Magnesium Research (1993) 6, 4, 379-394
Review paper
Magnesium and ageing. II. Clinical data: aetiological
mechanisms and pathophysiological consequences of magnesium
deficit in the elderly
1J. Durlach, 2V. Durlach,
3P. Bac, 4Y. Rayssiguier, 5M.
Bara, and 5A. Guiet-Bara
1SDRM, Hôpital St. Vincent-de-Paul, Paris,
France; 2Clinique Médical U62, Reims, France;
3Laboratoire de Physiopathologie du developpement,
Faculté de Pharmacie, Chatenay-Malabry, France;
4Laboratoire des Maladies Métaboliques, INRA,
Theix, France; 5Laboratoire de la Biologie de la
Reproduction, Université Pierre et Marie Curie, Paris,
France
Summary: Ageing constitutes a risk
factor for magnesium deficit. Primary magnesium deficit
originates from two aetiological mechanisms: deficiency and
depletion. Primary magnesium deficiency is due to insufficient
magnesium intake. Dietary amounts of magnesium are marginal in
the whole population whatever the age. Nutritional deficiencies
are more pronounced in institutionalized than in free-living
ageing groups. Primary magnesium depletion is due to
dysregulation of factors controlling magnesium status: intestinal
magnesium hypoabsorption, reduced magnesium bone uptake and
mobilization, sometimes urinary leakage,
hyperadrenoglucocorticism by decreased adaptability to stress,
insulin resistance and adrenergic hyporeceptivity. Secondary
magnesium deficit in ageing largely results from various
pathologies and treatments common to elderly persons,
i.e., non-insulin dependent diabetes mellitus and use of
hypermagnesuric diuretics.
Magnesium deficit may participate in the clinical
pattern of ageing, particularly in neuromuscular, cardiovascular
and renal symptomatologies. The consequences of
hyperadrenoglucocorticism- the simplest marker of which is
non-response to the dexamethasone suppression test - may include
immunosuppression, muscle atrophy, centralization of fat mass,
osteoporosis, hyperglycaemia, hyperlipidaemia, atherosclerosis,
and disturbances of mood and mental performance through
accelerated hippocampal ageing particularly. It seems very
important to point out that magnesium deficit and stress
aggravate each other in a true 'pathogenic vicious circle',
particularly in the stressful state of ageing. The importance of
magnesium deficit in the aetiologies of insulin resistance, and
the adrenergic, osseous, oncogenic, immune and oxidant
disturbances of ageing is still uncertain. Oral physiological
magnesium supplementation (5 mg Mg/kg/d) is the best diagnostic
tool for establishing the importance of magnesium deficiency. Too
few open and double blind studies on the effects of the treatment
of magnesium deficiency and of magnesium depletion in geriatric
populations have been done. Further study is necessary to assess
the true place of magnesium deficit in the pathophysiology of
ageing.
Keywords: Magnesium, ageing,
stress, oxidation, neuromuscular system, cardiovascular system,
kidney, bone, immunity, calcium, longevity, hippocampus,
hypothalamus, neurotoxicity, neuroplasticity, pituitary,
glucocorticoid, insulin, catecholamines, taurine, kainic acid,
dyslipidaemias, fibrinogenaemia, albuminaemia, oxidative stress,
antioxidant systems.
Introduction
The importance of magnesium in the pathophysiology of ageing
has been evaluated very differently by different
investigators.
Enthusiasts such as P. Delbet1 have seen in
magnesium a sort of panacea which may play the role of elixir
vitae in preventing all the hazards of senility.
Intellectual functions, sexual potency and skin quality are all
stimulated by oral magnesium supplementation alone.
On the other hand, various recent general reviews concerning
nutrient requirements and electrolytic abnormalities in the
elderly2-6 have entirely overlooked certain data
concerning magnesium status during ageing!
Between these two extremes, it is now possible to find a
balance. It seems to be well established that magnesium does not
constitute an elixir vitae. Conversely magnesium deficit
may play a role in the pathophysiology of ageing7-10.
