Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through D-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study
D
Non-RDBPC human or In-vivo animal trials
 

Introduction

Lower urinary tract symptoms (LUTS) become more prevalent in men as they age. (Zhang 2018) Benign prostatic hyperplasia (BPH), a common cause of LUTS, affects up to 50% of men over the age of 50 and, in the United States, approximately 70% of men aged 60–69 and 80% of those older than 70. (Ng 2024)

Supporting prostate health through targeted interventions may help prevent or mitigate symptomatic problems associated with aging. Strategies that reduce inflammation, optimize cellular function, and downregulate adverse gene expression have shown promising outcomes. When symptoms are already present, slowing BPH progression or prostate enlargement can help alleviate discomfort. (Edwards 2008)(Fontana 2020) The ingredients highlighted below are supported by evidence demonstrating efficacy in improving prostate-related symptoms.

Ingredients

Saw Palmetto (Serenoa repens) 

Dosing: 320–960 mg total per day, for a minimum of three months (Latil 2015)(Wyatt 2016)

Supporting evidence:

  • Research suggests that saw palmetto has anti-androgenic, pro-apoptotic, and anti-inflammatory properties, collectively contributing to its ability to relieve LUTS. (Kwon 2019) 
  • A one-year, non-randomized trial comparing 40 men with BPH treated with Serenoa repens alcohol extract to 30 untreated controls reported statistically significant improvements in urinary flow rates, reductions in prostate size, and lower International Prostate Symptom Scores (IPSS) in the treatment group. (Saidi 2017) 
  • A randomized, double-blind, tamsulosin-controlled clinical trial in men with BPH-related LUTS found that a hexanic extract of Serenoa repens reduced the expression of prostatic inflammatory markers better than tamsulosin. Specifically, the study reported a decrease in mean gene expression for 65.4% of the detected markers in the saw palmetto group, compared to 46.2% in the tamsulosin group. (Latil 2015)
  • A Cochrane review found that saw palmetto produced mild-to-moderate improvements in urinary symptoms and flow measures in men with BPH compared to placebo. Its effects were similar to those of finasteride in short-term studies. (Wilt 2002)
  • In a randomized biopsy study of the hexanic extract of Serenoa repens (HESr) in 97 men with histologically confirmed prostatic inflammation, the mean inflammation grading score in the treated group decreased from 1.55 to 0.79 at six months (p = 0.001). In comparison, the score in the control group (receiving no treatment) decreased from 1.44 to 1.23 (not statistically significant). (Gravas 2019)
Saw Palmetto (Serenoa repens) in the Fullscript catalog

Stinging Nettle (Urtica dioica) Root

Dosing: 300 mg twice daily for a minimum of eight weeks (Ghorbanibirgani 2013)(Khalafi-Kheydani 2022)

Supporting evidence:

  • In men who experience LUTS, stinging nettle root may help alleviate symptoms (e.g., frequency, urgency, and nocturia) by decreasing the synthesis of sex hormone-binding globulin (SHBG) and blocking its binding to the prostatic receptor. (Khalafi-Kheydani 2022)
  • In a randomized controlled trial (RCT), male patients diagnosed with BPH (n=100) were randomly assigned to receive stinging nettle root extract or a placebo. The participants receiving stinging nettle experienced clinical symptom relief compared to those receiving the placebo. (Ghorbanibirgani 2013)
  • In a randomized, placebo-controlled, double-blind multicenter trial with a 96-week follow-up, a fixed combination of Urtica root and Sabal fruit extracts was administered to elderly men with moderate-to-severe LUTS due to BPH. Over the observation period, the IPSS decreased by 53%, peak and average urinary flow rates increased by 19%, and residual urine volume decreased by 44% in the treatment group. (Lopatkin 2007)
Stinging Nettle (Urtica dioica) Root in the Fullscript catalog

Lycopene 

Dosing: 15 mg total per day, for at least six months (Schwarz 2008) 

Supporting evidence:

  • In an RCT, lycopene supplementation in men with BPH helped prevent disease progression and prostate enlargement, reduce prostate-specific antigen (PSA) levels, and improve IPSS scores compared to placebo. (Schwarz 2008)
  • In a phase II prospective, randomized, double-blind, placebo-controlled study, 40 men with histologically confirmed BPH were assigned to receive either a lycopene-rich whole tomato food supplement (WTFS) or a placebo for two months. Compared with those who received the placebo, men who took the WTFS reported improvements in LUTS (as measured by the IPSS) and quality of life. Additionally, total PSA levels decreased among participants with baseline values greater than 10 ng/mL who received the WTFS. (Cormio 2021) 
  • In men with symptomatic BPH (n=120), a study using lycopene 500 mg twice daily for 16 weeks demonstrated statistically significant improvements in LUTS (IPSS), quality of life, maximum urinary flow rate, and post-void residual compared to baseline. Prostate volume did not meaningfully change. (Li 2019) 
Lycopene in the Fullscript catalog

Beta-Sitosterol 

Dosing: 60–195 mg daily for 4–26 weeks (Wilt 2000) 

Supporting evidence:

  • A Cochrane review concluded that beta-sitosterol appears to improve urinary symptoms and flow measures, including IPSS (weighted mean difference [WMD] −4.9), peak urine flow (WMD 3.91 mL/sec), and post-void residual volume (WMD −28.62mL). (Wilt 2000) 
  • The authors of a double-blind, placebo-controlled clinical trial concluded that beta-sitosterol was associated with improved urinary symptom scores, maximum urinary flow rate, and post-void residual volume. However, the study’s findings suggest that these benefits depend on continued therapy. During the 18-month open-extension phase, men who discontinued treatment experienced a decline in symptom control and an increase in post-void residual volume. (Berges 2000)
  • A randomized, double-blind, placebo-controlled trial found that beta-sitosterol-enriched saw palmetto extract was more effective than standard saw palmetto extract in improving prostate symptom scores, reducing post-void residual volume and PSA levels, and inhibiting 5α-reductase activity over a 12-week treatment period compared with placebo. (Sudeep 2020) 

