Creatine Supplementation and Acute Sleep Deprivation: A Systematic Review of Cognitive,Psychomotor,and Mood Outcomes

Abstract

Background:

Acute sleep deprivation impairs cognitive, psychomotor, and mood outcomes, in part by reducing cerebral adenosine triphosphate (ATP) availability. Creatine supplementation may counter these effects by increasing phosphocreatine stores.

Methods:

Six databases were systematically searched (January 2006–May 2025) for studies investigating creatine’s effects on cognitive, psychomotor, and mood outcomes during acute sleep deprivation.

Results:

Results were synthesized narratively. Of 160 records, five studies met the inclusion criteria. Early investigations indicate a positive trend for creatine supplementation as an intervention for acute sleep deprivation, though effects may vary by cognitive domain.

Conclusion:

Despite favorable early results, research is sparse, and future high-quality trials are needed.

Keywords

cognition creatine creatine supplementation mood psychomotor function sleep deprivation

Introduction

Roughly one-third of Americans report insufficient sleep, which is linked to adverse health effects.^1,2 Acute sleep deprivation (ASD), defined as less than 48 h of wakefulness, is associated with adverse psychological and cognitive effects (e.g., decreased vigilance and short-term memory, slower reaction times, and impaired sustained attention).^3,4 Psychomotor performance may also be disrupted, but the effects are less clearly defined.⁵ Considering the prevalence and adverse effects of ASD, identifying practical interventions is a growing priority.

Creatine, a potential intervention for ASD, is an endogenously produced compound that supports rapid ATP resynthesis through the phosphocreatine (PCr) system.^6–8 During ASD, the PCr/inorganic phosphate ratio decreases, indicating reduced cerebral energy reserves.⁶ By replenishing PCr stores, creatine may help maintain ATP availability and mitigate negative ASD-related effects.^6,7 This report evaluates the existing literature on the role of creatine supplementation in cognitive, affective, and psychomotor domains during ASD.

Materials and Methods

This review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A literature search was performed across PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycInfo using a combination of subject headings, Medical Subject Headings (MeSH) terms, and keyword phrases related to creatine and sleep deprivation. A detailed description of search strategies is provided in Supplementary Appendix A. Results were limited to publications from January 1, 2006, to May 30, 2025. Prior to 2006, no studies were conducted investigating creatine supplementation as an intervention for sleep deprivation. After duplicate removal, two independent reviewers (N.W., R.H.) screened titles, abstracts, and full texts for eligibility with disagreements resolved by consensus.

Inclusion criteria

•

Healthy human participants, ≥18 years

•

Experimental studies involving ASD (≤48h)

•

Studies that meet the predefined population, intervention, comparison, outcomes (PICO) (Table 1)

•

Published in peer-reviewed journals

Table 1.

PICO Elements for Inclusion Criteria

PICO element	Description	Examples/clarification
Population	Healthy adults undergoing ASD	Athletes, students, military, etc
Intervention	Creatine supplementation	Acute or longer duration; any form of creatine supplement
Comparison	Placebo or no supplementation
Outcome	Cognitive, psychomotor, and mood performance during or after ASD

ASD, acute sleep deprivation; PICO, population, intervention, comparison, outcomes.

Exclusion criteria

•

Studies involving chronic sleep deprivation or insomnia

•

Reviews or commentaries

•

Studies not meeting the relevant PICO

The extracted data included study characteristics, creatine dosing regimen, cognitive, psychomotor, and mood outcomes. All results compatible within each domain were included. Effect direction, magnitude, and experimental conditions were recorded when available. Due to the small number of eligible studies and heterogeneity in study designs, a meta-analysis was not conducted. Findings were tabulated, and all included studies were considered as a single group for synthesis. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool by two independent reviewers (N.W. and R.H.). Certainty of evidence and publication bias were not formally assessed (few studies; no pooling).

Results

The search generated 120 publications. After removing duplicates (n = 55), 66 articles remained; 61 were excluded based on title/abstract or full-text review. Five studies met all inclusion criteria and were retained for analysis. No eligible studies were excluded (Fig. 1).

