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 supplement, but emerging research suggests it may also support brain function. Your brain uses enormous amounts of energy to think and remember, and creatine helps cells regenerate ATP, the molecule that powers this energy. Studies show that taking creatine can raise brain creatine levels by around 11% in eight weeks.
The strongest evidence comes from older adults aged 66 to 76, who showed meaningful improvements in working memory and cognitive performance when taking 5 grams daily for six weeks. People who eat little meat or fish, and vegetarians, show the largest benefits because their baseline brain creatine is lower. A small study of Alzheimer’s patients found cognitive improvements, but it had no control group, so those results are preliminary. The European Food Safety Authority declined to approve a formal health claim, saying the evidence was not yet strong enough, though they acknowledged the research is promising.
Creatine monohydrate is inexpensive, widely available, and has a strong safety record. The research is most consistent at 5 grams daily for ongoing use, though some studies used higher loading doses. Important gaps remain: we do not know the optimal dose for brain health, whether effects differ between men and women, or how long-term supplementation affects cognitive decline over years.
Verdict: If you are over 50, eat little meat, or are interested in protecting cognitive function as you age, creatine supplementation shows genuine promise based on current evidence, though it is not a substitute for sleep, exercise, and a balanced diet.
What if one of the most well-researched supplements in sports nutrition turned out to be equally interesting for your brain? Most people associate creatine with gym bags, protein shakes and muscle gain. But here’s the question worth sitting with: what if the same molecule that helps your muscles fire harder under pressure is also quietly running an energy support system inside your brain, and what if, especially as you age, topping it up could make a meaningful difference to how well you think, remember and process information?
Vitacuity has reviewed over 1.77 million research papers and selected the most relevant studies on this topic. What follows is an honest, careful look at what the science actually says, and what it doesn’t.
To understand why creatine might matter for your mind, you need to understand one thing about the brain: it is extraordinarily greedy for energy. Your brain accounts for roughly 2% of your body weight but consumes around 20% of your body’s energy at rest. Every time you hold a phone number in your head, recall where you left your keys, or follow a complex argument, your neurons are burning through adenosine triphosphate (ATP), the cellular currency of energy, at an impressive rate.
This is where creatine comes in. Creatine plays a central role in what’s called the phosphocreatine energy buffer system. Think of it like a rapid-response energy reserve. When your cells burn through ATP quickly, creatine phosphate donates a phosphate group to regenerate ATP almost instantly, buying your neurons a few critical extra moments of power before slower energy systems catch up [6].
Your body produces some creatine naturally (mainly in the liver and kidneys), and you get more from eating meat and fish. But your brain’s creatine stores are not limitless, and research using a technique called magnetic resonance spectroscopy, which can measure chemical concentrations inside the brain without surgery, has confirmed that oral creatine supplementation does measurably raise brain creatine levels [3, 14]. In one 2025 pilot trial, 20 g/day of creatine monohydrate raised whole brain creatine by 11% over eight weeks [3].
So the hypothesis is logical and biologically grounded: if brain energy supports cognitive performance, and creatine supports brain energy, does supplementation actually move the needle on how we think?
Evidence grade: Promising, some consistent human data, but study sizes are modest and findings are not uniform across all populations
The most compelling early human evidence came from a 2003 double-blind, placebo-controlled, crossover trial published in *Proceedings of the Royal Society B* [6]. Forty-five young adult vegetarians were given either 5 g/day of creatine monohydrate or a placebo for six weeks. The results were striking: creatine supplementation produced a significant improvement (p < 0.0001) in both working memory, measured using the backward digit span task, where you repeat a sequence of numbers in reverse, and intelligence test scores using Raven's Advanced Progressive Matrices. The researchers concluded that brain energy capacity plays a "dynamic and significant role" in influencing cognitive performance [6].
Why vegetarians? Because vegetarians have lower baseline dietary creatine intake (it comes from meat and fish), so they start from a lower brain creatine level, meaning supplementation has more room to make a difference. This is an important nuance we’ll come back to.
