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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Your brain is an energy-hungry organ that relies on a molecule called ATP to function. Creatine acts as an emergency energy reserve that can quickly replenish ATP when your brain is under stress. While your body produces some creatine naturally and you get more from meat and fish, many people, particularly older adults and vegetarians, may have suboptimal levels. Research shows creatine supplementation may help protect cognitive function during sleep deprivation, improve memory (especially in people over 65), and reduce mental fatigue under sustained mental effort.
The evidence is most compelling for three groups: adults over 50 with low meat intake, vegans and vegetarians, and people who regularly experience mental fatigue or brain fog. Studies suggest a daily dose of 3 to 5 grams of creatine monohydrate is effective, and the supplement has a strong safety record. However, most research studies are relatively small and short-term, and benefits appear minimal for younger, well-nourished people eating regular meat.
While the research is genuinely promising rather than conclusive, creatine is affordable and exceptionally safe, making it a reasonable option for people in these higher-benefit groups who want to give their brain’s energy system optimal support.
Verdict: Creatine shows promising evidence for protecting brain function under stress and improving memory in older adults and vegetarians, though larger, longer studies are still needed before drawing firm conclusions.
You probably know creatine as the thing serious gym-goers keep in their shaker bottles. Maybe you’ve dismissed it as a muscle supplement, something for people half your age who want to lift heavier. But what if creatine’s most important job isn’t in your biceps at all? What if the organ that needs it most is sitting between your ears, and quietly running low?
Here’s the thing most people don’t realise: your brain is one of the most energy-hungry organs in your body. It accounts for roughly 2% of your body weight but consumes a disproportionate share of your body’s energy. And creatine, that humble, affordable white powder, plays a critical role in keeping that energy system topped up. The research emerging on creatine and cognitive function is genuinely fascinating. It’s not hype. It’s bioenergetics. And the implications for anyone in their 40s, 50s or 60s who wants to stay sharp, resilient and mentally clear are worth understanding properly.
Vitacuity reviewed over 1.77 million research papers and identified the most relevant studies on this topic. Here is what the evidence actually shows.
To understand why creatine matters for your brain, you need to understand a little about how your brain makes energy.
Your brain runs almost entirely on ATP, adenosine triphosphate, which is essentially the universal currency of cellular energy. When your neurons fire, when you think, focus, remember or reason, ATP gets used up. The question is how quickly your brain can replenish it.
This is where creatine comes in. Creatine is stored in cells as phosphocreatine (PCr), which acts as a rapid-recharge buffer, a kind of emergency energy reserve that can regenerate ATP almost instantly when demand spikes. Think of it like a backup power generator that kicks in the moment your grid starts to dip [5].
The brain produces some of its own creatine, and you get more from food, primarily meat and fish. But here’s the catch: if you eat little or no animal protein, your brain’s creatine stores may be lower than optimal. And as you age, creatine metabolism may become less efficient, meaning the buffer your brain relies on gets thinner over time [13].
Creatine also appears to do more than just manage energy. Research suggests it has anti-inflammatory effects, reduces oxidative stress, and may interact with the muscle-brain axis, a communication pathway between skeletal muscle and the brain that influences neuroprotection and cognitive performance [5]. One particularly intriguing area of research involves something called BDNF (brain-derived neurotrophic factor), a protein often described as “fertiliser for the brain”, which creatine may help to upregulate indirectly through this muscle-brain axis [5].
Evidence grade: Promising, small human trials with consistent direction of effect
Some of the most compelling creatine-and-brain research comes from studies that deliberately stress the brain, through sleep deprivation, oxygen restriction, or sustained mental effort, and then measure what creatine does.
A 2006 double-blind study divided participants into a creatine group (5g, four times a day for 7 days) and a placebo group, then subjected them to 24 hours of sleep deprivation with mild exercise. At the 24-hour mark, the creatine group showed significantly less deterioration across multiple cognitive measures, including random movement generation, choice reaction time, balance, and mood state. The researchers noted that the tasks most protected by creatine were those placing heavy demands on the prefrontal cortex, the part of the brain responsible for decision-making, working memory and impulse control [15].
