The Contribution of Dietary Magnesium in Farm Animals and Human Nutrition.

Magnesium (Mg) is a mineral that plays an essential role as cofactor of more than 300 enzymes. Mg in farm animals' and human nutrition is recommended to avoid Mg deficiency, ensure adequate growth and health maintenance. Mg supplementation above the estimated minimum requirements is the best practice to improve farm animals' performances (fertility and yield) and food products' quality, since the performance of farm animals has grown in recent decades. Mg supplementation in pigs increases meat quality and sows' fertility; in poultry, it helps to avoid deficiency-related health conditions and to improve meat quality and egg production by laying hens; in dairy cows, it serves to avoid grass tetany and milk fever, two conditions related to hypomagnesaemia, and to support their growth. Thus, Mg supplementation increases food products' quality and prevents Mg deficiency in farm animals, ensuring an adequate Mg content in animal-source food. These latter are excellent Mg sources in human diets. Sub-optimal Mg intake by humans has several implications in bone development, muscle function, and health maintenance. This review summarizes the main knowledge about Mg in farm animals and in human nutrition.

Does fludrocortisone treatment cause hypomagnesemia in children with primary adrenal insufficiency?

Background/aim: Aldosterone is a mineralocorticoid that secreted from adrenal glands and a known factor to increase magnesium excretion by direct and indirect effects on renal tubular cells. Although the frequency of hypomagnesemia was found to be approximately 5% in adult studies, there is no study in the literature investigating the frequency of hypomagnesemia in children by using fludrocortisone, which has a mineralocorticoid activity. Materials and methods: A multi-center retrospective study was conducted, including children who were under fludrocortisone treatment for primary adrenal insufficiency and applied to participant pediatric endocrinology outpatient clinics. Results: Forty-three patients (58.1% male, 41.9% prepubertal) included in the study, whose median age was 9.18 (0.61-19) years, and the most common diagnosis among the patients was a salt-wasting form of congenital adrenal hyperplasia (67.4%). Mean serum magnesium level was 2.05 (±0.13) mg/dL, and hypomagnesemia was not observed in any of the patients treated with fludrocortisone. None of the patients had increased urinary excretion of magnesium. Conclusion: Unlike the studies performed in adults, we could not find any evidence of magnesium wasting effect of fludrocortisone treatment with normal or even high doses in children and adolescents.

Parathyroid hormone resistance from severe hypomagnesaemia caused by cisplatin.

Not required for Clinical Vignette.

Magnesium Deficiency Questionnaire: A New Non-Invasive Magnesium Deficiency Screening Tool Developed Using Real-World Data from Four Observational Studies.

Due to the high estimated prevalence of magnesium deficiency, there is a need for a rapid, non-invasive assessment tool that could be used by patients and clinicians to confirm suspected hypomagnesemia and substantiate laboratory testing. This study analyzed data from four large observational studies of hypomagnesemia in pregnant women and women with hormone-related conditions across Russia. Hypomagnesemia was assessed using a 62-item magnesium deficiency questionnaire (MDQ-62) and a serum test. The diagnostic utility (sensitivity/specificity) of MDQ-62 was analyzed using area under the receiver operating characteristic curve (AUROC). A logistic regression model was applied to develop a shorter, optimized version of MDQ-62. A total of 765 pregnant women and 8836 women with hormone-related conditions were included in the analysis. The diagnostic performance of MDQ-62 was "fair" (AUROC = 0.7-0.8) for women with hormone-related conditions and "poor" for pregnant women (AUROC = 0.6-0.7). The optimized MDQ-23 (23 questions) and MDQ-10 (10 questions) had similar AUROC values; for all versions of the questionnaire, there was a significant negative correlation between score and changes in total serum magnesium levels (p < 0.0001 for all comparisons; correlation coefficients ranged from -0.1667 to -0.2716). This analysis confirmed the value of MDQ in identifying women at risk of hypomagnesemia.

Cisplatin given at three divided doses for three consecutive days in metastatic breast cancer: an alternative schedule for one full dose with comparable efficacy but less CINV and hypomagnesaemia.

