The Use of Cranberry Juice to Prevent Minor Urinary Tract Infections - Article Example

 Introduction Alternative therapy through herbal medicines that block bacteria or cancer cells from adhering to their target cells, help prevent and treat a range of infections or cancers. The best studied and most well-known anti-adhesion herb is Cranberry, scientifically termed as Vaccinium macrocarpon. It has been shown to be useful in the prevention of urinary-tract infection in some patients (Yarnell & Abascal, 2008: 139). Urinary Tract Infection (UTI) is due to an inflammatory process in the bladder or kidneys caused by invasion of the tissues by micro-organisms (Wilson & Jenner, 2006: 215). Thesis Statement: The purpose of this paper is to systematically review five research papers, and to determine whether Cranberry juice can be used effectively in the prevention of urinary tract infections. Discussion Cranberry, Vaccinium macrocarpon is an Ericaceae family herb which contains proanthocyanidins which block the adhesion of Escherichia coli to human urothelium (Sen & Bagchi, 2001: 216) by the inhibition of bacterial cell wall synthesis and expression of adhesion molecules (Scalbert, 1991: 3875). Literature Review The diversity of microbial activity in medicinal herbs provides a therapeutic approach not available in antibiotic drugs, although the immediate curative results obtained from antibiotics are not experienced from cranberry (Yarnell & Abascal, 2008: 139). Sobota (1984) found from their research that undiluted fresh juice was most effective in the inhibition of E. coli bacterial adherence to buccal and uroepithelial cells. Similarly, Schmidt & Sobota (1988) discovered that cranberry juice could inhibit bacterial adherence of nonurinary E. coli isolates and Pseudomonas. Cranberry concentrate caused inhibition of P-fimbria (Ahuja et al, 1998), and proanthocyanidins are the compounds in cranberries that prevent uropathogenic Pfimbriated E. coli from adhering to the urinary tract (Howell et al, 1998). However, cranberry concentrate did not alter the frequency of urinary tract infection or bacteruria in children with neurogenic bladder treated with intermittent catheterization (Schlager et al, 1999). Haverkorn & Mandigers (1994) found that among seven hospitalized patients available for evaluation while awaiting transfer to a nursing home, fewer cases of bacteruria occurred when cranberry juice was consumed. Similarly, evidence from the research study conducted by Avorn et al (1994) on 153 nursing home patients, revealed that the consumption of 300 ml. of cranberry juice cocktail reduced the incidence of bacteruria from 28% to 15%. Moreover, the regular drinking of cranberry juice was proved to be protective against urinary tract infections in sexually active women, after adjusting for frequency of vaginal intercourse (Foxman et al, 1995). Research Methodology: Inclusion/ Exclusion Criteria and Databases Used A search was conducted to find five articles for review, based on the use of cranberries, in the form of juice or other products in the prevention and treatment of urinary tract infection. The key words used in the search were cranberry + cranberry juice + urinary tract infection. No exclusion key words were used. The main databases used in the search for research studies on the topic, were: Ebscohost, CINAHL, Highwire Press BMJ Publishing Group and PubMed Central. REVIEW OF FIVE RESEARCH ARTICLES Article 1. “Randomised Trial of Cranberry-Lingonberry Juice and Lactobacillus GG Drink for the Prevention of Urinary Tract Infections in Women” by Kontiokari et al (2001) The title of this randomized controlled trial is concise, including almost all the important elements except the control group used. The Abstract summarizes the comparative study between cranberry-lingonberry juice and Lactobacillus GG drink, with respect to the purpose of the study, the methods used and the findings. Sufficient information was provided to invoke interest in the topic of study. Some important factors that were not mentioned in the abstract including the frequency of sexual activity, and previous urinary tract diseases in the research sample. In the Introduction the research problem was clearly identified: whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. The problem of UTI particularly in women is serious, since up to 60% of women have a urinary tract infection at some time. The most important risk factor for UTI is sexual activity. The theoretical rationale for the study is that prevention of UTI is crucial because once the disease establishes itself, it recurs repeatedly in most affected women. Recurrences call for long-term antimicrobial