Serenoa repens for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: Current Evidence and Its Clinical Implications in Naturopathic Medicine

Abstract

Objectives:

Benign prostatic hyperplasia (BPH) commonly affects men above 40 years old. The progression of BPH is often accompanied with lower urinary tract symptoms (LUTS) that can significantly affect the quality of life of the patients. Serenoa repens (saw palmetto) is a popular herbal remedy indicated for LUTS/BPH. We reviewed the current research on the efficacy of S. repens on LUTS/BPH as a monotherapy as well as combination therapies.

Design:

Non-systematic searches were performed in PubMed for human studies and systematic reviews on the topic.

Results:

The latest evidence, based largely on the Cochrane review, suggests that S. repens is not superior to placebo in treating LUTS/BPH as a monotherapy, even at double and triple doses. Initial clinical trials on treatment of LUTS/BPH using S. repens with lycopene and selenium, as well as S. repens with Urtica Dioica, have shown positive results. S. repens is safe in its application. However, there is a high level of heterogeneity in the quality of S. repens products. We suggest that strong placebo effect, potentially influenced by positive patients' expectation on S. repens, shapes both the clinical practice outcomes and the findings of clinical trials. Hitherto, the totality of evidence continues to suggest that S. repens is a prudent therapeutic option as part of the naturopathic treatment for LUTS/BPH.

Conclusions:

The totality of evidence includes favorable patients' response from clinical experience, impact of placebo effect, early positive studies, subjective nature of symptom reporting, pharmacological properties of S. repens, and potential synergistic effects when combined with other therapies.

Introduction

Benign prostatic hyperplasia (BPH) is a common age-related condition that affects men above 40 years old. Subjective urinary symptoms such as hesitancy, weak flow, prolonged voiding, urge incontinence, and nocturia, which are collectively referred to as lower urinary tract symptoms (LUTS), are often developed due to the progression of BPH. LUTS/BPH can significantly affect the quality of life of the patients. Serenoa repens is a popular herb indicated for LUTS/BPH. Pharmacologically, S. repens can potentially inhibit the development and progression of LUTS/BPH through its antiandrogenic, anti-inflammatory, and antiproliferative effects. S. repens is an appealing alternative for the prevention and management of LUTS/BPH condition, especially for men who are fearful of the unwanted side-effects of conventional medications. In this article, the latest evidence regarding the efficacy of S. repens on LUTS/BPH as a monotherapy was reviewed, as well as combination therapies, and discuss its implications in naturopathic medicine, taking into consideration the clinical practice outcomes, quality, and safety of S. repens in the treatment of LUTS/BPH.

Background

Benign prostatic hyperplasia

BPH refers to the nonmalignant abnormal growth of the prostate. It affects men above 40 years old and is often considered to be an inevitable part of the male aging process.¹ In medical definition, BPH refers to the histologic hyperplasia of the stromal and epithelial tissues in the male prostate gland.¹

The development of histologic BPH is linked to men's androgen levels. Dihydrotestosterone (DHT), an androgen converted from testosterone by the enzyme 5-alpha-reductase type 2, plays an important role in the homeostasis of prostate cell proliferation and apoptosis.² Men with high serum concentrations of DHT are known to have an increased risk of developing BPH with urinary symptoms.³ Hence, the disruption of DHT-supported homeostasis leads to the pathophysiologic development of the histologic BPH.² In addition, chronic or acute inflammation of the prostate gland through a variety of mechanisms, such as infections or oxidative stress, may also be a contributing factor that triggers the cellular proliferation and hyperplastic growth of the prostate cells.⁴

Results from age-stratified autopsy studies worldwide show that 20% of men in their 40s have histologic BPH; the prevalence rate increases to more than half of the men in their 60s and continues to rise to 80%–90% for males in their 70s and 80s.⁵ Therefore, it is believed that, most men, if living long enough, will develop histologic BPH.⁶

