Thinking Nutrition

Beyond exercise: creatine’s growing role in brain, bone and women’s health

• Dr Tim Crowe • Episode 133

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Creatine is one of the most well-researched and effective sports nutrition supplements for improving exercise performance. But that isn’t what I’m going to talk about in this podcast episode. Instead, I want to give the spotlight to creatine’s new moment in the sun thanks to evolving research linking it to improving brain and bone health. And then tying all this together, I’ll profile why it may just be one supplement that women could especially benefit from over men during their reproductive lifespan and beyond.

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Creatine is one of the most well-researched and effective sports nutrition supplements for improving exercise performance. But that isn’t what I’m going to talk about in this podcast episode. Instead, I want to give the spotlight to creatine’s new moment in the sun thanks to evolving research linking it to improving brain and bone health. And then tying all this together, I’ll profile why it may just be one supplement that women could especially benefit from over men during their reproductive lifespan and beyond.

 At least for me, it seems creatine is all over social media feeds these days. But a search of Google trends shows the growing interest is real with an explosion in interest in this popular sports nutrition supplement in the last year with a doubling in search queries.

Have people rediscovered its well supported role in sports performance? The answer is only a very partial yes. Because most of the recent interest in creatine is decidedly outside of the world of the gym bros. Brain, bone and women’s health dominate this interest and the supplement is proving to be the darling of many health influencers.

So, let’s take a step back to talk about what creatine is and cover briefly its well-defined exercise role before I move onto those emerging areas.

Creatine is a naturally occurring compound found in our muscles and other body tissues in the form of creatine phosphate. It is the phosphate part of creatine that is a valuable aid in the rapid resynthesis of high-energy ATP from ADP during short-term maximal exercise such as sprinting or power weight training.

So, think of creatine as like a short-term anaerobic power source that the body can call upon when its energy needs are stretched. Theoretically, the more creatine phosphate that you have in your muscles, the higher the intensity at which you can train. High-intensity training stimulates the muscles to grow and adapt, which, in turn, improves performance. Win, win.

Because creatine is mostly found in our muscles, that means animal foods such as meat and fish make for excellent dietary sources. But our bodies can naturally produce it as well from the amino acids arginine, glycine and methionine. And of course, supplementing with creatine can boost muscle stores too. Though vegetarians do tend to have lower natural levels of creatine so there could be a case that supplementation could benefit them more.

So, what does the scientific evidence have to say about creatine and sports performance in general? There have been hundreds of clinical trials, reviews and meta-analyses done so this is one supplement that has been well-researched and is backed by real science, not bro science.

That large research base finds that the greatest benefits of creatine are in recovery from high-intensity bouts of exercise with short rest intervals. So, what that means is that it may not make a person run a faster 100m, but they’ll be able to run faster sprint times if they’re doing it repeatedly such as in intermittent activity sports like football where they may be high-intensity bursts of activity for less than 30 seconds followed by periods of relative rest.

There is also some evidence for a benefit of creatine supplementation to enhance endurance performance which results from increased or improved protein synthesis, glycogen storage and thermoregulation.

But probably the main benefit of taking creatine is in resistance weight training with positive adaptations including lean mass gains and improvements in muscular strength and power. Benefits have been reported in men and women, although most studies have been conducted on men. Hormonal effects are a major confounding difference between men and women so more about creatine’s role in women’s health later in the podcast.

How creatine helps with resistance training isn’t fully understood. Though is likely a combination of reasons such as altering gene expression of the muscle protein myosin, influencing insulin-like growth factor production, stimulating muscle growth regulatory factors, improving cellular hydration, and altering inflammation and oxidative stress responses. But let’s not forget one of the simpler explanations is that creatine supplementation can increase creatine phosphate stores and help with the resynthesis of ATP, thus enabling a larger volume or more intense training and through that a greater muscle hypertrophy response.