PURPOSE: Cisplatin, an effective medication for metastatic breast cancer (MBC), is recommended to be applied at the dose of 75 mg/m2 on day 1 every 3 weeks. However, the 75 mg/m2 schedule is often associated with a variety of side effects (such as vomiting and kidney toxicity), and time-consuming hydration treatment is usually needed. Divided dose (25 mg/m2 on day 1-3) without hydration is an alternative. This study aimed to compare the efficacy and toxicity profiles between these two dosage regimens. METHODS: Patients with MBC treated with cisplatin-based regimens in Fudan University Shanghai Cancer Center between December 2008 and June 2019 were retrospectively analyzed. Objective response rate (ORR), progression-free survival (PFS), and toxicity profiles were analyzed. RESULTS: 227 patients receiving a 1-day schedule and 256 patients receiving a 3-day schedule were included. Median PFS was 6.68 (5.66-7.70) months for patients in the 1-day schedule group and 6.70 (5.89-7.52) months for patients in the 3-day schedule group. There was no statistically significant difference in PFS between the two treatment groups (hazard ratio, 0.942; 95% CI 0.759 to 1.170; P = 0.589). The ORRs were comparable between the two groups. ORRs were 44.9% in 1-day schedule group and 44.5% in 3-day schedule group, respectively (P = 0.929). Compared with patients in the 3-day schedule group, patients in the 1-day schedule group experienced higher rates of chemotherapy-induced nausea and vomiting (CINV) (139 [61.2%] vs. 132 [51.6%], P = 0.033). The risk of hypomagnesaemia was also significantly higher (43.2% vs. 28.3%, P = 0.016) among patients receiving 1-day schedule (without magnesium supplementation). No other differences in adverse events were observed between the two groups. CONCLUSIONS: Cisplatin given at three divided doses with no hydration in MBC is a less toxic (less CINV and hypomagnesaemia) schedule with comparable efficacy. Thus, it may be a good alternative for one full-dose (75 mg/m2) schedule.

Magnesium and elderly patient: the explored paths and the ones to be explored: a review.

Magnesium is an essential bivalent cation. Its fine balance in human organism is extremely important and is involved in a wide range of functions. We need to maintain its amount in human organism within range considered as physiological. This is particularly true for elderly people, and especially for "frail" elderly people, whose systems and apparatuses are in a state of serious homeostatic precariousness. In fact, hypomagnesemia is involved in a very large range of pathological conditions (requiring multiple therapies) that could compromise elderly's autonomy. The aim of this review has been to go through the most important trials, in order to understand the direction taken by research during the last years and to detect the room for improvement in this field. We have tried to understand when magnesium content is truly physiological or pathological, and how we could prevent an inappropriately low magnesium intake in elderly people. First of all, we have remarked the absolute need of an adequate evaluation method for magnesium content in human organism. Current literature appropriately encourages the use of a synoptic assessment of magnesium serum concentration, urinary excretion, and dietary intake. We have also discussed the most important trials relating hypomagnesaemia with human pathology. Specific studies conducted on elderly patients have extensively demonstrated its decisive role in maintaining bone health, adequate glyco-metabolic compensation, a correct cardiac and vascular functional profile, and probably also a physiological psycho-cognitive profile. From the implications discussed above, therefore, it is essential to ensure physiological levels of magnesium in body, particularly in geriatric patient, itself more prone to a reduction in the level of cation. We have concluded, according to the literature, that the best way to prevent hypomagnesemia and its clinical implications in elderly subjects is represented by a proper diet (more fiber and complex carbohydrates, more vegetable proteins, less sugars and fats), which ensures an adequate supply of cation. If with diet alone (due to comorbidity or other concomitant factors) it has not been possible to guarantee suitable serum levels of cation, or in the case of a patient defined as "frail elderly", a reintegration therapy (per os) will be undertaken, after a careful analysis of renal function.

Correction of hypomagnesemia by dapagliflozin in patients with type 2 diabetes: A post hoc analysis of 10 randomized, placebo-controlled trials.

AIMS: Hypomagnesemia (serum magnesium [Mg] <0.74 mmol/L [<1.8 mg/dL]) is commonly observed in patients with type 2 diabetes (T2D). This study investigated the effect of treatment with dapagliflozin 10 mg on Mg concentrations in patients with T2D. METHODS: In this post hoc analysis, we used pooled data from 10 placebo-controlled studies of dapagliflozin over 24 weeks of treatment in patients with T2D. We evaluated the change in Mg in patients receiving dapagliflozin vs. placebo overall, and in subgroups with baseline hypomagnesemia and normal/hypermagnesemia (≥0.74 mmol/L [≥1.8 mg/dL]). We determined the proportion of patients with baseline hypomagnesemia who achieved Mg ≥0.74 mmol/L (≥1.8 mg/dL). RESULTS: A total of 4398 patients with T2D were included. The mean change from baseline to week 24 in Mg was significantly larger with dapagliflozin vs. placebo; difference, 0.06 mmol/L (95% confidence interval [CI]: 0.05, 0.06). The proportion of patients with Mg within the population reference range after 24 weeks of treatment was significantly higher with dapagliflozin vs. placebo; difference, 47.8% (95% CI: 41.4, 53.9). The proportion of patients displaying hypermagnesemia did not increase with dapagliflozin treatment. CONCLUSIONS: Treatment with dapagliflozin 10 mg resulted in correction of Mg concentrations in patients with T2D and hypomagnesemia.

