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OBJECTIVE: We explored whether initial treatment with the herbal drug uva ursi (UU) reduces antibiotic use in women with uncomplicated urinary tract infection (UTI) without increasing symptom burden and complication frequency compared with antibiotic treatment. METHODS: A double-blind randomized controlled trial was conducted in 42 family practices in Germany. The participants were adult women with suspected uncomplicated UTIs receiving either UU 105 mg 3 × 2 tablets for 5 days (intervention) or fosfomycin a 3-g single dose (control), and their respective placebos. Participants and investigators were blinded. The primary outcome included (1) antibiotic courses day 0-28 as superiority, and (2) symptom burden (sum of daily symptom scores) day 0-7, as non-inferiority outcome (margin 125%). Clinicaltrials.gov: NCT03151603. RESULTS: Overall, 398 patients were randomly allocated to groups receiving UU (n = 207) and fosfomycin (n = 191). The number of antibiotic courses was 63.6% lower (95% CI 53.6%-71.4%; p < 0.0001) in the UU group than in the fosfomycin group. The ratio of total symptom burden in the UU group compared with control was 136.5% (95% CI 122.7-151.9; p 0.95), failing non-inferiority. Eight women developed pyelonephritis in the UU group compared with two in the fosfomycin group (mean difference 2.8; 95% CI 0.2-5.9; p 0.067). Adverse events were similar between the groups. DISCUSSION: In women with uncomplicated UTIs, initial treatment with UU reduced antibiotic use but led to a higher symptom burden and more safety concerns than fosfomycin.

Uva-ursi leaf is widely used to treat symptoms of lower urinary tract infections. Here, we evaluated the in vitro inhibitory effects of uva-ursi extracts on 10 major human UDP-glucuronosyltransferases (UGT) isoforms. Of the 10 tested UGT isoforms, uva-ursi extracts exerted the strongest inhibitory effect on UGT1A1-mediated β-estradiol 3-glucuronidation with the lowest IC50 value of 8.45 ± 1.56 μg/mL. To identify the components of uva-ursi extracts showing strong inhibitory effects against UGT1A1, the inhibitory effects of nine major constituents of the extracts were assessed. Among the tested compounds, gallotannin exerted the most potent inhibition on UGT1A1, followed by 1,2,3,6-tetragalloylglucose; both demonstrated competitive inhibition, with Ki values of 1.68 ± 0.150 μM and 3.55 ± 0.418 μM. We found that gallotannin and 1,2,3,6-tetragalloylglucose also inhibited another UGT1A1-specific biotransformation, SN-38-glucuronidation, showing the same order of inhibition. Thus, in vitro UGT1A1 inhibitory potentials of uva-ursi extracts might primarily result from the inhibitory activities of gallotannin and 1,2,3,6-tetragalloylglucose present in the extracts. However, in rats, co-administration with uva-ursi extracts did not alter the in vivo marker for UGT1A1 activity, expressed as the molar ratio of AUCSN-38 glucuronide/AUCSN-38, because plasma concentrations of gallotannin and 1,2,3,6-tetragalloylglucose may be too low to inhibit the UGT1A1-mediated metabolism of SN-38 in vivo. The poor oral absorption of gallotannin and 1,2,3,6-tetragalloylglucose in uva-ursi extracts might cause the poor in vitro-in vivo correlation. These findings will be helpful for the safe and effective use of uva-ursi extracts in clinical practice.

