Reviewed: 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(18):1879-1887. doi: 10.1001/jama.2016.16141.
On October 27, 2016, the Journal of the American Medical Association (JAMA) published online a randomized, double-blind, placebo-controlled clinical study by Juthani-Mehta et al. from the Yale School of Medicine.1 The trial was designed to evaluate the effects of a cranberry (Vaccinium macrocarpon, Ericaceae) juice extract preparation on bacteriuria plus pyuria (the presence of bacteria and pus in the urine, respectively) in elderly female nursing home residents. The authors reported that administration of two capsules of a standardized cranberry extract (Ellura capsules, each containing 36 mg proanthocyanidins [PACs]; Pharmatoka; Rueil-Malmaison, France) for 12 months failed to provide a statistically significant difference in the percentage of patients with bacteriuria and pyuria compared to placebo. The authors also did not find any statistically significant differences in the secondary outcome measures, which included symptomatic urinary tract infections (UTIs), mortality, number of hospitalizations, presence of multidrug-resistant bacteria in the urine, antibiotic treatments for suspected UTIs, and total antimicrobial pharmaceutical drugs administered.
The study results were covered, often uncritically, by major media outlets. For example, an article in The New York Times titled “The Cure for UTIs? It’s Not Cranberries” inaccurately generalized the results of the study with its misleading headline.2 The study did not look at the effects of the cranberry extract preparation to cure, or even treat, existing UTIs, as the Times headline suggests, but rather at its efficacy in the prevention of bacteriuria and pyuria in older women.
According to data published by the same research group, 25-50% of women living in nursing homes suffer from bacteriuria.3 Since clinical trials evaluating conventional antibiotic treatments have not shown a reduction in urogenital infection-related diseases and deaths, the current medical practice guidelines for institutionalized adults do not recommend antibiotic treatments for bacteriuria or non-specific UTI symptoms because of escalating antibiotic resistance.4,5 Due to previous clinical trials that have shown positive outcomes for cranberry preparations in preventing the incidence and recurrence of UTIs, cranberry is seen as a potential alternative to low-dose antibiotics for UTI prevention.
The JAMA clinical study included 185 women aged 65 or older who lived in 21 nursing homes in the New Haven, Connecticut, area. The women had to speak English, have lived in the nursing home for at least four weeks, have a life expectancy of more than one month, and be able to provide a clean-catch urine sample. Exclusion criteria included the following: the women could not be on anti-infective therapy for recurrent UTIs, be undergoing dialysis for end-stage renal disease, be taking warfarin, have a history of kidney stones, have a bladder catheter, or be allergic to cranberry. In-service nurses were trained to collect appropriate urine samples in order to have valid results. Urine samples were evaluated every two months for the presence of bacteriuria (at least 100,000 colony-forming units of one or two types of bacteria per mL of urine) and pyuria (any presence of white blood cells in the urine).
From the 185 women that started the study, a follow-up after 12 months for the presence of bacteriuria and pyuria was possible for only 90 subjects; patients were lost due to protocol-unrelated deaths, transferral to hospice care, or development of urinary incontinence. While urine analyses after four and six months showed lower bacteriuria in the treatment group, the trend was reversed in the last six months of the study, but without reaching statistical significance at any time period. During the study period, a total of 350 UTIs were suspected, but only 22 (10 in the treatment group and 12 in the placebo group) were confirmed as symptomatic UTIs. The number of hospitalizations, presence of multidrug-resistant bacteria, antibiotic treatments for suspected UTIs, and total antimicrobials administered all trended in favor of the cranberry treatment, but the differences were not statistically significant. No treatment-related serious adverse events were observed. The frequency of protocol-related non-serious adverse events, including altered mental status, gastrointestinal discomfort, oral cavity issues, skin and soft tissue changes, and weight loss, was similar in both groups.
The authors concluded that cranberry administration does not reduce the occurrence of bacteriuria in older women living in nursing homes. However, 30% of the subjects in both arms had asymptomatic bacteriuria at enrollment, and none were treated with antibiotics prior to starting the study. Cranberry has not been consistently effective at reducing existing bacteriuria, as this could be considered a “treatment” effect, which would not be an anticipated result for cranberry. Strengths of this included the use of a standardized cranberry product, compliance with the dosage regimen, and use of objective criteria to evaluate treatment success. Shortcomings included the inability to obtain urine samples from many women as the study progressed due to subjects’ physical and mental impairments, the lack of an anti-adhesion* test, and the inability to assess the efficacy of cranberry supplementation in women with a history of recurrent UTIs.
