Creatine: Energy balance and healthy aging
Creatine is one of the most talked-about supplements in health and wellness, but what is it actually doing in the body — and why does it matter for mitochondria? In this episode, Georgia Truman breaks down creatine from first principles, unpacking the phosphocreatine system, its relationship to ATP production, and why it becomes increasingly important as we age.
How the phosphocreatine system recycles ATP and takes pressure off the mitochondria
Why muscle loss with age means losing creatine storage capacity too
The three mechanisms behind creatine's muscle-building effects, including cell swelling and satellite cell recruitment
What the research says about creatine and cognition, especially under sleep deprivation and stress
Why creatine may matter even more for women, thanks to estrogen's role in the phosphocreatine pathway
Practical dosing strategies — including loading protocols and pairing creatine with resistance training
Whether you're already taking creatine or just curious about the mitochondrial science behind it, this episode goes beyond the bodybuilding stereotype to show why creatine is a genuine bioenergetic tool for healthy aging.
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Hi, welcome back to the Mitopod. My name is Georgia Truman, and I'm the Scientific Affairs Manager for the Mitochondrial Collaborative Research Program. You can find us at mitoquinol.org. Today we are going to be talking about creatine. Now, I kind of feel like the health and wellness space is a little bit overloaded with information on creatine and
muscle health, performance, and maybe even brain health, cognition, or why it's important for women's health. I wanted to take a slightly different approach today. And because we are the mitopod and because we are obsessed with mitochondria, they are very, very important. I wanted to bring the creatine story back to the basics. What is creatine doing in the body? How does this relate to energy and mitochondrial function?
And then, of course, we will go into functionally what this might mean for your body, especially as you're going on a healthy aging and longevity journey.
So most people think that creatine is for bodybuilders, young men in their twenties and thirties that are looking to stack on muscle and get strong. But fundamentally I think we can bring it back. Creatine is one of the body's most important energy molecules. And of course, if we're talking about energy, we need to also speak about the mitochondria.
Creatine has been studied for over five decades, and there are hundreds of clinical trials that support safety and efficacy for creatine supplementation. So I'm going to take you through what creatine actually is, what it's doing in the body, and then how that relates to exercise and cognition, and why both of those things make it such an important molecule for aging well. So I've mentioned aging well and healthy aging.
This can be a bit of an ambiguous term that can be interpreted in many different ways depending on your lifestyle and your background. So I wanted to bring aging back to a fundamental principles of bioenergetics, the energy that is in our body. And as we age, we lose the ability to make and allocate energy. We know that as we age, our mitochondrial function can start to decline.
This then leads to a poor production of ATP, our cellular energy. It becomes less efficient. Because we are producing less energy, and as we age, we still have a demand for energy. We can start to see functional declines. So as we age, we do see a decline in muscle mass and in muscle strength. We can lose up to
10% of our muscle mass every decade after 30, and then 2 to 5% of our muscle mass for every year after 50. So it starts to accelerate the older that we get. We also see a dip in cognition with age. Now I'm not necessarily talking about Alzheimer's or dementia, but mild cognitive impairment where you've got a bit of brain fog, your memory's a bit fuzzy, you know, the words are not on the tip of your tongue.
This is really common and a part of this is to do with energy availability that is in the brain. Another thing that we need energy for is recovery from injury and illness. The immune system requires high amounts of ATP and cellular energy, as well as mitochondrial communication to the wider body. And as we age, we just don't have the capacity for these systems to be firing on all cylinders.
So most of the changes that we see with age are due to an energy deficit, meaning that the body requires more energy to fuel these cellular processes of repair and rebuilding. And our mitochondria are just not able to keep up with that demand.
And more than that, as we age, mitochondrial dysfunction starts to increase. And this is usually because of an increase in reactive oxygen species as we are making energy leading to oxidative stress. And this damages our DNA, damages proteins and cellular structures. So why am I talking about mitochondria specifically? When this episode is about creatine. Now, creatine and mitochondria are linked.
Because creatine and the phosphocreatine system is designed to help take that pressure off of the mitochondria by recycling ATP that is being made. So let's talk about how energy is made and how it's allocated. So first off, as we know, our mitochondria are the powerhouses of the cells. Yes, they do a lot more than just creating energy, but for the purpose of this discussion today, we're really honing in on ATP production.
So, mitochondria are responsible for creating that ATP from the food that we drink in the air that we breathe through oxidative phosphorylation. So, glycolysis happens in the cytosole. The substrates from glycolysis are then shunted into the mitochondria, so NADH.