A follow-up 2007 study extended this to 36 hours of sleep deprivation. The creatine group performed significantly better than the placebo group on complex central executive tasks, but only at the 36-hour mark, suggesting that creatine’s benefits may become most apparent when the brain is under prolonged, serious stress [11].
Perhaps the most striking of these studies came in 2015, when researchers supplemented 15 healthy adults with creatine for 7 days, raising brain creatine by an average of 9.2%, then exposed them to a hypoxic (low-oxygen) environment for 90 minutes. The hypoxia impaired a range of cognitive functions. But creatine supplementation specifically restored attentional capacity and increased corticomotor excitability. The authors concluded that creatine may protect the brain by maintaining neuronal membrane potentials when energy supply is compromised [8].
What this tells us is that creatine doesn’t just give your brain a general boost, it appears to act as a buffer against cognitive decline under conditions of energy stress. Sleep deprivation, prolonged mental effort, low oxygen, these all drain brain energy. Creatine helps maintain the reserve.
Evidence grade: Promising to Moderate, multiple RCTs with consistent findings in older adults
A 2023 systematic review and meta-analysis published in *Nutrition Reviews* analysed 10 randomised controlled trials (RCTs) examining the effect of creatine supplementation on memory in healthy humans. The overall result showed a statistically significant improvement in memory performance compared to placebo, with a standard mean difference (SMD) of 0.29 [7].
That number might sound modest, but here’s what makes it interesting: when the researchers looked at older adults specifically (aged 66–76), the effect size jumped dramatically to an SMD of 0.88, which is considered a large effect. In younger participants (aged 11–31), the effect was essentially zero. This age-dependent pattern makes biological sense: younger brains typically have adequate creatine stores and efficient energy metabolism. Older brains may be running closer to the edge, meaning that topping up creatine reserves makes a measurable difference [7].
This age-related finding was reinforced by a 2025 systematic review that searched eight electronic databases and identified six studies covering 1,542 participants (average age 55+). Five of the six studies, 83.3%, reported a positive relationship between creatine and cognition, with memory and attention showing the strongest benefits. The reviewers were honest about the limitations: two studies were rated “fair” quality and three were rated “poor”, meaning we need more rigorous trials before drawing firm conclusions. But the direction of effect is consistent [1].
A 2018 systematic review of six RCTs (281 participants) added nuance: short-term memory and intelligence/reasoning showed the most consistent improvements, while vegetarians responded better than meat-eaters on memory tasks, which makes sense given that plant-based diets contain little to no dietary creatine, meaning their baseline brain stores may be lower [10].
Evidence grade: Promising, human RCT data with mixed results depending on the type of cognitive task
A 2024 study took a novel approach: rather than spreading creatine doses over weeks, researchers gave participants a high single dose of creatine monohydrate (0.35g per kg of body weight) while they performed cognitive tests during sleep deprivation. The study found improvements in cognitive performance and measurable changes in cerebral high-energy phosphates, suggesting that even a one-off high dose can temporarily boost brain creatine availability and support cognition under stress [12].
A 2020 crossover trial with 14 healthy participants tested creatine (20g/day for 7 days) against placebo during a 90-minute mentally fatiguing Stroop task. The results were mixed but instructive: creatine supplementation improved accuracy on the Stroop task (+4.9% compared to placebo) and improved physical strength endurance, but it did not prevent mental fatigue from impairing visuomotor response time or short Flanker task accuracy. The authors suggested that creatine may be more effective during prolonged mental tasks (like a 90-minute football game) than during short bursts of cognitive effort [6].
Interestingly, the same study found that motivation and vigour scores were slightly lower in the creatine condition compared to placebo, a counterintuitive finding the researchers noted warrants further investigation. This is a good example of why honest science matters: the picture is nuanced, not uniformly positive.
Evidence grade: Promising, observational and mechanistic data, fewer RCTs in these specific groups
If you eat meat regularly, you’re getting creatine from your diet. If you don’t, you’re almost certainly not getting enough, and your brain may be paying the price quietly.
