title: Randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and ki67 labeling in prostate cancer patients.
abstract: BACKGROUND
  Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol.
  
  
  OBJECTIVE
  Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue.
  
  
  METHODS
  We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada.
  
  
  METHODS
  PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol.
  
  
  METHODS
  Vitamin D3 (400, 10 000, or 40 000 IU/d) was orally administered before radical prostatectomy.
  
  
  METHODS
  We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed.
  
  
  RESULTS
  Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P < .03) and were significantly higher in the 40 000-IU/d group than in every other dose group (P < .03). Prostate vitamin D metabolites correlated positively with serum levels (P < .0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P < .05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P < .02).
  
  
  CONCLUSIONS
  Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research.
authors: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors: Dennis
authors: D
authors: Wagner
authors: Dominique
authors: D
authors: Trudel
authors: Theodorus
authors: T
authors: Van der Kwast
authors: Larisa
authors: L
authors: Nonn
authors: Angeline Antonio
authors: AA
authors: Giangreco
authors: Doris
authors: D
authors: Li
authors: Andre
authors: A
authors: Dias
authors: Monique
authors: M
authors: Cardoza
authors: Sanda
authors: S
authors: Laszlo
authors: Karen
authors: K
authors: Hersey
authors: Laurence
authors: L
authors: Klotz
authors: Antonio
authors: A
authors: Finelli
authors: Neil
authors: N
authors: Fleshner
authors: Reinhold
authors: R
authors: Vieth
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D013194:Staining and Labeling; D046888:Tissue Array Analysis; D054928:Validation Studies as Topic; D014807:Vitamin D / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D014807:Vitamin D; D002762:Cholecalciferol