← The Neuro Experience
Loading summary
Transcript85 lines
- [00:00]
A
Question that comes up is, yes, it takes a long time to accumulate in the brain. How do we know it was the creatine or their natural defense or repair process? All we can conclude is that individuals who suffer head trauma, then in combination with creatine, they seem to improve over a long period of time, up to six months. Question begs, well, God, what if we got creatine into the brain before they suffered a concussion? Could it help?
- [00:26]
B
Darren, welcome to the neuro experience. How you doing?
- [00:29]
A
Excellent. Thanks so much for having me. I'm really excited to talk to you today, for sure. Yeah.
- [00:34]
B
Well, you are the person to talk about. I've been harping on about creatine for God knows how long actually. Surprisingly, I think it was around 20, 21. Not many people were talking about creatine in relation to brain health. And I put up a reel because I just found a wonderful study that was done on humans and it was done in correlation with NFL players, more so around how to protect the brain. And they were supplementing them with around 20 grams of creatine. Anyway, I put this reel up and it went viral and everyone just had this influence. People were like, oh, are you the girl that talks about creatine? I'm like, no. But yeah, so let's get straight into it. Let's talk about creatine where it lives in the body.
- [01:18]
A
Yeah, well, so I think, as you mentioned, it's sort of had a resurgence kind of looking at the neck up. But most of us are familiar that creatine is primarily synthesized in the liver and we produce about one to three grams a day, depending on your diet and other variables. But the, the brain actually will also produce creatine as well. We think about the same rate depending on the health of the individual and what you have going on in your daily life. So it's only two areas, the liver and the brain.
- [01:45]
B
Can we just stay on that for a moment? So the brain produces creatine.
- [01:50]
A
Yeah. So unlike muscle, which doesn't, the muscle is a vacuum. It likes to suck up as much creatine as it possibly can. And we store 95% in our muscle. But interestingly, the brain actually will create its own creatine supply. And that might help with our conversation why? Maybe the brain is a bit different in response to creatine supplementation or dietary creatine. Of course we'll talk about the blood brain barrier, but it kind of makes sense. If the organ is producing its own creatine, maybe it doesn't need as much if the individual is not metabolically stressed. And we can talk about conditions where we think creatine may help the brain a little bit more than others. So it is unique that the muscle and brain are quite different, as we know, and the brain is very picky with what gets in. Yeah.
- [02:36]
B
So where is it created? And is this created just all day.
- [02:40]
A
Every day in the muscle? Primarily it's going to be created in the, in the liver and then transported into the muscle. We can actually take up creatine in circulation that's made in the liver to the brain. It has to go through the blood brain barrier and some select transporters, but primarily the oligodendrocytes in the brain while allow it to get in and we naturally will produce it just like we do for muscle to maintain ATP levels. And lo and behold, in times of metabolic stress, our brain is inflamed. It has a lot of oxidative stress, jet lag, sleep deprivation, a lot of neurophysiological diseases may be implicated in those areas. And my view on cognition has changed a little bit just recently. So I'm sure we'll talk about that more as well. But yes, it can accumulate in the brain. It's very stubborn. It doesn't like to allow peripheral creatine in. But the nice thing is it can get there eventually over time. And we'll talk about dosing and how that might be different than muscle to the brain as well.
- [03:41]
B
What do you mean that it doesn't allow it in peripherally?
- [03:44]
A
Yeah. So the muscle, again, likes to suck it suck up like a vacuum cleaner cleaning your house. Well, the brain has a blood brain barrier, so it's very resistant, it's very selective to what gets in, and rightfully so. And then you piggyback that with, with creatine doorways or transporters that allow creatine into the, the tissue, they're very minimal at the brain, unlike muscle. So unlike muscle, which takes in a lot of creatine, the brain has a blood brain barrier or a force field, if you will, that says we don't want a lot of you in. And then of course, if it doesn't have a lot of doorways, it's very selective. So to put it in perspective terms, supplementation may increase muscle creatine stores anywhere from 20 to 40%. We're only starting to see maybe 10% max in the brain. So there's a huge distinction. Yeah.
- [04:34]
B
So I, you know, in preparation for this podcast, I was looking at the history of creatine and really quite surprising and maybe, you know, you can share your views because obviously there's probably a lot of, you know, different stories out there, but from my understanding, it was created by, I forget the scientist. I think he was a French scientist and he was experimenting with some Olympic athletes.
- [04:57]
A
And then, yeah, it was discovered in 1832 by a French biochemist, Gels Eugene Chervil.
- [05:03]
B
Yes.
