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Meta-Analysis
. 2012 Sep 12;2012(9):CD009402.
doi: 10.1002/14651858.CD009402.pub2.

Magnesium for skeletal muscle cramps

Scott R Garrison  1 , G Michael Allan, Ravneet K Sekhon, Vijaya M Musini, Karim M Khan
Affiliations
Meta-Analysis

Magnesium for skeletal muscle cramps

Scott R Garrison et al. Cochrane Database Syst Rev. .

Update in

  • Magnesium for skeletal muscle cramps.
    Garrison SR, Korownyk CS, Kolber MR, Allan GM, Musini VM, Sekhon RK, Dugré N. Garrison SR, et al. Cochrane Database Syst Rev. 2020 Sep 21;9(9):CD009402. doi: 10.1002/14651858.CD009402.pub3. Cochrane Database Syst Rev. 2020. PMID: 32956536 Free PMC article.

Abstract

Background: Skeletal muscle cramps are common and often presented to physicians in association with pregnancy, advanced age, exercise or disorders of the motor neuron (such as amyotrophic lateral sclerosis). Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this indication has never been evaluated by systematic review.

Objectives: To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps.

Search methods: We searched the Cochrane Neuromuscular Disease Group Specialized Register (11 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 3), MEDLINE (January 1966 to September 2011), EMBASE (January 1980 to September 2011), LILACS (January 1982 to September 2011), CINAHL Plus (January 1937 to September 2011), AMED (January 1985 to October 2011) and SPORTDiscus (January 1975 to September 2011).

Selection criteria: Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy.

Data collection and analysis: Two authors independently selected trials for inclusion and extracted data. Two authors assessed risk of bias. We attempted to contact all study authors and obtained patient level data for three of the included trials, one of which was unpublished. All data on adverse effects were collected from the included RCTs.

Main results: We identified seven trials (five parallel, two cross-over) enrolling a total of 406 individuals amongst whom 118 cross-over participants additionally served as their own controls. Three trials enrolled women with pregnancy-associated leg cramps (N = 202) and four trials enrolled idiopathic cramp sufferers (N = 322 including cross-over controls). Magnesium was compared to placebo in six trials and to no treatment in one trial.For idiopathic cramps (largely older adults presumed to have nocturnal leg cramps), differences in measures of cramp frequency, magnesium versus placebo, were small, not statistically significant, and without heterogeneity (I(2) = 0%). This includes the primary endpoint, percentage change from baseline in the number of cramps per week at four weeks (-3.93%, 95% confidence interval (CI) -21.12% to 13.26%, moderate quality evidence) and the difference in the number of cramps per week at four weeks (0.01 cramps/week, 95% CI -0.52 to 0.55, moderate quality evidence). The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also no different, being 8% lower in the magnesium group (95% CI -28% to 12%, moderate quality evidence). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity (moderate quality evidence) or cramp duration (low quality evidence).Meta-analysis was not possible for trials of pregnancy-associated leg cramps. The single study comparing magnesium to no treatment failed to find statistically significant benefit on a three-point ordinal scale of overall treatment efficacy. The two trials comparing magnesium to placebo differed in that one trial found no benefit on frequency or intensity measures while the other found benefit for both.Withdrawals due to adverse events were not significantly different than placebo. While we could not determine the number of subjects with minor adverse events, studies of oral magnesium generally described potential side effects as similar in frequency to placebo.

Authors' conclusions: It is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults experiencing skeletal muscle cramps. In contrast, for those experiencing pregnancy-associated rest cramps the literature is conflicting and further research in this patient population is needed. We found no randomized controlled trials evaluating magnesium for exercise-associated muscle cramps or disease state-associated muscle cramps (for example amyotrophic lateral sclerosis/motor neuron disease).

