Mineral and Metal Neurotoxicology, ed. M. Yasui, M
.J. Strong, K. Ota, & M. A. Verity, CRC Press: Boca Raton,
New York, London, Tokyo, 1997
Chapter 20
Mechanisms of Action on the Nervous System in Magnesium
Deficiency and Dementia
Jean Durlach and Pierre Bac
CONTENTS
20.1 Introduction
20.2 Mechanisms of Action of Magnesium
Deficiency on the Nervous System
20.2.3 Neuromuscular and Psychiatric
Data
20.3 Magnesium Depletion and
Dementias
20.3.1 Experimental Models of Mg
Depletions
20.3.1.1 Neurological
Degeneration Due to Al Load and Low Mg Intake
20.3.1.2 Mg Depletion Due to
Kainic Acid Plus Mg Deficiency
20.3.2 Possible Links Between
Dementias and Mg Depletion
20.4 Therapeutic Implications
20.4.1 Treatment of Magnesium
Deficiency
20.4.2 Magnesium Therapy and
Dementias
20.5 Conclusion
20.1 INTRODUCTION
Whatever the age, nervous forms of magnesium deficit represent
the most commonly seen form in clinical practice.1
First of all, it seems very important to discriminate between the
two types of magnesium deficit: magnesium deficiency and
magnesium depletion. In the case of magnesium
deficiency, the disorder corresponds to an insufficient
magnesium intake: it 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 failure of the mechanisms which
insure magnesium homeostasis or intervention of endogenous or
iatrogenic perturbating factors of the magnesium status.
Magnesium depletion requires more or less
specific correction of its causal dysregulation.1 It
should not be permitted today to extrapolate from physiological
data observed in overt acute magnesium deficiency to
physiological consequences of chronic magnesium deficiency.
Although acute and chronic magnesium deficiencies are
specifically reversible through oral magnesium supplementation
with physiological doses, the experimental and clinical symptoms
may differ. The typical pattern of chronic magnesium deficiency
is latent whereas overt signs are observed in acute magnesium
deficiency. The discrepancy between the patent and latent nervous
forms of magnesium deficiency suggests that in the latent form
there are compensatory factors which antagonize the nervous
hyperexcitability observed in the overt form.
The aim of this review is to study:
- The mechanisms of action of magnesium deficiency on the
nervous system as demonstrated by
- Electrophysiological data testifying to diffuse nervous
hyperexcitability (NHE)
- Biochemical data showing the mechanisms which may
induce overt and latent NHE
- Neuromuscular and neurotic psychiatric data
- The links between some types of magnesium depletions and
dementias.
- Therapeutical implications.
20.2 MECHANISMS OF ACTION OF
MAGNESIUM DEFICIENCY ON THE NERVOUS SYSTEM
We will analyze the mechanisms of action of magnesium
deficiency on the nervous system successively through
electrophysiological, biochemical, and clinical data.
20.2.1
Electrophysiological Data
Experimental and clinical electrophysiological procedures
allow us to neurophysiologically examine the effects of
magnesium deficiency on the cortical, subcortical, and
peripheral levels of the nervous system.
