Creatine, the supplement long associated with gym culture and muscle building, is emerging as one of the more promising compounds for supporting brain health — including in people living with Alzheimer’s disease. A 2024 systematic review and meta-analysis of 16 randomized controlled trials found that creatine supplementation showed significant positive effects on memory, attention time, and processing speed, with subgroup analysis revealing greater benefits in females, individuals aged 18-60, and those with existing diseases compared to healthy young males. For the millions of families navigating cognitive decline, that last detail matters most. The research is still young, but it is moving fast. In 2025, the CABA pilot trial at the University of Kansas provided the first human evidence that creatine supplementation is feasible in Alzheimer’s patients, showing an 11 percent increase in brain creatine levels along with moderate improvements in working memory and executive functioning.
Meanwhile, studies on sleep deprivation, traumatic brain injury, depression, and menopause-related cognitive changes are all pointing in the same direction: the brain needs energy, and creatine helps supply it. This article covers the science behind creatine’s role in brain metabolism, what the clinical evidence actually shows for different populations, where the gaps remain, and what caregivers and patients should consider before reaching for a supplement bottle. The brain uses roughly 20 percent of the body’s total resting energy despite being only about 2 percent of body mass, making it one of the most energy-hungry organs we have. Between 5 and 10 percent of the body’s creatine is stored in the brain, where it serves as a rapid energy reservoir. Understanding this basic biology helps explain why researchers have turned their attention from biceps to neurons — and why the results, while preliminary, have generated real scientific interest.
Table of Contents
- How Does Creatine Actually Support Brain Health Beyond the Gym?
- What the Alzheimer’s Research Actually Found — And What It Didn’t
- Sleep, Stress, and the Tired Brain
- Who Benefits Most — And Who Should Be Careful
- Creatine, Depression, and the Limits of Enthusiasm
- Traumatic Brain Injury and Neuroprotection
- Where the Science Goes From Here
- Conclusion
- Frequently Asked Questions
How Does Creatine Actually Support Brain Health Beyond the Gym?
Creatine works in the brain much the same way it works in muscle tissue, but the stakes are different. ATP, the cell’s primary energy currency, transfers its high-energy phosphate group to creatine to form phosphocreatine. When neurons face sudden spikes in demand — during complex problem-solving, during a stressful conversation, during the mental effort of remembering a name — phosphocreatine rapidly regenerates ATP to keep up. Think of it as a backup battery that kicks in when the main power supply is under strain. In a healthy young brain, this system runs smoothly. In an aging brain, or one affected by disease, the system often falters. This energy buffering role explains why creatine’s cognitive benefits tend to appear most clearly under conditions of stress or impairment.
The 2024 meta-analysis published in Frontiers in Nutrition found no significant effect on overall cognitive function or executive function in the general population — a detail that often gets lost in headlines. But in subgroups where the brain’s energy metabolism is already compromised, whether by age, disease, sleep deprivation, or dietary restriction, the effects become more pronounced. The distinction matters: creatine is not a nootropic that makes sharp minds sharper. It appears to be a compound that helps struggling brains work closer to their baseline. For comparison, consider the difference between giving a flashlight fresh batteries when the old ones are half-dead versus when they are already fully charged. The person with depleted batteries notices the difference immediately. The person whose flashlight was already bright may not notice much at all. This analogy tracks closely with what the research consistently shows across multiple populations and study designs.
What the Alzheimer’s Research Actually Found — And What It Didn’t
The CABA pilot trial deserves careful attention because it represents a genuine milestone, but it also needs to be understood in context. Conducted at the University of Kansas and published in Alzheimer’s & Dementia: Translational Research in 2025, the study was designed primarily to test whether creatine supplementation was even feasible and tolerable in Alzheimer’s patients — not to prove it works as a treatment. On that front, it succeeded. Participants showed an 11 percent increase in brain creatine levels, along with moderate improvements in working memory and executive functioning. For a pilot study, those are encouraging signals. However, this was a small trial, and pilot studies are designed to justify larger ones, not to change clinical practice. The improvements in working memory and executive functioning were moderate, not dramatic, and the study was not powered to detect whether those improvements translate into meaningful changes in daily functioning — the kind that a caregiver would notice.
If your mother can score slightly better on a cognitive test but still cannot remember to turn off the stove, the practical significance is limited. Larger, multi-site randomized controlled trials are still needed to confirm whether these benefits hold across broader Alzheimer’s populations, and a clinical trial for creatine monohydrate in mild TBI is already registered on ClinicalTrials.gov, suggesting the research community is taking the potential seriously. It is also worth noting what the European Food Safety Authority concluded in 2024 when it evaluated a health claim for creatine and cognitive function. EFSA found the evidence insufficient to establish a cause-and-effect relationship for the general population. This does not mean creatine does not help the brain. It means the evidence is not yet strong enough, particularly for healthy individuals, to make an official health claim. For people already dealing with cognitive decline, the risk-benefit calculation may look different — but that conversation belongs with a physician, not a supplement marketing page.
