Restoration of gut dysbiosis through Clostridium butyricum and magnesium possibly balance blood glucose levels: an experimental study.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by an elevated level of blood glucose due to the absence of insulin secretion, ineffectiveness, or lack of uptake of secreted insulin in the body. The improperly diagnosed and poorly managed DM can cause severe damage to organs in the body like the nerves, eyes, heart, and kidneys. This study was aimed at investigating the effect of Clostridium butyricum (probiotic) with magnesium supplementation to evaluate the effect on gut microbial dysbiosis and blood glucose levels. In the laboratory, 6-8 weeks old 24 male albino rats weighing 200-250 g were given free access to water and food. Diabetes was induced using streptozotocin (60 mg/kg) in overnight fasted rats. Diabetic rats were randomly divided into four groups (n = 6, 6 replicates in each group). Metformin (100 mg/kg/day) with a standard basal diet was provided to control group (G0), Clostridium butyricum (1.5 × 105 CFU/day) with standard basal diet was provided to treatment group (G1), magnesium (500 mg/kg/day) was provided to group (G2). Clostridium butyricum (1.5 × 105 CFU/day) and magnesium (300 mg/kg/day) in combination with a standard basal diet was provided to group (G3). Blood Glucose, Magnesium blood test and microbial assay were done. Random blood glucose levels were monitored twice a week for 21 days and were represented as mean of each week. The results conclude that Clostridium butyricum (1.5 × 105 CFU) is very effective in balancing random blood glucose levels from 206.6 ± 67.7 to 85.1 ± 3.8 (p = 0.006) compared to other groups (p > 0.005). The results of stool analysis showed that Clostridium butyricum as probiotic restores microbial dysbiosis as evident by the 105 CFU Clostridium butyricum load in G1, which was higher than G0, G2 and G3 which were 103 and 104 CFU respectively. The findings of this study conclude that Clostridium butyricum supplementation improved blood glucose levels and intestinal bacterial load in type II diabetes mellitus.

Magnesium and Vascular Calcification in Chronic Kidney Disease: Current Insights.

Magnesium (Mg) plays crucial roles in multiple essential biological processes. As the kidneys are the primary organ responsible for maintaining the blood concentration of Mg, people with chronic kidney disease (CKD) may develop disturbances in Mg. While both hyper- and hypomagnesemia may lead to adverse effects, the consequences associated with hypomagnesemia are often more severe and lasting. Importantly, observational studies have shown that CKD patients with hypomagnesemia have greater vascular calcification. Vascular calcification is accelerated and contributes to a high mortality rate in the CKD population. Both in vitro and animal studies have demonstrated that Mg protects against vascular calcification via several potential mechanisms, such as inhibiting the formation of both hydroxyapatite and pathogenic calciprotein particles as well as limiting osteogenic differentiation, a process in which vascular smooth muscle cells in the media layer of the arteries transform into bone-like cells. These preclinical findings have led to several important clinical trials that have investigated the effects of Mg supplementation on vascular calcification in people with CKD. Interestingly, two major clinical studies produced contradictory findings, resulting in a state of equipoise. This narrative review provides an overview of our current knowledge in the renal handling of Mg in health and CKD and the underlying mechanisms by which Mg may protect against vascular calcification. Lastly, we evaluate the strength of evidence from clinical studies on the efficacy of Mg supplementation and discuss future research directions.

The efficacy of magnesium supplementation for gestational diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of magnesium supplementation is unclear for the treatment of gestational diabetes. This meta-analysis aimed to study the efficacy of magnesium supplementation for glycemic control and pregnant outcomes in women with gestational diabetes. METHODS: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been systematically searched up to July 2023, and we included randomized controlled trials (RCTs) assessing the efficacy of magnesium supplementation for gestational diabetes. The meta-analysis was performed using the random-effect model or fixed-effect model based on the heterogeneity. RESULTS: Five RCTs and 266 patients were included in the meta-analysis. Overall, compared with control intervention for gestational diabetes, magnesium supplementation was able to significantly decrease FPG (MD = -7.33 mg/dL; 95 % CI = -7.64 to -7.02 mg/dL; P < 0.00001) and HOMA-IR (MD = -0.99; 95 % CI = -1.76 to -0.22; P = 0.01), but resulted in no obvious impact on serum insulin (MD = -4.17 µIU/mL; 95 % CI = -8.49 to 0.14 µIU/mL; P = 0.06), preterm delivery (OR = 0.42; 95 % CI = 0.06 to 2.95; P = 0.38), macrosomia (OR = 0.34; 95 % CI = 0.08 to 1.35; P = 0.13) or BMI change (MD = -0.01 kg/m2; 95 % CI = -0.06 to 0.04 kg/m2; P = 0.63). CONCLUSIONS: Magnesium supplementation may be effective for the treatment of gestational diabetes without taking insulin treatment.

