Dr. Rhonda Patrick: I'm interested in the brain and we've gone from— we've gone from the role of creatine. It seems to have multiple roles— anti-inflammatory, anti-catabolic. Right. It's obviously important for producing ATP, regenerating the ATP. What about the brain?

Dr. Darren Candow: What's super exciting, like, this is such an emerging area. So from the neck up, I think the next 20 to 30 years will be focused almost entirely on this. So, our liver produces creatine and our brain actually is unique. It also produces creatine, but the brain is very resistant. We have the blood-brain barrier for a really important reason. And the brain says, you know what, circulation, we don't need creatine in the blood. We're making our own.

So, an individual getting adequate sleep, no chronic disease, no metabolic diseases, no neurodegenerative diseases is producing adequate amounts of brain creatine. It could be as little as 1 to 3 grams.

Dr. Rhonda Patrick: Wow.

Dr. Darren Candow: Now, our brain is small from stature, but it uses 20% of our daily energy. And of course, as we all know, when you're really tired, sleep deprivation, running around chasing your children, most people that I know are really metabolically stressed, primarily from a cognition perspective. And that's where creatine seems to have the best lines of evidence. Sleep deprivation, hypoxia, jet lag. I was up at 3 o'clock this morning and flew down, so I'll be taking a really high dose today to hopefully offset the chance of inflammation or cognitive decline.

So, when we look at the totality of emerging evidence, it's split. Some studies don't see any effect, but the ones that do is in a population where they're either mentally fatigued, sleep deprivation, or during times of aging, and that's where memory comes into play. And, the common denominator seems to be the more the brain is stressed, the more creatine seems to come to the rescue. Same analogy from a muscle and bone perspective. So, uh, we can talk for hours just on the brain, and, uh, it's a very exciting area for sure.

Dr. Rhonda Patrick: Yeah. So, the brain is stressed. So, so brain aging, older adults.

Dr. Darren Candow: Yeah, that's, that's— aging is a stress on the brain.

Dr. Rhonda Patrick: It is. So, supplementing with how much creatine can improve cognition in, let's say, older adults?

Dr. Darren Candow: Yeah, as little as about 5 grams has been shown to have some potential But this is interesting. I just, you know, 20 minutes ago said that the loading phase wasn't needed for muscle. The best studies for the brain look at 20 grams a day for at least a week. So now you're in a conundrum. I'm looking at muscle, bone, and brain. And the theory here is that since the blood-brain barrier is very resistant to creatine, and unfortunately we have this really important glial cell called astrocytes, which are the most— the biggest in our central nervous system. It sort of acts as a filter from our blood into our cells, and it really determines what gets in. And it says, hey, foreign pathogens, no, you're not getting into the neuron or the cell.

So unfortunately, they don't have the creatine transporter, or doorway. So that's why uptake into the brain is very blunted. So the thought is to get an improvement in brain creatine stores, you need longer duration of supplementation or higher dosages. So the best lines of evidence using MRS have shown that higher 20 grams a day seem to be the most viable. There's been a single study looking at about 4 grams a day, but it took 3 months to accumulate in the brain. And unlike our muscle, which acts like a vacuum, it sucks in all the creatine from our blood. Our brain says, no, no, no, I'm only going to take what's in our blood, i.e., supplementation when need be. So that's why sleep deprivation seems to have the best lines of evidence or mental fatiguing challenges.

Dr. Rhonda Patrick: Yeah. Okay.

So let's— if you're, if you're someone like myself who's been supplementing with 5 grams a day for a year. Okay. That's enough time for it to eventually accumulate into the brain, presumably.

Dr. Darren Candow: Yeah, like that low dose, remember, you need about 2 to 3 grams. Now, I'm not sure about your diet, but you're going to need that just to maintain your muscle. And then comes down to your genetics. What's more in jeopardy? Is it your bones or brain? So again, the 5% that's remaining throughout the body is in your testes, heart, uh, bone, uh, and brain. So for me as a biological male, it's going to different areas compared to you as a biological female. But my hope is, wait a minute, let's go a bit higher so we're sort of, sort of, uh, checking off all the boxes.

My guess is 5 grams, you'd have a small increase in brain creatine content. Um, but if you have a really non-stressful life, the brain says no, go to the bone or we'll excrete it down the toilet. But if you're metabolically stressed, it's it's begging for more. I'd like you to be probably higher than 5, but I think it'd be interesting to look at some pre-post MRS scans. And, um, it's viable, it could be there. The study that did 4 grams was in long COVID. These individuals, brain fog, fatigue, headaches, things like that. So the brain was really begging for recovery.

