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Nutrients
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Magnesium Homeostasis and Magnesium Transporters in Human Health
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Magnesium Homeostasis and Magnesium Transporters in Human Health

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

Deadline for manuscript submissions: closed (5 November 2024) | Viewed by 16078

Special Issue Editors

Dr. Man Liu

E-Mail Website
Guest Editor
Cardiovascular Division, Department of Medicine, the Lillehei Heart Institute, University of Minnesota at Twin Cities, Minneapolis, MN 55455, USA
Interests: Mg homeostasis in cardiac diastolic dysfunction and HFpEF; Mg transporter TRPM7; Mg homeostasis in diabetic cardiomyopathy; arrhythmias; metabolic regulation of cardiac ion channels; the unfolded response regulation of cardiac ion channels
Prof. Dr. Samuel Dudley

E-Mail Website
Guest Editor
Cardiovascular Division, Department of Medicine, The Lillehei Heart Institute, University of Minnesota at Twin Cities, Minneapolis, MN 55455, USA
Interests: diastolic heart failure; arrhythmias; inflammation; oxidative stress; ion channel biology and regulation; mitochondrial function
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As the second most abundant intracellular divalent cation, magnesium (Mg) is essential for cell functions, such as ATP production, protein/DNA synthesis, protein activity, and mitochondrial function. Mg plays critical roles in heart rhythm, muscle contraction, and blood pressure. A significant decline in Mg intake has been reported in developed countries because of the increased consumption of processed food and filtered/deionized water, which can lead to hypomagnesemia (HypoMg). HypoMg is a predictor for cardiovascular and all-cause mortality and is commonly observed in cardiovascular diseases (CVD, such as heart failure, hypertension, arrhythmias, and diabetic cardiomyopathy). On the other hand, Mg supplementation has shown significant therapeutic effects in these conditions. Nevertheless, compared to Ca2+, Mg homeostasis and transporters are much less investigated. Cardiac Mg homeostasis is regulated and maintained by a series of sarcolemmal and mitochondrial transporters such as TRPM7, SLC41A1, MagT1, and CNNM2 on the sarcolemmal membrane and MRS2 and SLC41A3 on the mitochondrial membranes.  HypoMg has been associated with inflammation and oxidative stress for decades, both of which contribute to human health. Understanding how Mg and its transporters are regulated in human health can help develop easily translated therapy with Mg supplementation and new therapeutic strategies targeting Mg transporters.

Dr. Man Liu
Dr. Samuel Dudley
Guest Editors

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Keywords

  • heart failure
  • arrhythmias
  • hypertension
  • diabetic cardiomyopathy
  • inflammation
  • oxidative stress
  • mitochondria
  • metabolic dysregulation
  • human health
  • Mg supplementation

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Published Papers (6 papers)

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Editorial

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7 pages, 188 KiB  
Editorial
Magnesium Homeostasis and Magnesium Transporters in Human Health
by Man Liu and Samuel C. Dudley, Jr.
Nutrients 2025, 17(5), 920; https://doi.org/10.3390/nu17050920 - 6 Mar 2025
Viewed by 1003
Abstract
Magnesium (Mg2+) used to be considered only as a passive cation associated with ATP, but this special issue reinforces the idea that Mg2+ has many more roles [...] Full article
(This article belongs to the Special Issue Magnesium Homeostasis and Magnesium Transporters in Human Health)