BACKGROUND: The use of complementary/alternative medicine has garnered rising interest in recent years. Natural products including herbs, vitamins, and minerals are the most popularly consumed. The Internet is a ubiquitous source of information/market for these supplements. AIM: To systematically evaluate the dietary and herbal supplement recommended for patients with CKD and ESRD on the Internet, and try to distinguish between the claim of the manufacturer and proven scientific data. METHODS: A questionnaire assessing each website was formulated. Each product ingredient was recorded in the questionnaire by two independent reviewers and statistically analyzed. RESULTS: Of the 184 websites, 28% claimed to decrease CKD progression, 60% did not advise to consult a doctor before taking the supplement, and >90% did not mention any potential drug interaction, disease interaction, or caution in use during pregnancy or in children. The ten common plant ingredients claiming to be beneficial in kidney diseases were uva ursi, dandelion, parsley, corn silk, juniper, celery, buchu, horsetail, marshmallow, and stinging nettle. In contrast to their claims, these substances were not adequately studied in humans. The available animal studies showed detrimental effects and potential drug interactions with commonly used medications in the CKD/ESRD population. CONCLUSIONS: Nephrologists need to be cognizant of the lack of substantiated proven benefits of these substances and of the potential adverse effects in the animal models that can translate to the patients. Most importantly, the policy needs to change regarding the regulation of these products to prevent patient harm and misinformation. © 2014 S. Karger AG, Basel.

Antioxidant activity of green and black tea and extracts of medicinal plants and their ability to modulate antibiotic susceptibility in Escherichia coli were studied. Among a number of extracts tested the maximal capacity to scavenge DPPH radicals and chelate iron in chemical tests was found in green and black tea, Arctostaphylos uva-ursi and Vaccinium vitis-idaea. These extracts contained high level of polyphenols and in aerobic conditions exhibited prooxidant features, producing H2O2 and inducing expression of the katG gene encoding catalase HPI in E. coli cells. A good correlation between the polyphenol content and the ability of extracts to protect bacteria against peroxide stress was observed (r = 0.88). Polyphenol-rich extracts and iron chelators demonstrated the highest modulating effect on the antibiotic susceptibility by changing the time period before lysis started and by influencing the colony-forming ability of bacteria. The direction of the modulating effect was dependent on nature of antibiotic applied: under treatment with ciprofloxacin and ampicillin the extracts predominantly provided protective effects, while under treatment with kanamycin a bactericidal action was enhanced. Mechanism of modulating action of extracts on bacterial antibiotic susceptibility probably involves antioxidant, preferentially iron-chelating, or prooxidant properties of polyphenols.

We found that an extract of Arctostaphylos uva-ursi markedly reduced the MICs of beta-lactam antibiotics, such as oxacillin and cefmetazole, against methicillin-resistant Staphylococcus aureus. We isolated the effective compound and identified it as corilagin. Corilagin reduced the MICs of various beta-lactams by 100- to 2,000-fold but not the MICs of other antimicrobial agents tested. The effect of corilagin and oxacillin was synergistic. Corilagin showed a bactericidal action when added to the growth medium in combination with oxacillin.

Effects of water extract (UW-ext) from the leaf of Arctostaphylos uva-ursi (L.) Spreng (Bearberry leaf) on the antiallergic and antiinflammatory activities of dexamethasone ointment were investigated. One or 2% UW-ext ointment did not inhibit the ear swelling by picryl chloride-induced contact dermatitis (PC-CD) and carrageenin-induced paw edema. UW-ext augmented the inhibitory effect of dexamethasone ointment (0.005 or 0.025%) on these allergic and inflammatory models, but not the side effect of it. These results suggest that Bearberry leaf increases the inhibitory effect of dexamethasone on the allergic and inflammatory models.

A study was carried out to examine the combined effect of arbutin isolated from the leaves of Arctostaphylos uva-ursi (L.) Spreng. (Bearberry leaf) and indomethacin on Type IV allergic reaction-induced immuno-inflammation, carrageenin-induced edema and adjuvant-induced arthritis. Contact dermatitis caused by picryl chloride (PC-CD) and sheep red cell delayed type hypersensitivity (SRBC-DTH) was not inhibited by the oral application of arbutin at 2 divided doses immediately before and 16 h after the application, but arbutin at dose of 50 mg/kg 24 h after the application rapidly decreased the swelling of PC-CD. Arbutin (p.o.) plus indomethacin (s.c.) showed inhibitory effect on the swelling of PC-CD and SRBC-DTH stronger than that of indomethacin alone. When arbutin (p.o.) and indomethacin (s.c.) in a given portion were simultaneously administered, the inhibitory effect was more potent than that of indomethacin alone in both carrageenin-induced edema and adjuvant-induced arthritis. These results suggest that arbutin may increase the inhibitory action of indomethacin on PC-CD, SRBC-DTH, carrageenin-induced edema and adjuvant-induced arthritis, but further investigations are required to understand the mechanism involved.

