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Cited by 29Muscle metabolism and nutritionBiochemical effects in animalsNeurological Disorders and Treatments

The effects of creatine supplementation on cognitive performance—a randomised controlled study

Open access
Sandkühler, Julia Fabienne, Kersting, Xenia, Faust, Annika, Königs, Eva Kathrin, Altman, George, Ettinger, Ulrich, Lux, Silke, Philipsen, Alexandra +2 more·2023·BMC Medicine
DOI 10.1186/s12916-023-03146-5PMC PMC10647179

Published version of a preprint

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Abstract

Background: Creatine is an organic compound that facilitates the recycling of energy-providing adenosine triphosphate (ATP) in muscle and brain tissue. It is a safe, well-studied supplement for strength training. Previous studies have shown that supplementation increases brain creatine levels, which might increase cognitive performance. The results of studies that have tested cognitive performance differ greatly, possibly due to different populations, supplementation regimens, and cognitive tasks. This is the largest study on the effect of creatine supplementation on cognitive performance to date. Methods: Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each. We tested participants on Raven’s Advanced Progressive Matrices (RAPM) and on the Backward Digit Span (BDS). In addition, we included eight exploratory cognitive tests. About half of our 123 participants were vegetarians and half were omnivores. Results: Bayesian evidence supported a small beneficial effect of creatine. The creatine effect bordered significance for BDS ( p = 0.064, η 2 P = 0.029) but not RAPM ( p = 0.327, η 2 P = 0.008). There was no indication that creatine improved the performance of our exploratory cognitive tasks. Side effects were reported significantly more often for creatine than for placebo supplementation ( p = 0.002, RR = 4.25). Vegetarians did not benefit more from creatine than omnivores. Conclusions: Our study, in combination with the literature, implies that creatine might have a small beneficial effect. Larger studies are needed to confirm or rule out this effect. Given the safety and broad availability of creatine, this is well worth investigating; a small effect could have large benefits when scaled over time and over many people. Trial registration: The trial was prospectively registered (drks.de identifier: DRKS00017250, https://osf.io/xpwkc/ ).

AI snapshot

Written from the paper’s full text.

TL;DR

In a preregistered, double-blind, placebo-controlled crossover trial, creatine supplementation (5 g/day for 6 weeks) produced Bayesian evidence for a small cognitive benefit, with the effect bordering significance for Backward Digit Span but not Raven’s Advanced Progressive Matrices. Vegetarians did not benefit more than omnivores, exploratory cognitive tasks showed no indication of improvement, and side effects were reported significantly more often with creatine.

Key findings

  • For the primary outcomes, creatine effect bordered significance for BDS (p = 0.064, η2P = 0.029) but not RAPM (p = 0.327, η2P = 0.008); raw-score effects were 0.41 additional BDS items and 0.23 more RAPM matrices solved, corresponding to Cohen’s d = 0.17 for BDS and d = 0.09 for RAPM.
  • Bayesian evidence supported a small beneficial effect of creatine, but there was strong evidence against the large effect size reported by Rae et al. (BF10 < 2e−7 for the Rae-sized effect).
  • There was no indication that creatine improved performance on the eight exploratory cognitive tasks, and vegetarians did not benefit more than omnivores (no significant diet × supplement interaction for BDS p = 0.808 or RAPM p = 0.392).
  • Side effects were reported significantly more often for creatine than placebo (p = 0.002, RR = 4.25; 17% vs 4% any side effects).

Methods

  • Preregistered, randomised, double-blind, placebo-controlled crossover trial; participants took 5 g/day creatine monohydrate or placebo for 6 weeks each, with 6 weeks of placebo relied on for washout.
  • 123 participants were included, about half vegetarians and half omnivores; primary outcomes were Raven’s Advanced Progressive Matrices (RAPM) and Backward Digit Span (BDS), plus eight exploratory cognitive tests.
  • Main analysis used mixed ANOVA with supplement as within-subjects factor and supplement order/diet as between-subjects factors, supplemented by Bayesian analyses and robustness checks (trimming, winsorising, bootstrapped robust ANOVA).

Limitations

  • Stated: a larger sample would be needed to be powered for smaller but still relevant effects; 4% of data could not be analysed because it was not labelled with participant and timepoint; COVID-19 began mid-study and forced a switch from in-person to video-call testing; meat consumption was assessed as days per week, not grams per day; adherence was self-reported; brain creatine levels were not assessed; blinding was imperfect, with 59% correctly guessing supplement order (p = 0.08), likely aided by solubility differences and side effects.
  • Stated: mixing creatine in yoghurt to mask solubility may have affected absorption, though the authors judged absorption likely similar to cold water but worse than warm water.
  • Evident from the text: the BDS result was not robust across analyses (p-values ranged from 0.009 with 5% winsorisation to 0.370 with bootstrapped 20% trimming), and the study was powered for d = 0.45 while observed effects were much smaller (d = 0.09–0.17).

