Effect Modification of Vitamin D Supplementation by Histopathological Characteristics on Survival of Patients with Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial

Nutrients. 2019 Oct 22;11(10):2547. doi: 10.3390/nu11102547.


Some coauthors of this study previously performed the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative oral vitamin D supplementation (2,000 IU/day) in 417 patients with stage I to III digestive tract cancer from the esophagus to the rectum who underwent curative surgery (UMIN000001977). We conducted a post-hoc analysis of the AMATERASU trial to explore the effects of modification of vitamin D supplementation by histopathological characteristics on survival. Among patients with poorly differentiated adenocarcinoma, the 5-year relapse-free survival rate of patients supplemented with vitamin D was 91% compared with 63% in the placebo group (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08 to 0.78; P = 0.017; P for interaction = 0.023). Similarly, the 5-year overall survival rate was 92% in the vitamin D group compared with 72% in the placebo group (HR, 0.25; 95%CI, 0.07 to 0.94; P = 0.040; P for interaction = 0.012). In contrast, there were no significant effects in other histopathological characteristics between vitamin D and placebo groups. These findings generated the hypothesis that oral vitamin D supplementation may improve both relapse-free survival and overall survival in a subgroup of patients with poorly differentiated adenocarcinoma.

Keywords: Vitamin D; pathology; prognosis; supplementation; survival.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dietary Supplements
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Gastrointestinal Neoplasms* / diagnosis
  • Gastrointestinal Neoplasms* / drug therapy
  • Gastrointestinal Neoplasms* / mortality
  • Gastrointestinal Neoplasms* / pathology
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Vitamin D* / administration & dosage
  • Vitamin D* / therapeutic use


  • Vitamin D