Decoding Creatine: Muscle, Brain & Myths

The last time I was at the airport, I nearly missed my flight. Security pulled me over and did a full body scan after discovering a suspicious white powder in my backpack. This powder? Creatine. Yes, creatine, one of the most extensively studied performance-enhancing supplements in the world of exercise science and nutrition. And finally, after two doctorates, I'm finally catching up. Despite its popularity, few people truly understand how creatine works, what it's range of effects are. And in this video, I'm going to start to break it down for you. I'm going to explain what creatine is, how it enhances muscle performance, its emerging benefits for the brain, and how to use it— protocols for maximum benefit with minimal side effects. Let's dig in. Significantly increased lean body mass by 2.5 pounds. Makes it easier for your muscles to grow. Supports energy metabolism, muscle development. It makes sense that creatine would improve mental health. Consistently enhanced muscle gain, and even promoted fat loss, creatine also improves memory, particularly in older adults, and may even help counteract the negative metabolic and cognitive effects of sleep deprivation. So in the rest of this video, I'm gonna describe to you what creatine is, how it actually works in the body. Then we're gonna blaze through its benefits, citing human-controlled trials. We're gonna talk about muscle health, hypertrophy, and then move from brawn to brain to discuss its impacts on cognition, mental health, sleep, and so on. But before we dig in for real, I just want to mention more details can be found in the associated newsletter linked below in the caption. I keep extra details there so this video can remain as streamlined as possible to respect your time, and because the letter can serve as a growing living document. So if an amazing creatine paper drops tomorrow, I can just add it to the letter and you can find that information there. With that, Let's really start. What is creatine? Creatine is a naturally occurring compound made up of 3 amino acids: arginine, glycine, and methionine. The synthesis pathway is here, although you don't need to memorize it. Your body produces creatine in small amounts, and you also get some from food, especially meat and fish. However, supplementation allows you to saturate your tissues, starting with your muscles, with creatine to a degree that has measurable performance effects. Which we will get into citing the human controlled trial literature. Anyway, creatine, it's primarily stored in muscle tissue where it plays critical roles in cellular energy metabolism. Its main function is to help rapidly regenerate the energy currency of the cell. You might know it, ATP, adenosine triphosphate. So let's zoom in on creatine's role as an energy carrier. When you engage in intense physical activity, like sprinting, your muscles burn through ATP in a few seconds. But you can sprint for more than a few seconds, right? That's in part because once ATP is used, it becomes ADP—it loses a phosphate—and the cell needs a way to quickly replenish the ATP stores. So that's where phosphocreatine comes in. Phosphocreatine is simply creatine bonded to a phosphate group. And this phosphate group can be rapidly donated to ADP to regenerate the ATP pool, effectively restoring your energy supply Nearly instantly. Even glycolysis, if you know what that is, is slow by comparison. So by supplementing with creatine, you can increase your phosphocreatine stores. This effectively boosts your energy buffering system. And this leads to greater performance in high-intensity, short-duration efforts and quicker recovery between bursts of activity. But that's just creatine biochemistry 101, and I know you can handle more. So let's progressively overload your brain with some more information. Creatine's role in muscle physiology doesn't stop with this energy metabolism function. There are other mechanisms through which creatine can support muscle growth, also known as hypertrophy. So let's go through a few. You may have heard of this one. Creatine draws water into muscle cells. This increases intracellular hydration. And this cell swelling is more than just cosmetic. It acts as a signal that stimulates protein synthesis, and over time, this contributes to an increase in muscle mass. Now, here's where things get more complex, so bear with me, but I also think it gets more interesting, and you probably won't have heard this information elsewhere. When muscle fibers grow, they require additional nuclei to manage increased protein production. So, unlike most cells which contain only one nucleus, muscle cells are multinucleated—multiple nuclei—and these extra nuclei come from what are called satellite cells, a type of muscle stem cell that kind of sits around the muscle fiber. You can actually see the muscle cells here. Dark purple are nuclei dots. And the main point here is that multiple nuclei per muscle cell— there are multiple nuclei per muscle cell. Sorry, having trouble with English this morning. These come from satellite cells. So combined with resistance training, creatine stimulates satellite cell activity, which helps supply growing muscle fibers I don't know why I'm using my hands so much. "Zbyszczę naje dobre międa!" But it helps supply growing muscle fibers with the extra nuclei they need to expand. So in simple terms, creatine makes it easier for your muscles to grow by helping recruit