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/HYPOTHESIS: Hypomagnesaemia 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. METHODS: Using 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. RESULTS: We 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/INTERPRETATION: Despite 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 REGISTRATION: EudraCT number 2021-001243-27. FUNDING: This study was supported by a grant from the Dutch Diabetes Research Foundation (2017-81-014).

Trace element magnesium: a key player in hypertension management.

Magnesium deficit decreases nitric oxide production and oxidative stress, but calcium efflux in VSMC enhances proliferation, migration, and remodelling. These pathways contribute to cardiovascular disorders, hypertension, insulin resistance, sodium retention, fluid retention, and blood volume. Magnesium supplements could be beneficial.

Compounded Effervescent Magnesium for Familial Hypomagnesemia: A Case Report.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder affecting <1/1,000,000 people. It is caused by mutations in the CLDN16 (FHHNC Type 1) or CLDN19 (FHHNC Type 2) genes, which are located on Chromosomes 3q27 and 1p34.2, respectively. There are no drug therapies for this condition. Although magnesium salts represent an important class of compounds and exhibit various therapeutic actions as a supplement for magnesium deficiency in FHHNC, various formulations on the market have different bioavailability. We report the case of a patient with FHNNC first treated, in our Pediatric Institute, with high doses of magnesium pidolate and magnesium and potassium citrate. The patient began to neglect this therapy after experiencing frequent daily episodes of diarrhoea. Our pharmacy received a request for an alternative magnesium supplement that would better comply by ensuring a good magnesium intake which will result in adequate blood magnesium levels. In response, we developed a galenic compound in the form of effervescent magnesium. Here, we report on the promise of this formulation not only for better compliance than pidolate, but also for better bioavailability.

Magnesium Administration in Chronic Kidney Disease.

Awareness of the clinical relevance of magnesium in medicine has increased over the last years, especially for people with chronic kidney disease (CKD), due to magnesium's role in vascular calcification and mineral metabolism. The inverse association between serum magnesium and clinically relevant, adverse outcomes is well-established in people with CKD. Subsequent intervention studies have focused on the effect of magnesium administration, mainly in relation to cardiovascular diseases, mineral bone metabolism, and other metabolic parameters. The most commonly used routes of magnesium administration are orally and by increasing dialysate magnesium. Several oral magnesium formulations are available and the daily dosage of elemental magnesium varies highly between studies, causing considerable heterogeneity. Although data are still limited, several clinical studies demonstrated that magnesium administration could improve parameters of vascular function and calcification and mineral metabolism in people with CKD. Current clinical research has shown that magnesium administration in people with CKD is safe, without concerns for severe hypermagnesemia or negative interference with bone metabolism. It should be noted that there are several ongoing magnesium intervention studies that will contribute to the increasing knowledge on the potential of magnesium administration in people with CKD.

The Role of Hypomagnesemia in Cardiac Arrhythmias: A Clinical Perspective.

The importance of magnesium (Mg2+), a micronutrient implicated in maintaining and establishing a normal heart rhythm, is still controversial. It is known that magnesium is the cofactor of 600 and the activator of another 200 enzymatic reactions in the human organism. Hypomagnesemia can be linked to many factors, causing disturbances in energy metabolism, ion channel exchanges, action potential alteration and myocardial cell instability, all mostly leading to ventricular arrhythmia. This review article focuses on identifying evidence-based implications of Mg2+ in cardiac arrhythmias. The main identified benefits of magnesemia correction are linked to controlling ventricular response in atrial fibrillation, decreasing the recurrence of ventricular ectopies and stopping episodes of the particular form of ventricular arrhythmia called torsade de pointes. Magnesium has also been described to have beneficial effects on the incidence of polymorphic ventricular tachycardia and supraventricular tachycardia. The implication of hypomagnesemia in the genesis of atrial fibrillation is well established; however, even if magnesium supplementation for rhythm control, cardioversion facility or cardioversion success/recurrence of AF after cardiac surgery and rate control during AF showed some benefit, it remains controversial. Although small randomised clinical trials showed a reduction in mortality when magnesium was administered to patients with acute myocardial infarction, the large randomised clinical trials failed to show any benefit of the administration of intravenous magnesium over placebo.

Effect of magnesium supplementation on pregnancy outcome in gestational diabetes mellitus patients: A meta-analysis of randomized controlled trials.

