Re: Systematic Review on the Use of Cranberry Products to Prevent Urinary Tract Infections in Healthy Women

Cranberry (Vaccinium macrocarpon, Ericaceae) Urinary Tract Infection Systematic Review Date: 01-31-2018 HC# 011831-585 Fu Z, Liska D, Talan D, Chung M. Cranberry reduces the risk of urinary tract infection recurrence in otherwise healthy women: a systematic review and meta-analysis. J Nutr. 2017;147(12):2282-2288. In the United States, the most common urologic disease is urinary tract infection (UTI). Uncomplicated UTI in otherwise healthy individuals is more common in women than in men and is commonly treated with antibiotics. Women with recurrent UTI often receive multiple antibiotics within short periods of time, and, in some women, antibiotics are used prophylactically. This use of antibiotics increases the risk for developing antibiotic resistance and can lead to yeast infections. Cranberry (Vaccinium macrocarpon, Ericaceae) is often used by women to prevent and/or treat UTI. These authors conducted a systematic review and meta-analysis to evaluate the use of cranberry to prevent UTI in generally healthy women. Studies published before January 2011 were gathered from two published systematic reviews with search dates of November 2011 and July 2012. The authors searched EMBASE and MEDLINE for published reports of clinical trials from January 2010 to July 2017. They also conducted searches in international and US clinical trial registries for unpublished data. The authors sought reports of randomized, controlled trials that were conducted in generally healthy, nonpregnant women aged 18 years and older with a history of UTI, and that compared a cranberry intervention to a placebo or nontreatment control and reported the outcome as the number of participants experiencing a UTI. The authors estimated pooled risk ratios by using the cumulative incidence of participants with one or more UTI. Bias risk for each study was assessed as low, high, or unclear for the following: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other bias. The authors identified seven randomized, controlled trials that met the inclusion criteria. Three studies1-3 were included in previous meta-analyses, and four studies4-7 presented new data. Of the seven studies, three did not provide randomization information, one trial did not describe the allocation concealment, and two trials reported high rates (28% and 32%) of loss of subjects to follow-up. Other biases were found in four studies as follows: funding source (two studies), lack of information on UTI diagnosis (one study), and poor response to compliance (one study). The total number of participants ranged from 100 in Kontiokari et al.1 to 373 in Maki et al.4 Study durations ranged from six months (five studies) to 12 months (one trial). Another six-month study was followed up for 12 months after the study's end. In four trials,2,4-6 the participants were free of UTI at enrollment (total, 881 participants). In the other three trials,1,3,7 the combined total of participants (total, 632 participants) had a UTI at enrollment, which was treated and resolved before the start of the trial. Five trials used cranberry juice, one used both cranberry juice and tablets, and one used cranberry powder capsules. Six trials used a formulated placebo, and one used a control. Most trials used clinical symptoms to define UTI. In the four trials that also required confirmed bacteriuria, the diagnostic thresholds varied. All trials reported the cumulative incidence of participants with one or more UTI at follow-up. Data on UTI cumulative incidence included 1498 participants among the seven studies, with 796 in the cranberry groups and 702 in the placebo or control groups. [Note: Figure 2 and Table 3 both show 796 participants in the cranberry groups; however, the article text states there were 798 participants in the cranberry groups.] The risk for UTI recurrence was reduced by 26% among those who used cranberry products compared with those in the placebo or control groups. Among the participants who did not have a UTI at enrollment, the cranberry intervention reduced the risk for UTI recurrence by 35%. However, among the participants who were treated for UTI before the beginning of the study, the risk reduction was not statistically significant, with large uncertainty and heterogeneity observed. The results in the 12-month studies were similar to those of the six-month trials. Five studies reported on adverse effects or tolerance. Three of those studies compared adverse effects between groups, with two studies reporting that more participants in the placebo groups reported adverse effects compared with the cranberry treatment groups, and one study reporting similar numbers of participants experiencing adverse effects in both the placebo and cranberry groups. Most participants complained of gastrointestinal disturbances; no serious adverse effects were attributed to the cranberry interventions used. Among the limitations of this review are the facts that three studies reported high rates of loss to follow-up or selective reporting; differences in study populations suggest that the baseline risk for UTI was not similar across the populations; some trials lacked clear reporting of the randomization process; and the definition of UTI diagnosis differed among the trials. "To our knowledge, this is the first meta-analysis to focus on cranberry as a nutritive option to reduce the risk of recurrence of uncomplicated UTI in healthy nonpregnant women," write the authors. The authors point out that although some studies reported relief from UTI symptoms and reduction in uropathogenic bacteria in some participants, "studies using cranberry as a treatment were not included in this meta-analysis." Results of this meta-analysis suggest that "cranberry can be a potential nonpharmacologic approach for generally healthy women to prevent an uncomplicated recurrent UTI," conclude the authors. These findings should be confirmed in future studies. The study was supported by a grant from Ocean Spray Cranberries, Inc. (Lakeville-Middleboro, Massachusetts) to one of the authors (Liska). The company had no role in the study design, conduct, interpretation, or reporting. ―Shari Henson References 1Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ. 2001;322(7302):1571. 2Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol. 2002;9(3):1558-1562. 3Barbosa-Cesnik C, Brown MB, Buxton M, Zhang L, DeBusscher J, Foxman B. Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomized placebo-controlled trial. Clin Infect Dis. 2011;52(1):23-30. 4Maki KC, Kaspar KL, Khoo C, Derrig LH, Schild AL, Gupta K. Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection. Am J Clin Nutr. 2016;103(6):1434-1442. 5Vostalova 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(10):1559-1567. 6Stapleton AE, Dziura J, Hooton TM, et al. Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial. Mayo Clin Proc. 2012;87(2):143-150. 7Takahashi S, Hamasuna R, Yasuda M, et al. A randomized clinical trial to evaluate the preventive effect of cranberry juice (UR65) for patients with recurrent urinary tract infection. J Infect Chemother. 2013;19(1):112-117.