A 2024 narrative review highlighted that vegans and vegetarians typically have significantly lower creatine stores, and that supplementation in these groups improves both physical and cognitive performance more markedly than in omnivores [13]. The 2018 systematic review similarly found that vegetarians showed greater memory improvements from creatine than meat-eaters [10]. This isn’t surprising, it’s simply a matter of baseline. If you’re already deficient, topping up produces a bigger effect.
The same 2024 review also flagged an often-overlooked group: women. Women typically have lower baseline intramuscular creatine levels than men, and supplementation may help alleviate fatigue-related symptoms, particularly during the early follicular and luteal phases of the menstrual cycle. The evidence here is still early-stage, but it’s a plausible and biologically grounded direction [13].
Evidence grade: Early-stage, small feasibility studies, but mechanistically compelling
Some of the most thought-provoking recent research involves creatine and conditions defined by energy disruption in the brain.
A 2024 feasibility study in *Nutrients* gave 16g of creatine monohydrate daily for six weeks to 14 participants with ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome). Brain magnetic resonance spectroscopy (MRS) scans, which can directly measure creatine levels in specific brain regions, confirmed that creatine did successfully increase brain creatine concentrations in both the prefrontal cortex and the anterior cingulate cortex. Participants also reported improvements in fatigue and some aspects of cognition. Eleven of the 14 participants completed the study. The researchers were appropriately cautious, this was a feasibility study with no placebo control, but the direct brain imaging data is noteworthy [9].
A 2025 narrative review on post-viral fatigue syndrome (the broader category that includes long COVID-related cognitive fatigue) identified bioenergetic disruption and mitochondrial dysfunction as key features of the condition, and proposed creatine as a potential therapeutic target precisely because of its role in maintaining cellular energy homeostasis [4].
This is not to say creatine is a treatment for these conditions. The evidence is nowhere near that strong. But the mechanistic logic is sound, and the feasibility data is encouraging enough to warrant properly powered trials.
Let’s be honest about the gaps, because they matter.
The research is still relatively thin. The 2025 systematic review on cognition in older adults found only six eligible studies, and most were rated fair or poor quality. We need larger, longer, better-designed RCTs, especially in people over 55, before we can speak with real confidence [1].
The optimal dose isn’t settled. Studies have used everything from 2.2g to 20g per day, and the 2023 meta-analysis found that dose didn’t significantly influence outcomes [7]. This is unusual and suggests either that the effect is relatively dose-insensitive within a range, or that the studies weren’t well-powered enough to detect dose differences. We don’t yet know what the minimum effective dose for cognitive benefits actually is.
Short-term vs long-term effects are unclear. Most studies run for days to weeks. We don’t have good data on what creatine supplementation does to cognitive function over months or years, whether there are diminishing returns, or whether the brain adapts and downregulates its own creatine synthesis in response to supplementation [1].
The results are mixed for some cognitive domains. The 2018 systematic review found consistent effects for short-term memory and reasoning, but conflicting or null results for long-term memory, attention, executive function, reaction time and mental fatigue in some populations [10]. The 2020 trial found no effect on short visuomotor tasks even when a benefit appeared on sustained Stroop performance [6]. The effects appear to be context-dependent, more pronounced when the brain is under energy stress than when it’s cruising along normally.
The muscle-brain axis mechanism is still theoretical. The proposed pathway through which creatine may influence BDNF and neuroprotection via myokines is biologically plausible and exciting, but it remains a hypothesis requiring direct human testing [5].
Younger, well-nourished omnivores may see little benefit. The evidence consistently suggests that the cognitive effects of creatine are most pronounced in older adults, vegetarians/vegans, and people whose brains are under some form of energy stress. If you’re 32, eating steak twice a week and sleeping perfectly, creatine probably won’t noticeably sharpen your thinking [7][10].
Here’s how a sensible, well-informed person should think about this.
Creatine monohydrate is one of the safest, most well-researched and cheapest supplements in existence. The evidence for cognitive benefits is not at the level of “proven treatment”, but it’s genuinely promising, especially if you’re over 55, eat little or no meat, experience regular mental fatigue, or simply want to give your brain’s energy system the best possible foundation.
The case is particularly compelling in three groups:
If you’re 50+ and your diet is low in meat or fish: Your brain creatine levels are likely suboptimal. Supplementing makes straightforward sense. The risk-benefit calculation is clear, the risk of supplementing at normal doses is minimal (creatine is well-tolerated and has an excellent safety record), while the potential benefit to memory, attention and cognitive resilience is meaningful.