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

View protocol on Fullscript
References
  1. American Cancer Society. (2023, November 22). American Cancer Society recommendations for prostate cancer early detection. American Cancer Society; American Cancer Society. https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosis-staging/acs-recommendations.html
  2. Bell, K. J. L., Del Mar, C., Wright, G., Dickinson, J., & Glasziou, P. (2015). Prevalence of incidental prostate cancer: A systematic review of autopsy studies. International Journal of Cancer, 137(7), 1749–1757. https://doi.org/10.1002/ijc.29538
  3. Berges, R. R., Kassen, A., & Senge, T. (2000). Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18-month follow-up. BJU International, 85(7), 842–846. https://doi.org/10.1046/j.1464-410x.2000.00672.x
  4. Cormio, L., Calò, B., Falagario, U., Iezzi, M., Lamolinara, A., Vitaglione, P., Silecchia, G., Carrieri, G., Fogliano, V., Iacobelli, S., Natali, P. G., & Piantelli, M. (2021). Improvement of urinary tract symptoms and quality of life in benign prostate hyperplasia patients associated with consumption of a newly developed whole tomato-based food supplement: a phase II prospective, randomized double-blinded, placebo-controlled study. Journal of Translational Medicine, 19(1), 24. https://doi.org/10.1186/s12967-020-02684-3
  5. Edwards, J. L. (2008). Diagnosis and management of benign prostatic hyperplasia. American Family Physician, 77(10), 1403–1410. https://www.aafp.org/pubs/afp/issues/2008/0515/p1403.html
  6. Fontana, F., Raimondi, M., Marzagalli, M., Di Domizio, A., & Limonta, P. (2020). Natural compounds in prostate cancer prevention and treatment: Mechanisms of action and molecular targets. Cells, 9(2), 460. https://doi.org/10.3390/cells9020460
  7. Ghorbanibirgani, A., Khalili, A., & Zamani, L. (2013). The efficacy of stinging nettle (Urtica dioica) in patients with benign prostatic hyperplasia: A randomized double-blind study in 100 patients. Iranian Red Crescent Medical Journal, 15(1), 9–10. https://doi.org/10.5812/ircmj.2386
  8. Gravas, S., Samarinas, M., Zacharouli, K., Karatzas, A., Tzortzis, V., Koukoulis, G., & Melekos, M. (2019). The effect of hexanic extract of Serenoa repens on prostatic inflammation: results from a randomized biopsy study. World Journal of Urology, 37(3), 539–544. https://doi.org/10.1007/s00345-018-2409-1
  9. Khalafi-Kheydani, A., Mahmoodi, H., Sadat, Z., & Azizi-Fini, I. (2022). The effect of nettle root extract on urinary problems in older men with benign prostatic hyperplasia: A randomized clinical trial. Journal of Herbal Medicine, 34, 100568. https://doi.org/10.1016/j.hermed.2022.100568
  10. Kwon, Y. (2019). Use of saw palmetto (Serenoa repens) extract for benign prostatic hyperplasia. Food Science and Biotechnology, 28(6), 1599–1606. https://doi.org/10.1007/s10068-019-00605-9
  11. Latil, A., Pétrissans, M., Rouquet, J., Robert, G., & de la Taille, A. (2015). Effects of hexanic extract of Serenoa repens (Permixon® 160 mg) on inflammation biomarkers in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. The Prostate, 75(16), 1857–1867. https://doi.org/10.1002/pros.23059
  12. Li, Y.-Z., Liang, W.-N., Zhang, G.-W., Weng, Z.-Q., Zhong, Y., Xu, S., & Shang, X.-J. (2019). Efficacy and safety of lycopene in the treatment of benign prostatic hyperplasia with lower urinary tract symptoms. Zhonghua Nan Ke Xue, 25(11), 1001–1004. https://pubmed.ncbi.nlm.nih.gov/32233234/
  13. Lopatkin, N., Sivkov, A., Schläfke, S., Funk, P., Medvedev, A., & Engelmann, U. (2007). Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms–long-term follow-up of a placebo-controlled, double-blind, multicenter trial. International Urology and Nephrology, 39(4), 1137–1146. https://doi.org/10.1007/s11255-006-9173-7
  14. Ng, M., Leslie, S. W., & Baradhi, K. M. (2024, October 20). Benign prostatic hyperplasia. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK558920/
  15. Saidi, S., Stavridis, S., Stankov, O., Dohcev, S., & Panov, S. (2017). Effects of Serenoa repens alcohol extract on benign prostate hyperplasia. Pril (Makedon Akad Nauk Umet Odd Med Nauki), 38(2), 123–129. https://doi.org/10.1515/prilozi-2017-0030
  16. Schwarz, S., Obermüller-Jevic, U. C., Hellmis, E., Koch, W., Jacobi, G., & Biesalski, H.-K. (2008). Lycopene inhibits disease progression in patients with benign prostate hyperplasia. The Journal of Nutrition, 138(1), 49–53. https://doi.org/10.1093/jn/138.1.49
  17. Sudeep, H. V., Thomas, J. V., & Shyamprasad, K. (2020). A double blind, placebo-controlled randomized comparative study on the efficacy of phytosterol-enriched and conventional saw palmetto oil in mitigating benign prostate hyperplasia and androgen deficiency. BMC Urology, 20(1), 86. https://doi.org/10.1186/s12894-020-00648-9
  18. Wilt, T. J., Ishani, A., MacDonald, R., Stark, G., Mulrow, C. D., & Lau, J. (2000). Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database of Systematic Reviews, 1999(3), CD001043. https://doi.org/10.1002/14651858.cd001043
  19. Wilt, T., Ishani, A., & Mac Donald, R. (2002). Serenoa repens for benign prostatic hyperplasia. The Cochrane Database of Systematic Reviews, 3, CD001423. https://doi.org/10.1002/14651858.CD001423
  20. World Cancer Research Fund. (2024, October 4). Prostate cancer statistics. World Cancer Research Fund; World Cancer Research Fund. https://www.wcrf.org/preventing-cancer/cancer-statistics/prostate-cancer-statistics/
  21. Wyatt, G. K., Sikorskii, A., Safikhani, A., McVary, K. T., & Herman, J. (2016). Saw palmetto for symptom management during radiation therapy for prostate cancer. Journal of Pain and Symptom Management, 51(6), 1046–1054. https://doi.org/10.1016/j.jpainsymman.2015.12.315
  22. Zhang, A. Y., & Xu, X. (2018). Prevalence, burden, and treatment of lower urinary tract symptoms in men aged 50 and older: A systematic review of the literature. SAGE Open Nursing, 4, 237796081881177. https://doi.org/10.1177/2377960818811773