Skip to main content
Download PDF

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 volume 20, Article number: 86 (2020) Cite this article

Abstract

Background

The present clinical trial was conducted to evaluate the efficacy and tolerability of a standardized saw palmetto oil containing 3% β-sitosterol in the treatment of benign prostate hyperplasia (BPH) and androgen deficiency.

Methods

Subjects aged 40–65 years with symptomatic BPH were randomized to 12-week double-blind treatment with 500 mg doses of β-sitosterol enriched saw palmetto oil, conventional saw palmetto oil and placebo orally in the form of capsules (n = 33 in each group). BPH severity was determined using the International Prostate Symptom Score (IPSS), uroflowmetry, serum measurement of prostate specific antigen (PSA), testosterone and 5α-reductase. During the trial, the androgen deficiency was evaluated using Aging Male Symptoms (AMS) scale, the Androgen Deficiency in the Aging Male (ADAM) questionnaire, serum levels of free testosterone.

Results

Subjects treated with β-sitosterol enriched saw palmetto oil showed significant decrease in IPSS, AMS and ADAM scores along with reduced postvoiding residual volume (p < 0.001), PSA (p < 0.01) and 5α-reductase from baseline to end of 12-week treatment as compared to placebo. There was also a significant increment in the maximum and average urine flow rate (p < 0.001), and serum free testosterone level of subjects treated with enriched saw palmetto oil as compared to placebo.

Conclusion

This study demonstrates the efficacy of β-sitosterol enriched saw palmetto oil superior to conventional oil thus extending the scope of effective BPH and androgen deficiency treatment with improved quality of life through the intake of functional ingredients.

Trial registration

CTRI/2018/12/016724 dated 19/12/2018 prospectively registered. URL: http://ctri.nic.in/Clinicaltrials/advsearch.php

Peer Review reports

Background

Growing interest in the use of functional foods and dietary supplements for healthcare management has led to the availability of natural products in the market. However, development of nutraceuticals requires supportive evidence of efficacy and tolerability that must be clearly demonstrated with clinical trials [1]. Serenoa repens (saw palmetto) is one of the most studied plants for the treatment of lower urinary tract diseases (LUTS), especially mild to moderate prostatic diseases. Major bioactive principles attributing to the medicinal use of saw palmetto oil are the phytosterols and fatty acids. Explored mechanisms of action for saw palmetto oil includes inhibition of 5α-reductase, cyclooxygenase (COX) and 5-lipoxygenase (LOX). In addition, it exhibits antiproliferative effect on prostatic epithelial cells and antiestrogenic activity [2]. Thus, the candidature of saw palmetto preparations as alternative medicine to treat benign prostate hyperplasia has been the subject of clinical research.

Saw palmetto (SP) has been clinically tested either alone or in combination with other alpha-blockers and 5α-reductase inhibitors (5-ARIs). Guilianelli et al. demonstrated in a multicentre clinical trial that the use of SP extract for 6 months showed significant improvement in International Prostate Symptom (IPSS) score and uroflowmetry in subjects with BPH [3]. Sinescu et al. have reported the long-term efficacy of SP extract in improving the LUTS, urinary flow, erectile dysfunction and quality of life (QoL) [4]. In a recent double-blind, placebo-controlled study Ye et al. reported the improvements in LUTS and male sexual function followed by treatment with SP extract [5]. SP extract demonstrated equivalent efficacy when compared to treatments with other alpha-blockers and 5-ARIs [6,7,8].

Phytoconstituents such as sterols, fatty acids and vitamin E together contribute to the efficacy of SP extract in mitigating the BPH complications [9, 10]. Conventionally SP oil contains 0.2–0.3% β-sitosterol in addition to fatty acids. Here we have used a 3% β-sitosterol-containing SP oil for the clinical evaluation of therapeutic potential, alongside comparing with the conventional SP oil in a placebo-controlled trial. Previously we have demonstrated the improved efficacy of β-sitosterol-enriched SP oil as compared to the conventional oil in testosterone-induced BPH model rats [11]. Here we have provided the first ever clinical evidence on the improved efficacy of β-sitosterol-enriched SP extract superior to the conventional SP.

