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Magnesium: From In Vitro to Clinical Research
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Magnesium: From In Vitro to Clinical Research

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 101309

Special Issue Editors

Dr. Ligia J. Dominguez

E-Mail Website
Guest Editor
Geriatric Unit, Department of Medicine, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
Interests: nutrition; aging; type 2 diabetes; Alzheimer; cardiovascular disease
Special Issues, Collections and Topics in MDPI journals
Dr. Nicola Veronese

E-Mail Website
Guest Editor
Department DI.PE.CA, Geriatric Unit, University Hospital AOUP, University of Palermo, Palermo, Italy
Interests: osteoarthritis; frailty; sarcopenia; osteoporosis; comprehensive geriatric assessment; nutritional issues
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Mario Barbagallo

E-Mail Website
Guest Editor
Department DI.PE.CA, Geriatric Unit, University Hospital AOUP, University of Palermo, 90127 Palermo, Italy
Interests: Mediterranean diet; aging; diabetes; hypertension; dementia; magnesium
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is known that magnesium is essential for human health. Magnesium is essential for all cells, having a pivotal role in energy production and being a cofactor of over 600 enzymes involved in cell metabolism. Magnesium is naturally present in many foods, such as green leafy vegetables, nuts, and legumes; however, a consistent part of the worldwide population, including industrialized countries, cannot reach an appropriate intake of magnesium, often needing oral supplementations. Increasing novel literature on clinical and preclinical studies indicates that magnesium deficiency may impact several organs and systems, leading to various metabolic, cardiovascular, and neuronal diseases. Finally, new research indicates a potential role of magnesium in infectious diseases, including COVID-19.

With this Special Issue entitled “Magnesium: from in vitro to clinical research”, we aim to collect original and reviews to cover the updated importance of magnesium from a pathophysiological and clinical point of view.

Dr. Ligia J. Dominguez
Dr. Nicola Veronese
Prof. Dr. Mario Barbagallo
Guest Editors

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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.

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Editorial

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5 pages, 214 KiB  
Editorial
Magnesium—An Ion with Multiple Invaluable Actions, Often Insufficiently Supplied: From In Vitro to Clinical Research
by Mario Barbagallo, Nicola Veronese and Ligia J. Dominguez
Nutrients 2023, 15(14), 3135; https://doi.org/10.3390/nu15143135 - 13 Jul 2023
Cited by 2 | Viewed by 1138
Abstract
Magnesium (Mg) is a key ion for numerous metabolic processes, being a cofactor of over 600 enzymes involved in cell metabolism and multiple biological processes [...] Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)

Research

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13 pages, 1293 KiB  
Article
Association between Serum Magnesium and Fractures: A Systematic Review and Meta-Analysis of Observational Studies
by Ligia J. Dominguez, Nicola Veronese, Stefano Ciriminna, José Luis Pérez-Albela, Vania Flora Vásquez-López, Santiago Rodas-Regalado, Giovanna Di Bella, Angela Parisi, Federica Tagliaferri and Mario Barbagallo
Nutrients 2023, 15(6), 1304; https://doi.org/10.3390/nu15061304 - 07 Mar 2023
Cited by 3 | Viewed by 3217
Abstract
Magnesium, an essential cation for numerous cellular processes, is a major component of bone. However, its relationship with the risk of fractures is still uncertain. The present systematic review and meta-analysis aim to investigate the impact of serum Mg on the risk of [...] Read more.
Magnesium, an essential cation for numerous cellular processes, is a major component of bone. However, its relationship with the risk of fractures is still uncertain. The present systematic review and meta-analysis aim to investigate the impact of serum Mg on the risk of incident fractures. A systematic search was conducted using several databases including PubMed/Medline and Scopus from inception to 24 May 2022, including observational studies investigating serum Mg and the incidence of fractures considered as outcomes. Abstract and full-text screenings, data extractions, and risk of bias assessments were conducted by two investigators independently. Any inconsistencies were resolved by consensus with a third author. The Newcastle–Ottawa Scale was used to assess the study quality/risk of bias. Among 1332 records initially screened, 16 were retrieved as full-texts; of them, four papers were included in the systematic review with a total of 119,755 participants. We found that lower serum Mg concentrations were associated with a significantly higher risk of incident fractures (RR = 1.579; 95%CI: 1.216–2.051; p = 0.001; I2 = 46.9%). Our systematic review with meta-analysis suggests a strong association of serum Mg concentrations with incident fractures. Further research is needed to confirm our results among other populations and to assess whether serum Mg is potentially relevant in the prevention of fractures, which continue to increase and represent a significant health burden due to the associated disability. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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12 pages, 628 KiB  
Article
Prognostic Value of Magnesium in COVID-19: Findings from the COMEPA Study
by Anna La Carrubba, Nicola Veronese, Giovanna Di Bella, Claudia Cusumano, Agnese Di Prazza, Stefano Ciriminna, Antonina Ganci, Liliana Naro, Ligia J. Dominguez, Mario Barbagallo and on behalf of the COMEPA Group
Nutrients 2023, 15(4), 830; https://doi.org/10.3390/nu15040830 - 06 Feb 2023
Cited by 6 | Viewed by 3154
Abstract
Magnesium (Mg) plays a key role in infections. However, its role in coronavirus disease 2019 (COVID-19) is still underexplored, particularly in long-term sequelae. The aim of the present study was to examine the prognostic value of serum Mg levels in older people affected [...] Read more.