BACKGROUND: Almost half of all women will have at least one symptomatic urinary tract infection (UTI) in their lifetime. Although usually self-remitting, 74% of women contacting a health professional are prescribed an antibiotic, and in rare instances, they may progress to more severe infections. Therefore, the standard of care for the treatment of symptomatic uncomplicated UTIs is oral antibiotic therapy, which aims to achieve symptom resolution and prevent the development of complications such as pyelonephritis. Given that a number of UTIs are self-remitting, non-antibiotic treatments that may help reduce the severity or duration of symptoms or reduce the need for antibiotics may be of benefit. OBJECTIVES: This review aims to investigate the benefits and risks associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of symptomatic uncomplicated UTIs in non-pregnant adult women. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 18 November 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs looking at the effectiveness of NSAIDs in the treatment of symptomatic uncomplicated UTIs in non-pregnant adult women. The outcomes of interest were: 1) short-term resolution of symptoms (days 1 to 4); 2) medium-term resolution of symptoms (days 5 to 10); and 3) incidence of adverse events (including progression to sepsis or complicated UTI, hospitalisation or need for intravenous antibiotics, gastrointestinal complications, or death) up to 30 days from randomisation. DATA COLLECTION AND ANALYSIS: Screening, abstract selection, and data extraction were carried out independently by two authors, and any disagreements were resolved by discussion with a third author. Summary estimates of effect were obtained using a ra

BACKGROUND: Bearberry (Arctostaphylos uva-ursi) leaf is available as a treatment of uncomplicated cystitis in several European countries. The antimicrobial activity of its extracts and some of its individual constituents has been observed in vitro; however, the efficacy of bearberry compared with standard antimicrobial therapy has not been assessed yet. OBJECTIVE: The objective of the study is to assess the safety and non-inferiority of bearberry as an alternative therapy in the treatment of acute uncomplicated cystitis in comparison with standard antibiotic therapy (fosfomycin). METHODS AND ANALYSIS: This is a randomised controlled double-blinded multicentre trial. Eligible patients will be premenopausal women with a sum score of ≥6 for the typical acute uncomplicated cystitis symptoms (frequency, urgency, painful urination, incomplete emptying, suprapubic pain and visible haematuria) reported on the Acute Cystitis Symptom Score (ACSS) typical domain and pyuria. Patients will be randomly assigned to receive 3 g single dose of fosfomycin powder and two placebo tablets three times a day for 7 days or B a single dose of placebo powder and two tablets containing a dry extract of Uvae ursi folium. At least 504 patients (allocated as 1:1) will need to be enrolled to access non-inferiority with a non-inferiority limit of 14% for the primary endpoint.Improvement of symptoms of uncomplicated cystitis (based on the ACSS score) at day 7 is defined as the primary endpoint, whereas several secondary endpoints such as the number and ratio of patients with bacteriuria at day 7, frequency and severity of side effects; recurrence of urinary tract infection, concurrent use of other over the counter (OTC) medications and food supplements will be determined to elucidate more detailed differences between the groups. The number of recurrences and medications taken for treatment will be monitored for a follow-up period of 90 days (80-100 days). ETHICS AND DISSEMINATION: This study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/4225-1/2021/EKU). The results will be disseminated by publication of peer-reviewed manuscripts