- [05:04]
A
And then there was some other individuals in the food industry that were extracting creatine from meat in the 1920s. And then of course, most people are familiar with the athlete lymphocristi winning the gold medal. And then all of a sudden, when asked about what supplement he was on, he happened to just say creatine. And then that sort of caused the explosion from amazing creatine researchers in Europe, notably Eric Hal, Roger Harris and Paul Greenhalf. They kind of took that idea and really put it through experimental research. And lo and behold, supplementing the human body really seemed to improve creatine stores primarily in the muscle. And at that time we were only focused on muscle because creatine was thought of as an anaerobic metabolite. If you have more creatine in the muscle, you could get bigger, stronger, faster. And study after study consistently shown high dose creatine saturated your muscle stores. And that maybe allowed individuals to put more effort into the gym or on the field or whichever it is. And, and study after study just kept saying increase creatine in combination with exercise. It seemed to allow the individual to get some performance improvements. And so we did that for about 20, 25 years. And creatine became boring. It was like okay, monohydrate white powder. It seems to be effective. The safety profile was extremely great. And then it kind of went away. And we thought we knew everything until the resurgence, as you just alluded to probably in the last maybe decade, maybe two, we started to look at it from the whole body. We started to see benefits on bone health, hugely important for females. And then of course, from the neck up, it was starting to have promise for maybe concussion, neurophysiological diseases, huge benefits in muscular dystrophy. And now we're getting into an age pre and post Covid depression and anxiety. And I think the next 20 years will primarily be focused on the neck up because I think everybody in society has some type of metabolic stressor. I'm always sleep deprived. A lot of people flying around the world jet lagged. Can it have any implications for some of these chronic diseases? So we've now looked at it from a total body perspective and I think that's why the resurgence in this boring kind of white powder has kind of come to life again and starting to see a lot of potential for many applications.
- [07:27]
B
Yeah, I love, you know, I always say you're the only other person who has ever said neck up. I distinctly say that in all my podcasts because that's what I deal with. And I really love that you said neurophysiological aspects as well. As a neurophysiologist, I'm primarily involved in, you know, demyelinating disorders, MS, you know, Parkinson's. And I'm really excited to see the early research of creatine and Parkinson's disease, although early, I will add, evidently, Alzheimer's disease, post traumatic insults. But before we get into all of these and we're gonna, we're gonna sub specialize, you know, in this podcast, let's just understand what it is. And I'm talking like from a general population because people think, you know, because I get so many people asking me, but Louisa, do I have to supplement if I'm having red meat? And it's.
- [08:15]
A
Yeah, excellent question. So creatine is naturally produced and recognized in the body. So it's only made from three amino acids, arginine, glycine and methionine. So a comb, essential and non essential. Now you can get all those amino acids from plant based foods and animal based foods or complete proteins, but they simply come together to form the molecule called creatine. So we produce naturally, all healthy humans about 1 to 3 grams a day. We also excrete about that as well in the urine in a form of creatinine. So there's a nice equal balance.
- [08:48]
B
So vegan, some people always get those mixed up. Yes, creatinine kinase.
- [08:53]
A
And of course, when you go for your blood work, when they measure creatinine, it's going to be elevated if you're on supplementation. But vegans, vegetarians, anybody emphasizing a plant based diet or basically synthesizing a minimal amount that can keep your muscle cells very healthy. But the theory is that if you have more in the diet, and now the issue here becomes what foods have creatine at the highest concentrations. And it is animal based, it's red meat or seafood. However, to get the dose that we'll probably talk about today, to be effective, that means you're probably eating a couple servings of red meat or seafood a day that may be not very viable for the financial cost of food nowadays. You might have allergies, seafood preference with ethical treatment of animals, whatever it is, a lot of people are saying, I don't have the ability to get it through my diet. That's probably why supplementation is considered. And so yes, if you eat multiple servings of red meat or seafood a day, you're probably getting a pretty viable dose of creatine that has been shown to be effective. But what happens to the vegans and vegetarians or individuals who don't eat red meat or seafood per day? It's very difficult to get through the diet. And I think that's why supplementation has been shown to kind of be at least entertained. The lowest dose we sort of know to have any muscle benefits. This is not even close to what we think for the brain is about 3 grams a day. So that's about a steak and a half or two salmon fillets per day in addition to what we're synthesizing. So it's not impossible in today's society. Very difficult to do. But again, that's why I think supplementation is one of the. Creatine is one of the things that we think just like caffeine, you may have to consider it as a supplement. Unlike protein, which we can get viably through food. If you live in Scandinavian countries in the east coast of Canada, you can get the seafood and red meat if you like. But most people are emphasizing the plant based diet. So that's where I think creatine may be considered.
- [10:50]
B
And you know, to be honest, who's having two, you know, salmon steaks a day? Who's like, I mean, I, I'm a meat eater, but I'm not eating two like steaks a day.
