Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations.

BACKGROUND: There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES: We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS: Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.

Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels.

This study aimed to investigate the short-term effects of three magnesium (Mg) dietary supplements containing mineral immediately available for absorption on Mg biochemical status indices (ionized and total Mg), as well as their effects on electrolytes levels in healthy female young adults (n = 61). After a 10-days intervention period supplementation with powder/granulate containing Mg oxide led to an increase in both ionized Mg concentration and % in total Mg in comparison with the baseline. Supplementation with Mg citrate was associated with the significant increase in % of ionized fraction and decrease in serum total Mg concentration. By contrast, among participants consuming Mg carbonate in the form of effervescent tablets ionized Mg concentration and % in total Mg decreased, without detectable changes in serum total Mg. In conclusion, after the short-term supplementation period, Mg oxide demonstrated superior bioavailability compared to the other examined Mg supplements without affecting other minerals' levels.

Ionized Blood Magnesium in Sick Children: An Overlooked Electrolyte.

INTRODUCTION: Magnesium is a less frequently monitored electrolyte in critically ill patients. Hypomagnesemia is associated with increased need for mechanical ventilation, mortality and prolonged ICU stay. The present study was undertaken to identify the proportion of children with abnormal magnesium levels and correlate it with disease outcome. METHODS: This observational study included children aged 1 month to 12 years hospitalized at the emergency room. Heparinized blood was collected for determination of ionized magnesium, ionized calcium, sodium, potassium and lactate using Stat Profile Prime Plus (Nova Biomedical, Waltham, MA, USA). Clinical outcomes for duration of hospitalization, and death or discharge were recorded. RESULTS: A total of 154 (102 males) children with median (IQR) age of 11 (4, 49.75) months were enrolled. Sixty one (39.6%) had ionized magnesium levels below 0.42 mmol/l, 63 (40.9%) had normal levels and 30 (19.4%) had hypermagnesemia (>0.59 mmol/l). Hypomagnesemia was associated with hypocalcemia (p < 0.001), hyponatremia (p < 0.001) and hypokalemia (p < 0.02). A higher proportion of children with hypermagnesemia required ventilation than hypomagnesemia (26% vs. 9%) and succumbed (35% vs. 20%), respectively; p > 0.05. Ninety-three (60.3%) had hypocalcemia and 10 (6.5%) children had hypercalcemia. There was good correlation between ionized calcium and magnesium values (r = 0.72, p < 0.001). CONCLUSION: Both hypomagnesemia and hypermagnesemia were seen in critically ill children. Patients with hypomagnesemia had significantly higher proportion of other electrolyte abnormalities.

Association between ionized magnesium and postoperative shivering.

PURPOSE: Ionized magnesium (iMg) is considered to be the biologically active fraction of circulating total serum Mg (tMg). However, only the relationship between tMg and postoperative shivering has been studied. To our knowledge, hitherto no clinical studies have investigated the association between serum ionized magnesium concentration ([iMg]) and postoperative shivering. Therefore, we aimed to retrospectively examine this association, focusing on hypomagnesemia and depletion of [iMg]. METHODS: This retrospective study involved 421 patients who underwent pancreaticoduodenectomy under general anesthesia at our center from December 2012 to September 2019. Logistic regression analysis was performed to estimate the odds ratio (OR) for the incidence of postoperative shivering. RESULTS: Postoperative shivering developed in 111 out of 421 patients. The post-surgical concentration of [iMg] was significantly associated with postoperative shivering in the non-adjusted model, but not in the multivariable-adjusted model. In multivariable-adjusted analysis, progressive decrease of [iMg] by 0.1 mmol/L significantly increased the risk of postoperative shivering (OR: 1.64, 95% CI 1.02-2.64, p = 0.04). The multivariable-adjusted OR for postoperative shivering was 3.65 (95% CI 1.25-13.55, p = 0.02) in subjects with post-surgical [iMg] less than 0.6 mmol/L and decrease in [iMg] during surgery compared with those with post-surgical [iMg] more than 0.6 mmol/L and constant or increased of [iMg] during surgery. CONCLUSION: A decrease in the [iMg] during surgery was significantly associated with postoperative shivering. Subjects who had an [iMg] lower than 0.6 mmol/L post-surgery and decreased [iMg] during surgery had a significantly higher risk of postoperative shivering. Intraoperative depletion of [iMg] was significantly associated with shivering.

