McGuiness et al. Reasons for discontinuing the intervention and abandoning study are shown in Appendices 2 and 3. This research project was funded by the Ministry of Agriculture, Fisheries and Food of Quebec and Nutra Canada (now part of Diana Food Canada). Women less than 16 weeks pregnant were randomized into three groups: one consumed cranberries three times daily (n=58), another consumed cranberries only in the morning and then a placebo (n=67) and the third group consumed the placebo three times daily (n=63). Terris MK, Issa MM, Tacker JR. Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis. Clinical trials have been conducted to test the efficacy of cranberry products, mainly in the form of juices, but their results remain discordant [3]. Increasing resistance of pathogens to prescribed antibiotics, both in treatment and prophylaxis, as well as the side effects of antibiotics, reinforce the demand for alternatives that are effective and well tolerated [2]. We estimated that 15% of randomized participants would be lost to follow-up [15], therefore 148 women needed to be recruited in order for at least 126 participants to complete the 24-week intervention. Bacteriuria in 28.1% in placebo group and 15% in cranberry group (no significance). 2010;90(9):14738. These fimbriae bind to glycosphingolipids of the lipid double membrane of renal cells, which precedes renal parenchymal invasion (6). Jepson RG, Williams G, Craig JC. This randomized clinical trial is registered in ClinicalTrials.gov, identifier: NCT02572895. Using the current available data, the use of cranberries cannot be scientifically promoted for UTI prevention. Despite cranberry presentation, it is generally recommended to consume cranberries just prior or two hours after meals; it is also important to drink lots of water, mainly after preparations from dehydrated juices (11). Future studies should focus on PAC, the active compound in cranberries, instead of the whole fruit. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (218.5mg daily, n=72) or a control low dose (21mg daily, n=73) for a 24-week period. Correspondence to Bruschini H, Nicodemo AC and Srougi M provided revisions, additional aspects and details for the subject that were not present in the initial manuscript, along with contributions and article selection for table design. The only reported side effect, dyspepsia, led to a discontinuation of the intervention ofone participant in each group. Howell AB, Botto H, Combescure C, et al. Postgrad Med. Flavonoids are also aromatase inhibitors, which are crucial enzymes in estrogen biosynthesis. Secondary outcomes were symptomatic UTI with pyuria and symptomatic UTI with bacteriuria. Can J Urol. There are few studies assessing PAC excretion in humans (30,31). 1997;19(2):17986. J Nutr. Howell AB, Vorsa N, Der Marderosian A, Foo LY. The follow-up at six months did not determine a significantly longer UTI-free period in any of the regimens (46). Howell AB. The intake of 218.5mg PACs daily was associated with a non-statistically significant 24% reduction in the risk of symptomatic UTI compared to a daily dose of 21mg PACs during a 24-week follow-up period. 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 0.511.11). Asma B, Vicky L, Stephanie D, Yves D, Amy H, Sylvie D. Standardised high dose versus low dose cranberry Proanthocyanidin extracts for the prevention of recurrent urinary tract infection in healthy women [PACCANN]: a double blind randomised controlled trial protocol. Nutr J. A double-blind, randomized, placebo-controlled trial of cranberry supplements in multiple sclerosis. Despite data suggesting that PACs are the active moieties in cranberries, there is doubt regarding the route from ingestion through urinary excretion. Cookies policy. In women experiencing higher level of UTI (>5), certain factors that were not measured in our study could explain the mitigated response to PAC intake. No significant differences between the groups (, 305 patients with neurogenic bladder due to spinal cord injury, Group 1- methenamine hippurate (MH); 2- cranberry 800 mg; 3- MH + cranberry; and 4- placebo. Without adhesion, the bacteria cannot infect the mucosal surface. The number of patient withdrawals in most studies varied considerably, ranging from 0 to 55%. The All clinical investigation, laboratory analysis, data collection and assessment were blinded to the randomization allocation. The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation. Li et al. Data were obtained