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

Integrity signals

Registry

Crossref · 10.1186/s12916-023-03146-5

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 103 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Vegetarians did not benefit more from creatine than omnivores.

    “Vegetarians did not benefit more from creatine than omnivores.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Bayesian evidence supported a small beneficial effect of creatine.

    “Bayesian evidence supported a small beneficial effect of creatine.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was strong evidence in favour of the null hypothesis compared to the alternative hypothesis postulating the effect size found by Rae et al.

    “There was strong evidence in favour of the null hypothesis compared to the alternative hypothesis postulating the effect size found by Rae et al. [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rae et al. [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

  • Findingown data

    The creatine effect was not significant for RAPM (p = 0.327, η2P = 0.008).

    “The creatine effect bordered significance for BDS (p = 0.064, η2P = 0.029) but not RAPM (p = 0.327, η2P = 0.008).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Side effects were reported significantly more often for creatine than for placebo supplementation (p = 0.002, RR = 4.25).

    “Side effects were reported significantly more often for creatine than for placebo supplementation (p = 0.002, RR = 4.25).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 54
  • Classified as probably not a substantial claim. 47

  • May combine two claims.

    Findingown data

    The data was insensitive (BDS) or weakly favoured the null hypothesis (RAPM) when compared to the half-normal model based on Rae et al.

    “The data was insensitive (BDS) or weakly favoured the null hypothesis (RAPM) when compared to the half-normal model based on Rae et al. [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rae et al. [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    For BDS, the p-value for the supplement effect was 0.009 for the 5% winsorisation and 0.370 for the bootstrap ANOVA.

    “Most notably, the p-value for the supplement effect was 0.009 for the 5% winsorisation and 0.370 for the bootstrap ANOVA.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no significant interaction between diet and supplement, nor between diet, supplement, and supplement order, for BDS or RAPM.

    “There was no significant interaction between diet and supplement nor between diet, supplement, and supplement order for neither BDS (p = 0.808 and p = 0.559) nor RAPM (p = 0.392 and p = 0.606)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The result for RAPM was robust and for BDS much less so.

    “Thus, the result for RAPM was robust and for BDS much less so.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    In this study, half of the participants were vegetarians and half were omnivores.

    “In our study, half of the participants were vegetarians and half of them were omnivores.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cohen's d based on the estimated marginal means of the creatine and placebo scores was 0.09 for RAPM and 0.17 for BDS.

    “Cohen’s d based on the estimated marginal means of the creatine and placebo scores was 0.09 for RAPM and 0.17 for BDS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The preregistered frequentist analysis of RAPM and BDS found no significant effect at p < 0.05 (two-tailed), although the effect bordered significance for BDS.

    “The preregistered frequentist analysis of RAPM and BDS found no significant effect at p < 0.05 (two-tailed), although the effect bordered significance for BDS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no influence of diet, age, or sex on the creatine effect.

    “There was no influence of diet (vegetarian vs omnivore), age, or sex on this effect.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For RAPM, the data was very insensitive and very weakly favoured the alternative hypotheses.

    “For RAPM, the data was very insensitive, very weakly favouring the alternative hypotheses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    We found some indication of a creatine effect for the backward digit span (BDS) but not for the less demanding forwards digit span and block-tapping tasks.

    “In line with this, we found some indication of a creatine effect for the backward digit span (BDS) but not for the less demanding forwards digit span and block-tapping tasks.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

  • May combine two claims.

    Findingown data

    The creatine effect was not larger in the vegetarian subgroup of our study; it was smaller to a non-statistically significant extent.

    “However, the number of vegetarian participants in our study was still higher than theirs and the creatine effect was not larger in this subgroup (in fact, it was smaller to a non-statistically significant extent).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rae et al. [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

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

    Findingnone given

    Apart from the present study, which found no effect of sex, studies that included both men and women did not report the effect of sex.

    “Apart from the present study, which found no effect of sex, studies who included both men and women did not report the effect of sex.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

  • May combine two claims.

    Premisecitation

    Creatine is safe, well-tolerated, and cheap.

    “Creatine is safe, well-tolerated, and cheap [1].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, et al. International society of sports nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;13(14):18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vegetarians have lower serum and muscle creatine concentration, but comparable total brain creatine to omnivores.

    “Vegetarians have been found to have lower serum and muscle creatine concentration, but comparable total brain creatine to omnivores [22, 24, 25].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [22] Solis MY, Artioli GG, Otaduy MCG, da Leite CC, Arruda W, Veiga RR, et al. Effect of age, diet, and tissue type on PCr response to creatine supplementation. J Appl Physiol. 2017;123(2):407–14. source

      Not checked in the free run.

    • cites [24] Solis MY, de Salles PV, Artioli GG, Roschel H, Otaduy MC, Gualano B. Brain creatine depletion in vegetarians? A cross-sectional 1H-magnetic resonance spectroscopy (1H-MRS) study. Br J Nutr. 2014;111(7):1272–4. source

      Not checked in the free run.

