Oral Magnesium Supplementation Research Articles

Magnesium Supplementation Modifies Arthritis Synovial and Splenic Transcriptomic Signatures Including Ferroptosis and Cell Senescence Biological Pathways

Background: Rheumatoid arthritis (RA) is a common systemic autoimmune inflammatory disease that can cause joint damage. We have recently reported that oral magnesium supplementation significantly reduces disease severity and joint damage in models of RA. Methods: In the present study, we analyzed the transcriptome of spleens and synovial tissues obtained from mice with KRN serum-induced arthritis (KSIA) consuming either a high Mg supplemented diet (Mg2800; n = 7) or a normal diet (Mg500; n = 7). Tissues were collected at the end of a 15-day KSIA experiment. RNA was extracted and used for sequencing and analyses. Results: There was an enrichment of differentially expressed genes (DEGs) belonging to Reactome and Gene Ontology (GO) pathways implicated in RA pathogenesis such as RHO GTPases, the RUNX1 pathway, oxidative stress-induced senescence, and the senescence-associated secretory phenotype. Actc1 and Nr4a3 were among the genes with the highest expression, while Krt79 and Ffar2 were among the genes with the lowest expression in synovial tissues of the Mg2800 group compared with the Mg500 group. Spleens had an enrichment for the metabolism of folate and pterines and the HSP90 chaperone cycle for the steroid hormone receptor. Conclusions: We describe the tissue transcriptomic consequences of arthritis-protecting Mg supplementation in KSIA mice. These results show that oral Mg supplementation may interfere with the response to oxidative stress and senescence and other processes known to participate in RA pathogenesis. We provide new evidence supporting the disease-suppressing effect of increased Mg intake in arthritis and its potential to become a new addition to the therapeutic options for RA and other autoimmune and inflammatory diseases.

A clinical audit of hypomagnesaemia management at Scarborough General Hospital

BackgroundHypomagnesaemia is a common electrolyte disturbance that can lead to severe complications, including cardiac dysrhythmias and neuromuscular instability. Despite established guidelines by the York and Scarborough Teaching Hospitals NHS Foundation Trust, there is concern that these protocols are not consistently followed, potentially compromising patient outcomes. Objective: This audit aimed to evaluate the management of hypomagnesaemia at Scarborough General Hospital, focusing on adherence to trust guidelines and identifying areas for improvement in clinical practice. MethodsA retrospective analysis was conducted on 98 patients diagnosed with hypomagnesaemia between May and December 2023. Data on patient demographics, severity of hypomagnesaemia, ECG monitoring, treatment modalities and correction times were collected and analysed. The audit compared current practices against trust guidelines, specifically assessing the frequency of ECG monitoring, daily serum magnesium level checks, and the use of parenteral versus oral magnesium supplementation. ResultsThe audit revealed that 67% of patients had mild, asymptomatic hypomagnesaemia, while 33% presented with moderate to severe forms. ECGs were performed in 66% of cases, with 13.7% showing abnormalities. Despite guidelines recommending daily magnesium level monitoring, only 66% of patients received this care. Severe hypomagnesaemia was corrected within 3.5 days on average, while mild cases required 4.5 days. The frequent use of proton pump inhibitors was identified as a significant contributor to hypomagnesaemia. Notably, only half of the severe cases received the full recommended course of intravenous magnesium sulphate, with many being switched to oral supplementation prematurely. ConclusionWhile some aspects of hypomagnesaemia management at Scarborough General Hospital align with trust guidelines, significant gaps remain, particularly in monitoring practices and adherence to treatment protocols. These findings highlight the need for targeted educational initiatives and potential revisions to existing guidelines to improve patient outcomes.

Positive effects of magnesium supplementation in metabolic syndrome.