prophylaxis. However, increasing antimicrobial resistance indicates the need for alternative therapies. This conceptual framework and the research problem are in alignment with the authors’ hypothesis, and guide the research study (Kontiokari et al, 2001: 1). Method: The 150 women of an average age of 30 years, who were invited to participate in the study had a urinary tract infection caused by Escherichia coli, with its occurrence as more than 105 colony forming units per ml, in clean voided midstream urine. The participants were not taking anti-microbial prophylaxis. After giving informed consent, they were randomly allocated to three groups. The first group received 50 ml of cranberry-lingonberry juice concentrate per day for six months; the second group received 100 ml of Lactobacillus GG drink five days a week for one year, and the third group served as an open control group (Kontiokari et al, 2001: 1). The instruments described seem appropriate as measures of the variables under study. The first urinary tract infection, the index, was treated with standard anti-microbials. Women had to provide a urine sample clear of microbial growth three or more days after treatment, before follow-up. Questionnaires and self-report sheets were used. Whenever a participant had symptoms of UTI, a clean voided midstream urine sample was obtained for culture, and the analyses were performed. Sufficient information about the psychometric properties, the reliability and validity of the instruments, as well as the scientifically designed procedure are included. Results: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups. At six months, eight (16%) women in the cranberry group, nineteen (39%) in the lactobacillus group, and eighteen (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (Kontiokari et al, 2001: 1). The data coding and analysis are appropriate with regard to study design and hypothesis. The salient result, stating that cranberry juice can prevent urinary tract infections, is connected directly to the hypotheses. The Discussion and Conclusion reveal that the regular drinking of cranberry juice, but not lactobacillus seems to reduce the recurrence of urinary tract infection (Kontiokari et al, 2001: 1). The limitations of the study are clearly delineated, and the findings are discussed in depth. Future research should focus on the use of cranberry products such as capsules and tablets, for effectively reducing UTI. The references are sufficiently comprehensive, mostly within the last ten years. Bibliographic citations are used appropriately, using the Vancouver style numbering system for in-text citation given in superscript. General Impressions: The most important feature about this article is its emphasis on detail in methodology for optimizing the validity of the findings. The most compelling strengths of this study is that the open, randomized, controlled, 12-month follow-up trial is comprehensive and employs a large sample of research subjects. This study might be improved, by using only cranberry juice as one of the alternatives. Article 2. “A Randomized Trial to Evaluate Effectiveness and Cost Effectiveness of Naturopathic Cranberry Products as Prophylaxis Against Urinary Tract Infection in Women” by Stothers (2002) The title of the article has concisely described the key elements of the randomized, double blind controlled trial. The abstract systematically presents the purpose of the study, materials and methods, results and conclusions drawn from the research, and creates interest in the article. The dependent variable in the study are the cranberry products, and the independent variable is the effectiveness of the treatment in preventing UTI. In the Introduction, the hypothesis, the research question and the methodology of the research study are clearly stated. Cranberries are commonly believed to be effective in preventing and treating urinary tract infections (UTIs), and are one of the most commonly used herbal remedies (Jepson & Mihaljevik, 2004: 1). However, the evidence endorsing the use of cranberries in the prevention of UTI has not been strong. The author’s hypothesis is that patients receiving tablets of cranberry extract would experience a mean of at least 50% fewer UTIs. The method was a random one year study, with 150 sexually active women who provided informed consent, aged 21 through 72 years, divided into three groups of prophylaxis; placebo juice + placebo tablets versus placebo juice + cranberry tablets, versus cranberry juice + placebo tablets. Tablets were taken twice daily, and juice 250 ml three times daily. The outcome measures were scientifically calculated. The cost effectiveness was calculated