ALCOHOL. CLIN. EXP. RES. (USA), 1994, 18/5 (1057-1068)
It is not known why alcohol ingestion poses a risk for development of hypertension, stroke and sudden death. Of all drugs, which result in body depletion of magnesium (Mg), alcohol is now known to be the most notorious cause of Mg-wasting. Recent data obtained through the use of biophysical (and noninvasive) technology suggest that alcohol may induce hypertension, stroke, and sudden death via its effects on intracellular free Mg2+ ((Mg2+)(i)), which in turn alter cellular and subcellular bioenergetics and promote calcium ion (Ca2+) overload. Evidence is reviewed that demonstrates that the dietary intake of Mg modulates the hypertensive actions of alcohol. Experiments with intact rats indicates that chronic ethanol ingestion results in both structural and hemodynamic alterations in the microcirculation, which, in themselves, could account for increased vascular resistance. Chronic ethanol increases the reactivity of intact microvessels to vasoconstrictors and results in decreased reactivity to vasodilators. Chronic ethanol ingestion clearly results in vascular smooth muscle cells that exhibit a progressive increase in exchangeable and cellular Ca2+ concomitant with a progressive reduction in Mg content. Use of 31P-NMR spectroscopy coupled with optical-backscatter reflectance spectroscopy revealed that acute ethanol administration to rats results in dose-dependent deficits in phosphocreatine (PCr), the (PCr)/(ATP) ratio, intracellular pH (pH(i)), oxyhemoglobin, and the mitochondrial level of oxidized cytochrome oxidase aa3, concomitant with a rise in brain-blood volume and inorganic phosphate. Temporal studies performed in vivo, on the intact brain, indicate that (Mg2+)(i) is depleted before any of the bioenergetic changes. Pretreatment of animals with Mg2+ prevents ethanol from inducing stroke and prevents all of the adverse bioenergetic changes from taking place. Use of quantitative digital imaging microscopy, and mag-fura-2, on single-cultured canine cerebral vascular smooth muscle, human endothelial, and rat astrocyte cells reveals that alcohol induces rapid concentration-dependent depletion of (Mg2+)(i). These cellular deficits in (Mg2+)(i) seem to precipitate cellular and subcellular disturbances in cytoplasmic and mitochondrial bioenergetic pathways leading to Ca2+ overload and ischemia. A role for ethanol-induced alterations in (Mg2+)(i) should also be considered in the well-known behavioral actions of alcohol.
EUR. J. PHARMACOL. ENVIRON. TOXICOL. PHARMACOL. SECT. (Netherlands), 41993, 248/3 (229-236)
Acute ethanol exposure (8-570 mM) induced potent contractile
responses of rings in both basilar and middle cerebral arteries,
from dogs, sheep, piglets and baboons, in a dose-dependent
manner. The contractions were reproducible and not
tachyphylactic. The middle cerebral arteries were found to be
more sensitive to ethanol than the basilar arteries. No known
pharmacological antagonist, tested, exerted any effects on
ethanol-induced contractions. No differences in responsiveness to
ethanol in canine arteries were found between male and female
animals or between the presence and the absence of endothelial
cells. Removal of extracellular Ca2+ ((Ca2+)0) partially
attenuated ethanol-induced contractions, while withdrawal of
extracellular Mg2+ ((Mg2+)0) potentiated such contractions. In
the complete absence of (Ca2+)0, caffeine and ethanol induced
similar, transient contractions followed by relaxation in
K+-depolarized cerebral vascular tissue. Ethanol-induced
contractions were completely abolished by pretreatment of tissues
with caffeine. Our results suggest that:
(a) acute ethanol intoxication can induce direct contractions (independent of amine, prostanoid or opioid mediation) of diverse mammalian cerebral vascular tissues, including those from primates;
(b) these contractile responses are heterogeneous along the cerebrovascular tree and independent of endothelial cells;
(c) in addition to a need for (Ca2+)0, an intracellular release of Ca2+ is needed for ethanol to induce contractions; and
(d) hypomagnesemia or Mg deficiency potentiates the contractile effects of ethanol on brain vessels and may be a risk factor for ethanol-related, ischemic stroke events.
Neurotoxicology, 1991; 615-620
Low calcium/magnesium intake with excess amounts of aluminum and manganese are associated with the incidence of amyotrophic lateral sclerosis (ALS) in the Western Pacific. Two Japanese case reports of ALS showed markedly elevated concentrations of aluminum in the CNS. In 6 other cases of ALS and 5 neurologically normal controls it was found that aluminum concentrations in the precentral gyrus, internal capsule, crus cerebri and spinal cord were significantly higher in 2 ALS patients compared to the controls. Mean aluminum concentrations in 26 different central nervous system regions in the 2 patients were higher than controls and 4 of the ALS cases. Magnesium concentrations in 26 central nervous system regions were markedly reduced in the ALS cases. Calcium/magnesium ratios were significantly increased in ALS patients. The authors conclude that the high incidence of ALS in the Western Pacific may be due to calcium/magnesium dismetabolism resulting in excess deposition of aluminum.
Zeitschrift fur Kardiologie (Germany), 1996, 85/SUPPL. 6 (135-145)
The use of magnesium as an antiarrhythmic agent in ventricular and supraventricular arrhythmias is a matter of an increasing but still controversial discussion during recent years. With regard to the well established importance of magnesium in experimental studies for preserving electrical stability and function of myocardial cells and tissue, the use of magnesium for treating one or the other arrhythmia seems to be a valid concept. In addition, magnesium application represents a physiologic approach, and by this, is simple, cost-effective and safe for the patient. However, when one reviews the available data from controlled studies on the antiarrhythmic effects of magnesium, there are only a few types of cardiac arrhythmias, such as torsade de pointes, digitalis-induced ventricular arrhythmias and ventricular arrhythmias occurring in the presence of heart failure or during the perioperative state, in which the antiarrhythmic benefit of magnesium has been shown and/or established. Particularly in patients with one of these types of cardiac arrhythmias, however, it should be realized that preventing the patient from a magnesium deficit is the first, and the application of magnesium the second best strategy to keep the patient free from cardiac arrhythmias.
Japanese Circulation Journal (Japan), 1996, 60/11 (871-875)
Magnesium affects cardiac function, although until the recent development of a new ion selective electrode no method existed for measuring the physiologically active form of magnesium, free ions (iMg2+), in the blood. We investigated the antiarrhythmic effect of magnesium sulfate administered to critically ill patients with cardiac arrhythmias and reduced iMg2+ as determined using the ion-selective electrode. Eight patients with a low iMg2+ level (less than 0.40 mmol/L) were given intravenous magnesium sulfate (group L). Magnesium sulfate was also administered to patients with a normal iMg2+ level (more than 0.40 mmol/L) but who did not respond to conventional antiarrhythmic drugs (group N). Intravenous magnesium sulfate significantly increased the iMg 2+ level in patients in group L from 0.35plus or minus0.06 mmol/L (mean plus or minus SD) to 0.54 plus or minus 0.09 mmol/L (p<0.01), and had an antiarrhythmic effect in 7 of the 8 patients (88%). However, in group N patients, intravenous magnesium sulfate had an antiarrhythmic effect in only 1 of the 6 patients (17%) (p<0.05 vs group L). These results suggest that intravenous magnesium sulfate may be effective in the acute management of cardiac arrhythmias in patients with a low serum iMg2+ level.
Clinical Cardiology (USA), 1996, 19/4 (325-331)
The aim of this review is the utmost simplification of the cellular electrophysiologic background of ischemia-related arrhythmias. In the acute and subacute phase of myocardial infarction, arrhythmias can be caused by an abnormal impulse generation, abnormal automaticity or triggered activity caused by early or delayed afterdepolarizations (EAD and DAD), or by abnormalities of impulse conduction (i.e., reentry). This paper addresses therapeutic intervention aimed at preventing the depolarization of 'pathologic' slow fibers, counteracting the inward calcium (Ca) influx that takes place through the L-type channels (Ca antagonists), or hyperpolarizing the diastolic membrane action potential increasing potassium (K) efflux (K- channel openers) in arrhythmias generated by an abnormal automaticity (ectopic tachycardias or accelerated idioventricular rhythms). If the cause of enhanced impulse generation is related to triggered activity, and since both EAD and DAD are dependent on calcium currents that can app ear during a delayed repolarization, the therapeutic options are to shorten the repolarization phase through K-channel openers or Ca antagonists, or to suppress the inward currents directly responsible for the afterdepolarization with Ca blockers. Magnesium seems to represent a reasonable choice, as it is able to shorten the action potential duration and to function as a Ca antagonist.
