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Magnesium in Human Health and Disease
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Magnesium in Human Health and Disease

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (15 March 2021) | Viewed by 237875

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Sara Castiglioni

E-Mail Website
Guest Editor
Department of Biomedical and Clinical Sciences, Università di Milano, 20157 Milano, Italy
Interests: molecular and cellular biology;osteogenic and miogenic differentiation; magnesium; microgravity
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanna Farruggia

E-Mail Website
Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy
Interests: fluorescent biosensor; magnesium; cell proliferation; flow cytometry; nanoparticles
Dr. Concettina Cappadone

E-Mail Website
Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy
Interests: cancer; magnesium; MDR; cell cycle; bone; differentiation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Magnesium is an essential mineral for human health. Beside its structural role in the apatite crystals of the bones, magnesium is essential to all living cells, since it is fundamental for energy production and is a cofactor of enzymes involved in practically all metabolism. Magnesium antagonizes calcium and functions as a signal transducer asd well.

Magnesium is naturally present in many foods, including green leafy vegetables, whole grains, beans, nuts, and milk. However, in western countries, the daily dietary intake of magnesium is frequently found to be below the recommended level. This magnesium deficiency impacts cell, tissue, and organ functions, leading to many disorders including cardiovascular, neuronal, age-related, and neoplastic diseases.

Hypermagnesemia is a rare but serious electrolytic disorder, which can be fatal if not recognized and treated promptly. Hypermagnesemia occurs primarily in patients with acute or chronic kidney disease, but other pathological conditions, such as hypothyroidism and especially cortico-adrenal insufficiency, and the effect of various drugs, especially in already compromised patients, can allow the establishment of this condition.

This Special Issue entitled “Magnesium in Human Health and Disease” aims to collect high quality up-to-date original and review articles on the role of magnesium in human pathophysiologic conditions.

Dr. Sara Castiglioni
Prof. Giovanna Farruggia
Dr. Concettina Cappadone
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • magnesium homeostasis
  • magnesium transporters
  • magnesium channels
  • cardiovascular diseases
  • chronic diseases
  • age-related diseases
  • cancer

Published Papers (21 papers)

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Editorial

Jump to: Research, Review

4 pages, 195 KiB  
Editorial
Editorial of Special Issue “Magnesium in Human Health and Disease”
by Sara Castiglioni
Nutrients 2021, 13(8), 2490; https://doi.org/10.3390/nu13082490 - 21 Jul 2021
Cited by 6 | Viewed by 2867
Abstract
The fundamental role of magnesium in human health is extensively discussed in the review by Fiorentini and colleagues [...] Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)

