Influence of Vitamin D in Vascular Ageing: A Systematic Review

Abstract

Background: Vascular ageing comprising arterial stiffening, endothelial dysfunction, and vascular calcification contributes importantly to cardiovascular risk in aging populations. Vitamin D (serum 25-hydroxyvitamin D, active metabolites, VDR signaling) has plausible mechanistic links to vascular health, but the evidence remains unclear. Our objective in this article is to systematically review PubMed-indexed observational studies and randomized controlled trials (RCTs) on vitamin D status or supplementation and markers of vascular ageing.

Methods: We searched PubMed through September 2025 using specified search strings combining vitamin D terms and vascular ageing outcomes (arterial stiffness, endothelial function, vascular calcification). We included observational and RCT studies assessing associations or effects on pulse wave velocity (PWV), augmentation index (AIx), flow-mediated dilation (FMD) or vascular calcification. We extracted data for a PICOS summary, assessed trial bias (RoB2) and observational study quality (Newcastle-Ottawa Scale), and synthesized results qualitatively (given heterogeneity).

Results: The search yielded 312 unique PubMed hits; after screening and eligibility, 18 studies were included (9 observational, 9 RCTs). Observational studies consistently reported inverse associations between low serum 25-OH D and increased arterial stiffness or impaired endothelial function. Among RCTs, results were mixed: some trials in vitamin D–deficient populations (≥4 months, ≥2,000 IU/day) showed modest reductions in PWV, while others (especially in vitamin D–replete populations or short duration) showed null effects. Evidence on vascular calcification was sparse and inconclusive. Risk of bias varied: several trials lacked allocation concealment or had incomplete outcome data; observational studies often had residual confounding.

Conclusion: Observational data support an association of low vitamin D status with markers of vascular ageing. However, RCT evidence is inconsistent, with benefits largely restricted to vitamin D–deficient subgroups under sufficient dosing/duration. To guide clinical implications, larger, well-powered RCTs targeting deficient populations with standardized vascular ageing endpoints are needed.