Chemical Characterization, Antilipidemic Effect and Anti-Obesity Activity of Ludwigia octovalvis in a Murine Model of Metabolic Syndrome.

Ludwigia octovalvis (Jacq.) P.H. Raven is widely used in traditional medicine for different illnesses, including diabetes and hypertension. However, its impact on lipotoxicity and metabolic syndrome in vivo has not been addressed. Therefore, the aim of this study was to evaluate the effects of this plant on the metabolic syndrome parameters in a C57BL6J mouse hypercaloric diet model. L. octovalvis hydroalcoholic extract and its ethyl acetate fraction (25 mg/kg/day) were used for sub-chronic assessment (10 weeks). Additionally, four subfractions (25 mg/kg) were evaluated in the postprandial triglyceridemia test in healthy C57BL6J mice. The hydroalcoholic extract and ethyl acetate fraction significantly decreased body weight gain (-6.9 g and -1.5 g), fasting glycemia (-46.1 and -31.2 mg/dL), systolic (-26.0 and -22.5 mmHg) and diastolic (-8.1 and 16.2 mmHg) blood pressure, free fatty acid concentration (-13.8 and -8.0 µg/mL) and insulin-resistance (measured by TyG index, -0.207 and -0.18), compared to the negative control. A postprandial triglyceridemia test showed that the effects in the sub-chronic model are due, at least in part, to improvement in this parameter. L. octovalvis treatments, particularly the hydroalcoholic extract, improve MS alterations and decrease free fatty acid concentration. These effects are possibly due to high contents of corilagin and ellagic acid.

Inhibitory effect of Mexican oregano (Lippia graveolens Kunth) extracts on digestive enzymes in vitro, and beneficial impact on carbohydrates and lipids absorption in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Mexican oregano inhibits digestive enzymes in vitro its effect on the absorption of carbohydrates and lipids in vivo has not been addressed. AIM OF THE STUDY: Assess the effect of Mexican oregano (Lippia graveolens Kunth) on carbohydrates and lipids absorption in vivo. The antioxidant activity also was investigated. MATERIALS AND METHODS: Enzymatic inhibitory action of lipase, α-amylase, and α-glucosidase was evaluated in vitro. Oral lipid (OLTT) and starch tolerance tests (OSTT) were conducted with L. graveolens acetone (O-A) and ethanol (O-E) extracts (at 102 mg/kg body weight equivalent to a 1 g human doses) in male Wistar rats. The antioxidant activity was evaluated through inhibition of lipid peroxidation and scavenging radical. RESULTS: Both extracts exhibited higher inhibitory median concentration (IC50) of lipase activity (1.9 µg/µL for O-E and 1.8 µg/µL for O-A) than the positive control (Orlistat) (0.07 µg/µL). The IC50 of α-amylase was higher (41.8 µg/µL for O-E and 25.2 µg/µL for O-A) than the Acarbose (2.5 µg/µL); while α-glucosidase results showed not statistically differences between groups (∼1.7 µg/µL). The OLTT results showed that both extracts significantly reduced serum triglycerides (∼147 mg/dL for O-E and ∼155 mg/dL for O-A) as compared with negative control group (only lipid load). In the OSTT, glucose levels showed a significant decrease (∼31 mg/dL for O-E and ∼17 mg/dL for O-A) than the negative control group (only starch load). About in vitro antioxidant evaluation, not statistically differences between extracts and positive control (Trolox) were observed for scavenged free radicals (∼2.0 µg/µL); whereas O-A inhibited lipid peroxidation similar to the Trolox (∼0.8 µg/µL IC50). The main chemical composition of both extracts was coumaric acid, luteolin, rutinoside, naringenin, and carvacrol. CONCLUSIONS: Both extracts reduce lipid absorption; whereas O-E decreases carbohydrate absorption in vivo. Both extracts inhibit lipid peroxidation and scavenging free radicals in vitro.

Cost-effectiveness analysis of using oral magnesium supplementation in the treatment of prediabetes.