Chinese Pharmacological Bulletin (China), 1994, 10/5 (358-362)
The effect of tauring (Taur) alone and in combination with magnesium sulfate (MgSO4) on ischemia/reperfusion arrhythmia was investigated. The arrhythmia as produced by coronary artery occlusion for 10 min followed by reperfusion. In addition, the present study also observed the effect of MgSO4 alone and in combination with Taur on hemodynamics. The results showed that Taur (50-mg. kg-1) and MgSO4 (25 mg. kg-1) had partly antiarrhythmic effect. Taur (100, 150mg. kg-1) MgSO4 (50, 100mg. kg-1) had significantly antiarrhythmic effect. Taur (50 mg. kg-1) combined with MgSO4 (25 mg. kg-1) shortened the duration of ventricular tachycardia (VT) more than that either drug did alone. The hypotensive effect of MgSO4 (25 mg. kg-1) was not increased by coadministration of Taur, but the myocardial oxygen consumption was reduced. These findings indicate that Taur in combination with MgSO4 has more effect on reperfusion arrhythmia, and that the mechanism of antiarrhythmic effect of Taur and MgSO4 may be involved in the effect of defence on myocardium.
Indian Pediatrics (India), 1997, 34/5 (389-397)
Objective: To evaluate the effectiveness of early administration of intravenous magnesium sulfate (IV MgSO4) in children with acute severe asthma not responding to conventional therapy. Design: Randomized double-blind, placebo-controlled trial. Setting: Pediatric emergency service of a large teaching hospital. Subjects: 47 children aged between 1-12 years with acute severe asthma showing inadequate or poor response to 3 doses of nebulized salbutamol given at an interval of 20 min each. Intervention: The MgSO4 group received 0.2 mg/kg of 50% MgSO4 as intravenous (IV) infusion over 35 minutes and the placebo group received normal saline infusion in the same dose and at the same rate. MgSO4 solution and normal saline were coded and dispensed in identical containers. Decoding was done at the completion of the study. All the patients received oxygen, nebulized salbutamol, IV aminophylline and corticosteroids. Results: MgSO4 group showed early and significant improvement as compared to placebo group in PEFR and SaO2 at 30 min and 1, 2, 3 and 7 hours after stopping the infusion (p ranging from <0.05 to <0.01). The clinical asthma score also showed significant improvement in the MgSO4 group 1, 2, 3 and 11 hours after stopping the infusion (p < 0.01). Conclusion: Addition of MgSO4 to conventional therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma and PEFR in patients not responding to conventional therapy alone.
Clinical and Experimental Allergy (United Kingdom), 1997, 27/5 (546-551)
Background: Magnesium is a cation with smooth muscle relaxant and anti- inflammatory effects and may therefore have a role in the therapy of asthma. Several studies have investigated the effects of intravenous magnesium in acute or stable asthma, but little is known about the effects of inhaled magnesium. Objective: To measure the effects of a single inhaled nebulized dose of 180 mg magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate (AMP)) in asthmatic subjects. Methods: Two separate randomized, double blind, placebo controlled crossover studies. each involving 10 asthmatic subjects. In the histamine study, airway reactivity to histamine was measured and lung function allowed to recover spontaneously over 50 min before administering nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine was then measured at 5 and 50 min. In the AMP study, a single measurement of airway reactivity was made 5 min after magnesium or placebo. Results: In the histamine study, the provocative dose required to reduce FEV1 by 20% (PD20FEV1) was significantly lower after magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22- 1.82) doubling doses at 5 min (P=0.018), and 1.0 (0.3-1.7) doubling doses at 50 min (P = 0.01). In the AMP study, PD20FEV1 was also significantly lower at 5 min after magnesium than alter saline, by 0.64 (0.12-1.16) doubling doses (P = 0.023), though this difference was not statistically significant.
Chest (USA), 1997, 111/4 (858-861)
Background: Inhaled magnesium (Mg) seemed to have a mild protective (nonbronchodilator) effect against histamine and methacholine. Inhaled sodium metabisulfite (MBS) causes bronchoconstriction in asthma through indirect mechanisms that involve sensory, nerve stimulation, and it is extensively used to study airway hyperresponsiveness. We designed this double-blind, randomized, crossover, and placebo-controlled study to test the effect of nebulized Mg sulfate against indirect challenge with MBS. Methods: Ten asthmatic subjects (three male) aged 38.8 (3.29, SEM) years came on three occasions to perform MBS challenges 5 min after inhalation of either normal saline solution as placebo or Mg sulfate (4 mL; 286 mOsm). Doubling increasing concentrations of MBS were administered by continuous nebulization at tidal breathing during 1 min starting at 0.3 to 80 mg/mL until a 20% fall in FEV1 (PC20) from post saline solution baseline value was achieved. PC20 values were logarithmically transformed before analysis. Results: The mean baseline FEV1 at control day was 2.52 (0.14) L and 88.46 (4.28) percentage predicted, while the geometric mean MBS PC20 was 1.95 (1.38, geometric SEM) mg/mL. After placebo, the geometric mean PC20 was 2.26 (1.26) mg/mL. Inhaled Mg increased significantly the PC20 to 5.06 (1.52) mg/mL; p<0.05. Mg diminished the bronchoconstrictor response to MBS by 1.3 doubling doses (p=0.08). Conclusions: Inhaled Mg attenuates MBS-induced bronchoconstriction in these asthmatic subjects. This new feature of Mg, even modest in magnitude, emphasizes the necessity of studying the potential role of this cation in modulating airway response.
Journal of Pharmaceutical Sciences (USA), 1996, 85/10 (1026-1034)
Nedocromil sodium is used in the treatment of reversible obstructive airways diseases, such as asthma. The physicochemical, mechanical, and biological characteristics of nedocromil sodium can be altered by its conversion to other salt forms. In this study, three crystalline hydrates, the pentahydrate, heptahydrate, and decahydrate, of a bivalent metal salt, nedocromil magnesium (NM), were prepared. The relationships between these hydrates were studied through their characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Karl Fischer titrimetry (KFT), hot stage microscopy (HSM), ambient or variable temperature powder X- ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, solid-state nuclear magnetic resonance (SSNMR) spectroscopy, scanning electron microscopy (SEM), water uptake at various relative humidities (RH), intrinsic dissolution rate (IDR), and solubility measurements. The pentahydrate showed two dehydration steps, corresponding to two binding states of water, a more temperature-sensitive tetramer and a more stable monomer, deduced from the crystal structure previously determined. The heptahydrate and decahydrate each showed a dehydration step with a minor change in slope at about 50 degreeC, which was analyzed by derivative TGA and confirmed by DSC. HSM and variable temperature PXRD also confirmed the thermal dehydration behavior of the NM hydrates. The decahydrate underwent an apparently irreversible phase transformation to the pentahydrate at 75 degreeC at an elevated water vapor pressure. The PXRD, FTIR, and SSNMR of the decahydrate were similar to those of the heptahydrate, suggesting that the three extra water molecules in the decahydrate are loosely bound, but were significantly different from those of the pentahydrate. The rank order of both IDR and solubility in water at 25 degreeC was heptahydrate similar decahydrate pentahydrate, corresponding to the rank order of free energy with respect to the aqueous solution.
Ann Emerg Med (UNITED STATES) Nov 1992, 21 (11) p1337-42
STUDY OBJECTIVE: To determine the magnitude of the changes in serum potassium, magnesium, and phosphate during the treatment of acute bronchospasm with repeated doses of beta-adrenergic agonists. DESIGN: Prospective study of a convenience sample of asthmatic patients. SETTING: University teaching hospital emergency department. TYPE OF PARTICIPANTS: Twenty-three patients met the inclusion criteria of age of more than 16 years; a history of asthma or chronic obstructive pulmonary disease; and an acute exacerbation. INTERVENTIONS: Baseline peak expiratory flow rate and serum potassium, magnesium, and phosphate levels were measured. Nebulized albuterol (2.5 mg) was administered every 30 minutes until the patient was discharged from the ED. Before each albuterol treatment, repeat serum levels of potassium, magnesium, and phosphate were determined. MEASUREMENTS AND MAIN RESULTS: Baseline peak expiratory flow rate averaged 188 +/- 119 L/min. Serum potassium levels decreased significantly (P = .0001 by repeated-measures analysis of variance) from 4.10 +/- 0.468 (baseline) to 3.55 +/- 0.580 mmol/L (90 minutes) and 3.45 +/- 0.683 mmol/L (180 minutes). Potassium decreased to less than 3.0 mmol/L in 22% of patients at some point during the study. Magnesium decreased from 1.64 +/- 0.133 mmol/L (baseline) to 1.48 +/- 0.184 mmol/L (90 minutes) and 1.40 +/- 0.219 mmol/L (180 minutes) (P = .0001). Phosphate levels also decreased, from 3.74 +/- 1.029 (baseline) to 2.84 +/- 0.957 mmol/L (90 minutes) and 2.55 +/- 0.715 mmol/L (180 minutes) (P = .0001). CONCLUSION: Aggressive administration of nebulized albuterol during the emergency treatment of acute bronchospasm is associated with statistically significant decreases in serum potassium, magnesium, and phosphate. The mechanism and clinical significance of these findings are unknown and warrant further study.