Research

Jump to: Editorial, Review

14 pages, 14747 KiB  
Article
Magnesium Deficiency Alters Expression of Genes Critical for Muscle Magnesium Homeostasis and Physiology in Mice
by Dominique Bayle, Cécile Coudy-Gandilhon, Marine Gueugneau, Sara Castiglioni, Monica Zocchi, Magdalena Maj-Zurawska, Adriana Palinska-Saadi, André Mazur, Daniel Béchet and Jeanette A. Maier
Nutrients 2021, 13(7), 2169; https://doi.org/10.3390/nu13072169 - 24 Jun 2021
Cited by 7 | Viewed by 2725
Abstract
Chronic Mg2+ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg2+ is located in the skeletal muscle, Mg2+ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg2+ [...] Read more.
Chronic Mg2+ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg2+ is located in the skeletal muscle, Mg2+ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg2+ homeostasis. In the present study, we assessed whether Mg2+ deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology. C57BL/6J mice received either a control, mildly, or severely Mg2+-deficient diet (0.1%; 0.01%; and 0.003% Mg2+ wt/wt, respectively) for 14 days. Mg2+ deficiency slightly decreased body weight gain and muscle Mg2+ concentrations but was not associated with detectable variations in gastrocnemius muscle weight, fiber morphometry, and capillarization. Nonetheless, muscles exhibited decreased expression of several MgTHs (MagT1, CNNM2, CNNM4, and TRPM6). Moreover, TaqMan low-density array (TLDA) analyses further revealed that, before the emergence of major muscle dysfunctions, even a mild Mg2+ deficiency was sufficient to alter the expression of genes critical for muscle physiology, including energy metabolism, muscle regeneration, proteostasis, mitochondrial dynamics, and excitation–contraction coupling. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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11 pages, 2194 KiB  
Article
Magnesium Metabolism in Chronic Alcohol-Use Disorder: Meta-Analysis and Systematic Review
by Flora O. Vanoni, Gregorio P. Milani, Carlo Agostoni, Giorgio Treglia, Pietro B. Faré, Pietro Camozzi, Sebastiano A. G. Lava, Mario G. Bianchetti and Simone Janett
Nutrients 2021, 13(6), 1959; https://doi.org/10.3390/nu13061959 - 7 Jun 2021
Cited by 9 | Viewed by 4398
Abstract
Chronic alcohol-use disorder has been imputed as a possible cause of dietary magnesium depletion. The purpose of this study was to assess the prevalence of hypomagnesemia in chronic alcohol-use disorder, and to provide information on intracellular magnesium and on its renal handling. We [...] Read more.
Chronic alcohol-use disorder has been imputed as a possible cause of dietary magnesium depletion. The purpose of this study was to assess the prevalence of hypomagnesemia in chronic alcohol-use disorder, and to provide information on intracellular magnesium and on its renal handling. We carried out a structured literature search up to November 2020, which returned 2719 potentially relevant records. After excluding non-significant records, 25 were retained for the final analysis. The meta-analysis disclosed that both total and ionized circulating magnesium are markedly reduced in chronic alcohol-use disorder. The funnel plot and the Egger’s test did not disclose significant publication bias. The I2-test demonstrated significant statistical heterogeneity between studies. We also found that the skeletal muscle magnesium content is reduced and the kidney’s normal response to hypomagnesemia is blunted. In conclusion, magnesium depletion is common in chronic alcohol-use disorder. Furthermore, the kidney plays a crucial role in the development of magnesium depletion. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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14 pages, 3196 KiB  
Article
Assessment and Imaging of Intracellular Magnesium in SaOS-2 Osteosarcoma Cells and Its Role in Proliferation
by Concettina Cappadone, Emil Malucelli, Maddalena Zini, Giovanna Farruggia, Giovanna Picone, Alessandra Gianoncelli, Andrea Notargiacomo, Michela Fratini, Carla Pignatti, Stefano Iotti and Claudio Stefanelli
Nutrients 2021, 13(4), 1376; https://doi.org/10.3390/nu13041376 - 20 Apr 2021
Cited by 4 | Viewed by 3039
Abstract
Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma [...] Read more.
Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2–3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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13 pages, 502 KiB  
Article
Hypomagnesemia Is a Risk Factor for Infections after Kidney Transplantation: A Retrospective Cohort Analysis
by Balazs Odler, Andras T. Deak, Gudrun Pregartner, Regina Riedl, Jasmin Bozic, Christian Trummer, Anna Prenner, Lukas Söllinger, Marcell Krall, Lukas Höflechner, Carina Hebesberger, Matias S. Boxler, Andrea Berghold, Peter Schemmer, Stefan Pilz and Alexander R. Rosenkranz
Nutrients 2021, 13(4), 1296; https://doi.org/10.3390/nu13041296 - 14 Apr 2021
Cited by 11 | Viewed by 2773
Abstract