Fast forward twenty years, and the picture has grown more complex but remains genuinely interesting. The largest RCT on creatine and cognition to date, published in *BMC Medicine* in 2023, recruited 123 participants, roughly half vegetarians and half omnivores, in a preregistered, double-blind, placebo-controlled crossover design [7]. Participants took 5 g/day for six weeks. The results showed Bayesian evidence supporting a small beneficial effect of creatine on backward digit span (working memory), though it bordered statistical significance (p = 0.064). The authors were appropriately measured in their conclusions, noting that the effect, while small, is “well worth investigating” given creatine’s safety profile and wide availability, and that a small effect scaled across time and many people could still be meaningful [7].
Evidence grade: Promising, meta-analysis of RCTs, but significant heterogeneity in study designs
A 2023 systematic review and meta-analysis published in *Nutrition Reviews* pooled data from 10 randomised controlled trials examining creatine supplementation and memory performance in healthy individuals [8]. The headline finding: creatine supplementation improved memory compared to placebo, with a standard mean difference of 0.29 (95% CI: 0.04–0.53; p = 0.02) [8].
The most striking subgroup finding was in older adults aged 66–76 years, where the effect size jumped to 0.88 (95% CI: 0.22–1.55; p = 0.009), a notably larger signal than in younger participants aged 11–31, where the effect was not significant (SMD = 0.03; p = 0.72) [8].
This age-related pattern makes biological sense. As we age, our brain’s metabolic efficiency declines and our dietary creatine intake often decreases (we tend to eat less meat). Lower baseline creatine levels mean more room for supplementation to have an effect. A separate 2025 systematic review covering six studies and 1,542 participants aged 55 and older found that five out of six studies (83.3%) reported a positive relationship between creatine and cognition, particularly in the domains of memory and attention [2]. However, the quality of the evidence was rated as only one “good” study, two “fair” and three “poor”, so these findings are encouraging but should be treated as preliminary [2].
Evidence grade: Promising, small sample, single study, but mechanistically plausible
One particularly interesting angle is creatine’s effect not during normal rested conditions, but when the brain is under metabolic stress. A 2007 study published in *Physiology & Behavior* examined what happened when creatine supplementation met severe sleep deprivation [11].
Participants took 5 g of creatine monohydrate four times daily (20 g/day total) for seven days before undergoing 24 and 36 hours of sleep deprivation combined with moderate intermittent exercise. At 36 hours of sleep deprivation, the creatine group significantly outperformed the placebo group on a central executive task (p < 0.05), with the creatine group showing a linear improvement throughout the experiment while the placebo group showed no significant change [11].
This suggests creatine may be particularly useful as a cognitive buffer during periods of high demand, not just a baseline enhancer. The mechanism fits: sleep deprivation depletes brain energy reserves, and creatine helps maintain ATP availability under those conditions [14].
Evidence grade: Early stage, single-arm, open-label pilot trial, 20 participants, no placebo control
A 2025 pilot trial, the first human study to investigate creatine supplementation in people with confirmed Alzheimer’s disease, deserves careful attention and equally careful caveats [3]. Twenty participants with dementia due to probable Alzheimer’s disease (mean age 73.1 years) received 20 g/day of creatine monohydrate for eight weeks. There was no placebo arm.
The results were notable. Whole brain creatine increased by 11% (p < 0.001). Lymphocyte ATP production increased 2.9-fold (p = 0.004). And on cognitive measures: global fluid cognition improved by 4.4 points (p = 0.004), working memory improved by 8 points (p < 0.001), and executive function improved by 5 points (p = 0.05) [3].
These are meaningful numbers. But the trial design, no control group, open-label, only 20 people, means we cannot rule out placebo effects or natural variation. The researchers themselves describe it as a feasibility study justifying further investigation, not proof of efficacy [3]. A narrative review published in *Sports Medicine* in 2023 also highlights creatine’s potential for traumatic brain injury, depression and anxiety, while noting that sex and age differences in response remain poorly understood [14].
This is genuinely promising early-stage data. It is not a reason to abandon conventional treatment. It is a reason for larger, better-controlled trials to happen quickly.
Evidence grade: Conflicted, sufficient signal for further research, but not yet strong enough for a formal health claim
In 2024, the European Food Safety Authority (EFSA) evaluated a formal application for a health claim linking creatine to improved cognitive function [9]. Their conclusion was that a cause-and-effect relationship had not been established.
