Magnesium. An update on physiological, clinical and analytical aspects.

Magnesium (Mg(2+)) is an essential ion to the human body, playing an instrumental role in supporting and sustaining health and life. As the second most abundant intracellular cation after potassium, it is involved in over 600 enzymatic reactions including energy metabolism and protein synthesis. Although Mg(2+) availability has been proven to be disturbed during several clinical situations, serum Mg(2+) values are not generally determined in patients. This review aims to provide an overview of the function of Mg(2+) in human health and disease. In short, Mg(2+) plays an important physiological role particularly in the brain, heart, and skeletal muscles. Moreover, Mg(2+) supplementation has been shown to be beneficial in treatment of, among others, preeclampsia, migraine, depression, coronary artery disease, and asthma. Over the last decade, several hereditary forms of hypomagnesemia have been deciphered, including mutations in transient receptor potential melastatin type 6 (TRPM6), claudin 16, and cyclin M2 (CNNM2). Recently, mutations in Mg(2+) transporter 1 (MagT1) were linked to T-cell deficiency underlining the important role of Mg(2+) in cell viability. Moreover, hypomagnesemia can be the consequence of the use of certain types of drugs, such as diuretics, epidermal growth factor receptor inhibitors, calcineurin inhibitors, and proton pump inhibitors. This review provides an extensive and comprehensive overview of Mg(2+) research over the last few decades, focusing on the regulation of Mg(2+) homeostasis in the intestine, kidney, and bone and disturbances which may result in hypomagnesemia.

Magnesium in Man: Implications for Health and Disease

We investigated whether a relationship between risk of death and treatment effect could explain the disparate results between the preclinical and clinical sepsis trials of antiinflammatory agents over the last decade. A metaregression analysis of cited preclinical studies showed that the treatment effects of these agents were highly dependent on risk of death (p = 0.0001) and that animals were studied at significantly higher control mortality rates than humans (median [25th-75th quartile], 88% [79-96%] versus 39% [32-42%], p = 0.0001). An analysis of the clinical trials showed that antiinflammatory agents were also significantly more efficacious in septic patients with higher risk of death (p = 0.002) and were harmful in those with low risk. To test this relationship prospectively, we studied antiinflammatory agents in models employing differing doses of bacterial challenge to produce the full range of risk of death. We found that the efficacy of these agents, although very beneficial at high control mortality rates, was much reduced (p = 0.0001) and similar to those in human trials at moderate control mortality rates (i.e., 30 to 40%). The efficacy of antiinflammatory agents during sepsis is dependent on the risk of death, an observation that explains the apparent contradiction between preclinical and clinical trial results. Accounting for this relationship may be necessary for the safe and effective development of antiinflammatory therapies for sepsis.

https://www.atsjournals.org/doi/pdf/10.1164/rccm.200204-302OC

Risk and the efficacy of antiinflammatory agents : retrospective and confirmatory studies of sepsis

The term Dietary Reference Intakes (DRIs) is new to the field of nutrition. It refers to a set of at least four nutrient-based reference values that can be used for planning and assessing diets and for many other purposes. The development of DRIs replaces the periodic revisions of Recommended Dietary Allowances (RDAs), which have been published since 1941 by the National Academy of Sciences. This is a comprehensive effort being undertaken by the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences, with the involvement of Health Canada.

Dietary Reference Intakes

ratio, 0.856; 95% confidence interval, 0.71‐1.03; p .0943; I 2 45.1%), stratification of datasets by monotherapy mortality risk demonstrated substantial benefit in the most severely ill subset (monotherapy risk of death >25%; odds ratio, 0.51; 95% confidence interval, 0.41‐0.64; I 2 8.6%). Of those datasets that could be stratified by the presence of shock/critical illness, the more severely ill group consistently demonstrated increased efficacy of a combination therapy strategy (odds ratio, 0.49; 95% confidence interval, 0.35‐0.70; p < .0001; I 2 0%). An increased risk of death was found in low-risk patients (risk of death <15% in the monotherapy arm) exposed to combination therapy (odds ratio, 1.53; 95% confidence interval, 1.16‐2.03; p .003; I 2 8.2%). Meta-regression indicated that efficacy of combination therapy was dependent only on the risk of death in the monotherapy group. Conclusion: Combination therapy is optimal for management of high-risk, life-threatening infections, particularly those associated with septic shock but may be detrimental to low-risk patients. (Crit Care Med 2010; 38:000‐000)

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A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study.

