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By Lynn Keegan, RN, PhD, HNC, FAAN
Women frequently use cranberry juice and the extract from the ripe fruit (Vaccinium macrocarpon) to prevent and treat urinary tract infections (UTIs). The pilgrims first learned about cranberries from Native Americans whose folklore told of the benefits of ingesting cranberries for symptomatic relief of UTIs. Attempts to scientifically validate this lore have produced conflicting results.
Etiology and Prevalence of Urinary Tract Infections
The bacteria Escherichia coli is responsible for up to 90% of UTIs. Staphylococcus saprophyticus is the second major bacterial organism, causing 5-15% of cases in women. Other less common culprits include enteric gram-negative organisms such as Klebsiella, Proteus mirabilis, Ureaplasma urealyticum, and Enterococci. In most UTI cases, E. coli, which originates as a harmless microorganism in the intestines, spreads to the vaginal passage and then invades and colonizes the urinary tract. It is estimated that 25% of women have at least one UTI in their lifetime and others may have many more.1 More than seven million Americans visit physicians’ offices for UTIs each year.2
Five strategies are either presently advocated or under investigation for prevention and treatment of recurrent UTIs: antibiotics, including natural peptides; functional foods (i.e., cranberries); vaccines; probiotics; and miscellaneous, including avoidance of spermicides and maintenance of good hygiene.
The majority of women referred to specialists are prescribed long-term, low-dose antibiotics. However, given the magnitude of this problem, it is safe to state that large numbers of women are experimenting with alternative remedies such as drinking cranberry juice or ingesting herbal remedies to enhance their immune response. Vaccine development remains a long way from human use and has yet to be developed for organisms other than E. coli. The use of probiotics to restore the normal vaginal flora and provide a competitive bacterial barrier to pathogens is advocated by many as an alternative prevention approach.3
Mechanism of Action
In the 1920s, American scientists thought that cranberry juice acidified the urine. Cranberry extracts and juices contain hippuric acid, which during the 1920s was thought to exert a potent antibacterial effect against UTIs since bacteria prefer an alkaline pH for growth.4 However, in a 1984 study, Sobota et al showed that cranberry prevents the adhesion of E. coli to the bladder epithelium, thus making it easier to wash bacteria out with the urine.5 Two different constituents of cranberries inhibit E. coli adhesion: Fructose inhibits the type 1 fimbrial adhesion and proanthocyanidins seem to inhibit the P fimbrial adhesion of uropathogenic strains.6
Cranberry Juice Inhibits Bacterial Adherence
Attempts to account for the potential benefit derived from cranberry juice have focused on urine acidification and bacteriostasis. In the study mentioned above, Sobota demonstrated that cranberry juice is a potent inhibitor of bacterial adherence.5 Seventy-seven clinical isolates of E. coli were tested. Cranberry juice inhibited adherence by at least 75% in more than 60% of the clinical isolates. Cranberry cocktail was also given to mice in place of their normal water supply for a 14-day period. Urine collected from these mice inhibited adherence of E. coli to uroepithelial cells by approximately 80%. Anti-adherence activity could also be detected in human urine. Fifteen of 22 subjects showed significant anti-adherence activity in the urine one to three hours after drinking 15 oz of cranberry cocktail.
In a follow-up study based on Sobota’s results, researchers examined the effect of cranberry cocktail and juice on the adherence of E. coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macro-phages.7 Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae, but had no effect on a diarrheal isolate expressing a CFA/I adhesion. 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 in the cocktail; this sugar was about 10% as active as methyl a-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry, orange, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. The conclusion is that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells.
A six-month study in elderly women suggests that drinking 300 ml/d of cranberry juice cocktail reduced bacterial infections (bacteriuria) and associated influx of white blood cells into the urine (pyuria) by nearly 50%.8 This study showed that consumption of cranberry juice is more effective in treating than preventing bacteriuria and pyuria. Along with earlier reports on the ability of cranberry juice to inhibit bacterial adherence to urinary epithelial cells in cell culture, this work found that drinking cranberry juice each day is clinically useful.
