Summary
Blueberries for the prevention of urinary tract infections
Background
Blueberries contain proanthocyanidins (PACs), which inhibit the adherence of p‐fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry-based products have been widely used for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008 and 2012.
Goals
To evaluate the effectiveness of blueberry-based products for the prevention of UTIs in vulnerable populations.
Search methods
We searched the Cochrane Kidney and Transplant Specialized Register up to 13 March 2023, by contacting the archivist and using search terms relevant to this review. Studies in the Registry are identified by searching CENTRAL, MEDLINE and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov.
Selection criteria
We included all randomized controlled trials (RCTs) or quasi-randomised controlled trials of cranberry products compared with placebo, no specific treatment or another intervention (antibiotics, probiotics) for the prevention of UTIs.
Data collection and analysis
Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions, and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, treatment adherence). When appropriate, risk ratios (RR) with 95% confidence intervals (CI) were calculated. The quality of the studies was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the GRADE ( Grading of Recommendations Assessment, Development and Evaluation ) method.
Main results
For this update, 26 new studies were added, bringing the total number of included studies to 50 (8857 randomized participants). The risk of bias for sequence generation and allocation concealment was low in 29 and 28 studies, respectively. Thirty-six studies had a low risk of performance bias and 23 studies had a low risk of detection bias. Twenty-seven, 41, and 17 studies had a low risk of exclusion bias, reporting bias, and other biases, respectively.
Forty-five studies compared blueberry products with placebo or no specific treatment in six different groups of participants. In 26 of these 45 studies it was possible to perform meta-analysis of the outcome of symptomatic, culture-proven UTIs. Based on moderate-certainty evidence, blueberry-based products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84, I² = 69%).
When studies were divided into groups according to treatment indication, cranberry products probably reduced the risk of culture-proven symptomatic UTIs in women with recurrent UTIs (eight studies, 1555 participants: RR 0.74, CI 95%: 0.55 to 0.99; I² = 54%), in children (five studies, 504 participants: RR 0.46, 95% CI: 0.32 to 0.68; I² = 21%) and in people with susceptibility to UTIs due to an intervention (six studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61, I² = 0%).
However, based on low-certainty evidence, there may be little or no benefit in older men and women living in nursing homes or nursing homes (three studies, 1489 participants: RR 0.93, 95% CI). : 0.67 to 1.30; I² = 9%), pregnant women (three studies, 765 participants: RR 1.06, 95% CI: 0.75 to 1.50; I² = 3%) or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (three studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19, I² = 0%).
Other comparisons included cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry juice (one study), and different doses of PAC (two studies).
Compared with antibiotics , cranberry products may make little or no difference in the risk of culture-proven symptomatic UTIs (two studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (two studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared with probiotics, blueberry products may reduce the risk of culture-proven symptomatic UTIs (three studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56, I = 0 %). It is not clear whether efficacy differs between cranberry juice and tablets or between different doses of PAC, as the certainty of the evidence was very low.
The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between therapeutic compliance and the risk of repeated UTI. It was not possible to demonstrate a difference in the risk of UTIs between low, moderate, and high doses of PAC.
Authors’ conclusions This update adds 26 more studies, bringing the total number of studies to 50, with 8,857 participants. These data support the use of cranberry-based products to reduce the risk of culture-proven symptomatic UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs after interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems or pregnant women. |
Comments
Drinking cranberry juice has long been a mythical prevention strategy for women who develop a urinary tract infection, and new medical evidence shows that consuming cranberry products is an effective way to prevent a UTI before it starts.
A global study looking at the benefits of cranberry products published in Cochrane Reviews found that cranberry juice and its supplements reduced the risk of repeated symptomatic urinary tract infections in women by more than a quarter, in children by more than half. and in people susceptible to UTI after medical interventions by approximately 53%.
Cranberry juice and health care supplements that commonly include the fruit, such as capsules and tablets, have long been promoted as a readily available solution to preventing infection, but the most recent review in 2012, with evidence of 24 trials, showed no benefit from the products
The medical scientists behind this updated review from Flinders University and Westmead Children’s Hospital sought to update these findings, as an important step in determining the effectiveness of blueberry products, by looking at 50 more recent trials involving almost 9,000 participants.
“This incredible result did not really surprise us, as we are taught that when there is more and better evidence, the truth will eventually come to light. UTIs are horrible and very common; About a third of women will experience one, as will many older people and also people with bladder problems due to spinal cord injury or other conditions,” says the study’s lead author, Dr. Gabrielle Williams.
“Even in 1973, my mother was told to try cranberry juice to prevent her horrible and frequent urinary tract infections, and it has been a savior for her .” Despite her nagging about the evidence, she continued taking it daily, first as the unpleasant sour juice and in recent years, the easy-to-swallow capsules. As soon as she stops, the symptoms are back. As usual, it turns out mom was right! “Blueberry products may help some women prevent urinary tract infections.”
Flinders University epidemiologist Dr Jacqueline Stephens, co-author of the study, says if UTI persists without treatment, it can move to the kidneys and cause pain and further complications, including sepsis in very severe cases, so Prevention is the most effective way to reduce risks.
“Most urinary tract infections are treated effectively and fairly quickly with antibiotics, sometimes just one dose can cure the problem. Unfortunately, in some people UTIs keep coming back. Unsure if or how it works, some healthcare providers began recommending it to their patients. It was a harmless and easy option at the time. Even centuries ago, Native Americans supposedly ate blueberries for bladder problems, which led a little more recently to laboratory scientists exploring what was in blueberries that helped and how it might work.”
“The studies we analyzed included a variety of methods to determine the benefits of blueberry products. The vast majority compared cranberry products with a placebo or no UTI treatment and found that drinking cranberry juice or taking capsules reduced the number of UTIs in women with recurrent cases, in children, and in people susceptible to UTIs after medical interventions such as bladder radiotherapy. .”
“It is also important to note that few people reported side effects, the most common being stomach pain according to the results. "We also did not find enough information to determine whether cranberry products are more or less effective compared to antibiotics or probiotics in preventing more urinary tract infections."
The data also shows no benefit for older people, pregnant women, or people with problems emptying their bladder.
Lead author Professor Jonathan Craig, vice-president and executive dean of Flinders University’s School of Medicine and Public Health, says the real benefits of cranberry products became clear when researchers expanded the scope of the review to include the most recent clinical data available.
“This is a review of the totality of the evidence and, as new evidence emerges, new findings could occur. “In this case, the new evidence shows a very positive finding that cranberry juice can prevent urinary tract infections in susceptible people,” says Professor Craig.
“We have demonstrated the effectiveness of cranberry products for the treatment of UTIs using all the evidence published on this topic since the mid-1990s. "Previous versions of this review did not have enough evidence to determine efficacy and subsequent clinical trials showed mixed results, but in this updated review the volume of data has shown this new finding."
The study authors conclude that while cranberry products help prevent UTIs in women with frequent recurrence, more studies are needed to clarify who with UTIs would benefit most from cranberry products.
