JPBS

Creatine monohydrate (CrM) is one of the most well-researched and effective ergogenic supplements. Given the constant energy supply required by the brain, there has been a paradigm shift from CrM for skeletal muscle benefits to potentially improving brain bioenergetics, health and function. Accumulating research indicates that CrM is capable of increasing brain creatine stores which may help explain improvements in cognitive functioning particularly during times of metabolic stress (i.e., sleep deprivation, hypoxia, mental fatigue, and traumatic brain injury [TBI]). Due to the attenuation of creatine transport kinetics and the blood-brain barrier (BBB), speculation exists that higher doses of CrM are needed to optimize brain creatine levels. However, optimal CrM doses are currently unknown. Beyond these key variables, strategies such as glycocyamine supplementation (natural precursor to creatine), cyclocreatine supplementation (creatine analog), intranasal administration, and creatine transporter (CT1) modulation appear promising for increasing total and regional brain creatine levels which warrants further investigation. Collectively, higher doses of CrM have shown beneficial effects for older adults with Alzheimer’s Disease, young adults following acute periods of sleep deprivation, children suffering from TBI, and depression. The purpose of this narrative review is to (1) provide a comprehensive overview and rationale for the requirement of higher doses of CrM for brain bioenergetics, health and function and (2) identify areas of future research to further the field.

creatine; supplementation; brain bioenergetics; health; Alzheimer’s disease; sleep deprivation; traumatic brain injury; depression