- [10:59]
A
Yeah. And the other thing is with the, when you're cooking it just like a protein, it gets denatured and you might absorb the amino acids better way. So the thing with creatine is you want to maintain the integrity of that molecule. So when cooking the meat, it's going to denature some of the proteins. It's logical. It's going to denature some of the creatine to potentially creatinine. When creatine is heated, it will degrade to creatinine and it's unstable. So that's why we think the powder might be advantageous. Not essential, but it is very convenient. Yeah.
- [11:31]
B
Oh, in 20 years it'll then be, it'll be essential. It'll be part of the essential list.
- [11:35]
A
Yeah.
- [11:35]
B
So, so okay, so we're getting it, we can get it from, you know, it's naturally created in the body. We can also get it from foods such as red meat fish. And it helps with cell energy metabolism.
- [11:48]
A
That's correct.
- [11:48]
B
You know, the creation of ATP.
- [11:51]
A
That's right. So we can't have ATP decrease whatsoever. If it does, our cells go into cell death almost. And so the first line of support or defense is not glycolysis from carbohydrate or beta oxidation from fat. It's lo and behold, this creatine molecule and the basic pathways, it simply donates a phosphate group when muscles are contracting to maintain our cellular energy currency of the cell called ATP. So creatine really sacrifices itself. It donates a part of its molecule and that allows the muscle to have a high energy status. So at the end of the day, maybe the individual can run a bit faster or potentially recover in between sets greater. And that's where we really see the benefits from a muscle performance perspective. Maybe the second, third and fourth set, you can do more reps or more volume, that could translate into more benefits. So from a muscle or a neck down, I think exercise has to be there. You need to have exercise to unlock the potential of creatine. But the neck up is a little bit different. I think activities of daily living or even exercise can augment the benefits of creatine. But we're actually starting to see some, some data that creatine without exercise might have some cognitive effects.
- [13:03]
B
Yeah. And I want to focus on that. So let's, let's sub specialize right now.
- [13:08]
A
Okay.
- [13:09]
B
Let's talk about creatine as a protective mechanism. Concussions and actually I do want to ask you, what made you get into this field? Why are you pursuing a PhD in this?
- [13:22]
A
Yeah, I actually got into it by a little bit of an accident. I was doing my master's work in, in glutamine, the single amino acid. And of course you're a eager student and, and at the time, glutamine was popular amongst long duration athletes for potentially enhancing immune system. And when we decided to give a really massive dose of glutamine, which again is a non essential amino acid, to individuals performing resistance training, it proved to be worthless. It had no effect compared to placebo. And it kind of makes sense. Resistance training isn't that strenuous. It doesn't cause a bunch of inflammation systemically. And at the same time a colleague of mine doing his PhD was doing creatine research and I was really wanting to help out in a lot of studies. And lo and behold, we started to see some really viable results, not only in young individuals, but older population as well. And after that it's sort of taken on its life, its own. So we've been doing creatine research since 2000 and probably two. So it's been, you know, almost two decades of creatine research. We're a little bit more knowledgeable, but we have a long way to go in that area for sure. Yeah.
- [14:31]
B
Okay, let's. Let's go into concussions and talk about, like, head trauma, whether it's TBI and how creatine can serve as a neuroprotective mechanism.
- [14:42]
A
Yeah. So the brain is really active, as we all know. It probably utilizes about 20% of our energy expenditure. And one of the interesting things with a healthy brain, it can actually synthesize its own creatine. So its creatine levels seem to be pretty stable. The average person who says, I feel fine, would have adequate amounts of brain creatine levels. But a common denominator. When we started to look at all the data in individuals with tbi, that includes concussion, and you can even lump in here, individuals with neurophysiological conditions, depression comes to mind. A common denominator is they have a reduced amount of creatine in the brain. So the theory here is, what if we gave them supplementation to at least bring their brain creatine levels back to normal, could that offset or speed up recovery? And specifically for concussion, and this might be surprising, but there's only been one study done in humans. There's been a few in rats, but in humans it was in children. And within four hours after children suffered a tbi including concussion, they were immediately put on a placebo or creatine. The dose is interesting, 0.4 grams per kilogram. So, geez, you're like, that's quite high. Yeah, a lot higher. Again, smaller stature, medically supervised. And then they were put on this for up to six months and they were randomly allocated to a placebo.
- [16:06]
B
And.
