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Xing L, Gong Y, Liao G, Wang L, Chen L. Association between magnesium depletion score and all-cause and cause-specific mortality in patients with diabetic kidney disease. Diabetol Metab Syndr 2025; 17:130. [PMID: 40247397 PMCID: PMC12007323 DOI: 10.1186/s13098-025-01688-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 04/01/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND The prognostic value of Magnesium Depletion Score (MDS) in Diabetic Kidney Disease (DKD) patients is still unclear. This study aimed to determine the associations between MDS and long-term mortality in DKD population. METHODS Data were obtained from the National Health and Nutrition Examination Survey (NHANES III). MDS is calculated from four specific scoring items: estimated glomerular filtration rate (eGFR), heavy drinking, use of proton pump inhibitors (PPI), and use of diuretics. Multivariate Cox proportional hazards regression models was employed to explore the association between MDS and all-cause and cause specific mortality, with emphasis on age-specific analysis.Mediation analysis explored if metabolic indices mediate the relation between MDS and mortality. Sensitive analyses were performed to check the robustness of the main findings. RESULTS 3,179 patients with DKD were included in this study, with 1,698 females and 1,481 males. The multivariate Cox regression analyses showed higher MDS were significantly associated with the all-cause mortality of DKD population [MDS ≥ 3: adjusted hazard ratio (HR):1.932, 95% confidence interval (CI): 1.339-2.787,p < 0.001]. Meanwhile, the trend was also significant in cardiovascular mortality of the DKD population (MDS ≥ 3: HR = 3.688, 95%CI: 1.702-8.577,p < 0.001). Heavy drinking was the most influential factor among the four MDS scoring items that affects mortality outcomes. Mediation analysis showed increased MDS could slightly improve metabolic levels, but the improvement was insufficient to reverse the mortality outcome in DKD patients. Subgroup analysis manifested that the result was more applicable for patients over 60. The result of the sensitive analysis confirmed the robustness of the main conclusion. CONCLUSIONS Our study highlights the clinical prognostic value of MDS in predicting the survival of the DKD population, especially among patients over 60. The findings imply that reducing alcohol consumption and performing routine cardiovascular health assessments for DKD patients with MDS > 2 are important for prolonging DKD patients' survival time.
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Affiliation(s)
- Lingzhi Xing
- Faculty of Pediatrics, Chongqing Medical University, Chongqing, China
- The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing, China
| | - Yubowen Gong
- The First Clinical College, Chongqing Medical University, Chongqing, China
- The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing, China
| | - GuoJia Liao
- Faculty of Pediatrics, Chongqing Medical University, Chongqing, China
- The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing, China
| | - Liying Wang
- Department of Laboratory, Chongqing General Hospital, Chongqing University, Chongqing, China.
| | - Ling Chen
- The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing, China.
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Zhou Z, Yao X. The kidney reabsorption-related magnesium depletion score is associated with cardiovascular disease and longitudinal mortality in diabetic kidney disease patients. Diabetol Metab Syndr 2025; 17:38. [PMID: 39881367 PMCID: PMC11776169 DOI: 10.1186/s13098-025-01598-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 01/15/2025] [Indexed: 01/31/2025] Open
Abstract
BACKGROUND The kidney reabsorption is essential for maintaining magnesium homeostasis. This study aims to explore the relationship between kidney reabsorption-related magnesium depletion score (MDS) and the occurrence of cardiovascular disease (CVD) and prognosis in diabetic disease kidney (DKD) patients. METHODS We included 3199 DKD patients from the National Health and Nutrition Examination Survey (NHANES) database, including 1072 CVD patients. Weighted logistic regression analysis was used to explore the relationship between MDS and the occurrence of CVD. Weighted COX proportional hazards regression was used to explore the relationship between MDS and mortality. Stratified analysis was used to further validate. Finally, we assessed the predictive accuracy of MDS on survival outcomes in DKD patients using time-dependent receiver operating characteristic (ROC) curve analysis. RESULTS Survey-weighted multiple logistic regression analysis revealed that MDS ≥ 3, the incidence of CVD increased by 371%. During the follow-up period (median of 87 months), 1373 all-cause deaths (497 cardiovascular deaths) were recorded. In DKD patients, MDS ≥ 3, all-cause mortality increased 78% (P < 0.001) and cardiac mortality 76% (P = 0.08). Consistent results were also shown when stratified by age, sex, race, marital status, magnesium intake. The area under the curve (AUC) values for predicting 1-,2-,3-,4-, and 5-year mortality using MDS were 0.86, 0.66, 0.59, 0.57, and 0.55, for all-cause mortality and 0.9, 0.67, 0.62, 0.58, and 0.56 for cardiovascular mortality. CONCLUSION MDS, kidney reabsorption-related, is positively correlated with the incidence of CVD and longitudinal mortality in DKD patients.
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Affiliation(s)
- Zhengxi Zhou
- Department of Urology, Ningbo Mingzhou Hospital, Zhejiang, China.
| | - Xiaotian Yao
- Department of Urology, Ningbo Mingzhou Hospital, Zhejiang, China.
- The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
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Cao X, Feng H, Wang H. Magnesium depletion score and gout: insights from NHANES data. Front Nutr 2024; 11:1485578. [PMID: 39639938 PMCID: PMC11617175 DOI: 10.3389/fnut.2024.1485578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024] Open
Abstract
Objectives Gout is associated with hyperuricemia, and serum magnesium levels are negatively correlated with uric acid levels. Magnesium intake is also associated with a reduced risk of hyperuricemia. However, the relationship between the magnesium depletion score (MDS), which represents the systemic magnesium status, and gout is unclear. This study was conducted to investigate the association between MDS and gout as well as explore the impact of dietary magnesium intake on this relationship. Methods We analyzed 18,039 adults with gout data who participated in the National Health and Nutrition Examination Survey between 2007 and 2016. Magnesium deficiency status was assessed using the MDS, a comprehensive scoring tool. Considering the possible effects of dietary magnesium intake, weighted multivariable logistic regression and subgroup analyses were used to assess the correlation between MDS and gout. Results The overall prevalence of gout among adults in the United States between 2007 and 2016 was 4.7%. After adjusting for confounders, MDS and gout risk showed a significant positive correlation. Individuals with an MDS of 2 and ≥ 3 had higher odds of gout than those with an MDS of 0 (MDS = 2, odds ratio: 1.86 [1.18-2.93], p = 0.008; MDS = 3, odds ratio: 2.17 [1.37-3.43], p = 0.001; p for trend <0.001). Dietary magnesium intake did not moderate the correlation between MDS and gout risk. Conclusion A positive correlation exists between magnesium deficiency, as quantified using the MDS, and gout risk among adults in the United States. Additionally, dietary magnesium intake did not alter this association.
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Affiliation(s)
- Xu Cao
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Haixia Feng
- Department of Tuberculosis, Shandong Public Health Clinical Center, Jinan, Shandong, China
| | - Huijie Wang
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, China
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González-Recio I, Goikoetxea-Usandizaga N, Rejano-Gordillo CM, Conter C, Rodríguez Agudo R, Serrano-Maciá M, Zapata-Pavas LE, Peña-Sanfélix P, Azkargorta M, Elortza F, Herranz JM, Guillamon Thiery Á, Guerra-Ruiz AR, Jover R, Galicia-Garcia U, Martín C, Schaeper U, Delgado TC, Díaz-Moreno I, Díaz Quintana A, Buccella D, Nogueiras R, Argemi J, Ávila MA, Gratacós-Ginès J, Iruzubieta P, Pose E, Bataller R, Crespo J, Martínez-Cruz LA, Martínez-Chantar ML. Modulatory effects of CNNM4 on protein- l -isoaspartyl- O -methyltransferase repair function during alcohol-induced hepatic damage. Hepatology 2024:01515467-990000000-01101. [PMID: 39641635 DOI: 10.1097/hep.0000000000001156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 10/17/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND AND AIMS Alcohol-associated liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence and liver transplantation. Chronic alcohol consumption has been linked to magnesium (Mg 2+ ) deficiency, which can influence liver disease progression. The mechanisms underlying Mg 2+ homeostasis dysregulation in ALD remain elusive. This study aimed to investigate the role of the Mg 2+ transporter Cyclin M4 (CNNM4) in ALD by analyzing its expression patterns in patients with ALD and preclinical animal models. APPROACH AND RESULTS In this study, CNNM4 is upregulated in the liver of both patients with ALD and animal models. CNNM4 overexpression triggers Mg 2+ homeostasis dysregulation, linked to ALD progression. We propose a novel therapeutic approach for ALD treatment using N -acetylgalactosamine silencing RNA technology to specifically modulate Cnnm4 expression in the liver, improving mitochondrial function and alleviating endoplasmic reticulum stress. Notably, silencing Cnnm4 restores protein isoaspartyl methyltransferase (PCMT1) activity, essential for repairing ethanol-induced protein damage. Enhancing mitochondrial activity through Cnnm4-dependent mechanisms increases S -adenosylmethionine levels, crucial for PCMT1 function, highlighting the interconnected roles of mitochondrial health and protein homeostasis in ALD treatment. CONCLUSIONS These findings shed light on the dysregulation of Mg 2+ homeostasis in ALD, providing a promising therapeutic approach targeting CNNM4. N -acetylgalactosamine si Cnnm4 therapy boosts the repair processes of ethanol-damaged proteins through the upregulation of PCMT1 activity.