BACKGROUND: The use of alternative medicines is common in patients with diabetes mellitus. The primary aim of the present study was to determine the effects of cinnamon and Caucasian whortleberry (Vaccinium arctostaphylos L.) on blood glucose control, lipid profile and body mass index (BMI) in patients with type 2 diabetes (T2DM). METHODS: In all, 105 T2DM patients were recruited to the present randomized triple-blinded clinical trial. Patients were randomly divided into three groups and administered either placebo, cinnamon or whortleberry supplements (1 g/day) for 90 days. Fasting blood glucose (FBG), serum insulin, lipid profiles, and HbA1c were measured before and after the study. RESULTS: There were no significant differences in baseline characteristics among the three groups. After treatment, FBG, 2-h blood postprandial glucose and homeostasis model assessment of insulin resistance (HOMA-IR) scores were significantly reduced in patients in the whortleberry group, but not in the placebo group. After treatment, there was a significant difference in BMI between the cinnamon and control groups (P = 0.02). There were no significant differences in any variables between the cinnamon and whortleberry groups (P>0.05 for all). In addition, there was a significant decrease in all indices of glucose control in all the cinnamon and whortleberry groups (P < 0.05). CONCLUSIONS: There were no significant differences in blood glucose levels, insulin sensitivity or lipid profile among the three groups. However, the use of cinnamon and whortleberry in addition to conventional medical treatment is recommended to adjust weight and blood glucose levels in patients with T2DM, respectively. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Background. Dyslipidemia produces atherosclerosis, which in turn results in coronary artery disease (CAD). Atherosclerosis is being considered as an inflammatory disease. Vaccinium arctostaphylos L. is a plant with fruits rich in anthocyanins. The aim of this study was to evaluate the effects of fruit extract of this plant on serum levels of lipids, hs-CRP, and malondialdehyde (MDA) as a marker of oxidative stress, in hyperlipidemic adult patients. Methods. In this randomized, double-blind, placebo-controlled clinical trial, 50 hyperlipidemic adult patients were randomly and equally assigned to receive either medicinal (V. arctostaphylos fruit extract) or placebo capsules twice daily for 4 weeks. Each medicinal capsule contained 45 ± 2 mg of anthocyanins. Fasting serum levels of total cholesterol, TG, LDL-C, HDL-C, hs-CRP, and MDA were obtained before and after the intervention and compared. Results. V. arctostaphylos fruit extract significantly reduced total cholesterol (P < 0.001), LDL-C (P = 0.004), TG (P < 0.001), and MDA (P = 0.013) compared to placebo but did not have any significant effect on HDL-C (P = 0.631) and hs-CRP (P = 0.190). Conclusion. Fruit extract of Vaccinium arctostaphylos has beneficial effects on serum lipid profile and oxidative stress in hyperlipidemic adult patients. Therefore, it could be considered as a supplement for treatment of dyslipidemia and prevention of atherosclerosis development.

In a 4-week randomized placebo-controlled clinical trial we investigated the effect of 300 mg Blueberin, a phytomedicine containing 250 mg Blueberry leaves (Vaccinium arctostaphylos L, Ericaceae) extract providing minimum 50 mg 3,4-caffeoylquinic (chlorogenic) acid, and 50 mg myricetin, on fasting plasma glucose, alanine aminotransferases (ALT), aspartate aminotransferases (AST), glutamyltransferase (GGT) enzymes levels, and serum inflammatory C-Reactive proteins (CRP) in forty-two volunteer subjects (46+/-15 year of age, BMI 25+/-3 kgs/(m2)) diagnosed with Type 2 diabetes. During the 4-week trial, the Blueberin supplement was administered three times per day, 15-30 minutes prior to a meal along with 100 ml of water. Results of this trial revealed that the supplementation of Blueberin reduced fasting plasma glucose from 143+/-5,2mg/L to 104+/-5,7 mg/L (p<0,001), whereas there was no statistically significant changes in the Placebo group from 138+/-4,8 mg/L to 126+/-5,1mg/L (p>0,05). The reduction of fasting glucose was correlated with the reduction of serum CRP and in the Blueberin group from 5,18+/-1,4 mg/l to 2,14+/-1,8 mg/L (p<0,05), whereas in the Placebo group CRP levels were not significantly reduced from 5,11+/-1,7 mg/l to 4,94+/-1,1mg/L (p>0,05). Furthermore, the Blueberin also significantly reduced the levels of plasma enzymes ALT, AST and GGT, indicating that, in addition to anti-diabetes effects, the Blueberin also possess pharmacologically relevant anti-inflammatory properties.