If you want to take creatine for sports performance benefits the protocol here is pretty simple. You can either load with about 20 grams per day or about 0.3 grams per kilogram of bodyweight divided into doses across the day and doing that for about 5 in a row. After loading, a maintenance dose of a single 3-5 grams per day can be used. Alternatively, creatine muscle stores can be topped up by just doing the daily dosing of around 3 to 5 grams which will get you there in about a month. Although more recent research suggests that for creatine supplementation, it may be better to base it on a body weight level and a figure of 0.1 grams per kilogram of body weight combined with resistance training has been touted as well.

Just hold those dosing amounts in your mind as it will start to change as I move into some of the possible non-muscle benefits of creatine. So, let’s dive in.

Brain health

Let’s start with the brain. Creatine supplementation is increasingly studied for its potential to support brain health, particularly in areas such as memory, cognitive processing and neuroprotection. Evidence suggests creatine can increase brain creatine stores and may improve memory and cognitive function, especially in older adults and under conditions of stress or brain injury. The main mechanism involves enhancing brain energy metabolism, which is crucial for optimal brain function.

So, there’s a bit to unpack here so time to go deeper. Creatine is primarily synthesised in the liver and kidneys, but other organs like the brain can also produce it too. The brain is a big user of our daily energy requirements – coming in at around 20% of our energy needs so you can see a clear role for creatine in ATP production when mental demand is high.

While a healthy brain may produce enough creatine to meet these energy demands, supplementation could be beneficial during times of mental fatigue, ageing or in neurocognitive conditions. So, the rationale goes that under situations of metabolic stress, such as sleep deprivation or degenerative disease seen with ageing, the brain may become depleted of its creatine store,s leading to cognitive fatigue.

Beyond energy metabolism, creatine appears to provide neuroprotective benefits through several mechanisms. Research indicates that creatine supplementation can reverse mitochondrial dysfunction in neurodegenerative diseases. Animal studies have demonstrated that creatine supplementation could also help prevent losses of neurons that produce neurotransmitters such as dopamine.

So, what do human clinical trials have to say? Multiple systematic reviews and meta-analyses show that creatine supplementation can improve memory, particularly in older adults, and may enhance short-term memory and reasoning in healthy individuals.

The first of these reviews was in 2018. It included six randomised-controlled trials involving 281 healthy individuals. Doses used varied from 5 grams up to 20 grams per day. It found evidence that short-term memory and intelligence and reasoning were improved by creatine supplementation. Although they did find conflicting evidence regarding other domains of cognitive function such as long-term memory, attention, reaction time and mental fatigue. One interesting finding was that young adults in their 20s didn’t appear to see much benefit – it was older people who saw the most improvements, so this aligns with the idea that creatine supplementation has a stronger cognitive effect in the aged brain whereas in younger, unstressed individuals there is no such benefit. I’ll link to this review in the show notes. https://pmc.ncbi.nlm.nih.gov/articles/PMC6093191

But research never stands still and as new studies come out, it is possible to run larger reviews. Take for instance a systematic review from 2022 that included 10 randomised-controlled trials looking at creatine supplementation in healthy adults and its effect on memory. Doses of creatine ranged from 2.2 grams up to 20 grams, with 7 of the 10 studies using that higher 20 grams dose. A range of different tests were used to assess memory which I should say is a limitation of the work for making true comparability between study designs based on creatine dosage. Onto the results. Overall, there was a small but positive benefit in taking creatine on memory. But when you just looked at older adults aged 66 to 76 that benefit grew and was deemed to have a large effect and for me, is probably the most striking result of the research within the limitations of the wider research field due to the variability in study designs. And I’ll link to this review in the show notes. https://pmc.ncbi.nlm.nih.gov/articles/PMC9999677