and integrate new cellular command centers, nuclei, into the muscle fibers. Does that make sense? But we're not done with the how-to. Creatine alters gene expression and protein synthesis. In fact, creatine may enhance the expression of genes involved in muscle contractions, such as those coding for myosin heavy chain proteins. These are the workhorses of muscular force production, and by upregulating the genes that code for these proteins, creatine can help improve both muscle strength and quality over time. So stepping back, in summary, creatine is an energy-carrying molecule. It's synthesized from 3 amino acids in your body, But for optimal performance and muscle growth, dietary intake, either through food and/or supplementation, is recommended. Creatine-rich foods— naturally creatine-rich foods include meat and fish, especially fish. But supplementation can significantly enhance its benefits by saturating your muscles and, as we'll find out, your brain too. So again, to review, creatine supports energy metabolism and muscle development through serving as a rapid energy buffer for ATP, increasing muscle self-hydration, stimulating muscle stem cells, these satellite cells, to donate nuclei to growing muscle and enhancing the expression of key proteins involved in muscle contraction. There are more mechanisms, but I wanted to highlight those four. So now let's dive into some of the human clinical trial evidence, starting with a recent 2024 meta-analysis of randomized controlled trials published in the Journal of Strength and Conditioning Research. This study pooled data from parallel-arm randomized controlled trials that examined the effects of full-body resistance training with and without creatine supplementation. There were two major findings. First, compared to resistance training alone, creatine supplementation significantly increased lean body mass by 2.5 pounds, basically 2.5 pounds of muscle, or 1.14 kilograms if you're not in the United States. And two, creatine also led to a reduction in body fat, a decrease in body fat percent by 0. 8.88%, which is not nothing, and a decrease in total fat mass by 1.6 pounds. And of note, in this meta-analysis, co-ingestion of carbs did not further enhance muscle-building effects of creatine. So simply put, creatine supplementation consistently enhanced muscle gain and even promoted fat loss beyond resistance training alone. No extra carbs required. Other meta-analyses and randomized controlled trials have shown similar benefits. So consistently, creatine supplementation when combined with resistance training improves muscle strength strength and growth. But now, the big question: how do you use and dose creatine for muscular health? Here's the protocol. First, in general, an effective dose for muscular health is about 5 to 7 grams per day or more. For the best results, you want to stick with micronized creatine monohydrate. This is the most researched, well-tolerated, and reliable form—micronized creatine monohydrate. You can also engage in an optional loading phase. So if you're looking to maximize the benefits of creatine quickly, the most effective approach is to begin with this loading phase followed by a maintenance phase. So during the loading phase, you take 20 grams of creatine monohydrate daily for 5 to 7 days. You divide this 20 grams into 4 daily doses of 5 grams. Splitting the doses throughout the day and consuming creatine with food helps improve absorption and reduce the risk of gastrointestinal discomfort. 5 grams in a setting is probably fine. 20 grams, you're going to get some GI upset. Then after the loading phase, you can transition to a maintenance dose of approximately 5 grams per day taken once daily. Timing is flexible, but taking creatine with a meal generally is recommended to further minimize gastrointestinal issues. Okey-dokey. Now that we've gone over some of the science, although there's a lot more in store for you, I know a lot of you are probably wondering what specific creatine brand I use and what you might want to consider buying. Well, when it comes to reputation, quality, and rigorous third-party testing, you really can't go wrong with Momentous creatine monohydrate. This is the same type of creatine used in thousands of randomized controlled trials and by Olympic-level athletes, and it's extensively tested for things like heavy metals, banned substances, anything you don't want in your food supplements. And for what it's worth, you can rest assured this plug is free of influence from Big Creatine, which now that I say it has a funny double meaning, but specifically all the information you have received and will receive in the rest of this video was composed and released at staycuriousmetabolism.com in my newsletter. It was only thereafter that we connected with Momentous since it's what I happen to have been using and what I found vetted through my 100 Health app, so I wanted to get a discount code to share for you in case you wanted to try it. My personal preference is their pure, unflavored, no dyes and sweeteners micronized creatine monohydrate, but they also offer other delivery options depending on your preferences, including flavored versions and even lemon-lime creatine chews if that's more your thing. Usually I have this with food, like 5 grams of the creatine monohydrate mixed into a Greek yogurt after my workouts, maybe a little bit of salt.

I also love making creatine ice cream, and I'll, uh, drop the recipe below.