Conflicting evidence exists regarding the effectiveness of magnesium supplementation during pregnancy in gestational diabetes mellitus (GDM) patients. This meta-analysis examines the effect of magnesium on glycemic indices and metabolic status in GDM. We searched databases for randomized controlled trials (RCTs) conducted, and after applying inclusion and exclusion criteria, a total of four RCTs were considered eligible for the analysis. Outcome parameters included markers for glycemic control and metabolic status. A total of four RCTs with 198 participants (control = 99; magnesium supplemented = 99) were selected for the analysis. Magnesium supplementation resulted in a significant reduction in markers of glycemic control-fasting plasma glucose (standard mean difference ( µ ^ ) = -0.83; 95% CI: [-1.13, -0.54]; p-value <.0001), and insulin levels ( µ ^  = -0.95; 95% CI: [-1.38, -0.52]; p-value <.0001). Also, Mg intake resulted in altered oxidative stress markers TAC ( µ ^  = 1.09; 95% CI: [0.10, 2.07]; p-value = .03) of the pregnant women. No significant effect on GSH and CRP levels was observed. This study provides evidence of the positive effects of magnesium intervention on insulin sensitivity and oxidative stress in GDM patients.

Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial.

Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve fibromyalgia symptoms, but the level of evidence is still poor. This study is a randomized, controlled, double-blind trial in fibromyalgia patients that compared once a day oral magnesium 100 mg (Chronomag®, magnesium chloride technology formula) to placebo, for 1 month. The primary endpoint was the level of stress on the DASS-42 scale, and secondary endpoints were pain, sleep, quality of life, fatigue, catastrophism, social vulnerability, and magnesium blood concentrations. After 1 month of treatment, the DASS-42 score decreased in the magnesium and placebo groups but not significantly (21.8 ± 9.6 vs. 21.6 ± 10.8, respectively, p = 0.930). Magnesium supplementation significantly reduced the mild/moderate stress subgroup (DASS-42 stress score: 22.1 ± 2.8 to 12.3 ± 7.0 in magnesium vs. 21.9 ± 11.9 to 22.9 ± 11.9 in placebo, p = 0.003). Pain severity diminished significantly (p = 0.029) with magnesium while the other parameters were not significantly different between both groups. These findings show, for the first time, that magnesium improves mild/moderate stress and reduces the pain experience in fibromyalgia patients. This suggests that daily magnesium could be a useful treatment to improve the burden of disease of fibromyalgia patients and calls for a larger clinical trial.

Role of Magnesium Supplementation in Children with West Syndrome: A Randomized Controlled Clinical Trial.

OBJECTIVES: West syndrome is a severe epileptic encephalopathy of young age. It is characterized by a clinico-electrical triad of infantile epileptic spasms, regression or arrest of psychomotor development, and hypsarrhythmia. In the last two decades, the large progress in the development of newer antiepileptic drugs has allowed us to have a vast choice of treatment options to control spasms, although they often fail to do so. Thus, there is a need to explore other treatment options. MATERIALS & METHODS: Subjects in this open-labelled randomized control trial were included newly diagnosed children of age between 3 months and 5 years of both genders. A total of 52 children were recruited and randomized into two groups: an intervention group (n=30) and a non-intervention group (n=22). Magnesium sulphate was provided for the intervention group but not for the non-intervention one. Both groups received the rest of the treatments, including adrenocorticotropic hormone and antiepileptic drugs. The follow-up period was three months, at the end of which a per-protocol analysis was performed. RESULTS: There was no significant difference in seizure control and neurodevelopmental outcome between both groups, but electroencephalogram significantly improved in the intervention group compared to the control. Also, the clinical response was better in patients with normal initial serum magnesium levels in the intervention group (p=0.003) than in other patients. CONCLUSION: Magnesium supplementation may be helpful in children with West syndrome.

The effects of oral magnesium supplementation on glycaemic control in patients with type 2 diabetes: a systematic review and dose-response meta-analysis of controlled clinical trials.

