106: Creatine Demystified: Brain, Muscle & Metabolic Benefits with Dr. Ben Bikman

Think creatine's just for bodybuilders? Think again. Creatine does way more than just help us lifting weights. It helps your brain, supports heart health, improves blood sugar control and fights muscle loss, especially as you age. Studies show it boosts energy in your cells, improves recovery, and may even protect against insulin resistance. And no, it doesn't damage your kidneys. That's a myth. Decades of research prove it's safe for healthy people. This is lecture 106 of the Metabolic Classroom. Looking to improve your own metabolic health? Visit insuliniq.com for courses, coaching, consultations and a 10 day free community membership trial to dive deep into the science behind metabolic health. Become an insider@Benbickman.com, where you'll enjoy my exclusive content ad, free podcasts, livestream, Q and A Access and more. Welcome to the Metabolic Classroom. I'm Benjamin Bickman, a biomedical scientist and professor of cell biology. Today we're learning about one of the most fascinating molecules in human physiology. Creatine. You have most certainly heard of creatine, but this molecule is so much more than a gym bro supplement. It's actually a critical player in energy metabolism. Even now, as you're sitting and listening to this, with benefits spanning muscle power, brain function, and even a little bit of metabolic health. Today we're going to unpack the biochemistry of creatine, explore how you can get it, and review some of the robust evidence that has been shown for decades behind its many effects. I also want to highlight some of the lesser known benefits that you don't hear about. And then I want to debunk a common myth specifically centered around the kidneys. So if you need to grab your notebook, although there won't be a pop quiz, but let's get started. All right, let's in fact start with the basics. What is creatine and why does it matter? As I mentioned a moment ago, you are actually even now benefiting from the presence of creatine in your body. It is a naturally occurring compound found in cells throughout the body, creating chemically when you make it, it's derived from three amino acids, arginine, glycine and methionine. And your body will make it about a couple grams a day, mostly in the liver and in the kidneys. But you can also get it from food and supplements, which we'll cover soon. But here's where it gets interesting. It's that creatine's primary role is as a rapid response energy buffer in cells, especially in cells with high energy demands like the exercising mus, even the neurons of the thinking brain. To understand this, we need to talk about ATP, which stands for adenosine triphosphate. It is the cell's energy currency. Now, we often, we academics, we professors, like to refer to ATP as an energy currency because it is the money or the currency with which a cell will purchase something to get done. It's, it is the medium of exchange where when your muscles const or your brain fires a neuron, ATP will break down into adp, adenosine diphosphate. And that bond that breaks is considered a high energy bond. And then some other reaction can take advantage of that breaking of the bond. But as we break those bonds, we can start to get low on ATP. ATP stores within a cell are limited, and during something like, say, intense activity, like a sprint, heavy lift, or even intense thinking, you may deplete your ATP. This is where we have an intracellular rescuer, creatine phosphate. Once it's phosphorylated, the molecule creatine becomes creatine phosphate. And creatine phosphate is a donor. It is just standing by, ready to donate its phosphate to adp, which instantly generates ATP again. So we had an ATP molecule break down and give its energy, if you will, to some other reaction, like contracting a muscle, giving us then ADP. The triphosphate turned into the diphosphate, 3 to 2. And then creatine phosphate says to the diphosphate, hey, you're missing a phosphate. I have one that you can take. And gives up its own phosphate. This process is catalyzed by an enzyme called creatine kinase. Now remember, anytime you hear a molecule that ends with the ase ending, ASE is going to be an enzyme. And creatine kinase is lightning fast, and it allows the cells to keep producing this ATP during these very short, intense bursts. So think of creatine phosphate as a backup battery that kicks in when the main power grid ATP in this case, starts to run low. Now, creatine does more, and we're going to dive into its other effects later. But it's going to include some surprising things that have to do with cell membranes and oxidative stress. But for now, know that creatine is a versatile molecule, explaining its abundance in tissues that demand quick energy, like your biceps or your brain. But here's the deal. While your body makes some creatine and you can get it from diet, many