1. JAMA Intern Med. 2017 May 1;177(5):617-623. doi: 10.1001/jamainternmed.2016.9261.

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

Roguin Maor N(1), Alperin M(1), Shturman E(1), Khairaldeen H(1), Friedman M(1),
Karkabi K(1), Milman U(1).

Author information: 
(1)Clinical Research Unit, Clalit Health Services, Haifa and Western Galilee
District, Israel2Department of Family Medicine, Technion-Israel Institute of
Technology, Haifa, Israel.

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 (Pā€‰=ā€‰.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.

DOI: 10.1001/jamainternmed.2016.9261 
PMCID: PMC5818780
PMID: 28241153  [Indexed for MEDLINE]