Lower urinary tract symptoms

BPH is not considered a clinical condition until it is associated with LUTS. The symptoms are subjective and nonspecific, with hesitancy, weak flow, prolonged voiding, urge incontinence, and nocturia often reported. This is despite the presence of histologic features. It is assumed that the progression of histologic BPH causes the enlargement of the prostate gland in volume and weight, which compresses on the urethra and leads to bladder outflow obstruction and LUTS.⁷ Nevertheless, the relationship between LUTS and BPH is not straightforward.⁶ In fact, it is estimated that only about 10% of all men 40 and above will develop LUTS due to BPH (LUTS/BPH), and the prevalence rate of LUTS/BPH is 24% among men in their 80s.⁸ Chronic prostate inflammation, however, has been shown to be positively correlated with the severity of LUTS.⁹ Psychologic factors, such as stress, can also impact the progression of BPH leading to LUTS.¹⁰ LUTS can also be caused by other conditions such as prostatitis, prostate cancer, and urethral stricture. Hence, the diagnosis of LUTS/BPH can only be confirmed once other possible underlying causes have been ruled out.⁶

Medical treatment for LUTS/BPH involves the use of alpha-blockers (e.g., tamsulosin) and 5-alpha-reductase inhibitors (e.g., finasteride and dutasteride) to manage the condition in the long term. Surgery is often recommended for patients with moderate-to-severe LUTS/BPH or those with BPH-related complications.¹¹ Tamsulosin is often considered as a safe drug with mild and well-tolerated side-effects such as dizziness, fatigue, abnormal ejaculation, and rhinitis,¹² but finasteride and dutasteride have been linked to serious adverse effects, including sexual dysfunction, high-grade prostate cancer, and depression.¹³

Serenoa repens

S. repens, commonly known as “saw palmetto,” is a dwarf-palm tree originating from the swamps of the southeastern coast of North America. The berries of S. repens were used by the American Indians both as a medicine and as a food source long before the arrival of the Europeans. Liquid extracts or pressed oil of dried S. repens berries was traditionally used for a wide range of respiratory and genitourinary disorders in both men and women.¹⁴

The active constituents of S. repens extract are mainly free fatty acids (lauric acid, oleic acid, myristic acid, palmitic acid, and linoleic acid) and phytosterols (β-sitosterol, campesterol, and stigmasterol).¹⁵ The pharmacologic properties of S. repens extract include antiandrogenic, anti-inflammatory, and antiproliferative effects. These properties can inhibit the development and progression of LUTS/BPH. The free fatty acids in S. repens extract, especially lauric acid and linoleic acid, can inhibit the enzyme 5-alpha reductase leading to its antiandrogenic action.¹⁵ In an in vivo study, Bernichtein et al.¹⁶ demonstrated that S. repens extract downregulated the prostate pro-inflammatory cytokine profile and significantly reduced the CCR7, CXCL6, IL-6, and IL-17 expression. S. repens extract was also able to inhibit several steps of prolactin receptor signal transduction, and thus, effectively inhibited the prolactin-induced prostate growth.¹⁵ S. repens extract has also been shown to be more effective than tamsulosin in the reduction of inflammation biomarkers in LUTS/BPH patients in a clinical trial.¹⁷

Today, dietary supplements containing S. repens berries and extracts are widely available off the shelf in many countries. S. repens products are commonly considered to be the first line of defense against LUTS/BPH in many European countries.¹⁵ It is an appealing alternative for men who wish to prevent or manage LUTS/BPH without the side-effects of conventional medications.¹⁸