Methods

Investigational product

The investigational product was a standardized saw palmetto extract containing 3% β-sitosterol (VISPO™). VISPO and the conventional saw palmetto oil (SPO, 0.2% β-sitosterol) were prepared in-house from the berries (Florida, USA) using the supercritical fluid extraction method. The higher percentage of β-sitosterol in VISPO was achieved by column chromatography. The β-sitosterol content was quantified using LCMS analysis (Fig. 1). The extracts were then formulated into powder form with maltodextrin as excipient and filled in capsules (500 mg in weight). Each capsule contained 200 mg of extract. Placebo capsules consisted of maltodextrin only.

Fig. 1
figure 1

LCMS chromatograms of reference compound β-sitosterol (95%) (a), SPO (b) and VISPO (c)

Full size image

Ethics, consent and permissions

The Institutional Ethics Committee of Aman Hospital and Research Center, Vadodara, India approved the study protocol and informed consent form (AHRC/IEC/026/2018). This clinical study was registered in Clinical Trials Registry – India (CTRI/2018/12/016724 dated 19/12/2018).

Subjects

Ninety-nine male subjects aged 40–65 years, having mild-to-moderate BPH symptoms were enrolled into this clinical trial. Before enrolment, subjects were explained the study protocol approved by the Institutional Ethics Committee, and informed consent and consent to publish were obtained. The subjects having IPSS score > 7, Aging Male Symptoms (AMS) score ≥ 27, and responding positively to question 1 or 7 or any other three questions of the Androgen Deficiency in the Aging Male (ADAM) questionnaire, were included in the trial. Subjects with neurogenic bladder dysfunction, prostatic cancer, prostatitis, haematuria diabetes or any other chronic illness were excluded from the study.

Study design

This study was conducted in compliance with ICH-GCP (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use –Good Clinical Practice) guidelines and Helsinki Declaration Standards. This clinical study adheres to the CONSORT guidelines.

The study was performed at Aman Hospital and Research Center, Vadodara, India. The trial was designed as a double-blind, placebo-controlled, single-centered study including 99 male subjects randomised to three treatment arms: VISPO, SPO and placebo, on 1:1:1 ratio (n = 33 in each group). Block randomization was implemented for groupwise allocation of subjects wherein the participants received a xx-digit randomization number. The investigator and subjects were blinded of the interventions. The study medications were dispensed by the unblinded pharmacist at the site.

The subjects received oral doses of 500 mg capsules twice daily (after breakfast and dinner) for 12 weeks. The study treatment details are provided in Table 1. Following baseline visit, during the intervention period there were two visits at study site every 6 weeks. The details of study procedures scheduled at each visit are provided in supplementary file 1. The treatment compliance was monitored during the trial using subject diary.

Table 1 Details of study treatments
Full size table

Sample size

A sample size of 99 subjects (33 per group), was considered enough to detect a clinically important difference between groups with 80% power and a 5% level of significance. Considering an estimated potential dropout rate of 12%, the sample size was finalized as 99 (33 per group). For the sample size calculation IPSS and maximum urine flowrates were considered with a delta value of 2.35 (Supplementary file 2).

Study outcomes

The primary endpoints were determined as changes in IPSS, ADAM and AMS scores (subjective assessments). Objective assessment was based on post-void residual urine volume as measured by ultrasonography, and uroflowmetric determination of the maximum (Qmax) urine flowrate. The serum levels of prostate specific antigen (PSA), 5α-reductase and testosterone were measured at baseline and after 12 weeks of treatment using commercial kits. The general health status of subjects was assessed using the 12-tem Short Form Survey (SF-12) quality of life questionnaire. In SF-12, the questions are combined, scored, and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. Physical (PCS-12) and Mental Health Composite Scores (MCS-12) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The questionnaires used in the study are detailed in supplementary file 3.

The safety assessments included physical examination, vital signs, biochemical and hematological parameters (Aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, blood urea nitrogen (BUN) and complete blood count).

