Creatine for Brain & Cognitive Enhancement: A Nootropic Supplement?

When I first started lifting weights, the two marquee supplements being pimped out by every website, fitness YouTuber, and personal trainer at gyms included: whey protein and creatine monohydrate.  Because I ate plenty of protein and knew that creatine could be attained via my diet – I abstained from purchasing either of the aforementioned supplements.  Anyways, after consistently lifting weights for about 2 years, I finally took the plunge and decided to supplement with creatine monohydrate at a dose of 5 grams per day.

What finally compelled me to try creatine monohydrate?  The primary reason I opted to initiate creatine monohydrate supplementation had nothing to do with lifting more weight at the gym, rather, it was to potentially enhance cognitive function – any potential gym gains were perceived as a mere bonus.  At the time I read some studies indicating that creatine may bolster cognitive function among healthy individuals, as well as in persons exhibiting cognitive decline.

What is creatine?

Creatine is an organic acid that occurs naturally in vertebrates.  It was first identified in 1832 by Michel Eugène Chevreul who extracted it from skeletal muscle.  The main function of creatine within the body is to promote recycling of ATP (adenosine triphosphate), a form of cellular energy used by brain and muscle tissue.  Specifically, creatine recycles ADP (adenosine diphosphate) to ATP (adenosine triphosphate) by donating phosphate groups.

Because creatine is manufactured within the human body (from amino acids – glycine and arginine) it is not considered an essential nutrient.  Nevertheless, considering the fact that creatine can modulate energy within brain and muscle tissue, it is hypothesized that adequate creatine intake may augment performance.  Research unequivocally shows that creatine supplementation enhances muscular strength, athletic performance, muscle mass, and muscle recovery.

However, it remains unclear as to whether creatine may also augment brain and/or cognitive function.  Preliminary evidence indicates that creatine supplementation may prevent cognitive decline associated with sleep deprivation, oxygen deprivation, and/or physical exercise.  Moreover, cognitive benefits of creatine supplementation may be most apparent among those with lower-than-average dietary creatine intakes (e.g. vegans, vegetarians, etc.).

Examples of foods high in creatine:

  • Beef
  • Eggs
  • Lamb
  • Sashimi
  • Sushi
  • Tuna

How might creatine enhance cognitive function?

There are a multitude of ways by which high creatine intake via diet and/or supplementation may enhance cognitive function.

  • ATP synthesis: It is thought that creatine supplementation may alter the rates of ATP synthesis within mitochondria. Increased ATP synthesis may lead to more efficient neuronal firing to enhance cognition.
  • Brain metabolism: Creatine supplementation may modulate various aspects of brain metabolism to enhance cognitive processes.
  • Brain oxygenation: Neuroimaging data suggests that creatine increases oxygenation within the brain. Greater oxygenation might lead to cognitive enhancement.
  • Neuroplastic changes: Supplementation with creatine may increase neuroplasticity within the brain whereby connectivity changes and/or neural rewiring ensue to enhance cognition.

Other potential mechanisms

  • Anti-inflammatory
  • Oxidative stress reduction
  • Testosterone increases: Persons with low endogenous testosterone may derive cognitive enhancement from creatine supplementation via testosterone increases.

Note: If you know of any additional mechanisms by which creatine may enhance cognitive function, be sure to mention them in the comments section below so that I can add them to the list.

Cognitive Enhancement from Creatine

If creatine is effective as a cognitive enhancer, listed below are aspects of cognition that may improve with creatine supplementation (based on my interpretation of the research).

  • Abstract reasoning
  • Attentional capacity
  • Central executive function
  • Intelligence
  • Reaction time
  • Recall
  • Visuospatial ability
  • Verbal fluency
  • Working memory

Who is most likely to benefit from creatine supplementation for cognitive function?

Assuming some of the research generated accurate results, we can hypothesize that certain individuals may derive greater cognitive benefit from creatine than others.

  1. Vegetarians & vegans: Research consistently suggests that vegetarians and vegans derive significant cognitive benefit from supplementation with creatine. Because creatine is generally attained via consumption of animal products, it makes sense that vegetarians and/or vegans would have lower-than-usual concentrations of creatine in the body and brain.  Supplementation with creatine in these populations probably corrects a creatine deficit to enhance cognition.
  2. Individuals living in harsh environments: Research consistently indicates that supplementation with creatine prevents cognitive decline when persons are sleep deprived, intermittently exercised, and/or oxygen deprived. Individuals living in harsh environments (e.g. military personnel) may derive cognitive benefit from creatine supplementation.
  3. Elderly: Some research suggests that elderly persons are likely to derive significant cognitive benefit from creatine supplementation. Assuming these individuals don’t have any preexisting contraindications, creatine may increase muscle strength and bolster cognition.
  4. Individuals with neuropsychiatric conditions: Anyone with a neuropsychiatric disorder might benefit from supplementing with creatine due to the fact that it modulates neural activity, potentially correcting dysfunction. Current research suggests that persons with bipolar depression derive significant cognitive benefit from creatine supplementation whereby it increases their verbal fluency.

Creatine and Cognitive Function (Research)

Included below are all studies that I was able to find in which the effect of creatine on cognitive function was evaluated and/or discussed.  It is important to realize that not all studies were: large-scale, well-designed, conducted in humans, or conducted in healthy populations.  As a result of these limitations, you should realize that the findings reported in certain studies may inaccurately reflect the effects of creatine on cognitive performance.

I’ve done my best to write up brief synopses of each study in which the effects of creatine on cognition were reported.  However, if you want to thoroughly examine each study and gather additional details that weren’t mentioned – it is recommended to visit the cited “sources” listed beneath each synopsis.

2017: Cognitive effects of creatine monohydrate adjunctive therapy in patients with bipolar depression: Results from a randomized, double-blind, placebo-controlled trial.

Toniolo, Fernandes, Silva, et al. conducted a well-designed trial to assess the effects of creatine monohydrate on cognition among patients with bipolar disorder.  The creatine monohydrate was administered as an adjunct along with conventional bipolar disorder medications.  Because bipolar disorder is associated with varying degrees of cognitive impairment, it made logical sense to evaluate whether a relatively safe/low-risk dietary supplement like creatine might improve cognitive function among individuals with this neuropsychiatric condition.

  • Participants: 18 patients with bipolar depression
  • Design: Randomized, controlled, double-blinded
  • Groups: Creatine monohydrate (6 grams per day) vs. Placebo (control) – as adjuncts to bipolar medications
  • Duration: 6 weeks
  • Measures: Neuropsychological assessments (Wisconsin Card Sorting Test, Digit Span subtest of the Wechsler Adult Intelligence Scale-Third Edition, Stroop Color-Word Test, Rey-Osterrieth complex figure test, FAS Verbal Fluency Test) – evaluated at baseline and at the end of Week 6
  • Results: Recipients of creatine monohydrate (dose of 6 grams per day) exhibited statistically significant improvements on the verbal fluency test.

Does this study suggest cognitive benefit from creatine?

Yes.  Researchers concluded that supplementation with creatine monohydrate for 6 weeks seems to improve verbal fluency among persons with bipolar disorder.  Verbal fluency tests involve participants naming as many words as possible from a specific genre/category within a set amount of time (e.g. 1 minute).  For example, you might be told to name as many animals as possible over the span of 1 minute – the more unique animals that you name in this time period, the better your score on the verbal fluency test.

  • Cognitive domain: Verbal fluency

Limitations of this study

Despite the reported benefit of creatine monohydrate supplementation on verbal fluency, there are some serious limitations associated with this study.  It is necessary to consider that these limitations may have yielded results that do not accurately reflect the effect of creatine on cognition in patients with bipolar depression – or within the general population.