FIG. 1.

PRISMA flow diagram of the study selection through the systematic review process. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

The five studies varied in design, creatine dosing regimen, and sleep-deprivation paradigm, limiting direct comparability (Table 2). All populations consisted of healthy participants in their 20 sec undergoing total or partial ASD. Creatine monohydrate was administered either as a single acute dose or as a short loading regimen in each study. The outcomes are organized by functional domain to demonstrate the range of cognitive, psychomotor, and mood measures assessed across studies, as summarized below.

Table 2.

Characteristics and Outcomes of Studies Evaluating Creatine Supplementation During Acute Sleep Deprivation

Authors	Year	Location	Study type	Population: age (SD);M/F	Creatine type	Dose	Duration	Time points	Major results
									Cognitive				Psychomotor	Mood	SD effects:
									Executive function	Memory	Processing speed	Attention
McMorris et al.⁹	2006	United Kingdom	DB, placebo controlled	21.11 (1.85); 16/3	Creatine monohydrate	20 g/day	7 days	Baseline and after 6 h, 12 h, and 24 h of SD	RMG/ADJ: ΔADJ at 24 h significantly improved in creatine group at the 24 hour time point only (p < 0.05)	Forward/backward verbal recall: no significant differences forward/backward spatial recall: no significant differences	CRT: ΔCRT significantly faster at 24 h for creatine group (p < 0.05)					Balance test: no difference in sway magnitude along x/y axes, but the creatine intervention group had significantly higher # of corrections (p < 0.01) and lower sway per correction (p < 0.05)	Shortened POMS: fatigue: lower in creatine group (p < 0.005) vigor: less of a decline in creatine group (p < 0.02) anger, depression, and tension: no significant differences	Balance was significantly worse at 24 h and 36 h. There were also significant declines vigor and increase fatigue.
McMorris et al.¹⁰	2007	United Kingdom	DB, placebo controlled	21.11 (1.85); 19/0	Creatine monohydrate	20 g/day	7 days	Tested at baseline and 18 h, 24 h, and 36 h of SD	RNG: No significant main effect; Group x Time interaction- At 36 h, creatine group performed significantly better than placebo (p < 0.05) RED Significant main effect for creatine group (p < 0.005)	Written number recall: no significant effects	CRT: No significant effects		Dynamic balance test: no significant effects	Shortened POMS: no significant differences	Mood was significantly better at 18 h than 24 h and 36 h.
Cook et al.¹¹	2011	United Kingdom	RCT	20 (0.5); 10/0	Creatine monohydrate	50 and 100 mg/kg	90 min	7–9 h sleep or 3–5 h (SD) sleep the night before					Main effect: Significantly improved performance at both doses compared with placebo (p < 0.001) on both the dominant and non-dominant passing sides		Sleep deprivation impaired skill performance on both dominant and non-dominant sides (p < 0.001)
Gordji-Nejad et al.⁸	2024	Germany	DB, randomized, cross over	23 (2); 7/8	Creatine Monohydrate	0.35 g/kg	7.5 h	Testing at 11 h (baseline), 17 h, 19 h, and 21 h of SD	Creatine vs. baseline: pooled across 0, 2, 4 a.m language task: ↑5.6% (p = 0.003), numeric task: ↑9.6% (p = 0.001)Creatine vs. placebo:regional ↑PCr/Pi ↔ numeric task improvements	Creatine vs. baseline: positive correlations between WMT/SPAN and response in HEPCreatine vs. placebo: pooled across 0, 2, 4 a.m WMT accuracy: ↑10.3% (p = 0.005);	Creatine vs. baseline: numeric task at 0 p.m ↓24.5% (p = 0.0003); pooled across 0, 2, 4 a.m language ↓10.6% (p = 0.002), Logic ↓13.7% (p = 0.00001), numeric ↓18.4% (p = 2.8 × 10⁻⁷)Creatine vs. placebo: Pooled across 0, 2, 4 a.m WMT↓17.7% ( = 0.002) Language ↓29.1% (p = 2.0 × 10⁻⁶), Logic ↓16.0% (p = 0.0002), Numeric ↓24.0% (p = 1.02 × 10⁻⁵)	Creatine vs. baseline: Positive correlation between PVT and response in HEPCreatine vs. placebo: Negative correlation between PVT improvements and regional ATP-ß		Creatine vs. baseline: At 4 a.m KSS ↑145% (p < 0.009), FAT ↑122% (p < 0.009), both ↑ progressively vs. each prior timepoint.Creatine vs. placebo: Pooled at 2 a.m & 4 a.m FAT ↓8% (p = 0.002)	KSS ↑172% (p < 0.0002), FAT ↑141% (p < 0.0002), both ↑ progressively vs. each prior timepointPooled across 0, 2, 4 a.m WMT ↓7.8% (p = 0.0002), SPAN ↓18.7% (p = 0.002), Language speed ↓17.4% (p = 0.0001), PVT ↓6.2% (p = 0.001);
Gordji-Nejad et al.¹²	2025	Germany	DB, randomized, cross over	23 (2); 7/8	Creatine monohydrate	0.35 g/kg	7.5 h	Testing at 11 h (baseline), 17 h, 19 h, and 21 h of SD		Positive correlations—right hemisphere (regional):ΔPCr/Pi ↔ WMT ↑					Positive correlations—left hemisphere (regional):PCr/Pi ↑ ↔ Language task ↑ATP-ß ↑ ↔ WMT ↑, Logic task ↑ Positive correlations—right hemisphere (regional):PCr/Pi ↑ ↔ WMT ↑, Logic task ↑, PVT ↑ATP↓ ↔ KSS ↑, FAT ↑

