Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Objective: This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Methods: This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Results: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (–7.8 ± 9.2 vs. –1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (–3.2 ± 4.8 vs. –0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (–815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. –53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo. Conclusions: Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.

Effect of Alpha-Lipoic Acid Supplementation on Low-Grade Squamous Intraepithelial Lesions—Double-Blind, Randomized, Placebo-Controlled Trial

“…In the placebo group, spontaneous LSIL regression was observed in only 8.3% of patients, which is rather low considering that rates are predicted to be ranging from 40% to 70% over a period of 1–5 years [ 28 ]. Additionally, in available intervention studies that investigated the possibilities of nutritional supplementation in inducing the regression of LSIL, the rates of spontaneous regression observed in placebo groups were higher (52.0–56.0%) [ 11 , 12 , 13 , 28 ]. The reasons for the observed disagreement with the results obtained in this study might include the short monitoring period (3 months vs. 6 months in intervention trials or 1–5 years in observational studies) and a high median age of participants (37 and 41).…”

“…Unlike ours, those studies included a lower number of patients and investigated long-term supplementation protocols (6 months). Vahedpoor and co-workers [ 13 ] showed that 6-month vitamin D supplementation of patients with LSIL (one dose of 50,000 IU vitamin D supplement every 2 weeks) resulted in the regression of cervical intraepithelial neoplasia grade 1 (CIN1) in 84.6% of patients (n = 29). Similarly, supplementation with 5 mg of folic acid for 6 months resulted in 83.3% regression of CIN 1 (n = 29) [ 12 ], as well as the long-term supplementation (6 months) with 200 µg of organic form of selenium in 88% of women in the supplemented group (n = 28) [ 11 ].…”

“…On the other hand, taking selenium supplements (200 μg for 6 months) among patients with LSIL led to its regression and had beneficial effects on their metabolic profiles [ 11 ]. Folate supplementation (5 mg/day, 6 months) was efficient in inducing the regression of LSIL [ 12 ], and vitamin D (50,000 IU every two weeks for 6 months) prevented the recurrence of HSIL [ 13 ].…”

Effects of vitamin D supplementation on inflammatory response in patients with cancer and precancerous lesions: systematic review and meta-analysis of randomized trials.

“…One [21] more study was included via cross-referencing. Nine studies [13,[21][22][23][24][25][26][27][28] were nally included in this systematic review and eight studies were included in the meta-analyses with a total of 592 patients. Other studies were excluded based on prede ned criteria as depicted in Supplementary Table 2.…”

“…Moreover, a recent meta-analysis of RCTs reported a signi cant 35% reduction of CRC mortality by VID3S among patients with prior CRC diagnosis [12]. VID3S has also shown bene ts on recurrence and metabolic pro les in patients with adenomas [13].…”