Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study.

Am Heart J, 136(3):480-90 1998 Sep

BACKGROUND: Hypomagnesemia has been hypothesized to play a role in coronary heart disease (CHD), but few prospective epidemiologic studies have been conducted. METHODS AND RESULTS: We examined the relation of serum and dietary magnesium with CHD incidence in a sample of middle-aged adults (n=13,922 free of baseline CHD) from 4 US communities. Over 4 to 7 years of follow-up, 223 men and 96 women had CHD develop. After adjustment for sociodemographic characteristics, waist/hip ratio, smoking, alcohol consumption, sports participation, use of diuretics, fibrinogen, total and high-density lipoprotein cholesterol levels, triglyceride levels, and hormone replacement therapy, the relative risk of CHD across quartiles of serum magnesium was 1.00, 0.92, 0.48, and 0.44 (P for trend=0.009) among women and 1.00, 1.32, 0.95, and 0.73 (P for trend=0.07) among men. The adjusted relative risk of CHD for the highest versus the lowest quartile of dietary magnesium was 0.69 in men (95% confidence interval 0.45 to 1.05) and 1.32 in women (0.68 to 2.55). CONCLUSIONS: These findings suggest that low magnesium concentration may contribute to the pathogenesis of coronary atherosclerosis or acute thrombosis.

Oral magnesium successfully relieves premenstrual mood changes.

Obstet Gynecol, 78(2):177-81 1991 Aug

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.

The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes.

Diabetes Care, 83(5):682-6 1998 May

OBJECTIVE: Hypomagnesemia occurs in 25-38% of patients with type 2 diabetes. Several studies have suggested an association between magnesium (Mg) depletion and insulin resistance and/or reduction of insulin secretion in these cases. Our purpose was to evaluate if Mg supplementation (as magnesium oxide [MgO]) would improve metabolic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 128 patients with type 2 diabetes (32 men, 96 women, aged 30-69 years), treated by diet or diet plus oral antidiabetic drugs, in the Bahia Federal University Hospital, Brazil. Patients at risk for hypomagnesemia or with reduced renal function were excluded. This study was a clinical randomized double-blind placebo-controlled trial. Patients received either placebo, 20.7 mmol MgO, or 41.4 mmol MgO daily (elementary Mg) for 30 days. Mg concentrations were measured in plasma, in mononuclear cells, and in 24-h urine samples. Fasting blood glucose, HbA1, and fructosamine were used as parameters of metabolic control. RESULTS: Of the patients, 47.7% had low plasma Mg, and 31.1% had low intramononuclear Mg levels. Intracellular Mg in patients with diabetes was significantly lower than in the normal population (62 blood donors; 1.4 +/- 0.6 vs. 1.7 +/- 0.6 micrograms/mg of total proteins). No correlation was found between plasma and intracellular Mg concentrations (r = -0.179; P = 0.15) or between Mg concentrations and glycemic control (r = -0.165; P = 0.12). Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without (1.2 +/- 0.5 vs. 1.5 +/- 0.6 micrograms/mg). Similar findings were observed in patients with coronary disease (1.0 +/- 0.5 vs. 1.5 +/- 0.6 micrograms/mg). In the placebo and in the 20.7 mmol Mg groups, neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed. Replacement with 41.4 mmol Mg tended to increase plasma, cellular, and urine Mg and caused a significant fall (4.1 +/- 0.8 to 3.8 +/- 0.7 mmol/l) in fructosamine (normal, 1.87-2.87 mmol/l). CONCLUSIONS: Mg depletion is common in poorly controlled patients with type 2 diabetes, especially in those with neuropathy or coronary disease. More prolonged use of Mg in doses that are higher than usual is needed to establish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications.

Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium.

Headache, 31(5):298-301 1991 May

The effects of oral Magnesium (Mg) pyrrolidone carboxylic acid were evaluated in 20 patients affected by menstrual migraine, in a double-blind, placebo controlled study. After a two cycles run-in period, the treatment (360 mg/day of Mg or placebo) started on the 15th day of the cycle and continued till the next menses, for two months. Oral Mg was then supplemented in an open design for the next two months. At the 2nd month, the Pain Total Index was decreased by both Placebo and Mg, with patients receiving active drug showing the lowest values (P less than 0.03). The number of days with headache was reduced only in the patients on active drug. Mg treatment also improved premenstrual complaints, as demonstrated by the significant reduction of Menstrual Distress Questionnaire (MDQ) scores. The reduction of PTI and MDQ scores was observed also at the 4th month of treatment, when Mg was supplemented in all the patients. Intracellular Mg++ levels in patients with menstrual migraine were reduced compared to controls. During oral Mg treatment, the Mg++ content of Lymphocytes (LC) and Polymorphonucleated cells (PMN) significantly increased, while no changes in plasma or Red Blood Cells were found. An inverse correlation between PTI and Mg++ content in PMN was demonstrated. These data point to magnesium supplementation as a further means for menstrual migraine prophylaxis, and support the possibility that a lower migraine threshold could be related to magnesium deficiency.

Magnesium sulfate in exacerbations of chronic obstructive pulmonary disease.

Arch Intern Med, 155(5):496-500 1995 Mar 13

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease are commonly seen and difficult to treat. We sought to determine the bronchodilator efficacy of magnesium sulfate in this situation, as this compound is helpful in acute asthma. METHODS: Subjects who came to either of two Veterans Affairs emergency departments were randomized in a double-blind fashion to receive either 1.2 g of magnesium sulfate or placebo over 20 minutes after they first received albuterol, 2.5 mg by nebulization. Peak expiratory flow, dyspnea scores, arterial hemoglobin oxygen saturation by pulse oximetry, maximal inspiratory and expiratory pressures, and vital signs were monitored for 45 minutes after the start of magnesium sulfate or placebo treatment. RESULTS: Seventy-two individuals were studied. The peak expiratory flow increased 16.6% +/- 27.7% (mean +/- SD) in both groups after the initial albuterol treatment, from 121.2 +/- 55.7 L/min to 136.9 +/- 63.9 L/min. The peak expiratory flow increased from 136.7 +/- 69.7 L/min at the start of the infusion to 162.3 +/- 76.6 L/min at 30 minutes and 161.3 +/- 78.7 L/min at 45 minutes with magnesium sulfate treatment. The peak expiratory flow was 137.0 +/- 58.6 L/min on initiation of the intravenous infusion, 143.0 +/- 72.7 L/min at 30 minutes, and 143.3 +/- 70.5 L/min at 45 minutes in the placebo group. The difference in peak expiratory flow from initiation of the infusion to 30 and 45 minutes later (calculated as means of the 30- and 45-minute values) was significantly different for the two groups (25.1 +/- 35.7 L/min vs 7.4 +/- 33.3 L/min; P = 0.3); the difference was also significant when expressed as percentage increase (22.4% +/- 28.5% vs 6.1% +/- 24.4%; P = .01). There was a statistically nonsignificantly trend toward a reduced need for hospitalization in the magnesium sulfate group as compared with the placebo group (28.1% vs 41.9%; P = .25). There were no significant changes in the other parameters with either treatment. CONCLUSION: Magnesium sulfate, 1.2 g over 20 minutes after beta-agonist administration, is safe and modestly efficacious in the treatment of acute exacerbations of chronic obstructive pulmonary disease, and its bronchodilator effect is greater than that of a beta-agonist given alone and lasts beyond the period of magnesium sulfate administration.

Role of magnesium in the pathogenesis and treatment of migraines.

Clin Neurosci, 83(5):24-7 1998

The importance of magnesium in the pathogenesis of migraine headaches is clearly established by a large number of clinical and experimental studies. However, the precise role of various effects of low magnesium levels in the development of migraines remains to be discovered. Magnesium concentration has an effect on serotonin receptors, nitric oxide synthesis and release, NMDA receptors, and a variety of other migraine related receptors and neurotransmitters. The available evidence suggests that up to 50% of patients during an acute migraine attack have lowered levels of ionized magnesium. Infusion of magnesium results in a rapid and sustained relief of an acute migraine in such patients. Two double-blind studies suggest that chronic oral magnesium supplementation may also reduce the frequency of migraine headaches. Because of an excellent safety profile and low cost and despite the lack of definitive studies, we feel that a trial of oral magnesium supplementation can be recommended to a majority of migraine sufferers. Refractory patients can sometimes benefit from intravenous infusions of magnesium sulfate.

Effect of magnesium sulphate in patients with unstable angina. A double blind, randomized, placebo-controlled study [see comments]

Eur Heart J, 18(8):1269-77 1997 Aug

AIMS: Administration of intravenous magnesium sulphate has been shown to be protective during acute myocardial ischaemia and it may therefore have beneficial effects in unstable angina. The purpose of this study was to assess the effects of a 24-h infusion of magnesium in patients with unstable angina. METHODS AND RESULTS: Patients who presented with unstable angina with electrocardiographic changes were randomized to receive a 24-h intravenous infusion of magnesium or placebo within 12 h of admission. The primary endpoint was myocardial ischaemia, as assessed by 48 h Holter monitoring. Resting 12-lead ECGs, creatine kinase-MB release and urinary catecholamines were also assessed. Patients were followed for 1 month. Thirty-one patients received magnesium sulphate and 31 placebo. Baseline characteristics and extent of coronary disease were similar in both groups. On 48 h Holter monitoring, 14 patients (50%) had transient ST segment shifts in the magnesium group vs 12 patients (46%) in the placebo group. However, there were fewer ischaemic episodes in the magnesium group (51 vs 101, P < 0.001) and there was a trend towards an increase in the total duration of ischaemia in the placebo group compared to the magnesium group in the second 24 h (2176 min vs 719 min respectively, P = 0.08). Regression of T wave changes on the 24 h ECG occurred more frequently in patients who received magnesium compared to those treated with placebo (11 patients vs 0 patients respectively, P < 0.005). Creatine kinase-MB release was significantly less at 6 and 24 h in patients who received magnesium compared to those treated with placebo. Catecholamine excretion was lower in patients treated with magnesium than in those treated with placebo (adrenaline: 1.05 +/- 0.16 vs 1.61 +/- 0.32 ng.mmol-1 creatinine; noradrenaline: 9.99 +/- 1.82 vs 18.48 +/- 2.41 ng.mmol-1 creatinine respectively in the first 12 h sample, P < 0.05). CONCLUSIONS: Intravenous magnesium reduces ischaemic ECG changes, creatine kinase-MB release and urinary catecholamine excretion in the acute phase of unstable angina. Thus, magnesium may be a beneficial additional therapy for these patients. Further studies are required to confirm these finding.

