Creatine Supplementation and Brain Health

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.

A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation

“…It needs to be noted that Cr belongs to a set of seven putative systems biomarkers for Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis [ 145 ], which highlights its remarkable influence on neuron survival and function. Since it is not able to increase itself to the same extent as skeletal muscle, most of the research on enhancing Cr uptake using intermediate compounds (e.g., guanidinoacetate) or derivatives (e.g., Cr ethyl ester, dodecyl Cr ester, cyclocreatine, and Cr gluconate) is focused on the brain [ 18 ] and the heart [ 146 ]. Additionally, even if intracellular Cr levels increase after CrM (or Cr analogous) supplementation, the uptake is limited by CRT downregulation due to mechanisms that are not fully understood.…”

“…The CK/PCr system can be enhanced through supplementation with creatine monohydrate (CrM), which is the most studied, safe, and effective nutritional supplement to optimize physical performance [ 5 , 6 , 7 , 8 ], with potential benefits in health and disease [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. It seems that the elevation of intracellular PCr concentration causes a greater capacity for phosphagens to contribute to energy metabolism, while working to reduce the accumulation of Pi and H + and improving Ca 2+ handling as important mediators of fatigability in young and older adults [ 20 , 21 , 22 , 23 ].…”

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

“…Oral Cr supplementation has been shown to improve memory in healthy adults, and potential benefits for aging and stressed individuals have been described [222]. Additionally, Cr supplementation seems beneficial in reducing the severity or enhancing recovery from mild traumatic brain injury, but further studies are needed not only as a post-injury therapy but also as a neuroprotective agent in populations at high risk of mild traumatic brain injury [223].…”

Creatine Levels in Patients with Phenylketonuria and Mild Hyperphenylalaninemia: A Pilot Study

“…Albeit not conclusive, there is a wealth of literature indicating the beneficial role of Cr on brain health, specifically concerning cognitive processing [ 18 , 19 ], brain function and recovery from trauma [ 7 ]. Cr may be especially helpful in situations of acute stress (i.e., exercise or sleep deprivation) or in chronic pathologic conditions [ 18 , 20 ] ( Figure 1 ).…”

“…Albeit not conclusive, there is a we of literature indicating the beneficial role of Cr on brain health, specifically concern cognitive processing [18,19], brain function and recovery from trauma [7]. Cr may especially helpful in situations of acute stress (i.e., exercise or sleep deprivation) o chronic pathologic conditions [18,20] (Figure 1). A few studies showed that the supplementation of Cr may be an effective nutritional strategy to increase PCr content and energy status of the cell in healthy pediatric populations or with specific disorders [35][36][37], but probably not at the same extent as in the adult population [38].…”