And to round things out, a systematic review from 2024 could look at 16 randomised controlled trials involving 492 participants aged 21 to 76 years and which included both healthy adults and adults with specific conditions such as fibromyalgia, mild cognitive impairment associated with Parkinson’s disease and chronic schizophrenia under treatment. Overall, creatine supplementation could again demonstrate a small, but significant effect on memory as well as a small improvement in attention and moderate improvements in brain processing speed. But here is where it gets more interesting as benefits were more notable in the studies that involved adults with brain-related illnesses. But unlike the other two reviews I just mentioned, this one couldn’t see a significant benefit of creatine in adults over the age of 60. The duration of taking creatine for either less than 4 weeks or more than 4 weeks didn’t seem to be a factor in influencing the results. This finding suggests that the effects of creatine on cognitive function may reach a saturation point within a certain period. And I’ll link to the review in the show notes. https://pmc.ncbi.nlm.nih.gov/articles/PMC11275561

So, what could be going on here? Creatine could be enhancing memory through several biological pathways. The first is it increases energy supply to brain cells via phosphocreatine, crucial for resynthesising ATP levels in the brain. Secondly, creatine may improve neurotransmitter function while also acting as a neuromodulator by affecting the efficiency and plasticity of neuronal synapses which are essential for learning and memory. Additionally, creatine’s neuroprotective properties may reduce damage to the brain from oxidative stress.

Another area I want to touch on in the area of brain health is the potential role of creatine in mood disorders, particularly depression and anxiety. This is very much a nascent and evolving area, but research to date has indicated that people with mood disorders are more likely to have lower creatine levels in certain brain regions, particularly the prefrontal cortex, and that increasing levels by supplementation may help improve mood. While creatine may be helping to alter brain bioenergetics, preclinical evidence suggests that supplementing with creatine could also help with depression by modulating neurotransmitter receptors. Creatine might also improve depression by decreasing oxidative stress and increasing serum levels of BDNF, which is a protein involved in brain development and function.

Lots of ‘mights’, ‘maybes’ and ‘mays’ I know. So, what does the human clinical evidence say here? Looking at studies that at least used a placebo, one proof-of-concept study in 52 women with major depressive disorder published in 2012 found that adding 5 grams of creatine daily over 8 weeks in conjunction to the common anti-depressant SSRI Lexapro resulted in significantly greater improvements in depression scores as early as 2 weeks of treatment compared to women who were taking placebo in place of creatine but still taking Lexapro.

Interesting research indeed and why a new study only published this year helps to build on this, where in this case 100 adults with an equal split of men and women with major depressive disorder took 5 grams of creatine daily for 8 weeks or placebo. Unlike the previous study I mentioned where participants were taking anti-depressant medication, in this new study, participants had not taken any psychotropic medications in the 8 weeks before beginning the study. Instead, each participant received five 45-minute cognitive behavioural therapy sessions during the study.

So, what did they find? Depression symptoms improved in both groups which is not unexpected as the overall outlook for CBT as a treatment for depression is positive. But a greater improvement was seen in the group taking creatine. And it wasn’t a small difference as the benefit was deemed as clinically significant. In fact, as a group, those taking creatine moved from the classification of moderately severe depression to mild depression, while those taking the placebo remained in the moderately severe category even though their depression did improve. And 12 participants in the CBT plus creatine group achieved what was considered remission from depression with just 5 five in the CBT plus placebo group achieving clinical remission. The only adverse events of note where a higher incidence of gastrointestinal complaints in those taking the creatine and this was mostly confined to the first two weeks of taking the supplement. And I’ll link to this study in the show notes. https://pubmed.ncbi.nlm.nih.gov/39488067

Creatine supplementation is certainly showing some promise as a low-risk, low-cost adjunct treatment for mood disorders, in particular depression. And yes, absolutely, we need more high-quality randomised trials here rather than the smaller more specialised studies we currently have so these finding are certainly not applicable to everyone at this stage. But considering this supplement is already widely available and is super popular in the sports nutrition world, it could end up being part of the therapeutic toolbox in managing mental health conditions.

