All adult patients admitted to internal medicine wards at the Tel-Aviv Sourasky Medical Center between June 1st, 2007, and July 31st, 2022, for whom magnesium levels were measured, were included. Data from 85,466 patients were obtained. Patients were divided into four subgroups according to magnesium level at admission: severe hypomagnesaemia (serum magnesium ≤1.2mg/dL), mild hypomagnesaemia (magnesium >1.2mg/dL≤1.8mg/dL), eumagnesaemia (magnesium >1.8/≤2.55mg/dL), and hypermagnesaemia (magnesium >2.55). The primary outcome was 30-day mortality risk. Hypomagnesaemia was associated with the use of thiazides and proton pump inhibitors (p<0.001), while severe hypermagnesaemia was associated with reduced renal function (p<0.001). After adjusting for age, gender, the Charlson comorbidity index, creatinine, potassium, and calcium corrected for albumin, mild hypomagnesaemia was associated with lower 30-day mortality (HR: 0.87, 95%CI: 0.82-0.93, p<0.001), hypermagnesaemia was associated with higher 30-day mortality (HR: 2.86, 95%CI: 2.57-3.17, p<0.001), and severe hypomagnesaemia was not associated with survival change (HR: 0.82, 95%CI: 0.62-1.09, p=0.177). Hypermagnesaemia normalization (HR: 0.77, 95%CI: 0.63-0.93, p<0.001) and administration of magnesium supplements for mild (adjusted HR: 0.53, 95%CI: 0.36-0.79, p=0.002) or severe (HR: 0.34, 95%CI: 0.28-0.41, p<0.001) hypomagnesaemia were associated with reduced mortality. In hospitalized, non-critically ill medical patients, hypermagnesaemia confers a substantial 30-day mortality risk, which may be mitigated by its correction. Although hypomagnesaemia is not associated with worse outcome, its correction by supplementation may be of clinical benefit.

Low magnesium (Mg) intake increases the risk of various diseases such as anxiety disorder, depression, and diabetes. However, a reliable biomarker of mild Mg deficiency due to low Mg intake has not yet been identified. We speculate that metabolomics will be effective for biomarker discovery because Mg can affect various metabolic processes in the body. In the present study, we evaluated whether mild Mg deficiency affects growth, behaviour, and plasma and urinary metabolomes in rats. Mg levels in plasma and the femur, and urinary Mg excretion decreased by consuming a mildly low Mg diet, whereas body weight and food intake were not affected. Also, anxiety- and depression-like behaviours were not affected by Mg deficiency. These results indicate that the negative effects observed here are milder than those for severe Mg deficiency, as previously reported. Of the 93 annotated metabolites in plasma, only glycylglycine was moderately affected. Of the 122 annotated metabolites in urine, 29 were affected. A marked decrease in urinary excretion of some organic acids of the tricarboxylic acid cycle, particularly citric acid, was noticed. This study identifies urinary metabolites that may be useful biomarkers of mild Mg deficiency.

Ischemia/reperfusion (I/R) injury is a main issue in renal transplantation, and antioxidants attenuate I/R injury in different tissues. We investigated the protective effects of nano magnesium oxide (nano-MgO) on renal I/R injury in rats. Induction of I/R injury was performed through clamping the left renal pedicle for 20 minutes. Animals were administrated with nano-MgO (1.25, 2.5 and 5mg/kg) for 30 days by gavage, and were sacrificed for biochemical and histopathological studies. Our findings show that nano-MgO administration (2.5 and 5mg/kg) in rats with renal I/R injury significantly attenuated serum creatinine and urea levels (p<0.001), decreased malondialdehyde (MDA) levels and elevated antioxidant enzyme activities in renal homogenates (p<0.001), as evidenced by histopathological assessment, and caused a significant reduction in EGF immunoreactivity and EGFR expression in renal tissues (p<0.001). In conclusion, nano-MgO administration preserves renal function and prevents tissue damage after I/R injury in rats.

