Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial

Am J Clin Nutr. 2017 Jun;105(6):1372-1381. doi: 10.3945/ajcn.117.152736. Epub 2017 May 10.


Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion.Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo.Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)].Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m2): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg-1 · min-1, respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake (P > 0.1).Conclusions: Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults, despite using high-dose vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient populations. This trial was registered at as NCT02112721.

Keywords: RCT; insulin secretion; insulin sensitivity; obesity; random-ized trial; vitamin D.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Blood Glucose / metabolism
  • Body Composition
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / pharmacology*
  • Cholecalciferol / therapeutic use
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / prevention & control
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Male
  • Obesity / blood*
  • Overweight
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*


  • Blood Glucose
  • Insulin
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D

Associated data