This clinical notion relies on a substantial experimental
background, starting with the seminal paper by O. Heroux et
al. (1977) which showed that chronic marginal magnesium
deficiency reduced lifespan in rats11. Magnesium
deficit accelerates ageing through its various effects on the
neuromuscular, cardiovascular and endocrine apparatus, kidney and
bone, immunity, antistress and anti-oxidant
systems7-10,12.
The aim of the present review is to analyse successively the
aetiological mechanisms of magnesium deficit in ageing, its
physiopathological consequences, and lastly, the importance of
its treatment in elderly patients.
Aetiological mechanisms of magnesium deficit in ageing
Both primary and secondary magnesium deficits should be split
into magnesium deficiency and magnesium
depletion.
Magnesium deficiency is due to insufficient magnesium intake;
in animal experimentation, it constitutes the relevant model of a
magnesium deficient state. It merely requires oral physiological
magnesium supplementation. In developed countries, the marginal
magnesium intake induces a high prevalence of primary marginal
magnesium deficiency in human beings7,13-17.
Magnesium depletion is related to a dysregulation of the
control mechanisms of magnesium metabolism: either failure of the
mechanisms which ensure magnesium homeostasis or intervention of
endogenous or iatrogenic factors disturbing magnesium status.
Magnesium depletion requires more or less specific correction of
its causal dysregulation.
Ageing may induce both these types of magnesium deficit,
deficiency and depletion even though they both originate from
primary or secondary causes.
Primary magnesium deficiency of ageing
In developed countries, magnesium intake is marginal
throughout the entire population whatever the age: around 4
mg/kg/day instead of the 6 mg/kg/day recommended to maintain
satisfactory balance7,13-18. The high prevalence of
the marginal magnesium deficiency in 15-20 per cent of the
population seems consistent with the estimation of nutrient
deficiency using probability analysis13-16. These data
are particularly relevant to the health of aged
persons3,4,19. However, the elderly population is
extremely heterogeneous: diseases, handicaps, physical or
psychological impairments expose individuals to more severe
nutritional deficiencies3,4,19,20. Thus marginal
magnesium deficiency is observed in elderly people as well as in
the general population7,8,10,13,17,18,21-23, and in
free living ageing groups24, 33 as well as in
institutionalized elderly patients, although more pronounced in
the latter24,34-40, whatever countries are considered,
America, Australia or Europe. A positive correlation between
energy intake and magnesium intake is always
observed7,8,10,13-16,23,26.
Primary magnesium depletion of ageing--metabolic
dysregulations
Magnesium depletion is due to dysregulation of factors
controlling magnesium metabolism, either effectors (intestinal
absorption, bone storage and urinary excretion) or controls
(mainly neurohormonal controls of magnesium status, in particular
neuroendocrine metabolic alterations which intervene during
stress reaction and which may induce magnesium
depletion)41.
In the human, magnesium absorption decreases with age. Around
the age of seventy it becomes two-thirds of what it usually is at
around the age of thirty8-10, 17, 18. Exchangeable
pools of magnesium are reduced in elderly
patients42.
In particular cases, urinary magnesium leakage may be
increased 8-10,43, but usually urinary magnesium
excretion decreases or remains normal.
Hyperadrenoglucocorticism through decreased adaptability
to stress
Among the biological bases of ageing, it seems particularly
important to highlight the fact that senescence appears to be a
condition of decreased adaptability to stress4,44.
Selye et al. (1976) suggested in a seminal paper that
the cause of age-related phenomena resided in the progressive
breakdown of the neuroendocrine system which intervenes under
stress: humans are born with a fixed quantity of 'adaptative
energy' which is progressively reduced along with repeated
exposure to stressing factors45.
This clinical observation of a decreased adaptability to
stress due to ageing relies now on a rich and well-defined animal
experimental background. The age-related alterations in brain
function particularly concern the hippocampal pyramidal neurones.
