The Use of a Checklist to Optimize Electrolyte Replacement in the ICU.

Electrolyte replacement protocols are routinely used in intensive care units (ICU) to guide magnesium replacement. Guided by serum levels, these protocols include no patient-specific factors despite a literature showing ICU patients routinely have significant deficits despite normal serum levels. The authors developed a checklist to help identify patients requiring more aggressive magnesium replacement than the electrolyte replacement protocol would provide. The checklist included risk factors for having significant magnesium deficits and for developing arrhythmias. The checklist was retrospectively applied to 364 medical ICU patients. Diabetic patients prescribed outpatient diuretics were defined as the highest-risk population. A total of 88% of patients in this subgroup had normal magnesium levels. Despite averaging 3.4 risk factors per patient, only 3 of 32 patients received magnesium. Applying the checklist would have suggested additional repletion for at least 85% of patients. A checklist can help identify ICU patients who may require more aggressive magnesium supplementation than protocols will provide.

Impact of Magnesium and Ferritin Deficiency on Depression Among Adolescent Students.

BACKGROUND: Depression is considered the fourth-leading cause of health problems. It is the fourth-leading cause of health problems and disability, which causes 16% of the worldwide burden of disease and injury among adolescents. OBJECTIVE: The aim of the present study was to evaluate the possible association of magnesium (Mg) and ferritin deficiency with depression in adolescent students. PATIENTS AND METHODS: This case control study in secondary schools at Al-Ghanayem discrete. The total number included was 358 students. All were screened for depression by the Arabic version of the Beck questionnaire. The students who had positive score was selected as cases 86 and a matched same number of students with negative score was selected as controls. Serum level of ferritin and magnesium was measured in the 2 groups. RESULTS: There was statistically significant difference between the studied groups when comparing depression grade with each of ferritin and Mg Depressed group cases had lower mean values of ferritin and Mg. The ferritin cut-off level for the prediction of depression was (35.5 µg/dL, which had a sensitivity of 74.4% and a specificity of 75.6%. The magnesium cut-off levels for the prediction of depression were1.95 mg/dL and 104.5 ng/dL which had a sensitivity of 70% and 64%, respectively. CONCLUSION: There was a statistically significant negative correlation between depression severity and each of socio-economic status ferritin and Mg. Each of ferritin and Mg were predictors for depression.

Impact of Inducible Nitric Oxide Synthase Activation on Endothelial Behavior under Magnesium Deficiency.

Endothelial dysfunction is a crucial event in the early pathogenesis of cardiovascular diseases and is linked to magnesium (Mg) deficiency. Indeed, in endothelial cells, low Mg levels promote the acquisition of a pro-inflammatory and pro-atherogenic phenotype. This paper investigates the mechanisms by which Mg deficiency promotes oxidative stress and affects endothelial behavior in human umbilical vascular endothelial cells (HUVECs). Our data show that low Mg levels trigger oxidative stress initially by increasing NAPDH oxidase activity and then by upregulating the pro-oxidant thioredoxin-interacting protein TXNIP. The overproduction of reactive oxygen species (ROS) activates NF-κB, leading to its increased binding to the inducible nitric oxide synthase (iNOS) promoter, with the consequent increase in iNOS expression. The increased levels of nitric oxide (NO) generated by upregulated iNOS contribute to disrupting endothelial cell function by inhibiting growth and increasing permeability. In conclusion, we provide evidence that multiple mechanisms contribute to generate a pro-oxidant state under low-Mg conditions, ultimately affecting endothelial physiology. These data add support to the notion that adequate Mg levels play a significant role in preserving cardiovascular health and may suggest new approaches to prevent or manage cardiovascular diseases.

Association between magnesium deficiency score and sleep quality in adults: A population-based cross-sectional study.

