CoChat
Sign Up
Cited by 71Muscle metabolism and nutritionBiochemical effects in animalsNeurological Disorders and Treatments

Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials

Open access
Prokopidis, Konstantinos, Giannos, Panagiotis, Triantafyllidis, Konstantinos K, Kechagias, Konstantinos S, Forbes, Scott C, Candow, Darren G·2023·Nutrition Reviews
DOI 10.1093/nutrit/nuac064PMC PMC9999677
Open this paper in CoChat — free accountOpen PDF

Abstract

Context: From an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory. Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effects of creatine supplementation on memory performance in healthy humans. Data Sources: The literature was searched through the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until September 2021. Data Extraction: Twenty-three eligible RCTs were initially identified. Ten RCTs examining the effect of creatine supplementation compared with placebo on measures of memory in healthy individuals met the inclusion criteria for systematic review, 8 of which were included in the meta-analysis. Data Analysis: Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04–0.53; I2 = 66%; P = 0.02). Subgroup analyses revealed a significant improvement in memory in older adults (66–76 years) (SMD = 0.88; 95%CI, 0.22–1.55; I2 = 83%; P = 0.009) compared with their younger counterparts (11–31 years) (SMD = 0.03; 95%CI, −0.14 to 0.20; I2 = 0%; P = 0.72). Creatine dose (≈ 2.2–20 g/d), duration of intervention (5 days to 24 weeks), sex, or geographical origin did not influence the findings. Conclusion: Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years). Systematic Review Registration: PROSPERO registration no. 42021281027.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis found that creatine monohydrate supplementation improved memory performance versus placebo in healthy individuals, with a larger effect in older adults (66–76 years). However, heterogeneity was moderate and risk of bias was a concern, so the authors urge caution.

Key findings

  • Across 8 RCTs (225 participants: 74 males, 151 females; 122 creatine, 118 placebo), creatine supplementation improved memory versus placebo: SMD = 0.29, 95%CI 0.04–0.53; I² = 66%; P = 0.02.
  • Subgroup analysis showed a significant memory improvement in older adults (66–76 years): SMD = 0.88, 95%CI 0.22–1.55; I² = 83%; P = 0.009, but not in younger adults (11–31 years): SMD = 0.03, 95%CI −0.14 to 0.20; I² = 0%; P = 0.72.
  • Creatine dose (≈2.2–20 g/d), duration (5 days to 24 weeks), sex, or geographical origin did not influence findings. Powdered creatine monohydrate improved memory (SMD = 0.35, 95%CI 0.05–0.66; I² = 73%; P = 0.02), whereas encapsulated creatine did not (SMD = 0.04, 95%CI −0.30 to 0.39; I² = 0%; P = 0.80).
  • Significant improvements were seen under nonstressed conditions (SMD = 0.43, 95%CI 0.09–0.78; I² = 75%; P = 0.01) and with <15% loss to follow-up (SMD = 0.33, 95%CI 0.04–0.62; I² = 68%; P = 0.03), but not under stressed conditions or ≥15% loss.

Methods

  • Systematic review and meta-analysis of RCTs, conducted per PRISMA and registered in PROSPERO (CRD:42021281027). Searches of PubMed, Scopus, Web of Science, and Cochrane Library from inception until September 30, 2021 identified 23 eligible RCTs; 10 met inclusion criteria for systematic review and 8 for meta-analysis.
  • Inclusion criteria: healthy participants, creatine monohydrate supplementation, placebo comparator, and memory performance outcomes. Exclusions included non-RCTs, unavailable full text, comorbidities, and dietary restrictions such as vegetarian/vegan diets.
  • Random-effects meta-analysis using inverse-variance method and standardized mean differences when outcome units were inconsistent; heterogeneity assessed with Cochran’s Q and I²; sensitivity and subgroup analyses examined creatine form, stress condition, loss to follow-up, age, sex, treatment duration, and dose. Risk of bias assessed with Cochrane RoB 2.

