Background
Skeletal muscle cramps are common and often occur in association with pregnancy, advanced age, exercise, or motor neuron disorders (such as amyotrophic lateral sclerosis). Typically, these cramps have no obvious underlying pathology, which is why they are called idiopathic . Magnesium supplements are marketed for cramp prophylaxis although the effectiveness of magnesium for this purpose is unclear.
This is an update of a Cochrane review first published in 2012, and conducted to identify and incorporate more recent studies.
Goals
To evaluate the effects of magnesium supplementation compared to no treatment, placebo control, or other cramp treatments in patients with skeletal muscle cramps.
Search methods
On 9 September 2019, we searched the Cochrane Neuromuscular Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, CINAHL Plus, AMED and SPORTDiscus. We also searched the WHO ICTRP and ClinicalTrials.gov to find registered trials that may be ongoing or unpublished, and the ISI Web of Science to find studies citing the studies included in this review.
Selection criteria
Randomized controlled trials (RCTs) of magnesium supplements (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all cramp presentations). Comparisons of magnesium with no treatment, placebo control, or other treatment were considered.
Data collection and analysis
Two review authors independently selected trials for inclusion and extracted data. Two review authors assessed risk of bias. We attempted to contact all study authors when questions arose and obtained participant-level data for four of the included trials, one of which was unpublished. All data on adverse effects were obtained from the included RCTs.
Main results
We identified 11 trials (nine parallel groups, two crossover) involving a total of 735 participants, of which 118 participants in the crossover trial also acted as their own controls. Five trials included women with pregnancy-associated leg cramps (408 participants) and five trials included people with idiopathic cramps (271 participants, with 118 additionally crossed over to controls). Another study included 29 people with liver cirrhosis, only some of whom suffered muscle cramps. Magnesium was given as an oral supplement in all trials, except in one which was given as a series of slow intravenous infusions. Nine trials compared magnesium with placebo, one trial compared magnesium with no treatment, calcium carbonate or vitamin B, and another trial compared magnesium with vitamin E or calcium.
The one trial in people with liver cirrhosis and the five trials in participants with pregnancy-associated leg cramps were considered to be at high risk of bias. In contrast, the risk of bias was rated high in only one of five trials in participants with idiopathic rest cramps.
In the case of idiopathic cramps , mainly in older adults (mean age 61.6 to 69.3 years) with suspected nocturnal leg cramps (the most common condition), the differences in measurements of cramp frequency comparing magnesium with placebo were small, were not statistically significant, and showed minimal heterogeneity (I² = 0% to 12%). These include the main outcome, the percentage change from baseline in the number of cramps per week at four weeks (mean difference (MD) -9.59%; 95% confidence interval (CI): - 23.14% to 3.97%; three studies, 177 participants; moderate-certainty evidence) and the difference in the number of cramps per week at four weeks (MD -0.18 cramps/week, 95% CI: -0.84 to 0.49; five studies, 307 participants; moderate-certainty evidence).
The percentage of people who experienced a 25% or greater reduction in cramp rate from baseline also showed no difference (RR 1.04, 95% CI 0.84 to -1.29; three studies, 177 participants; evidence high certainty). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity or duration. This includes the number of participants rating their cramps as moderate or severe at four weeks (RR 1.33, 95% CI 0.81 to 2.21; two studies, 91 participants; moderate-certainty evidence); and the percentage of participants with most cramp durations of one minute or more at four weeks (RR 1.83, 95% CI 0.74 to 4.53; one study, 46 participants; evidence for certainty low).
We were unable to meta-analyze trials of leg cramps associated with pregnancy . The only study that compared magnesium to no treatment failed to find statistically significant beneficial effects on a three-point ordinal scale of overall treatment effectiveness. Of the three trials comparing magnesium with placebo, one found no beneficial effects on measures of frequency or intensity, another found beneficial effects for both, and a third reported inconsistent results in frequency that could not be fixed. .
The only study in people with liver cirrhosis was small and had limited reporting of cramps, but found no difference in the frequency or intensity of cramps.
The analysis of adverse events pooled all studies, regardless of the setting in which cramps occurred. Major adverse events (occurring in 2 of 72 participants receiving magnesium and 3 of 68 receiving placebo), and withdrawals due to adverse events, were not significantly different from placebo. However, in the four studies where this could be determined, more participants experienced mild adverse events in the magnesium group than in the placebo group (RR 1.51, 95% CI 0.98 to 2.33; four studies, 254 participants; low-certainty evidence). Overall, oral magnesium was associated with primarily gastrointestinal adverse events (e.g., diarrhea), experienced by 11% (10% in control) to 37% (14% in control) of participants.
Authors’ conclusions
Magnesium supplements are unlikely to provide clinically meaningful cramp prophylaxis for older patients with skeletal muscle cramps. In contrast, for those with pregnancy-associated night cramps, the literature is conflicting and additional research is needed in this patient population.
We found no RCTs evaluating magnesium for exercise-related muscle cramps or disease-state-associated muscle cramps (e.g., amyotrophic lateral sclerosis/motor neuron disease), except for a single small (inconclusive) study in people with cirrhosis of the liver, of which only some suffered cramps.
