The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials

British Journal of Cancer
Q1
Sep 2020
Citations:83
Influential Citations:5
Systematic Reviews / Meta-Analyses
90
S2 IconPDF Icon

Enhanced Details

Methods
Randomized controlled trials in adults. CRC-patient trials included metastatic and non-metastatic digestive tract cancers across multiple regimens; population-trial data come from large, non-cancer cohorts. CRC trials contributed seven trials with 957 CRC cases (three CRC-at-diagnosis trials and four population-analogue trials); meta-analysis included five trials (n=815). Trials varied in baseline vitamin D status, dosing, cancer stage, and adjunct therapies. Study designs were randomized; several trials reported hazard ratios for survival outcomes; a high-bias Golubic trial was excluded from the meta-analysis.
Intervention
AMATERASU: vitamin D3, 2000 IU/day, oral, for 3.5 years with standard chemotherapy. SUNSHINE: vitamin D3, 4000 IU/day (high-dose) plus standard chemotherapy vs 400 IU/day (standard-dose), oral, for 23 months. Golubic: vitamin D3, 2000 IU/day, oral, for 46 months with standard chemotherapy. Trivedi: vitamin D3, 100,000 IU every 4 months (oral) for 5 years. WHI: vitamin D3, 400 IU/day + calcium carbonate, oral, for 7 years. RECORD: vitamin D3, 800 IU/day ± calcium, oral, for 24–62 months. VITAL: vitamin D3, 2000 IU/day + omega-3s, oral, for 5 years (vs placebo).
Results
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 dosing and applicability to real-world follow-up and adjuvant chemotherapy regimens.
Limitations
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 and adherence.

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 vit...