Hypomagnesemia, a common condition, frequently goes unnoticed due to varying symptom severity. In the hospital setting, the link between adverse drug reactions and hypomagnesemia is not always clear, and some drug labels omit this risk, compounding the potential danger. We conducted a cross-sectional study by mining data from the FDA Adverse Event Reporting System (FAERS) covering Q1 2004 to Q4 2023. Using the Medical Dictionary for Regulatory Activities, we identified cases of hypomagnesemia, determined the signal drugs causing hypomagnesemia based on the drug name, and employed descriptive and disproportionality analysis methods for signal detection. From 17,381,220 adverse event reports, 11,228 individual safety reports (ISRs) involving hypomagnesemia were identified. Omeprazole led with 1,556 reports (20.75%), followed by pantoprazole, panitumumab, cetuximab, and esomeprazole. Disproportionality analysis revealed necitumumab as the drug with the strongest signal, followed by capreomycin, panitumumab, pantoprazole, and omeprazole. Among the top 50 drugs from the disproportionality analysis, 31 signal drugs had labels that did not mention the risk of hypomagnesemia. We issue warnings regarding drugs associated with specific combination therapies that cause adverse reactions leading to hypomagnesemia. Furthermore, to delve deeper into the relationship between drugs and hypomagnesemia, reliance on more credible research in this field is required.

The role of magnesium supplementation in reducing the risk of gestational diabetes (GD) has not been elucidated. To evaluate the effect of magnesium chloride (MgCl2) on the risk of developing GD in a model of obese rats with hydrochlorothiazide-induced hypomagnesemia. Female Wistar rats were allocated into a healthy control or obese group. Obesity was induced with an obesogenic diet and defined by a body weight 30% higher than that of the healthy control group. Once obesity was induced and before pregnancy, hypomagnesemia was generated using hydrochlorothiazide (5mg/kg body weight). Subsequently, the oestrous cycle was evaluated to proceed for mating. Once pregnancy was confirmed, the obese rats were allocated to an intervention group (IG) or control group (HOCG). Rats in the IG received MgCl2 (50mg/kg body weight, equivalent to 500mg per day in humans). Fasting glucose and ionized magnesium levels were determined on days 6, 15, and 20 of pregnancy. An oral glucose tolerance test was performed on day 15 of pregnancy. Rats in the IG had significantly increased ionized magnesium (p=0.009), decreased fasting (p=0.02) and two-hour post-load (p=0.04) glucose levels, and exhibited lower body weight gain than the HOCG (p<0.05). At the end of the study, 75% of the rats in the HOCG, but none in the IG, fulfilled the diagnostic criteria for GD. In obese hypomagnesaemic rats, magnesium supplementation, using MgCl2, reduces fasting and two-hour post-load glucose levels as well as the risk of developing GD, and induces lower body weight gain during pregnancy.

A physiological concentration of magnesium (Mg) is essential for optimal skeletal muscle function. Indeed, Mg plays a crucial role during the differentiation process (myogenesis), in muscle fiber composition, muscle contraction and performance. This narrative review describes in detail the relevance of Mg in skeletal muscle, highlighting the importance of adequate Mg intake to ensure optimal skeletal muscle cell function and performance in individuals of all ages.

Several recent studies support a role of dysregulated magnesium homeostasis in COVID-19. In the present narrative review, we focus on the neurological aspects of this disease, collectively known as neuroCOVID, and we propose some mechanisms by which alterations of magnesium may contribute to the involvement of the nervous system in the context of SARS-CoV-2 infection. Further fundamental, translational, and clinical research is needed to underpin the potential relationships between altered magnesium status and neuro-COVID, with potentially novel therapeutic implications.

