Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects

J Clin Endocrinol Metab. 2009 Oct;94(10):4023-30. doi: 10.1210/jc.2008-1212. Epub 2009 Jul 7.


Context: Vitamin D receptors are present in many tissues. Hypovitaminosis D is considered to be a risk factor for atherosclerosis.

Objective: This study explores the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects.

Design, setting, and patients: Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3 months. The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS).

Results: FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly lower than pretreatment levels (P < 0.001). A positive correlation between FMD and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels (r = 0.45; P < 0.05).

Conclusions: This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Atherosclerosis / etiology
  • Atherosclerosis / physiopathology
  • Biomarkers / blood
  • Blood Flow Velocity
  • Blood Pressure
  • Brachial Artery / physiopathology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Insulin Resistance*
  • Leptin / blood
  • Linear Models
  • Lipid Peroxidation* / drug effects
  • Male
  • Oxidative Stress* / drug effects
  • Risk Factors
  • Treatment Outcome
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / physiopathology*
  • Waist-Hip Ratio


  • Biomarkers
  • Leptin
  • Vitamin D
  • 25-hydroxyvitamin D