European Journal of Clinical Nutrition (2007) 61, 54–60

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ORIGINAL ARTICLE
Oral magnesium supplementation in asthmatic
children: a double-blind randomized placebo-
controlled trial
C Gontijo-Amaral1, MAGO Ribeiro1, LSC Gontijo1, A Condino-Neto1,2 and JD Ribeiro1
1
Department of Pediatrics and Center for Investigation in Pediatrics, State University of Campinas Medical School, Unicamp, Campinas, SP,
2
Brazil and Department of Immunology, Institute of Biomedical Sciences, University of Sa˜o Paulo, Sa˜o Paulo, SP, Brazil

Objective: To investigate the long-term effect of oral magnesium supplementation on clinical symptoms, bronchial reactivity,
lung function and allergen-induced skin responses in children and adolescents with moderate persistent asthma. Design: A
double-blind randomized parallel placebo-controlled study.
Setting and subjects: The patients were recruited from the Pediatric Outpatient Clinic, Division of Pulmonology, Allergy and
Immunology, and followed at the Center for Investigation in Pediatrics at State University of Campinas Hospital, Brazil. Thirty-
seven out of 72 patients met the study criteria. There were no dropouts.
Intervention: The 37 patients (aged 7–19 years, 19 males) were randomized in two groups: magnesium (n ¼ 18, 300 mg/day)
and placebo (n ¼ 19), during 2 months. Both patient groups received inhaled fluticasone (250 mg twice a day) and salbutamol
as needed. The primary outcome was bronchial reactivity evaluated with methacholine challenge test (PC20).
Results: After a follow-up of 2 months, the methacholine PC20 for testing bronchial reactivity has augmented significantly in
the magnesium group only. The skin responses to recognized antigens have also decreased in patients treated with
magnesium. The forced vital capacity (FVC), the forced expiratory volume at first second (FEV1), the forced expiratory flow at
25–75 and the FEV1/FVC ratio were similar in both groups. The magnesium group presented fewer asthma exacerbations
and used less salbutamol compared to the placebo group.
Conclusions: Oral magnesium supplementation helped to reduce bronchial reactivity to methacholine, to diminish their
allergen-induced skin responses and to provide better symptom control in pediatric patients with moderate persistent asthma
treated with inhaled fluticasone.
European Journal of Clinical Nutrition (2007) 61, 54–60. doi:10.1038/sj.ejcn.1602475; published online 21 June 2006

Keywords: magnesium; asthma; allergy; bronchial reactivity; skin response; inhaled steroids

Introduction processing (National Research Council (US), 1989). Recent reports

Magnesium is naturally obtained from whole seeds, grains, nuts and
vegetables. However, it is mostly lost after food
Correspondence: Professor C Gontijo-Amaral, R. Marquis de marica´, 81 ap.
401, Santo Anto`nio, Belo Horizonte. MG, 30.350, Brazil and Department of
Pediatrics and Center for Investigation in Pediatrics, CIPED, State University of
Campinas Medical School, UNICAMP, Rua Pedro Natalino Zaghi, 80,
Campinas, SP 13085.070, Brazil.
E-mails: clesiogontijo@litoral.com.br, clesiogontijo@terra.com.br
Guarantors: C Gontijo-Amaral and JD Ribeiro.
Contributors: CG-A conceived the idea and was responsible for study design,
execution, data analysis and preparation of the paper. JDR coordinated and
supervised the clinical trial. AC-N assisted with preparation of the paper and
data analysis. LSCG assisted with preparation of the paper. MAGOR helped
to perform pulmonary function tests.
Received 28 June 2005; revised 17 January 2006; accepted 27 March 2006;
published online 21 June 2006
show that before industrialization, magnesium intake was estimated
in 475–500 mg/day (Altura and Altura, 1991–92). However, it has
declined substantially during the last century. Current dietary surveys
show that the average magnesium intake in Western countries is often
below the Recommended Drug Allowance (280 and 350 mg/day, re-
spectively, for female and male adults) (National Research Council
(US), 1989; USDA, 1990). Asthma prevalence has increased
dramatically over the last 50 years (Chadwick and Cardew, 1997).
Epidemiological evidence indicates that low magnesium intake is
associated with airway hyper-reactivity and self-reported wheezing
(Britton et al., 1994; Soutar et al., 1997).
Trendelenburg first recognized the potential bronchodila-tor effect
of magnesium in 1912, when he observed bron-chial smooth-muscle
relaxation in cows, after magnesium

