A high omega-3, low omega-6 diet supplemented with fish oil has shown promise in reducing the Ki-67 index, a key biomarker for prostate cancer progression, according to results from the CAPFISH-3 trial presented at the 2025 ASCO Genitourinary Cancer Symposium. The study, a phase 2 randomized trial, suggests that dietary changes could play a role in slowing cancer cell growth in men with early-stage prostate cancer undergoing active surveillance.
The trial, led by Dr. William J. Aronson from UCLA, involved 100 men with grade group 1 or 2 prostate cancer on active surveillance. Participants were randomized to either a dietary intervention group or a control group. The intervention group followed a diet low in omega-6 fatty acids and high in omega-3 fatty acids, supplemented with 2.2 grams per day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) via fish oil capsules. They also received personalized dietary counseling to reduce fat intake to less than 30% of calories and to decrease consumption of foods high in omega-6 fatty acids, such as fried and processed foods, while increasing intake of omega-3 rich foods like salmon and tuna. The control group continued their regular diet without fish oil supplementation.
The primary endpoint of the trial was the change in the Ki-67 index from baseline to one year, measured from same-site prostate biopsies using the Artemis image-fusion device. Secondary endpoints included changes in pathologic features such as grade group and maximum tumor length, Decipher genomic score, serum prostate-specific antigen (PSA), testosterone, cytokines, and lipids.
Significant Reduction in Ki-67 Index
The results demonstrated a statistically significant difference in the change of Ki-67 index between the two groups (P = .043). The Ki-67 index decreased by approximately 15% in the dietary intervention group, from 1.34% at baseline to 1.14% at one year. In contrast, the control group experienced an increase of approximately 24% in the Ki-67 index, from 1.23% at baseline to 1.52% at one year.
"A high omega-3, low omega-6 diet with [fish oil] for 1-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," Dr. Aronson stated.
Other Biomarkers and Safety
While the Ki-67 index showed a significant reduction, there were no significant differences between the groups in secondary outcomes such as grade group, tumor length, Decipher genomic score, or PSA levels. The trial also yielded reduced levels of triglyceride and macrophage colony-stimulating factor in the intervention group.
Four patients in the dietary intervention group were withdrawn from the study due to adverse events related to fish oil supplementation, including gastrointestinal discomfort. This highlights the importance of monitoring for potential side effects when using fish oil supplements.
Implications and Future Directions
The findings suggest that a high omega-3, low omega-6 diet with fish oil supplementation may offer a non-invasive approach to slowing prostate cancer growth in men on active surveillance. However, the researchers caution that further, larger trials are necessary to confirm the long-term benefits of this dietary intervention on cancer progression, treatment outcomes, and survival rates.
"On the basis of the underlying antiprostate cancer mechanisms of a high omega-3, low omega-6 diet with FO supplements, future trials are warranted evaluating this intervention in varying stages of prostate cancer," the study authors concluded. Phase 3 trials are needed to validate these findings and to determine the optimal dietary strategies for managing prostate cancer.