Previous clinical trials have shown cranberry to be mainly effective in the prevention of recurrent UTIs,6-10 so the lack of benefits in this study may not come as a surprise since only 1% of the participants in the treatment group had three or more UTI episodes in the 12 months prior to enrollment. This clinical study suggests that there is no benefit to using cranberry to prevent the presence of bacteriuria in this particular population, but a number of recent clinical trials carried out with cranberry extracts provides evidence that cranberry does have a place in the therapeutic arsenal to prevent recurrent UTIs and radiation-induced cystitis.11
As such, the suggestion to “move on from cranberries,” as stated in a JAMA editorial12 by Lindsay E. Nicolle, MD, a professor in the department of internal medicine and medical microbiology at the University of Manitoba, is not supported when scientific evidence from all published clinical trials is taken into account. Results cannot be extrapolated beyond a negative effect of cranberry on the prevention of bacteriuria. This opinion was echoed by Kalpana Gupta, MD, an associate professor of medicine at Boston University School of Medicine, who commented that she is “not ready to walk away from cranberries,” and that “some women with recurrent UTIs may still want to discuss cranberry treatment with their doctors.”2
Concerns about the validity of the data also were raised in a statement issued by the Cranberry Institute, an organization dedicated to supporting research on cranberries and promoting cranberry health benefits, and in a letter written by Amy Howell, PhD, associate research scientist at the Philip E. Marucci Center for Blueberry and Cranberry Research and Extension at Rutgers University.13,14 Both statements listed characteristics of the clinical study design and results that do not support the conclusions expressed in Nicolle’s editorial.
—Stefan Gafner, PhD
* Anti-adhesion refers to the ability of cranberry PACs to inhibit bacterial adherence to the mucous membranes of the urinary tract. Anti-adhesion is one of the mechanisms by which cranberry exerts its benefits.
- 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(18):1879-1887.
- Hoffman J. The cure for UTIs? It’s not cranberries. The New York Times. October 27, 2016.
- Juthani-Mehta M, Datunashvili A, Tinetti M. Tests for urinary tract infection in nursing home residents. JAMA. 2014;312(16):1687-1688.
- Nicolle LE, Mayhew WJ, Bryan L. Prospective randomized comparison of therapy and no therapy for asymptomatic bacteriuria in institutionalized elderly women. The American Journal of Medicine. 1987;83(1):27-33.
- Rowe TA, Juthani-Mehta M. Diagnosis and management of urinary tract infection in older adults. Infect Dis Clin North Am. 2014;28(1):75-89.
- Stothers 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.
- Walker EB, Barney DP, Mickelsen JN, Walton RJ, Mickelsen Jr RA. Cranberry concentrate: UTI prophylaxis. J Fam Pract. 1997;45(2):167-168.
- Ferrara P, Romaniello L, Vitelli O, Gatto A, Serva M, Cataldi L. Cranberry juice for the prevention of recurrent urinary tract infections: A randomized controlled trial in children. Scand J Urol Nephrol. 2009;43(5):369-372.
- Sengupta K, Alluri KV, Golakoti T, et al. A randomized, double blind, controlled, dose dependent clinical trial to evaluate the efficacy of a proanthocyanidin standardized whole cranberry (Vaccinium macrocarpon) powder on infections of the urinary tract. Curr Bioact Comp. 2011;7(1):39-46.
- Caljouw MAA, van den Hout WB, Putter H, Achterberg WP, Cools HJM, Gussekloo J. Effectiveness of cranberry capsules to prevent urinary tract infections in vulnerable older persons: A double-blind randomized placebo-controlled trial in long-term care facilities. J Am Geriatr Soc. 2014;62(1):103-110.
- Bone K. Further evidence for the clinical efficacy of cranberry: A brief review of recent clinical trials. HerbalGram. 2016;112:29-33.
- Nicolle LE. Cranberry for prevention of urinary tract infection?: Time to move on. JAMA. 2016.
- Efficacy of cranberry products in urinary tract health. Cranberry Institute website. Available at: http://cranberryinstitute.org/JAMA%20Response%20Statement%20-%20For%20CI%20Website.pdf. Accessed November 2, 2016.
- Howell AB. Comments on JAMA study and editorial on cranberry and bacteriuria. Chatsworth, NJ: Rutgers University; 2016.