Statistical analysis

The general characteristics of the study subjects are summarized as mean ± standard deviation (SD) for continuous data. ANOVA was performed when equal variances were assumed to test between groups. Kruskal-Wallis test was performed when equal variances are not assumed. Paired t test was performed to test variables within groups.

Results

A total of 118 human volunteers were screened of which 99 subjects meeting the inclusion criteria were enrolled in the study. Of the 99 subjects randomized to three treatment groups (n = 33 in each group), 91 subjects completed the study. There were 8 dropouts in the study (reason: lost to follow up). The intention-to-treat (ITT) analysis was used to assess the outcome of the study. The participant flow through the study is presented in Fig. 2. The demographic characteristics of subjects between the groups were not significantly different (Table 2). The efficacy and safety analysis were performed using ITT population.

Fig. 2
figure 2

Subject participant flow chart

Full size image
Table 2 Demographic characteristics of subjects
Full size table

The comparative efficacy of VISPO against the conventional saw palmetto oil was evaluated primarily using IPSS, ADAM and AMS scores assessed at visit 1 (baseline), visit 2 (6 weeks) and visit 3 (12 weeks) of the study. At baseline there was no significant difference in the IPSS score between the groups while the values were decreased in VISPO and SPO groups during the study (Table 3). There was a significant decrease in the IPSS score from baseline value of 20.00 ± 4.41 to 18.06 ± 4.14 at visit 2 (p < 0.001) and 16.82 ± 4.03 at visit 3 (p < 0.001). The values were not significant for SPO group. In the placebo group there was a slight increase in IPSS score during the intervention period. The change in IPSS value from baseline to the end of treatment (visit 3) was significant in saw palmetto oil treated groups as compared to placebo (p < 0.001).

Table 3 Summary of International Prostate Symptom Score (IPSS) by visit and treatment
Full size table

In the present study ADAM questionnaire was used to screen for the severity of androgen deficiency in men (Table 4). The ITT population analysis revealed that VISPO group subjects showed a significant reduction of ADAM score from baseline (4.33 ± 1.67) to the end of study (3.73 ± 1.74) (p < 0.001) while SPO and placebo groups showed an increase in the mean ADAM score. The change in the score from baseline to visit 3 of VISPO group (− 0.61 ± 1.06) was significant (p < 0.01) compared to placebo (0.15 ± 0.94).

Table 4 Summary of Androgen deficiency in the aging male (ADAM) scoring by visit and treatment
Full size table

Further AMS scale was used to assess the symptoms of ageing and to measure the changes in severity of symptoms pre- and post-intervention (Table 5). AMS scale has three dimensions (sub-scales) i.e., psychological, somatic, and sexual subscale. The composite scores for each of the three sub-scales is based on adding up the scores of the items of the respective dimensions. The AMS total score from baseline to end of treatment decreased considerably in VISPO group (p < 0.001). SPO group showed non-significant reduction in the mean score. The change in total AMS score from baseline to visit 3 of VISPO (− 3.64 ± 4.76) and SPO (− 1.12 ± 4.14) groups were significant (p < 0.001) when compared to placebo (1.70 ± 3.37). Similar trend was observed in the AMS subscale analyses (Table 6). Importantly, there was a significant reduction (p < 0.001) in the AMS sexual subscale from baseline to the end of treatment in VISPO (− 1.24 ± 1.84) and SPO (− 0.12 ± 1.47) groups as compared to placebo (0.73 ± 1.26).

Table 5 Summary of total Aging male symptoms (AMS) score by visit and treatment
Full size table
Table 6 Summary of Aging male symptoms (AMS) subscale analysis
Full size table

Table 7 shows the urodynamic measurements obtained before and after the intervention period. The residual urine volume decreased significantly (p < 0.001) in VISPO group (from 112.55 ± 36.19 mL to 99.79 ± 29.27 mL) after the 12-week treatment. SPO group showed a slight improvement in residual urine volume, though not to a significant extent (110.12 ± 34.71 mL to 108.24 ± 33.22 mL). A significant improvement (p < 0.001) of Qmax was observed in the VISPO group (from 11.85 ± 2.06 mL/s to 14.27 ± 2.54 mL/s). In the SPO group a non-significant increase in the Qmax was recorded from 12.33 ± 1.61 mL/s to 12.82 ± 1.72 mL/s.