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Conflict of interest statement

Drs Garrison and Khan are co‐authors of a RCT which was included in this review. None of the co‐authors of this review have links, financial or otherwise, to any company or special interest group that is involved in the marketing of magnesium or other cramp related therapies.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Idiopathic rest cramps, magnesium versus placebo, outcome: 1.1 % Change in cramp frequency from baseline at 4 weeks.
4
4
Forest plot of comparison: 1 Idiopathic rest cramp efficacy, magnesium versus placebo, outcome: 1.3 Proportion of subjects with a ≥ 25% reduction in cramp frequency at 4 weeks.
5
5
Forest plot of comparison: 1 Idiopathic rest cramps, magnesium versus placebo, outcome: 1.6 Number of cramps per week at 4 weeks.
6
6
Forest plot of comparison: 1 Idiopathic rest cramp efficacy, magnesium versus placebo, outcome: 1.7 Cramp intensity (pain) on a 3 point scale (1 = mild, 2 = moderate, 3 = severe) at 4 weeks.
1.1
1.1. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 1 % Change in cramp frequency from baseline at 4 weeks.
1.2
1.2. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 2 % Change in cramp frequency from baseline at 12 weeks.
1.3
1.3. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 3 Proportion of subjects with a ≥ 25% reduction in cramp frequency at 4 weeks.
1.4
1.4. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 4 Proportion of subjects with a ≥ 25% reduction in cramps at 12 weeks.
1.5
1.5. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 5 Number of cramps per week at 4 weeks.
1.6
1.6. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 6 Number of cramps per week at 12 weeks.
1.7
1.7. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 7 Cramp intensity (pain) on a 3 point scale (1 = mild, 2 = moderate, 3 = severe) at 4 weeks.
1.8
1.8. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 8 Cramp intensity (pain) on a 3 point scale (1 = mild, 2 = moderate, 3 = severe) at 12 weeks.
1.9
1.9. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 9 Proportion of subjects rating their cramps as moderate or severe (i.e. ≥ 2 on the 3 point intensity scale) at 4 weeks.
1.10
1.10. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 10 Proportion of subjects rating their cramps as moderate to severe (i.e. with mean cramp intensity ≥2 on the 3 point intensity scale) at 12 weeks.
1.11
1.11. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 11 Proportion of subjects with the majority of cramp durations ≥ 1 minute at 4 weeks.
1.12
1.12. Analysis
Comparison 1 Idiopathic rest cramp efficacy, magnesium versus placebo, Outcome 12 Proportion of subjects with majority of cramp durations ≥ 1 minute at 12 weeks.
2.1
2.1. Analysis
Comparison 2 Adverse effects of treatment, magnesium versus placebo, Outcome 1 Withdrawals due to adverse events.
2.2
2.2. Analysis
Comparison 2 Adverse effects of treatment, magnesium versus placebo, Outcome 2 Number of subjects with major adverse events.
2.3
2.3. Analysis
Comparison 2 Adverse effects of treatment, magnesium versus placebo, Outcome 3 Number of subjects with minor adverse events.
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References

References to studies included in this review

Dahle 1995 {published data only (unpublished sought but not used)}
    1. Dahle LO, Berg G, Hammar M, Hurtig M, Larsson L. The effect of oral magnesium substitution on pregnancy‐induced leg cramps. American Journal of Obstetrics and Gynecology 1995;173(1):175‐80. [PUBMED: 7631676] - PubMed
Frusso 1999 {published data only (unpublished sought but not used)}
    1. Frusso R, Zárate M, Augustovski F, Rubinstein A. Magnesium for the treatment of nocturnal leg cramps: a crossover randomized trial. Journal of Family Practice 1999;48(11):868‐71. [PUBMED: 10907623] - PubMed
Garrison 2011 {published and unpublished data}
    1. Garrison SR, Birmingham CL, Koehler BE, McCollom RA, Khan KM. The effect of magnesium infusion on rest cramps: randomized controlled trial. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 2011;66(6):661‐6. [PUBMED: 21289017] - PubMed
Nygaard 2008 {published data only (unpublished sought but not used)}
    1. Nygaard IH, Valbø A, Pethick SV, Bøhmer T. Does oral magnesium substitution relieve pregnancy‐induced leg cramps?. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2008;141(1):23‐6. [PUBMED: 18768245] - PubMed
Roffe 2002 {published and unpublished data}
    1. Roffe C, Sills S, Crome P, Jones P. Randomised, cross‐over, placebo controlled trial of magnesium citrate in the treatment of chronic persistent leg cramps. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 2002;8(5):CR326‐30. [PUBMED: 12011773] - PubMed
Rosenbaum 2011 {unpublished data only}
    1. Rosenbaum L. Beneficial effects of magnesium supplementation on idiopathic muscle cramps. ClinicalTrials.gov Identifier: NCT00963638.
Sohrabvand 2006 {published data only (unpublished sought but not used)}
    1. Sohrabvand F, Shariat M, Haghollahi F. Vitamin B supplementation for leg cramps during pregnancy. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics 2006;95(1):48‐9. [PUBMED: 16919630] - PubMed