Limitations

  • The authors state that included studies did not assess baseline serum or brain creatine, so it remains inconclusive whether differential responder/non-responder effects are linked to baseline creatine levels or metabolic dimorphism.
  • The authors note methodological limitations: combining various memory assessment tools increased heterogeneity; several tests may have required auxiliary cognition such as attention; most studies did not assess dietary creatine intake; and included studies were of moderate quality by RoB 2.
  • The authors state publication bias could not be assessed because the number of included studies was too low. The text also makes evident that the meta-analysis included only 225 participants and that subgroup/sensitivity analyses did not reduce heterogeneity, especially since different memory outcomes were derived from the same populations in each study.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/nutrit/nuac064

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 40 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    High-dose creatine monohydrate supplementation (>5 g/d) was not associated with improvements in memory measures (SMD = 0.33; 95%CI, −0.07 to 0.74; I2 = 78%; P = 0.11).

    “creatine monohydrate supplementation in low doses (≤ 5 g/d) (SMD = 0.24; 95%CI, −0.04 to 0.52; I2 = 38%; P = 0.09) or high doses (> 5 g/d) (SMD = 0.33; 95%CI; −0.07 to 0.74; I2 = 78%; P = 0.11) was not associated with improvements in memory measures (Figure 3A).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Different memory assessment tools can be combined into a single measure of memory performance for meta-analysis.
    • Rests on an assumption: Baseline serum or brain creatine levels did not differ systematically between creatine and placebo groups or did not confound the effect of creatine on memory.
    • Rests on an assumption: Dietary creatine intake did not confound the observed effects of creatine supplementation on memory.
    • Rests on an assumption: Publication bias is absent or does not materially affect the meta-analysis findings.
    • Rests on an assumption: The included studies' moderate risk of bias does not invalidate the pooled effect estimate.
  • Findingown data

    Encapsulated creatine monohydrate had no effect on memory measures (SMD = 0.04; 95%CI, −0.30 to 0.39; I2 = 0%; P = 0.80).

    “but no effect of encapsulated creatine monohydrate was found (SMD = 0.04; 95%CI, −0.30 to 0.39; I2 = 0%; P = 0.80)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Different memory assessment tools can be combined into a single measure of memory performance for meta-analysis.
    • Rests on an assumption: Baseline serum or brain creatine levels did not differ systematically between creatine and placebo groups or did not confound the effect of creatine on memory.
    • Rests on an assumption: Dietary creatine intake did not confound the observed effects of creatine supplementation on memory.
    • Rests on an assumption: Publication bias is absent or does not materially affect the meta-analysis findings.
    • Rests on an assumption: The included studies' moderate risk of bias does not invalidate the pooled effect estimate.
  • Findingown data

    In cohorts with loss to follow-up exceeding 15%, no significant differences in memory were observed (SMD = 0.02; 95%CI, −0.26 to 0.29; I2 = 0%; P = 0.90).

    “while no significant differences were observed in cohorts in which the rate exceeded 15% (SMD = 0.02; 95%CI, −0.26 to 0.29; I2 = 0%; P = 0.90)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Different memory assessment tools can be combined into a single measure of memory performance for meta-analysis.
    • Rests on an assumption: Baseline serum or brain creatine levels did not differ systematically between creatine and placebo groups or did not confound the effect of creatine on memory.
    • Rests on an assumption: Dietary creatine intake did not confound the observed effects of creatine supplementation on memory.
    • Rests on an assumption: Publication bias is absent or does not materially affect the meta-analysis findings.
    • Rests on an assumption: The included studies' moderate risk of bias does not invalidate the pooled effect estimate.
  • Findingown data

    Low-dose creatine monohydrate supplementation (≤5 g/d) was not associated with improvements in memory measures (SMD = 0.24; 95%CI, −0.04 to 0.52; I2 = 38%; P = 0.09).