Naturopathic medicine

Naturopathic medicine is a form of complementary medicine based on both scientific and traditional knowledge. Naturopaths are guided by the holistic principles of the healing power of nature, identify and treat the cause, treat the whole person, first do no harm, doctor as teacher, and prevention.¹⁹ Treatment of a patient involves the use of herbal medicine and nutritional supplementation to support and harness the body's natural healing abilities. S. repens is commonly used in naturopathic treatment to address a wide range of male reproductive system disorders, including LUTS/BPH, prostatitis, erectile dysfunctions, and andropause.¹⁹ In evidence-informed naturopathic practice, current research evidence is used to validate the traditional use of a remedy while taking into consideration the clinical experiences, patient preferences, and values, as well as quality and safety for clinical decision-making.²⁰

Materials and Methods

Nonsystematic searches were performed in PubMed for human studies and systematic reviews (SRs) on the topic. The terms “Serenoa repens,” “S. repens,” “benign prostatic hyperplasia,” and “lower urinary tract symptoms” were used. Boolean terms AND and OR were also used with various combinations of these terms. With the large number of publications on the topic, only SRs were included in the review of S. repens as a monotherapy for LUTS/BPH. For S. repens as part of a combination therapy, an additional term “combination therapy” was used in the search. Publications on quality analysis and safety review of S. repens were also searched. Only English-language articles published through May 2016 were included in the search. A search was also performed in Google Scholar for any gray literature published in this area.

Results

S. repens as a monotherapy for LUTS/BPH

Systematic reviews

Extensive research has been done to assess whether S. repens has any specific effect on men diagnosed with LUTS/BPH. There has been several SRs conducted over the years to assess the results obtained from randomized placebo controlled trials (RCTs). An overview by Kim et al.²¹ on SRs of dietary supplements for LUTS/BPH has included three SRs on S. repens. These are summarized in Table 1.

Table 1.

A Summary of Systematic Reviews on Serenoa repens Versus Placebo for Benign Prostatic Hyperplasia with Lower Urinary Tract Symptoms

Systematic review	Description	Conclusion
Wilt et al.²²	A SR of 18 RCTs conducted before 1997 involving 2,939 patients. Studies are mostly short term using different preparations and vary widely in study design.	S. repens improved urologic symptoms and flow measures similar to finasteride with fewer adverse treatment events.
Boyle et al.²³	A meta-analysis of 14 RCTs and 3 open-label trials with 4,280 patients on Permixon^® versus placebo.	S. repens significantly improved peak flow rate and reduced in nocturia above placebo, with five-point reduction in the IPSS.
Tacklind et al.²⁴	A Cochrane systematic review of 32 RCTs involving 5,666 men, inclusive of two long-term high quality trials.	S. repens did not improve urinary flow measures or prostate size in men with LUTS/BPH, even at double and triple dosage.

BPH, benign prostatic hyperplasia; IPSS, International Prostate Symptom Score; LUTS, lower urinary tract symptoms; RCT, randomized placebo controlled trial; SR, systematic review.

In the first SR, Wilt et al.²² included 18 RCTs published between 1966 and 1997 for analysis. Two thousand nine hundred and thirty-nine men were involved in these trials. Among these trials, 16 were double blinded. The trials were short in duration with a mean of 9 weeks (range, 4–48 weeks), and the S. repens preparations varied significantly across different trials. Most trials did not report results that would allow for meta-analysis. Wilt et al.²² concluded that S. repens could improve urologic symptoms and flow measures similar to finasteride with fewer adverse treatment events. The authors called for further research with standardized preparations of S. repens to determine its long-term effectiveness in treating LUTS/BPH. The results from Wilt et al.²² were also published as the first Cochrane SR for this topic in 2000.²⁵

The second SR by Boyle et al.²³ was a meta-analysis of 14 RCTs and 3 open-label trials with 4,280 patients using Permixon^®, a proprietary standardized lipidosterolic (Hexane) extract of S. repens. Most of the trials included were short term in nature (≤90 days) with only 1 trial of 180 days, 2 trials of 360 days, and 1 trial longer than 1 year (720 days). Data from these trials were pooled and analyzed. The results showed that S. repens significantly improved peak flow rate (Qmax) and reduced nocturia above placebo, with a five-point reduction in the International Prostate Symptom Score (IPSS).