Table 7 Summary of urodynamic measurements by visit and treatment
Full size table

Assessment of serum BPH markers are presented in Table 8. Serum levels of PSA was decreased in the VISPO group from 2.77 ± 0.56 ng/mL to 2.70 ± 0.59 ng/mL while it was increased in SPO and placebo groups after the treatment. The subjects in VISPO group showed an increase in free testosterone levels (6.23 ± 1.16 to 6.46 ± 1.43) after treatment (p < 0.05). On the contrary there was a reduction of serum levels of free testosterone in SPO and placebo groups. The change in free testosterone from baseline to end of treatment was significant in VISPO group as compared to placebo (p < 0.05). There was a reduction in total testosterone noted in all the treatment groups. However, the data were not significant. 5α-reductase activity was non-significantly reduced in VISPO group from baseline to the end of 12-week treatment (445.90 ± 105.40 ng/L to 438.24 ± 98.56). However, it was noticed that unexpectedly, the enzyme activity was increased in SPO group towards the end of study.

Table 8 Summary of BPH marker analysis
Full size table

The Short-Form Health Survey (SF-12) is one of the most widely used questionnaire for assessing self-reported health-related quality of life. VISPO group subjects demonstrated a significant improvement (p < 0.001) in the quality of life as evident from the increase in the mean total score. Comparatively, SPO group showed moderate increase in the SF-12 total score. Both VISPO and SPO groups showed significant change in mean score from visit 1 to visit 3 as compared to placebo. The subset analysis revealed that VISPO group also showed significant improvement in PCS-12 and MCS-12 scores after 12-week treatment (p < 0.001), Fig. 3 shows the change in SF-12 scores from baseline to the end of treatment.

Fig. 3
figure 3

Mean change in SF-12 score of the study participants. The changes from baseline (visit 1) to the end of treatment (visit 3) in SF-12 total score (a), physical health composite (PCS-12) score and mental health composite (MCS-12) score (b) . The values are represented as mean ± SD (n = 33 in each group). The data were analysed by one way ANOVA followed by Scheffe test. ***p < 0.001 vs. placebo

Full size image

No serious adverse events (SAEs) were recorded during the study. The investigational products were well tolerated among the subjects. There were no significant alterations in the biochemical and haematological parameters among the subjects during the intervention period. The results of safety assessment are provided in supplementary file 4.

Discussion

SP extracts used extensively for treatment of LUTS in traditional medicine have been clinically validated for improving the conditions such as BPH [12]. These medicinal attributes of SP extracts are due to the synergistic effect of phytosterols and fatty acids [13]. Previously, we have demonstrated the improved efficacy of SP oil containing 3% β-sitosterol (VISPO) compared to the conventional oil in alleviating the symptoms of BPH in rats [11]. Results from preclinical studies prompted us to conduct the clinical trial to further confirm the effectiveness of VISPO.

Here we have clinically evaluated the efficacy of VISPO in comparison with conventional SP oil (SPO). Considering the prevalence of mild to moderate BPH symptoms in men from the age of 40 to 60 and above [14,15,16], subjects aged 40–65 years were included in the trial. This study was primarily focused on the changes in BPH symptoms assessed subjectively using the validated questionnaires. IPSS score is a convenient tool for the assessment of BPH-specific symptoms in order to evaluate the treatment outcomes [17, 18]. There was a significant decrease in the IPSS score from baseline (visit 1) to the end of treatment in VISPO and SPO groups indicating amelioration of BPH symptoms. Further we have used AMS scale and ADAM score as subjective measures of androgen deficiency. The age-related androgen deficiency associated with BPH must be considered for an effective therapeutic strategy [19]. The mean scores were markedly reduced in VISPO group following the treatment. It was interesting to note that the AMS sexual score was significantly reduced in VISPO group as compared to placebo. Several treatment strategies and surgical therapies for BPH have been associated with sexual side effects [20]. It is an important observation from our study that a 12-week ingestion of β-sitosterol enriched SP oil could markedly improve the sexual function among the subjects while the conventional SP oil exerted the moderate efficacy. In accordance with the subjective measurements, the urodynamic parameters such as PVR and Qmax were significantly improved in VISPO group as compared to placebo. The mean changes from baseline to the end of treatment were appreciable in VISPO group than SPO group. Previously, Oki et al., have demonstrated that SP extract could significantly improve the urodynamic symptoms and micturition reflex in rats [21].

