Supplements With Evidence In Mild Cognitive Impairment
Quick Read Mild cognitive impairment is a grey zone between normal age-related memory changes and dementia, and it may be
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Creatine is best known as a muscle-building supplement, but recent research suggests it may also support brain function. Your brain uses creatine as a rapid energy reserve, similar to how muscles do. When your brain’s energy demands spike, creatine helps regenerate the fuel that powers thinking, memory, and focus. Research also hints that creatine may directly influence how brain cells communicate and protect against age-related decline.
A 2024 analysis of 16 studies involving 492 people found that creatine improved memory and showed promising signals for processing speed and attention. The effect appears strongest in older adults and people who eat little or no meat, since dietary creatine comes almost exclusively from animal products. Studies also suggest creatine helps sustain mental performance during prolonged mental fatigue, though the benefits are modest rather than dramatic.
However, important gaps remain. The European Food Safety Authority has not yet confirmed a cause-and-effect relationship between creatine and improved thinking. Most studies used short-term loading doses of 20g daily for 5 to 7 days, not the lower daily doses most people actually take. We need larger, longer trials, particularly in older adults and people with cognitive concerns. Creatine is safe and inexpensive, but expectations should be realistic.
Verdict: Creatine shows genuinely promising but not yet proven benefits for brain speed and memory, particularly for older adults or non-meat eaters, though much larger research is needed before strong claims can be made.
What if the most interesting thing about the world’s most popular sports supplement had nothing to do with your muscles? For decades, creatine has been the quiet workhorse of the gym bag, reliable, cheap, and reassuringly well-researched for building strength and power. But in the last few years, a different question has started circulating in research labs: what is creatine actually doing to your brain?
Here’s the thing that might surprise you. Your brain is one of the most energy-hungry organs in your body, and it uses creatine in almost exactly the same way your muscles do, as a rapid-fire energy buffer, keeping things running when demand spikes. When you’re processing information quickly, holding a thought in working memory, or pushing through mental fatigue, your brain is burning through energy at a remarkable rate. And there’s a growing body of research asking whether topping up your creatine levels could make a meaningful difference to how sharply and quickly your brain performs.
The honest answer, as you’ll see below, is: probably yes, in certain circumstances, for certain people. But the story is more nuanced than the headlines suggest, and we think you deserve the full picture. Vitacuity analysed over 1.77 million research papers and selected the 15 most relevant studies on creatine and brain function for this piece. Here’s what the science actually says.
To understand why creatine might matter for your brain, you need to understand a little about how your brain makes energy, and what happens when it can’t keep up.
Your brain runs primarily on ATP (adenosine triphosphate), which is essentially the body’s universal energy currency. When a neuron fires, transmitting a signal, forming a memory, or processing a piece of information, it burns ATP. The problem is that ATP gets used up extremely quickly. Your brain needs a way to regenerate it almost instantaneously, and that’s exactly where creatine comes in.
Creatine is stored in the brain (and muscles) as phosphocreatine. Think of phosphocreatine as a rechargeable energy reserve sitting right next to your ATP supply. The moment ATP runs low, phosphocreatine donates a phosphate group to regenerate it, essentially acting as a rapid-response energy top-up system. This happens faster than any other energy pathway in the body [8].
When this system is working well, your brain can sustain high-energy cognitive demands, quick thinking, attention, memory retrieval, without faltering. When it’s under pressure (from sleep deprivation, mental fatigue, ageing, or simply low dietary creatine intake), the system strains, and cognitive performance can dip [8].
More recently, researchers have uncovered another intriguing layer. Creatine may not just be an energy buffer, it appears to act as a neuromodulator in the central nervous system, meaning it may directly influence how brain cells communicate [12]. Studies have shown it can interact with NMDA receptors, which play a key role in learning and memory. It also reduces oxidative stress and inflammation in the brain, two processes that accelerate with age and have been linked to cognitive decline [12].
There’s also a fascinating emerging theory about something called the muscle-brain axis. When creatine fuels exercise in your muscles, it may trigger the release of myokines, signalling molecules that travel from muscle to brain. One of the most important of these is BDNF (brain-derived neurotrophic factor), a protein often described as “fertiliser for the brain” that supports the growth and survival of neurons. Creatine supplementation may support this pathway, suggesting its benefits for the brain aren’t purely direct [5].
