Abstract & Commentary

Cranberry Juice Prophylaxis for UTIs: A Reason for Skepticism?

By Hal B. Jenson, MD, FAAP, Chief Academic Officer, Baystate Health, Springfield, MA; Professor of Pediatrics and Dean of the Western Campus of Tufts University School of Medicine, is Associate Editor for Infectious Disease Alert.

Dr. Jenson reports no financial relationships relevant to this field of study.

Synopsis: Cranberry juice was no better than placebo in preventing recurrent urinary tract infection in young women.

Source: Barbosa-Cesnik C, et al. Cranberry juice fails to prevent recurrent urinary tract infection: Results from a randomized placebo-controlled trial. Clin Infect Dis. 2011;52:23-30.

Recurrent urinary tract infections (UTI) in females is a common and distressing clinical problem. One commonly recommended intervention is attempted prophylaxis by regular ingestion of cranberry juice or other forms of cranberry, including tablets and extracts sold at health-food stores. The efficacy of this approach, however, has now been drawn into question.

Barbosa-Cesnik and colleagues at the University of Michigan randomized women 10-40 years of age with symptoms suggestive of uncomplicated UTI to receive, after treatment of their infection, cranberry juice or placebo for up to 6 months in a double-blind study. The primary endpoint of the study was the development of UTI occurring > 15 days after enrollment or, if < 15 days after enrollment, infection with an organism other than the index infection. Patients were re-evaluated at the time of recurrence or development of urinary tract symptoms and at visits 3 and 6 months after enrollment.

The cranberry juice was formulated to research standards and contained proanthocyanidin, which has been suggested to be the active component in preventing the adherence of Escherichia coli to uroepithelial cells, in a mean concentration of 112 mg per dose. The placebo was formulated to mimic the color and taste of cranberry juice. Both the test material and the placebo were sweetened with sucralose, and both contained ascorbic acid. Participants were to ingest 8 oz of their assigned product twice daily. Compliance was monitored by self-report. The study was designed to have an 80% power to detect a two-fold difference between groups using a two-sided test of significance and assuming a 30% incidence of UTI.

A total of 319 patients were randomized, but only 230 completed the entire protocol. All but 1% of the study subjects had a history of recurrent UTI. The rate of infection recurrence proved to be less than had been anticipated. The difference in infection incidence between groups was not statistically significant, with rates of 19.3% and 14.6% in the cranberry and placebo groups, respectively (p = .21, by log-rank test). Gastrointestinal complaints occurred twice as frequently in the cranberry juice recipients

Commentary

Cranberry juice contains a complex array of compounds, including polyphenolic antioxidants, one of which, proanthocyanidin, may account for the ability to inhibit adherence of E. coli to uroepithelial cells, and whose concentration in the whole juice was regulated in this trial. While widely used for prophylaxis of recurrent UTI in women, the evidence for its efficacy in this regard may be considered less than definitive. A 2008 Cochrane meta-analysis of available trials did conclude that "There is some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12-month period, particularly for women with recurrent UTIs. Its effectiveness for other groups is less certain."1 Of note, the analysts discarded from consideration 6 of 10 randomized trials because of methodological considerations and, of the remaining four, only one individual trial demonstrated a statistically significant benefit favoring cranberry prophylaxis. They further warned that "the large number of dropouts/withdrawals indicates that cranberry juice may not be acceptable over long periods of time. It is not clear what is the optimum dosage or method of administration (e.g. juice, tablets or capsules)."

In addition to gastrointestinal intolerance, a number of other potential downsides to cranberry juice prophylaxis must be considered, including weight gain (8 ounces of Ocean Spray cranberry juice contains 128 calories, but tablets contain minimal calories), possible increased risk of nephrolithiasis secondary to modest urinary acidification, and a potential pharmacokinetic interaction with warfarin.

In the study by Barbosa-Cesnik et al, the observed incidence of infection in the placebo group was lower than expected, a result that reduced the expected power of the analysis.

The authors also point out another potential problem in that both the cranberry juice and the placebo contained ascorbic acid (although the amount is not stated), but commercially available Ocean Spray cranberry juice is reported to contain 68 mg in an 8-ounce serving. In a small single-blind trial in which its prophylactic efficacy in pregnancy was examined, a daily dose of 100 mg of ascorbic acid was associated with a significant reduction in the incidence of UTI.2 Reproduction of these results in a larger, better-designed study would be welcome but, until this is done, its result must be viewed with skepticism.

The use of probiotics has been suggested as a potential means of preventing UTI recurrence, but a recent review concluded that there was no evidence that lactobacillus-containing products were effective in this regard.3 Based on limited evidence, estrogens topically applied to the vagina may have a modest effect in UTI prevention in postmenopausal women, but uncertainties regarding the type of estrogen and other factors remain.4

The study by Barbosa-Cesnik and colleagues appears to be the largest and best designed in print. Despite the drawbacks, including the potential confounding by the presence of ascorbic acid in the placebo, it would appear to be the current standard against which other studies must be compared. In the meantime, we need to view recommendations for the use of cranberry products for prevention of UTI with an element of skepticism.

References

  1. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001321.
  2. Ochoa-Brust GJ, et al. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86:783-787.
  3. Abad CL, Safdar N. The role of lactobacillus probiotics in the treatment or prevention of urogenital infections--a systematic review. J Chemother. 2009;21:243-252.
  4. Perrotta C, et al. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005131.