Standard electroencephalography (EEG) in humans exhibits
"diffuse irritative tracings" without focal lesions or
paroxysmal discharges. The recordings contain spikes, a pointed
appearance of alpha and/or theta waves, which is facilitated
more often by hyperventilation than by intermittent photic
stimulation. The polygraphic study of afternoon sleep may
complete the data of standard EEG: brevity of the time required
to fall asleep, superficial character of the sleep, frequency
of awakening, hypnoagnosia.1 The EEG in the
magnesium-deficient rat (electrocorticography) allows us to
make observations similar to those found in humans. Mg
deficiency induces electrocorticographic alterations in the rat
analogous with those seen in Mg deficiency in humans. Sleep
quality analysis shows particularly similar alterations of the
hypnograms.1,2
Electronystagmography shows functional impairment at the
level of the second vestibulo-ocular motoneuron which becomes
apparent mainly as the variable association of "paroxysmal
ocular states", i.e., a sequence of repetitive ocular
movements with vertical predominance over a period averaging 20
s, irregularity of evoked nystagmic responses, excessive
bilateral labyrinthine reflex activity, oblique or rotary
nystagmus, prolonged latency during pendular tests, and
differences between pendular nystagmic responses with the eyes
open and closed. Alterations in optokinetic tests confirm the
importance of subcortical functional
disturbances.1
Moreover, behavioral changes in the Mg-deficient rats are
due to hyperexcitability which first arises in deeper
structures -- in the whole limbic system and in the
hippocampus, particularly -- and which secondarily becomes
generalized by projecting on the neocortices. 3
Electromyography (EMG) shows peripheral NHE. A series of
autorhythmic events is observed (singlets, multiplets, complex
tonicoclonic activity) beating for more than 2 min during one
(or several) of the three facilitations tests:
tourniquet-induced ischemia lasting 10 min, a postischemic
phase measured 10 min after removal of the tourniquet, and
finally hyperventilation for a maximum of 5 min. A repetitive
EMG, whatever the intensity, constitutes the principal
neurophysiological mark of NHE due to Mg
deficiency.1
Skin conductance reflex might appear attractive as an
investigation tool of diffuse NHE due to Mg
deficiency,4 but this procedure still requires
further validation.
These neurophysiological procedures, mainly EEG, ENG, and
EMG, allow us to examine the effects of Mg deficiency on the
nervous system: Mg deficiency causes diffuse neuromuscular
hyperexcitability operating from the center to the periphery.
NHE affects the nervous system as a whole, but comparing the
impairments in its various sectors is less important than
determining the intra- or extracellular origin of
NHE.1,5
The long duration of experimental Mg deficiency required to
produce manifestations of NHE has led to the hypothesis of
concurrent reduction of intracellular Mg which represents "the
bulk" of the Mg pool. In Mg deficiency induced in young rats,
there is a direct correlation between the severity of
hyperexcitability and the decrease in the brain Mg level.
Clinical evidence includes patients with Mg deficiency but
without abnormalities of extracellular Mg, hypo- or
normomagnesemia in the same patient at different times, and a
reduction of the mean erythrocyte or lymphocyte Mg contents,
two forms of intracellular Mg. This demonstrates the possible
role of intracellular Mg in NHE due to Mg deficiency.
This NHE is not always accompanied by low levels of cerebral
Mg: these are only observed in severe Mg deficiency in young
rats. Usually, no changes have been found in brain Mg
concentrations during the course of Mg deficiency in adult
rats.5-7 It should be stressed that in Mg deficiency
there exist complex mechanisms to maintain normal, and even
increased, Mg concentration in the tissue which are of vital
importance in brain, liver, and brown fat.5-8 With
reduced plasma Mg levels, an extracellular origin of NHE due to
Mg deficiency may intervene, but plasma normomagnesemia has
also been observed with some Mg deficiencies.
An analysis of the relationship between extra- and
intracellular concentrations, clinical findings, and
electronystagmographic tracings have shown that more symptoms
of NHE occur when Mg deficiency predominates in one of the
intra- or extracellular compartments rather than when it
affects both equally.1,5 This electroclinical
observation highlights the importance of Mg distribution
disturbances in the physiopathological consequences of Mg
deficiency on the nervous system.
20.2.2 Biochemical
Data
During Mg deficiency, a complex neuroendocrinometabolic and
renal regulation may intervene for compensating its systemic
effects. The role of the blood-brain barrier which attenuates
the effect of the systemic regulating factors of Mg status and
of the humoral consequences of decompensated Mg deficiency in
the nervous system must not be overlooked. The biochemical
factors capable of increasing nervous excitability are
essentially local.1,5
20.2.2.1 Factors
Inducing NHE
Extrapolating from data observed in vitro, in
situ, or in other pharmacological manipulations to the
physiological basis of an Mg deficiency simply due to
insufficient intake1 remains a methodological
error.