Results from the literature search, which include study characteristics, study design, and significant results, including outcomes regarding cognitive function (executive function, memory, processing speed, attention, psychomotor tasks, mood, and effects of ASD.

ADJ, adjacency (% frequency of adjacent/repeated responses on random generation task); ATP-β, ß-adenosine triphosphate signal; CRT, choice reaction time; DB, double-blind; FAT, Fatigue scale; HEP, high energy phosphate; KSS, Karolinska Sleepiness Scale; PCr, phosphocreatine; Pi, inorganic phosphate ratio; POMS, profile of mood states; PVT, psychomotor vigilance task; RMG, random movement generation; RNG, random number generation task; RED, rapid executive divergence task; RCT, randomized controlled trial; SD, sleep deprivation; SPAN, digit span task; WMT, working memory task.

Executive function: Random movement generation (RMG) along with adjacency (ADJ); random number generation along with redundant responses; language, logic, and numeric tasks.

Memory: Forward and backward recall verbally and spatially; Written number recall; word memory test (WMT); forward memory digit span test (SPAN); Spatial N-Back (3-Back).

Processing speed: Choice reaction time (CRT); processing time during tests (e.g., language, logic, numeric, WMT).

Attention: Psychomotor vigilance test.

Psychomotor: Static balance test; dynamic balance test; rugby passing accuracy.

Mood: Shortened version of profile of mood; fatigue score; Karolinska Sleepiness Scores.

The studies assessed creatine’s role regarding cognitive and psychomotor function, mood, and biochemical markers during ASD (Table 2).

Risk of bias results are tabulated in Supplementary Table S1 and Supplementary Figure S1.

Discussion

In this review, the effects of creatine supplementation are evaluated across cognitive, psychomotor, and mood domains under conditions of ASD. Creatine appeared to mitigate some of the adverse effects of ASD; however, evidence remains limited.

Effects of acute sleep deprivation

ASD has been linked with multiple adverse effects on cognition, psychomotor performance, and mood.^3–5 Notably, among cognitive outcomes, the broader literature indicates that simpler tasks are more sensitive to the effects of sleep loss compared with complex tasks.³ In the included studies, executive function and recall were preserved, yet other cognitive domains including memory, processing speed, and attention demonstrated declines.^11,13,14 Psychomotor effects of ASD may also be task-specific. Previous work suggests that simple gross motor performance may be less affected, whereas performance decrements are more apparent for psychomotor tasks with higher cognitive demands.⁹ In this review, Cook et al. found that rugby players’ passing accuracy declined during later repetitions of a repeated passing task (repetitions 10–20 versus 1–10), suggesting increasing mental fatigue.¹¹ Furthermore, consistent with previous literature, ASD resulted in worsened mood and increased perceived fatigue.^4,11,13,14

The variability in impact of ASD on cognition and psychomotor function is likely due to the heterogeneity of the sleep deprivation period, task demands, circadian timing, and motor complexity; however, the negative trend combined with measured mood impairment supports the need for an effective intervention.

Effects of creatine supplementation

Metabolic response

Creatine supplementation increases brain PCr, but regional effects have not been thoroughly investigated.^6–8 In this review, Gordji-Nejad et al. reported greater decreases in ATP in the right hemisphere compared with the left during ASD; yet, following creatine supplementation, there was significantly greater ATP consumption in the left hemisphere compared with the right.^10,13 Greater creatine uptake was also observed in gray matter than white matter.¹⁰ The authors suggest these high-energy demand regions may be particularly responsive to creatine supplementation.^10,13 This observation may be supported by McMorris et al. who reported improved cognitive performance following creatine supplementation on tasks that had not declined during sleep deprivation.¹¹ Taken together, these results support the hypothesis that creatine increases the brain’s capacity to engage with metabolically demanding tasks during acute stress by enhancing local energy availability.

Cognitive function

Previous research on creatine’s cognitive benefits ranges from having no effect to moderate benefits.⁸ Potential explanations for these discrepancies include dose-dependent effects of creatine, sensitivity to acute stress states, differences in metabolic task demands, and variation in participant age. In this review, multiple studies reported improvements in cognition during sleep-deprived conditions following creatine supplementation, such as increased accuracy in language and numeric tasks as well as RMG/ADJ as compared with placebo.^13,14 Significant improvements were also seen in processing speed in CRT and number, logic, and language tasks both when compared with baseline and with placebo.^11,13,14 Other areas of cognition such as memory and attention did not improve significantly or had mixed results.^11,13,14 These task-specific effects may reflect that creatine is most beneficial when metabolic demand is high, such that tasks placing greater energy demand on the brain show larger performance benefits. Collectively, these findings suggest a favorable trend in creatine supplementation and that it may attenuate some of the negative consequences of ASD on cognition.

Psychomotor performance

Current research on creatine supplementation effects on psychomotor performance remains limited, largely confined to sport-specific contexts, and presents mixed findings. For instance, one study assessing soccer players reported improved dribbling but no change in kicking accuracy.¹⁵ In our review, psychomotor benefits of creatine primarily emerged during ASD rather than under rested conditions. McMorris et al. reported improved static balance only at 24 h of sleep deprivation, not at 6 or 12 h, and found no effect on dynamic stability.^11,14 Cook et al. found no effect on passing accuracy in rested rugby players; however, creatine supplementation preserved performance during ASD compared with placebo.¹² Overall, the available studies suggest that creatine might mitigate ASD-related decrements in psychomotor tasks, but the narrow range of tasks and small sample sizes limit the strength of these interpretations.

Mood

Prior work suggests that creatine can improve mood-related outcomes, including decreased fatigue and increased perceived energy, especially in individuals under stress.^7,8 In the context of ASD, significantly blunted increases in fatigue and sleepiness were reported, along with elevated feelings of vigor.^11,13,14 These findings support the broader literature on creatine’s mood-enhancing potential; however, further research is needed to confirm its efficacy.

Limitations

This review’s primary limitation is the small number of studies examining creatine supplementation during ASD. Although no study was judged to have high risk of bias, three of the five studies had some concerns related to randomization and deviations from intended interventions, which limits confidence in the findings. In addition, heterogeneity existed across studies in design, dosing, sleep-deprivation paradigms, and outcome measures, which precluded direct comparison and statistical analysis. Study populations were limited to healthy, young adults (primarily males), restricting generalizability and strength of conclusions. These limitations highlight the need to standardize dosing protocols and investigate other populations in future research.