Introduction: Magnesium (Mg2+) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) [...] Read more.
Introduction: Magnesium (Mg2+) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse. Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg2+ (median time of the Mg2+ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality. Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg2+ deficiency defined as a serum Mg2+ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg2+ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg2+ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04–2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23–3.41, p = 0.006). No group differences according to Mg2+ status in hospitalizations due to infections and infection incidence rates in the 12–24 months post-transplant were observed. In the Cox regression analysis, Mg2+ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70–1.89, p = 0.577). Conclusions: KTRs suffering from Mg2+ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg2+ supplementation on Mg2+ deficiency and viral infections in KTRs are needed. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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8 pages, 3076 KiB  
Article
Magnesium Influences Membrane Fusion during Myogenesis by Modulating Oxidative Stress in C2C12 Myoblasts
by Monica Zocchi, Daniel Béchet, André Mazur, Jeanette A. Maier and Sara Castiglioni
Nutrients 2021, 13(4), 1049; https://doi.org/10.3390/nu13041049 - 24 Mar 2021
Cited by 6 | Viewed by 3858
Abstract
Magnesium (Mg) is essential to skeletal muscle where it plays a key role in myofiber relaxation. Although the importance of Mg in the mature skeletal muscle is well established, little is known about the role of Mg in myogenesis. We studied the effects [...] Read more.
Magnesium (Mg) is essential to skeletal muscle where it plays a key role in myofiber relaxation. Although the importance of Mg in the mature skeletal muscle is well established, little is known about the role of Mg in myogenesis. We studied the effects of low and high extracellular Mg in C2C12 myogenic differentiation. Non-physiological Mg concentrations induce oxidative stress in myoblasts. The increase of reactive oxygen species, which occurs during the early phase of the differentiation process, inhibits myoblast membrane fusion, thus impairing myogenesis. Therefore, correct Mg homeostasis, also maintained through a correct dietary intake, is essential to assure the regenerative capacity of skeletal muscle fibers. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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12 pages, 276 KiB  
Article
Association of Magnesium Intake with Liver Fibrosis among Adults in the United States
by Meng-Hua Tao and Kimberly G. Fulda
Nutrients 2021, 13(1), 142; https://doi.org/10.3390/nu13010142 - 2 Jan 2021
Cited by 8 | Viewed by 4161
Abstract
Liver fibrosis represents the consequences of chronic liver injury. Individuals with alcoholic or nonalcoholic liver diseases are at high risk of magnesium deficiency. This study aimed to evaluate the association between magnesium and calcium intakes and significant liver fibrosis, and whether the associations [...] Read more.
Liver fibrosis represents the consequences of chronic liver injury. Individuals with alcoholic or nonalcoholic liver diseases are at high risk of magnesium deficiency. This study aimed to evaluate the association between magnesium and calcium intakes and significant liver fibrosis, and whether the associations differ by alcohol drinking status. Based on the National Health and Nutrition Examination Survey (NHANES) 2017–2018, the study included 4166 participants aged >18 years who completed the transient elastography examination and had data available on magnesium intake. The median liver stiffness of 8.2 kPa was used to identify subjects with significant fibrosis (≥F2). The age-adjusted prevalence of significant fibrosis was 12.81%. Overall total magnesium intake was marginally associated with reduced odds of significant fibrosis (p trend = 0.14). The inverse association of total magnesium intake with significant fibrosis was primarily presented among those who had daily calcium intake <1200 mg. There were no clear associations for significant fibrosis with calcium intake. Findings suggest that high total magnesium alone may reduce risk of significant fibrosis. Further studies are needed to confirm these findings. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
11 pages, 1232 KiB  
Article
Magnesium Absorption in Intestinal Cells: Evidence of Cross-Talk between EGF and TRPM6 and Novel Implications for Cetuximab Therapy
by Giuseppe Pietropaolo, Daniela Pugliese, Alessandro Armuzzi, Luisa Guidi, Antonio Gasbarrini, Gian Lodovico Rapaccini, Federica I. Wolf and Valentina Trapani
Nutrients 2020, 12(11), 3277; https://doi.org/10.3390/nu12113277 - 26 Oct 2020
Cited by 12 | Viewed by 3672
Abstract