  1. Small sample size: This study is underpowered as a result of its small sample size. The improvement in cognition among patients with bipolar depression over the span of 6 weeks may have been attributable to random chance – rather than creatine monohydrate.
  2. Lack of healthy controls: Because no healthy controls were involved in this study, it’s unknown as to whether enhanced verbal fluency solely occurs in patients with bipolar depression or other individuals (devoid of neuropsychiatric conditions) as well.
  3. Bipolar medications: A limitation that wasn’t mentioned, but that may be relevant, is the specific medications users are taking for their bipolar disorder. Certain medications may impair cognition to a greater extent than others OR be more/less synergistic with creatine monohydrate in terms of altering cognitive function – compared to others, thus confounding this trial.
  4. No improvement in other measures: If creatine monohydrate were a legitimate cognitive enhancer, perhaps statistically significant improvements on other neurophysiological tests should’ve been evident.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/27890303)

2017: Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

Merege-Filho, Otaduy, de Sá-Pinto, et al. conducted a study to determine whether the brains of children (i.e. youth) benefit from creatine supplementation.  Specifically, researchers sought to determine whether exogenous creatine intake altered brain creatine levels and if creatine supplementation alters cognitive performance – in children.

  • Participants: 67 healthy children (ages 10-12)
  • Design: Randomized, placebo-controlled, double-blinded
  • Groups: Creatine (0.3 g/kg body weight) vs. placebo
  • Duration: 1 week
  • Measures: Cognitive battery; neuroimaging (1H-MRS)
  • Results: Creatine supplementation did not significantly affect executive functions or verbal learning test scores of participants. Neuroimaging data revealed no significant differences in creatine concentrations within the brain among creatine and placebo groups.

It was concluded that creatine supplementation in children does not enhance cognitive performance or increase brain concentrations of creatine.  Researchers suggested that children likely rely on brain creatine synthesis – as opposed to exogenous creatine intake for maintenance of brain creatine homeostasis.

Does this study suggest cognitive benefit from creatine?

No. There was no substantial cognitive benefit attributable to creatine supplementation.

Limitations associated with this study

  1. Duration: The duration of this study was extremely short (just 5 days). Although creatine dosages were likely adequate, it’s possible that the short study duration may explain the lack of significant brain creatine concentration increases as a result of supplementation.  If creatine saturation never peaked throughout the body and/or brain as a result of supplementation – it’s possibly because supplementation was too short-term.  Perhaps longer-term supplementation would’ve yielded substantial increases in brain creatine and/or [potentially-corresponding] cognitive performance enhancement.
  2. Youth: The aim of this study was to investigate the effect of creatine supplementation on cognitive performance in youth, however, this does not help us understand how creatine supplementation influences cognitive performance in adults.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/28079396)

2015: Effects of creatine supplementation on learning, memory retrieval, and apoptosis in an experimental animal model of Alzheimer disease.

Mohammadi, Eshraghian, Zarindast, et al. sought to analyze the effect of creatine supplementation in an animal model of Alzheimer’s disease.  The thought was that, if creatine supplementation proves useful in this animal model trial, it may be worth evaluating in humans for the treatment of Alzheimer’s disease.

  • Participants: 32 male Wistar rats
  • Design: Randomized, controlled
  • Groups: AdCr+ (Aβ injection, creatine supplementation); AdCr- groups (Aβ injection, no creatine supplementation); sham group (saline injection); control group (no intervention)
  • Duration: 6 weeks
  • Measures: Morris Water Maze (MWM) to assess learning and memory retrieval; anti-apoptosis assays (TUNEL staining)
  • Results: Creatine supplementation failed to improve measures of cognitive function (learning and memory retrieval) in male Wistar rats after amyloid-beta injection.

The findings of this study indicate that creatine supplementation may not prove useful for the treatment of Alzheimer’s-related cognitive decline.

Does this research suggest cognitive benefit from creatine?

No.  After injection with amyloid-beta, creatine supplementation failed to improve measures of learning and memory retrieval in male Wistar rats.  What’s more, assays of neurons (brain cells) showed no differences in apoptosis (cell death) among the mice that received creatine compared to mice that received no creatine.  That said, because this study was conducted using animal models of Alzheimer’s, its results may be irrelevant to humans – especially health humans looking to use creatine as a cognitive enhancer.

Limitations of this study

  1. Animals not humans: This study was conducted using Wistar rats – not humans. Many substances that benefit rats do not benefit humans – and vice-versa.  For this reason, we cannot automatically assume that the lack of cognitive-enhancing effects observed in this study applies to humans.
  2. Creatine administration: In the study, creatine was administered after amyloid-beta injections. It’s possible that pre-treatment with creatine would’ve yielded different results and/or some sort of protective effect.
  3. Measures: Perhaps additional or different measures besides the Morris Water Maze would’ve discovered cognitive benefits associated with creatine.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/26793664)

2015: Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation.

Turner, Byblow, and Gant investigated the effect of creatine supplementation on cognitive function in oxygen-deprived humans.  It is widely known that insufficient oxygen impairs global brain functioning whereby cognitive impairment and neurodegeneration can occur.  Because creatine is thought to provide neuroprotection against hypoxia, it made logical sense to evaluate its effect during acute oxygen deprivation.

  • Participants: 15 healthy adults
  • Design: Placebo-controlled, double-blind
  • Groups: Creatine (5 grams per day) vs. placebo
  • Duration: 1 week
  • Measures: Neurocognitive tests; magnetic resonance spectroscopy; transcranial magnetic stimulation – administered at baseline and during a 90-minute hypoxic gas breathing protocol.
  • Methods: After a week of supplementation, a hypoxic gas mixture (10% oxygen) was administered for 90 minutes to induce global oxygen deficit and impair neuropsychological functions.
  • Results: Recipients of creatine monohydrate were protected against hypoxia-induced cognitive impairment. More specifically, recipients of creatine monohydrate exhibited increased corticomotor excitability and no significant change in attentional capacity – compared to the placebo recipients.

It was concluded that creatine supplementation appears neuroprotective among humans in oxygen-deprived conditions.  Researchers believe that creatine exerts a neuromodualtory effect within the brain to bolster energy availability, possibly via maintenance of neuronal membrane potentials.  Worth noting is the fact that brain creatine concentrations increased (as recorded by magnetic resonance spectroscopy) by 9.2% in a 7-day span.

Does this study suggest cognitive benefit from creatine?

Yes – in oxygen deprived conditions.  Based on the results of this study, it seems as though creatine supplementation may be protective against cognitive deficits attributable to oxygen deprivation.  This study does not indicate that creatine supplementation enhances cognitive function in normative (non-oxygen deprived) conditions.  That said, supplementation with creatine monohydrate may prove neuroprotective (against cognitive deficits) when neuronal energy is suboptimal.

  • Cognitive domain: Attentional capacity

Limitations of this study

Despite its favorable design, this study is not devoid of limitations.

  1. Sample size: There were only 15 participants in this study. With such a small sample, it’s possible that results on cognitive performance tests were attributable to random chance.
  2. Dosing/duration: The study involved administering 5 grams of creatine per day over a 1-week span. Although this clearly increased brain creatine levels, it’s likely that brain creatine levels never fully peaked from supplementation.  For this reason, it may have made more sense to either: a pre-trial “loading phase” to maximize creatine levels before the 5 grams per day dose; utilize a larger dose during the trial (e.g. 20 grams per day) for potentially-greater brain levels; or extend the duration of the trial (e.g. 4-8 weeks) to ensure adequate loading from the 5 gram-per-day dose.
  3. Oxygen deprivation: This study solely evaluated the effect of creatine supplementation on cognition of oxygen-deprived participants. Because there was no control setting in which oxygen levels were not adjusted, it remains unclear as to whether creatine supplementation enhances cognitive function among healthy adults in non-oxygen-deprived states.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/25632150)

2013: Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study.

Alves, Filho, Benatti, et al. organized a study to assess the effect of creatine supplementation on cognitive performance and emotional states of older women.