Research

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12 pages, 2204 KiB  
Article
Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPETM Microcapsules) Versus Other Magnesium Sources
by David Pajuelo, Justyna M. Meissner, Teresa Negra, Alan Connolly and Jose L. Mullor
Nutrients 2024, 16(24), 4367; https://doi.org/10.3390/nu16244367 - 18 Dec 2024
Viewed by 4157
Abstract
Background/Objectives: Magnesium (Mg)-based food supplements contribute to the maintenance of adequate levels of Mg that are essential for overall health and well-being. The aim of this double-blind, randomized, cross-over clinical study was to assess the plasma Mg levels in volunteers following the oral [...] Read more.
Background/Objectives: Magnesium (Mg)-based food supplements contribute to the maintenance of adequate levels of Mg that are essential for overall health and well-being. The aim of this double-blind, randomized, cross-over clinical study was to assess the plasma Mg levels in volunteers following the oral administration of a magnesium-based nutraceutical ingredient, MAGSHAPETM microcapsules (Mg-MS), in comparison to other commonly used magnesium sources, including the following: Mg Oxide (MgO), Mg Citrate (Mg-C), and Mg bisglycinate (Mg-BG). Methods: A total of 40 healthy women and men were put on a low-Mg diet for 7 days, and after 8 h of fasting, a blood sample was taken from a digital puncture before (0 h) and 1 h, 4 h, and 6 h after the oral intake of each product. Results: Our results showed that the blood plasma levels of Mg increased significantly at all tested time-points after the oral intake of Mg-MS, while the blood plasma levels of Mg increased significantly only after 1 and 4 h of the oral intake of MgO and Mg-C, respectively. However, no significant increase in Mg levels was observed upon the intake of Mg-BG. Interestingly, the Mg-MS microencapsulation technology was observed to enable a sustained increase in plasma Mg levels over the duration of this study, i.e., 1, 4, and 6 h after oral intake. A direct comparison of the increase in plasma Mg levels over the 6 h period revealed that the Mg-MS microencapsulation technology significantly increased Mg bioavailability compared to the non-microencapsulated MgO. Our study also showed that, compared to the other Mg sources tested, the Mg-MS microencapsulation technology reduced adverse side effects commonly associated with Mg supplementation, specifically with regard to increased intestinal motility and sensations of gastric heaviness following oral administration. Conclusions: Altogether, this clinical study introduced MAGSHAPETM microcapsules as a bioavailable and well-tolerated alternative to existing Mg-based ingredients used in food supplements. Full article
(This article belongs to the Special Issue Magnesium Homeostasis and Magnesium Transporters in Human Health)
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12 pages, 1330 KiB  
Article
Magnesium Supplementation Modifies Arthritis Synovial and Splenic Transcriptomic Signatures Including Ferroptosis and Cell Senescence Biological Pathways
by Teresina Laragione, Carolyn Harris and Pércio S. Gulko
Nutrients 2024, 16(23), 4247; https://doi.org/10.3390/nu16234247 - 9 Dec 2024
Viewed by 2540
Abstract
Background: Rheumatoid arthritis (RA) is a common systemic autoimmune inflammatory disease that can cause joint damage. We have recently reported that oral magnesium supplementation significantly reduces disease severity and joint damage in models of RA. Methods: In the present study, we analyzed the [...] Read more.
Background: Rheumatoid arthritis (RA) is a common systemic autoimmune inflammatory disease that can cause joint damage. We have recently reported that oral magnesium supplementation significantly reduces disease severity and joint damage in models of RA. Methods: In the present study, we analyzed the transcriptome of spleens and synovial tissues obtained from mice with KRN serum-induced arthritis (KSIA) consuming either a high Mg supplemented diet (Mg2800; n = 7) or a normal diet (Mg500; n = 7). Tissues were collected at the end of a 15-day KSIA experiment. RNA was extracted and used for sequencing and analyses. Results: There was an enrichment of differentially expressed genes (DEGs) belonging to Reactome and Gene Ontology (GO) pathways implicated in RA pathogenesis such as RHO GTPases, the RUNX1 pathway, oxidative stress-induced senescence, and the senescence-associated secretory phenotype. Actc1 and Nr4a3 were among the genes with the highest expression, while Krt79 and Ffar2 were among the genes with the lowest expression in synovial tissues of the Mg2800 group compared with the Mg500 group. Spleens had an enrichment for the metabolism of folate and pterines and the HSP90 chaperone cycle for the steroid hormone receptor. Conclusions: We describe the tissue transcriptomic consequences of arthritis-protecting Mg supplementation in KSIA mice. These results show that oral Mg supplementation may interfere with the response to oxidative stress and senescence and other processes known to participate in RA pathogenesis. We provide new evidence supporting the disease-suppressing effect of increased Mg intake in arthritis and its potential to become a new addition to the therapeutic options for RA and other autoimmune and inflammatory diseases. Full article
(This article belongs to the Special Issue Magnesium Homeostasis and Magnesium Transporters in Human Health)
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12 pages, 744 KiB  
Article
Serum Magnesium Is Associated with Long-Term Survival of Non-ST-Elevation Myocardial Infarction Patients
by Amitai Segev, Michael Shechter, Avishai M. Tsur, David Belkin, Hofit Cohen, Amir Sharon, Nira Koren Morag, Ehud Grossman and Elad Maor
Nutrients 2023, 15(19), 4299; https://doi.org/10.3390/nu15194299 - 9 Oct 2023
Cited by 1 | Viewed by 2375
Abstract
Background: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. Objective: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. Methods: A retrospective analysis of all patients admitted to [...] Read more.
Background: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. Objective: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. Methods: A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI. Patients with advanced chronic kidney disease were excluded. Clinical data were collected and compared between lower sMg quartile patients (Q1; sMg < 1.9 mg/dL) and all other patients (Q2–Q4; sMg ≥ 1.9 mg/dL). Results: The study cohort included 4552 patients (70% male, median age 69 [IQR 59–79]) who were followed for a median of 4.4 (IQR 2.4–6.6) years. The median sMg level in the low sMg group was 1.7 (1.6–1.8) and 2.0 (2.0–2.2) mg/dL in the normal/high sMg group. The low sMg group was older (mean of 72 vs. 67 years), less likely to be male (64% vs. 72%), and had higher rates of comorbidities, including diabetes, hypertension, and atrial fibrillation (59% vs. 29%, 92% vs. 85%, and 6% vs. 5%; p < 0.05 for all). Kaplan–Meier survival analysis demonstrated significantly higher cumulative death probability at 4 years in the low sMg group (34% vs. 22%; p log rank <0.001). In a multivariable analysis model adjusted for sex, significant comorbidities, coronary interventions during the hospitalization, and renal function, the low sMg group exhibited an independent 24% increased risk of death during follow up (95% CI 1.11–1.39; p < 0.001). Conclusions: Low sMg is independently associated with higher risk of long-term mortality among patients recovering from an NSTEMI event. Full article
(This article belongs to the Special Issue Magnesium Homeostasis and Magnesium Transporters in Human Health)
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Review

