Vitamin D Supplementation Modulates T Cell-Mediated Immunity in Humans: Results from a Randomized Control Trial

J Clin Endocrinol Metab. 2016 Feb;101(2):533-8. doi: 10.1210/jc.2015-3599. Epub 2015 Dec 14.


Context: Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse.

Objective: Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency.

Design: This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial.

Setting: This study was undertaken in a single academic medical center.

Participants: Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included.

Intervention: In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up.

Main outcome measure: Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure.

Results: Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, -219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, -69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06-1.11).

Conclusions: In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / blood
  • Adult
  • Cholecalciferol / blood
  • Cholecalciferol / therapeutic use*
  • Cohort Studies
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / blood
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Vitamin D Deficiency / blood
  • Vitamins / therapeutic use*


  • Vitamins
  • Cholecalciferol
  • Adenosine Triphosphate