Treatment of nocturnal leg cramps. A crossover trial of quinine vs vitamin E

Arch Intern Med. 1992 Sep;152(9):1877-80.


Objective: This study compared the efficacy and safety of quinine sulfate, vitamin E, and placebo in the treatment of nocturnal leg cramps.

Design: A random-order, double-blind, placebo-controlled crossover trial was performed.

Setting: The study was conducted at the Veterans Affairs Medical Center, White River Junction, Vt.

Participants: Twenty-seven male veterans, aged 38 to 73 years, who experienced at least six leg cramps per month were recruited through the general medicine walk-in clinic or were referred from other clinics. Fifty-five subjects were contacted, 30 were enrolled consecutively, and 27 completed the study.

Intervention: Subjects received, in random order, quinine sulfate (200 mg at supper and 300 mg at bedtime), vitamin E (800 U at bedtime), or placebo for 4-week periods. These periods were separated by 4-week washout intervals.

Outcome measures: Patients reported cramp frequency, severity, and sleep disturbance caused by cramps.

Results: Compared with treatment with placebo, quinine reduced the frequency of cramps and sleep disturbance, but not the average cramp severity. Thirteen of 27 patients had at least a 50% reduction in the number of cramps while receiving quinine; the response was usually seen within 3 days. There was evidence of a mild increase in side effects while subjects received quinine. Vitamin E was not effective in reducing leg cramp frequency, severity, or sleep disturbance.

Conclusions: Quinine sulfate, but not vitamin E, is superior to placebo in the treatment of nocturnal leg cramps.

Publication types

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

MeSH terms

  • Double-Blind Method
  • Humans
  • Leg
  • Male
  • Middle Aged
  • Muscle Cramp / drug therapy*
  • Quinine / therapeutic use*
  • Sleep Wake Disorders / prevention & control
  • Vitamin E / therapeutic use*


  • Vitamin E
  • Quinine