Psychiatry Res (IRELAND) Nov 1994, 54 (2) p199-210
Levels of calcium in plasma, red blood cells, and mononuclear blood cells, levels of calcium in plasma, and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind, placebo-controlled study of methylphenidate and dextroamphetamine in hyperactive boys. Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment, and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition. There was no change in magnesium levels in red blood cells or mononuclear blood cells. These measures were obtained 30 minutes before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m., 11:00 a.m., and noon on the last day of each 3-week phase. Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug x time interaction. Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy, the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use.
Psychiatr Pol (POLAND) May-Jun 1994, 28 (3) p345-53
The magnesium, zinc, copper, iron and calcium level of plasma, erythrocytes, urine and hair in 50 children aged from 4 to 13 years with hyperactivity, were examined by AAS. The average concentration of all trace elements was lower compared with the control group-healthy children from Szczecin. The highest deficit was noted in hair. Our results show that it is necessary to supplement trace elements in children with hyperactivity.
Wiad Lek (POLAND) Feb 1993, 46 (3-4) p120-2
In 142 girls and 107 boys aged 5-15 years serum magnesium level was determined by the colorimetric method. Decreased values were found in 24 children including 7 boys and 17 girls. In 21 of them neurotic reactions or concentration disturbances were observed.
J. CARDIOVASC. PHARMACOL. (USA), 1994, 23/6 (1004-1010)
Mg2+ influences the response of cerebral arteries to several agonists, but until now its effects on endothelin-1 (ET-1) had not been studied. We recorded and compared the responses of goat cerebrovascular bed to ET-1 and 5-hydroxytryptamine (5-HT) during various Mg2+ treatments. We performed experiments in vitro by recording isometric tension in isolated goat middle cerebral arteries and in vivo by recording cerebral blood flow (CBF) and other physiologic parameters in conscious goats. Cumulative addition of ET-1 (10-101-3 x 10-8M) and 5-HT (10-9-10-5M) contracted cerebral arteries concentration dependently in bath media containing 0 (Mg2+ free medium), 1 (control), and 10 mM Mg2+, but the influence of Mg2+ was different: Mg2+ deprivation increased sensitivity (EC50) and Mg2+ overload reduced contractility (E(max)) of cerebral arteries to 5-HT, whereas the ET-1 response did not change in these conditions. Cumulative addition of Mg2+ (10-4-3 x 10-2M) at the active tone induced by ET-1 (10-9M) and 5-HT (10-5M) elicited concentration-dependent relaxations of cerebral arteries, but the relaxant response was lower at the ET-1 precontraction. Infusions of ET-1 (0.1 nmol/min) and 5-HT (10 microg/min) directly into the cerebroarterial supply of the unanesthetized goats elicited a sustained decrease in CBF and an increase in cerebral vascular resistance. Magnesium sulfate, administered as increasing doses (10-300 mg) in the same way increased CBF and decreased cerebral vascular resistance, although this effect was less on ET-1-induced than on 5-HT-induced cerebral vasoconstriction. When infused intravenously (i.v.; 3 g/15 min), magnesium sulfate had no effect on the ET-1-induced cerebral vasoconstriction, but increased 5-HT-reduced CBF. ET-1 is a relatively Mg2+-resistant contractile stimulus in the cerebrovascular bed. This should be taken into account in consideration of the therapeutic potential of Mg2+ in cerebrovascular disorders in which ET-1 might be involved.
Arzneimittelforschung (GERMANY) Mar 1996, 46 (3) p302-6
Since in vitro experiments had excluded interactions between Fe-gluconate (Fe-gluc) and magnesium-L-aspartate hydrochloride (MAH) in aqueous solutions the present in vivo studies seemed to be justified. Animal studies: Rats were kept on magnesium-(Mg)- and iron-(Fe)- sufficient and deficient diets. The intragastral administration of Fe-gluc significantly increased plasma Fe after 3 h, either given alone, or in combination with MAH (inducing hypermagnesemia). Same results were obtained when fortified diets were offered to Fe/Mg-deficient animals. Human studies: The combination of Fe-gluc (2 x 50 mg Fe per day, per os) plus MAH (2 x 7.5 mmol Mg per day, p.o.) was well tolerated by healthy volunteers. Single dose experiments revealed that Fe-gluc alone and in combination with MAH increased plasma Fe levels during 3 h to the same extent. Two groups of pregnant women with moderately reduced hemoglobin levels either received Fe-gluc (out-patients) or its combination with MAH (at least temporarily hospitalised because of preterm labor). Treatments were well tolerated. Hemoglobin levels did not further decrease, as expected without Fe supplements, during the course of pregnancy, thus indicating the therapeutic availability of the electrolytes in both study groups. Progesterone-induced constipation is frequently observed during pregnancy; hence stool softening reported by 50% of the women receiving Fe-gluc plus MAH (versus 33% in the Fe-gluc group) can be regarded as desirable effect. It is concluded that MAH does not interfere with the enteral absorption of Fe-gluc when both electrolytes are orally administered together. Taking both electrolytes together instead of 2 to 3 h apart from each other, as actually recommended, means a less complicated dosage regimen and probably improves compliance.
J Int Med Res (ENGLAND) Sep-Oct 1989, 17 (5) p442-54
In a crossover study the effects of magnesium hydroxide on serum lipids, carbohydrates, vitamins A and E, uric acid and whole blood minerals were compared with those of a bulk laxative containing plantago rind and sorbitol in 64 constipated, elderly long-stay patients, 55 of whom were receiving diuretics. Hypomagnesaemia occurred in 11 (17%) patients after bulk laxative and in two (2%) patients after magnesium hydroxide treatment. There was a slight reduction in low values of high-density lipoprotein cholesterol and high values of triglycerides after magnesium hydroxide treatment. There were no significant differences in plasma lipids, whole blood minerals or vitamins A and E using either laxative. Negative correlations were found between the increase in serum concentrations of magnesium and glycosylated haemoglobin A1 (P less than 0.02) and the serum level of uric acid (P less than 0.01). These results suggest that the long-term effects of magnesium hydroxide and bulk laxative on the absorption of nutrients may not be significantly different. Magnesium hydroxide, however, may have beneficial effects on lipid disorders, impaired glucose tolerance and hyperuricaemia in magnesium deficiency due to diuretics and thus may be a favourable laxative for use in bedridden geriatric patients receiving diuretics.
Magnesium (SWITZERLAND) 1984, 3 (4-6) p315-23
Diabetes mellitus is the most common pathological state in which secondary magnesium deficiency occurs. Magnesium metabolism abnormalities vary according to the multiple clinical forms of diabetes: plasma magnesium is more often decreased than red blood cell magnesium. Plasma Mg levels are correlated mainly with the severity of the diabetic state, glucose disposal and endogenous insulin secretion. Various mechanisms are involved in the induction of Mg depletion in diabetes mellitus, i.e. insulin and epinephrine secretion, modifications of the vitamin D metabolism, decrease of blood P, vitamin B6 and taurine levels, increase of vitamin B5, C and glutathione turnover, treatment with high levels of insulin and biguanides. K depletion in diabetes mellitus is well known. Some of its mechanisms are concomitant to those of Mg depletion. But their hierarchic importance is not the same: i.e., insulin hyposecretion is more important versus K+ than versus Mg2+. Insulin increases the cellular inflow of K+ more than that of Mg2+ because there is more free K+ (87%) than Mg2+ (30%) in the cell. The consequences of the double Mg-K depletion are either antagonistic: i.e. versus insulin secretion (increased by K+, decreased by Mg2+) or agonistic i.e. on the membrane: (i.e. Na+K+ATPase), tolerance of glucose oral load, renal disturbances. The real importance of these disorders in the diabetic condition is still poorly understood. Retinopathy and microangiopathy are correlated with the drop of plasma and red blood cell Mg. K deficiency increases the noxious cardiorenal effects of Mg deficiency. The treatment should primarily insure diabetic control.