The Cochrane SR has subsequently been updated in 2002, 2009, and 2012. The latest Cochrane SR²⁴ included 32 RCTs involving 5,666 men for meta-analysis. The trial lengths range from 4 to 72 weeks, of which 27 trials were double blinded. In this latest update, Tacklind et al.²⁴ concluded that S. repens, at double and triple doses, did not improve urinary flow measures or prostate size in men with LUTS/BPH. This conclusion was drawn primarily from the three latest moderate to long-term trials, including the S. repens Treatment for Enlarged Prostates (STEP) study²⁶ and the Complementary and Alternative Medicine for Urologic Symptoms (CAMUS) study,²⁷ both supported by the United States National Institutes of Health. Both the STEP and CAMUS trials were considered high quality in the Cochrane SR because they were designed to overcome the methodological limitations of the earlier RCTs.

As such, the latest research evidence based largely on the most recent Cochrane SR suggests that S. repens is not superior compared to placebo in treating LUTS/BPH, even at double and triple doses.

Clinical practice outcomes

Few studies were done to evaluate the outcomes of LUTS/BPH with S. repens in clinical practice. A multicenter study by Giulianelli et al. conducted in routine clinical practice filled this gap.²⁸ In this study, 591 LUTS/BPH patients were treated with Permixon^®. The results showed statistically significant improvement in Qmax values, IPSS, and quality of life scores of the patients, especially in bladder voiding and LUTS, after 6 months of treatment.²⁸ Indeed, favorable outcomes in actual clinical practice were observed. Nevertheless, with the study not being a RCT, the results are unlikely to impact the findings of the Cochrane SR.

S. repens as a combination therapy for LUTS/BPH

Instead of using S. repens as a monotherapeutic agent, current research is focusing on the therapeutic efficacy of S. repens together with other therapies to treat LUTS/BPH. Clinical trials with S. repens as a combination therapy for LUTS/BPH are summarized in Table 2.

Table 2.

Summary of Clinical Trials with S. repens as a Combination Therapy for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia

Clinical trials	Total no. of patients	Combination, comparison (duration)	Conclusion
Morgia et al.²⁹	168	S. repens, lycopene, and selenium (SeR-Ly-Se) versus control (6 months)	SeR-Ly-Se may have an anti-inflammatory activity for the treatment of prostatic chronic inflammation in BPH.
Russo et al.³⁰	225	SeR-Ly-Se versus tamsulosin (1 year)	SeR-Ly-Se + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS.
Ryu et al.³¹	140	S. repens plus tamsulosin versus tamsulosin (1 year)	The combination treatment of S. repens plus tamsulosin is more effective than tamsulosin monotherapy in reducing storage symptoms in BPH patients.
Hizli and Uygur³²	60	S. repens plus tamsulosin versus tamsulosin (6 months)	Treatment by S. repens and tamsulosin seems to be effective alone. A combined therapy does not provide extra benefits.
Argirović and Argirović³³	265	S. repens plus tamsulosin versus tamsulosin (3 months)	Treatment by S. repens and tamsulosin seems to be effective alone. A combined therapy does not provide extra benefits.
Lopatkin et al.³⁴	219	S. repens plus Urtica dioica versus placebo (96 weeks)	Treatment with S. repens plus U. dioica provides a clinically relevant benefit over a period of at least 96 weeks and slows down the natural progression of BPH.
Pavone et al.³⁵	320	S. repens, U. dioica, P. pinaster (30 days to 1 year)	A marked reduction of LUTS was observed in 85% of evaluable cases, especially with pain and irritative symptoms.
Bercovich and Saccomanni³⁶	120	S. repens, U. dioica, avocado, and soy extract versus control (6 months)	The combined therapy seems to be highly effective for the treatment of LUTS in BPH patients and does not have negative side-effects.
Suardi et al.³⁷	36	S. repens, quercetin, and β-sitosterol versus control (3 months)	Patients treated with combined therapy showed an improvement in voiding function compared to controls but not statistically significant.
Coulson et al.³⁸	57	S. repens, Cucurbita pepo, Epilobium parviflorum, lycopene, and Pygeum africanum versus placebo (3 months)	The herbal preparation was shown to be well tolerated and have a significant positive effect on physical symptoms of BPH.

