UT FIX

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

D-Mannose

Oral D-mannose in recurrent urinary tract infections in women: a pilot study*

Abstract

Background In recurrent urinary tract infections (UTIs) usual prophylactic antibiotic regimes do not change the long-term risk of recurrence. Our aim was to evaluate the efficacy of D-mannose in the treatment and prophylaxis of recurrent UTIs. Methods In this randomized cross-over trial female patients were eligible for the study if they had an acute symptomatic UTI and three or more recurrent UTIs during the preceding 12 months.

Suitable patients were randomly assigned to antibiotic treatment with trimethoprim/sulfamethoxazole or to a regimen of oral D-mannose 1 g 3 times a day, every 8 hours for 2 weeks, and subsequently 1 g twice a day for 22 weeks.

They received the other intervention in the second phase of the study, with no further antibiotic prophylaxis. The primary endpoint was evaluation of the elapsed time to recurrence; secondary endpoints were evaluation of bladder pain (VASp) and urinary urgency (VASu).

Results: The results for quantitative variables were expressed as mean values and SD as they were all normally distributed (Shapiro–Wilk test). In total, 60 patients aged between 22 and 54 years (mean 42 years) were included. Mean time to UTI recurrence was 52.7 days with antibiotic treatment, and 200 days with oral D-mannose ( p < 0.0001). Conclusions Mean VASp, VASu score, and average numbers of 24-hour voidings decreased significantly. D-mannose appeared to be a safe and effective treatment for recurrent UTIs in adult women. A significant difference was observed in the proportion of women remaining infection free versus antibiotic treatment.

Source: Porru D, Parmigiani A, Tinelli C, et al. Oral d-mannose in recurrent urinary tract infections in women: a pilot study. J Clin Urol. 2014;7(3):208-213.

D-mannose: a promising support for acute urinary tract infections in women

Abstract

Objective: Urinary tract infections still represent a significant bother for women and result in high costs to the health system. D-mannose is a simple sugar; it seems able to hinder bacteria adhesion to the urothelium. The present study aimed to determine whether D-mannose alone is effective in treating acute urinary tract infections in women and its possible utility in the management of recurrences.

Patients and methods: This is a pilot study, performed between April 2014 and July 2015 at Department of Gynaecological Obstetrics and Urologic Sciences of “Sapienza” University of Rome. A D-mannose compound was administered twice daily for 3 days and then once a day for 10 days. Changes in patients’ symptoms, the therapeutic effects and changes in quality of life (QoL) were evaluated clinically and using a specifically validated questionnaire (UTISA). After described treatment, patients were randomized in receiving or not prophylaxis in the next 6 months.

Results: Mean UTISA scores recorded after completing the treatment, compared with baseline scores, showed a significant improvement of the majority of symptoms (p < 0.05). D-mannose seemed to have had a significant positive effect on UTIs’ resolution and QoL improvement (p = 0.0001). As a prophylactic agent administered for 6 months, it showed promising results (4.5% vs. 33.3% recurrences in treated and untreated patients respectively).

Conclusions: The results of this study suggest that D-mannose can be an effective aid in acute cystitis management and also a successful prophylactic agent in a selected population; however, more studies will certainly be needed to confirm the results of our pilot study.

Source: Domenici L, Monti M, Bracchi C, Giorgini M, Colagiovanni V, Muzii L, Benedetti Panici P. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. Eur Rev Med Pharmacol Sci. 2016 Jul;20(13):2920-5.

Why D-Mannose May Be as Efficient as Antibiotics in the Treatment of Acute Uncomplicated Lower Urinary Tract Infections—Preliminary Considerations and Conclusions from a Non-Interventional Study*

Abstract

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. D-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of D-mannose in the prevention of recurrent UTIs; these also provided limited evidence for the efficacy of D-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with D-mannose. Here, we present data from a post hoc analysis of this study to compare the cure rate of D-mannose monotherapy with that of antibiotics. The results show that D-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

Source: Wagenlehner, F.; Lorenz, H.; Ewald, O.; Gerke, P. Why D-Mannose May Be as Efficient as Antibiotics in the Treatment of Acute Uncomplicated Lower Urinary Tract Infections—Preliminary Considerations and Conclusions from a Non-Interventional Study. Antibiotics 2022, 11, 314.

