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1.
Using iron-based phosphate binders in phosphate reduction and anemia improvement in patients receiving dialysis: a meta-analysis of randomized controlled trials.
Zhu, Y, Rao, J, Liao, X, Ou, J, Li, W, Xue, C
International urology and nephrology. 2021;(9):1899-1909
Abstract
PURPOSE A study was conducted to determine whether iron-based phosphate binders (IBPBs) need to be preferred for hyperphosphatemia and anemia management in patients on dialysis. METHODS For this meta-analysis, we searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials that evaluated the efficacy and safety of IBPBs in decreasing phosphate and correcting anemia in dialysis patients. RESULTS Nineteen trials comprising 4719 participants were included. Compared with placebo, serum phosphate decreased significantly after treatment with ferric citrate (FC), fermagate (one study), and SBR759 (one study). Hemoglobin increased significantly after treatment with FC and sucroferric oxyhydroxide (PA21). In addition, FC and PA21 reduced serum intact parathyroid hormone (iPTH) and increased ferritin and transferrin saturation, but SBR759 did not. Compared with active treatment, the non-inferiority of IBPBs in reducing serum phosphate and iPTH was demonstrated. FC significantly improved serum hemoglobin and iron-related parameters and decreased the use of intravenous iron and erythropoiesis-stimulating agent, whereas PA21 did not increase serum hemoglobin level. The incidences of infection and hospitalization were similar between the two groups, with FC having a higher risk of diarrhea than the placebo and active treatments. CONCLUSION FC was associated with the control of hyperphosphatemia and the improvement of anemia. However, PA21 did not show superiority for alleviating anemia compared with the active treatment. Other IBPBs, such as fermagate and SBR759, remained poorly understood due to the limited number of studies. Further trials are required to assess the effect of IBPBs on the risk of cardiovascular events and all-cause mortality.
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Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.
Veronese, N, Dominguez, LJ, Pizzol, D, Demurtas, J, Smith, L, Barbagallo, M
Nutrients. 2021;(11)
Abstract
There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of diabetes. We therefore aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes, compared with a placebo. Several databases were searched investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or conditions at high risk of diabetes. Data were reported as standardized mean differences (SMDs) with their 95% confidence intervals (CIs) using follow-up data of glucose and insulin-sensitivity parameters. Compared with placebo, Mg supplementation reduced fasting plasma glucose in people with diabetes. In people at high risk of diabetes, Mg supplementation significantly improved plasma glucose per se, and after a 2 h oral glucose tolerance test. Furthermore, Mg supplementation demonstrated an improvement in insulin sensitivity markers. In conclusion, Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes. Moreover, our work indicates that Mg supplementation may improve insulin-sensitivity parameters in those at high risk of diabetes.
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The effect of magnesium supplementation on anthropometric indices: a systematic review and dose-response meta-analysis of clinical trials.
Rafiee, M, Ghavami, A, Rashidian, A, Hadi, A, Askari, G
The British journal of nutrition. 2021;(6):644-656
Abstract
The aim of this study was to determine the effects of Mg supplementation on anthropometric indices consisting of body weight, waist circumference (WC), BMI and body fat percentage. In this systematic review and dose–response meta-analysis, we searched PubMed, Cochrane Library, Scopus, Web of Science and Google Scholar from databases inception up to February 2020 for relevant randomised controlled trials. Quality of evidence was evaluated using the Cochrane Collaboration Tool. All the outcomes of this meta-analysis were pooled using the random effect model. Analysis of dose–response for Mg dosage was carried out using a fractional polynomial model. The systematic review and meta-analysis include twenty-eight randomised clinical trials, comprising 2013 participants. There were no significant changes in anthropometric indices after Mg supplementation in the overall analysis. However, subgroup analysis revealed that Mg supplementation decreases WC in subjects with BMI > 30 kg/m2 (obese) (twelve trials, n 997 participants; weighted mean difference = –2·09 cm, 95 % CI –4·12, –0·07, P = 0·040; I2 = 0 %). Dose–response analysis revealed a non-significant non-linear effect of supplementation dosage on anthropometric indices. The results suggest that Mg supplementation is associated with lower WC only in obese subjects. However, more high-quality studies are needed to clarify the nature of this association.
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Effect of oral magnesium supplementation for relieving leg cramps during pregnancy: A meta-analysis of randomized controlled trials.