INTRODUCTION: Uncomplicated urinary tract infection (UTI) in women is a common reason to present in general practice and is usually treated with antibiotics to reduce symptom severity and duration. Results of recent clinical trials indicate that non-antibiotic treatment approaches can also be effective. However, it remains unclear which patients would benefit from antibiotic treatment and which can effectively and safely be treated without antibiotics. This systematic review and meta-analysis aims to estimate the effect of treatment strategies to reduce antibiotic use in comparison with immediate antibiotic treatment and to identify prognostic factors and moderators of treatment effects. A further aim is to identify subgroups of patients benefiting from a specific therapy. METHODS AND ANALYSIS: A systematic literature search will be performed to identify randomised controlled trials which investigated the effect of treatment strategies to reduce antibiotic use in female adults with uncomplicated UTI compared with immediate antibiotic treatment. Therefore, the primary outcome of the meta-analysis is incomplete recovery. Anonymised individual patient data (IPD) will be collected. Aggregate data will be used for pairwise comparisons of treatment strategies using meta-analysis models with random effects accounting for potential between-study heterogeneity. Potential effect moderators will be explored in meta-regressions. For IPD, generalised linear mixed models will be used, which may be adjusted for baseline characteristics. Interactions of baseline variables with treatment effects will be explored. These models will be used to assess direct comparisons of treatment, but might be extended to networks. ETHICS AND DISSEMINATION: The local institutional review and ethics board judged the project a secondary analysis of existing anonymous data which meet the criteria for waiver of ethics review. Dissemination of the results will be via published scientific papers and presentations. Key messages will be promoted for example, via social media or press releases. PROSPERO REGISTRATION NUMBER: CRD42019125804. © Author(s) (or their employer(s)) 2020. Re-use permitted under

BACKGROUND: Capparis spinosa, Rosa canina, Securidaca securigera, Silybum marianum, Urtica dioica, Trigonella foenum-graecum and Vaccinium arctostaphylos are used traditionally as an herbal combination for treatment of diabetic patients in Iran. Despite the clinical evidence supporting their use in solitary form, no controlled human study has determined the efficacy and safety of their combination in treatment of diabetic patients. METHODS: A total 150 type II diabetic patients of both sexes under the oral anti-hyperglycemic drugs treatment (maximum 10 mg glyburide and 1000 mg metformin daily) were randomly assigned to three groups. The patients in each group received either herbal combination or placebo or metformin capsule daily for three months, without any change in their previous oral anti-hyperglycemic drugs dosage. Herbal combination, placebo and metformin capsules matched by shape and color were prepared in the Institute of Medicinal Plants Karaj, Iran. To assess the efficacy and safety of the treatments, the patients fasting plasma glucose, HbA1c, lipid profile, liver enzymes and renal function were determined at the beginning of the study and after three months. RESULTS: Results showed that after three months, the fasting plasma glucose, HbA1c and cholesterol levels in herbal combination were decreased significantly as compared to placebo group (20% and 12% respectively) and also compared to base line (25% and 15% respectively). The herbal combination was as effective as metformin in reduction of FPG (p = 0.001, p = 0.001) and HbA1c (p = 0.028 and p = 0.050 respectively) compared to placebo. No notable hepatic, renal and gastrointestinal side effects were observed in the trial groups. CONCLUSION: The results suggest that traditional herbal combination may safely improve glycemic control in type II diabetic patients with no significant adverse effect. [Formula: see text].

