Lower urinary tract symptoms (LUTS) are the result of this pathological process. In addition to having a major negative influence on quality of life, these changes in the structure of the gland can result in major clinical complications, such as recurrent urinary tract infections, acute urinary retention, and in severe cases, chronic renal damage.1
Prompt medical care of BPH is crucial for improving patient quality of life, alleviating psychological distress, and preventing complications. First-line therapies include alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and phosphodiesterase type 5 inhibitors (PDE5-I).2,3 However, comparing Dutasteride a 5-ARIs that reduces prostate volume and PSA levels, with phytochemical-based treatments (e.g., phycocyanin, palmitoylethanolamide “PEA”, and selenium), could provide insight into alternative therapies with potentially fewer side effects. Phytochemicals, with their anti-inflammatory and antioxidant properties, offer a potentially safer profile compared to traditional therapeutic approaches. Exploring different therapeutic options is essential for identifying complementary treatments for patients with specific needs, thereby expanding treatment possibilities for BPH.
Prostatic inflammation is thought to play a key role in the development of BPH and subsequent LUTS. Kwon et al. observed that in individuals with high-grade prostatic inflammation, a combination of alpha-blockers and 5-ARIs may be insufficient to reduce symptom severity.4 A meta-analysis of three randomized controlled trials showed that non-steroidal anti-inflammatory drugs (NSAIDs), administered for 4-24 weeks, improved symptoms by 2.9 IPPS points and flow by 0.89 ml/sec.5
Inflammation-targeting therapies, including nutraceuticals, represent a promising approach. Among these, palmitoylethanolamide (PEA), an endogenous fatty acid amide-signaling molecule recognized for its anti-inflammatory and neuroprotective properties, and phycocyanin, a protein derived from spirulina with potent antioxidant and anti-inflammatory activities, have demonstrated encouraging results in preclinical studies. The former exerts its effects through the down-regulation of mast cells, activation of two distinct receptor classes, Peroxisome Proliferator-Activated Receptor-alpha (PPAR-alpha) and Orphan G-Protein Coupled Receptor 55 (GPCR-55), and a potential reduction in dihydrotestosterone (DHT) levels, alongside a decreased expression of Transforming Growth Factor-beta (TGF-beta), ultimately improving the growth/apoptosis ratio.6
The latter primarily acts by inhibiting the enzymatic activity of Cyclooxygenase-2 (COX-2).7,8 Furthermore, the combined use of selenium and tomato extracts has demonstrated synergistic effects in lowering oxidative stress markers such as malondialdehyde (MDA) and nitrites (NO2) and opposing BPH, indicating new treatment options.9,10
Our study attempted to compare the efficacy of two therapies, with an emphasis on relieving LUTS, reducing PSA levels, and assessing prostate volume. We treated two similar patient groups with BPH: one received a phytochemical compound containing phycocyanin (250mg), PEA (200 mg), and selenium (55 mcg), while the other group was treated with Dutasteride. The study included 104 patients aged 50-70 years, with PSA levels between 4 and 10 ng/ml, a transrectal ultrasound prostate volume between 50 and 70 cc, a maximum urinary flow rate ≥10 ml/s, no suspicious nodules on digital rectal examination (DRE), no lesions on MRI (PI-RADS 1-2), negative previous prostatic biopsies or never biopsied, moreover no history of diabetes or chronic renal failure (serum creatinine > 2 mg/dl). Patients were separated into two groups: Group A (54 patients treated with the phytochemical compound) and Group B (50 patients treated with Dutasteride). All patients were monitored for 6 months after starting treatment, with PSA levels, prostate volume, and flowmetry parameters recorded.
Our study results demonstrated that both Dutasteride and the phytochemical complex (Ficoxpea®) significantly lowered PSA levels (both with p<0.0001), with Dutasteride contributing to a greater reduction (mean reduction of -2.743 ng/ml vs. -0.971 ng/ml). Urinary flow improved in both groups (p<0.0001), with a mean increase in the maximum urinary flow of +3.03 ml/min for Dutasteride and +13.02 ml/min for the phytochemical complex. Dutasteride substantially reduced prostate volume on transrectal ultrasound (TRUS), with a mean drop of -22.14 ml (p<0.0001), whereas the phytochemical complex exhibited a reduction of -10.04 ml (p<0.0001). The prostate volume reduction induced by Dutasteride was statistically more pronounced than that achieved with the phytochemical complex (p<0.0001).
Based to our results, treatment of BPH does not necessarily require 5-ARIs, which can significantly affect quality of life due to potential side effects including diminished libido, erectile dysfunction, and depression. However, Dutasteride's ability to control PSA levels, prostate volume, and improve urinary flow parameters, results consistent with our study. Although nutraceuticals like PEA, selenium, and phycocyanin are under researched, their principal action appears to be directed against inflammation and its related processes. Our findings indicate that the phytochemical complex considerably improved maximum urinary flow by +13.03 ml/s after six months of treatment, without significantly reducing prostate volume. This suggests that nutraceuticals may have a more substantial impact on urinary flow parameters, presumably due to its anti-inflammatory properties, than on prostate volume or PSA levels, where Dutasteride performed better on prostate volume.
Several studies reveal that targeting prostatic inflammation, which can range in intensity, is critical for managing urinary symptoms. Nutraceuticals appear to hold significant potential in this regard, as evidenced by studies demonstrating improvements in symptoms and urine flow after using nonsteroidal anti-inflammatory drugs (NSAIDs). This challenges the assumption that prostate volume reduction, the main focus of 5-ARIs treatment, is the primary factor causing urinary symptoms in BPH. However, it must be remembered to acknowledge the limitations of our work, including the small patient sample and the possible prior use of treatments such as Serenoa repens, which might have influenced the results.
Both the phytochemical complex and Dutasteride reduced PSA levels after six months of treatment. The phytochemical complex, which included phycocyanin, PEA, and selenium, provided a statistically significant improvement in urinary flow, while Dutasteride predominantly affected prostate volume. Nevertheless, the phytochemical complex proved effective in managing inflammation without the typical side effects of Dutasteride, such as gynecomastia and libido reduction.
The application of nutraceuticals for treating urinary symptoms associated with BPH is a growing topic of interest in Urology. Our research intends to contribute to the expanding literature comparing commonly used medications, such as Dutasteride (5-ARIs), with a combination of nutraceuticals. We believe this treatment has the potential to be used in a significant percentage of the BPH patient population in order to relieve urinary symptoms (LUTS), reduce PSA levels, and improve urinary flow, while simultaneously minimizing unwanted side effects.
Written by:
- Giuseppe Saitta, Urologo & Andrologo, ICCS Istituto Clinico Città Studi, Milan
- Riccardo Trovato, 1st year Resident, ICCS Istituto Clinico Città Studi, Milan
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- Ficarra V, Rossanese M, Zazzara M, et al. The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. Curr Urol Rep. 2014;15:463.
- Kahokehr A, Vather R, Nixon A, Hill AG. Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. BJU Int. 2013;111:304-11.
- D'Amico R, Genovese T, Cordaro M, et al. Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia. Antioxidants 2021;10:1014.
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- Arias-Chávez DJ, Mailloux-Salinas P, Ledesma Aparicio J, et al. Selenium in combination with a tomato lipid extract as a therapy for benign prostatic hyperplasia and its alterations in rats with induced BPH. J Cell Mol Med. 2023;27:3147-3156.
- [Kok DE, Kiemeney LA, Verhaegh GW, et al. A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate. Oncotarget. 2017;8:10565-10579.