Calcium and magnesium in drinking water and risk of death from cerebrovascular disease.

Stroke, 18(8):411-4 1998 Feb

BACKGROUND AND PURPOSE: Many studies have demonstrated a negative association between mortality from cardiovascular or cerebrovascular diseases and water hardness. This report examines whether calcium and magnesium in drinking water are protective against cerebrovascular disease. METHODS: All eligible cerebrovascular deaths (17133 cases) of Taiwan residents from 1989 through 1993 were compared with deaths from other causes (17133 controls), and the levels of calcium and magnesium in drinking water of these residents were determined. Data on calcium and magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation. The control group consisted of people who died from other causes, and the controls were pair matched to the cases by sex, year of birth, and year of death. RESULTS: The adjusted odds ratios (95% confidence interval) were 0.75 (0.65 to 0.85) for the group with water magnesium levels between 7.4 and 13.4 mg/L and 0.60 (0.52 to 0.70) for the group with magnesium levels of 13.5 mg/L or more. After adjustment for magnesium levels in drinking water, there was no difference between the groups with different levels of calcium. CONCLUSIONS: The results of the present study show that there is a significant protective effect of magnesium intake from drinking water on the risk of cerebrovascular disease. This is an important finding for the Taiwan water industry and human health.

Antiarrhythmic short-term protective magnesium treatment in ischemic dilated cardiomyopathy.

J Am Coll Nutr, 3(3):492-9 1990 Oct

The efficacy of magnesium sulfate (MgSO4) infusion in the treatment of ventricular arrhythmias was evaluated in 10 normomagnesemic patients: seven men and three women, aged 56-78 years (mean +/- SD, 63.8 +/- 9.3). All of the patients had ischemic dilated cardiomyopathy (IDC) and severe ventricular arrhythmias: multiform ventricular premature contractions (VPCs), couplets, runs of ventricular tachycardia (VT), and R-on-T phenomenon. Four had evidence of old myocardial infarction (MI), four had chronic ischemic cardiomyopathy, and two had effort angina pectoris. Dilated cardiomyopathy was diagnosed by chest X-ray (cardiothoracic ratio greater than 0.5) and echocardiogram (end-diastolic left-ventricular diameter greater than 56 mm). All of the patients underwent two successive 24-hr Holter monitoring at the time of admission and after 3, 5, and 10 days from the beginning of therapy. Ventricular arrhythmias were classified according to modified Lown criteria. Renal function was normal. Magnesium sulfate in 0.9% sodium chloride was given by slow infusions (50 mg/min/60 min) twice daily for 7 days. They were antiarrhythmic in all of the patients: VPCs and couplets mean values decreased from 7971 +/- 2612 to 321 +/- 141 (p less than 0.001) and from 405 +/- 113 to 7 +/- 4 (p less than 0.001), respectively; VT runs (33.8 +/- 5.8) disappeared by the fifth day of treatment. Both the heart rate and the QTc interval remained unchanged from baseline values. The slow magnesium infusion did not notably raise serum Mg when evaluated immediately after stopping the infusion, as compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous magnesium sulfate relieves cluster headaches in patients with low serum ionized magnesium levels.

Headache, 29(5):597-600 1995 Nov-Dec

Patients with cluster headaches have been reported to have low serum ionized magnesium levels. We examined the possibility that patients with cluster headaches and low ionized magnesium levels may respond to an intravenous infusion of magnesium sulfate. Thirty-eight infusions of magnesium sulfate were given to 22 patients with cluster headaches. The mean ionized magnesium level prior to 23 infusions which provided relief for at least 2 days and enabled the patient to skip two or more attacks, was 0.521 +/- 0.016 mmol/L; this value was 0.561 +/- 0.016 prior to 15 infusions which were ineffective. These latter 15 infusions were preceded by higher total magnesium levels. The ionized magnesium level prior to the 23 effective infusions was below 0.54 mmol/L in 19 patients. Five of the 15 ineffective infusions were accompanied by basal ionized magnesium levels below 0.54 mmol/L. In 76% of the infusions, there was a correlation between a response and an ionized magnesium level below 0.54 mmol/L. Nine patients (41%) obtained clinically meaningful improvement. Spontaneous remissions and a placebo effect might have accounted for some of the improvement. However, this should have applied equally to all patients, regardless of the ionized magnesium level. Measurements of ionized magnesium may prove useful in elucidating the pathogenesis of cluster headache and in identifying patients who may benefit from treatment with magnesium.

Antiarrhythmic action of pharmacological administration of magnesium in heart failure: a critical review of new data.

Magnes Res, 8(4):389-401 1995 Dec

Congestive heart failure is characterized by contractile dysfunction and frequent complex ventricular ectopy. Despite advances in therapy, mortality from heart failure is substantial, estimated at 10-80 percent per year, and sudden death is common. Magnesium is the second most common intracellular cation, strongly influences cardiac cell membrane function, and is an important catalyst of many enzymatic reactions in the myocyte. Epidemiological studies have implicated magnesium deficit in the genesis of sudden death. Patients with congestive heart failure are predisposed to magnesium deficit for many reasons, including neurohormonal activation, poor gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in these patients and has been linked to an increased frequency of complex ventricular ectopy. Several early, uncontrolled studies have suggested a beneficial effect of magnesium administration on ventricular arrhythmias in patients with congestive heart failure. Two recent randomized, double blind, placebo-controlled trials have shown that both intravenous and oral administration of magnesium chloride results in a significant reduction in the frequency and complexity of ventricular arrhythmias in patients with congestive heart failure. Magnesium administration is well tolerated and serious adverse effects are rare. The potential mechanisms of the antiarrhythmic action of magnesium and limitations of the available data are discussed. The evidence reviewed suggests that serum magnesium concentrations should be monitored and corrected in patients with congestive heart failure. Ventricular arrhythmias may respond to acute intravenous magnesium administration, which should be considered as early therapy. Further study is needed to define magnesium dose and the effect of concomitant potassium administration. A prospective clinical trial is warranted to determine the chronic effects of magnesium administration in patients with heart failure.

The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test.

Magnes Res, 10(2):149-56 1997 Jun

Children with ADHD are 'a group at risk' as far as their further emotional and social development and educational possibilities are concerned, and the consequences of the lack of an appropriate therapy appears to be serious. Some of these children do not respond to prevailing therapy methods. It is reported that dietetic factors can play a significant role in the etiology of ADHD syndrome, and magnesium deficiency can help in revealing hyperactivity in children. The aim of our work was to assess the influence of magnesium supplementation on hyperactivity in patients with ADHD. The examination comprised 50 hyperactive children, aged 7-12 years, who fulfilled DSM IV criteria for ADHD syndrome, with recognized deficiency of magnesium in the blood (blood serum and red blood cells) and in hair using atomic absorption spectroscopy. In the period of 6 months those examined regularly took magnesium preparations in a dose of about 200 mg/day. 30 of those examined with ADHD showed coexisting disorders specific to developmental age, and 20 of them showed disruptive behaviour. The control group consisted of 25 children with ADHD and magnesium deficiency, who were treated in a standard way, without magnesium preparations. 15 members of this group showed coexisting disorders specific for developmental age, and 10 members showed disruptive behaviour. Hyperactivity was assessed with the aid of psychometric scales: the Conners Rating Scale for Parents and Teachers, Wender's Scale of Behavior and the Quotient of Development to Freedom from Distractibility. In the group of children given 6 months of magnesium supplementation, independently of other mental disorders coexisting with hyperactivity, an increase in magnesium contents in hair and a significant decrease of hyperactivity of those examined has been achieved, compared to their clinical state before supplementation and compared to the control group which had not been treated with magnesium.

The influence of magnesium on visual field and peripheral vasospasm in glaucoma.

Ophthalmologica, 48(7):11-3 1995

Previous studies indicated calcium channel blockers to be of some help for normal-tension glaucoma patients. The present study evaluates the effect of magnesium, a 'physiological calcium blocker', in 10 glaucoma patients (6 with primary open-angle glaucoma, 4 with normal-tension glaucoma). All patients had a digital cold-induced vasospasm. Magnesium (121.5 mg) was administered twice a day for a month. After 4 weeks of treatment, the visual fields tended to improve. All three video-nailfold-capillaroscopic parameters [blood cell velocity (in mm/s) before and after cooling, cold-induced blood flow cessation (in seconds) as well as the number of capillaries per microscopic field which showed such a blood flow cessation] as well as digital temperature improved significantly. Systemic blood pressure and pulse rate remained stable. In conclusion, magnesium improves the peripheral circulation and seems to have a beneficial effect on the visual field in glaucoma patients with vasospasm.

Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial [see comments]

JAMA, 268(17):2395-402 1992 Nov 4

OBJECTIVE--To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery. DESIGN--Randomized, double-blind, placebo-controlled trial. SETTING--A tertiary acute-care 500-bed university teaching hospital. PATIENTS--Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied. INTERVENTIONS--Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass. RESULTS--Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia. CONCLUSIONS--Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period.

Intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II diabetes mellitus [see comments]

Diabetes Care, 15(7):835-41 1992 Jul

OBJECTIVE--Mg deficiency may be an important factor leading to cardiovascular disease. Diabetic subjects show an increase in platelet reactivity that can enhance the risks of vascular disease. In addition, diabetic patients have been reported to be at risk of developing extracellular Mg deficiency. However, the intracellular free Mg concentration and its role in the enhanced platelet reactivity in diabetes is not known. RESEARCH DESIGN AND METHODS--We evaluated the intracellular erythrocyte (RBC) Mg2+ concentration in 20 non-insulin-dependent (type II) diabetics. In addition, the effects of intravenous 3-h drip or 8 wk of oral Mg supplementation on intracellular RBC Mg2+ levels and platelet reactivity was studied. To more clearly evaluate the direct role of Mg in these effects, we induced isolated Mg deficiency in 16 nondiabetic control subjects with an Mg-free liquid diet for 3 wk. RESULTS--The intracellular RBC Mg2+ concentration of diabetic patients was significantly reduced compared with values in nondiabetic control subjects (166 +/- 7 vs. 204 +/- 7 microM, P less than 0.01). Serum Mg levels were also reduced in the diabetic patients compared with the control subjects (1.59 +/- 0.04 vs. 1.9 +/- 0.1 mEq/L, P less than 0.05). Oral Mg supplementation for 8 wk (400 mg/day) restored RBC Mg2+ concentration to normal without significantly changing serum Mg concentration. Both intravenous and oral Mg supplementation markedly reduced platelet reactivity in response to the thromboxane A2 analog, U46619. The Mg-free diet resulted in a significant reduction in RBC Mg2+ concentration and markedly enhanced the sensitivity of platelet aggregation to U46619 and ADP. CONCLUSIONS--These results suggest that type II diabetic patients have intracellular Mg2+ deficiency and that Mg deficiency may be a key factor in leading to enhanced platelet reactivity in type II diabetes. Therefore, Mg supplementation may provide a new therapeutic approach to reducing vascular disease in patients with diabetes.

Intracellular magnesium depletion relates to increased urinary magnesium loss in type I diabetes.

Horm Metab Res, 30(2):99-102 1998 Feb

We investigated whether erythrocyte magnesium (Mg) depletion exists in subjects with Type I diabetes. To this end, Mg levels in plasma, erythrocytes and urine were determined in 12 patients with Type I diabetes and compared with 12 healthy control subjects. Mean plasma Mg concentrations were comparable between diabetic patients and control subjects (0.90 +/- 0.29 mmol/l vs 1.04 +/- 0.14 mmol/l, respectively; p = 0.16). Mean erythrocyte Mg concentration was significantly lower in the diabetic group compared with the control group (1.41 +/- 0.56 mmol/l vs. 2.94 +/- 1.13 mmol/l, respectively; p < 0.0001). Mean urine Mg excretion was significantly elevated in the diabetic group with respect to the controls (6.86 +/- 3.5 mmol/g creatinine/24 h vs. 4.03 +/- 1.65 mmol/g creatinine/24 h, respectively; p = 0.02). As to the diabetic group, erythrocyte Mg concentration showed a significant inverse correlation with urine Mg excretion (r = -0.58, p = 0.049). There was no correlation between urine Mg concentration and glycosylated hemoglobin or fasting plasma glucose level. The data suggest that intracellular Mg depletion without significant hypomagnesemia is related to increased urinary Mg loss in patients with Type I diabetes. The urinary Mg loss is not correlated with the degree of metabolic control.

Effects of magnesium supplementation in hypertensive patients: assessment by office, home, and ambulatory blood pressures.

Hypertension, 136(2):260-5 1998 Aug

An increase in magnesium intake has been suggested to lower blood pressure (BP). However, the results of clinical studies are inconsistent. We studied the effects of magnesium supplementation on office, home, and ambulatory BPs in patients with essential hypertension. Sixty untreated or treated patients (34 men and 26 women, aged 33 to 74 years) with office BP 140/90 mm Hg were assigned to an 8-week magnesium supplementation period or an 8-week control period in a randomized crossover design. The subjects were given 20 mmol/d magnesium in the form of magnesium oxide during the intervention period. In the control period, office, home, and average 24-hour BPs (mean+/-SE) were 148.6+/-1.6/90.0+/-0.9, 136.4+/-1.3/86.8+/-0.9, and 133.7+/-1.3/81.0+/-0.8 mmHg, respectively. All of these BPs were significantly lower in the magnesium supplementation period than in the control period, although the differences were small (office, 3.7+/-1.3/1.7+/-0.7 mmHg; home, 2.0+/-0.8/1.4+/-0.6 mmHg; 24-hour, 2.5+/-1.0/1.4+/-0.6 mm Hg). Serum concentration and urinary excretion of magnesium increased significantly with magnesium supplementation. Changes in 24-hour systolic and diastolic BPs were correlated negatively with baseline BP or changes in serum magnesium concentration. These results indicate that magnesium supplementation lowers BP in hypertensive subjects and this effect is greater in subjects with higher BP. Our study supports the usefulness of increasing magnesium intake as a lifestyle modification in the management of hypertension, although its antihypertensive effect may be small.

Daily oral magnesium supplementation suppresses bone turnover in young adult males.

J Clin Endocrinol Metab, 83(8):2742-8 1998 Aug

This study examined the effects of daily oral magnesium (Mg) supplementation on bone turnover in 12 young (27-36 yr old) healthy men. Twelve healthy men of matching age, height, and weight were recruited as the control group. The study group received orally 15 mmol Mg (Magnosolv powder, Asta Medica) daily in the early afternoon with 2-h fasting before and after Mg intake. Fasting blood and second void urine samples were collected in the early morning on days 0, 1, 5, 10, 20, and 30, respectively. Total and ionized Mg2+ and calcium (Ca2+), and intact PTH (iPTH) levels were determined in blood samples. Serum biochemical markers of bone formation (i.e. C-terminus of type I procollagen peptide and osteocalcin) and resorption (i.e. type I collagen telopeptide) and urinary Mg level adjusted for creatinine were measured. In these young males, 30 consecutive days of oral Mg supplementation had no significant effect on total circulating Mg level, but caused a significant reduction in the serum ionized Mg+ level after 5 days of intake. The Mg supplementation also significantly reduced the serum iPTH level, which did not appear to be related to changes in serum Ca2+ because the Mg intake had no significant effect on serum levels of either total or ionized Ca2+. There was a strong positive correlation between serum iPTH and ionized Mg2+ (r = 0.699; P < 0.001), supporting the contention that decreased serum iPTH may be associated with the reduction in serum ionized Mg2+. Mg supplementation also reduced levels of both serum bone formation and resorption biochemical markers after 1-5 days, consistent with the premise that Mg supplementation may have a suppressive effect on bone turnover rate. Covariance analyses revealed that serum bone formation markers correlated negatively with ionized Mg2+ (r = -0.274 for type I procollagen peptide and -0.315 for osteocalcin), but not with iPTH or ionized Ca2+. Thus, the suppressive effect on bone formation may be mediated by the reduction in serum ionized Mg2+ level (and not iPTH or ionized Ca2+). In summary, this study has demonstrated for the first time that oral Mg supplementation in normal young adults caused reductions in serum levels of iPTH, ionized Mg2+, and biochemical markers of bone turnover. In conclusion, oral Mg supplementation may suppress bone turnover in young adults. Because increased bone turnover has been implicated as a significant etiological factor for bone loss, these findings raise the interesting possibility that oral Mg supplementation may have beneficial effects in reducing bone loss associated with high bone turnover, such as age-related osteoporosis.

New experimental and clinical data on the efficacy of pharmacological magnesium infusions in cerebral infarcts.

Magnes Res, 83(5):43-56 1998 Mar

Multiple metabolic processes have been identified within the critically perfused ischaemic penumbra on the margins of cerebral infarcts. Intervention in many of these processes has been neuroprotective, notably blockade of glutamate receptors such as the N-methyl D-aspartate (NMDA) receptor. Magnesium may act as a neuroprotective agent through vascular effects (increasing regional cerebral blood flow to ischaemic tissue, anticonstrictor effects against vascular mediators, vasodilatation of the cerebral circulation) or neuronal effects. Neuronal effects include block of the NMDA receptor ion channel, calcium antagonism at voltage-gated channels, enhanced buffering of intracellular calcium ions, and enhanced regeneration of adenosine triphosphate. Magnesium infusions of sulphate or chloride salts are significantly neuroprotective in standard animal focal cerebral ischaemia models, with benefits being evident at serum concentrations attainable in humans. Mg systemic infusion causes rises in cerebrospinal fluid and brain magnesium concentrations. Magnesium is also neuroprotective in other models of cerebral ischaemia. Three clinical trials in acute stroke have involved just over 100 patients. No adverse effects have been observed, and trends favouring magnesium treatment have been seen. A large multicentre clinical trial testing the efficacy of magnesium sulphate is underway, and should report within 4 years.

Usefulness of intravenous magnesium for multifocal atrial tachycardia in patients with chronic obstructive pulmonary disease.

Am J Cardiol, 18(1):91-3 1998 Jan 1

Intravenous magnesium is an effective drug for rate control in multifocal atrial tachycardia. In addition, magnesium may be helpful in restoring sinus rhythm.

Serum ionized magnesium: relation to blood pressure and racial factors.

