Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy.
Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control Western diet (omega-6:omega-3 ratio of 15:1) for four to six weeks prior to surgery. The primary endpoint was change in serum insulin-like growth factor I (IGF-1) between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E2 levels, omega-6:omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil versus Western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, four to six weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses, the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology.
Department of Urology, School of Medicine, University of California-Los Angeles, Box 951738, Los Angeles, CA 90095, USA. waronson@ucla.edu
William J
WJ
Aronson
Naoko
N
Kobayashi
R James
RJ
Barnard
Susanne
S
Henning
Min
M
Huang
Patricia M
PM
Jardack
Bingrong
B
Liu
Ashley
A
Gray
Junxiang
J
Wan
Ramdev
R
Konijeti
Stephen J
SJ
Freedland
Brandon
B
Castor
David
D
Heber
David
D
Elashoff
Jonathan
J
Said
Pinchas
P
Cohen
Colette
C
Galet
D018752:Diet, Fat-Restricted; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000097:blood; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage* / Q000097:blood; D005395:Fish Oils / Q000008:administration & dosage*; D006801:Humans; D007124:Immunoenzyme Techniques; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000178:diet therapy* / Q000473:pathology / Q000601:surgery
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I