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16 pages, 11002 KiB  
Review
Influence of Intravenous Magnesium Sulfate Infusion on the Subjective Postoperative Quality of Recovery: A Meta-Analysis of Randomized Controlled Trials
by Kuo-Chuan Hung, Li-Chen Chang, Chun-Ning Ho, Chih-Wei Hsu, Jheng-Yan Wu, Yao-Tsung Lin and I-Wen Chen
Nutrients 2024, 16(14), 2375; https://doi.org/10.3390/nu16142375 - 22 Jul 2024
Cited by 1 | Viewed by 2538
Abstract
This meta-analysis investigated the effects of intravenous magnesium sulfate on the postoperative recovery quality, as assessed using the Quality of Recovery (QoR) questionnaire, in adult surgical patients. Seven randomized controlled trials involving 622 patients were included. Compared with the placebo, magnesium sulfate significantly [...] Read more.
This meta-analysis investigated the effects of intravenous magnesium sulfate on the postoperative recovery quality, as assessed using the Quality of Recovery (QoR) questionnaire, in adult surgical patients. Seven randomized controlled trials involving 622 patients were included. Compared with the placebo, magnesium sulfate significantly improved the global QoR score on postoperative day 1 (standardized mean difference [SMD]: 1.24; 95% confidence interval: 0.70—1.78; p < 0.00001). It also enhanced specific QoR dimensions, with substantial effects on pain (SMD: 1, p < 0.00001) and physical comfort (SMD: 0.85, p < 0.0001), a moderate effect on emotional state (SMD: 0.65, p = 0.002), and small improvements in physical independence (SMD: 0.43, p < 0.00001) and psychological support (SMD: 0.37, p < 0.0001). In addition, magnesium sulfate reduced the intraoperative opioid consumption (SMD: −0.66, p < 0.0001), postoperative pain severity, and the incidence of postoperative nausea and vomiting (risk ratio: 0.48, p = 0.008). The extubation times were unaffected, whereas the post-anesthesia care unit stay was slightly prolonged. These findings highlight the potential of magnesium sulfate as a valuable adjunct for multimodal analgesia and enhanced recovery. Future studies should aim to elucidate the optimal dosing strategies, timing of administration, and specific surgical populations that may derive maximum benefits. Full article
(This article belongs to the Special Issue Magnesium Homeostasis and Magnesium Transporters in Human Health)
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Other