Am J Hypertens, 18(1):1420-4 1997 Dec

To study potential ionic factors predisposing to vascular disease in hypertension, particularly among black subjects, we used a recently developed combined magnesium and calcium specific, ion selective electrode apparatus to measure extracellular ionized calcium (Ca-ion), ionized magnesium (Mg-ion), and Ca-ion/Mg-ion ratios in the serum of fasting, nonmedicated white and black normotensive (n = 61) and hypertensive (n = 23) subjects, studied consecutively in a tertiary referral center. Both race and blood pressure status had independent effects on the distribution of Mg-ion values. Although Mg-ion levels for the group as a whole were lower in hypertensive versus in normotensive subjects (0.571+/-0.012 v 0.601+/-0.005 mmol/L; P < .01), this was only true of white subjects (0.579+/-0.021 v 0.620+/-0.006 mmol/L; P = .0095). The lack of a significant difference in Mg-ion levels between black hypertensive versus normotensive subjects (0.553+/-0.012 v 0.577+/-0.007 mmol/L, P = NS) was attributable to the significantly lower Mg-ion levels present in normotensive blacks compared to those in normotensive white subjects (0.577+/-0.007 v 0.620+/-0.006 mmol/L, P = .0001). Resultant Ca-ion/Mg-ion ratios were elevated in all black subjects and in white hypertensive subjects. These data support the presence among hypertensives and among black subjects (independently of blood pressure) of a consistent depletion of circulating magnesium and of an imbalance of calcium and magnesium that may potentiate vascular disease among these subjects.

Investigation of the effect of short-term change in dietary magnesium intake in asthma.

Eur Respir J, 18(10):2225-9 1997 Oct

Epidemiological evidence suggests that a low dietary intake of magnesium is associated with impaired lung function, bronchial hyperreactivity and wheezing. This study was designed to investigate whether short-term alterations of dietary magnesium intake have an effect on the clinical control of asthma. In a randomized, double-blind, placebo-controlled, cross-over study, 17 asthmatic subjects adhered to a low magnesium diet for two periods of 3 weeks, preceded and separated by a 1 week run-in/wash-out, in which they took either placebo or magnesium (400 mg x day(-1)) tablet supplementation. Forced expiratory volume in one second (FEV1) and the provocative dose of methacholine required to cause a 20% fall in FEV1 from baseline (PD20,FEV1) were measured at the beginning and end of each treatment period, and variation in peak expiratory flow (PEF) rate, bronchodilator use and symptom scores recorded throughout. Asthma symptom scores were significantly lower during the magnesium treatment period, the median (95% confidence interval) difference from placebo being 3.8 (0.5-7.0) symptom points per 7 days (p=0.02). However, there was no significant improvement in FEV1, PD20,FEV1, log amplitude percentage mean PEF variation or bronchodilator use during magnesium supplementation. A high magnesium intake was associated with improvement in symptom scores, though not in objective measures of airflow or airway reactivity, in these stable asthmatic subjects.

Platelet ionized magnesium, cyclic AMP, and cyclic GMP levels in migraine and tension-type headache.

Headache, 18(9):561-4 1997 Oct

Decreased serum and intracellular levels of magnesium have been reported in patients with migraine. It has been suggested that magnesium may play an important role in the attacks and pathogenesis of headaches. We measured ionized magnesium, cyclic AMP (adenosine monophosphate), and cyclic GMP (guanosine monophosphate) in platelets of patients with migraine, in patients with tension-type headache, and in healthy controls. The platelet level of ionized magnesium from patients with tension-type headache was significantly lower than the levels from the other two groups. The platelet level of cyclic AMP from patients with migraine was higher than those from the other groups. We found no significant differences in the platelet cyclic GMP levels among the three groups. It is suggested that reduced platelet ionized magnesium in patients with tension-type headache is related to abnormal platelet function, and that increased platelet cyclic AMP in patients with migraine is related to alteration of neurotransmitters in the platelet.

The effects of high oral magnesium supplementation on blood pressure, serum lipids and related variables in apparently healthy Japanese subjects.

Br J Nutr, 78(5):737-50 1997 Nov

In a double-blind, placebo-controlled study, thirty-three subjects were allocated to undergo either a 4-week treatment with oral Mg supplementation (Mg(OH)2; 411-548 mg Mg/d) or a placebo. The urinary excretion of Mg increased significantly in both the first 2 weeks and the following 2 weeks of Mg supplementation, while the urinary Na excretion also increased significantly over the experimental period. The systolic and diastolic blood pressure values decreased significantly in the Mg group, but not in the placebo group. The urinary aldosterone excretion and packed cell volume increased significantly during the last 2 weeks of the experimental period compared with the run-in period and first 2 weeks of supplementation. There was a statistically significant positive correlation between the values for urinary noradrenaline excretion and diastolic blood pressure at the end of the supplementation period (both expressed as a percentage of the run-in value). Statistically significant increases in lecithin-cholesterol acyltransferase (EC 2.3.1.43; LCAT), HDL-cholesterol and apolipoprotein AI were also observed after Mg supplementation. A significant positive correlation was observed between the levels of LCAT and urinary Mg excretion for the experimental period (expressed as a percentage of the run-in value). The total cholesterol:HDL-cholesterol ratio decreased significantly during the last 2 weeks of Mg supplementation compared with the first 2 weeks and the run-in periods, but this did not occur in the placebo group. These results suggest that Mg supplementation may lower blood pressure through the suppression of the adrenergic activity and possible natriuresis, while also improving the serum lipids through the activation of LCAT in human subjects.

Antiarrhythmic effects of increasing the daily intake of magnesium and potassium in patients with frequent ventricular arrhythmias. Magnesium in Cardiac Arrhythmias (MAGICA) Investigators.

J Am Coll Cardiol, 29(5):1028-34 1997 Apr

OBJECTIVES: This study sought to assess potential antiarrhythmic effects of an increase in the daily oral intake of magnesium and potassium in patients with frequent ventricular arrhythmias. BACKGROUND: Magnesium and potassium contribute essentially to the electrical stability of the heart. Despite experimental and clinical evidence for the antiarrhythmic properties of the two minerals, controlled data in patients with stable ventricular arrhythmias are lacking. METHODS: In a randomized, double-blind study, 232 patients with frequent ventricular arrhythmias ( 720 ventricular premature beats [VPBs]/24 h) confirmed at baseline and after 1 week of placebo therapy were subsequently treated over 3 weeks with either 6 mmol of magnesium/12 mmol of potassium-DL-hydrogenaspartate daily or placebo. RESULTS: Compared with placebo pretreatment, active therapy resulted in a median reduction of VPBs by -17.4% (p = 0.001); the suppression rate was 2.4 times greater than that in patients randomized to 3 weeks of placebo therapy (-7.4%, p = 0.038). The likelihood of a or = 60% (predefined criterion) or or = 70% suppression rate (calculated from the placebo-controlled run-in period) was 1.7 (25% vs. 15%, p = 0.044) and 1.5 times greater in the active than in the placebo group (20% vs. 13%, p = 0.085), respectively. No effect of magnesium and potassium administration was observed on the incidence of repetitive and supraventricular arrhythmias and clinical symptoms of the patients. CONCLUSIONS: To our knowledge, this study is the first to provide controlled data on the antiarrhythmic effect of oral administration of magnesium and potassium salts when directed to patients with frequent and stable ventricular tachyarrhythmias. A 50% increase in the recommended minimum daily dietary intake of the two minerals for 3 weeks results in a moderate but significant antiarrhythmic effect. However, with the given therapeutic regimen, repetitive tachyarrhythmias and patient symptoms remain unchanged.

Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate.

Med Hypotheses, 29(5):89-100 1996 Feb

By a variety of mechanisms, magnesium functions both intracellularly and extracellularly to minimize the cytoplasmic free calcium level, [Ca2+]i. This may be the chief reason why correction of magnesium deficiency, or induction of hypermagnesemia by parenteral infusion, exerts antihypertensive, anti-atherosclerotic, anti-arrhythmic and antithrombotic effects. Although the amino acid taurine can increase systolic calcium transients in cardiac cells (and thus has positive inotropic activity), it has other actions which tend to reduce [Ca2+]i. Indeed, in animal or clinical studies, taurine lowers elevated blood pressure, retards cholesterol-induced atherogenesis, prevents arrhythmias and stabilizes platelets--effects parallel to those of magnesium. The complex magnesium taurate may thus have considerable potential as a vascular-protective nutritional supplement, and might also be administered parenterally, as an alternative to magnesium sulfate, in the treatment of acute myocardial infarction as well as of pre-eclampsia. The effects of magnesium taurate in diabetes deserve particular attention, since both magnesium and taurine may improve insulin sensitivity, and also may lessen risk for the micro- and macrovascular complications of diabetes.

Systemic magnesium deficiency disclosed by magnesium loading test in patients with essential hypertension.

Hypertens Res, 29(1):39-42 1995 Mar

The present study was designed to determine whether magnesium (Mg) deficiency is present in patients with essential hypertension. We measured the retention of an intravenously administered Mg load (0.2 mmol/kg MgSO4 over 4 h), and serum and erythrocyte Mg concentrations in 17 inpatients with essential hypertension and in 15 normotensive controls. There was no significant difference between the two groups in erythrocyte Mg concentration (normotensives vs., hypertensives: 2.0 +/- 0.5 vs. 2.1 +/- 0.4 mmol/l cells), serum Mg concentration (normotensives vs. hypertensive: 2.1 +/- 0.2 vs. 2.1 +/- 0.2 mg/dl), or in urinary Mg excretion (normotensives vs. hypertensives: 65.8 +/- 25.5 vs. 73.7 +/- 26.7 mg/day). However, Mg retention was significantly higher in hypertensives than in normotensives (normotensives vs. hypertensives: 31.8 +/- 12.1 vs. 41.9 +/- 13.3%). These results suggest that a systemic Mg deficiency, which is undectectable by serum or erythrocyte Mg determination, may exist in patients with essential hypertension.

Effect of treatment with magnesium and potassium on mortality and reinfarction rate of patients with suspected acute myocardial infarction.

