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Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial.

ABSTRACT: BACKGROUND:Arterial stiffness is closely related to the process of atherosclerosis, an independent cardiovascular risk factor, and predictive of future cardiovascular events and mortality. Recently, we showed that magnesium citrate supplementation results in a clinically relevant improvement of arterial stiffness. It remained unclear whether the observed effect was due to magnesium or citrate, and whether other magnesium compounds may have similar effects. Therefore, we aim to study the long-term effects of magnesium citrate, magnesium oxide and magnesium sulfate on arterial stiffness. In addition, we aim to investigate possible underlying mechanisms, including changes in blood pressure and changes in gut microbiota diversity. METHODS:In this randomized, double-blind, placebo-controlled trial, a total of 162 healthy overweight and slightly obese men and women will be recruited. During a 24-week intervention, individuals will be randomized to receive: magnesium citrate; magnesium oxide; magnesium sulfate (total daily dose of magnesium for each active treatment 450?mg); or placebo. The primary outcome of the study is arterial stiffness measured by the carotid-femoral pulse wave velocity (PWVc-f), which is the gold standard for quantifying arterial stiffness. Secondary outcomes are office blood pressure, measured by a continuous blood pressure monitoring device, and gut microbiota, measured in fecal samples. Measurements will be performed at baseline and at weeks 2, 12 and 24. DISCUSSION:The present study is expected to provide evidence for the effects of different available magnesium formulations (organic and inorganic) on well-established cardiovascular risk markers, including arterial stiffness and blood pressure, as well as on the human gut microbiota. As such, the study may contribute to the primary prevention of cardiovascular disease in slightly obese, but otherwise healthy, individuals. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03632590 . Retrospectively registered on 15 August 2018.

SUBMITTER: Schutten JC

PROVIDER: S-EPMC6540466 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial.

Schutten Joëlle C JC Joris Peter J PJ Mensink Ronald P RP Danel Richard M RM Goorman Frans F Heiner-Fokkema M Rebecca MR Weersma Rinse K RK Keyzer Charlotte A CA de Borst Martin H MH Bakker Stephan J L SJL

Trials 20190528 1

<h4>Background</h4>Arterial stiffness is closely related to the process of atherosclerosis, an independent cardiovascular risk factor, and predictive of future cardiovascular events and mortality. Recently, we showed that magnesium citrate supplementation results in a clinically relevant improvement of arterial stiffness. It remained unclear whether the observed effect was due to magnesium or citrate, and whether other magnesium compounds may have similar effects. Therefore, we aim to study the ...[more]

PMID: 31138315

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Project description:BackgroundArterial stiffness and calcification propensity are associated with high cardiovascular risk and increased mortality in chronic kidney disease (CKD). Both magnesium and phosphate are recognized as modulators of vascular calcification and chronic inflammation, both features of CKD that contribute to arterial stiffness. In this paper, we outline the rationale and design of a randomized controlled trial (RCT) investigating whether 24 weeks of oral magnesium supplementation with or without additional phosphate-binding therapy can improve arterial stiffness and calcification propensity in patients with stage 3-4 CKD.MethodsIn this multi-center, placebo-controlled RCT, a total of 180 participants with an estimated glomerular filtration rate of 15 to 50 ml/min/1.73 m2 without phosphate binder therapy will be recruited. During the 24 weeks intervention, participants will be randomized to one of four intervention groups to receive either magnesium citrate (350 mg elemental magnesium/day) or placebo, with or without the addition of the phosphate binder sucroferric oxyhydroxide (1000 mg/day). Primary outcome of the study is the change of arterial stiffness measured by the carotid-femoral pulse wave velocity over 24 weeks. Secondary outcomes include markers of calcification and inflammation, among others calcification propensity (T50) and high-sensitivity C-reactive protein. As explorative endpoints, repeated 18F-FDG and 18F-NaF PET-scans will be performed in a subset of participants (n = 40). Measurements of primary and secondary endpoints are performed at baseline, 12 and 24 weeks.DiscussionThe combined intervention of magnesium citrate supplementation and phosphate-lowering therapy with sucroferric oxyhydroxide, in stage 3-4 CKD patients without overt hyperphosphatemia, aims to modulate the complex and deregulated mineral metabolism leading to vascular calcification and arterial stiffness and to establish to what extent this is mediated by T50 changes. The results of this combined intervention may contribute to future early interventions for CKD patients to reduce the risk of CVD and mortality.Trial registrationNetherlands Trial Register, NL8252 (registered December 2019), EU clinical Trial Register 2019-001306-23 (registered November 2019).

