Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D-deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial.

Randomized, placebo-controlled trial in overweight, vitamin D-deficient non-Western immigrants in the Netherlands at elevated diabetes risk. Participants were 20 to 65 years old, had BMI at least 27 kg/m^2, and had impaired fasting glucose or glucose intolerance; randomization was stratified by sex.

Oral vitamin D3, 1200 IU/day as three 400 IU tablets daily for 16 weeks, compared with placebo. Calcium carbonate 500 mg/day was given to all participants as background supplementation and was not the active test intervention.

Vitamin D3 raised serum 25(OH)D substantially but did not improve the main metabolic outcomes. In the intervention group, mean 25(OH)D increased from 25 +/- 11 nmol/L at baseline to 58 +/- 12 nmol/L after 2 months and 60 +/- 16 nmol/L after 4 months; the between-group difference at 4 months was 38 nmol/L (95% CI: 32.1, 43.9; P < 0.001). Despite this biochemical response, there was no significant effect on insulin sensitivity, beta-cell function, or metabolic syndrome incidence. A post hoc analysis found that among non-diabetic participants who reached 25(OH)D at least 60 nmol/L, the insulinogenic index increased (P = 0.040).

The trial was relatively short and the main clinical outcomes were negative despite a clear rise in 25(OH)D. The favorable insulinogenic index finding was post hoc and limited to a subgroup, which lowers confidence in that signal. Generalizability is limited to overweight, vitamin D-deficient non-Western immigrants with abnormal glucose metabolism.