people, especially athletes, those avoiding meat, or even those pushing their mental limits, may not have optimal levels. And that brings us to our next topic, where can you get creatine? There are three main ways your body makes it, or you eat it, or you supplement it. Now, those last two start to spill into each other a little bit, but let me unpack them. So as we get into the endogenous first, that is the ability of the body to make its own creatine. I mentioned this earlier, but our liver and kidneys will churn out about 1 to 2 grams of creatine daily, making it from the amino acids that I mentioned, arginine, glycine and methionine. This keeps most people ticking, but athletes or individuals that are uniquely nutritionally stressed or cognitively compromised, as we'll see, might need a little more. Low protein intake can also limit production. Now, second, let's speak about the dietary sources. Creatine is in animal foods. Red meat, fish and poultry. In particular, a pound of beef or salmon will give about 1 to 2 grams, the amount that the body would make on its own. Now, of course, vegetarians and vegans are going to miss out on this, and studies show that their muscle creatine can be about 20 to 30% lower, which absolutely can impact physical performance and even cognition. All right, now, beyond our ability to make it or eating the creatine from other animals that have made it, this is where the supplements come in and it's where things get a little interesting. Now, the king of all creatine supplements is creatine monohydrate. Chances are, if you have any form of creatine in your supplement cabinet, this is going to be the one. It's very cheap, it's very effective, and it is backed by decades of research. Now, standard dosing for creatine monohydrate is 3 to 5 grams daily, although very often it will include what's called a loading phase of up to 20 grams per day. Split up maybe over a couple doses, and they'll do that for a few days and then go to that lower, you know, maintaining dose, people will call it. However, as I'll get to in a bit, there is a trend of high single doses, up to 20 or 30 grams at one time. Some could do this for faster muscle saturation, just really getting that creatine into the muscle where the athlete wants it. But recent interest is actually more focused on the brain, especially for sleep deprivation. A paper just published last year in 2024 in the journal Scientific Reports found a single dose of about 20 to 30 grams. To be specific, it was 0.35 grams per kilogram. It boosted memory and processing speed in sleep deprived individuals. And the effects kicked in at about three hours and they even lasted for up to nine hours in this sleep deprived state. And this was all compared to a placebo. So it was a very well controlled trial. And they used the king of the creatine supplements, creatine monohydrate. But there are other forms that exist and they vary in cost. They also vary in efficacy, maybe being a little better or worse. And they also vary in how much evidence has been shown to support its use. Again, the reason I'm talking about creatine hydrate monohydrate is because that's the one that the overwhelming amount of evidence is, has been, has been based on. All right, now let's just mention the other ones though, just so you're aware. One is creatine hydrochloride, or sometimes just abbreviated as creatine HCl. It is more soluble, so you're going to digest it better. If you're taking a high dose of creatine monohydrate, it can upset your tummy and so you can use much lower doses of just about 1 to 2 grams. And it's considered to be worth multiples of that in creatine monohydrate because you absorb it so well. However, the evidence is a little fickle, not really showing too much of an advantage over creatine monohydrate, but it is much more expensive. There's also something called the creatine ethyl ester, which claims better absorption than monohydrate, but not as much evidence on it. There's a buffered creatine, which also is supposedly better absorbed with less GI distress. Then there's another form of creatine monohydrate called just micronized creatine, and it has just finer or smaller monohydrate particles, mixes a little better. When you put it in water, you're not going to get that little cloudy settling potential at the bottom. And thus it could have improved stomach issues where it's not going to upset your stomach. All right, now let's get to the meat of the matter. Now that you know where it can come from, what does creatine actually do? The research is in fact quite extensive. So I had to, for the sake of this brief mini lecture, trim it down to the most important and most validated things. But of course, the biggest of all of these is muscle power recovery, even some neurological outcomes, as we'll get to in just a moment. But let's start with the big one, which is muscle power and performance. Creatine is the