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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.


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.


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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145. Durlach, J. (1988): Methods of evaluating magnesium status. In: Magnesium in clinical practice, ed. J. Durlach, pp. 40-60. London: John Libbey.

146. Clemens, R.A. & Brown, R.C. (1986): Biochemical methods for assessing the vitamin and nutritional status of the elderly. Food Technol. 40, 71-81.

147. Henrotte, J.G. & Durlach, J. (1971): Magnésium et biométrie humaine. In: ler Symposium International sur le Déficit Magnésique en Pathologie Humaine I. Vol. des rapports, ed. J. Durlach, pp. 91-110. Vittel: SGEMV.

148. Landahl, S., Graffner. C., Jagenburg, R., Lunbborg, P. & Steen, B. (1980): Prevalence and treatment of hypomagnesemia in the elderly. Studies in a representative 70 year-old population and in geriatric patients. Aktuel Gerontol. 10, 397-402.

149. Welsh, D.W. & Ash, 0. (1984): Adult references interval for 12 chemistry analyses: influence of age and sex. Am. J. Clin. Pathol. 81, 71-76.

150. Leszek, G. & Del Campo, O. (1985): Role of magnesium in the dietotherapy of degenerative diseases. Importance of magnesium supplementation of diets of elderly patients. In: Magnesium deficiency: pathophysiology and treatment implications eds. M.J. Halpern & J. Durlach, pp. 239-243. Basel, New York: Karger.

151. Sherwood, R.A., Aryanagagam, P., Rocks, B.F. & Mandikar. G.D. (1986): Hypomagnesium in the elderly. Gerontology 32, 105-109.

152. Gueux, E., Duchene-Marullaz, P & Rayssiguier, Y. (1988): Plasma and erythrocyte magnesium levels in a French population. Magnes. Bull. 10, 77-80.

153. Yang, X.Y., Hossein, J.M., Ruddel, M.E. & Elin, R.J. (1990): Blood magnesium parameters do not differ with age. J. Am. Coll. Nutr. 9, 308-313.

154. Martin, B.J. (1990): The magnesium load test: experience in the elderly. Ageing2, 291-296.

155. Martin, B.J., Black, J. & McLelland, A.S. (1991): Hypomagnesemia in elderly hospital admissions: a study of clinical significance. Q. J. Med. 78, 177-184.

156. Martin, B.J., Lyon, T.D.B., Walker, W. & Fell, G.S. (1993): Mononuclear blood cell magnesium in older subjects: evaluation of its use in clinical practice. Ann. Clin. Biochem. 30, 23-37.

157. Cohen, L. & Kitzes, R. (1992): Characterization of the magnesium status of elderly people by the Mg tolerance test. Magnes. Bull. 14, 133-134.

158. Gullestad, L., Nes. M., Ronneberg, R., Midtvedt, K., Falch, D. & Kjekshus, J. (1994): Magnesium status in healthy free-living elderly Norwegians. J. Am. Coll. Nutr. (in press).

159. Tsunematsu, K., Tanuma, S. & Sakuma, Y.(1987): Lymphocyte Mg values in Japanese determined by microanalysing methods. J. Jpn Soc. Magnes. Res. 6, 33-43.

160. Durlach, J.(1982): Skeletal muscle adaptation to ageing and to respiratory and liver failure. Acta Med. Scand. (Suppl.) 654, 1-40.

161. Martin, B.J., Lyon, T.D.B. & Fell, G.S. (1991): Comparison of inorganic elements from autopsy tissue of young and elderly subjects. J. Trace Elem. Electrolytes Health Dis.5, 203-211.

162. Hesse, A., Classen, A., Knoll, M., Timmermann, F. & Valensieck, W. (1986): Dependence of urine composition on the age and sex of healthy subjects. Clin. Chim. Acta 160, 79-86.

163. Lôwik, M.D., Schrijver, J., Odink, J., Van Denberg, H., Wedel, M. & Hermhs, R.J.J. (1990): Nutrition and ageing: nutritional status of 'apparently healthy' elderly (Dutch nutrition surveillance system). J. Am. Coll. Nutr. 9, 18-27.

164. Nicolau, Y., Haus, E., Lakatua, D., Bogdan. C., Petrescu, E., Robu, E., Sackett-Lundeen, L. & Swoyer, J. (1985): Chronobiologic observations of Ca and Mg in the elderly. Endocrinologie 23, 39-53.

165. Nishimuta, M., Ono, K., Kodema, N.. Hattori, M., Tominaga, I., Hiraoka, A. & Miura, I. (1989): Age related increase in serum ultrafiltrable Ca and Mg in human. Magnes. Res.2, 129.

166. Nishimuta, M., Kodama, N. & Ono, K. (1989): Magnesiumuresis by risk factors for chronic degenerative diseases. In: Magnesium in health and disease, eds. Y. Itokawa & J. Durlach, pp. 279-284. London, Paris: John Libbey.

167. Hershey, C.O.. Hershey L.A., Wongmongkolrit T., Vames A.W. & Breslau D. (1985): Trace element content of brain in Alzheimer disease and ageing. Trace Elem. Med. 2, 40-43.