- [16:06]
A
And then when they measured subjective health measures, speech improvement, self care, self esteem, they all seem to improve at three and six months later, whereas the individuals on placebo did not improve at the same rate. So it was the first line of thinking where creatine may have the potential. Now, a couple caveats. Children, the brain is in massive repair mode. As soon as it's hit, it's immediately starting to regenerate. We don't know if that's the same rate of regeneration in the healthy brain. The dose was quite high. And then the other question that comes up is, yes, it takes a long time to accumulate in the brain. How do we know it was the creatine or their natural defense or repair process. All we can conclude is that individuals who suffer head trauma, then in combination with creatine, they seem to improve over a long period of time, up to six months. Question begs, well, God, what if we got creatine into the brain before they suffered concussion? Could it help? So that's where we're wrestling with right now. How do we get creatine randomly allocated to a healthy population and then, God forbid, when they suffer concussion, how do we measure it? Well, that's where we're struggling. We randomly allocate healthy individuals who are not on creatine to a group and then do we just sit back and wait for them to get a concussion? That's kind of what has to happen. I will piggyback a little bit here on animal research. In animals, we can pre or surgically cause head trauma. And in these models, when we gave creatine before inducing concussion, it really seemed to have some improvements. So we don't have a lot of data. We have some preliminary data in children that it has the potential to increase recovery. It certainly is not going to prevent a concussion, but the other way to look at it is certainly not having any detrimental effects. So I think if anybody's predisposed to head trauma, football players, soccer, the hockey, I think taking creatine before the season or during practice may be a viable tool that, God forbid, if you do get a concussion, it'll probably have some benefits somewhere else in the body, but it may actually have some improvements for recovery.
- [18:19]
B
That's interesting because I did read a study where they did get some college NFL players and it was, it was more so as a protective mechanism. And I do remember the dosage being 20 grams a day of creatine just to see if it was neuroprotective.
- [18:36]
A
Right. Yeah. And that's the, the long term trial. We need way more people to do a massive dose. And we can probably talk about the dose for the brain and it's very different than the bone and, or muscle. So we have an opinion paper coming out. Maybe the tissue that you're looking at will dictate the, the amount you're taking. I think it's going to be easier to just give an overall dose. But people say I don't really care about the brain, I'm only cared about the muscle or vice versa. The dose may, or duration of supplementation may influence that.
- [19:06]
B
Yeah, that's, that's, that's going to be huge for, for the NFL guys especially. Right?
- [19:13]
A
Yeah.
- [19:14]
B
Is the same mechanism of action happening in those guys to somebody with, let's just say a stroke, an ischemic infarct?
- [19:23]
A
Yeah. So the stroke's going to be a little bit different population. The only concern with stroke is if, if, if it's the same mechanisms on a muscle compared to the brain. So in muscle, remember, it drags in water. So that's where some people say, oh, I've increased body weight or whichever.
- [19:40]
B
Yeah.
- [19:41]
A
We don't know if it drags in water at the same concentrated rate into the brain. So that could be an area of caution for stroke. The last thing you want is swell parts of the brain in an individual with stroke. We don't think so. But again, there's only been some minimal data on a small population. It certainly can help improve rehabilitation from stroke. But we need some long term clinical trials to look at blood biomarkers and the osmotic potential in the brain as well.
- [20:08]
B
Yeah, I've got my dad, 72 years old at age 69. He had a right parietal lobe infarct. And you know, it was ischemic stroke. It was very, it was minor, but he's just, he still has some, you know, some cognitive decline and he's lost some function in his, in his lower extremities. But I've got him. You know, it took about, I would tell you, Darren, it took six months for him to believe that it wasn't drugs that I was giving him.
- [20:31]
A
For sure. For sure.
- [20:32]
B
Okay. We got there and then now we're at about, we're still at a minimal dose of 5 grams a day.
- [20:37]
A
Yeah, but he's doing it and I think that's great too because we, there's some new data. A good colleague from Norway just published a paper with COVID symptoms, but it simply showed that a lower dose. It was the first trial that we saw. But you need to take it for a long time. It'll eventually accumulate. So 95 will go to our muscle. We have trickle amounts going to other areas and that's probably why we thought for the longest time you need a really, really, really high dose of creatine for long periods of time. And I, I think it's not going to be feasible for your dad or anybody else. I think you're just going to say, make it easy for me. Give me one dose to take and you know, hopefully you take it on a daily basis for the rest of your life. I think that's the philosophy we're going to have to start adopting. I don't think it's viable to take certain dosages for certain tissues. It's hard enough to get people to exercise, let alone take supplementation. So I think we just gotta try to meet people head on and say, here's a dose based on science which we think will probably hit all avenues of the body.
- [21:40]
B
Yeah. That was the inspiration of a tweet I did today. I just found out actually, that only 24% of of US adults are actually meeting the physical activity guidelines, which I didn't actually know that because my whole world is based around exercise. I just think everyone's exercising.
- [21:56]
A
Yeah. And you know, the 150 minutes of aerobic and divide that by seven. So can you give me 22 minutes a day and throw in a couple weight training days? And some people are on the complete other extreme. But you're right. And I mean, up here in Canada, snow's on the ground, I see roads. We, you know, can't go outside in the winter time. So how are we going to achieve that? So it's, it doesn't surprise me, even with everything we're trying to promote, but we got to do better because most chronic diseases are going up and it's very dangerous. Yeah.