THERAPIE (France), 1994, 49/1 (1-7)
The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium: magnesium deficiency results in impaired insulin secretion while magnesium replacement restores insulin secretion. Furthermore, experimental magnesium deficiency reduces the tissues sensitivity to insulin. Subclinical magnesium deficiency is common in diabetes. It results from both insufficient magnesium intakes and increase magnesium losses, particularly in the urine. In type 2, or non-insulin-dependent, diabetes mellitus, magnesium deficiency seems to be associated with insulin resistance. Furthermore, it may participate in the pathogenesis of diabetes complications and may contribute to the increased risk of sudden death associated with diabetes. Some studies suggest that magnesium deficiency may play a role in spontaneous abortion of diabetic women, in fetal malformations and in the pathogenesis of neonatal hypocalcemia of the infants of diabetic mothers. Administration of magnesium salts to patients with type 2 diabetes tend to reduce insulin resistance. Long-term studies are needed before recommending systematic magnesium supplementation to type 2 diabetic patients with subclinical magnesium deficiency.
Endocrinology and Metabolism Clinics of North America (USA), 1995, 24/3
Magnesium depletion is more common than previously thought. It seems to be especially prevalent in patients with diabetes mellitus. It is usually caused by losses from the kidney or gastrointestinal tract. A patient with magnesium depletion may present with neuromuscular symptoms, hypokalemia, hypocalcemia, or cardiovascular complication. Physicians should maintain a high index of suspicion for magnesium depletion in patients at high risk and should implement therapy early.
DIABETOLOGIA (Germany, Federal Republic of), 1990, 33/9 (511-514)
Magnesium is an important ion in all living cells being a cofactor of many enzymes, especially those utilising high energy phosphate bounds. The relationship between insulin and magnesium has been recently studied. In particular it has been shown that magnesium plays the role of a second messenger for insulin action; on the other hand, insulin itself has been demonstrated to be an important regulatory factor of intracellular magnesium accumulation. Conditions associated with insulin resistance, such as hypertension or aging, are also associated with low intracellular magnesium contents. In diabetes mellitus, it is suggested that low intracellular magnesium levels result from both increased urinary losses and insulin resistance. The extent to which such a low intracellular magnesium content contributes to the development of macro- and microangiopathy remains to be established. A reduced intracellular magnesium content might contribute to the impaired insulin response and action which occurs in Type 2 (non-insulin-dependent) diabetes mellitus. Chronic magnesium supplementation can contribute to an improvement in both islet Beta-cell response and insulin action in non-insulin-dependent diabetes subjects.
Med Hypotheses. 1984 Feb. 13(2). P 139-51
Available evidence--some well-documented, some only preliminary--suggests that properly-designed nutritional insurance supplementation may have particular value in diabetes. Comprehensive micronutrient supplementation providing ample doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine, gamma-linolenic acid, and carnitine, may aid glucose tolerance, stimulate immune defenses, and promote wound healing, while reducing the risk and severity of some of the secondary complications of diabetes. Refs: 125.
Clin Chem (UNITED STATES) Nov 1980, 26 (12) p1662-5
Atomic absorption spectrometry was used to measure magnesium, calcium, and sodium, and emission spectrometry to measure potassium, in myocardium (left and right ventricles) of 26 control subjects who died of acute trauma. Results were expressed in mumol/g of proteins. Mg/Ca and K/Na ratios were also determined. The same measurements were made in 24 patients who died from acute myocardial infarction. Samples were also taken from the necrotic area. Mg/Ca and K/Na ratios were significantly higher in the left ventricle of both populations, thus providing evidence of anatomical and physiological differences between the two ventricles. As a result of cytolysis and anoxia, the Mg/Ca ratio was very significantly inverted, and the K/Na ratio very significantly smaller, In these clinical conditions arrhythmias could certainly be considered likely, and there is reason to believe that magnesium depletion may be a cause of arrhythmias.
Ann Thorac Surg (UNITED STATES) Apr 1995, 59 (4) p921-7
Hypomagnesemia and depletion of the body's magnesium stores is known to be associated with an increased incidence of both cardiac arrhythmias and neurological irritability. In a two-part prospective study we have evaluated whether magnesium deficiency is a significant occurrence in children treated in the intensive care unit after open heart operations, and subsequently have sought to identify how intraoperative metabolic changes were related to the resultant findings. In 41 children studied after operation the plasma magnesium concentration showed a significant decrease from 0.92 mmol/L (10th to 90th centile, 0.71 to 1.15 mmol/L) immediately after operation to 0.77 mmol/L (0.65 to 0.91 mmol/L) on the following morning. The subsequent change in grouped values was not significant but 14 (34.2%) and 7 (17.1%) possessed values of less than 0.7 mmol/L and 0.6 mmol/L, respectively. The occurrence of cardiac arrhythmias was not statistically related to the occurrence of hypomagnesemia. In 21 children perioperative changes in extracellular and tissue magnesium, potassium, and calcium content were measured. It was found that hemodilution with a prime low in magnesium caused a reduction from a median of 0.81 mmol/L to 0.61 mmol/L (p < 0.01). Plasma potassium level, however, was elevated from 3.7 mmol/L to 4.15 mmol/L (p < 0.05) and the ionized calcium content from 1.17 mmol/L (1.07 to 1.25 mmol/L) to 1.49 mmol/L (1.25 to 2.56 mmol/L) (p = 0.0009). The myocardial content of magnesium did not change significantly but skeletal muscle content was depleted from 6.75 mumol/g (2.85 to 8.35 mumol/g) to 5.65 mumol/g (2.45 to 7.2 mumol/g) (p < 0.01)
CARDIOVASC. DRUGS THER. (USA), 1991, 5/4 (677-680)
The possibility that a magnesium deficiency might be the underlying cause of vasospastic angina (VA) and the efficacy of Mg administration in its treatment were studied. Subjects included 15 patients with VA and 18 healthy subjects as the control group. The erythrocyte Mg content was measured by atomic absorption, and serum Mg was measured by conventional chemical assay. The efficacy of Mg administration was studied in seven patients with VA. The results were as follows: (a) The mean erythrocyte Mg content was less in the group with frequent episodes of angina (1.59 plus or minus 0.11 mg/dl) than in the group without angina (2.11 plus or minus 0.38 mg/dl, p < 0.01) and in the control group (2.22 plus or minus 0.29 mg/dl, p < 0.01). There was no significant difference between the control group and patients of each group with respect to serum Mg. (b) Coronary arterial spasm was induced by ergonovine maleate in seven patients and was completely inhibited by the administration of Mg sulfate (40-80 mEq, hourly) in six of these patients; in the remaining patient neither obvious ST change nor chest pain occurred. Thus, it was concluded that the measurement of erythrocyte Mg content is useful to determine how easily vasospasm might occur in VA and that the administration of Mg might be developed as a new therapy for spasm associated with a low erythrocyte Mg content.
CLIN. CARDIOL. (USA), 1990, 13/9 (663-665)
A 51-year-old man was diagnosed as having variant angina by documentation of typical ST elevation during anginal attack and also by showing coronary arterial spasm (#2 and #12) during hyperventilation on coronary arteriography. Large quantities of calcium blocking agents and nitrates could not improve his symptoms. Lack of intracellular magnesium was suspected from a daily excretion of urine magnesium (5.3 mEq) and magnesium tolerance test (56.7%). After hourly infusion of magnesium sulfate (80 mEq), coronary spasm could not be induced by ergonovine.
S. AFR. MED. J. (SOUTH AFRICA), 1983, 64/18 (697-698)
Magnesium deficiency may result from reduced dietary intake of the ion increased losses in sweat, urine or faeces. Stress potentiates magnesium deficiency, and an increased incidence of sudden death associated with ischaemic heart disease is found in some areas in which soil and drinking water lack magnesium. Furthermore, it has been demonstrated experimentally that reduction of the plasma magnesium level is associated with arterial spasm. Careful studies are required to assess the clinical importance of magnesium and the benefits of magnesium supplementation in man.
