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Magnesium Treatment for Asthma : Where Do We Stand? FREE TO VIEW

Marc Noppen, MD, PhD, FCCP
Author and Funding Information

Affiliations: Brussels, Belgium
 ,  Dr. Noppen is Associate Professor and Head of the Interventional Endoscopy Clinic, Respiratory Division, University Hospital AZ-VUB, and Faculty of Medicine, Free University of Brussels (VUB).

Correspondence to: Marc Noppen, MD, PhD, FCCP, Respiratory Division, Academic Hospital AZ-VUB, Laarbeeklaan 101, 1090 Brussels, Belgium; e-mail: marc.noppen@az.vub.ac.be



Chest. 2002;122(2):396-398. doi:10.1378/chest.122.2.396
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Published online

My name is John Doe, and I have asthma. I am concerned about my health, and I’m not sure whether I should take the steroids and other chemicals my physician has ordered me to. A friend suggested I should take magnesium. What shall I do? Well, I’m up-to-date and concerned, hence I consult the World Wide Web. I search for “asthma and magnesium,” and find … > 26,600 Web page matches! When looking for “corticosteroids and asthma,” or even for, eg, “anticholinergics and asthma,” I “only” find 17,400, and “only” 2,370 Web sites relate to anticholinergics and asthma. When browsing through the 26,600 pages, the evidence in favor of magnesium seems overwhelming. My friend was right: I should take magnesium!

You are a pulmonologist, and confronted with a concerned and allegedly well-informed John Doe, proudly facing you with > 25 kg of printouts. What do you say? Well, here’s “magnesium and asthma in a nutshell”!

Magnesium is primarily (99%) an intracellular cation. In contrast to calcium, the maintenance of magnesium homeostasis is highly dependent on dietary intake, and there is no known regulatory system that functions to mobilize magnesium from bone or elsewhere to maintain circulating extracellular levels.1Magnesium is involved in maintaining the ionic cellular balance, eg, by its role in the function of the cell membrane sodium-potassium adenosine triphosphatase pump.2 Magnesium is an obligate ion essential for the activation of > 300 enzymes,3 for virtually all hormonal reactions occurring in the body, and for the activity of adenylate cyclase.1 Finally, magnesium also acts as a calcium channel blocker.4Magnesium thus undoubtedly is a major player in many cellular and hormonal functions. And severe magnesium deficiency is dangerous: in critically ill patients, for instance, hypomagnesemia occurs in up to 65% of patients, and is associated with increased mortality rates.6 Severe magnesium deficiency can lead, among other things, to a variety of dysrhythmias, seizures, muscle weakness, and mental status changes, various endocrine dysfunctions, but also to bronchospasm and respiratory failure.1 Magnesium replacement hence undoubtedly is useful in these critically ill patients.3 But is it useful for John Doe’s asthma? To answer this question, it may be useful to apply Koch’s postulates: (1) Is magnesium a bronchodilator? (2) Is asthma characterized by/associated with magnesium deficiency states? (3) Is magnesium therapy useful in treating asthma?

1. Magnesium has been shown to cause bronchial smooth-muscle relaxation in vitro,7probably by its action as a “physiologic calcium antagonist,”8or by its action on adenyl cyclase activation.9Magnesium has been shown to cause bronchodilation in vivo1012 in children as well as in adults. Yes, magnesium is a bronchodilator.

2. The question of whether asthma is characterized by/associated with magnesium deficiency is less clear, and much more difficult to answer because of the difficulties in measurement and interpretation of intracellular vs extracellular (protein-bound, chelated, and ionized) forms.1,13Although magnesium levels have been shown to appear similar in asthmatics as compared to those in control subjects,14 other data suggest that low magnesium intake (which is a major determinant in magnesium homeostasis1) may be involved in the etiology of asthma and chronic obstructive airway disease. Britton et al,15 for instance, have shown in a random adult population sample study that a 100 mg/d higher magnesium intake was independently associated with a 27.7 mL (95% confidence interval, 11.9 to 43.5 mL) higher FEV1, and a reduction in the relative odds of bronchial hyperreactivity by a ratio of 0.82 (confidence interval, 0.72 to 0.93). Furthermore, β2-receptor agonist use can increase renal magnesium losses and thus lead to magnesium deficiency.,1 Nevertheless, it remains unclear from the available data whether all asthmatics have a lower magnesium content, and the available data do not support the need for systematic magnesium supplementation in these patients.

