Cochrane

Library
Cochrane Database of Systematic Reviews

Cranberries for preventing urinary tract infections (Review)

Williams G, Stothart CI, Hahn D, Stephens JH, Craig JC, Hodson EM

Williams G, Stothart CI, Hahn D, Stephens JH, Craig JC, Hodson EM.
Cranberries for preventing urinary tract infections.
Cochrane Database of Systematic Reviews 2023, Issue 11. Art. No.: CD001321.
DOI: 10.1002/14651858.CD001321.pub7.

www.cochranelibrary.com

Cranberries for preventing urinary tract infections (Review)

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

TABLE OF CONTENTS
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
SUMMARY OF FINDINGS.............................................................................................................................................................................. 3
BACKGROUND.............................................................................................................................................................................................. 5
OBJECTIVES.................................................................................................................................................................................................. 6
METHODS..................................................................................................................................................................................................... 6
RESULTS........................................................................................................................................................................................................ 8
Figure 1.................................................................................................................................................................................................. 9
Figure 2.................................................................................................................................................................................................. 13
Figure 3.................................................................................................................................................................................................. 14
DISCUSSION.................................................................................................................................................................................................. 21
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 23
ACKNOWLEDGEMENTS................................................................................................................................................................................ 24
REFERENCES................................................................................................................................................................................................ 25
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 33
DATA AND ANALYSES.................................................................................................................................................................................... 115
Analysis 1.1. Comparison 1: Any cranberry product versus placebo, control or no treatment, Outcome 1: Symptomatic UTI: 117
culture-verified UTI...............................................................................................................................................................................
Analysis 1.2. Comparison 1: Any cranberry product versus placebo, control or no treatment, Outcome 2: Clinical UTI: symptoms, 118
no culture..............................................................................................................................................................................................
Analysis 1.3. Comparison 1: Any cranberry product versus placebo, control or no treatment, Outcome 3: Microbiological UTI: 119
positive culture without known symptoms........................................................................................................................................
Analysis 1.4. Comparison 1: Any cranberry product versus placebo, control or no treatment, Outcome 4: Death......................... 119
Analysis 1.5. Comparison 1: Any cranberry product versus placebo, control or no treatment, Outcome 5: Gastrointestinal 120
adverse events......................................................................................................................................................................................
Analysis 2.1. Comparison 2: Cranberry juice or syrup versus placebo or control, Outcome 1: Symptomatic UTI: culture-verified 121
UTI..........................................................................................................................................................................................................
Analysis 2.2. Comparison 2: Cranberry juice or syrup versus placebo or control, Outcome 2: Clinical UTI: symptoms, no culture... 122
Analysis 3.1. Comparison 3: Cranberry tablets or powder versus placebo or control, Outcome 1: Symptomatic UTI: culture- 124
verified UTI............................................................................................................................................................................................
Analysis 3.2. Comparison 3: Cranberry tablets or powder versus placebo or control, Outcome 2: Clinical UTI: symptoms, no 125
culture....................................................................................................................................................................................................
Analysis 3.3. Comparison 3: Cranberry tablets or powder versus placebo or control, Outcome 3: Microbiological UTI: positive 125
culture without known symptoms.......................................................................................................................................................
Analysis 4.1. Comparison 4: Cranberry juice versus cranberry tablets or powder, Outcome 1: Symptomatic UTI: culture-verified 126
UTI..........................................................................................................................................................................................................
Analysis 5.1. Comparison 5: Cranberry dose: high versus low, Outcome 1: Symptomatic UTI: culture-verified UTI....................... 127
Analysis 5.2. Comparison 5: Cranberry dose: high versus low, Outcome 2: Microbiological UTI: positive culture without known 127
symptoms..............................................................................................................................................................................................
Analysis 5.3. Comparison 5: Cranberry dose: high versus low, Outcome 3: Clinical UTI without culture verification..................... 127
Analysis 6.1. Comparison 6: Cranberry product versus probiotics, Outcome 1: Symptomatic UTI: culture-verified UTI................ 128
Analysis 7.1. Comparison 7: Cranberry product versus antibiotics, Outcome 1: Symptomatic UTI: culture-verified UTI............... 129
Analysis 7.2. Comparison 7: Cranberry product versus antibiotics, Outcome 2: Clinical UTI: symptoms, no culture..................... 130
Analysis 8.1. Comparison 8: Cranberry + probiotic tablet versus placebo or control, Outcome 1: Symptomatic UTI: culture- 130
verified UTI............................................................................................................................................................................................
Analysis 9.1. Comparison 9: Cranberry product versus placebo or control: PAC dose, Outcome 1: Symptomatic UTI: culture- 132
verified UTI (low dose PAC < 40 mg/day)............................................................................................................................................
Analysis 9.2. Comparison 9: Cranberry product versus placebo or control: PAC dose, Outcome 2: Symptomatic UTI: culture- 133
verified UTI (moderate dose PAC 40 to 80 mg/day)...........................................................................................................................
Analysis 9.3. Comparison 9: Cranberry product versus placebo or control: PAC dose, Outcome 3: Symptomatic UTI: culture- 133
verified UTI (high dose PAC > 80 mg/day)...........................................................................................................................................
Analysis 10.1. Comparison 10: Cranberry product versus placebo or control: sponsor type, Outcome 1: Symptomatic UTI: 135
culture-verified UTI (commercial involvement)..................................................................................................................................