Prebiotic properties of mannose and its effect on specific resistance*

Abstract

Aim: Study prebiotic properties of mannose and its effect on colonization resistance in experiments in mice.

Materials and methods: Experimental dysbiosis was induced by introduction into non-linear mice of doxycycline hydrochloride. Prebiotic properties of mannose were studied by a single per oral administration to mice of increasing doses of preparation for a week compared with probiotics lactobacterin and bifidumbacterin. Lumen microflora was analyzed in feces. TNF-alpha level was determined by using a commercial kit OpTEIA ELISA Kit. Phagocytic activity of neutrophils and macrophages was studied in a cytochemical test of nitroblue tetrazolium reduction (NTT test) and by luminol-dependent chemiluminescence. Phagocytic activity and digestive ability of alveolar macrophages was studied.

Results: The ability of mannose along with probiotic preparations bifidumbacterin and lactobacterin to restore the composition and numbers of indigenous microflora of mice under the conditions of experimental dysbiosis was revealed. Per oral administration of mannose and probiotic strains together with mannose was established to cause stimulating effect on functional activity of macrophages increasing ingesting and digesting ability of the cells and facilitates reduction of TNF-alpha levels.

Conclusion: Mannose has a prebiotic effect; the ability of mannose to induce expression of pro- and anti-inflammatory cytokines gives evidence of immunostimulating properties of the monosaccharide.

Source: O S Korneeva, I V Cheremushkina, A S Glushchenko, N A Mikhaĭlova, A P Baturo, É E Romanenko, S A Zlygostev Prebiotic properties of mannose and its effect on specific resistance. Zh Mikrobiol Epidemiol Immunobiol. 2012 Sep-Oct;(5):67-70.

Vitamin D

Prevention and treatment of uncomplicated lower urinary tract infections in the era of increasing antimicrobial resistance—non-antibiotic approaches: a systematic review*

Purpose: Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10–20% of all infections treated in primary care units and 30–40% of those treated in hospitals. The risk of UTI in the female population is considered to be 14 times higher than in the male population. The prevalence of bacterial etiology results in a large consumption of broad-spectrum antibiotics, which in turn leads to increased rates of resistant uropathogens. Therefore, non-antibiotic prevention and treatment options are now of great importance.

Methods: A systematic literature search was performed for the last 20 years (1999–2019) and the efficiencies of these eight different non-antibiotic interventions were analysed and discussed.

Results: This article provides an overview on non-antibiotic options for management of UTI, including the application of cranberry products, the phytodrug Canephron N, probiotics, nonsteroidal anti-inflammatory drugs (NSAID), d-mannose, estrogens, vitamins, and immunotherapy.

Conclusions: The last 20 years of research on non-antibiotic approaches in UTI have not brought conclusive evidence that antibiotic usage can be replaced completely by non-antibiotic options. Hence, antibiotics still remain a gold standard for UTI treatment and prevention. However, changing the therapeutic strategy by including non-antibiotic measures in the management of UTI could be successful in avoiding antimicrobial resistance at least to some extent.

Source: Wawrysiuk S, Naber K, Rechberger T, Miotla P. Prevention and treatment of uncomplicated lower urinary tract infections in the era of increasing antimicrobial resistance-non-antibiotic approaches: a systemic review. Arch Gynecol Obstet. 2019 Oct;300(4):821-828. doi: 10.1007/s00404-019-05256-z. Epub 2019 Jul 26. PMID: 31350663; PMCID: PMC6759629.