BACKGROUND: The association between magnesium status and sleep quality is unclear. The aim of this study was to determine the relationship between renal reabsorption-related magnesium depletion score (MDS) and sleep quality. METHODS: This study was conducted through a cross-sectional survey of adults aged ≥20 years who participated in NHANES 2005-2014. We used weighted logistic regression to examine the association between MDS and sleep quality and performed trend tests to analyze for the presence of a dose-response relationship. Subgroup analyses were performed based on various sleep outcomes and covariates. RESULTS: A total of 20,585 participants were included in the study, with a mean age of 48.8 years and 50.7 % female. After adjusting for all covariates, we found a graded dose-response relationship between MDS and sleep trouble as well as sleep disorder. Further analyses revealed a significant positive association between MDS and sleep apnea (OR = 3.01; 95 % CI 1.37-6.62), but no association with restless legs, insomnia or insufficient sleep. In addition, subgroup analyses revealed that middle-aged, male, obese, low magnesium intake, and depressed patients were more prone to sleep trouble and sleep disorder; interestingly, MDS was positively associated with excessive sleep in subjects ≥60 years and without depression. CONCLUSIONS: Our study found a significant association between MDS and sleep quality, particularly sleep apnea, but adequate magnesium intake may be beneficial in mitigating this association. MDS may be associated with excessive sleep in older adults, but not with insufficient sleep or insomnia.

Transcription-related metabolic regulation in grafted lemon seedlings under magnesium deficiency stress.

Magnesium is one of the essential nutrients for plant growth, and plays a pivotal role in plant development and metabolism. Soil magnesium deficiency is evident in citrus production, which ultimately leads to failure of normal plant growth and development, as well as decreased productivity. Citrus is mainly propagated by grafting, so it is necessary to fully understand the different regulatory mechanisms of rootstock and scion response to magnesium deficiency. Here, we characterized the differences in morphological alterations, physiological metabolism and differential gene expression between trifoliate orange rootstocks and lemon scions under normal and magnesium-deficient conditions, revealing the different responses of rootstocks and scions to magnesium deficiency. The transcriptomic data showed that differentially expressed genes were enriched in 14 and 4 metabolic pathways in leaves and roots, respectively, after magnesium deficiency treatment. And the magnesium transport-related genes MHX and MRS2 may respond to magnesium deficiency stress. In addition, magnesium deficiency may affect plant growth by affecting POD, SOD, and CAT enzyme activity, as well as altering the levels of hormones such as IAA, ABA, GA3, JA, and SA, and the expression of related responsive genes. In conclusion, our research suggests that the leaves of lemon grafted onto trifoliate orange were more significantly affected than the roots under magnesium-deficient conditions, further indicating that the metabolic imbalance of scion lemon leaves was more severe.

Leaf diffusional capacity largely contributes to the reduced photosynthesis in rice plants under magnesium deficiency.

Numerous studies have clarified the impacts of magnesium (Mg) on leaf photosynthesis from the perspectives of protein synthesis, enzymes activation and carbohydrate partitioning. However, it still remains largely unknown how stomatal and mesophyll conductances (gs and gm, respectively) are regulated by Mg. In the present study, leaf gas exchanges, leaf hydraulic parameters, leaf structural traits and cell wall composition were examined in rice plants grown under high and low Mg treatments to elucidate the impacts of Mg on gs and gm. Our results showed that reduction of leaf photosynthesis under Mg deficiency was mainly caused by the decreased gm, followed by reduced leaf biochemical capacity and gs, and leaf outside-xylem hydraulic conductance (Kox) was the major factor restricting gs under Mg deficiency. Moreover, increased leaf hemicellulose, lignin and pectin contents and decreased cell wall effective porosity were observed in low Mg plants relative to high Mg plants. These results suggest that Kox and cell wall composition play important roles in regulating gs and gm, respectively, in rice plants under Mg shortages.

A Rare Case of Neonatal Hypomagnesemia with Secondary Hypocalcemia Caused by a Novel Homozygous TRPM6 Gene Variant.

BACKGROUND Familial hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disorder (OMIM# 602014) caused by mutations in the gene encoding transient receptor potential melastatin 6 (TRPM6)) on chromosome 9q22, a channel involved in epithelial magnesium resorption. While a plethora of studies have delineated various clinical manifestations pertinent to this mutation, the literature is devoid of connections between TRPM6 mutations and bleeding diathesis, or sudden infant death syndrome (SIDS). This report presents a case of familial HSH associated with the novel homozygous TRPM6 gene variant c.5281C>G p. (Arg1761Gly) chr9: 77354845. CASE REPORT This report details a 26-day-old neonate, born full term with optimal Apgar scores, who experienced an abrupt emergence of apnea, cyanosis, bilateral nasal bleeding, and diminished alertness. Despite the neonate's initially unremarkable clinical birth indicators, a meticulous assessment unveiled a pronounced family history of SIDS, including a sibling previously diagnosed with hypomagnesemia. Laboratory examination of the infant demonstrated severe hypomagnesemia and hypocalcemia, conditions which were promptly ameliorated following intravenous administration of magnesium and calcium. Whole-exome sequencing identified a homozygous TRPM6 gene mutation c.5281C>G p. (Arg1761Gly) at chr9: 77354845. This gene is crucial for magnesium regulation. The mutation involves a cytosine-to-guanine shift, resulting in an arginine to glycine amino acid substitution at position 1761 of the TRPM6 protein. CONCLUSIONS This report has highlighted that infantile hypomagnesemia may be associated with symptoms and signs that can mimic infection, or it can present with seizures. Although familial HSH is a rare genetic disorder that can be identified by genetic testing, correction of hypomagnesemia is the most important and immediate clinical management strategy.