One of the important age-related symptoms is the testosterone deficiency which may subsequently lead to the adverse effects on androgen-responsive organ functions [22, 23]. Longitudinal studies have found dramatic reduction in free testosterone levels in aging men [24, 25]. In the present study, treatment with VISPO showed slight increase in the free testosterone and was significantly better as compared to SPO treated group.

Interestingly, there was an insignificant reduction in the 5α-reductase activity in VISPO group from baseline to the end of treatment. Our findings suggest that VISPO could exert its efficacy through other mechanisms such as alpha-adrenergic or muscarinic receptor blockage. Previously, SP extract was shown to reduce the bladder muscarinic and purinergic receptors and micturition frequency in a rat model of cystitis [26]. Suzuki et al., reported significant binding activity of SP extract on autonomic receptors in rats [27]. Studies from Aebi et al. reported oleic acid, lauric acid, myristic acid and linoleic acid as major fatty acids in SP extract having potential binding activity with alpha-adrenergic or muscarinic receptors in addition to 5α-reductase inhibitory activity [9, 28]. In accordance with these reports and the results of present study, a synergistic effect of fatty acids and β-sitosterol could contribute to the improved functional attributes of VISPO possibly with multiple mode of action. Other explanatory mechanisms of action include the anti-inflammatory and apoptotic effects [29]. In a multicentered pilot study, Vela Navarrete et al., reported that a 3-month treatment with 160 mg SP extract (Permixon®) could significantly reduce the IPSS score alongside the inflammatory parameters IL-1β and TNF-α in prostate tissues of BPH patients [30]. In another study, Permixon treatment significantly reduced the cell number and proliferative indices in BPH tissues indicating the role of SP extract in the induction of apoptosis in BPH [31]. We have previously demonstrated the anti-inflammatory and anti-proliferative effects of VISPO in preclinical model of BPH [11].

In this double-blind placebo-controlled study, we have demonstrated the improvement in BPH symptoms and androgen deficiency as a function of higher β-sitosterol content in VISPO. β-sitosterol has been previously reported to have profound influence on the prostate health [32]. Berges et al. have published their research findings on β-sitosterol wherein a 6-month administration of 20 mg of the compound significantly reduced the prostate size, increased the urine flow rate, and improved the mean voiding time and quality of life score in BPH patients [33]. In another multicentric, placebo-controlled, double-blind study daily intake of β-sitosterol markedly reduced the IPSS score with an increased Qmax and decreased post-void residual urine volume among BPH patients [34]. β-sitosterol was previously shown to inhibit the 5α-reductase activity in hamster prostate [35]. Our results are in line with these literature as ingestion of 400 mg/day VISPO, the SP extract with higher β-sitosterol content showed superior efficacy compared to conventional SP oil. The overall increment in efficacy parameters observed in VISPO group could be due to the synergistic effect of higher β-sitosterol content and the conventionally present fatty acids in saw palmetto extract. Collectively, the different constituents in the extract may contribute to the efficacy of the extract via multiple mode of action [36].

Conclusion

The present study provides first ever clinical evidence on the improved efficacy of saw palmetto oil due to the enriched content of β-sitosterol. This comparative study clearly recommends the use of a phytosterol-enriched saw palmetto oil as a functional ingredient in dietary supplements for effective management of symptomatic BPH.