Control of metabolic predisposition to cardiovascular complications of chronic kidney disease by effervescent calcium magnesium citrate: a feasibility study.

AIMS: Cardiovascular (CV) complications are common in chronic kidney disease (CKD). Numerous metabolic disturbances including hyperphosphatemia, high circulating calciprotein particles (CPP), hyperparathyroidism, metabolic acidosis, and magnesium deficiency are associated with, and likely pathogenic for CV complications in CKD. The goal of this feasibility study was to determine whether effervescent calcium magnesium citrate (EffCaMgCit) ameliorates the aforementioned pathogenic intermediates. METHODS: Nine patients with Stage 3 and nine patients with Stage 5D CKD underwent a randomized crossover study, where they took EffCaMgCit three times daily for 7 days in one phase, and a conventional phosphorus binder calcium acetate (CaAc) three times daily for 7 days in the other phase. Two-hour postprandial blood samples were obtained on the day before and on the 7th day of treatment. RESULTS: In Stage 5D CKD, EffCaMgCit significantly increased T50 (half time for conversion of primary to secondary CPP) from baseline by 63% (P = 0.013), coincident with statistically non-significant declines in serum phosphorus by 25% and in saturation of octacalcium phosphate by 35%; CaAc did not change T50. In Stage 3 CKD, neither EffCaMgCit nor CaAc altered T50. With EffCaMgCit, a significant increase in plasma citrate was accompanied by statistically non-significant increase in serum Mg and phosphate. CaAc was without effect in any of these parameters in Stage 3 CKD. In both Stages 3 and 5D, both drugs significantly reduced serum parathyroid hormone. Only EffCaMgCit significantly increased serum bicarbonate by 3 mM (P = 0.015) in Stage 5D. CONCLUSIONS: In Stage 5D, EffCaMgCit inhibited formation of CPP, suppressed PTH, and conferred magnesium and alkali loads. These effects were unique, since they were not observed with CaAc. In Stage 3 CKD, neither of the regimens have any effect. These metabolic changes suggest that EffCaMgCit might be useful in protecting against cardiovascular complications of CKD by ameliorating pathobiologic intermediates.

Longitudinal Study of the Role of Epidermal Growth Factor on the Fractional Excretion of Magnesium in Children: Effect of Calcineurin Inhibitors.

BACKGROUND: It was shown in animal models and adults that the epidermal growth factor (EGF) is involved in the pathophysiology of calcineurin inhibitor (CNI) induced renal magnesium loss. In children, however, the exact mechanism remains unclear, which was set as the purpose of the present study. METHODS: Children with nephrotic syndrome and renal transplant children treated with CNI (n = 50) and non-CNI treated children (n = 46) were included in this study. Urine and serum samples were collected at three time points to determine magnesium, creatinine, and EGF. The magnesium intake was calculated from a food frequency questionnaire. RESULTS: Serum Mg2+ and urinary EGF/creatinine were significantly lower in the CNI treated children, with significantly more CNI-treated children developing hypomagnesaemia. In the latter patients, the fractional excretion of magnesium (FE Mg2+) was significantly higher. Urinary EGF, age, renal function, and serum magnesium were independent predictors of the FE Mg2+. Only 29% of the children reached the recommended daily intake of magnesium. The magnesium intake did not differ between hypomagnesemic and normomagnesemic patients and was not a predictor of the FE Mg2+. CONCLUSIONS: In CNI-treated children who developed hypomagnesemia, the FE Mg2+ was increased. The urinary EGF concentration, age, and renal function are independent predictors of the FE Mg2+.

Role of Magnesium Deficiency in Promoting Atherosclerosis, Endothelial Dysfunction, and Arterial Stiffening as Risk Factors for Hypertension.

