Written by Joyce Smith, BS. Magnesium oxide supplementation was found to be no more effective than placebo in reducing the frequency of nocturnal leg cramps (NLC) in older adults.
NLC are a common problem for our aging population, significantly disrupting nighttime sleep and quality of Life 1.These painful involuntary contraction affecting 60% of adults 2 appear to be idiopathic 3, but may have a number of potential predisposing factors that include hemodialysis, electrolyte imbalances and neurologic, endocrine, vascular, and medication-related conditions 4.The use of quinine, while it has shown some effectiveness in treating NLC, has been negated due to serious reactions to the drug 5. Magnesium is commonly used in Latin America and Europe 4, yet the benefit of magnesium citrate in treating older adults with NLC remains weak 6. A recent study investigating the effect of supplemental oral magnesium oxide and magnesium citrate on intracellular magnesium levels in healthy subjects found that the oxide form of magnesium was superior to citrate at increasing intracellular levels of magnesium 7.
The following randomized, placebo-controlled, clinical trial by Major and colleagues 8 investigated the ability of magnesium oxide supplementation to reduce the frequency and severity of NLC and subsequently improve quality of life and quality of sleep of older adults.
Ninety-four adults, 21 years of age or older (mean age 65), who experienced at least four documented episodes of NLC during the previous 2 week screening period, were recruited for the study. Those already taking magnesium supplements were also included in the study providing they agreed to stop taking their supplements 10 days prior to enrollment. Participants were allocated to either one tablet per night of oral magnesium oxide (865 mg; equivalent to 520 mg of elemental magnesium) or placebo for 4 weeks, during which time occurrence of NLC were recorded. At the baseline visit researchers, using self-reported questionnaires, collected data on patients’ demographic and clinical characteristics. Primary outcome was the mean difference in NLC per week; secondary outcomes were the severity and duration of NLC and quality of life and sleep duration.
Eighty-eight participants completed the study protocol. From the screening to the treatment period both the magnesium and placebo groups experienced significant reductions in NLC episodes, from about 8 -5 per week (48.4% -41.2% in magnesium group and 29.5% to 64.8% in placebo group) respectively. The difference in mean number of episodes per week between screening and study end was -3.41 for those who supplemented with magnesium and -3.03 for those taking the placebo, for a negligible between-group difference of 0.38 (P=0.67). At 4 weeks, no significant differences were found between the two groups in severity and duration of NLC or in quality of sleep or quality of life (P = 0.38 for treatment group and P = 0.30 for placebo group). No significant adverse effects could be attributed to either magnesium or placebo, leading the research team to conclude that magnesium oxide is no better than placebo for older adults with NLC.
In spite of the recent evidence demonstrating better intracellular absorption with magnesium oxide than with magnesium citrate 7, the decline in the number of weekly cramps was very similar for magnesium oxide and placebo in this study, suggesting that the mean decrease of NLC in both intervention and placebo groups may be due to a placebo effect which might explain the extensive use of magnesium today for leg cramps in our elderly populations.
This study reflects the results of only of 94 participants (43% recruited of the 220 planned). On April 1, 2014, the research team submitted their data for a blinded interim analysis. When the analysis results indicated that magnesium for the treatment of NLC is safe but probably not more effective than placebo, the committee recommended that the study be discontinued due to lack of efficacy.
Study limitations include a small number of participants and a short 4-week study duration. Participants were self-selected volunteers which may have contributed to a potential selection bias. However, Maor and colleagues state that the study results were not influenced by the demographic or clinical characteristics of the participants, including their use of supplements before enrollment.
Source: Maor, Noga Roguin, Mordechai Alperin, Elena Shturman, Hassan Khairaldeen, Moran Friedman, Khaled Karkabi, and Uzi Milman. “Effect of magnesium oxide supplementation on nocturnal leg cramps: a randomized clinical trial.” JAMA internal medicine 177, no. 5 (2017): 617-623.
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Posted November 2, 2020.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References:
- Hawke F, Chuter V, Burns J. Impact of nocturnal calf cramping on quality of sleep and health-related quality of life. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2013;22(6):1281-1286.
- Allen RE, Kirby KA. Nocturnal leg cramps. Am Fam Physician. 2012;86(4):350-355.
- Maisonneuve H, Chambe J, Delacour C, et al. Prevalence of cramps in patients over the age of 60 in primary care : a cross sectional study. BMC family practice. 2016;17(1):111.
- Monderer RS, Wu WP, Thorpy MJ. Nocturnal leg cramps. Curr Neurol Neurosci Rep. 2010;10(1):53-59.
- U.S. Food and Drug Administration. MedWatch Safety Alerts for Human Medical Products. 2020; https://healthdata.gov/dataset/medwatch-safety-alerts-human-medical-products-1. Accessed October 28, 2020.
- Garrison SR, Allan GM, Sekhon RK, Musini VM, Khan KM. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev. 2012;2012(9):Cd009402.
- Shechter M, Saad T, Shechter A, Koren-Morag N, Silver BB, Matetzky S. Comparison of magnesium status using X-ray dispersion analysis following magnesium oxide and magnesium citrate treatment of healthy subjects. Magnes Res. 2012;25(1):28-39.
- Roguin Maor N, Alperin M, Shturman E, et al. Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA Intern Med. 2017;177(5):617-623.