Availability of data and materials

The data sets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

BPH:

Benign prostate hyperplasia

SF-12:

The 12-item short form survey

PSA:

Prostate specific antigen

SP:

Saw palmetto

IPSS:

International prostate symptom score

AMS scale:

Aging males’ symptoms scale

ADAM:

Androgen deficiency in aging males

LUTS:

Lower urinary tract symptoms

PCS-12:

Physical health composite score

MCS-12:

Mental health composite score

ITT:

Intention-to-treat

ANOVA:

Analysis of variance

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

BUN:

Blood urea nitrogen

Qmax:

Maximum urine flowrate

5ARIs:

5α-Reductase inhibitors

References

  1. Cicero AF, Petrini O, Prasad C. Clinical studies with nutraceuticals and how to carry them out. Curr Top Nutraceut R. 2017;15:63–6.

    Google Scholar 

  2. Governa P, Giachetti D, Biagi M, et al. Hypothesis on Serenoa repens (Bartram) small extract inhibition of prostatic 5α-reductase through an in silico approach on 5α-reductase x-ray structure. Peer J. 2016;4:e2698.

    Article  Google Scholar 

  3. Giulianelli R, Pecoraro S, Sepe G, Leonardi R, Gentile BC, Albanesi L, et al. Multicentre study on the efficacy and tolerability of an extract of Serenoa repens in patients with chronic benign prostate conditions associated with inflammation. Arch Ital Urol Androl. 2012;84(2):94–8.

    PubMed  Google Scholar 

  4. Sinescu I, Geavlete P, Multescu R, et al. Long-term efficacy of Serenoa repens treatment in patients with mild and moderate symptomatic benign prostatic hyperplasia. Urol Int. 2011;86:284–9.

    Article  Google Scholar 

  5. Ye Z, Huang J, Zhou L, Chen S, Wang Z, Ma L, et al. Efficacy and safety of Serenoa repens extract among patients with benign prostatic hyperplasia in China: a multicenter, randomized, double-blind, placebo-controlled trial. Urology. 2019;129:172–9.

    Article  Google Scholar 

  6. Alcaraz A, Carballido-Rodríguez J, Unda-Urzaiz M, Medina-López R, Ruiz-Cerdá JL, Rodríguez-Rubio F, et al. Quality of life in patients with lower urinary tract symptoms associated with BPH: change over time in real-life practice according to treatment--the QUALIPROST study. Int Urol Nephrol. 2016;48(5):645–56.

    Article  Google Scholar 

  7. IuA P’, Lopatkin NA, Gorilovskiĭ LM, Vinarov AZ, Sivkov AV, Medvedev AA. The results of long-term permixon treatment in patients with symptoms of lower urinary tracts dysfunction due to benign prostatic hyperplasia. Urologiia. 2004;(2):3–7.

  8. Pytel YA, Vinarov A, Lopatkin N, Sivkov A, Gorilovsky L, Raynaud JP. Long-term clinical and biologic effects of the lipidosterolic extract of Serenoa repens in patients with symptomatic benign prostatic hyperplasia. Adv Ther. 2002;19(6):297–306.

    Article  CAS  Google Scholar 

  9. Abe M, Ito Y, Oyunzul L, Oki-Fujino T, Yamada S. Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free fatty acids contained in saw palmetto extract. Biol Pharm Bull. 2009;32(4):646–50.

    Article  CAS  Google Scholar 

  10. Cabeza M, Bratoeff E, Heuze I, Ramírez E, Sánchez M. Flores E effect of beta-sitosterol as inhibitor of 5 alpha-reductase in hamster prostate. Proc West Pharmacol Soc. 2003;46:153–5.

    CAS  PubMed  Google Scholar 

  11. Sudeep HV, Venkatakrishna K, Amrutharaj B, Anitha, Shyamprasad K. A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model. BMC Complement Altern Med. 2019;19(1):270.

