You’ve Been Lied To About Creatine… It’s Not Just for Muscle w/ Dan Pardi

Dan Pardi, my man. Welcome, welcome back. It's so exciting to see you again. This is our second interview together, which I'm super stoked about because it's a topic related to something that's pretty near and dear to me, something that transformed my health many, many years ago as we were discussing before we started the recording, and that is creatine. Creatine has seemed to have made a huge resurgence in the natural health and wellness space, and we're seeing some amazing results for people in a variety of health benefits. Outside of the gym. Yeah. And it's wonderful to know that there is something that's affordable and accessible to pretty much every single person that can have such a profound effect on their health and, and their wellness. So thank you for coming back again, and it's wonderful to see you.

Sachin, thank you so much for having me back on. I so enjoyed our last discussion, and I remember thinking at the end of it that I was really looking forward to the opportunity to connect again, and here we are. So, and this is a great subject, as you have queued up so well, and there's a lot of valuable information to share. Creatine can help a lot of people and help people beyond what it was originally conceived for or to be good for. And so happy to— happy and excited to get into it for you and your audience.

Amazing. So what are like 3 reasons? Because I know people's attention spans are, are short these days, right? And you have to hook them right from the very beginning. So what are 3 reasons that people should listen to this entire interview that we're going to have together?

Yeah, the, the original idea was that it's good for muscle and exercise performance, and that is real. And, but we also know that exercise and using your muscles is good for really the rest of the body. So that's one idea. Then, of course, the brain. A lot of research is happening now looking at creatine on the brain for various purposes. And that can include— we could make this a third category or we can put it under brain, but sleep. Sleep has interesting effects on sleep. And I won't go into all of them now, but it can essentially— it seems that it might help to support sleep processes. But also rescue you, if you will, from a poor night's sleep and help you perform much, much better than you would otherwise. And then I think another area, there's a lot, there's immune, there's gut, but female health across the lifespan is something that needs more attention because the benefits are profound. And I've been very excited to talk about those ideas. So those I think are 3 great areas to discuss or to think about, and that I'm sure we'll go into more detail on them in the course of this discussion.

I love it. I'm even more intrigued because once you said immune system, I was like, oh, I didn't even realize that there was a connection there. So this is gonna be really intriguing for me as well. There is a creatine zeitgeist. So I actually probed my community and audience based on the questions that people have. So there's certainly questions that people know that they have, and there's questions that they don't even know to ask. Yeah. What would be, what would be an example of a question that people should be asking more about creatine that they may not even be thinking about?

Oh gosh. Well, there's a lot. I think you, to answer this question, the, the research on creatine widened around 2010. Most of the research before that was on sports performance and exercise, and it is now, the most studied compound for exercise performance. And so, a whole podcast could be dedicated to what has been discovered there, and it's valuable. But around 2010, because this is really a fundamental and unique molecule that is supportive of our energy system, what parts of the body won't it connect to or support? And yeah, it does seem to have a greater impact on certain areas. But another area that is also quite interesting is the effects of creatine on our methylation process. And I'm happy to go into that now or just queue up that for within the discussion. But yeah, that is another big area. Okay.

Yeah, that's a, that's a question that I had for you later on that people may not even know to ask that because they don't know the relationship or the connection between creatine and methylation processes and Lot of people are getting their methylation genes tested because that's become a more public awareness, but they may not think of creatine to, to help with that. So yeah, let's, let's unpack that. So let's go right to the top. I want to come at this with a beginner's mind approach.

Great.

So what is creatine? Is this something we get in our diet? Is this something our body makes? Like, you know, tell us more about creatine itself.

Okay. So creatine is a nitrogen-containing compound, and it is really found around the body, but it's most abundantly found in muscle, and it's made of 3 amino acids. It's pretty simple. It's arginine, glycine, and methionine. And what it does is it is stored around the body, particularly in muscle, as phosphocreatine. So that's creatine plus a phosphate group. And as we know, the main energy currency of the, currency of the body is ATP or adenosine with 3 phosphates. And when adenosine with 3 phosphates loses one of its phosphates, that is how energy gets utilized in the body. So that then creates adenosine plus 2 phosphates and the body's trying to resynthesize ATP, 3-phosphate version, quickly. And what, what creatine does is when the body's having a hard time maintaining that pace of resynthesizing ATP, phosphocreatine gives its phosphate back to ADP to resynthesize ATP. So it's like a, it's like a, a reserve of cash, if you will, that you can tap into when spending is high to help keep things flowing. And that is really potently observed when we go back to the exercise content. So if somebody can do 8 reps and 8 reps only of a certain weight, let's say it's bicep curls, well, they could— if they take creatine for 2 weeks with a loading dose, they can now do 10 reps of that same weight. So it may— it adds energy into that system, that system that fails. And you run out of energy, you can't do any more reps. And so that is a good way to think of it, but that's not the only way to think about where it's contributing to energy. So that's a good way to think of it. And then you also asked about diet. So I'll tell you, I'll talk a little bit more about endogenous production and even where, you know, how much would we do, do we store in the body? So we store about somewhere between 120 to 170 grams of creatine. And about 95% of it is actually in your muscle. So the rest of the 5% is distributed around your brain, your heart, in males, and that's in testicles and some other tissue too. And, um, and most of creatine, as I mentioned, is phosphocreatine, but there is also, you know, about less than 40% is free creatine. And we do see that creatine stores decline with age, so about up to 8, 10, 8, up to 8 to 10% per decade after the age of 30. And the primary causes of that is reduced muscle mass, so less tissues to store creatine, but also reduced dietary intake. And right there, that gives us an understanding of how we can maybe manipulate things as we do get older. So those are all important areas to consider. And then we do make it. So the body makes creatine. It makes about 1 or 2 grams per day. And the way that the process works is it starts in the kidneys and then it moves into the liver. So the first step of the process starts in the kidneys. It goes to the liver where the compound is created, and then it goes into circulation. So most tissues are not making their own creatine or synthesizing it locally. They're pulling it in from the bloodstream. And if, since that's the case, then we would think that it's either getting in through passive diffusion or that there's a transporter. And indeed, there is a transporter that helps pull creatine into tissues. Uh, and then we also— so we'll make about 1 or 2 grams a day, and we'll also, depending on your diet, you will eat about 1 or 2 grams a day, possibly more depending on the sources of your calories. If you're a vegetarian or vegan, you virtually have no creatine in your diet that you're eating. And that is why people who are vegetarian or vegan tend to do very well, even more exaggerated. So, for example, they can increase their muscle creatine stores by 40%. It's a lot.

