Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial

Am J Clin Nutr. 2015 Aug;102(2):385-92. doi: 10.3945/ajcn.115.111682. Epub 2015 Jul 8.


Background: Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant.

Objective: The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)D(total).

Design: This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered 50,000 IU ergocalciferol/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure.

Results: On-study 25(OH)D(total) was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)D(total) rose from 18 ± 7 to 43 ± 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity; nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)D(total), or BMI.

Conclusion: In healthy persons with low 25(OH)D(total), ergocalciferol administration for 12 wk normalizes 25(OH)D(total) but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health.

Trial registration: NCT00491322.

Keywords: diabetes; ergocalciferol; glucose; insulin; insulin resistance; vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D 2 / blood
  • Adult
  • Biomarkers / blood
  • Boston / epidemiology
  • Calcifediol / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Dietary Supplements*
  • Double-Blind Method
  • Ergocalciferols / administration & dosage
  • Ergocalciferols / therapeutic use*
  • Female
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Longitudinal Studies
  • Male
  • Risk
  • Severity of Illness Index
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / diet therapy*
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / physiopathology
  • Young Adult


  • Biomarkers
  • Ergocalciferols
  • Insulin
  • 25-Hydroxyvitamin D 2
  • Calcifediol

Associated data