The quality of the evidence is downgraded by study quality (unclear allocation concealment) and by imprecise results (few patients and wide confidence intervals).
A Cochrane review [Abstract] 1 included 11 studies with a total of 735 subjects. Nine studies were parallel and 2 cross-over design. Five studies enrolled idiopathic cramp sufferers (n=271, with 118 additionally crossed over to control), 5 studies enrolled women with pregnancy-associated leg cramps (n=408), and 1 study enrolled 29 people with liver cirrhosis, only some of whom suffered muscle cramps. Magnesium (Mg) was compared to placebo in 9 studies, one study compared Mg to no treatment, calcium carbonate or vitamin B, and another study compared Mg to vitamin E or calcium. All studies provided Mg as an oral supplement, except for one study which provided magnesium as a series of slow intravenous infusions. No RCTs evaluating Mg for exercise-associated or disease-associated muscle cramps have been conducted.
For idiopathic cramps (largely older adults presumed to have nocturnal leg cramps), differences between Mg vs. placebo in measures of cramp frequency were not statistically significant. This includes the primary endpoint, percentage change from baseline in the number of cramps per week at 4 weeks (MD -9.59%, 95% CI -23.14% to 3.97%; 3 studies, n=177) and the difference in the number of cramps per week at 4 weeks (MD 0.18 cramps/week, 95% CI -0.84 to 0.49; 5 studies, n=307). The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also not different (RR 1.04, 95% CI 0.84 to 1.29; 3 studies, n=177). Similarly, no statistically significant difference was found at 4 weeks in measures of cramp intensity or duration.
Meta-analysis was not possible for studies of pregnancy-associated leg cramps. The single study comparing Mg to no treatment did not find statistically significant benefit on a 3-point ordinal scale of overall treatment efficacy. Three studies comparing Mg to placebo differed in that one study found no benefit on frequency or intensity measures, another found benefit for both, and a third reported inconsistent results for frequency.
Pooled results (regardless of the setting in which cramps occurred) for adverse events showed that major adverse events (occurring in 2/72 magnesium recipients and 3/68 placebo recipients), and withdrawals due to adverse events, were not significantly different from placebo. More participants experienced minor adverse events in the magnesium group than in the placebo group (RR 1.51, 95% CI 0.98 to 2.33; 4 studies, n=254), although the difference was not statistically significant. Overall, oral magnesium was associated with mostly gastrointestinal adverse events (e.g. diarrhoea), experienced by 11% (10% in control) to 37% (14% in control) of participants.
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