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February 2007

Magnesium in clinical medicine.

Until recently the physiological role of magnesium was essentially ignored. However, with the development of new technologies to measure the intracellular free concentration of magnesium ([Mg2+]i), the biologically important fraction, there has been an explosion of interest in the molecular, biochemical, physiological and pharmacological functions of magnesium. In addition improved methods for assessing magnesium status in the clinic have contributed to the further understanding of magnesium regulation in health and disease. Magnesium deficiency is now considered to contribute to many diseases and the role for magnesium as a therapeutic agent is being tested in numerous large clinical trials. This review focuses on clinical manifestations associated with magnesium deficiency and highlights the clinical significance of hypermagnesemia. Specific clinical conditions in which magnesium deficiency has been implicated to play a pathophysiological role, namely hypertension, ischemic heart disease, arrhythmias, prec-eclampsia, asthma and critical illness will be discussed and the possible therapeutic role of magnesium will be considered. Although there is still much to be learnt regarding the exact role of magnesium in clinical medicine, there are two conditions where magnesium is now considered the therapeutic agent of choice, pre-eclampsia and torsades de pointes. Future research, both at the fundamental and clinical levels, will certainly facilitate our understanding of how magnesium contributes to pathological processes and under what circumstances it should be used therapeutically.

Front Biosci. 2004 May 1;9:1278-93

Magnesium status and ageing: an update.

Ageing constitutes a risk factor for magnesium deficit. Primary magnesium deficit originates from two etiological mechanisms: deficiency and depletion. Primary magnesium deficiency is due to insufficient magnesium intake. Dietary amounts of magnesium are marginal in the whole population whatever the age. Nutritional deficiencies are more pronounced in institutionalized than in free-living ageing groups. Primary magnesium depletion is due to dysregulation of factors controlling magnesium status: intestinal magnesium hypoabsorption, reduced magnesium bone uptake and mobilisation, sometimes urinary leakage, hyperadrenoglucocorticism by decreased adaptability to stress, insulin-resistance and adrenergic hyporeceptivity. Secondary magnesium deficit in ageing largely results from various pathologies and treatments common to elderly persons: i.e. non insulin dependent diabetes mellitus and use of hypermagnesuric diuretics. Magnesium deficit may participate in the clinical pattern of ageing: mainly neuromuscular, cardiovascular and renal symptomatologies. The consequences of hyperadrenoglucocorticism--whose non response to dexamethasone suppression test appears the simplest marker--may concern immunosuppression, muscle atrophy, centralization of fat mass, osteoporosis, hyperglycemia, hyperlipidemia, atherosclerosis, disturbances in mood and mental performances through accelerated hippocampal ageing particularly. Treatment of magnesium deficiency requires simple oral physiological magnesium supplementation. Treatment of the different types of magnesium depletion leads to a more or less specific control of pathophysiological disturbances of the required magnesium substrate. Open and double blind studies on the effects of the treatments of magnesium deficiency and of magnesium depletions in geriatic populations are too scarce. Further study is necessary to assess the accurate place of magnesium deficit in the physiopathology of ageing.

Magnes Res. 1998 Mar;11(1):25-42

Intravenous magnesium sulphate in acute myocardial infarction—is the answer “MAGIC”?

The role of magnesium in coronary artery disease has been evaluated extensively during the last three decades. The intravenous application of magnesium in acute myocardial infarction is of major importance, the beneficial effects have been underlined in several studies. Magnesium is of significance in the pathomechanisms of reperfusion injury and reduction of malign arrhythmias in the critical acute phase of myocardial infarction, if applied intravenously. However, the promising results of LIMIT-2 could not be confirmed by the data of ISIS-4. The timing of magnesium therapy is probably the most important key factor. Similar to the guidelines of thrombolytic intervention, magnesium has to be administered as early as possible, at the latest before myocardial reperfusion has started. Nevertheless, because of conflicting results of prior trials doubts on the efficacy of intravenous magnesium in myocardial infarction still remain. The multinational, multicenter trial MAGIC has been set up to evaluate the optimal patient cohort as well as the ideal dose regimen for the application of intravenous magnesium sulphate in patients with acute myocardial infarction. The answer on the open questions on intravenous magnesium sulphate in myocardial infarction could be “MAGIC”.

Magnes Res. 2003 Mar;16(1):65-9

Calcium:magnesium ratio in local groundwater and incidence of acute myocardial infarction among males in rural Finland.

