A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia

Nutr Cancer. 2015;67(7):1104-12. doi: 10.1080/01635581.2015.1075560.


A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-mo repeat biopsy randomized trial among men with high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results for serum lycopene, prostate specific antigen (PSA) and insulin-like growth factor (IGF) proteins, histopathological review, and tissue markers for proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle inhibition (p27). Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene. Pre- and posttreatment biopsies were immunostained and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary analyses, pathologists blindly reviewed each biopsy to score histological features. Fifty-eight men completed the trial. Serum lycopene increased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo. We observed no meaningful differences in PSA, IGF-1, or IGF binding protein 3 concentrations between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy, or inflammation posttreatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group. Despite large differences in serum lycopene following intervention, no treatment effects were apparent on either the serum or benign tissue endpoints. Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated.

Trial registration: ClinicalTrials.gov NCT00416325.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Carotenoids / blood
  • Carotenoids / pharmacology*
  • Cell Proliferation / drug effects
  • Double-Blind Method
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / analysis
  • Kallikreins / blood
  • Lycopene
  • Male
  • Middle Aged
  • Minichromosome Maintenance Complex Component 2 / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / therapeutic use*
  • Prostate-Specific Antigen / blood
  • Prostatic Intraepithelial Neoplasia / diet therapy*
  • Prostatic Intraepithelial Neoplasia / metabolism
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / diet therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Solanum lycopersicum / chemistry*
  • Treatment Outcome


  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Plant Extracts
  • Carotenoids
  • Insulin-Like Growth Factor I
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2
  • Lycopene

Associated data

  • ClinicalTrials.gov/NCT00416325