A randomized, double-blind, placebo-controlled pilot study of add-on beta-sitosterol supplementation on treatment response in metastatic prostate cancer patients.

e17073 Background: Metastatic prostate cancer remains difficult to manage due to treatment resistance and cumulative toxicity of systemic therapies. Beta-sitosterol, a dietary phytosterol, has demonstrated anticancer activity in preclinical prostate cancer models and symptomatic benefit in benign prostatic hyperplasia, but clinical evidence in prostate cancer is lacking. Additionally, circulating ceramides are emerging as potential biomarkers of tumor burden and disease progression. This pilot trial was designed to evaluate the feasibility, safety, and preliminary clinical effects of beta-sitosterol in metastatic prostate cancer. The aim was to assess the effect of add-on beta-sitosterol supplementation on prostate-specific antigen (PSA) levels, urinary symptoms, safety, and tolerability in patients with metastatic prostate cancer, and to explore the relationship between baseline plasma ceramide levels and PSA. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group pilot trial conducted. Forty-one men with biopsy-proven metastatic prostate cancer were randomized to receive either beta-sitosterol 320 mg once daily (n≈20) or placebo (n≈21) for three months, in addition to standard therapy. The primary outcome was the least-squares mean difference in log₁₀ PSA at three months. Secondary outcomes included changes in International Prostate Symptom Score (IPSS) and safety. Plasma ceramide levels were measured at baseline using ELISA. Results: At three months, there was no statistically significant difference in log₁₀ PSA levels between the beta-sitosterol and placebo groups (p > 0.05). However, patients receiving beta-sitosterol showed a greater reduction in IPSS scores over follow-up, with a higher proportion shifting from moderate-to-severe symptoms to milder categories compared to placebo (p < 0.05). Beta-sitosterol was well tolerated, with no serious adverse events and only mild gastrointestinal complaints reported. Baseline plasma ceramide levels showed a significant positive correlation with PSA (Pearson correlation, p < 0.05), suggesting an association with tumor burden. Conclusions: Add-on beta-sitosterol was safe and improved urinary symptoms but did not significantly reduce PSA levels. Larger trials are required to confirm efficacy and validate ceramide as a prognostic biomarker. Clinical trial information: CTRI/2024/02/063329.