High Omega-3 Diet With Fish Oil Reduces Ki-67 Index in Prostate Cancer

In prostate cancer, a high omega-3, low-omega-6 diet with fish oil led to a Ki-67 index decrease: Dr_microbe - stock.adobe.com

For patients with prostate cancer, a high omega-3, low-omega-6 diet with fish oil for one year led to a reduction of prostate Ki-67 index, according to data from the CAPFISH-3 trial, which were presented at the 2025 ASCO Genitourinary Cancer Symposium.

The Ki-67 index decreased by 15% for patients who received the specialized diet and fish oil, compared with an increase of 24% in the control group who were instructed not to take fish oil.

“A high omega-3, low omega-6 diet with [fish oil] for one year resulted in a significant reduction in prostate Ki-67 index — compared with the control group — a biomarker for prostate cancer progression, metastasis and death,” first study author and lead investigator, Dr. William J. Aronson, stated in the presentation.

Aronson is a professor in the Department of Urology and chief of Urology at Olive View-UCLA Medical Center and chief of Urologic Oncology at West Los Angeles Veterans Affairs Medical Center.

The CAPFISH-3 trial was a single-center, randomized, open-label phase 2 trial for men who were on active surveillance for grade group 1 or 2 prostate cancer.

A total of 100 patients were randomly assigned to be treated on either the intervention (50 patients) or the control group (50 patients). Of those enrolled, six on the intervention group were not administered the allocated intervention, and three in the control group were not administered allocated intervention.

Diet intervention in the trial consisted of less than 30% of calorie intake from fat; decreased consumption of foods with high levels of omega-6 fatty acids like corn oil, fried foods, highly processed foods and chips; increased intake of omega-3 rich foods like salmon and tuna; a less than 4:1 ratio of omega-6 to omega-3; and 2.2 grams per day of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) intake via four oral fish oil capsules per day. Patients in the control group did not receive fish oil.

Eligible patients had a prostate biopsy performed with the Artemis image-fusion device, adenocarcinoma of the prostate, and elected to undergo active surveillance, according to the study’s Clinical Trial website. Additionally, patients had clinical stage T2c or less; Gleason grade 3 plus 4 or less; a prostate-specific antigen (PSA) less than 25; and a willingness to not consume lycopene, green tea or pomegranate juice/supplements during the one-year study.

Exclusion criteria include a diagnostic prostate biopsy with only one core cancer with less than 5% of tissue involved with cancer; received finasteride or dutasteride during the prior year; taken fish oil during the last three months; prior treatment for prostate cancer; an allergy to fish; and other medical conditions that exclude them from undergoing repeat prostate biopsy at one year.

In the intervention group, the median age was 64 years versus 64.5 years in the control group; maximum 3 plus 3 Gleason score was 35 (70%) and 35 (70%); 3 plus 4 Gleason score was 15 (30%) and 15 (30%); and median PSA was 5.9 and 5.6.

The primary trial end point was the change in Ki-67 index from baseline to one year using the Artemis device from same site biopsies with cancer compared between both trial groups. Secondary end points include pathologic features such as grade group and maximum tumor length, Decipher 22 gene classifier score, serum prostate specific antigen, testosterone, cytokines and lipids.

The trial also yielded reduced levels of triglyceride, reduced macrophage colony-stimulating factor levels, and no change in tumor volume, grade group, PSA and Decipher score.

One limitation of the trial was the duration of the year, and to determine the effects of these results on clinical end points further studies such as phase 3 and longer-term trials are needed.

According to trial investigators, the ratio of omega-6 to omega-3 in the American diet is 15:1, and linoleic acid constitutes 85% of polyunsaturated fat consumed in the American diet.

Reference: “A high omega-3, low omega-6 diet with fish oil for men with prostate cancer on active surveillance: The CAPFISH-3 randomized clinical trial” by Dr. William Aronson, et al. Journal of Clinical Oncology.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.