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Affiliation(s)
- Irene González-Recio
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Naroa Goikoetxea-Usandizaga
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain
| | - Claudia M Rejano-Gordillo
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Extremadura, University Institute of Biosanitary Research of Extremadura (INUBE), Badajoz, Spain
- Biofisika Institute (UPV/EHU, CSIC), UPV/EHU Science Park, and Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country UPV/EHU, Leioa, Spain
| | - Carolina Conter
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Rubén Rodríguez Agudo
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Marina Serrano-Maciá
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Leidy Estefanía Zapata-Pavas
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Patricia Peña-Sanfélix
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Mikel Azkargorta
- Proteomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Félix Elortza
- Proteomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - José María Herranz
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Pamplona, Spain
| | - Álex Guillamon Thiery
- Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Catalonia, Spain
| | | | - Ramiro Jover
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain
- Experimental Hepatology Joint Research Unit, IIS Hospital La Fe & Dep. Biochemistry, University of Valencia, Valencia, Spain
| | - Unai Galicia-Garcia
- Biofisika Institute (UPV/EHU, CSIC), UPV/EHU Science Park, and Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country UPV/EHU, Leioa, Spain
| | - César Martín
- Biofisika Institute (UPV/EHU, CSIC), UPV/EHU Science Park, and Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country UPV/EHU, Leioa, Spain
| | - Ute Schaeper
- Silence Therapeutics GmbH, Berlin, Berlin, Germany
| | - Teresa C Delgado
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - Irene Díaz-Moreno
- Institute for Chemical Research (IIQ), Scientific Research Centre "Isla de la Cartuja" (cicCartuja), University of Seville-CSIC, Seville, Spain
| | - Antonio Díaz Quintana
- Departamento de Bioquímica Vegetal y Biologia Molecular, Facultad de Biología, Universidad de Sevilla, Sevilla, Spain
| | - Daniela Buccella
- Department of Chemistry, New York University, New York, New York, USA
| | - Rubén Nogueiras
- Molecular Metabolism Lab, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Av. Barcelona, Campus Vida, Santiago de Compostela University, Santiago de Compostela, Spain
| | - JosepMaria Argemi
- Hepatology Program, Centro de Investigación Médica Aplicada (CIMA), Liver Unit, Clinica Universidad de Navarra (CUN), Instituto de Investigación de Navarra (IdisNA), University of Navarra, Pamplona, Spain
- Division of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Matías A Ávila
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Pamplona, Spain
| | - Jordi Gratacós-Ginès
- Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Catalonia, Spain
| | - Paula Iruzubieta
- Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL, Santander, Spain
| | - Elisa Pose
- Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Catalonia, Spain
| | - Ramón Bataller
- Division of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Javier Crespo
- Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL, Santander, Spain
| | - Luis Alfonso Martínez-Cruz
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
| | - María Luz Martínez-Chantar
- Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain
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Wang X, Zeng Z, Wang X, Zhao P, Xiong L, Liao T, Yuan R, Yang S, Kang L, Liang Z. Magnesium Depletion Score and Metabolic Syndrome in US Adults: Analysis of NHANES 2003 to 2018. J Clin Endocrinol Metab 2024; 109:e2324-e2333. [PMID: 38366015 PMCID: PMC11570370 DOI: 10.1210/clinem/dgae075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 01/25/2024] [Accepted: 02/05/2024] [Indexed: 02/18/2024]
Abstract
CONTEXT The association between magnesium status and metabolic syndrome (MetS) remains unclear. OBJECTIVE This study aimed to examine the relationship between kidney reabsorption-related magnesium depletion score (MDS) and MetS among US adults. METHODS We analyzed data from 15 565 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003 to 2018. MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. Weighted univariate and multivariable logistic regression were used to assess the association between MDS and MetS. Restricted cubic spline (RCS) analysis was conducted to characterize dose-response relationships. Stratified analyses by sociodemographic and lifestyle factors were also performed. RESULTS In both univariate and multivariable analyses, higher MDS was significantly associated with increased odds of MetS. Each unit increase in MDS was associated with approximately a 30% higher risk for MetS, even after adjusting for confounding factors (odds ratio 1.31; 95% CI, 1.17-1.45). RCS graphs depicted a linear dose-response relationship across the MDS range. This positive correlation remained consistent across various population subgroups and exhibited no significant interaction by age, sex, race, adiposity, smoking status, or alcohol consumption. CONCLUSION Higher urinary magnesium loss as quantified by MDS may be an independent linear risk factor for MetS in US adults, irrespective of sociodemographic and behavioral factors. Optimizing magnesium nutritional status could potentially confer benefits to patients with MetS.
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Affiliation(s)
- Xiaohao Wang
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
| | - Zhaohao Zeng
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518055, China
| | - Xinyu Wang
- Department of Nephrology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China
| | - Pengfei Zhao
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
| | - Lijiao Xiong
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
| | - Tingfeng Liao
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
| | - Runzhu Yuan
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
| | - Shu Yang
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
| | - Lin Kang
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
| | - Zhen Liang
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen 518055, China
- Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518055, China
- Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518055, China
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Tissot FLH, Cleveland D, Grigoryan R, Kipp MA, Shafiee RT, Miaou E, Chunduri R, Melton H, Tacail T, Razionale D. Magnitude and timescales of Ca isotope variability in human urine: implications for bone mass balance monitoring. Metallomics 2024; 16:mfae050. [PMID: 39504495 DOI: 10.1093/mtomcs/mfae050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 10/30/2024] [Indexed: 11/08/2024]
Abstract
Calcium (Ca) isotopes in blood/urine are emerging biomarkers of bone mineral balance (BMB) in the human body. While multiple studies have investigated Ca isotopes in patients suffering from diseases affecting BMB, comparatively little effort has been devoted to understanding the homeostasis of Ca isotopes in healthy individuals. Here, we report on a longitudinal study of the urine Ca isotope composition (δ44/42CaUrine) from 22 healthy participants (age 19-60) over timescales ranging from days to months. Data from a single participant collected over a 30-day period show that morning urine is an excellent proxy for 24-h pooled urine fractions. Data from all participants reveal large inter-individual variability in δ44/42CaUrine (up to 2.2‰), which is partly due to anthropometric differences, as shown by a correlation between the participants' body mass index (BMI) and δ44/42CaUrine values. In contrast, intra-individual data reveal encouraging stability (within ∼±0.2-0.3‰) over timescales >160 days, indicating that self-referencing approaches for BMB monitoring hold greater promise than cross-sectional ones. Our data confirm that intra-individual δ44/42CaUrine variations are mainly a function of Ca reabsorption in the kidney, but also reveal the impact of other (and at times equally important) drivers, such as diet, alcohol consumption, physical exercise, or fasting. We also find that a magnetic resonance imaging contrast agent (gadolinium) can lead to artifacts during Ca isotope analysis. Based on our results, a series of practical considerations for the use of Ca isotopes in urine as tracers of BMB are presented.