Int J Clin Pharmacol Ther, 34(5):219-25 1996 May

The aim of the study was to test whether magnesium and potassium administration can decrease both early and late cardiac event rates in 355 patients with suspected acute myocardial infarction (AMI). The study was conducted by a primary and secondary care research centre as a randomized, initially double-blind comparison for 4 weeks followed by a single blind period for 2 years. Patients with definite or possible AMI and unstable angina based on World Health Organization criteria were assigned within 24 hours of infarction to different groups. Treatment was administered for 3 days through intravenous infusion with either 8.12 mmol/day Mg (group A, n = 81), 10.49 mmol/day K (group B, n = 77) 10% dextrose solution (group C, n = 87) or a placebo containing 2% dextrose solution (group D, n = 81). After discharge from the hospital all groups were advised to follow a fat-reduced diet. Groups A, B, and C were also advised to take magnesium hydroxide or potassium chloride orally. Comparison of groups A and B with group D over 2 years indicated that treatment with magnesium or potassium was associated with increased (p < 0.05) serum magnesium and potassium, and significant reduction in the incidence of cardiac events (22 and 24 vs 41 patients), total mortality (9 and 10 vs 20 deaths), and ventricular ectopics (17 and 21 vs 44), respectively, in the groups. Group C showed no significant benefit. It is possible that magnesium and potassium infusion immediately after AMI and addition of Mg and K salts to the AMI regimen may enhance tissue levels of these cations, leading to significant reduction in complications and mortality after 2 years.

Acute myocardial infarction without thrombolytic therapy: beneficial effects of magnesium sulfate.

Herz, 34(5):73-6 1997 Jun

Only one third of hospitalized patients with acute myocardial infarction (AMI) receive thrombolytic therapy despite its proven benefits on outcomes. Elderly patients, have a greater risk of death during myocardial infarction; however, thrombolytic therapy appears to be less used in these patients, as compared to the general AMI-patients. In order to evaluate the impact of magnesium supplementation in AMI-patients without thrombolytic therapy, 194 patients participated in a prospective, randomized and placebo-controlled study: 96 patients received a 48-hour intravenous magnesium sulfate and 98 isotonic glucose as placebo. Magnesium infusion reduced the incidence of arrhythmias, congestive heart failure and in-hospital-mortality compared with placebo (27 vs. 40%, p = 0.04; 18 vs. 23%, p = 0.27; 4 vs. 17%, p <0.01, respectively); in the subgroup of elderly patients (>70 years), the benefit was also obvious (42 vs. 50%; 18 vs. 25%; 9 vs. 23%, p = 0.09, respectively). These data suggest that intravenous magnesium supplementation might be justified in order to reduce myocardial damage and mortality rate in subsets of high-risk patients such the elderly and/or patients not suitable for thrombolysis. Additional trials appear to be indicated to evaluate the potential benefit of magnesium in well defined specific subsets of AMT-patients.

Magnesium deficiency and cardiogenic shock after cardiopulmonary bypass.

Ann Thorac Surg, 34(5):572-7 1997 Aug

Magnesium is an important cation that has a key role in cellular processes of energy transfer and utilization involving adenosine triphosphate, and influences cell membrane functions. Its antiarrhythmic properties are well-known and it is widely recognized as an adjunct for the treatment of arrhythmias after myocardial infarction and cardiopulmonary bypass. Magnesium may influence hemodynamic performance through its effects on vascular tone, modulation of intracellular calcium, regulation of catecholamine activity, and its essential role in adenosine triphosphate metabolism. The potential for magnesium deficiency to affect cardiovascular performance may be especially relevant in ischemic states. We report a case of cardiogenic shock developing after cardiopulmonary bypass that was initially unresponsive to therapeutic intervention, but that resolved promptly after magnesium administration. The potential role of magnesium in enhancing hemodynamic performance is discussed, with a review of its cellular metabolic properties and activities.

Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium [see comments]

Am J Hypertens, 10(3):346-55 1997 Mar

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.

Magnesium taurate and fish oil for prevention of migraine.

Med Hypotheses, 8(6):461-6 1996 Dec

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.

Magnesium attenuates the neutrophil respiratory burst in adult asthmatic patients [see comments]

Acad Emerg Med, 3(12):1093-7 1996 Dec

INTRODUCTION: IV magnesium (Mg2+) has been proposed as an emergent treatment for acute asthma exacerbations. Recent studies have focused on the effects of Mg2+ on bronchial smooth muscle, yet asthma is primarily an inflammatory disease. OBJECTIVE: To assess the effects of Mg2+ on the neutrophil respiratory burst of adult patients with asthma. METHODS: A prospective, blind study of volunteer adult asthmatic patients was performed. The patients' polymorphonuclear neutrophils (PMNs) were isolated, purified, and placed into phosphate-buffered saline with the following test conditions: concentrations of magnesium chloride (MgCl2) added: 0 mmol MgCl2, 1 mmol MgCl2 (low), and 10 mmol MgCl2 (high) both with and without the calcium (Ca2+) ionophore A23187 (0.1 mmol). PMNs were activated using N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10 mumol), and the production of superoxide (O2-) was measured by the spectrophotometric reduction of cytochrome c. RESULTS: Mg2+ reduced activated PMN O2- production compared with that for no Mg2+ (1.0 +/- 0.1 nmol O2-/5 x 10(5) PMN/min) in both low (-0.52* +/- 0.3 nmol O2-/5 x 10(5) PMN/min) and high (-0.76* +/- 0.3 nmol O2-/5 x 10(5) PMN/min; *p < 0.05) concentrations. The addition of A23187 increased O2- production in both the high (0.53* +/- 0.02 nmol O2-/5 x 10(5) PMN/min) and the low (1.5* +/- 0.6 nmol O2-/5 x 10(5) x 10(5) PMN/min) Mg2+ groups, with no change in the control group (1.2 +/- 0.2 nmol O2-/10(5) PMN/min). CONCLUSIONS: In clinically relevant concentrations, Mg2+ attenuates the neutrophil respiratory burst in adult asthmatic patients. Mg2+ appears to affect PMNs by interfering with extracellular Ca2+ influx. Mg2+ may have a beneficial anti-inflammatory effect in asthmatic individuals.

Effects of dietary sodium substitution with potassium and magnesium in hypertensive type II diabetics: a randomised blind controlled parallel study.

J Hum Hypertens, 10(8):517-21 1996 Aug

We have previously demonstrated that modest sodium restriction has a hypotensive effect in hypertensive diabetic subjects. A randomised blind controlled study has therefore been performed to study the effect of replacement of added salt intake using a salt substitute (50% NaCl, 40% KCL, 10% Mg2+, supplied by Cederroth, Sweden), compared to added whole salt intake over a 9 month period of 40 hypertensive Type II diabetic subjects (mean age 62.5 +/- 7.8 years; 24 males and 16 females). After 3 months, there was a significant reduction in systolic blood pressure (SBP) in the salt substitution group (163.2 +/- 24.2 to 153.6 +/- 20.8 mm Hg; P < 0.03) which was maintained at 9 months, when compared to the whole salt group (151.5 +/- 20.6 vs 173 +/- 18.9 mm Hg; P < 0.05). No significant changes were observed in mean weight, fasting lipid or insulin levels or diabetic control (measured by glycosylated haemoglobin). A greater number of patients were withdrawn during the study period owing to consistent BP > 160/95 in the whole salt group (n = 10) compared to salt substitute (n = 4). No significant changes were observed in diastolic pressure, 24-h urine sodium or magnesium excretion, but urine potassium was significantly increased in the salt substitute group (58.8 to 77.3: P < 0.05). The results of this study suggest that substitution of sodium, by potassium and magnesium, produces a clinically significant reduction in SBP in hypertensive Type II diabetic patients, and should be a useful antihypertensive therapy in this patient group.

Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial [see comments]

J Pediatr, 129(6):809-14 1996 Dec

OBJECTIVE: To evaluate the efficacy of intravenous magnesium (IVMg) therapy for moderate to severe asthma exacerbations in pediatric patients. DESIGN: Randomized, double-blind, placebo-controlled, clinical trial. SETTING: Urban pediatric emergency department. PARTICIPANTS: Thirty-one patients aged 6 to 18 years who were being treated for an acute asthma exacerbation with peak expiratory flow rate (PEFR) less than 60% of the predicted value after receiving three beta 2-adrenergic nebulizer treatments. Interventions: Magnesium sulfate infusion, 25 mg/kg (maximum, 2 gm), or equivolume saline solution for 20 minutes. MEASUREMENTS AND RESULTS: Vital signs, O2 saturation by pulse oximetry, PEFR, forced vital capacity, forced expiratory volume at 1 second, and physical examination were serially recorded for 110 minutes, with serum magnesium concentrations measured before and after the 20-minute infusion. At 50 minutes the magnesium group had a significantly greater percentage of improvement from baseline in forced expiratory volume at 1 second (34% vs -1%; p = 0.05); this improvement was sustained and even greater at 110 minutes (75% vs 5%; p = 0.01). Results were similar for PEFR at 80 through 110 minutes (59% vs 20% at 110 minutes; p = 0.05) and for forced vital capacity (55% vs 8% at 80 minutes; p = 0.05). There were no significant intergroup differences in blood pressure at any point. Patients who received intravenous magnesium infusions were more likely to be discharged home from the emergency department than those who received placebo (4/15 vs 0/16; p = 0.03). CONCLUSIONS: Children treated with intravenous magnesium infusions for moderate to severe asthma had significantly greater improvement in short-term pulmonary function without any significant alteration in blood pressure, suggesting a role for this agent as an adjunct in the treatment of such patients.

Intravenous magnesium sulfate rapidly alleviates headaches of various types.

