MAGNESIUM

MAGNESIUM

Magnesium (Mg) is the second most abundant divalent intracellular cation in the body.[1]  It is involved in energy metabolism as well as protein and nucleic acid synthesis and is a cofactor in more than 300 enzymatic reactions.  The human body stores about 24-5g (1 mol) of Mg, stuff approximately 50-60% in bone and the rest in soft tissues, order and extracellular Mg is about 0.3-1% of the total body Mg.2  One-third of skeletal Mg is exchangeable and is believed to serve as a reservoir for maintaining normal extra-cellular Mg concentrations.[2], website [3]

MECHANISMS Regulating Serum Mg in the Body 

Magnesium uptake studies[4] demonstrate regulation of Mg absorption by a variety of factors.  The body maintains constant serum levels by depending on the availability of Mg in bone, in times of temporary Mg deficit.[5]  The organs responsible for Mg homeostasis are:  bone; the main Mg storage system of the body; the kidneys, responsible for Mg excretion; and the intestine, facilitating Mg uptake.[6]  About 50% of dietary Mg is absorbed (fractional absorption inversely proportional to the amount in diet).[7]  Mg is absorbed passively via para cellular transport in the intestine (80-90%), while the remaining Mg is absorbed via active Mg transporters.6  These transporters account for the fine-tuning of Mg regulation.6  Main excretion is via the kidneys and 90-95% of daily filtrated Mg is reabsorbed in the kidney6 (80% of serum Mg is filtered at the glomerulus[8]) and only 3% is finally excreted in the urine.8  The final Mg concentration is determined by the interplay between passive mechanisms and adjustment via active transporters

MAGNESIUM Balance

An altered Mg balance can be induced by three physiopathologic mechanisms: increased urinary losses; reduced intestinal absorption; and intracellular shift of the divalent cation.  The main treatment for Mg deficiency is by intravenous (IV) or oral Mg repletion.  Well-tolerated dosage of IV Mg ranges from 25 to 75 mg/kg over twenty minutes[9],[10] with minimal side effects and good safety profile.[11]  Renal Mg saving can be induced by potassium-sparing diuretics.[12]  Normal serum Mg is between 1.7-2.3 mg/dl or (0.75-0.95 mmol/l) irrespective of age. An altered Mg balance can be detected in various conditions and diseases, e.g. diabetes mellitus, cardiovascular disease, osteoporosis, chronic renal failure, nephrolithiasis and aplastic osteopathy.  Studies on Mg supplementation show conflicting outcomes.

 MAGNESIUM and Asthma

Magnesium sulfate (MgSO4) might be a therapeutic option in severe asthma exacerbations in children and adults.[13],[14] Acute asthma attacks consist of: increasing episodes of wheezing, coughing, tightness of the chest, or shortness of breath, with a decrease in airflow.[15]  Magnesium is a smooth-muscle relaxant (dose-dependent) and promotes bronchodilation by competing for the calcium (Ca) channel (inhibits Ca influx into the cytosol).  Mg can inhibit acetylcholine release from cholinergic nerve endings and inhibit histamine release from mast cells.  Mg does increase receptor affinity of the b2-agonist, which may also increase the bronchodilatory effect.[16]

THERAPEUTIC Treatments with Magnesium – Intravenous Magnesium Sulfate (MgSO4)

First clinical use of Mg for asthma was reported in 1936[17] and other reports show positive outcomes, both for prevention[18],[19] and treatment19,[20],[21],[22].  Current guidelines suggest the use of IV MgSO4 to improve pulmonary function and to reduce hospital admissions, as an adjunct therapy to standard treatments.[23],[24],[25]  Therapeutic benefits of MgSO4 have not been proven undoubtedly[26], but improved lung function and decreased hospital admissions have been suggested in several studies[27],[28],[29],[30] in children presenting severe exacerbations.  In a meta-analysis27 on IV MgSO4 as an adjunct treatment, additional benefits in moderate to severe acute asthma were observed in children treated with steroids and bronchodilators.  According to Cheuk et al four out of five (high quality studies) showed positive outcomes in the meta-analysis with results judged to be valid.