SCIENCE (USA), 1980, 208/4440 (198-200)
Isolated coronary arteries from dogs were incubated in Krebs-Ringer bicarbonate solution and exposed to normal, high, and low concentrations of magnesium in the medium. Sudden withdrawal of magnesium from the medium increased whereas high concentrations of magnesium decreased the basal tension of the arteries. The absence of magnesium in the medium significantly potentiated the contractile responses of both small and large coronary arteries to norepinephrine, acetylcholine, serotonin, angiotensin, and potassium. These data support the hypothesis that magnesium deficiency, associated with sudden death ischemic heart disease, produces coronary arterial spasm
HYPERTENSION (USA), 1993, 21/6 II (1024-1029)
Evidence suggests that magnesium deficiency may play an important role in cardiovascular disease. In this study, we evaluated the effects of a magnesium infusion and dietary-induced isolated magnesium deficiency on the production of thromboxane and on angiotensin II-mediated aldosterone synthesis in normal human subjects. Because insulin resistance may be associated with altered blood pressure, we also measured insulin sensitivity using an intravenous glucose tolerance test with minimal model analysis in six subjects. The magnesium infusion reduced urinary thromboxane concentration and angiotensin II-induced plasma aldosterone levels. The low magnesium diet reduced both serum magnesium and intracellular free magnesium in red blood cells as determined by nuclear magnetic resonance (186plus or minus10 (SEM) to 127plus or minus9 mM, p<0.01). Urinary thromboxane concentration measured by radioimmunoassay increased after magnesium deficiency. Similarly, angiotensin II-induced plasma aldosterone concentration increased after magnesium deficiency. Analysis showed that all subjects studied had a decrease in insulin sensitivity after magnesium deficiency (3.69plus or minus0.6 to 2.75plus or minus0.5 min- 1 per microunit per milliliterx10-4, p<0.03). We conclude that dietary- induced magnesium deficiency
1) increases thromboxane urinary concentration and
2) enhances angiotensin-induced aldosterone synthesis. These effects are associated with a decrease in insulin action, suggesting that magnesium deficiency may be a common factor associated with insulin resistance and vascular disease.
CAN. J. PHYSIOL. PHARMACOL. (CANADA), 1987, 65/4 (729-745)
Contractility of all types of invertebrate muscle is dependent
upon the actions and interactions of two divalent cations, viz.,
calcium (Ca2+) and magnesium (Mg2+) ions .
The data presented and reviewed herein contrast the actions of
several organic Ca2+ channel blockers with the natural,
physiologic (inorganic) Ca2+ antagonist, Mg2+,on
microvascular and macrovascular smooth muscles. Both direct in
vivo studies on microscopic arteriolar and venular smooth muscles
and in vitro studies on different types of blood vessels are
presented. It is clear from the studies done so far that of all
Ca2+ antagonists examined, only Mg2+ has the capability to
inhibit myogenic, basal, and hormonal-induced vascular tone in
all types of vascular smooth muscle. Data obtained with
verapamil, nimopidine, nitrendipine, and nisoldipine on the
microvasculature are suggestive of the probability that a
heterogeneity of Ca2+ channels, and of Ca2+ binding sites, exists
in different microvascular smooth muscles; although some appear
to be voltage operated and others, receptor operated, they are
probably heterogeneous in composition from one vascular region to
another. Mg2+ appears to act on voltage-, receptor-, and
leak-operated membrane channels in vascular smooth muscle. The
organic Ca2+ channel blockers do not have this uniform
capability; they demonstrate selectivity when compared with Mg2+.
Mg2+ appears to be a special kind of Ca2+ channel antagonist in
vasular smooth muscle. At vascular membranes it can
(i) block Ca2+ entry and exit,
(ii) lower peripheral and cerebral vascular resistance
(iii) relieve cerebral, coronary, and peripheral vasospasm, and
(iv) lower arterial blood pressure.
At micromolar concentrations (i.e., 10-100 muM), Mg2+ can cause significant vasodilatation of intact arterioles and venules in all regional vasculatures so far examined. Although Mg2+ is three to five orders of magnitude less potent than the organic Ca2+ channel blockers, it possesses unique and potentially useful Ca2+ antagonistic properties.
J. NUTR. MED. (United Kingdom), 1994, 4/2 (169-177)
Magnesium sulphate (MgSO4) in a 50% solution was injected initially intramuscularly and later intravenously into patients with peripheral vascular disease (including gangrene, claudication, leg ulcers and thrombophlebitis), angina, acute myocardial infarction (AMI), non-haemorrhagic cerebral vascular disease and congestive cardiac failure. A powerful vasodilator effect with marked flushing was noted after intravenous (IV) injection of 4-12 mmol of magnesium (Mg) and excellent therapeutic results were noted in all forms of arterial disease. This technique of rapidly securing very high initial blood levels of MgSO4 produces results in arterial disease which cannot be equalled by oral vasodilators or intramuscular (IM) or IV infusion therapy. It is suggested that the most important action of MgSO4 in AMI is to open up collateral circulation and relieve ischaemia thus reducing infarct size and mortality rates. Prophylactic use of MgSO4 and its effect on serum lipid, fibrinogen, urea and creatinine levels are discussed.
Nippon Rinsho (JAPAN) Jan 1996, 54 (1) p59-66
It is known that the peroxidation of LDL is a trigger for developing arteriosclerosis. The oxidized LDL is produced by either oxidative stress or a few oxidants. Selenium decreased in serum and some organs of stroke-prone spontaneously hypertensive rats (SHRSP), which is a cofactor of glutamine peroxidase. Serum magnesium decreased in patients with diabetes mellitus, with ischemic heart disease, with essential hypertension and with cerebral vascular lesions. Calcium to magnesium ratio was higher in some organs of SHRSP as compared to Wistar Kyoto rats (WKY). These changes accelerated vascular lesions in SHRSP. (21 Refs.)
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology ( USA), 1996, 12/1 (75-83)
There is compelling evidence that micronutrients can profoundly affect immunity. We surveyed vitamin supplement use and circulating concentrations of 22 nutrients and glutathione in 64 HIV-1 seropositive men and women and 33 seronegative controls participating in a study of heterosexual HIV-1 transmission. We assayed antioxidants (vitamins A, C, and E; total carotenes), vitamins B6 and B12, folate, thiamin, niacin, biotin, riboflavin, pantothenic acid, free and total choline and carnitine, biopterin, inositol, copper, zinc, selenium, and magnesium, HIV-infected patients had lower mean circulating concentrations of magnesium (p < 0.0001), total carotenes (p = 0.009), total choline (p = 0.002), and glutathione (p = 0.045), and higher concentrations of niacin (p < 0.0001) than controls. Fifty-nine percent of HIV+ patients had low concentrations of magnesium, compared with 9% of controls (p < 0.0001). These abnormal concentrations were unrelated to stage of disease. Participants who took vitamin supplements had consistently fewer low concentrations of antioxidants, across HIV infection status and disease stage strata (p = 0.0006). Nevertheless, 29% of the HIV+ patients taking supplemental vitamins had subnormal levels of one or more antioxidants. The frequent occurrence of abnormal micronutrient nutriture, as found in these HIV+ subjects, may contribute to disease pathogenesis. The low magnesium concentrations may be particularly relevant to HIV-related symptoms of fatigue, lethargy, and impaired mentation.
Am J Clin Nutr (UNITED STATES) Feb 1987, 45 (2) p469-75
Associations between blood pressure and intakes of 61 dietary variables assessed by 24-h recall method were investigated in 615 men of Japanese ancestry living in Hawaii who had no history of cardiovascular disease or treated hypertension. Magnesium, calcium, phosphorus, potassium, fiber, vegetable protein, starch, Vitamin-C, and vitamin D intakes were significant variables that showed inverse associations with blood pressure in univariate and a multivariate analyses. Magnesium had the strongest association with blood pressure, which supports recent interest in its relation to blood pressure. Nevertheless, it was not possible to separate the effect of magnesium from that of other variables because of the problem of high intercorrelation among many nutrients. While recommendations based upon cross-sectional studies must be viewed cautiously, these results suggest that foods such as vegetables, fruits, whole grains, and low-fat dairy items are major sources of nutrients that may be protective against hypertension.
Am J Hypertens (UNITED STATES) Mar 1997, 10 (3) p346-55
Magnesium is one of the most abundant ions present in living cells and its plasma concentration is remarkably constant in healthy subjects. Plasma and intracellular magnesium concentrations are tightly regulated by several factors. Among them, insulin seems to be one of the most important. In fact, in vitro and in vivo studies have demonstrated that insulin may modulate the shift of magnesium from extracellular to intracellular space. Intracellular magnesium concentration has also been shown to be effective on modulating insulin action (mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell responsiveness to depolarizing stimuli, by stimulating Ca2+-dependent K+ channels. A poor intracellular magnesium concentration, as found in non-insulin-dependent diabetes mellitus (NIDDM) and in hypertensive (HP) patients, may result in a defective tyrosine-kinase activity at the insulin receptor level and exaggerated intracellular calcium concentration. Both events are responsible for the impairment in insulin action and a worsening of insulin resistance in non-insulin-dependent diabetic and hypertensive patients. By contrast, in NIDDM patients daily magnesium administration, restoring a more appropriate intracellular magnesium concentration, contributes to improve insulin-mediated glucose uptake. Similarly, in HP patients magnesium administration may be useful in decreasing arterial blood pressure and improving insulin-mediated glucose uptake. The benefits deriving from daily magnesium supplementation in NIDDM and HP patients are further supported by epidemiological studies showing that high daily magnesium intake to be predictive of a lower incidence of NIDDM and HP. In conclusion, a growing body of studies suggest that intracellular magnesium may play a key role on modulating insulin-mediated glucose uptake and vascular tone. We further suggest that a reduced intracellular magnesium concentration might be the missing link helping to explain the epidemiological association between NIDDM and hypertension. (74 Refs.)
