Can take 40,000 IU of vitamin D daily before prostate cancer surgery – RCT March 2013

---

Randomized Clinical Trial of Vitamin D3 Doses on Prostatic Vitamin D Metabolite Levels and Ki67 Labeling in Prostate Cancer Patients.

J Clin Endocrinol Metab. 2013 Mar 5.
Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R.
Department of Nutritional Sciences (D.W., A.D., R.V.), University of Toronto, Toronto M56 3E2, Canada; Department of Pathology and Laboratory Medicine (D.W., D.L., A.D., R.V.), Mt Sinai Hospital, Toronto, Canada M5G 1X5; Departments of Pathology (D.T., T.V.d.K.) and Surgical Oncology (M.C., S.L., K.H., A.F., N.F.), University Health Network, Toronto, Canada M5G 2M9; Department of Pathology (L.N., A.A.G.), University of Illinois at Chicago, Chicago, Illinois 60607; and Surgery-Urology (L.K.), Sunnybrook Health Sciences Centre, Toronto, Canada M4N 3M5.

Context: 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.

Design and Setting:We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada.

Patients:PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol.Intervention:Vitamin D3 (400, 10 000, or 40 000 IU/d) was orally administered before radical prostatectomy.

Main Outcome Measures: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.

PMID: 23463655

---

A study of the micro RNA in the same trial

Tumor suppressor miRNAs, miR-100 and -125b, are regulated by 1,25-dihydroxyvitamin D in primary prostate cells and in patient tissue.
Cancer Prev Res (Phila). 2013 Mar 15.
Antonio Giangreco A, Vaishnav A, Wagner D, Finelli A, Fleshner N, van der Kwast T, Vieth R, Nonn L.
1Pathology, University of Illinois at Chicago.

MiR-100 and miR-125b are lost in many cancers and have potential function as tumor suppressors. Using both primary prostatic epithelial cultures and laser-capture-microdissected prostate epithelium from 45 patients enrolled in a vitamin D3 randomized trial, we identified miR-100 and -125b as targets of 1,25-dihydroxyvitamin D3 (1,25D). In patients, miR-100 and -125b levels were significantly lower in tumor tissue than in benign prostate. Similarly, miR-100 and -125b were lower in primary PCa cells than in cells derived from benign prostate. Prostatic concentrations of 1,25D positively correlated with these miRNA levels in both PCa and benign epithelium, demonstrating that PCa patients may still benefit from vitamin D3. In cell assays, upregulation of these miRNAs by 1,25D was vitamin D receptor-dependent. Transfection of pre-miR-100 and pre-miR-125b in the presence or absence of 1,25D decreased invasiveness of cancer cell, RWPE-2. Pre-miR-100 and pre-miR-125b decreased proliferation in primary cells and cancer cells respectively. Pre-miR-125b transfection suppressed migration and clonal growth of PCa cells while knockdown of miR-125b in normal cells increased migration indicates a tumor suppressor function. 1,25D suppressed expression of previously bona fide mRNA targets of these miRNAs, E2F3 and Plk1, in a miRNA-dependent manner.

Together, these findings demonstrate that vitamin D3 supplementation augments tumor suppressive miRNAs in patient prostate tissue, providing evidence that miRNAs could be key physiologic mediators of vitamin D3 activity in prevention and early treatment of PCa.

PMID: 23503652

---

Note from article by Vitamin D Council on this study behind a $5/month firewall

• Figure 1 shows final 25(OH)D to be about
  22 ng/ml in the 400 IU/day group,
  55 ng/ml in the 10,000 IU/day group,
  120 ng/ml in the 40,000 IU/day group.
• Even 40,000 IU was not enough to substantially reduce prostate growth marker (Ki67)

See also Vitamin D Life

• All items in category Prostate Cancer and Vitamin D 215 items
• 7X increase in stage IV Prostate Cancer survival when vitamin D greater than 32 ng – May 2013
• Vitamin D, Sunlight, and the Epidemiology of Prostate Cancer – Jan 2013
• Advanced prostate cancer 2X more likely if low vitamin D – Sept 2012
• Low risk Prostate Cancer decreased with 4,000 IU of vitamin D – July 2012
• Prostate cancer reduced in high vitamin D two studies – April 2012
• Advanced Prostate Cancer 2X more likely if less than 20ng of vitamin D – Oct 2011
• Epigenetics of prostate cancer and vitamin D – June 2010
• Search for microrna on Vitamin D Life 11 items as of March 2013
• 291 genes improved expression by 2000 IU of vitamin D – RCT March 2013
• The Anti-cancer Actions of Vitamin D – Jan 2013
• How Vitamin D prevents many cancers (c-MYC) – Nov 2012

Comment: Vitamin D probably better at prevention of prostate cancer

Vitamin D prevents for more health problems than it treats.
Also: The Prostate Cancer cases studied here were very advanced: Gleason 6-7
From WikiPedia

See also web

• Clinical Trials for Prostate Cancer with vitamin D INTERVENTION 22 listed as of March 2013
• Vitamin D Council on Prostate Cancer