168. Durlach, J. (1990): Magnesium depletion and pathogenesis of Alzheimer's disease. Magnes. Res. 3, 217-218.

169. Glick, J.L. (1991):Proposed mechanism for alteration of albumin structure and function in Alzheimer's disease. J. Theor. Biol. 148, 283-286.

170. Glick. J.L, (1990): Use of magnesium in the management of dementias. Med. Sci. Res.18, 831-833.

171. Borella, P., Giardino, A., Neri, M. & Anderma-Ker, E. (1990): Magnesium and potassium status in elderly subjects with and without dementia of the Alzheimer type. Magnes. Res.3, 282-289.

172. Durlach, J. (1988): Magnesium and therapeutics. In: Magnesium in clinical practice, ed. J. Durlach, pp. 217-246. London: John Libbey.

173. Bara, M., Guiet-Bara, A. & Durlach, J. (1988): Modification of human amniotic membrane stability after addition of magnesium salt. Magnes. Res. 1, 23-28.

174. Bara, M., Guiet-Bara, A. & Durlach, J. (1988): Analysis of membraneous effects: binding and screening. Magnes. Res. 1, 29-34.

175. Schmidbaur, H., Classen, H.G. & Helbig, J. (1990): Asparagin- und glutaminsaure als Liganden fur Alkaliund Erdalkali-metalle: Strukturchemische Beitrage zum Fragencomplex der Magnesiumtherapie. Angew. Chem. 102, 1122-1136.

176. Durlach, J., Durlach, V., Bara, M. & Guiet-Bara, A. (1992): A new method of in vitro pre-screening evaluation of several Mg salts. Meth. Find. Exp. Clin. Pharmacol.14, 305-310.

177. Singh, R.B. (1990): Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. Magnes. Trace Elem. Res. 9, 143-151.

178. Durlach. J. (1992): Almonds, monounsaturated fats magnesium and hypolipidemic diets. Magnes. Res. 5, 315.

179. Hese A., Weber A. & Miersch, W.D. (1988): Magnesium-Substitution durch Minerali-vasser. Therapie-Woche 38, 2510-2513.

180. Freedman, A.M., Cassidy, M.M. & Weglicki, W.B. (1991): Captopril protects against myocardial injury induced by magnesium deficiency. Hypertension 18, 142-147.

181. Jaffard R., Mocaer E., Lebrun C. & Beracoche A. (1991): Effets de la tianeptine sur l'apprentissage et la mémoire chez la souris. Amélioration de certains déficits induits par l'alcoolisation chronique et le vieillissement cérébral. Presse Med. 20, 1812-1816.

182. Delbende, C., Delarue, C., Lefebvre, H., Tranchand-Bunel, D., Sfafarezyk, A., Mocaer, E., Kamoun, A., Segou, S. & Vaudry, H. (1992): Glucocorticolds, transmitters and stress. Br. J. Psychiatry 160 (Suppl. 15), 24-34.

183. Croughs, R.M.J., Pjjnbert, A. & Koppeschaar, H.P.F. (1990): Heterogeneity in Cushing disease. Netherlands J. Med. 36, 217-220.

184. Pasturel, J. (1984): Le magnésium en gériatrie. Gaz. Med. 91, 1-3.

185. Merchan, R., Ribeilo. A. & Franco-Martinez, J. (1986): Essai thérapeutique en double aveugle contre placebo d'un sel de magnésium sur la symptomatologie fonctionnelle du 3ème âge. Gaz. Med. 93, 85-88.

186. Kinnunen, O., Karpannen, H. & Salokannel, J. (1989): Safety and the effects on electrolytes of magnesium hydroxyde and a bulk laxative in diuretic treated elderly patients. Magnes. Bull. 11, 68-74.

187. Kinnunen, O. & Salokannel, J. (1989): Comparison of the effects of magnesium hydroxyde and a bulk laxative on lipids carbohydrates, vitamin A and E and minerals in geriatric hospital patients in the treatment of constipations. J. Int. Med. Res. 17, 442-454.

188. Durlach, J., Durlach, V., Rayssiguier, Y., Bara, M. & Guiet-Bara, A. (1992): Magnesium and the cardiovascular system II. Clinical data. In: Molecular biology of atherosclerosis, ed. M.J. Halpern, pp. 513-521. London: John Libbey.

189. Durlach, J., Durlach, V., Rayssiguier, Y., Bara, M. & Guiet-Bara, A. (1992): Magnesium and blood pressure II. Clinical studies. Magnes. Res. 5, 147-153.

190. Simoes-Femandez, J. (1993): Magnesium and dyslipidemias. Clinical aspects (abst 116) Int. J. Toxicol. Occup. Environ. Health 2, 68-69.

191. Shechter, M. & Hod, H. (1991): Magnesium therapy in aged patients with acute myocardial infarction. Magnes. Bull. 13, 7-9.

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This page was first uploaded to The Magnesium Web Site on April 15, 1996