Summary of findings 1. Magnesium for idiopathic rest cramps (largely older adults).

Magnesium compared with placebo for skeletal muscle cramps
Patient or population: for effects on cramps, people (other than pregnant women) with muscle cramps (largely older adults); for adverse events, all populations Settings: outpatients recruited through primary care clinics or community advertising Intervention: magnesium supplements (oral or intravenous) Comparison: placebo
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Magnesium
People (other than pregnant women) with muscle cramps, largely older adults
Cramp frequency (percentage change from baseline at 4 weeks)	The mean percentage change in cramp frequency in the control groups was −28.7%	The mean percentage change in cramp frequency in the magnesium groups was an additional 9.59% lower (23.14% lower to 3.97% higher)	MD −9.59% (−23.14 to 3.97)	177 (3 studies)	⊕⊕⊕⊝ Moderatea due to imprecision	Magnesium probably results in little to no difference in cramp frequency (based on percentage change from baseline at 4 weeks). The 95% CI excludes a 25% reduction beyond placebo
Cramp frequency (responder analysis: 25% or better reduction at 4 weeks)	644 per 1000	669 per 1000 (541 to 830)	RR 1.04 (0.84 to 1.29)	177 (3 studies)	⊕⊕⊕⊕ High	Magnesium results in little to no difference in cramp frequency (based on the proportion of people responding at 4 weeks)
Cramp frequency (mean number of cramps per week on treatment at 4 weeks)	The mean number of cramps per week in the placebo groups while on treatment was 4.68	The mean number of cramps per week in the magnesium groups was 0.18 cramps per week lower (0.84 lower to 0.49 higher)	MD −0.18 cramps per week (−0.84 to 0.49)	307 (5 studies)	⊕⊕⊕⊝ Moderateb due to inconsistency	Magnesium probably results in little to no difference in cramp frequency (based on number of cramps per week at 4 weeks). The 95% CI excludes a 1 cramp per week reduction
Cramp intensity (moderate or worse at 4 weeks)	300 per 1000	399 per 1000 (243 to 663)	RR 1.33 (0.81 to 2.21)	91 (2 studies)	⊕⊕⊕⊝ Moderatec due to imprecision	Magnesium is unlikely to reduce the number of people with cramp intensity of moderate or worse at 4 weeks
Cramp duration (≥ 1 minute at 4 weeks)	227 per 1000	416 per 1000 (168 to 1000)	RR 1.83 (0.74 to 4.53)	46 (1 study)	⊕⊕⊝⊝ Lowd due to very serious imprecision	Magnesium may not reduce the number of people with a cramp duration ≥ 1 minute at 4 weeks
Adverse events: all populations
Major adverse events	33 per 1000	23 per 1000 (5 to 110)	RR 0.68 (0.14 to 3.31)	185 (3 RCTs)	⊕⊝⊝⊝ Very Lowe due to very serious imprecision and indirectness	It is uncertain as to whether magnesium differs from placebo in terms of major adverse events
Minor adverse events	198 per 1000	305 per 1000	RR 1.51 (0.98 to 2.33)	254 (4 studies)	⊕⊕⊝⊝ Lowf due to imprecision and indirectness	Although this difference was borderline for statistical significance, the number of people dropping out of the included studies was no different in the magnesium group than it was in the placebo group.
CI: confidence interval; IV: intravenous; MD: mean difference; RR: risk ratio
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderatecertainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

^aDowngraded once for imprecision since our investigator‐defined 25% minimum clinically important difference (MCID) is not derived from feedback from people with cramps. A smaller MD (e.g. 20%) might still be important to some people and is not yet ruled out. An additional consideration was that 1 unpublished study combined in this analysis was rated at high risk of bias for selective (incomplete) reporting. However this study was combined with 2 studies at low risk of bias with which its findings were consistent, and our initial downgrade for imprecision due to investigator‐defined MCID was considered a soft indication for a downgrade. Hence we chose not to add a second downgrade.
^bDowngraded once for inconsistency: although statistical heterogeneity was low and the CI excluded a '1 cramp per week' reduction, 3 of the 5 trials had point estimates exceeding a '1 cramp per week' reduction, with the overall estimate being pulled towards less benefit by 1 trial with 70% of the weighting in the analysis. Hence there is some inconsistency in the results.
^cDowngraded once for imprecision because the number of people with moderate to severe cramps was low (28). Although 1 of the 2 trials combined in analysis was at high risk of bias due to attrition (Roffe 2002), our high bias rating described the entire trial. We obtained and utilized patient level data for only the first period of this cross‐over study, which substantially mitigated the risk. Hence we did not carry out a second downgrade.
^dDowngraded twice for very serious imprecision as this estimate is based on a single trial with only 15 participants having cramps that lasted over a minute.
^eDowngraded 3 times ‒ twice for very serious imprecision, as this estimate is derived from only 5 events, and once for indirectness because we combined individuals with a variety of cramp syndromes (idiopathic rest cramps, pregnancy‐associated cramps, and liver‐cirrhosis‐associated cramps)
^fDowngraded once for imprecision because the number of people with minor adverse events was low (64), and downgraded once for indirectness because we combined individuals with a variety of cramp syndromes (idiopathic rest cramps, pregnancy‐associated cramps, and liver‐cirrhosis‐associated cramps)