And then through a series of reactions we have electrons being moved through the electron transport chain, pumping hydrogen into the mitochondrial matrix,
And that drives ATP production. But the issue is that ATP can't really be stored for future use. We actually only have about 250 grams of ATP in our body at any given time. But we need a lot more ATP than that to get us through very simple things in the day, but especially if we're going to be exercising or doing anything with a very high cognitive load.
So this is where creatine comes in. So creatine is a really important molecule that is stored in the body, mostly stored in muscles, and it's stored as phosphocreatine. So it's creatine with a phosphate group attached to it. Now phosphocreatine's purpose is to donate a phosphate group to adenosine diphosphate.
Which restores it back to adenosine triphosphate or ATP. So this is like recharging our energy battery. Now I just want to touch on ATP, what ATP actually is, because I think that it can help us visualize what creatine or phosphocreatine is doing. So ATP is also called adenosine triphosphate. It's an adenosine with three phosphate groups attached to it.
Now ATP itself isn't consumed and used for energy, but energy is actually stored within the phosphate bonds of the molecule. So when ATP or adenosine triphosphate, three phosphate groups, loses a phosphate, energy is released and it can be used to power chemical reactions. So when ATP is used, it turns into ADP, which is adenosine diphosphate for two phosphate groups.
So phosphocreatine donates a phosphate group to ADP with two phosphate groups, creating three phosphate groups, making ATP. Now, ATP is just a higher energetic state, and this is just all to do with recycling that ATP that is being made by the mitochondria. So at any given time, we have about 250 grams of ATP in the body.
But we actually recycle our body weight of ATP every single day. So this phosphocreatine system and creatine supplementation can be essential, especially if you are someone who is energetic, active in the gym, someone who likes to go for a run, or someone who is doing really cognitively demanding tasks. But why do we need the system? Can't mitochondria just make more ATP?
Now, the mitochondria are very excellent at producing a baseline level of energy for the body. But like I say, creatine becomes really important when the body is under energetic stress. So this can be brought on by exercise or cognitive load. And this is one of the reasons why creatine is stored in muscles specifically, and it can also be produced in the brain through a separate mechanism. When energy demand rises in one area of the body, so for example, you're going for a sprint.
You're gonna need a lot of ATP in your quadriceps. You know, they're gonna be moving really fast. They're gonna be doing a lot more than they would be doing at rest. So the phosphocreatine that is in the skeletal muscle of your quadriceps is gonna be able to recycle energy in an instant, really, really quickly, so that your muscles aren't relying solely on mitochondrial ATP production. Now, yes, skeletal muscle have some of the densest.
Numbers of mitochondria to produce ATP, but we still need the phosphocreatine system.
So why does creatine matter for healthy aging? We know it's important for our energy systems. Now one of the interesting things about aging is it's gonna place pressure on both sides of our energy equation. On one hand, our ability to produce and manage energy becomes insufficient because we have mitochondrial dysfunction,
And poor ATP production. Now mitochondrial dysfunction is recognized as a hallmark of aging, right? So it's associated with reduced ATP and an increase in oxidative stress and reduced cellular resilience. Now it's also a very dynamic hallmark of aging and it interacts with a lot of other systems that are happening. And then on the other hand, the systems that rely on energy, so muscle function, cognition.
And then cellular repair processes also place a significant demand on the need for ATP. So we make less energy, but we still need a lot of energy. And this is going to create an energy deficit. Another part of why creatine is important for aging is that creatine availability might decline. And there are several reasons why you might want to take supplemental creatine. So the first is that a lot of older adults
Tend to consume less daily creatine. The richest dietary source of creatine is going to be red meat and fish. And people, even if they're on a typical omnivorous diet, as we get older, we tend to eat less protein and opt for more carb-heavy meals. So older adults typically don't get as much creatine in their diet. And the other issue is that 95% of creatine is stored in your skeletal muscle.
And like I mentioned earlier, as we age, we progressively lose muscle mass and strength. but I'm particularly looking at muscle mass because we lose the amount of potential creatine storage capacity.
The good thing is that taking creatine can actually help us increase our capacity for creatine. So there have been a few meta-analyses done on creatine combined with resistance training in older adults. And they find in general there are better improvements in lean mass gain, so putting on more muscle in combination with strength and resistance training compared to just doing the training alone.
So if you take creatine, you do resistance training, you're going to put on more lean muscle, which then means that you have a better ability to store creatine. So it's like a really nice feedback loop. Now the important thing to remember is that for most of the outcomes of creatine on muscle and strength, you do need to be doing it in combination.
with exercise. If you're taking creatine but you're not doing resistance training, then you are gonna have very modest effects.
So if you are a practitioner and you are wanting to work up a supplement routine, but also maybe some lifestyle improvements for your patients, if you're going to recommend creatine, make sure that you are also including resistance training in there. Yes, creatine is good for building muscle,
But you do need to apply that stress as well.
