Magnesium supplementation alleviates premenstrual symptoms of fluid retention

We investigated the effect of a daily supplement of 200 mg of magnesium (as MgO) for two menstrual cycles on the severity of premenstrual symptoms in a randomized, double-blind, placebo-controlled, crossover study. A daily supplement of 200 mg of Mg (as MgO) or placebo was administered for two menstrual cycles to each volunteer, who kept a daily record of her symptoms, using a 4-point scale in a menstrual diary of 22 items. Symptoms were grouped into six categories: PMS-A (anxiety), PMS-C (craving), PMS-D (depression), PMS-H (hydration), PMS-O (other), and PMS-T (total overall symptoms). Urinary Mg output/24 hours was estimated from spot samples using the Mg/creatinine ratio. Analysis of variance for 38 women showed no effect of Mg supplementation compared with placebo in any category in the first month of supplementation. In the second month there was a greater reduction (p = 0.009) of symptoms of PMS-H (weight gain, swelling of extremities, breast tenderness, abdominal bloating) with Mg supplementation compared with placebo. Compliance to supplementation was confirmed by the greater mean estimated 24-hour urinary output of Mg (p = 0.013) during Mg supplementation (100.8 mg) compared with placebo (74.1 mg). A daily supplement of 200 mg of Mg (as MgO) reduced mild premenstrual symptoms of fluid retention in the second cycle of administration.

Factors Associated With Changes in Magnesium Levels in Asymptomatic Neonates: A Longitudinal Analysis

Background: Neonates and infants with hypomagnesemia present with seizures and psychomotor delay. Objectives: The present study evaluated the changes in magnesium (Mg) levels and factors associated with these in the first three days of life. Materials and Methods: We monitored 50 clinically asymptomatic neonates; they were not given any magnesium supplements even if they had hypomagnesemia at baseline. The variables analysed were: serum Mg; gestational age; birth weight; length; and the ponderal index. We used random effects (RE) models for longitudinal analysis of these data. Results: The mean standard deviation (SD) gestational age was 36.3 (3.6) weeks and the mean (SD) weight was 2604.2 (754.4) grams. About 31% of the neonates had hypomagnesemia (< 1.6 mg/dL) on day one; however, all had normal magnesium levels by day three of life (P < 0.001). At birth, after adjusting for intrauterine growth retardation status (IUGR), serum Mg levels were lower by 0.0097 mg/dL (95% CI: -0.019 to -0.0003) per 100 grams increase in weight of the neonate. After adjusting for IUGR status, the mean increase in the serum Mg levels was 0.14 mg/dL (95% confidence intervals [CI]: 0.10 to 0.18) per day. The per-day increase in magnesium levels was significantly higher in low birth weight babies (0.10, 95% CI: 0.01 to 0.18) compared with normal birth weight babies. Conclusions: Asymptomatic neonates may have a high prevalence of hypomagnesemia; however, the levels become normal without any magnesium supplementation. Even though regular monitoring of magnesium levels is useful, no supplements are required - particularly in clinically asymptomatic neonates.

Safety and Efficacy of Intravenous Colistin in Neonates With Culture Proven Sepsis

Background: Although it is well described among adults, intravenous colistin use and its associated toxicities in newborns are poorly understood. Objectives: We present our experience of efficacy and safety of intravenous colistin in the treatment of sepsis in term and preterm neonates. Patients and Methods: The records of neonates who received colistin between January 2013 and February 2014 were retrospectively reviewed. All neonates with culture proven nosocomial infections due to multidrug resistant organisms and treated continuously with colistin for more than 72 hours were included in the study. Results: Patients were evaluated for clinical and microbiological response to the drug and its and side effects. Twelve newborn infants with mean 31.8 ± 3.5 weeks gestational age and median 1482 (810 - 3200) gram birth weight were included. 11/12 (91.7%) patients showed microbiological clearance with intravenous colistin. One patient who had recurrent cerebrospinal fluid positive culture was treated with intraventricular colistin. The major side effects observed was hyponatremia and hypokalemia in 2 (16.6%) patients, all infants required magnesium supplementation. Conclusions: Intravenous colistin administration appears to be safe and efficacious for multidrug-resistant gram-negative infections in neonates, including preterm infants. However, we believe that large prospective controlled studies are needed to confirm its efficacy and safety in neonates.