Magnesium (Mg) plays a key role in infections. However, its role in coronavirus disease 2019 (COVID-19) is still underexplored, particularly in long-term sequelae. The aim of the present study was to examine the prognostic value of serum Mg levels in older people affected by COVID-19. Patients were divided into those with serum Mg levels ≤1.96 vs. >1.96 mg/dL, according to the Youden index. A total of 260 participants (mean age 65 years, 53.8% males) had valid Mg measurements. Serum Mg had a good accuracy in predicting in-hospital mortality (area under the curve = 0.83; 95% CI: 0.74–0.91). Low serum Mg at admission significantly predicted in-hospital death (HR = 1.29; 95% CI: 1.03–2.68) after adjusting for several confounders. A value of Mg ≤ 1.96 mg/dL was associated with a longer mean length of stay compared to those with a serum Mg > 1.96 (15.2 vs. 12.7 days). Low serum Mg was associated with a higher incidence of long COVID symptomatology (OR = 2.14; 95% CI: 1.30–4.31), particularly post-traumatic stress disorder (OR = 2.00; 95% CI: 1.24–16.40). In conclusion, low serum Mg levels were significant predictors of mortality, length of stay, and onset of long COVID symptoms, indicating that measuring serum Mg in COVID-19 may be helpful in the prediction of complications related to the disease. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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15 pages, 980 KiB  
Article
The Association of Serum and Dietary Magnesium with Depressive Symptoms
by Ming-Hui Chou, Yen Kuang Yang, Jung-Der Wang, Chung-Ying Lin and Sheng-Hsiang Lin
Nutrients 2023, 15(3), 774; https://doi.org/10.3390/nu15030774 - 02 Feb 2023
Cited by 8 | Viewed by 2919
Abstract
Depression is a leading cause of the global burden of disease and has a multifactorial etiology that includes nutrients. Magnesium status has been associated with depression with inconclusive results. The impact of chronic latent magnesium deficiency (CLMD, 0.75 ≤ serum magnesium < 0.85 [...] Read more.
Depression is a leading cause of the global burden of disease and has a multifactorial etiology that includes nutrients. Magnesium status has been associated with depression with inconclusive results. The impact of chronic latent magnesium deficiency (CLMD, 0.75 ≤ serum magnesium < 0.85 mmol/L) on depression has not yet been investigated. We assessed the association between serum magnesium levels/dietary magnesium intake and depressive symptoms by analyzing nationally representative data from Taiwan (Nutrition and Health Survey in Taiwan, NAHSIT). We used the 5-item Brief Symptom Rating Scale to measure depressive symptoms. Subgroup analysis by sex was also performed. Serum magnesium levels had a low correlation with dietary magnesium intake. Higher serum magnesium levels were associated with lower depressive scores and a lower risk of depressive symptoms, but dietary magnesium intake showed no association. Sex differences were found. Compared with subjects with serum magnesium <0.75 mmol/L, those with ≥0.85 mmol/L had lower depressive scores. In conclusion, serum magnesium was inversely associated with depressive symptoms, but dietary magnesium intake was not. Subjects with CLMD showed similar depressive scores and were at a similar risk of depressive symptoms to those with serum magnesium < 0.75 mmol/L. CLMD should be considered while assessing the association between magnesium status and depressive symptoms. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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11 pages, 663 KiB  
Article
Ionized Magnesium: Interpretation and Interest in Atrial Fibrillation
by Jean-Baptiste Bouillon-Minois, Louisa Khaled, Florence Vitte, Ludovic Miraillet, Romain Eschalier, Matthieu Jabaudon, Vincent Sapin, Lucas Derault, Samy Kahouadji, Marina Brailova, Julie Durif, Jeannot Schmidt, Fares Moustafa, Bruno Pereira, Emmanuel Futier and Damien Bouvier
Nutrients 2023, 15(1), 236; https://doi.org/10.3390/nu15010236 - 03 Jan 2023
Cited by 7 | Viewed by 2658
Abstract
Background: Magnesium (Mg) is often used to manage de novo atrial fibrillation (AF) in the emergency department (ED) and intensive care unit (ICU). Point of care measurement of ionized magnesium (iMg) allows a rapid identification of patients with impaired magnesium status, however, unlike [...] Read more.
