Dietary magnesium restriction affects hematopoiesis and triggers neutrophilia by increasing STAT-3 expression and G-CSF production.

BACKGROUND & AIMS: Magnesium (Mg2+) is able to modulate the differentiation and proliferation of cells. Mg2+ restriction can trigger neutrophilia, but the processes that result in this change have yet to be investigated and are not fully understood. Hematopoiesis is a complex process that is regulated by many factors, including cytokines and growth factors, and is strongly influenced by nutrient availability. In this context, our objective was to investigate the impact of the short-term restriction of dietary Mg2+ on bone marrow hematopoietic and peripheral blood cells, especially in processes related to granulocyte differentiation and proliferation. METHODS: Male C57BL/6 mice were fed a Mg2+ restricted diet (50 mg Mg2+/kg diet) for 4 weeks. Cell blood count and bone marrow cell count were evaluated. Bone marrow cells were also characterized by flow cytometry. Gene expression and cytokine production were evaluated, and a colony-forming cell assay related to granulocyte differentiation and proliferation was performed. RESULTS: Short-term dietary restriction of Mg2+ resulted in peripheral neutrophilia associated with an increased number of granulocytic precursors in the bone marrow. Additionally, Mg2+ restriction resulted in an increased number of granulocytic colonies formed in vitro. Moreover, the Mg2+ restricted group showed increased expression of CSF3 and CEBPα genes as well as increased production of G-CSF in association with increased expression of STAT3 protein. CONCLUSION: Short-term dietary restriction of Mg2+ induces granulopoiesis by increasing G-CSF production and activating the CEBPα and STAT-3 pathways, resulting in neutrophilia in peripheral blood.

Hypomagnesemia and its relation with chronic low-grade inflammation in obesity.

INTRODUCTION:: The accumulation of visceral fat in obesity is associated with excessive production of proinflammatory adipokines, which contributes to low-grade chronic inflammation state. Moreover, the literature has shown that mineral deficiency, in particular of magnesium, has important role in the pathogenesis of this metabolic disorder with relevant clinical repercussions. OBJECTIVE:: To bring updated information about the participation of hypomagnesemia in the manifestation of low-grade chronic inflammation in obese individuals. METHOD:: Articles published in PubMed, SciELO, LILACS and ScienceDirect, using the following keywords: "obesity," "magnesium" and "low grade inflammation." RESULTS:: Scientific evidence suggests that magnesium deficiency favors the manifestation of low-grade chronic inflammation in obese subjects. CONCLUSION:: From literature data, it is evident the participation of magnesium through biochemical and metabolic reactions in protecting against this metabolic disorder present in obesity.

Hypomagnesemia and its relation with chronic low-grade inflammation in obesity / Hipomagnesemia e sua relação com a inflamação crônica de baixo grau na obesidade

Summary Introduction: The accumulation of visceral fat in obesity is associated with excessive production of proinflammatory adipokines, which contributes to low-grade chronic inflammation state. Moreover, the literature has shown that mineral deficiency, in particular of magnesium, has important role in the pathogenesis of this metabolic disorder with relevant clinical repercussions. Objective: To bring updated information about the participation of hypomagnesemia in the manifestation of low-grade chronic inflammation in obese individuals. Method: Articles published in PubMed, SciELO, LILACS and ScienceDirect, using the following keywords: "obesity," "magnesium" and "low grade inflammation." Results: Scientific evidence suggests that magnesium deficiency favors the manifestation of low-grade chronic inflammation in obese subjects. Conclusion: From literature data, it is evident the participation of magnesium through biochemical and metabolic reactions in protecting against this metabolic disorder present in obesity.