Hypomagnesemia is very commonly observed in cancer patients, most frequently in association with therapy with cetuximab (CTX), a monoclonal antibody targeting the epithelial growth factor receptor (EGFR). CTX-induced hypomagnesemia has been ascribed to renal magnesium (Mg) wasting. Here, we sought to clarify whether [...] Read more.
Hypomagnesemia is very commonly observed in cancer patients, most frequently in association with therapy with cetuximab (CTX), a monoclonal antibody targeting the epithelial growth factor receptor (EGFR). CTX-induced hypomagnesemia has been ascribed to renal magnesium (Mg) wasting. Here, we sought to clarify whether CTX may also influence intestinal Mg absorption and if Mg supplementation may interfere with CTX activity. We used human colon carcinoma CaCo-2 cells as an in vitro model to study the mechanisms underlying Mg transport and CTX activity. Our findings demonstrate that TRPM6 is the key channel that mediates Mg influx in intestinal cells and that EGF stimulates such influx; consequently, CTX downregulates TRPM6-mediated Mg influx by interfering with EGF signaling. Moreover, we show that Mg supplementation does not modify either the CTX IC50 or CTX-dependent inhibition of ERK1/2 phosphorylation. Our results suggest that reduced Mg absorption in the intestine may contribute to the severe hypomagnesemia that occurs in CTX-treated patients, and Mg supplementation may represent a safe and effective nutritional intervention to restore Mg status without impairing the CTX efficacy. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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14 pages, 3137 KiB  
Article
Inhibition of Mg2+ Extrusion Attenuates Glutamate Excitotoxicity in Cultured Rat Hippocampal Neurons
by Yutaka Shindo, Ryu Yamanaka, Kohji Hotta and Kotaro Oka
Nutrients 2020, 12(9), 2768; https://doi.org/10.3390/nu12092768 - 10 Sep 2020
Cited by 10 | Viewed by 3719
Abstract
Magnesium plays important roles in the nervous system. An increase in the Mg2+ concentration in cerebrospinal fluid enhances neural functions, while Mg2+ deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of [...] Read more.
Magnesium plays important roles in the nervous system. An increase in the Mg2+ concentration in cerebrospinal fluid enhances neural functions, while Mg2+ deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg2+ due to the release of Mg2+ from mitochondria, followed by a decrease to below steady-state levels. Since Mg2+ deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg2+ decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg2+ extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg2+ release from mitochondria and Mg2+ extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg2+ concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg2+ regulation in neuronal survival under excitotoxicity. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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12 pages, 632 KiB  
Article
Magnesium Levels Modify the Effect of Lipid Parameters on Carotid Intima Media Thickness
by Serafi Cambray, Merce Ibarz, Marcelino Bermudez-Lopez, Manuel Marti-Antonio, Milica Bozic, Elvira Fernandez and Jose M. Valdivielso
Nutrients 2020, 12(9), 2631; https://doi.org/10.3390/nu12092631 - 28 Aug 2020
Cited by 13 | Viewed by 4132
Abstract
Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in [...] Read more.
Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in CKD. Furthermore, Mg levels have been associated with cardiovascular health. The present study aims to understand the relationships of Mg and lipid parameters with atherosclerosis in CKD. In this analysis, 1754 participants from the Observatorio Nacional de Atherosclerosis en Nefrologia (NEFRONA) cohort were included. Carotid intima media thickness (cIMT) was determined in six arterial territories, and associated factors were investigated by linear regression. cIMT correlated positively with being male, Caucasian, a smoker, diabetic, hypertensive, dyslipidemic and with increased age, BMI, and triglyceride levels, and negatively with levels of HDL cholesterol. First-order interactions in linear regression analysis showed that Mg was an effect modifier on the influence of lipidic parameters. Thus, cIMT predicted values were higher when triglycerides or LDL levels were high and Mg levels were low. On the contrary, when Mg levels were high, this effect disappeared. In conclusion, Mg acts as an effect modifier between lipidic parameters and atherosclerotic cardiovascular disease. Therefore, Mg levels, together with lipidic parameters, should be taken into account when assessing atherosclerotic risk. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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12 pages, 1430 KiB  
Article
Magnesium Deficiency Questionnaire: A New Non-Invasive Magnesium Deficiency Screening Tool Developed Using Real-World Data from Four Observational Studies
by Svetlana Orlova, Galina Dikke, Gisele Pickering, Sofya Konchits, Kirill Starostin and Alina Bevz