Arterial hypertension is a disease with a complex pathogenesis. Despite considerable knowledge about this socially significant disease, the role of magnesium deficiency (MgD) as a risk factor is not fully understood. Magnesium is a natural calcium antagonist. It potentiates the production of local vasodilator mediators (prostacyclin and nitric oxide) and alters vascular responses to a variety of vasoactive substances (endothelin-1, angiotensin II, and catecholamines). MgD stimulates the production of aldosterone and potentiates vascular inflammatory response, while expression/activity of various antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and the levels of important antioxidants (vitamin C, vitamin E, and selenium) are decreased. Magnesium balances the effects of catecholamines in acute and chronic stress. MgD may be associated with the development of insulin resistance, hyperglycemia, and changes in lipid metabolism, which enhance atherosclerotic changes and arterial stiffness. Magnesium regulates collagen and elastin turnover in the vascular wall and matrix metalloproteinase activity. Magnesium helps to protect the elastic fibers from calcium deposition and maintains the elasticity of the vessels. Considering the numerous positive effects on a number of mechanisms related to arterial hypertension, consuming a healthy diet that provides the recommended amount of magnesium can be an appropriate strategy for helping control blood pressure.

Deletion of claudin-10 rescues claudin-16-deficient mice from hypomagnesemia and hypercalciuria.

The tight junction proteins claudin-10 and -16 are crucial for the paracellular reabsorption of cations along the thick ascending limb of Henle's loop in the kidney. In patients, mutations in CLDN16 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis, while mutations in CLDN10 impair kidney function. Mice lacking claudin-16 display magnesium and calcium wasting, whereas absence of claudin-10 results in hypermagnesemia and interstitial nephrocalcinosis. In order to study the functional interdependence of claudin-10 and -16 we generated double-deficient mice. These mice had normal serum magnesium and urinary excretion of magnesium and calcium and showed polyuria and sodium retention at the expense of increased renal potassium excretion, but no nephrocalcinosis. Isolated thick ascending limb tubules of double mutants displayed a complete loss of paracellular cation selectivity and functionality. Mice lacking both claudin-10 and -16 in the thick ascending limb recruited downstream compensatory mechanisms and showed hypertrophic distal convoluted tubules with changes in gene expression and phosphorylation of ion transporters in this segment, presumably triggered by the mild decrease in serum potassium. Thus, severe individual phenotypes in claudin-10 and claudin-16 knockout mice are corrected by the additional deletion of the other claudin.

Magnesium in addiction - a general view.

Addiction is a dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and loss of control over drug-taking. Addiction is a brain disease. There is evidence that magnesium deficit is involved in addiction to various addictive substances (heroin, morphine, cocaine, nicotine, alcohol, caffeine, and others). Magnesium is involved in all the stages of addiction. Magnesium deficit enhances the vulnerability to psychoactive substance addiction. Stress and trauma reduce the brain magnesium level and at the same time favor addiction development. In experimental studies, administration of magnesium while inducing morphine dependence in rats reduced the dependence intensity. Magnesium reduces the NMDA receptor activity and the glutamatergic activity. Because stress and trauma induce hypomagnesemia with increased vulnerability to addiction, magnesium intake by people who are under prolonged stress could be a way to reduce this vulnerability and the development of addiction to different psychoactive substances. Anxiety and depression appear to be associated with increases in drug-related harm and addictive substance use. Magnesium anxiolytic effect could be important for the antiaddictive action. Addiction is characterized by relapses. Magnesium deficiency may be a contributing factor to these relapses.

Role of Magnesium in Oxidative Stress in Individuals with Obesity.

Adipose tissue is considered an endocrine organ that promotes excessive production of reactive oxygen species when in excess, thus contributing to lipid peroxidation. Magnesium deficiency contributes to the development of oxidative stress in obese individuals, as this mineral plays a role as an antioxidant, participates as a cofactor of several enzymes, maintains cell membrane stability and mitigates the effects of oxidative stress. The objective of this review is to bring together updated information on the participation of magnesium in the oxidative stress present in obesity. We conducted a search of articles published in the PubMed, SciELO and LILACS databases, using the keywords 'magnesium', 'oxidative stress', 'malondialdehyde', 'superoxide dismutase', 'glutathione peroxidase', 'reactive oxygen species', 'inflammation' and 'obesity'. The studies show that obese subjects have low serum concentrations of magnesium, as well as high concentrations of oxidative stress marker in these individuals. Furthermore, it is evident that the adequate intake of magnesium contributes to its appropriate homeostasis in the body. Thus, this review of current research can help define the need for intervention with supplementation of this mineral for the prevention and treatment of disorders associated with this chronic disease.