This part of the limbic system exerts an inhibitory influence on
the activity of the hypothalamo-pituitary-adrenal axis.
Hippocampal ageing induces a state of hyperglucocorticism. Target
cells for glucocorticoids are more highly concentrated in the
hippocampus than in any other brain region. Excess corticoid
receptor activation mediates neuronal degeneration through an
increased influx of calcium into the cells induced by a
deleterious increased release of excitatory amino acids - such as
kainic acid - associated with a decrease of protective inhibitory
amino acids - such as glycine, GABA and taurine. This new
hippocampal injury could in turn provoke a new imbalance of the
hypothalamo-pituitary-adrenal axis with a 'glucocorticoid
cascade' inducing a state of hyperadrenoglucocorticism. The
hippocampus is therefore a prime target area for investigation of
the events which accompany stress and in particular for the
regulation of stress-induced corticosteroid secretion. But the
hippocampus is also a basic structure for social life, being
involved in mood regulation, control of internal inhibition,
memory and learning. Long term potentiation of synaptic
transmission in the hippocampus appears as its privileged
investigation tool46-61. The differences between
normal physiological ageing processes and pathological brain
ageing processes may result from ageing-associated susceptibility
factors49,50 : genetic predispositions, infections
agents, environmental toxins or nutritional disorders. Magnesium
deficit could be one of these ageing-associated susceptibility
factors, particularly through: [1] the vicious circle initiated
between magnesium and stress41; [2] the relation
between magnesium and neuroplasticity62,63; and [3]
the links between magnesium and the hippocampus. These links have
been observed both in vitro64 and at
pharmacological doses65 but only once in vivo
on a physiological model66. Further experimental
research is necessary to evaluate the importance of this
hypothesis using, for example, either the model of hippocampal
ageing accelerated by chronic stress49 or the kainic
acid model47,61 under deficient or high magnesium
diet. With this latter experimental model in rats various
magnesium salts were used in order to increase the magnesium
intake. Their effects were subsequently compared according to
their respective anions as had been done previously with the
model of androgenic seizures in mice67. The best
protective effects were obtained with magnesium acetyl taurinate
which constitutes a powerful combination of taurine, the most
neuroprotective inhibitory amino acid55-59,64,67, and
of magnesium64,67,68. This impressive animal
experimental background on the alterations in stressor reactions
due to ageing show the importance of the clinical markers in the
failure of adaptability to stress in elderly patients.
Several clinical observations confirm the frequency of
hyperadrenoglucocorticism in ageing. Static investigations of
glucocorticoid may seem contradictory. Basal plasma
concentrations of glucocorticoids, whether measured as
17-hydrocorticosteroids as in the past, or now as immunoreactive
cortisol, have been found to show no change with age69,
70, to be increased in older men69 or to be
increased in the overall aged population44. The
highest cortisol values are observed in the stroke subgroup. A
significant positive correlation between age and log basal
cortisol levels has been found in the entire population as well
as in each group, whether healthy, or with dementia of
Alzheimer-type, or with stroke. Since the slopes of the
regression lines did not differ significantly, analysis of
covariance was carried out which showed a significant increase in
log basal cortisol levels with the age of patients (P < 0.001)
whatever the type of pathology44. In a study without
modification in the basal cortisol levels, a pronounced sex
difference existed in urinary cortisol excretion, men having
higher value69.An indirect proof of age-related
hypothalamic alteration may rely on the disruption of circadian
rhythm for plasma cortisol in elderly
subjects71-75.