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia.

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO4 ) to healthy horses. MgSO4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg2+ ). Objective data were analyzed using the Wilcoxon rank-sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg2+ increased nearly fivefold, ionized calcium (Ca2+ ) decreased by nearly 10%, and the Ca2+ to Mg2+ ratio declined more than 3.5-fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO4 .

Prospective study of serum and ionized magnesium pharmacokinetics in the treatment of children with severe acute asthma.

PURPOSE: Intravenous (IV) magnesium sulfate (MgSO4) is clinically useful as adjunct therapy in treating acute asthma exacerbations. Despite its clinical utility, the disposition of magnesium in children is poorly described. The purpose of this study is to describe the pharmacokinetics (PK) of ionized and total serum magnesium following IV MgSO4 administration in children with severe acute asthma. METHODS: Thirty-two children receiving 50 mg/kg IV MgSO4 for acute asthma exacerbations at Primary Children's Hospital in Salt Lake City, UT, were prospectively enrolled in the study. Blood samples were collected before, as well as 30 min and 2 h after each child's IV MgSO4 dose, and used to determine total serum and ionized magnesium concentrations. The collected data were analyzed using population PK techniques using NONMEM® software. RESULTS: Total serum magnesium concentrations were used to externally validate our previously published model constructed with retrospective data (median prediction error 10.3%, median absolute prediction error 18.1%). The mean (%CV) observed endogenous ionized magnesium concentration was calculated to be 6.0 mg/L (12%), approximately one third of the same value for endogenous total serum magnesium (17.6 mg/L (22%)) in this dataset. Weight was a significant predictor of both clearance and volume in a population PK model describing ionized magnesium concentrations. No adverse events were observed in this pediatric cohort. CONCLUSIONS: This prospective study supports and extends our previous PK analysis of total serum magnesium concentrations. Ionized and total serum magnesium followed similar PK profiles following IV MgSO4 administration in children. A single bolus infusion of IV MgSO4 was safe in this small sample of children receiving it for acute asthma.

A Direct Quantitative Analysis of Erythrocyte Intracellular Ionized Magnesium in Physiological and Pathological Conditions.

Magnesium (Mg2+) is an endogenous cation that is involved in many essential biological reactions. Abnormal Mg2+ metabolisms in the body affect important physiological and pathological processes. However, most endogenous Mg2+ markers fail to represent body Mg2+ status; they are disadvantageous in terms of representational capacity, applied range, operational convenience, etc. In this article, we evaluated some of the most popular Mg2+ marker candidates. A logical model of the blood Mg2+ compartments was established, which consisted of unstable Mg2+ pools, representative Mg2+ pools, and conserved Mg2+ pools. These pools were based on the metabolic efficiency of Mg2+ in an acute Mg2+ intake test. The results of this study showed that only the erythrocyte intracellular ionized Mg2+ (RBC [Mg2+]i), a representative Mg2+ pool, could effectively represent abnormal body Mg2+ metabolisms in various conditions, including dietary Mg2+ adjustments, aging and metabolic syndrome. These results suggest that RBC [Mg2+]i might be a widely applicable marker of body Mg2+ levels. On unified technology platform and evaluation system, this research compared the representative capacities of RBC [Mg2+]i, plasma Mg2+ concentration (plasma [Mg2+]), erythrocyte intracellular total Mg (RBC [Mg]total) and Mg retention in rats and mice under various Mg2+-metabolism-related physiological and pathological conditions. Our technique for the direct quantitative analysis of RBC [Mg2+]i may prove valuable for basic physiological research, dietary Mg2+ regulation, as well as clinical monitoring/intervention of Mg2+-metabolism-related pathology.

