Transcript of Most Replayed Moment: Can Creatine Offset Sleep Deprivation? Is It Really The Best Supplement?

When I asked you before this conversation started rolling, what you're really excited about at the moment, your response to me was, there was a few things, but one of them which lit up your face was creatine.

Yes. And it's funny because...

It lit up your face again.

Yeah. It's funny because creatine has been around for, I mean, ever, for decades. And it's always been, in my mind, it was like one of those gym bro things. I'm like, I don't need to be, I don't need creatine to get swole. And this was the thought for many, many years. And then over the last five years or so, the effects of creatine on the brain started to really get my interest. Anything that affects the brain, I really become interested in. And so that's kind of what did get me the most excited about creatine. But also I started doing a lot of resistance training. And so I was like, okay, here I am now. I'm like one of those gym guys. I'm doing the barbells, I'm doing the squats and the deadlifts and all that. And so why not give myself some of the creatine? Well, what is creatine, right? Why is it important? You talked about earlier, why doesn't our body just make more of these things that are so beneficial? We do make creatine. We make about, I don't know, our liver makes about one to three grams a day of creatine, and our brain also makes creatine.

And those are the two organs that make it. Creatine gets consumed by other tissues, like the muscle is probably the one that's the greediest because creatine is stored as phosphocreatine, but it's used to make energy, essentially. So it can increase muscle mass, it can increase muscle strength, in combination with resistance training because you're able to regenerate and make energy faster. So for example, I became interested in it after reading studies where people that supplemented with creatine that were engaged in resistance training were able to gain more lean body mass, they were able to gain more strength. It was increasing their training volume. So you can do one to two more reps. Of whatever exercise you're doing. It seems to decrease the recovery time between those sets as well. You're able to increase your training volume. Well, anything that's going to increase your training volume is going to then have the downstream effect of increasing the adaptations like increased muscle mass or increased muscle strength. I started supplementing with creatine about a year ago and I started supplementing with it for that reason, for the my training. And I was doing about five grams a day because that was really what was shown to be beneficial for muscle health in combination with resistance training.

And it's important for people to realize that supplementing with creatine by itself without any type of resistance training isn't going to grow your muscle. It's not going to make you stronger. You have to put in the effort because what creatine is doing, it's helping you make the energy quicker, right? And then being able to make that energy quicker means that you're able to then do that exercise better, harder, more of it, right? So it's sort of supercharging your exercise routine. And five grams a day was like, okay, perfect. That's what I'm doing. I'm doing five grams a day. And definitely noticed an effect on my training volume where I was doing more reps, So that was like, okay, a year ago, I had already been aware of the effects on the brain. I thought maybe the five grams a day would do that. So what are the effects on the brain? Well, your brain also consumes a lot of energy, you know, needs a lot of energy. So it does make its own creatine. But it turns out if you can give your brain more of that creatine, particularly under a period of anything that's causing stress, So let's say lack of sleep or let's say emotional, psychological stress or in my case, high cognitive load where you're just every day learning concepts, complex things, you're trying to remember them, you're putting ideas together and coming up with new hypotheses.

And you know, you're just studying a lot and it's very cognitively demanding and it's a type of stress on your brain. That's like my life, right? Under this condition of stress, depression is another one. That's a stress on your brain. Or neurodegenerative disease, that's a stress on your brain. So any kind of stressful condition, that's where creatine shines in the brain. I would argue that all of us who has the perfect amount of sleep never has stress, Nobody, right? There's always some sort of stress in the background. So that's when I was like, okay, so if you're the perfect person, you have no stress, you get the perfect amount of sleep every night, your brain makes enough creatine to kind of do what it needs to do. I know that I'm constantly under stress, so I'm like, okay, well, I think I need a boost. And this is where a lot of very interesting studies have come out of many different labs some out of Germany that looked at the dose of creatine and how it increases creatine levels in the brain. And this is why I now supplement with 10 grams a day. So the study out of Germany found that five grams a day of creatine, if you're supplementing with five grams a day, your muscles are greedily consuming it, particularly if you're working out.

They want it, they want it. After about five grams a day, especially over a few months, like you're saturating your muscle and that's enough, right? Anything above that kind of spills over to the brain. And so they, what this German study found was that 10 grams of creatine increased creatine levels in several different regions of the brain. And that was probably the most exciting, you know, I would say evidence that supplementing higher than five grams a day was actually doing something in terms of getting creatine into the brain. There have now been a variety of studies that have looked at different outcomes, right? So if you supplement with 10 grams of creatine or even go higher than that, like 20 grams of creatine. How does that affect cognitive function? Right? And so some of these studies have been done by Dr. Darren Kandow. He's at the University of Regina in Canada. And it's looked, they've looked at things like sleep deprivation. And it's been found that if you take someone and you sleep deprive them for 21 hours and give them about 25 to 30 grams of creatine, it completely negates the cognitive deficits of sleep deprivation.