Several epidemiologic studies have shown an association between calcium and magnesium and coronary heart disease mortality and morbidity. In this small-area study, we examined the relationship between acute myocardial infarction (AMI) risk and content of Ca, Mg, and chromium in local groundwater in Finnish rural areas using Bayesian modeling and geospatial data aggregated into 10 km times symbol 10 km grid cells. Data on 14,495 men 35-74 years of age with their first AMI in the years 1983, 1988, or 1993 were pooled. Geochemical data consisted of 4,300 measurements of each element in local groundwater. The median concentrations of Mg, Ca, and Cr and the Ca:Mg ratio in well water were 2.61 mg/L, 12.23 mg/L, 0.27 microg/L, and 5.39, respectively. Each 1 mg/L increment in Mg level decreased the AMI risk by 4.9%, whereas a one unit increment in the Ca:Mg ratio increased the risk by 3.1%. Ca and Cr did not show any statistically significant effect on the incidence and spatial variation of AMI. Results of this study with specific Bayesian statistical analysis support earlier findings of a protective role of Mg and low Ca:Mg ratio against coronary heart disease but do not support the earlier hypothesis of a protective role of Ca.

Environ Health Perspect. 2006 May;114(5):730-4

Magnesium intake and incidence of metabolic syndrome among young adults.

BACKGROUND: Studies suggest that magnesium intake may be inversely related to risk of hypertension and type 2 diabetes mellitus and that higher intake of magnesium may decrease blood triglycerides and increase high-density lipoprotein (HDL) cholesterol levels. However, the longitudinal association of magnesium intake and incidence of metabolic syndrome has not been investigated. METHODS AND RESULTS: We prospectively examined the relations between magnesium intake and incident metabolic syndrome and its components among 4,637 Americans, aged 18 to 30 years, who were free from metabolic syndrome and diabetes at baseline. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III definition. Diet was assessed by an interviewer-administered quantitative food frequency questionnaire, and magnesium intake was derived from the nutrient database developed by the Minnesota Nutrition Coordinating Center. During the 15 years of follow-up, 608 incident cases of the metabolic syndrome were identified. Magnesium intake was inversely associated with incidence of metabolic syndrome after adjustment for major lifestyle and dietary variables and baseline status of each component of the metabolic syndrome. Compared with those in the lowest quartile of magnesium intake, multivariable-adjusted hazard ratio of metabolic syndrome for participants in the highest quartile was 0.69 (95% confidence interval [CI], 0.52 to 0.91; P for trend <0.01). The inverse associations were not materially modified by gender and race. Magnesium intake was also inversely related to individual component of the metabolic syndrome and fasting insulin levels. CONCLUSIONS: Our findings suggest that young adults with higher magnesium intake have lower risk of development of metabolic syndrome.

Circulation. 2006 Apr 4;113(13):1675-82

Clinical efficacy of magnesium supplementation in patients with type 2 diabetes.

Effects of magnesium (Mg) supplementation on nine mild type 2 diabetic patients with stable glycemic control were investigated. Water from a salt lake with a high natural Mg content (7.1%) (MAG21) was used for supplementation after dilution with distilled water to 100mg/100mL; 300mL/day was given for 30 days. Fasting serum immunoreactive insulin level decreased significantly, as did HOMA squareR (both p < 0.05). There was also a marked decrease of the mean triglyceride level after supplementation. The patients with hypertension showed significant reduction of systolic (p < 0.01), diastolic (p = 0.0038), and mean (p < 0.01) blood pressure. The salt lake water supplement, MAG21, exerted clinical benefit as a Mg supplement in patients with mild type 2 diabetes mellitus.

J Am Coll Nutr. 2004 Oct;23(5):506S-509S

Role of magnesium in hypertension.

Magnesium affects blood pressure by modulating vascular tone and reactivity. It acts as a calcium channel antagonist, it stimulates production of vasodilator prostacyclins and nitric oxide and it alters vascular responses to vasoactive agonists. Magnesium deficiency has been implicated in the pathogenesis of hypertension with epidemiological and experimental studies demonstrating an inverse correlation between blood pressure and serum magnesium levels. Magnesium also influences glucose and insulin homeostasis, and hypomagnesemia is associated with metabolic syndrome. Although most epidemiological and experimental studies support a role for low magnesium in the pathophysiology of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of hypertension is unclear. The present review addresses the role of magnesium in the regulation of vascular function and blood pressure and discusses the implications of magnesium deficiency in experimental and clinical hypertension, in metabolic syndrome and in pre-eclampsia.

Arch Biochem Biophys. 2006 May 24

Aerosolized magnesium sulfate for acute asthma: a systematic review.

