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Associations of Serum Magnesium With Insulin Resistance and Testosterone in Women With Polycystic Ovary Syndrome.
Luo, X, Cai, WY, Ma, HL, Cong, J, Chang, H, Gao, JS, Shen, WJ, Wang, Y, Yang, XM, Wu, XK
Frontiers in endocrinology. 2021;:683040
Abstract
OBJECTIVE This article aimed to investigate whether serum magnesium is associated with insulin resistance index and testosterone level in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS Overall 1000 women with PCOS were enrolled in a randomized controlled trial and a cross-sectional analysis of the association of serum magnesium with glucose metabolism markers and testosterone was performed. Serum magnesium, glucose metabolism markers and testosterone were measured. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI). Multivariable linear regression and logistic regression models were used to estimate the association between serum magnesium, insulin resistance and testosterone. RESULTS In comparative analyses, women with higher quartile of serum magnesium had significantly lower fasting glucose, HOMA-IR and testosterone. Multiple linear regression showed serum magnesium was independently negatively associated with insulin, glucose, HOMA-IR, testosterone and positively associated with QUICKI (P for trend <0.05) after adjusting confounding covariates. Logistic regression showed serum magnesium in quartile 1 and 2 were independently associated with insulin resistance status (Quartile 1: OR: 2.15, 95%CI: 1.35-3.40, P = 0.001; Quartile 2: OR: 1.90, 95%CI: 1.20-3.02, P = 0.006), while quartile 1 was marginally associated with hyperandrogenemia status (Quartile 1: OR: 1.45, 95%CI: 0.99-2.11, P = 0.055) after adjusting confounding covariates. CONCLUSION The current findings suggest that lower serum magnesium was associated with aggravated insulin resistance and higher testosterone levels among women with PCOS.
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Relationship Between Dietary Magnesium Intake and Incident Heart Failure Among Older Women: The WHI.
Wu, WC, Huang, M, Taveira, TH, Roberts, MB, Martin, LW, Wellenius, GA, Johnson, KC, Manson, JE, Liu, S, Eaton, CB
Journal of the American Heart Association. 2020;(7):e013570
Abstract
Background Women represent a large proportion of the growing heart failure (HF) epidemic, yet data are lacking regarding optimal dietary and lifestyle prevention strategies for them. Specifically, the association between magnesium intake and HF in a multiracial cohort of women is uncertain. Methods and Results We included 97 725 postmenopausal women from the WHI (Women's Health Initiative) observational studies and placebo arms of the hormone trial. Magnesium intake was measured at baseline by a 122-item validated food-frequency questionnaire and stratified into quartiles based on diet only, total intake (diet with supplements), and residual intake (calibration by total energy). Incident hospitalized HF (2153 events, median follow-up 8.1 years) was adjudicated by medical record abstraction. In Cox proportional hazards models, we evaluated the association between magnesium intake and HF adjusting for potential confounders. Analyses were repeated on a subcohort (n=18 745; median-follow-up, 13.2 years) for whom HF cases were subclassified into preserved ejection fraction (526 events), reduced ejection fraction (291 events) or unknown (168 events). Most women were white (85%) with a mean age of 63. Compared with the highest quartile of magnesium intake, women in the lowest quartile had an increased risk of incident HF, with adjusted hazard ratios of 1.32 (95% CI, 1.02-1.71) for diet only (P trend=0.03), 1.26 (95% CI, 1.03-1.56) for total intake, and 1.31 (95% CI, 1.02-1.67) for residual intake. Results did not significantly vary by race. Subcohort analyses showed low residual magnesium intake was associated with HF with reduced ejection fraction (hazard ratio, 1.81, lowest versus highest quartile; 95% CI, 1.08-3.05) but not HF with preserved ejection fraction. Conclusions Low magnesium intake in a multiracial cohort of postmenopausal women was associated with a higher risk of incident HF, especially HF with reduced ejection fraction.
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Calcium: magnesium intake ratio and colorectal carcinogenesis, results from the prostate, lung, colorectal, and ovarian cancer screening trial.