If you’re a vegan or vegetarian: This is arguably the strongest case. Multiple studies show vegetarians and vegans respond more robustly to creatine supplementation for cognitive outcomes precisely because their baseline stores are lower [10][13]. Supplementing daily is the practical, evidence-supported default.
If you experience regular mental fatigue, brain fog or sleep disruption: The sleep deprivation research is consistent in one important respect, creatine appears to protect the prefrontal cortex under conditions of energy stress [11][15]. If your brain regularly runs on less than it needs, creatine may help maintain the reserve.
What dose? Studies showing cognitive benefits have used 3–5g per day for maintenance (the approach most commonly used in longer trials) up to loading doses of 20g per day for short periods. A sensible approach based on the available evidence is 3–5g daily as a consistent maintenance dose. Creatine monohydrate is the preferred form, it’s the most studied, most bioavailable, and the cheapest [13].
Timing? Creatine isn’t like caffeine, it doesn’t work immediately. Brain creatine levels take days to weeks to rise with supplementation [8]. Consistency matters more than timing.
Safety note: Creatine monohydrate has been studied extensively and has a strong safety profile at normal doses. It is not a stimulant and does not cause the jitteriness or sleep disruption associated with caffeine. Most people tolerate it very well, though taking it with food can reduce the rare occurrence of stomach discomfort.
The bottom line: this is a supplement that costs pennies per day, has decades of safety data behind it, and is showing consistent, if still emerging, evidence for cognitive benefits, particularly in the people most likely to be reading this. That’s a reasonable bet.
[1] Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults (2025). DOI: https://doi.org/10.1093/nutrit/nuaf135 | PubMed: https://pubmed.ncbi.nlm.nih.gov/40971619/
[2] 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: https://doi.org/10.3390/nu17243831 | PubMed: https://pubmed.ncbi.nlm.nih.gov/41470776/ | PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12736258/
[4] Creatine and post-viral fatigue syndrome: an update (2025). DOI: https://doi.org/10.1080/15502783.2025.2517278 | PubMed: https://pubmed.ncbi.nlm.nih.gov/40481620/ | PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147496/
[5] Creatine supplementation and muscle-brain axis: a new possible mechanism? (2025). DOI: https://doi.org/10.3389/fnut.2025.1579204 | PubMed: https://pubmed.ncbi.nlm.nih.gov/40771202/ | PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325066/
[6] Can Creatine Combat the Mental Fatigue-associated Decrease in Visuomotor Skills? (2020). DOI: https://doi.org/10.1249/MSS.0000000000002122 | PubMed: https://pubmed.ncbi.nlm.nih.gov/31403610/
[7] Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials (2023). DOI: https://doi.org/10.1093/nutrit/nuac064 | PubMed: https://pubmed.ncbi.nlm.nih.gov/35984306/ | PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999677/
[8] Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation (2015). PubMed: https://pubmed.ncbi.nlm.nih.gov/25632150/
[9] Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla (2024). DOI: https://doi.org/10.3390/nu16193308 | PubMed: https://pubmed.ncbi.nlm.nih.gov/39408275/ | PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11478479/
[10] Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials (2018). DOI: https://doi.org/10.1016/j.exger.2018.04.013 | PubMed: https://pubmed.ncbi.nlm.nih.gov/29704637/
[11] Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior (2007). PubMed: https://pubmed.ncbi.nlm.nih.gov/17046034/
[12] Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation (2024). PubMed: https://pubmed.ncbi.nlm.nih.gov/38418482/
[13] Creatine Supplementation Beyond Athletics: Benefits of Different Types of Creatine for Women, Vegans, and Clinical Populations, A Narrative Review (2024). DOI: https://doi.org/10.3390/nu17010095 | PubMed: https://pubmed.ncbi.nlm.nih.gov/39796530/ | PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723027/
[15] Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol (2006). DOI: https://doi.org/10.1007/s00213-005-0269-z | PubMed: https://pubmed.ncbi.nlm.nih.gov/16416332/
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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