Mechanism of zinc stress on magnesium deficiency in rice plants (Oryza sativa L.): Insights from magnesium isotopes.

Magnesium (Mg) and zinc (Zn) are essential nutrients for plants. Mg deficiency often occurs in rice plants grown in Zn-polluted soil. However, the mechanism for this correlation is unclear. Here, we performed culture experiments on rice plants (Oryza sativa L.) and used Mg isotopes to investigate mechanisms of Zn stress on plant Mg deficiency. Our results show that excess Zn can significantly reduce the uptake of Mg in rice tissues. The root displays positive Δ26Mgplant-nutrient values (δ26Mgplant-δ26Mgnutrient; 1.90 ‰ to 2.06 ‰), which suggests that Mg enters the root cells mainly via Mg-specific transporters rather than non-selective diffusion. The decreased Δ26Mgplant-nutrient values with increasing Zn supply can be explained by the competition between Zn and Mg, both of which combine with same transporters in roots. In contrast, the shoots (stem and leaf) display much lower δ26Mg values than roots, which suggests that the transport of Mg from roots to aerial biomass is mainly via free Mg ions, during which Zn cannot competitively inhibit the movement of Mg. Our study suggests that the Mg deficiency in rice plants can be caused by high Zn-levels in soils and highlights the necessity of soil Zn-remediation in solving Mg deficiency problems in rice plants.

Renal diseases that course with hypomagnesemia. Comments on a new hereditary hypomagnesemic tubulopathy.

Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule. In this paper, we review the initial description, the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described: type 3 Bartter and Gitelman diseases, Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The basic biochemical patterns observed in renal tubular hypomagnesemias and the modalities of transport and interaction that occur between the transporters involved in the reabsorption of magnesium in the distal convoluted tubule are described below. Finally, the recent report of a new renal disease with hypomagnesemia, type 2 hypomagnesemia with secondary hypocalcemia caused by reduced TRPM7 channel activity is described.

Magnesium Disorders: Core Curriculum 2024.

Magnesium is ubiquitous in nature. It sits at the origin of the food chain, occupying the center of chlorophyl in plants. In humans, magnesium is critical to diverse molecular and catalytic processes, including energy transfer and maintenance of the genome. Despite its abundance, hypomagnesemia is common and often goes undiagnosed. This is in spite of epidemiologic data linking low magnesium with chronic diseases including diabetes mellitus. Clinically significant hypermagnesemia is encountered less frequently, but the presentation may be dramatic. Advances in molecular biology and the elucidation of the genetic causes of magnesium disorders have enhanced our understanding of their pathophysiology. Treatment approaches are also changing. The repurposing of newer medications, such as sodium/glucose cotransporter 2 inhibitors, offers new therapeutic options. In this review we integrate knowledge in this rapidly evolving field to provide clinicians and trainees with a resource for approaching common clinical scenarios involving magnesium disorders.

Rare cause of recurrent hypocalcaemia and functional hypoparathyroidism due to hypomagnesaemia caused by TRPM6 gene mutation.

Magnesium is essential for the functioning and release of parathyroid hormone. Therefore, its deficiency can present as functional hypoparathyroidism. This case report describes a rare inherited disorder called congenital hypomagnesaemia with secondary hypocalcaemia due to TRPM6 gene mutation. This disease clinically and biochemically mimics hypoparathyroidism. However, unlike hypoparathyroidism, it can be treated only by long-term oral magnesium supplements. The patient presented to us with recurrent hypocalcaemic convulsions. The laboratory picture in each admission was similar to that of hypoparathyroidism. However, the hypocalcaemia persisted, and it was noticed to be associated with persistent hypomagnesaemia. A defect in the tubular magnesium reabsorption was postulated and a genetic analysis of the patient was done, which revealed a TRPM6 mutation causing hypomagnesaemia by excessive renal excretion of magnesium. The child responded well to oral magnesium supplements and is currently developmentally appropriate for her age and thriving well.

