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Hey everyone, Mikki here. You're listening to Mini Mikkipedia and today I want to chat about creatine and brain health. And I know that I've had I've chatted about creatine a number of times actually on this podcast and I've had the privilege of talking to Dr. Darren Kando about it who is one of the predominant researchers in this space. But I saw a thread on X actually which sort of piqued my interest in and around brain health and

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Obviously, you know creatine sort of begun as a supplement well known in both fitness circles and rugby players actually, so team sports boosting muscle performance, but it's now making waves in neuroscience for its potential to enhance brain health. And there was an X read by Nicholas Fabiano and he is a doctor and a researcher sharing insights from a new study published in the Journal of Psychiatry and Brain Science and

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the thread dived into how creatine supplementation can impact conditions like Alzheimer's, depression, and traumatic brain injury. So in that sense, it is emerging research, but it does offer some pretty exciting possibilities for mental health treatment and just neurological treatment in total. So while five grams of creatine per day is standard for muscle saturation, or even three to five grams, depending on your sort of level of tolerance and the dosing that you're doing,

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it might not be enough for brain. And that is the core focus of the research that Dr. Fabiano was talking about or highlighting. And the central thesis of the premise for using creatine for brain is that the brain does require high doses or different strategies to leverage creatine's potential. So creatine is a nitrogenous organic compound found in foods like meat and fish. It is also synthesized by the body.

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and it's widely used as a supplement as you know. So it is worth noting that women tend to have lower plasma levels of creatine and lower brain levels of creatine than men, likely because we have less muscle mass, generally speaking. And also women tend to eat less meat than men. Not all women, I probably rival a lot of men out there who enjoy good steak, but a lot of women sort of tend to limit.

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foods like red meat and animal protein where we find creatine. so vegetarians and vegans clearly wouldn't meet their creatine requirements just based on that endogenous production because we do need that additional sort of dietary support. Fish is another place where you find creatine. Anyway, so its role in energy production isn't just for muscles and that's via ATP, adenosine triphosphate, which is ourselves energy currency.

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It critical for the brain, which consumes about 20 % of the body's energy. So it's pretty disproportionate if you consider the size of the brain compared to the size of our muscle. And so the idea that a supplement that has been long found useful for strength and power and now recovery as well is also now being sort of highlighted as it's a supplement for the brain. And of course, if you have followed the literature around creatine, this is probably not news to you, but it's

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It's pretty awesome to continue to see some studies out supporting this. So what accumulating research does indicate is that creatine is capable of increasing brain creatine stores, which may help explain improvements in cognitive functioning, particularly during times of metabolic stress because of the role that creatine has at improving brain bioenergetics. However, because of the attenuation of creatine transport kinetics,

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and the blood brain barrier, it is proposed that higher doses of creatine are needed to optimize brain creatine levels, but we're unsure of what those optimal creatine doses are. So there have been many sort of clinical trials or reviews of creatine supplementation focusing on these brain creatine levels. These are measured via techniques like magnetic resonance spectroscopy, MRS, and the brain's

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High energy demands do make it sensitive to deficits in that ATP or our energy currency. And this is what creatine helps replenish. So if you can think of creatine as a backup generator for your brain's power plant, it does keep the lights on during high demand tasks like memory or problem solving. It's interesting when we look at research on people who are sleep deprived that a single high dose of creatine at around 0.35 grams per kg

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partially reverses metabolic alterations and fatigue related cognitive deterioration. And this has been known actually for some time and I've heard people talk about it in podcasts for years now that creatine acts like caffeine in the brain. So it takes up space in something called the adenosine receptor and not allowing the adenosine to attach to its receptor. When that happens, it means that we can stay alert because when adenosine attaches to its receptor,

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then we can start to feel relaxed and calm and start. It's the calming sort of restful about to go to sleep type feeling. So when you get caffeine on that receptor, we feel alert, we feel wired, we feel all of those things and creatine can do much of the same thing. Interestingly, of course you do need that high dose of about 0.35 grams per kg. And what studies show, they get this increase in creatine expression and