    • cites [25] Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exerc. 2003;35(11):1946–55. source

      Not checked in the free run.

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

    Premisecitation

    A systematic review tentatively suggests that creatine supplementation may improve short-term memory/working memory and intelligence/reasoning in healthy individuals.

    “A systematic review tentatively suggests that creatine supplementation may improve “short-term memory”/working memory and “intelligence/reasoning” in healthy individuals [7].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: a systematic review of randomized controlled trials. Exp Gerontol. 2018;15(108):166–73. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Rae et al. found that creatine supplementation had a large and highly significant positive effect on both BDS and RAPM in 45 young vegetarian adults.

    “Rae et al. [8] found creatine supplementation had a large and highly significant (i.e. p < 0.001) positive effect on both tasks.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rae et al. [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The brain synthesises its own creatine and might be more resistant to exogenous creatine.

    “the brain synthesises its own creatine and for that reason might be more resistant to exogenous creatine [22, 49].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Solis MY, Artioli GG, Otaduy MCG, da Leite CC, Arruda W, Veiga RR, et al. Effect of age, diet, and tissue type on PCr response to creatine supplementation. J Appl Physiol. 2017;123(2):407–14. source

      Not checked in the free run.

    • cites [49] Forbes SC, Cordingley DM, Cornish SM, Gualano B, Roschel H, Ostojic SM, et al. Effects of creatine supplementation on brain function and health. Nutrients. 2022;14(5). https://doi.org/10.3390/nu14050921. source

      Not checked in the free run.

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

    Premisecitation

    Benton and Donohoe found that creatine supplementation benefited memory only for vegetarians but not omnivores.

    “Another study comparing memory improvement under creatine supplementation in omnivores and vegetarians found that creatine supplementation benefited memory only for vegetarians but not omnivores [23].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. 2011;105(7):1100–5. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Typical supplementation doses of creatine (5 g per day) are equivalent to more than 1 kg of meat consumption per day, which is substantially higher than the combined dietary intake and synthesis in most people.

    “typical supplementation doses of creatine (5 g per day) are equivalent to more than 1 kg of meat consumption per day [13], which is substantially higher than the combined dietary intake and synthesis in most people [13].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Brosnan ME, Brosnan JT. The role of dietary creatine. Amino Acids. 2016;48(8):1785–91. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    There was one deviation from the preregistered analyses: preregistered t-tests were replaced with mixed ANOVAs.

    “There is one deviation from our preregistered analyses. We had preregistered t-tests, but this was a mistake in the preregistration. The t-test is not appropriate here because imbalances in the supplement order group sizes would bias the results. Instead, we conducted mixed ANOVAs”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Allocation concealment was performed using sequentially numbered, opaque sealed envelopes (SNOSE).

    “Allocation concealment was performed using sequentially numbered, opaque sealed envelopes (SNOSE).”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    The study follows the CONSORT reporting guidelines.

    “We follow the CONSORT reporting guidelines [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2011;9(8):672–7. source

      Not checked in the free run.

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

    Study design and conductown data

    Drop-outs were due to supplements failing to arrive (N = 2), stressful personal events (N = 2), no reason given (N = 2), and no time (N = 18).

    “Drop-outs were due to supplements failing to arrive (N = 2), dealing with stressful personal events (N = 2), no reason given (N = 2), and no time (N = 18).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Participants were not excluded based on adherence; the analysis was intention-to-treat.

    “We did not exclude participants based on adherence (intention-to-treat analysis).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The RAPM subtests are constructed to have equal levels of difficulty based on published normative performance data, and Rae et al. additionally verified this in an independent sample.

    “The subtests are constructed to have equal levels of difficulty based on the published normative performance data and Rae et al. [8] additionally verified this in an independent sample (N = 20).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rae et al. [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

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

    Study design and conductown data

    The trial was preregistered.

    “Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The trial was double-blind.

    “Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    If these were IQ tests, the increase in raw scores would mean 2.5 IQ points for BDS and 1 IQ point for RAPM.

    “If these were IQ tests, this increase in raw scores would mean 2.5 IQ points for BDS (using the standard deviations of a normative study [47] or our own baseline gives the same result, see Appendix). For RAPM, the improvement would be 1 IQ point (using the standard deviation of our own baseline, see Appendix).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Monaco M, Costa A, Caltagirone C, Carlesimo GA. Forward and backward span for verbal and visuo-spatial data: standardization and normative data from an Italian adult population. Neurol Sci. 2013;34(5):749–54. source

      Not checked in the free run.

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

    Study design and conductown data

    The trial was cross-over.

    “Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Outliers were not removed in the main analysis, but robustness checks including trimming and winsorising were conducted.

    “We did not remove outliers in our main analysis, but conducted robustness checks which included trimming and winsorising.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    In the blinding check, 43 of 73 participants guessed their supplement order correctly and 30 guessed incorrectly; the binomial probability of 43 or more correct guesses by chance was p = 0.080.

