Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseases

Neuromolecular Med. 2008;10(4):275-90. doi: 10.1007/s12017-008-8053-y. Epub 2008 Nov 13.


Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodegenerative disorders may prove to be useful as a therapeutic intervention. Creatine is a molecule that is produced both endogenously, and acquired exogenously through diet, and is an extremely important molecule that participates in buffering intracellular energy stores. Once creatine is transported into cells, creatine kinase catalyzes the reversible transphosphorylation of creatine via ATP to enhance the phosphocreatine energy pool. Creatine kinase enzymes are located at strategic intracellular sites to couple areas of high energy expenditure to the efficient regeneration of ATP. Thus, the creatine kinase/phosphocreatine system plays an integral role in energy buffering and overall cellular bioenergetics. Originally, exogenous creatine supplementation was widely used only as an ergogenic aid to increase the phosphocreatine pool within muscle to bolster athletic performance. However, the potential therapeutic value of creatine supplementation has recently been investigated with respect to various neurodegenerative disorders that have been associated with bioenergetic deficits as playing a role in disease etiology and/or progression which include; Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and Huntington's disease. This review discusses the contribution of mitochondria and bioenergetics to the progression of these neurodegenerative diseases and investigates the potential neuroprotective value of creatine supplementation in each of these neurological diseases. In summary, current literature suggests that exogenous creatine supplementation is most efficacious as a treatment paradigm in Huntington's and Parkinson's disease but appears to be less effective for ALS and Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Creatine / metabolism
  • Creatine / pharmacology*
  • Creatine / therapeutic use
  • Dietary Supplements
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / metabolism*
  • Mitochondrial Diseases / physiopathology
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / physiopathology
  • Phosphocreatine / metabolism


  • Phosphocreatine
  • Adenosine Triphosphate
  • Creatine