Clin Exp Hypertens (UNITED STATES) May 1994
The effects of dietary magnesium (Mg) supplementation on intralymphocytic free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were examined in the stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 10 weeks. After 40 day Mg supplementation (0.8% Mg in the diet), systolic blood pressure (SBP) was significantly lower in Mg supplemented group (Mg group) than the control group (0.2% Mg). [Ca2+]i was significantly lower and [Mg2+]i was significantly higher in Mg group than in the control group. Further, [Ca2+]i was positively and [Mg2+]i was negatively correlated with SBP. These results suggest that dietary Mg supplementation modifies [Ca2+]i and [Mg2+]i, and modulates the development of hypertension.
Nederlands Tijschrift voor de Klinische Chemie (Netherlands), 1996, 21/1
Experiences are described at a kidney stone clinic which was
established as part of the Department of Clinical Biochemistry
ten years ago. During this period, the investigational protocol
has changed from an in-patient to an out-patient scheme. The most
important metabolic abnormalities among calcium oxalate kidney
stone formers were hypercalciuria, hypernatriuria,
hyperuricosuria, increased blood urate, decreased blood phosphate
and hyperphosphaturia with decreased renal phosphate threshold.
These abnormalities were found in the majority of patients.
Oxalate output was, however, increased in less than 50 percent of
the patients. The effectivity of thiazides, allopurinol,
magnesium and phosphate supplementation was tested, and it was
(a) the effect of thiazides was significant, but calciuria normalized only in a few cases,
(b) the withdrawal of allopurinol led to a significant increase of urate parameters only in patients without a low-purine diet,
(c) a sufficient dose of magnesium and phosphate is necessary to achieve a therapeutic effect.
PRESSE MED. (FRANCE), 1987, 16/1 (25-27)
The inhibitory effect of magnesium on the first stages of renal calcium stone formation is modest in vitro and more pronounced in experimental in vivo studies. Magnesium deficiency has not yet been convincingly demonstrated in man. However, urinary magnesium concentrations are abnormally low in relation to urinary calcium concentrations in more than 25% of patients with kidney stones. A supplementary magnesium intake corrects this abnormality and prevents the recurrence of stones. Magnesium seems to be as effective against stone formation as diuretics. The modalities of magnesium therapy still have to be determined and its results confirmed. Magnesium, possibly added to drinking water, may well play a role in the primary prevention of renal calcium stones.
KLIN. WOCHENSCHR. (Germany, Federal Republic of), 1988, 66/3 (87-91)
An increased frequency of kidney stone formation is reported in patients with imflammatory bowel disease. In order to investigate its pathogenesis, the concentrations of factors known to enhance calcium oxalate stone formation (oxalate, calcium, uric acid) as well as of inhibitory factors for nephrolithiasis (magnesium, citrate) were determined in the urine of 86 patients with Crohn's disease and compared with those of 53 metabolically healthy controls. Six patients with Crohn's disease already had experienced calcium oxalate nephrolithiasis. Patients with Crohn's disease had significantly higher urinary oxalate and lower magnesium and citrate concentrations. Among all patients magnesium and citrate were significantly lower in those with a positive history of kidney stones. Our results demonstrate that the increased propensity for renal stone formation in patients with Crohn's disease is a result not only of increased urinary oxalate, but also of decreased urinary magnesium and citrate concentrations.
J. UROL. (BALTIMORE) (USA), 1986, 136/1 (181-183)
Different irrigating solutions are used clinically to dissolve uric acid, cystine and struvite stones. These studies were undertaken to assess the toxicity to the rabbit bladder epithelium of several commonly used formulations. Test solutions were infused antegrade through a left ureterotomy overnight. Bladders were removed and routine histological sections made. A pH 7.6 solution of NaHCO3 appeared harmless. The same solution with two percent acetylcysteine produced slight injury. All pH solutions caused significant damage to the urothelium. Hemiacidrin, which contains magnesium, produced less danger than did other pH 4 solutions without that cation. Our data tend to support Suby's conclusions that addition of magnesium reduces urothelial injury even though the presence of magnesium will slow dissolution of struvite.
ANN. CLIN. LAB. SCI. (USA), 1981, 11/4 333-336)
The effect of 100 mg of vitamin B6 twice a day on plasma and red blood cell (RBC) magnesium was evaluated in nine premenopausal subjects during the period of one month. According to reported normal ranges for plasma and RBC magnesium (1.7 to 2.3 and 4.7 to 7.0, mg per dl, respectively), three subjects had low plasma magnesium, and all subjects had low RBC magnesium during the control period. Following vitamin B6 administration, the mean plasma and RBC magnesium levels were significantly elevated, with a doubling of RBC levels after four weeks of therapy. These results support the postulate that vitamin B6 plays a fundamental role in the active transport of minerals across cell membranes.
UNITED KINGDOM CLIN. SCI. (ENGLAND), 1980, 58/3 (255-257)
Serum, urinary and erythrocyte magnesium concentrations were measured in groups of premenopausal, postmenopausal and oophorectomized women. Serum and urinary magnesium were both significantly higher in postmenopausal and oophorectomized women than in the premenopausal group. Oestrogen therapy reduced both serum and urinary magnesium values in oophorectomized women to premenopausal concentrations. Erythrocyte magnesium concentrations were not affected by menstrual status or oestrogen therapy.
GYNECOL. ENDOCRINOL. (United Kingdom), 1994, 8/1 (55-58)
Qualitative and quantitative differences in the dietary habits of postmenopausal women were studied to assess their influence on bone health and osteoporosis. A total of 194 postmenopausal women were studied with forearm DEXA densitometry. 70 were osteoporotic and 124 served as controls. Women had been menopausal for 5-7 years and had never been treated with hormone replacement or drug therapy. A 3-day dietary recall was completed on Sunday, Monday and Tuesday after the examination: the results were processed by computer and daily calcium, phosphorus and magnesium intakes were related to bone mineral content (BMC). Data were compared with Student's t-test and significance was assessed at p < 0.05. Regression analysis was performed to correlate BMC and intake levels. The dietary intake of calcium phosphorus and magnesium was significantly reduced in osteoporotic women and correlated with BMC. Calcium and magnesium intakes were lower than the recommended daily allowance even in normal women. The results suggest that nutritional factors are relevant to bone health in postmenopausal women, and dietary supplementation may be indicated for the prophylaxis of osteoporosis. Adequate nutritional recommendations and supplements should be given before the menopause, and dietary evaluation should be mandatory in treating postmenopausal osteoporosis.
Headache (UNITED STATES) Mar 1997, 37 (3) p142-52
In recent years, research implicating biochemical abnormalities in various pathological conditions has spiraled. Headache is an area in which numerous research studies have been conducted examining biochemical alterations. We have noticed several similarities in biochemical changes reported to occur in migraine and in experimental traumatic brain injury. The most common symptom in mild head injury or mild traumatic brain injury is headache which, in many instances, resembles migraine but has a poorly understood pathophysiology. Biochemical mechanisms believed to be similar in both conditions include: increased extracellular potassium and intracellular sodium, calcium, and chloride; excessive release of excitatory amino acids; alterations in serotonin; abnormalities in catecholamines and endogenous opioids; decline in magnesium levels and increase in intracellular calcium; impaired glucose utilization; abnormalities in nitric oxide formation and function; and alterations in neuropeptides. In this paper, these proposed biochemical alterations will be reviewed and compared. Very similar alterations suggest posttraumatic headache associated with mild head injury and migraine may share a common headache pathway. (114 Refs.)
Med Hypotheses (ENGLAND) Dec 1996, 47 (6) p461-6
Although the pathogenesis of migraine is still poorly understood, various clinical investigations, as well as consideration of the characteristic activities of the wide range of drugs known to reduce migraine incidence, suggest that such phenomena as neuronal hyperexcitation, cortical spreading depression, vasospasm, platelet activation and sympathetic hyperactivity often play a part in this syndrome. Increased tissue levels of taurine, as well as increased extracellular magnesium, could be expected to dampen neuronal hyperexcitation, counteract vasospasm, increase tolerance to focal hypoxia and stabilize platelets; taurine may also lessen sympathetic outflow. Thus it is reasonable to speculate that supplemental magnesium taurate will have preventive value in the treatment of migraine. Fish oil, owing to its platelet-stabilizing and antivasospastic actions, may also be useful in this regard, as suggested by a few clinical reports. Although many drugs have value for migraine prophylaxis, the two nutritional measures suggested here may have particular merit owing to the versatility of their actions, their safety and lack of side-effects and their long-term favorable impact on vascular health. (94 Refs.)