    “Forty-three (59%) guessed correctly and 30 (41%) guessed incorrectly. A binomial test reveals that the probability of 43 or more correct guesses out of 73 by pure chance is p = 0.080.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Participants and all staff who interacted with them were kept blinded to the allocation.

    “Participants and all staff who interacted with them were kept blinded to the allocation (also see intervention section).”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    All available participant data were analysed apart from two minor exceptions.

    “We analysed all available participant data apart from two minor exceptions (see Appendix).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Conditions causing brain creatine deficiency result in profound intellectual disability which can be reversed by creatine supplementation.

    “Conditions causing brain creatine deficiency result in profound intellectual disability which can be reversed by creatine supplementation [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Clark JF, Cecil KM. Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes. Pediatr Res. 2015;77(3):398–405. source

      Not checked in the free run.

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

    Study design and conductown data

    The robustness of the normality-assuming ANOVAs was checked with 20%-trimmed, 5%- and 20%-winsorised, and robust ANOVA using trimming and bootstrapping.

    “We checked the robustness of our normality-assuming ANOVAs by performing: an ANOVA on 20%-trimmed data, an ANOVA on 5%- and 20%-winsorised data, and a robust ANOVA which uses trimming and bootstrapping (performed with the sppb functions in the WRS2 R package).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The trial was prospectively registered (drks.de identifier: DRKS00017250).

    “The trial was prospectively registered (drks.de identifier: DRKS00017250, https://osf.io/xpwkc/).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The creatine and placebo powders differed in solubility.

    “The solubility was somewhat different: While the placebo powder was completely soluble in water and did not settle, the creatine powder slowly settled.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Rae et al. [8] is the only RCT on the effect of creatine supplementation on cognition with only vegetarian participants (healthy, under normal conditions) and they found a large creatine effect.

    “Rae et al. [8] is the only RCT on the effect of creatine supplementation on cognition with only vegetarian participants (healthy, under normal conditions) and they found a large creatine effect.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rae et al. [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

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

    Study design and conductown data

    All but one participant took the supplements in the order assigned to them.

    “All but one participant took the supplements in the order assigned to them.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The trial was randomised.

    “Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The trial was placebo-controlled.

    “Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Turner et al. chose a 5-week washout based on the muscle creatine literature and confirmed that brain creatine levels were back to normal after the washout.

    “We learned from private correspondence with Turner et al. [26] that they chose a liberal 5-week washout period for their brain creatine study based on the muscle creatine literature, which suggests 5 weeks is sufficient [27–29].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites Turner et al. [26] Turner CE, Byblow WD, Gant N. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. J Neurosci. 2015;35(4):1773–80. source

      Not checked in the free run.

    • cites [27] Hultman E, Söderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol. 1996;81(1):232–7. source

      Not checked in the free run.

    • cites [28] McKenna MJ, Morton J, Selig SE, Snow RJ. Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance. J Appl Physiol. 1999;87(6):2244–52. source

      Not checked in the free run.

    • cites [29] Preen D, Dawson B, Goodman C, Beilby J, Ching S. Creatine supplementation: a comparison of loading and maintenance protocols on creatine uptake by human skeletal muscle. Int J Sport Nutr Exerc Metab. 2003;13(1):97–111. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Given the high number of cognitive tasks in Benton and Donohoe, the chance of a false positive was high, so we regard their finding as exploratory.

    “However, given the high number of cognitive tasks in that study, the chance of a false positive was high, so we regard their finding as exploratory.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    As preregistered, the two confirmatory cognitive tasks are the Backward Digit Span and Raven's Advanced Progressive Matrices.

    “As preregistered, our two confirmatory cognitive tasks are the Backward Digit Span and Raven’s Advanced Progressive Matrices.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In summary, this study provides weak to moderate evidence for a small cognitive benefit of creatine and strong evidence against the effect size by Rae et al. being representative.

    “In summary, this study provides weak to moderate evidence for a small cognitive benefit of creatine and strong evidence against the effect size by Rae et al. [8] being representative.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rae et al. [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

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

    Interpretationown data

    The supplement-order interaction seems to reflect a learning effect.

    “This seems to reflect a learning effect (see Appendix).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Benton and Donohoe found that creatine supplementation benefited memory in vegetarians more than in omnivores, with no difference in baseline performance.

    “In contrast, Benton and Donohoe [23] found that creatine supplementation benefited memory in vegetarians more than in omnivores, with no difference in baseline performance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Benton and Donohoe [23] Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. 2011;105(7):1100–5. source

      Not checked in the free run.

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

    Study design and conductnone given

    The order of the two supplements was randomised with Excel by the pharmacy of the University Hospital Heidelberg.

    “The order of the two supplements was randomised with Excel by the pharmacy of the University Hospital Heidelberg.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    After noticing the solubility difference, participants were asked to stir the powder into yoghurt or food with a similar consistency.