Recent data show that magnesium supplementation decreases systolic and diastolic blood pressure values depending on the blood pressure levels and improves metabolic parameters in cardiovascular disease. In this context, we conducted a prospective, randomized, double-blind study on serum and ionized magnesium, systolic and diastolic blood pressure values, interleukin-6, vitamin D, and metabolic profile in 27 patients (13 male/14 female, age: 60.2±12.5 years) with metabolic syndrome. All patients received 400 mg of oral magnesium supplementation daily. Parameters were measured before and after 6 and 12 weeks of treatment. 27 patients served as controls without additional magnesium treatment (10 male/17 female, age: 64.6±13.2 years). There was no significant change in serum magnesium after 6 and 12 weeks of magnesium supplementation and in controls. Ionized magnesium significantly increased from 0.56±0.05 to up to 0.63±0.08 mmol/L (mean ± SD) (p<0.01). The ionized Ca++/Mg++ ratio was significantly increased at baseline in about 32% of all patients; after 12 weeks of magnesium supplementation, the Ca++/Mg++ ratio decreased significantly from 2.32±0.22 to 2.04±0.24 at the end of the study (mean ± SD, p<0.05). In the magnesium-treated group, there was a significant decrease in systolic and diastolic blood pressure values after 12 weeks (systolic: 134.6±6.8 to 126.3±5.6 mmHg, diastolic: 84.1±3.9 to 79.4±1.6 mmHg) (mean ± SD) (p<0.01). Additional magnesium supplementation decreased interleukin-6 values significantly from 4.94±3.30 to 4.53±6.89 pg/mL after 6 weeks to 3.01±1.32 pg/mL after 12 weeks (mean±SD) (p<0.01). In the control group, interleukin-6 was 3.73±4.36 pg/mL before the start of the supplementation, 4.87±4.35 pg/mL after 6 weeks, and 4.41±3.15 pg/mL after 12 weeks (means ± SD) (n.s.). In patients receiving magnesium supplementation, vitamin D levels significantly improved from 17.93±8.96 to 24.41±10.20 ng/mL (mean±SD) (p<0.05). HbA1c and serum cholesterol values improved under magnesium therapy, but the improvement did not reach significance. For statistical analysis, Mann-Whitney-U-Test was used. Using supplementation with 400 mg magnesium for 12 weeks in patients with metabolic syndrome, ionized magnesium concentrations significantly increased, while serum magnesium did not change significantly. Both systolic and diastolic blood pressure values decreased significantly in the magnesium-treated group. Magnesium supplementation also significantly decreased interleukin-6 levels and increased vitamin D in patients. HbA1c and cholesterol levels improved with magnesium supplementation, but the improvement did not reach significance. The anti-inflammatory effects of magnesium as well as anti-arteriosclerotic effects of magnesium therapy are beneficial for patients with metabolic syndrome at high risk of cardiovascular disease and mortality.

Oral magnesium supplementation improves glycemic status in subjects with prediabetes: a randomized double-blind placebo-controlled trial

Oral magnesium supplementation improves glycemic status in subjects with prediabetes: a randomized double-blind placebo-controlled trial

Is oral magnesium supplementation effective in reducing symptoms following concussion in pediatric patients?

Is oral magnesium supplementation effective in reducing symptoms following concussion in pediatric patients?

A Rare Compound Heterozygous Mutation of TRPM6 Gene in Hereditary Hypomagnesemia with Secondary Hypocalcemia: A Cause of Refractory Seizures in an Infant

Background: Hypomagnesemia is an important cause of refractory hypocalcemic seizures. Among the causes of hypomagnesemia, genetic defects are rare. Clinical Description: A 20-month-old boy presented with a history of repeated hypocalcemic convulsions since 1 month of age. Besides seizures, the infant was thriving well and otherwise asymptomatic. Management and Outcome: On investigation, he had low serum calcium, normal vitamin D, low parathormone, and very low serum magnesium (0.5 mg/dl) levels, with normal sodium, potassium levels, and renal functions. The child was initiated on parenteral magnesium supplementation and subsequently discharged on high-dose oral magnesium supplementation. As further investigations ruled out common causes of hypomagnesemia, clinical exome sequencing was done, which revealed a compound heterozygous state with two variants in the TRPM6 gene NM_017662.5, one being a missense variant (chr9: c.5614T&gt;C, [p.Trp1872Arg]/Heterozygous) and the other being a frameshift deletion (chr9: c.1939_1946delGCAATGGC, [p.Ala647Profs*2]/Heterozygous). The child maintained normal serum magnesium levels at follow-up and was seizure-free. Conclusion: Hereditary hypomagnesemia with secondary hypocalcemia is a rare cause of refractory seizures with onset since early infancy. Here, a compound heterozygous variant of the TRPM6 gene was identified as the cause of this condition.

