Evidence is lacking except for pregnancy-associated cramps
The effectiveness and safety of magnesium has been established for eclampsia and pre-eclampsia, arrhythmia, severe asthma, and migraine.11 There is some evidence for efficacy of magnesium supplementation in treatment of leg cramps in pregnant women but not for other people.2,12
A recent systematic review evaluated the effect of magnesium versus placebo for the treatment of nocturnal leg cramps and found the overall effect of magnesium to be insignificant.2 Seven trials were included, one assessed magnesium infusion versus placebo and the rest assessed oral magnesium therapy but dose and frequency of therapy varied between all studies.
A sub-analysis of three of the studies involving only pregnant women showed a significant difference between the magnesium and placebo groups in the median number of leg cramps experienced per week.2 However the studies only contained a small number of participants (n=361 in total and n=198 in the subgroup analysis), and therefore was underpowered to detect meaningful differences between groups. In addition selection bias may have impacted results as participants were included in the analysis whose leg complaints may have been confused with disorders not known to be associated with magnesium deficiency (ie, restless leg syndrome).
Another recent systematic review evaluated a further seven studies in patients with leg cramp treated with magnesium.12 The elemental magnesium dose given varied between studies. The populations included 322 mostly older patients and 202 women with pregnancy-associated leg cramps. After four weeks of treatment, differences in percentage change from baseline of cramps per week between magnesium and placebo groups were small and not statistically significant.
The authors concluded that magnesium is unlikely to provide a meaningful benefit in reducing the frequency or severity of idiopathic leg cramps in older people.12 The second review also included three further studies on pregnant women; while a meta-analysis was not possible with these, results from the individual studies were considered and found to be mixed. One study found magnesium reduced cramp frequency and pain while the other two found no benefit.12 Although two of the studies were similar in design and setting,13,14 their outcomes were different; this may have been because one of the studies lacked baseline measurement of cramp frequency. If cramp frequency before intervention was not comparable between participants in these studies, it is not appropriate to compare the number of cramps experienced during the treatment period.
Oral magnesium supplementation is well tolerated
Both meta-analyses found that magnesium is well tolerated with the most frequent adverse effects affecting the gastrointestinal system (diarrhoea, nausea, vomiting, flatulence and constipation).2,12
Moderate-to-severe and symptomatic hypermagnesaemia is usually due to excessive supplemental intake of magnesium (eg, as antacids, enemas or by intravenous infusion), most often in patients with kidney impairment. Be aware of the most common clinical features of moderate-to-severe hypermagnesaemia which are usually neuromuscular (eg, loss of deep tendon reflexes, muscle paralysis, depressed conscious state and respiratory depression). Other signs include anorexia, nausea, skin flushing, hypotension, bradycardia/heart block and cardiac arrest.15
When considering magnesium supplements, ensure patients take a product containing magnesium only. Some magnesium supplements are combined with potassium and may contribute to hyperkalaemia in people taking ACE inhibitors or other medicines which cause potassium retention.3 Consider assessing kidney function in people using medicines that may impair or adversely affect kidney function16 and watch for signs of toxicity.15