By Seema Gupta, MD, MSPH

Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV

Dr. Gupta reports no financial relationships relevant to this field of study.

SYNOPSIS: A small randomized, double-blind, placebo-controlled trial demonstrated that oral magnesium oxide was not superior to placebo for older adults suffering from nocturnal leg cramps.

SOURCE: Maor NR, Alperin M, Shturman E, et al. Effect of magnesium oxide supplementation on nocturnal leg cramps: A randomized clinical trial. JAMA Intern Med. Published online Feb. 20, 2017. doi:10.1001/jamainternmed.2016.9261. [Epub ahead of print].

Nocturnal leg cramps (NLC) are sudden, involuntary, painful, and palpable muscle contractions lasting seconds to minutes, occurring most often at night. They are common, occurring in nearly 50% of adults > 50 years of age.1 There is no gender preference, but the prevalence and frequency increases with age. An exact understanding of the mechanism is lacking. Therefore, most cases of NLC occurring in adults seem to be idiopathic, but there can be potential predisposing factors. These include metabolic disorders such as hemodialysis and electrolyte imbalance; neurologic, endocrine, and vascular disorders; and prolonged sitting or inappropriate leg positioning. Certain medications, such as beta-agonists, beta-blockers with intrinsic sympathomimetic activity, potassium-sparing diuretics, angiotensin II receptor antagonists, benzodiazepines, oral contraceptives, and thiazide-like diuretics, also may be associated.

Quinine has been among the most studied pharmacotherapy for NLC and has been found to be low to moderately effective in reducing the frequency and intensity of NLC attacks.2 However, the FDA has issued warnings about the use of quinine for NLC because of the associated risk of serious and life-threatening side effects, such as cardiac arrhythmias, thrombocytopenia, and severe hypersensitivity reactions.3 On the other hand, magnesium is used commonly for NLC, and, other than diarrhea occurring with high doses, oral magnesium supplements generally are considered safe and relatively free of adverse effects. Although initial trials demonstrated the effectiveness of magnesium in treating NLC in pregnant women, subsequent studies have failed to demonstrate efficacy in older adults.4 However, none of these studies have used oral magnesium oxide, and there is some evidence that, as opposed to magnesium citrate, magnesium oxide may be able to increase intracellular magnesium levels.

Maor et al hypothesized that the oral magnesium oxide supplementation may reduce the frequency and severity of NLC and subsequently improve quality of life and quality of sleep for older adults. The researchers conducted a randomized, double-blind, placebo-controlled clinical trial in northern Israel where 94 adults (39% male; mean age, 65 years) with four or more NLCs during the previous two weeks were randomized to once-nightly magnesium oxide (865 mg; equivalent to 520 mg of elemental magnesium) or placebo for four weeks. During the treatment period, both the magnesium and placebo groups experienced reductions in NLC episodes, from about eight weekly to five weekly. At four weeks, no significant differences were found between the two groups in severity or duration of NLCs or in quality of sleep or quality of life. No significant adverse effects were attributed to either magnesium or placebo. The authors concluded that oral magnesium oxide was not superior to placebo for older adults experiencing NLC.

COMMENTARY

NLCs can cause substantial distress and sleep disruption for many Americans. In practice, physicians often have very little to offer in terms of either a clear explanation of the etiology or treatment options. Often, preventive recommendations include stretching exercises for the affected muscle group, avoiding dehydration, and addressing secondary predisposing factors. Minerals and vitamin supplementation, including vitamin B complex and iron supplementation in iron deficiency states, also have demonstrated some benefits. Similarly, other pharmaceutical options may include trials of diphenhydramine, calcium channel blockers, and gabapentin to avoid the routine use of quinine because of its safety risk profile. In the Maor et al study, oral magnesium oxide was not found to be superior to placebo in treatment of NLC. However, it is noteworthy that there was a decrease in the mean number of NLCs per week from approximately eight to five in both groups, suggesting a rather significant placebo effect, which also may explain the wide use of magnesium by both patients and physicians. Clinically, it is an interesting finding that we must keep in mind when deciding whether to recommend magnesium for NLC, even though it was not found to be superior to placebo.

REFERENCES

  1. Abdulla AJ, Jones PW, Pearce VR. Leg cramps in the elderly: Prevalence, drug and disease associations. Int J Clin Pract 1999;53:494-496.
  2. El-Tawil S, Al Musa T, Valli H, et al. Quinine for muscle cramps. Cochrane Database Syst Rev 2015;(4):CD005044.
  3. U.S. Food and Drug Administration. Serious risks associated with using Quinine to prevent or treat nocturnal leg cramps. Available at: http://bit.ly/2ns0T7r. Accessed March 11, 2017.
  4. Garrison SR, Allan GM, Sekhon RK, et al. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev 2012;(9):CD009402.