The Effectiveness of Cranberry Products to Reduce Urinary Tract Infections in Females

A Literature Review

Peggy Wang, BS, BSN, RN

Urol Nurs. 2013;33(1):38-45.

Abstract and Introduction

Abstract

Cranberry products, especially cranberry juice, have been posited to prevent or treat urinary tract infections (UTIs) in females. Antimicrobial resistance has been correlated to repeated antibiotic treatment. Thus, evaluating cranberry products as a possible alternative to conventional antibiotic therapy is appropriate. This review of the literature evaluated research in which cranberry-based products are used to prevent or treat UTIs.

Introduction

Urinary tract infections (UTIs) result from bacterial invasion of the urinary tract, causing inflammation of the uroepithelium (Shankel, 2007). An infection is present when clinical laboratory results reveal the presence of asymptomatic bacterial colonization greater than 100,000 bacteria of the same strain per milliliter of urine in two consecutive voided specimens, or the presence of bacterial colonization greater than 100 bacteria of the same strain per milliliter of urine in a single catheterized urine specimen (Nicolle et al., 2005). UTIs are typically classified according to the anatomical site involved (Jancel & Dudas, 2002). Infections involving the kidneys, or pyelonephritis, are accompanied by upper back and flank pain, fever, chills, nausea, and vomiting (Shankel, 2007). Bladder infections, or cystitis, are characterized by pelvic pressure, lower abdominal discomfort, dysuria, and hematuria (Shankel, 2007). The clinical manifestation of urethritis, which indicates involvement of the urethra, is typically dysuria (Shankel, 2007).

UTIs are the most prevalent nosocomial infections and ac count for 38% of the 2 million hospitalacquired infections (HAIs) that occur annually (Clancey, 2010). According to the Centers for Disease Control and Prevention (CDC), UTIs comprised more than 560,000 infections in 2002 (Gould et al., 2010), increasing hospital costs by $400 million to $500 million per year (Foxman, 2002) and causing more than 13,000 deaths annually (Klevens et al., 2007).