OBJECTIVES: To evaluate the antihypertensive efficacy and safety of a standardized Vaccinium arctostaphylos (V. arctostaphylos) berry hydro-alcoholic extract in the overweight/obese hypertensive patients. DESIGN: Randomized placebo-controlled trial. SETTING: Baqiyatallah hospital (Tehran, Iran). INTERVENTIONS: The antihypertensive efficacy and safety of 3-month intake of 400 mg extract capsule three times daily alongside standardized anti-hypertensive regimen in the treatment of 50 patients was compared with the placebo (n = 50). MAIN OUTCOME MEASURES: SBP (systolic blood pressure), DBP (diastolic blood pressure), body mass index, waist circumference, CBC (complete blood count), blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), BUN (blood urea nitrogen) and creatinine. RESULTS: SBP decreased from 152.1 ± 7.7 to 140.5 ± 10.7 in the V. arctostaphylos group and from 152.9 ± 8.1 to 150.8 ± 9.3 in the placebo group (P < 0.001). DBP decreased from 90.3±8 to 82.1±8.8 in the V. arctostaphylos group and from 89.6 ± 7.8 to 87.6 ± 7.9 in the placebo group (P < 0.001). The extract capsule had no significant effect on the other parameters (P > 0.05). Moreover, no drug side effect and adverse interaction with other antihypertensive drugs was observed in the patients. CONCLUSIONS: V. arctostaphylosberry extract improves blood pressure control and has safety and tolerability in the overweight/obese hypertensive patients taking standard antihypertensive drugs.

OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

BACKGROUND: Uncomplicated urinary tract infections (UTI) are common in general practice and usually treated with antibiotics. This contributes to increasing resistance rates of uropathogenic bacteria. A previous trial showed a reduction of antibiotic use in women with UTI by initial symptomatic treatment with ibuprofen. However, this treatment strategy is not suitable for all women equally. Arctostaphylos uva-ursi (UU, bearberry extract arbutin) is a potential alternative treatment. This study aims at investigating whether an initial treatment with UU in women with UTI can reduce antibiotic use without significantly increasing the symptom burden or rate of complications. METHODS: This is a double-blind, randomized, and controlled comparative effectiveness trial. Women between 18 and 75 years with suspected UTI and at least two of the symptoms dysuria, urgency, frequency or lower abdominal pain will be assessed for eligibility in general practice and enrolled into the trial. Participants will receive either a defined daily dose of 3 × 2 arbutin 105 mg for 5 days (intervention) or fosfomycin 3 g once (control). Antibiotic therapy will be provided in the intervention group only if needed, i.e. for women with worsening or persistent symptoms. Two co-primary outcomes are the number of all antibiotic courses regardless of the medical indication from day 0-28, and the symptom burden, defined as a weighted sum of the daily total symptom scores from day 0-7. The trial result is considered positive if superiority of initial treatment with UU is demonstrated with reference to the co-primary outcome number of antibiotic courses and non-inferiority of initial treatment with UU with reference to the co-primary outcome symptom burden. DISCUSSION: The trial's aim is to investigate whether initial treatment with UU is a safe and effective alternative treatment strategy in women with UTI. In that case, the results might change the existing treatment strategy in general practice by promoting delayed prescription of antibiotics and a reduction of antibiotic use in primary care. TRIAL REGISTRATION: EudraCT: 2016-000477-21 . Clinical trials.gov: NCT03151603 (registered: 10 May 2017).

BACKGROUND: Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use. METHODS/DESIGN: Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below: Group 1 - Uva-ursi + advice to take ibuprofen Group 2 - Placebo + advice to take ibuprofen Group 3 - Uva-ursi + no advice to take ibuprofen Group 4 - Placebo + no advice to take ibuprofen Patients and physicians will be blinded to the randomised group for the herb. The main outcome is symptom severity at days 2-4 recorded in a validated, self-report diary used in previous studies. Secondary outcomes include antibiotic use and symptom duration. In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint. In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package. DISCUSSION: The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN43397016 . Registered on 11 February 2015.