    Article  Google Scholar 

  12. Cicero AFG, Allkanjari O, Busetto GM, Cai T, Larganà G, Magri V, et al. Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer. Arch Ital Urol Androl. 2019;91(3):139-52.

  13. Opoku-Acheampong AB, Penugonda K, Lindshield BL. Effect of saw palmetto supplements on androgen-sensitive LNCaP human prostate Cancer cell number and Syrian hamster flank organ growth. Evid Based Complement Alternat Med. 2016;2016:8135135.

    Article  Google Scholar 

  14. Safarinejad MR. Prevalence of benign prostatic hyperplasia in a population-based study in Iranian men 40 years old or older. Int Urol Nephrol. 2008;40(4):921–31.

    Article  Google Scholar 

  15. Chicharro-Molero JA, Burgos-Rodriguez R, Sanchez-Cruz JJ, del Rosal-Samaniego JM, Rodero-Carcia P, Rodriguez-Vallejo JM. Prevalence of benign prostatic hyperplasia in Spanish men 40 years old or older. J Urol. 1998;159(3):878–82.

    Article  CAS  Google Scholar 

  16. Arrighi HM, Metter EJ, Guess HA, Fozzard JL. Natural history of benign prostatic hyperplasia and risk of pros-tatectomy. The Baltimore longitudinal study of aging. Urology. 1991;38(1 suppl):4–8.

    Article  CAS  Google Scholar 

  17. O'Leary MP, Wei JT, Roehrborn CG. Miner M; BPH registry and patient survey steering committee. Correlation of the international prostate symptom score bother question with the benign prostatic hyperplasia impact index in a clinical practice setting. BJU Int. 2008;101(12):1531–5.

    Article  Google Scholar 

  18. Roy A, Singh A, Sidhu DS, Jindal RP, Malhotra M, Kaur H. New visual prostate symptom score versus international prostate symptom score in men with lower urinary tract symptoms: a prospective comparison in Indian rural population. Niger J Surg. 2016;22(2):111–7.

    Article  Google Scholar 

  19. Martov AG, Ergakov DV. Age-related androgen deficiency and benign prostatic hyperplasia: how to improve the rehabilitation of patients after transurethral surgery? Urologiia. 2016;6:110–7.

    Google Scholar 

  20. Voznesensky I, Shaw E, DeLay KJ, Yafi F, Hellstrom WJG. Benign prostatic hyperplasia treatment options and their effects on sexual function. Sexual Med Rev. 2017;5(1):87–102.

    Article  Google Scholar 

  21. Oki T, Suzuki M, Nishioka Y, Yasuda A, Umegaki K, Yamada S. Effects of saw palmetto extract on micturition reflex of rats and its autonomic receptor binding activity. J Urol. 2005;173(4):1395–9.

    Article  Google Scholar 

  22. Cauley JA, Ewing SK, Taylor BC, Fink HA, Ensrud KE, Bauer DC, et al. Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density--the osteoporotic fractures in men study. J Clin Endocrinol Metab. 2010;95:4314–23.

    Article  CAS  Google Scholar 

  23. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263–8.

    Article  CAS  Google Scholar 

  24. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Baltimore longitudinal study of aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore longitudinal study of aging. J Clin Endocrinol Metab. 2001;86:724–31.

    Article  CAS  Google Scholar 

  25. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002;87:589–98.

    Article  CAS  Google Scholar 

  26. Nasrin S, Masuda E, Kugaya H, Osano A, Ito Y, Yamada S. Effects of saw palmetto extract on urodynamic parameters, bladder muscarinic and purinergic receptors and urinary cytokines in rats with cyclophosphamide-induced cystitis. Low Urin Tract Symptoms. 2014;6(1):57–63.

    Article  Google Scholar 

  27. Suzuki M, Oki T, Sugiyama T, Umegaki K, Uchida S, Yamada S. Muscarinic and alpha 1-adrenergic receptor binding characteristics of saw palmetto extract in rat lower urinary tract. Urology. 2007;69:1216–20.