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Table 1. Clinical Trials Using Cranberry Products for Prophylaxis of Urinary Tract Infections
A. Cranberry Juice and Cocktail Trials
Author	Evidence Type/Level	Sample Composition and Size	Intervention	Results	Comments
Barbosa-Cesnik et al., 2011	Randomized controlled trial Level II	319 female college students with acute UTI	8 ounces of 27% cranberry juice (intervention) vs. placebo (control) BID for 6 months.	No statistical difference in UTI incidence. Intervention group experienced a slightly higher recurrence rate (20.0% vs. 14.0%, p = 0.21).	• Placebo may have contained some amount of cranberry juice. • Results may have been influenced by adequate hydration. • Study attrition was 28%, resulting in a less than powered study population.
Cowan et al., 2011	Randomized control trial Level II	128 adult patients (females = 60; males = 68) with bladder or cervical cancer	Cranberry juice (intervention) vs. placebo (control) BID for 6 weeks (during radiotherapy and 2 weeks after treatment).	No statistical difference in UTI incidence. Intervention group experienced a decrease in urinary symptoms and UTIs (82.5% vs. 89.3%, p = 0.240, adjusted odds ratio 0.48, 95% CI: 0.14 to 1.63).	• Participants reported difficulty with compliance to the intervention. • 32 participants completed all study activities (n = 14 in control group; n = 18 in intervention group). • Study participation was restricted to patients with bladder or cervical cancer undergoing radiotherapy, limiting generalizability to those not meeting these prerequisites. • Lack of pre-study data, which may influence pre-study UTI incidence.
Ferrara et al., 2009	Randomized control trial Level II	84 female children with recurrent UTIs	Intervention of 50 ml cranberry juice daily (n = 28) vs, 100 ml lactobacillus GG probiotic 5 days per month (n = 27) vs. no intervention (control, n = 29) for 6 months.	Cranberry juice intervention significantly reduced recurrence of UTIs when compared to lactobacillus and placebo (p < 0.05).	• Small sample size.
Wing et al., 2008	Randomized Control Trial Level II	188 pregnant women (< 16 weeks gestation) receiving prenatal care	Initially, the control group (n = 63) received study placebo TID; Study Group A (n = 58) received 240 ml cranberry juice TID; and Study Group B (n = 67) received the intervention q AM. Protocol altered to BID during data collection. Subjects received treatment from less than 16 weeks gestation until delivery.	Intervention appeared to have a protective effect for asymptomatic bacteriuria and symptomatic UTI's during pregnancy. Study Group A had a 57% reduction in the frequency of asymptomatic bacteriuria and 41% reduction in frequency of UTIs. Study Group B and the Control Group had a nonstatistically significant (p = 0.71) increased risk for at least one UTI when compared to Study Group	• Small sample size. • Lack of bioassay to document compliance. • Alteration in study protocol during data collection. • End point (delivery) varied the length of time intervention was provided
Efros et al., 2010	Prospective clinical trial Level IV	28 healthy adult women with 2 UTIs or more in previous 6 months	UTI-STAT with Proantinox® (concentrated cranberry liquid blend) at 15, 30, 45, 60, and 75 mL daily for 12 weeks vs. baseline data gathered prior to intervention.	Overall, 91% of these participants remained free of recurrent UTI for 3 months: • Maximal tolerated dose of UTI-STAT = 75 mL/d, recom mended dose = 60 mL/d. • Significant reduction in worry about UTIs from baseline to week 12 (70.6 ± 14.8 versus 89.6 ± 17.2, p = 0.0097) and significant increase in QOL (85.0 ± 6.4 versus 97.2 ± 5.6, p = 0.045).	• Study data consists of selfdisclosed assessment (SF-36, AUA symptom index) and laboratory results (urine and blood sample). • AUA symptom index has not be validated with this population. • Intervention was well tolerated.
Nishizaki et al., 2009	Controlled clinical trial Level IV	31 children (girls = 13; boys = 18) hospitalized for vesicoureteral reflux (VUR)	100 ml of 50% concentrated cranberry juice for 3 to 27 months (intervention, n = 12) vs. 5 to 10 mg/kg cefaclor for 5 to 15 months (control, n = 19).	Cranberry juice is comparable to cefaclor prophylaxis for prevention of recurrent UTI: • 2 children in the intervention group had a recurrent infection. • 2 children in the control group developed breakthrough UTI. • No significant difference in the risk of recurrent UTI between study groups (p > 0.05).	• Small sample size. • Data collected from one study site.
Lee et al., 2007	Randomized controlled trial Level II	305 (female = 53; male = 252) communitydwelling patients over the age of 16 years with neuropathic bladder related to spinal cord injury (SCI)	Group A received 1 g methenamine hippurate (MH) + 800 mg cranberry BID; Group B received 1 g MH + cranberry placebo BID; Group C received 800 mg cranberry + MH placebo BID; Group D received cranberry placebo + MH placebo. • Participants received treatment for 6 months or until first symptomatic UTI.	Patients receiving cranberry tablets (Groups A and C) did not have a significantly longer UTIfree period compared to cranberry placebo (Groups B and D) (HR 0.93, 95% CI: 0.67 to 1.31, p = 0.70).	• Non-significant results could be due to study sample size, but approaching significance may have clinical relevance. • Study participation was restricted to post-SCI patients with neurogenic bladder who have mostly supra or infrasacral UTIs; thus, generalizability is limited.
McMurdo et al., 2008	Randomized controlled trial Level II	137 women aged 45 years and over with 2 or more antibiotic-treated UTIs in previous 12 months	500 mg cranberry capsule intervention) vs. 100 mg trimethoprim (control) for 6 months.	Control had a very limited advantage over cranberry extract in preventing recurrent UTIs. 28% of participants had an antibiotictreated UTI (25 in cranberry group, 14 in trimethoprim group), difference in proportions RR = 1.616 (95% CI: 0.93, 2.79; p = 0.084). Non-significant difference in time to first recurrence of UTI (p = 0.100) between study groups. Median time to recurrence of UTI was 84.5 days for cranberry group, 91 days for trimethoprim group (p = 0.479).	• Study sample was limited to older individuals. Further study is necessary to see if findings apply to younger individuals as well.
Beerepoot et al., 2011	Randomized, double-blind, non-inferiority trial Level II	221 premenopausal women with recurrent UTIs	500 mg cranberry capsules BID + placebo nightly (intervention) vs. 480 mg TMP-SMX nightly + placebo BID (control) for 12 months.	TMP-SMX more effectively prevented recurrent UTIs than cranberry capsules. Mean number of patients with UTI was significantly higher in cranberry (μ = 4.0; 95% CI: 2.3–5.6) than TMP-SMX group (μ = 1.8, 96% CI: 0.8 to 2.7) (p = 0.02). Median time to 1st symptomatic UTI was 4 months in the intervention group and 8 months in the control group.	• Inability to assure compliance with intervention. • Optimum dosage of intervention remains unclear.
Botto & Neuzillet, 2010	Historically controlled pilot study Level IV	15 postcystectomy patients (females = 2, males = 13) over the age of 59 years who underwent a bladder replacement procedure	Cranberry capsules highly dosed in PAC A (intervention) vs. no treatment (control) for 13–60 months.	Cranberry capsules significantly decreased the number of patients who developed UTIs; 1 out of 15 participants developed a positive urine culture. The intervention group had a significant decrease in number of positive urine cultures (p < 0.0001), rate of symptoms of pain or fever (p = 0.03), and urinary incontinence (p = 0.03).	• The historically controlled design prevented bias of participation selection. • Variation in population gender limits the ability to apply results to females.
Bailey et al., 2007	Open label pilot study Level VI	12 adult women who sought treatment for at least 6 UTIs in the proceeding year.	1 cranberry capsule (200mg) BID for 12 weeks.	No participant experienced a UTI during the period. Anecdotal data, collected 2 years later, reported that 8 out of 12 participants continued to take cranberry and remained free from UTIs.	• Insufficient information regarding phenolics or proanthocyanidin (active compounds in cranberry) given in study. • The optimal dose of cranberry remains unknown.