administration. Rosello and Pla originally demonstrated, in 1936, a
bronchodilator effect of magnesium in asthmatic patients. In vitro
studies showed the relaxant effect of magnesium on vascular (Altura
et al., 1984) and bronchial (Spivey et al., 1990) tones.
The mechanism for a beneficial effect of magnesium on pulmonary
function is not completely clear. It is apparently brought by
competition with calcium entry through voltage-and receptor-
operated calcium channels, as well as by inhibition of intracellular
calcium release (Saris et al., 2000). However, inhibition of
cholinergic transmission (Del Castillo and Engbaek, 1954),
stimulation of nitric oxide (Kemp et al., 1994) and prostacyclin
(Nadler et al., 1987) synthesis, and stabilization of mast cells and T-
lymphocytes (Bois, 1963) can also contribute, at least in part, for the
beneficial effect of magnesium in asthma.
Intravenous (Noppen et al., 1990; Ciarallo et al., 1996; Silverman
et al., 2002) or inhaled magnesium (Plaisance et al., 1994) has been
shown to be beneficial for the control of acute asthma in adults and
children. There are two studies about oral magnesium
supplementation in adult patients. The first of them, performed by
Hill et al. in 1997, shows that short-term change in dietary
magnesium improves the clinical symptoms but not the lung function
tests in adult with asthma. The second study, published in 2003 by
Fogarty et al. showed that magnesium had no effect in adults with
asthma. To date, the effect of oral magnesium in children with
chronic persistent asthma has not been evaluated yet.
The aim of this study was to investigate the effect of magnesium
given as oral supplementation on the control of asthma symptoms,
bronchial reactivity, lung function and allergen-induced skin
responses in children and adolescents with moderate persistent
asthma treated with inhaled fluticasone. We hypothesized that
magnesium given as oral supplementation can help to control chronic
persistent asthma in children.
Materials and methods
Subjects and study design
Thirty-seven children and adolescents (19 males, 18 females; 35
Caucasians, 2 Blacks; age 7–19 years; height 117–173 cm; and
weight 20–60 kg) were included. The patients were recruited from
Pediatric Outpatient Clinic, Division of Pulmonology, Allergy and
Immunology, and followed at the Center for Investigation in
Pediatrics at State University of Campinas Hospital, Brazil. The
inclusion criteria were as follows: patients with clinical history of
recurrent and reversible symptoms of airway obstruction, high serum
IgE levels, positive skin tests to at least one of the tested recognized
allergens and family history of allergy. All of them had persistent
moderate atopic asthma, diagnosed in accordance to the current
Global Initiative for Asthma
Oral magnesium in asthmatic children
C Gontijo-Amaral et al
55
(GINA) criteria. (NIH Publication No. 02-3659) (National Institutes
of Health, 2002).
None of the patients had received systemic steroids, theophylline,
leukotriene modifiers or oral beta2-adrenergic agents, for at least 1
month before the study. None was taking any treatment likely to
affect magnesium absorption or excretion, including diuretics,
digoxine or calcium-containing medications. Smokers and patients
with infec-tions or chronic diseases were not included.
All children were using inhaled steroid as a usual procedure in
moderate cases of asthma. There was a run-in period of 1 week. At
this period, the patients could use in-haled salbutamol (100 mg/dose)
if necessary and the inhaled steroid was switched to fluticasone (250
mg twice a day, Flixotide Diskus), before starting the protocol. We
have used medications at this period owing to the ethically
responsible procedures in those cases and in accordance with the
current GINA criteria for moderated persistent asthma.