as dollar cost per UTI prevented. Specific clinical scenarios for cost savings were identified. During the 12 months’ protocol, symptoms of lower UTI were treated with a culture-specific prescription of antibiotics for 3 days, and then prophylaxis was restarted. Compliance as well as side effects were monitored (Stothers, 2002: 1559). The results indicate that both cranberry juice and cranberry tablets decreased in a statistically significant manner the number of patients experiencing at least one symptomatic Urinary Tract Infection (UTI) each year, respectively reduced to 20% and 18%, as compared with placebo which was reduced to 32%. The greatest cost savings occurred when patients experienced > 2 symptomatic UTIs per year, assuming 3 days antibiotic coverage, and had > 2 days of missed work, or required protective undergarments for urgency incontinence. As compared to placebo, total antibiotic consumption was less annually in both the treatment groups. Cranberry tablets were twice as cost effective as organic juice for prevention (Stothers, 2002: 1559). The graph depicting compliance with treatment regimens is non-duplicative of the text. Discussion and Conclusion on the results of this study indicate that cranberries are an effective means of preventing urinary tract infections in women who experience recurrent UTIs. The authors found that only 19% women experienced UTIs when treated with cranberry juice, whereas 32% of women were affected by UTIs when receiving placebo juice. The 40% fewer women in the former group who experienced UTI, had only half the number of UTIs per year. Further, there was also a decrease in UTI in the placebo group as compared to the previous year, due to the increased volume of liquid consumed in the placebo juice (Stothers, 2002: 1562). Low-level prophylactic antibiotic regimens are effective for women with recurrent UTIs. However, there is growing evidence of increasing reports of antibiotic resistant strains (Bennett & Brown, 2000: 349). Since cranberry juice is not specific to any particular bacterial strain, and does not create resistance, it is preferable to antibiotics. The authors conclude that cranberry juice, and cranberry tablets with increased fluid intake are more effective than fluid intake alone in preventing recurrent UTI in sexually active women. Contrastingly, other research studies have demonstrated that the use of cranberry products such as capsules or tablets have not resulted in reduction of UTI (McGuiness et al, 2002: 4; Linsenmeyer et al, 2004: 29; Lee et al, 2006: 1 & Waites et al, 2004: 35). The compelling strength of this study is the large study sample with three prophylactic groups, for higher validity of results. Article 3. “Consumption of Sweetened Dried Cranberries Versus Unsweetened Raisins for Inhibition of Uropathogenic Escerichia coli Adhesion in Human Urine: A Pilot Study” by Greenberg et al (2005) The title describes the study comprehensively and concisely, using all the key words. The Abstract has a structured summary of the study’s purpose, methods and findings, and invokes interest towards reading the article. The dependent variables in the study are sweetened dried cranberries and unsweetened raisins, while the independent variable is the extent to which uropathogenic Escherichia coli is observed in human urine, due to inhibition of adhesion in the urinary tract. Introduction: Major findings from earlier studies such as that by Kontiokari et al (2001), Stothers (2002), and Howell et al (1998) have been cited. Greenberg et al (2005: 877) state that bacteria including E. coli have different types of adhesins on their pili or fimbriae that allow the organism to adhere to epithelial cells and proliferate. The proanthocyanidins (PACs), inhibit the mannose-resistant (P-fimbriated) adhesins found in strains of E. coli and other types of bacteria (Howell et al, 1998: 1085). Thus, in vitro cranberry juice inhibits bacterial adhesion to uroepithelium. Treatment with antibiotics for recurrent UTI results in the bacterial strain becoming immune to the antibiotic; hence alternative treatment with cranberries is more effective. Method: The research sample in this pilot study consisted of five subjects with culture-confirmed UTI, and four urine samples were collected from each. Before enrolment in the research study, all the subjects were treated with appropriate antibiotics for their infections. E. coli isolates were incubated separately in each of the four samples from each subject. Bacteria were harvested from the urine and tested for the ability to prevent adhesion of P-fimbriated E. coli bacteria using a mannose-resistant hemagglutination assay with human red blood