    “After we noticed it (after the first 40 participants), we asked participants to stir the powder into yoghurt or food with a similar consistency, as we had found no perceptible difference then.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The one participant who took the wrong order was analysed with their actual, not assigned, supplement order.

    “This participant was analysed with their actual, not their assigned, supplement order.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The Greenhouse-Geisser correction was applied to all analyses and did not change any value.

    “We applied the Greenhouse–Geisser correction to all our analyses but the correction did not change any value.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    In the normal ANOVA, the most extreme values made the effect of creatine appear smaller by inflating the variance, while relying on possibly unjustified assumptions of normality made the effect of creatine appear larger.

    “This seems to suggest that in the normal ANOVA, the most extreme values made the effect of creatine appear smaller by inflating the variance, while relying on possibly unjustified assumptions of normality made the effect of creatine appear larger.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    RAPM substantially correlates with general intelligence and predicts academic achievement, though it is not a pure measure of g.

    “RAPM, while not a pure measure of g [66], substantially correlates with general intelligence [66] and predicts academic achievement [67].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [66] Gignac GE. Raven’s is not a pure measure of general intelligence: Implications for g factor theory and the brief measurement of g. Intelligence. 2015;1(52):71–9. source

      Not checked in the free run.

    • cites [67] Roth B, Becker N, Romeyke S, Schäfer S, Domnick F, Spinath FM. Intelligence and school grades: a meta-analysis. Intelligence. 2015;1(53):118–37. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The mathematical processing and logical reasoning tasks differ from RAPM in being easier to solve, less varied and complex, requiring less creativity and providing no progression in difficulty.

    “Both tasks seem to differ from RAPM in being easier to solve, less varied and complex, requiring less creativity and providing no progression in difficulty.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The omnivore findings are mixed while the only study on vegetarians [8] is positive, but as it is only one study, it is not a strong indication.

    “The omnivore findings are mixed while the only study on vegetarians [8] is positive, but as it is only one study, it is not a strong indication.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The effect of creatine supplementation on strength is well-studied and generally large.

    “The effect of creatine supplementation on strength is well-studied and generally large.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The real effect of creatine on BDS performance might lie in the middle like our study.

    “Ignoring the differences in populations for a moment, it might simply be that the real effect of creatine on BDS performance lies in the middle like our study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Alves et al. [61] found no effect of creatine on strength, which goes against a large body of literature.

    “One of the two studies on healthy elderly participants, Alves et al. [61], also tested the effect of creatine on strength and found no effect, which goes against a large body of literature.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Alves et al. [61] Alves CRR, Merege Filho CAA, Benatti FB, Brucki S, Pereira RMR, de Sá Pinto AL, et al. Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study. PLoS One. 2013;8(10):e76301. source

      Not checked in the free run.

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

    Premisecitation

    Ostojic et al. [62] found a significant positive correlation between performance in the Digit Symbol Substitution Test and amount of meat consumed in 1340 elderly adults in the USA.

    “Ostojic et al. [62] (1340 elderly adults in the USA) found a significant positive correlation between performance in the Digit Symbol Substitution Test and amount of meat consumed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ostojic et al. [62] Ostojic SM, Korovljev D, Stajer V. Dietary creatine and cognitive function in U.S. adults aged 60 years and over. Aging Clin Exp Res. 2021;33(12):3269–74. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Noise in RAPM was lower in the present study than in Rae et al. [8], so noise does not explain the smaller effect.

    “Noise in RAPM was lower in the present study than in Rae et al. [8], so this does not explain the result.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147–50. source

      Not checked in the free run.

    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

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

    Interpretationreasoning

    The reason we found an effect for BDS but not for exploratory short-term memory tasks might be that BDS is more difficult and thus requires a higher ATP turnover, which is where creatine helps.

    “The reason why we found an effect for BDS, which is a short-term memory task, but not for our exploratory short-term memory tasks, might be that BDS is probably more difficult and thus requires a higher ATP turnover, which is where creatine helps.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

  • May combine two claims.

    Interpretationcitation

    Our negative finding for the Stroop task is in line with two studies and in contrast with one study which found a creatine effect for this task.

    “Our negative finding for the Stroop task, a test of inhibition, is again in line with the same two studies [21, 61] and in contrast with one study which found a creatine effect for this task [57].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21] Merege-Filho CAA, Otaduy MCG, de Sá-Pinto AL, de Oliveira MO, de Souza GL, Hayashi APT, et al. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study. Appl Physiol Nutr Metab. 2017;42(2):128–34. source

      Not checked in the free run.

    • cites [61] Alves CRR, Merege Filho CAA, Benatti FB, Brucki S, Pereira RMR, de Sá Pinto AL, et al. Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study. PLoS One. 2013;8(10):e76301. source

      Not checked in the free run.

