and sort of provide more information.

32:54
And what about sex differences in the brain, Darren? Are there any? Yeah, interesting. So there's slight sex differences in muscle only from a minimal perspective. Males and females respond exceptionally well. The brain says not really. So it's very interesting. Diet really doesn't influence brain creating content. You could have a vegan versus a carnivore, same level. Age.

33:15
can respond differently as well, but we're not seeing any big sex differences there as well. So unlike muscle, the brain is kind of a unique aspect of the body and we're not seeing any of the big effects there. We see a few in rodents, but not really a lot in healthy humans. Oh, interesting. Darren, is there anything in particular that would affect an absorption, I guess an individual's absorption?

33:40
or response to creatine. Obviously you've mentioned the vegan vegetarian. So if you have low baseline levels, you're more likely to respond greater. Anything else? We think the amount you're already eating, as you just mentioned, but also age could play a role. So we theorize that as you got older, maybe your creatine kinetics got a little bit weaker or impaired.

34:03
And when we've done some meta-analysis, we showed that in the lower limbs, phosphocreatine was sort of impaired in the larger muscles like the quadriceps. And so that's why maybe older adults respond so well with supplementation when they do squat or leg press. So again, that's the third area we think maybe age as another effect. And then physical activity. The more you maintain physical activity, that's gonna maintain your creatine stores. It won't increase them, but it will maintain it. The more inactive you are, they do get reduced.

34:33
Again, one of the big take homes here is to maintain physical activity as long as you can. And when you see the escalators or whatever, bypass those, take the stairs, because you're recruiting more of the muscles in the lower body, which sort of disappears as we get older. Yeah, nice one. And I think it's such a good important message because our modern environment is just set up to make life as easy as possible, but it's only really easy in the moment because we're really just sort of like kicking the can down the road otherwise. Yep, exactly. Yeah. Yeah, nice one.

35:02
Darren, and just because people are, you know, even though you've said that it doesn't appear to matter when you take creatine, but just that you exercise, that'll open up those channels for a lot long for several hours. Did I hear that correctly? Yeah, you can take it before, during, after. I like to take it in close proximity to exercise because it sort of increases or releases those doorways that allow creatine in.

35:30
But there's other studies taking it with breakfast or late in the evening also had some beneficial effects. So the nice thing is the timing may not be that crucial. I think one of the best times to take it is in close proximity to exercise before, during or after. Yeah. And then with anything in particular, you mentioned protein helps with it. And yeah, how would that look? Yeah. So if you take it with protein, the...

35:52
The vast majority of the amino acids in the protein stimulate insulin, and insulin is a main vehicle to allow things into the cell. So you can take it with a carbohydrate or with a protein. You can also, that's why I usually recommend to sprinkle some creatine on your food. You get all the benefits of the food matrix, and of course, creatine has no taste, so you just mix it in, and that's very viable as well. You can take it with water, so the bioavailability is there.

36:16
For those that are sensitive to sugar, or they don't want it, or protein, that's totally fine. And again, the best thing is prior muscle contractions is a great way to do that as well. Yeah, nice one. And just finally to finish up, and this has really been an excellent update on our previous podcast, endurance exercise. Like are there any updates in the endurance space with creatine?

36:38
Yeah, that's an excellent segue. We put out a big review article last year. And of course, creatine only was for weight lifters before. And then we started to look at, well, what was soccer and swimming and sports like that? And very happy to say that when you look at the body of evidence from intermittent sport activities, such as soccer, swimming, or a lot of the sports coming up at the Olympics, creatine had some improvements on agility, performance in the sport, and recovery.

37:02
And then there's been two landmark studies in Ironman and long duration Marathon where creatine was taken before each race and when they finished when they measured these things called cytokines Which give an indication of inflammation all those inflammatory markers were reduced In other words, those individuals could probably recover after the long race to get ready for the next subsequent one as well So it had some anti-inflammatory effects of long duration aerobics. So

37:29
We can't forget the endurance athletes. It seems to have some beneficial effects. The other now new push is what about all the cognitive effects it might have for long duration aerobic exercise. Some of these ultra marathons and things like that where you're mentally fatigued triathlon could create a not only have a performance effect, but also a cognitive effect, you know, last hour of a race or maybe at the Olympics, second half of the soccer match could have a role.