Vitamin D deficiency as a risk factor for urinary tract infection in women at reproductive age*

Vitamin D deficiency is a pandemic problem and an ever-increasing issue in human nutrition and health. Vitamin D (serum 25-hydroxyvitamin D) deficiency causes many health problems such as autoimmune diseases, Crohn’s disease, diabetes, inflammation, asthma, hypertension, and cancer. Vitamin D3 (cholecalciferol) deficiency has been documented as a persistent problem among adults, children, and elderly persons in most of the countries. Our main objective of this study was to determine the hypothesis that the vitamin D deficiency among women can lead to them developing frequent urinary tract infections. Vitamin D has a potential role in immune regulation and it prevents infections especially urinary tract infections (UTI). Therefore it has a positive regulatory role in both acute and recurrent infections especially in women of reproductive ages. As women at this age group have specific differences in their urinary tract and the reproductive organ anatomy, make them more prone for micro-organisms' invasion, The present study was carried out to ascertain certain relation between serum 25-hydroxyvitamin D levels and UTI in women while contemplating the significance of knowing the risk factors associated with UTI and also finding ways to avoid serious complications. 75 women with (case group) UTI were differentiated with 35 healthy with no UTI (control group) and 40 women with UTI and their serum 25-hydroxyvitamin D levels were checked in a case control study. The women were between 17–52 years of age. Using ELISA, Serum 25-hydroxyvitamin D levels were measured. Analysis and comparison of the results were done among the two groups. Vitamin D mean levels in the case group were considerably lower when in comparison with the control group (11.09 ± 7.571 ng/mL vs. 24.08 ± 11.95 ng/mL, P < 0.001).

Source: Ali SB, Perdawood D, Abdulrahman R, Al Farraj DA, Alkubaisi NA. Vitamin D deficiency as a risk factor for urinary tract infection in women at reproductive age. Saudi J Biol Sci. 2020 Nov;27(11):2942-2947. doi: 10.1016/j.sjbs.2020.08.008. Epub 2020 Aug 8. PMID: 33100850; PMCID: PMC7569126.

Vitamin D strengthens the bladder epithelial barrier by inducing tight junction proteins during E. coli urinary tract infection*

Abstract

Tight junction proteins are pivotal to prevent bacterial invasion of the epithelial barrier. We here report that supplementation with vitamin D can strengthen the urinary bladder lining. Vitamin D deficient and sufficient mice were infected with Escherichia coli (E. coli) transurethrally to cause urinary tract infection. In addition, bladder biopsies were obtained from postmenopausal women before and after a 3-month period of supplementation with 25-hydroxyvitamin D3 (25D3) and ex vivo infected with E. coli. In biopsies, obtained before E. coli infection, vitamin D had no impact on tight junction proteins. However, during E. coli infection, vitamin D induced occludin and claudin-14 in mature superficial umbrella cells of the urinary bladder, as demonstrated by immunohistochemistry. Increased cell-cell adhesion consolidating the epithelial integrity is thereby promoted. We here describe a novel role of vitamin D in the urinary tract supporting vitamin D supplementation to restore the bladder epithelial integrity.

Source: Mohanty S, Kamolvit W, Hertting O, Brauner A. Vitamin D strengthens the bladder epithelial barrier by inducing tight junction proteins during E. coli urinary tract infection. Cell Tissue Res. 2020 Jun;380(3):669-673. doi: 10.1007/s00441-019-03162-z. Epub 2020 Jan 13. PMID: 31930458; PMCID: PMC7242269.

Cranberry Fruit Extract 30% proanthocyanidin

Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial*

Objectives: The present study forms part of the ISRCTN16968287 clinical assay. The objective of this study was to determine the effectiveness of cranberry syrup in the prophylaxis of recurrent urinary tract infection (UTI).

Design: Phase III randomized clinical trial.

Setting: The study was conducted at the San Cecilio Clinical Hospital (Granada, Spain).

Participants: A total of 192 patients were recruited. The subjects were aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI (more than two episodes of infection in the last 6 months), associated or otherwise with vesicoureteral reflux of any degree, or renal pelvic dilatation associated with UTI. Criteria for exclusion from recruitment to the study included the co-existence of UTI with other infectious diseases or with metabolic diseases, chronic renal insufficiency, and the presence of allergy or intolerance to any of the components of cranberry syrup or trimethoprim.