Magnesium in cystic fibrosis - Systematic review of the literature

BACKGROUND The metabolism of sodium, potassium, and chloride and the acid-base balance are sometimes altered in cystic fibrosis. Textbooks and reviews only marginally address the homeostasis of magnesium in cystic fibrosis. METHODS We performed a search of the Medical Subject Headings terms (cystic fibrosis OR mucoviscidosis) AND (magnesium OR hypomagnes[a]emia) in the US National Library of Medicine and Excerpta Medica databases. RESULTS We identified 25 reports dealing with magnesium and cystic fibrosis. The results of the review may be summarized as follows. First, hypomagnesemia affects more than half of the cystic fibrosis patients with advanced disease; second, magnesemia, which is normally age-independent, relevantly decreases with age in cystic fibrosis; third, aminoglycoside antimicrobials frequently induce both acute and chronic renal magnesium-wasting; fourth, sweat magnesium concentration was normal in cystic fibrosis patients; fifth, limited data suggest the existence of an impaired intestinal magnesium balance. Finally, stimulating observations suggest that magnesium supplements might achieve an improvement in respiratory muscle strength and mucolytic activity of both recombinant and endogenous deoxyribonuclease. CONCLUSIONS The first comprehensive review of the literature confirms that, despite being one of the most prevalent minerals in the body, the importance of magnesium in cystic fibrosis is largely overlooked. In these patients, hypomagnesemia should be sought once a year. Furthermore, the potential of supplementation with this cation deserves more attention.

Effect of magnesium sulphate and L-tryptophan and genotype on the feed intake, behaviour and meat quality of pigs

Sixty-nine entire male pigs with different halothane genotype (homozygous halothane positive – nn-, n=36; and homozygous halothane negative – NN-, n=33) were fed with a supplementation of magnesium sulphate (Mg) and/or L-tryptophan (Trp) in the diet for 5 days before slaughter. Animals were housed individually and were submitted to stressful ante mortem conditions (mixed in the lorry according to treatments and transported 1h on rough roads). Individual feed intake was recorded during the 5-day treatment. At the abattoir, pig behaviour was assessed in the raceway to the stunning system and during the stunning period by exposure to CO2. Muscle pH, colour, water holding capacity, texture and cathepsin activities were determined to assess meat quality. The number of pigs with an individual feed intake lower than 2kg/day was significantly different among diets (P<0.05; Control: 8.7%; Mg&Trp: 43.5%; Trp: 17.4%) and they were considered to have inadequate supplement intake. During the ante mortem period, 15.2% of pigs included in the experiment died, and this percentage decreased to 8.7% in those pigs with a feed intake > 2kg/day, all of them from the stress-sensitive pigs (nn). In general, no differences were observed in the behaviour of pigs along the corridor leading to the stunning system and inside the CO2 stunning system. During the stunning procedure, Trp diet showed shorter periods of muscular excitation than control and Mg&Trp diets. The combination of a stressful ante mortem treatment and Mg&Trp supplementation led to carcasses with high incidence of severe skin lesions. Different meat quality results were found when considering all pigs or considering only those with adequate supplement intake. In this later case, Trp increased pH45 (6.15) vs Control diet (5.96) in the Longissimus thoracis (LT) muscle (P<0.05) and pH at 24h (Trp: 5.59 vs C: 5.47) led to a higher incidence of dark, firm and dry (DFD) traits in SM muscle (P<0.05). Genotype affected negatively all the meat quality traits. Seventy-five percent of LT and 60.0% of the SM muscles from nn pigs were classified as pale, soft and exudative (PSE), while none of the NN pigs showed these traits (P<0.0001). No significant differences were found between genotypes on the incidence of DFD meat. Due to the negative effects observed in the Mg&Trp group in feed intake and carcass quality, the utilization of a mixture of magnesium sulphate and tryptophan is not recommended

Effect of supplementation with MgCO3 and L-tryptophan on the welfare and on the carcass and meat quality of two halothane pig genotypes (NN and nn)

Sixty-one animals with different Halothane genes (homozygous halothane positive, n=34; and homozygous halothane negative, n=27) were fed with three diets (controlgroup, with no supplement; magnesium (Mg) group with 1.28g MgCO3/kg and tryptophan (Trp) group with 5g L-Trp/kg) during the last 5 days before slaughter. Animals were submitted to minimal stress ante mortem conditions. Pig behaviour was recorded at the experimental farm, raceway to the CO2 stunning system and during the stunning period. Corneal reflexes were recorded after stunning as well. There were no differences in feed intake among diets (p>0.05) during the 5 days of treatment. The halothane positive (nn) group had lower intake than the halothane negative (NN) group (p<0.01). The behaviour of the pigs in the raceway did not differ (p>0.05) among treatments or halothane genotype. A significant (p<0.001) interaction diet*halothane was found in the time to appear the first retreat attempt during the exposure to the CO2 system. In the nn group, the time of performing the first retreat attempt was later in the Mg (p<0.05) than the Control group. Moreover, in the Mg group, the nn had a later (p<0.05) first retreat attempt than the NN. Thus, Mg supplementation could have a positive effect on welfare of nn pigs. The nn had a lower proportion of animals that showed corneal reflexes after stunning than NN, indicating a higher effectiveness of the stunning method in nn pigs. Neither Mg nor Trp affected carcass quality and meat quality parameters, although significant differences were found between genotypes