Ionized and total serum magnesium in hemodialysis: predictors and variability. A longitudinal cross-sectional study.

BACKGROUND: Ionized Magnesium (ion-Mg) represents the active biological fraction of the serum magnesium content. The assessment of total serum Mg (tot-Mg) might not accurately identify patients with hypo-or hyper-magnesaemie. In hemodialysis, serum tot-Mg levels in the upper part of the distribution, have been associated with reduced mortality and fewer vascular calcifications; thus, resulting in the tendency to increase the Mg concentration in the dialysate, traditionally set at 0.5 mmol/L. METHODS: Single-center study in chronic hemodialysis patients, designed in two phases, cross-sectional and longitudinal, aimed to investigate: (1) the sensitivity for pathological values of ion-Mg compared to tot-Mg (2) the predictors of ion-Mg developing ad hoc equations; (3) the inter- and intra-individual variabilities of ion-Mg; and (4) the risk factors for hypermagnesemia. Tot-Mg, ion-Mg, and covariates of 42 hemodialysis sessions, in 42 patients during the cross-sectional phase and of 270 sessions in 27 patients in the longitudinal one were analysed. RESULTS: Ion-Mg significantly correlates with tot-Mg: ß = 0.52; r = 0.88, p < 0.001. Multiple linear regressions in normo- and hypo-albuminemic patients gave the following results: ion-Mg = tot-Mg/2-K+/50 + Ca2+/5-HCO3-/100 and ion-Mg = tot-Mg/2 + albumin/100. Ion-Mg showed a high temporal variability in the longitudinal phase (between months p < 0.001; winter vs. summer, p < 0.027). A high intra-individual variability was also found: coefficient of variation 0.116. Comparing patients with high and low intra-individual variability, we found: age 67 vs. 77 years; p < 0.001; urea 26.3 ± 0.5 vs. 21.2 ± 0.4 mmol/L, p < 0.001; nPCR 0.92 ± 0.1 vs. 0.77 ± 0.1 g/kg day, p < 0.001; PTH 46.3 ± 4 vs. 28.5 ± 3 pmol/L, p < 0.001. CONCLUSIONS: Ion-Mg can be useful in unmasking unrecognized hyper- and hypo-magnesemic and false hyper-magnesemic patients. Ion-Mg is characterized by high intra- and inter-individual variabilities particularly in younger women and those with better nutrition. Patients with greater variability could potentially be at risk if exposed to higher concentrations of magnesium in the dialysate. An interventional study, with controlled increase of magnesium concentrations in the dialysate has been planned.

Assessment of preeclampsia risk by use of serum ionized magnesium-based equation.

BACKGROUND: Preeclampsia is a common medical complication in pregnancy. It has been reported to be associated with decreased serum magnesium levels. However, there has not been evidence demonstrating utilization of change in magnesium for prediction of preeclampsia. The purpose of this study was to develop magnesium fraction-based equations which took other significant clinical risk factors into consideration for prediction of preeclampsia. METHODS: We collected serum total and ionized magnesium ionized magnesium levels from 84 pregnant women diagnosed with preeclampsia after week 20 of pregnancy. The ionized magnesium fraction was then calculated by the percentage ratio of ionized and total magnesium level. RESULTS: Sixty-four (76.19%) women had normal pregnancy and 20 (23.81%) developed preeclampsia. The ionized magnesium fraction was significantly lower in preeclampsia group (23.95 ± 4.7% vs. 26.28 ± 2.3%, p = .04). Additionally, lower ionized magnesium fraction (24.67%), teenage and elderly primigravida were significantly associated with preeclampsia (OR = 4.41, 95% CI: 1.46-13.40, OR = 5.47, 95% CI: 1.85-35.42 and OR = 11.11, 95% CI: 1.09-113.78, respectively). Consequently, we attempted to develop ionized magnesium fraction-based equations calculate risk scores for preeclampsia. The area of ROC for predictive accuracy of the model was 0.77 (p < .001) and ROC suggested that the score of 0.27 would be a threshold for screening preeclampsia with 70% sensitivity and 81% specificity. CONCLUSIONS: Ionized magnesium fraction may have been appropriate for screening of preeclampsia. We suggested blood testing on total and ionized magnesium concentrations as well as calculation of ionized magnesium fraction in addition to routine antenatal care for better screening of the disease.