A double-blind randomized parallel placebo-controlled study was
performed between January 2001 and December 2002. Patients were
randomized into two groups: magne-sium-glycine (MG, n ¼ 18)
given per oral, 300 mg/day during 2 months, and placebo-control
(PC, n ¼ 19). Glycine was used as placebo, so the difference between
the two groups was only the presence or absence of magnesium. Both
patient groups received inhaled fluticasone (250 mg twice a day).
During the study period, patients used pressured metered dose inhaler
containing salbutamol (100 mg/dose), if necessary.
The patients’ compliance was checked fortnightly and included the
revision of a diary containing information about the number of days
using inhaled salbutamol and the number of days with asthma
exacerbation episodes. Asthma exacerbation episodes were defined as
at least one of the following clinical symptoms: wheezing, chest
tightness and coughing.
The randomization, drug manipulation and dispensing were blind
and carried out independently from the recruit-ment and assessment
of participants. A pharmacist prepared capsules containing either
placebo (glycine) or MG, and randomly dispensed the capsules with
variations A and B. The magnesium or glycine powder presented a
similar appearance. The randomization code was broken at the end of
the study (Peto et al., 1976). If the patients used less than 80% of the
doses/month of fluticasone or magnesium/ placebo, they would be
excluded.
The experimental protocol included clinical evaluation, serum
dosage of magnesium, skin response to recognized antigens, lung
function tests and assessment of bronchial responsiveness by
methacholine challenge test. All of them performed at the beginning
and after 60 days of magnesium or placebo administration. The
primary outcome was bronchial reactivity evaluated with
methacholine challenge test (PC20) and the secondary outcomes were
asthma symptoms, lung function and allergen-induced skin re-
sponses.
European Journal of Clinical Nutrition
 Oral magnesium in asthmatic children
C Gontijo-Amaral et al
56
Written informed consent was obtained from all patient’s parents
and healthy individuals before the study. The Medical School Ethics
Committee approved the experimen-tal protocol in accordance with
the Brazilian Ministry of Health, Resolution 196/96.
Lung function and methacholine tests
Pulmonary function tests included the following parameters: forced
vital capacity (FVC), forced expiratory volume at first second
(FEV1), mid-expiratory flow at 25–75% of vital capacity (FEF25–75)
and FEV1/FVC ratio. Nasal clamp was used in all patients, the
parameters were recorded as the best of three blows and the room
temperature was controlled at 23–251C. Patients had not presented
respiratory infections during the previous 15 days. The pulmonary
function values of FVC, FEV1 and FEF25–75 were described and
analyzed as percent predicted values for the study subjects. The
predicted values were based on the Polgar–Promadah normal values
(Polgar and Promadhat, 1971).
Methacholine challenge test was adapted and performed according
to the American Thoracic Society criteria, with the provocative
concentration causing a 20% fall in FEV1 (PC20) as a measure of
airway responsiveness (Crapo et al., 2000). Briefly, FEV1 was
measured using a dry bellows spirometer after 15 min rest in the
seated position, and taking the best of three flows (CPFS/D
MedGraphics; BREEZE PF Version 3.8 B for Windows 95/98/NT
software). Methacholine aerosols (Sigma, code A2251, St Louis, MI,
USA) were delivered from a series of De Vilbiss handheld nebulizers
(646 model). Subjects inhaled doubling doses of methacholine (from
0.125 to 40 mg/ml) during rapid inspiration from functional residual
capacity to total lung capacity. Subjects were asked to hold their
breath for 3 s after inhalation, and then to exhale slowly for 3 s. FEV1
