By Traci Pantuso, ND, MS

Adjunct Faculty, Bastyr University, Seattle; Owner, Naturopathic Doctor Harbor Integrative Medicine, Bellingham, WA

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

SUMMARY POINTS

  • Cranberries contain numerous constituents, including A-type proanthocyanidins, which inhibit Escherichia coli adhesion to uroepithelial cells in vitro and ex vivo.
  • The study authors found no significant difference in the presence of bacteriuria plus pyuria over one year in patients administered cranberry capsules.

SYNOPSIS: Cranberry capsules containing 72 mg of proanthocyanidins administered by mouth daily to women residing in nursing homes for one year did not have a significant effect on bacteriuria plus pyuria.

SOURCE: Juthani-Mehta M, Van Ness PH, Bianco L, et al. Effect of cranberry capsules on bacteriuria plus pyuria among older women in nursing homes: A randomized clinical trial. JAMA 2016;316:1879-1887.

Urinary tract infection (UTI) is the most commonly diagnosed infection among nursing home residents and is the most common reason for antimicrobial use in older adults.1 Cranberries contain numerous constituents, including A-type proanthocyanidins, which inhibit Escherichia coli adhesion to uroepithelial cells in vitro and ex vivo.2 Juthani-Mehta et al conducted a double-blind, placebo-controlled, efficacy trial in women 65 years of age or older who resided in 21 nursing homes located within 50 miles of New Haven, Connecticut, between Aug. 24, 2012, and Oct. 26, 2015. Of 5,045 individuals screened for participation in this study, 185 were randomized into the study. Long-term care residents who were 65 years of age or older, female, and English-speaking were screened for participation.

The exclusion criteria for this study included individuals staying in the nursing home for less than one month, taking chronic or suppressive antibiotic or anti-infective therapy for recurrent UTI, with history of nephrolithiasis, undergoing dialysis for end-stage renal disease, receiving warfarin therapy, having pressure of an indwelling bladder catheter, with allergy to or current use of cranberry products, or unable to produce a baseline clean catch urine specimen.

Ninety-two participants were randomized into the treatment group and 93 into the control group. (See Table 1.) Two cranberry capsules containing a total of 72 mg of proanthocyanidins (equivalent to 20 ounces of cranberry juice) were administered to the treatment group, while the placebo group received two placebo capsules each day for one year. The primary outcome of this study was bacteriuria and pyuria measured every two months for one year. The secondary outcomes measured were numbers of symptomatic UTI, all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics for suspected UTI, and total antimicrobial prescriptions. Bacteriuria was defined as at least 105 colony-forming units per milliliter of one or two organisms. Pyuria was defined as any number of white blood cells in the urine. The statistical analysis performed was intention-to-treat with a two-sided P value of 0.05, which was considered statistically significant.

Table 1: Study Demographics

Demographics

Total Participants (n = 185)

Treatment Group

(n = 92)

Control Group

(n = 93)

Age, mean (SD)

86.4 (8.2)

87.1 (8.4)

85.6 (8.0)

Hispanic ethnicity

6 (3.2)

3 (3.3)

3 (3.2)

White race

167 (90.3)

83 (90.2)

84 (90.3)

The overall adherence to the administration of the oral capsules was 80.1%, with 77.5% in the treatment group and 82.6% in the control group. No significant difference was found between the treatment and control groups on the percentage of urine specimens that were positive for bacteriuria and pyuria during the study (adjusted rates, 29.1% vs. 29.0%; odds ratio, 1.01; 95% confidence interval, 0.61-1.66; P = 0.98). No significant differences were found between the cranberry and placebo groups among the secondary outcomes: symptomatic UTI (10 vs. 12 episodes), mortality (17 vs. 16 deaths), or hospitalizations (33 vs. 50 episodes). The authors also found no significant differences between the placebo and cranberry group on the bacteriuria associated with multidrug-resistant gram-negative bacilli, antibiotics administered for suspected UTIs, or total antimicrobial utilization.