Sodium/Glucose Cotransporter 2 Inhibitors and Magnesium Homeostasis: A Review.

Magnesium (Mg2+), also known as "the forgotten ion," is the second most abundant intracellular cation and is essential in a broad range of intracellular physiological and biochemical reactions. Its deficiency, hypomagnesemia (Mg2+<1.8mg/dL), is a prevalent condition and routinely poses challenges in its management in clinical practice. Sodium/glucose cotransporter 2 (SGLT2) inhibitors have emerged as a new class of drugs with treating hypomagnesemia as their unique extraglycemic benefit. The beneficial effect of SGLT2 inhibitors on magnesium balance in patients with diabetes with or without hypomagnesemia has been noted as a class effect in recent meta-analysis data from randomized clinical trials. Some reports have demonstrated their role in treating refractory hypomagnesemia in patients with or without diabetes. Moreover, studies on animal models have attempted to illustrate the effect of SGLT2 inhibitors on Mg2+homeostasis. In this review, we discuss the current evidence and possible pathophysiological mechanisms, and we provide directions for further research. We conclude by suggesting the effect of SGLT2 inhibitors on Mg2+homeostasis is a class effect, with certain patients gaining significant benefits. Further studies are needed to examine whether SGLT2 inhibitors can become a desperately needed novel class of medicines in treating hypomagnesemia.

Associations of the magnesium depletion score and magnesium intake with diabetes among US adults: an analysis of the National Health and Nutrition Examination Survey 2011-2018.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS: MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

Hereditary hypomagnesemia with secondary hypocalcemia caused by a novel mutation in TRPM6 gene.

OBJECTIVES: Hereditary hypomagnesemia with secondary hypocalcemia (HSH), which results from variations in the transient receptor potential melastatin 6 (TRPM6) genes, is a rare hereditary cause of extremely low serum magnesium levels. We describe an infant with triggered seizures due to hypomagnesemia and a novel mutation in TRPM6 gene was identified. CASE PRESENTATION: A 10-month-old boy presented with multidrug resistant seizures, and axial hypotonia due to severe hypomagnesemia. Electroencephalography and neuroimaging of the patient was normal. He had a favorable outcome with magnesium supplement. In this study, the patient underwent clinical exome sequencing (CES) which detected a novel homozygous variant in the TRPM6 gene: NM_017662.5: c.5571-3C>G. After replacing his magnesium orally, he was free from seizures and had an encouraging outcome at the twelfth-month follow-up. CONCLUSIONS: HSH often presents with developmental issues, treatment-resistant seizures, and increased neuromuscular excitability. Untreated hypomagnesemia can potentially be fatal and severely impair cognitive function. Clinical suspicion is essential for early diagnosis and treatment.

Association of Magnesium Depletion Score with Congestive Heart Failure: Results from the NHANES 2007-2016.

The magnesium depletion score (MDS) is considered a new valuable and reliable predictor of body magnesium status. This study aimed to explore the association between MDS and congestive heart failure (CHF) among US adults. A total of 19,227 eligible participants from the 2007-2016 National Health and Nutrition Examination Survey were enrolled in this study and then divided into three groups according to the level of MDS (none to low: MDS=0-1, middle: MDS=2, high: MDS=3-5). Sample-weighted logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) exploring the independent relationship between MDS and CHF. The estimated prevalence of CHF increased with the increasing level of MDS (none to low: 0.86%, middle: 4.06%, high: 13.52%; P < 0.001). Compared to those in the none-to-low group, participants in the middle and high groups were at significantly higher risk of CHF after adjusting for various covariates (model 3: OR=1.55, 95%CI: 1.05-2.30, P < 0.001; OR=3.20, 95%CI: 2.07-4.96, P < 0.001; respectively). Subgroup analyses indicated that adequate dietary magnesium intake could reduce the risk of CHF in participants who did not meet the recommended dietary allowance (RDA) for magnesium. Besides, there was an interaction between coronary artery disease and MDS on CHF (P for interaction < 0.001). These findings indicated that MDS, a novel indicator estimating magnesium deficiency, is associated with the risk of CHF in non-institutionalized US civilians. Participants whose dietary magnesium intake reaches the RDA might be at lower risk.