Actually, not only does it negate the cognitive deficits of sleep deprivation, it makes people function better than if they were well rested. That's where I was like, wait a minute. There's many times when I'm traveling, I'm jet lagged, lots of times that I'm sleep deprived and I have to be doing a podcast or a presentation, whatever. And in those situations I go up from my 10 grams to more like 20 grams, like today, for example. I wasn't really sleep deprived, but you know, there's a lot of high cognitive demand. This is a long podcast. There's all that stuff. And so I went up to 20 grams today on my creatine. And I, well, I will say even at the 10 grams for me, we were talking about this with respect to being in ketosis. I don't feel that mid-afternoon crash when I have the creatine. Not being on a ketogenic diet, not being in ketosis. It's very clear for me, and I have done this, where sometimes I only do five grams, and then if I do that, I'll notice, I'm like, why am I tired right now? So there's something interesting, and maybe it's placebo.

I'm going to throw that out there, very possible. But I don't know, maybe the creatine is, again, it's able to regenerate that energy quicker, and so that's also beneficial for the brain. And now I would say all these creatine researchers, a lot of them are shifting to the brain. It used to be all muscle focused, and now people are super interested in what creatine is doing to the brain, especially if you're supplementing with more of it. And this is important for people that are under a stressful situation, but also for vegans, because creatine is found in food, mostly in animal products like meat and poultry and fish, dairy. A lot of vegans don't eat that. And I've had so many of my vegan friends, I've got them on the creatine and it's changed their lives. I mean, they're like, this is incredible. Can you imagine someone who's not getting any creatine from their diet because they eat no meat, and all of a sudden they start supplementing with 5, 10 grams of creatine, and it's like they have energy. Some people say they require less sleep, which is kind of interesting. That's kind of a comment I've heard many, many times from people is that, It's like their brain doesn't need as much sleep.

They have more energy. So I've been a big fan of the creatine, not only for the muscle, especially because, you know, working out is something that's very important, but for the brain as well.

I always thought of creatine as something that you took and you kind of had to load up on. And then over a couple of weeks or months, the effects would kick in. But you're telling me that if I had creatine in the morning, that same day, I would experience potentially improved cognition if I have a big enough dose.

Yes, so great question. A lot of studies that have been done that you're referring to have been done in the context of exercise and muscular performance. And the reason why people have to load up on, like they do a loading phase, let's say 20 grams, and then they go down to this sort of maintenance phase of five grams is because it takes, I don't know, I think it's about a month or so before you can saturate your muscular stores of creatine.

And then you're- what does that mean?

It means that the creatine, which is actually stored in your muscle as phosphocreatine, is there and ready to be used to make energy. So it takes, again, it takes about a month or so to do that, unless you are really giving your muscles a high dose, right? So the five grams a day, it can only do it for so many days, and then finally you get saturated. When you do this loading phase, you kind of just accelerate that whole process. And so that's why when people are doing these experiments where they wanna test the effects of creatine, they want the participants to have really high levels of creatine in their muscles quick because they don't wanna do a month-long experiment, right? They want the experiment to be like a couple of weeks or a week. So that was kind of the whole concept behind this loading phase. If you're not someone who's going to some kind of competition, you know, like your CrossFit games or something, you don't really need to do that loading phase if you've already been supplementing with five grams a day for like a month. When it comes to the brain, what's happening if you get above that five grams, that's pretty much all consumed by the muscle, you're having some left over in circulation and the brain takes it up and it takes it up, right?

What it really shines is under that stressful condition, which again, for me, I feel like every day is like cognitively demanding for me because I'm constantly learning new material or learning new information or working on things, right? And so there's a lot of cognitive stress on my brain. I feel like I'm constantly under that stress. And that's where getting the creatine in your brain helps you make that energy quicker. And so that's why, like, I've been jet-lagged and have to give a talk at 5:00 a.m. in the morning, my biological time after not getting sleep. And I've done 25 grams of creatine. And it's insane how much it helps me. Again, it could be placebo because I'm anticipating that effect, which is fine. Placebo is a real thing. It's great. I'm all about it. But there's some evidence also that this works, right? That the creatine is helping under that sleep deprivation and that stressful condition.