Sleep, Stress, and the Tired Brain
One of the most consistent findings in the creatine and cognition literature involves sleep deprivation, a condition that reliably degrades cognitive performance and is distressingly common among caregivers of people with dementia. A 2024 study published in Scientific Reports found that a single high dose of creatine (0.35 grams per kilogram of body weight) improved cognitive performance during sleep deprivation, preventing drops in brain pH and boosting processing speed. The maximum cognitive effect occurred four hours after oral administration and lasted up to nine hours. For a caregiver running on four hours of broken sleep, that finding has obvious practical appeal. Earlier research had already established a pattern. A study using 5 grams per day for seven days prior to 24-hour sleep deprivation showed positive effects on mood state and tasks dependent on the prefrontal cortex — the brain region responsible for planning, decision-making, and impulse control.
These are exactly the capacities that erode when you are exhausted, and exactly the capacities that caregivers need most. The prefrontal cortex is also one of the regions most affected in early Alzheimer’s disease, which raises the question of whether the mechanisms involved in protecting cognition during sleep deprivation might overlap with those relevant to neurodegeneration. That said, using a high single dose of creatine as an acute cognitive aid is quite different from taking a daily maintenance dose over months. The single-dose study used 0.35 grams per kilogram, which for a 70-kilogram person works out to about 24.5 grams — roughly five times the standard daily dose used in most supplementation studies. This is not necessarily dangerous, but it is a much larger amount than what most people take, and gastrointestinal side effects become more likely at higher doses. Anyone considering this approach should discuss it with a doctor first.
Who Benefits Most — And Who Should Be Careful
The research consistently suggests that creatine’s cognitive benefits are most pronounced in populations with lower baseline creatine levels or compromised brain energy metabolism. Vegetarians and vegans are a clear example. Because creatine is found primarily in meat and fish, people who avoid these foods tend to have lower creatine stores. A study of 45 vegetarian and vegan college students found that 5 grams per day for six weeks increased mental capacity, with vegetarians showing better memory improvements than omnivores in the same trial. For an older vegetarian experiencing mild cognitive complaints, this is a relevant data point. Women navigating menopause may also stand to benefit. A 2025 randomized controlled trial called CONCRET-MENOPA found that medium-dose creatine hydrochloride in perimenopausal and menopausal women was superior to placebo in enhancing reaction time and increasing frontal brain creatine levels.
The reaction time change was notable: the placebo group saw a 6.6 percent worsening while the creatine group saw only a 1.2 percent change. Frontal brain creatine levels increased by 16.4 percent in the supplementation group compared to just 0.9 percent in the placebo group. Given that menopausal cognitive fog is a common complaint and few interventions have shown clear benefits, this trial adds creatine to a short list of options worth discussing with a healthcare provider. But not everyone should supplement freely. The 2024 review published in PMC noted that creatine may trigger manic episodes in patients with bipolar disorder. This is not a theoretical concern — it is grounded in case reports and the biological plausibility of creatine’s effects on brain energy and neurotransmitter systems. People with bipolar disorder, or a family history of it, should approach creatine supplementation with caution and medical supervision. Similarly, the largest study to date, a 2023 analysis published in BMC Medicine, found no significant cognitive improvement from creatine in a broader population sample, reinforcing that benefits are not universal.
Creatine, Depression, and the Limits of Enthusiasm
The connection between creatine and depression is one of the more intriguing threads in this research area, but it also illustrates why caution matters. A 2024 review concluded that creatine reduces depressive symptoms, particularly when combined with SSRIs, and may improve brain energy metabolism and neuroplasticity. In a small study of eight patients with treatment-resistant depression, 3 to 5 grams per day for four weeks reduced Hamilton Depression Rating Scale scores from 23.14 to 12.57 and Hamilton Anxiety scores from 18.71 to 12.00. Those are substantial improvements in a population that had not responded to standard treatment. An 8-week pilot randomized controlled trial from 2024 added further evidence, finding that creatine as an add-on to cognitive behavioral therapy produced significantly lower PHQ-9 depression scores compared to placebo plus CBT. For people with dementia who also experience depression — a common combination that affects up to 40 percent of Alzheimer’s patients — this dual benefit is worth investigating.
Depression in dementia often responds poorly to standard antidepressants, and any additional tool that might help deserves serious study. The limitation is scale. Eight patients is not enough to draw firm conclusions. Even the larger pilot trials have been small by the standards of clinical medicine. And the bipolar caution cannot be overstated: depression is sometimes the presenting face of bipolar disorder, especially in older adults who may not have had a manic episode in years. Starting creatine without a thorough psychiatric history could be genuinely harmful in these cases. The enthusiasm in online wellness communities about creatine for mental health often omits these caveats, and that omission could have real consequences.
Traumatic Brain Injury and Neuroprotection
The traumatic brain injury research is particularly compelling for its potential implications in aging. In animal models, mice given creatine for three or five days before a controlled cortical injury showed a 21 percent and 36 percent reduction in cortical damage, respectively, compared to placebo. A randomized study of 39 children and adolescents with TBI found that creatine administration for six months improved duration of post-traumatic amnesia and reduced ICU stays. The U.S.