Background: Magnesium (Mg) is often used to manage de novo atrial fibrillation (AF) in the emergency department (ED) and intensive care unit (ICU). Point of care measurement of ionized magnesium (iMg) allows a rapid identification of patients with impaired magnesium status, however, unlike ionized calcium, the interpretation of iMg is not entirely understood. Thus, we evaluated iMg reference values, correlation between iMg and plasmatic magnesium (pMg), and the impact of pH and albumin variations on iMg levels. Secondary objectives were to assess the incidence of hypomagnesemia in de novo AF. Methods: A total of 236 emergency department and intensive care unit patients with de novo AF, and 198 control patients were included. Reference values were determined in the control population. Correlation and concordance between iMg and pMg were studied using calcium (ionized and plasmatic) as a control in the whole study population. The impact of albumin and pH was assessed in the discordant iMg and pMg values. Lastly, we assessed the incidence of ionized hypomagnesemia (hypoMg) among de novo AF. Results: The reference range values established in our study for iMg were: 0.48–0.65 mmol/L (the manufacturers were: 0.45–0.60 mmol/L). A strong correlation was observed between pMg and iMg (r = 0.85), but, unlike for calcium values, there was no significant impact of pH and albumin in iMg/pMg interpretation. The incidence of hypoMg among de novo AF patients was 8.5% (12.7% using our ranges). When using our ranges, we found a significant link (p = 0.01) between hyopMg and hypokalemia. Conclusion: We highlight the need for more accurate reference range values of iMg. Furthermore, our results suggest that blood Mg content is not identical to that of calcium. The incidence of ionized hypomagnesemia among de novo AF patients in our study is 8.5%. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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16 pages, 1208 KiB  
Article
Subclinical Cardiovascular Disease Markers in Relation to Serum and Dietary Magnesium in Individuals from the General Population: The KORA-MRI Study
by Nuha Shugaa Addin, Christopher L. Schlett, Fabian Bamberg, Barbara Thorand, Jakob Linseisen, Jochen Seissler, Annette Peters and Susanne Rospleszcz
Nutrients 2022, 14(23), 4954; https://doi.org/10.3390/nu14234954 - 22 Nov 2022
Cited by 3 | Viewed by 1392
Abstract
Several studies have implied a role of magnesium in the development of cardiovascular disease (CVD). Thus, magnesium might serve as a potential risk marker for early CVD. Therefore, we investigated the association of serum magnesium and dietary magnesium intake with markers of subclinical [...] Read more.
Several studies have implied a role of magnesium in the development of cardiovascular disease (CVD). Thus, magnesium might serve as a potential risk marker for early CVD. Therefore, we investigated the association of serum magnesium and dietary magnesium intake with markers of subclinical CVD in a population-based study. We used cross-sectional data from the sub-study of the Cooperative Health Research in the Region of Augsburg (KORA-FF4). Markers of subclinical CVD, namely, left and right ventricular structure and function and carotid plaque and carotid wall thickness, were derived by magnetic resonance imaging (MRI). Multivariable-adjusted regression models were applied to assess the relationship between serum and dietary magnesium and MRI-derived subclinical CVD markers. Among 396 included participants (mean age: 56.3 ± 9.2 years; 57.8% male), 181 (45.7%) had low serum magnesium levels (<2.07 mg/dL). Among 311 subjects with complete dietary data (mean age: 56.3 ± 9.1 years; 56.3% male), 154 (49.5%) had low dietary magnesium intake (≤155.2 mg/1000 kcal/day). Serum and dietary magnesium were not correlated (p-value = 0.5). Serum magnesium was significantly associated with presence of carotid plaque (OR 1.62, p-value 0.033). Dietary magnesium was associated with higher left ventricular end-systolic and end-diastolic volume (0.04 mL/m2, 0.06 mL/m2; p-value 0.011, 0.013, respectively), and also with a decrease in left ventricular remodeling index and mean diastolic wall thickness (−0.001 g/mL/m2, −0.002 mm/m2; p-value 0.004, 0.029, respectively). In summary, there was no consistent association of serum and dietary magnesium with imaging markers of subclinical CVD. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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12 pages, 2351 KiB  
Article
Reduction in Serum Magnesium Levels and Renal Function Are Associated with Increased Mortality in Obese COVID-19 Patients
by Patricia Pulido Perez, Jorge Alberto Póndigo de los Angeles, Alonso Perez Peralta, Eloisa Ramirez Mojica, Enrique Torres Rasgado, Maria Elena Hernandez-Hernandez and Jose R. Romero
Nutrients 2022, 14(19), 4054; https://doi.org/10.3390/nu14194054 - 29 Sep 2022
Cited by 6 | Viewed by 2302
Abstract
Several studies provide evidence that obesity is a significant risk factor for adverse outcomes in coronavirus disease 2019 (COVID-19). Altered renal function and disturbances in magnesium levels have been reported to play important pathophysiological roles in COVID-19. However, the relationship between obesity, renal [...] Read more.
