Vitamin D and Colorectal Cancer
Colorectal cancer has one of the strongest ecological correlations with vitamin D status of any malignancy — incidence rises with latitude, falls with sun exposure, and is inversely related to serum 25(OH)D. Randomised trial evidence for prevention is modest; for survival after diagnosis, it is more encouraging.
Observational evidence
Meta-analyses (Ma 2011, Song 2018) find adults in the highest quintile of 25(OH)D have ~30% lower colorectal cancer incidence than the lowest. The dose-response is linear across the sufficient range, suggesting even mid-normal 25(OH)D may not be optimal. Mendelian randomisation is mixed — some studies support causation, others do not.
Prevention RCTs
- VITAL (2019) — 25,000 adults; 2,000 IU/day for 5.3 years: no reduction in colorectal cancer incidence overall. Longer follow-up analyses (2023) hint at reduction in later years.
- Vitamin D/Calcium Polyp Prevention Study (Baron 2015) — 2,259 adults with prior adenoma; 1,000 IU vitamin D + 1,200 mg calcium did NOT reduce adenoma recurrence at 3–5 years.
- WHI-CaD — 400 IU vitamin D + 1,000 mg calcium × 7 years: no colorectal cancer reduction.
- Doses tested may be too low for a prevention signal; the ongoing D-Health Trial and higher-dose trials will inform this.
Survival — the SUNSHINE trial
SUNSHINE (2019) randomised 139 patients with metastatic colorectal cancer to high-dose vitamin D (8,000 IU/day loading for 2 weeks, then 4,000 IU/day) vs standard-dose (400 IU/day) alongside chemotherapy. The high-dose arm showed significantly longer progression-free survival (13.0 vs 11.0 months, HR 0.64, p = 0.02). Overall survival did not reach significance but trended favourably. The results are being confirmed in the larger SOLARIS trial.
Non-metastatic disease
Observational studies of stage I–III colorectal cancer show 25(OH)D at diagnosis correlates with better disease-free and overall survival. Ng 2019 (Cheney) reported 2,000 IU/day vitamin D + omega-3 supplementation improved chemotherapy tolerance. Higher-quality confirmatory trials pending.
Practical guide
- Colorectal cancer diagnosis: test 25(OH)D; target ≥ 30 ng/mL, some oncologists 40–50.
- 2,000–4,000 IU/day cholecalciferol appropriate for most patients; higher in metastatic disease under specialist supervision (SUNSHINE regimen).
- Vitamin D is adjunctive to standard therapy (surgery, chemotherapy, targeted therapy, immunotherapy for MSI-H tumours).
- Screening — vitamin D does not replace age-appropriate colonoscopy / FIT / Cologuard.