A study on the impact of Magnesium on the Glycemic regulation

Objectives: The present study was to evaluate the impact of magnesium on glycemic regulation and also evaluate the changes of glycemic control indicators in type 2 diabetes mellitus patients. Methods: A total of 50 subjects aged 30–60 years with the FBS of more than 126 mg/dL who had been recently diagnosed with T2D (maximum one year) and were being treated with antidiabetic drugs were enrolled in the present study. All the subjects were instructed to follow a prescribed diet plan for one week to stabilize their serum glucose level (30% of total energy as fat, 15% of energy as protein, and 55% of energy as carbohydrate-focused, from complex carbohydrates). Both groups were instructed to consume a healthy diet of fruits and vegetables (five serving per day), legumes, nuts and whole grains. The intervention group consisted of 25 participants who were on Mg supplementation for three months. The control group (25 participants) were not received any type of supplement throughout the intervention period. Body weight and height were measured to calculate body mass index (BMI). All measurements and indicators were taken at the base line (Pre) and after three months of intervention (post changes). Results: Mean age group of intervention and control group was not significant (p=0.118). In both group, males were more preponderance than females. When we compared the mean BMI, HbA1C, C-peptide (ng/mL), HOMA.?%, and Mg (mg/dL) between intervention and control group subjects respectively. P-value was found to be 0.512, 0.588, 0.117, 0.606, 0.317, and 0.235 respectively. Mean FBS of interventional group patients was significantly (p=0.011) reduced in post intervention as compared to pre intervention. While in control group, mean FBS was not significant differences (p=0.184). Mean Ca of interventional group subjects was extreme significantly (p&lt;0.0001) decreased in post intervention as compared to preintervention. While in control group subjects, mean Ca was not significantly decreased in post-test as compared to pre-test. In interventional group subjects, mean Mg was highly significantly (p=002) increased in post intervention as compared to pre intervention. While in control group subjects, mean Mg level was extreme significantly (p&lt;0.0001) reduced in post-test as compared to pre-test. Conclusions: Oral magnesium supplement significantly decreases the fasting blood sugar level. And it reduces the insulin resistance and improves the glycaemic control indicators in type 2 diabetes mellitus patients. Key words: Magnesium, glycaemic control indicators, type 2 diabetes mellitus.

Intestinal Oxalate Absorption, Enteric Hyperoxaluria, and Risk of Urinary Stone Formation in Patients with Crohn's Disease.

Nephrolithiasis is a common urologic manifestation of Crohn's disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn's disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [13C2]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn's disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [13C2]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis.

How much magnesium sulfate is needed to "keep total serum magnesium above 2.0 mg/dL"?

For patients at increased risk of life-threating ventricular arrythmias, hospitalists often administer intravenous magnesium sulfate to maintain total serum magnesium concentration (TsMg) above 2 mg/dL. How long each dose keeps TsMg above this threshold is not well known, however. We collected TsMg values from 12,618 veterans who were given 24,363 doses of intravenous magnesium sulfate during 14,901 hospitalizations for acute heart failure. Across dose amounts, the average TsMg dropped below 2.0 mg/dL within 24 h of administration. When we limited our analysis to 2 g doses (the most common dose) and adjusted for baseline TsMg, estimated glomerular filtration rate, oral magnesium supplementation, and loop diuretic dosing, we found that less than half of the adjusted TsMg values remained above 2.0 mg/dL just 12 h after dose administration. Hospitalists should expect, on average, to administer 2 g intravenous magnesium sulfate at least twice daily to maintain total serum magnesium above 2 mg/dL.

Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial

Aims/hypothesisHypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown.MethodsUsing a randomised, double-blind (both participants and investigators were blinded to the participants’ treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18–40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic–euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up.ResultsWe recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg−1 min−1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms.Conclusions/interpretationDespite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels.Trial registrationEudraCT number 2021-001243-27.FundingThis study was supported by a grant from the Dutch Diabetes Research Foundation (2017–81–014).Graphical

Abstract #1408162: Comparison of Different Doses of Sodium-Glucose Ttransporter-2 Inhibitors (SGLT2i) to SGLT2i with Magnesium Infusions for Refractory Hypomagnesaemia in a Patient with Monogenic Diabetes Type-5 (MODY-5)

MODY-5 is a rare autosomal dominant form of monogenic diabetes attributed to deletions of chromosome 17q12 with impaired expression of HNF1β (Hepatocyte Nuclear Factor 1 homeobox Beta. The deficient HNF1B down regulated the expression of FXYD2. Refractory hypomagnesemia is commonly observed in patients with MODY-5 due to downregulated FXYD2 which blocked the encoding of the γ (gamma) subunit of the Na+-K+-ATPase and indirectly led to hypomagnesemia. SGLT2i have been associated with small but significant increases in serum magnesium (sMg) levels in patients with diabetes. We report our patient's experience comparing the use of SGLT2i at different doses to SGLT2i with Mg infusions for refractory hypomagnesemia in a patient with MODY-5. 29 y/o Caucasian female with family history of young onset diabetes was diagnosed with MODY-5 at the age of 19 years old when she was found to have kidney cysts that were noted incidentally on MRI spine. She presents to our clinic with hypertension, catamenial headaches, hyperuricemia, refractory hypomagnesemia to oral magnesium supplements (400mg twice a day) due to Mg wasting syndrome, congenital pancreatic atresia and exocrine pancreatic insufficiency. sMg levels have been <1.0mg/dl for 2 years and was symptomatic due to it such as fatigue, headaches and muscle aches. Most lately, she could not tolerate more than 1000mg twice a day of oral magnesium due to diarrhea. Prior to starting SGLT2i her sMg was <1.0mg/dl and fractional excretion of magnesium (FEMg) was 14.5% (normal FEMg <4% in the setting of hypomagnesemia). She was started on canagliflozin 100mg and was titrated to 300mg; which has improved her sMg level from 0.9 mg/dl to 1.2mg/dl and was stable with this dose for weeks. FEMg data was not available for the dose change of canagliflozin. She was also started on amiloride 5mg daily. sMg levels have dropped to <1 md/dL when the canagliflozin has been stopped due to insurance but improved again after starting empagliflozin. On 10mg of empagliflozin compared to 25mg of empagliflozin the sMg level has not changed and remained at 1.1mg/dl level but the FEMg improved from 10% to 7.25%. She continued to have symptoms of hypomagnesemia, so she was started on magnesium sulfate 2gm in 100ml normal saline infused over 12hrs 3 times a week for 6 months. Her symptoms improved after the infusion, but they wear off quickly. Magnesium infusions improved the sMg to 1.5mg/dl but the FEMg was 12.6%. Did not improve. Lately due to treatment burden of Magnesium infusion, they were decreased to 2 times per week. SGLT2i improve refractory hypomagnesemia due to Mg wasting syndrome. Her sMg improved to >1 mg/dL with SGLT2i. There was no difference in sMg comparing low versus high doses of empagliflozin, but an improvement in FEMg. Adding magnesium infusion to SGLT2i slightly improved sMg, but at the expense of burden of the disease treatment.