    “creatine monohydrate supplementation in low doses (≤ 5 g/d) (SMD = 0.24; 95%CI, −0.04 to 0.52; I2 = 38%; P = 0.09) or high doses (> 5 g/d) (SMD = 0.33; 95%CI; −0.07 to 0.74; I2 = 78%; P = 0.11) was not associated with improvements in memory measures (Figure 3A).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Different memory assessment tools can be combined into a single measure of memory performance for meta-analysis.
    • Rests on an assumption: Baseline serum or brain creatine levels did not differ systematically between creatine and placebo groups or did not confound the effect of creatine on memory.
    • Rests on an assumption: Dietary creatine intake did not confound the observed effects of creatine supplementation on memory.
    • Rests on an assumption: Publication bias is absent or does not materially affect the meta-analysis findings.
    • Rests on an assumption: The included studies' moderate risk of bias does not invalidate the pooled effect estimate.
  • Findingown data

    In cohorts with loss to follow-up below 15%, creatine supplementation significantly improved memory (SMD = 0.33; 95%CI, 0.04-0.62; I2 = 68%; P = 0.03).

    “in cohorts in which loss to follow-up was below 15%, significant improvements in memory were seen (SMD = 0.33; 95%CI, 0.04–0.62; I2 = 68%; P = 0.03)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Different memory assessment tools can be combined into a single measure of memory performance for meta-analysis.
    • Rests on an assumption: Baseline serum or brain creatine levels did not differ systematically between creatine and placebo groups or did not confound the effect of creatine on memory.
    • Rests on an assumption: Dietary creatine intake did not confound the observed effects of creatine supplementation on memory.
    • Rests on an assumption: Publication bias is absent or does not materially affect the meta-analysis findings.
    • Rests on an assumption: The included studies' moderate risk of bias does not invalidate the pooled effect estimate.
  • May combine two claims. 11
  • Classified as probably not a substantial claim. 14

  • May combine two claims.

    Findingown data

    Sex did not affect memory outcome measures (females and males, SMD = 0.26; 95%CI, −0.05 to 0.57; I2 = 69%; P = 0.10; females, SMD = 0.39; 95%CI, −0.07 to 0.86; I2 = 62%; P = 0.10; males, SMD = −0.12; 95%CI, −1.02 to 0.78; P = 0.79).

    “or sex ([females and males, SMD = 0.26; 95%CI, −0.05 to 0.57; I2 = 69%; P = 0.10], [females, SMD = 0.39; 95%CI, −0.07 to 0.86; I2 = 62%; P = 0.10], [males, SMD = −0.12; 95%CI, −1.02 to 0.78; P = 0.79]) (Figure 3D).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Different memory assessment tools can be combined into a single measure of memory performance for meta-analysis.
    • Rests on an assumption: Baseline serum or brain creatine levels did not differ systematically between creatine and placebo groups or did not confound the effect of creatine on memory.
    • Rests on an assumption: Dietary creatine intake did not confound the observed effects of creatine supplementation on memory.
    • Rests on an assumption: Publication bias is absent or does not materially affect the meta-analysis findings.
    • Rests on an assumption: The included studies' moderate risk of bias does not invalidate the pooled effect estimate.

  • May combine two claims.

    Interpretationcitation

    The amount of either endogenous creatine synthesis or dietary creatine intake may be sufficient to maintain adequate brain creatine stores, and a higher exogenous dose of creatine is not required.

    “the results suggest that the amount of either endogenous creatine synthesis or dietary creatine intake may be sufficient to maintain adequate brain creatine stores45 and that a higher exogenous dose of creatine is not required, despite the limited ability of creatine to cross the blood-brain barrier.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Brosnan ME, Brosnan JT. The role of dietary creatine. Amino Acids. 2016; 48: 1785– 1791. 26874700 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Creatine-deficient syndromes that deplete brain creatine stores are characterized by mental and developmental disorders such as learning delays and seizures, and these symptoms can be partially reversed by creatine supplementation.