    • cites [57] VAN Cutsem J, Roelands B, Pluym B, Tassignon B, Verschueren JO, De Pauw K, et al. Can creatine combat the mental fatigue-associated decrease in visuomotor skills? Med Sci Sports Exerc. 2020;52(1):120–30. source

      Not checked in the free run.

    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

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

    Interpretationreasoning

    In sum, two studies found much larger creatine effects for RAPM than the present study, while a third study did not find a significant effect; possibly the real effect lies in the middle like our study.

    “In sum, two studies found much larger creatine effects for RAPM than that in the present study, while a third study did not find a significant effect. Possibly the real effect lies in the middle like our study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    We did not find a convincing reason for why our BDS result is different from the two other studies with young, healthy adults; the difference is not explained by diet, age, or noise.

    “Overall, we did not find a convincing reason for why our BDS result is different from the two other studies with young, healthy adults. The difference is not explained by diet, age, or noise.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

  • May combine two claims.

    Interpretationreasoning

    Many confounders are possible in observational studies of dietary creatine and cognition, such as health influencing both diet and cognitive performance, differences in lifestyle, and components in meat other than creatine.

    “Many confounders are possible in these observational studies, such as health influencing both diet and cognitive performance, differences in lifestyle, and components in meat other than creatine.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Our negative finding for the long-term memory part of the VLMT is in line with two studies assessing long-term memory and in contrast with one study which found a creatine effect for this domain.

    “Our negative finding for the long-term memory part of the VLMT is in line with two studies assessing long-term memory [21, 61] and in contrast with one study which found a creatine effect for this domain [55].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21] Merege-Filho CAA, Otaduy MCG, de Sá-Pinto AL, de Oliveira MO, de Souza GL, Hayashi APT, et al. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study. Appl Physiol Nutr Metab. 2017;42(2):128–34. source

      Not checked in the free run.

    • cites [61] Alves CRR, Merege Filho CAA, Benatti FB, Brucki S, Pereira RMR, de Sá Pinto AL, et al. Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study. PLoS One. 2013;8(10):e76301. source

      Not checked in the free run.

    • cites [55] McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007;14(5):517–28. source

      Not checked in the free run.

    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Theory and evidence generally suggest that sleep-deprived and older participants have a larger cognitive benefit from creatine supplementation.

    “This is surprising, seeing as theory and evidence generally suggest that sleep-deprived and older participants have a larger cognitive benefit from creatine supplementation (more on this below).”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The negative finding by Rawson et al. could be explained by the creatine effect in the reasoning domain being smaller than suggested by Rae et al. and Ling et al.

    “Alternatively, the negative finding by Rawson et al. could also be explained by the creatine effect in the reasoning domain being smaller than suggested by the findings of Rae et al. and Ling et al.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Rawson et al.

      Not checked in the free run.

    • cites Rae et al.

      Not checked in the free run.

    • cites Ling et al.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    One reason why creatine did not impact most cognitive tasks in this study might be that most participants were relatively young.

    “So, one reason why creatine did not impact most of the cognitive tasks in this study might be that most of our participants were relatively young (mean = 31, sd = 10, median = 28).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.
    • Rests on an assumption: The creatine supplementation protocol increased brain creatine levels.

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

    Study design and conductnone given

    We assessed baseline days per week of meat consumption but not grammes per day of consumption.

    “We assessed baseline days per week of meat consumption (median = 3.5, mean = 3.7, SD = 2.0), but not grammes per day of consumption.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline meat consumption in days per week adequately classifies participants' dietary creatine intake.

  • Probably not a substantial claim: may not pass S1 (asserted).

    Premisecitation

    It has been claimed that creatine supplementation is more likely to benefit older adults more than younger ones.

    “It has been claimed that creatine supplementation is more likely to benefit older adults more than younger ones [7, 68, 69].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: a systematic review of randomized controlled trials. Exp Gerontol. 2018;15(108):166–73. source

      Not checked in the free run.

    • cites [68] Prokopidis K, Giannos P, Triantafyllidis KK, Kechagias KS, Forbes SC, Candow DG. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(4):416–27. source

      Not checked in the free run.

    • cites [69] Prokopidis K, Giannos P, Triantafyllidis KK, Kechagias KS, Forbes SC, Candow DG. Author’s reply: Letter to the Editor: Double counting due to inadequate statistics leads to false-positive findings in “Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials.” Nutr Rev. 2023. https://doi.org/10.1093/nutrit/nuac111. source

      Not checked in the free run.

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

    Study design and conductnone given

    Adherence was self-reported and not checked with blood samples.

    “Adherence was self-reported and not checked with blood samples.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Participants adhered to the creatine supplementation protocol.

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

    Study design and conductnone given

    Despite the large sample size compared to other studies, a larger sample size would be needed to be powered for effects that are smaller but still relevant.

    “Despite the large sample size compared to other studies, a larger sample size would be needed to be powered for effects that are smaller but still relevant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    There have only been three RCTs on the effect of creatine on cognition in healthy women and three in healthy men; one study with women found a creatine effect and two did not; two studies with men found a creatine effect and one did not.

