Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial.
Level 2 - randomized trial
Secondary analysis of a double-blind randomized controlled trial
PubMed 32556518 · doi:10.1007/s00198-020-05500-2
What was done
A secondary analysis of the Calgary Vitamin D Study, a 3-year, single-center, double-blind randomized controlled trial. Community-dwelling adults aged 55–70 years with baseline serum 25-hydroxyvitamin D of 30–125 nmol/L were randomized 1:1:1 to daily vitamin D3 at 400 IU (n = 105), 4,000 IU (n = 96), or 10,000 IU (n = 101). Tibial artery calcification was measured in milligrams of hydroxyapatite (mgHA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6, 12, 24, and 36 months, evaluated via constrained linear mixed-effects models.
What was found
Among 302 analyzed participants (mean age 62 years, mean baseline 25(OH)D 78.9 nmol/L), 85 (28%) had detectable tibial artery calcification at baseline (mean 2.8 mgHA, 95% CI 1.7–3.9). In these 85 individuals, calcification increased by 0.020 mgHA/month (95% CI 0.012–0.029) over 3 years, with no significant difference between the three dose groups (p = 0.645 for group-by-time interaction). No participants developed new arterial calcifications during the study period.
Why it matters
High-dose vitamin D supplementation (up to 10,000 IU daily) is frequently used but carries theoretical concerns regarding vascular calcification; these results indicate 3 years of high-dose intake neither accelerates nor prevents peripheral arterial calcification in vitamin D-replete adults.
Limits
This was a secondary analysis, not the primary pre-specified trial outcome. Findings are limited to peripheral (tibial) artery calcification and may not generalize to coronary or aortic vessels. Participants were predominantly healthy, vitamin D-replete older adults at baseline, limiting applicability to severely vitamin D-deficient individuals or patients with established cardiovascular disease.
Cited by
- partial In a 3-year clinical trial where humans took 10,000 IU of vitamin D daily without vitamin K2, participants developed no arterial calcification, and those with pre-existing calcification experienced no progression.