So I think it's important to pause on why muscle keeps coming up in the conversations about aging. Because I don't want you to hear this and think, okay, we need to put on more muscle because we need to be strong or because it's going to reduce our frailty index, you know, less falls. And this is absolutely true. But also, muscle is really important as a metabolic organ. And I think this is.
Particularly important for women who are dealing with issues with their metabolism as they go through perimenopause and menopause. So skeletal muscle is the body's largest site of glucose disposal. Okay, so it is able to hold on to a lot of the sugar that we intake through carbohydrates. As well as being a glucose sink, it's also an endocrine organ.
The muscle is a secretory tissue and it releases myokines into the body that do have an effect on metabolism. So muscle's not just this passive tissue or a structural component of the body. It is a metabolically active organ that helps to signal to the rest of the body.
So how do we actually build this muscle? And what is the evidence for creatine? I've said that creatine is a buffer, like an energy buffer, and that is its primary role. But the way that it is supporting muscle function and increasing lean muscle mass, there are three mechanisms that are running alongside each other. So yes, first the phosphorcreatine system and ATP recycling.
The second is going to be cell swelling. So creatine is osmotically active, which means that it draws water towards it. And because creatine is stored in muscle cells, it means it's pulling water into those muscle cells. Now, when people take creatine, some of them note that they feel a bit swollen. This is because you are getting more water into your muscles. Now, this is not the same thing as fluid retention that is underneath the skin.
That a lot of people associate with bloating. So we've got two different mechanisms there. But cell swelling, especially in the muscles, actually acts as an anabolic signal. So a signal to put on more muscle and build more protein. So it actually activates mTOR signaling as well as the MAPK pathway. So this is gonna then increase the expression of myogenic regulatory factors to put on more muscle protein.
The third one, which is a little bit more complex, is through increasing satellite cell recruitment. So muscle fibers are huge cells, right?
And there is a lot of cytoplasm and a lot of organelles that need to be regulated by one single nucleus. This is very difficult to do.
So what actually happens is that these muscle cells have little satellite cells that sit on their surface and they are able to donate nuclei to the muscle fiber. So it is a symbiotic well, actually I'm not even sure if it's a symbiotic relationship. It might be a bit of a parasitic relationship where these muscle cells are being
supported by these satellite cells to help them grow. Now there have been some clinical studies, and we can go back to 2006 actually to see some of the evidence of this, that creatine is actually able to support satellite cell recruitment even in young men.
So in this trial, there were 41 young men who took creatine for 16 weeks. They first started with a loading phase, which is 20 grams of creatine over six days. And then for the remainder of the trial, they took six grams of creatine per day. And they actually took it with a carbohydrate because taking your creatine alongside carbohydrate and protein potentially can help with intake into the muscle.
What they found was at week four, the amount of satellite cells per muscle fiber had roughly doubled in the creatine group. So more recruitment of satellite cells. What was interesting was that this effect didn't last until 16 weeks. But it did hang around for about two to three months. And this was not seen in the placebo group. So we think that satellite cell recruitment might
be especially beneficial for young muscle fibers, but maybe not something that sticks around.
indefinitely.
So what does this mean?
So, in a meta-analysis looking at twenty-two different trials that involved resistance training and creatine in older adults, those that took creatine saw an increase of about 1.37 kilograms more muscle mass than those that just had the placebo and training. So, in other words, if you take creatine,
and do resistance training, you are going to put on more muscle than if you just do creatine alone. And there's also improvements in upper and lower body strength. Interestingly, there was more improvement in upper body strength than lower body strength. and for older adults that take creatine and do resistance training, we do see improvements in sit to stand
performance. Now sit to stand is a test that is done to assess strength and mobility and it is related to frailty outcomes. So incredibly important as we are aging.
Now, creatine may also be quite important for women, especially those that are going through periomenopause and menopause. We know that estrogen impacts levels of creatine kinase. If we have less estrogen, we have less creatine kinase. Now, this is the enzyme that is responsible for creating phosphocreatine. So very important for energy allocation.
As we go through perimenopause and menopause, estrogen fluctuates. Then in menopause we have a decline in estrogen.
So our phosphocreatine system is affected by these hormonal changes. Now, on top of that, women typically consume less dietary creatine because they are taking in less protein. There are also some studies to indicate that endogenous synthesis, so making creatine on your own, not necessarily taking it in through the diet, is less efficient in women than it is for men.
What this does mean, however, is that supplementing creatine may be more beneficial for women than men.