Several studies provide evidence that obesity is a significant risk factor for adverse outcomes in coronavirus disease 2019 (COVID-19). Altered renal function and disturbances in magnesium levels have been reported to play important pathophysiological roles in COVID-19. However, the relationship between obesity, renal function, circulating magnesium levels, and mortality in patients with COVID-19 remains unclear. In this retrospective cohort study, we characterized 390 hospitalized patients with COVID-19 that were categorized according to their body mass index (BMI). Patients were clinically characterized and biochemical parameters, renal function, and electrolyte markers measured upon admission. We found that in patients who died, BMI was associated with reduced estimated glomerular filtration rate (eGFR, Rho: −0.251, p = 0.001) and serum magnesium levels (Rho: −0.308, p < 0.0001). Multiple linear regression analyses showed that death was significantly associated with obesity (p = 0.001). The Cox model for obese patients showed that magnesium levels were associated with increased risk of death (hazard ratio: 0.213, 95% confidence interval: 0.077 to 0.586, p = 0.003). Thus, reduced renal function and lower magnesium levels were associated with increased mortality in obese COVID-19 patients. These results suggest that assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce mortality among obese COVID-19 patients. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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17 pages, 918 KiB  
Article
The Response of the Human Umbilical Vein Endothelial Cell Transcriptome to Variation in Magnesium Concentration
by Lujain A. Almousa, Andrew M. Salter, Marcos Castellanos, Sean T. May and Simon C. Langley-Evans
Nutrients 2022, 14(17), 3586; https://doi.org/10.3390/nu14173586 - 31 Aug 2022
Cited by 2 | Viewed by 1479
Abstract
Vascular endothelial cells have a critical role in the maintenance of cardiovascular function. Evidence suggests that endothelial function may be compromised under conditions of magnesium deficiency, which increases vulnerability to inflammation. Whole genome transcription analysis was used to explore the acute (24 h) [...] Read more.
Vascular endothelial cells have a critical role in the maintenance of cardiovascular function. Evidence suggests that endothelial function may be compromised under conditions of magnesium deficiency, which increases vulnerability to inflammation. Whole genome transcription analysis was used to explore the acute (24 h) effects of magnesium on human umbilical vascular endothelial cells (HUVEC) cultured in low (0.1 mM) or high (5 mM) concentrations. With low magnesium 2728 transcripts were differentially expressed compared to the 1 mM control cultures and 3030 were differentially expressed with high magnesium. 615 transcripts were differentially expressed under both conditions, of which only 34 showed a concentration-dependent response. Analysis indicated that cellular organisation and biogenesis and key cellular processes such as apoptosis were impacted by both low and high conditions. High magnesium also influenced protein binding functions, intracellular signal transduction, metabolic and catalytic processes. Both conditions impacted on stress-related processes, in particular the inflammatory response. Key mediators of calcium-dependent regulation of gene expression were responsive to both high and low magnesium conditions. The HUVEC transcriptome is highly sensitive to acute changes in the concentration of magnesium in culture medium. The findings of this study support the view that whilst inflammation is an important process that is responsive to magnesium, the function of the endothelium may be impacted by other magnesium-induced changes including maintenance of cellular integrity, receptor expression and metabolic functions. The high proportion of transcripts that did not show a concentration-dependent response suggests variation in magnesium may elicit indirect changes, possibly mediated by other ions. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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11 pages, 2197 KiB  
Article
Magnesium—A Potential Key Player in Inflammatory Bowel Diseases?
by Georgiana-Emmanuela Gilca-Blanariu, Anca Trifan, Manuela Ciocoiu, Iolanda Valentina Popa, Alexandru Burlacu, Gheorghe G. Balan, Andrei Vasile Olteanu and Gabriela Stefanescu
Nutrients 2022, 14(9), 1914; https://doi.org/10.3390/nu14091914 - 03 May 2022
Cited by 9 | Viewed by 5547
Abstract
The altered magnesium status in inflammatory bowel disease (IBD) patients may have a significant clinical imprint considering its role in cell signaling and genomic stability, as well as its involvement in IBD patients’ fatigue. Our study pioneers the investigation of magnesium hair concentration [...] Read more.