Yeah. So that was the thing that I noticed right away when I— so I'm vegetarian, grew up vegetarian. And I would work out and I would get stronger.

Yeah.

And, you know, I felt like I was putting in all this effort, but I just wouldn't have the same volume as other people who I was stronger than. I was just like scratching my head. And then in comes creatine.

Yeah.

And it just like, I put on like 20 pounds, my strength gains went up significantly and it kind of, I felt like it leveled the playing field for me as a vegetarian to my meat eating counterparts. And it was just like, it's such an amazing, like, I guess for lack of a better term, a hack for me.

Yeah.

So I can, I can attest to the, the delta for, for somebody who's a vegetarian.

How much weight would you gain when you would go on creatine?

Actually not that much. Like, well, I mean, now that I'm at my, my, my current weight.

Yeah.

When I started, I mean, I, I started the creatine, but I also, as a result of that, started lifting heavier. So it's hard to attribute all the gain to like one thing.

That's right.

'Cause I didn't stop working out, but I put on about 20 pounds. So I went from about 145 to 165. And I've been, I've kind of kept that weight on ever since. Like I've never gone back down to my original weight, so to speak.

Yeah, yeah. I, I asked because I was— I'm definitely, and I've always been, a hyper-responder. So I'll gain like 10 pounds of muscle when I go on creatine, and it happens really fast. But watching the scale, it's like, oh my gosh. But it is all, you know, we can get into this because a common question which we can often comes up, you know, later after you discuss more about what it is, but, oh, is this going to be bloating? But it's not. It's the— it is a hydrophilic molecule, so water stuffing, and so it gets pulled into your muscle tissue and it pulls in water with it. So, your muscles feel a little bit fuller like they do maybe after a workout. It's not going to make somebody look like they've been doing steroids for years. Some people kind of have that concern, but it is something that will make your muscles feel more tight in that pleasant way. Like, you know, they're feeling full like I said, like you just finished a workout. But going back to need, I mean, the common cited amount that you eat from a diet if you're an omnivore is about 1 or 2 grams a day. But there's actually precedence from hunter-gatherer intake levels that could go 5 to 10 grams of creatine ingestion per day. So, there are hominid evolution, we have, there were periods at least where we would have very large amounts of meat intake. And if you were to translate ingesting those large quantities of meat and fish, which again, major parts of the human diet under human evolution, then you would estimate that the actual amount of dietary intake is somewhere closer up, but closer to 5 grams per day and up to 10. So there's precedence for these now increased doses that we're seeing supplementally.

Okay. So yeah, so when someone's taking 5 to 10 grams, uh, or, you know, really it, any amount, one of the things that comes up is side effects. And I know that creatine is one of the most studied, you know, dietary supplements ever from what I understand, or it's really up there. Mm-hmm. Let's talk about safety profile cuz that's something I know people have concerns and questions about.

Yeah, so this is an incredibly safe compound. This has been tested directly And it's really, if you think of it more like a food source, and if you think about even the levels that were probably like we just discussed common during human evolution, taking 5 grams a day is not something that you are evolutionarily unfamiliar with. And again, even up to 10. So the concerns were primarily around creatinine. Which is a breakdown product of creatine. So when creatine is broken down, you see higher levels of creatinine. And for doctors, when they see elevated levels of creatinine independent of creatine supplementation, that is a possible sign of your kidneys are not working as well as they should. The question then was, well, is this causing kidney issues or are we just seeing elevated creatinine because you're taking elevated creatine levels? And that has now— so the, the concern was, is this hard on your kidneys? That started from the very beginning of usage. That's been studied directly, and there's really no evidence that there is any problems on the kidneys with long-term usage of this, a 5-gram dose of creatine, which is most common. So when you want to qualify your statement there. And if someone's taking 50 grams a day, I've never heard of that, but just some ridiculous number, well, that would need to be studied directly. But a, again, a 5 or 10 gram dose, uh, not only has been studied to be healthy and not problematic, but I would be surprised if it was given the fact that it's contained, it can, it's contained in the food that we eat if you're eating meat. Okay. Yeah.

And it's like 5 to 10 grams might sound like a high dose to somebody, but once you say that this is not a super physiological dose, it's something our body is capable of handling and maybe we're just not getting enough because of the way we eat now and seasonality. I know that during certain seasons we would probably have eaten more meat than others.

Yeah.

And you know, when you, perhaps when you hunt an animal and you're eating a lot all at once, right? 'Cause you don't have refrigeration and methods to store the food, so you're consuming as much as you can all at once.

Yes.

So it's not like an excessive dose. I know some people recommend as high as 20 grams for, you know, for jet lag and cognitive function and things like that. Have those types of dosages been studied, or is that— is the jury still out there?

I would be cautious with those only not because of signs that there's— there are issues, but because those doses haven't been studied. And I would say that those are more evolutionarily unfamiliar. So taking— now, what we have studied, which is quite common is taking 20 grams a day for a short period of time, mostly a week, sometimes 4 weeks. Lots of early research studied that. So acutely elevating your creatine, your daily creatine intake to top off muscle stores was the goal. And that's now been seen to occur, topping off, maximizing muscle stores in as little as 5 to 7 days. Um, now if you don't want to do that You can also just take 5 grams a day, some even 3, and then have that lead to the same place. You're going to do the same thing but more slowly. You're going to top off your muscle creatine stores. Like I said, so if you're an omnivore, you are— the common cited figure is about 20%. You're going to increase your muscle creatine by about 20%. If you are a vegetarian or a vegan, that amount is closer to 40%. So, again, that's just in muscle. But now in the brain, there is less of an increase, but there's also— I've seen figures somewhere across the research body between 5% and 15% increases in brain creatine stores. So, different tissues are going to have a max capacity that is different than other tissues in the body. So, a lot of times when we think about, oh, you're going to increase your stores of creatine that has mostly been around muscle. But yeah, so we're, like I said, we're, I think we're at the tip of the iceberg with what is to be understood ultimately on creatine in the body. And that's exciting for me. It means that we're going to see a lot more. There's now signals for all sorts of areas, and we're going to see a lot more work because of that.