Monitoring of ionized magnesium in hemodialysis patients: A useful tool to allow a personalized prescription of dialysate composition.

BACKGROUND AND AIMS: The dialysate magnesium (Mg) concentration is a major determinant of Mg balance in hemodialysis. This study aimed to assess the systemic variations of total (tMg) and ionized Mg (iMg) during a dialysis session using acetate or citrate fluids and 0.5 or 0.75 mM Mg. MATERIALS AND METHODS: 134 patients in maintenance hemodialysis were assigned to a dialysis session with 4 different dialysates: acetate fluid with 0.5 mM Mg (1) or 0.75 mM Mg (2), citrate fluid with 0.5 mM Mg (3) or 0.75 mM Mg (4). Ionized form was measured by direct ion-selective electrode. RESULTS: A Mg loss was observed in both acetate (0.12 and 0.08 mmol/L) and citrate (0.13 and 0.14 mmol/L for tMg and iMg, respectively) fluid groups containing 0.5 mM Mg. The use of acetate and citrate dialysates with 0.75 mM Mg led to a significant median intra-dialytic increase of 0.15 and 0.08 mmol/L for tMg, respectively. A significant augmentation in iMg concentration with acetate (0.11 mmol/L) but not with citrate dialysate (0.02 mmol/L) was observed. CONCLUSION: While a dialysate Mg concentration at 0.5 mM leads to a negative balance, increasing the concentration to 0.75 mM significantly raises post-dialysis circulating Mg. Monitoring of iMg should allow a personalized prescription in dialysate Mg.

Magnesium matters: unveiling hidden risks in kidney transplant patients through total and ionized magnesium profiling.

Background: In kidney transplant (KT) patients, magnesium (Mg2+) deficiency is widespread. It is often encountered early after KT, may persist longer, and is frequently promoted by calcineurin inhibitors (CNIs) and tubular leakage. Studies demonstrated an association between post-KT hypomagnesemia and allograft dysfunction. The concentration of the active form, the ionized Mg2+ (iMg2+), is not measured clinically, and total Mg2+ (tMg2+) and iMg2+ correlations are conflicting. We assess the cross-sectional prevalence of hypomagnesemia in KT patients. The correlation of demographic and anthropometric parameters was also studied. Methods: A prospective, single-center analysis of KT patients was conducted at the University Hospital of Bern, Switzerland (March 2023-August 2023). Blood samples were collected at least twice for the majority of patients. tMg2+ has been quantified from a plasma sample at the Clinical Chemistry Department of the University Hospital of Bern. The PRIME® ES analyzer (Nova Biomedical, USA) provided results for iMg2+. The following co-variables were considered: age, comorbidities, kidney disease, KT history, estimated glomerular filtration rate (eGFR), and treatment (including Mg2+ supplementation and immunosuppression). Results: A total of 208 measurements in 104 patients were performed [once in 9/104 patients (8.7%), twice in 86/104 (82.7%), and three times in 9/104 (8.7%)]. Compared to that in healthy volunteers (51 measurements in 51 participants), mean iMg2+ was significantly lower in KT patients {KT: 0.46 mmol/L [interquartile range (IQR): 0.40-0.50], volunteers: 0.57 mmol/L (IQR 0.54-0.61), p < 0.01}. Overall, iMg2+ and tMg2+ showed strong category agreement (r2 = 0.93, p < 0.01). In linear regression, low iMg2+ correlated with CNI exposure. For 110/208 measurements (52.9%), a reduced iMg2+ (cutoff: 0.42 mmol/L) was shown. In 58/208 (27.9%), both values were reduced, and 52/208 (25%) had isolated reduced iMg2+. In principal component analysis, patients with isolated low iMg2+ clustered with patients with low iMg2+ and tMg2+. Conclusion: iMg2+ and tMg2+ were strongly correlated. A substantial proportion of patients show isolated low iMg2+. Currently, it is unclear if these patients suffer from Mg2+ deficiency.