- [22:28]
B
Yes. Speaking of chronic diseases going up, a popular theme on the podcast is Alzheimer's disease. And, and what we know is that Right now around 55 million people, secretly, I believe there's more than that. But 55 million people worldwide currently have Alzheimer's disease. That number is said to triple by the year 2050. Let's talk. Yeah, it's unbelievable. And when you really understand that, you know, when we look at the 100% gene penetration, we know that there's only around 3 to 5% of those 55 million people got that got there through through genetics, and around 95% got there through lifestyle factors. Controversial topic, but that's, you know, that's my stance. So let's talk about how. Well, let's talk about how creatine may help in the. I won't say prevention. Let's just call it a cognitive decline patient.
- [23:24]
A
Right. So even if you put in all the vascular dimensions, let's put it all into sort of one umbrella with the amyloid plaques and the towels. And so the research is so minimal, we can't actually have a, a valid conclusion yet. And, and of course, we don't want to be doing any of these studies. That means people have these conditions. And of course we have AN N of 0 and this condition. But you just mentioned some staggering numbers. And from A global perspective. It's mind boggling. So there's no data right now in humans. They've done a couple of experimental models in rodents and it has shown some, not all, some preliminary promise. But there is a new paper recently published in the last month where they've sort of laid the foundation for a clinical trial upcoming. I'm also part of a group in Iowa that is looking at potentially getting Alzheimer's in a small PIL study to look at not the prevention obviously, but the rehabilitation and performing activities of daily living. So we're going to be measuring some cognitive tasks. Maybe the brain, if it's stimulated, can regenerate or maybe creatine can help offset that. We do see some problems with creatine after a mentally fatiguing task improving some measures of cognitive ability. So I think there's some potential, and I use that word very loosely, we have no long term clinical trials with this. I think the issue is that you're going to need to randomize a few hundred people into a study. This will probably have to be a multi center, multi country study even where we're looking at individuals with that as well. So in theory there's some potential, but we have no data. So right now we can't even make a viable conclusion. We hope some study will come out showing some benefits, but I don't think there'd be any negatives. But again, we can't even make any general population conclusions with that.
- [25:18]
B
Yeah, to me when you hear the word it helps with cell energy metabolism. I mean most diseases are in some form a disease of the metabolism in some form. Right. And it just makes so much sense.
- [25:34]
A
Right.
- [25:34]
B
To just, you know.
- [25:36]
A
Yeah, the, the mechanism across all these conditions that have shown improvements. It's very similar to muscle. It seems like it's almost anti inflammatory or it's decreasing reacted oxidative spec, improving mitochondrial function in the cell, including the brain. So there's some mechanistic reasons to suggest it could have some potential. But we haven't looked at any of the effects of creatine on any protein kinases in the brain. We've, we've shown it increases content. But what does that really mean? And so there's oh, I would say 20, 30, 40 more years of research just, just at the tip of the iceberg in the brain especially. And then you have to also look at different parts of the brain respond differently. Gray matter, white matter, different lobes. So again maybe that's the area where people around the world and there's some great researchers in Brazil and Norway that are starting to look at the mechanisms of this as well. From a depression. Right. In the US and Utah, there's phenomenal psychiatric work going on on looking at that. Maybe creatine can be considered in combination with depressive medications to help offset some of those symptoms of ptsd, anxiety and depression. So there's a lot of emerging research coming out. It's exciting, but it's so in its infancy. We got to have a little caution before we say hey, take creatine, it's going to solve all the issues. We know. Obviously, yes, that's not the case. It might be adding or hopefully potentially improving some aspects.
- [27:08]
B
Well, yeah, the, the depression. You know, I posted something as well on my reel and it was the, it was a study that was done early research on depression and creatine. And I forget the mechanism of action though because depression is on a scale, you know, it's like is it major depression? Is it, you know.
- [27:25]
A
Yeah, it was in that one. I'm aware, aware of a couple. Even with dietary creatine, the correlation was more creatine in your diet through food depressive symptoms came down. Now you might say, well the foods that have creatine also have omega 3 fatty acids.
- [27:39]
B
Acids, protein, tryptophan, which is the precursor to serotonin.
- [27:43]
A
Yeah, it's high quality foods potentially. So that's what we always emphasize first. But there was a correlation there and maybe they have a better lifestyle if they are eating proper nutrition. That could be explained. But then you look at the supplementation studies and it was the decrease in the inflammatory response that seemed to seem to be the effectiveness. So something that creatine doesn't get as much due from the anti catabolic or the effect at the mitochondria. But I think that's something that we will see a lot more of coming down the line.
- [28:12]
B
Yeah, Darren. So I'm hoping my mum's listening to this. My parents tune in now. My mother has. Yeah, they think I'm on the radio. No, so, so my mother, 70 years old and she has osteoporosis or a very early stage. And so you've mentioned how, you know how prevalent this is and, and how good creatine is for the bone. Correct. So let's, let's explore that.
