No Effect of High-Dose Vitamin D Supplementation on Glycemic Status or Cardiovascular Risk Factors in Subjects With Prediabetes

Randomized, placebo-controlled trial in adults with prediabetes, defined by impaired fasting glucose and/or impaired glucose tolerance, without diabetes. The active vitamin D arm randomized 256 participants and 242 completed and were analyzed per protocol; mean age was 62.3 ± 8.1 years, 62.9% were male, and mean BMI was 30.1 ± 4.1 kg/m2. The study was conducted in Tromsø, Norway.

The active regimen was oral cholecalciferol (vitamin D3) 20,000 IU per week, given as identical-looking capsules for 6 months, compared with placebo. Participants were not allowed to take vitamin D supplements above 400 IU/day during the trial.

High-dose vitamin D did not improve glycemic status or cardiovascular risk factors over 1 year in adults with prediabetes. Serum 25(OH)D rose substantially in the vitamin D group, increasing by 45.8 ± 24.2 nmol/L versus 3.4 ± 16.9 nmol/L with placebo (P < 0.001), and PTH fell by 0.5 pmol/L versus a 0.2 pmol/L increase with placebo (P < 0.001). Total cholesterol fell by 0.16 mmol/L and LDL cholesterol by 0.17 mmol/L versus placebo (P < 0.05), but HDL cholesterol decreased and the TC/HDL ratio did not differ significantly. There were no significant between-group differences in glycemic indices, blood pressure, or hs-CRP after baseline adjustment; one participant developed transient hypercalcemia and no major adverse effects were seen.

The trial showed no benefit on the main clinical outcomes despite clear biochemical repletion, which limits clinical interpretability. Results come from a single Norwegian prediabetes cohort, and the active arm had 242 per-protocol analyzable participants, so generalizability and power for smaller effects may be limited. The intervention was only 6 months of dosing with 12-month follow-up, and one hypercalcemia case led to exclusion.