The best proof of the association with ageing between
decreased hypothalamo-pituitary sensitivity and negative feedback
regulation by glucocorticoid relies on dynamic investigation, and
mainly on the dexamethasone suppression test. Older subjects in
all diagnostic categories (normal ageing, dementia, depression)
have higher post-dexamethasone plasma cortisol levels. A chronic
stressful state is characteristic of the ageing process. The
increased stress susceptibility is closely related to the ageing
process itself and not so much to any particular age-related
pathological conditions such as depression or
dementia44,69,76,77. The central alterations of
glucocorticoid receptors in the hippocampus of aged animals may
be mirrored in mononuclear leucocyte corticosteroid receptors; in
the human, the mean number of type I and type 11 corticosteroid
receptors in mononuclear leucocytes was significantly lower in
aged subjects. This situation probably represents a concomitant
of the normal ageing process78. Analysis of the
effects of corticotropin releasing hormone (CRH) on the aged
hypothalamo-pituitary-adrenal axis compared with those of
dexamethasone confirmed a stepwise decrease in corticotropic
sensitivity to the negative feedback signal leading to positive
glucocorticoid feedback, an enhanced cosecretion of ACTH
secretagogues such as vasopressin or a combination of
both79 Lastly, the responses of plasma ACTH, cortisol
and dehydroepiandrosterone to CRH in healthy ageing men are
compatible with two hypothesis: (1) a diminished sensitivity of
ACTH secretion to negative feedback regulation by glucocorticoid
in elderly subjects; (2) an ACTH-independent age-related
diminution in adrenal androgen secretion, with preserved
glucocorticoid secretion. These alterations in the adrenal
biosynthesis of steroids favour cortisol
production69.
It is now well established that ageing represents a chronic
stressful state. This dysregulation may constitute an important
factor in magnesium depletion in elderly subjects41
and act through heterogeneous mechanisms. As in animal
experiments where dysregulation of the
hypothalamopituitary-adrenal axis varies according to species,
strains and gender51, in humans it may have different
targets: i.e. CRH, AVP, ACTH, or the binding and
secretion of glucocorticoids69-79. Among its
consequences, hyperglucocorticism may be one of the main
non-genetic factors of secondary insulin
resistance80-86 in elderly subjects.
Insulin resistance
Carbohydrate intolerance develops as part of the ageing
process. Its appears to be the consequence of peripheral
resistance caused by a postreceptor defect in target insulin
action. There is no effect of age on insulin receptor number and
affinity on circulating monocytes. If it is possible that
monocyte insulin receptors fail to mirror insulin receptors in
other important target tissues, this post-receptor defect in
target insulin action in aged men agrees with previous reports in
elderly rodents of effects on various insulin
receptors10,87-90. This post-receptor impairment of
insulin action is of the same type as secondary cortisol-induced
insulin resistance in man80-86.
Magnesium appears to be a second messenger for insulin.
Insulin resistance working through hyperinsulinaemia may induce a
shift between extracellular and intracellular compartments. Thus
insulin resistance in ageing might be a factor of extracellular
magnesium depletion91-93. Therefore it appears very
important to evaluate insulin sensitivity. The reference method
is the euglycaemic hyperinsulinaemic clamp technique, but is an
expensive and time consuming tool. In clinical practice, and in
geriatrics particularly, a simple insulin tolerance test
(intravenous bolus of 0.1 IU/kg of regular insulin, with glucose
sampling at -5, 0, 3, 5. 7, 10 min.) could be an easy, quick and
low cost method to evaluate insulin
resistance94-95.
Adrenergic receptor hyporeceptivity
Ageing induces peripheral and central hypoactivity of
adrenergic receptors96,97. This decreased sensitivity
may modify magnesium movements through the cell membrane seem
linked with adrenergic receptors, in particular, which might be
atypical98.
To sum up, primary magnesium deficit in ageing represents the
combination of magnesium deficiency due to insufficient intake
and magnesium depletion induced by various mechanisms including
intestinal malabsorption, reduced bone uptake and mobilization,
increased urinary losses, chronic stress, insulin resistance and
hypoadrenergic receptivity.
However, the pathological aspects of ageing must also be
considered in relation to secondary magnesium deficit.
Secondary magnesium deficit of ageing
Elderly patients are susceptible to illness predisposing to
two types of magnesium deficit: either pathological magnesium
deficit induced by disease or iatrogenic magnesium deficit due to
the side effects of medical treatments.
