Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps: A Randomized Clinical Trial

Abstract

Importance: Magnesium supplements are widely marketed for prophylaxis of nocturnal leg cramps (NLC) despite no evidence of significant benefit.

Objective: To determine whether magnesium oxide is better than placebo for NLC prophylaxis.

Design, setting, and participants: A randomized, double-blind, placebo-controlled clinical trial of 2 weeks eligibility screening followed by 4 weeks of treatment was conducted in northern Israel, from February to October 2013. An intention-to-treat data analysis was performed from March 22, 2014, to April 17, 2016. We used a volunteer sample of community-dwelling individuals experiencing NLC, 21 years or older, with 4 or more documented episodes of NLC during 2 weeks of screening.

Interventions: Capsules containing either magnesium oxide or a similar-looking placebo to be taken orally, once daily at bedtime for a period of 4 weeks.

Main outcomes and measures: The primary outcome was the difference in the mean number of NLC per week between the screening and treatment phases. Secondary outcomes included severity and duration of NLC, quality of life, and quality of sleep.

Results: Of the 166 volunteers, 72 (43%) were excluded, of whom 15 declined to participate and 57 did not meet the inclusion criteria. Of the 94 individuals (39% male; mean [SD] age, 64.9 [11.1] years) randomly assigned to magnesium oxide (48) or placebo (46), 6 did not complete the study protocol (3 in each group). Mean (SD) change of NLC was -3.41 (4.05) (from 7.84 [5.68] to 4.44 [5.66]) and -3.03 (4.53) (from 8.51 [5.20] to 5.48 [4.93]) per week in the magnesium oxide and placebo groups, respectively, a difference between groups of 0.38 (0.48) NLC per week (P = .67 in an intention-to-treat analysis). There were no between-group differences in the severity and duration of NLC, quality of life, or quality of sleep.

Conclusions and relevance: Oral magnesium oxide was not superior to placebo for older adults experiencing NLC. The decrease in the mean number of NLC per week, from the screening to the treatment phase in both groups, is probably a placebo effect that may explain the wide use of magnesium for NLC.

Trial registration: clinicaltrials.gov Identifier: NCT01709968.

Figure 1.. Study Flow Diagram

^aOther reasons include incomplete documentation of nocturnal leg cramps during screening phase or failure to attend scheduled appointments, serum creatinine level greater than 2 mg/dL, concurrent illness, and physicians’ instructions. SI conversion factor: To convert serum creatinine level to micromoles per liter, multiply by 88.4.

Figure 2.. Frequency of Nocturnal Leg Cramps (NLC) per Week by Treatment Group During the Entire Study

Values at screening phase refer to the mean number of nocturnal leg cramps per week during the 2 weeks of screening; error bars represent standard errors.