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Affiliation(s)
- François L H Tissot
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Dylan Cleveland
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Rosa Grigoryan
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Michael A Kipp
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Roxana T Shafiee
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Emily Miaou
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Rithika Chunduri
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Hayward Melton
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Theo Tacail
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
| | - Dan Razionale
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, United States
- Department of Earth, Environmental and Planetary Sciences, Brown University, Providence, RI 02912, United States
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Shringi S, Raker CA, Chonchol M, Tang J. Alcohol Intake and Prevalent Kidney Stone: The National Health and Nutrition Examination Survey 2007-2018. Nutrients 2024; 16:2928. [PMID: 39275244 PMCID: PMC11397207 DOI: 10.3390/nu16172928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 08/23/2024] [Accepted: 08/29/2024] [Indexed: 09/16/2024] Open
Abstract
The association of alcohol intake with kidney stone disease (KSD) is not clear based on current clinical evidence. We examined the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and used logistic regression analyses to determine the independent association between alcohol intake and prevalent KSD. In total, 29,684 participants were eligible for the final analysis, including 2840 prevalent stone formers (SFs). The mean alcohol intake was 37.0 ± 2.4 g/day among SFs compared to 42.7 ± 0.9 among non-SFs (p = 0.04). Beer [odds ratio (OR) = 0.76, 95% CI: 0.61-0.94, p = 0.01] and wine (OR = 0.75, 95% CI: 0.59-0.96, p = 0.03) intakes were strongly associated with lower odds of prevalent KSD, while liquor intake had no association. Furthermore, the effects of beer and wine intakes on stone formation were dose-dependent. The OR for comparing participants drinking 1-14 g/day of beer to non-drinkers was 1.41 (95%CI: 0.97-2.05, p = 0.07), that of >14-≤28 g/day of beer to non-drinkers was 0.65 (95% CI: 0.42-1.00, p = 0.05), that of >28-≤56 g/day of beer to non-drinkers was 0.60 (95% CI: 0.39-0.93, p = 0.02), and that of >56 g/day of beer to non-drinkers was 0.34 (95% CI: 0.20-0.57, p < 0.001). Interestingly, the effect of wine intake was only significant among participants drinking moderate amounts (>14-28 g/day), with an OR of 0.54 (95% CI: 0.36-0.81, p = 0.003) compared to non-drinkers, but this effect was lost when comparing low-level (1-14 g/day) and heavy (>28 g/day) wine drinkers to non-drinkers. These effects were consistent in spline models. This study suggests that both moderate to heavy beer intake and moderate wine intake are associated with a reduced risk of KSD. Future prospective studies are needed to clarify the causal relationship.
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Affiliation(s)
- Sandipan Shringi
- Division of Kidney Diseases and Hypertension, Alpert Medical School of Brown University, Providence, RI 02903, USA
| | - Christina A Raker
- Lifespan Biostatistics, Epidemiology, Research Design, and Informatics Core, Providence, RI 02903, USA
| | - Michel Chonchol
- Division of Kidney Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Jie Tang
- Division of Kidney Diseases and Hypertension, Alpert Medical School of Brown University, Providence, RI 02903, USA
- Division of Kidney Diseases and Hypertension, Department of Medicine, Brown Physicians Inc., 375 Wampanoag Trail, East Providence, RI 02915, USA
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8
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Ansu Baidoo VY, Cara KC, Dickinson SL, Brown AW, Wallace TC, Chung M, Gletsu-Miller N. Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations. J Nutr 2023; 153:3458-3471. [PMID: 37844840 DOI: 10.1016/j.tjnut.2023.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 09/14/2023] [Accepted: 10/03/2023] [Indexed: 10/18/2023] Open
Abstract
BACKGROUND There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.
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Affiliation(s)
| | - Kelly C Cara
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States
| | - Stephanie L Dickinson
- School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Andrew W Brown
- University of Arkansas for Medical Sciences, Little Rock, AR, United States; Arkansas Children's Research Institute, Little Rock, AR, United States
| | - Taylor C Wallace
- Department of Nutrition and Food Studies, George Mason University, Fairfax, VA, United States; Think Healthy Group, Inc., Washington, DC, United States; Center for Magnesium Education & Research, Pahoa, HI, United States
| | - Mei Chung
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States
| | - Nana Gletsu-Miller
- School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States.
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9
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Sullivan KV, Assantuh Y, Grigoryan R, Costas-Rodríguez M, Bolea-Fernandez E, Lapauw B, Van Laecke S, Vanhaecke F. Serum Mg Isotopic Composition Reveals That Mg Dyshomeostasis Remains in Type 1 Diabetes despite the Resolution of Hypomagnesemia. Int J Mol Sci 2023; 24:15683. [PMID: 37958667 PMCID: PMC10647222 DOI: 10.3390/ijms242115683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/23/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
Hypomagnesemia was historically prevalent in individuals with type 1 diabetes mellitus (T1DM), but contemporary results indicate an incidence comparable to that in the general population, likely due to improved treatment in recent decades, resulting in better glycemic control. However, a recent study found a significant difference between the serum Mg isotopic composition of T1DM individuals and controls, indicating that disruptions to Mg homeostasis persist. Significant deviations were also found in samples taken one year apart. To investigate whether the temporal variability in serum Mg isotopic composition is linked to the transient impact of administered insulin, Mg isotope ratios were determined in serum from 15 T1DM individuals before and one hour after insulin injection/meal consumption using multi-collector inductively coupled plasma-mass spectrometry. Consistent with results of the previous study, significant difference in the serum Mg isotopic composition was found between T1DM individuals and 10 sex-matched controls. However, the average difference between pre- and post-insulin injection/meal T1DM samples of 0.05 ± 0.13‱ (1SD) was not significant. No difference was observed for controls before (-0.12 ± 0.16‱) and after the meal (-0.10 ± 0.13‱) either, suggesting a lack of a postprandial Mg isotopic response within one hour of food consumption, and that the timing of the most recent meal may not require controlling for when determining serum Mg isotopic composition.
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Affiliation(s)
- Kaj Vaughan Sullivan
- Atomic and Mass Spectrometry—A&MS Research Unit, Department of Chemistry, Ghent University, 9000 Ghent, Belgium; (K.V.S.)
| | - Yasmina Assantuh
- Atomic and Mass Spectrometry—A&MS Research Unit, Department of Chemistry, Ghent University, 9000 Ghent, Belgium; (K.V.S.)
| | - Rosa Grigoryan
- The Isotoparium, Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA
| | - Marta Costas-Rodríguez
- Atomic and Mass Spectrometry—A&MS Research Unit, Department of Chemistry, Ghent University, 9000 Ghent, Belgium; (K.V.S.)
- Centro de Investigación Mariña, Departamento de Química Analítica y Alimentaria, Grupo QA2, Universidade de Vigo, 36310 Vigo, Spain
| | - Eduardo Bolea-Fernandez
- Atomic and Mass Spectrometry—A&MS Research Unit, Department of Chemistry, Ghent University, 9000 Ghent, Belgium; (K.V.S.)
- Department of Analytical Chemistry, Aragón Institute of Engineering Research (I3A), University of Zaragoza, 50009 Zaragoza, Spain
| | - Bruno Lapauw
- Department of Endocrinology, Ghent University Hospital, 9000 Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, 9000 Ghent, Belgium
| | - Steven Van Laecke
- Renal Division, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Ghent, Belgium
| | - Frank Vanhaecke
- Atomic and Mass Spectrometry—A&MS Research Unit, Department of Chemistry, Ghent University, 9000 Ghent, Belgium; (K.V.S.)
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10
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Lu J, Li H, Wang S. The kidney reabsorption-related Magnesium Depletion Score is associated with increased likelihood of abdominal aortic calcification among US adults. Nephrol Dial Transplant 2022; 38:1421-1429. [PMID: 35881469 DOI: 10.1093/ndt/gfac218] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Kidney reabsorption has a vital role in magnesium homeostasis. This study aimed to determine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and abdominal aortic calcification (AAC). METHODS We obtained the data of 2640 individuals from the National Health and Nutrition Examination Survey (NHANES) database and analyzed the relationship between MDS and AAC scores. MDS is a scoring system developed to predict status of magnesium deficiency that fully considered the pathophysiological factors influencing the kidneys' reabsorption capability. AAC was quantified by the Kauppila score system based on dual-energy X-ray absorptiometry. We performed stratified analysis and multiple equation regression analysis. R and EmpowerStats were used for data analysis. RESULTS A total of 2640 participants were included with the mean AAC score of 1.47 ± 0.07. Participants in higher MDS tended to have higher AAC scores (MDS scored 0: 0.75 (0.56, 0.93), MDS scored 1: 1.02 (0.84, 1.21), MDS scored 2: 2.34 (1.80, 2.87), MDS scored 3: 3.19 (2.46, 3.92), MDS ≥ 4: 4.99 (3.49, 6.49)). Compared with those in the lowest MDS scored 0, the highest subgroup (MDS ≥ 4) was associated with a higher AAC score (β = 4.24, 95% CI: 2.78-5.70, p < 0.001), and the association was not altered (β = 1.81, 95% CI: 0.54-3.09, p = 0.002) after adjusting for numerous covariates. Subgroup analyses showed that stronger associations between MDS and AAC score were detected in adults with lower levels of magnesium intake and older (all p for interaction < 0.05). CONCLUSIONS The MDS is a promising tool for identifying individuals with magnesium deficiency status who may benefit from dietary magnesium supplementation to reduce the risks of AAC.
