Does Oral Magnesium Ease the Wheeze?

Abstract & Commentary

By James C. Scheer, DO, MS. Dr. Scheer is Associate Medical Director, NorthEast Internal & Integrative Medicine of Carolinas Medical Center-NorthEast in Concord, NC; he reports no financial relationship to this field of study.

Synopsis: In a randomized placebo controlled trial, 55 adults with mild-to-moderate asthma were assigned 340 mg of daily oral magnesium citrate or a placebo for 6.5 months. Patients who received the Mg showed significant improvements in objective measures of bronchial reactivity to methacholine and peak expiratory flow rate and in subjective measures of asthma control and quality of life.

Source: Kazaks AG, et al. 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: 83-92.

Magnesium (mg) is naturally found in whole grains, nuts, seeds and vegetables. Due to food processing and current food preferences, inadequate dietary Mg intake is common. Less than one-half of adults in the United States consumes the RDA of 310-420 mg daily.1

Asthma incidence is increasing and is correlated with poverty, air quality, allergens, and suboptimal nutrition. The cost of asthma is about $18 billion per year, with more than half attributed to hospitalizations.

Epidemiological studies have found a relationship between low dietary Mg intakes and the prevalence and management of asthma. The demonstration of low cellular concentrations of Mg in asthmatics support a physiological role of low Mg status in asthma.2-4 Through intracellular interactions of Mg with calcium and influence of Mg on the cell membrane, it has been established that Mg confers bronchodilitary and anti-inflammatory properties that can improve asthma control.5

The aim of the current study by Kazacks et al was to examine the effects of 6.5 months of oral Mg supplementation on measures of asthma control and Mg status in men and women with mild-to-moderate asthma. Fifty-five adults ages 21-55 years with mild-to-moderate asthma who used only beta-agonists and/or inhaled corticosteroids (ICS) as asthma medications were enrolled. Subjects were randomly assigned to consume 170 mg twice a day of Mg citrate or placebo for 6.5 months. Multiple measures of Mg status were measured, including serum, erythrocyte, urine, dietary, ionized, and IV Mg. Markers of asthma control were methacholine challenge test and pulmonary function test (PFT) results. Subjective validated questionnaires on asthma quality of life and control were completed by participants. Markers of inflammation, including C-reactive protein and exhaled nitric oxide, were determined.

The concentration of methacholine required to cause a 20% drop in forced expiratory volume in 1 minute (FEV1) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate (PEFR) showed a 5.8% predicted improvement over time (P = 0.03) in those consuming the Mg. There was significant improvement in asthma quality-of-life mean score units (P < 0.01) and in overall asthma control score only in the Mg group (P = 0.05) after 6.5 months of supplementation. However, despite these improvements, there were no significant changes in any of the physiologic markers of Mg status. The authors concluded that adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.

Commentary

According to the National Asthma Education and Prevention Program, intravenous Mg is beneficial for the control of acute asthma in children and adults.6 The role of inhaled Mg, however, is still controversial in the acute asthma setting. It has been hypothesized, based on a series of seven cases, that Mg throat lozenges may have a role in the rescue treatment of acute asthma;7 however further controlled studies are needed.

In children with chronic asthma, a study was conducted investigating the effects of 300 mg of oral Mg supplementation on clinical symptoms, bronchial reactivity, lung functions, and allergen-induced skin responses in 37 children ages 7-19 years with moderate persistent asthma.8 After 2 months of therapy, the Mg group had reduced airway reactivity and skin responses to known allergens, as well as fewer asthma exacerbations and reduced need for rescue medications compared to the control group. It is notable that both groups were taking fluticasone, an inhaled corticosteroid.

The results of the current study are consistent with this pediatric study and are the first to demonstrate a benefit of oral Mg supplementation for asthma control in adults.