So you said creatine's 3 amino acids. Does that mean it's a peptide? Or like how, what, uh, it's a compound.

Yeah. So the compound is, is joining those 3 different, um, uh, those 3 different amino acids. And, um, yeah, like I said, it's an organic, um, nitrogen-containing compound. Um, and, uh, yeah, so that's, that's, you know, the best way to think of it.

Okay. And then the other question that comes up for me is, is there a negative feedback loop? So if we're taking creatine, does that suppress or alter our own production of it?

I, that, that is a good question and I, I'm gonna go back and look into that more specifically because, but I, it's, I don't think that it is anything that would be irreversible.

Okay.

So, but the body would, would, is, there's all sorts of feedback loops in the body and so if you have an ample supply of creatine dietarily, including supplemental creatine, there would be less need for your body to make creatine. And the exact feedback loop there is not one that I am necessarily well-versed in, but I would imagine that your endogenous production, you're kind of easing some of that burden, and which gets into the methylation discussion actually.

Okay. Yeah, let's, let's dive into that cuz yeah, first of all, maybe very just high level, what is methylation? Why does it matter? And then how does creatine affect it?

Yeah, yeah. So methylation is a very important process in the body. We have these methyl groups and methylation means that these methyl groups are attached to different compounds. They're used in different processes in the body. So for example, in repair of DNA, for the synthesis and the breakdown of neurotransmitters and also in detoxification. So when something in the body is metabolized and your body wants to get rid of that breakdown product, it'll get methylated, which tags it for excretion. And so the amount of methyl groups that we have in the body is a finite resource. Now, creatine is actually one of the largest consumers— creatine synthesis is one of the largest consumers of methyl groups. It actually accounts for up to 70% of daily methylation reactions. So it is a very heavy user of your methyl groups. Yeah. And so, and that's just in order to produce that 1 or 2 grams. So if you are supplementing with creatine, there's really a decreased need for endogenous synthesis and this spares you know, your methyl groups for the other processes that your body needs. So in a way it, uh, and this is especially helpful for individuals with the MTHFR polymorphisms, um, or methylation issues that maybe, you know, other types of methylation issues. People like that can really benefit from creatine supplementation to reduce the methylation demand.

Yeah. And especially if people aren't getting like dark leafy greens or good sources of, you know, methyl compounds in their diet, then, you know, it, it sounds like we're pushing the reaction backwards. So it takes less resources to create the amount of creatine that we need because we're getting it from an outside source.

That's right. Yeah. Yeah. Even for things like phosphatidylcholine production, which is important for our membranes, those, those are all very methylation-intensive processes. So creatine ingestion is gonna spare methyl groups for other really important processes in the body.

You know that, so I love that because we do DNA testing on our clients to identify if their need for phosphatidylcholine is high. And we see that quite often. Mm-hmm. And people have a lot of cognitive issues when their phosphatidylcholine, when their choline levels are on the lower side, you know, they'll forget the word they're trying to say or they'll walk into a room and forget why and they'll just have these lapses in their cognitive function.

Yeah.

And we'll see that their need for phosphatidylcholine is high, we supplement it and, and you know, things bump up. But now you're, what I'm is that giving them creatine will also help, I guess, increase the levels of, of choline that's available to them for all the functions that choline has in the body.

That's right. And, and it's a really interest— so I'd be curious to see if your testing of that changes with creatine supplementation, but still only about 10% of the population is getting the daily requirement for choline. And this not only helps with brain processes, memory, cognition, but even exercise, which we wrote a blog on that recently. And so people that have adequate amounts of choline actually make faster gains in the gym in response to their training. So yeah, so even if you're taking more creatine, also make sure that you're getting adequate amounts of choline in your daily diet and through one form or another.

But yeah, that was a high-need nutrient for me, phosphatidylcholine, from a genetic perspective. So it wasn't a lab test telling me I was low, but my need was very high. And as a vegetarian, you know, choline is found in eggs and chicken and liver and stuff like that. And so I really didn't have sources of creatine in my diet or, or choline in my diet.

Yeah.

And I feel like I've been supplementing those two things, creatine for many, many years and the choline, you know, probably in the last two years. And I can tell it's made a pretty big difference for me cognitively. Yeah. I would try to find a word and I'm like, I know the word, how come I can't say it? Yeah. And then once I learned that about my choline needs being so high, I started supplementing with it and the, the lights just kind of turned back on, so to speak. It was, it was pretty remarkable actually, the difference it made. So if you're saying that 90% of people are not getting enough choline in their diet, it could be a potentially good supplement for them to take. And of course the creatine is gonna help offset that demand as well.

Yeah, exactly. So they're, they are supporting that pro— the, the process of adequate phosphatidylcholine and choline through different mechanisms, both important.

Hmm. Now there's just like with most supplements, there's different forms, right? And yeah, I, I remember when creatine first came onto the market, we're talking like, you know, almost 25 years ago when it started becoming more mainstream in, in the bodybuilding and the fitness world, you know, every week there'd be somebody coming out and saying, you know, try this creatine or it's attached to this amino acid or it's creatine HCL. And of course, everyone says their format's the best. And then, you know, fast forward a little bit, I, I came to learn that creatine monohydrate is all you need and it's usually the most affordable and accessible version. So tell us about the, maybe the different forms of creatine and is it hype or is there actually a difference? Is it, you know, there's creatine HCL which comes up often, there's CreaPure, which I believe is a patented molecule if I'm not mistaken. And there's creatine monohydrate. There might be other forms as well, but I'd love to get your take on that.