Pathological secondary magnesium deficit of
ageing
Among the various diseases which may induce secondary
magnesium deficit99 and which are frequently observed
in elderly subjects, diabetes mellitus is one of the main causes
of magnesium depletion10. Insulin resistance in ageing
appears as a first step before non-insulin-dependent
diabetes54,90,100. When glucose tolerance becomes
impaired in older subjects a significant negative correlation may
be observed between plasma and/or erythrocyte magnesium
concentrations, fasting blood sugar and basal insulinaemia
7,10,40,43,92,101-104. The causes of diabetic
magnesium deficit are extremely complex. Magnesium deficiency due
to an insufficient intake may only represent an adjuvant
mechanism of diabetic magnesium deficit which can be treated by
simple oral physiological supplementation. The major magnesium
problem in diabetes is a typical depletion-type magnesium
deficit. Its treatment is very difficult and requires the
correction of complex mechanisms which are either pathological
(disturbances of insulin levels and effects, endogenous deficit
of endogenous vitamin D, deficiency of vitamin B-6, taurine loss)
or iatrogenic, for example, high doses of insulin and
biguanides7,92,104. Alcohol addiction and cigarette
smoking constitute two other factors in magnesium deficit in
elderly subjects7,10,40. Among the complex mechanisms
of magnesium deficit secondary to chronic alcoholism it is
important to stress reduced magnesium intake105.
Iatrogenic secondary magnesium deficit of ageing
Iatrogenic secondary magnesium deficit is especially important
as there is an overconsumption of drugs among aged
patients106. Let us quote, for example, magnesium
depletion due to the use of diuretics. Long term treatment with
loop diuretics rather than thiazides may induce magnesium
depletion due to an excess urinary loss7,10,99.
Thus, through primary and secondary magnesium deficiency and
depletion, ageing constitutes one major risk factor for magnesium
deficit8-10,22,107.
Pathophysiological consequences of magnesium deficit
in ageing
Numerous well documented experimental animal studies have
shown that magnesium deficiency may bring about stigmata of
accelerated ageing in various organs and
systems7-12,67,91,108-132.
Clinical and paraclinical consequences of chronic
magnesium deficit in ageing
Whatever the age, clinical forms of chronic magnesium deficit
are polymorphous and without specificity, but the clinical and
paraclinical consequences on the nervous system should be studied
first7,133-135. Subjective symptomatology includes
non-specific central, peripheral and autonomic manifestations.
Central symptoms seem largely 'neurotic': anxiety,
hyperemotionality, fatigue, headaches, insomnia,
light-headedness, dizziness, nervous fits, sensation of 'a lump
in the throat', 'nuchalgia' and 'blocked breathing'. Peripheral
signs are common: acroparathesiae, cramps, myalgias. Functional
disorders include chest pain, sine materia dyspnoea,
precordialgia, palpitations, extrasystoles, dysrhythmias and
Raynaud's syndrome. The dysautonomic disturbances involve both
the sympathetic and parasympathetic nervous systems causing
orthostatic hypotension or borderline hypertension. In elderly
patients hyperemotivity, tremor, asthenia, sleep disorders and
amnesic and cognitive disturbances are particularly important.
Chronic magnesium deficit may be associated with benign senescent
forgetfulness, but not with malignant senescent forgetfulness
usually associated with cognitive functional alterations10,
136. On physical examination one should systematically look
for a genuine Chvostek sign as well as a non-ejection systolic
click or a mid-to-end systolic or parasystolic murmur. An
electromyogram is useful to look for repetitive tetanic stigmata
and an echocardiogram to define mitral valve prolapse. In
cardiovascular and renal forms of magnesium deficit, various
magnesium-dependent changes may be sought, for example the blood
lipid profile, basal glycaemia and insulin sensitivity, albumin,
fibrinogen, and in the urine creatinine and microalbuminuria.