The most comprehensive evidence we have comes from a 2024 systematic review and meta-analysis published in *Frontiers in Nutrition*, which pooled data from 16 randomised controlled trials involving 492 participants aged between 20.8 and 76.4 years [10].
The headline findings: creatine supplementation showed statistically significant positive effects on memory (standardised mean difference of 0.31, 95% CI: 0.18–0.44) and meaningful signals in attention and information processing speed [10]. These are the domains most consistently supported across studies, and processing speed in particular is directly relevant to the kind of mental sharpness that tends to fade in midlife.
Evidence grade: Promising. Sixteen RCTs is a reasonable base, but with only 492 total participants, the sample sizes are still modest. The direction of effect is consistent, but we need larger, longer trials before we call this settled science.
One of the most practically useful studies on this topic was a 2023 trial published in *Brain Sciences*, which directly investigated whether dose matters [7]. Thirty participants (11 male, 19 female) were randomised to receive either 10g per day of creatine, 20g per day of creatine, or a placebo for six weeks.
The researchers used functional near-infrared spectroscopy (fNIRS), a brain imaging technique that measures oxygen flow in the prefrontal cortex, alongside a cognitive test battery covering processing speed, episodic memory, and attention [7]. The prefrontal cortex is the region most associated with executive function: planning, decision-making, and holding information in working memory.
The results suggested that higher doses (20g/day) produced more measurable changes in prefrontal cortex activation during cognitive tasks than lower doses, which raises important questions about what dose is actually needed to shift brain creatine levels meaningfully [7].
Evidence grade: Promising. Thirty participants is small, and six weeks is a relatively short window. But the use of brain imaging to directly measure prefrontal activation, not just task performance, adds an interesting mechanistic layer.
A 2025 systematic review in *Nutrition Reviews* focused specifically on creatine and cognition in adults aged 55 and over, arguably the population where the stakes are highest [3].
The review identified six eligible studies with a total of 1,542 participants (55.7% female). The findings were striking in their consistency: five of the six studies (83.3%) reported a positive relationship between creatine and cognition, particularly in the domains of memory and attention [3].
Why might older adults respond more strongly? The leading hypothesis is that ageing naturally depletes brain creatine levels, meaning the baseline is lower and the potential benefit of supplementation is proportionally greater. Vegetarians and vegans, who consume no dietary creatine from meat, may similarly start from a lower baseline, which could explain findings from the 2018 systematic review suggesting vegetarians respond better to creatine supplementation in memory tasks than meat-eaters [9].
Evidence grade: Promising. The methodological quality of the included studies was mixed, only one rated “good,” two “fair,” and three “poor” by the reviewers’ own assessment [3]. The signal is encouraging but the evidence base needs strengthening with better-designed trials.
One of the more consistent findings across studies is that creatine appears most useful when the brain is under stress, specifically, when it’s mentally fatigued.
A 2020 crossover trial published in *Medicine & Science in Sports & Exercise* tested this directly [6]. Fourteen healthy participants completed a 90-minute mentally fatiguing task (the Stroop colour-word test, a well-validated measure of sustained cognitive effort) under two conditions: after seven days of creatine loading at 20g per day, and after seven days of placebo. The conditions were separated by a five-week washout period.
The results? Creatine improved accuracy on the sustained Stroop task by 4.9% compared to placebo (p = 0.026) [6]. Importantly, it didn’t prevent all the effects of mental fatigue, visuomotor response time and Flanker accuracy (a measure of shorter cognitive tasks) were still impaired in both conditions. This suggests creatine may be most useful for sustaining performance over prolonged periods of mental effort, rather than providing a blanket cognitive boost [6].
The researchers also noted that handgrip strength endurance was higher in the creatine condition (p = 0.022), confirming the supplement was physiologically active, the brain effects weren’t an isolated finding [6].
Evidence grade: Promising. Small sample size (14 participants), but the crossover design (where each participant acts as their own control) strengthens the reliability of the findings. The dose used, 20g/day for 7 days, is a loading protocol that most people won’t be taking day-to-day.
An earlier systematic review published in *Experimental Gerontology* in 2018 examined six RCTs involving 281 individuals [9]. The review concluded that short-term memory and intelligence/reasoning may be improved by creatine administration in healthy individuals. For other domains, long-term memory, attention, reaction time, executive function, the results were genuinely conflicting [9].