Now there have been some systematic reviews and meta-analysis performed, especially in Frontiers and Nutrition in 2024. I will have the paper in the show notes. This looked at 16 randomized control trials that had 942 participants from 20 years old to 76, and they were looking at creatine monohydrate for cognition. Now it was
Interesting when they looked at the subgroup analysis because they found that improvements for attention time and processing speed were more pronounced in females.
Now this may be because women have lower dietary creatine, so it is potential that they had a creatine scarce system.
But in general, how is creatine affecting cognition? the brain is around 2% of body mass, but takes up about 20% of resting energy expenditure. And it actually runs its own creatine kinase system. It synthesizes creatine locally and uptake from circulation is constrained by one of the transporters of the blood.
brain barrier. So it's very different than the muscular creatine phosphate system.
So brain creatine is going to rise less and it does it a lot more slowly than muscle creatine does on the same oral dose. The brain is gonna guard the creatine pull a lot more tightly. It's gonna be much more highly regulated than muscle
This is why we see in a lot of the clinical trial evidence that in young people creatine may not really improve cognition or short-term memory. However, if you are an older adult or someone who is going through a lot of stress, or even for people that are not eating protein in their diet at a high amount, for example, vegetarians, creatine might help to support cognition in these ways.
There was a really interesting study in 2024 that was just looking at a single high dose of creatine at 0.3 grams per kilogram. And this was given during 21 hours of sleep deprivation. And what they found was creatine was able to increase the amount of cerebral phosphorcreatine and ATP. And it also improved processing speed and cognitive performance upon waking.
So this is quite an interesting find because it does challenge that assumption that you need to have weeks of loading to help to move brain creatine at all. at least for those who are sleep deprived, there is a mechanism and some evidence there for acute creatine dosing.
When we talk about dosing, generally five grams a day or five to seven grams a day is appropriate for most adults. If you want to get really technical, you can say 0.1 grams per kilogram of body weight. Five grams is just a way to be very practical about it. Now, the type of creatine that you might want to take is creatine monohydrate.
This is where all of the clinical trial evidence lies. And all of the studies that I have been talking about are using creatine monohydrate. Now you might want to use a micronized version of creatine monohydrate. This is going to make it a lot easier to dissolve. And some people do prefer water washed creatine.
Typically, like I said, a five gram dose is sufficient. You would call this a maintenance dose. Some people would want to go through a loading phase, which is generally around 20 grams per day split into four doses for about five to seven days. You could do this if you are on a vegetarian diet, so you have a low protein intake, maybe if you're going through a particularly stressful period of time, or if you feel like you are
Depleted in some way, maybe you haven't been eating particularly well, you could do a loading phase to bring up your creatine stores first. In terms of when to take your creatine, I think consistency is what is going to matter the most here. Yes, you could take it one to two hours before you were going to be doing your resistance training or heading to the gym, but just making sure that you are taking the dose ideally at the same time every day. It just helps with habit stacking.
you may want to take your creatine alongside a carbohydrate or a combination of carbohydrates and protein because this is thought to help to improve
Uptake of creatine into muscle. Now, this is the dosing method that was used for the study that was looking at satellite cell migration. So this is a part of the clinical literature, but it is not necessarily a must-do. The biggest thing that I can say about taking creatine is making sure that you pair it with training. You are not going to see those improvements in muscle mass or muscle strength.
if you are not training alongside your creatine supplementation.
So to summarize all of this, creatine is a bioenergetic buffer. It's not a stimulant, it's not an anabolic steroid, and it's not necessarily a mitochondrial nutrient, but it does have a role in bioenergetics, which is why we wanted to talk about it here on the mitopod. For muscle, creatine is working through multiple actions. So we have that instant ATP recycling.
Because we are working on the phosphorcreatine system. Then we have that osmotic cell swelling. So that's going to signal our anabolic processes through mTOR and MAPK. And then we have satellite cell activation to help support those really big muscle fiber cells. We know that the strongest evidence for midlife and older adults is pairing creatine at about 5 grams per day or 0.1 milligrams per day.
Per kilogram a day alongside resistance training. And that is where you're going to see those increases in muscle mass and muscle strength. For women, creatine supplementation is going to be important because low levels of estrogen can interrupt that phosphocreatine pathway, meaning that taking supplementary creatine when you're going through perimenopause and menopause, or even through different stages of your menstrual cycle when estrogen is dipping.
can be really helpful. One for supporting bioenergetics, ATP availability, but also training, Strength, putting on muscle, and potentially even cognition more than men. Creatine is very safe with three to five grams a day. And you can also load 20 grams a day for a week. That is safe to do.
So I will leave you with this. Mitochondria make the energy, and creatine makes sure that that energy is at the place and at the right time that it is needed. Aging well depends on healthy mitochondria and healthy energy allocation.
