Creatine and Mental Performance: A Guide

By Drew Griffiths
BSc Sports & Exercise – Loughborough University – First Class Hons
MSc Exercise & Nutrition Science – University of Liverpool

Introduction

Creatine typically emerges in discussions concerning muscular adaptation and strength enhancement, often in contexts saturated with the particular atmosphere of training facilities: the rhythmic clank of dropped weights, that distinct smell of rubber mats and cleaning solution lingering in the air, protein shakers rattling about in gym bags like some kind of tribal percussion. That is where most individuals first encounter it, which is fine.

Here is the thing though, or rather, the thing that warrants closer examination. Creatine does not terminate its biological activity at skeletal muscle tissue. Your brain, that three-pound lump of particularly demanding tissue, consumes energy at rates that would make your quadriceps jealous, more than you probably realise when you are tired on a wet Tuesday afternoon staring at a screen and everything cognitive feels like wading through treacle.

Creatine plays a role, quite a substantial one actually, in how neural cells manage that energy. This has led to growing research interest in mood regulation, attentional capacity, mental fatigue, and even certain psychiatric conditions. The literature is expanding faster than most supplement categories, and that happens more than people admit when there is genuine mechanistic plausibility behind the hype.

I have to say, this is not a miracle supplement that will transform your consciousness or solve existential dread. It is also not merely marketing vapour. The truth, as tends to be the case with most things in applied neuroscience, sits somewhere practical and useful in the middle, waiting for people to stop shouting at each other online about it.

This guide is written to help you understand what creatine can and cannot do for mental performance and psychological wellbeing, presented with appropriate academic rigour but without the inaccessible terminology that makes most neuroscience papers read like they were written by someone actively trying to confuse you.

https://www.researchgate.net/figure/Infographic-of-the-benefits-of-creatine-supplementation-in-women-vegans-and-clinical_fig3_387534443

What creatine actually does in the brain

Creatine functions as a phosphate shuttle in cellular bioenergetics, which sounds tremendously complicated but is actually rather elegant when you break it down. In simple terms, it helps cells recycle energy more efficiently, particularly when metabolic demand exceeds immediate ATP (adenosine triphosphate, the molecular currency your cells use for energy) availability. It helps keep the lights on, so to speak, when demand is high and supply struggles to keep pace.

Your brain operates at extraordinary metabolic intensity throughout the day, consuming roughly twenty percent of your total energy expenditure despite representing only two percent of body mass. Thinking. Remembering. Regulating mood. Processing stress. That cognitive and emotional work accumulates, and the energy bill, metabolically speaking, adds up faster than most people appreciate.

Creatine acts as a temporal buffer in this system. It helps regenerate ATP by donating phosphate groups when the primary energy production pathways, your mitochondria (those are the microscopic power stations inside each cell, converting nutrients into usable energy), cannot keep up with neural demand. Short bursts of intense cognitive work. Stress responses. Sleep deprivation. These scenarios tax the system.

When energy supply struggles, cognitive and emotional functioning deteriorates in predictable ways. Focus fades like someone gradually turning down the brightness on your mental screen. Mood dips, sometimes subtly, sometimes dramatically. Mental tasks feel heavier than they should, like trying to run through water. Nobody likes that feeling (I don’t think).

The brain synthesises some creatine endogenously through enzymatic pathways, and it also imports creatine through specific membrane transporters. If those synthesis or transport systems fail, or rather when they fail because genetic disorders do exist here, serious neurological problems manifest. Developmental issues. Behavioural difficulties. Intellectual disability. That alone, the severity of creatine deficiency syndromes, tells you how fundamental creatine is to normal neural operation.

Supplementing creatine aims to top up those cerebral stores, not flood them into supraphysiological ranges, just support them when metabolic demand is high or when dietary intake is low. There is also accumulating evidence, though I should say the mechanisms are not fully mapped, that creatine interacts with neurotransmitter systems linked to mood regulation. Glutamate, the primary excitatory neurotransmitter. GABA, the primary inhibitory one. The systems that keep your thoughts steady rather than frantic or flat.

Another detail. Creatine appears to support mitochondrial function more broadly, beyond just the phosphocreatine system. When mitochondria struggle, whether through age, stress, or genetic variation, fatigue and depressed mood often follow like uninvited guests. Not always, but often enough that the correlation is clinically relevant.

Creatine and depression

Depression frequently presents with disrupted cerebral energy metabolism. That is not opinion or speculation as such. That pattern shows up consistently across neuroimaging studies, phosphorus magnetic resonance spectroscopy, and post-mortem tissue analysis, though I realise that last one is rather grim to mention.

Several clinical trials, mostly small but reasonably well-controlled, have explored creatine as an adjunctive treatment alongside standard antidepressant medication. Not instead of pharmacotherapy. Not as monotherapy. As an add-on. The distinction matters enormously. That’s why I’m writing in weird short sentences.