3. Is magnesium therapy useful in treating acute asthma attacks? In this issue of CHEST (see page 489), Silverman and colleagues and three review articles (two meta-analyses1617 and a Cochrane review18) supply a solid evidence-based answer: 2 g of MgSO4 in adults and 25 to 100 mg/kg in children administered as a 10- to 20-min IV infusion undoubtedly improves pulmonary function when used as an adjunct to standard therapy, albeit only in the most severe cases. And although it is still uncertain whether adding MgSO4 to conventional therapy significantly influences hospitalization rates, need for ICU treatment, or final outcome, all authors agree that MgSO4 is beneficial in patients presenting with acute severe asthma, also because MgSO4 is extremely safe, and inexpensive.

So, I would inform John Doe of the following: (1) Magnesium certainly is an extremely important, essential ion, necessary for the normal function of numerous cellular functions. (2) Magnesium can relax (bronchial) smooth muscle. There is, however, no unequivocal evidence that all asthmatics have a shortage of magnesium (also because this is extremely difficult to measure), and there currently is no proof that using dietary magnesium supplements has a beneficial effect in asthma treatment. (3) It is proven, however, that in (very) severe acute asthma attacks, IV magnesium treatment improves pulmonary function when used in addition to conventional treatment.

Some questions, however, remain unanswered: Are there subgroups of patients, eg, in terms of response to β-agonist therapy, or in terms of inhaled steroid use, in whom magnesium treatment is more or less useful? What is the optimal dosage and duration of treatment ? Are the measured beneficial effects of magnesium therapy only due to its bronchodilator effects, or do anti-inflammatory effects also play a role?19

Finally, Mr. Doe, there is no correlation between the number of Web citations on a therapeutic subject and its real importance. “Homeopathy and asthma” for instance, yields > 35,000 Web pages. Corticosteroids are much less “popular” on the Web, but their increasing use undoubtedly has decreased asthma morbidity and mortality! Strikingly, only approximately one third of patients in the population of Silverman and colleagues with severe asthma (as demonstrated by the previous hospitalizations and past intubation for asthma) received inhaled steroid therapy at the time of hospital admission. It is highly probable that the inadequate outpatient management of these patients may be, at least in part, responsible for their acute severe asthma in the first place! Therefore, Mr. Doe, I would advise you to meticulously take the inhaled corticosteroids that were prescribed to you, instead of your magnesium supplements. This probably will keep you out of the emergency department. But should acute severe asthma nevertheless occur, IV magnesium therapy certainly should be added to conventional treatment.

References

Dacey, JM (2001) Hypomagnesemic disorders.Crit Care Clin17,155-173. [PubMed] [CrossRef]
 
Flatman, P, Lew, V The magnesium dependence of sodium pump mediated sodium-potassium and sodium-sodium exchange in intact human red cells.J Physiol1981;315,421-446. [PubMed]
 
Zaloga, GP, Roberts, PR Calcium, phosphorus and magnesium disorders. Ayres, SM Greuvik, NA Holbrook, PRet al eds.Textbook of critical care 4th ed.2000,905-928 WB Saunders. Philadelphia, PA:
 
White, R, Hartzell, H Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes.Science1988;239,778-780. [PubMed]
 
Ryzen, E, Wagers, PW, Singer, FR, et al Magnesium deficiency in a medical ICU population.Crit Care Med1985;13,19-21. [PubMed]
 
Chernow, B, Bamberger, S, Stroiko, M, et al Hypomagnesemia in patients in the postoperative intensive care unit.Chest1989;95,391-397. [PubMed]
 
Spivey, WH, Skobellof, EM, Levin, RM Effect of magnesium chloride on rabbit bronchial smooth muscle.Ann Emerg Med1990;19,1107-1112. [PubMed]
 
Iseri, LT, French, JH Magnesium: nature’s physiologic calcium blocker.Am Heart J1984;108,188-193. [PubMed]
 
Brandt, DR, Ross, EM Cathecholamine-stimulated GTPase cycle: multiple sites of regulation by β-adrenergic receptor and Mg2+ studied in reconstituted receptor-Gs vesicles.J Biol Chem1986;261,1656-1664. [PubMed]
 
Noppen, M, Vanmaele, L, Impens, N, et al Bronchodilating effect of intravenous magnesium sulfate in acute severe bronchial asthma.Chest1990;97,373-376. [PubMed]
 
Skobeloff, EM, Spivey, WH, McNamara, RM, et al Intravenous magnesium sulfate for the treatment of acute severe asthma in the emergency department.JAMA1989;262,1210-1213. [PubMed]
 
Ciarallo, L, Sauer, A, Shannon, MW Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial.J Pediatr1996;129,809-814. [PubMed]
 
Fiser, R, Torres, A, Butch, A, et al Ionized magnesium concentrations in critically ill children.Crit Care Med1998;26,2048-2052. [PubMed]
 
deValck, HW, Struyvenberg, A, Van Rijn, HJM Extracellular and intracellular magnesium concentrations in asthmatic subjects.Eur Respir J1993;6,1122-1125. [PubMed]
 
