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

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. This trial was registered at clinicaltrials.gov as NCT00491322.