Yeah, so there's creatine ethyl ester, creatine monohydrate, creatine hydrochloride. So you're right, once the market for creatine started to explode, which was in the mid-'90s— this was after the Barcelona Olympics where the British, the British Olympic team came out that they had been using creatine. And the story behind that is fascinating because it was this mad dash. There was only a kilo of creatinine in the global supply when a researcher, Roger Harris, handed a research paper to Steve Jennings, who was working directly with the Olympic team, and said, "Hey, this could really improve ballistic sports performance like in sprinting by up to 3%," which for a sprinting event, for example, that's a lot. That's the difference between winning gold or not even making the final race. And so there was a lot of excitement when Linford Christie won the 100-meter dash that year, reported that he'd been taking creatine. And then within the next couple of years, the market in the United States had grown to about $30 million. Just a few years after that, by 1998, it had gone up to $150 million. So it's not uncommon at all. That new, new ideas that we discover in science are first then tested in athletes. And once the reputation of something being actually effective gets out there, then everybody wants to take it, even if they're not a professional athlete but are training really hard. And that's exactly, that's exactly what happened. So then in response to that, people were trying to carve out part of this growing addressable market and saying, all right, what if we could create a better version? And I want to be really fair here because without question, the preponderance of the evidence, all the research that we talk about pretty much is using creatine monohydrate. And there's less research, often research that is done by people that are— have some sort of financial connection to the new form, which I don't dismiss outright. But you always have to take that information with a grain of salt and be aware that there could be incentives there that you're not— that would, you know, position the new formula in a maybe, um, in a beneficial light beyond what a non— a scientist that doesn't have those financial ties might, might say. Um, and so, yeah, so I'm weirdly— I'm pulling for all these different forms to carve out a unique benefit. Like, maybe we find that creatine hydrochloride ends up being better for purpose X. At the moment, the right— I think the right thing to do is to take creatine monohydrate, because again, when you're hearing benefits of creatine, you are hearing the benefits of creatine monohydrate.

So that's the most researched form is what I'm understanding you're saying.

Most researched, uh, let cost less. There's, there's, uh, all sorts of reasons to be taking that version.

Okay. And you know, we, we talked about creatine and, and the, uh, and the brain.

Yeah.

So I'm curious if, if you have any awareness around this, if, if there's certain forms that cross certain barriers like the blood-brain barrier better than others. And I know that's a probably a loaded question, but I'm just curious if, if that's come across your desk at all.

There's a paper that did look, it was the Cremonopa study looking at two forms of creatine in women. On the brain, and it looked at creatine ethyl ester and creatine hydrochloride, and they showed impressive effects on the brain, but they didn't also test creatine monohydrate. And so we don't know. It's hard to discern if those effects stand out because if, let's say, you, you see one paper that shows creatine increases brain creatine levels only X percent, let's say 10%, and this one increases it 13% or 15%. It's hard to compare those studies. Was the creatine in the brain assessed in the exact same way? What was the population of the people? What were the conditions of the study? And so unless— people do that all the time. They'll compare this percentage to that percentage, and that might not be real. So we do see that creatine monohydrate increases brain stores of creatine, again, somewhere between 5% and 15%. So at this point in time, there really, it doesn't appear to be good reason to be spending more money on a different form. Yeah.

Thank you. Yeah. Another question that, you know, with, with all supplements that comes up is contraindications. So I'm curious, I think I know the answer, but I, I just wanna pose it anyways. Is there, are there any contraindications? Cancer, pregnancy, what age can people start taking it if, if there is, if there is age guidelines around it. Yeah, so I'm just curious around that.

Those are all really good questions and unfortunately a lot of those areas are studied less because, because of the importance of that situation. You don't want to add something into the mix that could be problematic. Well, nobody should say that creatine is a, uh, something that is going to cure cancer. There's some evidence that the rate of cancer in people taking creatine is lower than those who are not taking creatine. Now, um, there could be some reason for that. That reasons are very possibly due to the immune system effects that I hearkened to in the beginning. And so I'd love to see more research on that. I would absolutely love to see more research on that. What about for pregnant women? That's another area that I would love to see more research on, but it tends to be one of those areas that is not— doesn't have much information on it because the last thing you want to do is do anything to upset that, to disturb that very delicate situation in a negative way. Yeah.

So I guess if a female is pregnant wanting to increase her creatine levels and eating more animal protein, would be a food, food-sourced way of, of doing that.

Yeah. Yes.

Yeah. How about age? My, you know, my son's 15, he's a vegetarian as well and I, I love to see him bulk up a little bit. So I'm, I'm curious if there's any age guidelines around something like this.

There are not age guidelines. However, I have a 12-year-old boy and I have him taking 2 or 3 grams of creatine per day. We know that during puberty, um, it is a period of tremendous growth. The whole body is changing. The demand— the demands on the energy system are great. And so can creatine— and I'm not sure if your son is physically active. My son does jiu-jitsu and wrestles, and he's got a lot going on in his life. And so I am giving him a, a modest amount that is helping his body have enough energy to do all the things he's trying to do, whether they're conscious or subconscious or non-conscious processes that he's just entering into. And so, yeah, I feel good about that given what I understand of how this works.

Okay, wonderful. I know he's going to be excited about that, so he'll start putting it in his drinks. Question about, you know, we talked about dosage, timing I think would be a, a good question. And then if there's any synergistic things that we can take. So I'll tell you kind of what I heard growing up and you can demystify these things or, or debunk the myths.

Yeah.

Is that you'd wanna take creatine with like a fruit juice or a grape juice or something like that to get it into the cells better and faster. You'd wanna increase your hydration because it does bind to, to water molecules. And that you would take it before and right after your workout. So take me on, take me on a little dosage tour here, like when to take it, you know, how to split it up with workouts, off days, if there's any chasers or anything I should be taking with it as well.

We just published a blog on this last Friday.

Oh, perfect.

And And there is evidence that taking creatine with some foods that might stimulate insulin can drive an increase, acute increase in creatine stores in muscles. But in the grand scheme of things, it doesn't actually make a big— it doesn't, it doesn't matter. Like we're adding complication to something when Sometimes the best thing to do is just keep it simple. Take it at the same time every day. Don't worry about it. You don't need to take it within a window of time to optimize effects. And, and I'm all about optimization and figuring that out, but when we do add complication, it might mean that a person is less consistent with taking their daily creatine instead of just taking it in the morning, 5 grams when you wake up. Morning's a good time to do it. We can talk about that then. You're now making sure you have to have it with you. It's an extra thing to think about that might not actually be worth it. So there was a, there was a really interesting study done. And in that study, they had within the same person, they did, they took creatine before working out and then they did the one side of the body and then they did the other side of the body and they had them take it after working out. Didn't matter. Within, after a couple of weeks, they had maintained the exact same amount of strength gains on both sides. And so again, let's not complicate this more in an, in a way that's not really necessary. Um, yeah, so that's, that is, I think, the best thing to focus on when it comes to what to take it with. Now, your comment about hydration is important. So because this is pulling in water into your muscles, you don't have to take in an extra amount of water, but you should be adequately hydrated. And so if anybody is ever experiencing some cramping in the beginning stages, they're probably just not drinking enough water, and the creatine is pulling in water into muscles, and so it can cause some cramps. Make sure that you're adequately hydrated. So drink the recommended glasses of water per day, and you're good.