Taking it one step further, creatine supplementation is showing promising potential for both reducing concussion risk and managing traumatic brain injury effects through multiple neuroprotective mechanisms. The altered cerebral energy availability and injury induced cerebral blood flow combined with low brain creatine levels seen in traumatic brain injuries has led researchers to propose a potential therapeutic role of creatine supplementation. Driven largely by animal studies, with only limited human research so far, the initial results look promising for improving recovery outcomes both in cognition and symptoms such as headaches and fatigue and even potentially reducing the effects of concussive impacts when taken pre activity which has certainly attracted the interest of many athletes participating in high-impact contact sports.

It’s well beyond the scope of this episode to go a lot deeper in this area, but if you want to read more, I’ll link to an excellent 2023 review paper on the potential applications of creatine supplementation for brain health and function in the show notes. https://pmc.ncbi.nlm.nih.gov/articles/PMC10721691

And the review paper on this topic was led by Dr Darren Candow from the University of Regina in Canada who is one of the world-leading researchers and experts on creatine and I’ve drawn on much of his work and that of his collaborators for this podcast. He’s also very active on social media and shares a lot of breaking research and provides commentary on the evolving topic of creatine so it’s well worth following him on Instagram to keep up with the latest development.So I’ll link to his Insta profile in the show notes. https://www.instagram.com/dr.darrencandow

And just from a bit more left field tying together several areas where creatine may be of benefit, we are now seeing research into creatine supplementation for long COVID. Long COVID is associated with reduced tissue creatine levels and impaired bioenergetics, which may contribute to the fatigue and cognitive symptoms. Several recent studies suggest creatine at doses of 4 to 8 grams per day may help reduce fatigue and improve other symptoms in people with long COVID. While the evidence is still preliminary and based on small sample sizes, findings indicate potential benefits so expect more research to come out.

Bone health

So, that’s the brain. What about bone? Is there any credence to claims that creatine supplementation helps maintain healthy bones? The answer is a qualified ‘yes’ as it seems that it requires both creatine and resistance exercise together for a synergistic effect as creatine on its own doesn’t seem to impact bone health that much.

As creatine enhances muscle mass and strength, then stronger muscles mean stronger muscle contractions which means greater loading on bones, potentially improving bone density. Creatine could also have a role in enhancing the activity of the bone osteoblast cells that are part of the bone building mechanism. Creatine can also help reduce inflammation – chronic inflammation is linked to greater bone loss.

But intriguingly, an effect of creatine with resistance exercise may not be all about changes in bone mineral density but instead changes in bone geometry which go on to give greater integral strength properties of the bone, making them more resistant to fracture.

From a limited evidence base so far, I would say the evidence is strongest for creatine and resistance training improving the bone health of older adults and postmenopausal women. This is nicely illustrated in a 2023 clinical trial looking at the effect of creatine supplementation and resistance exercise in postmenopausal women. This was a 2-year randomised-controlled trial involving 237 women with an average age of 59 years. Each woman undertook a similar resistance training and walking program over that time, but one group received creatine at a dose of 0.14 grams per kilogram of body weight while the other group took a placebo. Based on their average body weight, that put the daily dose of creatine in the 10 grams per day ballpark. And I’ll link to the study in the show notes. https://pmc.ncbi.nlm.nih.gov/articles/PMC10487398

So, what were the bone health outcomes? Aligning with previous research, there didn’t seem to be much of an effect of taking creatine on improving bone mineral density on top of the exercise program. Taking creatine though did give a significant improvement in the differences in geometry of the bones between the groups of women, in particular the neck of the femur which is a major part of our hip joint and very susceptible to fracture with falls, especially in older people. The more favourable bone geometry in those taking creatine was seen in the femur and were predictive of greater bone strength, greater resistance to bending, greater resistance against bending under compressive loads, and greater thickness of the dense out layer of the bone called cortex. All the sorts of things that could help reduce the risk of fracture from a fall if creatine could help preserve bone geometry over many years.

And on top of the bone health benefits, those taking creatine saw a greater increase in lean tissue mass and walking speed, although it didn’t appear to improve overall strength though this could have been masked by the substantial strength gains seen in both groups of women from the resistance training program.

