Vitamin D, cancer, and dysregulated phosphate metabolism

Recently reported findings from major clinical trials show no cancer protection from vitamin D supplementation, and results from observational studies of vitamin D in cancer prevention are inconsistent. There is a need for new hypotheses to guide investigations of the controversies surrounding vitamin D supplementation and cancer. Bioactive vitamin D, 1,25(OH)2D, is an endocrine factor that regulates phosphate homeostasis by increasing dietary phosphate intestinal absorption. When phosphorus serum levels are high, as in hyperphosphatemia, an endocrine feedback mechanism lowers bioactive vitamin D which reduces intestinal phosphate absorption. Low vitamin D levels have been associated with cancer incidence, and tumorigenesis is associated with high levels of dysregulated phosphate in the body. In this mini-review, the author hypothesizes that hyperphosphatemia may be an intermediating factor in the association of lowered vitamin D levels and increased risk for tumorigenesis. Furthermore, this article challenges the UVB–vitamin D-cancer hypothesis which proposes that reduced cancer incidence at lower geographic latitudes is related to high levels of vitamin D from UVB exposure. The author proposes that reduced phosphorus content and availability in tropical and subtropical soil, and lower dietary phosphate intake from consumption of tropical and subtropical crops (as in the Mediterranean diet), may mediate the association of reduced cancer risk with lower latitudes.