The vegetarian finding is worth dwelling on. Creatine is found almost exclusively in meat and fish. If you eat little or no animal protein, your baseline brain creatine levels may be meaningfully lower, and supplementation may therefore produce a more pronounced effect. This isn’t a reason for meat-eaters to dismiss creatine, but it does explain some of the inconsistency in results across studies [9].
Evidence grade: Promising. Six studies, 281 participants, the evidence base has grown since, but the core findings have broadly held.
The neuromodulator review from 2023 adds important mechanistic depth [12]. Beyond energy buffering, creatine appears to interact directly with NMDA receptors, the same receptors involved in synaptic plasticity and long-term potentiation, which are the cellular processes underlying learning and memory formation. Creatine also shows neuroprotective effects in laboratory models of neurological disease, reducing neuronal cell loss and dampening excitotoxicity [12].
This matters because it suggests creatine’s cognitive effects might not be purely about energy supply. It could be doing something more fundamental in how brain cells signal to each other, though much of this evidence comes from animal and cell studies rather than human trials.
Evidence grade: Early stage for the neuromodulator mechanism. Mechanistically compelling, but human trial evidence for these specific pathways remains limited.
Here’s where intellectual honesty is essential, and where some of the most authoritative voices in the field are urging caution.
In 2024, the European Food Safety Authority (EFSA), the body that evaluates health claims for European consumers, reviewed 23 human intervention studies on creatine and cognitive function [11]. Their conclusion was pointed: a cause-and-effect relationship has not been established between creatine supplementation and improvement in cognitive function. The panel noted that the acute effect on working memory appeared specifically at 20g/day for 5–7 days and was not reliably replicated at lower doses or with continuous supplementation [11].
A 2025 critical review in *The Journal of Nutrition* made a related argument: public and commercial enthusiasm for creatine as a cognitive enhancer has surged well ahead of the evidence, and cognitive and structural biases in how research is interpreted may be partly responsible [2]. This isn’t a dismissal of creatine’s potential, the authors explicitly say they’re not dismissing it, but a call for greater rigour before strong claims are made [2].
Several other gaps in the evidence deserve honest mention:
Dose and duration remain unclear. The studies that show the clearest effects tend to use loading doses (20g/day for 5–7 days) that most people would never maintain. It’s not yet established what happens with the lower chronic doses (3–5g/day) most commonly recommended [11].
We don’t know if brain creatine actually increases with supplementation in the doses studied. Surprisingly few studies have directly measured brain creatine concentrations alongside cognitive outcomes [8]. The brain is much harder to get creatine into than muscle, partly due to the blood-brain barrier.
The population question is unresolved. Most trials have been conducted in young, healthy adults or small samples of older adults. We don’t have robust data on people with early cognitive impairment, mild dementia, or other clinical conditions, arguably the populations most likely to benefit [3].
The muscle-brain axis hypothesis is intriguing but speculative. The idea that creatine supports BDNF production through exercise-induced myokine signalling is mechanistically plausible, but this is emerging research and the human trial evidence is not yet there [5].
Study quality is variable. The 2025 systematic review of older adult studies rated only one of its six included studies as “good” quality [3]. Much of the positive evidence comes from cross-sectional dietary studies, which show associations but cannot prove causation.
So, what should a sensible, informed person actually do with all of this?
Start with what’s clear. Creatine is one of the safest, most-studied supplements in existence. It has decades of safety data behind it. The question isn’t really about risk, it’s about whether there’s meaningful benefit for your brain specifically.
The honest picture is this: the evidence for creatine and cognitive function is genuinely promising, not proven. The most consistent signals are for processing speed, short-term memory, and sustained mental performance under fatigue. The effects appear strongest in older adults and people with low baseline dietary creatine (vegetarians and vegans in particular). And the dose that shows the clearest effects in trials is often a loading dose of 20g/day for 5–7 days, not the 3–5g/day maintenance dose most commonly used.
Here’s how to think about that practically:
If you’re 40–65, eat little or no meat, and are noticing any slowing in mental sharpness or energy, creatine supplementation is a low-risk, low-cost intervention worth trying. Start with 3–5g of creatine monohydrate daily, the most studied form, and give it 4–6 weeks. You don’t need to do a loading phase, though some studies suggest it may accelerate how quickly brain creatine levels rise.