    “As an example of the importance of creatine in humans, creatine-deficient syndromes that deplete brain creatine stores are characterized by mental and developmental disorders such as learning delays and seizures17,18; importantly, these symptoms can be partially reversed by creatine supplementation.19–21”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [17] Bender A, Klopstock T. Creatine for neuroprotection in neurodegenerative disease: end of story? Amino Acids. 2016; 48: 1929– 1940. 26748651 source

      Not checked in the free run.

    • cites [18] Mercimek-Andrews S, Salomons GS. Creatine deficiency disorders. In: Adam MP, Mirzaa GM, Pagon RA, et al, eds. Gene Reviews [internet]. University of Washington; 2009. https://www.ncbi.nlm.nih.gov/books/NBK3794/ 20301745

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [19] Kaldis P, Hemmer W, Zanolla E, et al ‘Hot spots’ of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus. Dev Neurosci. 1996; 18: 542– 554. 8940630 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The quality of included studies was assessed using version 2 of the Cochrane risk-of-bias 2 tool for randomized trials (RoB 2) and evaluated by 3 independent reviewers.

    “The quality of included studies was assessed using version 2 of the Cochrane risk-of-bias 2 tool for randomized trials (RoB 2) and evaluated by 3 independent reviewers (K.P., P.G., and K.K.T.).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Discrepancies in the literature search process were resolved by a third investigator.

    “Discrepancies in the literature search process were resolved by a third investigator (K.S.K.).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other researchers have failed to find beneficial effects of creatine supplementation on measures of memory in children, adults, and older adults.

    “Other researchers, however, have failed to find beneficial effects of creatine supplementation on measures of memory in children,36 adults27,28,30,34 and older adults.25,35”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [36] Merege-Filho CAA, Otaduy MCG, de Sá-Pinto AL, et al Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study. Appl Physiol Nutr Metab. 2017; 42: 128– 134. 28079396 source

      Not checked in the free run.

    • cites [27] McMorris T, Harris RC, Howard AN, et al Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiol Behav. 2007; 90: 21– 28. 17046034 source

      Not checked in the free run.

    • cites [28] McMorris T, Harris RC, Swain J, et al Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology (Berl). 2006; 185: 93– 103. 16416332 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Sensitivity analysis was performed to evaluate the robustness of reported statistical results by discounting the effects of creatine form, stress conditions, and rate of participants lost during follow-up.

    “Furthermore, sensitivity analysis was performed to evaluate the robustness of reported statistical results by discounting the effects of creatine form (encapsulated vs powder), conditions of stress (normal vs stressed [following hypoxia, sleep deprivation, or exhaustive exercise]), and rate of participants lost during follow-up (< 15% loss vs ≥ 15% loss).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In vitro, creatine elevates phosphocreatine and ATP levels and increases oxidative phosphorylation in synaptosomes and isolated brain mitochondria.

    “In vitro, creatine elevates phosphocreatine and ATP levels11 and increases oxidative phosphorylation in synaptosomes and isolated brain mitochondria.12”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Brewer GJ, Wallimann TW. Protective effect of the energy precursor creatine against toxicity of glutamate and β‐amyloid in rat hippocampal neurons. J Neurochem. 2000; 74: 1968– 1978. 10800940 source

      Not checked in the free run.

    • cites [12] Monge C, Beraud N, Kuznetsov AV, et al Regulation of respiration in brain mitochondria and synaptosomes: restrictions of ADP diffusion in situ, roles of tubulin, and mitochondrial creatine kinase. Mol Cell Biochem. 2008; 318: 147– 165. 18629616 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Snow et al found that 4 weeks of creatine supplementation in mice increased coupled respiration in isolated hippocampal mitochondria and improved memory.

    “More recently, Snow et al16 found that 4 weeks of creatine supplementation in mice increased coupled respiration in isolated hippocampal mitochondria and improved memory.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Snow WM, Cadonic C, Cortes-Perez C, et al Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB. Learn Mem. 2018; 25: 54– 66. 29339557 PMC5772392 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    The inconsistent findings across individual studies may be related to methodological differences (dosage and duration), population characteristics (age, sex, geographical origin), or low sample size.

