The effect of vitamin D supplementation on cancer incidence in the randomised controlled D-Health Trial: implications for policy and practice.

Abstract

Meta-analyses suggest that vitamin D supplementation reduces cancer mortality. As mortality is a function of incidence and survival, if use of vitamin D supplements does reduce cancer mortality, it must affect one or both of these parameters. Trials have found little evidence that vitamin D supplementation affects cancer incidence, but results were generally imprecise. We analysed data from the D-Health Trial, a randomised controlled trial of 60,000 IU of vitamin D₃ per month or matching placebo. 21,315 adults aged 60-85 years were recruited and supplemented for up to 5 years. We captured cancer diagnoses through linkage to state cancer registries. This analysis included 21,308 participants (vitamin D, n=10,660; placebo, n=10,648). The number of participants diagnosed with at least one cancer (excluding keratinocyte cancers) in the vitamin D and placebo groups was 1,336 and 1,304, respectively. We found no difference in cancer incidence between the two groups (HR 1.02; 95% CI 0.95-1.10). Similarly, there was minimal difference when cutaneous melanomas were excluded (HR 1.04; 95% CI 0.95-1.14). Analyses of individual cancers (prostate, breast, colorectal, lung, melanoma) did not demonstrate any effect of vitamin D, although the confidence intervals were relatively wide. These results provide convincing evidence to confirm the lack of effect of vitamin D on cancer incidence overall. The disconnect between effects on incidence and mortality would imply an effect on cancer survival. Determining whether any survival benefit is driven by vitamin D status prior to or after cancer diagnosis will be extremely challenging - indeed it may not be possible. Thus, it would be reasonable to consider whether population-wide supplementation or supplementation of cancer patients should be recommended now.