Cephalalgia (NORWAY) Jun 1996, 16 (4) p257-63
In order to evaluate the prophylactic effect of oral magnesium, 81 patients aged 18-65 years with migraine according to the International Headache Society (IHS) criteria (mean attack frequency 3.6 per month) were examined. After a prospective baseline period of 4 weeks they received oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12 weeks or placebo. In weeks 9-12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group compared to the baseline (p < 0.05). The number of days with migraine and the drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Duration and intensity of the attacks and the drug consumption per attack also tended to decrease compared to placebo but failed to be significant. Adverse events were diarrhea (18.6%) and gastric irritation (4.7%). High-dose oral magnesium appears to be effective in migraine prophylaxis.
Headache (UNITED STATES) Jun 1996, 36 (6) p357-61
Headache has often been described in the hyperexcitability syndrome which recognizes an alteration of calcium and magnesium status in its etiopathogenesis. Moreover, in migraine patients magnesium has been shown to play an important role as a regulator of neuronal excitability and, therefore hypothetically, of headache. The present research involves a neurophysiological evaluation and magnesium status assessment of a group of headache patients. Nineteen patients (15 women and 4 men) with episodic tension-type headache and 30 patients (27 women and 3 men) with migraine without aura were examined. An ischemic test was carried out on the right arm with electromyographic (EMG) recording of motor unit potential activity during the interictal period. The determination of extracellular (serum and saliva) and intracellular (red and mononuclear blood cells) magnesium was also performed. The EMG test was positive in 25 of 30 migraine patients and in 2 of 19 tension-type headache patients. Between the two patient groups, there were no significant variations in the concentration of extracellular and white blood cell magnesium, while the red blood cell concentration of this mineral in the group of migraineurs was significantly reduced with respect to that in the group of tension-type headache patients (P < 0.05). The positive EMG test was significantly associated with a low concentration of red blood cell magnesium (P < 0.0001). These results confirm previous findings by demonstrating different etiopathogenic mechanisms as the basis of migraine and tension-type headache. Migraine seems to be related to an altered magnesium status, which manifests itself by a neuromuscular hyperexcitability and a reduced concentration in red blood cells.
Acta Neurologica Scandinavica (Denmark), 1995, 92/1 (109-111)
There are few reports of Mg in MS and none dealing with Mg content in erythrocytes. Mg concentration was determined in serum and in erythrocytes with the help of a BIOTROL Magnesium Calmagite colorimetric method (average sensitivity: 0.194 A per mmol/I) and a Hitachi autoanalyzer in 24 MS patients (7 men and 17 women, age 29-60; 37 years on average with the duration of the disease: 3-19; 11 years on average, at clinical disability stages according to the Kurtzke scale: 1-7; 3.2 on average, in remission stage. A statistically significant decrease (p < 0.001) of Mg concentration in erythrocytes and no changes in plasma of MS patients were found. The results obtained suggest the presence of changes in membrane of erythrocytes which could be connected with their shorter life and with affection of their function.
ACTA NEUROL. SCAND. (Denmark), 1990, 81/3 (197-200)
Magnesium (Mg) concentrations were studied in the brains of 4 patients with definite multiple sclerosis (MS) and 5 controls. The magnesium contents were determined by inductively coupled plasma emission spectrometry in autopsy samples taken from 26 sites of central nervous system tissues, and visceral organs such as liver, spleen, kidney, heart and lung. The average Mg content in the CNS tissues, as well as visceral organs except for spleen, of MS patients showed a significantly lower value than that seen in control cases. The most marked reduction of Mg content was observed in CNS white matter including demyelinated plaques of MS samples. Whether or not these significantly lower Mg contents found in CNS and visceral organs of MS patients may play an essential role in the demyelinating process remain unclear, requiring further studies on MS pathogenesis from the point of metal metabolism.
MED. HYPOTHESES (UK), 1986, 21/2 (193-200)
Magnes Res (ENGLAND) Dec 1992, 5 (4) p295-302
The proposed aetiologies of multiple sclerosis (MS) have included immunological mechanisms, genetic factors, virus infection and direct or indirect action of minerals and/or metals. The processes of these aetiologies have implicated magnesium. Magnesium and zinc have been shown to be decreased in central nervous system (CNS) tissues of MS patients, especially tissues such as white matter where pathological changes have been observed. The calcium content of white matter has also been found to be decreased in MS patients. The interactions of minerals and/or metals such as calcium, magnesium, aluminium and zinc have also been evaluated in CNS tissues of experimental animal models. These data suggest that these elements are regulated by pooling of minerals and/or metals in bones. Biological actions of magnesium may affect the maintenance and function of nerve cells as well as the proliferation and synthesis of lymphocytes. A magnesium deficit may induce dysfunction of nerve cells or lymphocytes directly and/or indirectly, and thus magnesium depletion may be implicated in the aetiology of MS. The action of zinc helps to prevent virus infection, and zinc deficiency in CNS tissues of MS patients may also be relevant to its aetiology. Magnesium interacts with other minerals and/or metals such as calcium, zinc and aluminium in biological systems, affecting the immune system and influencing the content of these elements in CNS tissues. Because of these interactions, a magnesium deficit could also be a risk factor in the aetiology of MS.
IDEGGYOG.SZLE (HUNGARY), 1973, 26/7 (307-312)
A study of the action of magnesium on the centrocecal scotoma in multiple sclerosis revealed that the scotomas were transiently reduced by magnesium infusions or that calcium ionization was modified by alkalinization or Na EDTA.
Osteoporosis International (United Kingdom), 1996, 6/6 (453-461)
Osteoporosis and magnesium (Mg) deficiency often occur in malabsorption syndromes such as gluten-sensitive enteropathy (GSE). Mg deficiency is known to impair parathyroid hormone (PTH) secretion and action in humans and will result in osteopenia and increased skeletal fragility in animal models. We hypothesize that Mg depletion may contribute to the osteoporosis associated with malabsorption. It was our objective to determine Mg status and bone mass in GSE patients who were clinically asymptomatic and on a stable gluten-free diet, as well as their response to Mg therapy. Twenty-three patients with biopsy-proven GSE on a gluten-free diet were assessed for Mg deficiency by determination of the serum Mg, red blood cell (RBC) and lymphocyte free Mg2+, and total lymphocyte Mg. Fourteen subjects completed a 3-month treatment period in which they were given 504-576 mg MgCl2 or Mg lactate daily. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin were measured at baseline and monthly thereafter. Eight patients who had documented Mg depletion (RBC Mg2+ < 150 microM) underwent bone density measurements of the lumbar spine and proximal femur, and 5 of these patients were followed for 2 years on Mg therapy. The mean serum Mg, calcium, phosphorus and alkaline phosphatase concentrations were in the normal range. Most serum calcium values fell below mean normal and the baseline serum PTH was high normal or slightly elevated in 7 of the 14 subjects who completed the 3-month treatment period. No correlation with the serum calcium was noted, however. Mean serum 25-hydroxyvitamin D, 1,25-dihydroxy vitamin D and osteocalcin concentrations were also normal. Despite only 1 patient having hypomagnesemia, the RBC Mg2+ (153 + or - 6.2 microM; mean plus or minus SEM) and lymphocyte Mg2+ (182 plus or minus 5.5 microM) were significantly lower than normal (202 + or - 6.0 microM, P < 0.001, and 198 + or - 6.8 microM, p < 0.05, respectively). Bone densitometry revealed that 4 of 8 patients had osteoporosis of the lumbar spine and 5 of 8 had osteoporosis of the proximal femur (T-scores less than or equal to -2.5). Mg therapy resulted in a significant rise in the mean serum PTH concentration from 44.6 + or - 3.6 pg/ml to 55.9 plus or minus 5.6 pg/ml (p < 0.05). In the 5 patients given Mg supplements for 2 years, a significant increased in bone mineral density was observed in the femoral neck and total proximal femur. This increase in bone mineral density correlated positively with a rise in RBC Mg2+. This study demonstrates that GSE patients have reduction in intracellular free Mg2+, despite being clinically asymptomatic on a gluten-free diet. Bone mass also appears to be reduced. Mg therapy resulted in a rise in PTH, suggesting that the intracellular Mg deficit was impairing PTH secretion in these patients. The increase in bone density in response to Mg therapy suggests that Mg depletion may be one factor contributing to osteoporosis in GSE.
