The effect of vitamin D replacement on markers of vascular health in stroke patients - a randomised controlled trial.

BACKGROUND AND AIMS: Low vitamin D levels are associated with increased incidence of future cardiovascular events and are common in stroke patients. We tested whether vitamin D supplementation could reduce blood pressure and improve markers of vascular health in patients who had previously suffered a stroke. METHODS AND RESULTS: Randomised, placebo-controlled, double-blind trial. Community-dwelling patients with a history of stroke and baseline 25-hydroxyvitamin D levels <75 nmol/L received 100,000 units of oral vitamin D2 or placebo at baseline. Office and 24 h blood pressure, endothelial function measured by flow-mediated dilatation of the brachial artery, cholesterol, oxidised low density lipoprotein, B-type natriuretic peptide and heart rate turbulence were measured at baseline, 8 weeks and 16 weeks. 58 patients were randomised. Mean age was 67 years, mean baseline blood pressure 128/72 mmHg, mean baseline 25-hydroxyvitamin D level was 38 nmol/L. Serum 25-hydroxyvitamin D levels were higher in the intervention group at 8 weeks compared to placebo (54 vs 42 nmol/L, P = 0.002) and remained higher at 16 weeks. Office systolic and diastolic blood pressure showed no significant change between groups at 8 weeks (systolic 126.1 vs 131.3 mmHg; adjusted P = 0.97); (diastolic 73.1 vs 74.9 mmHg, adjusted P = 0.15). Flow mediated dilatation was significantly higher in the intervention group at 8 weeks (6.9% vs 3.7%, adjusted P = 0.007) but was not significantly different at 16 weeks. CONCLUSIONS: High dose oral vitamin D supplementation did not improve blood pressure but produced short-term improvement in endothelial function in stroke patients with well-controlled baseline blood pressure. CLINICAL TRIALS REGISTRATION: ISRCTN28737567.

The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Low 25-hydroxyvitamin D levels predict future cardiovascular events and are common in patients with type 2 diabetes. We compared the effect of 100,000 and 200,000 IU doses of vitamin D(3) on endothelial function, blood pressure and markers of glycaemic control in patients with type 2 diabetes. METHODS: This was a randomised, parallel group, placebo-controlled trial. Patients with type 2 diabetes and baseline 25-hydroxyvitamin D levels <100 nmol/l were enrolled from community and hospital-based diabetes clinics. Participants were assessed in a university department of clinical pharmacology and received a single oral dose of placebo or vitamin D(3) (100,000 IU or 200,000 IU) at baseline, randomly allocated via numbered bottles prepared offsite; participants and investigators were both blinded to treatment allocation. Endothelial function, office blood pressure, B-type natriuretic peptide, insulin resistance and glycosylated haemoglobin were measured at baseline, and at 8 and 16 weeks. RESULTS: We randomised 61 participants to the three groups (placebo 22, 100,000 IU vitamin D(3) 19, 200,000 IU vitamin D(3) 20). There was no significant difference in the primary outcome of endothelial function at 8 weeks (placebo 5.2%, n = 22; 100,000 IU 4.3%, n = 19; 200,000 IU 4.9%, n = 17) or at 16 weeks. Insulin resistance and glycosylated haemoglobin did not improve with either dose of vitamin D(3). On covariate analysis, systolic blood pressure was significantly lower in both treatment arms than in the placebo group at 8 weeks (placebo 146.4 mmHg, 100,000 IU 141.4 mmHg [p = 0.04 vs placebo], 200,000 IU 136.8 mmHg [p = 0.03 vs placebo]). B-type natriuretic peptide levels were significantly lower in the 200,000 IU group by 16 weeks (placebo 34 pg/ml, 200,000 IU 21 pg/ml, p = 0.02). No significant excess of adverse effects was noted in the treatment arms. CONCLUSIONS/INTERPRETATION: High-dose vitamin D(3) improved systolic blood pressure and B-type natriuretic peptide levels, but not endothelial function, insulin resistance or glycosylated haemoglobin in patients with type 2 diabetes.