A total of 3,830 adverse events occurred during the study period, which is to be expected with the study population. Of these adverse events, only 14 were considered to be protocol-related and non-serious; they included altered mental status, gastrointestinal disturbance, weight loss, oral cavity disturbance, and/or a skin and soft tissue event. These 14 adverse events were similar between the placebo and treatment groups.

COMMENTARY

In this study, Juthani-Mehta et al found no benefit to women taking two cranberry capsules containing 72 mg of proanthocyanidins on bacteriuria or pyuria. The strengths of this study include the double-blind, randomized, controlled trial design with cranberry capsules that were standardized to proanthocyanidin concentration. The dose of 72 mg of proanthocyanidins is comparable to the amount of proanthocyanidins in 20 ounces of cranberry juice.

The authors also used the objective outcome of bacteriuria and pyuria and the use of the National Healthcare Safety Network criteria for symptomatic UTI. The limitations of this study were that participants were unable to be catheterized to obtain urine samples, so only patients who could provide a clean catch urine specimen were randomized. Only 65% of the planned urine specimens were able to be collected. Another important variable that was not controlled in this study was hydration status, which may reduce bacteriuria and urinary symptoms in older women. Anti-adhesion of E. coli to uroepithelial cells was not tested in the urine samples of the participants; this may have been an objective measure of not only adherence to the treatment but also evaluation of mechanism of action. Lavigne et al previously demonstrated that adhesion by E. coli to a uroepithelial cell line can be measured ex vivo in urine collected from participants taking cranberry products orally.3 There is limited generalizability of this study to non-white older women and women not residing in nursing homes as the participants in this study were older than 65 years of age and predominately white.

The evidence for the use of cranberry products to prevent UTIs is a controversial topic, with some studies showing benefit and others demonstrating no effect.4 The most recent 2012 Cochrane Review, which included 24 studies with 4,473 participants, investigating cranberry products and the prevention of UTI found no benefit and concluded that cranberry products should not be recommended for the prevention of UTI.5 The previous Cochrane review, published in 2008, included 10 studies with 1,049 participants and found that there was some evidence that cranberry may decrease the incidence of symptomatic UTI.6 This study is important in that it used a narrow UTI definition and objective measures (bacteriuria plus pyuria) as the primary outcome compared to a number of previous studies.

Although Juthani-Mehta et al reported no conflict of interest, the cranberry and the placebo capsules used in this study were manufactured and donated by Pharmatoka, which manufactures and sells Ellura, a cranberry capsule standardized to 36 mg of proanthocyanidin per capsule, in the United States. Ellura is marketed as “helping to maintain a clean urinary tract” and is a cranberry juice extract. It is unclear whether the cranberry capsules in this study were a cranberry juice extract. There are numerous compounds in cranberries, such as flavonoids, phenolic acid, triterpenoids, and anthocyanins.2 These other compounds also may prevent UTIs, and cranberry juice extract may not provide the complex mixture of bioactive components that are found in whole cranberry fruit.2 Although this study did not find benefit in the incidence of bacteriuria and pyuria or symptomatic UTI in this population consuming cranberry capsules, cranberry still may have benefit in other demographics as per past research.

REFERENCES

  1. Rowe TA, Juthani-Mehta M. Diagnosis and management of urinary tract infection in older adults. Infect Dis Clin North Am 2014;28:75-89.
  2. Vostalova J, Vidlar A, Simanek V, et al. Are high proanthocyanidins key to cranberry efficacy in the prevention of recurrent urinary tract infection? Phytother Res 2015;29:1559-1567.
  3. Lavigne JP, Bourg G, Combescure C, et al. In-vitro and in-vivo evidence of dose-dependent decrease of uropathogenic Escherichia coli virulence after consumption of commercial Vacccinium macrocarpon (cranberry) capsules. Clin Microbiol Infect 2008:14:350-355.
  4. Nicolle LE. Cranberry for prevention of urinary tract infection? Time to move on. JAMA 2016;316:1873-1874.
  5. Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2012;10:CD001321. doi:10.1002/14651858.CD001321.
  6. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2008: CD001321. doi: 10.1002/14651858.CD001321.pub4.