PILOT STUDY OF DIETARY FAT RESTRICTION AND FLAXSEED SUPPLEMENTATION IN MEN WITH PROSTATE CANCER BEFORE SURGERY: EXPLORING THE EFFECTS ON HORMONAL LEVELS, PROSTATE-SPECIFIC ANTIGEN, AND HISTOPATHOLOGIC FEATURES WENDY DEMARK-WAHNEFRIED,DAVID T. PRICE, THOMAS J. POLASCIK,CARY N. ROBERTSON, E. EVERETT ANDERSON,DAVID F. PAULSON,PHILIP J. WALTHER, MELISSA GANNON, AND ROBIN T. VOLLMER ABSTRACT Objectives. Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. Methods. Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate- specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynu- cleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). Results. The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 6 39 mg/dL to 174 6 42 mg/dL), total testosterone (422 6 122 ng/dL to 360 6 128 ng/dL), and free androgen index (36.3% 6 18.9% to 29.3% 6 16.8%) (all P ,0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 6 5.2 ng/mL and 8.5 6 7.7 ng/mL, respec- tively, for the entire sample (P 5 0.58); however, among men with Gleason sums of 6 or less (n 5 19), the PSA values were 7.1 6 3.9 ng/mL and 6.4 6 4.1 ng/mL (P 5 0.10). The mean proliferation index was 7.4 6 7.8 for the historic controls versus 5.0 6 4.9 for the diet-treated patients (P 5 0.05). The distribution of the apoptotic indexes differed significantly (P 5 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P 5 0.049 and P 5 0.017, respectively). Conclusions. These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy. UROLOGY 58: 47–52, 2001. © 2001, Elsevier Science Inc. P rostate carcinoma is the leading cancer among American men. 1 Previousresearch suggests that lifestyle factors are associated with the etiol- ogy and progression of prostate cancer, with diet assumed to play a strong role. 1,2 Currently, how- ever, no dietary interventions have proven efficacy Monetary support for this research was provided by the National Cancer Institute (K07-CA62215) and the Committee for Urologic Research, Education and Development at Duke University Medi- cal Center, Durham, North Carolina. From the Division of Urologic Surgery, Duke University Medical Center and Department of Surgical Pathology and Cytopathology, Durham Veterans Affairs Medical Center, Durham, North Carolina Reprintrequests: Wendy Demark-Wahnefried, Ph.D.,R.D., L.D.N., Division of Urologic Surgery, Box 2619 Duke University Medical Center, Durham, NC 27710 Submitted: January 22, 2001, accepted (with revisions): Feb- ruary 27, 2001 ADULT UROLOGY © 2001, E LSEVIER S CIENCEINC . 0090-4295/01/$20.00 ALL RIGHTS RESERVED PII S0090-4295(01)01014-7 47