Trial of d-alpha-tocopherol in Huntington's disease

Am J Psychiatry. 1995 Dec;152(12):1771-5. doi: 10.1176/ajp.152.12.1771.


Objective: Evidence suggests that the neuropathology of Huntington's disease, a neuropsychiatric disorder due to a mutation on chromosome 4, results from excessive activation of glutamate-gated ion channels, which kills neurons by oxidative stress. Therefore, the authors hypothesized that alpha-tocopherol, which reduces oxyradical damage to cell membranes, might slow the course of Huntington's disease.

Method: A prospective, double-blind; placebo-controlled study of high-dose d-alpha-tocopherol treatment was carried out with a cohort of 73 patients with Huntington's disease who were randomly assigned to either d-alpha-tocopherol or placebo. Patients were monitored for changes in neurologic and neuropsychologic symptoms.

Results: Treatment with d-alpha-tocopherol had no effect on neurologic and neuropsychiatric symptoms in the treatment group overall. However, post hoc analysis revealed a significant selective therapeutic effect on neurologic symptoms for patients early in the course of the disorder.

Conclusions: Antioxidant therapy may slow the rate of motor decline early in the course of Huntington's disease.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / therapeutic use*
  • Chromosomes, Human, Pair 4 / genetics
  • Double-Blind Method
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Isomerism
  • Oxidative Stress / drug effects
  • Placebos
  • Prospective Studies
  • Treatment Outcome
  • Vitamin E / pharmacology
  • Vitamin E / therapeutic use*


  • Antioxidants
  • Placebos
  • Vitamin E