Does Cranberry Juice Prevent Urinary Tract Infections?

By Jessie Yu

Faculty Peer Reviewed

A healthy 21-year-old female college student presents to clinic after one day of dysuria and increased frequency. You diagnose her with a recurrent urinary tract infection (UTI), and as you hand her a prescription for empiric antibiotic treatment, she asks you if drinking cranberry juice will prevent these in the future…

Drinking cranberry juice to prevent urinary tract infections (UTIs) has been a traditional folk remedy for hundreds of years.[1] Stroll into any New York City pharmacy and you will find that cranberry-extract tablets are not in the vitamins section–they are on the same shelves as the UTI medications. As concerns regarding antibiotic-resistant bacteria and the high cost of prescription medications continue to mount, patients and physicians are searching for cheap and effective pharmacologic alternatives. However, is there solid evidence for using cranberries to treat UTIs?

URINARY TRACT INFECTIONS

Urinary tract infections (UTIs) are the second most common infection in the United States.[2] They occur when uropathogens from fecal flora colonize the vaginal introitus and invade the urethra and bladder. Cystitis comprises about 95% of all symptomatic UTIs, and Escherichia coli (E coli) cause 80-85% of infections in healthy young persons.[3,4] Acute cystitis occurs in people of all ages and both genders, but the highest incidence occurs among sexually active 18-24 year old women. Overall, 40-50% of adult females have experienced at least one UTI in their lifetimes.[3]

Recurrent UTIs are a common problem in young women; approximately 27% of women recur within 6 months of the first infection.[5] The majority of recurrences are reinfections by a different strain of bacteria.[6] Disparate factors like ABO blood type[7], glycolipid receptor expression on uroepithelial cells[8], intercourse with a new partner during the past year [8,9], vaginal colonization with enterobacteriaceae[10], and even the use of spermicide-diaphragms[11], are all thought to affect the propensity for recurrent UTIs.

CRANBERRY HISTORY

Cranberries (Vaccinium macrocarpon) are a native North American fruit.[12] Cranberry juice has been manufactured since at least 1683. In addition to being consumed for food, cranberries have a long medicinal history. American Indians used the berries to draw poison from arrow wounds, calm nerves, and treat bladder and kidney ailments. American whalers and mariners ate cranberries to prevent scurvy while travelling the high seas.[1,13] Indeed, cranberry has a very good safety profile, and unless the patient is at risk for uric-acid kidney stones, on warfarin, or taking aspirin, there are not many contraindications.[12]

CRANBERRY AS PREVENTIVE THERAPY?

For decades, cranberry was believed to prevent UTIs by acidifying the urine[14], but this theory has now largely been debunked.[15] Current data suggest that specific components within cranberries may directly inhibit uropathogen adherence to uroepithelial cells or prevent bacterial growth.

Proanthocyanidins give cranberries their intense red color; these molecules appear to inhibit the adherence of p-fimbriated E coli to uroepithelial cells.[16] Cranberry also contains fructose, and some data suggest that it too may interfere with adhesion of type 1 fimbriated E coli to the uroepithelium.[17] The ascorbic acid content of cranberries may also play a role in decreasing urinary bacterial growth.[18] While the pharmacologically active component of cranberries remains debated, several recent in vitro studies generated interesting data suggesting that cranberry decreases bacterial adhesion to uroepithelial bladder cells in a concentration-dependent manner.[19] Pinzόn-Arango and colleagues also demonstrated that the longer E coli were exposed to either cranberry juice or proanthocyanidin alone, the more bacterial attachment decreased, and this effect was reversed by removing the cranberry juice or proanthocyanidin.[20]

Despite advances in basic science, data from human trials have not established the clinical merit of cranberry as a preventive treatment for recurrent UTIs. Many studies are limited by small sample size; inadequate control, randomization, and blinding; and weak statistical analysis. There is also no measureable marker to confirm medication compliance among study subjects. Finally, it is difficult to compare data across trials, as there is no standard form of cranberry used and no established unit for proanthocyanidin concentration.

The Cochrane Database published several meta-analyses that have attempted to synthesize the data from this disparate body of literature. Jepson and colleagues (2000) assessed the literature for randomized trials regarding treating UTIs with cranberry and concluded that there was no good quality evidence to support this use.[21] However, in a separate 2008 paper, they found that data seemed more optimistic regarding the use of cranberry in preventing symptomatic UTIs. They identified 4 good quality, randomized or quasi-randomized clinical trials, and found that together these papers showed that cranberry products significantly reduced the incidence of symptomatic UTIs at 12 months (overall RR=0.65, 95%CI: 0.46-0.90) compared with placebo. They concluded that cranberry may especially decrease the risk of recurrence in women with recurrent UTIs.[22]