gold standard for high intensity short duration activities. And creatine has been shown to increase strength by up to about 10% and power output by potentially up to 15%. Power being a function of physical measurement of just the strength over time, something like jumping or sprinting. And that is all versus placebo. So it's been done in well controlled trials. Now that is huge for elite and competitive weightlifting and sprinting or similarly aggressive activities. And of course it works by boosting ATP regeneration, allowing harder, longer efforts and enhancing even the size of muscle and protein synthesis. A 1999 study showed that creatine users gained 2 to 4 pounds more of lean mass than placebo after 12 weeks of resistance training. Now, I should add that part of that is going to be water. That where creatine gets saturated into a muscle, water will also follow that. Now what about recovery? I'd mentioned that because creatine also aids recovery. Intense exercise causes muscle damage and inflammation. And creatine can help. A 2004 report found creatine reduced muscle damage markers by 20 to 40% after the most damaging of all exercises, eccentric exercise. So that would be like the negative, the so called negative of a movement which can tear the muscle more than the concentric or the positive movement. It also can speed glycogen resynthesis so muscles refuel faster. All of this is just to say that there's the potential for less soreness and you being able to recover and be more ready for your next workout. Now, I've alluded to the brain and there are indeed benefits. Creatine is not just for muscles, it is a brain booster. And our brain uses about 20% of our body's ATP and neurons rely on creatine phosphate for that rapid energy regeneration, just getting ATP up there whenever it needs it. In fact, creatine improves short term memory and reasoning in healthy adults, especially under stress or sleep deprivation. This is particularly true for people who may be creatine deficient. A 2007 study showed vegetarians that were just given 5 grams of creatine daily, which is pretty modest for six weeks, had better working memory and processing speed. For Alzheimer's, the evidence is early but quite promising. Alzheimer's involves, of course, as you know, impaired brain energy metabolism. And creatine can help. This is a concept I've described previously. Looking at the energetic origin of Alzheimer's disease and challenging the plaque based origin of Alzheimer's disease. And let me just reiterate something I spent an entire episode previously discussing, which is Alzheimer's disease is Not a result of plaques in the brain. The plaques in the brain are simply coincident and probably themselves a manifestation of metabolic problems. Alzheimer's disease is an. Is a metabolic problem. It is the brain going hungry. So what if we can restore that energy? And that's where we have some evidence, including a 2011 study that showed creatine slowed cognitive decline in early stage Alzheimer's. Now, that is an active area of research, so it wouldn't surprise me if we revisited this topic. In a year or two, there are going to be even more studies that we could mention. But creatine has also been shown to have potential in Parkinson's and traumatic brain injury, protecting neurons and reducing damage. So people coming in having had some impact or hit to the head, traumatic brain injury, tbi, it's not uncommon for them to get infused a cocktail of things like ketones and lactate in order to try to ensure that the brain has abundant energy. Well, wouldn't you know it, Creatine also makes the cut in these cognitive cocktails. There's also a little evidence to suggest that creatine may even help reduce depression, which, again, looking at the energetic origins of memory and mood problems, it's no surprising. It's no surprise that if you can increase creatine, you increase creatine phosphate, which enhances your ability to regenerate ATP in the brain and these neurons that are perhaps going hungry, and you reduce the risk of the problem. Okay, now I know what you're thinking. Since this is the metabolic classroom, you've been waiting to talk about whole body metabolism and insulin resistance. Well, unfortunately, there isn't too much on that topic. But what has been done is worth mentioning. One study showed creatine can reduce blood glucose spikes after or in the midst of a glucose tolerance test, providing some pretty strong evidence of improved glycemic control. Indeed, there's a mechanism that has been revealed, which is that creatine supplementation can enhance GLUT4 translocation. Now, you'll recall from earlier discussions, because you're such clever students, that when the muscle takes in glucose, it does so by opening this transporter that is called the glucose transporter 4 or GLUT 4. Normally, that's only going to happen when insulin either comes and knocks on that door of the