This is worth understanding carefully, because EFSA’s bar for a health claim is deliberately very high, and their reasoning is instructive rather than dismissive. The panel noted that the acute effects of creatine on working memory were observed in two studies at a loading dose of 20 g/day for 5–7 days, but were not consistently seen at lower doses of 2.2–14 g/day or with continuous lower-dose supplementation [9]. They also noted that the available mechanistic evidence was considered weak for regulatory purposes.
This doesn’t mean creatine doesn’t work for the brain. It means the evidence hasn’t yet met the strict threshold required to put a specific claim on a product label. The research picture is more nuanced than a binary yes/no: dose matters, baseline creatine status matters, age matters, and the cognitive domain being tested matters. Conflicted findings in nutrition science almost always reflect these kinds of methodological differences rather than a genuine contradiction in reality [9].
There are real and important gaps in this research, and intellectual honesty requires spelling them out.
Dose is genuinely unresolved. The strongest cognitive signals in the research appear at higher loading doses of 20 g/day for 5–7 days. The more commonly recommended long-term dose of 3–5 g/day shows smaller, more inconsistent effects [6, 7, 9]. We don’t yet know whether a loading phase followed by maintenance dosing is the optimal brain protocol, the data simply don’t exist yet at scale.
Baseline creatine level almost certainly matters. The clearest evidence for cognitive benefit appears in populations with lower baseline creatine, vegetarians and older adults [6, 8, 15]. For omnivores with a regular meat intake, the effect may be smaller. No study has yet stratified participants by objectively measured brain creatine levels at baseline and tracked cognitive outcomes accordingly.
The sex question is open. Several studies hint at differential responses between men and women, and the 2025 Alzheimer’s pilot found mitochondrial respiration improvements specifically in female participants [3]. A 2023 review flagged sex and age differences as a key gap in the literature [14]. This area needs dedicated investigation.
Most evidence is in healthy populations. The 2025 systematic review of older adults noted that almost all included studies examined community-dwelling healthy individuals, not people with mild cognitive impairment or early-stage dementia [2]. The Alzheimer’s pilot was the first human study in a clinical population and was tiny and uncontrolled.
Long-term data is thin. The longest human trials reviewed here run to 24 weeks. We have no data on whether sustained supplementation over years changes cognitive trajectory meaningfully, which is ultimately the question that matters most for healthy ageing.
Animal studies remain animal studies. A 2025 rat study on spatial working memory using the Morris water maze is included in our research base [1, 10]. Rodent results in cognitive research frequently do not translate directly to humans, interesting as a mechanistic signal, but not a basis for human recommendations.
Here’s how a sensible, well-informed person should think about creatine and the brain.
The evidence for creatine improving working memory in older adults and in people under cognitive stress is genuinely promising, not hype, not certainty, but real signal worth acting on. The meta-analysis finding a standard mean difference of 0.88 in adults aged 66–76 is not trivial [8]. The biological mechanism is well understood [6, 14]. And creatine monohydrate has one of the strongest safety profiles of any supplement studied, no serious adverse effects have been identified at normal doses in healthy adults.
Here is the practical logic:
If you are over 50, or if you eat little meat or fish: Your baseline brain creatine is likely lower than it could be. The case for supplementing is straightforward. Creatine monohydrate is inexpensive, widely available, and the research consistently shows the largest cognitive benefit in exactly this population [2, 8].
What dose? The evidence for cognitive effects is most consistent at around 5 g/day for sustained use, with some evidence that a short loading phase of 20 g/day for 5–7 days may produce more acute effects [9]. A sensible approach is to start with 5 g/day, a level used in most of the longer trials, taken consistently. This is a low-cost, low-risk intervention.
How to take it: Creatine monohydrate powder dissolved in water is the most studied form. It doesn’t need to be taken at a specific time of day. Consistency matters more than timing.
What to expect: This is not a nootropic that produces a noticeable effect in the first week. Think of it as long-term infrastructure, supporting the energy systems your brain relies on, especially as the metabolic demands of life accumulate. If you are a meat-eater in your 30s looking for a dramatic mental edge, the evidence doesn’t strongly support that expectation. If you are in your 50s or 60s, eating a plant-heavy diet, and interested in doing everything reasonable to support cognitive resilience over the coming decades, creatine deserves a place in that conversation.