One study focused specifically on women with major depressive disorder. Creatine was added to their existing SSRI regimen. Mood scores, measured on the Hamilton Depression Rating Scale, improved faster in the creatine group. Remission rates increased. That matters when weeks of feeling terrible feel long, when you are eating cold pasta in the car after therapy because you cannot face going home yet.

A broader systematic review, was published in 2022, synthesised data across multiple trials and found moderate evidence for benefit, at least in some populations. Not across the board. Not for everyone. But enough signal in the noise to take seriously rather than dismiss as placebo effects or publication bias.

Dosages varied across studies, which complicates things. Participants varied. Study duration varied. Some trials used five grams daily. Others went higher, up to ten grams. That inconsistency limits our ability to draw strong conclusions about optimal dosing protocols, and that happens more than people admit in supplement research where pharmaceutical rigour is often absent.

One detail worth noting, and the data here is genuinely interesting. Women may respond more robustly than men to creatine for mood. Hormonal differences. Neurochemical differences. Differences in creatine transporter expression and kinetics. All differ slightly between sexes. The research is still catching up here, trying to map these interactions properly, which is rough because it means we are giving advice based on incomplete data.

Creatine is not a cure for depression. It may help support cellular energetics where depression has drained them. That is all we can say with confidence.

Cognitive performance and mental stamina

Creatine has been studied in healthy adult populations as well, not just clinical contexts, which gives us a broader picture of its cognitive effects. Under stress conditions. Sleep deprivation. Intense mental load. Creatine sometimes helps, though effect sizes are typically small to moderate.

Working memory, the cognitive system that holds information temporarily while you manipulate it, shows improvement in several studies. Reaction time tasks. Certain problem-solving paradigms. The effects are real but modest, which means they might matter in real-world contexts even if they do not revolutionise your cognitive capacity overnight.

I saw a discussion, I think it was on Reddit, where a student described revision week before finals. Long nights in the library. Cold coffee going lukewarm in a chipped mug. Brain fog settling in like weather. After a couple of weeks on creatine, they reported feeling steadier, not sharper exactly, just steadier, like the cognitive fatigue accumulated more slowly. That tracks reasonably well with what the controlled research shows, at least in my experience reading the literature. Although, it could be complete bollocks. I personally have seen significant increases in strength for example, but don’t recall any elevation in mood as such.

Older adults may benefit as well, possibly more than younger populations. Brain energy metabolism declines with age, mitochondrial function deteriorates, phosphocreatine stores drop. Creatine supplementation may help slow that slide. Memory consolidation. Executive planning. Mental endurance during cognitively demanding tasks. The effects are modest but potentially meaningful for quality of life, particularly for individuals experiencing age-related cognitive decline without dementia.

Again, nothing dramatic here. But useful fam.

Neuroprotection and long-term brain health

Animal studies, primarily in rodent models, show creatine protecting neurons in experimental models of Parkinson’s disease and Huntington’s disease. Less cell loss. Better motor outcomes. Slower disease progression. All the good stuff. The data is fairly consistent across multiple research groups, which increases confidence in the findings.

That does not automatically translate to humans, and I have to say the history of neuroscience is littered with compounds that worked beautifully in mice and failed spectacularly in human trials. But the mechanistic plausibility is there. The likely mechanism involves energy support and reduced oxidative stress. Cells that cope better with metabolic and oxidative challenges tend to last longer, much like a well-maintained engine versus one run constantly at redline.

Long-term human data remains limited. We have decades of safety data for creatine use in athletic contexts, but specific longitudinal studies tracking cognitive outcomes over twenty or thirty years do not really exist yet. This is an area to watch with interest rather than act on aggressively with strong recommendations.

Safety and tolerance

Creatine is one of the most extensively studied supplements available, which is actually saying something given how poorly most supplements are researched. For healthy adults, daily doses around three to five grams are considered safe even with long-term use extending years or decades, based on available safety monitoring data.

Side effects, when they appear at all, are usually mild. Some people notice gastrointestinal discomfort, particularly if they take too much at once or on an empty stomach. Occasionally muscle cramps. Adequate hydration usually helps, though the cramp mechanism is not entirely clear and might be coincidental rather than causal.

Kidney health concerns emerge frequently in online discussions, often stated with tremendous confidence by people who have not actually read the research. Studies in healthy individuals show no adverse effects on renal function. People with existing kidney disease should absolutely speak to a healthcare professional first because the safety data in that population is limited.

Interactions with psychiatric medications are not well mapped in the literature, which is frustrating but honest. No serious issues have been flagged in case reports or observational studies. Monitoring is sensible if you are taking antidepressants or mood stabilisers alongside creatine. Not out of fear, just prudence.