cells (Foo et al, 2000: 173). Bacterial antiadhesion activity was scored microscopically on a 0% to 100% adhesion inhibition scale, which has been used in other bacterial antiadhesion studies involving urine (Howell & Foxman, 2002 & Howell et al, 2005). Activity was recorded as the percentage of antiadhesion activity detected for each undiluted urine sample, with 100% being equal to complete adhesion inhibition, and 0% being equal to no antiadhesion activity (Greenberg et al, 2005: 875). A drawback is that the study sample is small, and the results are briefly stated, with insufficient information about the psychometric properties such as reliability and validity of the instruments. However, the materials used and the scientific procedure is clearly and chronologically described, facilitating future replication of the study. Results: Of the original offending E. coli isolated, only one strain demonstrated P-fimbriation. One of the urine samples collected after dried cranberry consumption demonstrated 50% antiadherence activity, two demonstrated 25% activity, and two did not show any increased activity. None of the control urine samples or the post-raisin consumption samples demonstrated any inhibitory activity (Greenberg et al, 2005: 877). The data coding and analysis is appropriate in view of the study’s design and hypothesis, which relate directly to the results. The Table depicting the effects of dried cranberries and raisins on adherence of Escherichia coli endorses the text. Discussion and Conclusion: Due to the increasing prevalence of antibiotic-resistant bacteria, prevention is considered to be more important, as compared to cure. Urine pH was found to be only marginally affected after subjects consumed up to 4 litres of cranberry juice cocktail daily (Bodel et al, 1959: 881), the quantities of cranberry juice needed to lower urine pH significantly were well beyond normally consumed volumes. Hence, the previous hypothesis of acidification caused by cranberries bringing about reduction of UTI was eliminated (Greenberg et al, 2005: 876). The complete absence of data on dried cranberries was addressed by this pilot study. It was found that consumption of a single serving of dried cranberries may elicit bacterial antiadhesion activity in human urine similar to that of a single serving of cranberry juice cocktail. Future studies should investigate the dose-response and pharmacokinetics of the active compounds in sweetened and unsweetened dried cranberries. “Consumption of dried cranberries is considered to be a viable alternative to cranberry juice for prevention of UTI” (Greenberg et al, 2005: 877). The references list is sufficiently comprehensive and current, most of the resources being from the last ten years. Bibliographic citations are used appropriately in the text. General Impressions: The article is well structured and organised. Since it was found that dried cranberries are as effective as the juice in reducing the infection, the product can be procured in larger quantities, preserved, transported and used, without decline in the quality of the product. This study may be improved by including a wider sample, with a greater number of subjects, as well as a group that is given a placebo. Article 4. “Effect of Ingesting Cranberry Juice on Bacterial Growth in Urine” by Tong et al (2006) The title describes the study concisely, without extraneous words. The abstract summarised the purpose of the study, to investigate whether cranberry juice has antibacterial effects in urine. Acidification was excluded as a possible antibacterial factor. Evidence from several clinical trials, such as those reviewed above, indicates that cranberry juice has a significant effect in preventing urinary tract infections (UTIs), inhibiting bacterial adherence to cells (Howell, 2002: 273; Zafriri et al, 1989: 92). Introduction: The authors presented a theoretical rationale for the study. The dependent variable in this research study is cranberry juice ingestion, and the independent variable is bacterial growth in urine. Literature on cranberry juice’s antibacterial activity in urine is inadequate. In a preliminary study by Lee et al (2000: 1691), which found that concentrated cranberry juice has some antibacterial activity, cranberry juice was studied, not the resultant urine samples. The research method describes the size of the sample, selection, assignment procedures, and method of study. Ten young, healthy Chinese adult volunteers were recruited, five men and five women, of an average age, height and weight and their informed consent was obtained. The subjects had free access to food and water, but drugs and health supplements were not