Dr. Rhonda Patrick: Yeah. Okay, so you just mentioned the best studies showing any improvement in— and when we're talking about improvement, we're talking about cognition, we're talking about like memory.

Dr. Darren Candow: Memory.

Dr. Rhonda Patrick: Okay. Yeah.

You said 20 grams, right? Which is definitely what I don't want. The, the swelling part of that, which happens around 20 grams.

Dr. Darren Candow: Yes.

Dr. Rhonda Patrick: So have there been studies looking at 10 grams? Is that like a sweet spot?

Dr. Darren Candow: The seminal study was out of Germany and they did 2 versus 4 versus 10. And this is where I personally take at least 10. And they use MRS studies and they only— they showed that about 10 doubled the percent increase in brain creatine content. But they also measured it in the gray matter, the white matter, and I believe the thalamus, and it all improved by about 10%. Now, it was a small sample size because to run an MRS is super expensive. So statistically it wasn't there, but the percent improvements were, were a lot higher.

And when you look at all the other data, 10 grams seems to be a very viable dose to not only check off the box, definitely for muscle, we're now checking off the box for brain. And now we're— or sorry, bone. And then we're also checking off the, the box for brain as well. So I personally take about 10 grams a day on average, but during times of metabolic stress, sleep deprivation, or jet lag, I'll increase it to 20. So today I will take 20 grams because I flew down from Canada. I'll take 20 grams again tomorrow, but when I get back home, I'll decrease it back down to 10. If any is being excreted down the toilet, I'm totally fine with that. Creatine is very cost effective. But I wanna make sure I'm maximizing all my abilities.

And the immune system, especially in Canadian winters, is really heightened and, uh, activated. And I really have found in the last few years I'm, I'm not getting flu-like symptoms. Uh, hopefully that's from exercise or diet, but, uh, who knows, maybe creatine is helping because there are some anti-inflammatory effects.

Dr. Rhonda Patrick: You, um, you, you went to another area that I definitely wanna talk about, but like before that, so 20 grams, then you're saying acutely when you're in this sleep-deprived state, jet lag, you know, let's say fill in the blank type of you know, extreme stress. Um, is that immediate? So let's say like you, you miss— you're like up late, you had— you're up late one night and you have something to do the next morning or the next day, you have to be like on your game.

If you take that 20 grams either at night— would you take it at night like before you go to sleep or in the morning, or does it matter? And will it have an effect immediately?

Dr. Darren Candow: Yeah, and I love learning, and this is just— so 20 grams might be too low, surprisingly, to your viewers. So another study came out of Germany, they used a very elegant design. It was a crossover and they gave 0.35 grams per kilogram. So even if you're only 70 kilograms, that's 25 grams in a bolus dose. And they measured it for 21 hours of sleep deprivation and it really improved memory cognition and it increased brain creatine content. So that high a dose, not only does it get into your plasma or blood really quickly. Probably in about 3 hours it's peaking.

When your brain is stressed, it's being taken in quite readily. So, during times of metabolic stress, it seems to work. Now, the argument is, how do I know I'm going to be stressed tomorrow? How do I know I'm going to have a bad night's sleep? You don't. So that's why I think taking a higher daily dose might be a safety. But the days you're like, oh, I didn't sleep at all and I have a big presentation later, or me as a professor teaching 4 classes a term, I've really increased the amount. I would say I might be the most saturated person on the planet because I've been taking creatine for decades. There's no reason to stop. We can talk about cycling or continuous, but I'm even taking more in hope that it's getting into my brain.

Again, 20 years ago it was just muscle, then we've evolved into the bone, and now we're getting into the brain. And I think a university student's midterm week, final exam, staying up all night cramming, maybe creatine could really improve their ability to score better on tests. And when you look at the mental fatiguing studies, that's when creatine seems to work. After you've done a whole bunch of fatiguing exercises— or sorry, taking creatine before— it really speeds up your ability to maintain memory and cognition. And we can talk about neurofilament things in the brain or BDNF, and, and that's some of the mechanisms primarily in rodents. So there are some mechanisms showing that creatine is decreasing oxidative stress or really having some potential for neuronal health, which now you think of Alzheimer's, dementia, neurodegenerative diseases. So I'm super excited to see where this is going for the next 20 or 30 years.

Dr. Rhonda Patrick: Yeah.