INTRODUCTION: Evidence from clinical trials supports the efficacy of oral magnesium supplementation in the treatment of glucose-related disorders. Thus, we evaluate the cost-effectiveness of using oral magnesium chloride (MgCl2) in prediabetes treatment. METHODS: A cost-effectiveness analysis was performed. For such purpose, we used original information from a randomized controlled clinical trial. Analysis was carried out based on a health services provider perspective, a 10-year time horizon, and 3% discount rate for costs and effectiveness. Taking into account risk factor profiles, a Markov micro-simulation model was used, and a probabilistic sensibility analysis was performed. RESULTS: The oral MgCl2 was dominant with lower cost and greater effectiveness as compared with placebo. As compared with placebo, 22.3% and 22.0% of men using MgCl2 did not develop diabetes or cardiovascular disease. The cost per person of using MgCl2 as compared with placebo, in the individuals without complications, was $2206 versus $4048 USD for men, and $1984 versus $3272 USD for women. The sensitivity analysis confirmed the robustness of the base case. CONCLUSIONS: Our results suggest that using oral MgCl2 for at least 4 months, in adults with prediabetes and hypomagnesemia, is a cost-effective option for reducing complications and direct medical costs.

The relevance of magnesium homeostasis in COVID-19.

PURPOSE: In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions. METHODS: By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19. RESULTS: Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation. CONCLUSION: We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase.

Beneficial Effects of Plant-Derived Natural Products on Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease is becoming in one of the most prevalent liver diseases that leads to liver transplantation. This health problem is a multisystem disease with a complex pathogenesis that involves liver, adipose tissue, gut, and muscle. Although several pharmacological agents have been investigated to prevent or treat non-alcoholic fatty liver disease, currently there is no effective treatment for the management of this chronic liver disease. Nonetheless, the use of natural products has emerged as a alternative therapeutic for the treatment of hepatic diseases, including non-alcoholic fatty liver disease, due to its anti-inflammatory, antioxidant, antidiabetic, insulin-sensitizing, antiobesity, hypolipidemic, and hepatoprotective properties. In the present review, we have discussed the evidence from experimental and clinical studies regarding the potential beneficial effects of plant-derived natural products (quercetin, resveratrol, berberine, pomegranate, curcumin, cinnamon, green tea, coffee, garlic, ginger, ginseng, and gingko biloba) for the treatment or prevention of non-alcoholic fatty liver disease.

Hypoglycemic and antioxidant effects of green tomato (Physalis ixocarpa Brot.) calyxes' extracts.

The aim of this study was to evaluate the hypoglycemic and antioxidant potential of green tomato (Physalis ixocarpa Brot.) calyxes' extracts. Three methods were used to obtain the extracts: maceration (M), ultrasound-assisted (US), and infusion. Regarding in vitro hypoglycemic evaluation, glucose diffusion assay and enzymatic inhibitory action of α-amylase and α-glucosidase were performed. Whereas, for in vivo assessment an oral starch tolerance test (OSTT) was tested with aqueous extracts [infusion (40 mg/kg b. wt.), maceration (M) water (98 mg/kg b. wt.), and US water (82.24 mg/kg b. wt.)] on male Wistar rats. Additionally, in vitro antioxidant activity of P. ixocarpa calyxes' was evaluated through inhibition of scavenging radical assay and lipid peroxidation. Extracts decreased the glucose diffusion in a range of 18%-56% compared with the negative control. Additionally, extracts inhibited α-amylase (above 80%) and α-glucosidase enzymes (above 90%). All groups treated with P. ixocarpa calyxes' significantly reduced the glucose levels at 120 min (infusion = 13.3%, M Water = 12.7%, and US Water = 19.4%) in comparison with the negative control, and similar levels to acarbose at 120 min (13.1%). Finally, extracts showed IC50 values in a range of 2.5-6.6 µg/µl for radical scavenging, and 118-199 µg/µl for lipid oxidation. Our results show that P. ixocarpa calyxes' extracts induce hypoglycemia and antioxidant effects in vitro and in vivo. PRACTICAL APPLICATIONS: The green tomato is usually consumed in Mexico, the United States, and Central America. This fruit grows inside a calyx, which is considered an agro-food waste. However, some regions of Latin America have a traditional medicine purpose for diabetes affections. To the best of our knowledge, there are no published data that supports its hypoglycemic action. The information provided will be useful to nutraceutical applications that allow value-added products and sustainable green tomato production.

Zinc deficiency is an independent risk factor for prehypertension in healthy subjects.