COMPARATIVE ANALYSIS OF SERUM MAGNESIUM &amp; ZINC LEVELS AND THEIR ASSOCIATIONS WITH PRETERM LABOUR

Background: Preterm is dened as babies born alive before 37 weeks of pregnanc, it occurs when there is a regular contraction of uterus which results in opening of cervix after 20 weeks and before 37 weeks of gestation. preterm labour is spontaneous but it can also be due to a biochemical changes in body functions at the cellular level of trace elements such as magnesium and zinc. The main objective of this study is to nd the association of hypomagnesaemia and low zinc levels in preterm delivered women and to compare the maternal serum magnesium and zinc levels between Preterm and Term delivered mothers. Methods: A Comparative study was done in the Department of Biochemistry, Andhra Medical College, Visakhapatnam. Atotal of 126 women who were admitted to the labour room at Department of Obstetrics and gynaecology, King George Hospital, Visakhapatnam were selected for this study. All the subjects were divided into two groups as Preterm Consists of 63 women with spontaneous preterm labour delivered between 28- 37 weeks and Term Consists of 63 Women with Term labour after 37 weeks. Results: Women with Preterm labour had a signicantly low serum magnesium level with a mean serum magnesium level of 1.8 mg/dl with SD of 0.38 whereas the patients with Term labour had a mean serum magnesium level of 2.09 mg/dl with SD of 0.50 and also low zinc levels in Preterm labour with mean zinc levels of 51.28 µg/dl with SD 10.9 whereas patients with Term labour had mean serum zinc levels of 56.5 µg/dl with SD 9.7. The difference of serum magnesium and zinc levels observed between the study population and control population is independent of factors like maternal age, parity, gestational age, Blood pressure and socioeconomic status. In this study there is non signicant weak correlation was found between Demographic data and parametric data. Conclusions:Serum magnesium and zinc levels can be used as predictors for preterm labour. Spontaneous preterm delivery can be avoided by early assessment of maternal magnesium and zinc status and also by simple oral supplementation of magnesium and zinc which might provide an easy and inexpensive means to decrease the problems related to preterm labour. There is a further scope for research on serum magnesium and zinc levels based on gestational age.

The Effect of Oral Magnesium Supplement on Pre-eclampsia and Perinatal Outcomes in Pregnancy: A Meta-Analysis of Randomized Controlled Trials

Background: Magnesium is one of the most important nutritional factors that have a beneficial effect on pregnant women. Many studies evaluated the role of oral magnesium supplements as a non-pharmacological intervention for mother and neonatal protection in terms of these outcomes. There is a conflict between several clinical trials about the efficacy of oral magnesium supplements during pregnancy. Therefore, in this review, we represent class 1 evidence and address an unmet clinical need on the efficacy of different types of oral magnesium in pre-eclampsia, and prenatal outcomes in pregnant women.&#x0D; Method: During the preparation of this meta-analysis, we followed the PRISMA statement guidelines. A literature search of the Web of Sciences, Cochrane Central Register of Controlled Trials, and PubMed were conducted from inception until September 2022. We included randomized controlled trials (RCTs) comparing oral magnesium whether citrate, oxide, or aspartate hydrochloride with a placebo. The records of quality studies were screened and extracted. Additionally, the pre-eclampsia, preterm birth, and neonatal intensive care unit (NICU) admissions data were pooled as odds ratio (OR) in a fixed-effect model using Review Manager (v.3). Subgroup analysis was performed to investigate the efficacy of each type of oral magnesium on the outcomes.&#x0D; Results: Five RCTs were included in this meta-analysis with a total of 2370 patients. The overall effect did not favor either of the two groups in terms of pre-eclampsia (OR= 0.99, 95% CI, [0.72, 1.37], p = 0.9), preterm birth (OR= 0.87, 95% CI, [0.62, 1.22], p = 0.4), and NICU admissions (OR= 1.37, 95% CI, [0.84, 2.22], p = 0.2). Based on the subgroup analysis findings, the use of oral magnesium supplements whether citrate, oxide, or aspartate hydrochloride in this population did not significantly increase or decrease the incidence of pre-eclampsia, preterm birth, and NICU admissions when compared with the control group.&#x0D; Conclusion: Ultimately, oral magnesium supplementation whether citrate, oxide, or aspartate hydrochloride may not have a beneficial effect on maternal and fetal outcomes during pregnancy. Therefore, the current evidence is insufficient to confirm the efficacy of oral magnesium for care practice among pregnant women. Despite that, these results need to be affirmed by major RCTs using magnesium supplements which have related to neonatal and maternal outcomes.

Hypomagnesemia as a Risk Factor and Accelerator for Vascular Aging in Diabetes Mellitus and Chronic Kidney Disease.