I was reading about a study in 2025 where they gave creatine to people that had depressive symptoms alongside CBT training. And the people that had creatine and the cognitive behavioral therapy training experienced a greater improvement in their depression symptoms than those who just received the cognitive behavioral therapy. Which is incredible.

It's fascinating. I mean, depression is a type of brain stress, right? I mean, we know inflammation plays a role in depression. We know oxidative stress plays a role in depression. And there have now been some animal studies that have shown creatine is somehow having an anti-inflammatory effect. That hasn't all been worked out. So I don't know if it's all just the energy component of it. It could also be this other sort of newly identified role that creatine is playing in sort of having an anti-inflammatory effect. And I don't know enough about that. I don't know that there's enough even known about that, but I do know that it exists. And it's fascinating, but because, again, I think where creatine really shines in the brain, and it's been shown study after study, is under some kind of stressful condition, depression or sleep deprivation or there's a new study that came out, it was published, I don't know, a month ago or so, showing that it was a very small pilot study, and I want to caveat this, there was no placebo control, but it did show that giving people with Alzheimer's disease creatine, I believe it was 20 grams a day, did improve their cognition.

And so again, this is a whole new field where now we're looking at creatine in the brain not just the gym bros and not just the muscular effects, but in the brain and how it's affecting the brain and being beneficial for cognition, for brain aging, for depression.

Is there a link or an association with cancer outcomes and creatine? I was wondering, 'cause there was a study that I was looking at earlier. Yeah, this one. It says a 2025 study of 25,000 people each found that for each additional 0. Nine grams of creatine over a two day average was linked to a 14% reduction in cancer risk, which was in the Frontiers Journal and reported by the BBC.

Yeah, that it's like a new unexplored, you know, association here where it's like, I don't know why creatine is doing it. Is it the anti-inflammatory effect? Is it? Who knows? But again, I mean, I was aware of that study and it's like a whole new area that needs to be explored where You know, some people were worried about creatine actually causing cancer. I've actually had people ask me that question. And it's actually the opposite where it seems to be reducing cancer risk.

Some of the other sort of misconceptions around creatine are that it's going to, I mean, there was this stereotype that people take it, they get massive muscles and they become bloated. So I think that put a lot of women off in particular, according to some research that we actually did just to understand perceptions of creatine in my investment fund. But the other one was hair loss. People think, There's some sort of association with hair loss, i.e. if you take creatine, you're more likely to lose your hair.

Right. So there was this one study that was published, I don't even know how many decades ago, maybe you can pull it up, but it was in rugby players, I believe, and these rugby players that were given, I believe it was a high dose, maybe it was 20 grams, I can't remember the exact dose, but they had increased levels of dihydrotestosterone, DHT. Which is something that is linked to androgenic alopecia. So this would be, you know, basically your, the DHT can affect the hair follicle and keep it in this like stunted phase where it's not growing. And so that can cause hair loss. And that one study didn't measure hair loss. It just, again, looked at the DHT, the dihydrotestosterone levels. It's never been replicated. There's, after so many decades, It's never had any animal evidence showing that this actually causes hair loss. Nothing has really come up showing that this is something to be concerned about. So I take it as, okay, it's like a one off thing. Who knows what was going on here, but like you would think if it was real, it would be replicated after, when was it published?

2009.

2009.

Yeah. So it was a group of rugby players. They were given 25 grams a day of creatine. Um, but there was actually a study, a randomized controlled trial done in 2025 this this year with 45 resistant trained men all given five grams a day of creatine over 12 weeks. And there was no significant difference found in their hair outcomes or DHT versus placebo.

There we go. When was that published?

2025.

Oh, this year.

Randomized, double-blind, placebo-controlled.

Amazing. Thank you. I mean, to get also to your other point about the water weight gain, I know this is a real thing, because also several of my girlfriends were concerned about this as well. And it's funny, creatine does bring water into the cell, but that's actually, it's not a bad thing, right? And you're really not going to get a big gain in weight. I mean, I can't imagine, there's nothing more than like two pounds, if anything at all. So I do think that is sort of something that's, I don't know, it's a fear that's not justified in my opinion. I mean, you gain four pounds of water weight when you're on your menstrual cycle.

Yeah. You mentioned fasting. There's been lots of conversation around fasting, around whether it's good, bad, how long to fast, or whether just restricting your calories is the same as fasting. A lot of people talk about autophagy. My girlfriend talks about water fasting. What is your perspective on the role of fasting, how we should do it, if we should do it, when we should do it, who should do it?