Nutrients 2020, 12(7), 2062; https://doi.org/10.3390/nu12072062 - 11 Jul 2020
Cited by 7 | Viewed by 4802
Abstract
Due to the high estimated prevalence of magnesium deficiency, there is a need for a rapid, non-invasive assessment tool that could be used by patients and clinicians to confirm suspected hypomagnesemia and substantiate laboratory testing. This study analyzed data from four large observational [...] Read more.
Due to the high estimated prevalence of magnesium deficiency, there is a need for a rapid, non-invasive assessment tool that could be used by patients and clinicians to confirm suspected hypomagnesemia and substantiate laboratory testing. This study analyzed data from four large observational studies of hypomagnesemia in pregnant women and women with hormone-related conditions across Russia. Hypomagnesemia was assessed using a 62-item magnesium deficiency questionnaire (MDQ-62) and a serum test. The diagnostic utility (sensitivity/specificity) of MDQ-62 was analyzed using area under the receiver operating characteristic curve (AUROC). A logistic regression model was applied to develop a shorter, optimized version of MDQ-62. A total of 765 pregnant women and 8836 women with hormone-related conditions were included in the analysis. The diagnostic performance of MDQ-62 was “fair” (AUROC = 0.7−0.8) for women with hormone-related conditions and “poor” for pregnant women (AUROC = 0.6−0.7). The optimized MDQ-23 (23 questions) and MDQ-10 (10 questions) had similar AUROC values; for all versions of the questionnaire, there was a significant negative correlation between score and changes in total serum magnesium levels (p < 0.0001 for all comparisons; correlation coefficients ranged from −0.1667 to −0.2716). This analysis confirmed the value of MDQ in identifying women at risk of hypomagnesemia. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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13 pages, 2834 KiB  
Article
Variations in Magnesium Concentration Are Associated with Increased Mortality: Study in an Unselected Population of Hospitalized Patients
by Justyna Malinowska, Milena Małecka and Olga Ciepiela
Nutrients 2020, 12(6), 1836; https://doi.org/10.3390/nu12061836 - 19 Jun 2020
Cited by 24 | Viewed by 3847
Abstract
Dysmagnesemia is a serious disturbance of microelement homeostasis. The aim of this study was to analyze the distribution of serum magnesium concentrations in hospitalized patients according to gender, age, and result of hospitalization. The study was conducted from February 2018 to January 2019 [...] Read more.
Dysmagnesemia is a serious disturbance of microelement homeostasis. The aim of this study was to analyze the distribution of serum magnesium concentrations in hospitalized patients according to gender, age, and result of hospitalization. The study was conducted from February 2018 to January 2019 at the Central Clinical Hospital in Warsaw. Laboratory test results from 20,438 patients were included in this retrospective analysis. When a lower reference value 0.65 mmol/L was applied, hypermagnesemia occurred in 196 patients (1%), hypomagnesemia in 1505 patients (7%), and normomagnesemia in 18,711 patients (92%). At a lower reference value of 0.75 mmol/L, hypomagnesemia was found in 25% and normomagnesemia in 74% of patients. At a lower reference value of 0.85 mmol/L, hypomagnesemia was found in 60% and normomagnesemia in 39% of patients. Either hypo- or hyper-magnesemia was associated with increased risk of in-hospital mortality. This risk is the highest in patients with hypermagnesemia (40.1% of deaths), but also increases inversely with magnesium concentration below 0.85 mmol/L. Serum magnesium concentration was not gender-dependent, and there was a slight positive correlation with age (p < 0.0001, r = 0.07). Large fluctuations in serum magnesium level were associated with increased mortality (p = 0.0017). The results indicate that dysmagnesemia is associated with severe diseases and generally severe conditions. To avoid misdiagnosis, an increase of a lower cut-off for serum magnesium concentration to at least 0.75 mmol/L is suggested. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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11 pages, 703 KiB  
Article
Circulating Ionized Magnesium as a Measure of Supplement Bioavailability: Results from a Pilot Study for Randomized Clinical Trial
by Jiada Zhan, Taylor C. Wallace, Sarah J. Butts, Sisi Cao, Velarie Ansu, Lisa A. Spence, Connie M. Weaver and Nana Gletsu-Miller
Nutrients 2020, 12(5), 1245; https://doi.org/10.3390/nu12051245 - 28 Apr 2020
Cited by 13 | Viewed by 13162
Abstract
Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg [...] Read more.
Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL•24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL•24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg•24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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Review