Pharmacological Mg excess causes some systemic reactions
which are not the opposite of physiological effects of Mg.
For example pharmacological load of Mg increases release of
calcitonin and nitric oxide (NO).9,10 In contrast,
physiological Mg supplementation, far from acting similarly,
reduces high levels of calcitonin1 (as well as of
calcitonin gene-related peptide11and of
NO12 released in the case of Mg deficiency.
The great stability of brain Mg during Mg deficiency
particularly disagrees with the very notion of extrapolating
from in vitro or in situ, extra- or
intracellular Mg data1,5 to in vivo
physiological data. This leads to suggesting an updated
scheme of the factors which cause NHE5: Mg
deficiency would induce a diffuse NHE through a neuronal
depolarization which derives from the sum of its direct
cellular effects in the neural cells and from several
mediated reactions.5
20.2.2.1.1 Direct Cellular
Effects
Mg deficiency results in three basic effects:
disturbances in cellular Ca distribution, decreased second
messenger nucleotidic ratio,5 and increased
susceptibility to peroxydation.12-14 Through
membranous and postmembranous alterations, Mg deficiency
brings about a cellular Ca load with subcellular
distribution modifications.5 Mg deficiency
reduces 3',5'-cyclic adenosine monophosphate (cAMP)
concentration and increases 3',5'-cyclic guanosine
monophosphate (cGMP) concentration, perhaps through
inhibition of adenylate cyclase and activation of guanylate
cyclase.5 Mg-deficient animals show an increased
susceptibility to in vivo oxydative stress and the
tissues of these animals are more susceptible to in
vitro peroxydation, affecting lipid
particularly.12-14 Protein oxydation in
Mg-deficient rat brains occurs early. A significant
increase of protein carbonyls is observed within 2 to 3
weeks of a Mg-deficient diet. These changes take place
prior to any detectable tissue damage, dysfunction, or
changes in cellular glutathione.15
Mg deficiency may increase formation of free radicals
directly, but also indirectly through
free-radical-triggered mechanisms.12 ,15
20.2.2.1.2 Mediated Local
Effects
NHE due to Mg deficit is also linked to modifications in
the turnover of various types of neurotransmitters:
monoamines, amino acids, but also nitric oxide,
neuropeptides, and cytokines.
Neurotransmitters - NHE due to Mg
deficiency mainly depends on modifications in the turnover
of several neuromediators and neuromodulators. They
associate an increased turnover of the monoamines:
serotonin (5HT), acetylcholine, catecholamines (dopamine
and noradrenaline, mainly), and of excitatory amino acids
(aspartic and glutamic acids, mainly) with a decreased
turnover of inhibitory amino acids (γ-amino butyric
acid and taurine, mainly).5 As a great number of
in vitro studies on Mg and NMDA16
receptors have suggested that the latter had predominant
and almost exclusive importance, their in vivo
role has often been overestimated.2 If hyper
NMDA receptivity enters into the mechanisms of NHE due to
Mg deficiency as confirmed in vivo,17 a
hyperreceptivity concerning other non-NMDA receptors of
excitatory amino acids may also intervene.18 The
genuine complexity of biology must not be disregarded just
because the present trend is towards focusing on NMDA
receptors at the expense of many other receptors.
