Major adverse events (occurring in 2 out of 72 magnesium recipients and 3 out of 68 placebo recipients), and withdrawals due to adverse events, were not significantly different from placebo. Our analysis of adverse events pooled all studies, regardless of the setting in which cramps occurred. The single study in people with liver cirrhosis was small and had limited reporting of cramps, but found no difference in terms of cramp frequency or cramp intensity. Of the three trials comparing magnesium to placebo, one found no benefit on frequency or intensity measures, another found benefit for both, and a third reported inconsistent results for frequency that could not be reconciled. The single study comparing magnesium to no treatment failed to find statistically significant benefit on a three‐point ordinal scale of overall treatment efficacy. We were unable to perform meta‐analysis for trials of pregnancy‐associated leg cramps. 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 2 studies, 91 participants moderate‐certainty evidence) and the percentage of participants with the majority of cramp durations of one minute or more at four weeks (RR 1.83, 95% CI 0.74 to 4.53, 1 study, 46 participants low‐certainty evidence). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity or cramp duration. The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also no different (RR 1.04, 95% CI 0.84 to 1.29 3 studies, 177 participants high‐certainty evidence). This includes the primary endpoint, 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% 3 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 5 studies, 307 participants moderate‐certainty evidence). In contrast, we rated the risk of bias high in only one of five trials in participants with idiopathic rest cramps.įor idiopathic cramps, largely in older adults (mean age 61.6 to 69.3 years) presumed to have nocturnal leg cramps (the commonest presentation), differences in measures of cramp frequency when comparing magnesium to placebo were small, not statistically significant, and showed minimal heterogeneity (I² = 0% to 12%). We judged the single trial in people with liver cirrhosis and all five trials in participants with pregnancy‐associated leg cramps to be at high risk of bias. Nine trials compared magnesium to placebo, one trial compared magnesium to no treatment, calcium carbonate or vitamin B, and another trial compared magnesium to vitamin E or calcium. All trials provided magnesium as an oral supplement, except for one trial which provided magnesium as a series of slow intravenous infusions. Another study enrolled 29 people with liver cirrhosis, only some of whom suffered muscle cramps. Five trials enrolled women with pregnancy‐associated leg cramps (408 participants) and five trials enrolled people with idiopathic cramps (271 participants, with 118 additionally crossed over to control). We identified 11 trials (nine parallel‐group, two cross‐over) enrolling a total of 735 individuals, amongst whom 118 cross‐over participants additionally served as their own controls.
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