Serum phosphate and magnesium in children recovering from severe acute undernutrition in Ethiopia: an observational study.

BACKGROUND: Children with severe acute malnutrition (SAM) have increased requirements for phosphorus and magnesium during recovery. If requirements are not met, the children may develop refeeding hypophosphatemia and hypomagnesemia. However, little is known about the effect of current therapeutic diets (F-75 and F-100) on serum phosphate (S-phosphate) and magnesium (S-magnesium) in children with SAM. METHODS: Prospective observational study, with measurements of S-phosphate and S-magnesium at admission, prior to rehabilitation phase and at discharge in children aged 6-59 months admitted with SAM to Jimma Hospital, Ethiopia. Due to shortage of F-75, 25 (35 %) children were stabilized with diluted F-100 (75 kcal/100 ml). RESULTS: Of 72 children enrolled, the mean age was 32 ± 14 months, and edema was present in 50 (69 %). At admission, mean S-phosphate was 0.92 ± 0.34 mmol/L, which was low compared to normal values, but increased to 1.38 ± 0.28 mmol/L at discharge, after on average 16 days. Mean S-magnesium, at admission, was 0.95 ± 0.23 mmol/L, and increased to 1.13 ± 0.17 mmol/L at discharge. At discharge, 18 (51 %) children had S-phosphate below the normal range, and 3 (9 %) had S-phosphate above. Most children (83 %) had S-magnesium above normal range for children. Both S-phosphate and S-magnesium at admission were positively associated with serum albumin (S-albumin), but not with anthropometric characteristics or co-diagnoses. Using diluted F-100 for stabilization was not associated with lower S-phosphate or S-magnesium. CONCLUSION: Hypophosphatemia was common among children with SAM at admission, and still subnormal in about half of the children at discharge. This could be problematic for further recovery as phosphorus is needed for catch-up growth and local diets are likely to be low in bioavailable phosphorus. The high S-magnesium levels at discharge does not support that magnesium should be a limiting nutrient for growth in the F-100 diet. Although diluted F-100 (75 kcal/100 mL) is not designed for stabilizing children with SAM, it did not seem to cause lower S-phosphate than in children fed F-75.

Magnesium in pregnancy.

Magnesium deficiency is prevalent in women of childbearing age in both developing and developed countries. The need for magnesium increases during pregnancy, and the majority of pregnant women likely do not meet this increased need. Magnesium deficiency or insufficiency during pregnancy may pose a health risk for both the mother and the newborn, with implications that may extend into adulthood of the offspring. The measurement of serum magnesium is the most widely used method for determining magnesium levels, but it has significant limitations that have both hindered the assessment of deficiency and affected the reliability of studies in pregnant women. Thus far, limited studies have suggested links between magnesium inadequacy and certain conditions in pregnancy associated with high mortality and morbidity, such as gestational diabetes, preterm labor, preeclampsia, and small for gestational age or intrauterine growth restriction. This review provides recommendations for further study and improved testing using measurement of red cell magnesium. Pregnant women should be counseled to increase their intake of magnesium-rich foods such as nuts, seeds, beans, and leafy greens and/or to supplement with magnesium at a safe level.

[Magnesium deficiency and stress: Issues of their relationship, diagnostic tests, and approaches to therapy].

Magnesium plays an important role in the functions of the central nervous system. It takes part in the regulation of the cell membrane, the transmembrane transport of calcium and sodium ions, and metabolic reactions that produce, accumulate, transfer, and utilize energy, free radicals, and their oxidation products. The magnesium-containing substances include many sequestered antigens, such as glial fibrillary acidic protein, S100, and neuron-specific enolase; magnesium may act as a neuroprotector that is able to modulate the regulation of blood-brain barrier permeability. Investigations have demonstrated a relationship between the manifestations of stress reactions (anxiety, autonomic dysfunction, and maladjustment) and magnesium deficiency (MD). Thus, mental and physical stresses cause an increase in magnesium elimination from the body. MD in turn enhances a response to stress, by paradoxically aggravating its sequels. Compensation for MD increases the ability of the nervous system to resist stress. The valid diagnosis of MD present difficulties; namely, a blood magnesium concentration decrease below 0.8 mmol/l is evidence of MD; but the constant blood level of magnesium may be long maintained due to its release from the bone tissue depot. So it is necessary to keep in mind the clinical manifestations of MD. The authors have developed and tested a simple rapid MD assessment test and a stress resistance self-rating test. The proposed tests will help to screen stress resistance and MD in outpatient settings.