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Background Magnesium supplements may have beneficial effects on arterial stiffness. Yet, to our knowledge, no head-to-head comparison between various magnesium formulations in terms of effects on arterial stiffness has been performed. We assessed the effects of magnesium citrate supplementation on arterial stiffness and blood pressure and explored whether other formulations of magnesium have similar effects. Methods and Results In this randomized trial, subjects who were overweight and slightly obese received either magnesium citrate, magnesium oxide, magnesium sulfate, or placebo for 24 weeks. The total daily dose of magnesium was 450 mg/d. The primary outcome was carotid-to-femoral pulse wave velocity, which is the gold standard method for measuring arterial stiffness. Secondary outcomes included blood pressure and plasma and urine magnesium. Overall, 164 participants (mean±SD age, 63.2±6.8 years; 104 [63.4%] women) were included. In the intention-to-treat analysis, neither magnesium citrate nor the other formulations had an effect on carotid-to-femoral pulse wave velocity or blood pressure at 24 weeks compared with placebo. Magnesium citrate increased plasma (+0.04 mmol/L; 95% CI, +0.02 to +0.06 mmol/L) and urine magnesium (+3.12 mmol/24 h; 95% CI, +2.23 to +4.01 mmol/24 h) compared with placebo. Effects on plasma magnesium were similar among the magnesium supplementation groups, but magnesium citrate led to a more pronounced increase in 24-hour urinary magnesium excretion than magnesium oxide or magnesium sulfate. One serious adverse event was reported, which was considered unrelated to the study treatment. Conclusions Oral magnesium citrate supplementation for 24 weeks did not significantly change arterial stiffness or blood pressure. Magnesium oxide and magnesium sulfate had similar nonsignificant effects. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03632590.

Background: Direct methods for the assessment of intra-erythrocyte magnesium (dIEM) require extensive sample preparation, making them labor intensive. An alternative, less labor intensive method is indirect calculation of intra-erythrocyte magnesium (iIEM). We compared dIEM and iIEM and studied determinants of dIEM and iIEM, plasma magnesium and 24-h urinary magnesium excretion in a large population-based cohort study., Methods: dIEM and iIEM were measured using a validated inductively coupled plasma mass spectrometry (ICP-MS) method in 1669 individuals from the second screening from the LifeLines Cohort Study. We used linear regression analyses to study the determinants of IEM, plasma magnesium and 24-h urinary magnesium excretion., Results: Mean dIEM and iIEM were 0.20 ± 0.04 mmol/10 12 cells and 0.25 ± 0.04 mmol/10 12 cells, respectively. We found a strong correlation between dIEM and iIEM (r = 0.75). Passing-Bablok regression analyses showed an intercept of 0.015 (95% CI: 0.005; 0.023) and a slope of 1.157 (95% CI: 1.109; 1.210). In linear regression analyses, plasma levels of total- and LDL -cholesterol, and triglycerides were positively associated dIEM, iIEM, and plasma magnesium, while glucose and HbA1c were inversely associated with plasma magnesium., Conclusions: We observed a strong correlation between dIEM and iIEM, suggesting that iIEM is a reliable alternative for the labor intensive dIEM method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

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 (PWV c-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.

Background: Low circulating magnesium (Mg) is associated with an increased risk of developing type 2 diabetes mellitus (T2DM). We aimed to study the performance of a nuclear magnetic resonance (NMR)-based assay that quantifies ionized Mg in EDTA plasma samples and prospectively investigate the association of Mg with the risk of T2DM., Methods: The analytic performance of an NMR-based assay for measuring plasma Mg was evaluated. We studied 5747 subjects free of T2DM at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study., Results: Passing⁻Bablok regression analysis, comparing NMR-measured ionized Mg with total Mg measured by the Roche colorimetric assay, produced a correlation of r = 0.90, with a slope of 1.08 (95% CI: 1.00⁻1.13) and an intercept of 0.02 (95% CI: -0.02⁻0.08). During a median follow-up period of 11.2 (IQR: 7.7⁻12.0) years, 289 (5.0%) participants developed T2DM. The association of NMR-measured ionized Mg with T2DM risk was modified by sex (P interaction = 0.007). In women, we found an inverse association between Mg and the risk of developing T2DM, independent of adjustment for potential confounders (HR: 1.80; 95% CI: 1.20⁻2.70). In men, we found no association between Mg and the risk of developing T2DM (HR: 0.90; 95%: 0.67⁻1.21)., Conclusion: Lower NMR-measured plasma ionized Mg was independently associated with a higher risk of developing T2DM in women, but not in men., Competing Interests: E.J.J., I.S., J.D.O., and M.A.C. are employees of LabCorp.