Objective: To assess whether zinc deficiency is associated with prehypertension (preHTN) in apparently healthy subjects. Design: Apparently healthy women and men, aged 20 to 60 years were enrolled into a case-control study. Individuals with and without preHTN were allocated into the case and control groups, respectively. Hypertension, liver disease, renal disease, smoking, pregnancy, diabetes, malignancy, hypernatremia, hypomagnesemia, medical treatment, and use of supplements containing zinc were exclusion criteria. PreHTN was defined by systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) of 120-139 mmHg and/or of 80-89 mmHg, respectively, and the zinc deficiency by serum zinc levels < 74 µg/dL in men and < 70 µg/dL in women. Results: In total, 142 subjects (90 women and 52 men) were enrolled and allocated in the case (n = 71) and control (n = 71) groups. In the overall population, the frequency of zinc deficiency was 11.1%; individuals in the case group showed significant higher frequency of zinc deficiency as compared with the control group (16.9% vs 5.5%, p = 0.04). The logistic regression analysis showed a significant association between zinc deficiency and preHTN (OR = 4.61; 95% CI: 1.24-17.12, p = 0.02). Conclusion: Our results suggest that zinc deficiency is associated with the presence of preHTN in apparently healthy subjects.

Hypoglycemic and antioxidant properties of konjac (Amorphophallus konjac) in vitro and in vivo.

The aim of this study was to evaluate the hypoglycemic and antioxidant potential of konjac in vitro and in vivo. Glucose diffusion and enzymatic starch digestion of konjac were assayed using α-amylase and α-glucosidase. Oral glucose tolerance test (OGTT) and oral starch tolerance test (OSTT) were performed at dose of 102 mg/Kg of body weight (equivalent to 1 g/meal in humans). Additionally, the antioxidant activity of konjac was evaluated through inhibition of lipid peroxidation. The konjac decreased glucose diffusion by 36% and 19% compared with the negative and positive controls, respectively. Additionally, konjac inhibited α-amylase and α-glucosidase activities by 14% and 90%, respectively. After OSTT, group treated with konjac showed significant lower glucose levels compared with control group (p = .03). Finally, konjac reduced lipid peroxidation in human plasma (93%) compared with the negative control. Our results suggest that konjac exhibits hypoglycemic and antioxidant activities in vitro and in vivo. PRACTICAL APPLICATIONS: Because the use of herbal products have emerged as an attractive therapeutic option for chronic diseases, konjac administration may be an adjuvant for the treatment of type 2 diabetes.

Hypoglycemic and antioxidant effects of five commercial turmeric (Curcuma longa) supplements.

We evaluate the hypoglycemic and antioxidant effects of five commercial turmeric (Curcuma longa) supplements: (1) bulk samples, (2) turmeric root from India, (3) curcuma turmeric Pronat® , (4) turmeric & black pepper Swanson® , and (5) C3 complex® turmeric curcumin. Glucose diffusion and enzymatic starch digestion assays, using α-amylase and α-glucosidase, were performed. The antioxidant activity of turmeric supplements was measured through lipid peroxidation inhibition and the scavenging radical assay. A starch dose of 102 mg/Kg of body weight (equivalent to 1 g/day in humans) was used to perform the oral starch tolerance test (OSTT) in Wistar male rats. All turmeric supplements decreased glucose diffusion and α-glucosidase enzyme activity, and inhibited lipid peroxidation. The rats that received bulk samples and CT showed significantly lower glucose levels than rats receiving acarbose and those of negative control group. Our results show that biological activities of turmeric supplements vary according to the commercial presentation. PRACTICAL APPLICATIONS: The study results suggest that the hypoglycemic and antioxidant effects of five commercial turmeric supplements vary among them. The information provided would be useful to physicians and individuals using these supplements.

Effect of resveratrol supplementation on lipid profile in subjects with dyslipidemia: A randomized double-blind, placebo-controlled trial.

OBJECTIVES: The aim of this study was to explore the effect of resveratrol supplementation on lipid profile in individuals with dyslipidemia. METHODS: Apparently healthy men and non-pregnant women 20 to 65 y of age with new diagnosis of dyslipidemia were enrolled in a randomized double-blind, placebo-controlled trial and randomly allocated to receive either resveratrol 100 mg/d or placebo (sucrose 0.5 g/d) for 2 mo. Smoking, alcohol intake, diabetes, acute or chronic renal or hepatic diseases, malignancy, cardiovascular disease, serum triacylglycerol levels ≥400 mg/dL, low-density lipoprotein cholesterol levels ≥190 mg/dL, and consumption of lipid-lowering drugs or supplements containing resveratrol were exclusion criteria. RESULTS: Seventy-one individuals with new diagnosis of dyslipidemia were enrolled and randomly allocated to the resveratrol (n = 35) or placebo groups (n = 36). At baseline, there were no significant differences between the study groups. After intervention period, individuals in the resveratrol group showed a significant decrease in total cholesterol (201.4 ± 34.4 versus 220.6 ± 37.4, P = 0.04) and triacylglycerol (133.4 ± 55.3 versus 166.7 ± 68.5, P = 0.04) concentrations compared with the placebo group, without significant statistical differences for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels. CONCLUSION: The results suggest that resveratrol supplementation significantly reduces total cholesterol and triacylglycerol concentrations in individuals with dyslipidemia.

