Effect of Vitamin D Supplementation on Cardiometabolic Outcomes in Older Australian Adults—Results from the Randomized Controlled D-Health Trial

<b>Background/Objectives</b>: Observational studies have found inverse associations between 25-hydroxyvitamin D concentration and risk of hypertension, hypercholesterolemia and type 2 diabetes (T2D). More robust evidence from large-scale randomized controlled trials, however, is limited or inconclusive. <b>Methods</b>: The D-Health Trial (N = 21,315) is a randomized, double-blind, placebo-controlled trial of supplementation with monthly doses of 60,000 international units of oral vitamin D₃, conducted in Australians aged 60-84 years. Commencing treatment with anti-hypertensive, lipid-modifying, or anti-diabetic drugs was used as a surrogate for incident hypertension, hypercholesterolemia, and T2D, respectively. Outcomes were ascertained via linkage with the Australian Pharmaceutical Benefits Scheme database. Follow-up began 6 months after randomization; we excluded participants without linked data, and those who were prevalent cases or who died prior to start of follow-up. Flexible parametric survival models were used to estimate the effect of vitamin D supplementation on each outcome. <b>Results</b>: We included 10,964 participants (vitamin D, <i>n</i> = 5456 [49.8%]; placebo, <i>n</i> = 5508 [50.2%]) in the analysis of hypertension, 12,126 participants (vitamin D, <i>n</i> = 6038 [49.8%]; placebo, <i>n</i> = 6088 [50.2%]) in the analysis of hypercholesterolemia, and 17,846 (vitamin D, <i>n</i> = 8931 [50.0%]; placebo, <i>n</i> = 8915 [50.0%]) in the analysis of T2D. Over a median follow-up of 4.6 years, 2672 (24.4%), 2554 (21.1%), and 779 (4.4%) participants developed hypertension, hypercholesterolemia, and T2D, respectively. Vitamin D supplementation had no material effect on the incidence of any of hypertension (HR 1.00; 95% CI 0.93 to 1.08), hypercholesterolemia (HR 1.05; 95% CI 0.97 to 1.13), or T2D (HR 0.97; 95% CI 0.84 to 1.12). <b>Conclusions</b>: Monthly supplements of vitamin D did not alter the incidence of any of the three conditions in older, largely vitamin D-replete Australians.