Resumo Introdução: O acúmulo de gordura visceral na obesidade está associado à produção excessiva de adipocinas pró-inflamatórias, o que contribui para o estado de inflamação crônica de baixo grau. A literatura também tem mostrado que a deficiência de minerais, em particular do magnésio, possui papel importante na patogênese desse distúrbio metabólico com repercussões clínicas relevantes. Objetivo: Trazer informações atualizadas sobre a participação da hipomagnesemia na inflamação crônica de baixo grau em indivíduos obesos. Método: Bases de dados Pubmed, SciELO, Lilacs e ScienceDirect, utilizando as palavras-chave: "obesity", "magnesium" e "low grade inflammation". Resultados: As evidências científicas sugerem que a deficiência de magnésio favorece a manifestação da inflamação crônica de baixo grau em indivíduos obesos. Conclusão: É evidente a participação do magnésio, por meio de reações bioquímicas e metabólicas, na proteção contra esse distúrbio metabólico presente na obesidade.

Role of Magnesium in Oxidative Stress in Individuals with Obesity.

Adipose tissue is considered an endocrine organ that promotes excessive production of reactive oxygen species when in excess, thus contributing to lipid peroxidation. Magnesium deficiency contributes to the development of oxidative stress in obese individuals, as this mineral plays a role as an antioxidant, participates as a cofactor of several enzymes, maintains cell membrane stability and mitigates the effects of oxidative stress. The objective of this review is to bring together updated information on the participation of magnesium in the oxidative stress present in obesity. We conducted a search of articles published in the PubMed, SciELO and LILACS databases, using the keywords 'magnesium', 'oxidative stress', 'malondialdehyde', 'superoxide dismutase', 'glutathione peroxidase', 'reactive oxygen species', 'inflammation' and 'obesity'. The studies show that obese subjects have low serum concentrations of magnesium, as well as high concentrations of oxidative stress marker in these individuals. Furthermore, it is evident that the adequate intake of magnesium contributes to its appropriate homeostasis in the body. Thus, this review of current research can help define the need for intervention with supplementation of this mineral for the prevention and treatment of disorders associated with this chronic disease.

Magnesium deficiency results in an increased formation of osteoclasts.

Magnesium (Mg(2+)) deficiency is a frequently occurring disorder that leads to loss of bone mass, abnormal bone growth and skeletal weakness. It is not clear whether Mg(2+) deficiency affects the formation and/or activity of osteoclasts. We evaluated the effect of Mg(2+) restriction on these parameters. Bone marrow cells from long bone and jaw of mice were seeded on plastic and on bone in medium containing different concentrations of Mg(2+) (0.8 mM which is 100% of the normal value, 0.4, 0.08 and 0 mM). The effect of Mg(2+) deficiency was evaluated on osteoclast precursors for their viability after 3 days and proliferation rate after 3 and 6 days, as was mRNA expression of osteoclastogenesis-related genes and Mg(2+)-related genes. After 6 days of incubation, the number of tartrate resistant acid phosphatase-positive (TRACP(+)) multinucleated cells was determined, and the TRACP activity of the medium was measured. Osteoclastic activity was assessed at 8 days by resorption pit analysis. Mg(2+) deficiency resulted in increased numbers of osteoclast-like cells, a phenomenon found for both types of marrow. Mg(2+) deficiency had no effect on cell viability and proliferation. Increased osteoclastogenesis due to Mg(2+) deficiency was reflected in higher expression of osteoclast-related genes. However, resorption per osteoclast and TRACP activity were lower in the absence of Mg(2+). In conclusion, Mg(2+) deficiency augmented osteoclastogenesis but appeared to inhibit the activity of these cells. Together, our in vitro data suggest that altered osteoclast numbers and activity may contribute to the skeletal phenotype as seen in Mg(2+) deficient patients.

Calcium and magnesium status is not impaired in pregnant women.