Oral Magnesium Supplementation and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

The objective of the study was to evaluate the efficacy of oral magnesium supplementation in the improvement of metabolic syndrome (MetS) and its components. This is a randomized double-blind, placebo-controlled clinical trial that enrolled 198 individuals with MetS and hypomagnesemia who were randomly allocated to receive either 30 mL of magnesium chloride 5% solution, equivalent to 382 mg of elemental magnesium (n = 100), or placebo solution (n = 98), daily for 16 weeks. Serum magnesium levels <1.8 mg/dL defined hypomagnesemia. At final conditions, a total of 48 (48%) and 76 (77.5%) individuals had MetS in the magnesium and placebo groups (P = 0.01), respectively. At baseline, percent of individuals with 3, 4, and 5 criteria of MetS in the magnesium group were 60.0%, 37.0%, and 3.0%, respectively, and in the control group 55.1%, 35.7%, and 9.2%, respectively. Between basal and final conditions, changes in the components of MetS were significantly higher in the magnesium than placebo groups: -3.6 ± 3.3 mmHg, P = 0.001 for systolic blood pressure; -5.5 ± 1.7 mmHg, P = 0.005 for diastolic blood pressure; -12.4 ± 3.6 mg/dL, P < 0.005 for fasting glucose; -61.2 ± 24 mg/dL, P = 0.003 for triglycerides; and 0.9 ± 0.4 mg/dL, P = 0.06 for high-density lipoprotein cholesterol. Magnesium supplementation improves MetS by reducing blood pressure, hyperglycemia, and hypertriglyceridemia.

Effect of oral magnesium supplementation on the transcription of TRPM6, TRPM7, and SLC41A1 in individuals newly diagnosed of pre-hypertension. A randomized, double-blind, placebo-controlled trial.

A stringent regulation of influx and efflux of magnesium by cation transporters seems to play an important role in the regulation of blood pressure (BP). With this regard, we evaluate the effect of oral magnesium supplementation on the transcription of TRPM6, TRPM7, and SLC41A1, in individuals with incident pre-hypertension (preHTN). For such purpose, we conducted a randomized, double-blind, placebo-controlled trial that compared 18 individuals who received oral magnesium lactate (360 mg elemental magnesium) versus 18 individuals who received placebo, during 4 months. Diagnosis of hypertension or normal BP, diabetes, alcohol intake, chronic diarrhea, use of diuretics, intake of magnesium supplementation, and reduced renal function were exclusion criteria. Regarding the transcription analysis of TRPM6, TRPM7, and SLC41A1 using RT-qPCR, leukocyte-rich plasma was obtained and total RNA was isolated with the kit Direct-zol™ RNA MiniPrep (Zymo). The leukocyte TRPM6 mRNA relative expression showed a significant increase (2.1 ± 1.37 and 0.8 ± 0.4, P<0.05), whereas the mRNA relative expression of both leukocyte TRPM7 (0.8 ± 1.1 and 0.9 ± 0.6, pNS) and SLC41A1 (0.9 ± 1.0 and 0.7 ± 0.6, pNS) showed no significant differences, between the magnesium and placebo groups, respectively. Oral magnesium supplementation increases the leukocyte TRPM6 mRNA relative expression, in subjects with new diagnosis of preHTN.

