Studies in vitro and in vivo demonstrated that the physiologically active vitamin D metabolite (1,25(OH)D or calcitriol), which exerts its action via the vitamin D Receptor (VDR), has antiproliferative effects in various cell types and was found to regulate the expression of tumor-related genes, mediate inhibition of cell growth, adhesion, migration, metastases and angiogenesis. Furthermore, a number of epidemiologic showed inverse associations of cancer incidence with high 25-hydroxycholecalciferol (25(OH)D). However, observational studies suffer from reverse causation bias and intervention studies did not confirm these associations. Discrepancies with randomised clinical trials (RCTs) suggest that low 25(OH)D could be just a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status (measured by 25OHD) is reported in a wide range of disorders.
More convincing results were found for mortality, in fact evidence comes not only from observational studies but also from clinical trials. A meta-analysis of observational studies showed a nonlinear relationship of overall mortality risk with increasing circulating 25(OH)D, with optimal concentrations around 30-35 ng/ml. A meta-analysis of randomized clinical trials in healthy subjects showed that current doses of vitamin D supplements are associated with a significant decrease in overall mortality for vitamin D3 supplementation, whereas no association with vitamin D2 supplementation was found.
Recent evidence suggests to investigate the link of vitamin D with cancer survival and mortality, identifying this topic as one of the most promising area of research.