Cranberries for preventing urinary tract infections (Review) i

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 10.2. Comparison 10: Cranberry product versus placebo or control: sponsor type, Outcome 2: Symptomatic UTI: 136
culture-verified UTI (no commercial involvement)............................................................................................................................
Analysis 11.1. Comparison 11: Cranberry product versus placebo or control: culture threshold, Outcome 1: Symptomatic UTI: 138
culture-verified UTI (# 108 CFU/L).......................................................................................................................................................
Analysis 11.2. Comparison 11: Cranberry product versus placebo or control: culture threshold, Outcome 2: Symptomatic UTI: 139
culture-verified UTI (< 108 CFU/L).......................................................................................................................................................
APPENDICES................................................................................................................................................................................................. 139
WHAT'S NEW................................................................................................................................................................................................. 146
HISTORY........................................................................................................................................................................................................ 146
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 147
DECLARATIONS OF INTEREST..................................................................................................................................................................... 147
SOURCES OF SUPPORT............................................................................................................................................................................... 147
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 147
INDEX TERMS............................................................................................................................................................................................... 147

Cranberries for preventing urinary tract infections (Review) ii

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

[Intervention Review]

Cranberries for preventing urinary tract infections

Gabrielle Williams1, Christopher I Stothart2, Deirdre Hahn3, Jacqueline H Stephens4, Jonathan C Craig4,5, Elisabeth M Hodson5,6

1Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia. 2Scottish Collaboration for Public Health
Research & Policy, University of Edinburgh, Edinburgh, UK. 3Department of Nephrology, The Children's Hospital at Westmead,
Westmead, Australia. 4College of Medicine and Public Health, Flinders University, Adelaide, Australia. 5Cochrane Kidney and Transplant,
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia. 6Sydney School of Public Health, The University
of Sydney, Sydney, Australia

Contact: Elisabeth M Hodson, emhodson@exemail.com.au.

Editorial group: Cochrane Kidney and Transplant Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 11, 2023.

Citation: Williams G, Stothart CI, Hahn D, Stephens JH, Craig JC, Hodson EM. Cranberries for preventing urinary tract infections.
Cochrane Database of Systematic Reviews 2023, Issue 11. Art. No.: CD001321. DOI: 10.1002/14651858.CD001321.pub7.

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

Background
Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the
bladder. Cranberry products have been used widely 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.

Objectives
To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.

Search methods
We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 through contact with the Information Specialist
using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE,
conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria
All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other
intervention (antibiotics, probiotics) for the prevention of UTIs were included.

Data collection and analysis

At least 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, adherence to therapy). Risk ratios (RR) with 95% confidence
intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence
in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results
For this update, 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk
of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk
of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias,
reporting bias and other bias, respectively.

Cranberries for preventing urinary tract infections (Review) 1

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Forty-five studies compared cranberry products with placebo, water or no specific treatment in six different groups of participants. Twenty-
six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence,
cranberry 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 the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with
recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I2 = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI
0.32 to 0.68; I2 = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37
to 0.61; I2 = 0%). However, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR
0.93, 95% CI 0.67 to 1.30; I2 = 9%; moderate certainty evidence), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50;
I2 = 3%; moderate certainty evidence), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies,
464 participants: RR 0.97, 95% CI 0.78 to 1.19; I2 = 0%; low certainty evidence).

Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry
liquid (one study), and different doses of PACs (two studies).

Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies,
385 participants: RR 1.03, 95% CI 0.80 to 1.33; I2 = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30,
95% CI 0.79 to 2.14; I2 = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3
studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or
between different doses of PACs, 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 a 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 compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs
could be demonstrated between low, moderate and high doses of PACs.

Authors' conclusions
This update adds a further 26 studies, taking the total number of studies to 50 with 8857 participants. These data support the use of
cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people
susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder
emptying problems, or pregnant women.

