COMMENTARY
Magnesium Research
(1995) 8, 4, 403-405
Commentary on recent clinical advances:
Magnesium depletion, magnesium deficiency and asthma
Key words: Asthma, magnesium, deficiency and
depletion
The basic differences between the two types of magnesium
deficit, magnesium deficiency and magnesium depletion, have been
highlighted for several years (see reviews1,2. In the
case of magnesium deficiency, the disorder results from an
insufficient magnesium intake and merely requires oral
physiological magnesium supplementation. In the case of magnesium
depletion, the disorder which induces magnesium deficit is
related to a dysregulation of the control mechanisms of magnesium
metabolism: either a failure of the mechanisms which ensure
magnesium homeostasis, or intervention of endogenous or
iatrogenic factors that disturb magnesium status. Magnesium
depletion requires a more or less specific correction of its
causal dysregulation.
The differential diagnosis between these two types of
magnesium deficit is of major importance. Distinguishing between
magnesium deficit, deficiency and depletion is closer to a
heuristic concept than a semantic specification2.
Recent clinical data on disturbances of magnesium items in asthma
testify to this.
A study by Fantidis et al.3 aims to
determine whether asthma per se may affect magnesium
status. Their exclusion criteria include any subjects with
pathological or iatrogenic causes for potential secondary
magnesium deficit (that is, pregnancy, breast-feeding,
gastrointestinal, cardiovascular or metabolic diseases, recent
convalescence; treatment with contraceptives, calcium
antagonists, diuretics, digoxin, laxatives, vitamin D, and so
on), or with signs suggestive of potential primary magnesium
deficit (that is, frequent cramps, palpitations or spasms,
tumour, asthenia, anorexia, anxiety, etc). All the subjects of
the control group (n = 21) were healthy and had neither allergic
disturbances nor asthma. The study group (n = 50) included
asthmatic patients who may be divided either into three subgroups
according to the severity of the disease (mild, moderate, and
severe asthma), or into two sub-groups differentiating intrinsic
(n = 33) and extrinsic (n = 17) asthma. In all study subjects
serum, plasma, erythrocyte and polymorphonuclear magnesium
concentrations were measured by atomic absorption
spectrophotometry, and serum sodium, potassium and calcium
concentrations and erythrocyte potassium concentrations were also
measured. Polymorphonuclear cell magnesium content (pn Mg) was
expressed as mg Mg/ng DNA. In patients with asthma the dosages
were carried out in the interval between attacks.
While the magnesium concentrations and those of the other ions
were normal in serum and erythrocytes, the (pn Mg) was lower
(0.88 mg Mg/ng DNA ± 0.61; 
1 s
± 1 SD) than in the control group (1.84 ± 0.9).
There was no correlation between the different types of asthma or
the degree of asthmatic severity and low pn Mg. This
intracellular magnesium investigation enables the patients with
asthma to be divided into two subgroups: one with a normal pn Mg
(around one third of the cases; pn Mg = 1.88 ± 0.9), and
another (around two thirds of the cases) with a highly
significant decrease in pn Mg (pn Mg = 0.38 ± 0.28;
P < 0.001). Stepwise discriminant analysis showed
that pn Mg content discriminated between the control group and
either the whole group of asthmatics or the low pn Mg subgroup of
asthmatics.
Unaware of the basic difference between magnesium depletion
and magnesium deficiency, the authors stress that "in view of the
fact that serum and erythrocyte magnesium were normal and that
the levels of other ions in erythrocyte were also normal, the
reason of the low pn Mg content of (asthmatic) patients is
unclear. One explanation may be that the regulation of magnesium
flux differs from one cell type to another". We entirely agree
with this remark: an isolated decrease in cellular magnesium
should originate from a dysregulation of magnesium status, which
exactly defines magnesium depletion. This magnesium depletion,
present in two thirds of the cases of asthma and absent in one
third of the cases must be either a marker of polynuclear
disturbances in asthmatic individuals or a pathophysiological
mechanism which contributes to the pathogenesis of some symptoms
in two thirds of asthma cases. Further research will be necessary
to elucidate the reason for and possibly cure the dysregulation
of pn Mg in two thirds of asthma cases. It seems premature to
write: "in asmathics with low pn Mg content magnesium may improve
the condition by normalizing intracellular magnesium content'.
Appropriate intervention trials may yield valuable information on
this". It should be remembered that simple and non-toxic oral
physiological magnesium supplementation never controls magnesium
depletion. Pharmacological magnesium interventions may induce
toxicity. Beneficial effects of intravenous magnesium therapy
have only been observed in the treatment of acute asthma and not
in bronchial asthma between attacks4.
In addition, it is well established that basophils are target
cells for IgE molecules in asthma. Basophils only constitute a
small proportion of the polymorphonuclear cells and it is
hazardous to infer from a decreased total in pn Mg content that
the basophil pn Mg content is consequently reduced.