In vivo and in vitro relationship between ionized magnesium and ionized calcium.

OBJECTIVES: The objective of this study was to determine the in vivo correlation of ionized magnesium (iMg) with ionized calcium (iCa), total calcium, albumin and pH. In addition, the analytical interference of iCa on iMg measurement on the Stat Profile Prime Plus (Nova Biomedical) and vice versa was defined. METHODS: In vivo correlation of iCa, iMg and pH was studied in 238 paired blood gas samples of 109 different patients admitted to the intensive care unit. Albumin and total magnesium (tMg) were measured in heparinized plasma samples. Measurement of iMg was performed with the ion selective magnesium electrode (ISE) of the Stat Profile Prime Plus (Nova Biomedical) and iCa and pH were measured with a Rapid Point 500 blood gas analyzer (Siemens). Albumin, total calcium and total magnesium were analyzed with a Siemens Atellica CH. Analytical interference of iCa with iMg and vice versa was investigated using unbuffered saline solutions. RESULTS: In the studied patient population, no significant correlations were observed between iMg and iCa, albumin, and pH. An inverse relationship was observed between iCa and Mg-ISE. For every 0.1 mmol/L change in iCa concentration, the iMg concentration deviated by 0.01 mmol/L at an iMg concentration of 0.5 mmol/L and by 0.013 mmol/L at an iMg concentration of 1.0 mmol/L. The measurement of iCa was not affected by iMg. CONCLUSIONS: In vivo, no correlation was observed between iMg with iCa, albumin and pH. Interference of iCa on iMg measurement was noted, with a maximum deviation of ±0.02 mmol/L iMg across the reference range of iCa (1.15-1.32 mmol/L). Additionally, the iCa measurement was not affected by the iMg concentration.

Ionized Magnesium: Interpretation and Interest in Atrial Fibrillation.

BACKGROUND: Magnesium (Mg) is often used to manage de novo atrial fibrillation (AF) in the emergency department (ED) and intensive care unit (ICU). Point of care measurement of ionized magnesium (iMg) allows a rapid identification of patients with impaired magnesium status, however, unlike ionized calcium, the interpretation of iMg is not entirely understood. Thus, we evaluated iMg reference values, correlation between iMg and plasmatic magnesium (pMg), and the impact of pH and albumin variations on iMg levels. Secondary objectives were to assess the incidence of hypomagnesemia in de novo AF. METHODS: A total of 236 emergency department and intensive care unit patients with de novo AF, and 198 control patients were included. Reference values were determined in the control population. Correlation and concordance between iMg and pMg were studied using calcium (ionized and plasmatic) as a control in the whole study population. The impact of albumin and pH was assessed in the discordant iMg and pMg values. Lastly, we assessed the incidence of ionized hypomagnesemia (hypoMg) among de novo AF. RESULTS: The reference range values established in our study for iMg were: 0.48-0.65 mmol/L (the manufacturers were: 0.45-0.60 mmol/L). A strong correlation was observed between pMg and iMg (r = 0.85), but, unlike for calcium values, there was no significant impact of pH and albumin in iMg/pMg interpretation. The incidence of hypoMg among de novo AF patients was 8.5% (12.7% using our ranges). When using our ranges, we found a significant link (p = 0.01) between hyopMg and hypokalemia. CONCLUSION: We highlight the need for more accurate reference range values of iMg. Furthermore, our results suggest that blood Mg content is not identical to that of calcium. The incidence of ionized hypomagnesemia among de novo AF patients in our study is 8.5%.