PLAIN LANGUAGE SUMMARY

Cranberries for preventing urinary tract infections

What is the issue?

Cranberries (as cranberry juice, tablets or capsules) have been used for many years to prevent urinary tract infections (UTIs). Cranberries
contain proanthocyanidins (PACs), substances that can prevent bacteria from sticking to the walls of the bladder. This may help prevent
infections and reduce the need for working people to take time for medical appointments. However, there is currently no established
regimen for what PACs dose to use and no formal regulation by health authorities of cranberry products. In particular, the dose suggested
may not be included on the package.

What did we do?

We analysed the results of randomised controlled trials (RCTs), which compared the occurrence of UTIs in people taking a cranberry product
with those taking a placebo or no treatment. We also analysed the results of RCTs comparing a cranberry product with other treatments
such as antibiotics or probiotics.

What did we find?

We found 50 RCTs involving 8857 people. Forty-five RCTs compared cranberry with a placebo or no treatment. Taking cranberries as a juice,
tablets or capsules reduced the number of UTIs in women with recurrent UTIs, in children with UTIs and in people susceptible to UTIs
following an intervention such as bladder radiotherapy. However, UTIs did not appear to be reduced in elderly institutionalised men and
women, in adults with neuromuscular bladder dysfunction and incomplete bladder emptying, or in pregnant women. Few people reported
any side effects with the most common being tummy pain. We did not find enough information to determine if cranberry products are
more or less effective compared with antibiotics or probiotics in preventing further UTIs.

Conclusions

Cranberry products may help to prevent UTIs which cause symptoms in women with frequent UTIs, in children with UTIs and in people
who have undergone an intervention involving the bladder. However, further assessment is required in well-designed and prospectively
registered RCTs to clarify further who with UTIs would benefit from cranberry products.

Cranberries for preventing urinary tract infections (Review) 2

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cranberries for preventing urinary tract infections (Review)
SUMMARY OF FINDINGS

Summary of findings 1. Any cranberry product versus placebo or control for preventing urinary tract infection

Library
Cochrane
Cranberry product versus placebo or control for preventing UTI

Patient or population: preventing UTI

Setting: multiple different settings
Intervention: any cranberry product

Better health.
Informed decisions.
Trusted evidence.
Comparison: placebo or control

Outcomes Anticipated absolute effects* (95% CI) Relative effect No. of partici- Certainty of the
(95% CI) pants evidence
Risk with place- Risk with any cranberry (RCTs) (GRADE)
bo/control product

Symptomatic, culture-verified UTI 243 per 1,000 180 per 1,000 RR 0.74 1555 (8) ⊕⊕⊕⊝
(134 to 241) (0.55 to 0.99) MODERATE 1
Women with recurrent UTI

Symptomatic, culture-verified UTI 113 per 1,000 105 per 1,000 RR 0.93 1489 (3) ⊕⊕⊕⊝
(76 to 147) (0.67 to 1.30) MODERATE 2
Elderly men and women in institutions

Symptomatic, culture-verified UTI 289 per 1,000 153 per 1,000 RR 0.53 428 (4) ⊕⊕⊕⊝
(104 to 225) (0.36 to 0.78) MODERATE 3
Children

Symptomatic, culture-verified UTI 440 per 1,000 427 per 1,000 RR 0.97 464 (3) ⊕⊕⊝⊝
(343 to 524) (0.78 to 1.19) LOW 2 3
Adults with bladder emptying issues or multiple
sclerosis

Cochrane Database of Systematic Reviews

Symptomatic, culture-verified UTI 231 per 1000 109 per 1000 RR 0.47 1434 (6) ⊕⊕⊝⊝
LOW 2 3
People with a susceptibility to a UTI due to an in- 85 to 141 (o.37 to 0.61)
tervention

Gastrointestinal adverse events 41 per 1,000 54 per 1,000 RR 1.33 2166 (10) ⊕⊕⊕⊝
(41 to 73) (1.00 to 1.77) MODERATE 2

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio; UTI: urinary tract infection

GRADE Working Group grades of evidence

3
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cranberries for preventing urinary tract infections (Review)
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is
substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.