The age-old axiom that one is as old as his or her vessels are, calls for ongoing critical re-examination of modifiable risk factors of accelerated vascular ageing in chronic kidney diseases. Attempts to modulate vascular risk with cholesterol-lowering agents have largely failed in advanced chronic kidney disease (CKD). In addition to nitrogen waste products, many pathological biochemical processes also play a role in vascular calcification in chronic kidney damage. Magnesium, a cation vital for the body, may substantially reduce cardiovascular diseases' risk and progression. This narrative review aimed to address the relationship between hypomagnesemia and vascular calcification, which promotes further cardiovascular complications in diabetes, aging, and CKD. Articles with predefined keywords were searched for in the PubMed and Google Scholar databases with specific inclusion and exclusion criteria. We hypothesized that a decrease in serum magnesium levels contributes to increased vascular calcification and thereby increases cardiovascular mortality. In summary, based on existing evidence in the literature, it appears that simple and inexpensive oral magnesium supplementation may reduce the cardiovascular mortality of patients who are already severely affected by such diseases; in this context, the concept of 'normal' vs. 'ideal' serum magnesium levels should be carefully re-examined.

Preispitivanje uloge magnezijuma u istraživanjima epilepsije i zbrinjavanju pacijenata sa epilepsijom

Magnesium is a bioessential mineral with multiple neuroactive effects. Mg2+ ion stabilizes excitable membranes. Epilepsy is the third most frequent chronic neurological condition characterized by spontaneous reappearance of unprovoked epileptic seizures, whose underlying mechanisms are not completely understood yet. A literature review on the role of magnesium in basic and clinical epileptology has been made in order to enlighten the importance of magnesium deficiency in the mechanisms of epileptic brain hyperexcitability, as well as the significance of including magnesium into the management of epilepsy patients. Neuronal magnesium requirements are high. The concentration of magnesium in the cerebrospinal fluid (CSF) is even higher than in the blood. In experimental epilepsy research, perfusing hippocampal slices with artificial CSF containing low concentration of extracellular Mg2+ is a frequently used animal model of spontaneously induced epileptiform activity. Magnesium deficiency is the most frequent clinically unrecognized electrolyte disbalance, often overlooked in epilepsy patients. Serum and CSF Mg2+ concentrations are lower in patients with epilepsy, as compared to healthy controls. Hypomagnesaemia increases seizure frequency and the risk of sudden unexpected death in pharmacoresistant epilepsy. Oral magnesium supplements help achieve better seizure control. Parenterally administered Mg2+ efficiently controls seizures in several epileptic encephalopathies in adults and children (in eclampsia, uremia, porphyria, febrile seizures, infantile spasms), and also helps control status epilepticus. Subclinical magnesium deficiency, very frequent in general population, acts as a factor contributing to seizure generation in epilepsy. It is recommended to assess magnesium status in epilepsy patients. This literature review reveals the therapeutic potential of magnesium as a simple antiepileptic agent, which exceeds its current clinical use.

Author Correction: Oral supplementation of α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D stabilizes cervical changes in women presenting risk factors for preterm birth.

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (23): 8879-8886. DOI: 10.26355/eurrev_202212_30560-PMID: 36524507-published online on December 15, 2022. After publication, the authors found out that in Figure 1 a box, including 63 patients included in the final analysis was missing. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/30560.

Oral supplementation of α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D stabilizes cervical changes in women presenting risk factors for preterm birth.

Recently, the PTB risk has been related to the objective measurement of cervical length (CL), since a CL of less than 25 mm is an accurate predictor of increased risk of PTB. Primary prevention of preterm labor is based on the early identification of symptoms and on pharmacological treatments with tocolytic drugs for inhibition of uterine contractions that are associated with a shortening of the cervix. Unfortunately, most of these drugs have important side effects. This study aimed to evaluate whether the administration of a combination of oral α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D to pregnant women presenting risk factors for PTB could reduce the rate of cervical shortening at 19-22 weeks of gestational age. A total of 122 women attending the first-trimester aneuploidy screening at 11-14 weeks of pregnancy and presenting risk factors for PTB were included in the study. Cervical length significantly decreased in the control group compared with the treatment group (-3.86 ± 1.97 vs. 1.50 ± 1.26; p=0.02). Although the rate of preterm birth did not significantly decrease (9.5% vs. 5.1%), admission for threatened PTB was statistically reduced in the treatment group compared with the control group (3.4% vs. 14.3%). Oral supplementation of ALA, magnesium, vitamin B6 and vitamin D significantly counteracted cervix shortening in pregnant women presenting risk factors for PTB.