37:56
I think that's probably a main focal point for a lot of coaches and athletes here now, creating use to be just for performance, but there's potential there for some cognitive aspects and that's an area to also consider taking up. Yeah, nice one. And with regards to that cognition, if I'm thinking about an ultra marathon where you might be out for several hours, would you consider taking it throughout the event?

38:20
That's an excellent idea. I don't see a reason why not. The only downfall with that approach is that creatine about five grams is needed and it will get in the blood about an hour and it will last. So if you're thinking of how long the race will go, you may wanna take it before. The other thing is by consuming it during, some people may be susceptible to a little bit of GI tract irritation. So that's...

38:45
a really logical strategy. It's never been done, but you may wanna just take it beforehand and then it'll sorely accumulate over time. But yeah, maybe small micro doses during the race, could that be accelerated into the body? We don't know that, but that's a really good, interesting idea. Yeah, and a lot of endurance athletes I talked to are a little bit concerned with that water retention aspect, which as you mentioned earlier on, more likely to occur in males. And I understand it's transient. Am I right about that?

39:14
It is. I kind of look at it from the marathon perspective. You kind of want that because if the water is being in the muscle, you're going to have reduced risk of dehydration and muscle cramping and things like that, especially in the hot environments. But it is transient. So even if you do notice acute water retention, it probably subsides in as little as maybe a week to 10 days. And we know this because when we start our research studies and we measure the person's weight and we measure it at the end,

39:42
it's never usually changed. And what's happened is lean tissue typically goes up, fat mass will stay the same or go down. So the water retention fluctuation was irrelevant. Okay, and you mentioned lean mass. So that's obviously where the water is being held. It's not like they've got this increase in muscle mass or anything. Yeah, so we theorize most will go into our muscle, but again, we can't argue against organ and increase in osmotic properties of the blood.

40:06
connective tissue, so we theorize it goes up in muscle, but that's not 100% proven or the case, yeah. Yeah, nice one. Well, Darren, this has been your wealth of information and it's great because you've answered all of my questions and also talked about because studies that are coming out of your lab, anything else that we should be sort of interested in with regards to creatine and upcoming research?

40:33
I think there's a whole plethora of new things coming out, everything from creatine in pregnancy, the young females, which is so needed. And that'll be interesting. I know they're looking at blood biomarkers in children to see the effects. We're really starting to focus on female health across the lifespan. So in the next few years, we're gonna be looking at new studies on bone health, individuals doing at-home exercise, the timing of creatine. So stay tuned. It's still interesting and exciting, and I'm just happy to be part of it.

41:03
Yeah, amazing. And how can people find out more information from you in your lab? Yeah, I think the easiest is on Instagram at Dr. Darren Kandel. I think I try to post a lot of research, not just on Create Team, but a lot of things that are interesting to a lot of people. And we usually post all our research bindings there. So that just seems to be the easiest. Yeah. Yeah, no, that sounds great. It is. It's a really informative channel. Darren, thanks so much. You enjoy the rest of your day. Yes. Thanks so much for having me. Take care.

41:43
So hopefully you guys really enjoyed that and I was super interested to hear the different dosing recommendations particularly in light of the brain actually. And I've talked a lot about creatine's role in helping alleviate sleep deprivation because of the action of creatine in the brain. And so it was really nice to be able to update my understanding of the amount that you might need for that to be super beneficial. Which is

42:09
certainly a lot more than what you would get just from those general performance benefits. And it was also really great to chat to him about the amount you might get in a normal diet. This is what you need from supplementing. So that is definitely another key take home for me. So as I said, I've got links to where you can find Darren in the show notes. And next week on the podcast, SuperStote to bring to you my conversation I have with Dr David Unwin.

42:37
Until then though, you can catch me over on Instagram, Twitter, and threads at Miki Willardin, Facebook @mikkiwillidenNutrition, head to my website, mikkiwilliden.com, and sign up to my recipe portal, Access, where you get access to some amazing meals, low cost, high value, super tasty, to help support your nutrition-related goals. All right, team, have the best week. See you later.