These interesting data only allow us to conclude that between
attacks and in two thirds of asthma cases a dramatic magnesium
depletion is observed in the bulk of pn Mg, the origin and
significance of which are so far unknown.
The importance of magnesium deficiency in the physiopathology
of asthma has been recently claimed after a large epidemiological
study conducted in 2,633 adults5. Britton showed that
high dietary magnesium intake is associated with better lung
function and a reduced risk of airway hyperreactivity and
wheezing. It might be therefore inferred that a low magnesium
intake, that is, magnesium deficiency, could be involved in the
aetiology of asthma and chronic obstructive airways
disease5. But this remains to be proven. Coexistence
does not, mean causality. Only the specific reversibility of the
symptoms through the control of the magnesium deficiency will
really demonstrate the existence of an aetiopathogenic link. A
study showing that plasma, erythrocyte and mononuclear leucocyte
concentrations of magnesium do not differ significantly from
those of healthy controls is at variance with the hypothesis of
the existence of magnesium deficiency in asthmatic
patients3,6. Nonetheless, though magnesium deficiency
does not seem to be a cause for asthma per se, primary
magnesium deficiency may coexist with asthma and constitute a
'decompensatory' factor for asthma through both nervous
hyperexcitability and various disturbances of immunity, the
biochemical bases of which may combine decreased nucleotidic
ratio (AMPc/GMPc), increased intracellular Ca2+,
degranulation of basophils, enhanced production of IgE, an
inflammatory state which may depend on cytokines, neuropeptides,
prostaglandin D2 and leukotdenes3,7-10. Over a half of
the patients with reaginic allergy, which may induce asthma,
present with chronic primary magnesium deficiency, most often
associated with symptoms of tetany (Chvostek sign and repetitive
EMG tracings). Conversely the frequency of allergic antecedents
is high in cases of latent tetany due to primary magnesium
deficit8. Oral physiological magnesium therapy may
then enhance the effect of specialized treatment.
It is only when primary magnesium deficiency decompensates
asthma that oral physiological magnesium supplementation becomes
beneficial as an adjuvant treatment of asthma8.
To sum up, the dramatic decrease in pn Mg observed in two
thirds of the cases of an asthmatic group constitutes a marker or
a pathophysiological factor in these particular cases. The
mechanism of this magnesium depletion being unknown, it does not
involve any therapeutic consequences for the time being.
Conversely, when chronic primary magnesium deficiency coexists
with asthma it constitutes a decompensatory factor whose control
with simple oral physiological magnesium supplementation must
help in asthma therapy.
References
1. Halpern, M.J. (1985): Magnesium physiopathology II.
Magnesium deficiency and depletion. In: Proceedings of 1st
European Congress on Magnesium, eds. M.J. Halpern & J.
Durlach, pp. 9-23. Basel: Karger.
2. Durlach, J. (1995): Editorial policy of Magnesium
Research: General consideration the quality criteria for
biomedical papers and some complementary guidelines for the
contributors of Mag. Res. 8,
191-206.
3. Fantidis, P., Cacho, J.R., Marin, M., Jarabo, R.M., Solera,
J. & Herrero, E. (1995): Intracellular (polymorphonuclear)
magnesium content in patients with bronchial asthma between
attacks. J. R. Soc. Med. 88,
441-445.
4. Durlach, J., Durlach, V., Bac, P., Bara, M. &
Guiet-Bara, A. (1994): Magnesium and therapeutics. Magnes.
Res. 34, 313-328.
5. Britton, J. (1994): Dietary magnesium, lung function,
wheezing and airway hyperreactivity in a random population
sample. Lancet 344, 357-362.
6. de Walk, H.W., Kok, P.T.M., Struyvenberg, A., Van Rijn,
H.J.M., Halboom, J.R.E., Kreukniet, J. & Lammers, J.W.J.
(1993): Extracellular and intracellular magnesium concentrations
in asthmatic patients. Eur. Respir. J.
6, 1122-1125.
7. Durlach, J., Poenaru, S., Rouhani, S., Bara, M. &
Guiet-Bara, A. (1987): The control of central neural
hyperexcitability in magnesium deficiency. In: Nutrients and
brain function. ed. W.B. Essman, pp. 48-71. Basel:
Karger.
8. Durlach, J. (1988): Allergic forms of primary magnesium
deficit. In: Magnesium in clinical practice, ed. J.
Durlach, pp. 101-102; p. 245. London, Paris: John Libbey.
9. Hunziker, N. (1990): Magnesium and its role in allergy. In:
Metal ions in biological systems, Vol. 26. Compendium on
magnesium, eds. H. Sigel & A. Sigel, pp. 531-547.
New-York: M. Dekker.
10. McCoy, H. & Kenney, M.A. (1992): Magnesium and immune
function: recent findings. Magnes. Res.
5, 281-293.
Jean Durlach
President, SDRM
Editor-in-Chief Magnesium Research
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