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Affiliation(s)
- Jian Lu
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Han Li
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Shixiang Wang
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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11
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Wang J, Xing F, Sheng N, Xiang Z. Associations of the Dietary Magnesium Intake and Magnesium Depletion Score With Osteoporosis Among American Adults: Data From the National Health and Nutrition Examination Survey. Front Nutr 2022; 9:883264. [PMID: 35711538 PMCID: PMC9194572 DOI: 10.3389/fnut.2022.883264] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 05/06/2022] [Indexed: 11/25/2022] Open
Abstract
Objectives The study aimed to explore the associations between dietary magnesium (Mg) intake and magnesium depletion score (MDS) among American adults with osteoporosis. Methods The continuous data from the National Health and Nutrition Examination Survey 2005–2006, 2007–2008, 2009–2010, 2013–2014, and 2017–2018 were merged to ensure a large and representative sample and a total of 14,566 participants were enrolled for the analysis. The weighted multivariate linear regression model was performed to assess the linear relationship between dietary Mg intake and osteoporosis. Further, the non-linear relationship was also characterized by smooth curve fitting (SCF) and weighted generalized additive model (GAM). In addition, the odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between the MDS and osteoporosis were assessed by weighted logistic regression models. Results After adjusting all covariates, the weighted multivariable linear regression models demonstrated that the dietary Mg intake negatively correlated with osteoporosis, especially in participants aged 55 years or older. In addition, the non-linear relationship characterized by SCF and weighted GAM showed that the dietary Mg intake presented an L-shaped association with osteoporosis among females aged 55 years or older. Moreover, the weighted logistic regression model demonstrated that compared with MDS 0, the OR between MDS ≥3 and osteoporosis was 2.987 (95% CI 1.904, 4.686) in the male-middle intake group. Moreover, compared with MDS 0, the ORs between MDS ≥3 and osteoporosis was 5.666 (95% CI 3.188, 10.069) in the female-low intake group and 1.691 (95% CI 1.394, 2.051) in the female-middle intake group. Conclusion The present study indicated that in people with a daily intake of Mg level below the recommended daily intake (RDI), the dietary Mg intake and Mg bioavailability represented by MDS have a negative correlation with osteoporosis. According to the results, the combination of MDS and dietary Mg intake may be more comprehensive and rigorous in screening the population with osteoporosis. Therefore, early monitoring and interventions for osteoporosis may be necessary for those with insufficient dietary Mg intake or high MDS scores.
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12
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Al Alawi AM, Berhane T, Majoni SW, Falhammar H. Patients characteristics and health outcomes in patients hospitalized with hypomagnesemia: a retrospective study from a single center in the Northern Territory of Australia. Intern Med J 2021; 52:1544-1553. [PMID: 34219349 DOI: 10.1111/imj.15442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 06/19/2021] [Accepted: 06/23/2021] [Indexed: 11/27/2022]
Abstract
AIM This research aimed to study the clinical and biochemical characteristics and health outcomes of patients admitted and found to have hypomagnesemia in an Australian hospital with a high proportion of Indigenous Australians. METHODS A retrospective cohort study was conducted of all patients with hypomagnesemia hospitalised between 1st August 2008 and 31st December 2014 at Royal Darwin Hospital (RDH). All relevant demographic, clinical, and biochemical were collected from patients' medical records. The hospital database was reviewed in January 2018 for mortality of all included patients. RESULTS 876 patients had been admitted with a confirmed diagnosis of hypomagnesemia during the study period, with mean follow up period of 4.0 ±2.7 years. The mean age at admission was 52.4 ± 19.1 years, 52.2% were females and, 56.5% were Indigenous Australians. Chronic kidney disease (99.7%), excessive alcohol consumption (45.7%), hypertension (43.9%), and respiratory diseases (15.0%) were the most common conditions in these patients. Hypomagnesemia was associated with prolonged length of hospital stay. Most patients did not receive treatment for hypomagnesaemia during admission. During the follow-up period, 38.6% of patients died, and the most common causes of death were malignancies (29.9%). CONCLUSION Hypomagnesemia was a common and under-treated condition in hospitalised patients and was associated with poor health outcomes. Therefore, hospitals should develop guidelines for replacing and monitoring magnesium levels during hospitalisation, achieving better outcomes. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Abdullah M Al Alawi
- Department of Medicine, Sultan Qaboos University Hospital, Muscat, Oman.,Division of Medicine, Royal Darwin Hospital, Darwin, NT, Australia
| | - Thomas Berhane
- Division of Medicine, Royal Darwin Hospital, Darwin, NT, Australia
| | - Sandawana William Majoni
- Division of Medicine, Royal Darwin Hospital, Darwin, NT, Australia.,Northern Territory Medical Program, Flinders University School of Medicine, Darwin, NT, Australia.,Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
| | - Henrik Falhammar
- Division of Medicine, Royal Darwin Hospital, Darwin, NT, Australia.,Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Stockholm, Sweden.,Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.,Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
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13
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Fan L, Zhu X, Rosanoff A, Costello RB, Yu C, Ness R, Seidner DL, Murff HJ, Roumie CL, Shrubsole MJ, Dai Q. Magnesium Depletion Score (MDS) Predicts Risk of Systemic Inflammation and Cardiovascular Mortality among US Adults. J Nutr 2021; 151:2226-2235. [PMID: 34038556 PMCID: PMC8349125 DOI: 10.1093/jn/nxab138] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/17/2021] [Accepted: 04/20/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Kidney reabsorption of magnesium (Mg) is essential for homeostasis. OBJECTIVES We developed and validated models with the kidney reabsorption-related magnesium depletion score (MDS) to predict states of magnesium deficiency and disease outcomes. METHODS MDS was validated in predicting body magnesium status among 77 adults (aged 62 ± 8 y, 51% men) at high risk of magnesium deficiency in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169) using the magnesium tolerance test (MTT). We then validated MDS for risk stratification and for associations with inflammation and mortality among >10,000 US adults (weighted: aged 48 ± 0.3 y, 47% men) in the NHANES, a nationally representative study. A proportional hazards regression model was used for associations between magnesium intake and the MDS with risks of total and cardiovascular disease (CVD) mortality. RESULTS In the PPCCT, the area under the receiver operating characteristic (ROC) curve (AUC) for magnesium deficiency was 0.63 (95% CI: 0.50, 0.76) for the model incorporating the MDS with sex and age compared with 0.53 (95% CI: 0.40, 0.67) for the model with serum magnesium alone. In the NHANES, mean serum C-reactive protein significantly increased with increasing MDS (P-trend < 0.01) after adjusting for age and sex and other covariates, primarily among individuals with magnesium intake less than the Estimated Average Requirement (EAR; P-trend < 0.05). Further, we found that low magnesium intake was longitudinally associated with increased risks of total and CVD mortality only among those with magnesium deficiency predicted by MDS. MDS was associated with increased risks of total and CVD mortality in a dose-response manner only among those with magnesium intake less than the EAR. CONCLUSIONS The MDS serves as a promising measure in identifying individuals with magnesium deficiency who may benefit from increased intake of magnesium to reduce risks of systemic inflammation and CVD mortality. This lays a foundation for precision-based nutritional interventions.