In the Program for the Analysis of Clinical Strategies, Brigham and Women’s Hospital researchers sought to determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women.9 In a randomized, double-blind, placebo-controlled trial, a volunteer sample of 153 women (mean age, 78.5 years) were randomly assigned to one of two groups. They either consumed 300 ml/d of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content. A baseline urine sample and six clean-voided urine samples were collected at approximately one-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells. Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering ³ 105/ml) with pyuria that were only 42% of the odds in the control group (P = 0.004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P = 0.006). These findings suggest that ingestion of cranberry beverage reduced the frequency of bacteriuria with pyuria in older women.
The Cochrane Renal Group, a subset of the Cochrane Database System Review Company in Edinburgh, UK, developed a search strategy to assess the effectiveness of cranberries for the treatment of UTIs.10 Companies involved with the promotion and distribution of cranberry preparations were contacted; electronic databases and the Internet were searched using English and non-English language terms; and reference lists of review articles and relevant trials were also searched. The selection criteria included all randomized or quasi-randomized controlled trials of cranberry juice or cranberry products for the treatment of UTIs. Trials of men, women, and children were included. Reviewers independently assessed whether the studies met the inclusion criteria. Further information was sought from the authors of papers containing insufficient information to make a decision about eligibility. The reviewers’ found no trials that fulfilled all of the inclusion criteria and concluded that no well-designed randomized trials assessing the effectiveness of cranberry juice for the treatment of UTIs have been conducted.
In a second Cochrane investigation on UTI prevention, a small number of poor quality trials gave no reliable evidence of the effectiveness of cranberry juice and other cranberry products.11 The large number of dropouts/withdrawals indicated that cranberry juice may not be acceptable long-term. Other cranberry products, such as cranberry capsules, may be more acceptable. On the basis of the available evidence, the researchers could not recommend cranberry juice for the prevention of UTIs in susceptible populations.
The use of cranberries has also been tried in other groups. One study examined the effect of cranberry prophylaxis on rates of bacteriuria and symptomatic UTI in children with neurogenic bladder receiving clean intermittent catheterization.12 The double-blind, placebo-controlled, crossover study included 15 children who received cranberry concentrate or placebo concentrate for six months (three months receiving one concentrate, followed by three months of the other). During each weekly home visit, a sample of bladder urine was obtained by intermittent catheterization. Signs and symptoms of UTI, medication usage, and juice consumption were recorded. During consumption of cranberry concentrate, the frequency of bacteriuria remained high. Of the 151 samples obtained during consumption of placebo, 75% (114) were positive for a pathogen (³ 104 colony-forming units/ml) compared with 75% (120) of the 160 samples obtained during consumption of cranberry concentrate. E. coli remained the most common pathogen during placebo and cranberry periods. Three symptomatic infections each occurred during the placebo and cranberry periods. No significant difference was observed in the acidification of urine in the placebo group vs. the cranberry group (median, 5.5 and 6.0, respectively). The frequency of bacteriuria in patients with neurogenic bladder receiving intermittent catheterization was 70% and cranberry concentrate had no effect on bacteriuria in this population.
In another study, seven juices (cranberry, blueberry, grapefruit, guava, mango, orange, and pineapple) were examined; only cranberry and blueberry prevented bacterial bladder adhesion.13 Although blueberries have not been as thoroughly studied as cranberries, they also may prove to be an alternative treatment for UTI.
Conclusion and Recommendation
Cranberry juice and extract have biologic effects against bacterial adhesion in the bladder. No significant adverse effects have been noted in this long-used folk remedy that is both safe and well tolerated. For those concerned about the high sugar content of cranberry juice, oral capsule extracts are an available option.
To assess cranberry juice’s effectiveness in treating UTIs, well-designed, parallel-group, double-blind trials comparing cranberry juice and other cranberry products vs. placebo are needed. Outcomes should include reduction in symptoms, sterilization of the urine, side effects, and adherence to therapy. Dosage (amount and concentration) and duration of therapy should also be assessed. This area is ripe for more investigation by inquisitive holistic nurse researchers. Studies could relate to dose intake, use of cranberry products in control and experimental groups combined with antibiotics, or contrasting and comparing the effects of cranberry in children, adults, and the elderly.
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