In the present study, we investigated whether magnesium sulphate activates the L-arginine/NO/cGMP pathway and elicits peripheral antinociception. The male Swiss mice paw pressure test was performed with hyperalgesia induced by intraplantar injection of prostaglandin E2. All drugs were administered locally into the right hind paw of animals. Magnesium sulphate (20, 40, 80 and 160 μg/paw) induced an antinociceptive effect. The dose of 80 μg/paw elicited a local antinociceptive effect that was antagonized by the non-selective NOS inhibitor, L-NOArg, and by the selective neuronal NOS inhibitor, L-NPA. The inhibitors, L-NIO and L-NIL, selectively inhibited endothelial and inducible NOS, respectively, but were ineffective regarding peripheral magnesium sulphate injection. The soluble guanylyl cyclase inhibitor, ODQ, blocked the action of magnesium sulphate, and the cGMP-phosphodiesterase inhibitor, zaprinast, enhanced the antinociceptive effects of intermediate dose of magnesium sulphate. Our results suggest that magnesium sulphate stimulates the NO/cGMP pathway via neuronal NO synthase to induce peripheral antinociceptive effects.

The objective of the present research is to develop and optimize a chewable tablet containing synergistic combination of magnesium orotate dihydrate (MOD), cholecalciferol (CHOL) and menaquinone-7 (MK-7) as per product development guidelines of ICH Q8 (R2). The effects of critical variables on quality attributes of chewable tablets were evaluated using 30 runs based design of experiment (DoE) after risk assessment. Optimized formulation was found to be the one that was prepared with moderate granulation time of 7.23 min and contained 14 mg/tablet binder, 31 mg/tablet disintegrant and 11.377 mg/tablet lubricant. Prepared tablets were evaluated for prescribed pharmacopoeial and regulatory quality checks. Optimized formulation was found to have very low disintegration time of 6.06 min and 87.39% dissolution of MOD within 15 min in acidic media (0.1 N HCl), which ensure that the developed formulation behaves as a solution following oral administration. Stability studies under accelerated conditions revealed that the developed formulation can retain its quality characteristics throughout its shelf life. Pharmacokinetics study of chewable tablets in male Wistar rats shows that the time to reach maximum plasma or serum concentration (Tmax) was 3 h for MOD and 6 h for both CHOL and MK-7. Maximum plasma or serum concentration (Cmax) of MOD, CHOL and MK-7 was found to be 7.233 ± 1.159, 8.182 ± 0.783 and 8.331 ± 0.863 μg/mL [mean ± standard deviation (SD)], respectively. The area under the curve (AUC 0-t) for MOD, CHOL and MK-7 was 80.692 ± 11.197, 124.325 ± 17.101 and 126.568 ± 12.064 μg.mL.h-1 (mean ± SD), respectively. Comparison of pharmacokinetic data of chewable tablets with a mixture of pure drugs proves that the developed formulation can efficiently deliver all the three nutrients in blood and is capable to elicit desired pharmacological response.

This study aimed to determine the relationship between hospital-acquired dysmagnesemia and in-hospital mortality in critically ill patients. A retrospective cohort study was conducted on critically ill patients who had normal serum magnesium levels on admission. Data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. The normal range of serum magnesium was 1.6-2.6 mg/dL. In-hospital serum magnesium levels were categorized based on the occurrence of hospital-acquired hypomagnesemia and hypermagnesemia. Hospital-acquired hypomagnesemia and hypermagnesemia in the same patient were defined as a patient with the lowest level of serum magnesium of <1.6 mg/dL and the highest level of serum magnesium of >2.6 mg/dL, respectively. The in-hospital outcomes were collected. The findings revealed that 27.2% of patients developed hospital-acquired dysmagnesemia. In-hospital mortalities were 8.8% in patients with persistently normal serum magnesium levels, 12.2% in patients with hospital-acquired hypomagnesemia only, 18.4% in patients with hospital-acquired hypermagnesemia only, and 20.6% in patients with both hospital-acquired hypomagnesemia and hypermagnesemia. Compared to patients with persistently normal serum magnesium in hospital, those with hospital-acquired hypermagnesemia only [odds ratio (OR) = 1.346, P < 0.001] and those with both hospital-acquired hypomagnesemia and hypermagnesemia (OR = 1.333, P = 0.001) were significantly associated with higher in-hospital mortality. Hospital-acquired dysmagnesemia was common among critically ill patients. Hospital-acquired dysmagnesemia, especially hospital-acquired hypermagnesemia, was significantly associated with increased in-hospital mortality in critically ill patients.