Okay. Another question that came up, and I'm curious about this too, is about temperature. So does adding creatine to some, like a hot liquid like your coffee, I've seen people do that. So I'm just wondering if, if it's degraded by temperature or impacted by temperature at all.

Yes, it is actually. So the acidity of a lot of people added to coffee, I do that now and again, but the acidity and the temperature can break down creatine into creatinine. And it can degrade it like 15%. So again, I don't worry too much about it. This is a long-term thing. The quality— Qualia's creatine product has a little bit of sea salt in it, and Greg, our chief formulator, he's our chief product officer, said, oh yeah, that actually can bring out— the salt can bring out some of the flavors in the coffee. So a lot of people that know coffee really well, they'll put a little sprinkle of sea salt in their coffee anyway. I was like, oh God, I have to try this. So sometimes I—

yeah, yeah, I didn't know that.

Yeah, let me know what you think. I'm curious. Uh, but would it— it's going to be more problematic if you let your coffee sit for a long period of time. So if you make it, you put it in there and you drink it, great. You're probably getting a little bit less of the creatine, but it's not a substantial amount. Uh, and so often, most often, I'll just put it in water and I'll drink it straight.

Okay, perfect.

Yeah.

Yeah. We talked about a lot of things. Is there anything I haven't asked you that you feel like people need to know about creatine?

Yeah. So I think one of the most interesting effects is not only the positive effects that we're seeing on the brain, cuz what I did mention that you will see an increase in stores of creatine in the brain that is then affecting the bioenergetics of all— the brain is a very energy-intensive hungry organ, right? We know it's 2% of our body weight, it's taking in 20% of— it's burning 20% of our fuel. But there is definitely some work now that's looking at how it might affect neuroplasticity or supporting neurotrophic support, so like BDNF or N-acetyl aspartate, which is involved in memory, acting as a neuromodulator. So, the net effects from those mechanistic pathways is going to be possibly increases in cognition. We've seen that. We've seen that in terms of increased reaction time, memory, mood, planning, various ways that it's been investigated, changes in mood, mood stabilization. So, with energy available, being able to maintain a normal baseline of mood, which is great. Possibly some disease-specific benefits, which are now being looked at now. Um, and then of course the changes on sleep and the sleep ones, the sleep benefits have been really huge for me.

So tell me about that.

Yeah. Um, we wrote a blog on a site that I started called HumanOS. Probably 5 or 6 years ago, posing the question, does creatine reduce your need for sleep? Because people were taking— people who had— it was discovered empirically that people would take creatine and they would sleep less. They're like, I feel like I have, quote unquote, insomnia, right? I'm sleeping less, but I feel fine. Do I just need less sleep? And So that is— we've seen all sorts of weird things. So there's a study that I mentioned in a talk that I've recently given in a webinar where female athletes were doing the exact same training protocol, and one group was receiving 5 grams of creatine a day for 6 weeks. The other group was doing the same training but no creatine, and the group that was taking creatine slept 48 more minutes per day. That was very impressive. Um, and it wasn't— it was sleeping more into a normal amount. We tend to think of, oh well, when you're resting, you're not using very much energy. You're still using energy. Sleep is a very active process. It— the energy demand is less than daytime activities, but you're—

it's—

the brain is still doing things to process the memories that you process memory to purge out, to detoxify compounds that build up over the course of the day.

So the—

and it's also good to then think, well, how is then, you know, creatine actually supporting this? Again, remember, it's donating its phosphate group to help resynthesize ATP when the demand for ATP is high. And where this really seems to be beneficial is not just on getting an adequate amount of sleep, but also if you've experienced sleep loss. And that's where I have had really tremendous benefit. So it's not uncommon where people will get 25-30% less sleep than what's ideal for them. And under those types of conditions, you can feel miserable. You can feel it, it's almost painful. The day just needs to go by. You can't think very well. You feel this constant sleep pressure. And if you think about what sleep pressure is, that is a scientific term that we— the neural correlate. So what is sleep pressure, this idea of sleep pressure, actually in the brain? It is the buildup of free adenosine in the brain that causes you to have this mounting sense of sleepiness. Now, the reason we don't feel sleepier and sleepier across the day is because the brain has a way of counteracting that building sleep pressure, and that is by increasing the amount of what we call wake drive, which is a coordination of multiple different wake-generating neurons in the brain. So dopaminergic neurons, serotonergic neurons, histaminergic neurons from histamine, all coordinated by something called hypocretin, which sits at the seat of the hypothalamus. It's like the symphony conductor director saying, okay, play louder, louder, louder, and that increased volume of wake drive is counteracting that sleep pressure. But guess where we feel that sleep pressure? The middle of the afternoon. There is a dip in your wake-generating drive, and that's when you feel tired. That's when you take a nap. That's when cultures that take a siesta take their siesta. And then after that window, We refer to that as the wake maintenance zone. In fact, the best alertness that a person can experience across an entire 16-hour of their day can be after that period, because that's when your alertness drive is working to its maximum. Then right before bed, that wake drive switches off, and guess what? It's like Wile E. Coyote that runs out into the— off the cliff and then hangs there for a minute and then drops. Well, you have all this unopposed sleep pressure that's built up, and that initiates sleep, drives slow-wave sleep, and wears off over the night. It's this beautiful dance that is occurring. But that correlate of sleep pressure is free adenosine. And so when you take more creatine, you're actually absorbing some of that free creatine, and it keeps your alertness really, really, uh, good. It's not a stimulant, right? It's not going to feel like a cup of caffeine, but it's going to create a sense of, I feel perfectly alert in the middle of the day. And so there's been plenty of studies that have looked at this, going all the way back to 2007. A researcher, Terry McMorris, did— he looked at creatine supplementation under conditions of sleep deprivation in an older population, and there was a complete preservation of their skills even though they didn't— they got about half sleep that they would have liked to. That study was followed up by a researcher Christian Cook in the Journal of International Society for Sports Nutrition. And they were looking at elite rugby players on only 3 hours of sleep. And without creatine on board, their skills, all the skills that they are expert at, just dropped off. They couldn't do any of it. And with creatine on board, they actually performed all of those skills at a very high level. In fact, there was no decrement from their baseline performance. Now, in each of those studies, there, we're talking about doses that are higher than what's common. And probably the most definitive study in this entire field was, um, in 2024 by, it was in Scientific Reports, um, by a researcher, Ali Ghorji Najjad. And this one was so interesting because, yes, he showed, just like those previous studies, that there was a preservation of skill under conditions of sleep deprivation where you would otherwise expect real decrement. But he also showed why. And the reason why is that when you're sleep deprived, brain ammonia levels rise, brain acidity rises, and what that does is it opens up— it makes the brain more absorbent for creatine. So more creatine gets in. And in that study, they tested 0.35 milligrams per kilogram. And so for somebody my size, you know, if you're like 150 pounds, then you're going to be taking about 25 grams, um, on the day that you have only got— when you're feeling that the effects of sleep deprivation. And that's going to make, at least according to if your experience mirrored what the study showed, you're gonna actually feel just fine.