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Affiliation(s)
- Lei Fan
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Xiangzhu Zhu
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andrea Rosanoff
- Center for Magnesium Education and Research (CMER), Pahoa, HI, USA
| | | | - Chang Yu
- Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Reid Ness
- Department of Medicine, Division of Gastroenterology, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Douglas L Seidner
- Center for Human Nutrition, Department of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgical Institute, Cleveland Clinic, OH, USA
| | - Harvey J Murff
- Veterans Health Administration–Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA
| | - Christianne L Roumie
- Veterans Health Administration–Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA
| | - Martha J Shrubsole
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Qi Dai
- Address correspondence to QD (e-mail: )
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14
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Vatsalya V, Gala KS, Mishra M, Schwandt ML, Umhau J, Cave MC, Parajuli D, Ramchandani VA, McClain CJ. Lower Serum Magnesium Concentrations are associated With Specific Heavy Drinking Markers, Pro-Inflammatory Response and Early-Stage Alcohol-associated Liver Injury§. Alcohol Alcohol 2020; 55:164-170. [PMID: 32047901 DOI: 10.1093/alcalc/agaa001] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 12/16/2019] [Accepted: 01/23/2020] [Indexed: 12/11/2022] Open
Abstract
AIM Chronic heavy alcohol intake frequently causes liver inflammation/injury, and altered mineral metabolism may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking, changes in serum magnesium levels and biochemical evidence of liver injury in alcohol-use-disorder (AUD) patients who had no clinical signs or symptoms of liver injury. We also aimed to identify any sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. METHODS 114 heavy drinking alcohol-dependent (AD) female and male patients aged 21-65 years without clinical manifestations of liver injury, who were admitted to an alcohol treatment program, were grouped by alanine aminotransaminase (ALT) levels: ≤ 40 IU/L, as no liver injury (GR.1), and ALT>40 IU/L as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic biochemistry results, fatty acid panel, serum magnesium and drinking history data were collected at admission; and study-specific measures were evaluated. RESULTS In all AD patients, lower magnesium was significantly associated with the heavy drinking marker and heavy drinking days past 90 days (HDD90). A lower serum magnesium concentration was observed in AD patients with mild liver injury. Females of both groups had mean levels of magnesium in the deficient range. A clinically significant drop in magnesium levels was observed only in the GR.2 (mild liver injury) male AD patients. Females showed a significant association between low magnesium levels and the ω6:ω3 polyunsaturated fatty acids (PUFAs) ratio. CONCLUSIONS Specific heavy drinking markers showed an association with lower magnesium levels. Low serum magnesium levels are common in subjects with AUD and appear to be associated with the onset of liver injury.
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Affiliation(s)
- Vatsalya Vatsalya
- Department of Medicine, University of Louisville, Louisville, KY, USA.,Robley Rex VA Medical Center, Louisville, KY, USA.,Hepatology and Toxicology Center, University of Louisville, Louisville, KY, USA.,Alcohol Research Center, University of Louisville, Louisville, KY, USA
| | - Khushboo S Gala
- Department of Medicine, University of Louisville, Louisville, KY, USA
| | - Maithili Mishra
- Department of Computer Engineering, University of Southern Florida, Tampa, FL, USA
| | - Melanie L Schwandt
- National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - John Umhau
- National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - Matthew C Cave
- Department of Medicine, University of Louisville, Louisville, KY, USA.,Robley Rex VA Medical Center, Louisville, KY, USA.,Hepatology and Toxicology Center, University of Louisville, Louisville, KY, USA.,Alcohol Research Center, University of Louisville, Louisville, KY, USA.,Department of Pharmacology and Toxicology, Louisville, KY, USA
| | - Dipendra Parajuli
- Department of Medicine, University of Louisville, Louisville, KY, USA.,Robley Rex VA Medical Center, Louisville, KY, USA
| | | | - Craig J McClain
- Department of Medicine, University of Louisville, Louisville, KY, USA.,Robley Rex VA Medical Center, Louisville, KY, USA.,Hepatology and Toxicology Center, University of Louisville, Louisville, KY, USA.,Alcohol Research Center, University of Louisville, Louisville, KY, USA.,Department of Pharmacology and Toxicology, Louisville, KY, USA
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15
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Wu J, Meng QH. Current understanding of the metabolism of micronutrients in chronic alcoholic liver disease. World J Gastroenterol 2020; 26:4567-4578. [PMID: 32884217 PMCID: PMC7445863 DOI: 10.3748/wjg.v26.i31.4567] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 06/22/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) remains an important health problem worldwide. Perturbation of micronutrients has been broadly reported to be a common characteristic in patients with ALD, given the fact that micronutrients often act as composition or coenzymes of many biochemical enzymes responsible for the inflammatory response, oxidative stress, and cell proliferation. Mapping the metabolic pattern and the function of these micronutrients is a prerequisite before targeted intervention can be delivered in clinical practice. Recent years have registered a significant improvement in our understanding of the role of micronutrients on the pathogenesis and progression of ALD. However, how and to what extent these micronutrients are involved in the pathophysiology of ALD remains largely unknown. In the current study, we provide a review of recent studies that investigated the imbalance of micronutrients in patients with ALD with a focus on zinc, iron, copper, magnesium, selenium, vitamin D and vitamin E, and determine how disturbances in micronutrients relates to the pathophysiology of ALD. Overall, zinc, selenium, vitamin D, and vitamin E uniformly exhibited a deficiency, and iron demonstrated an elevated trend. While for copper, both an elevation and deficiency were observed from existing literature. More importantly, we also highlight several challenges in terms of low sample size, study design discrepancies, sample heterogeneity across studies, and the use of machine learning approaches.
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Affiliation(s)
- Jing Wu
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Qing-Hua Meng
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
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16
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Ismail A. Magnesium deficiency in perioperative and postoperative mortality and morbidity. Ann R Coll Surg Engl 2019; 101:536. [PMID: 31359760 DOI: 10.1308/rcsann.2017.0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Aaa Ismail
- Mid-Yorkshire Trust.,Leeds Teaching Hospitals, West Yorkshire, UK
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17
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Grochowski C, Blicharska E, Baj J, Mierzwińska A, Brzozowska K, Forma A, Maciejewski R. Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review. Molecules 2019; 24:E1361. [PMID: 30959950 PMCID: PMC6480471 DOI: 10.3390/molecules24071361] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 04/03/2019] [Accepted: 04/06/2019] [Indexed: 01/03/2023] Open
Abstract
The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.
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Affiliation(s)
- Cezary Grochowski
- Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
- Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, 20-090 Lublin, Poland
| | - Eliza Blicharska
- Department of Analitical Chemistry, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Aleksandra Mierzwińska
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland; (A.M.); (K.B.); aforma@o2pl (A.F.)
| | - Karolina Brzozowska
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland; (A.M.); (K.B.); aforma@o2pl (A.F.)
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland; (A.M.); (K.B.); aforma@o2pl (A.F.)
| | - Ryszard Maciejewski
- Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
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Marzec-Wróblewska U, Kamiński P, Łakota P, Szymański M, Wasilow K, Ludwikowski G, Jerzak L, Stuczyński T, Woźniak A, Buciński A. Human Sperm Characteristics with Regard to Cobalt, Chromium, and Lead in Semen and Activity of Catalase in Seminal Plasma. Biol Trace Elem Res 2019; 188:251-260. [PMID: 29959647 DOI: 10.1007/s12011-018-1416-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 12/12/2017] [Indexed: 11/25/2022]
Abstract
We analyzed cobalt (Co), chromium (Cr), and lead (Pb) concentrations in human semen and catalase CAT activity in seminal plasma and the effects of their relations on the sperm quality. We obtained semen samples from men (n = 168) undergoing routine infertility evaluation. Studies included two groups based on the ejaculate parameters: I (n = 39; normal ejaculate; normozoospermia); II (n = 129; pathological spermiogram). We examined relationships and differences between Co, Cr, and Pb concentrations in seminal plasma, CAT activity, and semen parameters. We did not establish differences in Co, Cr, and Pb concentrations and CAT activity from men between normozoospermic and those with pathological spermiogram. We found a significantly lower Co concentration and CAT activity in males with normal sperm motility than in asthenozoospermic males. We found significantly lower Co and a higher Pb concentration in males with normal morphology of spermatozoa than in teratozoospermic males. We found a significantly higher Pb concentration in the individuals with consumption of alcohol than in those without consumption. There were significant correlations between Co and Pb concentrations, sperm progressive motility (A + B, i.e., fast and slow progressive motility; Co-negatively; Pb-positively), and normal morphology of spermatozoa (Co-negatively; Pb-positively). We found a significant negative correlation between Cr concentration and slow progressive motility, and between CAT activity and volume of ejaculate. Co, Cr, and Pb levels and CAT activity were related to sperm characteristics and male fertility. The impact of alcohol may be manifested by a disturbance in Pb equilibrium in the body. Co and Pb influence progressive motility and normal morphology of human spermatozoa. Thus, Co and Pb levels in semen may be a useful diagnostic in male infertility. Most of the results of this study are in contrast to expectations. Namely, Pb is a toxic element and its harmful effects (poor semen quality) may be expected already at relatively low level of Pb exposure and are particularly visible with increasing of Pb. Co and Cr(III) are essential elements and harmful effects may be expected at their deficiency and/or overexposure.