S. repens, lycopene, and selenium

A triple therapeutic approach of combining S. repens with lycopene and selenium (SeR-Ly-Se) (Profluss^®) for the treatment of LUTS/BPH has been proposed.³⁹ The potential synergistic effects of such combination include enhancing anti-inflammatory activity, inhibiting growth factor expressions, and increasing prostatic cell apoptosis.²⁹ In clinical studies, the enhanced anti-inflammatory activity of SeR-Ly-Se has been confirmed through a 6-month RCT with 168 BPH subjects. The group treated with SeR-Ly-Se had significant reduction in the density of pro-inflammatory cytokines compared to the control group.²⁹ The result from a multicenter double-blinded RCT involving 225 patients also shows that combining SeR-Ly-Se with tamsulosin can achieve the greatest effect in symptom improvement (reduction of IPSS and postvoid residual volume, as well as the increment of Qmax) compared to either SeR-Ly-Se or tamsulosin alone.⁴⁰ In a related study, the efficacy of SeR-Ly-Se versus S. repens alone was evaluated in a trial involving 102 patients with chronic prostatitis/chronic pelvic pain syndrome. IPSS and maximum peak flow rate improved more in patients treated with SeR-Ly-Se group than S. repens alone.⁴¹ Expert opinion now favors SeR-Ly-Se over S. repens alone in the treatment of LUTS/BPH as current data hint at higher efficacy.³⁰ Larger RCT to better assess SeR-Ly-Se is still needed.

S. repens and tamsulosin

Many earlier trials used S. repens to compare with tamsulosin in the treatment of LUTS/BPH.⁴² Several recent trials have considered using S. repens and tamsulosin as a combination therapy. The results are mixed. In a 1-year randomized open-label study of 140 Korean men with LUTS/BPH, the combination therapy of S. repens and tamsulosin was found to be more effective than tamsulosin monotherapy in reducing storage symptoms of patients.³¹ Nonetheless, two other earlier trials found that a combined therapy of S. repens and tamsulosin did not provide any additional benefits in the treatment of LUTS/BPH compared to S. repens or tamsulosin as monotherapy.^32,33

S. repens and Urtica dioica (Nettle)

In a 96-week, double-blind placebo-controlled trial, S. repens extract was combined with Urtica dioica root extract in the ratio of 160/120 mg (PRO 160/120) for LUTS/BPH treatment involving 219 subjects. PRO 160/120 was found to be effective in the reduction of overall IPSS, increasing the peak and average urinary flow rate and reducing the residual urinary volume.³⁴

S. repens has also been used in association with U. dioica and Pinus pinaster in the treatment of LUTS/BPH. Pavone et al.³⁵ reported the results from the clinical treatment outcomes of 320 LUTS/BPH patients using S. repens, U. dioica, and P. pinaster during 2007 and 2008. LUTS reduction was observed in 85% of evaluable cases, especially regarding pain and irritative symptoms. However, no change in flow rate and prostate volume was observed.