Liu, J, Song, G, Zhao, G, Meng, T
Taiwanese journal of obstetrics & gynecology. 2021;(4):609-614
Abstract
Leg cramps are one of the common symptoms during pregnancy. About 30%-50% of pregnant women experience leg cramps twice a week. Leg cramps may cause severe pain and sleep disturbance, hinder performance of daily activities and may lengthen the duration of pregnancy and the type of childbirth. Several randomized controlled trial (RCT) studies focused on the effects of the magnesium supplement for relieving leg cramps. However, the results were inconsistent. Five databases were searched from their inception to July 2, 2020. We summarized the weighted mean difference (WMD) with 95% CIs for "the frequency of leg cramps after treatment", and summarized the odds ratio (OR) with 95% confidence intervals (CIs) for "recovery from leg cramps" and "side effects". Four RCTs with a total of 332 pregnant women were identified. The frequency of leg cramps after treatment was not decreased in the treatment group compared to the control group (WMD = -0.47, 95% CI: -1.14-0.20, P = 0.167). Magnesium supplementation cannot improve the recovery from leg cramps compared to the control group (OR = 0.47, 95% CI: 0.14-1.52, P = 0.207). Magnesium supplementation had no significant side effects in the treatment group compared to the control group (OR = 1.82, 95% CI: 0.90-3.69, P = 0.094). Oral magnesium supplementation is not effective in the treatment of leg cramps during pregnancy. PROSPERO CRD42020196572.
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The association between circulating magnesium and clinically relevant outcomes in patients with chronic kidney disease: A systematic review and meta-analysis.
Leenders, NHJ, Vermeulen, EA, van Ballegooijen, AJ, Hoekstra, T, de Vries, R, Beulens, JW, Vervloet, MG
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3133-3147
Abstract
BACKGROUND & AIMS Despite modern treatment, risk for cardiovascular disease and mortality in patients with chronic kidney disease (CKD) is unacceptably high. Observational studies have shown associations of magnesium with risk for several clinical outcomes in CKD of variable magnitude. The aim of this review is to provide a systematic overview and meta-analysis of longitudinal studies assessing the association of plasma magnesium concentration with clinically relevant outcomes in adult patients with chronic kidney disease, with a minimal follow-up of 6 months. Primary outcomes of interest were all-cause mortality, cardiovascular mortality, cardiovascular events, sudden death and hospitalisation. METHODS The electronic databases PubMed, Embase and The Cochrane Library were searched using terms relating to plasma magnesium and CKD patients, and two authors independently selected eligible studies. Study quality was assessed according to the Newcastle-Ottawa Scale. Results of studies with a comparable magnesium exposure and outcome measure, were pooled using a random-effects meta-regression analysis. RESULTS The search yielded 6156 records of which 33 studies, involving 348,059 patients, met the eligibility criteria. Finally, 22 studies could be included in the meta-analysis. Higher magnesium was associated with a lower risk for all-cause mortality (HR 0.90 [0.87-0.94] per 0.1 mmol/L increase of magnesium) and cardiovascular mortality and events (HR 0.85 [0.77-0.94] per 0.1 mmol/L). CONCLUSIONS Magnesium concentration is inversely associated with all-cause mortality and cardiovascular mortality and events. Therefore, increasing magnesium may improve risk in patients with chronic kidney disease. This meta-analysis forms a firm base for future prospective trials to test whether increasing plasma magnesium, indeed has beneficial effects on clinical outcomes.
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Association of magnesium intake with type 2 diabetes and total stroke: an updated systematic review and meta-analysis.