Highly Efficient & Specific Repair of MAGT1 Mutation in Xmen Patient T Cells and Hematopoietic Stem Cells

Introduction: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) is a congenital glycosylation disorder with combined immune deficiency due to Magnesium Transporter 1 (MAGT1) mutations. Defective glycosylation of Natural Killer Group 2D (NKG2D), an activating receptor expressed on CD8 and NK cells critical for cytotoxicity, results in EBV lymphoproliferative disease and an inverted CD4:CD8 ratio in many XMEN patients. Oral magnesium supplementation for XMEN patients was not helpful, and hematopoietic stem cell transplants (HSCT) are complicated by high mortality. CRISPR-Cas9-AAV inserts MAGT1 specifically at endogenous locus but relies on double strand DNA breaks and adeno-associated virus donor that triggers DNA damage response. To address this, we evaluated base editing approach to repair a MAGT1 mutation that affects multiple patients with XMEN disease. We observed highly efficient mutation repair of XMEN T cells (75.5%) and hematopoietic stem cells (71.9%) to restore MAGT1 function and persistence of gene correction following transplant into immunodeficient mice. Materials and methods: Peripheral blood hematopoietic stem cells (HSPCs, CD34+) and mononuclear cells (PBMC) were collected from XMEN patients and healthy donors (HD) after G-CSF and plerixafor mobilization. PBMCs were stimulated (anti-CD3/anti-CD28, IL-2 (100 IU/mL), in ImmunoCult™-XF T cell expansion medium for 5-7 days prior to editing. HSPCs were cultured in StemSpan™ SFEM II Stem Cell Factor, Thrombopoietin, Fms-like tyrosine kinase 3 ligand (all 100ng/mL) and UM171 for two days prior to editing. Base editing is performed by electroporation (MaxCyte Inc.) of cells with ABE8e SpRY (CELLSCRIPT LLC.) and synthetic guide (Synthego) RNAs. For in vitro killing activity, T cells were co-cultured with EBV-B cells at a ratio of 1:1 for 48 hours and analyzed for apoptosis (Apoptracker Green+ 7AAD-), necrosis (Apoptracker Green+ 7AAD+) and degranulation (CD8+ CD107a+). HSPCs were transplanted into mice two days after EP and harvested 17-20 weeks after transplant. Results:Base editing of XMEN T cells: Flow cytometric analysis 2 days post BE show restored expression of biomarker NKG2D in XMEN CD8+ T cells (75.5%) compared to HD (93.2%) and naïve XMEN (2.39%). CD8+ cytotoxic activity against EBV-B cells was restored in BE XMEN patient cells; as indicated by increased apoptosis (BE: 6.78%, naïve: 4.82%, HD: 8.17%), necrosis (BE: 9.35%, naïve: 4.54%, HD: 7.19%), and degranulation (BE: 22.80%, naïve: 15.50%, HD: 21.40%), compared to naïve MAGT1 CD8+ T cells.In an in vivo tumor model, BE XMEN T cells injected into mice with induced luminescent EBV-B cell tumors lysed tumors and reduced average bioluminescence flux (photons/sec) (7 weeks) (8.23 × 107 ± 1.06 × 108) compared to naïve T cells (3.39 × 109 ± 2.22 × 109 and HD T cells (1.45 × 109 ± 2.22 × 109). Base editing of HSPCs: Immunodeficient NSGS pups transplanted with BE XMEN HSPCs engrafted and differentiated normally into lymphocytes with a normalized CD4:CD8 ratio in spleen (BE: 0.79 ± 0.14, naïve: 3.45 ± 1.1, HD: 1.3 ± 0.40) and peripheral blood (BE: 2.16 ± 0.84, naïve: 5.56 ± 2.32, HD: 1.79 ± 0.70) (Fig 1a). Importantly, restoration of biomarker NKG2D expression selectively on CD8+ T cells in spleen (BE: 80.5% ± 8.61%, naïve: 3.63% ± 1.45%, HD: 68.9% ± 10.32%) and peripheral blood (BE: 86.1% ± 2.88%, naïve: 2.25% ± 1.45%, HD: 62.6% ± 12.44%) (Fig 1b) confirmed correction of MAGT1 function in the glycosylation of critical NKG2D protein. High throughput targeted sequencing of on-target locus shows minimal bystander edits and additional off-target analysis is ongoing. Conclusion: Our data show highly efficient and specific base editing repair of MAGT1 mutation in XMEN T lymphocytes and CD34+ HSPCs. BE XMEN T cells increased cytotoxic activity in vitro and killing of tumor cells in mice. In vivo studies with mice transplanted with BE CD34+ HSPCs also confirm long term engraftment and differentiation into CD8+ T cells with restored NKG2D necessary for activation and cytolytic activity of CD8+ T and NK cells. The highly efficient and specific correction with base editing holds great promise for gene therapy for XMEN disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Beneficial effects of adding magnesium to desalinated drinking water on metabolic and insulin resistance parameters among patients with type 2 diabetes mellitus: a randomized controlled clinical trial