Plasma ionized calcium and magnesium concentrations and prevalence of subclinical hypocalcemia and hypomagnesemia in postpartum grazing Holstein cows from southern Chile.

The objective was to determine the plasma concentrations of ionized Ca (iCa) and Mg (iMg) and to establish the prevalence of subclinical hypocalcemia (SCHC) and hypomagnesemia (SCHM) in dairy cows at calving (within 6 hours of parturition) and at 7 days postpartum (pp) in Chilean grazing herds with spring parturitions. Plasma iCa and iMg were assessed using a clinical analyzer. A total of 113 and 175 cows in 18 herds selected at random were sampled at calving and at 7 days pp, respectively. From these 18 herds, 11 herds provided reliable records of lactation number and 8 cows per herd were scored for body condition and sampled at calving and then at 7 days pp. Ionized Ca concentrations for the 18 herds were 0.99 ± 0.16 mmol/L (calving) and 1.01 ± 0.13 mmol/L [7 d pp (P > 0.05)]. Ionized Mg concentrations were 0.58 ± 0.12 mmol/L and 0.51 ± 0.09 mmol/L (P ≤ 0.05). For the 11 herds, iCa concentrations at calving were 1.06 mmol/L (lactation 1), 1.02 mmol/L (lactation 2) and 0.89 mmol/L (lactation ≥ 3), while iMg concentrations were 0.63 mmol/L, 0.60 mmol/L, and 0.61 mmol/L, respectively. Herd prevalence for SCHC (iCa < 1.0 mmol/L) at calving was 64.8%. Prevalence by parity was 40%, 54.5% and 86.7% for lactations 1, 2 and ≥ 3, respectively. Herd prevalence of SCHC on day 7 pp was 30.1%. For SCHM (iMg < 0.52 mmol/L) prevalence was 21.6% and 48.9% at calving and at 7 days pp, respectively.

The Stability of Analytes of Ionized Magnesium Concentration and Its Reference Range in Healthy Volunteers.

This study aimed to determine the stability of refrigerated analytes of iMg concentration at different time intervals and to establish iMg reference range in a cohort of healthy Omani volunteers (≥18 years). The concentrations of iMg were measured using the direct ion-selective electrode technique. Pearson's and Lin's concordance correlation coefficients along with the Bland-Altman plot were used to assess the levels of agreement between iMg concentrations of fresh and refrigerated blood samples at different time intervals. The study included 167 volunteers (51% females) with a median age of 21 (range: 20-25) years. The median, 2.5th, and 97.5th percentiles for fresh iMg reference ranges were 0.55, 0.47, and 0.68 mmol/L, respectively. The overall agreement between the fresh and refrigerated iMg concentrations was poor (rho-c = 0.51; p < 0.001). However, according to Altman's definition, iMg concentrations of the refrigerated samples for a period of ≤1 h had an excellent correlation with the fresh iMg concentrations (Lin's rho-c = 0.80), with a small average bias difference of 0.009 (95%CI; -0.025-0.043). A cut-off refrigeration period within ≤1 h at 2-8 °C can be considered an alternate time frame for the gold standard measurement (fresh or within 0.5 h).

Relationship between short-term self-reported dietary magnesium intake and whole blood ionized magnesium (iMg2+) or serum magnesium (s-Mg) concentrations.