Headache, 36(3):154-60 1996 Mar

BACKGROUND: Circumstantial evidence points to the possible role of magnesium deficiency in the pathogenesis of headaches and has raised questions about the clinical utility of magnesium as a therapeutic regimen in some headaches. METHODS: We evaluated the efficacy of intravenous infusion of 1 gram of magnesium sulfate (MgSO4) for the treatment of patients with headaches and attempted to correlate clinical responses to the basal serum ionized magnesium (IMg2+) level. We also determined if patients with certain headache types exhibit low serum IMg2+ as opposed to total serum magnesium. Using a case-control comparison at an outpatient headache clinic, a consecutive sample of patients presenting with a moderate or severe headache of any type were included in the study. Of the 40 patients in the study (mean age 38.2 +/- 9.4 years; range 14 to 55; 11 men [39.2 +/- 7.3 years] and 29 women [37.8 +/- 10.2 years]), 16 patients had migraines without aura, 9 patients had cluster headaches, 4 patients had chronic tension-type headaches, and 11 had chronic migrainous headaches. Total serum magnesium was measured with atomic absorption spectroscopy and a Kodak Ektachem DT-60. Sensitive ion selective electrodes were utilized to measure serum IMg2+ and ionized calcium (ICa2+); ICa2+/IMg2+ ratios were calculated. RESULTS: Complete elimination of pain was observed in 80% of the patients within 15 minutes of infusion of MgSO4. No recurrence or worsening of pain was observed within 24 hours in 56% of the patients. Patients treated with MgSO4 observed complete elimination of migraine-associated symptoms such as photophobia and phonophobia as well as nausea. Correlation was noted between immediate and 24-hour responses with the serum IMg2+ levels. Immediate pain relief was observed in 32 (80%) of 40 patients (P <0.001). In 18. of the 32 patients, pain relief persisted for at least 24 hours (P ><0.005). Of these 18 patients, 16 (89%) had a low serum IMg2+ level. Total magnesium levels in contrast in all subjects were within normal range (0.70-0.99 mmol/L). No side effects were observed, except for a brief flushed feeling. Of the 8 patients with no relief, only 37.5% had a low IMg2+ level. Patients demonstrating no return of headache or associated symptoms within 24 hours of intravenous MgSO4 exhibited the lowest initial basal levels of IMg2+. Non-responders exhibited significantly elevated total magnesium levels compared to responders. Although most subcategories of headache types investigated (ie, migraine, cluster, chronic migrainous) exhibited low serum IMg2+ during headache and prior to intravenous MgSO4, the patients with cluster headaches exhibited the lowest basal levels of IMg2+ (P ><0.01). All headache subjects except for the chronic tension group exhibited rather high serum ICa2+/IMg2+ ratios (P ><0.01, compared to controls). CONCLUSIONS: Intravenous infusion of 1 gram of MgSO4 results in rapid relief of headache pain in patients with low serum IMg2+ levels. Measurement of serum IMg2+ levels may have a practical application in many types of headache patients. Low serum and brain tissue ionized magnesium levels may precipitate headache symptoms in susceptible patients.

Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study.

Cephalalgia, 16(4):257-63 1996 Jun

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.>< 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.

Relation between severity of magnesium deficiency and frequency of anginal attacks in men with variant angina.

J Am Coll Cardiol, 28(4):897-902 1996 Oct

OBJECTIVES: We evaluated whether the severity of magnesium deficiency was correlated with the frequency of attacks of variant angina. BACKGROUND: Magnesium deficiency may be associated with the development of variant angina. However, the relation between the activity of variant angina and magnesium deficiency remains to be elucidated. METHODS: We assessed the body magnesium status of 18 men with variant angina: Group 1 (> or = 4 attacks/week, n = 7) and Group 2 (< 4 attacks/week, n = 11). Concentrations of magnesium were determined in serum, urine, mononuclear cells and erythrocytes, and the 24-h magnesium retention rate was determined. RESULTS: Group 1 showed a higher 24-h magnesium retention rate (mean +/- SEM 63.5 +/- 7.6% vs. 24.9 +/- 2.7%, p < 0.01) and a lower intracellular concentration of magnesium in mononuclear cells and erythrocytes than did Group 2 (respectively, 156.3 +/- 13.5 vs. 212.1 +/- 6.9 fg/cell, p < 0.01; and 3.5 +/- 0.5 vs. 5.2 +/- 0.4 fg/cell, p < 0.05), demonstrating the presence of magnesium deficiency in Group 1. The 24-h magnesium retention rate and intracellular concentrations of magnesium in mononuclear cells and erythrocytes correlated well with the frequency of anginal attacks (r = 0.78, p < 0.01; r = -0.78, p < 0.01; r = -0.62, p < 0.01, respectively) for all patients. CONCLUSIONS: Data suggest that the magnesium status of men with variant angina is closely related to disease activity.

Safety, tolerability, and efficacy of a glucose-insulin-potassium-magnesium-carnitine solution in acute myocardial infarction.

Am J Cardiol, 78(4):477-9 1996 Aug 15

Fifty-four patients with AMI were treated with a front-loaded 15-hour infusion of hypertonic glucose, insulin, potassium, magnesium, and L-carnitine in addition to usual therapy. This metabolic solution was well tolerated, free of serious side effects, and reduced the incidence of morbid events.

Cognitive behaviour therapy for the chronic fatigue syndrome. Evening primrose oil and magnesium have been shown to be effective [letter; comment]

BMJ, 312(7038):1096; discussion 1098 1996 Apr 27

Magnesium in drinking water and death from acute myocardial infarction.

Am J Epidemiol, 143(5):456-62 1996 Mar 1

The relation between death from acute myocardial infarction and the level of magnesium in drinking water was examined using mortality registers and a case-control design. The study area comprised 17 municipalities in the southern part of Sweden that have different magnesium levels in the drinking water. Cases were men in the area who had died of acute myocardial infarction between ages 50 and 69 years during the period 1982-1989 (n = 854). The controls were men of the same age in the same area who had died from cancer during the same time period (n = 989). In both groups, only men who consumed water supplied from municipal waterworks were included in the study. The subjects were divided into quartiles according to the drinking water levels of magnesium and calcium and the quotient between magnesium and calcium. The odds ratios for death from acute myocardial infarction in the groups were inversely related to the amount of magnesium in drinking water. For the group with the highest levels of magnesium in drinking water, the odds ratio adjusted for age and calcium level was 0.65 (95 percent confidence interval 0.50-0.84). There was no such relation for calcium. For the magnesium/calcium quotient, the odds ratio was lower only for the group with the highest quotient. These data suggest that magnesium in drinking water is a important protective factor for death from acute myocardial infarction among males.

Magnesium and ascorbic acid supplementation in diabetes mellitus.

Ann Nutr Metab, 39(4):217-23 1995

The effect of magnesium (Mg) and ascorbic acid (AA) supplementation on metabolic control was assessed in 56 outpatient diabetics. A 90-day run-in period was followed by two 90-day treatment periods, during which Mg (600 mg/day) and AA (2 g/day) were administered in a randomized double-blind cross-over fashion. A decrease in systolic and diastolic blood pressure (132 +/- 3 vs. 138 +/- 4 and 77 +/- 2 vs. 82 +/- 2 mm Hg; p < 0.05) was observed in insulin-dependent diabetes mellitus subjects during Mg supplementation. No beneficial effect of Mg supplementation was observed on glycemic control, lipids or blood pressure in non-insulin-dependent diabetes mellitus (NIDDM) subjects. AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose (9.1 +/- 0.5 vs. 10.1 +/- 0.6 mmol/l; p < 0.05) and HbA1c (8.5 +/- 0.3 vs. 9.3 +/- 0.3%; p < 0.05) improved. Beneficial effects of AA supplementation on cholesterol (5.9 +/- 0.2 vs. 6.2 +/- 0.2 mmol/l; p < 0.05) and triglycerides (2.2 +/- 0.2 vs. 2.5 +/- 0.2; p < 0.05) were also observed in NIDDM subjects. The results suggest that high-dose AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids.

Magnesium status, serum HDL cholesterol, and apolipoprotein A-1 levels.

J Pediatr Gastroenterol Nutr, 20(3):316-8 1995 Apr

To determine the relationship between low magnesium status and lipids, we divided 27 patients with microscopic hematuria and normal renal function into two groups according to magnesium retention, as measured by a magnesium-loading test, and compared their serum lipid and apolipoproteins. Patients with low magnesium status (n = 7) had significantly lower levels of cholesterol, HDL cholesterol, and apolipoprotein A-1 than those with normal magnesium status (n = 20); however, there were no significant differences between the groups in serum concentrations of magnesium and apolipoprotein B. These data suggest that magnesium deficiencies are associated with low serum concentration of HDL cholesterol and apolipoprotein A-1.

Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study.

J Clin Epidemiol, 48(7):927-40 1995 Jul

The objective of this study was to examine the relationships of serum and dietary magnesium (Mg) with prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus, fasting insulin, and average carotid intimal-medial wall thickness measured by B-mode ultrasound. A cross-sectional design was used. The setting was the Atherosclerosis Risk in Communities (ARIC) Study in four US communities. A total of 15,248 participants took part, male and female, black and white, aged 45-64 years. Fasting serum Mg, lipids, fasting glucose and insulin were measured; as was usual dietary intake by food frequency questionnaire and carotid intima-media thickness by standardized B-mode ultrasound methods. The results showed that serum Mg levels and dietary Mg intake were both lower in blacks than whites. Mean serum Mg levels were significantly lower in participants with prevalent CVD, hypertension, and diabetes than in those free of these diseases. In participants without CVD, serum Mg levels were also inversely associated with fasting serum insulin, glucose, systolic blood pressure and smoking. Dietary Mg intake was inversely associated with fasting serum insulin, plasma high density lipoprotein-cholesterol, systolic and diastolic blood pressure. Adjusted for age, race, body mass index, smoking, hypertension, Low density lipoprotein-cholesterol, and field center, mean carotid wall thickness increased in women by 0.0118 mm (p = 0.006) in diuretic users and 0.0048 mm (p = 0.017) in nonusers for each 0.1 mmol/l decrease in serum Mg level; the multivariate association in men was not significant. In conclusion, low serum and dietary Mg may be related to the etiologies of CVD, hypertension, diabetes, and atherosclerosis.