Rosiglitazone prevents sirolimus-induced hypomagnesemia, hypokalemia, and downregulation of NKCC2 protein expression

Alexandre CS, Braganca AC, Shimizu MH, Sanches TR, Fortes MA, Giorgi RR, Andrade L, Seguro AC. Rosiglitazone prevents sirolimus-induced hypomagnesemia, hypokalemia, and downregulation of NKCC2 protein expression. Am J Physiol Renal Physiol 297: F916-F922, 2009. First published August 5, 2009; doi:10.1152/ajprenal.90256.2008.-Sirolimus, an antiproliferative immunosuppressant, induces hypomagnesemia and hypokalemia. Rosiglitazone activates renal sodiumand water-reabsorptive pathways. We evaluated whether sirolimus induces renal wasting of magnesium and potassium, attempting to identify the tubule segments in which this occurs. We tested the hypothesis that reduced expression of the cotransporter NKCC2 forms the molecular basis of this effect and evaluated the possible association between increased urinary excretion of magnesium and renal expression of the epithelial Mg(2+) channel TRPM6. We then analyzed whether rosiglitazone attenuates these sirolimus-induced tubular effects. Wistar rats were treated for 14 days with sirolimus (3 mg/kg body wt in drinking water), with or without rosiglitazone (92 mg/kg body wt in food). Protein abundance of NKCC2, aquaporin2 (AQP2), and TRPM6 was assessed using immunoblotting. Sirolimus-treated animals presented no change in glomerular filtration rate, although there were marked decreases in plasma potassium and magnesium. Sirolimus treatment reduced expression of NKCC2, and this was accompanied by greater urinary excretion of sodium, potassium, and magnesium. In sirolimus-treated animals, AQP2 expression was reduced. Expression of TRPM6 was increased, which might represent a direct stimulatory effect of sirolimus or a compensatory response. The finding that rosiglitazone prevented or attenuated all sirolimus-induced renal tubular defects has potential clinical implications.

Supplementation of soft drinks with metallic ions reduces dissolution of bovine enamel

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Inorganic and organic trace mineral supplementation in weanling pig diets

A study was conducted to evaluate the s of dietary inorganic and organic trace minerals in two levels of supplementation regarding performance, diarrhea occurrence, hematological parameters, fecal mineral excretion and mineral retention in metacarpals and liver of weanling pigs. Seventy piglets weaned at 21 days of age with an average initial body weight of 6.70 ± 0.38 kg were allotted in five treatments: control diet (no added trace mineral premix); 50% ITMP (control diet with inorganic trace mineral premix supplying only 50% of trace mineral requirements); 50% OTMP (control diet with organic trace mineral premix supplying only 50% of trace mineral requirements); 100% ITMP (control diet with inorganic trace mineral premix supplying 100% of trace mineral requirements); and 100% OTMP (control diet with organic trace mineral premix supplying 100% of trace mineral requirements). Feed intake and daily weight gain were not affected by treatments, however, piglets supplemented by trace minerals presented better gain:feed ratio. No differences were observed at calcium, phosphorus, potassium, magnesium, sodium and sulfur excreted in feces per kilogram of feed intake. Treatments did not affect calcium, phosphorus, magnesium, sulfur and iron content in metacarpals. Trace mineral supplementation, regardless of level and source, improved the performance of piglets.

High Cholesterol Feeding May Induce Tubular Dysfunction Resulting in Hypomagnesemia

Background/Aims: Hypomagnesemia may induce hypercholesterolemia, but the contrary has not been described yet. Thus, magnesium homeostasis was evaluated in rats fed a cholesterol-enriched diet for 8 days. This study has a relevant clinical application if hypomagnesemia, due to hypercholesterolemia, is confirmed in patients with long-term hypercholesterolemia. Methods: Both hypercholesterolemic (HC) and normocholesterolemic rats (NC) were divided into sets of experiments to measure hemodynamic parameters, physiological data, maximum capacity to dilute urine (C-H2O), variations (Delta) in [Ca2+](i) and the expression of transporter proteins. Results: HC developed hypomagnesemia and showed high magnesuria in the absence of hemodynamic abnormalities. However, the urinary sodium excretion and C-H2O in HC was similar to NC. On the other hand, the responses to angiotensin II by measuring Delta [Ca2+](i) were higher in the thick ascending limb of Henle's loop (TAL) of HC than NC. Moreover, high expression of the cotransporter NKCC2 was found in renal outer medulla fractions of HC. Taken together, the hypothesis of impairment in TAL was excluded. Actually, the expression of the epithelial Mg2+ channel in renal cortical membrane fractions was reduced in HC. Conclusion: Impairment in distal convoluted tubule induced by hypercholesterolemia explains high magnesuria and hypomagnesemia observed in HC. Copyright (C) 2011 S. Karger AG, Basel

