Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation

J Neurosci. 2015 Jan 28;35(4):1773-80. doi: 10.1523/JNEUROSCI.3113-14.2015.


Impairment or interruption of oxygen supply compromises brain function and plays a role in neurological and neurodegenerative conditions. Creatine is a naturally occurring compound involved in the buffering, transport, and regulation of cellular energy, with the potential to replenish cellular adenosine triphosphate without oxygen. Creatine is also neuroprotective in vitro against anoxic/hypoxic damage. Dietary creatine supplementation has been associated with improved symptoms in neurological disorders defined by impaired neural energy provision. Here we investigate, for the first time in humans, the utility of creatine as a dietary supplement to protect against energetic insult. The aim of this study was to assess the influence of oral creatine supplementation on the neurophysiological and neuropsychological function of healthy young adults during acute oxygen deprivation. Fifteen healthy adults were supplemented with creatine and placebo treatments for 7 d, which increased brain creatine on average by 9.2%. A hypoxic gas mixture (10% oxygen) was administered for 90 min, causing global oxygen deficit and impairing a range of neuropsychological processes. Hypoxia-induced decrements in cognitive performance, specifically attentional capacity, were restored when participants were creatine supplemented, and corticomotor excitability increased. A neuromodulatory effect of creatine via increased energy availability is presumed to be a contributing factor of the restoration, perhaps by supporting the maintenance of appropriate neuronal membrane potentials. Dietary creatine monohydrate supplementation augments neural creatine, increases corticomotor excitability, and prevents the decline in attention that occurs during severe oxygen deficit. This is the first demonstration of creatine's utility as a neuroprotective supplement when cellular energy provision is compromised.

Keywords: cognition; corticomotor excitability; creatine; dietary supplementation; hypoxia; neural metabolism.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Blood Pressure
  • Cognition Disorders / diet therapy*
  • Cognition Disorders / etiology*
  • Creatine / administration & dosage*
  • Creatine / metabolism
  • Dietary Supplements*
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology
  • Female
  • Heart Rate
  • Humans
  • Hypoxia* / complications
  • Hypoxia* / diet therapy
  • Hypoxia* / pathology
  • Male
  • Middle Aged
  • Motor Cortex / metabolism
  • Motor Cortex / physiology*
  • Neural Conduction / physiology
  • Neuroprotective Agents / administration & dosage*
  • Neuropsychological Tests
  • Transcranial Magnetic Stimulation
  • Ulnar Nerve / physiopathology
  • Young Adult


  • Neuroprotective Agents
  • Aspartic Acid
  • N-acetylaspartate
  • Creatine