In another 6-month RCT with 120 patients, S. repens extract was combined with U. dioica, as well as avocado and soy extract (Pluvio^®), for the treatment of LUTS/BPH. The treated group was reported to have a marked benefit in terms of quality of life measured by IPSS, uroflow, residual urine, and nocturia, even though prostate-specific antigen and prostate volume were not significantly affected.³⁶

S. repens, quercetin, and β-sitosterol

In a small nonrandomized control study involving 36 LUTS/BPH patients with obstructive symptoms eligible for surgery, the effect of a combination therapy of S. repens, quercetin, and β-sitosterol (Difaprost^®) was evaluated. The study found a clinically significant reduction of postvoid residual volume and a slight increase in Qmed after 3 months of treatment. However, the result was not statistically significant. Therefore, future trials with a large number of patients over a long period were suggested.³⁷

S. repens, Cucurbita pepo, Epilobium parviflorum, lycopene, and Pygeum africanum

A combination of S. repens, Cucurbita pepo, Epilobium parviflorum, lycopene, and Pygeum africanum (ProstateEZE Max) was tested in a double-blind placebo-controlled RCT with 57 otherwise healthy males aged 40–80 years that presented with medically diagnosed LUTS/BPH. This study found a significant reduction in IPSS total median score in the active group (36%) compared to the placebo group (8%) after 3 months of intervention. The active group also showed a significant reduction in both day- and night-time urinary frequency.³⁸

In view of these results, research on the application of S. repens combination therapies in addressing LUTS/BPH will remain an ongoing topic with new evidence expected in the future.

Safety of S. repens usage

A SR of adverse events of S. repens by Agbabiaka et al.⁴³ showed that the adverse events associated with S. repens were mild, infrequent, and reversible comparable to those with placebo. Abdominal pain, diarrhea, nausea, fatigue, headache, decreased libido, and rhinitis were the most frequently reported events. More serious adverse events, such as death and cerebral hemorrhage, were reported in isolated case reports only, with the causality being questionable. In addition, there was no drug interaction reported. Such findings were consistently reported in all the major SRs as well. More recently published case reports of adverse events include a high risk of bleeding, hepatitis, and pancreatitis. However, these adverse events may be caused by quality issues and contamination of the S. repens products due to the high variability in the S. repens products available on the market.⁴⁴ Therefore, S. repens is generally accepted to be extremely safe in its application.

Quality issues with S. repens products

Penugonda and Lindshield⁴⁵ quantified the major fatty acids and phytosterols in 20 commercially available S. repens products and found a high level of heterogeneity in the amount of active components across different products. For example, the range of total fatty acids in these products varies from 94.1% to negligible. Overall, S. repens products in liquid form were found to contain the highest fatty acids and phytosterol quantities, followed by powder, dried berries, and tincture forms.

Even in its liquid forms, the active components of S. repens products can vary significantly due to the different extraction techniques used to prepare the extract. The variety of the extractive techniques makes one S. repens extract different from another in terms of bioactive composition. As such, the extraction techniques could affect the quality and the clinical effects of different S. repens products.⁴⁶ Currently, the hexane extraction of lipidosterolic composition from S. repens is the most investigated in clinical trials. To date, there is no comparative study on the clinical effects of different types of S. repens extract.

Discussion

Despite promising results from earlier studies and favorable outcomes observed in clinical practice, the latest research evidence suggests that S. repens, as a monotherapy, is not superior compared to placebo in treating LUTS/BPH. With the quality varied across different S. repens extracts, whether the clinical results obtained from one S. repens extract can be extrapolated to others has been questioned. However, with multiple high-quality clinical trials using different S. repens extracts which were well characterized, quality of S. repens extract is unlikely to be the determining factor for the negative results.^26,27,47

To reconcile the discrepancy between clinical practice outcomes and research evidence, the following salient points were offered for consideration:

1. The placebo effect in LUTS/BPH treatment is inherently strong due to the subjective nature of the urinary symptoms. It has been shown that symptomatic improvement of any medical treatment (not only S. repens) of LUTS/BPH is partly due to the placebo effect as evidenced by the strong placebo response in virtually all placebo-controlled RCTs.⁴⁸

2. Patients' expectations can potentially exert a greater impact on the clinical outcomes than a drug's pharmacologic activity.⁴⁹ S. repens with its strong reputation to be a safe and natural, nondrug alternative for the management of LUTS/BPH due to its excellent safety records, long-standing traditional use, and positive results from many earlier clinical trials, all of which may influence patients' expectations and responses to treatment.

