Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

Prostate. 2011 Sep;71(12):1287-93. doi: 10.1002/pros.21346. Epub 2011 Feb 9.


Background: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (Figueiredo et al., J Natl Cancer Inst 2009; 101(6): 432-435). As tumor cells in culture proliferate directly in response to available folic acid, the goal of our study was to determine if there is a similar relationship between patient folate status, and the proliferative capacity of tumors in men with prostate cancer.

Methods: Serum folate and/or prostate tissue folate was determined in 87 randomly selected patients undergoing surgery for prostate cancer, and compared to tumor proliferation in a subset.

Results: Fasting serum folate levels were positively correlated with prostate tumor tissue folate content (n = 15; r = 0.577, P < 0.03). Mean serum folate was 62.6 nM (7.5-145.2 nM), 39.5% of patients used supplements containing folic acid (n = 86). The top quartile of patients had serum folates above 82 nM, six times the level considered adequate. Of these, 48% reported no supplement use. Among 50 patients with Gleason 7 disease, the mean proliferation index as determined by Ki67 staining was 6.17 ± 3.2% and 0.86 ± 0.92% in the tumors from patients in the highest (117 ± 15 nM) and lowest (18 ± 9 nM) quintiles for serum folate, respectively (P < 0.0001).

Conclusions: Increased cancer cell proliferation in men with higher serum folate concentrations is consistent with an increase in prostate cancer incidence observed with folate supplementation. Unexpectedly, more than 25% of patients had serum folate levels greater than sixfold adequate. Nearly half of these men reported no supplement use, suggesting either altered folate metabolism and/or sustained consumption of folic acid from fortified foods.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carcinoma / blood*
  • Carcinoma / pathology*
  • Cell Proliferation*
  • Fasting / blood
  • Folic Acid / blood*
  • Folic Acid / pharmacology
  • Humans
  • Immunohistochemistry / methods
  • Incidence
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology*
  • Staining and Labeling


  • Ki-67 Antigen
  • Folic Acid