Yeah. So for all the practitioners traveling or the people traveling across different timelines, different countries, this could be a, and if they have to like be on the next day or, you know, performing at their best, this could be a great tool for especially speakers or attendees of conferences or, you know, a lot of, a lot of people when they travel, they, they might lose a day or to just acclimatizing. So this could help them enjoy wherever they're traveling to much better.

That's absolutely right. Imagine, you know, you've, you're, you're going over to Europe and you're doing a presentation. You've just flown. You're now having to get up at a time that is like 3 in the morning, your time biologically, and you're given the first talk. Creatine is going to help you feel much, much better. So think about how caffeine works. Caffeine works by blocking the adenosine receptor. Creatine works by absorbing the free, the free, uh, adenosine. So one is blocking the signal and the other one is reducing it. And so the combination can be great, but that this not only matters for the situation, the important situation you articulated, but what about shift work? What about— there's all sorts of reasons why we find ourselves in a situation where we have to perform at a time when we don't really feel like it or we're not going to be our best. And creatine is probably the number one— I don't know anything nearly as powerful as creatine at helping restore or preserve performance under those types of conditions.

I think we may have started a whole new category, cold brew creatine.

Yeah, yeah, yeah. Now the acidity, remember the acidity can also have an effect. So I don't know if you're gonna have like a can of, of this that, um, unless you can control the pH. Uh, but yeah, so traveling with it. Um, another thing that actually I recommend, and this is more for fun, but let's say you get invited to a dinner on a Friday night and the dinner starts at a time where you're Usually winding down and going to bed. When that situation arises for me, I'll take creatine. I'll take 10 grams of creatine around 5:00 PM. And again, you don't feel stimulated. I feel perfectly normal and I have energy to be more social. I don't feel depleted. I have good— I can recall words. I don't mumble through things. So it's, it's really great. So yeah, creatine has a lot of benefits, but this is one of the biggest ones in my mind, at least acutely.

Okay. You know, one thing you said that just makes me wanna just unpeel this a little bit more is that because of the effects of the brain after sleep deprivation creates the conditions for better creatine absorption.

And that makes sense.

I'm assuming that you would take it the morning of versus the night before. Is that accurate?

That's right. Yeah. Yeah, that's right. So now this is where a conversation around dose is really important because taking that amount of creatine all at once is very likely going to cause GI upset. It's going to move right through you. Remember, it's a water-loving molecule. And so, yeah, that can be problematic. So what I do in situations like that is I'll take 5 grams, wait a half an hour, take 5, wait a half an hour, take 5. So you want to space it out a little bit.

Okay.

And then you also want to learn how you do in a situation like that. So if you're doing a really big race, I would say learn how your body responds to creatine before you test a much larger dose than you typically take.

Good advice. I think that's important to keep in mind, especially if you're speaker number one, right? On, at an event.

Yeah, exactly.

Yeah. So yeah, maybe even experiment, you know, without traveling and just see, you know, what works in terms of spacing the dosage out.

That's what I recommend. Yeah. See how you do, get familiar with it. There's plenty of reasons why we're gonna feel like we just didn't get a perfect night's sleep. When that arises, be ready, try it out, assess your risk, and then try that protocol where you space it out a little bit and learn, learn how you do.

Okay.

Yeah.

Now I know some people have complained about bloating when they take creatine, and since you kind of hinted on, you know, the, the kind of the possibility of GI upset, is it too much that they're taking all at once? Is it because they're taking it with other molecules that they shouldn't be, or, you know, what can you speak to that? If, is that even a thing? I never experienced that, but I know some people do.

Yeah. Yeah. I guess we have to define what we mean by bloating. So is it GI bloating? Is it creating gas? So that I've not heard of, but I think what people mean is I've gained water. Am I going to feel puffy? And there's a big difference between that extracellular water, if you had you know, a massive bowl of ramen, you might experience if you're salt sensitive. Um, this is different, right? In fact, you'd imagine creatine to have the opposite effect because creatine, again, is not just sitting in the extracellular space, it's getting pulled into your muscles. And so the hydration, that extra water is going into your muscles. And again, when I gain 10 pounds, that's different. I'm a hyper-responder. So first of all, you know, I weigh 220 pounds. So I'm big, bigger. And then secondly, I, um, I respond— I gain more weight than typical. So if you're 130-pound female, you know, you might gain a couple of pounds, but again, the feeling that you're going to get is pretty much the feeling that you have after you do, you know, a yoga class or a fitness class. Like, you—

that's how your muscles just feel a little bit more Yeah, I think that distinction is important because it's a totally different feeling in your body as well. Water retention versus water retention in the muscle. Yeah, it, it's that good pump you feel after you work out, which I know I like. Can't speak for women. Yeah. But I certainly know that that's a, for me that's a good feeling to feel that fullness in the muscle.

Definitely. And it's not even as much as like after a full workout where you're really pumped up, it's a very slight, it's like a half an hour after that maybe. Be a slight change that you may or may not be able to notice, but you, that's what you notice if you notice anything.