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Affiliation(s)
- Urszula Marzec-Wróblewska
- Collegium Medicum in Bydgoszcz, Faculty of Medicine, Department of Medical and Biochemical Biology, Department of Ecology and Environmental Protection, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL, 85-094, Bydgoszcz, Poland
- Collegium Medicum in Bydgoszcz, Faculty of Pharmacy, Chair and Department of Biopharmacy, Nicolaus Copernicus University in Toruń, dr. A. Jurasz St. 2, PL, 85-089, Bydgoszcz, Poland
| | - Piotr Kamiński
- Collegium Medicum in Bydgoszcz, Faculty of Medicine, Department of Medical and Biochemical Biology, Department of Ecology and Environmental Protection, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL, 85-094, Bydgoszcz, Poland.
- Faculty of Biological Sciences, Department of Biotechnology, University of Zielona Góra, Prof. Szafran St. 1, PL, 65-516, Zielona Góra, Poland.
| | - Paweł Łakota
- Faculty of Animal Biology, Department of Animal Biotechnology, University of Technology and Life Sciences, Mazowiecka St. 28, 85-084, Bydgoszcz, Poland
| | - Marek Szymański
- Collegium Medicum in Bydgoszcz, Faculty of Medicine, University Hospital No. 2, Department of Obstetrics, Female Pathology and Oncological Gynecology, Nicolaus Copernicus University in Toruń, Ujejski St. 75, 85-168, Bydgoszcz, Poland
- NZOZ Medical Center Co. Prof. dr. hab. med. Wiesław Szymański, Dr. hab. med. Marek Szymański, Waleniowa St. 24, 85-435, Bydgoszcz, Poland
| | - Karolina Wasilow
- NZOZ Medical Center Co. Prof. dr. hab. med. Wiesław Szymański, Dr. hab. med. Marek Szymański, Waleniowa St. 24, 85-435, Bydgoszcz, Poland
- Collegium Medicum in Bydgoszcz, Faculty of Medicine, University Hospital No. 2, Family Medicine Clinic, Nicolaus Copernicus University in Toruń, Ujejski St. 75, 85-168, Bydgoszcz, Poland
| | - Grzegorz Ludwikowski
- Collegium Medicum in Bydgoszcz, Faculty of Medicine, University Hospital No. 2, Department of Clinical Andrology, Nicolaus Copernicus University in Toruń, Szpitalna St. 19, 85-092, Bydgoszcz, Poland
| | - Leszek Jerzak
- Faculty of Biological Sciences, Department of Nature Protection, University of Zielona Góra, Prof. Szafran St. 1, PL, 65-516, Zielona Góra, Poland
| | - Tomasz Stuczyński
- Faculty of Mathematics Informatics and Landscape Architecture, The John Paul II Catholic University of Lublin, Konstantynów 1 H, PL, 20-708, Lublin, Poland
| | - Alina Woźniak
- Collegium Medicum in Bydgoszcz, Department of Medical and Biochemical Biology, Nicolaus Copernicus University, Karłowicz St. 24, PL, 85-092, Bydgoszcz, Poland
| | - Adam Buciński
- Collegium Medicum in Bydgoszcz, Faculty of Pharmacy, Chair and Department of Biopharmacy, Nicolaus Copernicus University in Toruń, dr. A. Jurasz St. 2, PL, 85-089, Bydgoszcz, Poland
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Workinger JL, Doyle RP, Bortz J. Challenges in the Diagnosis of Magnesium Status. Nutrients 2018; 10:E1202. [PMID: 30200431 PMCID: PMC6163803 DOI: 10.3390/nu10091202] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 08/24/2018] [Accepted: 08/27/2018] [Indexed: 12/31/2022] Open
Abstract
Magnesium is a critical mineral in the human body and is involved in ~80% of known metabolic functions. It is currently estimated that 60% of adults do not achieve the average dietary intake (ADI) and 45% of Americans are magnesium deficient, a condition associated with disease states like hypertension, diabetes, and neurological disorders, to name a few. Magnesium deficiency can be attributed to common dietary practices, medications, and farming techniques, along with estimates that the mineral content of vegetables has declined by as much as 80⁻90% in the last 100 years. However, despite this mineral's importance, it is poorly understood from several standpoints, not the least of which is its unique mechanism of absorption and sensitive compartmental handling in the body, making the determination of magnesium status difficult. The reliance on several popular sample assays has contributed to a great deal of confusion in the literature. This review will discuss causes of magnesium deficiency, absorption, handling, and compartmentalization in the body, highlighting the challenges this creates in determining magnesium status in both clinical and research settings.
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Affiliation(s)
- Jayme L Workinger
- Human Nutrition and Pharma, Balchem Corporation, 52 Sunrise Park Road, New Hampton, NY 10958, USA.
| | - Robert P Doyle
- Department of Chemistry, Center for Science and Technology, Syracuse University, 111 College Place, Syracuse, NY 13244, USA.
| | - Jonathan Bortz
- Human Nutrition and Pharma, Balchem Corporation, 52 Sunrise Park Road, New Hampton, NY 10958, USA.
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DiNicolantonio JJ, O'Keefe JH, Wilson W. Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart 2018; 5:e000668. [PMID: 29387426 PMCID: PMC5786912 DOI: 10.1136/openhrt-2017-000668] [Citation(s) in RCA: 134] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 10/06/2017] [Accepted: 11/07/2017] [Indexed: 12/15/2022] Open
Abstract
Because serum magnesium does not reflect intracellular magnesium, the latter making up more than 99% of total body magnesium, most cases of magnesium deficiency are undiagnosed. Furthermore, because of chronic diseases, medications, decreases in food crop magnesium contents, and the availability of refined and processed foods, the vast majority of people in modern societies are at risk for magnesium deficiency. Certain individuals will need to supplement with magnesium in order to prevent suboptimal magnesium deficiency, especially if trying to obtain an optimal magnesium status to prevent chronic disease. Subclinical magnesium deficiency increases the risk of numerous types of cardiovascular disease, costs nations around the world an incalculable amount of healthcare costs and suffering, and should be considered a public health crisis. That an easy, cost-effective strategy exists to prevent and treat subclinical magnesium deficiency should provide an urgent call to action.
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Affiliation(s)
- James J DiNicolantonio
- Department of Preventive Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA
| | - James H O'Keefe
- Department of Preventive Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA
| | - William Wilson
- Hospital Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts, USA
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Ordak M, Maj-Zurawska M, Matsumoto H, Bujalska-Zadrozny M, Kieres-Salomonski I, Nasierowski T, Muszynska E, Wojnar M. Ionized magnesium in plasma and erythrocytes for the assessment of low magnesium status in alcohol dependent patients. Drug Alcohol Depend 2017; 178:271-276. [PMID: 28683422 DOI: 10.1016/j.drugalcdep.2017.04.035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 03/16/2017] [Accepted: 04/20/2017] [Indexed: 01/20/2023]
Abstract
BACKGROUND Studies on the homeostasis of magnesium in alcohol-dependent patients have often been characterized by low hypomagnesemia detection rates. This may be due to the fact that the content of magnesium in blood serum constitutes only 1% of the average magnesium level within the human body. However, the concentration of ionized magnesium is more physiologically important and makes up 67% of the total magnesium within a human organism. There are no data concerning the determination of the ionized fraction of magnesium in patients addicted to alcohol and its influence on mental health status. METHODS This study included 100 alcohol-dependent patients and 50 healthy subjects. The free magnesium fraction was determined using the potentiometric method by means of using ion-selective electrodes. The total magnesium level was determined by using a biochemical Indiko Plus analyzer. In this study, different psychometric scales were applied. RESULTS Our results confirm the usefulness of ionized magnesium concentrations in erythrocytes and plasma as a diagnostic parameter of low magnesium status in alcohol-dependent patients. CONCLUSIONS The lower the concentration of ionized magnesium, the worse the quality of life an alcohol-dependent person might experience. In the case of total magnesium, no such correlation was determined.
