The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials
Br J Cancer. 2020 Sep 15. doi: 10.1038/s41416-020-01060-8
Peter G Vaughan-Shaw 1 2, Louis F Buijs 1 2, James P Blackmur 1 2, Evi Theodoratou 2 3, Lina Zgaga 4, Farhat V N Din 1 2, Susan M Farrington 1 2, Malcolm G Dunlop 5 6
NOTE: This meta-analysis, like many others, ignores dose size yet still finds a benefit
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Background: Low circulating vitamin D levels are associated with poor colorectal cancer (CRC) survival. We assess whether vitamin D supplementation improves CRC survival outcomes.
Methods: 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.
Results: 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.
Conclusions: 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.
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