I think it depends on what your goal is. So you mentioned people talk about calorie restriction and really, you know, is the fasting just about the calorie restriction? And I think when it comes to weight loss, losing weight, predominantly, hopefully, fat, not muscle, then calorie restriction is the main thing to do here. And intermittent fasting is sort of a tool to get you there. In other words, people that are doing intermittent fasting tend to eat fewer calories, and that's been shown in several studies, even if they aren't counting their calories. Because they are limited in the amount of time they're eating, and then they're fasting for a longer period of time, they end up just consuming naturally fewer calories.

Being in a calorie deficit, is that going to put you into the ketogenic state that you get from not fasting?

No, not necessarily, no. It's not. So you can be in a calorie deficit, but it depends, right? So when you're in the fasted state, what's important here is you're activating a bunch of pathways that don't become active when you're in a fed state. And there's a lot of biochemical reactions that sort of dictate all that. But you mentioned autophagy, right? And that's the big one. And that's happening only when you're really in a fasted state.

What is it?

There's different types of it. So generally speaking, it's the clearing out of damaged stuff within your cell. So what is damaged stuff? It can be protein aggregates. For example, if we think about in neurons, amyloid beta protein aggregates. So autophagy could play a role in clearing that out.

The plaques and stuff you get in your brain.

Exactly. But you also get plaques in your cardiovascular system. So autophagy can play a role in clearing that out. But it also could be fragments of DNA, it can be all sorts of gunk and stuff that just can accumulate inside of your cell. And so you're kind of getting rid of that. Also, it can be even on the level of, let's say, it's the organelle level, so you can actually have your mitochondria. We talked about mitochondria being the major source of energy inside of our cells. Mitochondria are very important for the health of all of our cells, our neurons, our muscle, because they produce energy. But mitochondria also accumulate a lot of damage quite easily because they produce energy and they use oxygen to do that. They make a lot of what's called reactive oxygen species. So these are things that can really react with our DNA, with proteins inside of our cells, with lipids, so the cell membranes. So your mitochondria don't really have a repair system like our DNA does. So we have DNA repair enzymes that can repair damage to our DNA, right? That's where magnesium comes in. Magnesium is required for these enzymes to be activated to repair damage to our DNA to prevent cancer.

Our mitochondria don't have that kind of repair system. They have another repair system, and one of it is what's called mitophagy, which is kind of a sub part of autophagy. And it's where the mitochondria, they accumulate damage, you can essentially take that mitochondria and get rid of it. Or a piece of that mitochondria that damage and get rid of it through this sort of autophagy type of thing, but it's called mitophagy. And that happens with other types of what are called organelles within our cells. So this autophagy process, this autophagy is sort of a general term, but it's essentially the cleaning out of damage, it's the repair process for damage, and it's something that happens most of the time when we're in a fasted state, which typically happens when we're sleeping.

How long do I have to be in a fasted state for?

I mean, it depends. I would say that we haven't really worked that out great in humans because people aren't measuring biomarkers of autophagy in humans. There have been some studies that have looked at being in a fasted state for like 16 hours, and essentially once you break through that part of depleting all your liver glycogen, that's an important precursor for activating autophagy. So I mentioned earlier that happens after about 12 hours, right? So as you get to 12, 13, 14, 15, 16 hours, then you're probably getting to that state of autophagy. However, there's such limited evidence on that in humans. A lot of it comes from animal studies. With that caveat, I will say that you can get a lot of benefits So some of the metabolic benefits for fasting include improved glucose levels, improved blood pressure regulation, metabolic effects improved, for example, weight loss, right? Now, can you get all of that from just doing caloric restriction versus doing like this intermittent fasting, right? You can get a lot of it, but there have been studies showing that doing this sort of intermittent fasting is beneficial for some of these metabolic parameters outside of the caloric, being in a caloric deficit.

What does that mean, metabolic parameters?

Again, glucose regulation, blood pressure, your blood pressure control as well. So these things have been shown in people that are doing time-restricted eating. So they're basically doing a type of intermittent fasting where, especially if they're doing a really compressed window, so they're eating all their food within six hours and then fasting for like 18. Hours, that's really beneficial, right? Because, and even if they have the same amount of calories as people that are calorically restricted, they've compared those head to head. People that are doing the fasting have better improvements in their glucose regulation, better improvements in, in, their blood pressure than people that are even still eating fewer calories, but not doing the fasting component.

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