Deficiencies in calcium (Ca) and magnesium (Mg) are associated with various complications during pregnancy. To test the hypothesis that the status of these minerals is inadequate in pregnancy, a cross-sectional study was conducted of the dietary intake and status of Ca and Mg in pregnant women (n = 50) attending a general public university hospital in Brazil. Dietary intake was assessed from 4-day food records; levels of plasma Mg, erythrocyte Mg, and urinary Ca and Mg excretion were determined by flame atomic absorption spectroscopy; and type I collagen C-telopeptides were evaluated by enzyme-linked immunosorbent assay. Probabilities of inadequate Ca and Mg intake were exhibited by 58 and 98% of the study population, respectively. The mean levels of urinary Ca and Mg excretion were 8.55 and 3.77 mmol/L, respectively. Plasma C-telopeptides, plasma Mg, and erythrocyte Mg were within normal levels. Multiple linear regression analysis revealed positive relationships among urinary Ca excretion, Ca intake (P = .002) and urinary Mg excretion (P < .001) and between erythrocyte Mg and Mg intake (P = .023). It is concluded that the Ca and Mg status of participants was adequate even though the intake of Ca and Mg was lower than the recommended level.

Effects of magnesium intake deficiency on bone metabolism and bone tissue around osseointegrated implants.

OBJECTIVES: This study evaluated the effect of magnesium dietary deficiency on bone metabolism and bone tissue around implants with established osseointegration. MATERIALS AND METHODS: For this, 30 rats received an implant in the right tibial metaphysis. After 60 days for healing of the implants, the animals were divided into groups according to the diet received. Control group (CTL) received a standard diet with adequate magnesium content, while test group (Mg) received the same diet except for a 90% reduction of magnesium. The animals were sacrificed after 90 days for evaluation of calcium, magnesium, osteocalcin and parathyroid hormone (PTH) serum levels and the deoxypyridinoline (DPD) level in the urine. The effect of magnesium deficiency on skeletal bone tissue was evaluated by densitometry of the lumbar vertebrae, while the effect of bone tissue around titanium implants was evaluated by radiographic measurement of cortical bone thickness and bone density. The effect on biomechanical characteristics was verified by implant removal torque testing. RESULTS: Magnesium dietary deficiency resulted in a decrease of the magnesium serum level and an increase of PTH and DPD levels (P ≤ 0.05). The Mg group also presented a loss of systemic bone mass, decreased cortical bone thickness and lower values of removal torque of the implants (P ≤ 0.01). CONCLUSIONS: The present study concluded that magnesium-deficient diet had a negative influence on bone metabolism as well as on the bone tissue around the implants.

Effect of severe dietary magnesium deficiency on systemic bone density and removal torque of osseointegrated implants.

PURPOSE: This study evaluated the effect of severe magnesium (Mg) dietary deficiency on systemic bone density and biomechanical resistance of bone tissue to the removal torque of osseointegrated implants. MATERIALS AND METHODS: The sample consisted of 45 rats; each received a titanium implant in their tibial metaphysis. After 60 days, the animals were divided into three groups (n = 15) according to their dietary Mg: the control group received the recommended content of Mg, group Mg1 received a 75% reduction in dietary Mg content, and group Mg2 was fed a diet with a 90% reduction in Mg content. Animals were sacrificed 150 days after implant placement. Serum concentrations of Mg were measured and the effect of Mg deficiency on systemic bone density was evaluated by densitometry of the lumbar vertebrae and femur. Biomechanical characteristics were measured by resistance of the bone tissue to removal of the implants. RESULTS: Lower Mg serum concentrations were found for the Mg1 and Mg2 groups; however, densitometric analysis and torque evaluations showed a statistically significant difference only in the Mg2 group (P < .05). There was a statistically significant difference in removal torque between the Mg2 group and the control group. CONCLUSIONS: This study showed that a severe deficiency of Mg decreased the systemic bone density and removal torque of osseointegrated implants.