was measured 1 min after each inhalation. A 5-min interval was
observed between inhala-tion of different methacholine
concentrations. The chal-lenge was interrupted when the FEV1 had
fallen by 20% or more from the baseline value. PC20FEV1 was
calculated by linear interpolation on a log dose–response plot.
Reversion of PC20FEV1 was accomplished by inhaled salbutamol
(two doses of 200 mg). FEV1 was recorded after 10 min, as the best
of three blows. Methacholine challenge testing was not carried out on
any subject who had an FEV1 of o70% of that predicted.
Serum dosage of magnesium
Serum dosage of magnesium was collected in all patients, before and
after the study period. To dosage serum magnesium, it was used an
atomic absorption method, with equipment Variant Spectra AA 250-
plus.
Allergy skin tests
Allergen skin sensitivity to the most relevant antigens for southeast
Brazil – Dermatophagoides pteronyssinus, Dermato-
European Journal of Clinical Nutrition
phagoides farinae and Blomia tropicalis – with histamine and saline
controls (IPI/ASAC, Sa˜oPaulo, Brasil) was estimated by standard
allergen skin-prick test methods, measuring the response to each
allergen as the mean of two right-angled diameters, one of which was
the largest measurable diameter of weal. The skin test response was
recorded after 15 min and considered positive if the mean diameter of
the weal was at least 3 mm, corrected for the mean diameter of
negative control weal if necessary (Demoly et al., 1998). The patients
were regarded as being atopic if they had one or more positive skin-
prick tests. The same physician performed the prick tests between
0800 and 2400 hours, before and after the study period, using the
same lot of antigens. There is no significant seasonal variation
regarding inhaled antigens in this region of Brazil.
Statistical analysis
The sample size of 16 patients for each group was determined before
starting the study, considering appropriate calcula-tions for
randomized clinical trials and the possibility of a type II error. The
primary outcome used in designing the study was PC20FEV1
methacholine, log transformed. A mean log 10 PC20FEV1 value of
0.16 was chosen based on a study performed by Hill et al. (1997),
considering a standard deviation (s.d.) of 0.57 base units and a sample
error of 0.57 base units, we calculated that 16 subjects in each group
would be required for 80% power at the 5% level of significance
(Montgomery, 1991). Descriptive statistics was performed. The
results were represented as bar graphs and tables showing the mean
and s.d.
The Student’s t-test was used to compare age, height, weight and
body index mass. w2 and Fisher’s exact tests were used to analyze
respectively sex and race. The Mann– Whitney U-test was used to
compare asthma exacerbation episodes and the number of days of
inhaled salbutamol use. Analysis of variance (ANOVA for repeated
measures) fol-lowed by Tukey and profile tests were used to analyze
pulmonary function, skin-prick test, serum dosage of magnesium and
methacoline challenge test data. Methaco-line challenge test, FEV1
and FVC was log transformed. P-values lower than 0.05 were
considered significant (Milliken and Johnson, 1984).
Results
Thirty-seven out of 72 patients screened to participate in this study
met the study criteria. There were no dropouts. No adverse effects
were reported from patients in either group.
Randomization resulted in an equivalent distribution of patients
regarding age, sex, race, weight, height and body mass index (BMI).
These results are shown in Table 1. Both groups presented
appropriate compliance.
Figure 1 shows that patients who received magnesium presented
fewer asthma exacerbation episodes, and used less
 Oral magnesium in asthmatic children
C Gontijo-Amaral et al
57
Table 1 Demographic characteristics of asthmatic patients