    “There have only been three RCTs on the effect of creatine on cognition in healthy women and three in healthy men. One of the studies with women found a creatine effect and two did not find an effect (one of these with only elderly participants). Two of the studies with men (one of these with sleep-deprived participants) found a creatine effect and one did not find an effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A meta-analysis by Prokopidis et al. found that creatine supplementation significantly improved memory in older adults (aged 66-76 years) but not younger adults.

    “A meta-analysis by Prokopidis et al. [68, 69] on RCTs with healthy participants on an omnivore diet found that creatine supplementation significantly improved memory in older adults (aged 66–76 years) but not younger adults.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Prokopidis et al. [68, 69]

      Not checked in the free run.

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

    Interpretationcitation

    Mixing creatine in yoghurt rather than water might have negatively affected creatine absorption, because the lower water content and usually cold temperature of yoghurt would decrease creatine solubility.

    “Mixing creatine in yoghurt rather than water might have negatively affected creatine absorption, because the lower water content and usually cold temperature of yoghurt would decrease creatine solubility [77].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] Harris RC, Nevill M, Harris DB, Fallowfield JL, Bogdanis GC, Wise JA. Absorption of creatine supplied as a drink, in meat or in solid form. J Sports Sci. 2002;20(2):147–51. source

      Not checked in the free run.

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

    Premisecitation

    The side effects of creatine are well-known and not dangerous.

    “The side effects of creatine are well-known and not dangerous [1, 4–6].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [1] Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, et al. International society of sports nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;13(14):18. source

      Not checked in the free run.

    • cites [4] Kutz MR, Gunter MJ. Creatine monohydrate supplementation on body weight and percent body fat. J Strength Cond Res. 2003;17(4):817–21.

      Not checked in the free run.

    • cites [5] Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008;28(3):172–8. source

      Not checked in the free run.

    • cites [6] de Silva AD, Pertille A, Barbosa CG, de Oliveira Silva JA, de Jesus DV, Ribeiro AG, et al. Effects of creatine supplementation on renal function: a systematic review and meta-analysis. J Ren Nutr. 2019;29(6):480–9. source

      Not checked in the free run.

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

    Interpretationreasoning

    The largest contributing factor to correct guesses was likely the difference in the solubility between the powders, followed by negative and positive side effects.

    “The largest contributing factor to correct guesses was likely the difference in the solubility between the powders, followed by negative and positive side effects.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The placebo and creatine supplements were sufficiently indistinguishable to maintain blinding.

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

    Study design and conductnone given

    The COVID-19 pandemic started in the middle of the study, might have added noise to the data, and meant that we had to switch from in-person cognitive testing to testing via video call.

    “The COVID-19 pandemic started in the middle of the study, might have added noise to the data, and meant that we had to switch from in-person cognitive testing to testing via video call.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The switch from in-person to video-call cognitive testing did not materially affect the cognitive measures.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Supplementing creatine is safe, easy, and very cheap.

    “Supplementing creatine is safe, easy, and very cheap.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [1] Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, et al. International society of sports nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;13(14):18. source

      Not checked in the free run.

    • cites [4] Kutz MR, Gunter MJ. Creatine monohydrate supplementation on body weight and percent body fat. J Strength Cond Res. 2003;17(4):817–21.

      Not checked in the free run.

    • cites [5] Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008;28(3):172–8. source

      Not checked in the free run.

    • cites [6] de Silva AD, Pertille A, Barbosa CG, de Oliveira Silva JA, de Jesus DV, Ribeiro AG, et al. Effects of creatine supplementation on renal function: a systematic review and meta-analysis. J Ren Nutr. 2019;29(6):480–9. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The meta-analysis included only two studies with elderly participants, only one of which found a creatine effect, and did not include Hammett et al. [56], which might have changed the conclusion.

    “The meta-analysis included only two studies (N = 25 and N = 32) with elderly participants [55, 61], only one of which found a creatine effect. For reasons unknown to us, the meta-analysis did not include Hammett et al. [56], who found a large creatine effect on memory in young adults and might have changed the conclusion.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [55] McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007;14(5):517–28. source

      Not checked in the free run.

    • cites [61] Alves CRR, Merege Filho CAA, Benatti FB, Brucki S, Pereira RMR, de Sá Pinto AL, et al. Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study. PLoS One. 2013;8(10):e76301. source

      Not checked in the free run.

    • cites Hammett et al. [56] Hammett ST, Wall MB, Edwards TC, Smith AT. Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal. Neurosci Lett. 2010;479(3):201–5. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Our educated guess is that creatine absorption when mixed in yoghurt is similarly effective as in cold water but worse than in warm water.

    “Overall, our educated guess is that creatine absorption when mixed in yoghurt is similarly effective as in cold water but worse than in warm water.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Some of the data (4%) could not be analysed because it was not labelled with the participant and timepoint.

