**Background:** Prostate cancer is the most common cancer among men in Canada, with 24,600 new cases in 2022. Radical prostatectomy, a main treatment for intermediate- to high-grade disease, is associated with adverse effects including sexual dysfunction and urinary incontinence that impair quality of life. Long-chain omega-3 fatty acids (LCn3) have anti-inflammatory properties that may improve quality of life by suppressing cytokine synthesis. Prior observational studies suggested associations between fish consumption and better urinary function, but no prospective trial had evaluated the causal effect of LCn3 supplementation on prostate cancer-specific quality of life after prostatectomy.
**Methods:** This was a randomized, double-blind, placebo-controlled trial conducted at CHU de Québec-Université Laval. Eligible participants were men ≥18 years with aggressive localized prostate cancer (Gleason ≥7, ISUP Grade group ≥2) who chose radical prostatectomy. Between February 2015 and June 2017, 130 patients were enrolled and randomized 1:1 to receive either 3.75 g/day of fish oil rich in EPA (as monoglyceride, providing 3.3 g LCn3 daily; n=65) or 3.75 g/day of high-oleic sunflower oil placebo (n=65). Supplementation began on average 7 weeks (range 4–10 weeks) before surgery and continued for one year post-surgery. Quality of life was assessed at randomization and every 3 months using the EPIC-26 (5 domains scored 0–100, higher=better) and IPSS (0–35, lower=better). Linear mixed models with intention-to-treat and per-protocol (≥80% adherence) analyses were performed, adjusted for BMI, NCCN risk, and age. Inverse probability of censoring weights addressed missing data.
**Key Results:** Baseline characteristics were generally balanced, though the MAG-EPA group had more participants with BMI ≥30 (35% vs 23%), higher NCCN risk (31% vs 15%), and higher grade group ≥4 (26% vs 9%). At randomization, both groups had high quality-of-life scores except for sexual function. As expected, at 3 months post-surgery, urinary incontinence, urinary irritation, and sexual function deteriorated in both groups. At 12 months, the intention-to-treat analysis showed no statistically significant between-group differences for any domain. The urinary irritation score improved by 5.6 points from randomization in the MAG-EPA group (p=0.007) versus 1.0 in placebo (p=0.62), with a between-group difference of 3.5 (p=0.11). In the per-protocol analysis, the between-group difference for urinary irritation at 12 months was 5.5 (95% CI: 0.4 to 10.6, p=0.03), which the authors note represents a clinically meaningful change (threshold 5–7 points). Bowel function improved significantly within the MAG-EPA group at 12 months (DM=3.8, p=0.009) but no between-group difference was found (DM=−0.6, p=0.69). No significant differences were observed for urinary incontinence, sexual function, hormonal function, or IPSS scores between groups. EPA levels in red blood cell membranes increased to 4% in the MAG-EPA group versus 0.8% in placebo at 12 months. Adherence was excellent (93% overall). Adverse events were similar between groups (10.8% placebo vs 15.9% MAG-EPA), with withdrawal due to adverse events in 1 (1.5%) placebo and 5 (7.9%) MAG-EPA participants.
**Clinical Implications:** This first randomized trial of LCn3 supplementation for prostate cancer-specific quality of life after radical prostatectomy did not demonstrate a statistically significant benefit in the primary intention-to-treat analysis. However, the per-protocol finding of a clinically meaningful 5.5-point improvement in urinary irritation suggests a potential benefit that warrants further investigation. The lack of effect on urinary incontinence and sexual function may reflect the predominant surgical impact on these domains and the 12-month follow-up being insufficient for late functional recovery. The study's limitations include a relatively small sample size (n=130), baseline imbalances in prognostic factors, and a generally healthy study population with a mean omega-6:omega-3 ratio of 6.3, which may limit generalizability. Larger trials are needed to confirm these findings and determine whether patients with lower baseline LCn3 intake might derive greater benefit.