- [28:42]
A
Yeah, it's an area that we, by accident, so to speak, it wasn't designed to look at. And then there was a cellular study done about two decades ago where they sort of incubated osteoblast cells or the cells that are involved in bone formation with creatine. And they, they sort of got energized and they proliferated and the activity got substantially better. So that sort of gave a little bit of lineage to say, well, if the osteoblast cells are more energized in the presence of creatine, could that cause an increase in bone strength and potentially bone mineral density? And in combination with studies in Brazil and here in Canada, we sort of have a picture painted that we're semi confident on some of the things. So, for example, creatine without exercise will have no bone benefits. So this is really critical for your mom watching. She needs to exercise and hopefully she's doing that anyway. But if a female or an older male was to take creatine, we're not seeing any good data to suggest that the bone will respond without mechanical stimuli from exercise. Then we've actually looked at it in combination with exercise in two populations, postmenopausal females, and then you have healthy older males. The best results seem to be in postmenopausal females. And creatine in combination with resistance training three days a week, not daunting, but three days a week for up to a year, has been shown to reduce the rate of bone mineral density loss in the hip. And we think the hip is clinically significant because falling on icy roads, if you suffer hip fracture, you need surgery, and then you come inactive. And then even in healthy populations, including males and healthy postmenopausal females, creatine in combination with resistance training actually increase bone surface and size. So therefore you may be able to withstand a fall and not suffer a fracture. And in our latest study, which took almost a decade, I probably started with hair. Now I have no hair left. We looked at two years of postmenopausal females, a large sample, over 200. But this is where the dose got a little interesting. In our previous study, we gave about 10 grams a day, or, sorry, about 8 grams a day, 0.1 gram per kilogram. And we thought, well, we didn't see any improvement in lean tissue, very minimal in strength. Maybe they need more. It's similar, similar to what we think of with protein. Maybe older adults need more. So in this big clinical trial, we gave 0.14 gram per kilogram. So if you go on the scale and you're 70 kilograms, you're taking about eight and a half. What is that? About 10 grams of creatine per day. So on average, across all individuals, that was about 11 grams of creatine monohydrate. Every day for two straight years. So it was the longest trial to combine the two. And it did improve or creatine improved measures of bone geometry, specifically around that hip region again. So at the end of the day, we have some data to suggest specifically in postmenopausal females, that the skeleton is maybe getting stronger. It might be able to withstand more falls or fractures a little bit better. Exercise needs to be there. And we think without exercise, creatine will probably have no effect. It won't improve bone mineral density, in other words, it won't increase it, but at least it'll help attenuate the rate of loss. So I think for any female listening, all the studies have been in post menopausal females primarily. I would love to do a study in young females. Maybe we can build up the bone in those peak height velocity years, get the bone super strong and large, and then when the rate of aging starts to occur after the fourth or fifth decade, maybe the rate of loss will be attenuated. And so those are the areas we're starting to look at. So, for example, if your, if your mom is taking creatine now for maybe the, the cognitive benefits, she might not have even expected any bone benefits, but there is some data to suggest it might preserve the integrity of the skeleton.
- [32:38]
B
All right, so we're going to up her dose. When I go there in Australia, I'm just going to up the dose of both of them.
- [32:44]
A
Yeah. So the, the, that begs a question. What about a dosing strategy? Maybe you're saying, you know, 8 to 10 grams has all that's been shown. Could five work? Work? We don't know because we've never tested it. But the theory here is if the majority go to your muscle, you kind of might need a little bit more trickling in. And now this begs an even better question. Well, we've talked about brain, we've talked about bone, we've talked about muscle. What's the dose that might hit all those areas? And when you average out the dosages, according to science, right now it's about 10 grams a day, 20 for the brain, 10 or so for the bone, and maybe three or four for the muscle. When you average it out is about 10. But most people say that's too high of a dose. For me, I just want to get it through my diet or take three grams a day. I would imagine over time, if you're taking this in weeks and weeks on end, it'll accumulate and trickle in. So I'm okay. If you're taking three to five grams a day. My hope is that with exercise over time it will accumulate into some positive effects. But some dosing studies need to be done. We've done a study in young adults, 10 and 20 grams and there was no difference but no benefits. So we're not really sure the effects.
- [33:58]
B
How about where are we at with female fertility? Because I think I've read some early research there as well around, oh, what was it? I don't know whether it was ovarian health or egg production, I'm not sure. But I did read something around creatine and female fertility.