The current systematic review and meta-analysis were conducted to evaluate the effects of oral Mg supplementation on glycaemic control in type 2 diabetes mellitus (T2DM) patients. Related articles were found by searching the PubMed, SCOPUS, Embase and Web of Science databases (from inception to 30 February 2020). A one-stage robust error meta-regression model based on inverse variance weighted least squares regression and cluster robust error variances was used for the dose-response analysis between Mg supplementation and duration of intervention and glycaemic control factors. Eighteen eligible randomised clinical trials were included in our final analysis. The dose-response testing indicated that the estimated mean difference in HbA1c at 500 mg/d was -0·73 % (95 % CI: -1·25, -0·22) suggesting modest improvement in HbA1c with strong evidence (P value: 0·004). And in fasting blood sugar (FBS) at 360 mg/d was -7·11 mg/dl (95 % CI: -14·03, -0·19) suggesting minimal amelioration in FBS with weak evidence (P value: 0·092) against the model hypothesis at this sample size. The estimated mean difference in FBS and HbA1c at 24 weeks was -15·58 mg/dl (95 % CI: -24·67, -6·49) and -0·48 (95 % CI: -0·77, -0·19), respectively, suggesting modest improvement in FBS (P value: 0·034) and HbA1c (P value: 0·001) with strong evidence against the model hypothesis at this sample size. Oral Mg supplementation could have an effect on glycaemic control in T2DM patients. However, the clinical trials so far are not sufficient to make guidelines for clinical practice.

Preventive effect of 20 mEq and 8 mEq magnesium supplementation on cisplatin-induced nephrotoxicity: a propensity score-matched analysis.

PURPOSE: The protective effect of magnesium (Mg) supplementation against cisplatin (CDDP)-induced nephrotoxicity has been widely described; however, the optimal dose of Mg supplementation is unclear. The aim of this study was to investigate whether 20 mEq of Mg supplementation is more effective than 8 mEq Mg in preventing CDDP-induced nephrotoxicity, as well as the associated risk factors, in cancer patients treated with CDDP-based chemotherapy. METHODS: Pooled data of 272 patients receiving 20 mEq or 8 mEq Mg supplementation to CDDP-based chemotherapy from a multicenter, retrospective, observational study were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify the risk factors for renal failure induced by each treatment dose. RESULTS: There was no significant difference in the incidence of nephrotoxicity between the 8 mEq and 20 mEq groups (P = 0.926). There was also no significant difference in the severity of nephrotoxicity, elevated serum creatinine levels, and decreased estimated creatinine clearance levels between the two groups. Cardiac disease and albumin levels were identified as independent risk factors for CDDP-induced nephrotoxicity. CONCLUSION: We did not find an advantage of 20 mEq over 8 mEq Mg supplementation in terms of a preventive effect against CDDP-induced nephrotoxicity. The optimal dose of Mg supplementation for the prevention of CDDP-induced nephrotoxicity remains unknown, and further studies are warranted.

Chronic magnesium deficiency causes reversible mitochondrial permeability transition pore opening and impairs hypoxia tolerance in the rat heart.

Chronic magnesium (Mg) deficiency induces and exacerbates various cardiovascular diseases. We previously investigated the mechanisms underlying decline in cardiac function caused by chronic Mg deficiency and the effectiveness of Mg supplementation on this decline using the Langendorff-perfused isolated mouse heart model. Herein, we used the Langendorff-perfused isolated rat heart model to demonstrate the chronic Mg-deficient rats (Mg-deficient group) had lower the heart rate (HR) and left ventricular pressure (LVDP) than rats with normal Mg levels (normal group). Furthermore, decline in cardiac function due to hypoxia/reoxygenation injury was significantly greater in the Mg-deficient group than in the normal group. Experiments on mitochondrial permeability transition pore (mPTP) using isolated mitochondria revealed that mitochondrial membrane was fragile in the Mg-deficient group, implying that cardiac function decline through hypoxia/reoxygenation injury is associated with mitochondrial function. Mg supplementation for chronic Mg-deficient rats not only improved hypomagnesemia but also almost completely restored cardiac and mitochondrial functions. Therefore, proactive Mg supplementation in pathological conditions induced by Mg deficiency or for those at risk of developing hypomagnesemia may suppress the development and exacerbation of certain disease states.

Magnesium supplementation for glycemic status in women with gestational diabetes: a systematic review and meta-analysis.

OBJECTIVE: The effect of magnesium supplementation on glycemic status in women with gestational diabetes remains controversial and this meta-analysis aims to explore the efficacy of magnesium supplementation for gestational diabetes. METHODS: We have searched PubMed, Excerpta Medica database, Web of science, Elton B. Stephens. Company, and Cochrane library databases. The meta-analysis included randomized controlled trials (RCTs) assessing the effect of magnesium supplementation for gestational diabetes and was performed using the random-effect model. RESULTS: Four RCTs were included in the meta-analysis. Overall, compared with placebo in gestational diabetes, magnesium supplementation was associated with significantly reduced fasting plasma glucose (standard mean difference [SMD] = -0.99; 95% confidence interval [CI] = -1.28 to -0.70; p < .00001), serum insulin (SMD = -0.75; 95% CI = -1.24 to -0.26; p = .003), homeostasis model assessment of insulin resistance (SMD = -0.74; 95% CI = -1.10 to -0.39; p < .0001) and increased quantitative insulin sensitivity check index (SMD = 0.47; 95% CI = 0.12 to 0.82; p = .008). In addition, low-density lipoprotein-cholesterol (SMD = -0.39; 95% CI = -0.73 to -0.04; p = .03) and total cholesterol (SMD = -0.62; 95% CI = -0.97 to -0.27; p = .0005) were also obviously decreased in the magnesium group than those in the control group. CONCLUSION: Magnesium supplementation benefits glycemic control for gestational diabetes.