Characteristics Magnesium group Placebo control group P-value/test

Sex (%) M12 (66.67) F6 (33.33) M7 (36.84) F12 (63.16) 0.07 w2

Mean age (year) 10.8973.36 11.4272.93 0.6103 Student’s t test
Race (%) 18 C (100) 17 C (89.47)–2 b (10.53) 0.2568 Fisher’s test
Weight (kg) 40.39712.38 39.00712.05 0.7316 Student’s t test
Height (cm) 145.5716.58 147.3717.26 0.7448 Student’s t test
BMI (kg/m2) 18.6272.88 17.5372.60 0.2359 Student’s t test

Abbreviation: BMI ¼ body mass index.

25 *p=0.0024 serum magnesium concentration was 2.1070.18 mg/dl in the

magnesium group and 2.1170.18 mg/dl in the placebo control group
days

20 (the reference range in our laboratory is 1.58– 2.55 mg/dl). After the
*p<0.0001
2 months of supplementation with magnesium or placebo, the mean
15 MG
of

serum magnesium con-centration was 2.1370.16 mg/dl in the

Num
ber

PC magnesium group and 2.0870.14 mg/dl in the placebo control group.

10
5 variance (ANOVA for repeated measures) between the two groups
0 skin-prick test data (papules diameter). After
Asthma Inhaled
exacerbation salbutamol
Figure 1 Clinical evaluation. Asthmatic children and adolescents
who received oral magnesium supplementation (MG) during 2
months presented fewer days of asthma exacerbation episodes
and inhaled salbutamol compared to placebo control group (PC).
(*Po0.05, Mann–Whitney test).
inhaled salbutamol (Po0.05 in both circumstances, Mann– Whitney
test), which was not observed in the PC group.
Table 2 presents lung function test values for both groups. After 2
months of oral magnesium supplementation or placebo, the analysis
of the interaction of groups versus time data (ANOVA for repeated
measure) have not shown significant changes in FVC (P ¼ 0.2383),
FEV1 (P ¼ 0.1207), FEF25–75% (P ¼ 0.1267) and FEV1/FVC ratio
(P ¼ 0.0857). In the analyses between groups, both presented similar
FVC, FEV1, FEF25–75%, and FEV1/FVC ratio values (in all
situations, Tukey’s test). The comparison within groups (effect of
time) showed that after 2 months of oral magnesium supplementation,
the FVC, FEV1, FEF25–75% and FEV1/FVC ratio values have
increased significantly in MG group patients (in all situations, profile
test). In the placebo group, only the FEV1 and FEF25-75% values
increased significantly during the study period (in both situations,
profile test).
Figure 2 shows the methacoline test data. After 2 months of oral
magnesium supplementation or placebo, a higher dose of methacoline
was necessary to induce a 20% fall in the FEV1 in patients of the MG
group compared to the PC group (Po0.05, Tukey’s test).
At the beginning of the study, all the patients were within the
normal range of magnesium. At that time, the mean
There were no statistically significant differences in the analyses of
with respect to serum magnesium levels (P ¼ 0.128). Table 3 shows
2 months of oral magnesium supplementation or placebo, the analysis
of the interaction of groups versus time data (ANOVA for repeated
measures) have shown significant changes in tests performed with D.
peronyssinus (P ¼ 0.0012), D. farinae (P ¼ 0.0002), Blomia (P ¼
0.0091), but not with the negative control saline (P ¼ 0.3850). In the
analyses between groups, the MG group showed smaller papule
diameter values (D. peronyssinus and D. farinae) compared to PC
group (Po0.05 in both situations, Tukey’s test). The comparison
within groups (profile test) showed that after 2 months of oral
magnesium supplementation, the papule diameter values for D.
peronyssinus (P ¼ 0.004), D. farinae (P ¼ 0.001) and Blomia (P ¼
0.013) values have decreased significantly in MG group patients, but
not in the PC group patients.
Discussion
Our results showed that after 2 months, children and adolescents with
moderate persistent asthma who were treated on regular basis with
inhaled fluticasone and received oral magnesium supplementation
presented a significant improvement in bronchial responsiveness, as
assessed by the methacholine test. They presented a significant
clinical improvement, as shown by a fewer number of asthma
exacerbation episodes and less use of inhaled salbutamol, as well. The
skin responses to recognized antigens such as D. farinae and D.
pteronyssinus have also decreased in patients supplemented with
magnesium.
The literature shows only two studies investigating the effect of
oral magnesium, both in adults and showing conflicting results (Hill
et al., 1997; Fogarty et al., 2003). To

European Journal of Clinical Nutrition

 Oral magnesium in asthmatic children
C Gontijo-Amaral et al
58
Table 2 Lung function tests data of patients from the MG or placebo control group during the study period: mean, s.d. and P-values of the within-(Profile
test) and between- (Tukey’s test) group comparisons

Variables (%) Magnesium group (n ¼ 18) Placebo-control group (n ¼ 19) P-value BG

Before After P-value WG Before After P-value WG

FVCa 78.678.9 88.9714.8 0.023 77.176.9 81.5710.0 0.080 0.1274

FEV1a 59.179.05 73.5716.3 0.006 59.577.0 65.478.7 0.013 0.2118
FEF 25–75 37.5712.7 54.1718.5 0.004 38.9711.9 46.3714.7 0.036 0.4076
FEV1/ FVC 74.878.7 82.579.1 0.001 77.4710.0 80.379.1 0.143 0.9266

Abbreviations: FEV1, the forced expiratory volume at first second; FEF25–75%, the forced expiratory flow at 25–75%; FVC, forced vital capacity; MG, magnesium
group.
aLog transformed (Log ).
10
WG ¼ within-group comparison (effect of time) – Profile test.
BG ¼ between-group comparison (effect of group) – Tukey’s test.
Bold values indicate Po0.05.