- [34:17]
A
Yeah, Stacey Ellery and Abby Smith Ryan are correct. Yes. And it just came out yesterday. So Stacey already put in another study that placental growth and the mother during gestation, the creatine can really enhance fetal development or energetic metabolism. Now obviously caution is hugely promoted here. I get this question all the time. But what we're starting to see is a creatine dose which is recognized by the body, body can actually have some potential beneficial effects for pregnancy and the fetal development. And then you combine that in the beneficial effects in children, adults, older adults. We're starting to see it's hard to find someone on the planet who may not benefit in some form. You may not get massive benefits, but it seems to have some application. And then people say, why is that? Well, I say, well, we naturally produce it. It's recognized by the body. It's simply three amino acids. If you take it in at a slightly higher dose, the body recognizes and stores it. And if it doesn't, you just appeat down the toilet, basically. So it's not something like a steroid or a chemical or a drug effect. And that's probably why the safety profile seems to be spectacular for creatine at.
- [35:28]
B
Recommended dosages that's even for kids, because I don't, I can't tell you how many questions I get. Louisa, is my 12 year old okay to have it? And from what I, I've seen it, it is, yeah.
- [35:39]
A
It's no different than us taking it. The accumulating research was presented at the American College of Sports Medicine in Denver by two good colleagues of mine in the States and, and lo and behold, just like healthy humans or healthy adults, recommended dosage seems to be very viable, very well tolerated and effective. What hasn't been done though is blood biomarkers. So we have a lot of blood biomarkers on kidney and liver function in adults and they are collected right now and being analyzed. But by guess is they're going to be fine, especially in children, those kidneys and liver and blood cell counts. I would imagine creatine is going to have no adverse effect. If anything, it would have an adverse effect in populations that are predisposed to renal and hepatic failure, such as older adults. And again, in that long term study, we measured kidney and liver function annually and there wasn't a greater increase from creatine or placebo. So I'm pretty confident it's been study after study after study. It's almost getting very boring. But creatine seems to be one of the safest, most effective compounds that most people can at least consider.
- [36:46]
B
And yet so many people still attribute creatine to kidney failure. Stop it.
- [36:53]
A
We're updating, yeah, we're updating a meta analysis now. There was one in 2019, no greater effects. And with the additional studies, we're speculating no greater effects as well. And you know, it's not a steroid. I went bald before I took creatine. That's another problem.
- [37:09]
B
I was gonna bring up dht.
- [37:10]
A
Yep. And of course serum DHC has nothing to do with the follicles. So it's, it's. Yeah, maybe because it was so effective in athletes, people thought, oh, it was. It's too good to be true. It doesn't work for everybody. Some people will take creatine and may not respond because probably you have a lot of, of creatine in your diet, like a carnivore diet diet. You may not experience any beneficial effect. You probably don't even need supplementation. But a lot of people say, I can't afford all that meat or I don't. I choose not to eat meat or seafood for whatever reason. It's, it's something to at least consider. Of course, I come across as a salesman trying to sell it. I'm just giving you what science says. Lots of studies say creatine did not work in this study. And you look at the beneficial effects. It's no different than omega 3s and protein. There's lots of studies that say it doesn't work in a certain population. But until we randomize 8 billion people into a study, we're always going to have those limitations and standard error.
- [38:07]
B
So it doesn't cause hair loss. How did this myth even come about?
- [38:11]
A
Yeah, you know, we, to answer that, we don't even know if it does or doesn't because the question come in rugby players, they measured high dose creatine on dht, which is a precursor from testosterone linked to hair follicle loss. And yes, it did increase. But of course every time we go to the doctor, they'll say there's a range for cholesterol and blood glucose and DHT levels went up, but they were within the normal reference range. And immediately, and still to this day, people say, well, if serum blood DHT went up, that must have caused you to go bald. And I say, to answer this question, we've never shown it causes baldness, but we've never shown it doesn't. The only way I can answer it is I've studied well over a thousand individuals, really high dose creatine, and not a single person has ever come to me and say, hey, hey Darren, I don't know what you're giving me, but my hair is falling out. And I think that's the first thing they would tell me is like, whoa, you know, it's a side effect, my hair's falling out. We've never recorded it, no one's ever told me. So it's still that subjective idea. Does it cause baldness? We don't know.
- [39:14]
B
Okay, so let's now move into dosages and let's also talk about this whole preloading phase, which I don't really agree with. I mean, look, and you also mentioned that, that it may take what, around three months for it to actually have an effect. Like let's, yeah, let's get on to dosages.
