Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial

Summary Although high-dose vitamin D supplementation is common, effects on arterial calcification remain unexplored. Tibial artery calcification was identified and quantified over 3 years in participants randomized to 400, 4000, or 10,000 IU vitamin D 3 daily. High-dose vitamin D supplementation did not affect the development or progression of arterial calcification. Introduction To determine whether vitamin D supplementation has a dose-dependent effect on development and progression of arterial calcification. Methods This was a secondary analysis of the Calgary Vitamin D Study, a 3-year, double-blind, randomized controlled trial conducted at a single-center in Calgary, Canada. Participants were community-dwelling adults aged 55–70 years with serum 25-hydroxyvitamin D 30–125 nmol/L. Participants were randomized 1:1:1 to receive vitamin D 3 400, 4000, or 10,000 IU/day for 3 years. Tibial artery calcification was identified and quantified (in milligrams of hydroxyapatite, mgHA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6, 12, 24, and 36 months. Changes in calcification over time and treatment group interaction were evaluated using a constrained linear mixed effects model. Results Of 311 randomized participants, 302 (400: 105, 4000: 96, 10,000: 101) were eligible for analysis of arterial calcification (54% male, mean (SD) age 62 (4) years, mean (SD) 25-hydroxyvitamin D 78.9 (19.9) nmol/L). At baseline, 85 (28%) had tibial artery calcification, and mean (95% CI) calcification quantity was 2.8 mgHA (95% CI 1.7–3.9). In these 85 participants, calcification quantity increased linearly by 0.020 mgHA/month (95% CI 0.012–0.029) throughout the study, with no evidence of a treatment-group effect ( p = 0.645 for interaction). No participants developed new arterial calcifications during the study. Conclusions In this population of community-dwelling adults who were vitamin D replete at baseline, supplementation with vitamin D 400, 4000, or 10,000 IU/day did not have differential effects on the development or progression of arterial calcification over 3 years. Trial registration clinicaltrials.gov (NCT01900860)