Library
Cochrane
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1 Inconsistency: increased heterogeneity

2 Imprecision: small studies and wide CIs
3 Increased risk of bias: allocation and blinding

Better health.
Informed decisions.
Trusted evidence.
Cochrane Database of Systematic Reviews
4
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

BACKGROUND Description of the intervention

Description of the condition Cranberries belong to a group of evergreen dwarf shrubs of

subgenus Oxycoccus and genus Vaccinium. In North America,
The term urinary tract infection (UTI) refers to the presence of a cranberry refers to Vaccinium macrocarpon. Cranberries comprise
'threshold' number of bacteria in the urine (usually ≥ 108 colony nearly 90% water, but they also contain various organic substances
forming units (CFU)/L) with or without pyuria (urinary white cell such as quinic acid, malic acid and citric acid, as well as glucose
count (WCC) > 100/µL) together (usually) with symptoms involving and fructose. Products made from cranberries include juice, syrup,
the bladder, ureters and kidneys. UTIs are classified into UTIs which jam, tablets and powder. The active ingredient of cranberry is
involve only the bladder (cystitis) or urethra (urethritis), and febrile proanthocyanidin (PAC) (Howell 2010). Processing cranberries into
UTIs, which also involve the kidneys (pyelonephritis). various products, such as tablets or capsules, can reduce the PAC
concentration (Howell 2010) so that some products may contain
Most UTIs involve the lower urinary tract (acute cystitis). These little or no PAC. In addition, the complexities of the PAC structures
can occur in women and men but are more common in women. mean that the measurement of PAC content may not be accurate
About 60% of women over the age of 18 years will suffer or reproducible (Prior 2010). To ensure potency in cranberry
one or more UTIs (Kwok 2022). The symptoms include dysuria, products, levels of PACs must be quantified in a replicable manner,
urgency, frequency and occasionally haematuria. Many women and the 4-dimethylaminocinnamaldehyde method is currently
have symptoms suggestive of UTIs but have either no bacterial the most validated standard method for quantifying PACs in
growth or counts < 108 CFU/L on repeated urine cultures. It is now cranberry products (Prior 2010). A randomised controlled trial
accepted that the microbiological diagnosis of UTIs in an otherwise (RCT) evaluating the dosage effect of cranberry powder in healthy
normal symptomatic woman is a colony count of ≥ 106 CFU/L. volunteers compared with placebo found that to achieve an ex-
Symptoms of pyelonephritis include flank or back pain, fever, chills vivo bacterial anti-adhesion effect in urine, 36 mg of cranberry PACs
with shaking, general ill feeling, plus those symptoms of a lower equivalence was effective, though 72 mg offered more prolonged
UTI. Although most people who present to a doctor or hospital efficacy (Howell 2010). Therefore, based on this study in healthy
have symptomatic UTIs, some people can be asymptomatic, and volunteers, cranberry products containing PACs levels of 36 to 72
only those asymptomatic people who are at high risk of developing mg are currently recommended.
further infections (pregnant women and the elderly) are considered
to need treatment (Kwok 2022). About 30% of women may have How the intervention might work
recurrent UTIs, with an average of two to three episodes per year
The belief that eating cranberries would be beneficial may have
(Kwok 2022; Roberts 1979; Wong 1984).
started centuries ago from the Native Americans who would eat
UTIs are one of the most common medical conditions requiring cranberries as a remedy for UTIs and other illnesses. Early studies
inpatient or outpatient treatment. In Australia, recurrent episodes attributed the antibacterial effects of cranberry to acidification of
of pyelonephritis account for more than 76,000 hospital admissions the urine by increasing the excretion of hippuric acid (Blatherwick
per year at an annual cost of AUD$909 million. In the USA, 1923; Kinney 1979). Several studies, however, found no difference
recurrent episodes of pyelonephritis and associated complications or only transient differences in the level of hippuric acid (Kahn
necessitate over one million hospital admissions annually (Patton 1967; McLeod 1978). More recent research suggests that cranberries
1991), with costs estimated to be greater than two billion dollars prevent bacteria (particularly Escherichia coli) from adhering to the
per year (Foxman 2002). Specific subpopulations are at increased uroepithelial cells lining the bladder wall (Schmidt 1988; Zafriri
risk of developing symptomatic UTIs. These groups include infants, 1989). Without adhesion, E. coli cannot infect the mucosal surface
pregnant women, patients with spinal cord injuries with or of the urinary tract. In vitro, this adhesion is reduced by two
without catheters, patients with diabetes or multiple sclerosis, components of cranberry: fructose, which inhibits adherence of
patients with acquired immunodeficiency disease syndrome, type 1 (mannose specific) fimbriated E. coli (Foo 2000; Howell
patients with underlying urologic abnormalities, and patients with 2007), and PACs, which inhibits the adherence of p-fimbriated (a-
asymptomatic bacteriuria who undergo an invasive procedure galactose-(1-4) specific) E. coli (Zafriri 1989). PACs have A- and B-
(Foxman 2002). Although UTIs can occur in both men and women, type linkages, but It is only the PACs with A-type linkages (found
they are about 50 times more common in young adult women in cranberry juice) which prevent the adhesion of E. coli to the
than in young adult men. Most UTIs arise from the ascending route bladder wall (Howell 2002; Howell 2005). PACs with B-type linkages
of infection, so the shorter urethra in women may allow bacteria are present in other sources, including commercial apple and grape
to ascend more easily into the bladder. The annual incidence of juice and dark chocolate, but these products do not have any anti-
acute uncomplicated UTIs is 7% for women of all ages, peaking adhesion properties (Howell 2005). As the anti-adhesion activity
at 15 to 24 years and in women older than 65 (Giesen 2010). Up decreases over time, it is recommended that cranberry products
to 30% of women who have a UTI may have a recurrence within should be consumed in the morning and in the evening (Howell
six to 12 months (Epp 2010). UTIs often occur in clusters with 2010).
long periods (several months) where patients are symptom-free
(Stapleton 1997). In children, UTIs occur more commonly in boys
Why it is important to do this review
than girls up to the age of 12 months, but overall, UTIs occur UTIs are an important public health problem since they affect
about three times more often in girls than boys (1% to 3% in boys, more than 150 million people each year worldwide (Flores-Mireles
3% to 7% in girls) (Hellstrom 1991; Winberg 1974). Children often 2015). Most people experience uncomplicated UTIs without fever.
present with a fever and non-specific symptoms such as lethargy Some people experience recurrent uncomplicated UTIs, resulting
(tiredness), vomiting or poor feeding. in a significant health problem which impacts their quality of
life. Prevention of recurrence has often relied on long-term use