    Article  Google Scholar 

  28. Abe M, Ito Y, Suzuki A, Onoue S, Noguchi H, Yamada S. Isolation and pharmacological characterization of fatty acids from saw palmetto extract. Anal Sci. 2009;25(4):553–7.

    Article  CAS  Google Scholar 

  29. Suzuki M, Ito Y, Fujino T, et al. Pharmacological effects of saw palmetto extract in the lower urinary tract. Acta Pharmacol Sin. 2009;30(3):227–81.

    Article  Google Scholar 

  30. Vela Navarrete R, Garcia Cardoso JV, Barat A, Manzarbeitia F, López FA. BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double-blind pilot clinical assay. Eur Urol. 2003;44(5):549–55.

    Article  CAS  Google Scholar 

  31. Vacherot F, Azzouz M, Gil-Diez-de-Medina S, Colombel M, De La Taille A, Lefrere Belda MA, et al. Induction of apoptosis and inhibition of cell proliferation by the lipido-sterolic extract ofSerenoa repens (LSESr, Permixon®) in benign prostatic hyperplasia. Prostate. 2000;45(3):259–66.

    Article  CAS  Google Scholar 

  32. Wilt T, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J. Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2000;2:CD001043.

    Google Scholar 

  33. Berges R, Windeler J, Trampisch H, Senge T. Group β-SS. Randomised, placebo-controlled, double-blind clinical trial of β-sitosterol in patients with benign prostatic hyperplasia. Lancet. 1995;345:1529–32.

    Article  CAS  Google Scholar 

  34. Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto study group. Br J Urol. 1997;80(3):427–32.

    Article  CAS  Google Scholar 

  35. Cabeza M, Bratoeff E, Heuze I, Ramírez E, Sánchez M, Flores E. Effect of β-sitosterol as inhibitor of 5α-reductase in hamster prostate. Proc West Pharmacol Soc. 2003;46:153–5.

    CAS  PubMed  Google Scholar 

  36. Kwon Y. Use of saw palmetto (Serenoa repens) extract for benign prostatic hyperplasia. Food Sci Biotechnol. 2019;28(6):1599–606.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Gouthamchandra K., and staff members of Biomedicinal Research Laboratory, R&D Center, Vidya Herbs Pvt. Ltd., for their technical support.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. R&D Center for Excellence, Vidya Herbs Pvt. Ltd, #14A, Jigani I phase, Bangalore, Karnataka, 560 105, India

    H. V. Sudeep & K. Shyamprasad

  2. Leads Clinical Research and Bio services Private Ltd., Bangalore, India

    H. V. Sudeep & Jestin V. Thomas

Authors
  1. H. V. Sudeep
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jestin V. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Shyamprasad
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All the authors have read and approved the manuscript. Conceptualization, KS; Protocol design, HVS and JVT; Study supervision, JVT; Study monitoring and coordination, HVS; writing – original draft preparation, HVS and JVT; review and editing, HVS and KS.

Corresponding author

Correspondence to H. V. Sudeep.

Ethics declarations

Ethics approval and consent to participate

This clinical trial was approved by the Institutional ethics committee of Aman hospital and research center, Vadodara, India. Subjects meeting all inclusion and no exclusion criteria signed a written informed consent and enrolled in the study.

Consent for publication

Subject consent was taken for publication and a statement that consent to publish is included in the manuscript.

Competing interests

We have read and understood the BMC policy on declaration of interests and declare that there are no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Additional file 1: Supplementary file 1.

Schedule of study procedures

Additional file 2: Supplementary file 2.

Sample size calculation

Additional file 3: Supplementary file 3.

Questionnaires used in the study (Subjective assessment)

Additional file 4: Supplementary file 4.

Safety evaluation data

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sudeep, H.V., Thomas, J.V. & Shyamprasad, K. 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 Urol 20, 86 (2020). https://doi.org/10.1186/s12894-020-00648-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12894-020-00648-9

Keywords

  • Saw palmetto oil
  • β-Sitosterol
  • Benign prostate hyperplasia
  • Androgen deficiency
  • Safety

BMC Urology

ISSN: 1471-2490

Contact us