Project description:BackgroundDevelopment of instruments capable of detecting early stage vascular disease has increased interest in employing arterial stiffness (e.g. pulse wave velocity (PWV), augmentation index (AIx)) and endothelial dysfunction (e.g. reactive hyperemia index (RHI)) to diagnose atherosclerotic disease before occurrence of a cardiovascular event. However, amongst the equipment designed for this purpose, there is insufficient information regarding each of these parameters to establish appropriate cutoffs to distinguish between healthy and unhealthy blood vessels. To address these limitations, the study was designed to establish the upper arterial stiffness and endothelial function thresholds in a healthy population, by comparing the outputs from different instruments capable of measuring PWV, AIx and RHI.MethodsA systematic comparison of PWV, AIx and RHI was conducted to determine the inter-relationships between these parameters of vascular functionality. Outputs were obtained non-invasively using three instruments, the VP-1000 (VP), SphygmoCor (SC), and EndoPAT (EP), in 40 apparently healthy males and females.ResultsCorrelations were found between the brachial-ankle PWV and radial-ankle PWV (by VP and SC), and PWV (VP) with AIx (SC). The interchangeability of these outputs was demonstrated by the Bland Altman test, making it feasible to extrapolate cut-offs for radial-ankle PWV and AIx equivalent to brachial-ankle PWV that signify healthy vessels. In contrast, RHI showed no association with AIx, suggesting these endothelial and arterial parameters are functionally distinct.ConclusionsIt was concluded that it is possible to compare the vascular function outputs of different instruments and identify healthy from unhealthy vessels, even though the approaches for quantifying the underlying physiological processes may differ. In this way, non-invasive determination of arterial function could be a new paradigm for detecting existing early stage asymptomatic atherosclerotic disease in individuals using techniques that are amenable to the clinical setting.

Project description:Dietary magnesium intake has been favorably associated with reduced risk of metabolic outcomes in observational studies; however, few randomized trials have introduced a systems-biology approach to explore molecular mechanisms of pleiotropic metabolic actions of magnesium supplementation.We examined the effects of oral magnesium supplementation on metabolic biomarkers and global genomic and proteomic profiling in overweight individuals.We undertook this randomized, crossover, pilot trial in 14 healthy, overweight volunteers [body mass index (in kg/m(2)) ?25] who were randomly assigned to receive magnesium citrate (500 mg elemental Mg/d) or a placebo for 4 wk with a 1-mo washout period. Fasting blood and urine specimens were collected according to standardized protocols. Biochemical assays were conducted on blood specimens. RNA was extracted and subsequently hybridized with the Human Gene ST 1.0 array (Affymetrix, Santa Clara, CA). Urine proteomic profiling was analyzed with the CM10 ProteinChip array (Bio-Rad Laboratories, Hercules, CA).We observed that magnesium treatment significantly decreased fasting C-peptide concentrations (change: -0.4 ng/mL after magnesium treatment compared with +0.05 ng/mL after placebo treatment; P = 0.004) and appeared to decrease fasting insulin concentrations (change: -2.2 ?U/mL after magnesium treatment compared with 0.0 ?U/mL after placebo treatment; P = 0.25). No consistent patterns were observed across inflammatory biomarkers. Gene expression profiling revealed up-regulation of 24 genes and down-regulation of 36 genes including genes related to metabolic and inflammatory pathways such as C1q and tumor necrosis factor-related protein 9 (C1QTNF9) and pro-platelet basic protein (PPBP). Urine proteomic profiling showed significant differences in the expression amounts of several peptides and proteins after treatment.Magnesium supplementation for 4 wk in overweight individuals led to distinct changes in gene expression and proteomic profiling consistent with favorable effects on several metabolic pathways. This trial was registered at clinicaltrials.gov as NCT00737815.

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Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial.

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Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial.

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