Saw palmetto extracts potently and noncompetitively inhibit human alpha1-adrenoceptors in vitro

BACKGROUND: We wanted to test whether phytotherapeutic agents used in the treatment of lower urinary tract symptoms have alpha1-adrenoceptor antagonistic properties in vitro. METHODS: Preparations of beta-sitosterol and extracts of stinging nettle, medicinal pumpkin, and saw palmetto were obtained from several pharmaceutical companies. They were tested for their ability to inhibit [3H]tamsulosin binding to human prostatic alpha1-adrenoceptors and [3H]prazosin binding to cloned human alpha1A- and alpha1B-adrenoceptors. Inhibition of phenylephrine-stimulated [3H]inositol phosphate formation by cloned receptors was also investigated. RESULTS: Up to the highest concentration which could be tested, preparations of beta-sitosterol, stinging nettle, and medicinal pumpkin were without consistent inhibitory effect in all assays. In contrast, all tested saw palmetto extracts inhibited radioligand binding to human alpha1-adrenoceptors and agonist-induced [3H]inositol phosphate formation. Saturation binding experiments in the presence of a single saw palmetto extract concentration indicated a noncompetitive antagonism. The relationship between active concentrations in vitro and recommended therapeutic doses for the saw palmetto extracts was slightly lower than that for several chemically defined alpha1-adrenoceptor antagonists. CONCLUSIONS: Saw palmetto extracts have alpha1-adrenoceptor-inhibitory properties. If bioavailability and other pharmacokinetic properties of these ingredients are similar to those of the chemically defined alpha1-adrenoceptor antagonists, alpha1-adrenoceptor antagonism might be involved in the therapeutic effects of these extracts in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.     

Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia

PURPOSE: We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial. MATERIALS AND METHODS: We randomized 44 men 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies. RESULTS: Saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25. 2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). The mechanism of action appeared to be nonhormonal but it was not identified by tissue studies of apoptosis, cellular proliferation, angiogenesis, growth factors or androgen receptor expression. We noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. CONCLUSIONS: Saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. The secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo (not statistically significant). However, saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies.     

Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms

Objectives. To assess the effects of saw palmetto on urinary symptoms, sexual function, and urinary flow rate in men with lower urinary tract symptoms using a double-blind, randomized, placebo-controlled trial.Methods. The eligible patients were 45 years of age or older and had an International Prostate Symptom Score of 8 or greater. After a 1-month placebo run-in period, 85 men were randomized to receive saw palmetto or placebo for 6 months. Patients were evaluated using the International Prostate Symptom Score, a sexual function questionnaire, and by measurement of the urinary flow rate.Results. The mean symptom score decreased from 16.7 to 12.3 in the saw palmetto group compared with 15.8 to 13.6 in the placebo group (P = 0.038). The quality-of-life score improved to a greater degree in the saw palmetto group, but this difference was not statistically significant. No change occurred in the sexual function questionnaire results in either group. The peak flow rate increased by 1.0 mL/s and 1.4 mL/s in the saw palmetto and placebo groups, respectively (P = 0.73).Conclusions. Saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo. Saw palmetto had no measurable effect on the urinary flow rates. The mechanism by which saw palmetto improves urinary symptoms remains unknown.     

Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?

BACKGROUND: To test whether saw palmetto extracts, which act as alpha1-adrenoceptor antagonists in vitro, also do so in vivo in man. METHODS: In a placebo-controlled, double-blind, four-way cross-over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human alpha1-adrenoceptor subtypes. RESULTS: Saw palmetto extract treatment did not result in alpha1-adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. CONCLUSIONS: Despite their alpha1-adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause alpha1-adrenoceptor antagonism in man in vivo.     

沙芭特在非细菌性前列腺炎症中的抗炎、抗纤维化及促进上皮细胞凋亡作用的研究

目的 探讨锯叶棕果实提取物沙芭特在非细菌性前列腺炎中的效应及其机制.方法 前列腺上皮细胞RWPE-1经M1表型的单核巨噬细胞THP-1细胞上清液共培养,治疗组加用沙芭特(10μg/ml)培养,MTS检测细胞增殖,流式细胞术检测细胞凋亡,RT-PCR、ELISA及West-ern blot检测炎症、纤维化及凋亡相关的蛋白分子(IL-1β、IL-17、TNF-α、Fas、COX2、Bax、TGF-β、DDR1、α-SMA及CollagenⅠ)的表达.消痔灵前列腺注射诱导大鼠非细菌性前列腺炎模型,用von Frey纤维检测沙芭特治疗前后各组大鼠的痛觉敏感性,然后麻醉SD大鼠,腔静脉取血后摘取前列腺组织并称重,免疫组化及ELISA检测炎症因子的表达,masson染色检测纤维化.结果 沙芭特抑制RWPE-1的增殖并促进其凋亡.M1表型THP-1条件培养液能促进上皮细胞表达IL-1β、TNF-α及COX-2,沙芭特处理能抑制炎症刺激所致的炎症因子表达,Western blot检测表明沙芭特处理能抑制COX-2、DDR1、SMA及CollagenⅠ的表达,增加Fas及Cleaved-caspase 3的表达.消痔灵100μl每侧叶注射可以成功诱导前列腺炎症模型,沙芭特60mg/kg能减少大鼠前列腺组织炎症因子的表达,缩小前列腺体积,降低大鼠痛觉敏感性.结论 沙芭特能抑制前列腺上皮细胞RWPE-1的增殖并促进其凋亡,减小前列腺体积,抑制炎症因子及纤维化相关分子的表达,减轻前列腺炎症及纤维化从而起到治疗作用.     

锯叶棕果实提取物治疗BPH引起的下尿路症状疗效观察

目的:探讨锯叶棕果实提取物治疗BPH引起的下尿路症状的疗效。方法:采用锯叶棕果实提取物单药治疗30例前列腺增生伴下尿路症状患者8周,分别比较患者治疗前后的最大尿流率、前列腺体积、剩余尿量、IPSS评分及QOL评分的变化情况。结果:治疗8周后,患者的最大尿流率、剩余尿量、IPSS评分及QOL评分均有明显改善,前列腺体积则无明显变化。所有患者均无明显不良反应。结论:锯叶棕果实提取物能有效改善BPH患者的下尿路症状。     

Saw Palmetto (Serenoa repens) in Men with Lower Urinary Tract Symptoms: Effects on Urodynamic Parameters and Voiding Symptoms

Objectives. To assess the effects of saw palmetto on voiding symptoms and urodynamic parameters in men with lower urinary tract symptoms (LUTS) presumed secondary to benign prostatic hyperplasia (BPH).Methods. Fifty men with previously untreated LUTS and a minimum International Prostate Symptom Score (IPSS) of 10 or greater were treated with a commercially available form of saw palmetto (160 mg twice per day) for 6 months. The initial evaluation included measurement of peak urinary flow rate, postvoid residual urine volume, pressure-flow study, and serum prostate-specific antigen (PSA) level. Patients completed an IPSS, serum PSA was determined, and flow rate was measured every 2 months during the course of the study. A urodynamic evaluation was repeated at the completion of the 6-month trial.Results. The mean IPSS (±SD) improved from 19.5 ± 5.5 to 12.5 ± 7.0 (P <0.001) among the 46 men who completed the study. Significant improvement in the symptom score was noted after treatment with saw palmetto for 2 months. An improvement in symptom score of 50% or greater after treatment with saw palmetto for 2, 4, and 6 months was noted in 21% (10 of 48), 30% (14 of 47), and 46% (21 of 46) of patients, respectively. There was no significant change in peak urinary flow rate, postvoid residual urine volume, or detrusor pressure at peak flow among patients completing the study. No significant change in mean serum PSA level was noted.Conclusions. Saw palmetto is a well-tolerated agent that may significantly improve lower urinary tract symptoms in men with BPH. However, we were unable to demonstrate any significant improvement in objective measures of bladder outlet obstruction. Placebo-controlled trials of saw palmetto are needed to evaluate the true effectiveness of this compound.     

What do I tell patients about saw palmetto for benign prostatic hyperplasia?

Saw palmetto is widely used to treat lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Although there is passionate support for herbal and complementary therapies for LUTS, clinical evidence is mixed. Because there is a well-recognized, profound placebo effect in tests of efficacy for agents treating LUTS, it is imperative that all therapies be tested in placebo-controlled trials. This article reviews evidence of the efficacy and safety of saw palmetto for men with LUTS caused by BPH, with particular emphasis on published randomized clinical trials and the upcoming Complementary and Alternative Medicine for Urologic Symptoms (CAMUS) trial.     

Knowledge and prevalence of use of saw palmetto and other herbal products among men with prostate disease in Trinidad and Tobago

Objective

To investigate the knowledge and prevalence of use of saw palmetto and other herbal products among men attending the urology outpatient clinic at San Fernando General Hospital.

Saw palmetto and lower urinary tract symptoms: What is the latest evidence?

The use of dietary supplements for treating a wide range of health conditions has grown rapidly in the United States. In the field of men’s health, the most common dietary supplement used is an extract of the berry of the saw palmetto plant, with which men commonly selfmedicate in order to treat lower urinary tract symptoms. Throughout the past two decades, substantial literature has emerged examining the biologic and clinical effects of saw palmetto extracts. Several lines of evidence suggest that saw palmetto may exert physiologic effects consistent with a beneficial clinical effect on the mechanisms of benign prostatic hyperplasia. Although most clinical studies tend to suggest a modest efficacy benefit of saw palmetto, more recent studies are less consistent and the precise clinical value of saw palmetto for treating lower urinary tract symptoms remains undefined. Overall, there appear to be few safety concerns with short-term use of this herbal medicine, although large-scale and longer-term safety studies have not been performed. Higher-quality studies are currently underway to better define the potential benefits and risks of plant-based extracts for treating symptoms related to benign prostatic hyperplasia.     

Synergistic effect of vitamin E and selenium in human prostate cancer cell lines

Vitamin E and selenium are the two most popular dietary supplements used to prevent prostate cancer. The hypothesis that these antioxidants reduce prostate risk is being tested in the selenium and vitamin E chemoprevention trial (SELECT). We hypothesize that selenium potentiates vitamin E-induced inhibition of prostate cancer cell growth in vitro. Prostate cancer cell populations growing asynchronously were treated with a combination of vitamin E and selenium and processed for flow cytometric analysis. Prostate cancer cells treated with a combination of the antioxidants revealed that selenium potentiates vitamin E-induced inhibition of LNCaP cells in vitro. This was demonstrated by a reduction in the percentage of cells in the S phase. This crucial finding confirms our previous observations that antioxidant molecules act via distinct mechanistic pathways. These independent biological effects can be exploited in order to augment the anticancer properties of individual agents. These data also validate the two factorial design of the SELECT trial, permitting pairwise comparisons between agents in combination and alone.     

Dietary habits and nutritional status of renal transplant patients.

BACKGROUND: Although dialysis nutritional problems are well described, nutritional problems after renal transplantation (RT) have received little attention. METHODS: Body composition as assessed by dual-energy x-ray absorptiometry in 115 stable patients 6.6 +/- 5.9 years after RT and repeated 2.9 years later, when a 3-day dietary history was obtained in 79 patients. RESULTS: Patients diet was generally sufficient, but was characterized by a high fat intake and deficiencies in folic acid, vitamin D, thiamine, iodine, selenium, and iron intake. Patients were often overweight, and at any given weight had a 4% to 5% higher proportion of body fat than normal. Loss of fat weight was related to high initial fat weight, long RT duration, and low plasma bicarbonate, but not steroid dose. CONCLUSION: Dietary advice concerning fat intake is indicated for RT patients, and nutritional supplements with folic acid and vitamin D are generally required. Their main nutritional problem is obesity. This is not adequately measured by body mass index, which should be supplemented by dual-energy x-ray absorptiometry. Attention should be paid to the prevention of acidosis.     

Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial

BACKGROUND: Increased dietary vitamin E intake is associated with a reduced incidence of asthma, and combinations of antioxidant supplements including vitamin E are effective in reducing ozone induced bronchoconstriction. A study was undertaken to investigate the effect of supplementation with vitamin E for 6 weeks on bronchial hyperresponsiveness in atopic adults with asthma. METHODS: 72 participants from a clinical trial register of adults with asthma were randomised to receive 500 mg natural vitamin E or matched placebo for 6 weeks in a placebo controlled, double blind parallel group clinical trial. Inclusion criteria included age 18-60 years, maintenance treatment of at least one dose of inhaled corticosteroid per day, a positive skin prick test to one of three common allergens, and bronchial hyperresponsiveness to methacholine (defined as a dose provoking a 20% fall in forced expiratory volume in 1 second (FEV(1)) (PD(20)) of 12.25 micromol). Secondary outcomes were FEV(1), forced vital capacity, mean morning and evening peak flow, symptom scores, bronchodilator use, and serum immunoglobulin E levels. RESULTS: In the primary intention to treat analysis the change in PD(20) was similar in the vitamin E and placebo groups with a mean difference of +0.25 doubling doses of methacholine (95% confidence interval -0.67 to +1.16 greater with vitamin E). There was no effect of vitamin E supplementation on any other measure of asthma control, either in the intention to treat or per protocol analysis. There was also no effect of vitamin E supplementation on serum immunoglobulin levels. CONCLUSION: Dietary supplementation with vitamin E adds no benefit to current standard treatment in adults with mild to moderate asthma.     

Symptomatic Vitamin A Deficiency following Biliopancreatic Diversion

Background: Biliopancreatic diversion (BPD) is an effective operation for morbid obesity. Fat-soluble vitamin deficiencies are known complications of this procedure, with incidence rates reported as high as 6%. Case Report: A-36-year old morbidly obese female with BMI 60.6 kg/m² underwent laparoscopic adjustable gastric banding, followed 2 years later by BPD in an attempt to control her weight. Following BPD, she failed to attend outpatient appointments and was poorly compliant with daily multivitamins and monitoring of serum vitamin and mineral levels. She developed symptomatic vitamin A deficiency, with vitamin A levels <0.1 umol/L, and night blindness, as well as deficiencies of vitamins D, E and K, zinc and selenium. Her vitamin deficiencies were corrected with appropriate supplements and her night blindness resolved. Discussion: This case raises the issues of preoperative screening of patients and compliance, as well as life-long postoperative monitoring of serum vitamin and mineral levels. With better compliance with outpatient appointments, prescribed multivitamins and oral vitamin A tablets, as well as regular monitoring of serum vitamin and mineral levels, vitamin deficiencies and their consequences, such as night blindness, may be avoided.     

Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men

Numerous studies have reported beneficial effects of antioxidant drugs on semen quality, but there is no well-defined therapeutical protocol in male infertility. This study aimed to test the effects of vitamin E and selenium supplementation on lipid peroxidation and on sperm parameters. The study included 54 voluntary and infertile men who produced semen samples for spermiogram and for spectrophotometric measurement of a lipid peroxidation marker, the malondialdehyde (MDA), and produced blood samples for high-performance liquid chromatography assessment of serum vitamin E level. The trial was randomized and open. Twenty-eight men were supplemented daily by vitamin E (400 mg) and selenium (225 microg), during 3 months. The remaining 26 patients received vitamin B (4,5 g/day) for the same duration. Only 20 patients achieved their treatment and returned for control analysis. MDA concentrations in sperm were much less than in seminal plasma and motility and viability were inversely correlated with semen MDA levels. In contrast to vitamin B supplementation, vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility. The results confirm the protective and beneficial effects of vitamin E and selenium on semen quality and advocate their use in male infertility treatment.     

Role of vitamins, minerals and supplements in the prevention and management of prostate cancer

The authors review the current literature on the complementary and alternative medicines most frequently utilized by prostate cancer patients and those at risk for the disease. Products covered are vitamin E, vitamin A, selenium, zinc, soy, lycopene, pomegranate juice, green tea and omega-3 fatty acids. There is no definitive proof that any of the nutritional supplements discussed can impact the course of prostate cancer or its development. The authors believe that simply taking a standard daily multivitamin should be sufficient to ensure that patients have the appropriate levels of vitamins and minerals without risking the over utilization of vitamins, minerals, and supplements which can lead to numerous negative side effects.     

The effect of adding PTH(1–84) to conventional treatment of hypoparathyroidism: A randomized,placebo‐controlled study

In hypoparathyroidism, plasma parathyroid hormone (PTH) levels are inadequate to maintain plasma calcium concentration within the reference range. On conventional treatment with calcium supplements and active vitamin D analogues, bone turnover is abnormally low, and BMD is markedly increased. We aimed to study the effects of PTH‐replacement therapy (PTH‐RT) on calcium‐phosphate homeostasis and BMD. In a double‐blind design, we randomized 62 patients with hypoparathyroidism to daily treatment with PTH(1–84) 100 µg or similar placebo for 24 weeks as add‐on therapy to conventional treatment. Compared with placebo, patients on PTH(1–84) reduced their daily dose of calcium and active vitamin D significantly by 75% and 73%, respectively, without developing hypocalcemia. However, hypercalcemia occurred frequently during the downtitration of calcium and active vitamin D. Plasma phosphate and renal calcium and phosphate excretion did not change. Compared with placebo, PTH(1–84) treatment significantly increased plasma levels of bone‐specific alkaline phosphatase (+226% ± 36%), osteocalcin (+807% ± 186%), N‐terminal propeptide of procollagen 1 (P1NP; +1315% ± 330%), cross‐linked C‐telopeptide of type 1 collagen (CTX; +1209% ± 459%), and urinary cross‐linked N‐telopeptide of type 1 collagen (NTX; (+830% ± 165%), whereas BMD decreased at the hip (?1.59% ± 0.57%), lumbar spine (?1.76% ± 1.03%), and whole body (?1.26% ± 0.49%) but not at the forearm. In conclusion, the need for calcium and active vitamin D is reduced significantly during PTH‐RT, whereas plasma calcium and phosphate levels are maintained within the physiologic range. In contrast to the effect of PTH(1–84) treatment in patients with osteoporosis, PTH‐RT in hypoparathyroidism causes a decrease in BMD. This is most likely due to the marked increased bone turnover. Accordingly, PTH‐RT counteracts the state of overmineralized bone and, during long‐term treatment, may cause a more physiologic bone metabolism. © 2011 American Society for Bone and Mineral Research     

Protective effect on vitamin D2 on bone apposition from the inhibitory action of hydrocortisone in rats

Using the technique of short interval sequential tetracycline labeling, it was documented that the apposition of mineralized bone matrix in adult male Sprague-Dawley rats was inhibited by hydrocortisone. The inhibition occurred as early as six days after the onset of the treatment and was dose dependent over a dose range of 0.62 to 20 mg per kg body weight per day. Vitamin D2 supplements by injection protected bone from this hydrocortisone action. 64 I. U. of vitamin D2 injected daily was able to prevent the inhibition of bone apposition by 20 mg per kg body weight per day of hydrocortisone. The results imply that vitamin D or its metabolites may compete with hydrocortisone in some cellular mechanisms and support the usefulness of vitamin D supplements in the treatment and the prevention of steroid-induced osteoporosis.