Nitric oxide, peptides, and cytokines -
An increased production of nitric oxide and of various
inflammatory peptides - such as substance P, CGRP, and VIP
- is observed in Mg-deficient rats. All these substances
might directly intervene as neurotransmitters in the
physiopathology of NHE due to Mg deficiency; but NO could
also mediate an increase in cGMP whereas inflammatory
neuropeptides might stimulate production of inflammatory
cytokines and of free radicals.12-14 During the
progression of Mg deficiency in a rodent model, dramatic
increases of inflammatory cytokines were observed:
interleukins 1 and 6 (IL1, IL6) and tumor necrosis factor
(α(TNFα ). Increase of these various cytokines
was neither concomitant nor constant, according to species
and strains.12-14,19 So far, their importance in
the physiopathology of NHE has not been clearly defined but
we have observed with P. Maurois that audiogenic seizures
in Mg-deficient mice might be correlated with possible
TNFα release. According to the strains of mice, there
is a parallelism between production of TNFα. induced
by bacterial lipopolysaccharides and NHE. However,
coexistence does not mean causality and further research
focusing on the effects of specific TNFα antibody on
the production of audiogenic seizures will be necessary.
Opioid peptide activity could be reduced since, in the
complex mechanisms of opioid action, Mg at the
physiological level may be most often an agonist of
δ, µ, and κ opioid
receptors.5,20
The sum of these direct and mediated local factors may
bring about overt NHE due to Mg deficiency. Frequency of
latent forms of this NHE postulates the existence of local
compensatory factors which may control NHE.5
20.2.2.2 NHE
Compensatory Factors
The local compensatory factors instrumental in the latency
of NHE due to Mg deficiency may also be direct and
mediated.
20.2.2.2.1 Direct Compensatory
Factors
Since Mg can more or less be replaced by a natural
polyamine in many biochemical reactions, an
"Mg-substitutive" increase in polyamines might decrease the
direct cellular effects of Mg deficiency. This
"Mg-vicariant" increase in polyamines may be a factor
regulating the alterations of protein synthesis and
particularly that of Ca2+ and Mg2+
binding proteins.5 Increased formation of free
radicals may be antagonized by the cell antioxidant system:
enzymes such as superoxide dismutase and glutathione
peroxidase, antioxidant vitamins such as E, A, and C,
selenium, and sulfur compounds such as glutathione and
taurine.8, 14-18
20.2.2.2.2 Mediated Compensatory
Factors
Some types of adenylate cyclase-receptors may contribute
to a compensatory increase in the cAMP/cGMP
ratio.5 The main compensatory factors are
mediated by the increase of several physiological
neuroprotective agents: inhibitory
aminoacids1,5,10,21-23 and perhaps
melatonin.24 The particular efficiency of
N-acetyl-amino compounds such as Mg N-acetyl-amino
taurinate and melatonin might depend on a decreased
activity of the Mg-dependent N-acetyl-amino transferase in
the nervous system (EC 2.3.1.5.).10,21-24 The
main mediated compensatory factor is taurine (TA) with the
help of its peptidic congener: γ-L-glutamyl taurine
(GTA).5
When these direct and mediated compensatory factors are
effective, NHE remains latent. It is patent when
compensatory factors are insufficient. Their failure may
depend on several reasons:
1 . Sufficient amounts of amino acids - precursors of
neuromediators and neuromodulators - must be available in
the nervous system. It is important to have qualitatively
and quantitatively a sufficient protein intake and
sufficient amino acid transport across the blood-brain
barrier, eventually facilitated by a homeostatic reactive
hyperinsulinism. Both may be lacking.
2. If a compensatory high release of cAMP counteracts
the decrease of cAMP/cGMP ratio, it inhibits the TA
biosynthesis through the reduction of cystine dioxygenase
activity.
3. Efficient brain metabolism and, particularly
enzymatic activity, is necessary. However, Mg deficiency
frequently alters protein biosynthesis and induces
enzymatic hypoactivity.
4. Finally, the number of excitatory factors appears
larger than that of compensatory factors during Mg
deficiency in the nervous system.5
However, one should not overlook the schematic nature of
this general pattern which covers both a homogeneous
explanation of the diffuse character of the symptomatic NHE
due to Mg deficiency and the possibility of the Mg
deficient latent form.