References to studies excluded from this review

Aagaard 2005 {published data only}
    1. Aagaard NK, Andersen H, Vilstrup H, Clausen T, Jakobsen J, Dorup I. Magnesium supplementation and muscle function in patients with alcoholic liver disease: a randomized, placebo‐controlled trial. Scandinavian Journal of Gastroenterology 2005;40(8):972‐9. [PUBMED: 16173138] - PubMed
Bachem 1986 {published data only}
    1. Bachem MG, Scheffler K, Jastram U, Pfeiffer EF. Effectiveness of oral magnesium substitution in type I diabetic patients with nocturnal leg cramps [Effektivität einer peroralen Magnesiumsubstitution bei Typ‐I‐Diabetikern mit nächtlichen Wadenkrämpfen]. Magnesium‐Bulletin 1986;8(3):280‐3.
Bartl 1982 {published data only}
    1. Bartl W, Riss P. Pathophysiology and therapy of magnesium deficiency in pregnancy [Zur Pathophysiologie und Therapie des Magnesiummangels in der Schwangerschaft]. Zeitschrift für Geburtshilfe und Perinatologie 1982;186(6):335‐7. - PubMed
Hammar 1987 {published data only}
    1. Hammar M, Berg G, Solheim F, Larsson L. Calcium and magnesium status in pregnant women. A comparison between treatment with calcium and vitamin C in pregnant women with leg cramps. International Journal for Vitamin and Nutritional Research 1987;57(2):179‐83. [PUBMED: 3308737] - PubMed
Häringer 1981 {published data only}
    1. Häringer E. Calf cramps at night: A deficiency of magnesium? [Wadenkrämpfe in der Nacht: Fehlt Magnesium?]. Ärtzliche Praxis 1981;33:2653‐4.
Riss 1983 {published data only}
    1. Riss P, Bartl W, Jelincic D. Clinical aspects and treatment of calf muscle cramps during pregnancy [Zur Klinik und Therapie von Wadenkrämpfen in der Schwangerschaft]. Geburtshilfe und Frauenheilkunde 1983;43(5):329‐31. [PUBMED: 6553557] - PubMed
Weller 1998 {published data only}
    1. Weller E, Bachert P, Meinck HM, Friedmann B, Bärtsch P, Mairbäurl H. Lack of effect of oral Mg‐supplementation on Mg in serum, blood cells, and calf muscle. Medicine and Science in Sports and Exercise 1998; Vol. 30, issue 11:1584‐91. - PubMed

