Markers of subclinical atherosclerosis in premenopausal women with vitamin D deficiency and effect of vitamin D replacement

Atherosclerosis. 2014 Dec;237(2):784-9. doi: 10.1016/j.atherosclerosis.2014.10.096. Epub 2014 Oct 29.


Background: Recent studies have revealed a relationship between vitamin D deficiency and atherosclerosis. This study aims to investigate the impact of vitamin D deficiency and replacement on markers of subclinical atherosclerosis in young premenopausal women in whom vitamin D deficiency is prevalent.

Methods: Thirty-one premenopausal vitamin D deficient women and 27 age and gender-matched control subjects were enrolled in this study. Markers of subclinical atherosclerosis including carotid intima-media thickness (cIMT), flow-mediated dilatation (FMD), endothelial progenitor cell (EPC) count and cytokine levels were determined at baseline. All measurements were repeated at 6-month follow-up in vitamin D-deficient subjects after vitamin D replacement.

Results: Vitamin D deficient premenopausal women had lower FMD (9.9 ± 1.3 vs. 13.8 ± 1.7%, p < 0.001) and EPC counts at baseline. This population also had lower IL-10 and higher IL-17 levels. A 6-month vitamin D replacement therapy resulted in a significant increase in FMD (9.9 ± 1.3 vs. 11.4 ± 1.4%, p < 0.001) and EPC counts. Furthermore, cytokine profile shifted toward a more anti-inflammatory phenotype including elevated IL-10 and decreased IL-17 levels. cIMT was not different between patient and control groups and did not change following vitamin D replacement. Change in 25(OH)D and IL-17 levels were independent predictors of the change in FMD measurements following vitamin D replacement.

Conclusion: This study demonstrates that endothelial function is impaired in otherwise healthy vitamin D deficient young premenopausal women and improves with 6-month replacement therapy. Immune-modulatory effects of vitamin D may, at least partly, be responsible for its beneficial effects on vascular health.

Keywords: Endothelial function; Endothelial progenitor cell count; Inflammation; Subclinical atherosclerosis; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atherosclerosis / blood*
  • Biomarkers / metabolism
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Cell Count
  • Cytokines / blood
  • Endothelial Cells / cytology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Immune System
  • Inflammation
  • Interleukin-17 / metabolism
  • Premenopause
  • Stem Cells / cytology
  • Vitamin D / therapeutic use*
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / drug therapy


  • Biomarkers
  • Cytokines
  • Interleukin-17
  • Vitamin D