Conclusion

Based on a small number of studies, creatine supplementation shows a possible benefit on cognition, psychomotor function, and mood during ASD. However, differences in study design and small sample sizes preclude firm conclusions. Given the prevalence of sleep deprivation, future trials in more diverse populations with standardized dosing protocols and real-world performance outcomes are needed to determine if creatine may serve as a low-risk, accessible intervention to support brain function during ASD.

Authors’ Contributions

N.W.: Conceptualization, methodology, database search, screening and study selection, data extraction, and writing. R.H.: Methodology, database search, screening and study selection, data extraction, and writing. M.C.: Supervision, methodology guidance, validation, writing—review and editing, and resources.

Availability of Data

All data analyzed during this study are included in this published article or are available from the corresponding author upon request.

Footnotes

Author Disclosure Statement

This review was not registered nor was a protocol prepared On behalf of all authors, the corresponding author states that there is no conflict of interest.

Funding Information

No funding was received to support the preparation of this article.

Supplemental Material

References

1. Kecklund

, Axelsson

. Health consequences of shift work and insufficient sleep. BMJ 2016;355:i5210; doi: 10.1136/bmj.i5210

2. Pankowska

, Lu

, Wheaton

, et al. Prevalence and geographic patterns of self-reported short sleep duration among us adults. Prev Chronic Dis 2023;20:E53; doi: 10.5888/pcd20.220400

3. Lim

, Dinges

. A meta-analysis of the impact of short-term sleep deprivation on cognitive variables. Psychol Bull 2010;136(3):375–389; doi: 10.1037/a0018883

4. Palmer

, Bower

, Cho

, et al. Sleep loss and emotion: A systematic review and meta-analysis of over 50 years of experimental research. Psychol Bull 2024;150(4):440–463; doi: 10.1037/bul0000410

5. Umemura

, Pinho

, Duysens

, et al. Sleep deprivation affects gait control. Sci Rep 2021;11(1):21104; doi: 10.1038/s41598-021-00705-9

6. Andres

, Ducray

, Schlattner

, et al. Functions and effects of creatine in the central nervous system. Brain Res Bull 2008;76(4):329–343; doi: 10.1016/j.brainresbull.2008.02.035

7. Forbes

, Cordingley

, Cornish

, et al. Effects of creatine supplementation on brain function and health. Nutrients 2022;14(5):921; doi: 10.3390/nu14050921

8. Gordji-Nejad

, Matusch

, Kleedörfer

, et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Sci Rep 2024;14(1):4937; doi: 10.1038/s41598-024-54249-9

9. McMorris

, Harris

, Swain

, 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(1):93–103; doi: 10.1007/s00213-005-0269-z

10.

10. McMorris

, Harris

, Howard

, et al. Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiol Behav 2007;90(1):21–28; doi: 10.1016/j.physbeh.2006.08.024

11.

11. Cook

, Crewther

, Kilduff

, et al. Skill execution and sleep deprivation: Effects of acute caffeine or creatine supplementation—a randomized placebo-controlled trial. J Int Soc Sports Nutr 2011;8(1):2; doi: 10.1186/1550-2783-8-2

12.

12. Gordji-Nejad

, Matusch

, Kleedörfer

, et al. Hemispheric asymmetry in high-energy phosphate consumption during sleep-deprivation is balanced by creatine. Front Neurosci 2025;19:1515761; doi: 10.3389/fnins.2025.1515761

13.

13. Avgerinos

, Spyrou

, Bougioukas

, Kapogiannis

. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol 2018;108:166–173; doi: 10.1016/j.exger.2018.04.013

14.

14. Fullagar

HHK

, Skorski

, Duffield

, et al. Sleep and athletic performance: The effects of sleep loss on exercise performance, and physiological and cognitive responses to exercise. Sports Med 2015;45(2):161–186; doi: 10.1007/s40279-014-0260-0

15.

15. Ostojic

. Creatine Supplementation in young soccer players. Int J Sport Nutr Exerc Metab 2004;14(1):95–103; doi: 10.1123/ijsnem.14.1.95

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