This micronized form and consuming it with food optimizes GI tolerance even for those with the most sensitive stomachs. So if you want to try it yourself, you can use the code STAYCURIOUS for up to 35% off your first order at livemomentous.com. Or you can just check the link below. Anyway, back to the main video. Now, let's move beyond muscles to the brain. Creatine also improves memory, particularly in older adults, as has been shown in randomized controlled trials. This makes sense because phosphocreatine is also an important energy molecule in the brain, just like it is in the muscles. Just to give you a flavor of the data, in one randomized controlled trial, older adults aged 68 to 85 were randomized to receive 20 grams of creatine daily— we'll get to why 20 grams in a minute— split into 4 groups 4 doses, or placebo control, and the results showed a significant positive effect of creatine on memory tasks. There even appear to be benefits in neurodegenerative diseases like Alzheimer's disease. You can find more details in the letter on that, but just briefly, as a PhD in neurodegenerative diseases by trade—Alzheimer's and Parkinson's—if I needed to compile a list of 3 supplements to take for Alzheimer's prevention, they might be low-dose lithium orotate—see this video for more—high-dose omega-3s—at least 2 grams of EPA and DHA per day—and high-dose creatine—at 10 to 20 grams per day. Now, I say high-dose creatine because while the benefits on muscles are seen at lower doses—say 5 grams per day—it's typically thought that the brain responds best to higher doses—say 10 to 20 grams, depending on your body size—since muscle stores need to be saturated first before creatine can effectively spill over and be taken up by the brain. There's also early evidence suggesting that creatine can benefit cognition and mood-related symptoms in conditions like depression, bipolar disorder, and other mental health disorders. The initial data are promising. For example, in one double-blind randomized placebo-controlled trial, creatine supplementation combined with cognitive behavioral therapy, a tried and true form of therapy, significantly improved depression compared to CBT alone. Again, this makes sense biologically. As one review article put it, and I'll just quote them, "Impaired brain energy metabolism and alterations in neuronal plasticity are among the leading hypotheses in the pathogenesis—the origins—of psychiatric disorders." So logic would suggest that interventions like creatine that modulate energetic, oxidative, and neurotrophic parameters would improve therapeutic efficacy in psychiatric patients. So TL;DR, it makes sense that creatine would improve mental health. And creatine may also help offset some of the metabolic and cognitive disturbances caused by sleep deprivation. For example, in one controlled study, participants were sleep deprived for 21 hours and assessed through a battery of cognitive tests and brain scans. The intervention in this case was a single dose of creatine given at 0.35 grams per kilogram of body weight. It's a pretty high dose, that's about 25 grams for a 70-kilogram person. And they found "Creatine supplementation improved cognitive performance compared to the control and partially reversed the metabolic dysfunction associated with nearly 24 hours of sleep deprivation." So in summary, creatine appears to enhance cognition, particularly in older adults, and may improve memory even in Alzheimer's disease. It shows promise for supporting mental health conditions such as depression and may even help counteract the negative metabolic and cognitive effects of sleep deprivation. That's not to say you should get sleep deprived and can fully offset it, but in a pinch. Now, to achieve these brain-related benefits, higher doses of creatine are generally required, typically between 10 and 20 grams per day. These doses are best tolerated when divided into 3 or 4 smaller servings of 5 grams per day or less, as said earlier, taken with food throughout the day. Now, we're getting to the end, but I want to clear up some common myths and misconceptions about creatine. Myth number one: Myth 1: Creatine causes hair loss. One frequent concern is that creatine causes hair loss. This is a myth, as demonstrated by my caterpillar eyebrows. But in terms of controlled trial data, a recent 2025 RCT involving 45 men assigned participants to either a creatine group, 5 grams per day, or a placebo control, and the study found no negative effects on hair follicle health or hair growth. Myth busted. Creatine does not harm your hair. Myth 2: Creatine harms kidneys. This is another myth. And while creatine supplementation can increase levels of a marker called creatinine, kind of like creatine with an extra I-N, this does not reflect actual kidney damage. And as a note, increased muscle mass can actually naturally raise creatinine levels. There's a fun fact for you in terms of interpreting your own health data. But there are no human data showing that creatine harms kidneys in healthy individuals. Moving on, Myth 3: Creatine is a steroid. Creatine is not a steroid. That was easy. Hasta la vista, baby. Myth 4: You need to cycle creatine. There is no evidence that cycling on and off creatine provides any particular benefits for health, safety, and effectiveness. Continued use of creatine at standard doses is safe as far as I'm aware. I do drop a few more myths in the letter below. But those are the big 4 I wanted to hit. So that's more or less what I have for you. In review, creatine is one of those rare supplements that actually lives up to its hype. It's safe, affordable, and backed by decades of research. Not just for muscle performance, but increasingly for brain health and full body health as well. 5 grams of micronized creatine is a good starting dose. Best consumed with food, and if you go to higher doses for brain health, split your doses up across the day. Now, let me know what questions you still have, what I missed, and how you use creatine. And remember, don't bring it in a little plastic baggie to the airport. Stay curious. Thanks for listening.

Some of you were asking for a little behind the scenes on video production, so I thought I may as well oblige. I work at weird hours. Right now, it's just before 5 in the morning. This is the view from my apartment. In Boston. So I'm gonna do some intros right now. So I put on my recording shirt, this black sweater. I got, uh, my ring light here for behind me. It helps with lighting, and that'll be the studio light I turn on. Sometimes I use a teleprompter for the intro, sometimes I don't, but I'll be seated right there. Afterwards I'll stand up, and you can see that's where I'll be standing. I've got my props. I'm gonna be doing the Creatine video, so here's my little prop of the white baggie for the opening hook, and then social proof for my sardine fast video. I'm in the middle of that right now, having a lot of fun. So, uh, yeah, this is what I do.