These classical data should be supplemented by investigations of
oxidative stress such as malonedialdehyde and thiobarbituric acid
reactive substances and of various magnesium-dependent elements
of the antioxidant systems, i.e. taurine, reduced
glutathione, glutathione-peroxidase, Se, vitamin A, vitamin
E7-10,12,41,58,87-95,132 and by studies on adrenergic
receptivity9,10,124,138. The consequences of
hyperadrenoglucocorticism caused by decreased adaptability to
stress44,69-79 seem to be of particular importance in
elderly people and may play a major role in a number of metabolic
and degenerative changes observed during ageing, for example
immunosuppression, muscle atrophy, centralization and
internalization of the fat mass, osteoporosis, hypercalcaemia,
hyperglycaemia, hyperlipidaemia, arteriosclerosis, and
disturbances in mood and mental performance46,51. This
hyperglucocorticism may be the key of the reduced fat-free lean
mass induced by ageing, associated with a gradual but persistent
increase of fat mass with a shift in fat disposition pattern;
this is one risk factor137-139 for diabetes and
cardiovascular diseases. It seems important to point out that
magnesium deficit and stress aggravate each other in a true
'pathogenic vicious circle'41 which is particularly
important in the stressful state of ageing.
Today, it appears difficult to assess the importance of
magnesium deficit in the development of insulin resistance in
ageing. Experimental and clinical data showed that magnesium
deficit could bring about either diabetogenic or insulinlike
effects91,92,104. For example in vitro and
ex vivo data in rats showed that insulin receptor
activity was decreased140,141 both during ageing and
during magnesium deficiency. But conversely in marginal magnesium
deficiency in rats slightly enhanced peripheral insulin
sensitivity was observed!142. Paolisso's studies in
the human103, because of several biases, fail to
substantiate the notion of insulin resistance in
ageing10,102.
There is much controversy about the role of magnesium deficit
in the pathophysiology of senile
osteoporosis7,8,10,143, in immunodepression of aged
persons7-10,123 and in oncology10,117. The
fact that there are normal subcellular concentrations of
magnesium in benign nodular hyperplasia of the human prostate
does not suggest that magnesium plays a part in this
process144. In pseudo-allergic and allergic
conditions, plasma IgE, histamine and acetylcholine
hyperreceptivity may be investigated7.
Indices of magnesium deficit in ageing
Static extracellular and intracellular magnesium
concentrations
The intracellular location of nearly all of the magnesium
stores makes evaluation of changes in the magnesium pool
difficult. Anomalies of intracellular or extracellular magnesium,
whatever the age of the individual, provide less proof of a
precise disturbance in the magnesium pool than does evidence of
an anomaly in magnesium metabolism133,145,146.
Plasma and erythrocyte magnesium concentrations are usually
normal, sometimes decreased, sometimes
increased24,147-158. These discrepancies seem to
depend mainly on the heterogeneity of the mechanisms inducing
magnesium deficit and of the alterations in renal function due to
ageing. They may also be due to the effects of illness.
One study alone has shown a decrease in lymphocyte
magnesium159. The lowering of magnesium (and
potassium) concentrations in skeletal muscle might only mirror
inactivity10,159-161. However, the same alterations
are also observed in the myocardium161. Daily
magnesuria is most often reduced158,162,163 in
relationship with an insufficient magnesium intake (and sometimes
with renal failure). But it may also be increased164,
because of an age-related increase in serum ultrafiltrable
magnesium concentration 165, and also through the
influence of pathological and iatrogenic
factors7,10,43,99,151,166. A massive decrease in brain
magnesium was described by P. Delbet1 in association
with a decrease in cerebrospinal fluid magnesium
concentration165. However, recent data do not support
the view that there is a decrease in brain magnesium due to
ageing167.