There is evidence that increasing the consumption of water containing magnesium can improve glucose metabolism and insulin resistance in patients with type 2 diabetes mellitus (T2DM). This trial was undertaken with the objective of evaluating the effect of adding different concentrations of magnesium chloride to the desalinated drinking water on the glycemic, metabolic, and insulin resistance parameters among patients with T2DM. A randomized cross-sectional controlled clinical trial was conducted to evaluate the effects of adding magnesium chloride supplement to desalinated drinking water consumed by patients with T2DM on the glycemic and metabolic parameters and indicators of insulin sensitivity. The total number of patients with T2DM who successfully completed the trial is 102. Patients were randomly allocated into three groups: the first group received bottled water without added magnesium (0 mg/L) (Group A, n = 37); the second group received bottled water with a low level of magnesium (20 mg/L) (Group B, n = 33); and the third group received drinking water with a high level of magnesium (50 mg/L) (Group C, n = 32). The daily consumption of elemental magnesium for a period of 3 months resulted in significant improvement in HbA1C (8.0 vs 8.2%, p = 0.04), insulin level (7.5 vs 9.9 μIU/mL, p = 0.03), and homeostasis model assessment-estimated insulin resistance (HOMA.IR) (2.5 vs 2.9, p = 0.002) in group C. However, there was no significant improvement in fasting blood glucose (FBS) level or lipid profile. The results of this study suggest that oral magnesium supplementation at the given dose of 50 mg/L daily added to drinking water could improve long-term glycemic control indicators and reduce insulin resistance in patients with T2DM.

Effect of oral magnesium supplement on cardiometabolic markers in people with prediabetes: a double blind randomized controlled clinical trial

To evaluate the effect of magnesium supplementation on insulin resistance and cardiovascular markers in people with prediabetes. A 12 week double-blind placebo-controlled randomized clinical trial was conducted at Isfahan Endocrine and Metabolism Research Center, Iran, on people with prediabetes (n = 86) to compare the effects of magnesium oxide 250 mg/day versus a placebo on anthropometric indices, blood pressure, fasting glucose, insulin, HOMA-IR index, C-reactive protein, uric acid and lipid profile. Both groups had similar distributions of anthropometric and biochemical variables at baseline. Those who received magnesium supplementation had significantly higher levels of HDL-cholesterol compared to the placebo group at the end of the study (49.7 ± 10.9 vs 43.6 ± 7.2 mg/dL, P = 0.003). The mean changes of HOMA-IR index, total cholesterol, LDL-cholesterol, triglyceride, uric acid and C-reactive protein levels as well as anthropometric indices and blood pressure in supplemented and placebo groups did not differ significantly. Magnesium supplementation increased HDL-cholesterol levels in people with prediabetes. However, other cardiometabolic markers were not improved by magnesium supplementation at the above dosage and duration.