from women who presented themselves to the research facility in order to provide a urine sample in 70 out of 104 symptomatic UTI episodes. Li M, Andrew MA, Wang J, Salinger DH, Vicini P, Grady RW, et al. One important property of E. coli is its adherence to the host tissue. Women were recruited in the Laval University community in Quebec City, Canada, through e-mail list serves and local clinician referrals as well as posters in medical clinics, social media, paid advertising and word of mouth. PubMed Participants were asked if they were aware of which treatment group they were assigned to in order to validate the effectiveness of blinding procedures. The hazard ratio for the difference between the number of subjects who had experienced a first symptomatic UTI by the end of the 24-week period was 0.73 (95% CI 0.451.16; Fig. Compliance based on number of returned capsules at 24weeks was similar in both groups (92.9% in the high dose group vs 92.7% in the lowdose group, student t-test p=0.9). Oral Consumption of Cranberry Juice Cocktail Inhibits Molecular-Scale Adhesion of Clinical Uropathogenic Escherichia coli. [18]. Statistical analysis confirmed that number of recurrent UTI was indeed a modifying factor. IIHospital das Clnicas da Faculdade de Medicina da Universidade de So Paulo, Department of Infectious and Parasitic Diseases, So Paulo/SP, Brazil. 5-(3,4-Dihydroxyphenyl)--valerolactone and its sulphate conjugates, representative circulating metabolites of flavan-3-ols, exhibit anti-adhesive activity against uropathogenic Escherichia coli in bladder epithelial cell. Additionally, adherence to treatment was not high; some trials observed less than 80% adherence (13,53). Pathogenesis of urinary tract infection. There are some concerns about the potential for cranberries to cause thrombocytopenia and nephrolithiasis (58,59). Potential mechanisms of this interaction have included the salicylate content of the juice (68) and the presence of CYP enzyme-inhibiting flavonoids. [19] (1.13 /1year) or Stothers et al. National Library of Medicine No significant differences between groups regarding bacteriuria or symptomatic UTI. compared daily intake of 41mg PACs from cranberry juice cocktail compared to a placebo beverage on the incidence of symptomatic UTI during a 24-week follow-up. Cranberries have been tested for their clinical relevance in many different conditions. Article Am J Clin Nutr. In: Services NIoEiHaS, ed. Lewis AJ, Richards AC, Mulvey MA. Recurrent urinary tract infections remain challenging to treat because the main treatment option is long-term antibiotic prophylaxis; however, this poses a risk for the emergence of bacterial resistance. PubMedGoogle Scholar. Howell AB, Botto H, Combescure C, Blanc-Potard AB, Gausa L, Matsumoto T, et al. Among participants with less than 5 UTIs in the 12months preceding enrolment (n=97), the age-adjusted annualized incidence rate of UTI in the high dose group was 1.32 (95%CI 0.812.13) compared to 2.29 (95%CI 1.663.16) in the low-dose group (IRR=0.57, 95%CI 0.330.99) (Table 6). No statistically significant protective effect was observed for cranberry consumption in this population (49). This article reviews the key methods in using cranberries as a preventive measure for lower urinary tract infections, including in vitro studies and clinical trials. One study evaluated the use of cranberry juice to prevent UTIs during pregnancy (45). Google Scholar. (37) demonstrated that cranberry juice could decrease E. coli adhesion up to 8 hours after consumption. The control dose was standardized at 1% PACs which is comparable to the majority of cranberry products approved by Health Canada [8]. The protocol, consent form and all procedures were approved by the institutional ethics committee of Laval University. In the case of imbalanced groups, we generated relative rate estimates adjusted for potential confounding variables. In order to provide mechanistic insight explaining different levels of recurrence, feces and urine samples are being analysed and results will be published in a future article. Goulet J, Nadeau G, Lapointe A, Lamarche B, Lemieux S. Validity and reproducibility of an interviewer-administered food frequency questionnaire for healthy French-Canadian men and women. Some authors believe that intact PACs may not be active in vivo because they are too large to be absorbed as intact molecules in the gastrointestinal tract (27,28). 