European Journal of Cancer · Nov 2026
Vitamin D supplementation, cancer incidence and mortality: Randomized trials revisited
By Wang Y, Sha S, Gwenzi T et al.
Background Vitamin D insufficiency and deficiency are highly prevalent among older adults globally and have been associated with increased cancer mortality in observational studies. Large randomized trials (VITAL and D-Health) found no reductions in cancer incidence or mortality with vitamin D supplementation but included mostly vitamin D-sufficient populations. Methods Using UK Biobank (UKB) data, we conducted analyses informed by the VITAL and D-Health designs, applying their eligibility criteria and assuming the serum 25-hydroxyvitamin D (25(OH)D) increases observed in the trials (30 and 38 nmol/L, respectively). Populations meeting the trial criteria were weighted to match the trial baseline 25(OH)D distributions. To emulate alternative targeted interventions, analyses were restricted to vitamin D-insufficient or -deficient individuals (25(OH)D <50 or <30 nmol/L, respectively). Multivariable Cox models estimated associations per 30 or 38 nmol/L higher baseline 25(OH)D concentration over the corresponding trial follow-up periods. Results In analyses reflecting the original VITAL or D-Health 25(OH)D distributions, no association with cancer incidence or mortality was observed for the 25(OH)D increases achieved in the trials. However, inverse associations with cancer mortality were observed among vitamin D-insufficient and -deficient individuals, with hazard ratios (95% confidence intervals) of 0.93 (0.86–1.02) and 0.87 (0.77–0.97) in the VITAL-type cohort, and 0.92 (0.85–0.99) and 0.87 (0.80–0.96) in the D-Health-type cohort. Conclusion Increases in 25(OH)D concentrations achieved in the trials were associated with substantially lower cancer mortality among vitamin D-insufficient and -deficient individuals. Null effects on cancer incidence and mortality observed in the trials were to be expected given the lack of associations between 25(OH)D and these outcomes among vitamin D replete populations.