allowed for one week before and during the study. Subjects were on their own controls. At a particular time on the first day they drank 750 ml of distilled water, and at the same time on the second day they drank 750 ml of 100% cranberry juice. On both days midstream urine samples were collected at 3-hour intervals, except for the period between 15 to 21 hours, and stored at -20 degrees Centigrade. Total urine volume was also recorded (Tong et al, 2006: 1417). The instruments are appropriate for measuring the variables which were studied, and are reliable and valid. However, small sample size and lack of randomization, are some of the deficiencies in the research study. Urinary acidification was not considered as the main factor responsible for cranberry juice’s effects on UTIs (Raz et al, 2004: 1413; Howell, 2002: 273). Bacterial growth may be influenced by lowered urinary pH. Hence, the authors adjusted the urine samples to a fixed pH value to eliminate this potential confounding variable. The samples were divided into two portions, half were inoculated with Escherichia coli, and stored at 370C. After incubation, colony counts were performed. The results section is clearly structured and written. “The lag phases for water and cranberry juice treatments were approximately two hours, and did not differ significantly between the two groups” (Tong et al, 2006: 1418). For all the subjects’ samples, there was good linearity of bacterial growth. Statistically significant differences were not observed in rate constants between the water and cranberry juice groups. The data coding and analysis are appropriate to the study’s design and hypothesis. The salient results are connected directly to the hypothesis, and the data tables support the text. Discussion and Conclusion: “When bacteria are transferred from one medium to another, where chemical differences exist between the two media, there is typically a lag in cell division” (Tong et al, 2006: 1418). A lag phase of physiological adaptation of around two hours was observed in the E. coli growth curve in pH-adjusted monosodium urate (MSU) samples. No difference was observed in the lag phases of the study samples between the cranberry juice and control groups. In the subsequent logarithmic phase, the cell number multiplies at a logarithmic rate determined by the conditions of the medium and the culture (Sleigh & Timbury, 1994). A similar growth constant was observed after water and cranberry juice ingestion. The evidence indicates that the adaptation and cell division of E. coli in urine are the same after consumption of water or cranberry juice. Thus, the urine collected after ingestion of cranberry juice does not appear to have bactericidal or bacteriostatic activities against E. coli (Tong et al, 2006: 1418). It is evident that the use of cranberry juice is not feasible for the treatment of UTIs. The limitation of the study is the small sample size. References: Most of the sources are from the last nine years. The works cited are comprehensive, to reflect the existing literature on the topic, and in-text citations are used appropriately throughout the text. General Impressions: The article is clearly structured; and confirms the non-effectiveness of cranberry juice in the treatment of UTI. The significant finding is that alternative herbal therapy has its limitations, especially in preventing or treating more severe cases of urinary tract infections. Using larger research samples in randomized controlled trials in future would strengthen the validity of the results. Article 5. “Inhibitory Activity of Cranberry Juice on Adherence of Type 1 and Type P Fimbriated Escherichia coli to Eucaryotic Cells” by Zafriri et al (1989) The title of the article describes the study clearly using all the relevant key words Abstract: The abstract comprehensively summarises the study’s purpose, methods and findings, evoking interest towards reading the article. The dependent variable in the study is the inhibitory activity of cranberry juice, the independent variable is the adherence of Type 1 and Type P Fimbriated E. coli to eucaryotic cells; and cranberry juice cocktail is used as another dependent variable in the study. Introduction: Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (Sobota, 1984: 1013). The authors Zafriri et al (1989) have investigated the effect of the cocktail containing cranberry juice and the cranberry juice alone, on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. The research problem has been clearly identified and stated. Bacterial adhesion to mucosal cells is an important step forward in the development of infection (Beachey, 1981: 325). This has been supported by research evidence in urinary tract infections (Kunin, 1987: 140; Reid & Sobel, 1987: 470). Since the adherence of many bacterial species to epithelial cells is mediated by lectin-sugar interactions, the consumption of foods containing lectins or carbohydrates might affect the infection process (Gibbons & Dankers, 1983: 561). The authors’ (Zafriri et al, 1989) hypothesis and research question are logical in the context of the conceptual framework and research problem; and clearly define the purpose of the study. Method: Cranberry juice cocktail inhibited the adherence of urinary isolates expressing Type 1 fimbriae and Type P fimbriae. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria (Zafriri et al, 1989: 92). Results: Fructose is absorbed more slowly than glucose in the alimentary tract. Thus, since fructose is present in the cocktail at levels that are at least ten times higher than those required for the inhibition of Type 1 fimbriated E. coli, inhibitory levels of the sugar may be attained in the colon, where most E. coli reside (Zafriri et al, 1989: 92). Discussion and Conclusion: A diet rich in fructose may result in secretion of fructose in the urine. The authors (Zafriri et al, 1989: 92) conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies should investigate whether these inhibitors play a role in vivo. Another possibility is that drinking cranberry juice cocktail may affect the urinary concentrations of Tamm-Horsfall glycoprotein, which is known to interfere with the adherence of type 1 E. coli to human kidney cells (Dulawa et al, 1988: 87). The authors (Zafriri et al, 1989: 92) have included information about the psychometric properties such as reliability and validity of the instruments used for measuring the variables. The study design and procedures are thoroughly described and are appropriate to the research problem, conceptual framework, and research questions. The salient results are connected directly to the hypothesis. The tables and figures are clearly labeled, support the article, and are not duplicative of the text. References: The reference list of the article is comprehensive, including articles from the last few years and a few works from the last three to four decades. General Impressions: The study addresses the important problem of inhibition of bacterial adhesion to bladder cells being considered accountable for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections. The article has advanced new evidence for the prevention of urinary tract infections, with the help of cranberry juice and cranberry juice cocktails. Conclusion This paper has highlighted the use of Cranberry juice to prevent minor Urinary Tract Infections (UTI). Research and clinical testing suggest that the juice may be more useful in prevention rather than in the treatment of UTI. This is because cranberries do not have potent direct toxicity to bacterial cells and antiadhesive effects are not likely to be of much help in infections that are already established. Cranberry exerts bacteriostatic effects by reducing bacterial adhesion to host tissues (Braun & Cohen, 2007: 266). The clinical evidence suggests that the use of cranberry cocktails, dried and sweetened cranberries, and tablets/ capsules with water intake are effective in preventing UTI. However, drinking cranberry juice 10 or more ounces per day gives optimal results. Further, using the tablet or capsule form of cranberry extract may result in adverse side effects such as raising urinary oxalate levels (Freeman, 2004: 449). --------------------------------------- References Ahuja, S., Kaack, B. & Roberts, J. (1998). Loss of fimbrial adhesion with the addition of vaccinum macrocarpon to the growth medium of P-fimbriated Escherichia coli. Journal of Urology, 159: 559-562. Avorn, J., Monane, M., Gurwitz, J.H., Glynn, R.J., Choodnovsky, I, & Lipsitz, L.A. (1994). Reduction of bacteruria and pyuria after ingestion of cranberry juice. Journal of the American Medical Association (JAMA), 271 (10): 751-754. Beachey, E.H. 1981. Bacterial adherence: adhesin-receptor interactions mediating the attachment of bacteria to mucosal surfaces. Journal of Infectious Diseases, 143: 325-345. Bennett, J. & Brown, C.M. (2000). Use of herbal remedies by patients in a health maintenance organization. Journal of the American Pharmacists’ Association, 40 (3): 349-351. 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Alternative and Complementary Therapies, 14 (3): 139-144. Zafriri, D., Ofek, I., Adar R., Pocino, M. & Sharon, N. (1989). Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherischia coli to eucaryotic cells. Antimicrobial Agents and Chemotherapy, 33: 92-98. Read More