According to Albuali[31] low magnesium status is a common electrolyte disorder in children with acute severe asthma and IV MgSO4 therapy is a safe and effective adjunct to standard treatments.  According to Lalloo et al IV MgSO4 is a second or third-line treatment strategy for poorly responding patients.  In a systematic review by Song et al, there are clear beneficial effects of IV MgSO4 in treatment of adult subjects suffering from severe/life-threatening exacerbations.  In the same review, less evidence is found on the role of nebulized MgSO.  In a systematic review[32] on the effects of treatments for acute asthma in adults, the effect of MgSO4 was not specific.  In another systematic review on treatments for chronic and acute asthma in adults, the effects of MgSO4 was unclear[33]

THERAPUTIC Effect of Oral Magnesium

CHILDREN with Asthma

In a double-blind randomized parallel placebo-controlled study[34], the long-term effect of oral magnesium was examined.  The evaluation was on clinical symptoms, allergen-induced skin responses, bronchial reactivity and lung function, in children and adolescents with moderate persistent asthma.  Subjects were randomized into two groups and received magnesium-glycine (MG) orally, 300 mg/d during two months and placebo-control (glycine only) alongside allopathic treatment.  The study revealed better clinical results/decrease in both bronchial reactivity and skin reaction to recognized allergens in subjects receiving oral magnesium supplementation in combination with inhaled fluticasone.

ADULTS with Asthma

According to Hill et al[35] short-term changes in dietary magnesium improved clinical symptoms, but not the lung function tests.  According to Fogary et al[36] oral magnesium had no effect on asthma.  Quoted from Kazaks et al[37] “improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life” was observed in a randomized placebo controlled trial.

THERAPUTIC Effect of Inhaled (Nebulized) MaSO4

Evaluation of inhaled magnesium has been investigated[38],[39] and in addition to a b-agonist can decrease hospital admission rates and improve pulmonary function in subjects with severe asthma.[40]  Other studies revealed no benefit in improving lung function when compared to an inhaled b-agonists alone.[41],[42]  Regarding paediatric use, further studies are still needed.

 CONCLUSION

Magnesium is an important mineral in the human body.  Regulation of Mg absorption is controlled by a variety of factors.  The body maintains constant serum levels by depending on the availability of Mg in bone only in times of temporary Mg deficit.  Altered Mg balance can be detected in various conditions and diseases.  Evidence reveals conflicting outcomes on using magnesium supplementation in cases of asthma.  There is some evidence on effective treatments, especially when IV MgSO4 is used as an adjunct to conventional therapy.  There is inconsistent evidence on oral supplementation and nebulized MgSO4.                                                          

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REFERENCES

1 Elin RJ. Magnesium: the fifth but forgotten electrolyte. Am J Clin Pathol 1994;102(5):616-22.

2 Elin RJ. Assessment of magnesium status. Clin Chem 1987;33:1965-1970.

3 Cashman KD, Flynn A. Optimal nutrition: calcium, magnesium and phosphorus. P Nutr Soc 1999;58:477-487.

4 Kesteloot H, Joossens JV. The relationship between dietary intake and urinary excretion of sodium, potassium, calcium and magnesium: Belgian Interuniversity Research on Nutrition and Health. J Hum Hypertens 1990;4:527-533

5 Alfrey AC, Miller NL, Trow R. Effect of age and magnesium depletion on bone magnesium pools in rats. J Clin Invest 1974;54:1074-1081

6 Baaij J, Hoenderop J, Bindels R. Regulation of magnesium balance: lessons learned from human genetic disease. Clin Kidney J 2012;5(1):i15-i24.

7 National Instiute of Health. Magnesium. [Internet] Reviewed November 2013.

8 Musso CG. Magnesium metabolism in health and disease. Int Urol Nephrol 2009,41(2):357-62.

9 Rowe BH, Bretzlaff JA, Bourdon C, et al. Intravenous magnesium sulfate treatment for acute asthma in the emergency department: a systematic review of the literature. Ann Emerg Med 2000;36(3).181-190.

10 Markovitz B. Does magnesium sulphate have a role in the management of paediatric status asthmaticus? Arch Dis Child 2002;86(5):381-382.

11 Glover ML, Machado C, Totapally BR. Magnesium sulfate administered via continuous intravenous infusion in pediatric patients with refractory wheezing. J Crit Care 2002;17(4):255-258.

12 Mohammed S, Goodacre S. Intravenous and nebulised magnesium sulphate for acute asthma systematic reviews and meta-analysis. Emerg Med J 2007:24(12):823-830.

13 Jones BP, Paul A. Management of acute asthma in the pediatric patient: an evidence-based review. Pediatr Emerg Med Pract 2013,10(5):23-24.

14 Song WJ, Chang YS. Magnesium sulfate for acute asthma in adults: a systematic literature review. Asia Pac Allergy 2012;2(1):76-85. [Accessed 7 March 2014]. Available from: doi: 10.5415/apallergy.2012.1.76

15 Lalloo UG, Ainslie GM, Abdool-Gaffar MS, Awotedu AA, Feldman C, Greenblatt M, et al. Guideline for the management of acute asthma in adults: 2013 update. S Afr Med J 2012;103(3 Pt 2):189-98.