cell or the muscle cell is contracting and relaxing, like during exercise. But creatine phosphate enhances that GLUT4 movement, which in turn enhances the ability of the muscle to pull in glucose, which in turn can help result in better blood glucose control. But there's even evidence to suggest that creatine supplementation, in the absence of any other changes, in other words, no other lifestyle habits, can improve glycemic control in people with type 2 diabetes. So from the athlete to the sedentary type 2 diabetic, each can justify their supplementing with creatine and claim various benefits. Now, speaking of benefits, before we debunk a common creatine myth, I want to take a little moment to teach you about some of the lesser known benefits that most people, even some of these fitness supplement enthusiasts, might not know about. Because beyond powering ATP regeneration, creatine has remarkable effects on cellular health. That could explain why it's so promising for myriad problems, including things like Alzheimer's disease. These include cell membranes, oxidative stress, and even some influencing of gene expression, as you'll see. All right, so first, let's talk about membrane stabilization. Creatine, especially in its creatine phosphate form, actually supports a type of lipid called phospholipids in the cell membrane. So phospholipids are one of the main components of the fatty parts of the membrane. And when the phospholipids are supported, it makes the membranes more robust. This is like reinforcing the walls of a fortress. It's protecting the muscle and brain cells and any other cells from damage during intense activity or stress, like a heavy deadlift or some sort of neurological crisis or early cognitive decline. A 2000 in the year 2000 published review in Physiological Reviews showed creatine integrates into lipid bilayers, which is the structure of the cell membrane, reducing the leakage of harmful ions and preserving the integrity of the cell. So this is something that could really be a game changer for neurons in Alzheimer's, where membrane damage can very much disrupt signaling along the membrane of the neuron. Now, second I mentioned there's the ability of creatine to reduce oxidative stress. Oxidative stress happens when reactive oxygen species are produced and then just begin bouncing around like a harmful pool ball, banging into various molecules, proteins, lipids, DNA, et cetera. In this regard, creatine acts a little bit like a shield, indirectly boosting antioxidant enzymes like a big one called superoxide dismutase, and maybe even directly mopping up some of these rogue molecules. In fact, creatine supplementation was shown to cut oxidative damage in muscle and brain cells in a 2002 study, showed it scavenges these superoxide radicals. And the superoxide radical is One of the, it's essentially the first product of what we call reactive oxygen species. There's a series of events where one reactive oxygen species becomes another and then becomes another. When we talk about the superoxide radical, we're talking about it at the very beginning. This is huge for Alzheimer's where oxidative stress has been shown to really be one of the ravaging, having a ravaging role in the neuron. By stabilizing mitochondria and curbing these harmful molecules, creatine could protect the brain cells directly, tying it into some of the benefits we've discussed. Now third gene expression. Creatine doesn't just fuel muscles, it can flip genetic switches for growth. It has been shown to upregulate genes like IGF1 and some myogenic or muscle building factors which can drive muscle protein synthesis. Creatine combined with resistance training has been shown boost IGF one expression which absolutely leads to bigger, stronger muscles. That's one of the things the bodybuilders want to take advantage of. It also does so probably by activating some of these genes called MYOD and myogenin which are key players in muscle repair. Now of course this is not just for bodybuilders. It can absolutely be a tool that is leveraged by older adults who want to fight sarcopenia or muscle wasting and even support neural repair in neurodegenerative diseases by enhancing some of these energy dependent signaling pathways. So why does any of this matter? These effects like stronger membranes, less, less oxidative damage and these genetic boosts, if you will really do make creatine a multi tool for the cell, a workhorse that's involved in multiple beneficial aspects of the cell. And then for Alzheimer's, a topic that I just can't help but stay close to in this regard, that could stabilize these neurons, reduce the oxidative stress and really support myriad repairing processes. This is the kind of evidence that is generally overlooked when it comes to creatine. It's not just a performance enhancer and it's not just focused on ATP. It is a cellular protector with a pretty far reaching