Effect of Magnesium Supplementation on Plasma C-reactive Protein Concentrations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Results of previous clinical trials evaluating the effect of magnesium supplementation on inflammatory markers are controversial. OBJECTIVE: A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to evaluating the effect of oral magnesium supplementation on plasma C-reactive protein (CRP) concentrations. METHOD: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (from inception to August 09, 2016) to identify RCTs, evaluating the effect of magnesium on CRP levels. A random-effects model and a generic inverse variance method were used to compensate for the heterogeneity of studies. Publication bias, sensitivity analysis, and meta-regression assessments were conducted using standard methods. RESULTS: Overall, the impact of magnesium supplementation on plasma concentrations of CRP was assessed in 11 studies. Magnesium treatment was not found to significantly affect plasma concentrations of CRP (WMD: -0.11 mg/L, 95% CI: -0.75, 0.52, p=0.727). When the analysis was stratified to compare subgroups of studies in populations with baseline plasma CRP values of ≤ 3 and > 3 mg/L, a significant reduction of CRP values was observed in the latter subgroup (WMD: -1.12 mg/L, 95% CI: -2.05, -0.18, p=0.019) but not in the former group (WMD: 0.61 mg/L, 95% CI: -0.10, 1.32, p=0.090). The difference between subgroups was statistically significant (p=0.004). CONCLUSION: Results of the present meta-analysis indicated that magnesium supplementation reduces CRP levels among individuals with inflammation (CRP levels > 3 mg/dL). This finding suggests that magnesium supplements may have a beneficial role as an adjuvant for the management of low-grade chronic systemic inflammation.

Impact of Nutritional Intervention on Length of Hospital Stay and Mortality among Hospitalized Patients with Malnutrition: A Clinical Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to evaluate the impact of a nutritional intervention on hospital stay and mortality among hospitalized patients with malnutrition. METHODS: Hospitalized patients with a diagnosis of malnutrition were enrolled and randomly allocated to either an intervention or control group. Participants in the intervention group received an individualized nutrition plan according to energy and protein (1.0-1.5 g/kg) intake requirements as well as dietary advice based on face-to-face interviews with patients and their caregivers or family members. Individuals in the control group received standard nutritional management according to the Hospital Nutrition Department. Nutritional status and disease severity were assessed using nutritional risk screening. Length of hospital stay was defined by the number of days of hospitalization from hospital admission to medical discharge. Reference to another service or death were criteria for study withdrawal. To evaluate mortality, individuals were followed up for 6 months after hospital discharge. Hospital stay and mortality were the intention-to-treat analysis. RESULTS: A total of 55 patients with an average age of 57.1 ± 20.7 years were included into intervention (n = 28) and control (n = 27) groups, respectively. At basal condition, nutritional status, measured by nutritional risk screening score, was similar between the study groups (4.1 ± 0.8 vs 4.2 ± 1.2, p = 0.6). The average hospital stay was lower in the intervention group compared to the control group (6.4 ± 3.0 vs 8.4 ± 4.0 days, p = 0.03). Finally, the mortality rate at 6 months of follow-up was similar in both groups (hazard ratio [HR] = 0.85; 95% confidence interval [CI], 0.17-4.21). CONCLUSIONS: Results of this study suggest that, in hospitalized patients with malnutrition, nutritional intervention and dietary advice decrease hospital stay but not mortality.

Effect of magnesium supplementation on lipid profile: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We performed a meta-analysis of randomized controlled trials (RCTs) in order to evaluate the effect of oral magnesium supplementation on lipid profile of both diabetic and non-diabetic individuals. METHODS: PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (from inception to February 23, 2016) to identify RCTs evaluating the effect of magnesium on lipid concentrations. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on lipid concentrations. RESULTS: Magnesium treatment was not found to significantly affect plasma concentrations of any of the lipid indices including total cholesterol (WMD 0.03 mmol/L, 95% CI -0.11, 0.16, p = 0.671), LDL-C (WMD -0.01 mmol/L, 95% CI -0.13, 0.11, p = 0.903), HDL-C (WMD 0.03 mmol/L, 95% CI -0.003, 0.06, p = 0.076), and triglycerides concentrations (WMD -0.10 mmol/L, 95% CI -0.25, 0.04, p = 0.149). In a subgroup analysis comparing studies with and without diabetes, no difference was observed between subgroups in terms of changes in plasma total cholesterol (p = 0.924), LDL-C (p = 0.161), HDL-C (p = 0.822), and triglyceride (p = 0.162) concentrations. CONCLUSIONS: Results of the present meta-analysis indicated that magnesium supplementation showed no significant effects on the lipid profile of either diabetic or non-diabetic individuals.

Magnesium in metabolic syndrome: a review based on randomized, double-blind clinical trials.