Zhao, B, Zeng, L, Zhao, J, Wu, Q, Dong, Y, Zou, F, Gan, L, Wei, Y, Zhang, W
BMJ open. 2020;(3):e032240
Abstract
OBJECTIVE The detailed associations between type 2 diabetes (T2D) and total stroke and magnesium intake as well as the dose-response trend should be updated in a timely manner. DESIGN Systematic review and meta-analyses. DATA SOURCES PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov were rigorously searched from inception to 15 March 2019. ELIGIBILITY CRITERIA Prospective cohort studies investigating these two diseases were included. DATA SYNTHESIS Relative risk (RR) and 95% CI in random effects models as well as absolute risk (AR) were pooled to calculate the risk of T2D and stroke. Methodological quality was assessed by the Newcastle-Ottawa Scale. RESULTS Forty-one studies involving 53 cohorts were included. The magnitude of the risk was significantly reduced by 22% for T2D (RR 0.78 (95% CI 0.75 to 0.81); p<0.001; AR reduction 0.120%), 11% for total stroke (RR 0.89 (95% CI 0.83 to 0.94); p<0.001; AR reduction 0.281%) and 12% for ischaemic stroke (RR 0.88 (95% CI 0.81 to 0.95); p=0.001; AR reduction 0.246%) when comparing the highest magnesium intake to the lowest. The inverse association still existed when studies on T2D were adjusted for cereal fibre (RR 0.79; p<0.001) and those on total stroke were adjusted for calcium (RR 0.89; p=0.040). Subgroup analyses suggested that the risk for total and ischaemic stroke was significantly decreased in females, participants with ≥25 mg/m2 body mass index and those with ≥12-year follow-up; the reduced risk in Asians was not as notable as that in North American and European populations. CONCLUSIONS Magnesium intake has significantly inverse associations with T2D and total stroke in a dose-dependent manner. Feasible magnesium-rich dietary patterns may be highly beneficial for specific populations and could be highlighted in the primary T2D and total stroke prevention strategies disseminated to the public. PROSPERO REGISTRATION NUMBER CRD42018092690.
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Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies.
Veronese, N, Demurtas, J, Pesolillo, G, Celotto, S, Barnini, T, Calusi, G, Caruso, MG, Notarnicola, M, Reddavide, R, Stubbs, B, et al
European journal of nutrition. 2020;(1):263-272
Abstract
PURPOSE To map and grade all health outcomes associated with magnesium (Mg) intake and supplementation using an umbrella review. METHODS Umbrella review of systematic reviews with meta-analyses of observational studies and randomized controlled trials (RCTs) using placebo/no intervention as control group. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values, 95% prediction intervals, heterogeneity, small-study effects and excess significance. For meta-analyses of RCTs, outcomes with a random-effect p value < 0.005 and a high-GRADE assessment were classified as strong evidence. RESULTS From 2048 abstracts, 16 meta-analyses and 55 independent outcomes were included (36 in RCTs and 19 in observational studies). In RCTs of Mg versus placebo/no active treatment, 12 over 36 outcomes reported significant results (p < 0.05). A strong evidence for decreased need for hospitalization in pregnancy and for decreased risk of frequency and intensity of migraine relapses in people with migraine was observed using the GRADE assessment. In observational studies, 9/19 outcomes were significant (p < 0.05). However, only one outcome presented highly suggestive evidence (lower incidence of type 2 diabetes in people with higher Mg intake at baseline) and one suggestive (lower incidence of stroke associated with higher Mg intake at baseline). CONCLUSION Strong evidence according to the GRADE suggests that Mg supplementation can decrease the risk of hospitalization in pregnant women and reduce the intensity/frequency of migraine. Higher Mg intake is associated with a decreased risk of type 2 diabetes and stroke with highly suggestive and suggestive evidence, respectively, in observational studies.
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Association between reduced serum levels of magnesium and the presence of poor glycemic control and complications in type 1 diabetes mellitus: A systematic review and meta-analysis.
Rodrigues, AK, Melo, AE, Domingueti, CP
Diabetes & metabolic syndrome. 2020;(2):127-134
Abstract
OBJECTIVE To evaluate the association between reduced serum magnesium levels and poor glycemic control and/or complications in patients with type 1 diabetes mellitus through a systematic review and meta-analysis. METHODS The articles were selected using the Medline/PubMed, Web of Science, Scopus and Scielo databases. Eligibility criteria were cross-sectional, cohort or case-control observational studies that assessed the association between reduced magnesium levels and poor glycemic control and/or complications in patients with type 1 diabetes mellitus. RESULTS Nine articles were included in the systematic review and two in the meta-analysis, all articles being cross-sectional. Among the seven studies that were designed to evaluate glycemic control, five showed an association between reduced levels of magnesium and poor glycemic control, and these findings were corroborated by the meta-analysis. Among the two studies in which dyslipidemia was evaluated, both showed higher levels of triglycerides, total cholesterol and LDL cholesterol, and lower levels of HDL cholesterol in patients with lower levels of magnesium as compared to those with higher magnesium levels. The three studies that evaluated diabetes kidney disease and the two studies that evaluated diabetic retinopathy found divergent results. CONCLUSION There is an association between reduced levels of magnesium and poor glycemic control in patients with type 1 diabetes mellitus, however, this needs further studies.