2010;10:94. Manage cookies/Do not sell my data we use in the preference centre. Caloric load in some formulations was also the cause of some withdrawals. 50 ml of cranberry-lingonberry juice (7.5 g of cranberries); 20% reduction in UTIs in cranberry group. The study coordinator obtained written informed consent from all study participants. Gettman MT, Ogan K, Brinkley LJ, Adams-Huet B, Pak CY, Pearle MS. Effect of cranberry juice consumption on urinary stone risk factors. Cranberry has been shown to inhibit the adhesion of uropathogenic Escherichia coli to uroepithelial cells [4]. Flavonoids, the major constituent of cranberries, have an established effect on the cytochrome P450 (CYP) drug-metabolizing enzyme. Symptomatic UTI incidences of 7.4% with placebo and 3.7% with cranberry (, 300 ml/day of cranberry juice and placebo. Foxman B, Barlow R, DArcy H, Gillespie B, Sobel JD. In vitro activity of cranberries against bacteria. Svanborg C, Godaly G. Bacterial virulence in urinary tract infection. 25 UTIs in the cranberry group and 14 in the trimethoprim group; relative risk 1.616, 188 pregnant women; gestation of <16 weeks, 240 mg of cranberry juice (27%) 3 times/day (group A) or 240 mg once daily (group B) or placebo (group C), Withdrawal rate of 38.8% (A 50.7%; B 39.7%; C 55.5%). 19 children withdrew. No differences for symptomatic UTIs comparing groups of intervention to placebo. 2). The in vitro anti-adherence effect of cranberries is dose-dependent (15,19,24,25). A study conducted by Vostavola et al. Ejrnaes K, Stegger M, Reisner A, et al. Schmidt DR, Sobota AE. Total PAC content of each treatment was validated at INAFs analytical laboratory using the 4-dimethylaminocinnamaldehyde (BL-DMAC) method [9] (Appendix 1). We also experienced technical issues such as delays in delivery to the microbiology laboratory and improperly stored samples. 1). Lee YL, Najm WI, Owens J, Thrupp L, Baron S, Shanbrom E, et al. Women with antibiotic treatment for symptomatic UTI during the study period continued to take the cranberry capsules and remained in the study for 24weeks. Evaluation of cranberry tablets for the prevention of urinary tract infections in spinal cord injured patients with neurogenic bladder. Terms and Conditions, Foo LY, Lu Y, Howell AB, Vorsa N. The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Recommended doses of dried, concentrated juice extract range from 600 to >1,200 mg/day (56) divided into two or three daily doses. Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study. By using this website, you agree to our Urinary tract infection (UTI) is one of the main reasons for emergency medical consultation. Di Martino P, Agniel R, David K, Templer C, Gaillard JL, Denys P, et al. The current hypothesis is that cranberries work principally by preventing the adhesion of type 1 and p-fimbriae strains (particularly from E. coli) to the urothelium (17-20). Women that discontinued the intervention were asked to present themselves at the 12 and 24-week visit to complete intention to treat analysis. Cowan CC, Hutchison C, Cole T, Barry SJ, Paul J, Reed NS, et al. Compliance according to daily intake journals was comparable in both groups, 87.3% in the high dose group and 88.8% in the lowdose group (Student t-test, p=0.6). We enrolled sexually active non-pregnant women aged 18years and over presenting with recurrent UTI as diagnosed by a physician (defined as2 UTIs in the past 6months or3 UTIs in the past 12months). Lee BB, Haran MJ, Hunt LM, Simpson JM, Marial O, Rutkowski SB, et al. Bacterial adhesion is accomplished by the binding of lectins exposed on the cell surfaces of these fimbriae to complementary carbohydrates on the host tissues. Springer Nature. Even for this indication, further clinical trials (double-blinded, randomized, placebo-controlled) displayed no differences between cranberry consumption and controls. No potential conflict of interest was reported. 2011;52(5):e10320. Our cohort had a higher mean incidence of UTI prior to study enrolment (mean UTI=2.4/6months and 3.9/1year) compared to similar trials such as Maki et al. Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. Data was entered electronically and original study forms will be kept locked at the study site and maintained in storage for a period of 25years after the completion of the study. FOIA Indeed, Escherichia coli (E. coli) account for most cases (2,3,5). The main protein structure related to this phenomenon is the adhesin protein, and its name is based on its shape: pili or fimbriae (2). Virulence. There were four UTIs and 23 cases of asymptomatic bacteriuria, but there was no significant difference with regard to the numbers of UTIs between the groups. A prospective, double-blinded, placebo-controlled, crossover study. Anti-microbial Activity of Urine after Ingestion of Cranberry: A Pilot Study. Cite this article. Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria. To evaluate UTIs and lower urinary tract symptoms in male and female patients undergoing radiotherapy treatment for bladder or cervical cancer, cranberry juice was administered twice daily for six weeks in a randomized, double-blind, placebo-controlled trial. In Brazil, the usual dose intake would cost between US $1,000 to $1,200 annually. Ofek I, Mirelman D, Sharon N. Adherence of Escherichia coli to human mucosal cells mediated by mannose receptors. They randomized patients with spinal cord injuries into two groups (i.e., 500 mg of cranberries or placebo). Phase 1, N=20 (16 women, 4 men); phase 2 (7 women, 2 men) N=9. For patients with IC, two randomized trials have been published, both in adults with spinal cord injuries. After 12 months, 24%, 43% and 38%, of the CB, Lactobacillus GG and control groups, respectively, had experienced at least 1 UTI. Over this time period, they observed UTIs in 18.5%, 42.3%, and 48.1% of the children in each group, respectively (p<0.05). The study with the largest number of participants (n=305) is made up of four different treatment groups (1- methenamine hippurate (MH); 2-cranberries 800 mg; 3-MH + cranberries; and 4-placebo). Foda MM, Middlebrook PF, Gatfield CT, Potvin G, Wells G, Schillinger JF. During their participation, women were asked to contact the study coordinator if they presented symptoms of UTI to schedule a visit at INAF in order to confirm the clinical diagnosis, provide a urine sample and receive an appropriate antibiotic prescription. BMC Fam Pract. This discrepancy is mainly explained by a lack of compliance, lack of statistical power and variable PAC concentrations in the tested products. Clin Infect Dis. Similarly, Maki et al. A total of 45 symptomatic UTIs were diagnosed in the high dose PAC group compared to 59 in the lowdose group. 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 0.330.99). However, the addition of vitamins C and E exert a stabilizing influence (57). Dudonn SVTV, Forato AF, Dub P, Roy D, Pilon G. Modulatory effects of a cranberry extract co-supplementation with Bacillus subtilis CU1 probiotic on phenolic compounds bioavailability and gut microbiota composition in high-fat diet-fed mice. The Poisson regression model was used to compare the incidence of symptomatic UTI during the 24-week follow-up. One study had 74 participants divided in two groups receiving either 2 g of cranberries or placebo. Bioactive compounds in cranberries and their role in prevention of urinary tract infections. Cranberry PACs were manufactured by Nutra Canada (now part of Diana Food Canada) and similar in size, smell and taste. However, a systematic evaluation of in vitro and in vivo interactions determined that cranberries could inhibit warfarin hydroxylation in vitro, but cranberry juice had no effect on warfarin clearance in vivo. Common preparations with cranberries include fresh, whole berries, gelatinized products, juices (usually 10-25% pure juice) and capsules (10-16). Accessed 24 Jan 2017. Moreover, urine cultures were incomplete for a proportion of urine samples provided by symptomatic participants. Cranberry products are the most promising natural health alternatives for the prevention of UTIs [3]. They conducted a six-month, randomized trial comparing a 50 ml daily cranberry-lingonberry juice to 100 ml, five days per month of Lactobacillus GG drink containing 4107 colony-forming units or placebo. 2010;11:78. Invasion of host cells and tissues by uropathogenic bacteria. In our study, pyuria was present in 81% and bacteriuria was confirmed in 49% of the urine samples provided by participants during symptomatic UTI. Urologic diseases in America project: trends in resource use for urinary tract infections in women. Uesawa Y, Mohri K. Effects of cranberry juice on nifedipine pharmacokinetics in rats. Spinal-injured neuropathic bladder antisepsis (SINBA) trial. No statistical difference was observed. Foda et al. A placebo-controlled study using volunteers found that cranberries increased sensitivity to the dynamic effects of warfarin. Side effects were evaluated at each visit and participants were asked to document symptoms in their daily journal.