If you’re a meat-eater with no particular concerns, the evidence is thinner, your baseline creatine levels are likely higher, and the incremental benefit smaller. That said, creatine is safe, inexpensive, and the downside risk is essentially nil at normal doses. If you’re exercising regularly (which amplifies the muscle-brain axis benefits via BDNF), there’s a reasonable case for including it.
If you’re hoping creatine will sharply boost your cognitive performance on its own, manage expectations carefully. This isn’t a cognitive supercharger. The effects, where they appear, are modest and meaningful, not dramatic. Think of it less as a performance enhancer and more as supporting the brain’s energy infrastructure, particularly under conditions of fatigue or ageing.
One practical footnote worth emphasising: creatine monohydrate is the form used in virtually all the research cited here. Fancier, more expensive forms have not demonstrated superior brain uptake in humans. The cheap, well-studied version is the one to choose.
The broader picture is genuinely exciting. Creatine is a molecule we’ve had in plain sight for decades, primarily thought of as a gym supplement, that may turn out to have a meaningful role in supporting brain health across the lifespan. The research isn’t finished, but the direction of travel is encouraging, and the risk of waiting for certainty while doing nothing is real for anyone in the 40–65 age window where brain energy metabolism starts to naturally decline.
As always, we’ll be watching the research, and we’ll update you when the evidence moves.
[1] Effects of Creatine Monohydrate Loading on Sleep Metrics, Physical Performance, Cognitive Function, and Recovery in Physically Active Men: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial (2025). DOI: 10.3390/nu17243831 | https://pubmed.ncbi.nlm.nih.gov/41470776/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12736258/
[2] Creatine Supplementation for Cognition: A Critical Perspective on Promise, Proof, and Public Perception (2025). DOI: 10.1016/j.tjnut.2025.07.016 | https://pubmed.ncbi.nlm.nih.gov/40744234/
[3] Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults (2025). DOI: 10.1093/nutrit/nuaf135 | https://pubmed.ncbi.nlm.nih.gov/40971619/
[4] Response to Letters to the Editor Received on Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults (2025). DOI: 10.1093/nutrit/nuaf261 | https://pubmed.ncbi.nlm.nih.gov/41405448/
[5] Creatine supplementation and muscle-brain axis: a new possible mechanism? (2025). DOI: 10.3389/fnut.2025.1579204 | https://pubmed.ncbi.nlm.nih.gov/40771202/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325066/
[6] Can Creatine Combat the Mental Fatigue-associated Decrease in Visuomotor Skills? (2020). DOI: 10.1249/MSS.0000000000002122 | https://pubmed.ncbi.nlm.nih.gov/31403610/
[7] Dose-Response of Creatine Supplementation on Cognitive Function in Healthy Young Adults (2023). DOI: 10.3390/brainsci13091276 | https://pubmed.ncbi.nlm.nih.gov/37759877/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526554/
[8] Creatine Supplementation and Brain Health (2021). DOI: 10.3390/nu13020586 | https://pubmed.ncbi.nlm.nih.gov/33578876/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916590/
[9] Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials (2018). DOI: 10.1016/j.exger.2018.04.013 | https://pubmed.ncbi.nlm.nih.gov/29704637/
[10] The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis (2024). DOI: 10.3389/fnut.2024.1424972 | https://pubmed.ncbi.nlm.nih.gov/39070254/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275561/
[11] Creatine and improvement in cognitive function: Evaluation of a health claim pursuant to article 13(5) of regulation (EC) No 1924/2006 (2024). DOI: 10.2903/j.efsa.2024.9100 | https://pubmed.ncbi.nlm.nih.gov/39564533/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574456/
[12] Creatine Activity as a Neuromodulator in the Central Nervous System (2023). https://pubmed.ncbi.nlm.nih.gov/38226371/
[15] The Effect of Creatine Nitrate and Caffeine Individually or Combined on Exercise Performance and Cognitive Function: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial (2024). https://pubmed.ncbi.nlm.nih.gov/38542677/
This article is for informational purposes only and does not constitute medical advice. Food supplements should not be used as a substitute for a varied and balanced diet and healthy lifestyle. If you are pregnant, breastfeeding, taking medication or have a medical condition, consult your doctor before taking any supplement. These statements have not been evaluated by the Food and Drug Administration (FDA) or the Medicines and Healthcare products Regulatory Agency (MHRA). This product is not intended to diagnose, treat, cure, or prevent any disease.
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