OBJECTIVE: Since we and others have shown that supplemental magnesium raises whole blood ionized magnesium (iMg2+) we investigated the relationships between self-reported dietary magnesium intake and concentrations of whole blood iMg2+ and serum magnesium (s-Mg). METHODS: We obtained whole blood iMg2+ concentrations, as well as s-Mg concentrations, from a pilot, three-arm, randomized, controlled, crossover bioavailability study of magnesium supplements (n = 23; 105 measures). Dietary magnesium intake was assessed using three-day food records and the Nutrition Data System for Research (NDSR, University of Minnesota, MN, USA). Whole blood iMg2+ was measured with an electrode analyser (NOVA Biochemical, Waltham, MA, USA), whereas s-Mg was measured using atomic absorption spectroscopy. A linear mixed-effects model was employed with dietary magnesium as the outcome variable and iMg2+, s-Mg, study treatment and study visit as fixed effects. We adjusted age, gender, race and body mass index covariates. RESULTS: Values for dietary magnesium, iMg2+ and s-Mg were 303.8 ± 118.9 mg/day, 1.3 ± 0.1 mg/dL and 2.2 ± 4.1 mg/dL, respectively. No association was found between dietary magnesium intake and iMg2+ -125 ± 176.95 (p = .49) or s-Mg -9.33 ± 5.04 (p = .08). CONCLUSIONS: Whole blood iMg2+ and s-Mg concentrations do not reflect short-term self-reported dietary intake in adults. Further research is needed to determine whether blood biomarkers of magnesium may reflect dietary magnesium intake.Key messagesDietary intake of magnesium, a shortfall nutrient, may be objectively measured using blood biomarkers of magnesium.Serum magnesium and whole blood iMg2+ were not associated with short-term dietary intake of magnesium.

Sample stability and heparin interference in ionized calcium and ionized magnesium measurements in horses using the Stat Profile Prime Plus co-oximetry electrolyte analyzer.

BACKGROUND: The determination of iCa and iMg is important in veterinary medicine, but their immediate determination in whole blood is not always possible. Their stability in other sample types and the existence of interferences must be evaluated before its use. OBJECTIVES: We aimed to analyze the effects of storage time on the stability of iCa, iMg, and other analytes in whole blood, plasma, and serum samples in horses and assess the interference of heparin in these measurements. METHODS: Whole blood, heparin-plasma, and serum samples from 10 horses were stored at 4°C and analyzed 1, 2, 3, 4, 5, 6, 7, 8, 24, 48, and 168 hours after sample collection using the Stat Profile Prime Plus Vet equipment (Nova Biomedical, Waltham, MA, USA). Results were analyzed by ANOVA or mixed-effect models. RESULTS: The concentration of iCa, iMg, total calcium (tCa), total magnesium (tMg), and the ratios iCa/tCa and iMg/tMg did not differ up to 168 hours when compared to the initial time. Total Ca, iMg, and tMg were not significantly different among sample types, but iCa concentrations were slightly but significantly lower in plasma. Freezing at -20°C did not affect iCa, iMg, tCa, and tMg. The pH increased in serum and plasma after 8 hours, and a mild negative correlation existed between plasma iCa concentration and pH. A negative correlation was observed also between the ratios iCa/tCa or iMg/tMg and pH in plasma and serum. A significant decrease in iCa and iMg was detected when comparing homemade syringes at high heparin concentration (~200-300 U heparin/mL) and commercial lithium-heparin tubes (20-30 U/mL). CONCLUSIONS: Samples stored at 4°C can be used to determine iCa and iMg concentrations up to 7 days after collection. Other metabolites are stable for up to 8 hours; heparin interference should be taken into account if using homemade heparin syringes.

Incidence of ionized hypomagnesemia in adult patients undergoing noncardiac major surgery: a prospective observational trial