Zhao, J, Giri, A, Zhu, X, Shrubsole, MJ, Jiang, Y, Guo, X, Ness, R, Seidner, DL, Giovannucci, E, Edwards, TL, et al
British journal of cancer. 2019;(9):796-804
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BACKGROUND We aimed to evaluate the associations between calcium and various stages of colorectal carcinogenesis and whether these associations are modified by the calcium to magnesium (Ca:Mg) ratio. METHODS We tested our hypotheses in the prostate lung, colorectal and ovarian cancer screening trial. RESULTS Calcium intake did not show a dose-response association with incident adenoma of any size/stage (P-trend = 0.17), but followed an inverse trend when restricted to synchronous/advanced adenoma cases (P-trend = 0.05). This inverse trend was mainly in participants with Ca:Mg ratios between 1.7 and 2.5 (P-trend = 0.05). No significant associations were observed for metachronous adenoma. Calcium intake was inversely associated with CRC (P-trend = 0.03); the association was primarily present for distal CRC (P-trend = 0.01). The inverse association between calcium and distal CRC was further modified by the Ca:Mg ratio (P-interaction < 0.01); significant dose-response associations were found only in participants with a Ca:Mg ratio between 1.7 and 2.5 (P-trend = 0.04). No associations for calcium were found in the Ca:Mg ratio above 2.5 or below 1.7. CONCLUSION Higher calcium intake may be related to reduced risks of incident advanced and/or synchronous adenoma and incident distal CRC among subjects with Ca:Mg intake ratios between 1.7 and 2.5.
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Dietary Magnesium Is Positively Associated With Skeletal Muscle Power and Indices of Muscle Mass and May Attenuate the Association Between Circulating C-Reactive Protein and Muscle Mass in Women.
Welch, AA, Kelaiditi, E, Jennings, A, Steves, CJ, Spector, TD, MacGregor, A
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2016;(2):317-25
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Age-related loss of skeletal muscle mass and strength are risk factors for sarcopenia, osteoporosis, falls, fractures, frailty, and mortality. Dietary magnesium (Mg) could play a role in prevention of age-related loss of skeletal muscle mass, power, and strength directly through physiological mechanisms or indirectly through an impact on chronic low-grade inflammation, itself a risk factor for loss of skeletal muscle mass and strength. In a cross-sectional study of 2570 women aged 18 to 79 years, we examined associations between intakes of Mg, estimated using a food-frequency questionnaire (FFQ), dual-energy X-ray absorptiometry (DXA)-derived measures of muscle mass (fat-free mass as a percentage of body weight [FFM%], fat-free mass index [FFMI, kg/m(2)]), leg explosive power (LEP), and grip strength (n = 949 only). We also examined associations between circulating hs-CRP (C-reactive protein) and muscle mass and LEP, and explored the potential attenuation of these relationships by Mg. We compared our findings with those of age and protein intake. Endpoints were calculated by quintile of Mg and adjusted for relevant confounders. Significant positive associations were found between a higher Mg and indices of skeletal muscle mass and LEP, and also with hs-CRP, after adjustment for covariates. Contrasting extreme quintiles of Mg intake showed differences of 2.6% for FFM% (p trend < 0.001), 0.4 kg/m(2) for FFMI (p trend = 0.005), and 19.6 watts/kg for LEP (p trend < 0.001). Compared with protein, these positive associations were 7 times greater for FFM% and 2.5 times greater for LEP. We also found that higher hs-CRP was negatively associated with skeletal muscle mass and, in statistical modeling, that a higher dietary Mg attenuated this negative relationship by 6.5%, with greater attenuation in women older than 50 years. No association was found between Mg and grip strength. Our results suggest that dietary magnesium may aid conservation of age-related loss of skeletal muscle mass and power in women of all ages.
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A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children.
Brousseau, DC, Scott, JP, Badaki-Makun, O, Darbari, DS, Chumpitazi, CE, Airewele, GE, Ellison, AM, Smith-Whitley, K, Mahajan, P, Sarnaik, SA, et al
Blood. 2015;(14):1651-7
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Magnesium, a vasodilator, anti-inflammatory, and pain reliever, could alter the pathophysiology of sickle cell pain crises. We hypothesized that intravenous magnesium would shorten length of stay, decrease opioid use, and improve health-related quality of life (HRQL) for pediatric patients hospitalized with sickle cell pain crises. The Magnesium for Children in Crisis (MAGiC) study was a randomized, double-blind, placebo-controlled trial of intravenous magnesium vs normal saline placebo conducted at 8 sites within the Pediatric Emergency Care Applied Research Network (PECARN). Children 4 to 21 years old with hemoglobin SS or Sβ(0) thalassemia requiring hospitalization for pain were eligible. Children received 40 mg/kg of magnesium or placebo every 8 hours for up to 6 doses plus standard therapy. The primary outcome was length of stay in hours from the time of first study drug infusion, compared using a Van Elteren test. Secondary outcomes included opioid use and HRQL. Of 208 children enrolled, 204 received the study drug (101 magnesium, 103 placebo). Between-group demographics and prerandomization treatment were similar. The median interquartile range (IQR) length of stay was 56.0 (27.0-109.0) hours for magnesium vs 47.0 (24.0-99.0) hours for placebo (P = .24). Magnesium patients received 1.46 mg/kg morphine equivalents vs 1.28 mg/kg for placebo (P = .12). Changes in HRQL before discharge and 1 week after discharge were similar (P > .05 for all comparisons). The addition of intravenous magnesium did not shorten length of stay, reduce opioid use, or improve quality of life in children hospitalized for sickle cell pain crisis. This trial was registered at www.clinicaltrials.gov as #NCT01197417.
