Vitamin D and Colorectal Cancer: Current Perspectives and Future Directions

Abstract

Vitamin D is considered to be the main mediator of the beneficial effects of sun exposure. In humans, highest expression of Vitamin D receptors is found in the intestinal tract. In addition, 1 alpha,25-dihydroxyvitamin D3 (or calcitriol), the most active Vitamin D metabo-lite, plays important homeostatic roles in the intestine, particularly calcium absorption. Vitamin D deficiency is defined as a serum 25-hydroxyvitamin D [25(OH)D] level of < 20 ng/mL. Previous studies show that higher circulating 25(OH)D levels are associated with reduced risk of colorectal cancer (CRC) and improved survival. Most research to date has been conducted in animals, specif-ically mice. Although human studies have a limited number of participants, one study recruiting a large cohort of patients with ad-vanced or metastatic CRC revealed that higher plasma 25(OH)D levels are associated with improved overall and progression-free survival. However, the effects of Vitamin D supplementation on incidence and mortality of CRC remain inconclusive. Although Vi-tamin D may help to prevent cancer, there is a paucity of research demonstrating conclusively that Vitamin D alters prognosis after chemotherapy. Here, we review the mechanisms by which Vitamin D affects CRC, as well as the results of clinical, epidemiological, and human intervention studies. We also discuss current perspectives and future directions regarding Vitamin D and CRC.