  • Participants: 56 older women (~66.8 years)
  • Design: Randomized, controlled, double-blinded
  • Groups: Creatine; Creatine plus strength training; Placebo (sans training); Placebo plus strength training
  • Duration: 24 weeks
  • Measures: Cognitive function (memory, selective attention, inhibitory control); emotional status (Geriatric Depression Scale) – at baseline, after 12 weeks, and after 24 weeks
  • Results: Creatine supplementation failed to enhance cognitive performance or alter emotional status.

Researchers concluded that creatine supplementation may not alter cognition nor emotional states of healthy older women.

Did this study show cognitive benefit from creatine?

No – not in older women.  There was no apparent cognitive benefit attained from supplementation with adequately-dosed creatine monohydrate over a 24-week period in older women (avg. age of 66.8).  Because this sample only included older women, it’s unknown as to how creatine may affect cognition in older men or younger men and women.

Limitations associated with this study

This study was well-designed, used a larger sample than most, utilized proper creatine dosing, and was conducted over a long-term.  Nevertheless, there are a few limitations associated with this study that are worth noting.

  1. Female-only: The sample in this study was limited to female participants. Although it’s reasonable to suspect similar outcomes in males, it’s possible that a mixed sample (males and females) or a male-only sample would’ve yielded different results.  Perhaps there are sex-specific effects of creatine whereby cognitive enhancement might only occur in males.
  2. Older adults: Though the purpose of the study was to evaluate the effect of creatine in older adults, the results cannot be generalized to younger persons (e.g. teenagers, young adults, middle aged adults). It’s possible that effects of creatine on cognition are mediated in part by age.
  3. Sample size: The sample size was larger than most studies in which the effects of creatine on cognition were investigated. Still, because a sample of just 56 participants is relatively modest, it’s possible that the findings inaccurately represented the effect of creatine on cognition and/or emotional status.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/24098469)

2013: Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial.

Alves, Santiago, Lima, et al. organized a study to test the effect of creatine supplementation on individuals diagnosed with fibromyalgia.  One of the many measures recorded in the study was cognitive function.  Cognitive function was assessed with a battery of tests including:  Mini-Mental State Examination, Stroop Test, Trail-Making Test, Digit Span Test, and Delayed Recall Test.

  • Participants: 28 women with fibromyalgia
  • Design: Randomized, placebo-controlled, double-blinded
  • Groups: Creatine vs. placebo
  • Duration: 16 weeks
  • Measures: Muscle function, aerobic conditioning, cognitive function, quality of sleep, quality of life, kidney function, and adverse effects.
  • Results: Muscle strength and isometric strength significantly increased in the creatine group compared to placebo recipients. However, creatine supplementation did not yield changes in aerobic conditioning, pain, cognitive function, quality of sleep, or quality of life.

It was concluded that creatine may be a beneficial supplement for improving muscle function in patients with fibromyalgia.  That said, there was no evidence to suggest that creatine enhances cognitive performance among individuals with fibromyalgia.

Does this study suggest cognitive benefit from creatine?

No.  This study reported no changes in cognitive performance after 16 weeks of creatine supplementation at dose of 5 grams per day.  There was a trend for improvement on the Delayed Recall Test (measuring incidental memory) among creatine recipients, but this was not of statistical significance (p = 0.07).

Limitations of this study

  1. Sample size: This study incorporated a relatively small sample size (28 women). It’s possible that the outcome may inaccurately reflect the effect of creatine on cognition as a result of the limited sample.
  2. Female-only: The sample in this study was comprised solely of women. It’s unknown as to whether men might’ve responded differently to creatine supplementation in terms of cognitive performance.
  3. Fibromyalgia diagnosis: All participants in this study had been formally diagnosed with fibromyalgia, and for this reason, it is unclear as to whether similar outcomes (e.g. no cognitive enhancement) would’ve occurred in healthy persons.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/23554283)

2011: The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores.

Benton and Donohoe sought to determine how short-term creatine supplementation affects cognitive functioning in vegetarians versus omnivores.  Because creatine influences brain functioning (as evidenced by neuroimaging studies) and is attained primarily via consumption of meat, fish, and other animal products – it was hypothesized that vegetarians may derive cognitive enhancement from its supplementation.

  • Participants: 121 adult females
  • Design: Randomized, placebo-controlled, double-blinded
  • Groups: Creatine (20 grams) vs. placebo; vegetarians vs. omnivores
  • Duration: 5 days
  • Measures: Verbal fluency; vigilance
  • Results: Creatine supplementation did not significantly improve measures of verbal fluency and vigilance. That said, creatine supplementation improved memory in vegetarian recipients.

Does this research suggest cognitive benefit from creatine?

Yes – only in vegetarians. This study reported that creatine supplementation appears to enhance memory in vegetarians and/or vegans.  Logically, one would assume that the observed improvement in memory function among vegetarian/vegan recipients of creatine might be due to either: the reversal of a creatine deficiency or the optimization of previously suboptimal creatine concentrations within the brain (each of which are attributable to lack of creatine in the diet).

  • Cognitive domain: Memory

Limitations of this study

There are a couple of limitations associated with this study that are worth brief mentions.

  1. Duration: Although the daily dosage of creatine (20 grams) administered in this study was high, the duration of the study may have been inadequate for maximizing concentrations of creatine within the brain via supplementation. For this reason, one might speculate that an extra couple of days, or weeks may have yielded different results – such as cognitive enhancement among all recipients.
  2. Female-only: This study solely included female participants. It’s possible that different outcomes would’ve been observed in a study that incorporated both sexes.  Moreover, it’s possible that creatine supplementation yields sex-specific effects such that its ability to enhance aspects of cognition is more pronounced in one sex compared to the other.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/21118604)

2011: Skill execution and sleep deprivation: effects of acute caffeine or creatine supplementation – a randomized placebo-controlled trial.

Cook, Crewther, Kilduff, et al. conducted a trial in which the acute effects of creatine and caffeine supplementation were assessed in 10 sleep-deprived elite rugby players.  Before the testing phase of the study, the 10 ruby players initially familiarized themselves with a repetitive rugby passing skill.  After familiarization with the skill, the rugby players underwent 10 trials in which their performances on the repetitive passing skill were assessed after varying amounts of sleep: 7-9 hours of sleep (5 trials) and 3-5 hours of sleep (5 trials).

Approximately 1.5 hours prior to each of the 10 trials, participants ingested either: creatine, caffeine, or a placebo.  Researchers then determined whether acute ingestion of creatine and/or caffeine altered their performance versus the placebo.

  • Participants: 10 rugby players
  • Design: Placebo-controlled, blinded
  • Groups: Creatine (50 or 100 mg/kg) vs. caffeine (1 or 5 mg/kg) vs. placebo
  • Duration: 10 rugby passing skill trials
  • Measures: Passing skill performance; saliva (cortisol and testosterone levels)
  • Results: Both acute creatine (50 or 100 mg/kg) and caffeine (1 or 5 mg/kg) administration protected against performance declines on the passing skill after sleep deprivation – whereas placebo administration resulted in significant declines in performance after sleep deprivation.  Administration of the 100 mg/kg dose of creatine yielded higher concentrations of salivary testosterone compared to the placebo, but statistical significance was not reached (p = 0.067).  Administration of the 5 mg/kg dose of caffeine significantly increased salivary cortisol compared to the placebo.

Researchers concluded that the acute administration of creatine or caffeine appears to protect against sleep deprivation-related performance degeneration in elite athletes.  Considering this finding, it may be useful for professional athletes to supplement with creatine and/or caffeine prior to games whenever short on sleep and/or sleep deprived.

Does this study suggest cognitive benefit from creatine?