Pregnancy and breastfeeding data is limited. Best avoided there until we have better safety information. Not the end of the world to wait.

Summary comparison

Who might find this useful

Students and academics. Periods of heavy cognitive load can drain cerebral energy reserves rather quickly, particularly during examination periods or research deadlines when sleep becomes optional and meals become whatever you can eat while reading. Creatine may support mental stamina during these phases. Effects depend substantially on dietary habits and baseline creatine stores, which means vegetarians often respond more noticeably than omnivores.

Older adults. Age-related decline in brain energy metabolism is common, almost universal really. Creatine supplementation may help with memory retention and mental fatigue, particularly when combined with regular physical exercise and adequate nutrition. I remember a coach once saying that ageing athletes need to work smarter because working harder stops being an option eventually. Same principle applies to cognitive ageing.

People managing mood disorders. Some clinicians are exploring creatine as an adjunctive treatment. Never a replacement for standard care. Never monotherapy. Medical supervision matters here, not because creatine is dangerous but because depression is serious and managing it properly requires professional guidance.

High-performance professionals. Occupations that demand sustained focus under conditions of fatigue or stress may benefit from creatine’s metabolic support. Surgeons. Pilots. Air traffic controllers. Emergency medicine. Shift workers generally. The evidence is early but interesting, though I would not stake my career on it yet.

Vegetarians and vegans. Dietary creatine comes almost entirely from animal tissue, primarily meat and fish. Plant-based diets typically result in lower baseline creatine stores, which means supplementation tends to show clearer and more consistent cognitive effects in these populations. If you have been vegan for years and never supplemented, you might be surprised by the difference, which is fine, that is just biochemistry not moral judgment about dietary choices.

Common mistakes to avoid

Expecting instant results the day you start supplementing. Creatine accumulates gradually. Give it two weeks minimum. Ideally four.

Taking far more than needed because you think more equals better. It does not. Excess just gets excreted. You are literally making expensive urine.

Ignoring hydration, then blaming creatine for feeling rough. Creatine pulls water into cells. Drink accordingly.

Buying low-quality products with additives or poor purity. Creatine monohydrate is cheap to produce. If a product is expensive, you are paying for marketing not quality.

Skipping medical advice when health issues exist, particularly kidney conditions or psychiatric diagnoses. This is not being overly cautious. This is being sensible about medication interactions and underlying physiology.

Assuming everyone responds identically. Genetic variation in creatine transporters and synthesis enzymes means responses vary. Some people notice substantial effects. Others notice nothing. That part is rough when you were hoping for improvement, but it is honest.

Buyer checklist

Pure creatine monohydrate, preferably micronised for better mixability though this is cosmetic not functional.

Clear dosage guidance on packaging.

Third-party testing certification from organisations like Informed Sport or NSF.

Simple ingredient list without proprietary blends or unnecessary additives.

Proper storage packaging that keeps moisture out because creatine degrades when wet.

Sensible pricing, which for basic creatine monohydrate should be quite inexpensive.

Transparent brand support if you have questions, though most reputable companies are fine here.

Maintenance and use

Store in a cool dry place, not the bathroom where humidity accumulates. Use clean dry scoops to prevent moisture contamination. Check expiry dates though creatine is fairly stable. Take consistently, same time daily if possible though timing matters less than people think. Drink enough water throughout the day. No need to cycle on and off despite what bodybuilding forums claim, that advice is a hangover from the steroid world where cycling actually matters.

Now what

If you are curious, if this has sparked genuine interest rather than just vague supplement enthusiasm, start slowly and simply. A basic creatine monohydrate powder. Around three to five grams daily, mixed into whatever liquid you prefer though avoid hot beverages because heat degrades it. Give it time, at least a month, to assess effects properly.

• Some studies use 20g per day. I would recommend starting at 5g x 2 per day and assessing GI distress/comfort before increaseing.

Pay attention to how you actually feel, not just performance metrics on paper. Energy levels throughout the day. Mood stability when stress accumulates. Mental fatigue during demanding cognitive work. Subjective wellbeing matters more than hitting some arbitrary benchmark in a reaction time task.

If you manage a health condition or take medication regularly, particularly psychiatric medication, speak to a healthcare professional first. That is sensible not paranoid. They might say it is fine. They might want to monitor you. Either way, you have acted responsibly.

Creatine is not magic, despite what supplement marketing suggests with its glossy photographs of impossibly fit people looking intensely focused while holding shakers. But used appropriately, with realistic expectations and proper context, it can be a quiet support in the background, like a good assistant who helps your brain keep up when life demands more of it than usual, when you are sitting on the floor of your flat at midnight with notes spread everywhere and that smell of old coffee lingering and tomorrow still feels impossible but slightly less so than it did an hour ago.