Stress intensifies release of catecholamines and corticosteroids that increase survival of normal animals when their lives are threatened. When magnesium (Mg) deficiency exists, stress paradoxically increases risk of cardiovascular damage including hypertension, cerebrovascular and coronary constriction and occlusion, arrhythmias and sudden cardiac death (SCD). In affluent societies, severe dietary Mg deficiency is uncommon, but dietary imbalances such as high intakes of fat and/or calcium (Ca) can intensify Mg inadequacy, especially under conditions of stress. Adrenergic stimulation of lipolysis can intensify its deficiency by complexing Mg with liberated fatty acids (FA), A low Mg/Ca ratio increases release of catecholamines, which lowers tissue (i.e. myocardial) Mg levels. It also favors excess release or formation of factors (derived both from FA metabolism and the endothelium), that are vasoconstrictive and platelet aggregating; a high Ca/Mg ratio also directly favors blood coagulation, which is also favored by excess fat and its mobilization during adrenergic lipolysis. Auto-oxidation of catecholamines yields free radicals, which explains the enhancement of the protective effect of Mg by anti-oxidant nutrients against cardiac damage caused by beta-catecholamines. Thus, stress, whether physical (i.e. exertion, heat, cold, trauma--accidental or surgical, burns), or emotional (i.e. pain, anxiety, excitement or depression) and dyspnea as in asthma increases need for Mg. Genetic differences in Mg utilization may account for differences in vulnerability to Mg deficiency and differences in body responses to stress.

Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).

The latent tetany syndrome (LTS) parallels CFS in its neuromuscular and psychiatric manifestations, as well as in inner ear disturbances: vestibular in CFS and FM, as well as in LTS, and increased vulnerability to noise-induced deafness in LTS. Microvascular damage to the cochlea is seen in Mg deficiency, noise-induced deafness, and might be a

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Review and Hypothesis: Might Patients with the Chronic Fatigue Syndrome Have Latent Tetany of Magnesium Deficiency

Come with us to read a new book that is coming recently. Yeah, this is a new coming book that many people really want to read will you be one of them? Of course, you should be. It will not make you feel so hard to enjoy your life. Even some people think that reading is a hard to do, you must be sure that you can do it. Hard will be felt when you have no ideas about what kind of book to read. Or sometimes, your reading material is not interesting enough.

Magnesium in cellular processes and medicine

Because cardiovascular disease (CVD), which is far less common in young women than in men, but increases in prevalence in the postmenopausal years to that of men, estrogen repletion therapy (ERT) or combined hormone replacement therapy (HRT), has been widely used to protect against development of both CVD and osteoporosis, and possibly to delay or prevent cognitive loss or Alzheimer's disease (AD). To test the validity of favorable findings in many small-scale studies, and in clinical practice, a large-scale trial: the Women's Health Initiative (WHI) was undertaken by the National Institutes of Health (NIH), a trial that was prematurely ended because of increased CVD complications, despite some lessening of hip fractures. This paper suggests that the customary high intake of calcium (Ca)-advised to protect against osteoporosis, and the marginal magnesium (Mg) intake in the USA, might well be contributory to the adverse CV effects, that were all thromboembolic in nature. The procoagulant effect of estrogen is intensified by Ca; Mg-which counteracts many steps in the coagulation cascade and inhibits platelet aggregation and adhesion-is commonly consumed in sub-optimal amounts. The high American dietary Ca/Mg ratio might also be contributory to the WHI failure to confirm ERT's favorable mental effects. Discussed are mechanisms by which Mg enhances estrogen's central nervous system protective effects. Mg's improvement of cerebral blood flow, which improves brain metabolism, can also enhance removal of the beta amyloid peptide, accumulation of which is implicated in AD.

Mildred S. Seelig

Papers

Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).

Review and Hypothesis: Might Patients with the Chronic Fatigue Syndrome Have Latent Tetany of Magnesium Deficiency

Magnesium in cellular processes and medicine

Benefits and Risks of Sex Hormone Replacement in Postmenopausal Women

Magnesium in acute myocardial infarction: still an open question.