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Serum magnesium and the incidence of coronary artery disease over a median 27 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study and a meta-analysis.
Rooney, MR, Alonso, A, Folsom, AR, Michos, ED, Rebholz, CM, Misialek, JR, Chen, LY, Dudley, S, Lutsey, PL
The American journal of clinical nutrition. 2020;(1):52-60
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Abstract
BACKGROUND Low serum magnesium (Mg) concentrations have been associated with higher coronary artery disease (CAD) risk. A previous Atherosclerosis Risk in Communities (ARIC) Study article that evaluated the Mg-CAD association, based on 319 events occurring over 4-7 y, identified a sex-interaction whereby the inverse Mg-CAD association was much stronger among women than men. More than 1700 additional ARIC CAD events have since accrued. OBJECTIVE We aimed to test our hypothesis that serum Mg is inversely and independently associated with long-term CAD risk in ARIC and in a meta-analysis with other prospective studies. METHODS A total of 14,446 ARIC study participants (baseline mean ± SD age: 54 ± 6 y, 57% women, 27% African American) were followed for incident CAD through 2017. CAD events were defined by myocardial infarction or CAD mortality. Serum Mg was modeled as quintiles based on mean visit 1 (1987-1989) and visit 2 (1990-1992) concentrations. Cox regression models were used. We also conducted a random-effects meta-analysis incorporating these contemporary ARIC findings. RESULTS Over a median follow-up of 27 y, 2131 incident CAD cases accrued. Overall, low serum Mg was associated with higher CAD risk after adjustment for demographics, lifestyle factors, and other CAD risk factors than was higher serum Mg (HR Q1 compared with Q5: 1.28; 95% CI: 1.11, 1.47; P-linear trend <0.001). The association was stronger among women (HR Q1 compared with Q5: 1.53; 95% CI: 1.22, 1.92) than men (HR: 1.11; 95% CI: 0.92, 1.34) (P-interaction = 0.05). In the meta-analysis including 5 studies, the pooled RR (95% CI) for CAD in the lowest compared with the highest circulating Mg category was 1.18 (1.06, 1.31) (I2 = 22%, P-heterogeneity = 0.27). CONCLUSIONS In this large community-based cohort and updated meta-analysis, low circulating Mg was associated with higher CAD risk than was higher Mg. Whether increasing Mg concentrations within healthy limits is a useful strategy for CAD prevention remains to be seen.
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Serum magnesium, mortality, and cardiovascular disease in chronic kidney disease and end-stage renal disease patients: a systematic review and meta-analysis.
Xiong, J, He, T, Wang, M, Nie, L, Zhang, Y, Wang, Y, Huang, Y, Feng, B, Zhang, J, Zhao, J
Journal of nephrology. 2019;(5):791-802
Abstract
BACKGROUND Previous studies reported that magnesium deficiency was associated with vascular calcifications, atherosclerosis and cardiovascular disease, which might play an independent pathogenic role in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. However, the results of these studies were somewhat underpowered and inconclusive. METHODS Literature was identified by searching PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL). We included studies that investigated the association between serum magnesium with mortality risk in CKD and ESRD patients. Unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. RESULTS Twenty studies involving 200,934 participants were included, and the results showed that there was a strong association between hypomagnesemia and the risk of all-cause mortality in patients with CKD and ESRD (HR 1.32; 95% CI 1.19-1.47; p < 0.00001) (hypomagnesemia vs. normal magnesium or hypermagnesemia) after multivariable adjusted. On the contrary, hypermagnesemia was inversely associated with all-cause mortality in patients with CKD and ESRD (HR 0.86; 95% CI 0.79-0.94; p = 0.001) (per unit increase). Moreover, a significant association between hypermagnesemia and decreased risk of cardiovascular mortality was observed (HR 0.71; 95% CI 053-0.97, p = 0.03) in the adjusted model. In addition, subgroup analysis found that hypomagnesemia was strongly associated with increased all-cause mortality in hemodialysis patients (HR 1.29; 95% CI 1.12-1.50; p = 0.0005) (hypomagnesemia vs. normal magnesium or hypermagnesemia). CONCLUSIONS Our results indicate that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in patients with CKD and ESRD. Further studies evaluating benefits of magnesium correction in CKD and dialysis patients with hypomagnesemia should be performed.