Primary outcome measures: The primary objective was to determine the risk of UTI associated with each intervention.

Results: Of the 198 patients initially eligible, 192 were finally included in the study to receive either cranberry syrup or trimethoprim. UTI was observed in 47 patients, 17 of whom were males and 30 females. We recruited 95 patients diagnosed with recurrent UTI on entry; during follow-up, 26 patients had a UTI (27.4%, 95% CI: 18.4%–36.3%). Six patients (6.3%) were male and 20 (21.1%) were female. Eighteen patients (18.9% of the total, 95% CI: 11%–26.3%) receiving trimethoprim had a UTI and eight patients (8.4% of the total, 95% CI: 2.8%–13.9%) were given cranberries. Sixty-six percent of the episodes of UTI recurrence were caused by Escherichia coli, with no significant differences being found between the two treatment branches. No differences were observed between the two treatment branches in the rate of resistance to antibiotics.

Conclusion: Our study confirms that cranberry syrup is a safe treatment for the pediatric population. Cranberry prophylaxis has noninferiority with respect to trimethoprim in recurrent UTI. (European Clinical Trials Registry EuDract 2007-004397-62) (ISRCTN16968287).

Source: Uberos J, Nogueras Ocana M, Fernandez-Puentes V, Rodriguez-Belmonte R, Narbona-López E, Molina Carballo A, Munoz-Hoyos A. Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial. Open Access Journal of Clinical Trials. 2012;4:31-38

Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: A systematic review and meta-analysis with trial sequential analysis*

Abstract

The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P < 0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution.

Source: Xia JY, Yang C, Xu DF, Xia H, Yang LG, Sun GJ. Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: A systematic review and meta-analysis with trial sequential analysis. PLoS One. 2021 Sep 2;16(9):e0256992. doi: 10.1371/journal.pone.0256992. PMID: 34473789; PMCID: PMC8412316.

High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial*

Abstract

Purpose: Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection.

Material and methods: We recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as ≥ 2 in the past 6 months or ≥ 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 × 18.5 mg daily, n = 72) or a control low dose (2 × 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria.

Results: In response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51–1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33–0.99). No major side effects were reported.

Conclusion: High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year.

Source: Babar A, Moore L, Leblanc V, Dudonné S, Desjardins Y, Lemieux S, Bochard V, Guyonnet D, Dodin S. High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial. BMC Urol. 2021 Mar 23;21(1):44. doi: 10.1186/s12894-021-00811-w. PMID: 33757474; PMCID: PMC7986024.

Propolis

Propolis potentiates the effect of cranberry (Vaccinium macrocarpon) against the virulence of uropathogenic Escherichia coli*

Abstract

Uropathogenic Escherichia coli (UPEC), the most prevalent bacteria isolated in urinary tract infections (UTI), is now frequently resistant to antibiotics used to treat this pathology. The antibacterial properties of cranberry and propolis could reduce the frequency of UTIs and thus the use of antibiotics, helping in the fight against the emergence of antibiotic resistance. Transcriptomic profiles of a clinical UPEC strain exposed to cranberry proanthocyanidins alone (190 µg/mL), propolis alone (102.4 µg/mL) and a combination of both were determined. Cranberry alone, but more so cranberry + propolis combined, modified the expression of genes involved in different essential pathways: down-expression of genes involved in adhesion, motility, and biofilm formation, and up-regulation of genes involved in iron metabolism and stress response. Phenotypic assays confirmed the decrease of motility (swarming and swimming) and biofilm formation (early formation and formed biofilm). This study showed for the first time that propolis potentiated the effect of cranberry proanthocyanidins on adhesion, motility, biofilm formation, iron metabolism and stress response of UPEC. Cranberry + propolis treatment could represent an interesting new strategy to prevent recurrent UTI.

