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April 12, 2024 4 min read

The modern lifestyle is impacted by work pressure and potential sleep deprivation, which leads to more accidents, decrements in performance and chronic diseases.  

To diminish these negative consequences, psychoactive substances such as caffeine garnered immense popularity in recent decades. Creatine is very appreciated by the sports community and an ergogenic aid to enhance physical peak performance. Recently, creatine has gained recognition as being a crucial supplement for cognitive performance.

Changes in creatine-related metabolites were observed in sleep disorders and sleep deprivation(1).

Central nervous system uptake of exogenous creatine from the periphery is marginal and takes a long time. Most studies investigating the effect of creatine supplementation on cerebral metabolites, require a minimum period of 1 week or longer.  Hence, most studies investigating the effect of creatine supplementation on cerebral metabolites, require a minimum period of 1 week or longer.

There is some preliminary data indicates that intra-cellular creatine uptake on a short time scale is possible under certain conditions.

A recent landmark study aimed to prove whether a high extracellular availability of creatine can compensate for metabolic changes and cognitive impairment during sleep deprivation. This study specifically investigated the kinetics of cerebral phosphate-metabolites and cognitive performance in a time range of 8 hours after acute single dose creatine (0.35 g/kg) versus placebo during the first two-thirds of a night without sleep while assessing cognitive tasks(2).

Major Findings

Administering a high dose of creatine has been shown to reverse partially cellular stress-induced effects caused by sleep deprivation.

This research showed a maximum effect 4 hours after administration with improvements lasting as long as 9 hours in:

  • - Cognitive Performance: The creatine group demonstrated enhanced memory and faster processing speed (processing speed was improved compared to non-sleep deprived state), compared to the placebo group
  • - Stabilized Brain pH Levels: Creatine helped avoid a drop in brain pH levels, which typically occurs during sleep deprivation. This maintenance of pH levels is believed to be critical for maintaining normal brain function.
  • - Changes in Brain Energy Metabolism: An increase in the phosphocreatine/inorganic phosphate ratio, indicating changes in the brain's energy metabolism in response to creatine supplementation.

These results challenge previous notions that acute supplementation does not increase intra-cellular creatine levels in the brain suggesting that, intra-cellular creatine uptake on a short time scale is possible under certain conditions.

The ideal conditions for this to occur are the following:

  • - Increased energy demand by brain cells (e.g., sleep deprivation)
  • - Increased extracellular creatine availability (e.g., high-dosed supplementation)

Mechanism of Action

It is indicated that the sleep deprivation combined with cognitive activity as a crucial factor triggering multiple mechanisms. Sleep deprivation has been reported to increase cerebral ammonia levels, induce abnormalities in adenosine and metabolic response in hyperammonemia(3).

Hyperammonemia induces an increase in creatine transport and activates the SLC6A8 expression in astrocytes, leading to an increased creatine uptake in microcapillary endothelial cells(4)

The property of protecting the brain from excess ammonium is why creatine has been proposed as a suitable candidate for treating hyperammonemia patients to protect their developing central nervous system(5).

Another mechanism explaining the increased creatine uptake concerns the cerebral intra—or extracellular activity. The passage of creatine against the concentration gradient between plasma and brain cells is assured by active transport via the sodium and insulin-dependent creatine transporter (SLC6A8)(6).

Hence, it can be assumed that creatine uptake is more effective at higher transmembrane sodium/potassium gradient and higher insulin. Higher acidification-induced sodium hydrogen antiporter protein activity also has the potential to release more insulin, a further condition for an increased creatine uptake(7).


This research demonstrates that administering a high single dose of creatine can partially reverse metabolic alterations and fatigue-related cognitive deterioration. This research revises the established assumption that creatine supplementation only works over a longer period.

The critical factor appears to be the enhanced energy demand of the neuronal cells in combination with an increased extracellular creatine availability. This unique combination seems to overcome the main obstacle, namely the marginal intracellular creatine uptake by brain cells.

It can be concluded that creatine has the potential to be used in prolonged cognitive activity during sleep deprivation.  Future research needs to investigate the appropriate dose and determine more accurately the time point at which creatine reaches its maximum effect.

It's no secret creatine has many benefits on the brain and body. Whether you get it from food or you get it from supplements the key is to make sure you get it every day.

If you're looking to support your cognitive function there is no better combination than the Ultimate Brain Stack.

The Ultimate Brain Stack contains ATP-Fusion (5,000 mg of creatine and 220 mg of sodium) and FOCUSED-AF (our world-class nootropic comprised of 10 powerful brain-boosting ingredients) to provide a full range of nutrients to support a high-performance brain.




    1.    Harper DG, Plante DT, Jensen JE, et al: Energetic and cell membrane metabolic products in patients with primary insomnia: a 31-phosphorus magnetic resonance spectroscopy study at 4 tesla. Sleep 36:493-500, 2013
    2.    Gordji-Nejad A, Matusch A, Kleedorfer S, et al: Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Sci Rep 14:4937, 2024
    3.    Pinna V, Magnani S, Sainas G, et al: Physical Capacity and Energy Expenditure of Cavers. Front Physiol 8:1067, 2017
    4.    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 31:230-9, 2008
    5.    Béard E, Braissant O: Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem 115:297-313, 2010
    6.    Ohtsuki S, Tachikawa M, Takanaga H, et al: The blood-brain barrier creatine transporter is a major pathway for supplying creatine to the brain. J Cereb Blood Flow Metab 22:1327-35, 2002
    7.    Baldini N, Avnet S: The Effects of Systemic and Local Acidosis on Insulin Resistance and Signaling. Int J Mol Sci 20, 2018

Dr. Paul Henning

About Dr. Paul

I'm currently an Army officer on active duty with over 15 years of experience and also run my own health and wellness business. The majority of my career in the military has focused on enhancing Warfighter health and performance. I am passionate about helping people enhance all aspects of their lives through health and wellness. Learn more about me