One honest note on the regulatory caution: EFSA did not approve a health claim, and that matters [9]. But regulatory approval and practical wisdom are not the same thing. A supplement that is safe, cheap, widely studied, and shows consistent positive trends in the population most at risk of cognitive decline is worth taking seriously, even before the perfect trial has been published. Apply common sense: the downside risk here is low; the potential upside is meaningful.
Creatine is not a miracle. It is not going to reverse cognitive decline or replace sleep, exercise and a good diet. But it may quietly help keep the lights on in exactly the brain circuits you most want to protect. That’s worth knowing.
[1] Effect of Creatine Monohydrate on Spatial Working Memory, Body Weight, and Food Intake in Male and Female Rats. (2025). DOI: 10.3390/nu17132218 | https://pubmed.ncbi.nlm.nih.gov/40647322/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251355/
[2] Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults. (2025). *Nutrition Reviews*. DOI: 10.1093/nutrit/nuaf135 | https://pubmed.ncbi.nlm.nih.gov/40971619/
[3] Creatine Monohydrate Supplementation in Alzheimer’s Disease, Feasibility Pilot Trial (PMID: 41445099). (2025). *Alzheimer’s & Dementia*. DOI: 10.1002/alz70858_100477 | https://pubmed.ncbi.nlm.nih.gov/41445099/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739067/
[4] 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). *Nutrients*. DOI: 10.3390/nu17243831 | https://pubmed.ncbi.nlm.nih.gov/41470776/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12736258/
[5] Response to Letters to the Editor Received on Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults. (2025). *Nutrition Reviews*. DOI: 10.1093/nutrit/nuaf261 | https://pubmed.ncbi.nlm.nih.gov/41405448/
[6] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. (2003). *Proceedings of the Royal Society B: Biological Sciences*. DOI: 10.1098/rspb.2003.2492 | https://pubmed.ncbi.nlm.nih.gov/14561278/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1691485/
[7] Sterr J et al. The effects of creatine supplementation on cognitive performance, a randomised controlled study. (2023). *BMC Medicine*. DOI: 10.1186/s12916-023-03146-5 | https://pubmed.ncbi.nlm.nih.gov/37968687/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647179/
[8] Prokopidis K et al. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. (2023). *Nutrition Reviews*. DOI: 10.1093/nutrit/nuac064 | https://pubmed.ncbi.nlm.nih.gov/35984306/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999677/
[9] EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA). Creatine and improvement in cognitive function: Evaluation of a health claim pursuant to article 13(5) of regulation (EC) No 1924/2006. (2024). *EFSA Journal*. DOI: 10.2903/j.efsa.2024.9100 | https://pubmed.ncbi.nlm.nih.gov/39564533/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574456/
[10] Effect of Creatine Monohydrate on Spatial Working Memory, Body Weight, and Food Intake in Male and Female Rats. (2025). [Duplicate citation, same study as [1]]. DOI: 10.3390/nu17132218 | https://pubmed.ncbi.nlm.nih.gov/40647322/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251355/
[11] McMorris T et al. Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. (2007). *Physiology & Behavior*. https://pubmed.ncbi.nlm.nih.gov/17046034/
[12] Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults. (2025). [Duplicate citation, same study as [2]]. *Nutrition Reviews*. DOI: 10.1093/nutrit/nuaf135 | https://pubmed.ncbi.nlm.nih.gov/40971619/
[13] Creatine Monohydrate Supplementation in Alzheimer’s Disease, Feasibility Pilot Trial (PMID: 41445099). (2025). [Duplicate citation, same study as [3]]. *Alzheimer’s & Dementia*. DOI: 10.1002/alz70858_100477 | https://pubmed.ncbi.nlm.nih.gov/41445099/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739067/
[14] Forbes SC et al. “Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function. (2023). *Sports Medicine*. DOI: 10.1007/s40279-023-01870-9 | https://pubmed.ncbi.nlm.nih.gov/37368234/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10721691/
[15] Avgerinos KI et al. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. (2018). *Experimental Gerontology*. DOI: 10.1016/j.exger.2018.04.013 | https://pubmed.ncbi.nlm.nih.gov/29704637/
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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