Magnesium supplementation and osteoporosis.

Nutr Rev, 48(7):71-4 1995 Mar

The objective of this study was to examine the relationships of serum and dietary magnesium (Mg) with prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus, fasting insulin, and average carotid intimal-medial wall thickness measured by B-mode ultrasound. A cross-sectional design was used. The setting was the Atherosclerosis Risk in Communities (ARIC) Study in four US communities. A total of 15,248 participants took part, male and female, black and white, aged 45-64 years. Fasting serum Mg, lipids, fasting glucose and insulin were measured; as was usual dietary intake by food frequency questionnaire and carotid intima-media thickness by standardized B-mode ultrasound methods. The results showed that serum Mg levels and dietary Mg intake were both lower in blacks than whites. Mean serum Mg levels were significantly lower in participants with prevalent CVD, hypertension, and diabetes than in those free of these diseases. In participants without CVD, serum Mg levels were also inversely associated with fasting serum insulin, glucose, systolic blood pressure and smoking. Dietary Mg intake was inversely associated with fasting serum insulin, plasma high density lipoprotein-cholesterol, systolic and diastolic blood pressure. Adjusted for age, race, body mass index, smoking, hypertension, Low density lipoprotein-cholesterol, and field center, mean carotid wall thickness increased in women by 0.0118 mm (p = 0.006) in diuretic users and 0.0048 mm (p = 0.017) in nonusers for each 0.1 mmol/l decrease in serum Mg level; the multivariate association in men was not significant. In conclusion, low serum and dietary Mg may be related to the etiologies of CVD, hypertension, diabetes, and atherosclerosis.

Osteoporosis treated with magnesium lactate.

Acta Univ Palacki Olomuc Fac Med, 31(5):99-106 1991

33 patients with senile, 18 patients with postmenopausal and 9 patients with medicamentous (corticosteroids) osteoporosis were treated with single therapy of Mg lactate (37 patients) and with the combined one of Mg lactate and Na fluoride (23 patients). They were evaluated in three periods of half a year, one year, two years. The better results were achieved with the single therapy than with the combined one and in the senile and postmenopausal osteoporosis than in the medicamentous one. Pain and restricted spine movement were influenced favourably. Kyphosis and x-ray findings were stabilized.

Sudden death of athletes: is it due to long-term changes in serum magnesium, lipids and blood sugar?

J Basic Clin Physiol Pharmacol, 3(2):153-64 1992 Apr-Jun

In young, apparently healthy, trained Israeli men, strenuous effort was reported to give rise to persistent magnesium (Mg) deficiency and a parallel long-term increase of cholesterol, triglycerides and blood sugar parallel 1-3. The relationship of Mg deficiency to the pathogenesis of cardiovascular disease has been increasingly documented during the last decade. Several authors have highlighted the phenomenon of sudden deaths in sport and have suggested that it is associated with cardiovascular disease. The association is discussed between Mg deficiency and increase of blood lipids and sugar, found as a sequel to strenuous effort, and cardiovascular morbidity and mortality risk reported in athletes. It is postulated that sudden death of athletes and other intensely training individuals during exertion, is mediated by the deleterious cardiovascular effects of persistent magnesium deficiency and the resultant hyperlipaemia and hyperglycaemia, which, as we have documented, follows strenuous effort.

Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia.

Women Health, 19(2-3):117-31 1992

In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.

Calcium, magnesium and aluminum concentrations in Parkinson's disease.

Neurotoxicology, 13(3):593-600 1992 Fall

Concentrations of calcium (Ca) and aluminum (Al) were measured by neutron activation analysis and that of magnesium (Mg) by inductively coupled plasma emission spectrometry in 26 regions of Parkinson's disease (PD) and control brains. Ca concentration was unchanged in all anatomic subregions of PD brains compared with control brains. Mg concentration was lower in cortex, white matter, basal ganglia and brain stem of PD brains compared to control brains (p <0.01). Al concentration in the substantia nigra, caudate nucleus and globus pallidus was higher in PD brains compared to controls (p ><0.05) and significantly higher in gray matter and the basal ganglia (p ><0.01). These studies are consistent with other observations linking high concentrations of Al and low levels of Mg in the pathogenesis of CNS degeneration and PD.

Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics.

Alcohol Clin Exp Res, 16(5):986-90 1992 Oct

Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics.

Magnesium deficiency and diabetes mellitus. Causes and effects.

Postgrad Med, 16(5):217-9, 222-4 1992 Oct

A large body of evidence demonstrates the prevalence and adverse clinical consequences of magnesium deficiency in patients with diabetes mellitus. It would be prudent for physicians who treat these patients to consider magnesium deficiency as a contributing factor in many diabetic complications and in exacerbation of the disease itself. Repletion of the deficiency or prophylactic supplementation with oral magnesium may help avoid or ameliorate such complications as arrhythmias, hypertension, and sudden cardiac death and may even improve the course of the diabetic condition.

Magnesium deficiency and sudden death [editorial]

Am Heart J, 15(7):544-9 1992 Aug

A link between Mg deficiency and sudden death is suggested by a substantial number of studies published over the past three decades. Data come from epidemiologic, autopsy, clinical, and animal studies. They suggest that: (1) Sudden death is common in areas where community water supplies are Mg-deficient. (2) Myocardial Mg content is low in people who die of sudden death. (3) Cardiac arrhythmias and coronary artery vasospasm can be caused by Mg deficiency and (4) Intravenous Mg reduces the risk of arrhythmia and death immediately after acute myocardial infarction. Because of these data, Mg supplementation has been proposed as a possible method of reducing the risk of sudden death. Suggested ways of supplementing Mg include public education to change dietary habits, addition of Mg to community water supplies, fortification of foods, and oral supplementation. Despite the substantial number of studies linking Mg deficiency with sudden death, no prospective studies have yet investigated whether large-scale Mg supplementation is useful for the primary prevention of sudden death.

Daily magnesium supplements improve glucose handling in elderly subjects [see comments]

Am J Clin Nutr, 55(6):1161-7 1992 Jun

We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations (2.18 +/- 0.04 vs 1.86 +/- 0.03 mmol/L, P less than 0.01) in twelve aged (77.8 +/- 2.1 y) vs 25 young (36.1 +/- 0.4 y), nonobese subjects. Subsequently, aged subjects were enrolled in a double-blind, randomized, crossover study in which placebo (for 4 wk) and chronic magnesium administration (CMA) (4.5 g/d for 4 wk) were provided. At the end of each treatment period an intravenous glucose tolerance test (0.33 g/kg body wt) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed. CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action. Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action. In aged patients, correction of a low erythrocyte magnesium concentration may allow an improvement of glucose handling.

Serum and salivary magnesium levels in migraine and tension-type headache. Results in a group of adult patients.

Cephalalgia, 55(6):21-7 1992 Feb

We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations (2.18 +/- 0.04 vs 1.86 +/- 0.03 mmol/L, P less than 0.01) in twelve aged (77.8 +/- 2.1 y) vs 25 young (36.1 +/- 0.4 y), nonobese subjects. Subsequently, aged subjects were enrolled in a double-blind, randomized, crossover study in which placebo (for 4 wk) and chronic magnesium administration (CMA) (4.5 g/d for 4 wk) were provided. At the end of each treatment period an intravenous glucose tolerance test (0.33 g/kg body wt) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed. CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action. Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action. In aged patients, correction of a low erythrocyte magnesium concentration may allow an improvement of glucose handling.

Red blood cell magnesium and chronic fatigue syndrome [see comments]

Lancet, 337(8744):757-60 1991 Mar 30

The hypotheses that patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium and that magnesium treatment would improve the wellbeing of such patients were tested in a case-control study and a randomised, double-blind, placebo-controlled trial, respectively. In the case-control study, 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15). In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17). Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved from the maximum to the minimum. By contrast, 3 of the 17 patients on placebo said that they felt better (difference 62%, 95% CI 35 to 90), and 1 patient had a better energy score. Red cell magnesium returned to normal in all patients on magnesium but in only 1 patient on placebo. The findings show that magnesium may have a role in CFS.

The influence of extracellular magnesium on cell damage induced by ATP depletion in human fibroblasts.

Scand J Clin Lab Invest, 337(8744):11-5 1991 Feb

Magnesium is an essential ion for the structural and functional integrity of cells. We have examined whether a low extracellular magnesium concentration contributes to cell damage induced by ATP depletion in a model system of quiescent fibroblasts. Cell damage assessed by the release of lactate dehydrogenase was slightly, but significantly increased in the absence of Mg2+. The increased cell damage may be caused by an increased Mg2+ loss during ATP depletion, by an altered cell membrane permeability for potassium and sodium, or by a disturbed balance between Mg2+ and Ca2+.

Magnesium status and digoxin toxicity.

Br J Clin Pharmacol, 337(8744):717-21 1991 Dec

Eighty-one hospital patients receiving digoxin were separated into groups with and without digoxin toxicity using clinical criteria. Serum digoxin, sodium, potassium, calcium, creatinine, magnesium and monocyte magnesium concentrations were compared. 2. Subjects with digoxin toxicity had impaired colour vision (P less than 0.0001, Farnsworth-Munsell 100 hue test) and increased digoxin levels (1.89 (1.56-2.21) vs 1.34 (1.20-1.47) nmol l-1, P less than 0.01) (mean (95% confidence limits], though there was considerable overlap between two groups. 3. Subjects with digoxin toxicity had lower levels of serum magnesium (0.80 (0.76-0.84) vs 0.88 (0.85-0.91) mmol l-1, P less than 0.01) and monocyte magnesium (6.40 (5.65-7.16) vs 8.76 (7.81-9.71) mg g-1 DNA, P less than 0.01), but there were no significant differences in other biochemical parameters. A greater proportion of toxic subjects were receiving concomitant diuretic therapy (20/21 vs 37/60, P less than 0.05). 4. Magnesium deficiency was the most frequently identified significant electrolyte disturbance in relation to digoxin toxicity. In the presence of magnesium deficiency digoxin toxicity developed at relatively low serum digoxin concentrations.