Nutrition Reviews (USA), 1995, 53/3 (71-74)
Among other things, magnesium regulates active calcium transport. As a result, there has been a growing interest in the role of magnesium (Mg) in bone metabolism. A group of menopausal women were given magnesium hydroxide to assess the effects of magnesium on bone density. At the end of the 2-year study, magnesium therapy appears to have prevented fractures and resulted in a significant increase in bone density.
ACTA OBSTET. GYNECOL. SCAND. (Denmark), 1994, 73/6 (452-455)
We measured plasma Cu, Zn and Mg levels in 40 women suffering from premenstrual tension syndrome (PMTS) and in 20 control subjects by atomic absorption spectrophotometer. Mean plasma Cu, Zn and Mg levels, the Zn/Cu ratio were 80.2 plus or minus 6.00 microg/dl, 112.6 plus or minus 8.35 microg/dl, 0.70 plus or minus 0.18 mmol/l, and 1.40 plus or minus 0.10 in the PMTS group; and 77.0 plus or minus 4.50 microg/dl, 117.4 plus or minus 9.50 microg/dl, 0.87 plus or minus 0.10 mmol/l, and 1.51 plus or minus 0.05 in the control group respectively. The mean Mg level and the Zn/Cu ratio were significantly lower in PMTS patients than in the control group. Plasma Mg and Zn levels were diminished significantly during the luteal phase compared to the follicular phase in PMTS group. Mg deficiency may play a role in the etiology of PMTS.
OBSTET. GYNECOL. (USA), 1991, 78/2 (177-181)
Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster 'pain' was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster 'negative affect'. In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes.
ANN. CLIN. BIOCHEM. (UK), 1986, 23/6 (667-670)
Plasma and erythrocyte magnesium were measured in 105 patients with premenstrual syndrome (PMS) using a simple atomic absorption spectroscopy method. The erythrocyte magnesium concentration for the patients with PMS was significantly lower than that of a normal population. The plasma magnesium did not show this difference. The significance of this apparent cellular deficiency of magnesium is discussed.
Journal of Rheumatology (Canada), 1996, 23/6 (990-994)
Objective. To determine nutrient intake of patients with active rheumatoid arthritis and compare it with the typical American diet (TAD) and the recommended dietary allowance (RDA). Methods. 41 patients with active RA recorded a detailed dietary history. Information collected was analyzed for nutrient intake of energy, fats, protein, carbohydrate, vitamins and minerals, which were then statistically compared with the TAD and the RDA. Results. Both men and women ingested significantly less energy from carbohydrates (women 47.4% (6.4) vs 55% RDA, p = 0.0001; men = 48.9% (7.4), p = 0.025) and more energy from fat (women = 36.8% (4.5) vs 30% RDA. p = 0.001 and men = 35.2% (5.9) p = 0.02). Women ingested significantly more saturated and mono-unsaturated fat than the RDA (p = 0.02 and p = 0.04 respectively) while men ingested significantly less polyunsaturated fat (PUFA)(p = 0.0001). Both groups took in less fiber (p = 0.0001). Deficient dietary intake of pyridoxine was observed vs the RDA for both sexes (men and women p = 0.0001). Deficient folate intake was seen vs the TAD for men (p = 0.02) with a deficient trend in women (p = 0.06). Zinc and magnesium intake was deficient vs the RDA in both sexes (p values less than or equal to 0.001) and copper was deficient vs the TAD in both sexes (p = 0.004 women and p = 0.02 men). Conclusion. Patients with RA ingest too much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine, zinc and magnesium vs the RDA and copper and folate vs the TAD. These observations, also documented in previous studies, suggest that routine dietary supplementation with multivitamins and trace elements is appropriate in this population.
Trace Elements and Electrolytes (Germany), 1996, 13/2 (85-87)
Plasma, intraleukocytic and intraerythrocytic zinc, copper, and magnesium levels of patients with rheumatoid arthritis who were and were not receiving tenoxicam have been determined. The results of the patients who were not receiving tenoxicam are as follows: plasma levels (micromol/l): zinc 15.4 plus or minus 0.41 (arithmetic mean + standard error of the mean), copper 21.2 plus or minus 0.82, magnesium 1,120 plus or minus 15.8. Intraleukocytic levels (ng/106 cells) zinc 17.5 plus or minus 2.64, copper 0.451 plus or minus 0.064, magnesium 60.0 plus or minus 5.68. Intraerythrocytic levels (microg/1010 cells): zinc 5.20 plus or minus 0.61, copper 2.64 plus or minus 0.44, magnesium 66.1 plus or minus 4.87. There was no significant difference between all 3 element levels of patients who were or were not receiving tenoxicam. Plasma, leukocyte, and erythrocyte zinc levels of both groups of patients were lower (p < 0.001), copper levels were higher (p < 0.001) than those of healthy subjects. Plasma and leukocyte magnesium levels of both groups of patients and only erythrocyte magnesium levels of patients receiving tenoxicam were higher (p < 0.01) than those of healthy control group.
American Journal of Emergency Medicine (USA), 1997, 15/2 (182-187)
Intravenous magnesium has been suggested as a treatment for certain emergency conditions for more than 60 years. It is currently proposed to be beneficial in treating asthma, preeclampsia, eclampsia, myocardial infarction, and cardiac arrhythmias. The use and efficacy of the drug, however, are controversial. This article discusses the current state of magnesium sulfate research and therapy.
DIS. MON. (USA), 1988, 34/4 (166-218)
Magnesium is an important element for health and disease. Magnesium, the second most abundant intracellular cation, has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Approximately half of the total magnesium in the body is present in soft tissue, and the other half in bone. Less than 1% of the total body magnesium is present in blood. Nonetheless, the majority of our experimental information comes from determination of magnesium in serum and red blood cells. At present, we have little information about equilibrium among and state of magnesium within body pools. Magnesium is absorbed uniformly from the small intestine and the serum concentration controlled by excretion from the kidney. The clinical laboratory evaluation of magnesium status is primarily limited to the serum magnesium concentration, 24-hour urinary excretion, and percent retention following parenteral magnesium. However, results for these tests do not necessarily correlate with intracellular magnesium. Thus, there is no readily available test to determine intracellular/total body magnesium status. Magnesium deficiency may cause weakness, tremors, seizures, cardiac arrhythmias, hypokalemia, and hypocalcemia. The causes of hypomagnesemia are reduced intake (poor nutrition or IV fluids without magnesium), reduced absorption (chronic diarrhea, malabsorption, or bypass/resection of bowel), redistribution (exchange transfusion or acute pancreatitis), and increased excretion (medication, alcoholism, diabetes mellitus, renal tubular disorders, hypercalcemia, hyperthyroidism, aldosteronism, stress, or excessive lactation). A large segment of the U.S. population may have an inadequate intake of magnesium and may have a chronic latent magnesium deficiency that has been linked to atherosclerosis, myocardial infarction, hypertension, cancer, kidney stones, premenstrual syndrome, and psychiatric disorders. Hypermagnesemia is primarily seen in acute and chronic renal failure, and is treated effectively by dialysis.
SCAND. J. CLIN. LAB. INVEST. SUPPL. (United Kingdom), 1994, 54/217
It is clear now that although different ionophores for ionized Mg (Img2+) have been designed by several groups, each of these has a distinctly different K(MgCa). In view of this, it is important to determine whether each of these ion selective electrodes (ISE's) yield identical results for IMg2+ in sera from healthy and diseased humans. Using such an approach, we determined, in a blinded-and random manner, IMg2+ with both the NOVA and KONE ISE's for IMg2+ in two independent laboratories. No significant differences were found either for sera from healthy human volunteers or diseased patients. We did, however, note several interesting findings: 1. randomly, selected hospitalized patients exhibit a much higher incidence of abnormalities for IMg2+ (57-71%) than that noted previously for total Mg (TMg) measurements; and 2. coronary heart disease, rectal cancer and multiple sclerosis patients exhibit extracellular deficits in ionized free Mg.
PRESSE MED. (France), 1988, 17/12 (584-587)
Magnesium ion is of great importance in physiology by its intervention in 300 enzymatic systems, its role in membrane structure and its function in neuromuscular excitability. The skeleton is the first pool of magnesium in the body. Intestinal absorption, renal metabolism, bone accretion and resorption of magnesium are very similar to those of calcium. Magnesium metabolism is accurately controlled, in particular by parathyroid hormone, 25 - dihydroxy vitamin D3, calcitonin, catecholamine and estrogens. The main regulation mechanisms of magnesium metabolism are located in the kidney which is the principal excretory organ.
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