16 Classen HG, Jacob R, Schimatschek H. Interaction of magnesium with direct and indirect-acting sympathomimetic amines. Magnes Bull 1987;9:80-87.

17 Kowal A, Panaszek B, Barg W, Obojski A. The use of magnesium in bronchial asthma: a new approach to an old problem. Arch Immunol Ther Exp 2007;55:35-39.

18 McNamara RM, Spivey WH, Skobeloff E, Jacubowitz S. Intravenous magnesium sulfate in the management of acute respiratory failure complicating asthma. Ann Emerg Med 1989;18-197-199.

19 Shan Z, Rong Y, Yang W, Wang D, Yao P, Xie J, et al. Intravenous and nebulized magnesium sulfate for treating acute asthma in adults and children: a systematic review and meta analysis. Respir Med 2013;107:321-30.

20 Okayama H, Aikawa T, Okayama M, Sasaki H, Mue S, Takishima T. Bronchodilating effect of intravenous magnesium sulfate in bronchial asthma. JAMA 1987;257:1076-1078.

21 Shedd GC, Noe SM. Intravenous magnesium sulfate reduces rates of mechanical ventilation in pediatric asthma. Adv Emerg Nurs J 2014;36(1):3-8.

22 Torres S, Sticco N, Bosch JJ, Iolster T, Saiaba A, Rocca Rivarola M, et al. Effectiveness of magnesium sulfate as initial treatment of acute severe asthma in children, conducted in a tertiary-level university hospital: a randomized, controlled trial. Arch Argent Pediatr 2012;110(4):291-6.

23 Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA). Updated 2010.

24 Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma: summary report 2007. National Asthma Education and Prevention Program (National Heart Lung and Blood Institute). Bethesda, MD: U.S. Dept of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; Updated 2008.

25 British Guideline on the Management of Asthma 2008. British Thoracic Society, Scottish Intercollegiate Guidelines Network. Revised 2011.

26 Scarfone RJ, Loiselle JM, Joffe MD, Mull CC, Stiller S, Thompson K, et al. A randomized trial of magnesium in the emergency department treatment of children with asthma. An Emerg Med 2000;36(6):572-578.

27 Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Arch Dis Child 2005;90(1):74-77.

28 Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with moderate to severe acute asthma. Arch Pediatr Adolesc Med 2000;154(10):979-983.

29 Markovitz B. Does magnesium sulphate have a role in the management of paediatric status asthmaticus? Arch Dis Child 2002;86(5):381-382.

30 Rowe BH, Camargo CA Jr. The role of magnesium sulfate in the acute and chronic management of asthma. Curr Opin Pulm Med 2008,14(1):70-76

31 Albuali WH. The use of intravenous and inhaled magnesium sulphate in management of children with bronchial asthma. J Matern Fetal Neonatal Med 2014.

32 Rodrigo G. Asthma in adults (acute). Clin Evid 2011;1513:1-76.

33 Dennis RJ, Solarte I, Rodrigo G. Asthma in adults. Clin Evid 2010;011501:1-47.

34 Gontijo-Amara C, Ribeiro MA, Gontijo LS, Condino-Neto A, Ribeiro JD. Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-controlled trial. Eur J Clin Nutr 2007;61:54-60.

35 Hill J, Micklewright A, Lewis S, Britton J. Investigation of the effect of short-term change in dietary magnesium intake in asthma. Eur Respir J 1997;10:2225-2229.

36 Fogarty A, Lewis SA, Scrivener SL, Antoniak M, Pacey S, Prigle M, et al. Oral magnesium and vitamin  C supplements in asthma: a parallel group randomized placebo-controlled trial. Clin Exp Allergy 2003;33:1355-1359.

37 Kazaks AG, Uiu-Adams JY, Albertson TE, Shenoy SF, Stern JS. Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial. J Asthma 2010;47(1):83-92.

38 Coates AL, Leung K, Vecellio L, et al. Testing of nebulizers for delivering magnesium sulfate to pediatric asthma patients in the emergency department. Resp Care 2011;56(3):314-318.

39 Gallegos-Solorzano MC, Perez-Padilla R, Hernandez-Zenteno RJ. Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department. Pulm Pharmacol Ther 2010;23(5):432-437.

40 Blitz M, Blitz S, Beasley R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev 2009(3).

41 Hill J, Britton J. Dose-response relationship and time-course of the effect of inhaled magnesium sulphate on airflow in normal and asthmatic subjects. Br J Clin Pharmacol 2012;40(6):539-544.

42 Villeneuve EJ, Zed PJ. Nebulized magnesium sulfate in the management of acute exacerbations of asthma. Ann Pharmacother 2006;40(6):1118-1124.

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