Calcium and magnesium status in pregnant women. A comparison between treatment with calcium and vitamin C in pregnant women with leg cramps. Does oral magnesium substitution relieve pregnancy-induced leg cramps? Randomised, cross-over, placebo controlled trial of magnesium citrate in the treatment of chronic persistent leg cramps. The effect of oral magnesium substitution on pregnancy-induced leg cramps.
60 pregnant women underwent a double blind trial with calcium or ascorbic acid (1 g twice daily) as treatment for leg cramps. There was no significant difference between the two treatment groups with respect to clinical improvement. In 14 out of 60 patients the symptoms were totally abolished and in another 27 patients the symptoms were significantly decreased by the treatment (irrespective of drug used). In 17 patients the symptoms were unaffected while only two patients experienced an increase in frequency of their leg cramps during therapy. Serum total and ionized calcium concentrations, serum total magnesium and albumin concentrations were determined and were not significantly changed throughout therapy in any of the groups. No biochemical differences were found between the different treatment regimens or between those patients relieved or not relieved of their symptoms. Serum magnesium concentrations were at or just below the lower normal limit (for non pregnant women) in treated women and pregnant controls. Our aim was to assess the effect of 360mg magnesium oral substitution daily among pregnant women suffering from leg cramps in pregnancy, defined as painful cramps different from restless legs symptoms.
                In a double blind randomised controlled trial healthy pregnant women between 18 and 36 weeks of pregnancy suffering from painful leg cramps, at least twice a week, were invited to participate. Forty-five women were enrolled initially, 38 completed the treatment and were treated during 2 weeks with either magnesium (360mg=15mmol magnesium lactate and magnesium citrate, Nycoplus Magnesium), or placebo tablets. Serum magnesium and calcium were investigated together with urine magnesium and magnesium-creatinin ratio on day 1 and day 15. Frequency and intensity of leg cramps were recorded. The study was powered to detect a 50% reduction in leg cramps.
                Registration of pain frequency and intensity during the two study weeks demonstrated no significant differences between the two groups. Mean number and intensity of cramps were 9.5 (S.D. 5.1) and 13.2 (S.D. 6.5) in the magnesium group, compared to 7.7 (S.D. 4.7) and 11.4 (S.D. 8.5) in the placebo group. Baseline magnesium levels were 0.77 and 0.74mmol/L in the magnesium group and the placebo group, respectively No significant differences between the two groups, or within the groups, were found when comparing serum values of serum magnesium and total calcium at inclusion time and at the end of the treatment. There was a statistically significant increase in magnesium excretion in the magnesium treatment group (p<0.01). The number of dropouts was two in the treatment group and five in the control group.
                No significant effect on frequency or intensity of leg cramps in pregnant women of magnesium treatment with 360mg daily could be detected in this trial. Nocturnal leg cramps are common and distressing. The only treatment of proven effectiveness is quinine, but this has a number of side effects. Magnesium salts have been shown to reduce leg cramp distress in pregnancy. This study tests whether magnesium citrate is effective in the treatment of leg cramps in non-pregnant individuals by conducting in a randomised, double-blind, cross-over placebo-controlled trial.
                Volunteers suffering regular leg cramps were recruited. Magnesium citrate equivalent to 300 mg magnesium and matching placebo were given for 6 weeks each. The number of cramps recorded in the cramp diary during the final 4 weeks of magnesium and placebo treatment, severity and duration of cramps and the participants' subjective assessment of effectiveness were analysed.
                In subjects who started with placebo (n=29) the median (95% CI) number of cramps was 9 (6-17) on placebo and 5 (4-8) on magnesium. For the group starting with magnesium (n=17) the median no of cramps was 9 (5-13) on magnesium and 8 (4-14) on placebo. There was no significant carry-over effect (p=0.88), but a highly significant period effect (p=0.008). There was a trend towards less cramps on magnesium (p=0.07). There was no difference in cramp severity and duration between the groups. Significantly more subjects thought that the treatment had helped after magnesium than after placebo 36 (78%) and 25 (54%) respectively, (p=0.03). Diarrhoea was recorded as a side effect of magnesium.
                The results suggest that magnesium may be effective in treatment of nocturnal leg cramps. Further evaluation is recommended. Our purpose was to determine whether women with pregnancy-related leg cramps would benefit from oral magnesium supplementation.
                Seventy-three women with pregnancy-related leg cramps were interviewed about their symptoms in a prospective, double-blind, randomized trial. Initial serum magnesium levels and diurnal magnesium excretion was determined in 50% of the patients. Oral magnesium or placebo was given for 3 weeks, after which new interviews and laboratory analyses were performed.
                Serum magnesium levels in these patients were at or below the lower reference limit, as is also often the case in healthy pregnant patients. Oral magnesium substitution decreased leg cramp distress (p < 0.05 compared with the placebo group, p < 0.001 compared with initial complaints), but did not significantly increase serum magnesium levels, excess magnesium being excreted as measured by an increase in urinary magnesium levels (p < 0.002).
                Oral magnesium supplementation seems to be a valuable therapeutic tool in the treatment of pregnancy-related leg cramps.
The evidence that calcium reduces cramp is weak and seems to depend on placebo effect. The evidence for sodium chloride is stronger but the results of the sodium chloride trial may no longer be relevant because of dietary changes which include an increased sodium intake in the general population. It is not possible to recommend multivitamins with mineral supplementation, as it is not clear which ingredient, if any, is helping. If a woman finds cramp troublesome in pregnancy, the best evidence is for magnesium lactate or citrate taken as 5mmol in the morning and 10mmol in the evening.
[Note: The five citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]