Okay. And then, and this might be bro science, so please forgive me, we're here to learn. I heard that once you're finished a canister, and usually canister lasts about a month depending on the size you're buying, then you take some time off and cycle on and off. I'm just curious, is there any truth to that or is it okay to just keep taking 5 grams every day?

It's totally fine to take 5 grams a day. The funny thing here is that creatine was really conflated with other substances that bodybuilders were taking. And so the idea, of course, if they're— if someone's taking anabolic steroids, is that you cycle it, where you take something for a period of time and then you stop taking it, which lets your body reset so you don't completely shut down your own ability to create, let's say, testosterone. And there, none of that applies here for creatine. So again, it's— again, think of it more like a food than anything else. You're— it's fine if you do, if you want to take time off for a purpose. You don't have to. There's not a physiologic reason to do that, but you can if you'd like.

Okay. Um, Cutting weight. So for people who are, you know, competitive bodybuilders or, you know, fitness competitors or people who just wanna cut or, or lean out a little bit, I know from what I'm gathering, the water is mainly retained in the muscle.

Yeah.

Does it affect cutting if, if somebody's looking to feel or look more shredded?

I would have to direct that question to somebody who is really involved in the science of weight cutting for aesthetic fitness purposes. I really, I do respect those people quite a lot because they have everything, all of your water and your sodium and your potassium and your protein and your calories dialed into a science. Yeah. So that you look different than you typically look for about 8 hours. And it's amazing that we can do that with our bodies. And, but I'd be curious to know, learn from somebody in that field, what they've experimentally deduced with using creatine. I don't know the answer offhand myself.

Yeah. I, I don't either. And, and I know that you don't wanna mess with somebody's cut, right?

No.

And so there, that's a whole different ball of wax when you're dealing in that world.

Yeah. I'll say this, I wouldn't be surprised if creatine is supportive of what you're, of the aesthetic goals you're after. Hmm. But I would defer to somebody who has a lot more experience than I do in that particular domain.

Yeah, cuz it sounds like intuitively from what you shared today, it sounds like it would pull the water into the muscle. So volumizing the muscle and, and reducing the amount of circulating extra fluid.

Totally. It's such a science of, of manipulation of water in, in across a, so yeah, typically what a fitness competitor who's getting up on stage and posing will do is they're gonna cut calories up to 12 weeks, and they're going to, you know, maybe bulk up before that. They start to then try to reduce their body fatness. They change their training. And then somewhere a week out, they're going to start changing everything dramatically to manipulate water so that there is the least amount of extracellular water and you have the— but without losing any muscle fullness. And so, if you look at a fitness competitor of any sort 24 hours after they were on stage, they don't look nearly as shredded as they did just hours before that. And that is all water manipulation.

Yeah. So, you know, not our audience necessarily, but if that is you, then look into it. It could be something that enhances your aesthetic outcome.

Yeah, yeah. It's certainly a favorite of the bodybuilding community and has been so for a long time and for good reason.

We've talked about, you know, essentially so, so many benefits of creatine and I, I just wanna first of all, thank you. And secondly, I, I, I guess just to make sure if people are listening to this, And asking on behalf of those that might be thinking this or asking this question, are there any potential side effects or is there anyone that shouldn't use creatine specific explicitly?

I would like to see more research on somebody that has known kidney issues. And in a, in an abundance of caution, I would want, you could argue this could be good for somebody who has issues because you're reducing the burden of the kidneys on having to make the first step of creatine synthesis. I'd like to see that explored, but I wouldn't want to casually say, oh, there's no problem, uh, on— in somebody that has existing kidney disease just because we haven't seen creatine cause kidney issues. So that is something that needs to be researched directly, and I don't know if anybody is doing that. Other than that, there really isn't a major thing that stands out for creatine consumption. But I think overall it seems like it's going to be good for far more uses than even we're aware of now. Like, like with women, I mean, that's a, that's one that I've been very motivated to present on, to talk about. And there's very specific changes that the natural hormonal cycle has on the creatine system. It's like this hormonal tuning that is— that occurs. So when there is an— if you're— if a woman is in an estrogen-dominant phase, that really accelerates all aspects of the creatine system. So you see increased synthesis, you see increased transporter activity. You see increased creatine kinase. Creatine kinase is the enzyme that then both breaks down phosphocreatine to donate the phosphate group and also builds it back up, so it's bidirectional. And so the opposite is true with progesterone. It slows everything down. So you see decreased kinase activity, you see decreased synthesis, you see, um, even modest changes in transporter activity as well, pulling creatine in. And so that's why this luteal phase, it feels like, you know, people might describe it as like, it feels like I'm running through sand. Everything's harder, workouts are harder, you feel mentally dull. And so what is exciting is that with the ingestion of creatine supplementally, that this could actually help stabilize the fluctuations, the, the natural vicissitudes and hormones that a woman experiences during her cycle. Then during perimenopause, things get extra weird, um, where the, the hormones are all over the place for about a decade. And then postmenopausal, we know with estrogen loss there's changes in the mitochondria, are less efficient, recovery slows, strength declines. There's all of these problems, and there's actual direct research in this group. So 7 days of creatine, you see like 11-pound increases in leg press. So real strength changes in just a short period of time. And so not— it really feels that for women, creatine supplementation is something that can benefit you really throughout life and in really important ways. We also know that, for example, bone post-menopause, the— we see women suffer from bone loss more than men, and that osteoclasts, which are cells that break down bone, those become overactive when estrogen is missing. And so this is, you know, there can be like a 10% decrease in bone mass within the first 5 years after menopause. And there's now, there's multiple reasons why creatine could be good. There is direct evidence looking at creatine and the actual bone per cell more and train with more weight, which is one of the greatest stimuli for preserving your muscle. So, it becomes even more important when a woman enters into menopause. And that's one of the reasons why I'm so excited. Also, the changes that women experience on sleep and anxiety, right? There's a GABA-active metabolite of progesterone that when that diminishes can make it really hard for women to sleep, it can cause anxiety. And again, with creatine on board, that might actually help stabilize energy in the prefrontal cortex and also in, you know, kind of specific hemispheres spheres that might then help equal out mood, reduce the feeling of anxiousness, and even stabilize sleep.