The altered magnesium status in inflammatory bowel disease (IBD) patients may have a significant clinical imprint considering its role in cell signaling and genomic stability, as well as its involvement in IBD patients’ fatigue. Our study pioneers the investigation of magnesium hair concentration patterns in an adult population of IBD patients. The hair magnesium concentration in IBD patients is compared to healthy controls in order to identify correlations between the magnesium status and relevant parameters related to disease activity, psychological status, and sleep quality. We report a significantly lower hair magnesium concentration within the IBD group compared to healthy controls (95%CI: 0.006–0.062; p = 0.017) and lower levels in CD compared to UC (95%CI: −0.061–−0.002; p = 0.038). We identified a borderline statistical significance between the hair magnesium concentration and UC disease activity (95%CI; −0.679–0.008; p = 0.055) and a significantly lower magnesium concentration in patients who reported increased sleep latency (95%CI −0.65–−0.102; p = 0.011) or decreased sleep duration (95%CI −0.613–−0.041; p = 0.028). Our results advance several hypotheses with substantial clinical impact to be confirmed in future studies. Magnesium levels appear to be modified in IBD patients, which suggests it either plays a primary role in disease pathophysiology or a is result of the disease’s evolution. Magnesium could be used in predictive models for clinical/subclinical disease activity. Moreover, magnesium supplementation may improve IBD evolution and sleep quality for patients with a deficit of this mineral. However, confirmatory evidence-based studies are needed to generate specific dosing, time of supplementation, and optimum monitoring of magnesium status in IBD patients. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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15 pages, 2538 KiB  
Article
Effect of a Combination of Magnesium, B Vitamins, Rhodiola, and Green Tea (L-Theanine) on Chronically Stressed Healthy Individuals—A Randomized, Placebo-Controlled Study
by Lionel Noah, Veronique Morel, Claire Bertin, Etienne Pouteau, Nicolas Macian, Christian Dualé, Bruno Pereira and Gisèle Pickering
Nutrients 2022, 14(9), 1863; https://doi.org/10.3390/nu14091863 - 29 Apr 2022
Cited by 13 | Viewed by 8022
Abstract
The effect of a combination of magnesium, vitamins B6, B9, B12, rhodiola and green tea/L-theanine (Mg-Teadiola) on stress was evaluated in chronically stressed, otherwise healthy individuals. Effects on stress-related quality-of-life parameters (sleep and perception of pain) were also explored. Adults with stress for [...] Read more.
The effect of a combination of magnesium, vitamins B6, B9, B12, rhodiola and green tea/L-theanine (Mg-Teadiola) on stress was evaluated in chronically stressed, otherwise healthy individuals. Effects on stress-related quality-of-life parameters (sleep and perception of pain) were also explored. Adults with stress for ≥1 month, scoring ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire, were randomized (1:1) to receive oral Mg-Teadiola (n = 49) or a placebo (n = 51), for 28 days, with a follow-up assessment on Day 56 (NCT04391452). The primary endpoint was the change in the DASS-42 stress score from baseline to Day 28 with Mg-Teadiola versus placebo. The DASS-42 stress scores significantly decreased from baseline to Day 28 with Mg-Teadiola versus placebo (effect size, 0.29; 95% CI [0.01, 0.57]; p = 0.04). Similar reductions were observed on Day 14 (p = 0.006) and Day 56 (p = 0.02). A significant reduction in sensitivity to cold pain (p = 0.01) and a trend for lower sensitivity to warm pain was observed (p = 0.06) on Day 28. Improvements in daytime dysfunction due to sleepiness (Pittsburgh Sleep Quality Index-7 component score) were reported on Day 28, and were significant on Day 56 (p < 0.001). Mg-Teadiola is effective in managing stress in otherwise healthy individuals. Its beneficial effects on sleep and pain perception need further investigation. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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24 pages, 1843 KiB  
Article
Magnesium Status and Calcium/Magnesium Ratios in a Series of Cystic Fibrosis Patients
by Marlene Fabiola Escobedo-Monge, Enrique Barrado, Joaquín Parodi-Román, María Antonieta Escobedo-Monge, Marianela Marcos-Temprano and José Manuel Marugán-Miguelsanz
Nutrients 2022, 14(9), 1793; https://doi.org/10.3390/nu14091793 - 25 Apr 2022
Cited by 8 | Viewed by 3266
Abstract
Magnesium (Mg) is an essential micronutrient that participates in various enzymatic reactions that regulate vital biological functions. The main aim was to assess the Mg status and its association with nutritional indicators in seventeen cystic fibrosis (CF) patients. The serum Mg and calcium [...] Read more.