Yes – in sleep deprived conditions.  In this study, creatine was administered acutely prior to the performance of a skill passing task.  The administration of creatine prevented performance decline on the skill passing task.  Because performance of a skill passing task requires cognitive engagement, it’s likely that acutely-administered creatine enhanced cognitive function in sleep deprived individuals.  Though the type of cognition used and extent of cognitive taxation may not have been the same as if the participants were instructed to solve a complex mathematical equation, it’s very likely that cognition influenced the athletic skill-based task.  If I were to guess, I’d say that creatine mostly enhanced visuospatial ability, a domain of cognition.

  • Cognitive domain: Visuospatial ability

Limitations of this study

  1. Sample size: The sample utilized for this study was small, consisting of just 10 participants. Given this small sample, it’s possible that the results of the study do not accurately reflect the effect of acute creatine administration on performance.  A larger sample would provide more reliable results.
  2. Acute administration: In this study, creatine was administered acutely – 1.5 hours before the performance of a skill-based task. Given the fact that ongoing supplementation of creatine is usually needed for it to reach maximal saturation and concentrations within the body and brain, it’s likely that creatine levels never peaked within the athletes.  Although the dosing used for this study was greater than usual, assuming athletes weighed an average of 200 lbs., they would’ve received approximately 9 grams of creatine at the 100 mg/kg dose – not an overwhelming amount, even for loading.  Had the athletes been receiving creatine for an extended duration at a dose of 5 grams per day, creatine concentrations would’ve peaked within the body and brain.  Attaining peak creatine levels via ongoing supplementation may have yielded more substantial performance enhancement than an acute creatine spike (as occurred in this study).

(Source: https://www.ncbi.nlm.nih.gov/pubmed/21324203)

2010: Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal.

Hammett, Wall, Edwards, and Smith conducted a study to determine the effect of creatine monohydrate on fMRI BOLD (blood oxygen level dependent) responses.  Additionally, the researchers evaluated the effect of creatine monohydrate on cognitive performance.

  • Participants: 22 healthy volunteers
  • Design: Randomized, controlled
  • Groups: Creatine vs. Placebo – The creatine recipients received 20 grams per day for 5 days, then 5 grams per day for 2 days.
  • Duration: 1 week
  • Measures: BOLD fMRI response (visual cortex); cognitive performance tasks – at baseline and after 1 week.
  • Results: Creatine supplementation decreased magnitude of BOLD response by 16% and enhanced memory span by 26%. No significant changes in BOLD responses or cognitive measures were observed in the placebo recipients.

Researchers concluded that creatine monohydrate supplementation appears to modulate neural activity.  This modulation of neural activity may yield cognitive enhancement, particularly in the domain of memory span.

Did the results suggest cognitive benefit from creatine?

Yes. It seems as though creatine monohydrate enhances cognitive performance in healthy individuals.

  • Cognitive domain: Memory span

Limitations associated with this study

  1. Sample size: Although fMRI data strengthen the quality of this study, it’s possible that the small sample size yielded inaccurate data. Because creatine is known to modulate brain activity, it’s unlikely that observed changes in fMRI BOLD responses were due to random chance.  However, it’s still possible that the observed changes were in fact due to random chance – especially given the small sample.  Moreover, there’s a strong possibility that observed cognitive improvements among creatine recipients were due to random chance (as a result of the small sample).
  2. Duration: The study duration was 1 week. This increases likelihood of retesting effects on cognitive measures.  Moreover, perhaps a longer-term study (e.g. 4-6 weeks) would’ve showed more substantial change on fMRI BOLD response and/or cognitive performance.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/20570601)

2009: Cognitive effects of creatine ethyl ester supplementation.

Ling, Kritikos, Tiplady conducted a study to determine if supplementation with creatine ethyl ester, a format distinct from that of creatine monohydrate, affected cognitive function.  The study incorporated a robust design and adequate measures of cognitive performance.

  • Participants: 34 healthy participants
  • Design: Randomized, placebo-controlled, double-blind
  • Groups: Creatine ethyl ester (5 grams) vs. placebo
  • Duration: 2 weeks
  • Measures: 5 cognitive tests (PC-based): Memory recall, spatial ability, response inhibition, reaction time, and IQ.
  • Results: Recipients of creatine ethyl ester (5 grams per day) exhibited significant improvement on several cognitive tasks involving: memory, attention, reaction time, and some measures of accuracy. There were also marked improvements in IQ scores among creatine recipients at the end of 2 weeks compared to baseline.  (Significant changes in IQ scores may have been due to re-testing and/or the atypically low scores at baseline, however, the potential effect of creatine shouldn’t be dismissed). Moreover, self-reports from creatine recipients indicate reductions in fatigue as a result of supplementation.

It was concluded that creatine ethyl ester (CEE) supplementation, at a dose of 5 grams per day, may enhance cognitive performance in healthy individuals.  Researchers speculate the cognitive enhancement derived from creatine ethyl ester could be equivalent to or superior than that of creatine monohydrate.  The cognitive benefits derived from creatine ethyl ester were hypothesized as being attributable to creatine ethyl ester’s modulation of energy capacity within the brain during cognitively-demanding tasks.

Does this study suggest cognitive benefit from creatine?

Yes.  This study indicates that supplementation with creatine ethyl ester (5 grams per day) for a period of 2 weeks may significantly enhance several domains of cognitive performance.  As of current, this is one of the only studies in which cognitive enhancement was observed across multiple cognitive domains in healthy individuals who supplemented with creatine.

  • Cognitive domains: memory, attention, reaction time, IQ (?)

Limitations of this study

There are some limitations associated with this study that necessitate mentioning.

  1. Sample size: The sample size in this study was small with just 34 participants. For this reason, we must consider that the cognitive improvements exhibited by creatine recipients may have been due to random chance – rather than the actual creatine.  Perhaps a larger sample would’ve discovered no significant differences in cognitive performance among creatine and placebo recipients.
  2. Duration: The study was conducted over a relatively short-term, which may have influenced results. Retesting cognitive measures just 2 weeks after the same measures may have yielded significant retesting effects.  Perhaps some of the retesting effects could’ve been avoided if the trial was longer.  This would’ve increased the time between baseline/endpoint tests and may have minimized retesting effects; the more time between tests – the tougher it is to remember the initial tests.  Moreover, it’s possible that after 2 weeks, concentrations of creatine in the brain might not have peaked.  If brain concentrations of creatine failed to peak, it’s possible that a longer-term trial would’ve resulted in peak brain creatine levels, and potentially greater cognitive enhancement among recipients than was observed in this study.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/19773644)

2008: Creatine supplementation does not improve cognitive function in young adults.

Rawson, Lieberman, Walsh, et al. conducted a small-scale study to evaluate whether supplementation with creatine could enhance cognition in young adults (average age 21).  Prior research discovered that creatine supplementation bolsters cognitive performance after sleep deprivation (in persons of all ages).  That said, no research had been conducted in which the effect of creatine on cognitive performance was assessed in normative (non-sleep-deprived) conditions.

  • Participants: 22 healthy participants
  • Design: Randomized, placebo-controlled, double-blind
  • Groups: Creatine (0.03 g/kg/day) vs. placebo
  • Duration: 6 weeks
  • Measures: Neurocognitive tests including: simple reaction time (RT), code substitution (CS), code substitution delayed (CSD), logical reasoning symbolic (LRS), mathematical processing (MP), running memory (RM), and Sternberg memory recall (MR).
  • Results: No significant cognitive benefits were observed among recipients of creatine.

Researchers concluded that supplementation with creatine (0.03 g/kg/day) does not improve cognitive function in non-sleep deprived young adults.  It was stated that creatine supplementation may only enhance cognitive function and psychomotor performance among persons with preexisting cognitive impairment (e.g. due to a genetic disorder, neurodegeneration, sleep deprivation, oxygen restriction, etc.).

Does this study suggest cognitive benefit from creatine?