Background: The present study aimed to investigate the incidence of preoperative ionized hypomagnesemia and compare with that of total hypomagnesemia. Methods: This prospective observational study included 536 patients aged >20 years who were scheduled for elective surgery. Total and ionized magnesium levels were evaluated before and after the surgery. Based on these levels, patients were classified into the following groups: ionized hypo- (<0.42 mmol/L), normo- (0.42-0.59 mmol/L) and hypermagnesemia (>0.59 mmol/L), as well as total hypo- (<1.9 mg/dL[0.78 mmol/L]), normo- (1.9-2.7 mg/dL[0.78-1.11 mmol/L]) and hypermagnesemia (>2.7 mg/dL [1.11 mmol/L]). The primary objective was to establish the incidence of preoperative ionized hypomagnesemia. Results: There was a marked difference between the incidence of preoperative ionized and total hypomagnesemia (28% vs. 19%; p<0.001). The postoperative values of ionized magnesium, ionized calcium, and albumin were significantly lower than the respective preoperative values (p<0.001 for all three variables). Conclusion: The incidence of hypomagnesemia, determined by ionized magnesium concentration, was higher than that determined by total magnesium concentration.

Nuclear Magnetic Resonance-Measured Ionized Magnesium Is Inversely Associated with Type 2 Diabetes in the Insulin Resistance Atherosclerosis Study.

The aims were to optimize a nuclear magnetic resonance (NMR)-based assay for quantifying ionized or free magnesium and investigate its association with type 2 diabetes (T2D). A high-throughput, ionized magnesium assay was optimized and evaluated. Plasma magnesium was quantified, and associations with T2D were ascertained in Insulin Resistance Atherosclerosis Study (IRAS) participants. Coefficients of variation for the ionized magnesium assay ranged from 0.7−1.5% for intra-assay and 4.2−4.7% for inter-assay precision. In IRAS (n = 1342), ionized magnesium was significantly lower in subjects with prediabetes and T2D than in normoglycemic subjects, and lower in participants with T2D than those with prediabetes (p < 0.0001). Cross-sectional regression analyses revealed that magnesium was associated with T2D at baseline in models adjusted for multiple clinical risk factors (p = 0.032). This association appeared to be modified by sex, in such a way that the associations were present in women (OR = 0.54 (95% CI 0.37−0.79), p = 0.0015) and not in men (OR = 0.98 (95% CI 0.71−1.35), p = 0.90). Longitudinal regression analyses revealed an inverse association between magnesium and future T2D in the total population (p = 0.035) that was attenuated by LP-IR (p = 0.22). No interactions were detected between magnesium and age, race, BMI, glucose, insulin, triglycerides, or LPIR for the prospective association with future T2D. However, a significant interaction between magnesium and sex was present, now with a trend for an association in men (OR = 0.75 (95% CI 0.55−1.02), p = 0.065 and absence of an association in women (OR = 1.01 (0.76−1.33), p = 0.97). Conclusions: lower ionized magnesium, as measured by an NMR-based assay optimized for accuracy and precision, was associated cross-sectionally with T2D at baseline and longitudinally with incident T2D in IRAS.

Correlation of Ionized Magnesium with the Parameters of Oxidative Stress as Potential Biomarkers in Patients with Anxiety and Depression: A Pilot Study.

Background: Magnesium (Mg) is the second most abundant intracellular cation. Ionized Mg is the only active form of Mg. The concentration of ionized Mg could be a potentially novel biomarker for anxiety and depression. Aim: The aim of this study was to assess the serum concentration of ionized Mg and its correlation with biomarkers of oxidative stress and inflammation in patients with anxiety and depression. Methods: In this study included 93 respondents were divided into 3 groups: C (control group-18 respondents); A (patients with anxiety disorder, dissociative/conversion disorders and somatoform disorders-36 patients); D (patients with depression-39 patients). Clinical diagnosis was based on ICD-10 criteria. Blood samples were used for standard laboratory analysis, ionized Mg analysis, oxidative stress, and inflammatory parameters. Results: Statistical significance was recorded between healthy volunteers and patients (anxiety/depression) in ionized Mg values. In anxious patients, malondialdehyde (MDA) had a positive correlation between the parameters of oxidative stress with ionized Mg. In depressive patients, MDA had a positive correlation, and glutathione peroxidase 1 (GPX1) a negative correlation with the concentration of ionized Mg. Conclusion: Ionized Mg and its correlation with parameters of oxidative stress could be potential biomarkers in anxious and depressive patients.