- [39:32]
A
So there's three common types of strategies. One, which is the most popular is the creatine loading as you refer to. So this is where this is typically the athletes or power individuals or individuals really needing a quick rapid boost for an event, a game, whichever it is. So 20 grams a day for five to seven days. So immediately you think, well geez, if we're only producing about 3 grams a day, day, taking 20 grams a day is quite a bit. It's very effective to saturate your muscle and it's been shown time after time to lead to a lot of muscle improvements. The only downfall with this is this is where it can cause some acute GI tract stress or acute adverse effects. Typically this is where people experience net water retention or weight gain is during the loading phase, which does subside after you stop the loading phase and then go down to a maintenance dose dose which is as little as 2 to 5 grams a day. So again, 20 grams a day for 5 to 7 days and then you reduce it down to about 2 to 5 grams a day. A very viable, safe and effective strategy. What we use in our lab is under the hypothesis that the larger you are, you may have more doorways to allow creatine into the cell, no different than caffeine. So we do 0.1 gram all the way up to 0.15 gram per kilogram. So if you're 70 kilograms, you're taking 7 grams a day, all the way up to about 10 depending on the individual. We divide that typically in a couple dosages throughout the day. Again shown to be very safe and effective. And then thirdly, which I think is for pretty much anybody to consider, it's 3 grams a day for the rest of your life. That's the lowest dose that we've shown in a muscle perspective to saturate the body. You, that's a half a teaspoon. Put it in yogurt, water, whatever. It's super easy. You can go on about your day. And we think you can probably get muscle benefits with that over time. So those are the three most popular. The loading phase, the relative body weight, size, or 3 to 5 grams, even if you want to take a bit more. Those are three simple, convenient strategies. Doesn't matter when you take it. You don't need to take it like caffeine before you work out. You can take it during your workout, before you go to bed, whatever it is. So the timing we think is irrelevant. But those are the three most popular dosing strategies.
- [41:50]
B
From a muscle perspective, I always argue that five grams a day, I, I say five grams a day. Yeah. And I say that to both men and women. And I'm speaking from a brain perspective.
- [42:00]
A
Yeah. So, and you're totally right. So the, the evidence behind that is Roger Harris in 1992 showed that 5 grams will spike in the blood and repeat, a 5 gram dosages will maintain plasma levels, which will eventually hope less accumulate in a tissue. So you're right on there. And the other way to look at it is even if we take the lowest dose, 3 grams, well, remember, we excrete about 2 grams a day anyway. So the difference 3 and 2 will equal a 5 gram net dosage. So 5 grams a day is extremely viable, safe, and been shown repeatedly to be effective. So by taking 5 grams, there's no issues whatsoever there.
- [42:37]
B
How many grams do you take?
- [42:39]
A
I take 10 based on a whole body perspective. So I know the effects from the brain and now especially bone. Remember, the lowest dose for bone was about 8, so I take about 10 grams a day. I put 5 grams of my Greek yogurt in the morning and then in my water ball. I actually like to drink it during my workout. So I know people put branches. I just put it with water and I drink it after every set. Now, on my cardio days, I also. So I have a peloton, so I'll drink it during my peloton workout. But if I go for a long walk, I'm like, I'll just take it another time of the day. If I miss this, taking a second dose, no problem. Like, I'm pretty confident it's been accumulating. The other thing is, once your muscles are saturated, you can stop creatine completely. And it takes 30 days for those levels to come back to baseline. And there's some data that it takes five weeks in the brain to come back. So the brain likes to lock it in. And the muscle, once creatine's in the muscle, it hardly likes to. To leave. So if you say, hey, I'm going to Mexico and land the beach for two weeks, don't worry, worry, those creatine benefits will still be there. And even if you're active, you know, active walking, whichever, that helps maintain some of the creatine stores in the body as well. It won't increase it, but it can help maintain activity. So it's one of these things that I think gets a lot of press, rightfully so, but it's not that difficult. And, you know, if you miss a day or here, or if you miss supplementation and you can have a salmon, fill it with supper. There's two or three grams. It's not that difficult to do. Not nearly as difficult as probably getting your total daily protein amount count, which should be emphasized way more. So I use the analogy the big cake is resistance exercise. The icing on top is protein. And then if you put a cherry or sprinkle, that's creatine. Creatine is not giving you the. The big effect that you think it is, but it has to be there with the others. I think from a synergistic perspective, Darren, you're a pioneer.
- [44:34]
B
I'm so excited to follow your research. I cannot wait. Where, where can more people. People are finding out about you. So where can we find you? I know that you're on Instagram.
- [44:44]
A
Yeah, I think the easiest is at Instagram @ Dr. Darren Candle. That's usually the avenue now where we promote research or conferences or things coming up. And I like to tweet other people's research too, on all areas to promote healthy living, but that's probably the easiest place for sure.
- [44:59]
B
I'll link it all. Darren, thank you so much for coming on. The neuroexperience podcast.
- [45:03]
A
Thank you for having me. Appreciate it. Thank you.
- [45:06]
C
It's okay not to be perfect with finances. Experian is your big financial friend and here to help. Did you know you can get matched with credit cards on the app? Some cards are labeled no Ding Decline, which means if you're not approved, they won't hurt your credit scores. Download the Experian app for free today. Applying for no Ding Decline cards won't hurt your credit scores. If you aren't initially approved, initial approval will result in a hard inquiry which may impact your credit scores.
- [45:33]
B
Experian.