No.  Zero benefits were observed across a host of cognitive domains among persons who received creatine for 6 weeks.  This study indicates that creatine supplementation for the specific sake of enhancing cognition in healthy young adults might be futile.

Limitations associated with this study

Though this study reported no significant cognitive benefit from supplementation with creatine, there are some notable limitations that warrant discussing.

  1. Sample size: The sample size of this study was extremely small (just 22 participants). With such a small sample, it’s possible that the lack of observed effect was attributable to random chance.  A larger sample would’ve strengthened the finding that creatine supplementation isn’t beneficial among young adults.
  2. Dosage: The dosage of creatine administered was likely suboptimal to observe a significant effect. Researchers administered creatine at doses of 0.03 grams per kg of body weight.  An average man in the U.S. currently weighs approximately 196 lbs. (88 kg), and in this study, would’ve received a daily creatine dose of ~2.67 grams.  To maximize concentrations of creatine in the brain, it is generally recommended to ingest at least 5 grams per day.  It’s possible that participants in this study didn’t receive adequate doses of creatine to enhance cognition.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/18579168)

2007: Creatine supplementation and cognitive performance in elderly individuals.

McMorris, Mielcarz, Harris, et al. organized a study in which the effect of creatine supplementation on cognitive performance was evaluated in elderly persons.  Although the study was well-designed, in my opinion, the study was too short (it should’ve been at least 1-2 weeks longer) to evaluate the full potential of creatine as a cognitive enhancer.

  • Participants: 32 elderly participants
  • Design: Randomized, placebo-controlled, double-blind
  • Groups: Creatine (5 grams, q.i.d.) vs. placebo
  • Duration: 2 weeks
  • Measures: Random number generation, forward/backward number recall, forward/backward spatial recall, long-term memory tests
  • Results: Creatine supplementation significantly improved cognitive performance on forward number recall, forward/backward spatial recall, and long-term memory tests

Does this study suggest cognitive benefit from creatine?

Yes – in elderly participants.  Although the chief purpose of this study was to elucidate the effect of creatine supplementation on cognitive performance in elderly persons, it does now allow us to determine whether creatine enhances cognitive performance in non-elderly individuals.  Because most elderly individuals exhibit age-related cognitive decline, based on the results of this study, it’s possible that creatine might prove useful in non-elderly individuals with preexisting cognitive deficits.

  • Cognitive domains: Recall and memory

Limitations associated with this study

There are some notable limitations associated with this study, including its sample size and duration.

  • Sample size: The sample size in this study was small (32 participants). Due to the small sample size, it’s possible that the results of this study were more attributable to random chance than creatine supplementation.
  • Duration: The duration of this study was relatively short, possibly too short for participants to reap maximal cognitive benefits from creatine supplementation. The group given creatine (Group 1) only received creatine for 1 week, however, this was at a high dose of 20 grams (5 grams, q.i.d.). (In case you didn’t bother reading the study, Group 1 received a placebo for one week before initiation of creatine supplementation).  In any regard, due to the short-term treatment phase with creatine, it’s possible that concentrations of creatine within the brain never reached peak saturation.  Lack of peak creatine saturation within the brain may yield results that undermine the full potential of creatine as a cognitive enhancer [among the elderly].

(Source: https://www.ncbi.nlm.nih.gov/pubmed/17828627)

2007: Lack of efficacy of 5 grams daily of creatine in schizophrenia: a randomized, double-blind, placebo-controlled trial.

Kaptsan, Odessky, Osher, and Levine conducted a study to evaluate the effect of creatine on neuropsychiatric functions of patients with schizophrenia.  It is known that patients with schizophrenia often exhibit atypical energy metabolism throughout the brain.  Because creatine may aid in the regulation of brain energy metabolism, its effects were worth investigating among patients formally diagnosed with schizophrenia.

  • Participants: 10 patients with schizophrenia
  • Design: Randomized, placebo-controlled, double-blind
  • Groups: Creatine monohydrate (3-5 grams) vs. placebo
  • Duration: 3 months
  • Measures: Positive/Negative Syndrome Scale (PANSS); Clinical Global Impressions (CGI); cognitive battery
  • Results: Creatine monohydrate (3-5 grams per day) supplementation failed to improve neuropsychiatric (PANSS/CGI) and neurocognitive (cognitive battery) tests among patients with schizophrenia.

Researchers concluded that, although safe, creatine monohydrate supplementation does not appear useful in the treatment of schizophrenia.  More specifically, no improvements were observed among recipients of creatine monohydrate in neuropsychiatric symptoms and neurocognitive functions over the span of 3 months.  However, researchers emphasize that further research may be warranted (probably due to the limitations of this study).

Did this study suggest cognitive benefit from creatine?

No. The results of this study indicated that creatine monohydrate supplementation does not improve cognitive performance among patients with schizophrenia, even when administered daily for an extended duration (3 months).  That said, the sample of this study was limited to patients diagnosed with schizophrenia.  For this reason, we should assume that findings (e.g. no cognitive improvement) generalize to healthy individuals.

Limitations associated with this study

  1. Sample size: The sample size in this study was extremely small (10 participants). It’s possible that the lack of observed therapeutic effect (associated with creatine supplementation) was a consequence of the small sample size.  Perhaps a larger sample would’ve yielded substantial improvement in various neuropsychiatric or neurocognitive domains.  Moreover, it’s possible that with such a small sample, there are confounding effects from neuropsychiatric medications (perhaps, on average, the neuropsychiatric medications used by creatine recipients were more antagonistic to the therapeutic neuropsychiatric effects of creatine).
  2. Dosing: The dosage of creatine administered in this study may have been too low for some. Because I don’t have full access to the paper, I’m unsure of whether all creatine recipients titrated up to 5 grams per day – or if some may have been receiving below 5 grams.  If less than 5 grams of creatine were ingested per day by several or most of the creatine recipients, this may have resulted in a lack of effect – attributable to suboptimal dosing.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/17592912)

2007: Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior.

McMorris, Harris, Howard et al. sought to investigate the effect of creatine supplementation on cognitive performance, psychomotor function, and mood state among sleep-deprived and moderately-exercised individuals.  For the study, researchers recruited male college students (majoring in Sports Science) each of whom were compensated for their participation.

  • Participants: 20 paid volunteers (~21 years of age)
  • Design: Randomized, controlled, double-blind
  • Groups: Creatine (5 grams, q.i.d.) vs. placebo
  • Duration: 1 week
  • Measures: Cognitive function; psychomotor function; mood; effort; hormone levels (cortisol and melatonin) – at baseline, then again after 1 week while sleep-deprived (18-hours, 24-hours, and 36-hours after sleep deprivation with moderate exercise).
  • Results: Creatine recipients exhibited significantly superior performance on a central executive task at the 36-hour sleep deprivation test – compared to the placebo recipients. Creatine recipients also exhibited significant linear performance improvements on the central executive task throughout the experiment whereas the placebo group did not.

Researchers concluded that ongoing creatine monohydrate supplementation may enhance central executive task performance in sleep-deprived individuals.

Did this study suggest cognitive benefit from creatine?

Yes – but only after 36 hours of sleep deprivation.  No significant differences were observed in cognitive performance among creatine recipients and placebo recipients after 18 hours and 24 hours of sleep deprivation, yet after 36 hours of sleep deprivation, creatine users exhibited superior central executive task performance compared to placebo users.  Though this study supports the idea that creatine might enhance cognition, the enhancement only seems to occur when sleep deprived for an extended duration – not a very common scenario for most.

  • Cognitive domain: Central executive function

Limitations associated with this study

This study is riddled with limitations including: tiny sample size, limited duration, and participant characteristics (male-only, young adults, college students).