Women’s health

This now leads me onto the final part of the episode and that’s bringing together much of this research I’ve outlined and putting forward the case why creatine may just be one supplement that will have a positive bias in helping women more than men.

On average, women have lower creatine body stores than men while their diet is more likely to lower in naturally occurring creatine. So already there is a case that supplementation may offer more benefits to women. And then there is the impact of hormonal changes on creatine metabolism over a woman’s reproductive lifespan, especially contrasting the pre and post-menopausal time periods. Sex hormones, predominantly estrogen and progesterone, are known to affect activity and expression of key enzymes needed for the production of creatine and its transport to various tissues so you can see already a case for how creatine production kinetics can change over a woman’s reproductive lifespan.

So, let’s focus particularly on the peri- and post-menopausal stages of a woman’s life. Those hormonal changes have real biologic effects on bone, brain and muscle health and the direction of those changes aren’t so favourable. Those are areas that creatine is known to have a positive role in, yet its own metabolism is also altered to the down side by those same hormonal changes. Many people are now connecting the dots between looking at creatine supplementation as a way to help manage many of these changes – especially when you combine it with the overwhelming benefits that resistance exercise can already have in muscle and bone health.

Then there are the hormonal-related cognitive and mood changes that can happen at this time of a woman’s life. Enter creatine again as a potential supplement that could be one way to help address this.

I’m not going to unpack every study and mechanism here as it relates to women’s health as I’ve already presented a lot of the general literature for brain, bone and muscle health in this podcast. But if you want to go deeper, then there is an excellent review paper I can recommend covering specifically creatine supplementation in women’s health across the lifespan by Dr Abbie Smith-Ryan published in 2021 and I’ll link to this paper in the show notes. https://pmc.ncbi.nlm.nih.gov/articles/PMC7998865

Taking the findings directly from this review paper which was supportive for creatine being even more effective in women for its brain benefits while also working to improve muscle and bone health it arrived at advice for a supplementation protocol. It can either be a loading phase of 0.3 grams of creatine per kilogram of body weight per day for 5 to 7 days and then moving onto a maintenance dose of 5 grams per day. Or just do a routine daily dose of 5 grams to reach muscle saturation by 4 weeks and then maintain from there. For brain saturation, the research is still unclear what an effective dose may be but points to higher doses of 15 to 20 grams per day for 3–7 days, followed by 5 to 10 grams per day for ongoing use. Treat these recommendations as guidelines though with scope for individual personalisation.

And those recommendations while they were focussed on more women’s health, aren’t really that different to what is recommended for men as well.

So, if you’re more focused on muscle and sports benefits, then you can either load with about 20 grams of creatine for 5 to 7 days then a maintenance dose of 3 to 5 grams per day or just skip straight to the maintenance dose. These are absolute numbers, and everyone is different in body type, so there is a case that people with more muscle mass would need more hence an alternative relative dosing strategy which can range from 0.1 up to even 0.3 grams per kilogram body weight per day. What this is saying is that there is a lot of scope for experimenting for what dose works for you especially if you get any GI problems so you can change the dose or timing.

When it comes to brain and bone health though, much less is known about the optimal creatine supplementation protocol for improving these measures because simply, there is far less research here compared to the exercise and muscle literature. For bone health you would be looking at doses of 8 grams per day and above. For brain health benefits several well-designed studies have used doses of 20 grams per day or 0.3 grams per kilogram per day for at least 7 days. Alternatively, a lower dose regimen of about 5 grams per day for several months would likely ensure enough time for the creatine to get into the brain as the blood brain barrier is less permeable to creatine compared to our muscles.

Drawing upon expert commentary on this area the case is made that 10 grams per day could an effective dose for brain, bone and muscle health with higher doses during times of metabolic stress such as cognitive fatigue maybe providing additional benefits and this is where some have advocated that 20 g/day could be effective for short periods of time.

