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: Type 2 diabetes is associated with both impaired insulin action at target tissues and impaired insulin secretion in pancreatic beta cells. Mitochondrial dysfunction may play a role in both insulin resistance and impaired insulin secretion. Plasma creatine has been proposed as a potential marker for mitochondrial dysfunction. We aimed to investigate the association between plasma creatine and incident type 2 diabetes.Methods: We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the general population‐based PREVEND study. The study outcome was incident type 2 diabetes, defined as a fasting plasma glucose ≥7.0 mmol/L (126 mg/dl); a random sample plasma glucose ≥11.1 mmol/L (200 mg/dl); self‐report of a physician diagnosis or the use of glucose‐lowering medications based on a central pharmacy registration. Associations of plasma creatine with type 2 diabetes were quantified using Cox proportional hazards models and were adjusted for potential confounders.Results: We included 4735 participants aged 52 ± 11 years, of whom 49% were male. Mean plasma creatine concentrations were 36.7 ± 17.6 µmol/L, with lower concentrations in males than in females (30.4 ± 15.1 µmol/L vs. 42.7 ± 17.7 µmol/L; p for difference <.001). During 7.3 [6.2–7.7] years of follow‐up, 235 (5.4%) participants developed type 2 diabetes. Higher plasma creatine concentrations were associated with an increased risk of incident type 2 diabetes (HR per SD change: 1.27 [95% CI: 1.11–1.44]; p < .001), independent of potential confounders. This association was strongly modified by sex (p interaction <.001). Higher plasma creatine was associated with an increased risk of incident type 2 diabetes in males (HR: 1.40 [1.17–1.67]; p < .001), but not in females (HR: 1.10 [0.90–1.34]; p = .37).Conclusion: Fasting plasma creatine concentrations are lower in males than in females. Higher plasma creatine is associated with an increased risk of type 2 diabetes in males.

Objective: Increasing magnesium intake might reduce the risk of cardiovascular disease (CVD). Whether potential effects on cortisol contribute to these beneficial effects on cardiovascular health remains unclear. We therefore studied effects of long‐term oral magnesium supplementation on glucocorticoid metabolism, specifically on the excretion of urinary cortisol, cortisone and their metabolites, as well as on the ratios reflecting enzymatic activity of 11β‐hydroxysteroid dehydrogenases (11β‐HSDs) and A‐ring reductases.Design: A post‐hoc analysis of a randomized trial with allocation to a magnesium supplement (350 mg/day) or a placebo for 24‐week.Patients: Forty‐nine overweight men and women, aged between 45 and 70 years.Measurements: Cortisol, cortisone and their metabolites (tetrahydrocortisol [THF], allo‐tetrahydrocortisol [allo‐THF] and tetrahydrocortisone [THE]) were measured in 24‐h urine samples. Enzymatic activities of 11β‐HSD overall and of 11β‐HSD type 2 were estimated as the urinary (THF + allo‐THF [THFs])/THE and cortisol/cortisone ratios, respectively. A‐ring reductase activity was assessed by ratios of THF/allo‐THF, allo‐THF/cortisol, THF/cortisol and THE/cortisone.Results: After 24‐week, urinary cortisol excretion was decreased in the magnesium group as compared with the placebo group (−32 nmol/24‐h, 95% CI: −59; −5 nmol/24‐h, p = .021). Ratios of THFs/THE and cortisol/cortisone were decreased following magnesium supplementation by 0.09 (95% CI: 0.02; 0.17, p = .018) and 0.10 (95% CI: 0.03; 0.17, p = .005), respectively. No effects were observed on A‐ring reductase activity.Conclusions: We observed a beneficial effect of magnesium supplementation towards a lower 24‐h urinary cortisol excretion together with an increased activity of 11β‐HSD type 2. Our findings may provide another potential mechanism by which increased magnesium intake lowers CVD risk (ClinicalTrials.gov identifier: NCT02235805).

Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary magnesium excretion and hypomagnesaemia, in kidney transplant recipients (KTR). Plasma magnesium and 24-h urinary magnesium excretion were measured in 686 stable outpatient KTR with a functioning allograft for ≥1 year from the TransplantLines Food and Nutrition Biobank and Cohort-Study (NCT02811835). PPIs were used by 389 KTR (56.6%). In multivariable linear regression analyses, PPI use was associated with lower plasma magnesium (β: −0.02, P = 0.02) and lower 24-h urinary magnesium excretion (β: −0.82, P < 0.001). Moreover, PPI users had a higher risk of hypomagnesaemia (plasma magnesium <0.70 mmol/L), compared with non-users (Odds Ratio (OR): 2.12; 95% confidence interval (CI) 1.43–3.15, P < 0.001). This risk tended to be highest among KTR taking high PPI dosages (>20 mg omeprazole Eq/day) and was independent of adjustment for potential confounders (OR: 2.46; 95% CI 1.32–4.57, P < 0.005). No interaction was observed between PPI use and the use of loop diuretics, thiazide diuretics, tacrolimus, or diabetes (P_interaction > 0.05). These results demonstrate that PPI use is independently associated with lower magnesium status and hypomagnesaemia in KTR. The concomitant decrease in urinary magnesium excretion indicates that this likely is the consequence of reduced intestinal magnesium absorption. Based on these results, it might be of benefit to monitor magnesium status periodically in KTR on chronic PPI therapy.

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.