Table 3 Skin-prick tests data for D. pteronyssinus, D. farinae and B. *p<0.05

tropicalis with histamine (positive control) and saline (negative control)
of patients from the magnesium group or placebo control group during
the study period (mean and standard deviation)
0.8

(M)
Magnesium Placebo-control

Methachol
group (n ¼ 18) group (n ¼ 19) 0.6 MG
ine
Mean s.d. Mean s.d.
0.2 PC
0.4
Saline before (mm) 0 0 0 0
Saline after (mm) 0 0 0 0
Histamine before (mm) 5.94 2.07 7.47 2.27
Histamine after (mm) 5.61 1.65 7.79 1.90 0
D. pteronyssinus before (mm) 5.50 3.37 7.05 4.09 Before After
D. pteronyssinus after (mm) 3.72 2.56 8.00 3.70
D. farinae before (mm) 4.61 3.50 5.32 2.56 Figure 2 Methacholine-induced bronchial challenge. After 2 months
D. farinae after (mm) 3.17 3.09 6.26 2.84 of magnesium supplementation, the dose of methacholine
B. tropicalis before (mm) 6.06 4.65 6.11 3.65 necessary to induce a 20% fall in the FEV1 was significantly higher
B. tropicalis after (mm) 3.89 3.66 6.47 4.22 in the magnesium group (MG) compared to the placebo control
group (PC) (*Po0.05, Tukey’s test).
Abbreviations: B. tropicalis, Blomia tropicalis; D. pteronyssinus, Dermatopha-
goides pteronyssinus; D. farinae, Dermatophagoides farinae; s.d., standard
deviation.
most likely explanation for their findings was that their participants
were already well controlled on conventional asthma medications,
date, these two important studies about the use of oral magnesium in and under that circumstances nutrient supplementation had nothing to
asthmatic patients are very different in the number of participants and add.
duration of intervention. In the study performed by Hill et al. (1997), Our study was the first performed in children and adolescents,
17 asthmatic subjects adhered to a low magnesium diet for two aiming to investigate the effects of oral magnesium given on a regular
periods of 3 weeks, preceded and separated by a 1-week run-in/wash- basis. Up to the time of the study outline, there was no available data
out, in which the patients took either magnesium (400 mg/day) or in children, which could be used as parameter for an improved
placebo tablet supplementation. A high magnesium intake was planning, considering effective doses of magnesium, length of the
associated with improvement in symptom scores, although not in treatment period and possible side or beneficial effects. Some of these
objective measures of airway reactivity. Taken together, the authors aspects were, however, based on studies performed in adult patients
suggested that a more extended study period of the effect of a high (Britton et al., 1994; Hill et al., 1997); others were obtained on
magnesium intake, sustained over a longer period, was necessary to updates revision of physiological, clinical and analytical aspects of
investigate the beneficial role of magnesium in asthma control in the use of magnesium in different diseases (Saris et al., 2000).
adult patients. Besides, in the study performed by Fogarty et al.
(2003), 100 asthmatic patients received supplementation with
magnesium (450 mg/day) during 16 weeks. There was no evidence of Assessment of age, weight, height, race and sex indicated that our
any beneficial effect of magnesium supple-mentation in these population was homogeneous, and moreover that it presented
patients. The authors suggested that the characteristics similar to those of other studies performed in asthmatic
children. Even after being rando-mized, all the two groups remained
with similar demo-