  1. Sample size: The sample size in this study was very small (20 participants). With such a small sample size, it’s relatively difficult to know whether the findings in this study accurately reflect the effect of creatine on cognition in sleep deprived states.  Perhaps a larger sample would’ve discovered more significant cognitive enhancement from creatine, or possibly no cognitive enhancement at all.
  2. Duration: The duration of this study was 1 week, which for studying the effects of creatine, may be too short. It may take between 2-4 weeks for creatine concentrations to peak within the brain as a result of supplementation.  If creatine concentrations never reached maximal saturation in the brain prior to endpoint assessments, it’s possible that the cognitive enhancing effects of creatine were underestimated.
  3. Male-only: This study was limited to male participants. It’s possible that a mixed sample and/or female-only sample would’ve yielded different outcomes such as: no significant cognitive enhancement from creatine or even more significant cognitive enhancement from creatine.
  4. Young adults: The study was limited in that its sample contained only young adults (avg. age 21). It’s possible that participants of other ages such as middle-aged or elderly adults may have responded differently to creatine supplementation.
  5. College students: One thing to consider here is that by using only college students in the sample, we may not have attained an accurate representation of creatine’s effect on cognition in the general population. Perhaps college students have better cognitive function (on average) and wouldn’t derive as much cognitive benefit from creatine supplementation as non-college students and/or less intelligent populations.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/17046034)

2007: Use of creatine containing preparation e.g. for improving memory, retentivity, long-term memory and for preventing mental fatigue condition, comprising e.g. Ginkgo biloba, ginseng and niacin.

Gastner, Selzer, Hans-Peter, and Hammer organized a trial to evaluate, or perhaps showcase, the effect of creatine monohydrate as a standalone agent, as well as with ginkgo biloba extract – on cognitive performance.  It should be noted that the authors of this study have a patent for a neuroprotective (or cerebroprotective) agent containing creatine monohydrate.  In any regard, this was a well-designed trial with a moderate sample size.

  • Participants: 100 healthy adults (18-64 years of age)
  • Design: Randomized, placebo-controlled, double-blinded
  • Groups: Creatine (1.5 grams); Ginkgo biloba extract (120 mg); Creatine plus Ginkgo biloba; Placebo (1.5 grams) – each given twice per day via soft gel capsules
  • Duration: 6 weeks
  • Measures: Cognitive tests (Raven’s Advanced Progressive Matrices; Uchida-Kraepelin serial calculation test; Backward Digit Span) – at baseline and after 6 weeks.
  • Results: No formal documentation discussing the results of this trial has been published. Creatine monohydrate recipients exhibited significant improvements on all cognitive tests – compared to the placebo.  However, the most substantial cognitive enhancement was observed among recipients of creatine monohydrate plus ginkgo biloba extract.

Because researchers failed to report standard deviations and never conducted a statistical analysis of their data, it’s difficult to elucidate the extent of cognitive enhancement derived from supplementation with creatine as a standalone or as part of a combination (with ginkgo biloba extract).  Nevertheless, considering the baseline and endpoint test scores, it’s reasonable to suspect that significant cognitive enhancement might’ve been attained from creatine supplementation.

Does this study suggest cognitive benefit from creatine?

Yes.  Creatine monohydrate supplementation at just 3 grams per day (1.5 grams, b.i.d.) over the span of 6 weeks significantly enhanced several domains of cognitive performance in healthy adults.  That said, even greater cognitive enhancement was attained when creatine was co-administered with ginkgo biloba extract.

  • Cognitive domains: Abstract reasoning; cognitive speed; working memory

Limitations associated with this study

There are several limitations associated with this trial that need to be mentioned, including: conflict of interest, omission of data, and creatine dosing.

  1. Conflict of interest: Though this study wasn’t published in any medical journals, the researchers behind this trial have an overt conflict of interest. A patent was filed for a nootropic (cognitive-enhancing) formula containing both creatine and ginkgo biloba.  Coincidentally, results indicated that simultaneous creatine and ginkgo biloba supplementation yielded significant cognitive enhancement among participants – compared to a placebo.
  2. Data: While authors of this trial are not obligated to share data, some believe that it’s impossible to know whether creatine and/or ginkgo biloba supplementation legitimately enhanced cognition of participants on the basis that no standard deviations were reported. Moreover, no statistical analysis of the data was ever conducted.
  3. Dosing: Perhaps most surprising about this study is that the dosage of creatine administered was just 3 grams per day (in 2 doses of 1.5 grams). By most standards, this would be a suboptimal dose for ensuring that creatine reaches peak saturation within the brain.  Assuming creatine levels never reached the maximum limits in the brains of participants, it’s possible that the cognitive enhancing properties of creatine were not as prominent as they could’ve been at a higher dose (e.g. 5 grams per day).

(Source: https://www.google.com/patents/DE102007030495A1)

2006: Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol.

McMorris, Harris, Swain, et al. conducted a randomized controlled study to elucidate the effect of creatine supplementation on cognitive function and psychomotor performance in sleep-deprived, mildly-exercised college students.  Because creatine levels decrease in the brain after sleep deprivation, it was thought that creatine supplementation may prove useful for ameliorating sleep deprivation-induced cognitive deficits.

  • Participants: 19 healthy adults (~21 years of age)
  • Design: Randomized, placebo-controlled, double-blind
  • Groups: Creatine (5 grams) vs. placebo – each administered 4 times per day
  • Duration: 1 week
  • Measures: Random movement generation; verbal/spatial recall; choice reaction time; static balance; mood state; and hormone level tests – each administered at baseline and after 7 days following sleep deprivation for 6 hours, 12 hours, and 24 hours with intermittent exercise.
  • Results: Creatine recipients exhibited significantly less change in random movement generation, choice reaction time, balance, and mood – compared to placebo recipients.

Researchers concluded that creatine supplementation enhances performance on tasks that are known to tax the prefrontal cortex among sleep-deprived individuals.  What’s more, creatine supplementation favorably affected mood after sleep deprivation, whereas placebo supplementation did not.

Does this study suggest cognitive benefit from creatine?

Yes – but only after 24 hours of sleep deprivation.  After just 6 hours and 12 hours of sleep deprivation, there were no differences in cognitive performance among creatine recipients and placebo recipients.  However, when the sleep deprivation was increased to 24 hours, performance differences were observed on prefrontal cortex-taxing tasks.

  • Cognitive domains: Central executive function; reaction time

Limitations associated with this study

  1. Sample size: The sample size utilized for this study was small (19 participants). Because there were just 19 participants, it’s possible that the findings reported in this study not accurately reflect the effects of creatine on cognitive function in sleep deprived persons.
  2. College students: The sample in this study consisted solely of college students. It’s possible that college students might be less likely to derive cognitive benefit from creatine supplementation due to exhibiting superior baseline cognitive performance (on average) compared to non-college students.
  3. Male-dominant: There were a few females (3) participating in this study, however, the sample was predominantly male. Perhaps more females and/or a female-only sample would’ve generated different outcomes – possibly related to sex-specific effects of creatine.
  4. Young adults: Because this study solely incorporated young adults, it’s unknown as to whether findings would be similar among middle-aged or elderly individuals.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/16416332)

2003: Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial.

Rae, Digney, McEwan, and Bates organized a trial to determine the effect of creatine monohydrate on the cognitive function of healthy adults who consumed vegetarian diets.

  • Participants: 45 young adults (vegetarian)
  • Design: Randomized, placebo-controlled, double-blind
  • Groups: Creatine (5 grams) vs. placebo
  • Duration: 6 weeks
  • Measures: Intelligence test scores; working memory performance
  • Results: Creatine supplementation significantly improved intelligence test (Raven’s Advanced Progressive Matrices) and working memory test (backward digit span) scores.

It was concluded that creatine supplementation appears to enhance cognitive performance among vegetarians.  Researchers believe that the cognitive benefit derived from creatine may be attributable to its modulation of energy capacity within the brain, ultimately speeding up cognitive processing.