BACKGROUND: The use of MgSO(4) is one of numerous treatment options available during exacerbations of asthma. While the efficacy of therapy with IV MgSO(4) has been demonstrated, little is known about inhaled MgSO(4). OBJECTIVES: A systematic review of the literature was performed to examine the effect of inhaled MgSO(4) in the treatment of patients with asthma exacerbations in the emergency department. METHODS: Randomized controlled trials were eligible for inclusion and were identified from the Cochrane Airways Group “Asthma and Wheez*” register, which consists of a combined search of the EMBASE, CENTRAL, MEDLINE, and CINAHL databases and the manual searching of 20 key respiratory journals. Reference lists of published studies were searched, and a review of the gray literature was also performed. Studies were included if patients had been treated with nebulized MgSO(4) alone or in combination with beta(2)-agonists and were compared to the use of beta(2)-agonists alone or with an inactive control substance. Trial selection, data extraction, and methodological quality were assessed by two independent reviewers. The results from fixed-effects models are presented as standardized mean differences (SMDs) for pulmonary functions and the relative risks (RRs) for hospital admission. Both are displayed with their 95% confidence intervals (CIs). RESULTS: Six trials involving 296 patients were included. There was a non-significant increase [corrected] in pulmonary function between patients whose treatments included nebulized MgSO(4) and those whose treatments [corrected] did not (SMD, 0.22; 95% CI, -0.02 to 0.47 [corrected] five studies); there was also a trend toward reduced [corrected] hospitalizations in patients whose treatments included nebulized MgSO(4) (RR, 0.67; 95% CI, 0.41 to 1.09; four studies). Subgroup analyses demonstrated that lung function improvement was similar in adult patients and in those patients who received nebulized MgSO(4) in addition to a beta(2)-agonist. CONCLUSIONS: The use of nebulized MgSO(4), particularly in addition to a beta(2)-agonist, in the treatment of an acute asthma exacerbation appears to produce benefits with respect to improved pulmonary function and may reduce the number of hospital admissions.

Chest. 2005 Jul;128(1):337-44

Magnesium deficiency and osteoporosis: animal and human observations.

Although osteoporosis is a major health concern for our growing population of the elderly, there continues to be a need for well-designed clinical and animal studies on the link between dietary magnesium (Mg) intake and osteoporosis. Relatively few animal studies have assessed the skeletal and hormonal impact of long-term low Mg intake; however, these studies have demonstrated that Mg deficiency results in bone loss. Potential mechanisms include a substance P-induced release of inflammatory cytokines as well as impaired production of parathyroid hormone and 1,25-dihydroxyvitamin D. Abnormal mineralization of bones may also contribute to skeletal fragility. Clinical studies have often varied greatly in study design, subject age, menopausal status and outcome variables that were assessed. Most studies focused on female subjects, thus pointing to the great need for studies on aging males. According to the U.S. Department of Agriculture, the mean Mg intake for males and females is 323 and 228 mg/day, respectively. These intake levels suggest that a substantial number of people may be at risk for Mg deficiency, especially if concomitant disorders and/or medications place the individual at further risk for Mg depletion. In this paper, we will review animal and human evidence of the association of Mg deficiency with osteoporosis and explore possible mechanisms by which this may occur.

J Nutr Biochem. 2004 Dec;15(12):710-6

Bioavailability of US commercial magnesium preparations.

Magnesium deficiency is seen with some frequency in the outpatient setting and requires oral repletion or maintenance therapy. The purpose of this study was to measure the bioavailability of four commercially-available preparations of magnesium, and to test the claim that organic salts are more easily absorbed. Bioavailability was measured as the increment of urinary maginesium excretion in normal volunteers given approximately 21 mEq/day of the test preparations. Results indicated relatively poor bioavailability of magnesium oxide (fractional absorption 4 per cent) but significantly higher and equivalent bioavailability of magnesium chloride, magnesium lactate and magnesium aspartate. We conclude that there is relatively poor bioavailability of magnesium oxide, but greater and equivalent bioavailability of magnesium chloride, lactate, and aspartate. Inorganic magnesium salts, depending on the preparation, may have bioavailability equivalent to organic magnesium salts.

Magnes Res. 2001 Dec;14(4):257-62

Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.

Literature data on the bioavailability of various Mg forms provide scarce information on the best Mg salt to be used in animal and human supplementation. This study aimed to investigate the bioavailability of different forms of Mg in rats using Mg stable isotopes. Eighty male Wistar rats aged 6 weeks were fed a semi-purified Mg-depleted diet for three weeks. The rats were then randomised into ten groups and received, for two more weeks, the same diet repleted with Mg (550 mg Mg/kg) as: oxide, chloride, sulphate, carbonate, acetate, pidolate, citrate, gluconate, lactate or aspartate. After 10 days of Mg-repleted diet, the rats received orally 1.8 mg of an enriched 26Mg. Faeces and urine were then collected for 4 consecutive days. Isotope ratios in faeces and urine were determined. The Mg absorption values obtained varied from 50% to 67%. Organic Mg salts were slightly more available than inorganic Mg salts. Mg gluconate exhibited the highest Mg bioavailability of the ten Mg salts studied. Urinary 26Mg excretion varied from 0.20 mg to 0.33 mg, and feeding with the organic pidolate, citrate, gluconate and aspartate salts resulted in higher urinary 26Mg excretion than with inorganic salts. Ultimately, 26Mg retention was higher in the rats receiving the organic salts such as gluconate, lactate and aspartate than in those receiving the inorganic salts. Taken together, these results indicate that 26Mg is sufficiently bioavailable from the ten different Mg salts studied in the present experiment, although Mg gluconate exhibited the highest bioavailability under these experimental conditions.

Magnes Res. 2005 Dec;18(4):215-23