potential. Now let's keep that in mind as we tackle the myth that scares people away from creatine. This is a myth that just won't die and to this day continues to persist. That is the myth that creatine damages your kidneys. If you've mentioned creatine to perhaps a conventional doctor or a friend, you've probably heard this before. And let's clear the air with some science the concern comes from confusion about creatinine. Not creatine, but creatinine with that extra in creatinine. Creatinine is a waste product form formed when creatine from muscles or just supplements is used up. As your muscles tap creatine phosphate or any cell to regenerate ATP, some of the creatine will naturally be degraded into creatinine. And creatinine is then a product to just be eliminated. It's used, it's, it's the evidence that creatine has served its purpose. And so the kidneys will then filter and excrete the creatine product, creatinine, into the urine to be dumped from the body. Now it's no surprise if you are loading your body with creatine supplement. Like through supplementation, you're going to have a lot more creatine in the body, which also means you're going to be getting rid of more creatine. So blood and urine creatinine levels should absolutely be expected to go up. Now unfortunately, a blood test might flag this as high, sparking some concern of kidney damage. But here's the truth. Elevated creatinine from creatine is a normal sign of metabolism. It's not a sign of harm. Now creatinine is commonly used as a signal where the physician wants to get an idea of how the kidneys are working. What they would need to know is that if a person is taking creatine as a supplement, boosting their levels to much higher, to a higher level, it's no surprise that the creatinine excretion is going to be naturally higher. It's like seeing more exhaust from a revving car engine. It's just a byproduct. It's not a sign of a broken motor. If you see more exhaust coming, you're revving the engine more. Now decades of research backed this up. A 2008 study followed athletes taking up to 20 grams daily for five years. And there were no changes in kidney function like the most famous being glomerular filtration rate or gfr. A second review article confirmed creatine safety for healthy kidneys, even with very long term use. Now of course, if you have a pre existing kidney condition, by all means, just check in with your clinician. Remember, I'm just your friendly neighborhood scientist, I'm not your doctor. But for healthy folks, the data is quite clear. Creatine is safe at even surprisingly high doses. Now, what could you do if you're active you're building muscle or you want a sharper brain, you could consider creatine and my general advice is a few points. First, I'd just suggest sticking with the most tested and cheapest, which is creatine monohydrate, standard or micronized. It is proven, it is affordable, it is effective. But of course stay hydrated. Creatine will pull water into muscles, so make sure that you're really staying hydrated as you are increasing your use of creatine. And then if you're looking for specific gains, be patient and expect the gains to be somewhat subtle. It'll take some time and then you're going to especially with things like cognitive improvements, you might not be very cognitive declined in failing cognitively in the first place. So just be reasonable in what you expect the results to be like. Now, for those of you who may be deliberately avoiding meat, vegetarians and vegans, I would suggest that creatine is extraordinarily relevant. Your levels very likely may be a little low depending on what your demands are in your body, and creatine supplementation could be an absolute game changer from biceps or brains like I mentioned earlier. Now beyond that for older adults, I'm also incredibly warm when it comes to creatine use. It could be very helpful not only for muscle to help reduce muscle loss, but even brain and bone and just overall health of your cells. High doses for sleep deprivation is one of the areas that is very promising and it's something that I find quite exciting as a person who chronically struggles with poor sleep. And decades of data have just really shown that creatine is a very safe, very effective supplement. That's it for today's metabolic classroom. Creatine is a remarkable molecule, bridging a lot of things like muscle and brain and metabolism and even cellular protection. I hope you feel like you know a lot more about this topic than you did a few minutes ago. And until next time, remember, more knowledge, better health Looking to improve your own metabolic health? Visit insuliniq.com for courses, coaching, consultations and a 10 day free community membership trial to dive deep into the science behind metabolic health. Become an insider@Benbickman.com where you'll enjoy my exclusive content ad, free podcasts, live stream Q and A access and more.