The role of magnesium in clinical biochemistry: an overview.

Ann Clin Biochem, 78(2):19-26 1991 Jan

Magnesium is the second most abundant intracellular cation. It is essential for a wide variety of metabolically important reactions, in particular those involving ATP. Hypomagnesaemia is surprisingly common in hospital populations but is sometimes either undetected or overlooked. Serum magnesium concentrations provide a guide to magnesium status but while hypomagnesaemia is a reliable indicator of magnesium deficiency, normomagnesaemia does not exclude magnesium depletion. A wide variety of conditions predispose to magnesium depletion. Clinical magnesium deficiency has potentially fatal consequences in vulnerable groups of patients and should be excluded in all such cases. Magnesium deficiency may result in hypokalaemia, hypocalcaemia or other disturbances of electrolyte homeostasis, refractory cardiac arrhythmias, or increased sensitivity to digoxin. The capacity to measure serum and urine magnesium concentrations rapidly, regularly and reliably should be part of the repertoire of all clinical chemistry laboratories involved in the care of critically ill patients.

Central nervous system magnesium deficiency.

Arch Intern Med, 151(3):593-6 1991 Mar

The central nervous system concentration of magnesium (Mg++) appears to have a critical level below which neurologic dysfunction occurs. Observations presented suggest that the interchange of the Mg++ ion between the cerebrospinal fluid, extracellular fluid, and bone is more rapid and dynamic than is usually believed. This is especially so when the hypertrophied parathyroid gland is associated with significant skeletal depletion of Mg++ as judged by history rather than serum level. Magnesium, much like calcium, has a large presence in bone and has a negative feedback relationship with the parathyroid gland. A decline in central nervous system Mg++ may occur when the skeletal buffer system orchestrated largely by the parathyroid glands is activated by an increase in serum calcium. Observations in veterinary medicine and obstetrics suggest that the transfer of Mg++ from the extracellular fluid into bone during mineralization processes may be extensive. If the inhibition of the hypertrophied parathyroid gland is prolonged and the skeletal depletion of Mg++ extreme, serious neurologic symptoms, including seizures, coma, and death, may occur. Noise, excitement, and bodily contact appear to precipitate neurologic symptoms in Mg+(+)-deficient human subjects as it has been documented to occur in Mg+(+)-deficient experimental animals. The similarity of the acute central nervous system demyelinating syndromes with reactive central nervous system Mg++ deficiency is reviewed.

Hypomagnesemia and the parathyroid hormone-vitamin D endocrine system in children with insulin-dependent diabetes mellitus: effects of magnesium administration [see comments]

J Pediatr, 118(2):220-5 1991 Feb

Because insulin-dependent diabetes mellitus is associated with altered electrolyte metabolism and a derangement of the parathyroid hormone (PTH)-vitamin D endocrine system, we studied 23 children with diabetes (age 9.4 +/- 2.5 years) and found lower serum values for total and ionized calcium, magnesium, intact PTH, calcitriol, and osteocalcin than in age- and sex-matched control subjects. All patients were given magnesium orally (6 mg/kg daily of elemental magnesium) for up to 60 days. During treatment, serum magnesium, total and ionized calcium, intact PTH, calcitriol, and osteocalcin concentrations significantly increased, reaching control values. After a 3-day low-calcium diet, the patients had a significantly reduced delta-increment of PTH and calcitriol in comparison with values obtained during hypomagnesemia. After magnesium repletion, the delta-increments of both PTH and calcitriol, in response to the low-calcium diet, were not significantly different from control values. These data suggest that magnesium deficiency plays a pivotal role in altering mineral homeostasis in insulin-dependent diabetes mellitus.

Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment.

Magnes Res, 3(3):197-215 1990 Sep

Prophylactic treatment of postmenopausal osteoporosis with oestrogen and calcium, often in combination, disregards the likelihood that an excess of each agent may increase magnesium requirements and decrease serum Mg levels. Relative or absolute Mg deficiency, which is likely in the Occident where the Mg intake is commonly marginal, can militate against optimal therapeutic bone response, Mg being important for normal bone structure, and can increase the risk of adverse effects. Although oestrogen has cardiovascular protective effects (expressed by the lower incidence of heart disease in premenopausal women than in men, and also in postmenopausal women given low dosage oestrogen replacement treatment), high dosage oestrogen oral contraceptives have caused increased intravascular blood clotting with resultant thromboembolic cardio- and cerebrovascular accidents. This might be contributed to by the oestrogen-mediated shift of circulating Mg to soft and hard tissues, which in persons with marginal Mg intakes may lead to suboptimal serum levels. If the commonly recommended dietary Ca/Mg ratio of 2/1 is exceeded (and it can reach as much as 4/1 in countries with low to marginal Mg intakes), relative or absolute Mg deficiency may result, and this may increase the risk of intravascular coagulation, since blood clotting is enhanced by high Ca/Mg ratios. Mechanisms by which Ca activates the various steps in blood coagulation that are also stimulated by oestrogen are considered here, as are the multifaceted roles of Mg that favourably affect blood coagulation and fibrinolysis, through its activities in lipoprotein and prostanoid metabolism.

Angiotensin converting enzyme inhibitors, thiazide diuretics and magnesium balance. A preliminary study.

Magnes Res, 3(3):193-6 1990 Sep

Serum and mononuclear cell magnesium content were determined in a cross-sectional study performed in four groups of hypertensive patients on chronic treatment with atenolol (n = 11), enalapril (n = 10), thiazide diuretics (n = 12), or enalapril + thiazides (n = 11). Our study shows that in patients treated with the thiazides alone, in spite of normal serum potassium and magnesium levels, mononuclear cell magnesium was decreased. To the extent that mononuclear Mg content mirrors the body ion stores, our results indicate that thiazides induce a Mg depletion not detectable by monitoring serum levels.

Magnesium, schizophrenia and manic-depressive disease.

Neuropsychobiology, 3(3):79-81 1990

Plasma magnesium (Mg) levels were estimated in 15 schizophrenic, 10 depressed, 6 manic and 6 presenile Alzheimer's disease patients and compared with those in 303 healthy controls. The schizophrenic and depressed patients showed lower levels, but the levels were normal in the other two groups. Mg levels increased on achieving clinical remission in the schizophrenic patients. A hypothesis is proposed according to which the high level of stress found in severely ill psychiatric patients can lead to marginal Mg deficiency in susceptible individuals. This could exacerbate symptoms such as anxiety, fear, hallucinations, weakness and somatic complaints.

Magnesium and glucose homeostasis.

Diabetologia, 3(9):511-4 1990 Sep

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 diabetic subjects.

Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones.

Magnes Trace Elem, 3(2):61-9 1990

Recent findings are reviewed indicating that changes in dietary boron and magnesium affect calcium, and thus bone, metabolism in animals and humans. In animals, the need for boron was found to be enhanced when they needed to respond to a nutritional stress which adversely affected calcium metabolism, including magnesium deficiency. A combined deficiency of boron and magnesium caused detrimental changes in the bones of animals. However, boron deprivation did not seem to enhance the requirement for magnesium. In two human studies, boron deprivation caused changes in variables associated with calcium metabolism in a manner that could be construed as being detrimental to bone formation and maintenance; these changes apparently were enhanced by low dietary magnesium. Changes caused by boron deprivation included depressed plasma ionized calcium and calcitonin as well as elevated plasma total calcium and urinary excretion of calcium. In one human study, magnesium deprivation depressed plasma ionized calcium and cholesterol. Because boron and/or magnesium deprivation causes changes similar to those seen in women with postmenopausal osteoporosis, these elements are apparently needed for optimal calcium metabolism and are thus needed to prevent the excessive bone loss which often occurs in postmenopausal women and older men.

Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population sample

Lancet 344 (8919): 357-62 94328809

Magnesium is involved in a wide range of biological activities, including some that may protect against the development of asthma and chronic airflow obstruction. We tested the hypothesis that high dietary magnesium intake is associated with better lung function, and a reduced risk of airway hyper-reactivity and wheezing in a random sample of adults. In 2633 adults aged 18-70 sampled from the electoral register of an administrative area of Nottingham, UK, we measured dietary magnesium intake by semiquantitative food-frequency questionnaire, lung function as the 1-sec forced expiratory volume (FEV1), and atopy as the mean skin-prick test response to three common environmental allergens. We measured airway reactivity to methacholine in 2415 individuals, defining hyper-reactivity as a 20% fall in FEV1 after a cumulative dose of 12.25 mumol or less. Mean (SD) daily intake of magnesium was 380 (114) mg/day. After adjusting for age, sex, and height, and for the effects of atopy and smoking, a 100 mg/day higher magnesium intake was associated with a 27.7 (95% CI, 11.9-43.5) mL higher FEV1, and a reduction in the relative odds of hyper-reactivity by a ratio of 0.82 (0.72-0.93). The same incremental difference in magnesium intake was also associated with a reduction in the odds of self-reported wheeze within the past 12 months, adjusted for age, sex, smoking, atopy, and kilojoule intake, by a ratio of 0.85 (0.76-0.95). Dietary magnesium intake is independently related to lung function and the occurrence of airway hyper-reactivity and self-reported wheezing in the general population. Low magnesium intake may therefore be involved in the aetiology of asthma and chronic obstructive airways disease.

Magnesium deficiency produces insulin resistance and increased thromboxane synthesis

Hypertension 21(6 Pt 2): 1024-9 93279768

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 (186 +/- 10 [SEM] to 127 +/- 9 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 (3.69 +/- 0.6 to 2.75 +/- 0.5 min-1 per microunit per milliliter x 10(-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.