Because of the heterogenicity of NHE due to Mg
deficiency, a special study of each parameter of this
scheme in each brain area is necessary to obtain a better
understanding of these complex phenomena.5
20.2.3 Neuromuscular and
Psychiatric Data
NHE due to Mg deficiency results in a nonspecific clinical
pattern which associates peripheral and autonomic neuromuscular
signs and central or rather psychiatric symptoms. Neuromuscular
disturbances include acroparesthesias, muscle fasciculations,
cramps, and myalgias occurring more frequently than tetanoid or
tetanic attacks, and various autonomic functional complaints
such as cardiac palpitations, precordial pain, extrasystolae,
Raynaud's syndrome, hepatobiliary dyskinesia, gastrointestinal
cramps and spasms, and asthma-like dyspnea.
Psychiatric symptoms consist of anxiety, hyperemotionality,
asthenia, headache, insomnia, dizziness, nervous fits,
lipothymias, and sensations of a "lump in the throat" and of
"blocked breathing". On encountering this nonspecific pattern,
the signs of neuromuscular hyperexcitability are of much
greater importance. Chvostek's sign must be sought
systematically. The sign is positive in 85% of cases examined.
Trousseau's sign, less sensitive than Chvostek's sign, is
observed only in cases of obvious hyperexcitability. The
hyperventilation test can complete the search for Chvostek's
sign and may give greater sensitivity to the Trousseau's sign
(Von Bonsdorff's test).
Neurophysiological tracings and routine Mg assessment (at
least plasma and red blood cell Mg; if possible evaluation of
Mg intake and daily magnesuria, calcemia, and calciuria) may
complete the clinical examination. However, the diagnosis of Mg
deficiency mainly requires an Mg oral loading test. The dose of
Mg to be administered is 5 mg/kg/day for at least 1 month. At
this physiological dose level, oral magnesium supplement is
totally devoid of the pharmacodynamic effects of parenteral
magnesium. Correction of symptoms by this oral Mg load
constitutes the best proof that they were due to Mg deficiency
and may represent the beginning of its treatment.
1,4,10
Psychiatric forms of Mg deficiency have been well
identified. Personality disorders are of the neurotic type. For
example the Minnesota Multiphasic Personality Inventory (MMPI)
finds a direct correlation between the "neurotic triad"
(hypochondria, depression, and hysteria) and the EMG marks of
NHE due to Mg deficiency.1,4 With all the
psychometric evaluations, and with the DSM III R interview
particularly, the clinical pattern induced through Mg
deficiency was always neurotic (for example: generalized
anxiety, panic attack disorders, and depression) but never
psychotic. Mg deficiency never induces
dementia.1,4,25,26 Although a neurosis pattern due
to Mg deficiency is frequently observed and simply cured
through oral physiological supplementation, neuroses are
preeminently conditioning factors for stress. Neuroses may
therefore very frequently produce secondary Mg depletion. They
require their own specific antineurotic treatment and not mere
oral Mg physiological supplementation, but both genuine forms
of neurosis due to primary neural Mg deficiency and Mg
depletion secondary to a neurosis may exist. These two
conditions may be concomitant and reinforce each other. In
these stressful patients it may be difficult to establish the
primacy of one or the other. In practice, physiological oral Mg
supplements may be added to psychiatric treatments, at least at
the start.1,10
It is imperative to emphasize that the nervous consequences
of Mg deficiency remain functional with anatomical integrity
for a long time. They are completely reversible since they can
be restored to normal with simple oral physiological Mg
supplementation,1,5,10 but it should also be pointed
out that a prolongation of untreated chronic Mg deficiency can
produce irreversible lesions1,5 with histological
changes: morphological changes in the rat hippocampus,
degeneration of the Purkinje cells, glial aberration of
positive Gomori cells, and neurovasculitis. When Mg deficiency
secondary to alcoholism was corrected, no alcoholic
encephalopathy was observed within a period of 5
years.1,5 These processes could account for the
clinical and paraclinical data that persist after treatment of
NHE due to Mg deficiency.1,5 They are especially of
concern during the early development of the nervous system. The
constitutional characteristics of the nervous forms of primary
chronic Mg deficiency could arise from undetected maternal Mg
deficiency.1,5 An early maternal Mg deficiency could
be the fountainhead of more severe impairments: sudden infant
death syndrome8,28 some forms of infantile
convulsions or psychiatric disturbances,1,5 and even
in adults, cardiovascular diseases and noninsulin-dependent
diabetes mellitus.28 The protocol of the multicenter
trials of maternal Mg physiological supplementation should be
followed not only on the mother, the fetus, and the neonate,
but also on the child throughout life from infancy to older
age.28
20.3 MAGNESIUM DEPLETION AND
DEMENTIAS
Although Mg deficiency might not result in dementia, some
types of Mg depletion can play a role in the physiopathology of
several types of dementia.