Magnesium (Mg) is an essential micronutrient that participates in various enzymatic reactions that regulate vital biological functions. The main aim was to assess the Mg status and its association with nutritional indicators in seventeen cystic fibrosis (CF) patients. The serum Mg and calcium (Ca) levels were determined using standardized methods and the dietary Mg intake by prospective 72 h dietary surveys. The mean serum Ca (2.45 mmol/L) and Mg (0.82 mmol/L) had normal levels, and the mean dietary intake of the Ca (127% DRI: Dietary Reference Intake) and Mg (125% DRI) were high. No patients had an abnormal serum Ca. A total of 47% of the subjects had hypomagnesemia and 12% insufficient Mg consumption. One patient had a serum Mg deficiency and inadequate Mg intake. A total of 47 and 82% of our series had a high serum Ca/Mg ratio of >4.70 (mean 4.89) and a low Ca/Mg intake ratio of <1.70 (mean 1.10), respectively. The likelihood of a high Ca/Mg ratio was 49 times higher in patients with a serum Mg deficiency than in normal serum Mg patients. Both Ca/Mg ratios were associated with the risk of developing cardiovascular disease (CVD), type 2 diabetes (T2D), metabolic syndrome (MetS), and even several cancers. Therefore, 53% of the CF patients were at high risk of a Mg deficiency and developing other chronic diseases. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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8 pages, 802 KiB  
Article
Magnesium-to-Calcium Ratio and Mortality from COVID-19
by Fernando Guerrero-Romero, Moises Mercado, Martha Rodriguez-Moran, Claudia Ramírez-Renteria, Gerardo Martínez-Aguilar, Daniel Marrero-Rodríguez, Aldo Ferreira-Hermosillo, Luis E. Simental-Mendía, Ilan Remba-Shapiro, Claudia I. Gamboa-Gómez, Alejandra Albarrán-Sánchez and Miriam L. Sanchez-García
Nutrients 2022, 14(9), 1686; https://doi.org/10.3390/nu14091686 - 19 Apr 2022
Cited by 16 | Viewed by 5022
Abstract
Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to [...] Read more.
Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6–29.1) in the whole population, 4.93 (95%CI 1.4–19.1, p = 0.003) in men, and 3.93 (95%CI 1.6–9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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10 pages, 990 KiB  
Article
Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials
by Nicola Veronese, Damiano Pizzol, Lee Smith, Ligia J. Dominguez and Mario Barbagallo
Nutrients 2022, 14(3), 679; https://doi.org/10.3390/nu14030679 - 05 Feb 2022
Cited by 26 | Viewed by 11067
Abstract
Magnesium (Mg) may have several beneficial effects on human health outcomes. One hypothesized mechanism eliciting such effects is the action of Mg on serum inflammatory parameters. However, studies on this topic to date have several important limitations. Therefore, the present systematic review and [...] Read more.
Magnesium (Mg) may have several beneficial effects on human health outcomes. One hypothesized mechanism eliciting such effects is the action of Mg on serum inflammatory parameters. However, studies on this topic to date have several important limitations. Therefore, the present systematic review and meta-analysis aimed to summarize the current state of the art of all randomized control trials (RCTs) investigating the effects of Mg supplementation versus placebo on serum parameters of inflammation. We searched several databases until 23 November 2021 for RCTs. Eligible studies were RCTs investigating the effect of oral Mg supplementation vs. placebo and having serum inflammatory markers as an outcome. Among 2484 papers initially screened, 17 randomized controlled trials (889 participants; mean age: 46 years; females: 62.5%) were included. Generally, a low risk of bias was present. In meta-analysis, Mg supplementation significantly decreased serum C reactive protein (CRP) and increased nitric oxide (NO) levels. In descriptive findings, Mg supplementation significantly reduced plasma fibrinogen, tartrate-resistant acid phosphatase type 5, tumor necrosis factor-ligand superfamily member 13B, ST2 protein, and IL-1. In conclusion, Mg supplementation may significantly reduce different human inflammatory markers, in particular serum CRP and NO levels. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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9 pages, 472 KiB  
Article
Associations of Serum Magnesium with Brain Morphology and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities-Neurocognitive Study
by Aniqa B. Alam, DaNashia S. Thomas, Pamela L. Lutsey, Srishti Shrestha and Alvaro Alonso
Nutrients 2021, 13(12), 4496; https://doi.org/10.3390/nu13124496 - 16 Dec 2021
Cited by 4 | Viewed by 2921
Abstract
Circulating magnesium has been associated with a lower risk of dementia, but the physiologic effects by which magnesium may prevent neurological insults remain unclear. We studied 1466 individuals (mean age 76.2 ± 5.3, 28.8% black, 60.1% female) free of prevalent stroke, with measured [...] Read more.