Interestingly, new data from one of the largest, most rigorous studies regarding cranberry and UTI prevention was published in January 2011. Barbosa-Cesnik and co-authors reported that treatment with cranberry did not significantly decrease symptomatic UTI recurrence compared with placebo. This was a double-blind, randomized, placebo-controlled trial with 319 college-aged women. Cranberry and placebo groups were comprised of subjects with similar socio-demographic variables and UTI risk factors. Follow-up was 6 months or until a second UTI occurred, whichever came first. The study used an intention-to-treat analysis and was designed to detect a twofold difference between treatment and placebo (α=0.05; power=99%). The overall UTI recurrence rate was 16.9%; surprisingly, the cranberry group actually had a slightly higher recurrence rate than the placebo group (19.3% vs 14.6%, p=0.21). Even when authors adjusted the data to account for frequency of sexual activity and history of UTI, there continued to be no difference in recurrence risk between the groups. While the authors acknowledge that prior studies have reached more favorable conclusions regarding the efficacy of cranberry juice, they assert that many of these studies were either not blinded or statistically underpowered. They also speculate that the reason the two groups had similar recurrence rates may have been due to 1) an unanticipated active ingredient that was also present in the placebo—perhaps ascorbic acid, or 2) the study design caused participants in both groups to improve hydration and increase urinary frequency, thereby decreasing bacterial growth and mild symptoms.[23]

CURRENT TREATMENT GUIDELINES

The jury is still out on whether cranberry should be recommended to women who suffer from recurrent uncomplicated UTIs. The American College of Obstetricians and Gynecologists’ guidelines state that in both prophylactic and intermittent therapies for non-pregnant women with uncomplicated acute bacterial cystitis, antibiotics are the first-line treatment.[24] While these same guidelines also acknowledge that some data suggest cranberry may decrease the recurrence of symptomatic UTIs, they caution that parameters necessary for therapeutic effects have not been determined or optimized.[24]

Jessie Yu is a 4th year medical student at NYU School of Medicine

Peer Reviewed by Vinh Pham, MD, Assistant Professor of Medicine (Infectious Disease and Immunology), NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

1. Cranberry history. Cranberry Marketing Committee Web site. http://www.uscranberries.com/cranberries/history.html accessed 12/2010. Published 2006. Accessed December 10, 2010.

2. U.S. Dept. of Health and Human Services. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1999–2000. Vital and health statistics. Series 13, No. 157. Published September, 2004. Accessed December 10, 2010.

3. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002:113 Suppl 1A:5S-13S.

4. Hooton TM, Besser R, Foxman B, Fritsche TR, Nicolle LE. Acute uncomplicated cystitis in an era of increasing antibiotic resistance: a proposed approach to empirical therapy. Clin Infect Dis. 2004:39(1):75-80.

5. Foxman B. Recurring urinary tract infection: incidence and risk factors. Am J Public Health. 1990:80(3):331-333.

6. Ikäheimo R, Siitonen A, Heiskanen T, Kärkkäinen U, Kuosmanen P, Mäkelä PH. Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women. Clin Infect Dis. 1996:22(1):91-99.

7. Ziegler T, Jacobsohn N., Fünfstück R. Correlation between blood group phenotype and virulence properties of Escherichia coli in patients with chronic urinary tract infection. Int J Antimicrob Agents. 2004:24 Suppl 1):S70-75.

8. Stapleton A, Nudelman E, Clausen H, Hakomori S, Stamm WE. Binding of uropathogenic Escherichia coli R45 to glycolipids extracted from vaginal epithelial cells is dependent on histo-blood group secretor status. J Clin Invest. 1992:90(3):965-972.

9. Scholes D, Hooton TM, Roberts PL, Stapleton AE, Gupta K, Stamm WE. Risk factors for recurrent urinary tract infection in young women. J Infect Dis. 2000:182(4):1177-1182.

10. Stamey TA, Sexton CC. The role of vaginal colonization with enterobacteriaceae in recurrent urinary infections. J Urol. 1975:113(2):214-217.

11. Fihn SD, Boyko EJ, Normand EH, et al. Association between use of spermicide-coated condoms and Escherichia coli urinary tract infection in young women. Am J Epidemiol. 1996:144(5):512-520.

12. Cranberry (Vaccinium macrocarpon): natural drug information. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2010. Accessed December 10, 2010.

13. American Cranberry (Vaccinium macrocarpon). Research Guides. University of Wisconsin- Madison. http://researchguides.library.wisc.edu/content.php?pid=87646&sid=652165. Updated July 8, 2010. Accessed December 10, 2010.

14. Blatherwick NR, Long ML. Studies on urinary acidity. The increased acidity produced by eating prunes and cranberries. J Biol Chem. 1923:57:815-818.

15. Sobota AE. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol. 1984:131(5):1013-1016.

16. Howell AB, Botto H, Combescure C, et al. Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study. BMC Infect Dis. 2010:10:94-104.

17. Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eukaryotic cells. Antimicrob Agents Chemother. 1989:33(1):92-98.

18. Carlsson S, Wiklund NP, Engstrand L, Weitzberg E, Lundberg JO. Effects of pH, nitrite, and ascorbic acid on nonenzymatic nitric oxide generation and bacterial growth in urine. Nitric Oxide. 2001:5(6):580-586.

19. Di Martino P, Agniel R, David K, et al. Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial. World J Urol. 2006:24(1):21-27.

20. Pinzόn-Arango PA, Liu Y, Camesano TA. Role of cranberry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment. J Med Food. 2009:12(2):259-270.

21. Jepson RG, Mihaljevic L, Craig J. Cranberries for treating urinary tract infections. Cochrane Database System Rev. 2000:(2):CD001322.

22. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database System Rev. 2008:23(1):CD001321.

23. Barbosa-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.

24. American College of Obstetricians and Gynecologists. Treatment of Urinary Tract Infections in Nonpregnant Women. Washington, DC: American College of Obstetricians and Gynecologists; 2008. ACOG Practice Bulletin No. 91. http://www.guideline.gov/content.aspx?id=12628