Magnesium supplementation did not reduce serum calciprotein crystallization and arterial stiffness in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Background: Medial arterial calcification (MAC) and increased arterial stiffness contribute to cardiovascular disease risk in type 2 diabetes mellitus (T2DM). Experimental studies suggest that magnesium supplementation may halt arterial calcification and improve arterial stiffness. Objectives: This study aimed to evaluate the effect of 6-mo oral magnesium citrate supplementation on calciprotein crystallization (T₅₀) and carotid-femoral pulse wave velocity (cfPWV) in individuals with T2DM and peripheral MAC. Methods: This double-blind, placebo-controlled trial randomly assigned 74 participants with T2DM [78% males, 72 (68–76) y] with peripheral MAC and cfPWV≥12.0 m/s to magnesium citrate (350 mg/d; n = 37) or placebo (n = 37). Nephelometry-based T₅₀ measurements, cfPWV measurements, and 24-h urine collections were obtained at baseline, 3 and 6 mo. Longitudinal analysis of covariance adjusted for baseline T₅₀ and cfPWV was used to study the treatment effects on T₅₀ and cfPWV. Results: Baseline mean T₅₀ and cfPWV were similar between the magnesium group (T₅₀ 348 ± 54 min; cfPWV 15.9 ± 2.2 m/s) and the placebo group (362 ± 54 min; 15.6 ± 2.0 m/s). Magnesium in serum and in 24-h urine were lower in the magnesium group [0.74 (0.71–0.77) mmol/L and 3.30 (2.06–4.71) mmol/24 h] compared with the placebo group [0.81 (0.74–0.86) mmol/L and 4.31 (3.09–5.54) mmol/24 h]. Supplementation increased 24-h urine magnesium excretion (P < 0.001), but not serum magnesium concentration (P = 0.073) over time in the magnesium group relative to the placebo group. Magnesium supplementation did not increase T₅₀ [ẞ = 6 min (–11, 22), P = 0.491] but did increase cfPWV [ẞ = 0.8 m/s (0.1, 1.5), P = 0.021] over 6 mo in the magnesium group relatively to the placebo group, but the statistical significance was lost after adjusting for clinically relevant baseline differences [T₅₀: ẞ = 7 min (–12, 25), P = 0.482; cfPWV: ẞ = 0.5 m/s (–0.2, 1.3), P = 0.180]. Conclusions: Six-month magnesium citrate supplementation did not reduce calciprotein crystallization and arterial stiffness in older individuals with T2DM with peripheral MAC. Daily supplementation of 350 mg appears to be ineffective in this population, possibly attributable to normomagnesemia and preserved renal function.This study was registered at the Dutch Trial Register (CCMO) as NL81281.029.22 and at ISRCTN as 60460377.