Circulating magnesium has been associated with a lower risk of dementia, but the physiologic effects by which magnesium may prevent neurological insults remain unclear. We studied 1466 individuals (mean age 76.2 ± 5.3, 28.8% black, 60.1% female) free of prevalent stroke, with measured serum magnesium and with available MRI scans obtained in 2011–2013, participating in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Cross-sectional differences in frontal, temporal, parietal, and occipital lobe volume, along with deep grey matter, total brain, and white matter hyperintensity volume across serum magnesium (categorized into quintiles and per standard deviation increases) were assessed using multiple linear regression. We also examined associations of magnesium with the prevalence of cortical, subcortical, and lacunar infarcts using multiple logistic regression. After adjusting for demographics, biomarkers, medications, and cardiometabolic risk factors, higher circulating magnesium was associated with greater total brain volume and frontal, temporal, and parietal lobe volumes (volumes 0.14 to 0.19 standard deviations higher comparing Q5 to Q1). Elevated magnesium was also associated with lower odds of subcortical infarcts (OR (95%CI): 0.44 (0.25, 0.77) comparing Q5 to Q1) and lacunar infarcts (OR (95%CI): 0.40 (0.22, 0.71) comparing Q5 to Q1). Elevated serum magnesium was cross-sectionally associated with greater brain volumes and lower odds of subclinical cerebrovascular disease, suggesting beneficial effects on pathways related to neurodegeneration and cerebrovascular damage. Further exploration through prospective analyses is needed to assess increasing circulating magnesium as a potential neuroprotective intervention. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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11 pages, 791 KiB  
Article
Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
by Nicola Veronese, Ligia J. Dominguez, Damiano Pizzol, Jacopo Demurtas, Lee Smith and Mario Barbagallo
Nutrients 2021, 13(11), 4074; https://doi.org/10.3390/nu13114074 - 15 Nov 2021
Cited by 16 | Viewed by 11069
Abstract
There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of diabetes. We therefore aimed to investigate the effect of oral Mg supplementation on glucose [...] Read more.
There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of diabetes. We therefore aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes, compared with a placebo. Several databases were searched investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or conditions at high risk of diabetes. Data were reported as standardized mean differences (SMDs) with their 95% confidence intervals (CIs) using follow-up data of glucose and insulin-sensitivity parameters. Compared with placebo, Mg supplementation reduced fasting plasma glucose in people with diabetes. In people at high risk of diabetes, Mg supplementation significantly improved plasma glucose per se, and after a 2 h oral glucose tolerance test. Furthermore, Mg supplementation demonstrated an improvement in insulin sensitivity markers. In conclusion, Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes. Moreover, our work indicates that Mg supplementation may improve insulin-sensitivity parameters in those at high risk of diabetes. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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Review

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29 pages, 1509 KiB  
Review
The Role of Magnesium in the Pathogenesis of Metabolic Disorders
by Marta Pelczyńska, Małgorzata Moszak and Paweł Bogdański
Nutrients 2022, 14(9), 1714; https://doi.org/10.3390/nu14091714 - 20 Apr 2022
Cited by 32 | Viewed by 11668
Abstract
Magnesium (Mg) is an essential nutrient for maintaining vital physiological functions. It is involved in many fundamental processes, and Mg deficiency is often correlated with negative health outcomes. On the one hand, most western civilizations consume less than the recommended daily allowance of [...] Read more.
Magnesium (Mg) is an essential nutrient for maintaining vital physiological functions. It is involved in many fundamental processes, and Mg deficiency is often correlated with negative health outcomes. On the one hand, most western civilizations consume less than the recommended daily allowance of Mg. On the other hand, a growing body of evidence has indicated that chronic hypomagnesemia may be implicated in the pathogenesis of various metabolic disorders such as overweight and obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM), hypertension (HTN), changes in lipid metabolism, and low-grade inflammation. High Mg intake with diet and/or supplementation seems to prevent chronic metabolic complications. The protective action of Mg may include limiting the adipose tissue accumulation, improving glucose and insulin metabolism, enhancing endothelium-dependent vasodilation, normalizing lipid profile, and attenuating inflammatory processes. Thus, it currently seems that Mg plays an important role in developing metabolic disorders associated with obesity, although more randomized controlled trials (RCTs) evaluating Mg supplementation strategies are needed. This work represents a review and synthesis of recent data on the role of Mg in the pathogenesis of metabolic disorders. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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18 pages, 1009 KiB  
Review
Magnesium Orotate and the Microbiome–Gut–Brain Axis Modulation: New Approaches in Psychological Comorbidities of Gastrointestinal Functional Disorders
by Cristina Schiopu, Gabriela Ștefănescu, Smaranda Diaconescu, Gheoghe G. Bălan, Nicoleta Gimiga, Elena Rusu, Cosmin Alec Moldovan, Bogdan Popa, Elena Tataranu, Andrei Vasile Olteanu, Alexandra Boloș and Cristinel Ștefănescu
Nutrients 2022, 14(8), 1567; https://doi.org/10.3390/nu14081567 - 09 Apr 2022
Cited by 10 | Viewed by 7409
Abstract
Magnesium orotate has been cited in the medical literature for the past three years as a possible adjuvant in some pediatric and adult gastroenterological disorders associated with dysbiosis. Studies also focus on the possibility of adding magnesium orotate in psychiatric disorders’ treatment, such [...] Read more.