But, I really need to say that everyone’s mileage here will be different as effects of creatine vary based on individual context and dosage. Some people experience significant benefits while others notice minimal effects especially for cognitive responses. As many as 30% of people may not respond favourably to creatine supplementation because of factors such as age, sex, muscle mass, initial creatine stores, habitual dietary intake of creatine and physical activity levels. And some of these factors may be tissue dependent where some factors are more relevant to the muscles while others to the brain.

There’s a lot more to uncover here, hence treat the dosing recommendations as a starting point and use your own personal experience as a guide.

As for what form of creatine to take, it is creatine monohydrate that dominates the market and that’s all you need to worry about as that’s the form used in just about all the research studies I have talked about in this podcast. And it is usually the cheapest form as a bonus. Creatine monohydrate is simply creatine with a water molecule added to it which dissolves in the body and releases creatine that is identical to that which is produced in the body. Micronised and many other forms are just a more refined version that can have some improved solubility characteristics because it has been processed into smaller particles and for some this could be a little easier on the gut if GI issues present to you. And if you do experience any GI issues with creatine, it is more a signal to lower the dose or spread it out over the course of the day.

Forms like creatine hydrochloride, creatine malate and other variations of creatine are more just marketing to help ‘up sell’ creatine because it must be ‘better’ because it is a ‘new’ form, but there is little research to show that any of these forms are better for a biological effect compared to the gold standard of creatine monohydrate. Creatine monohydrate is the cheapest and most effective form and that’s all you need to look for if considering trialling it.

The time of day you take it doesn’t seem to really matter nor is there any real strong rationale to take it pre or post exercise – go with what works for you and your training. There is though some experimental evidence showing that caffeine and creatine may counteract each other so this is one case where it may be better to split your coffee and creatine by at least an hour although the doses of caffeine needed to be of a concern are probably more than you’ll find in a single cup of coffee.

Is creatine safe to take? Creatine has shown an excellent safety profile across a huge number of studies, with minimal adverse effects reported even with long-term use. A small amount of weight gain from increased water retention and some short-term gastrointestinal problems are probably the only side-effects a person is likely to encounter. Creatine is after all a substance that is naturally present in our diet and our body makes on its own. This safety profile is especially important given the research now supporting its benefits in a range of health outcomes that may require extended periods of supplementation to achieve and maintain benefits.

So, let’s wrap all this up. Creatine is one of the few nutritional supplements for which research has consistently shown a sports performance benefit. But research into its benefits is now growing well outside of exercise performance. Creatine supplementation offers potential for supporting brain health through mechanisms involving energy metabolism, neuroprotection, and cognitive enhancement particularly for people experiencing cognitive challenges or at risk for cognitive decline. And the body effects of creatine may even extend into our bones.

For a woman in particular, creatine is one supplement that could offer a combination of all these benefits at the times when it is needed the most arising from reproductive hormonal changes that happen throughout her life.

But please treat everything I’ve presented here today as a snapshot of the current research landscape – a landscape that will continue to evolve I have no doubt and one that certainly is worth keeping up to date with. For every listener, you can evaluate the research yourself and determine if creatine supplementation is of value to you or not for whatever health or performance outcomes you are interested in.

This podcast episode was about producing a fair assessment of the current state of the evidence. If you want glowing and glossy evangelical hype about the cure-all properties of creatine supplementation then you’ll have no trouble finding that on social media singing its praises. But I’m not singing from that song sheet as creatine is not that. Creatine can be a useful supplement that can help some people for a range of reasons, be it for sports performance or helping to lift a brain fog, so treat it as a supplement that is just one lifestyle change that is in your control that can be trialled.

So that’s it for today’s show. You can find the show notes either in the app you’re listening to this podcast on, or else head over to my webpage www.thinkingnutrition.com.au and click on the podcast section to find this episode to read the show notes.

If you find this podcast of value, then please consider sharing it with your friends and colleagues. This all helps to increase the reach of the podcast, which means a big win for credible evidence-based nutrition messages and making the world a slightly less confusing place.

I’m Tim Crowe and you’ve been listening to Thinking Nutrition. 

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