BACKGROUND: Type 2 diabetes mellitus is a common disease. Preliminary data indicate that Vaccinium arctostaphylos L. (Caucasian whortleberry) has a potential effect in glycemic control. Thus, the efficacy and safety of a standardized whortleberry fruit hydroalcoholic extract in the treatment of type 2 diabetic patients were studied. METHODS: This randomized double-blind placebo-controlled clinical trial consisted of 37 patients aged 40-60 years with type 2 diabetes who were resistant to conventional oral anti-hyperglycemic drugs. The patients were treated with the whortleberry fruit hydroalcoholic extract (1 capsule = 350 mg, every 8 h for 2 months) in combination with anti-hyperglycemic drugs, and the effects on the blood levels of fasting glucose, 2-hour postprandial glucose, glycosylated hemoglobin (HbA1c), and liver/kidney function were tested, evaluated, and compared with a placebo group (n = 37). RESULTS: The extract significantly lowered the blood levels of fasting glucose, 2-h postprandial glucose, and HbA1c (p = 0.007, p <0.001, and p = 0.005, respectively) without any significant effects on the liver/kidney function (p >0.05) compared with placebo at the end. No adverse effects were reported. CONCLUSION: Whortleberry may safely improve glycemic control in type 2 diabetic patients.

Dyslipidemia is a common contributory cause of cardiovascular disease. Vaccinium arctostaphylos L. (Caucasian whortleberry) fruit is rich of anthocyanins. Anthocyanins may exert cardioprotective effects by various mechanisms such as favorably modulating dyslipidemia. Therefore, in this randomized double-blind placebo-controlled clinical trial with hyperlipidemic (hypercholesterolemic and/or hypertriglyceridemic) patients aged 20-60 years, the effects of taking a standardized whortleberry fruit hydroalcoholic extract (one 350 mg capsule every 8 h for 2 months) on fasting blood levels of lipids, creatinine and liver enzymes including SGOT and SGPT were evaluated in 40 patients and compared with the placebo group (n = 40). The extract lowered the blood levels of total cholesterol (P < 0.001), triglyceride (P = 0.002) and low-density lipoprotein cholesterol (LDL-C) (P = 0.002), but increased the blood high-density lipoprotein cholesterol (HDL-C) levels (P < 0.001) without any significant effects on the blood levels of SGOT, SGPT and creatinine (P > 0.05) compared with the placebo group at the endpoint. Whortleberry reduced total cholesterol, triglyceride and LDL-C 27.6%, 19.2% and 26.3%, respectively, but increased HDL-C 37.5% compared with baseline. No adverse effects were reported. Short-term treatment with whortleberry fruit appears safe and improves lipid profile in hyperlipidemic patients.

Bearberry leaves and preparations made from them are traditionally used for urinary tract infections. The urinary excretion of arbutin metabolites was examined in a randomized crossover design in 16 healthy volunteers after the application of a single oral dose of bearberry leaves dry extract (BLDE). There were two groups of application using either film-coated tablets (FCT) or aqueous solution (AS). The urine sample analysis was performed by a validated HPLC coolarray method (hydroquinone) and a validated capillary electrophoresis method (hydroquinone-glucuronide, hydroquinone-sulfate). The total amounts of hydroquinone equivalents excreted in the urine from BLDE were similar in both groups. With FCT, 64.8% of the arbutin dose administered was excreted; with AS, 66.7% was excreted (p = 0.61). The maximum mean urinary concentration of hydroquinone equivalents was a little higher and peaked earlier in the AS group versus the FCT group, although this did not reach statistical significance (Cur max = 1.6893 micromol/ml vs. 1.1250 micromol/ml, p = 0.13; tmax (t midpoint) = 3.60 h vs. 4.40 h, p = 0.38). The relative bioavailability of FCT compared to AS was 103.3% for total hydroquinone equivalents. There was substantial intersubject variability. No significant differences between the two groups were found in the metabolite patterns detected (hydroquinone, hydroquinone-glucuronide, and hydroquinone-sulfate).