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30 pages, 685 KiB  
Review
Crosstalk of Magnesium and Serum Lipids in Dyslipidemia and Associated Disorders: A Systematic Review
by Mihnea-Alexandru Găman, Elena-Codruța Dobrică, Matei-Alexandru Cozma, Ninel-Iacobus Antonie, Ana Maria Alexandra Stănescu, Amelia Maria Găman and Camelia Cristina Diaconu
Nutrients 2021, 13(5), 1411; https://doi.org/10.3390/nu13051411 - 22 Apr 2021
Cited by 43 | Viewed by 7003
Abstract
Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of [...] Read more.
Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of lipid abnormalities and related disorders, such as the metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease. In this review, we explored the associations of Mg (dietary intake, Mg concentrations in the body) and the lipid profile, as well as the impact of Mg supplementation on serum lipids. A systematic search was computed in PubMed/MEDLINE and the Cochrane Library and 3649 potentially relevant papers were detected and screened (n = 3364 following the removal of duplicates). After the removal of irrelevant manuscripts based on the screening of their titles and abstracts (n = 3037), we examined the full-texts of 327 original papers. Finally, after we applied the exclusion and inclusion criteria, a number of 124 original articles were included in this review. Overall, the data analyzed in this review point out an association of Mg concentrations in the body with serum lipids in dyslipidemia and related disorders. However, further research is warranted to clarify whether a higher intake of Mg from the diet or via supplements can influence the lipid profile and exert lipid-lowering actions. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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44 pages, 1615 KiB  
Review
Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency
by Diana Fiorentini, Concettina Cappadone, Giovanna Farruggia and Cecilia Prata
Nutrients 2021, 13(4), 1136; https://doi.org/10.3390/nu13041136 - 30 Mar 2021
Cited by 158 | Viewed by 46718
Abstract
Magnesium plays an important role in many physiological functions. Habitually low intakes of magnesium and in general the deficiency of this micronutrient induce changes in biochemical pathways that can increase the risk of illness and, in particular, chronic degenerative diseases. The assessment of [...] Read more.
Magnesium plays an important role in many physiological functions. Habitually low intakes of magnesium and in general the deficiency of this micronutrient induce changes in biochemical pathways that can increase the risk of illness and, in particular, chronic degenerative diseases. The assessment of magnesium status is consequently of great importance, however, its evaluation is difficult. The measurement of serum magnesium concentration is the most commonly used and readily available method for assessing magnesium status, even if serum levels have no reliable correlation with total body magnesium levels or concentrations in specific tissues. Therefore, this review offers an overview of recent insights into magnesium from multiple perspectives. Starting from a biochemical point of view, it aims at highlighting the risk due to insufficient uptake (frequently due to the low content of magnesium in the modern western diet), at suggesting strategies to reach the recommended dietary reference values, and at focusing on the importance of detecting physiological or pathological levels of magnesium in various body districts, in order to counteract the social impact of diseases linked to magnesium deficiency. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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12 pages, 1094 KiB  
Review
Magnesium Oxide in Constipation
by Hideki Mori, Jan Tack and Hidekazu Suzuki
Nutrients 2021, 13(2), 421; https://doi.org/10.3390/nu13020421 - 28 Jan 2021
Cited by 32 | Viewed by 15969
Abstract
Magnesium oxide has been widely used as a laxative for many years in East Asia, yet its prescription has largely been based on empirical knowledge. In recent years, several new laxatives have been developed, which has led to a resurgence in interest and [...] Read more.