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 +/- 8.3 years old, FEV1: 49.3 +/- 19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

Successful Improvement of Frequency and Symptoms of Premature Complexes after Oral Magnesium Administration

Background: Premature ventricular and supraventricular complexes (PVC and PsVC) are frequent and often symptomatic. The magnesium (Mg) ion plays a role in the physiology of cell membranes and cardiac rhythm. Objective: We evaluated whether the administration of Mg Pidolate (MgP) in patients with PVC and PsVC is superior to placebo (P) in improving symptoms and arrhythmia frequency. Methods: Randomized double-blind study with 60 consecutive symptomatic patients with more than 240 PVC or PsVC/h on 24-hour Holter monitoring who were selected to receive placebo or MgP. To evaluate symptom improvement, a categorical and a specific questionnaire for symptoms related to PVC and PsVC was made. Improvement in premature complex density (PCD) per hour was considered significant if percentage reduction was >= 70% after treatment. The dose of MgP was 3.0 g/day for 30 days, equivalent to 260mg of Mg element. None of the patients had structural heart disease or renal failure. Results: Of the 60 patients, 33 were female (55%). Ages ranged from 16 to 70 years old. In the MgP group, 76.6% of patients had a PCD reduction >70%, 10% of them >50% and only 13.4% <50%. In the P group, 40% showed slight improvement, <30%, in the premature complexes frequency (p < 0.001). Symptom improvement was achieved in 93.3% of patients in the MgP group, compared with only 16.7% in the P group (p < 0.001). Conclusion: Oral Mg supplementation decreases PCD, resulting in symptom improvement. (Arq Bras Cardiol 2012;98(6):480-487)

Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy

Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 (V(1393)I, K(1584)E) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6(V(1393)I) and TRPM6(K(1584)E), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T(1391)) and TRPM6(S(1583)). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6(V(1393)I) and TRPM6(K(1584)E) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6(V(1393)I) and TRPM6(K(1584)E) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6.

Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement

Claudins are major components of tight junctions and contribute to the epithelial-barrier function by restricting free diffusion of solutes through the paracellular pathway. We have mapped a new locus for recessive renal magnesium loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of the claudin multigene family, in patients affected by hypomagnesemia, renal failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules and the retina. The identified mutations interfere severely with either cell-membrane trafficking or the assembly of the claudin-19 protein. The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina.

An unusual patient with hypercalciuria, recurrent nephrolithiasis, hypomagnesemia and G227R mutation of Paracellin-1. An unusual patient with hypercalciuria and hypomagnesemia unresponsive to thiazide diuretics

A 19-year-old female patient with hypercalciuria and recurrent nephrolithiasis/urinary tract infection unresponsive to thiazide type diuretics is presented. The patient first experienced nephrolithiasis at the age of 4 years. Afterwards, recurrent passages of stones and urinary tract infection occurred. On diagnostic evaluation at the age of 19 years, she also had hypocitraturia and hypomagnesemia. Her serum calcium concentrations were near the lower limit of normal (8.5-8.8 mg/dl; normal range: 8.5-10.5), her serum magnesium concentrations were 1.15-1.24 mg/dl (normal range: 1.4-2.5) and urinary calcium excretion was 900 mg/24 h. PTH concentrations were increased (110-156 pg/ml; normal range: 10-65). We tried to treat the patient with hydrochlorothiazide at a dose of 50 mg/day. During treatment with thiazide diuretics, PTH concentration remained high and the patient had recurrent urinary tract infections and passages of stones. Serum magnesium concentration did not normalize even under the parenteral magnesium infusion. Her mother had a history of nephrolithiasis 20 years ago. Severe hypomagnesemia in association with hypercalciuria/urinary stones is reported as a rare autosomal recessive disorder caused by impaired reabsorption of magnesium and calcium in the thick assending limp of Henle's loop. Recent studies showed that mutations in the CLDN16 gene encoding paracellin-1 cause the disorder. In exon 4, a homozygous nucleotide exchange (G679C) was identified for the patient. This results in a point mutation at position Glycine227, which is replaced by an Arginine residue (G227R). The mother was heterozygous for this mutation. G227 is located in the fourth transmembrane domain and is highly conserved in the claudin gene family. This case indicates the pathogenetic role of paracellin-1 mutation in familial hypomagnesemia with hypercalciuria and nephrocalcinosis and further underlines the risk of stone formation in heterozygous mutation carriers.