20.3.1 Experimental
Models of Mg Depletions
Various types of more or less severe Mg depletion are used:
genetic models (in rats and mice) and acquired models: either
secondary to an irreversible (or partially reversible) cause
(such as traumatic brain injury) or reversible. In the latter
case, the models associate a low Mg intake with diverse types
of Mg stress.10,22,23 Two types of experimental Mg
depletions will be highlighted because of their possible link
with dementia.
20.3.1.1
Neurological Degeneration Due to Al Load and Low Mg
Intake
Garden soil and drinking water in some Western Pacific
areas with high incidence of amyotrophic lateral sclerosis
and parkinsonism-dementia (ALS-PD) contain high
concentrations of polluting metals such as Al, Fe, and Mn,
and low concentrations of common metals such as Mg and Ca.
Decreased exposure to traditional sources of foodstuffs and
drinking water resulted in a dramatic decline in ALS-PD.
These data as well as the links between aluminum load,
magnesium status, and dialysis encephalopathy -- more
hypothetically, Alzheimer's disease -- highlight the interest
of corresponding experimental studies. With a high Al diet
alone, Al content in the nervous system in rats showed no
difference with a control group although serum Al was high.
No degenerative process was observed. However, with an
insufficient intake of Mg the same Al load induced an
increase in Al and Ca concentrations in the nervous system
and neurodegeneration with precipitation of insoluble
hydroxyapatites.28
20.3.1.2 Mg
Depletion Due to Kainic Acid Plus Mg Deficiency
Hippocampal injury of ageing may originate from an
increased calcium influx in pyramidal neurones resulting from
the deleterious effects of increased release of excitatory
aminoacids associated with a decrease of neuroprotective
factors. Kainic acid acting through its specific receptors
generates toxicity in the hippocampus, whereas Mg deficiency
- a model of accelerated ageing - decreases Mg
neuroprotection.23 In this model physiological Mg
supplementation and pharmacological doses of Na
acetyltaurinate were ineffective. On the other hand, Mg
acetyltaurinate at pharmacological doses had preventive and
curative effects in both the short and long
terms.23
These two types of experimental Mg depletion models may be
useful for screening various treatments of psychiatric
disturbances possibly linked with Al load and ageing
insults.21,23,29
20.3.2 Possible Links
Between Dementias and Mg Depletion
Established links between some types of dementias and Mg
depletion are presently scarce, but the experimental models of
two types of Mg depletion, perhaps related to the
physiopathology of some dementias, constitute promising tests
for screening potentially efficient drugs both in these Mg
depletions and in the related types of dementias.
20.4 THERAPEUTIC
IMPLICATIONS
It seems obvious to contrast the specific, easy, and efficient
treatment of the nervous form of Mg deficiency with the difficult
problems set by the treatment of certain types of Mg depletion
playing a possible role in the physiopathology of some
dementias.
