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Background: Chronic Prostatitis/Chronic Pelvic Pain syndrome NIH-class III is a widespread condition affecting men universally, with existing treatments showing limited success. This study evaluated the efficacy and safety of a natural supplement, composed of Serenoa repens, Solanum lycopersicum, lycopene, and bromelain, in managing symptoms of this condition among a substantial patient group. Methods: In this prospective study, 245 patients diagnosed with Chronic Prostatitis/Chronic Pelvic Pain syndrome NIH-class III were treated with the aforementioned supplement, alongside lifestyle alterations, such as refraining from spicy foods, alcohol, caffeine, and cycling, for a duration of three months. Patients' progress was assessed at one and three months using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptom Index (IPSS), quality of life (QoL) scores, and changes in total prostate-specific antigen (PSA) levels. Results: The supplement was well received with no serious adverse events reported. Significant improvements were observed in NIH-CPSI scores, IPSS, QoL scores, and a substantial decrease in total PSA levels at three months compared to baseline, with a positive trend noted from one-month to three-month evaluations. This was consistent in either patients with predominantly voiding or storage urinary symptoms. Conclusions: Our results suggest that this natural supplement in conjunction with lifestyle changes could offer a safe and effective alternative treatment for patients suffering from Chronic Prostatitis/Chronic Pelvic Pain syndrome NIH-class III. However, these findings require validation through further large-scale randomized controlled trials. [ABSTRACT FROM AUTHOR]