In the particular case of Alzheimer's disease a significant
decrease in intracellular magnesium deposits in hippocampal
neurones was observed168, 170 and signs of altered
magnesium distribution were shown in disturbed leucocyte
magnesium concentrations171. But this specific
hippocampal magnesium deficiency contrasts with the remarkable
stability of magnesium concentration in nervous tissue observed
during experimental magnesium deficiency in
rats111,120. Alterations of albumin might be the
origin of this hippocampal depletion168,170.
To sum up, a decrease of any magnesium concentration does not
alone constitute a marker of a deficit in the magnesium pool but
simply highlights the existence of some disturbance of magnesium
metabolism. In magnesium deficiency, the typical model of which
is represented both in animal experiments and in humans by
insufficient magnesium intake, the specific correction by
physiological magnesium supplements of a symptomatology will be
the most convincing evidence of the causal role of magnesium in
the aetiopathogenesis of this deficiency. In magnesium depletion
forms of deficit linked to dysregulation of magnesium status, the
diagnosis relies on regression of the dysfunction when it is
accessible to effective treatment - in parallel with the
symptomatology145.
Dynamic Investigations of magnesium
status
Loading tests easily allow a diagnosis of magnesium deficiency
to be made whereas diagnosing magnesium depletion is difficult
since it requires identification and possible subsequent control
of the mechanisms of the dysregulation7,133,145.
Oral physiological magnesium load test
Effect of oral physiological magnesium supplementation (5 mg
Mg/kg/day) is the best tool for establishing the importance of
magnesium deficiency in the pathophysiology of ageing. Its
effects on extracellular and intracellular indices of magnesium
status and on all the nonspecific clinical and paraclinical items
need to be assessed7,10,133,145.
Parenteral magnesium load test
This is the quickest tool for diagnosing magnesium deficiency,
but it can only be carried out on magnesium indices, since
non-specific clinical and paraclinical indices are modified by
the pharmacological effects of parenteral
magnesium7,133,145. It has been used in
ageing154,156,157 to evaluate the importance of
magnesium deficiency. It seems, however, difficult to carry out
in the elderly because of bone and kidney alterations due to
ageing, and difficulties in obtaining accurate urine samples.
This test thus appears to be of limited value in older
subjects10,154.
Dynamic investigations of magnesium
depletion
The diagnosis relies on the specific correction of the
dysregulating factor5 of magnesium status which
induces magnesium depletion and of the symptomatology generated
by this magnesium depletion.
Dynamic investigation is difficult because the dysregulation
is often difficult to identify and even sometimes not accessible
to effective control7,10,145.
Treatment of the magnesium deficit in ageing
Whatever the age of the patient, the treatment of magnesium
deficit is easy with magnesium deficiency and difficult with
magnesium depletion. Secondary forms evidently require their own
specific treatments7,172.
Control of magnesium deficiency
This requires simple oral physiological magnesium
supplementation (5 mg Mg/kg/day). Supplementation should be
achieved using a high magnesium density nutrient13-15.
Magnesium bioavailability depends on physico-chemical factors
(hexahydrated crystallized form)7,112 and on the
selected anion173-176. Vegetarian
diets28,177,178 result in high and efficient magnesium
intakes but the causes of their beneficial effects may not be
limited to their magnesium content only. Magnesium supplements
may be also provided by magnesium in water, whether in its
natural form - from the tap or bottled or in an artificial form
by addition of a soluble magnesium salt to ordinary
water7,13-15,112,172.179.
Control of magnesium depletion
This is most often difficult. It would be highly desirable to
specifically treat the aetiological mechanisms of magnesium
depletion. Sometimes this is possible; for instance a diuretic
inducing hyper-magnesuria and insulin resistance can be replaced
by a magnesium-sparing diuretic, by a partial magnesium analogue
such as a calcium antagonist i.e. verapamil, or by a
sulphydryl-containing angiotensin converting enzyme inhibitor,
i.e. captopril172,180.