A growing body of evidence shows the effect of magnesium on serum glucose, HDL-cholesterol, and triglycerides levels, as well as on blood pressure, which strongly suggests that magnesium might play an important role in metabolic syndrome (MetS), a cluster of risk factors for cardiovascular disease and type 2 diabetes. We performed a systematic review of clinical evidence derived from randomized, double-blind, controlled clinical trials, regarding the efficacy of magnesium supplementation on the components of MetS. Using the electronic databases of Medline, Embase, and the Cochrane Controlled Trials Register up to May 2016, we looked for randomized controlled trials focused on the effects of oral magnesium supplementation on insulin sensitivity, glucose, triglyceride and HDL-cholesterol levels, as well as its effects on high blood pressure, irrespective of the magnesium salt used, and with a duration of at least four weeks. Crossover studies, irrespective of blinding criteria, were not included. Results of this review show that magnesium supplementation in individuals with hypomagnesemia can be effective in the treatment of MetS.

A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control.

A systematic review and meta-analysis was conducted to evaluate the effect of oral magnesium supplementation on insulin sensitivity and glucose control in both diabetic and non-diabetic individuals. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (from inception to November 25, 2015) to identify RCTs evaluating the effect of magnesium on insulin sensitivity and glucose control. A random-effects model and generic inverse variance method were used to compensate for the heterogeneity of studies. Publication bias, sensitivity analysis, and meta-regression assessments were conducted using standard methods. The impact of magnesium supplementation on plasma concentrations of glucose, glycated hemoglobin (HbA1c), insulin, and HOMA-IR index was assessed in 22, 14, 12 and 10 treatment arms, respectively. A significant effect of magnesium supplementation was observed on HOMA-IR index (WMD: -0.67, 95% CI: -1.20, -0.14, p=0.013) but not on plasma glucose (WMD: -0.20mmol/L, 95% CI: -0.45, 0.05, p=0.119), HbA1c (WMD: 0.018mmol/L, 95% CI: -0.10, 0.13, p=0.756), and insulin (WMD: -2.22mmol/L, 95% CI: -9.62, 5.17, p=0.556). A subgroup analysis comparing magnesium supplementation durations of <4 months versus ≥4 months, exhibited a significant difference for fasting glucose concentrations (p<0.001) and HOMA-IR (p=0.001) in favor of the latter subgroup. Magnesium supplementation for ≥4 months significantly improves the HOMA-IR index and fasting glucose, in both diabetic and non-diabetic subjects. The present findings suggest that magnesium may be a beneficial supplement in glucose metabolic disorders.

Obesity and hypomagnesemia.

BACKGROUND: Whether low serum magnesium is an epiphenomenon related with obesity or, whether obesity per se is cause of hypomagnesemia, remains to be clarified. OBJECTIVE: To examine the relationship between body weight status and hypomagnesemia in apparently healthy subjects. METHODS: A total of 681 healthy individuals aged 30 to 65years were enrolled in A cross-sectional study. Extreme exercise, chronic diarrhea, alcohol intake, use of diuretics, smoking, oral magnesium supplementation, diabetes, malnutrition, hypertension, liver disease, thyroid disorders, and renal damage were exclusion criteria. Based in the Body Mass Index (BMI), body weight status was defined as follows: normal weight (BMI <25kg/m2); overweight (BMI ≥25<30 BMIkg/m2); and obesity (BMI ≥30kg/m2). Hypomagnesemia was defined by serum magnesium concentration ≤0.74mmol/L. A multiple logistic regression analysis was used to compute the odds ratio (OR) between body weight status (independent variables) and hypomagnesemia (dependent variable). RESULTS: The multivariate logistic regression analysis showed that dietary magnesium intake (OR 2.11; 95%CI 1.4-5.7) but no obesity (OR 1.53; 95%CI 0.9-2.5), overweight (OR 1.40; 95%CI 0.8-2.4), and normal weight (OR 0.78; 95%CI 0.6-2.09) were associated with hypomagnesemia. A subsequent logistic regression analysis adjusted by body mass index, waist circumference, total body fat, systolic and diastolic blood pressure, and triglycerides levels showed that hyperglycemia (2.19; 95%CI 1.1-7.0) and dietary magnesium intake (2.21; 95%CI 1.1-8.9) remained associated with hypomagnesemia. CONCLUSIONS: Our results show that body weight status is not associated with hypomagnesemia and that, irrespective of obesity, hyperglycemia is cause of hypomagnesemia in non-diabetic individuals.

Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come.

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health.