20.4.1 Treatment of
Magnesium Deficiency
Physiological oral Mg supplementation (5 mg/kg/day) is
simple and can be carried out in the diet or with Mg salts. To
correct in vivo experimental or clinical Mg deficiency
all Mg salts have a comparable bioavailability, but evidently
their anions have their own importance. This treatment is
totally atoxic since it palliates Mg deficiency by simply
normalizing the Mg intake.1,10 It is able to cure
all the functional symptoms of Mg deficiency: signs of
neuromuscular hyperexcitability and psychiatric symptoms which
frequently mimic a neurotic pattern. It prevents irreversible
stigmata of NHE due to primary or secondary magnesium
deficiency, alcoholic encephalopathy in chronic alcoholism
particularly.1,5 It is necessary to highlight the
curative and preventive importance of oral physiological
maternal Mg supplementation, not only during pregnancy but also
in the child throughout life from infancy to older age, to
possibly prevent the so-called constitutional factor of
neurolability, some cases of sudden infant death syndrome,
infantile convulsions, or psychiatric diseases, and even in
adult cardiovascular diseases and noninsulin-dependent diabetes
mellitus.1,5,8,10,28
20.4.2 Magnesium Therapy
and Dementias
With perhaps the one exception of the treatment of autism
through very high pharmacological doses of vitamin B6 and high
doses of Mg1,5,10,25,30 we cannot presently control
the dysregulations of Mg status in Alzheimer's disease,
dialysis encephalopathy, and ALS-PD. We can only advise some
prophylactic measures. However, if an insufficient Mg intake
(i.e., Mg deficiency) would add up to depletion cases,
then an Mg deficit would be observed associating deficiency and
depletion. The correction of Mg deficiency through simple oral
supplementation therefore constitutes an adjuvant treatment of
this possible component of Mg deficit.1,10
In some cases, the interest of pharmacological Mg therapy
may be discussed. However, pharmacological Mg therapy may
induce toxicity since it creates Mg overload. High oral doses
of Mg (10 mg/kg/day) are advisable for chronic indications and
the parenteral route is suitable for acute indications. Mg
infusions can only be envisaged in intensive care units with
careful monitoring of pulse, blood pressure, deep tendon
reflexes, hourly diuresis, and electrocardiogram and
respiratory recordings. It is presently difficult to evaluate
the chronic toxicity of long-term high oral Mg doses: they may
bring latent complications which may reduce life
span.1,10 Neuromuscular hypoexcitability due to
hypermagnesemia only occurs when plasma Mg is more than twice
normal levels. The blood-brain barrier gives priority to the
peripheral action of Mg overload.1,10 In
vivo, this neuroprotection seems essentially indirect
through the beneficial effects on antithrombotic platelet and
endothelial functions and on vasospasm, mainly by acting as a
calcium antagonist.1,9,10 Except for a pathological
disruption of the blood-brain barrier, direct neuroprotection
is observed with massively increased plasma Mg which cannot be
practically carried out in human beings.10 In
experimental models, the best protective effects with
pharmacological doses of Mg were obtained with Mg
acetyltaurinate, an Mg salt of the N-acetylamino-derived
compound from taurine, the most neuroprotective inhibitory
aminoacid.21,23 Further study should evaluate its
clinical therapeutic effects.
20.5 CONCLUSION
Two different types of links between Mg deficit and the
nervous system should be emphasized.
1 . NHE due to Mg deficiency with neuromuscular and
psychiatric symptoms is well recognized nowadays. Induced by
insufficient Mg intake, the primary or secondary acute or chronic
nervous forms of Mg deficiency remain reversible over a long
period by simply normalizing the Mg intake. Untreated chronic
forms may however bring about irreversible organic disorders. The
psychiatric forms of Mg deficiency may fit into a neurotic
pattern, but never result in dementia.
2. In contrast, the relationships between some
types of Mg depletion due to various dysregulations of Mg status
and some dementias have not been clearly defined yet. However,
some epidemiological, experimental and clinical data are
promising and new paths remain open in this very interesting
field of neuroscience research.
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