Magnesium oxide has been widely used as a laxative for many years in East Asia, yet its prescription has largely been based on empirical knowledge. In recent years, several new laxatives have been developed, which has led to a resurgence in interest and increased scientific evidence surrounding the use of magnesium oxide, which is convenient to administer, of low cost, and safe. Despite these advantages, emerging clinical evidence indicates that the use of magnesium oxide should take account of the most appropriate dose, the serum concentration, drug–drug interactions, and the potential for side effects, especially in the elderly and in patients with renal impairment. The aim of this review is to evaluate the evidence base for the clinical use of magnesium oxide for treating constipation and provide a pragmatic guide to its advantages and disadvantages. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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16 pages, 1484 KiB  
Review
Magnesium in Obesity, Metabolic Syndrome, and Type 2 Diabetes
by Gabriele Piuri, Monica Zocchi, Matteo Della Porta, Valentina Ficara, Michele Manoni, Gian Vincenzo Zuccotti, Luciano Pinotti, Jeanette A. Maier and Roberta Cazzola
Nutrients 2021, 13(2), 320; https://doi.org/10.3390/nu13020320 - 22 Jan 2021
Cited by 102 | Viewed by 23926
Abstract
Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the [...] Read more.
Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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22 pages, 2338 KiB  
Review
Mg2+ Transporters in Digestive Cancers
by Julie Auwercx, Pierre Rybarczyk, Philippe Kischel, Isabelle Dhennin-Duthille, Denis Chatelain, Henri Sevestre, Isabelle Van Seuningen, Halima Ouadid-Ahidouch, Nicolas Jonckheere and Mathieu Gautier
Nutrients 2021, 13(1), 210; https://doi.org/10.3390/nu13010210 - 13 Jan 2021
Cited by 15 | Viewed by 4479
Abstract
Despite magnesium (Mg2+) representing the second most abundant cation in the cell, its role in cellular physiology and pathology is far from being elucidated. Mg2+ homeostasis is regulated by Mg2+ transporters including Mitochondrial RNA Splicing Protein 2 (MRS2), Transient [...] Read more.
Despite magnesium (Mg2+) representing the second most abundant cation in the cell, its role in cellular physiology and pathology is far from being elucidated. Mg2+ homeostasis is regulated by Mg2+ transporters including Mitochondrial RNA Splicing Protein 2 (MRS2), Transient Receptor Potential Cation Channel Subfamily M, Member 6/7 (TRPM6/7), Magnesium Transporter 1 (MAGT1), Solute Carrier Family 41 Member 1 (SCL41A1), and Cyclin and CBS Domain Divalent Metal Cation Transport Mediator (CNNM) proteins. Recent data show that Mg2+ transporters may regulate several cancer cell hallmarks. In this review, we describe the expression of Mg2+ transporters in digestive cancers, the most common and deadliest malignancies worldwide. Moreover, Mg2+ transporters’ expression, correlation and impact on patient overall and disease-free survival is analyzed using Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Finally, we discuss the role of these Mg2+ transporters in the regulation of cancer cell fates and oncogenic signaling pathways. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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15 pages, 4942 KiB  
Review
Effectively Prescribing Oral Magnesium Therapy for Hypertension: A Categorized Systematic Review of 49 Clinical Trials
by Andrea Rosanoff, Rebecca B. Costello and Guy H. Johnson
Nutrients 2021, 13(1), 195; https://doi.org/10.3390/nu13010195 - 10 Jan 2021
Cited by 21 | Viewed by 12406
Abstract
Trials and meta-analyses of oral magnesium for hypertension show promising but conflicting results. An inclusive collection of 49 oral magnesium for blood pressure (BP) trials were categorized into four groups: (1) Untreated Hypertensives; (2) Uncontrolled Hypertensives; (3) Controlled Hypertensives; (4) Normotensive subjects. Each [...] Read more.
Trials and meta-analyses of oral magnesium for hypertension show promising but conflicting results. An inclusive collection of 49 oral magnesium for blood pressure (BP) trials were categorized into four groups: (1) Untreated Hypertensives; (2) Uncontrolled Hypertensives; (3) Controlled Hypertensives; (4) Normotensive subjects. Each group was tabulated by ascending magnesium dose. Studies reporting statistically significant (p < 0.05) decreases in both systolic BP (SBP) and diastolic BP (DBP) from both baseline and placebo (if reported) were labeled “Decrease”; all others were deemed “No Change.” Results: Studies of Untreated Hypertensives (20 studies) showed BP “Decrease” only when Mg dose was >600 mg/day; <50% of the studies at 120–486 mg Mg/day showed SBP or DBP decreases but not both while others at this Mg dosage showed no change in either BP measure. In contrast, all magnesium doses (240–607 mg/day) showed “Decrease” in 10 studies on Uncontrolled Hypertensives. Controlled Hypertensives, Normotensives and “magnesium-replete” studies showed “No Change” even at high magnesium doses (>600 mg/day). Where magnesium did not lower BP, other cardiovascular risk factors showed improvement. Conclusion: Controlled Hypertensives and Normotensives do not show a BP-lowering effect with oral Mg therapy, but oral magnesium (≥240 mg/day) safely lowers BP in Uncontrolled Hypertensive patients taking antihypertensive medications, while >600 mg/day magnesium is required to safely lower BP in Untreated Hypertensives; <600 mg/day for non-medicated hypertensives may not lower both SBP and DBP but may safely achieve other risk factor improvements without antihypertensive medication side effects. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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21 pages, 1459 KiB  
Review
Magnesium Status and Stress: The Vicious Circle Concept Revisited
by Gisèle Pickering, André Mazur, Marion Trousselard, Przemyslaw Bienkowski, Natalia Yaltsewa, Mohamed Amessou, Lionel Noah and Etienne Pouteau
Nutrients 2020, 12(12), 3672; https://doi.org/10.3390/nu12123672 - 28 Nov 2020
Cited by 55 | Viewed by 45926
Abstract
Magnesium deficiency and stress are both common conditions among the general population, which, over time, can increase the risk of health consequences. Numerous studies, both in pre-clinical and clinical settings, have investigated the interaction of magnesium with key mediators of the physiological stress [...] Read more.
Magnesium deficiency and stress are both common conditions among the general population, which, over time, can increase the risk of health consequences. Numerous studies, both in pre-clinical and clinical settings, have investigated the interaction of magnesium with key mediators of the physiological stress response, and demonstrated that magnesium plays an inhibitory key role in the regulation and neurotransmission of the normal stress response. Furthermore, low magnesium status has been reported in several studies assessing nutritional aspects in subjects suffering from psychological stress or associated symptoms. This overlap in the results suggests that stress could increase magnesium loss, causing a deficiency; and in turn, magnesium deficiency could enhance the body’s susceptibility to stress, resulting in a magnesium and stress vicious circle. This review revisits the magnesium and stress vicious circle concept, first introduced in the early 1990s, in light of recent available data. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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14 pages, 642 KiB  
Review
Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate
by Jeanette A. Maier, Gisele Pickering, Elena Giacomoni, Alessandra Cazzaniga and Paolo Pellegrino
Nutrients 2020, 12(9), 2660; https://doi.org/10.3390/nu12092660 - 31 Aug 2020
Cited by 28 | Viewed by 20339
Abstract
Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials [...] Read more.
Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines. Full article
(This article belongs to the Special Issue Magnesium in Human Health and Disease)
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