European Journal of Clinical Nutrition


graphic characteristics without statistically significant differ-ences.
It is interesting to point out that only those patients who received
oral magnesium presented fewer asthma exacerba-tion episodes and
required less inhaled salbutamol. If magnesium modulates the late-
phase allergic response or chronic inflammation also remains to be
determined. Analyzing the clinical data, the children spent 20–25% of
the study time with exacerbations. We do not believe that it must be
occurred a sub-optimal treatment, once all the patients received free
pressured metered dose inhaler fluticasone (Flixotide Diskus,
GlaxoSmithKline, Ware, Hert-fordshire, England) and the usage was
checked by the physician fortnightly. Besides, another explanation
was an overestimate of the asthma exacerbations, in view of the
simplicity of our diary, once it would be used to the same patient and
family.
In this study, we provide evidence that oral supplementa-tion of
magnesium potentially modulates the early phase allergic reaction as
long as it decreases skin reactivity to recognized inhaled allergens,
such as D. farinae and D. pteronyssinus. These are important
allergens in southeast Brazil. To date, some reports show that
magnesium inhibits mast cell activation in vitro, under specific
circumstances (Bois, 1963). Future studies are necessary to test
bronchial immediate response to inhaled allergens in patients who
received oral magnesium supplementation. In addition, the potential
use of magnesium in the treatment of atopic dermatitis and asthma
remains to be determined. Particu-larly, magnesium has a strong
relation with the immune system, in both nonspecific and specific
immune response, also known as innate and acquired immune
response (Tam et al., 2003).
Although the assessment of serum magnesium concentra-tions is
not an accurate reflection of the magnesium status of muscle, bone
and other tissue, it is commonly used in clinical practice. However,
there is a poor correlation between serum and intracellular
magnesium concentrations, most probably because only 1% of total
body magnesium reserves can be found in the whole blood (Quame,
1993). This way, our results is in accordance with recent studies of
serum dosage of magnesium in asthmatic patients (Fantidis et al.,
1995; Zervas et al., 2000). Intracellular ionized magnesium
concentration in erythrocytes, polymorpho-nuclear and mononuclear
leukocytes have been described recently and reflect more closely
skeletal, cardiac and smooth muscle magnesium concentrations
(Fantidis et al., 1995; Saris et al., 2000; Zervas et al., 2000). These
techniques, however, are expensive and time consuming. Because of
this, it was not suitable for use in our study.
In the analyses of lung function tests, our findings were similar to
those reported among adults (Hill et al., 1997), because at the end, we
observed a small but not significant improvement in FEV1, FVC,
FEF25–75% and FEV1/FVC ratio. A possible explanation was that
both group patients were using a considerable dose of fluticasone
(250 mg twice a day)
Oral magnesium in asthmatic children
C Gontijo-Amaral et al
59
and so the differences between the groups were not so evident. The
analyses within groups lend some support to this interpretation.
Besides, the increase in the FEV1 and FEF25–75% values, during the
course of the study, for both magnesium and placebo groups, were
probably because of the effect of the treatment with fluticasone.
Future studies with another type of protocol are now indicated.
In this paper, we report on the decrease of bronchial reactivity to
methacholine after 2 months of oral magnesium supplementation. The
mechanism for this inhibitory effect of magnesium on bronchial
reactivity also remains to be determined. It can be explained by
possible direct effects of magnesium blocking muscharinic receptors
(Del Castillo and Engbaek, 1954) or by its indirect effects, that is, the
decrease of bronchial reactivity to methacholine owing to the
modulation of the allergic reaction by magnesium, as evidenced in
this paper by the decrease of skin reactivity of allergic patients to
recognized antigens. To date, magnesium blocks calcium channels,
activates sodium and calcium pumps, inhibits the calcium’s
interaction with myosin and diminish calcium release from
sarcoplasmatic reticulum, altogether promoting a bronchial relaxant
effect (Altura et al., 1984; Britton et al., 1994).
Our double-blind randomized study shows that children and
adolescents with moderate persistent asthma who received inhaled
fluticasone in combination with oral magnesium supplementation
presented better clinical results and a decrease in both bronchial
reactivity and skin reaction to recognized antigens, showing a
potential and important beneficial effect of magnesium, a low-cost
mineral, for the control of asthma. Future large-scale studies are
necessary to assess definitely the potential role of magnesium in the
general treatment of asthma in children.
Acknowledgements
We thank the statistical advice of Helymar Machado and Cleide M
Silva, Albion Laboratory for providing magnesium, GlaxoSmitKline
for providing fluticasone and salbutamol and Ao-Pharmaceˆutico for
drug manipulation. C Gontijo-Amaral was supported by
Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior,
CAPES. Ministry of Education, Brazil.
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