Additional references

ADRAC 2002
    1. Adverse Drug Reactions Advisory Committee. Quinine and profound thrombocytopenia. Australian Adverse Drug Reactions Bulletin 2002;21(3):10.
AHFS 2010
    1. Magnesium sulfate. In: McEvoy GK editor(s). American Hospital Formulary Service (AHFS) Drug Information. 2010. Bethesda, MD: American Society of Health‐System Pharmacists, 2010:2282‐5.
al‐Ghamdi 1994
    1. al‐Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview. American Journal of Kidney Diseases 1994;24(5):737‐52. - PubMed
Bilbey 1996
    1. Bilbey DL, Prabhakaran VM. Muscle cramps and magnesium deficiency: case reports. Canadian Family Physician 1996;42:1348‐51. - PMC - PubMed
Cohen 1990
    1. Cohen L, Laor A. Correlation between bone magnesium concentration and magnesium retention in the intravenous magnesium load test. Magnesium Research 1990;3(4):271‐4. - PubMed
Eclampsia Trialists 1995
    1. The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995;345(8963):1455‐63. - PubMed
El‐Tawil 2011
    1. El‐Tawil S, Al Musa T, Valli H, Lunn MPT, El‐Tawil T, Weber M. Quinine for muscle cramps. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD005044.pub2] - DOI - PubMed
FDA 2006
    1. Drug products containing quinine; enforcement action dates. Federal Register 2006; Vol. 71, issue 241:75557–60.
Garrison 2012
    1. Garrison SR, Dormuth CR, Morrow RL, Carney GA, Khan KM. Nocturnal leg cramps and prescription use that precedes them: a sequence symmetry analysis. Archives of Internal Medicine 2012;172(2):120‐6. - PubMed
Graham 1960
    1. Graham LA, Caesar JJ, Burgen AS. Gastrointestinal absorption and excretion of Mg 28 in man. Metabolism 1960;9:646‐59. - PubMed
Hall 1973
    1. Hall RC, Joffe JR. Hypomagnesemia. Physical and psychiatric symptoms. JAMA 1973;224(13):1749‐51. - PubMed
Higgins 2008
    1. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Katzberg 2010
    1. Katzberg HD, Khan AH, So YT. Assessment: symptomatic treatment for muscle cramps (an evidence‐based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2010;74(8):691‐6. - PubMed
Lim 1972
    1. Lim P, Jacob E. Magnesium status of alcoholic patients. Metabolism 1972;21(11):1045‐51. - PubMed
McGee 1990
    1. McGee SR. Muscle cramps. Archives of Internal Medicine 1990;150(3):511‐8. - PubMed
Medsafe 2007
    1. Medsafe Pharmacovigilance Team, New Zealand Medicines and Medical Devices Safety Authority. Quinine ‐ not for leg cramps anymore. Prescriber Update 2007;28(1):2‐6.
Miller 2005
    1. Miller TM, Layzer RB. Muscle cramps. Muscle and Nerve 2005;32(4):431‐42. - PubMed
Naylor 1994
    1. Naylor JR, Young JB. A general population survey of rest cramps. Age and Ageing 1994;23(5):418‐20. - PubMed
Quamme 1993
    1. Quamme GA. Laboratory evaluation of magnesium status. Renal function and free intracellular magnesium concentration. Clinics in Laboratory Medicine 1993;13(1):209‐23. - PubMed
Quamme 2008
    1. Quamme GA. Recent developments in intestinal magnesium absorption. Current Opinion in Gastroenterology 2008;24(2):230‐5. - PubMed
Ryzen 1985
    1. Ryzen E, Elbaum N, Singer FR, Rude RK. Parenteral magnesium tolerance testing in the evaluation of magnesium deficiency. Magnesium 1985;4(2‐3):137‐47. - PubMed
Schwellnus 2008
    1. Schwellnus MP, Drew N, Collins M. Muscle cramping in athletes‐‐risk factors, clinical assessment, and management. Clinics in Sports Medicine 2008;27(1):183‐94, ix‐x. - PubMed
Shils 1969
    1. Shils ME. Experimental human magnesium depletion. Medicine (Baltimore) 1969;48(1):61‐85. - PubMed
Somjen 1966
    1. Somjen G, Hilmy M, Stephen CR. Failure to anesthetize human subjects by intravenous administration of magnesium sulfate. Journal of Pharmacology and Experimental Therapeutics 1966;154(3):652‐9. - PubMed
Vickers 2001
    1. Vickers AJ. The use of percentage change from baseline as an outcome in a controlled trial is statistically inefficient: a simulation study. BMC Medical Research Methodology 2001;1:6. [DOI: 10.1186/1471-2288-1-6] - DOI - PMC - PubMed
Young 2002
    1. Young G, Jewell D. Interventions for leg cramps in pregnancy. Cochrane Database of Systematic Reviews 2002, Issue 1. [DOI: 10.1002/14651858.CD000121] - DOI - PubMed

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