Impact of Vitamin D3 Supplementation on Cancer Progression and Survival Rates among Vitamin D-Deficient Cancer Patients: A Multicenter Randomized Controlled Trial

Background: Evidence linking vitamin D status with cancer outcomes is biologically plausible, but clinical findings remain inconsistent. Objective: To evaluate whether vitamin D3 supplementation affects cancer progression and survival in vitamin D-deficient patients. Methods: In this multicenter randomized controlled trial, 500 adults aged 18-75 years with a confirmed malignancy and serum 25-hydroxyvitamin D below 30 ng/mL were enrolled at five oncology centers in Khyber Pakhtunkhwa, Pakistan. Participants received vitamin D3 (2000-2200 IU/day) plus standard care or standard care alone. Outcomes included serum vitamin D, cancer progression according to RECIST 1.1, overall survival, tumor response, and associations between vitamin D change and clinical outcomes. Analyses included Kaplan-Meier methods, Cox regression, and Pearson correlation. Results: Mean serum vitamin D increased from 12.5 to 33.5 ng/mL in the intervention group (p < 0.01). Patients who achieved levels above 30 ng/mL had survival rates of 85-95% (95% CI: 82.3-97.2%), compared with 70% (95% CI: 65.4-74.6%) among severely deficient patients. Vitamin D change correlated with survival time (r = 0.72, p = 0.01), and progression-free survival favored supplementation (log-rank p < 0.01). Benefits were consistent across the evaluated cancer types (interaction p = 0.28). Conclusion: In vitamin D-deficient patients receiving cancer treatment, vitamin D3 supplementation corrected deficiency and was associated with slower progression and better survival. These findings support further confirmatory trials before routine oncologic adoption. Clinical Trial Registration: NCT05621746; registered November 14, 2022.