Source: Ranfaing J, Dunyach-Remy C, Louis L, Lavigne JP, Sotto A. Propolis potentiates the effect of cranberry (Vaccinium macrocarpon) against the virulence of uropathogenic Escherichia coli. Sci Rep. 2018 Jul 16;8(1):10706. doi: 10.1038/s41598-018-29082-6. PMID: 30013052; PMCID: PMC6048107.

A Multicenter, Randomized, Placebo-Controlled Study Evaluating the Efficacy of a Combination of Propolis and Cranberry (Vaccinium macrocarpon) (DUAB®) in Preventing Low Urinary Tract Infection Recurrence in Women Complaining of Recurrent Cystitis*

Abstract

Objectives: The purpose of the study was to compare the efficacy of a product containing cranberry and propolis (DUAB) to placebo for reducing frequency of cystitis in women with recurrent acute cystitis.

Method: A multicenter, placebo-controlled, randomized study of women aged >18 years with at least 4 episodes of cystitis in the previous 12 months was performed. The number of cystitis episodes over a 6-month follow-up was the primary end point.

Results: Forty-two women were included in the cranberry + propolis group, and 43 women were in the placebo group. The mean age was 53 ± 18 years, with 6.2 ± 3.6 cystitis episodes in the previous year, with no differences between the 2 groups. The mean number of infections was lower in the propolis + cranberry group (respectively, 2.3 ± 1.8 vs. 3.1 ± 1.8). The total number of cystitis episodes in the first 3 months was lower in the propolis + cranberry group (0.7 ± 1.1 vs. 1.3 ± 1.1, p = 0.0257) after adjusting for water consumption. The mean time to onset of the first urinary tract infection (UTI) was also significantly longer in the propolis + cranberry group (69.9 ± 45.8 days vs. 43.3 ± 45.9, p = 0.0258). Tolerance to the treatments was good and comparable in both groups.

Conclusions: We demonstrate for the first time that cranberry and propolis supplementation significantly reduces the incidence of UTIs during the first 3 months and delays the onset of an episode of cystitis.

Source: Bruyère F, Azzouzi AR, Lavigne JP, Droupy S, Coloby P, Game X, Karsenty G, Issartel B, Ruffion A, Misrai V, Sotto A, Allaert FA. A Multicenter, Randomized, Placebo-Controlled Study Evaluating the Efficacy of a Combination of Propolis and Cranberry (Vaccinium macrocarpon) (DUAB®) in Preventing Low Urinary Tract Infection Recurrence in Women Complaining of Recurrent Cystitis. Urol Int. 2019;103(1):41-48. doi: 10.1159/000496695. Epub 2019 May 22. PMID: 31117097.

UT FIX

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

D-Mannose

Oral D-mannose in recurrent urinary tract infections in women: a pilot study*

Abstract

D-mannose: a promising support for acute urinary tract infections in women

Abstract

Why D-Mannose May Be as Efficient as Antibiotics in the Treatment of Acute Uncomplicated Lower Urinary Tract Infections—Preliminary Considerations and Conclusions from a Non-Interventional Study*

Abstract

Prebiotic properties of mannose and its effect on specific resistance*

Abstract

Vitamin D

Prevention and treatment of uncomplicated lower urinary tract infections in the era of increasing antimicrobial resistance—non-antibiotic approaches: a systematic review*

Vitamin D deficiency as a risk factor for urinary tract infection in women at reproductive age*

Vitamin D strengthens the bladder epithelial barrier by inducing tight junction proteins during E. coli urinary tract infection*

Abstract

Cranberry Fruit Extract 30% proanthocyanidin

Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial*

Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: A systematic review and meta-analysis with trial sequential analysis*

Abstract

High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial*

Abstract

Propolis

Propolis potentiates the effect of cranberry (Vaccinium macrocarpon) against the virulence of uropathogenic Escherichia coli*

Abstract

A Multicenter, Randomized, Placebo-Controlled Study Evaluating the Efficacy of a Combination of Propolis and Cranberry (Vaccinium macrocarpon) (DUAB®) in Preventing Low Urinary Tract Infection Recurrence in Women Complaining of Recurrent Cystitis*

Abstract

References: