Effects of a prebiotic formulation on the composition of the faecal microbiota of people with functional constipation.

PURPOSE: Prebiotics are defined as substances which selectively promote beneficial gut microbes leading to a health benefit for the host. Limited trials have been carried out investigating their effect on the microbiota composition of individuals afflicted by functional constipation with equivocal outcomes. In a 21-day randomised, controlled clinical trial involving 61 adults with functional constipation, a prebiotic formulation with partially hydrolysed guar gum and acacia gum as its main ingredients, significantly increased complete spontaneous bowel motions in the treatment group. This follow-up exploratory analysis investigated whether the prebiotic was associated with changes to the composition, richness, and diversity of the faecal microbiota. METHODS: Participants provided a faecal specimen at baseline and on day 21 of the intervention period. Whole genome metagenomic shotgun sequencing comprehensively assessed taxonomic and functional composition of the microbiota. RESULTS: Linear mixed effects regression models adjusted for potential confounders showed a significant reduction in species richness of 28.15 species (95% CI - 49.86, - 6.43) and Shannon diversity of 0.29 units (95% CI - 0.56, - 0.02) over the trial period in the prebiotic group. These changes were not observed in the control group, and functional composition was unchanged in both groups. CONCLUSION: In adults with functional constipation, the intake of a prebiotic formulation was associated with a decline of species richness and Shannon diversity. Further research regarding the associations between prebiotics and the composition and function of the gut microbiota is warranted.

Functional constipation and the effect of prebiotics on the gut microbiota: a review.

Functional constipation is a significant health issue impacting the lives of an estimated 14 % of the global population. Non-pharmaceutical treatment advice for cases with no underlying medical conditions focuses on exercise, hydration and an increase in dietary fibre intake. An alteration in the composition of the gut microbiota is thought to play a role in constipation. Prebiotics are non-digestible food ingredients that selectively stimulate the growth of a limited number of bacteria in the colon with a benefit for host health. Various types of dietary fibre, though not all, can act as a prebiotic. Short-chain fatty acids produced by these microbes play a critical role as signalling molecules in a range of metabolic and physiological processes including laxation, although details are unclear. Prebiotics have a history of safe use in the food industry spanning several decades and are increasingly used as supplements to alleviate constipation. Most scientific research on the effects of prebiotics and gut microbiota has focussed on inflammatory bowel disease rather than functional constipation. Very few clinical studies evaluated the efficacy of prebiotics in the management of constipation and their effect on the microbiota, with highly variable designs and conflicting results. Despite this, broad health claims are made by manufacturers of prebiotic supplements. This narrative review provides an overview of the literature on the interaction of prebiotics with the gut microbiota and their potential clinical role in the alleviation of functional constipation.

A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain.

BACKGROUND: Peripheral neuropathy is a common complication of diabetes. The management of the associated neuropathic pain remains difficult to treat. OBJECTIVE: This study explored the safety, tolerability and efficacy of a palmitoylethanolamide (PEA) formulation in treating diabetic-related peripheral neuropathic pain (PNP). Secondary outcomes included systemic inflammation, sleep and mood changes in patients diagnosed with type 1 and type 2 diabetes and PNP. DESIGN: This study was a single-centre, quadruple-blinded, placebo-controlled trial with 70 participants receiving 600 mg of PEA or placebo daily, for 8 weeks, with a 94% rate of study participation completion. Primary outcomes were neuropathic pain and specific pain types (the BPI-DPN and NPSI). The secondary outcomes were sleep quality (MOS sleep scale), mood (DASS-21), glucose metabolism and inflammation. RESULTS: There was a significant reduction (P ≤ 0.001) in BPI-DPN total pain and pain interference, NPSI total score and sub-scores, except for evoked pain (P = 0.09) in the PEA group compared with the placebo group. The MOS sleep problem index and sub-scores significantly improved (P ≤ 0.001). DASS-21 depression scores significantly reduced (P = 0.03), but not anxiety or stress scores. Interleukin-6 and elevated C-reactive protein levels significantly reduced in the PEA group (P = 0.05), with no differences in fibrinogen between groups (P = 0.78) at treatment completion. There were no changes in safety pathology parameters, and the treatment was well tolerated. CONCLUSIONS: The study demonstrated that the PEA formulation reduced diabetic peripheral neuropathic pain and inflammation along with improving mood and sleep. Further studies on the mechanistic effectiveness of PEA as an adjunct medicine and as a monotherapy pain analgesic are warranted. CLINICAL TRIAL REGISTRATION: Registry name: Australian New Zealand Clinical Trials Registry (ANZCTR), Registration number: ACTRN12620001302943, Registration link: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380826 , Actual study start date: 20 November 2020.

A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis.

BACKGROUND: The aim of the study was to assess the safety, tolerability and efficacy of palmitoylethanolamide (PEA) when dosed at 300 mg and 600 mg per day on symptoms of knee osteoarthritis. METHODS: This was a single site, comparative, double-blind placebo controlled study in adults with mild to moderate knee osteoarthritis with 111 participants randomized to receive 300 mg PEA, 600 mg PEA or placebo each day, in divided doses b.i.d, for 8 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The secondary outcomes were the Numerical Rating Scales (NRS) for pain, the Depression Anxiety Stress Scale (DASS), the Perceived Stress Scale (PSS), the Pittsburg Sleep Quality Index (PSQI), the Short Form Health Survey (SF-36), the use of rescue pain medication and clinical safety assessment. RESULTS: There was a significant reduction in the total WOMAC score in the 300 mg PEA (p = 0.0372) and the 600 mg PEA (p = 0.0012) groups, the WOMAC pain score (300 mg PEA, p = 0.0074; 600 mg PEA, p = < 0.001), the WOMAC stiffness score (PEA 300 mg, p < 0.0490; 600 mg PEA, p = 0.001) and in the WOMAC function score in the 600 mg PEA group (p = 0.033) compared to placebo. The NRS pain evaluations for "worst pain" and "least pain" were significantly reduced in the 300 mg PEA group (p < 0.001, p = 0.005) and the 600 mg PEA group (p < 0.001, p < 0.001) compared to placebo. There was a significant reduction in anxiety (DASS) in both active treatment groups (300 mg PEA, p = 0.042; 600 mg PEA group (p = 0.043) compared to placebo. There were no changes in the clinical markers and the product was well tolerated. CONCLUSIONS: The study demonstrated that palmitoylethanolamide may be a novel treatment for attenuating pain and reducing other associated symptoms of knee osteoarthritis. Further studies on the pharmacological basis of this anti-inflammatory effect are now required.

Aromatherapy for treatment of postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common, unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been suggested as an addition to the available treatment strategies. This review was originally published in 2012 and updated in 2017. OBJECTIVES: The main objective was to establish the efficacy and safety of aromatherapy comparable to standard pharmacological treatments for PONV in adults and children. SEARCH METHODS: We searched CENTRAL; MEDLINE; Embase; CINAHL; CAM on PubMed; Informit; LILACS; and ISI Web of Science as well as grey literature sources and the reference lists of retrieved articles up to March 2017. The original search was performed in August 2011. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) where aromatherapy was used to treat PONV. Interventions were all types of aromatherapy compared to placebo or with standard antiemetics. Primary outcomes were severity and duration of PONV. Secondary outcomes were adverse reactions, use of rescue antiemetics and patient satisfaction. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias in the included studies and extracted data. For dichotomous outcome variables, we used a random-effects model and calculated risk ratio (RR) with associated 95% confidence interval (95% CI). For continuous outcome variables, we used a random-effects model and calculated standardized mean difference (SMD) with associated 95% CI. We used the GRADE software to compile 'Summary of findings' tables. MAIN RESULTS: We included seven new studies with 663 participants in the 2017 update; five RCTs and two CCTs. These were added to the nine previously included studies (six RCTs and three CCTs with a total of 373 participants) for a total of 16 included studies and 1036 participants in this updated review. The mean age and range data for all participants were not reported for all studies. We identified two registered trials that met the inclusion criteria for this review; however there are no results for these studies yet.Overall, the GRADE assessment of evidence quality ranged from moderate to very low. The method of randomization in 11 of the 12 included RCTs was explicitly stated and adequate. Incomplete or methodologically diverse reporting of data affected the completeness of the analysis. Data on additional aromatherapies were added in the 2017 update (blended aromatherapy products, and peppermint products). Heterogeneity of outcome measures and time points between studies affected the completeness of the analysis.In the summary of the findings of six studies, we did not find aromatherapy to be effective in reducing nausea severity in comparison to placebo (SMD -0.22, 95% CI -0.63 to 0.18, P value = 0.28, 241 participants, level of evidence: low). Those participants receiving aromatherapy were no more likely to be free of nausea at the end of the treatment period than those receiving placebo (RR 3.25, 95% CI 0.31 to 34.33, P value = 0.33, 4 trials, 193 participants, evidence level: very low), however they were less likely to require rescue antiemetics (RR 0.60, 95% CI 0.37 to 0.97, P value = 0.04, 7 trials, 609 participants, evidence level: low). There were no data reported on adverse events or patient satisfaction for this comparison.A specific comparison of peppermint aromatherapy to placebo did not show evidence of an effect on nausea severity at five minutes post-treatment in the pooled results (SMD -0.18, 95% CI -0.86 to 0.49, P value = 0.59, 4 trials, 115 participants, evidence level: low). There were no data reported on nausea duration, use of rescue antiemetics, adverse events or patient satisfaction for this comparison.When we pooled studies comparing isopropyl alcohol to standard antiemetic treatment in a GRADE summary of findings, in terms of nausea duration, there was a significant effect on the time in minutes to a 50% reduction in nausea scores (SMD -1.10, 95% CI -1.43 to -0.78, P value < 0.00001, 3 trials, 176 participants, evidence level: moderate). Fewer participants who received isopropyl alcohol required rescue antiemetics (RR 0.67, 95% CI 0.46 to 0.98, P value = 0.04, 215 participants, 4 trials, evidence level: moderate). Two studies with 172 participants measured patient satisfaction; there were high levels of satisfaction across both aromatherapy and standard treatment groups and no differences found (evidence level: low). There were no data reported on nausea severity or adverse events for this comparison.There was no difference in effectiveness between isopropyl alcohol vapour inhalation and placebo for reducing the proportion of participants requiring rescue antiemetics (RR 0.39, 95% CI 0.12 to 1.24, P value = 0.11, 291 participants, 4 trials, evidence level: very low). There were no data reported on nausea severity, nausea duration, adverse events or patient satisfaction for this comparison. AUTHORS' CONCLUSIONS: Overall, for nausea severity at the end of treatment, aromatherapy may have similar effectiveness to placebo and similar numbers of participants were nausea-free. However, this finding is based on low-quality evidence and therefore very uncertain. Low-quality evidence also suggests that participants who received aromatherapy may need fewer antiemetic medications, but again, this is uncertain. Participants receiving either aromatherapy or antiemetic medications may report similar levels of satisfaction with their treatment, according to low-quality evidence.

Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study.

This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.

Influence of a Specialized Trigonella foenum-graecum Seed Extract (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy Menstruating Women, a Randomised Placebo Controlled Study.

The aim of the study was to evaluate the effect of Trigonella foenum-graecum (fenugreek) seed extract on sex hormones and sexual function in healthy menstruating women who reported low sexual drive. This short term, single site, double blind, randomised, placebo-controlled study was conducted on 80 women, aged 20 to 49 years. Participants were randomised to either an oral dose of a standardised T. foenum-graecum seed extract (libifem) at a dose of 600 mg/day or placebo over two menstrual cycles. Dehydroepiandrosterone sulfate, progesterone, androstenedione, total and free testosterone, estradiol (E2), luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and cholesterol were measured at baseline and 8 weeks. The individual aspects of sexual function were measured using the Derogatis interview for sexual functioning and female sexual function index self-administered questionnaires. Stress, fatigue and quality of the relationship with partner were also measured using the PSS (Perceived Stress Scale), MFI-20 (Multidimensional Fatigue Inventory) and DAS (Dyadic Adjustment Scale) quality of life measures, respectively. There was a significant increase in free testosterone and E2 in the active group as well as sexual desire and arousal compared with the placebo group. The results indicate that this extract of T. foenum-graecum may be a useful treatment for increasing sexual arousal and desire in women.

Aromatherapy for treatment of postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting is a common and unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been suggested as a possible addition to the available treatment strategies. OBJECTIVES: This review sought to establish what effect the use of aromatherapy has on the severity and duration of established postoperative nausea and vomiting and whether aromatherapy can be used with safety and clinical effectiveness comparable to standard pharmacological treatments. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3); MEDLINE; EMBASE; CINAHL; CAM on PubMed; Meditext; LILACS; and ISI Web of Science as well as grey literature sources and the reference lists of retrieved articles. We conducted database searches up to August 2011. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) where aromatherapy was used to treat postoperative nausea and vomiting. Interventions were all types of aromatherapy. Aromatherapy was defined as the inhalation of the vapours of any substance for the purposes of a therapeutic benefit. Primary outcomes were the severity and duration of postoperative nausea and vomiting. Secondary outcomes were adverse reactions, use of rescue anti-emetics and patient satisfaction with treatment. DATA COLLECTION AND ANALYSIS: Two review authors assessed risk of bias in the included studies and extracted data. As all outcomes analysed were dichotomous, we used a fixed-effect model and calculated relative risk (RR) with associated 95% confidence interval (95% CI). MAIN RESULTS: The nine included studies comprised six RCTs and three CCTs with a total of 402 participants. The mean age and range data for all participants were not reported for all studies. The method of randomization in four of the six included RCTs was explicitly stated and was adequate. Incomplete reporting of data affected the completeness of the analysis. Compared with placebo, isopropyl alcohol vapour inhalation was effective in reducing the proportion of participants requiring rescue anti-emetics (RR 0.30, 95% CI 0.09 to 1.00, P = 0.05). However, compared with standard anti-emetic treatment, isopropyl alcohol was not effective in reducing the proportion of participants requiring rescue anti-emetics (RR 0.66, 95% CI 0.39 to 1.13, P = 0.13) except when the data from a possibly confounded study were included (RR 0.66, 95% CI 0.45 to 0.98, P = 0.04). Where studies reported data on patient satisfaction with aromatherapy, there were no statistically significant differences between the groups (RR 1.12, 95% CI 0.62 to 2.03, P = 0.71). AUTHORS' CONCLUSIONS: Isopropyl alcohol was more effective than saline placebo for reducing postoperative nausea and vomiting but less effective than standard anti-emetic drugs. There is currently no reliable evidence for the use of peppermint oil.

An Exploratory Study of the Safety and Efficacy of a Trigonella foenum-graecum Seed Extract in Early Glucose Dysregulation: A Double-Blind Randomized Placebo-Controlled Trial.

Background: This was an exploratory study to assess the safety and efficacy of a specialized Trigonella foenum-graceum L. seed extract for supporting healthy blood glucose metabolism in a pre-diabetic cohort. Methods: Fifty-four participants were randomised to receive 500 mg/day of T. foenum-graecum seed extract or matching placebo daily for 12 weeks. Fasting blood glucose (FBG), post-prandial glucose (PPBG), HbA1c, fasting insulin (FI), post-prandial insulin (PPI) and C-peptide were assessed at baseline, week 6 and week 12. Lipid levels, liver enzymes and C-reactive protein (CRP), along with safety markers and tolerability were also assessed at baseline and week 12. Results: By week 12 there was a significant difference in FBG (p < 0.001), PPBG (p = 0.007) and triglycerides (p = 0.030) between treatment groups, with no changes in HbA1c (p = 0.41), FI (p = 0.12), PPI (p = 0.50) or C-peptide (p = 0.80). There was no difference in total cholesterol (p = 0.99), high-density lipoprotein (p = 0.35), low density lipoprotein (p = 0.60) or CRP (p = 0.79). There was no change in safety markers and the treatment was well tolerated. Conclusions: The results of the study indicated that T. foenum-graecum seed extract may influence blood glucose metabolism and larger studies are warranted to evaluate efficacy and potential mechanisms of action.

Physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and mineral formulation.

The aim of the clinical study was to evaluate the effect of Testofen, a standardized Trigonella foenum-graecum (Fenugreek) extract and mineral formulation, on male libido (sexual drive, urge or desire) in a double blind randomized placebo controlled study. The study recruited 60 healthy males aged between 25 and 52, without erectile dysfunction and randomized to an oral dose (two tablets per day) of the active treatment (600 mg Testofen per day) or placebo for 6 weeks. The primary outcome measure was the DISF-SR (male) self-administered QOL total score and the four domain scores. The secondary outcome was specific quality of life parameters. Testofen had an overall positive effect on physiological aspects of libido. In particular, there was a significant increase in the subdomains of sexual arousal and orgasm. Testofen had a positive effect on QOL in self-reported satisfaction with muscle strength, energy and well-being but did not have an effect on mood or sleep. Serum prolactin and testosterone levels remained within the reference range. It was concluded that Testofen demonstrated a significant positive effect on physiological aspects of libido and may assist to maintain normal healthy testosterone levels.

A Double-Blind Randomized Placebo-Controlled Study Assessing the Safety, Tolerability and Efficacy of a Herbal Medicine Containing Pycnogenol Combined with Papain and Aloe vera in the Prevention and Management of Pre-Diabetes.

Background: Herbal medicines present attractive options to patients with chronic diseases. Undertaking clinical studies with patients presenting with symptomless pre-T2D can lead to significant limitations. Methods: A 12-week randomized double-blind placebo-controlled clinical study was conducted that investigated the safety and efficacy of an herbal formulation administered orally for the treatment of pre-type 2 diabetes (pre-T2D). Results: A numerically greater proportion of subjects in the interventional arm had impaired fasting glucose (IFG) at week 12 compared to the control arm (71.0% vs. 69.0%, p = 0.75). Fewer participants had impaired glucose tolerance (IGT) at 12 weeks in the intervention arm compared to the control arm (unadjusted 58.3% vs. 66.7%, p = 0.65; adjusting for baseline IGT, p = 0.266). In a subgroup analysis, subjects with a baseline fasting plasma glucose (FPG) level in the range of 6.1-6.9 mmol/L demonstrated a non-significant lower proportion of IFG at week 12 in the intervention arm compared to the control arm (60.0% vs. 41.7% p = 0.343). Total blood cholesterol and triglyceride levels remained unchanged from baseline to week 12 in both treatment groups. Conclusions: This study suggests that a polyherbal medicine was not effective for reducing the metabolic markers associated with pre-T2D over a 12-week period. Therefore, larger studies with well-defined endpoints and of longer duration are warranted.

A randomized, double-blind placebo-controlled study of intranasal standardized cinnamon bark extract for seasonal allergic rhinitis.

OBJECTIVES: The aim of the study was to assess the safety and efficacy of a nasal spray containing a polyphenol-rich standardized extract of cinnamon bark (Cinnamomum zeylanicum) (IND02) for the treatment of seasonal allergic rhinitis (SAR). METHODS: This study was a randomized, double-blind, placebo-controlled study conducted in otherwise healthy men and women, aged between 18 and 75 years old, who were experiencing acute SAR symptoms. Participants were randomized in a 1:1 ratio to a nasal spray containing either IND02 (100 µg/100 µL) or matching placebo in each nostril, twice a day, for seven days. RESULTS: The outcome measures were the rhinoconjunctivitis quality of life questionnaire (RQLQ), the total daily symptom score comprising of day-time nasal, day-time eye, and night-time nasal symptom scores, the Work Productivity and Activities Impairment (WPAI:SHP), the Pittsburgh Sleep Quality Index (PSQI), the Perceived Stress Scale (PSS) and laboratory clinical parameters. RESULTS: The IND02 group showed a statistically and clinically significant reduction in total RQLQ and the sub-domains; activity limitation, sleep problems, nose symptoms, eye symptoms, non-nose/eye symptoms, practical problems and emotional function. There was a significant reduction in the total daily symptom score and sub-domains of total day-time nasal, total day-time eye and total night-time nasal symptoms scores, and total work impairment and regular activity impairment in the IND02 group compared with the placebo group after treatment. The laboratory clinical parameters remained within healthy normal reference range. CONCLUSION: The use of a nasal spray of a standardized extract of cinnamon bark (IND02) over seven days reduced symptom severity and improved quality of life, work productivity and regular daily activities in participants experiencing SAR.