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areas of the brain such as the hippocampus, the cerebral cortex, the cerebellum, the brain stem, and also of course the spinal cord, and you get reduced symptoms of mood disorders such as depression and anxiety, and you have an increased cognitive functioning, memory, reasoning, attention, et cetera. So that's pretty compelling research. And in Alzheimer's patients, there was recently a study that was published in Translational Research and Clinical Interventions,

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showing that creatine monohydrate for patients with Alzheimer's helped improve or increased brain creatine levels and improved cognition. I don't need to tell you that Alzheimer's is a devastating neurodegenerative disease and it does have limited treatment options. So this result is a pretty big deal. So 20 grams, as I said, that's quite a high dose. That's four times that typical five gram dose that I was mentioning earlier that helps with that sort of muscle recovery and strength and power.

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So it does suggest that the brain's creatine transporter may need more to achieve those therapeutic levels. And to have an improved cognition could mean better memory or daily functioning for patients. So if you can imagine someone with Alzheimer's suddenly remembering a family story they hadn't recalled in years, know, that's the kind of hope that this study sort of sparks. And albeit it was a pilot trial and it was small, it was still pretty compelling. And it is sort of

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postulated that impaired brain energy metabolism, including dysfunction in the creatine system, may contribute to the development and progression of Alzheimer's disease, giving rise to the plausibility of creatine making a difference. And this study was done over eight weeks and what they found that serum creatine was elevated at weeks four and eight and brain total creatine increased by 11%. Cognition improved on global and fluid composites, list sorting,

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oral reading tests and overall what a pilot study does is it tries to test the theory that a particular intervention is feasible and that's what this study was able to show and it provides that preliminary evidence for future efficacy and the mechanism for it. Interestingly, as of May this year, the effectiveness of creating treatment for Parkinson's hasn't really been found to date but

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I I guess it's sort of a watch this space situation. In depression, increasing creatine intake from four grams to 10 grams daily doubled brain creatine levels with frontal lobe creatine levels inversely correlated with depression scores. And this is again another compelling finding for mental health. Depression affects millions of people and current treatments like antidepressants can take weeks to work if they work at all or they have side effects.

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So creatine's potential to boost mood by enhancing energy in the frontal lobe, which is a key area for emotional regulation, is pretty exciting. Imagine if a simple supplement like that could lift the fog of depression alongside therapy way much faster than therapy alone. Like this is pretty awesome. And the fact that there was this dose escalation, so they started to see benefits when the dose went from four grams to 10 grams,

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does of course suggest like a dose response relationship here. I'm not suggesting that it doesn't level out at some point, but more was clearly better. And it's worth noting that the frontal lobe is critical for executive functioning and mood and low creatine levels may impair that brain energy availability. So it worsens depressive symptoms. This study was done actually on adolescent females and they had

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SSRI resistant depression. So they weren't actually responding to therapy. So that's super interesting. And just so you know, the study design, were, the participants were getting either two, four or 10 grams daily for eight weeks. And they used that magnetic resonance spectroscopy MRS to measure brain function. And they used a scale called the child's depression rating scale revised CDRS.

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are to determine those depressive symptoms. if you look at the charts in the paper, there's just this clear dose response relationship from baseline through to week eight. So it's absolutely worth trialing creatine. It's completely safe from adolescence upwards. There's no reason to suggest it isn't. And there were no increase in adverse outcomes or side effects by taking the larger dose or no differences between the groups at least. And then

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Brain injury, traumatic brain injury is another area of interest when regarding creatine supplementation. And studies have found, again in children and adolescents, that a high dose of creatine of 0.4 grams per kg body weight for six months reduced the duration of amnesia, the length of intensive care unit stay, and improved neurophysical and cognitive functioning. So this was performed on 39 children and adolescents actually between years one,