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Serum magnesium, phosphorus, and calcium are associated with risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) Study.
Lutsey, PL, Alonso, A, Michos, ED, Loehr, LR, Astor, BC, Coresh, J, Folsom, AR
The American journal of clinical nutrition. 2014;(3):756-64
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BACKGROUND Heart failure (HF) is a major source of morbidity and mortality, particularly among the elderly. Magnesium, phosphorus, and calcium are micronutrients traditionally viewed in relation to bone health or chronic kidney disease. However, they also may be associated with risk of cardiovascular disease through a broad range of physiologic roles. OBJECTIVE With the use of data from the Atherosclerosis Risk in Communities (ARIC) cohort, we tested the hypotheses that the incidence of HF is greater among individuals with low serum magnesium and those with high serum phosphorus and calcium. DESIGN A total of 14,709 African Americans (27%) and whites from the ARIC cohort [aged 45-64 y at baseline (1987-1989)] were observed through 2009. Proportional hazards regression was used to explore associations between biomarkers and incident HF. Serum calcium was corrected for serum albumin. Models were adjusted for demographics, behaviors, and physiologic characteristics. RESULTS A total of 2250 incident HF events accrued over a median follow-up of 20.6 y. Participants in the lowest (≤1.4 mEq/L) compared with the highest (≥1.8 mEq/L) category of magnesium were at greater HF risk (HR: 1.71; 95% CI: 1.46, 1.99). For phosphorus, there appeared to be a threshold whereby only those in the highest quintile were at greater HF risk [HR(Q5 vs Q1): 1.34; 95% CI: 1.16, 1.54]. Higher concentrations of calcium were also associated with greater risk of HF [HR(Q5 vs Q1): 1.24; 95% CI: 1.07, 1.43]. Results were not modified by race, sex, or kidney function and were similar when incident coronary heart disease was included as a time-varying covariate. CONCLUSIONS Low serum magnesium and high serum phosphorus and calcium were independently associated with greater risk of incident HF in this population-based cohort. Whether these biomarkers will be useful candidates for HF risk prediction or targets for prevention remains to be seen.
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Methodology of the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) phase 3 trial: Part 2 - prehospital study methods.
Saver, JL, Starkman, S, Eckstein, M, Stratton, S, Pratt, F, Hamilton, S, Conwit, R, Liebeskind, DS, Sung, G, Sanossian, N, et al
International journal of stroke : official journal of the International Stroke Society. 2014;(2):220-5
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RATIONALE In acute stroke, the volume of salvageable brain tissue is maximal at onset and declines rapidly with time. Prehospital start of clinical trial interventions would enable delivery of neuroprotective agents, such as magnesium sulfate, to stroke patients in the hyperacute period when they are potentially most effective. AIMS A broad aim of the FAST-MAG study is to develop and validate techniques to perform pivotal trials of neuroprotective therapies for acute stroke in the prehospital setting. In tandem with an accompanying general trial design article, this manuscript provides a detailed overview of several novel prehospital study methods employed in the NIH FAST-MAG Trial. DESIGN Multicenter, randomized, double-blinded, placebo-controlled, pivotal clinical trial. Special Prehospital Procedures Distinctive prehospital methods deployed in FAST-MAG include: identifying likely stroke patients using the Los Angeles Prehospital Stroke Screen; eliciting explicit informed consent from patients or on scene legally authorized representatives via cellphone discussion with off-scene physicians; paramedic rating of pretreatment stroke severity using the Los Angeles Motor Scale; assigning patients to a study arm using blinded, pre-encounter randomization; facilitating continuity of study infusion from the field to the ED by stocking ambulances with study kits including both field and hospital doses; and electronic fax consent signature documentation by geographically separated subjects and enrolling physicians. DISCUSSION The suite of prehospital trial methods developed for the FAST-MAG Trial enable enrollment of patients in very early time windows, including the hyperacute, 'golden hour' period immediately after stroke onset.