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Affiliation(s)
- Michal Ordak
- Department of Psychiatry, Medical University of Warsaw, Poland; Department of Pharmacodynamics, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Poland.
| | - Magdalena Maj-Zurawska
- Laboratory of Basic Aspects of Analytical Chemistry, Faculty of Chemistry, University of Warsaw, Poland; Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Poland
| | | | - Magdalena Bujalska-Zadrozny
- Department of Pharmacodynamics, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Poland
| | | | | | | | - Marcin Wojnar
- Department of Psychiatry, Medical University of Warsaw, Poland
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Marzec-Wróblewska U, Kamiński P, Łakota P, Ludwikowski G, Szymański M, Wasilow K, Stuczyński T, Buciński A, Jerzak L. Determination of Rare Earth Elements in Human Sperm and Association with Semen Quality. ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2015; 69:191-201. [PMID: 25762379 PMCID: PMC4490166 DOI: 10.1007/s00244-015-0143-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Accepted: 02/28/2015] [Indexed: 05/11/2023]
Abstract
The aim of the present study was to measure lanthanum (La), cerium (Ce), europium (Eu), and gadolinium (Gd) concentrations in human semen and correlate the results with sperm quality. The median semen content of La was 19.5 µg kg(-1) dry weight (dw) (range 2.27-269), of Ce was 41.9 µg kg(-1) dw (range 4.52 to 167), of Eu was 0.68 µg kg(-1) dw (range 0.06-1.95), of Gd was 3.19 µg kg(-1) dw (range 0.38-12.0), and of calcium (Ca) was 4063 mg kg(-1) dw (range 484-17,191). Concentrations of La, Ce, Eu, Gd, and Ca were significantly lower in nondrinkers' semen than in semen from drinkers. Significant differences were detected between La, Ce, Eu, Gd, and Ca concentrations in semen from nondrinkers and moderate drinkers. Concentrations of La, Ce, and Gd in semen of short-term smokers were significantly lower than those in extremely long-term smokers. Significant differences were also detected between La concentration in semen from a group of short-term smokers and that of a group of long-term smokers. Positive correlations were found between La, Ce, Eu, Gd, and Ca concentrations in semen. La, Ce, Gd, and Ca concentrations in semen were positively associated with progressive motility and percentage of normal spermatozoa. Positive correlations were found between Ca and sperm concentration. Concentrations of La, Ce, and Gd were negatively associated with sperm concentration, whilst Ca concentration was negatively associated with volume of ejaculate. At the examined level, La, Ce, Eu, and Gd did not affect sperm quality, whereas alcohol consumption and smoking might have increased the level of rare earth elements in semen.
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Affiliation(s)
- Urszula Marzec-Wróblewska
- Department of Biopharmacy, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, dr. A. Jurasz St. 2, 85-089 Bydgoszcz, Poland
- Department of Ecology and Environmental Protection, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, M. Skłodowska-Curie St. 9, 85-094 Bydgoszcz, Poland
| | - Piotr Kamiński
- Department of Ecology and Environmental Protection, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, M. Skłodowska-Curie St. 9, 85-094 Bydgoszcz, Poland
- Department of Biotechnology, Faculty of Biological Sciences, University of Zielona Góra, Prof. Szafran St. 1, 65-516 Zielona Gora, Poland
| | - Paweł Łakota
- Department of Animal Biotechnology, Faculty of Animal Biology, University of Technology and Life Sciences, Mazowiecka St. 28, 85-084 Bydgoszcz, Poland
| | - Grzegorz Ludwikowski
- Department of Clinical Andrology, Faculty of Medicine, University Hospital No. 2, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Szpitalna St. 19, 85-092 Bydgoszcz, Poland
| | - Marek Szymański
- Department of Obstetrics, Female Pathology and Oncological Gynecology, University Hospital No. 2, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Ujejski St. 75, 85-168 Bydgoszcz, Poland
- NZOZ Medical Center Co. Prof. dr. hab. med. Wiesław Szymański, Dr. med. Marek Szymański, Waleniowa St. 24, 85-435 Bydgoszcz, Poland
| | - Karolina Wasilow
- NZOZ Medical Center Co. Prof. dr. hab. med. Wiesław Szymański, Dr. med. Marek Szymański, Waleniowa St. 24, 85-435 Bydgoszcz, Poland
- Family Medicine Clinic, University Hospital No. 2, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Ujejski St. 75, 85-168 Bydgoszcz, Poland
| | - Tomasz Stuczyński
- Department of Soil Structure, Institute of Agriculture and Soil Cultivation, Czartoryskich St. 8, 24-100 Puławy, Poland
| | - Adam Buciński
- Department of Biopharmacy, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, dr. A. Jurasz St. 2, 85-089 Bydgoszcz, Poland
| | - Leszek Jerzak
- Department of Nature Protection, Faculty of Biological Sciences, University of Zielona Góra, Prof. Szafran St. 1, 65-516 Zielona Gora, Poland
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Davies BE. The UK geochemical environment and cardiovascular diseases: magnesium in food and water. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2015; 37:411-427. [PMID: 25528218 DOI: 10.1007/s10653-014-9671-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 12/10/2014] [Indexed: 06/04/2023]
Abstract
Cardiovascular diseases (CVDs) contribute approximately one-third to noncommunicable diseases in the UK. The central role of magnesium in CVDs (enzyme activity, cardiac signalling, etc.) is well established. Mortality and morbidity rates for CVDs may be inversely related to water hardness, suggesting a role for environmental magnesium. Published official and quasi-official data sources were evaluated to establish a model magnesium intake for a representative adult: standardised reference individual (SRI), standardised reference male (SRM) or standardised reference female (SRF). For typical dietary constituents, only tap water is probably locally derived and bottled water may not be. Fruits and vegetables are imported from many countries, while meat, dairy and cereal products represent a composite of UK source areas. Alcoholic beverages provide magnesium, there is doubt about its absorptive efficiency, and they are not locally derived. A simple model was devised to examine the effect of varying dietary contributions to total daily intake of magnesium. Omitting tap or bottled water, the combined intake, solid food plus alcoholic beverages, is 10.57 mmol Mg (84.5 % RNI) for the SRM and for the SRF, 8.10 mmol Mg (71.7 % RNI). Consumers drinking water derived from reservoirs or rivers, or supplementing it with the purest bottled water, improve their magnesium intake only slightly compared with water containing no magnesium. Choosing bottled water with high magnesium content when the public supply derives from rivers or reservoirs partially satisfies magnesium needs. Real improvement in SRI magnesium nutrition is seen only where water is hard. However, this conclusion cannot be validated until new measurement technologies for body magnesium become available.
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Yuen AW, Sander JW. Can magnesium supplementation reduce seizures in people with epilepsy? A hypothesis. Epilepsy Res 2012; 100:152-6. [DOI: 10.1016/j.eplepsyres.2012.02.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Revised: 01/31/2012] [Accepted: 02/05/2012] [Indexed: 12/15/2022]
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Peacock JM, Ohira T, Post W, Sotoodehnia N, Rosamond W, Folsom AR. Serum magnesium and risk of sudden cardiac death in the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 2010; 160:464-70. [PMID: 20826254 DOI: 10.1016/j.ahj.2010.06.012] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2009] [Accepted: 06/04/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND We hypothesized that serum magnesium (Mg) is associated with increased risk of sudden cardiac death (SCD). METHODS The Atherosclerosis Risk in Communities Study assessed risk factors and levels of serum Mg in a cohort of 45- to 64-year-old subjects in 1987-1989 (n = 14,232). After an average of 12 years of follow-up, we observed 264 cases of SCD, as determined by physician review of all suspected cases. We used proportional hazards regression to evaluate the association of serum Mg with risk of SCD. RESULTS Individuals in the highest quartile of serum Mg were at significantly lower risk of SCD in all models. This association persisted after adjustment for potential confounding variables, with an almost 40% reduced risk of SCD (hazard ratio 0.62, 95% CI 0.42-0.93) in quartile 4 versus 1 of serum Mg observed in the fully adjusted model. CONCLUSIONS This study suggests that low levels of serum Mg may be an important predictor of SCD. Further research into the effectiveness of Mg supplementation for those considered to be at high risk for SCD is warranted.