    “Some of the data (4%) could not be analysed because it was not labelled with the participant and timepoint.”
    Quote in the paperNot a substantial claim
83 of 83

  • The paper relies on this without support.

    Online cognitive assessments via video call are equivalent to in-clinic laboratory assessments.

    “Due to the contact restrictions due to the COVID-19 pandemic, after 04/2020, participants were tested online via video call instead.”

  • The paper relies on this without support.

    Self-reported adherence accurately reflects actual supplement intake.

    “Adherence (self-reported) was high (Table 2).”

  • The paper relies on this without support.

    The placebo supplement (maltodextrin) has no cognitive effects.

    “The placebo supplement consisted of maltodextrin powder “Maltodextrin 6” produced by the company Nutricia (Frankfurt am Main, Germany).”

  • The paper relies on this without support.

    Participants adhered to the creatine supplementation protocol.

    “Adherence was self-reported and not checked with blood samples.”

  • The paper relies on this without support.

    The creatine supplementation protocol increased brain creatine levels.

    “A major limitation is that brain creatine levels were not assessed.”

  • The paper relies on this without support.

    The placebo and creatine supplements were sufficiently indistinguishable to maintain blinding.

    “Unfortunately, it is difficult to achieve perfect blinding when side effects occur with higher frequency in the creatine condition.”

  • The paper relies on this without support.

    The switch from in-person to video-call cognitive testing did not materially affect the cognitive measures.

    “The COVID-19 pandemic started in the middle of the study, might have added noise to the data, and meant that we had to switch from in-person cognitive testing to testing via video call.”

  • The paper relies on this without support.

    Baseline meat consumption in days per week adequately classifies participants' dietary creatine intake.

    “We assessed baseline days per week of meat consumption (median = 3.5, mean = 3.7, SD = 2.0), but not grammes per day of consumption.”
8 of 8

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.

  • BDS confidence interval is not centred on its reported estimate

    Minor

    The reported 95% confidence interval has a midpoint of 0.30, not the reported mean difference of 0.41. The RAPM interval in the same table is centred on its estimate.

    Reported 0.41 · recomputed 0.3

  • BF10 is defined in the opposite direction from its interpretation

    Minor

    The text defines BF10 as comparing the likelihood of the null hypothesis to the alternative, but then says values above 1 favour the alternative.

2 of 2

Cites

Flagged first, then by citations

1 of the 76 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. Kutz MR, Gunter MJ. Creatine monohydrate supplementation on body weight and percent body fat. J Strength Cond Res. 2003;17(4):817–21.
  2. Wechsler D. Manual for the Wechsler Adult Intelligence Scale. 1955;110. Available from: https://psycnet.apa.org/fulltext/1955-07334-000.pdf.
  3. Brickenkamp R. Test d2: Aufmerksamkeits-Belastungs-Test Hogrefe. Testzentrale: Göttingen, Germany; 2002.
  4. Bäumler G, Stroop JR. Farbe-Wort-Interferenztest nach JR Stroop (FWIT). Verlag für Psychologie: Hogrefe; 1985.
  5. Aschenbrenner S, Tucha O, Lange KW. Regensburger Wortflüssigkeits-Test: RWT. Verlag für Psychologie: Hogrefe; 2000.
  6. Pires LAM, Forbes SC, Candow DG, Machado M. Creatine supplementation on cognitive performance following exercise in female Muay Thai athletes. NeuroSports. 2021;1(1):6.

Cited by

Sorted by citations

Related

Authors
Sandkühler, J. F., Kersting, X., Faust, A., Königs, E. K., Altman, G., Ettinger, U., Lux, S., Philipsen, A., Müller, H., & Brauner, J.
Affiliations
  • University of Bonn (DE)
  • University Hospital Bonn (DE)
  • Manchester University NHS Foundation Trust (GB)
  • Witten/Herdecke University (DE)
Corresponding author
Sandkühler, Julia Fabienne
ORCID
Venue
BMC Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-11-15
Volume
21
Issue
1
Pages
440-440
ISSN
1741-7015 (ISSN-L)
DOI
10.1186/s12916-023-03146-5
PMC
PMC10647179
OpenAlex
W4388698718
Semantic Scholar
74c738e7dd8053cc8b7716e1592a7cf97c5f284e
Cited by
29
References
76
Citations by year
2026: 11 · 2025: 10 · 2024: 7 · 2023: 1
FWCI
4.18
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Medicine (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Effective Ventures Foundation
  • Effective Altruism Foundation
  • Paul Christiano
  • Rheinische Friedrich-Wilhelms-Universität Bonn
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, cognitive performance, Raven's Advanced Progressive Matrices, backward digit span, vegetarian diet, omnivorous diet, adverse effects, dietary supplementation
MeSH terms
Bayes Theorem, Brain, Cognition, Creatine, Double-Blind Method, Humans, 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 ›

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