Did this study suggest cognitive benefit from creatine?

Yes – in vegetarians. This study observed that creatine monohydrate supplementation enhanced cognitive function in healthy adults adhering to vegetarian diets.  It is unknown as to whether cognitive enhancement via creatine supplementation would also occur in non-vegetarians.

  • Cognitive domains: Intelligence; working memory

Limitations of this study

  1. Lack of non-vegetarian control: A non-vegetarian control group would’ve helped us understand whether cognitive enhancement among creatine recipients was solely attributable to correction of a preexisting deficit (common in vegetarians). If non-vegetarians also exhibited marked cognitive enhancement from creatine supplementation, it’s possible that cognitive benefits may have been due to attainment and maintenance of maximal creatine saturation within the brain – rather than from correcting an underlying deficiency.
  2. Sample size: The sample size of this study was relatively small (45 participants).

(Source: https://www.ncbi.nlm.nih.gov/pubmed/14561278)

2002: Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation.

Watanabe, Kato, and Kato implied that, because creatine supplementation is known to prevent peripheral fatigue, its effects on mental or cognitive fatigue were worth investigating.

  • Participants: 24 healthy volunteers
  • Design: Randomized, placebo-controlled, double-blinded
  • Groups: Creatine (8 grams per day) vs. placebo
  • Duration: 5 days
  • Measures: Calculation task (cognition); magnetic resonance spectroscopy (neuroimaging)
  • Results: Creatine supplementation significantly reduced cognitive fatigue and reduced task-evoked cerebral oxygenated hemoglobin (suggestive of increased oxygenation throughout the brain).

It was concluded by researchers that creatine supplementation may effectively reduce mental fatigue.  Based on the neuroimaging data, researchers suspect that creatine supplementation may reduce cognitive fatigue via increasing brain oxygenation.

Does this study suggest cognitive benefit from creatine?

Yes.  It seems as though creatine supplementation enhances cognitive endurance via elicitation of an anti-fatigue effect.  Although researchers do not use the terms “cognition” or “cognitive” anywhere in their paper, most would agree that mental fatigue influences cognitive function.  The greater a person’s mental fatigue, the poorer his/her cognitive performance is likely to be.

  • Cognitive domain: Cognitive endurance.

Limitations of this study

  1. Sample size: The sample size of this study was small, making it difficult to know if the outcome accurately reflects the effect of creatine on mental performance.
  2. Duration: The study was conducted over an extremely short-term (just 5 days). With such a limited duration of supplementation, creatine concentrations within the brain may not have peaked (or reached maximal saturation).  If creatine levels in the brain never peaked within 5 days, it’s possible that results may not adequately portray the full extent of creatine’s anti-fatigue effect.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/11985880)

Note: If you know of any additional studies that weren’t included above in which the effect of creatine on cognitive function was evaluated – be sure to share it in the comments section so that I can update this article.

Limitations associated with Research of Creatine for Cognitive Enhancement

Below is a list of limitations that I’ve compiled associated with the research of creatine as a cognitive enhancer.  These limitations make it difficult to know whether creatine supplementation truly facilitates cognitive enhancement.

  1. Sample sizes: In the majority of studies, the sample sizes used to determine whether creatine is effective as a cognitive enhancer are too small. With such small sample sizes, it’s impossible to know whether the outcomes accurately reflect the typical effects of creatine on cognitive function.
  2. Special populations: Many of the studies tested the effects of creatine in special populations such as: patients with medical conditions (e.g. bipolar depression, fibromyalgia, schizophrenia), persons consuming non-standard diets (e.g. vegetarians), specific age groups (e.g. young adults), and/or specific sexes (e.g. female-only).
  3. Special conditions: Numerous studies investigated the effect of creatine in special conditions such as after: sleep deprivation, intermittent exercise, and/or oxygen deprivation. Results of these studies do not allow us to know whether similar responses to creatine would occur in normative conditions.
  4. Study durations: Most studies tested the effects of creatine on cognition over the short-term (e.g. 1 week). Because it takes time for creatine to reach maximal concentrations within the body and brain, participants in short-term studies probably never attained peak creatine levels.  Failure to attain peak creatine levels in the brain may have undermined the cognitive enhancing potential of creatine.
  5. Dosages of creatine: A subset of studies administered dosages of creatine that may have been too low to observe any cognitive enhancement. Any dosage under 5 grams per day should be considered suboptimal.
  6. Conflicts of interest: There may have been conflicts of interest in several of the trials in which the effects of creatine on cognition were evaluated. In particular, the trial conducted by Gastner et al. discovered significant cognitive enhancement from creatine, yet they have a patent for a nootropic supplement containing creatine.
  7. Measures: Non-standard measures of cognitive function were utilized in several of the trials in which the effects of creatine on cognition were evaluated.

Recommendations for future research of creatine on cognition and brain function

If you or anyone you know plans on researching the effects of creatine on cognitive function, I hope you’ll consider some of my recommendations for future studies.  In my opinion, it’s better to conduct one high quality trial than many undersized, poorly designed, and/or suboptimally-dosed ones.

  • Conditions: Test the effects of creatine on cognitive function in normal conditions – not after sleep deprivation, exercise-induced fatigue, or oxygen deprivation.
  • Design: Implement a randomized, double-blinded, placebo-controlled design.
  • Dosing: Creatine should be administered at high doses (e.g. 20 grams per day) during a 5-day initial loading phase, followed by 5 grams per day thereafter for maintenance.
  • Duration: Future studies should be conducted over a minimum span of 6 weeks to ensure creatine levels peak within the brain.
  • Measures: Use standard measures of cognitive function like Ravens Advanced Progressive Matrices. Also consider using neuroimaging in a subset of participants to evaluate whether changes in brain creatine levels correlate with possible cognitive enhancement.
  • Sample size: Recruit as large of a sample as possible for a future study – preferably at least 100 participants.
  • Sample specifics: Only test the effects of creatine in healthy adults devoid of medical conditions. Include both males and females in the sample, as well as adults of all ages.

Based on the research, does creatine enhance cognition?

Unknown.  Despite the fact that many studies have investigated the effect of creatine on cognition, there are so many limitations associated with the research that it’s relatively impossible to know whether creatine legitimately enhances cognitive function – especially among healthy individuals in normal conditions.  If I were to speculate, I’d hypothesize that regular supplementation with creatine at sufficient doses may enhance aspects of brain function, which in turn, may yield cognitive enhancement in a subset of the population.

It should be stated that there’s no evidence to suggest that creatine supplementation negatively affects aspects of cognitive performance.  Moreover, there are obvious mechanisms by which creatine supplementation augments general brain function such as by upregulating oxygenation – this has been confirmed with neuroimaging data.  This considered, it’s fair to suspect that creatine supplementation probably decreases likelihood of cognitive decline (due to environmental factors) and possibly enhances cognitive function.

That said, the degree to which most individuals derive cognitive enhancement from creatine may be subject to significant individual variation based on: preexisting neurochemistry, genetics, epigenetic expression, age, sex, and environmental factors.  Certain people may claim that creatine supplementation significantly enhances cognitive performance, whereas others may report no subjective change in cognitive function.  Nevertheless, it’s possible that cognitive enhancing effects derived from creatine are very subtle, and in most cases, unnoticeable.

FAQ: Creatine for Cognitive Enhancement

I’ve created a little “frequently asked questions” (FAQ) section for this article for individuals who are interested in using creatine as a cognitive enhancer.  None of this should be taken as medical advice regarding creatine.  If you have any question, always talk to your doctor – the following are merely my personal opinions and may be subject to inaccuracies.

Is it safe for you to take creatine?

