This is a narrative review of the evidence supporting
vitamin D's anticancer actions. The first section reviews the findings from ecological studies of
cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of
cancer. Meta-analyses of observational studies reported the inverse correlations of serum
25-hydroxyvitamin D [25(
OH)D] with the incidence of 12 types of
cancer. Case-control studies with a 25(
OH)D concentration measured near the time of
cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(
OH)D with time. There is no evidence that undiagnosed
cancer reduces 25(
OH)D concentrations unless the
cancer is at a very advanced stage. Meta-analyses of
cancer incidence with respect to dietary intake have had limited success due to the low amount of
vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce
cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-
vitamin D-
cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of
vitamin D compounds. This paper will review studies showing the inhibition of
tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)2D3 and other
vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of
metastases. In sum, the available mechanistic data support the global protective action of
vitamin D against several important types of
cancer.