Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders

Ann Neurol. 2001 May;49(5):561-74.


Substantial evidence indicates that bioenergetic dysfunction plays either a primary or secondary role in the pathophysiology of cell death in neurodegenerative and neuromuscular disorders, and even in normal aging. Agents that ameliorate bioenergetic defects may therefore be useful in therapy. Creatine, which increases muscle and brain phosphocreatine concentrations, and may inhibit the activation of the mitochondrial permeability transition, protects against neuronal degeneration in transgenic murine models of amyotrophic lateral sclerosis and Huntington's disease and in chemically mediated neurotoxicity. Initial studies of creatine use in humans appear promising; however, further long-term, well-designed trials are needed. Coenzyme Q10, Gingko biloba, nicotinamide, riboflavin, carnitine, lipoic acid, and dichloroacetate are other agents which may have beneficial effects on energy metabolism, but the preclinical and clinical evidence for efficacy in neurological diseases remains limited. These compounds are widely used as dietary supplements; however, they must be subjected to rigorous evaluation through randomized, double-blinded trials to establish efficacy, cost-effectiveness and safety in neurological disorders.

Publication types

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

MeSH terms

  • Animals
  • Creatine / therapeutic use*
  • Energy Metabolism / drug effects*
  • Humans
  • Nervous System Diseases / drug therapy*


  • Creatine