10 pages, 310 KiB  
Opinion
Beyond Ion Homeostasis: Hypomagnesemia, Transient Receptor Potential Melastatin Channel 7, Mitochondrial Function, and Inflammation
by Man Liu and Samuel C. Dudley, Jr.
Nutrients 2023, 15(18), 3920; https://doi.org/10.3390/nu15183920 - 9 Sep 2023
Cited by 7 | Viewed by 2426
Abstract
As the second most abundant intracellular divalent cation, magnesium (Mg2+) is essential for cell functions, such as ATP production, protein/DNA synthesis, protein activity, and mitochondrial function. Mg2+ plays a critical role in heart rhythm, muscle contraction, and blood pressure. A [...] Read more.
As the second most abundant intracellular divalent cation, magnesium (Mg2+) is essential for cell functions, such as ATP production, protein/DNA synthesis, protein activity, and mitochondrial function. Mg2+ plays a critical role in heart rhythm, muscle contraction, and blood pressure. A significant decline in Mg2+ intake has been reported in developed countries because of the increased consumption of processed food and filtered/deionized water, which can lead to hypomagnesemia (HypoMg). HypoMg is commonly observed in cardiovascular diseases, such as heart failure, hypertension, arrhythmias, and diabetic cardiomyopathy, and HypoMg is a predictor for cardiovascular and all-cause mortality. On the other hand, Mg2+ supplementation has shown significant therapeutic effects in cardiovascular diseases. Some of the effects of HypoMg have been ascribed to changes in Mg2+ participation in enzyme activity, ATP stabilization, enzyme kinetics, and alterations in Ca2+, Na+, and other cations. In this manuscript, we discuss new insights into the pathogenic mechanisms of HypoMg that surpass previously described effects. HypoMg causes mitochondrial dysfunction, oxidative stress, and inflammation. Many of these effects can be attributed to the HypoMg-induced upregulation of a Mg2+ transporter transient receptor potential melastatin 7 channel (TRMP7) that is also a kinase. An increase in kinase signaling mediated by HypoMg-induced TRPM7 transcriptional upregulation, independently of any change in Mg2+ transport function, likely seems responsible for many of the effects of HypoMg. Therefore, Mg2+ supplementation and TRPM7 kinase inhibition may work to treat the sequelae of HypoMg by preventing increased TRPM7 kinase activity rather than just altering ion homeostasis. Since many diseases are characterized by oxidative stress or inflammation, Mg2+ supplementation and TRPM7 kinase inhibition may have wider implications for other diseases by acting to reduce oxidative stress and inflammation. Full article
(This article belongs to the Special Issue Magnesium Homeostasis and Magnesium Transporters in Human Health)
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