We are not sleeping well.
Sleep loss has become a near-normal part of adult life. Long workdays, study pressure, social demands, and late-night screen time lead many young adults to view rest as optional. Yet this trade-off has a real cost. Even modest sleep restriction slows thinking, increases mistakes, weakens mood, and raises the risk of accidents.1 Over months and years, the pattern links with metabolic issues, immune changes, heart disease, and mental health challenges.2
Alongside the call to "get more sleep" for long-term health, scientists are seeking ways to manage unavoidable acute sleep loss, attempting to meet the realities of shift work, exam season, and life's deadlines. Some research now focuses on what happens to brain energy systems during sleep loss, and whether nutrition can support them. One compound drawing interest is creatine. Best known for its role in sports nutrition, creatine plays a central role in cell energy balance, including in the brain.3 Studies using at least a week of supplementation have shown increases in brain total creatine and phosphocreatine, shifts in ATP and glutamate levels, and improvements in certain cognitive tasks.4-6 These changes move in the opposite direction to what happens during sleep loss, which raises an intriguing hypothesis: If sleep deprivation strains brain energy systems, could higher creatine availability help buffer the impact?
Recent work has begun to test this idea directly by examining whether the brain can utilise creatine acutely during sleep deprivation, rather than only after long-term intake.1 The theory is simple. When the brain faces higher energy demand and limited recovery time, it may be more ready to draw creatine from the bloodstream. If correct, this would suggest a new tool for managing short-term sleep debt in situations where rest is limited, yet mental performance remains crucial.
New ways to combat sleep debt.
To explore this theory, researchers designed a study using an acute, high oral dose of creatine—0.35 grams per kilogram of body weight. This dose is far above the typical daily supplementation. It serves to push creatine levels in the blood to a point where uptake by the brain could be observed, if it were to occur. Participants then stayed awake through the night, creating a controlled sleep-deprivation setting. Over several hours, the team measured brain chemistry using magnetic resonance spectroscopy and assessed cognition with memory, reaction, and reasoning tasks.1
The focus was on markers associated with cellular energy and neuronal integrity. Total creatine (tCr) reflects available energy storage, while N-acetylaspartate (tNAA) relates to neuron structure and function. Their ratio helps reveal how well brain cells cope with stress. Researchers also tracked phosphocreatine (PCr) and inorganic phosphate (Pi), two molecules that shift as the brain produces and uses ATP. The PCr/Pi ratio serves as a snapshot of the brain's energy balance, with higher values indicating more stored energy and less metabolic strain.
Measurements began about three and a half hours after creatine intake and continued for nine hours. This timing aligned with known peaks in serum creatine after ingestion. Cognitive tests repeated throughout the night allowed the team to observe both the onset and duration of any performance effects. By comparing these changes to a placebo condition, the researchers could determine whether creatine significantly altered how the brain responded to the stress of staying awake.
Creatine's solution for sleep.
The results were notable. Participants who received creatine showed higher total creatine levels in key brain regions, along with reduced feelings of fatigue compared to the placebo group. These biochemical changes appeared around three and a half hours after ingestion and lasted through the final measurement at nine hours. The increase in creatine uptake was striking because the brain is typically slow to import creatine from the blood. Most creatine inside the central nervous system is made internally through enzymes such as AGAT and GAMT. In individuals with deficiencies in these enzymes, it can take months of supplementation to restore normal levels, highlighting the limitations of normal transport.7 In this study, however, the sleep-deprived brain rapidly absorbed creatine, suggesting a shift in cellular behaviour under stress.
Cognitive performance also improved. Processing speed increased, particularly in tasks involving numbers and language, about four hours after supplementation. Working memory and reaction time also showed benefits. These changes echoed earlier findings from longer-term creatine studies but appeared here after only a single dose. In fact, in some cases, performance exceeded the wake-time baseline, meaning that creatine did not simply prevent decline; it provided a short-term boost beyond normal rested function.