Previous studies of Mg supplementation in chronic asthmatic adult patients have shown little or no improvement in pulmonary function or measures of inflammation. A 3-week intervention trial of 300 mg of oral Mg demonstrated improvement in subjective symptoms and frequency of bronchodilator use that were of borderline clinical significance.9 Neither that study nor a 16-week Mg supplementation study by Fogarty et al using 450 mg per day of Mg chelate showed improvement in lung function or bronchial reactivity.10 It is possible that the duration of these prior studies was not sufficient to see changes in Mg stores that affect asthma control.

It has been shown previously that while hypomagnesemia is associated with severe asthma, individuals with mild or moderate asthma have normal Mg concentrations.3 In the current study, participants were not Mg-deficient at enrollment as shown by % IV retention and other Mg status measures. (It is generally accepted that % IV Mg retention after a loading dose is a good indicator of Mg tissue levels.) In addition, they showed no significant change in Mg status over the course of the study. However, there was still an apparent benefit from Mg supplementation. The authors speculate that the bronchial and subjective improvements shown in this group may be owing to some therapeutic effect of consistent, increased Mg exposure.

Limitations of the study include the lack of mention of medication use in each group during the trial. In addition, at enrollment, 70% of the Mg group was using ICS, while only 52% of the placebo group did. The authors state that the medication may not have been an issue because many of the participants did not take ICS consistently during the study period. However, it should be noted that corticosteroids constitute one group of medications that can deplete tissue magnesium levels over time. Also, given that mean PFT values for both the Mg and placebo groups at enrollment were > 80% predicted, this indicates that study participants already had reasonably well-controlled asthma, limiting the capability of Mg supplementation to more significantly improve PFT. The authors also admit that they did not control for potentially important factors that could have an effect on pulmonary function, including allergic status, gastroesophageal reflux, or proper use of inhalers.

Despite these limitations, this study adds to the growing body of evidence that Mg is an important mineral that may improve asthma control. While Mg is recommended as beneficial in IV form for acute asthma, there is still need for a well-designed study to substantiate its benefit in oral form in chronic mild-to-moderate asthma in less-than-well-controlled participants. Given the low cost and safety of oral Mg in the doses discussed (300-450 mg/d of Mg citrate), it is a nutritional supplement that may well prove to be a valuable adjunctive therapy in all forms of chronic asthma.

References

1. Ford E, et al. Dietary magnesium intake in a national sample of US adults. J Nutr 2003;133:2879-2882.

2. Emelyanov A, et al. Reduced intracellular magnesium concentrations in asthmatic patients. Eur Respir J 1999;13:38-40.

3. Alamoudi O. Hypomagnesemia in chronic, stable asthmatics: Prevalence, correlation with severity and hospitalization. Eur Respir J 2000;16:427-431.

4. Dominguez L, et al. Bronchial reactivity and intracellular magnesium: A possible mechanism for the bronchodilating effects of magnesium in asthma. Clin Sci (Lond) 1998;95:137-142.

5. Britton J, et al. Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population sample. Lancet 1994;344:357-362.

6. National Asthma Education and Prevention Program: Expert Panel Report 2: Guidelines for the diagnosis and management of asthma (EPR-2 1997). NIH Publication no. 97-4051. Bethesda, Maryland: DHHS: NIH; NHLBI; National Asthma Education and Prevention Program; 1997.

7. Eby G. Rescue treatment and prevention of asthma using magnesium throat lozenges: Hypothesis for a mouth-lung biologically closed electric circuit. Med Hypotheses 2006;67:1136-1141.

8. Gontijo-Amaral C, et al. Oral magnesium supplementation in asthmatic children: A double-blind randomized placebo-controlled trial. Eur J Clin Nutr 2007;61:54-60.

9. Hill J, et al. Investigation of the effect of short-term change in dietary magnesium intake in asthma. Eur Resp J 1997;10:2225-2229.

10. Fogarty A, et al. Oral magnesium and vitamin C supplements in asthma: A parallel group randomized placebo-controlled trial. Clin Exp Allergy 2003;33:1355-1359.