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Ismail Y, Ismail AA, Ismail AAA. The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for "normal" results. Clin Chem Lab Med 2010; 48:323-7. [PMID: 20170394 DOI: 10.1515/cclm.2010.077] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND A major use of serum magnesium measurements in clinical practice is to identify patients with deficiency. However, numerous studies have shown that magnesium deficiency is common and may be present in over 10% of hospitalized patients, as well as in the general population. An important cause for under diagnosis of deficiency is that serum magnesium, the most commonly used test, can be normal despite negative body stores. This article focuses on the limitations of "normal" magnesium results and highlights the importance of lifestyle or "modus vivendi" as a pragmatic means of identifying those individuals potentially at risk for negative body magnesium stores. METHODS Researched peer reviewed articles on magnesium published between 1990 and 2008 in MEDLINE and EMBASE, using database keywords "magnesium, deficiency, diagnosis, treatment and hypomagnesaemia". Bibliographies of retrieved articles have been searched and followed. We have also performed a manual search of each individual issue in which most of these reports have appeared. RESULTS In 183 peer reviewed studies published from 1990 to 2008, magnesium deficiency was associated with increased prevalence and risk in 11 major conditions. Similarly, in 68 studies performed over the same period, magnesium deficiency was found to predict adverse events and a decreased risk of pathology was noted when supplementation or treatment was instituted. CONCLUSIONS The perception that "normal" serum magnesium excludes deficiency is common among clinicians. This perception is probably enforced by the common laboratory practice of highlighting only abnormal results. A health warning is therefore warranted regarding potential misuse of "normal" serum magnesium because restoration of magnesium stores in deficient patients is simple, tolerable, inexpensive and can be clinically beneficial.
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Sex-dependent alterations in erythrocyte trace element levels and antioxidant status after a month of moderate daily red wine consumption. Eur J Gastroenterol Hepatol 2010; 22:185-91. [PMID: 19786878 DOI: 10.1097/meg.0b013e3283316219] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE We tested the hypothesis whether trace elements and antioxidant status change in a sex-dependent manner may contribute to sex-dependent hepatic effects of moderate daily wine consumption. PATIENT AND METHODS Twenty-one healthy young men and women were enrolled to this study who consumed red wine 0.3 and 0.2 l per day, respectively, for a month. Blood was taken at baseline (BV) and at end of the study (EV). Red cell trace element levels, red cell and plasma antioxidant status and serum routine blood chemistry were assessed at baseline and at the end of the study. RESULTS No sign of hepatotoxicity was detected. BV level of some trace elements (i.e. Zn, Pb) and Zn/Cu ratios were higher in women than in men. Ca, Mg, Pb, Sr and Zn levels and the Zn/Cu ratio had lower EV than BV in women. In men, Al, Ca, Li, Pb and Sr levels had lower EV than BV. The tested antioxidant parameters improved in both the sexes. CONCLUSION Although no hepatotoxicity was observed, changes in trace element content were detected after 1 month of moderate red wine consumption. The most remarkable sex-specific alteration was the decrease of Zn levels and of the Zn/Cu ratio in women. Given the protective effect of Zn against liver damage, this finding suggests a possible contribution of decreased Zn levels to sex-dependent effects of red wine.
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Abstract
Magnesium (Mg) deficiency commonly occurs in critical illness and correlates with a higher mortality and worse clinical outcome in the intensive care unit (ICU). Magnesium has been directly implicated in hypokalemia, hypocalcemia, tetany, and dysrhythmia. Moreover, Mg may play a role in acute coronary syndromes, acute cerebral ischemia, and asthma. Magnesium regulates hundreds of enzyme systems. By regulating enzymes controlling intracellular calcium, Mg affects smooth muscle vasoconstriction, important to the underlying pathophysiology of several critical illnesses. The principle causes of Mg deficiency are gastrointestinal and renal losses; however, the diagnosis is difficult to make because of the limitations of serum Mg levels, the most common assessment of Mg status. Magnesium tolerance testing and ionized Mg2+ are alternative laboratory assessments; however, each has its own difficulties in the ICU setting. The use of Mg therapy is supported by clinical trials in the treatment of symptomatic hypomagnesemia and preeclampsia and is recommended for torsade de pointes. Magnesium therapy is not supported in the treatment of acute myocardial infarction and is presently undergoing evaluation for the treatment of severe asthma exacerbation, for the prevention of post-coronary bypass grafting dysrhythmias, and as a neuroprotective agent in acute cerebral ischemia.
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Affiliation(s)
- Garrison M Tong
- University of Southern California, School of Medicine, Los Angeles, CA 90089-9317, USA
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Hornyak M, Haas P, Veit J, Gann H, Riemann D. Magnesium Treatment of Primary Alcohol-Dependent Patients During Subacute Withdrawal: An Open Pilot Study With Polysomnography. Alcohol Clin Exp Res 2004; 28:1702-9. [PMID: 15547457 DOI: 10.1097/01.alc.0000145695.52747.be] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Sleep electroencephalogram alterations and insomnia complaints persist after alcohol withdrawal in dependent patients and are considered strong predictors of relapse. Although disturbances of magnesium household due to alcohol consumption are well known, the relationship of magnesium metabolism and sleep disturbances has not been investigated in this patient group. We conducted an open pilot study to evaluate the effects of magnesium treatment on the sleep of primary alcohol-dependent patients during subacute withdrawal. METHODS Patients were treated with 30 mmol magnesium daily over 4 weeks. Eleven of the 14 included patients were evaluated. Patients were free of any kind of psychotropic medication or other substances known to influence sleep. Polysomnographic recordings with monitoring of periodic leg movements in sleep (PLMS) were performed for two consecutive nights 2 weeks after acute withdrawal (baseline) and 4 weeks later at the end of the treatment period. After the baseline polysomnography, patients were investigated by the magnesium loading test to verify magnesium depletion. RESULTS We found a significant decrease of sleep onset latency from 40.6 to 21.7 min (p = 0.03) and a significant improvement of subjective sleep quality, as assessed by the Pittsburgh Sleep Quality Index, from 8.1 to 5.8 (p = 0.05) during magnesium treatment. Changes in PLMS indices revealed two subgroups of patients: one with an increase of PLMS from 30.7 to 39.4 per hour of sleep (n = 4) and the other one with a decrease of PLMS from 8.9 to 2.1 per hour of sleep (p = 0.04). Patients with PLMS decreases seemed to have a more favorable prognosis: total sleep time, gamma-glutamyltransferase, carbohydrate-deficient transferrin, and Beck Depression Inventory scores improved significantly during treatment in this group. The magnesium loading test revealed a magnesium deficiency in only one patient, five patients showed normal retention values, and the remaining five patients had an increased magnesium excretion, indicating a possible continued renal magnesium loss during abstinence. CONCLUSIONS The results of this study should be interpreted with caution, because no control group with placebo was investigated. Both subjective and, partly, objective parameters of sleep improved during the 4-week study period. Further research is needed to clarify the relationship of magnesium metabolism and sleep alterations.
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Affiliation(s)
- Magdolna Hornyak
- Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Hauptstrasse 5, D-79104 Freiburg, Germany.
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Aagaard NK, Andersen H, Vilstrup H, Clausen T, Jakobsen J, Dørup I. Decreased muscle strength and contents of Mg and Na,K-pumps in chronic alcoholics occur independently of liver cirrhosis. J Intern Med 2003; 253:359-66. [PMID: 12603504 DOI: 10.1046/j.1365-2796.2003.01100.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVES To evaluate the influence of established liver cirrhosis on muscle strength and muscle contents of magnesium (Mg), potassium (K) and sodium, potassium pumps (Na,K-pumps) in chronic alcoholic patients. DESIGN An open cross-sectional study. SETTING AND SUBJECTS Forty consecutive chronic alcoholics (18 with cirrhosis and 22 without cirrhosis) admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, or to a collaborating alcoholism treatment centre, and 36 healthy control subjects. MAIN OUTCOME MEASURES Evaluation of participant's subjective physical ability and measurement of maximum isokinetic muscle strength and muscle mass, as well as measurements of Mg, K and Na,K-pumps in skeletal muscle. RESULTS Maximum isokinetic muscle strength and muscle mass were equally reduced in patients with and without cirrhosis (P < 0.01 all). In keeping with this, both groups of patients felt equally physically restricted. Muscle Mg was reduced to the same extent in the two groups of patients (by 12 and 9%, P < 0.001, both), whereas the muscle K content was only significantly lower in the cirrhotic patients (10%, P < 0.001). The muscle content of Na,K-pumps was reduced by 14%, (P < 0.01) in the cirrhotic patients and by 8% (P < 0.05) in the noncirrhotic patients. CONCLUSION Our alcoholic patients complained of physical disability, had reduced skeletal muscle mass, isokinetic muscle strength, content of muscle Mg and content of Na,K-pumps. There was no difference between patients with and without cirrhosis. It appears that it is the heavy alcohol intake, and not the cirrhosis per se, that is responsible for the observed defects.
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Affiliation(s)
- N K Aagaard
- Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
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