Department of Defense published an information paper in 2025 acknowledging creatine’s neuroprotective potential in TBI, and a clinical trial for creatine monohydrate in mild TBI is currently registered on ClinicalTrials.gov. The relevance to dementia caregiving may seem indirect, but falls among older adults are a leading cause of traumatic brain injury, and TBI is itself a risk factor for later dementia. If creatine has neuroprotective properties — if it can reduce the extent of brain damage when injury occurs — then ongoing supplementation might offer a layer of protection that goes beyond day-to-day cognitive support. This remains speculative for now, but the convergence of evidence from multiple research domains is what makes the overall picture worth paying attention to.
Where the Science Goes From Here
The next few years should clarify much of what remains uncertain. The registered clinical trial for creatine in mild TBI, combined with the momentum from the CABA Alzheimer’s pilot, suggests that larger and more rigorous studies are on the way. The menopause research opens another population-specific avenue that could yield clearer guidance. And as the scientific community grapples with the EFSA finding that current evidence is insufficient for a general health claim, the push will be toward the kind of large, multi-site randomized controlled trials that can settle the question for specific populations even if the general claim remains unproven.
For caregivers and patients watching this space, the practical takeaway is that creatine is not a cure, not a proven treatment, and not a substitute for established interventions — but it is no longer just a gym supplement, either. It is a compound with a plausible biological mechanism, a growing body of supportive evidence in vulnerable populations, and a safety profile that, with the notable exception of bipolar disorder, is generally considered favorable. Discussing it with a neurologist or psychiatrist is reasonable. Expecting miracles from it is not.
Conclusion
Creatine’s journey from weight room staple to neuroscience research subject reflects a broader shift in how we think about brain health: as fundamentally an energy problem. The brain’s enormous metabolic demands make it vulnerable to any disruption in energy supply, whether from aging, disease, sleep deprivation, dietary restriction, or injury. Creatine’s role as a rapid ATP regenerator positions it as a logical candidate for supporting brain function under these conditions, and the research — from the 2024 meta-analysis to the 2025 Alzheimer’s pilot to the menopause and depression trials — generally supports that logic, with important caveats about study size and population specificity.
For families dealing with dementia or cognitive decline, creatine is worth knowing about and worth discussing with a medical provider. It is not a replacement for comprehensive care, established medications, structured cognitive activities, or social engagement. But as a low-cost, widely available supplement with a decades-long safety record in other contexts, it occupies an unusual position: genuinely promising, not yet proven, and unlikely to cause harm for most people. That combination — promising enough to investigate, safe enough to consider, honest enough to acknowledge the limits — is rarer than it should be in the world of brain health supplements.
Frequently Asked Questions
How much creatine should someone take for brain health?
Most cognitive studies have used 5 grams per day of creatine monohydrate, the same dose commonly used in fitness contexts. The 2025 menopause study used creatine hydrochloride at a medium dose. The sleep deprivation study that used a single high dose of 0.35 grams per kilogram showed acute effects but is not representative of typical daily supplementation protocols. Start with the standard 5-gram dose and discuss any adjustments with your doctor.
Is creatine safe for older adults with kidney concerns?
Creatine is metabolized into creatinine, which is filtered by the kidneys and often used as a marker of kidney function. In healthy individuals, standard doses of creatine have not been shown to damage kidneys. However, creatine supplementation can artificially elevate creatinine levels on blood tests, potentially causing confusion about kidney function. Older adults with existing kidney disease should consult their physician before starting creatine, and anyone on creatine should inform their doctor before routine blood work.
Does the form of creatine matter for brain benefits?
Creatine monohydrate is the most studied form and the one used in the majority of cognitive research, including the CABA Alzheimer’s pilot trial. Creatine hydrochloride was used in the 2025 menopause study. There is no strong evidence that more expensive or exotic forms of creatine are superior for brain health. Monohydrate remains the best-supported and most cost-effective choice.
Can creatine help with brain fog during menopause?
The 2025 CONCRET-MENOPA trial found that creatine supplementation in perimenopausal and menopausal women improved reaction time and increased frontal brain creatine levels compared to placebo. While this is only one study, it directly addresses the cognitive complaints common during menopause. More research is needed, but the initial results are encouraging.
Should someone with bipolar disorder take creatine?
No, not without close psychiatric supervision. Research has identified a risk that creatine may trigger manic episodes in individuals with bipolar disorder. This applies to people with diagnosed bipolar disorder and potentially to those with undiagnosed or subclinical forms. If there is any history of mania or bipolar disorder in the patient or their family, creatine should only be considered under direct medical guidance.
Will creatine help a healthy person think better?
Probably not in a noticeable way. The 2024 meta-analysis found no significant effect on overall cognitive function in healthy populations, and the largest study to date (2023, BMC Medicine) found no significant cognitive improvement in a broad population sample. The benefits appear most clearly in people whose brain energy metabolism is already compromised — by age, disease, diet, sleep deprivation, or hormonal changes.