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to 18 years and the researchers found that the administration of creatine improved results in several parameters, including duration of post-traumatic amnesia, I mentioned, duration of intubation, intensive care unit stay, disability, good recovery, self-care, communication, locomotion, sociability, personality and behavior, and neurophysical and cognitive function. Now, 0.4 grams per kg of body weight daily, just as a

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put that into perspective, that's about 28 grams for a 70 kilogram person. I do, even though this was done in child, children and adolescents, there's no reason to suggest that this would cause any harm if you were an adult, right? And a TBI is super common actually. So I'm thinking concussions here as well, obviously. It is a traumatic brain injury. It's common in sports, accidents or military settings. And it can cause those long-term cognitive and physical deficits.

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So this finding suggests that creatine could be a game changer for recovery. So you can imagine that someone playing rugby has a concussion and has this like post concussion fatigue, is unable to really do much, really struggles with recovery, with memory, like a whole host of things. Like creatine would well be worth trying. It suggests that recovery could be faster because of the supplement. Now it was over six months.

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So do be mindful of that. That's not a sort of short duration. So I do think this underscores the need for sustained treatment. So you yourself has had a TBI or you know people who've had concussion, this wouldn't be a bad thing to sort of think about. Because the thing with a traumatic brain injury is it disrupts that brain energy metabolism and it does lead to that neuronal damage. And creatine's got this potential neuroprotective effects.

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potentially stabilizing mitochondrial function and reducing the oxidative stress. The study's outcomes on the amnesia duration and the ICU stay were clinically significant as well. It's worth noting that the blood brain barrier does limit creatine uptake. So that's why we've got these higher doses of creatine than that standard dose that's often recommended. And there are some ideas out there to help enhance delivery or synthesis. So,

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looking at things like intranasal administration, bypassing the blood brain barrier. in summary then, and I'll put a link to the psychiatry and brain study, which was the Alzheimer's study, as I mentioned, and also the TBI and the depression study, is that creatine could potentially be an ally for brain health. so it's always really important when this new information comes out, just to evaluate, how important is it to you to sort of

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jump on board a different supplement or protocol because of the new science that's emerging. But if you sort of recognize yourself or others around you in any of these buckets, I think creatine could well be worth exploring. And I think this thread does really highlight this sort of paradigm shift because creatine was once this sort of cheap and widely available supplement. It still is both of those things. The sports and it's just

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being repurposed for these neurological and psychiatric conditions. And that does align with growing interest in other metabolic therapies, such as ketogenic diets. And I've spoken to a number of people on this podcast about that, including Dr. Matthew Phillips. It's a really accessible supplement. It's available at any supplement store. And it could just be a good adjunct to other therapies where other therapies fall short. And the fact that creatine helped

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in people who were not responsive to typical SSRI treatment, I think really speaks to that. Some challenges though, and I guess caveats are that these were high doses and whilst there were no significantly different side effects from these high doses of creatine in the studies I mentioned, it didn't mean that people didn't have side effects. Things like gastrointestinal discomfort is certainly one of the main ones, so GI issues and

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Whilst these studies are promising, these are pretty small sample sizes or they're of relatively short duration. So the long-term efficacy and safety probably need a little bit more research. But I will pop the studies in the show notes for this. And I hope at the very least, just even these few things sort of give you a little bit of, I don't know, hope. Like who doesn't want a sharper mind as we age? And this is a potential tool

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in the toolbox for the mental health crisis that is pretty much occurring certainly in New Zealand. We hear about this a lot, but also at that global scale. So it could absolutely be worth checking out. And I mean, you're probably taking it anyway because people talk about creating all the time. But now you know some more of its application in areas other than sport and exercise, really in recovery. All right, team, have a great week. You'll find me on Instagram, threads and X @mikkiwilliden.

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Facebook @mikkiwillidenNutrition or head to my website, MikkiWilliden.com and book a one-on-one call with me. Have a great day.