DeficiÛncia de magnésio na resistÛncia O insulina, síndrome metabólica e diabetes mellitus / Magnesium deficiency on insulin resistance, metabolic syndrome and diabetes mellitus

Hipomagnesemia é, em geral, pouco diagnosticada na prática clínica diária. Niveis séricos normais podem ser visto mesmo na presenþa de grave depleþÒo (deplecion) intracelular. O magnésio é importante cofator (cofactor) metálico de mais de 300 reaþ§es enzimáticas, incluindo aquela de tirosina-cinase, na sub-unidade beta do receptor de insulina, fundamental para la sinalizaþÒo (señalización) intra-celular deste horm¶nio (hormona). Uma importante reduþÒo dos niveis de magnésio em paciente com diabetes mellitus, resistÛncia Ô insulina , hipertensÒo arterial e síndrome metabólica (SM). Entretanto, permanece controverso (controvertido) o potencial de benefício da reposiþÒo deste ion (ión) em pacientes com estas patologias. Este artigo revisa os principais trabalhos publicados relacionando os temas: magnésio, resistÛncia insulínica diabetes mellitus e síndrome metabólica, além (además) de tratar de dados ainda (datos todavía) nÒo publicados sobre a prevalÛncia de hipomagnesemia e deficiÛncia intra-celular do ion em pacientes com SM.(AU)

Deficiência de magnésio na resistência à insulina, síndrome metabólica e diabetes mellitus / Magnesium deficiency on insulin resistance, metabolic syndrome and diabetes mellitus

Hipomagnesemia é, em geral, pouco diagnosticada na prática clínica diária. Niveis séricos normais podem ser visto mesmo na presença de grave depleção (deplecion) intracelular. O magnésio é importante cofator (cofactor) metálico de mais de 300 reações enzimáticas, incluindo aquela de tirosina-cinase, na sub-unidade beta do receptor de insulina, fundamental para la sinalização (señalización) intra-celular deste hormônio (hormona). Uma importante redução dos niveis de magnésio em paciente com diabetes mellitus, resistência â insulina , hipertensão arterial e síndrome metabólica (SM). Entretanto, permanece controverso (controvertido) o potencial de benefício da reposição deste ion (ión) em pacientes com estas patologias. Este artigo revisa os principais trabalhos publicados relacionando os temas: magnésio, resistência insulínica diabetes mellitus e síndrome metabólica, além (además) de tratar de dados ainda (datos todavía) não publicados sobre a prevalência de hipomagnesemia e deficiência intra-celular do ion em pacientes com SM.

Deficiência de magnésio e resistência à insulina em pacientes com diabetes mellitus tipo 2 / Magnesium deficiency and insulin resistance in patients with type 2 diabetes mellitus

O magnésio é um íon predominantemente intra-celular, que participa como co-fator de mais de 300 reações enzimáticas, dentre elas na atividade da tirosino-cinase. Sua deficiência pode aumentar a resistência periférica à insulina, especialmente em pacientes com síndrome metabólica e diabetes mellitus tipo 2 (DM2). Este trabalho avaliou, em 27 pacientes com DM2 descompensado, o conteúdo intra-celular de magnésio, correlacionando-o com índices laboratoriais de resistência insulínica e controle glicêmico. Hipomagnesemia foi encontrada em 75 por cento dos pacientes e déficit intra-celular em 30,8 por cento. Houve correlação negativa do Mg intra-celular (Mg IC) com HbA1 e com IMC. 59,2 por cento dos pacientes apresentaram HOMA IR > 3,5, e tendência para correlação negativa com o Mg IC, porém sem significância estatística. Apesar do número pequeno de pacientes, ressalta-se que uma vez que deficiência de magnésio é comum em pacientes com diabetes, sua relação com resistência insulínica deve ser mais estudada.

[Magnesium deficiency and insulin resistance in patients with type 2 diabetes mellitus]. / Deficiência de magnésio e resistência à insulina em pacientes com diabetes mellitus tipo 2.

