Lipidosterolic Extract Of Serenoa Repens Research Articles

Serenoa Repens (Saw Palmetto) for Lower Urinary Tract Symptoms (LUTS): The Evidence for Efficacy and Safety of Lipidosterolic Extracts. Part III

Parts I and II of this three-part series indicated how a global review of both English-language and non-English language papers, plus a focus on a lipidosterolic extract of Serenoa repens (LSESr) having a standardized fatty acid profile, have together engendered new insights about the biological activity of LSESr vs. LUTS. In this last part, data from the world literature is presented that confirms that LSESr efficacy is the predominant finding in clinical trials. Despite two placebo-controlled clinical trials performed in the U.S. that failed to confirm a benefit of LSESr vs. placebo in LUTS, the global body of the peer-reviewed literature attests not only to efficacy but also to safety. Results will be presented of important trials that compare LSESr to alpha-blockers such as tamsulosin (Flomax®) as well as to 5α-reductase inhibitors such as finasteride (Proscar®) that demonstrate consistent findings of near equivalency between LSESr and these pharmacologic agents. Studies relating data indicative of an additive effect or synergy between LSESr and tamsulosin will also be presented. The heightened effectiveness of LSESr in men with severe LUTS vs. moderate LUTS expands the importance of our scrutiny of the global literature concerning LSESr. Of great consequence are the contributions of non-English language peer-reviewed publications that have consistently provided evidence of LSESr efficacy in treating LUTS/BPH. These peer-reviewed articles have shown that the effect of LSESr is not that of a placebo. Finally, a comparison of the LSESr extraction products used in the treatment of LUTS, and a discussion of the milieu factors that affect the natural history of LUTS and influence the outcome of clinical trials, complete this detailed analysis of LSESr vs. LUTS.

Serenoa Repens (Saw Palmetto) for Lower Urinary Tract Symptoms (LUTS): The Evidence for Efficacy and Safety of Lipidosterolic Extracts. Part II

Part I of this 3-part series provided the groundwork for understanding the role of a standardized lipidosterolic extract of Serenoa repens (LSESr) in the treatment of LUTS. It documented that a treatment having a high therapeutic index (i.e., a ratio of benefit to adverse reactions) is a critical need in the demographic context of a rapidly growing elder population. Part I described the clinical symptomatology of LUTS and how it is quantified. A critique of the reports from four authoritative bodies: the European Scientific Cooperative on Phytotherapy (ESCOP), Cochrane 2012, the European Medicines Agency (EMA), and the AUA (American Urological Association) was presented. The foundation above then fine-tuned our search to require (a) consistent evaluability criteria, (b) the quantification of clinical findings, (c) the need to focus on studies employing a standardized LSESr product meeting the fatty acid profile set forth by the European Medicines Agency (EMA) and the US Pharmacopeia and (d) a global assessment of scientific investigations published in all languages and not limited to only English. With the above four constraints, “new” findings about LSESr vs. LUTS are presented. How did the search strategy and selection criteria lead to new understandings about the role of LSESr vs. LUTS? How safe is LSESr in contrast to its counterpart prescription drugs? Of the proposed major mechanisms of action of LSESr (e.g., 5-alpha reductase inhibition and anti-inflammatory activity), what are the key points? After initiating treatment with LSESr, when is clinical improvement seen? How durable is LSESr in ameliorating LUTS? Can LSESr prevent the progression of BPH?

Serenoa repens (Saw palmetto) for Lower Urinary Tract Symptoms (LUTS): The Evidence for Efficacy and Safety of Lipidosterolic Extracts. Part I

Lower urinary tract symptoms (LUTS) are classically characterized as being related to storage (e.g., frequency, urgency, and nocturia) or flow (e.g., weak stream, intermittency, straining, and incomplete emptying). Conventional prescription medications such as α1-blockers and 5α-reductase inhibitors are used to treat progressive LUTS in men. Due to the adverse events associated with these prescription drugs, many patients with mild-to-moderate LUTS may decide to initiate treatment with non-prescription medications and/or dietary supplements. The lipidosterolic extract of Serenoa repens (LSESr), at a recommended daily dose of 320 mg/day, has been the focus of numerous peer-reviewed studies and review articles concerning the treatment of LUTS, from the first publication in 1983 by Boccafoschi to the most recent publication in 2021 by Russo. Although it seems improbable that the beneficial effect of LSESr reflects a placebo effect given the consistent degree of efficacy comparing various studies published in different countries over a span of almost 40 years, this has been the prevailing impression stemming from essentially three publications in the Western medical literature. In addition, despite publications reporting findings of almost identical efficacy using LUTS endpoints such as the International Prostate Symptom Score (IPSS), the quality of life score (QoL), and the peak urinary flow (Qmax) in comparing LSESr with the α-blocker tamsulosin or the 5α-reductase inhibitor finasteride, and despite the recognized acceptance of the hexane lipidosterolic extract product (Permixon®) as an herbal medicine in Europe showing value in the treatment of LUTS, the use of LSESr remains controversial in the US. Contributing to such an opposing view in the US are the wide variability in quality, composition, and dosage of Serenoa products, the commercial prevalence of dried berry powder supplements, and the lack of awareness of a standardized Serenoa phytotherapy lipidosterolic profile. Can the controversy over the efficacy of LSESr in the context of LUTS be resolved? By understanding the main literature that has led to clinical practice guidelines for Serenoa repens for LUTS in Europe and the US, and by an in-depth analysis of the totality of the clinical literature concerning dose, extraction method, and quality of the Serenoa product used, it should be possible to answer this question. Given the extent of this global analysis, this report is presented in three sections. Part I introduces LUTS. What are the demographics of LUTS? What symptoms are assessed by LUTS, and how do we quantify LUTS? Why would a non-prescription item be a valuable consideration in LUTS treatment versus other treatment options? What is basic information about Serenoa repens, and what defines a standardized LSESr product? What are the published trials that have affected the acceptability of Serenoa repens in the treatment of LUTS? Finally, a major portion of Part I discusses the four major reviews of Serenoa repens versus LUTS that have influenced how it is accepted in the USA, in Europe, and in other parts of the world. Part I, therefore, lays the groundwork and is foundational for the important findings relating to LUTS and Serenoa repens that will be presented as Parts II and III in subsequent review articles.

The Role of a Lipido-Sterolic Extract of Serenoa Repens in the Management of Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia

The Role of a Lipido-Sterolic Extract of Serenoa Repens in the Management of Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia

Evaluation of Male Sexual Function in Patients with Lower Urinary Tract Symptoms (LUTS) Associated with Benign Prostatic Hyperplasia (BPH) Treated with a Phytotherapeutic Agent (Permixon ®), Tamsulosin or Finasteride

Objectives: Sexual function is one of the aspects in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) that has gained increasing attention. We compared the influence on men's sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with Tamsulosin and Finasteride using a specific validated questionnaire exploring patient's sexual functions. Methods: A database was created comprising patients from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon vs. Tamsulosin and Permixon 160 mg vs. 320 mg including a total of 2511 patients. Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates and prostate volume were recorded. The MSF-4 questionnaire, including 4 items that explore the patient's interest in sex, quality of erection, achievement of orgasm and ejaculation, was used across the studies. This questionnaire was demonstrated as highly reproducible and both psychometrically and clinically valid across different cultures. Correlation coefficients were given to assess the linear relationship between continuous variables. Results: At 3 months, there were no statistically significant differences between the three treatment groups in terms of I-PSS or Qmax evolutions (all p values > 0.05). At 6 months, as compared to pretreatment data, there was a slight increase in sexual disorders in Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly improved with Permixon therapy (−0.2). Ejaculation disorders were the most frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on the specific MSF-4 question 4). There was no correlation between the evolution of the MSF-4 scores and the evolution in I-PSS neither in patients treated with Permixon, Finasteride or Tamsulosin. However, there was a slight correlation between the MSF-4 score at baseline and the I-PSS at baseline ( r 2 = 0.032). Although there was a correlation between the MSF-4 and age at baseline ( r 2 = 0.1452), there was no correlation between the evolution in MSF-4 during therapy and the age of the patients. Conclusion: The present study demonstrates that Permixon therapy has no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, especially on ejaculation, although these effects were rare and in line with previous reports about these two drugs.

The role of a lipido-sterolic extract of Serenoa repens in the management of lower urinary tract symptoms associated with benign prostatic hyperplasia.

OBJECTIVE To examine the clinical profile of medication derived from a lipido-sterolic extract of Serenoa repens (saw palmetto) for managing lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS We reviewed clinical trials involving extracts of S. repens, focusing on the benefit/risk ratio in patients with BPH. RESULTS S. repens extract significantly reduces the symptoms of BPH, increases urinary flow, improves the quality of life and is well tolerated. CONCLUSION Analysis of the overall clinical database indicates that extract of S. repens may be considered a viable first-line therapy for treating LUTS.

The mechanism on which the lipido-sterolic extract of serenoa repens (permixon®) inhibits both isoforms of 5αreductase without interfering with PSA production in the prostate

The mechanism on which the lipido-sterolic extract of serenoa repens (permixon®) inhibits both isoforms of 5αreductase without interfering with PSA production in the prostate

Comparison of a Phytotherapeutic Agent (Permixon) with an α-Blocker (Tamsulosin) in the Treatment of Benign Prostatic Hyperplasia: A 1-Year Randomized International Study

While the lipido-sterolic extract of Serenoa repens (LSESr)-Permixon((R))-has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. Eight hundred and eleven men with symptomatic BPH (I-PSS> or =10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4mg/day (N=354) or Permixon 320mg/day (N=350). I-PSS, QoL and Q(max) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269). At 12 months, I-PSS decreased by 4.4in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Q(max) was similar in both treatment groups (1.8ml/s Permixon, 1.9ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.

The inhibition of nephrocalcinosis in an animal model with the lipido-sterolic extract of serenoa repens, Permixon®

The inhibition of nephrocalcinosis in an animal model with the lipido-sterolic extract of serenoa repens, Permixon®

Induction of apoptosis and inhibition of cell proliferation by the lipido-sterolic extract of Serenoa repens (LSESr, Permixon in benign prostatic hyperplasia.

To determine the mechanism by which prostate volume increases during the development of BPH and to evaluate the effect of LSESr (Permixon), a phytotherapeutic agent, we investigated apoptosis and cell proliferation in the stroma and epithelium of normal prostate and of BPH tissues from patients treated with or without LSESr. MIB-1 staining and the in situ end-labeling assay were used to evaluate the proliferative-apoptotic balance in normal prostates and in BPH tissues. Quantitative assessment was performed using an image analysis system. In normal prostates, there was no significant difference between apoptotic and proliferative indices. Cell numbers and proliferative indices were higher in BPH than in normal prostates, while apoptosis values were similar. In the BPH treated group, LSESr significantly inhibited proliferation and induced cell death in both epithelium and stroma. Induction of apoptosis and inhibition of cell proliferation are likely to be the basis for the clinical efficacy of LSESr.

Effect of the Lipidosterolic Extract of Serenoa repens (Permixon®) and Its Major Components on Basic Fibroblast Growth Factor-Induced Proliferation of Cultures of Human Prostate Biopsies

Objective: To assess the effect of the lipidosterolic extract of Serenoa repens (LSESr) on in vitro cell proliferation in biopsies of human prostate Material and Methods: Cell proliferation was assessed by incorporation of [³H]thymidine followed by historadiography. Results: Basic fibroblast growth factor (b-FGF) induced a considerable increase in human prostate cell proliferation (from +100 to +250%); the glandular epithelium was mainly affected, minimal labeling being recorded in the other regions of the prostate. Similar results were observed with epidermal growth factor (EGF), although the increase in cell proliferation was not recorded in some cases. Lovastatin, an inhibitor of hydroxymethylglutaryl coenzyme A, antagonized both the basal proliferation and the growth factor-stimulated proliferation of human prostate epithelium (EGF, mean inhibition ≈80–95%; b-FGF, mean inhibition ≈40–90%). Geraniol, a precursor of both farnesyl pyrophosphate and geranylgeranyl pyrophosphate, and farnesol, the precursor of farnesyl pyrophosphate, increased cell proliferation only in some prostate specimens, this effect being antagonized by lovastatin. LSESr did not affect basal prostate cell proliferation, with the exception of two prostate specimens in which a significant inhibition of basal proliferation was observed with the highest concentration of LSESr (30 µg/ml). In contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell cultures; this effect was significant for the highest concentration of LSESr (30 µg/ml). In some prostate samples, a similar inhibition was also noted with lower concentrations. Unsaturated fatty acids (UFA), in the range 1–30 ng/ml, did not affect the basal prostate cell proliferation, only a slight increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10 or 30µg/ml) markedly inhibited the b-FGF-induced cell proliferation down to the basal value. Lupenone, hexacosanol and the unsaponified fraction of LSESr markedly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect on basal cell proliferation was noted. Conclusions: Despite the large variability in the response of the prostate samples to b-FGF, these results indicate that LSESr and its components affect the proliferative response of prostate cells to b-FGF more than their basal proliferation.

Distribution study of radioactivity in rats after oral administration of the lipido/sterolic extract of Serenoa repens (Permixon) supplemented with [1-14C]-lauric acid, [1-14C]-oleic acid or [4-14C]-beta-sitosterol.

The study carried out on rats given orally the n-hexane lipido/sterolic extract of Serenoa repens (LSESR), supplemented with [14C]-labelled oleic or lauric acids or beta-sitosterol, demonstrated that radioactivity uptake in prostatic tissues shows the highest level in the case of administration of LSESR supplemented with [14C]-labelled oleic acid. This was clearly demonstrated on a rat with an induced fibro-muscular hyperplasia of the prostate and by quantitative measurements of radioactivity. Ratios of radioactivity in tissues compared to plasma show an uptake of radioactivity greater in prostate as compared to other genital organs, i.e. the seminal vesicles or to other organs such as liver.

Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia.

Serenoa repens (Permixon) has been available for several years for the treatment of men with benign prostatic hyperplasia (BPH). The drug is the n-hexane lipidosterolic extract of the dwarf American palm (also known as Serenoa repens) and is a complex mixture of various compounds. A number of pharmacodynamic effects have been demonstrated with the lipidosterolic extract of Serenoa repens (LSESR), suggesting multiple mechanisms of action including in vitro inhibition of both type 1 and type 2 isoenzymes of 5 alpha-reductase and interference with binding of dihydrotestosterone to cytosolic androgen receptors in prostate cells. In controlled clinical trials in men with BPH, oral administration of Serenoa repens 160 mg twice daily for 1 to 3 months was generally superior to placebo in improving subjective symptoms, such as dysuria, as well as objective parameters. The frequency of nocturia was reduced by 33 to 74%, while urinary frequency during the day decreased by 11 to 43% and peak urinary flow rate increased by 26 to 50% with Serenoa repens. Corresponding values for placebo were 13 to 39%, 1 to 29% and 2 to 35%. The only large comparative trial conducted to date, in which > 1000 men with moderate BPH were randomised to receive Serenoa repens 160 mg twice daily or finasteride 5 mg once daily for 6 months, demonstrated similar efficacy between the two drugs. No statistically significant difference was demonstrated between treatment groups for improvement in patient self-rated quality-of-life scores and the primary end-point of objective symptom score; International Prostate Symptom Score improved by 37% with Serenoa repens compared with 39% with finasteride. In much smaller comparative trials, few significant differences were demonstrated between Serenoa repens and alpha 1-receptor antagonists, and larger randomised trials of adequate duration are required to better compare the clinical efficacy of these drugs. The most frequently reported adverse events in clinical trials with Serenoa repens have been minor gastrointestinal problems (e.g. nausea and abdominal pain). In conclusion, Serenoa repens is well tolerated and has greater efficacy than placebo and similar efficacy to finasteride in improving symptoms in men with BPH. Although there is a need for further comparative studies, particularly with alpha 2-receptor antagonists, available data indicate that Serenoa repens is a useful alternative to alpha 1-receptor antagonists and finasteride in the treatment of men with BPH.

Effects of the lipidosterolic extract of Serenoa repens (Permixon) on human prostatic cell lines.

Permixon is a drug used in the treatment of benign prostatic hyperplasia. We studied its androgenic and antiandrogenic effects in the prostatic cell lines LNCaP and PC3, respectively responsive and unresponsive to androgen stimulation. We performed FACScan analysis to investigate toxicity, 3H thymidine and 35S methionine incorporation to determine antiproliferative and metabolic effects, electron microscopy to study ultrastructural changes and cotransfection experiments to elucidate the role of wild type androgen receptor. In LNCaP cell line, Permixon induced a double proliferative/differentiative effect, not observed in PC3 cells. In PC3 cells cotransfected with wild-type androgen receptors and CAT reporter genes under the control of a androgen responsive element, the drug inhibited androgen-induced CAT transcription. Our data indicate a role of the androgen receptor in mediating the effects of Permixon in LNCaP cells. Cotransfection experiments in PC3 cells support a clear antiandrogenic action of the drug.

EFFECT OFSERENOA REPENSEXTRACT (PERMIXONR) ON ESTRADIOL/TESTOSTERONE-INDUCED EXPERIMENTAL PROSTATE ENLARGEMENT IN THE RAT

The effect of the lipidosterolic extract ofSerenoa repens(LSESR) on experimental prostate enlargement was investigated in three groups of rats: shams treated with LSESR (sham rats), castrated animals treated with estradiol and testosterone (castrated rats), castrated animals treated with estradiol/testosterone and treated with LSESR (castrated and treated rats). Following three months of continuous hormonal treatment, the weight of prostates in estradiol/testosterone-treated castrated rats was significantly increased in comparison with sham-operated rats. Such an increase started rapidly, reached a maximum by 30 days and remained at a plateau or slightly declined thereafter. The increase of prostate total weight induced by the hormone treatment was inhibited by administration of LSESR. Indeed, the weight was significantly lower at day 60 and day 90 for the dorsal and lateral regions of the prostate. The weight of the ventral region of the prostate was significantly lower after 30 and 60 days treatment with LSESR. These results demonstrate that administering LSESR to hormone-treated castrated rats inhibits the increase in prostate wet weight. This effect of LSESR may explain the beneficial effect of this extract in human benign prostatic hypertrophy.

Permixon ® [lipido sterolic extract of serenoa repens (LSESr)] inhibits b-FGF- and EGF-induced proliferation of human prostate organotypic cell lines

Permixon ® [lipido sterolic extract of serenoa repens (LSESr)] inhibits b-FGF- and EGF-induced proliferation of human prostate organotypic cell lines