The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials
What this study found
Vitamin D3 supplementation is associated with a clinically meaningful improvement in colorectal cancer survival: overall adverse outcomes reduced by about 30% (HR 0.70; 95% CI 0.48–0.93). Among trials enrolling CRC patients at diagnosis, progression-free survival improved (HR 0.65; 95% CI 0.36–0.94). Population trials showed a possible improvement in CRC-specific survival (HR 0.76; 95% CI 0.39–1.13). No heterogeneity or publication bias detected. Authors conclude that supplementation may meaningfully improve CRC survival and call for well-designed, adequately powered RCTs to define optimal…
- Study & population
- Randomized controlled trials in adults.
- Intervention
- AMATERASU: vitamin D3, 2000 IU/day, oral, for 3.5 years with standard chemotherapy.
- Key limitation
- Small number of trials and participants; regimens and outcomes were heterogeneous; Golubic trial excluded from meta-analysis due to high risk of bias; incomplete reporting of HRs for some trials; limited data on cancer stage, adjuvant therapy, and genetic factors; generalizability may be limited to trial conditions…
View source
Open PDFOriginal abstract
Low circulating vitamin D levels are associated with poor colorectal cancer (CRC) survival. We assess whether vitamin D supplementation improves CRC survival outcomes. PubMed and Web of Science were searched. Randomised controlled trial (RCTs) of vitamin D supplementation reporting CRC mortality were included. RCTs with high risk of bias were excluded from analysis. Random-effects meta-analysis models calculated estimates of survival benefit with supplementation. The review is registered on PROSPERO, registration number: CRD42020173397. Seven RCTs (n = 957 CRC cases) were identified: three trials included patients with CRC at outset, and four population trials reported survival in incident cases. Two RCTs were excluded from meta-analysis (high risk of bias; no hazard ratio (HR)). While trials varied in inclusion criteria, intervention dose and outcomes, meta-analysis found a 30% reduction in adverse CRC outcomes with supplementation (n = 815, HR = 0.70; 95% confidence interval (CI): 0.48–0.93). A beneficial effect was seen in trials of CRC patients (progression-free survival, HR = 0.65; 95% CI: 0.36–0.94), with suggestive effect in incident CRC cases from population trials (CRC-specific survival, HR = 0.76; 95% CI: 0.39–1.13). No heterogeneity or publication bias was noted. Meta-analysis demonstrates a clinically meaningful benefit of vitamin D supplementation on CRC survival outcomes. Further well-designed, adequately powered RCTs are needed to fully evaluate benefit of supplementation in augmenting ‘real-life’ follow-up and adjuvant chemotherapy regimens, as well as determining optimal dosing.