Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial (Publication with Expression of Concern)

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000 IU vitamin D3 supplements (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6 months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P = 0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+ 12.3 +/- 11.4 vs. -0.1 +/- 3.7 ng/mL, P < 0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (-5.3 +/- 7.3 vs. + 2.4 +/- 5.9 mu IU/mL, P < 0.001), homeostasis model of assessment-insulin resistance (-1.2 +/- 1.6 vs. + 0.5 +/- 1.2, P < 0.001), homeostatic model assessment-Beta cell function (P = 0.005) and a significant elevation in quantitative insulin sensitivity check index (+ 0.03 +/- 0.04 vs. -0.007 +/- 0.02, P < 0.001) comparedwith the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+ 15.5 +/- 10.3 vs. + 4.0 +/- 13.4 mu mol/L, P = 0.001), total antioxidant capacity (TAC) (P = 0.04), total glutathione (GSH) (+ 11.8 +/- 153.5 vs. -294.2 +/- 595.1 mu mol/L, P = 0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (-0.8 +/- 1.0 vs. 0.03 +/- 1.4 mu mol/L, P = 0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels.