Effect of Vitamin D Supplementation on Survival of Digestive Tract Cancer Patients with Low Bioavailable 25-Hydroxyvitamin D Levels: A Post Hoc Analysis of the AMATERASU Randomized Clinical Trial

Vitamin D has been shown to suppress the growth of cancer cells. Cancer cells are believed to take up bioavailable 25-hydroxyvitamin D (25[OH]D) (i.e., not bound to vitamin-D-binding protein (DBP)) more efficiently than DBP-bound 25(OH)D. Our aim was to use this bioavailable 25(OH)D, rather than total 25(OH)D, as a biomarker of vitamin D deficiency to investigate whether vitamin D supplementation improves the relapse-free survival (RFS) of patients with digestive tract cancer from the esophagus to the rectum by conducting a post hoc analysis of the AMATERASU trial (UMIN000001977). The bioavailable 25(OH)D levels were calculated via an equation using data of serum total 25(OH)D, albumin, and DBP levels, and DBP genotypes (rs7041 and rs4588). We estimated bioavailable 25(OH) levels in 355 patients. In a subgroup of patients with low bioavailable 25(OH)D levels (<median) (n = 177), 5 year RFS was 77% in the vitamin D group vs. 58% in the placebo group (hazard ratio, 0.54; 95% confidence interval, 0.31–0.95; p = 0.03), whereas no significant difference was seen in a subgroup of patients with high bioavailable 25(OH)D levels (p for interaction = 0.046). We hypothesize that vitamin D supplementation may be effective in improving RFS among digestive tract cancer patients with low bioavailable 25(OH)D levels.