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Dietary magnesium intake is inversely associated with mortality in adults at high cardiovascular disease risk.
Guasch-Ferré, M, Bulló, M, Estruch, R, Corella, D, Martínez-González, MA, Ros, E, Covas, M, Arós, F, Gómez-Gracia, E, Fiol, M, et al
The Journal of nutrition. 2014;(1):55-60
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The relation between dietary magnesium intake and cardiovascular disease (CVD) or mortality was evaluated in several prospective studies, but few of them have assessed the risk of all-cause mortality, which has never been evaluated in Mediterranean adults at high cardiovascular risk. The aim of this study was to assess the association between magnesium intake and CVD and mortality risk in a Mediterranean population at high cardiovascular risk with high average magnesium intake. The present study included 7216 men and women aged 55-80 y from the PREDIMED (Prevención con Dieta Mediterránea) study, a randomized clinical trial. Participants were assigned to 1 of 2 Mediterranean diets (supplemented with nuts or olive oil) or to a control diet (advice on a low-fat diet). Mortality was ascertained by linkage to the National Death Index and medical records. We fitted multivariable-adjusted Cox regressions to assess associations between baseline energy-adjusted tertiles of magnesium intake and relative risk of CVD and mortality. Multivariable analyses with generalized estimating equation models were used to assess the associations between yearly repeated measurements of magnesium intake and mortality. After a median follow-up of 4.8 y, 323 total deaths, 81 cardiovascular deaths, 130 cancer deaths, and 277 cardiovascular events occurred. Energy-adjusted baseline magnesium intake was inversely associated with cardiovascular, cancer, and all-cause mortality. Compared with lower consumers, individuals in the highest tertile of magnesium intake had a 34% reduction in mortality risk (HR: 0.66; 95% CI: 0.45, 0.95; P < 0.01). Dietary magnesium intake was inversely associated with mortality risk in Mediterranean individuals at high risk of CVD. This trial was registered at controlled-trials.com as ISRCTN35739639.
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Methodology of the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) phase 3 trial: Part 1 - rationale and general methods.
Saver, JL, Starkman, S, Eckstein, M, Stratton, S, Pratt, F, Hamilton, S, Conwit, R, Liebeskind, DS, Sung, G, Sanossian, N, et al
International journal of stroke : official journal of the International Stroke Society. 2014;(2):215-9
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RATIONALE Prehospital initiation by paramedics may enable delivery of neuroprotective therapies to stroke patients in the hyperacute period when they are most effective in preclinical studies. Magnesium is neuroprotective in experimental stroke models and has been shown to be safe with signals of potential efficacy when started early after onset of human cerebral ischemia. AIMS (a) To demonstrate that paramedic initiation of the neuroprotective agent magnesium sulfate in the field is an efficacious and safe treatment for acute stroke; (b) To demonstrate that field enrollment of acute stroke patients is a practical and feasible strategy for phase 3 stroke trials, permitting enrollment of greater numbers of patients in hyperacute time windows. DESIGN Multicenter, randomized, double-blinded, placebo-controlled, pivotal clinical trial. STUDY PROCEDURES The study is enrolling 1700 patients (850 in each arm) with likely acute stroke, including both cerebral infarction and intracerebral hemorrhage patients. Inclusion criteria are: (a) likely stroke as identified by the modified Los Angeles Prehospital Stroke Screen (mLAPSS), (b) age 40-95, (c) symptom onset within 2 h of treatment initiation, and (d) deficit present ≥15 min. Paramedics administer a loading dose of magnesium sulfate (Mg) or matched placebo in the field, 4 grams over 15 min. In the Emergency Department, a maintenance infusion follows, 16 grams Mg or matched placebo over 24 h. OUTCOMES The primary endpoint is the modified Rankin Scale measure of global disability, assessed using the Rankin Focused Assessment, 90 days after treatment. Secondary efficacy endpoints include the NIHSS (neurologic deficit), Barthel Index (activities of daily living), and the Stroke Impact Scale (quality of life).