Abstract

There is a robust and compelling body of evidence supporting the ergogenic and therapeutic role of creatine supplementation in muscle. Beyond these well-described effects and mechanisms, there is literature to suggest that creatine may also be beneficial to brain health (e.g., cognitive processing, brain function, and recovery from trauma). This is a growing field of research, and the purpose of this short review is to provide an update on the effects of creatine supplementation on brain health in humans. There is a potential for creatine supplementation to improve cognitive processing, especially in conditions characterized by brain creatine deficits, which could be induced by acute stressors (e.g., exercise, sleep deprivation) or chronic, pathologic conditions (e.g., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer’s disease, depression). Despite this, the optimal creatine protocol able to increase brain creatine levels is still to be determined. Similarly, supplementation studies concomitantly assessing brain creatine and cognitive function are needed. Collectively, data available are promising and future research in the area is warranted.

Highlights

  • The Effects of Creatine Supplementation on Brain Creatine LevelsWhile muscle exclusively relies on dietary ingestion and endogenous synthesis from the liver, can synthesize creatine

  • The ergogenic effects of creatine supplementation are well documented, with evidence supporting its efficacy in increasing muscle strength, lean mass, and exercise performance/muscle function, when combined with exercise in different populations, from athletes to a wide spectrum of patient populations [1,2,3]

  • N-phosphoryl group from phosphorylcreatine (PCr) to adenosine diphosphate (ADP), resynthesizing adenosine triphosphate (ATP) and spatial energy buffering, transferring energy from the mitochondria to the cytosol. These mechanisms are responsible for facilitating ATP homeostasis during high energy turnover, maintaining a low ADP concentration and reducing Ca2+ leakage from the sarcoplasmic reticulum and impairment of force output of the muscle [4,5,6]

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Summary

The Effects of Creatine Supplementation on Brain Creatine Levels

While muscle exclusively relies on dietary ingestion and endogenous synthesis from the liver, can synthesize creatine. Brain creatine content may rely less on exogenous creatine than muscle [20,21,24,28], which could theoretically involve a down-regulated response in brain creatine synthesis upon supplementation Alternative to this hypothesis is the demonstration that the brain lacks the expression of creatine transporter in the astrocytes involved in the blood–brain barrier, implying a limited permeability of the brain to the circulating creatine [29], which is in line with the lack of increase in brain creatine following supplementation reported by some studies [24,28,30]. These data are of relevance considering the inherent capacity of the brain to synthesize creatine and its theoretical impaired ability to transport creatine through the blood–brain barrier, warranting further research on alternative strategies to increase brain creatine

Creatine Supplementation and Cognition
Findings
Conclusions and Future Directions
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