Magnesium orotate has been cited in the medical literature for the past three years as a possible adjuvant in some pediatric and adult gastroenterological disorders associated with dysbiosis. Studies also focus on the possibility of adding magnesium orotate in psychiatric disorders’ treatment, such as major depression and anxiety. The most relevant element in these studies is the efficiency of magnesium orotate therapy in cases with both gastroenterological and psychiatric symptoms. This article proposes a literature review, focused on the studies published in the last three years, targeting magnesium orotate treatment and probiotic supplementation in patients with both digestive and psychiatric symptoms. Moreover, this review will compare the efficiency of magnesium orotate and probiotics within both the pediatric and adult communities, focusing on the possibility of gut–brain axis modulation and its involvement in the clinical evolution of these patients. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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12 pages, 475 KiB  
Review
Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine—From Theory to Practice
by Izabela Domitrz and Joanna Cegielska
Nutrients 2022, 14(5), 1089; https://doi.org/10.3390/nu14051089 - 05 Mar 2022
Cited by 16 | Viewed by 12330
Abstract
So far, no coherent and convincing theory has been developed to fully explain the pathogenesis of migraine, although many researchers and experts emphasize its association with spreading cortical depression, oxidative stress, vascular changes, nervous excitement, neurotransmitter release, and electrolyte disturbances. The contribution of [...] Read more.
So far, no coherent and convincing theory has been developed to fully explain the pathogenesis of migraine, although many researchers and experts emphasize its association with spreading cortical depression, oxidative stress, vascular changes, nervous excitement, neurotransmitter release, and electrolyte disturbances. The contribution of magnesium deficiency to the induction of cortical depression or abnormal glutamatergic neurotransmission is a likely mechanism of the magnesium–migraine relationship. Hence, there is interest in various methods of assessing magnesium ion deficiency and attempts to study the relationship of its intra- and extracellular levels with the induction of migraine attacks. At the same time, many clinicians believe that magnesium supplementation in the right dose and form can be a treatment to prevent migraine attacks, especially in those patients who have identified contraindications to standard medications or their different preferences. However, there are no reliable publications confirming the role of magnesium deficiency in the diet as a factor causing migraine attacks. It also seems interesting to deepen the research on the administration of high doses of magnesium intravenously during migraine attacks. The aim of the study was to discuss the probable mechanisms of correlation of magnesium deficiency with migraine, as well as to present the current clinical proposals for the use of various magnesium preparations in complementary or substitute pharmacotherapy of migraine. The summary of the results of research and clinical observations to date gives hope of finding a trigger for migraine attacks (especially migraine with aura), which may turn out to be easy to diagnose and eliminate with pharmacological and dietary supplementation. Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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2 pages, 216 KiB  
Reply
Reply to Scarpati, G.; Piazza, O. Comment on “Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686”
by Fernando Guerrero-Romero, Moises Mercado, Martha Rodríguez-Morán, Claudia Ramírez-Renteria, Gerardo Martínez-Aguilar, Daniel Marrero-Rodríguez, Aldo Ferreira-Hermosillo, Luis E. Simental-Mendía, Ilan Remba-Shapiro, Claudia I. Gamboa-Gómez, Alejandra Albarrán-Sánchez and Miriam L. Sanchez-García
Nutrients 2022, 14(16), 3443; https://doi.org/10.3390/nu14163443 - 22 Aug 2022
Cited by 4 | Viewed by 1168
Abstract
We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...] Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
2 pages, 407 KiB  
Comment
Comment on Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686
by Giuliana Scarpati and Ornella Piazza
Nutrients 2022, 14(16), 3442; https://doi.org/10.3390/nu14163442 - 22 Aug 2022
Cited by 1 | Viewed by 1375
Abstract
We read with great interest the article by Romero et al. [...] Full article
(This article belongs to the Special Issue Magnesium: From In Vitro to Clinical Research)
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