3. In the CAMUS trial, with successful blinding, patients were not aware whether they were taking either S. repens or placebo. Both groups of patients experienced improvement in their symptom scores after treatment.²⁷ However, participants who experienced better symptom relief were found to be 2.6 times more likely to guess that they were taking S. repens.⁵⁰ This finding demonstrated a positive perception of S. repens among LUTS/BPH patients, which may possibly affect the study results.

Hence, it may be the patients' perceptions and expectations on S. repens that further amplify the placebo effect and shape the results of the RCTs, as well as clinical practice outcomes, more than the actual pharmacologic activity of S. repens. In clinical practice, clearly, if a LUTS/BPH patient is currently taking S. repens, has confidence in its efficacy, experiences improved urinary symptoms, and enjoys a better quality of life, there is no reason to stop the treatment, especially when S. repens is known to be safe. Nonetheless, practitioners should be aware of the strong placebo effect at play in such a case.

Studies of combination therapies of S. repens, particularly SeR-Ly-Se and S. repens plus U. dioica, have demonstrated some promising results in the treatment of LUTS/BPH with the support of multiple positive clinical trials. However, mostly proprietary formulations were used in these clinical trials casting doubt over the applicability of the results in general. Moving forward, well-designed long-term clinical trials are needed to independently validate the efficacy of these combination therapies for LUTS/BPH using standardized extracts and formulations.

Combination therapies of S. repens are more closely reflective of the use of S. repens in naturopathic clinical practice. Unlike conventional medicine, S. repens is rarely prescribed alone in naturopathic medicine. Herbal remedy is prescribed based on the concept of pharmacologic synergy that multiherb prescriptions often exhibit pharmacologic and therapeutic superiority in comparison to any isolated single constituent.⁵¹ Even though S. repens possesses antiprostatic pharmacologic properties individually,¹⁵ naturopathic LUTS/BPH prescription often combines S. repens with not only lycopene and selenium but also other herbs (e.g., C. nurvala, U. dioica, C. pepo, E. parviflorum, and P. africanum) and nutraceuticals (e.g., β-sitosterol, pumpkin seeds, and zinc) to harness their synergistic effects.¹⁹

In view of the current available evidence, it was suggested that when S. repens is selected as a treatment option, it should be prescribed in combination with other herbs and nutraceuticals inclusive of lycopene, selenium, and/or U. dioica to enhance its efficacy. The prescription can even be used for patients currently on tamsulosin, as there is clearly no contraindication and may possess further synergistic effect. Taking into consideration the heterogeneity in the product quality, only high-quality S. repens products from reputable companies with clear documentation on the amount of the fatty acids and phytosterol contents should be used in clinical practice. In addition, due to the dissimilarity in the active compounds in different product forms, liquid extract of S. repens should be the preferred option for naturopathic prescriptions.

Conclusions

In conclusion, current research evidence, based largely on the most recent Cochrane review, weighs against the use of S. repens as a monotherapy for LUTS/BPH. Strong placebo effect, likely to be influenced by positive patients' expectation on S. repens, shapes both the clinical practice outcomes and the findings of clinical trials. Considering the combination of favorable patients' response from clinical experiences, early positive studies, excellent safety records, pharmacologic properties, and potential synergistic effects when combined with other therapies, S. repens may remain as a remedy for LUTS/BPH in naturopathic treatment, which favors multiherb formulations. S. repens should be prescribed, preferably in liquid extract form, in combination with lycopene, selenium, and/or U. dioica to enhance its therapeutic effects toward symptomatic relief of LUTS/BPH. However, care should be taken to ensure only high-quality S. repens products are used in clinical practices for optimal efficacy and safety assurance.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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