Improving diagnosis and treatment of hypomagnesemia.

Magnesium is one of the most abundant cations in the body and acts as a cofactor in more than 600 biochemical reactions. Hypomagnesemia is a highly prevalent condition, especially in subjects with comorbid conditions, but has received less attention than other electrolyte disturbances. This review will discuss magnesium physiology, absorption, storage, distribution across the body, and kidney excretion. After reviewing the regulation of magnesium homeostasis, we will focus on the etiology and clinical presentation of hypomagnesemia. The role of laboratory medicine in hypomagnesemia will be the main purpose of this review, and we will discuss the laboratory tests and different samples and methods for its measurement. Although free magnesium is physiologically active, total serum magnesium is the most commonly used measurement in laboratory medicine and is apt for clinical purposes; however, it is not appropriately used, and many patients with hypomagnesemia remain undiagnosed and not treated. Using information technologies, laboratory medicine can largely improve the diagnosis and treatment of hypomagnesemia through the design and establishment of automatic demand management and result management interventions by acting in the first and last steps of the laboratory cycle, test requests, and actions taken after test results, to unmask patients with hypomagnesemia and improve the number of patients undergoing treatment.

[Severe hypomagnesemia in a man with alcohol dependence: a forgotten electrolyte in a neglected population]. / Ernstig magnesiumtekort bij alcoholverslaving.

BACKGROUND: Symptoms of acute alcohol withdrawal like tremors, seizures and delirium are commonly treated with benzodiazepines and vitamins. When complaints are not reacting to this treatment, an alternative diagnosis must be considered. Although hypomagnesemia is present in at least 30 percent of the patients with alcohol dependence, it can provoke and maintain these complaints. CASE DESCRIPTION: We present a 43-year-old man with alcohol dependence, who shows neurological, muscular, and cardiac consequences of an undiagnosed hypomagnesemia. CONCLUSION: In daily clinical practice there is not enough attention for magnesium deficits, especially in patients with alcohol dependence. Serious complications can be prevented by recognizing and treating magnesium deficiency more adequately.

Role of magnesium-L-Threonate in alleviating skin/muscle incision and retraction induced mechanical allodynia and anxiodepressive-like behaviors in male rats.

Chronic postsurgical pain (CPSP) and its emotional comorbidities poses health burden to patients who have received the surgical treatment. However, its underlying mechanism remains unclear. Emerging studies indicate that magnesium deficiency is associated with neurological diseases, and magnesium supplement confers protection under these disease conditions. In this study, we examined the role and mechanism of magnesium deficiency in the pathology of surgery-induced allodynia and negative emotion using a rat model of skin/muscle incision and retraction (SMIR) and investigated the therapeutic effects of magnesium supplementation by oral magnesium-L-Threonate (L-TAMS) in SMIR-injured rats. In the SMIR model, rats developed mechanical allodynia and anxiodepressive-like behaviors. Further, SMIR caused microglia and astrocyte activation and enhanced expression of pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) in the anterior cingulate cortex (ACC). Importantly, magnesium ion (Mg2+) levels decreased in the serum and cerebrospinal fluid (CSF) of SMIR-injured rats, which exhibited high correlation with pain and emotion behavioral phenotypes in these rats. Repeated oral administration of L-TAMS increased serum and CSF levels of Mg2+ in SMIR-injured rats. Notably, L-TAMS administration reversed SMIR-induced mechanical allodynia and anxiodepressive-like behaviors but did not affect pain and emotional behaviors in sham rats. Moreover, L-TAMS administration suppressed SMIR-caused glial activation and proinflammatory cytokine expression in the ACC but had no such effect in sham rats. Together, our study demonstrates the contributing role of magnesium deficiency in the pathology of surgery-induced chronic pain and negative emotion. Moreover, we suggest that L-TAMS might be a novel approach to treat CPSP and its emotional comorbidities.

Magnesium-An Ion with Multiple Invaluable Actions, Often Insufficiently Supplied: From In Vitro to Clinical Research.

Magnesium (Mg) is a key ion for numerous metabolic processes, being a cofactor of over 600 enzymes involved in cell metabolism and multiple biological processes [...].