Effects of magnesium supplementation on improving hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes: A pooled analysis of 24 randomized controlled trials.

Background: Previous studies have demonstrated that diabetes is often accompanied with lower magnesium status. However, practical details regarding the influences of magnesium intervention on hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes (T2D) need to be further investigated. Methods: Web of Science, ScienceDirect, and PubMed were searched for relevant literatures published through April 30, 2022, and high-quality data were pooled to evaluate the effects of magnesium supplementation on glycemic, circulating lipids, and blood pressure control in T2D, and to explore the associated practical details. Results: Pooled analyses of 24 randomized controlled trials with 1,325 T2D individuals revealed that subjects who received magnesium supplementation had statistically significant reductions in fasting plasma glucose, glycated hemoglobin, systolic blood pressure and diastolic blood pressure, with WMD values of -0.20 mM (95% CI: -0.30, -0.09), -0.22% (95% CI: -0.41, -0.03), -7.69 mmHg (95% CI: -11.71, -3.66) and -2.71 mmHg (95% CI: -4.02, -1.40), respectively. Detailed subgroup analyses demonstrated that health status of participants including age, body mass index, country, duration of disease, baseline magnesium level and baseline glycemic control condition as well as magnesium formulation, dosage and duration of intervention influenced the effects of magnesium addition. Dose-effect analysis showed that 279 mg/d for 116 d, 429 mg/d for 88 d and 300 mg/d for 120 d are the average optimal dosages and durations for improving glycemic, circulating lipids, and blood pressure controls, respectively. Conclusion: Our findings provide clinically relevant information on the adjuvant therapy of magnesium for improving hyperglycemia, hypercholesterolemia, and hypertension in T2D.

Dietary Magnesium Alleviates Experimental Murine Colitis through Modulation of Gut Microbiota.

Nutritional deficiencies are common in inflammatory bowel diseases (IBD). In patients, magnesium (Mg) deficiency is associated with disease severity, while in murine models, dietary Mg supplementation contributes to restoring mucosal function. Since Mg availability modulates key bacterial functions, including growth and virulence, we investigated whether the beneficial effects of Mg supplementation during colitis might be mediated by gut microbiota. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, and fecal consistency. Gut microbiota were analyzed by 16S-rRNA based profiling on fecal samples. Mg supplementation improved microbiota richness in colitic mice, increased abundance of Bifidobacterium and reduced Enterobacteriaceae. KEEG pathway analysis predicted an increase in biosynthetic metabolism, DNA repair and translation pathways during Mg supplementation and in the presence of colitis, while low Mg conditions favored catabolic processes. Thus, dietary Mg supplementation increases bacteria involved in intestinal health and metabolic homeostasis, and reduces bacteria involved in inflammation and associated with human diseases, such as IBD. These findings suggest that Mg supplementation may be a safe and cost-effective strategy to ameliorate disease symptoms and restore a beneficial intestinal flora in IBD patients.

Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial.

Magnesium status and vitamin B6 intake have been linked to mental health and/or quality of life (QoL). In an 8-week Phase IV randomised controlled study in individuals with low magnesemia and severe/extremely severe stress but who were otherwise healthy, greater stress reduction was achieved with magnesium combined with vitamin B6 than with magnesium alone. We present a previously unreported secondary analysis of the effect of magnesium, with and without vitamin B6, on depression, anxiety, and QoL. Adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 were randomised 1:1 to magnesium + vitamin B6 combination (Magne B6® ; daily dose 300 and 30 mg, respectively) or magnesium alone (Magnespasmyl® ; daily dose 300 mg). Outcomes included changes from baseline in DASS-42 depression and anxiety scores, and QoL (Short Form-36 Health Survey). DASS-42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks. Improvement in QoL continued over 8 weeks. Participants' perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than magnesium alone (Week 4). In conclusion, magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia.

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.

Magnesium in Obesity, Metabolic Syndrome, and Type 2 Diabetes.

Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.