The reduced adaptability to stress in the elderly might be
improved with [1] tricyclic tianeptine, mainly effective on the
hippocampus54,181,182, [2] sodium valproate, which can
decrease ACTH secretion172,183 (both acting at a
pharmacological level), and [3] a combination of taurine and
magnesium which could be active at a physiological
level55-59,62-68. It is often difficult to do more
than provide a specific control of magnesium depletion, either by
pharmacological decrease in a possible hypermagnesuria, or by
physiological doses of vitamin D, or by pharmacological doses of
vitamin B-6; physiological antioxidants such as vitamin E,
vitamin C, vitamin A, sulphur, amino acids, reduced glutathione
and selenium can also be used172.
Urinary infection constitutes a transient contraindication to
magnesium therapy: magnesium creates the risk of precipitating
ammonium-magnesium-phosphates. There is only one absolute
contraindication to magnesium therapy: overt renal
insufficiency10, 172.
Therapeutic magnesium trials in ageing
Open and double-blind trials of the treatment of magnesium
deficit in geriatric populations are presently scarce. Since the
early paper by Delbet1, multiple open studies have
shown the beneficial effects of magnesium in the
elderly1,10,43,150,184.
Some double-blind studies have, however, recently been
conducted, one concerning psychic symptomatology using various
psychometric evaluations185, another dealing with
electrolytic disturbances186, and lastly, two studies
related to plasma lipid profile187 and glucose
intolerance103,187.
Various recent studies have shown the effectiveness of
magnesium supplementation in several atherogenous
dyslipidaemias189,189. Oral physiological magnesium
supplementation is effective in these cases if there is magnesium
deficiency, but not otherwise190.
Pharmacological use of bolus doses or infusions of parenteral
magnesium in acute myocardial infarction does not require a
pre-existing alteration in the magnesium status to induce
beneficial effects. It seems particularly well tolerated, perhaps
because of a background of magnesium deficit due to ageing. Since
older patients are unsuitable candidates for thrombolytic
therapy, magnesium therapy could be a welcome alternative therapy
for acute myocardial infarction188,191.
Conclusion
Ageing constitutes a risk factor for magnesium deficit.
Primary magnesium deficit of the elderly originates from two
aetiological mechanisms: deficiency and depletion.
Primary magnesium deficiency is due to insufficient magnesium
intake. Dietary intakes of magnesium are marginal in the whole
population at whatever age. Nutritional deficiencies are more
pronounced in institutionalized than in free-living ageing
groups.
Primary magnesium depletion is due to dysregulation of factors
controlling magnesium metabolism: intestinal magnesium
hypoabsorption, reduced bone magnesium uptake and mobilization,
sometimes urinary losses, decreased sensitivity to negative
feedback regulation by glucocorticoid-inducing
hyperadrenoglucocorticism, insulin resistance and adrenergic
hyporeceptivity. Secondary magnesium deficit of ageing depends
largely on various pathologies and treatments common to elderly
persons: i.e. non insulin-dependent-diabetes mellitus
and the use of hypermagnesuric diuretics.
Magnesium deficit may participate in the clinical pattern of
ageing - neuromuscular, cardiovascular and renal symptomatologies
mainly. The consequences of hyperadrenoglucocorticism may concern
immunosuppression, muscle atrophy, centralization of the fat
mass, osteoporosis, hyperglycaemia, hyperlipidaemia,
arteriosclerosis, and disturbances of mood and mental
performance, through accelerated hippocampal ageing particularly.
It seems very important to point out that magnesium deficit and
stress aggravate each other in a true pathogenic vicious circle,
particularly harmful in the stressful state of ageing. The
importance of magnesium deficit in the aetiology of insulin
resistance, adrenergic, osseous, oncogenic, immune and oxidant
disturbances of ageing is still uncertain. Oral physiological
magnesium supplementation is the best diagnostic tool for
establishing the importance of magnesium deficiency. Too few open
and double-blind studies of the effects of treatments of
magnesium deficiency and of magnesium depletion in geriatric
populations have been done. Further study is necessary to assess
the accurate place of magnesium deficit in the pathophysiology of
ageing.
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