Effects of omega-3 supplementation on psychological symptoms in men with prostate cancer: Secondary analysis of a double-blind placebo-controlled randomized trial.

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One‐year MAG‐EPA (omega‑3) supplementation did not improve depression, anxiety, fear of cancer recurrence, insomnia, fatigue, or cognitive complaints in men treated for prostate cancer with RP, beyond what was seen with placebo.

Introduction

This study evaluated the effect of a 1‐year eicosapentaenoic acid monoacylglyceride (MAG‐EPA; active treatment) supplementation compared to high oleic acid sunflower oil (HOSO; placebo) on depression and other psychological symptoms (anxiety, fear of cancer recurrence (FCR), insomnia, fatigue, and cognitive complaints) in men with prostate cancer.

Method

• This was a secondary analysis of a phase IIb, randomised, double‐blind, placebo‐controlled trial.

• Participants (n=130) were randomly assigned (1:1) to MAG‐EPA (n = 65) or HOSO (n = 65) 4–10 weeks before undergoing their post‐radical prostatectomy (RP). Psychological measures were collected at baseline (V0), and at 3 (V2), 6 (V3), 9 (V4), and 12 (V5) months following RP.

• Participants had to take their capsules 7.5 weeks on average prior to RP and to continue for 1‐year post‐RP.

• Self‐report scales were used to assess medical history, health behaviours, psychological and somatic symptoms, and quality of life including depression (HADS‐D, PHQ‐9), anxiety (HADS‐A), FCRI, insomnia (ISI), fatigue (FSI), and cognitive complaints (FACT‐Cog).

Results

• Linear mixed models showed significant time effects on HADS‑A, FCRI, ISI, and FACT‑Cog‑Impact (post hoc, Bonferroni‑corrected); HADS‑D and FSI‑days effects were not significant post‑correction.

• No significant group, time, or interaction effects on PHQ‑9 (p = 0.74, 0.10, 0.48) or other FSI/FACT‑Cog subscales.

• FACT‑Cog‑Impact showed a significant group×time interaction, F(4, 123.4) = 5.07, p < 0.001, driven by a placebo‑only increase at V3 vs. V0, V2, V4.

• Effect sizes (V0–V5) were small (<0.20) for all outcomes except FCRI (ES = 0.36), with a greater reduction in the placebo than the MAG‑EPA group.

• Clinical anxiety and FCR proportions decreased significantly over time, however there were no significant time/interaction effects for clinical depression, insomnia, fatigue, or cognitive impairment proportions.

• HADS‑D improved over time only among those with clinical depression at baseline. Whereas, HADS‑A, FCRI, ISI, FSI improved regardless of baseline status, with no MAG‑EPA vs. placebo differences.

Conclusion

These findings did not support the efficacy of omega‐3 supplementation in alleviating depression, anxiety, FCR, insomnia, fatigue, and subjectively assessed cognitive impairments in men treated for prostate cancer with RP.

• Omega‑3 (MAG‐EPA) supplementation may not be sufficient as a stand‑alone strategy for managing depression or other psychological symptoms in men undergoing treatment for prostate cancer.

• Through an interdisciplinary approach, nutritional healthcare practitioners should recognise anxiety, fear of cancer recurrence, or other psychological red flags in men with prostate cancer and, where appropriate, refer clients to other healthcare providers alongside nutritional care.

• Further randomised controlled studies that enrol participants with clinical levels of depression are needed to strengthen the statistical power and capacity to test the antidepressant effect of MAG‐EPA in men treated for prostate cancer with RP.

• Future studies should consider selecting or stratifying participants based on baseline omega‑6: omega‑3 ratio since participants with a ratio already close to optimal (as in this trial) may have limited capacity to benefit further from supplementation.