Okay. You know, one thing you said about methylation, I was just trying to connect the dots and, and please tell me if it's different than what I'm thinking, but when estrogen is high, we clear estrogen out through phase 3 detoxification. Which requires methylation. So if we're under-methylating, then the creatine can help us in that regard by, you know, kind of filling in that methylation gap that might occur for women, especially around that time of their cycle. 'Cause I know glutathione production increases when estrogen increases. I guess it's the body's way of trying to clear things out through the detox pathways. So would that be a, a correct line of thinking around that?

Yeah, yeah. So if, if up to 70% of your daily methylation needs is going towards creatine, then again, if you're supplementing with it, you're preserving the, the, the rare methyl groups for detoxification processes, neurotransmitter synthesis, phosphatidylcholine production. And so you imagine if you are an undermethylator by genotype, you're at the right phase of— or you're in the wrong phase of a cycle, the disadvantaged one. You could imagine how these types of insufficiencies all contribute to exaggerated expression. And so, that's why I think the field has a lot of excitement due to the very specific challenges that women do face due to the hormonal fluctuations naturally and then of course perimenopause and menopause that this can be contributing extra special benefit. Now, that's not to say that this is not also great for men. It's just that due to these specific hormonal changes in women, this could be even have, have all the benefits in men plus.

Right. And, you know, historically it's been mostly men that have been taking this, you know, for against performance gains in the gym. And now if there's something that can benefit women, it sounds like even, you know, sign quite significantly more than men just given the shifts that women's bodies go through around that time.

Yeah. And you know, there's also dietary gaps. So women will produce about 80% of the creatine that men will. So less, there's a 20% difference there, but they lose less. So there's less turnover and, but they also have less muscle mass. And so And they're also more likely to be vegetarian and vegan and not consume as much meat. So the dietary gap is, is perhaps a greater need for, for women, even if they're not, you know, outright vegetarian or vegan. So just another reason for the value of supplemental creatine.

Okay. Now Qualia makes a wonderful creatine. I'd, I'd love for you to share a little bit more about that and I know there's specific compounds in there. You mentioned the salt. I believe there's a, a form of magnesium that's in there as well. So tell us a little bit more about the formulation and, and we'd love to have people try it as well.

Yeah, so the thought process behind creating this product was one, creatine is an awesome product and we wanted to enter into the space because we're not just a formulation company, but we do a lot of education too. And through education, you can now affect more people to— in a way where they have an expanded appreciation of its value and then get more people to benefit from what it can do. And so we almost felt of it as like a responsibility. We start all of our formulation initiatives saying, all right, well, if— how would we optimize this? What would you do if you could optimize it? And so we use— it's really just— there's just 3 ingredients in our product. The majority of the creatine is called Opti-Creatine, which is creatine monohydrate, but it's micronized. So creatine monohydrate is pretty gritty. It's like they're grains of salt or sand. And so, anybody who's taken creatine, I'm sure you know this, you put it in your cup, you drink it, and there's a lot left on the cup or the glass. And you have to rinse it a couple of times to get it in. And that might be where people like, "I don't really like how creatine tastes." It has probably to do less with taste and more with texture that it is gritty. Micronized creatine takes creatine monohydrate and it pulverizes it So it dissolves much better. And while that doesn't sound super significant, it can be if it leads to better compliance, because that's what we're after. Like, this is something that you take now every day for the rest of your life, very possibly. The other ingredients that are in there is Creatine Magna Power, which is 40 milligrams of magnesium that is chelated. So it's elemental magnesium that is chelated to creatine. And the reason we thought that to be interesting is because a lot of people don't know this, but about 90 to 95% of your ATP in your cells is not free ATP. It's bound to magnesium to form the magnesium, magnesium ATP complex. And so in fact, the reason it does this is because ATP by itself carries a very heavy negative charge and it makes it hard for enzymes to handle. And so what magnesium does is it adds this slight positive charge to the phosphates and that then makes it a lot— it makes it usable. So your ATP really becomes usable when it's bound to magnesium in your cells. Think of, think of that, that 50% of the United States is insufficient. Doesn't mean deficient, but insufficient. They're not getting the recommended amount. And we saw this as an opportunity if we're supporting the energy system that we can then combine these two in this magnesium creatine combo to then help with energy production on, on that plane as well. And then the last part is the sea salt. And so the creatine transporter, um, requires some chloride and some sodium. That's exactly what sea salt is. So there's about 250 milligrams of sea salt in there, so it's 100 milligrams of sodium and 150 of chloride. And both of those are involved in not only getting creatine into the body but also getting it into cells. And so that was what we felt was a reasonable, useful step in optimizing, particularly, potentially, particularly in the brain, but really possibly all cells. So that's, that was our formulation. So tastes better, um, supporting energy in a variety of ways, getting better, getting into cells better. And, uh, and we were really proud of that formula. So we're like, okay, let's bring this to market.

Wonderful.

Yeah.

Thank you. Thank you.

Yeah.

So much, so much about this one molecule and I, I know we can probably talk for another 2 hours about it and yeah, we'll have to do a part 2. I know there's a lot of emerging research and yeah, and new use cases for creatine. So, you know, if our schedules align again, maybe we'll do a part 2 in the near future as more information becomes available because, you know, something that people can take every day, something that's very accessible, affordable, very safe. It's, there's not very many compounds that have been around this long, studied this much that can have such tremendous benefits across, you know, different sexes, different age groups.

Yeah.

Starting at, you know, a pretty young age too. So thank you for all this insight that you've offered today and absolutely we'll be sure to share the link to where people can learn more about the Qualia, Qualia Creatine and try it out for themselves. I think that's a great place for any practitioners to start or somebody who's new to creatine, take a good quality product, right? It's going into your body and you want, you wanna take a product that is evidence-based and gives you the maximum advantage and benefit from the very product that you're taking. So thank you again, Dan. This has been very enlightening. I'm gonna have to go back and watch this again. I was trying to take notes as you were speaking and there's just so many golden nuggets here. So thank you once again.

Thank you so much, Sachin, for having me back on. I, I think you're right. I think in a year we could have an equally long discussion and not cover anything that we covered this time, just based off of topics we didn't discuss, but also especially work that is going to come out between now and then. And so it is definitely a topic to continue watching, but regardless of the topic or the time. Uh, I'd always look forward to another discussion with you. So thanks for having me on.

Thank you. Well, have a wonderful, uh, amazing day. And to all of our listeners, have an amazing, healthy, whole, and happy day. Bye for now.