On the metabolic side, creatine appeared to protect against the typical energy decline associated with sleep deprivation. The PCr/Pi ratio rose rather than fell, indicating that energy stores were better preserved. Regions that typically show depletion during sleep loss maintained more stable levels, suggesting reduced cellular strain. Together, these shifts meaningfully blunted the metabolic and cognitive effects of staying awake.
Why did this happen? The authors propose a mechanism tied to the physiology of sleep deprivation. Lack of sleep raises ammonia levels in the brain, alters adenosine signalling, and affects gene expression involved in creatine transport.8 Laboratory research indicates that high ammonia levels can trigger increased activity of the creatine transporter SLC6A8, particularly in astrocytes, and enhance creatine movement across microcapillary endothelial cells.9 In other words, the stressed brain may open the gate for creatine when energy pressure rises and extracellular creatine is abundant. That combination—higher demand and higher supply—appears to enable a surge in uptake that does not usually occur. Some researchers have already suggested creatine as a way to help manage hyperammonaemia in clinical settings due to its protective effect on brain tissue.
The pattern seen here supports that idea. Sleep deprivation likely primed the brain to take in creatine; the high oral dose provided the extra supply needed; and together, they created a window where brain energy systems remained more stable despite the lost sleep. This does not replace sleep, nor does it override biological limits. However, it points toward a controlled, time-limited strategy for supporting mental performance when rest is temporarily restricted.
The Takeaway.
Taken together, these findings suggest that a high single dose of creatine can soften some of the metabolic strain and cognitive decline linked with acute sleep deprivation. The study challenges the long-standing assumption that creatine only works with steady, multi-week intake. Instead, it highlights a scenario where the brain's energy needs rise sharply and transport pathways become more active, allowing rapid uptake when creatine is available in high supply.
For practical use, this suggests a potential tool for periods of prolonged wakefulness when high mental performance is crucial—such as overnight study sessions, time-sensitive work shifts, travel-related sleep disruptions, or emergency duty. In the study, cognitive benefits began within hours and peaked around four hours after intake, lasting up to nine hours.
Still, creatine should not be seen as a substitute for sleep, nor as a cure-all for chronic sleep loss. More work is needed to understand dosing, frequency, and safety in real-world contexts. Yet, the results open a promising line of research into how nutrition and brain energy systems interact during one of modern life's most common stressors: not getting enough sleep.
References.
- Gordji-Nejad, A. et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Scientific Reports 14, 4937 (2024). https://doi.org:10.1038/s41598-024-54249-9
- Medic, G., Wille, M. & Hemels, M. E. H. Short- and long-term health consequences of sleep disruption. Nature and Science of Sleep 9, 151-161 (2017). https://doi.org:10.2147/NSS.S134864
- Forbes, S. C. et al. Effects of Creatine Supplementation on Brain Function and Health. Nutrients 14 (2022). https://doi.org:10.3390/nu14050921
- Rae, C., Digney, A. L., McEwan, S. R. & Bates, T. C. Oral creatine monohydrate supplementation improves brain performance: a double–blind, placebo–controlled, cross–over trial. Proceedings of the Royal Society of London. Series B: Biological Sciences 270, 2147-2150 (2003).
- Bender, A. et al. Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 67, 1262-1264 (2006). https://doi.org:10.1212/01.wnl.0000238518.34389.12
- Dechent, P., Pouwels, P. J. W., Wilken, B., Hanefeld, F. & Frahm, J. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 277, R698-R704 (1999). https://doi.org:10.1152/ajpregu.1999.277.3.R698
- Braissant, O. & Henry, H. AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: a review. J Inherit Metab Dis 31, 230-239 (2008). https://doi.org:10.1007/s10545-008-0826-9
- Haulicǎ, I. et al. The influence of deprivation of paradoxical sleep on cerebral ammonia metabolism. Journal of Neurochemistry 17, 823-826 (1970). https://doi.org:https://doi.org/10.1111/j.1471-4159.1970.tb03356.x
- Bélanger, M. et al. Hyperammonemia induces transport of taurine and creatine and suppresses claudin-12 gene expression in brain capillary endothelial cells in vitro. Neurochemistry International 50, 95-101 (2007). https://doi.org:https://doi.org/10.1016/j.neuint.2006.07.005