Ageratum conyzoides L. inhibits 5-alpha-reductase gene expression in human prostate cells and reduces symptoms of benign prostatic hypertrophy in otherwise healthy men in a double blind randomized placebo controlled clinical study.

A double-blind, randomized, placebo-controlled clinical trial assessed the efficacy and safety of Ageratum conyzoides in treating benign prostatic hypertrophy (BPH). In this study, 109 men with medically diagnosed BPH, aged 41-76 years, were administered the investigational product, A. conyzoides extract at a dose of 250 mg/d or placebo, q.d. for 12 weeks. The primary outcome measures were the International Prostate Symptom Score (IPSS), daily urinary frequency and safety evaluations. The secondary outcome measures were testosterone, dihydrotestosterone, oestradiol, sex hormone binding globulin (SHBG), Dehydroepiandrosterone sulfate (DHEA-S) and cortisol levels, and prostate specific antigen (PSA), lipids, blood glucose, the Aging Male's Symptom (AMS) Score and sexual function assessed by Derogatis Interview for Sexual Functioning-Self Report (DISF-SR). The effect of A. conyzoides L extract on gene expression of 5-alpha-reductase in human prostate cells was also investigated to elucidate a potential mechanism of action. The clinical study, showed a significant reduction in total IPSS score (p < 0.01) and day- and night-time urinary frequency (P < 0.01) over time after treatment with A. conyzoides. Steroid hormones, SHBG, PSA levels, lipids, and blood glucose remained within healthy reference range in both groups. There were no changes in AMS or DISF-SR in either group. Gene arrays demonstrated that A. conyzoides extract was effective in reducing the expression of mRNA coding for 5-alpha-reductase types 2 and 1 in human prostate epithelial cells. The overall results indicate that A. conyzoides may be an effective treatment for reducing symptoms of BPH in healthy men, in part, through inhibition of 5-alpha-reductase enzyme activity. © 2017 BioFactors, 43(6):789-800, 2017.

A phase II randomised double-blind placebo-controlled clinical trial investigating the efficacy and safety of ProstateEZE Max: a herbal medicine preparation for the management of symptoms of benign prostatic hypertrophy.

OBJECTIVE: The aim of the clinical trial was to evaluate the efficacy and safety of ProstateEZE Max, an orally dosed herbal preparation containing Cucurbita pepo, Epilobium parviflorum, lycopene, Pygeum africanum and Serenoa repens in the management of symptoms of medically diagnosed benign prostate hypertrophy (BPH). DESIGN: This was a short-term phase II randomized double-blind placebo controlled clinical trial. SETTING: The trial was conducted on 57 otherwise healthy males aged 40-80 years that presented with medically diagnosed BPH. INTERVENTION: The trial participants were assigned to receive 3 months of treatment (1 capsule per day) with either the herbal preparation (n = 32) or a matched placebo capsule (n = 25). OUTCOME MEASURES: The primary outcome measure was the international prostate specific score (IPSS) measured at baseline, 1, 2 and 3 months. The secondary outcomes were the specific questions of the IPSS and day-time and night-time urinary frequency. RESULTS: There was a significant reduction in IPSS total median score in the active group of 36% as compared to 8% for the placebo group, during the 3-months intervention (p < 0.05). The day-time urinary frequency in the active group also showed a significant reduction over the 3-months intervention (7.0-5.9 times per day, a reduction of 15.6% compared to no significant reduction change for the placebo group (6.2-6.3 times per day) (p < 0.03). The night-time urinary frequency was also significantly reduced in the active group (2.9-1.8, 39.3% compared to placebo (2.8-2.6 times, 7%) (p < 0.004). CONCLUSION: The herbal preparation (ProstateEZE Max) was shown to be well tolerated and have a significant positive effect on physical symptoms of BPH when taken over 3 months, a clinically significant outcome in otherwise healthy men.