Britton, J, Pavord, I, Richards, K, et al Dietary magnesium, lung function, wheezing and airway hyperreactivity in a random adult population sample.Lancet1994;344,357-362. [PubMed]
 
Rowe, BH, Bretzlaff, JA, Bourdon, C, et al Intravenous magnesium sulfate for acute asthma in the emergency department: a systematic review of the literature.Ann Emerg Med2000;36,181-190. [PubMed]
 
Alter, HJ, Koepsell, TD, Hilty, WM Intravenous magnesium as an adjuvant in acute bronchospasm: a meta-analysis.Ann Emerg Med2000;36,191-197. [PubMed]
 
Rowe BH, Bretzlaff JA, Bourdon C, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department (Cochrane Review). Available at: http://www.update-software.com/ccweb/cochrane/revabstr/ab001490.htm. Accessed July 2, 2002.
 
Cairns, CB, Kraft, M Magnesium attenuates the neutrophils respiratory burst in adult asthmatic patients.Acad Emerg Med1996;3,1093-1097. [PubMed]
 

Figures

Tables

References

Dacey, JM (2001) Hypomagnesemic disorders.Crit Care Clin17,155-173. [PubMed] [CrossRef]
 
Flatman, P, Lew, V The magnesium dependence of sodium pump mediated sodium-potassium and sodium-sodium exchange in intact human red cells.J Physiol1981;315,421-446. [PubMed]
 
Zaloga, GP, Roberts, PR Calcium, phosphorus and magnesium disorders. Ayres, SM Greuvik, NA Holbrook, PRet al eds.Textbook of critical care 4th ed.2000,905-928 WB Saunders. Philadelphia, PA:
 
White, R, Hartzell, H Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes.Science1988;239,778-780. [PubMed]
 
Ryzen, E, Wagers, PW, Singer, FR, et al Magnesium deficiency in a medical ICU population.Crit Care Med1985;13,19-21. [PubMed]
 
Chernow, B, Bamberger, S, Stroiko, M, et al Hypomagnesemia in patients in the postoperative intensive care unit.Chest1989;95,391-397. [PubMed]
 
Spivey, WH, Skobellof, EM, Levin, RM Effect of magnesium chloride on rabbit bronchial smooth muscle.Ann Emerg Med1990;19,1107-1112. [PubMed]
 
Iseri, LT, French, JH Magnesium: nature’s physiologic calcium blocker.Am Heart J1984;108,188-193. [PubMed]
 
Brandt, DR, Ross, EM Cathecholamine-stimulated GTPase cycle: multiple sites of regulation by β-adrenergic receptor and Mg2+ studied in reconstituted receptor-Gs vesicles.J Biol Chem1986;261,1656-1664. [PubMed]
 
Noppen, M, Vanmaele, L, Impens, N, et al Bronchodilating effect of intravenous magnesium sulfate in acute severe bronchial asthma.Chest1990;97,373-376. [PubMed]
 
Skobeloff, EM, Spivey, WH, McNamara, RM, et al Intravenous magnesium sulfate for the treatment of acute severe asthma in the emergency department.JAMA1989;262,1210-1213. [PubMed]
 
Ciarallo, L, Sauer, A, Shannon, MW Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial.J Pediatr1996;129,809-814. [PubMed]
 
Fiser, R, Torres, A, Butch, A, et al Ionized magnesium concentrations in critically ill children.Crit Care Med1998;26,2048-2052. [PubMed]
 
deValck, HW, Struyvenberg, A, Van Rijn, HJM Extracellular and intracellular magnesium concentrations in asthmatic subjects.Eur Respir J1993;6,1122-1125. [PubMed]
 
Britton, J, Pavord, I, Richards, K, et al Dietary magnesium, lung function, wheezing and airway hyperreactivity in a random adult population sample.Lancet1994;344,357-362. [PubMed]
 
Rowe, BH, Bretzlaff, JA, Bourdon, C, et al Intravenous magnesium sulfate for acute asthma in the emergency department: a systematic review of the literature.Ann Emerg Med2000;36,181-190. [PubMed]
 
Alter, HJ, Koepsell, TD, Hilty, WM Intravenous magnesium as an adjuvant in acute bronchospasm: a meta-analysis.Ann Emerg Med2000;36,191-197. [PubMed]
 
Rowe BH, Bretzlaff JA, Bourdon C, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department (Cochrane Review). Available at: http://www.update-software.com/ccweb/cochrane/revabstr/ab001490.htm. Accessed July 2, 2002.
 
Cairns, CB, Kraft, M Magnesium attenuates the neutrophils respiratory burst in adult asthmatic patients.Acad Emerg Med1996;3,1093-1097. [PubMed]
 
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