    “While multifactorial, these inconsistent findings across individual studies may be related to methodological differences (dosage and duration of creatine supplementation), population characteristics (age, sex, geographical origin), or low sample size.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Benton and Donohoe found better memory following creatine supplementation (20 g/d for 5 days) in vegetarians compared with meat eaters.

    “In a direct comparison of omnivores and vegetarians, Benton and Donohoe24 found better memory following creatine supplementation (20 g/d for 5 days) in vegetarians compared with meat eaters.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. 2011; 105: 1100– 1105. 21118604 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Creatine supplementation increases brain creatine content and the ratio of phosphocreatine to ATP in humans.

    “Creatine supplementation increases brain creatine content and the ratio of phosphocreatine to ATP.4,5”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Dechent P, Pouwels P, Wilken B, et al Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol Regulat Integr Comparat Physiol. 1999; 277: R698– R704. 10484486 source

      Not checked in the free run.

    • cites [5] Pan JW, Takahashi K. Cerebral energetic effects of creatine supplementation in humans. Am J Physiol Regulat Integr Comparat Physiol. 2007; 292: R1745– R1750. PMC3570026 17185404 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Two authors extracted data independently.

    “Two authors (K.P. and P.G.) extracted data independently.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Disagreements between authors were resolved by a third reviewer.

    “Disagreements between authors were resolved by a third reviewer (K.K.T.).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Two independent reviewers searched PubMed, Scopus, Web of Science, and the Cochrane library from inception until September 30, 2021.

    “Two independent reviewers (K.P. and P.G.) searched PubMed, Scopus, Web of Science, and the Cochrane library from inception until September 30, 2021.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The protocol was registered in the PROSPERO database (CRD:42021281027).

    “The protocol was registered in the PROSPERO (International Prospective Register of Systematic Reviews) database (CRD:42021281027).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The systematic review and meta-analysis was conducted in accordance with PRISMA guidelines.

    “This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.40”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Page MJ, McKenzie JE, Bossuyt PM, et al The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021; 10: 89. 33781348 PMC8008539 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vegetarians have a lower creatine content in muscle and are more responsive to creatine supplementation.

    “Vegetarians have a lower creatine content in muscle and are more responsive to creatine supplementation.38”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Burke DG, Chilibeck PD, Parise G, et al Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exerc 2003; 35: 1946– 1955. 10.1249/01.MSS.0000093614.17517.79 14600563 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A previous RCT found that word recall response declined following creatine supplementation (20 g/d for 5 days) in meat-eaters compared with vegan and vegetarian participants, and post-supplementation comparisons revealed significantly greater memory in vegetarians compared with omnivores.

    “A previous RCT found that word recall response declined following creatine supplementation (20 g/d of creatine for 5 days) in meat-eaters compared with vegan and vegetarian participants, and post-supplementation comparisons revealed a significantly greater memory in vegetarians compared with omnivores.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. 2011; 105: 1100– 1105. 21118604 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Most of the included studies did not assess creatine intake from dietary consumption, which may have altered the findings.

    “Furthermore, most of the included studies did not assess creatine intake from dietary consumption, which may have altered the findings.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. 2011; 105: 1100– 1105. 21118604 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The lack of homogeneity in outcomes of memory performance illustrates an unmet demand for common assessment tools.

    “The lack of homogeneity in outcomes of memory performance illustrates an unmet demand for common assessment tools that could be used by both researchers and practitioners in the pursuit of results with higher precision and accuracy.”
    Quote in the paperNot a substantial claim
21 of 21

  • The paper relies on this without support.

    Different memory assessment tools can be combined into a single measure of memory performance for meta-analysis.

    “Memory performance was considered the main outcome in the analysis and comprised multiple measures of memory from comparable studies, with no restrictions placed on the tool used for assessment.”
    “In particular, several memory tests were combined to increase the statistical power (including short-term, long-term, and working memory).”

  • The paper relies on this without support.

    Baseline serum or brain creatine levels did not differ systematically between creatine and placebo groups or did not confound the effect of creatine on memory.