I don’t know if creatine is safe for you.  Never take creatine without first consulting a medical doctor to ensure that it’s safe in accordance with your age, medical status, and/or medication regimen.  Unless you have kidney issues, creatine is probably going to be safe.  Moreover, if you start taking creatine and notice any adverse effects – stop taking it and seek immediate medical attention.  There are some concerns that creatine may negatively affect glucose homeostasis and/or induce balding.

Could creatine negatively impact cognition?

It’s possible.  If you’re using contaminated creatine or simply are a person with a baseline neurochemical signature (mediated by your genes) that performs better without creatine – perhaps supplementation could be detrimental.  If you supplement with creatine and perform worse on cognitively-demanding tasks, I’d recommend ceasing supplementation.  Moreover, it’s possible that creatine supplementation may enhance certain aspects of cognition while simultaneously compromising others (such as in a “tradeoff”).

What type of creatine is best for enhancing cognition?

Creatine monohydrate or creatine ethyl ester.  Most studies have tested the effect of creatine monohydrate on cognition and some have reported benefit.  Only one study has evaluated the effect of creatine ethyl ester (CEE) on cognitive function, however, its effects were not directly compared to those of creatine monohydrate.  At this time, it remains unclear as to which type of creatine would prove most efficacious as a cognitive enhancer.

Based on evidence indicating that both formats of creatine elicit similar biologic effects, I wouldn’t suspect that one is somehow superior to the other in terms of facilitating cognitive enhancement.  It’s possible that one format may exhibit quicker and/or more efficient uptake into the brain, however, this has never been researched.  Moreover, if a chemist wanted to, perhaps a form of creatine could be synthesized specifically to predominantly increase brain creatine levels (rather than peripheral levels in muscle tissue).

What dosage of creatine should you take to enhance cognition?

5 grams per day.  Research indicates that supplementation with creatine monohydrate at 20 grams per day for 5 days (loading phase), followed by 5 grams per day thereafter may enhance cognitive function.  If you plan on taking creatine for an extended duration, there’s not really any need to do a “loading phase” of 20 grams per day for 5 days.  If you’re ever confused about dosing, follow guidelines on the specific creatine product that you purchased.

How long will you need to take creatine to get results?

It depends (1 to 8 weeks).  If you don’t utilize a 5-day loading phase, it may take longer to reap cognitive enhancement from creatine compared to if you initiate and maintain dosing at 5 grams per day.  Although studies have reported cognitive enhancement from creatine supplementation after just 5 days, my guess is that to attain maximal cognitive benefit, it’ll take at least 2 to 8 weeks.  If you don’t notice any cognitive enhancement after 8 weeks of supplementation at 5 grams per day – creatine probably isn’t having any effect.

Will everyone notice cognitive enhancement from creatine?

No. Firstly, creatine is probably not an effective cognitive enhancer in every user due to individual variables (e.g. genetics, neurochemistry, etc.).  Secondly, among those who reap cognitive enhancement from creatine supplementation, many may not be self-aware enough to know that they’re benefitting.  In some cases, the cognitive enhancement derived from creatine may be so subtle that, without randomized cognitive testing, it would be impossible for most users to subjectively report a favorable change in cognitive performance.

How is cognition affected if you stop taking creatine?

Reversion to baseline.  Assuming you attained cognitive benefit from creatine, if you stop taking it for several weeks, the creatine-related cognitive enhancement will subside.  You will not dip below cognitive baseline such as may occur after using a pharmaceutical cognitive enhancer like dextroamphetamine.  (There won’t be any withdrawal symptoms when you cease creatine).  Moreover, you may not even notice a change in cognition if the benefit you attained from creatine supplementation was subtle.

Do I personally use creatine as a cognitive enhancer?

Over the past 3 years, I used creatine monohydrate at a dosage of 5 grams per day (without any breaks) as a supplement to potentially enhance cognitive function while simultaneously improving my gym performance (bodybuilding, strength training, etc.).  In February 2017, I developed peripheral neuropathic pain affecting my median and radial nerves.  As of March 2017, I discontinued supplementation with creatine on speculation that it might exacerbate my nerve issues.

Medical professionals were unsure of whether creatine supplementation might exacerbate my neurological condition, however, all 5 of my doctors said that it was probably fine to continue using creatine monohydrate at the 5 gram per day dosage.  Nevertheless, I hypothesized that creatine may increase water retention within my hands and/or wrists, possibly increasing interstitial wrist pressure whereby nerve issues and corresponding symptoms are exacerbated.  Because I figured that creatine could exacerbate my condition and/or inhibit peripheral nerve recovery from damage – I ceased supplementation.

Had my nerve condition never emerged, I’d still be using creatine monohydrate at a dose of 5 grams per day.  Subjectively, I believe that creatine monohydrate supplementation modestly enhances my cognitive performance – especially when administered with other supplements.  That said, my subjective opinion of creatine’s effects on my own cognition could be inaccurate as I never bothered doing cognitive batteries “before” and “after” supplementation to gauge benefits.

What type of creatine do I recommend for cognition?

Creatine monohydrate or creatine ethyl ester.  As I’ve mentioned, most studies reporting cognitive benefit from creatine utilized creatine monohydrate.  One study reported significant cognitive benefit from creatine ethyl ester.  In my opinion, both supplements are likely to be somewhat equivalent in terms of their cognitive effects.  If you suspect that one format could be superior to the other for cognitive enhancement, I’d recommend trying each for 4 to 8 weeks – then determine whether one seems to work better for you.

What specific brands of creatine supplements do I recommend?

If you’re supplementing with creatine, it’s imperative that you do some research to ensure that you’re getting a quality product.  Quality should be your top priority.  By quality, I mean you’ll want to buy a creatine product that is devoid of heavy metals and potentially-problematic ingredients – as well as a product that has an accurate label (amount of creatine per serving).

Lastly, you’ll probably want to ensure that you aren’t getting ripped off (i.e. overpaying) for your creatine product.  Fortunately, the company Labdoor has already tested many popular brands of creatine for label accuracy, purity, and heavy metal content.  Below are my top 3 recommendations for creatine based on the Labdoor results.

  1. MyProtein Creatine Monohydrate
  2. Bulk Supplements Creatine Monohydrate
  3. NOW Sports Creatine Monohydrate

Note: The above products contain affiliate links, meaning, if you buy through my links I’ll earn a commission (you’ll help support my content).

Final thoughts on creatine as a cognitive enhancer

In closing, I think that creatine supplementation may prove useful for some as a cognitive enhancer.  Success with creatine as a cognitive enhancer will be subject to significant individual variation.  Furthermore, it’s possible that the administration of other supplements and/or drugs along with creatine may increase or decrease its cognitive enhancing effects.  (For example: One trial reported greater enhancement from creatine plus ginkgo biloba extract than standalone creatine).

Assuming a medical doctor says creatine supplementation is safe for you, it may be worth trying to determine whether it enhances your cognition.  If you don’t notice any cognitive enhancement effect after supplementing with creatine for 4 to 8 weeks – you may be a non-responder.  If you notice some subjective cognitive enhancement from creatine supplementation – it may be worth continuing.

Have you used creatine as a cognitive enhancer?

If you’ve used creatine specifically to enhance cognition, I’d appreciate if you documented some details associated with your creatine supplementation in the comments section.  I’ve organized a list of questions that may help myself and other readers understand your experience with creatine.  Although you do not need to answer any of these questions to leave a comment, the more information you provide, the better.

  • What dosage of creatine do you take per day?
  • What specific type of creatine do you use? (e.g. monohydrate, ethyl ester, etc.)
  • For how long have you been using creatine on a daily basis?
  • What specific brand of creatine do you use?
  • Have you subjectively noted any cognitive enhancement as a result of using creatine?
  • If you think that creatine enhanced your cognition, in what ways has it helped?
  • On a scale from 1 to 10, with 10 being highest efficacy, what would you rate creatine as a cognitive enhancer (in your experience)?
  • Would you personally recommend using creatine as a cognitive enhancer?

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