Magnesium is a predominantly intracellular ion, and it is a cofactor in more than 300 enzymatic reactions, like tyrosinokinase activity. Its deficiency may increase insulin resistance, especially in patients with metabolic syndrome or type 2 diabetes. This study evaluated in 27 patients with poorly controlled type 2 diabetes if there was correlation between intracellular magnesium levels, laboratorial indexes of insulin resistance and glycemic control. Decreased serum and intracellular magnesium depletion were found in 75% and 30.8% of patients, respectively. A negative correlation between intracellular magnesium levels (ICMg) and BMI and HbA1 was found. The homeostasis model assessment for insulin resistance (HOMA-IR) was higher than 3.0 in 59.2% of patients and there was a tendency to negative correlation with ICMg levels, although without statistical significance. Despite the small number of patients, this study shows that magnesium deficiency is frequent in patients with diabetes and its correlation with insulin resistance should be more studied.

Relación entre las principales alteraciones metabólicas con las cardiovasculares durante el trasplante hepático / Relationship between the main metabolic and cardiovascular alterations during liver transplantation

El principal objetivo fue describir la evolución de las concentraciones de calcio iónico sanguíneo (Ca2+), potasio sanguíneo (K+) y magnesio iónico sérico (Mg2+); y su relación con las alteraciones cardiovasculares durante el trasplante ortotópico de hígado (TOH). Se estudiaron 92 pacientes adultos tratados con TOH. Se encontró una correlación inversa entre las concentraciones Mg2+ y citrato para todos los pacientes. El Mg2+ al igual que el Ca2+, es quelado por el citrato y su evolución es una imagen especular a la del citrato. En estos pacientes, no se observó ninguna disritmia que pueda ser atribuida directamente a la hipomagnesemia iónica. En conclusión, los bajos niveles preoperatorios, junto con las trasfusiones masivas de hemoderivados y el incremento de las pérdidas renales, provocan una progresiva hipomagnesemia iónica en los pacientes tratados con TOH. Se propone que la concentración de Mg2+ sea monitorizada y eventualmente tratada, al igual como se realiza con el Ca2+ y el K=

Relación entre las principales alteraciones metabólicas con las cardiovasculares durante el trasplante hepático / Relationship between the main metabolic and cardiovascular alterations during liver transplantation

El principal objetivo fue describir la evolución de las concentraciones de calcio iónico sanguíneo (Ca2+), potasio sanguíneo (K+) y magnesio iónico sérico (Mg2+); y su relación con las alteraciones cardiovasculares durante el trasplante ortotópico de hígado (TOH). Se estudiaron 92 pacientes adultos tratados con TOH. Se encontró una correlación inversa entre las concentraciones Mg2+ y citrato para todos los pacientes. El Mg2+ al igual que el Ca2+, es quelado por el citrato y su evolución es una imagen especular a la del citrato. En estos pacientes, no se observó ninguna disritmia que pueda ser atribuida directamente a la hipomagnesemia iónica. En conclusión, los bajos niveles preoperatorios, junto con las trasfusiones masivas de hemoderivados y el incremento de las pérdidas renales, provocan una progresiva hipomagnesemia iónica en los pacientes tratados con TOH. Se propone que la concentración de Mg2+ sea monitorizada y eventualmente tratada, al igual como se realiza con el Ca2+ y el K= (AU)

Hipomagnesemia y su relación con trastornos del ritmo cardíaco

La infusión de sales de magnesio ha sido eficaz para la supresión de algunos trastornos del ritmo cardíaco, por lo cual se ha involucrado la hipomagnesemia en la génesis de los mismos. Nosotros investigamosla presencia de arritmias cardíacas recurrentes y sostenidas en un grupo de 27 pacientes sometidos a cirugía cardíaca bajo circulación extracorpórea, modelo clínico óptimo para producir hipomagnesemia. Aunque observamos una disminución significativa en la concentración sérica del ion, incluso hasta las 48 horas del postoperatorio, en ningún caso encontramos trastornos del ritmo atribuibles a este estado. El efecto anticálcico del magnesio puede ser responsable de manera indirecta del supuesto efecto antiarrítmico de este catión