    “A limitation, however, is that the included studies did not assess baseline levels of serum or brain creatine.”
    “As such, it was not possible to determine whether non-responders had lower brain creatine levels than responders.”

  • The paper relies on this without support.

    Dietary creatine intake did not confound the observed effects of creatine supplementation on memory.

    “Furthermore, most of the included studies did not assess creatine intake from dietary consumption, which may have altered the findings.24”

  • The paper relies on this without support.

    Publication bias is absent or does not materially affect the meta-analysis findings.

    “Finally, it was not possible to assess publication bias, which could affect the quality of evidence, because the number of included studies was too low.”

  • The paper relies on this without support.

    The included studies' moderate risk of bias does not invalidate the pooled effect estimate.

    “However, a moderate risk of bias and significant heterogeneity between studies were observed, and therefore caution is warranted.”
    “The included studies were of moderate quality, according to the Cochrane RoB 2 tool.”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Turner supplementation duration differs between text and table

    Minor

    The text assigns study 30 a two-week duration, while its Table 2 row specifies seven days.

  • Turner table row lists 30 people by sex but a total of 15

    Minor

    The row reports 20 males and 10 females under a total of 15. Its creatine and placebo columns each list 15 participants, consistent with a crossover trial, but not with the reported total-sex entry.

    Reported 15 · recomputed 30

  • Reported dose-category counts exceed the number of studies

    Minor

    The dose categories are reported as seven studies at 20 g/d and one study at each of four other doses, totaling 11 studies, although the review includes 10. The 20-g/d statement also cites only six studies.

    Reported 10 · recomputed 11

  • Merege-Filho total lists zero males despite males in both groups

    Minor

    The creatine and placebo groups list 19 males each, whereas the total column reports zero males.

    Reported 0 · recomputed 38

  • McMorris 2007a is classified as mixed-sex despite an all-male table row

    Minor

    Study 27 appears in the list of mixed-sex studies, but Table 2 reports 19 males and no females for that study.

  • Rawson male count differs between total and group columns

    Minor

    The two groups list 6 males each, giving 12 rather than the 13 males in the total column.

    Reported 13 · recomputed 12

  • Adult-only population criterion conflicts with inclusion of children

    Minor

    Table 1 specifies healthy adults as the included population, but Table 2 includes a study whose participants were aged 10-12 years.

7 of 7

Cites

Flagged first, then by citations

1 of the 47 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Mercimek-Andrews, 2009, Gene Reviews
  2. Smolarek, 2020, Effect of 16 weeks of strength training and creatine supplementation on strength and cognition in older adults: a pilot study, J Exerc Physiol Online, 23, 88

Cited by

Sorted by citations

Related

Authors
Prokopidis, K., Giannos, P., Triantafyllidis, K. K., Kechagias, K. S., Forbes, S. C., & Candow, D. G.
Affiliations
  • University of Liverpool (GB)
  • Imperial College London (GB)
  • Musgrove Park Hospital (GB)
  • Chelsea and Westminster Hospital NHS Foundation Trust (GB)
  • Brandon University (CA)
  • University of Regina (CA)
Corresponding author
Prokopidis, Konstantinos
ORCID
Venue
Nutrition Reviews
Publisher
Oxford University Press (OUP)
Published
2022-08-19
Volume
81
Issue
4
Pages
416-427
ISSN
  • 0029-6643 (ISSN-L)
  • 1753-4887
DOI
10.1093/nutrit/nuac064
PMC
PMC9999677
OpenAlex
W4294349271
Semantic Scholar
5fe0a800083cd633d5cfa653d91907b09f2b1b89
Cited by
71
References
47
Citations by year
2026: 20 · 2025: 22 · 2024: 24 · 2023: 5
FWCI
1.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrition Reviews (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › Biochemical effects in animals
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
creatine supplementation, memory, brain energy metabolism, older adults, cognitive performance, healthy individuals
MeSH terms
Aged, Cognition, Creatine, Humans, Randomized Controlled Trials as Topic, Dietary Supplements

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review