Cranberries for preventing urinary tract infections (Review) 5

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

of low-dose antibiotics, but there are adverse effects, including Exclusion criteria
diarrhoea as well as the development of antibiotic-resistant
• Studies of the acute treatment of UTIs. These are analysed in a
bacteria. Cranberry products have been suggested in some but
separate review by the same authors (Jepson 1998b)
not all guidelines as an alternative to antibiotic prophylaxis in
people with recurrent uncomplicated UTIs without fever and other • Studies of any urinary tract condition not caused by a bacterial
systemic symptoms (Kwok 2022). Therefore, it is important to infection (e.g. interstitial cystitis - a chronic inflammation of the
review the evidence from RCTs in different patient populations to bladder wall)
determine the benefits and harms of cranberry for the prevention
Types of interventions
of uncomplicated UTIs.
Any cranberry product (e.g. cranberry capsules, tablets, powder,
The acute treatment of UTIs with cranberry products has been juice or extract) taken by participants for at least one month.
reviewed previously (Jepson 1998b). Cranberry products included in this review could contain small
amounts of other compounds (e.g. D-mannose or propolis extract)
OBJECTIVES provided that these were not antibiotics.
The aim of this review was to assess the effectiveness and adverse Types of outcome measures
effects of cranberries in the prevention of UTIs in susceptible
populations such as women with recurrent UTIs, children, elderly We included all studies meeting the inclusion criteria listed above.
institutionalised men and women, pregnant women, people with We did not report all the outcomes reported in individual studies.
neuromuscular dysfunction of the bladder and reduced bladder We limited reporting to the clinically relevant outcomes listed
emptying, and people with susceptibility for UTIs due to an below.
intervention. We wished to test the following hypotheses:
The bacteriological criteria for diagnosis of UTIs include
1. Cranberry products are more effective than placebo or no microbiological confirmation from mid-stream urine (MSU)
treatment in the prevention of UTIs in susceptible populations. specimen or catheter specimen. An MSU with a single pathogenic
2. Cranberry products are more effective than other treatments in organism and a colony count ≥ 108 CFU/L is generally considered
the prevention of UTIs in susceptible populations. consistent with a UTI. Some clinicians use a lower colony count (≥
3. Different cranberry products (juice, capsules, tablets, powder, 107 CFU/L). Some clinicians also require concurrent pyuria (white
concentrate) may differ in the effectiveness of preventing UTIs cells in the urine) to confirm a UTI. Lower bacterial colony counts
in susceptible populations. may be used if the urine specimen is obtained by a catheter or by
supra-pubic aspiration.
METHODS
Primary outcomes
Criteria for considering studies for this review • The number of participants in each group with symptomatic,
Types of studies culture-verified UTIs. Symptomatic UTIs were defined as having
one or more symptoms of dysuria, frequency, urgency, and/or
RCTs and quasi-RCTs (e.g. those studies which randomised fever
participants by date of birth or case record number) and all • The number of participants with symptoms of UTIs without
types of study design (parallel group, multi-arm and cross-over) of culture verification
cranberry products (available as juice, tablets, capsules or powder)
• The number of participants with culture-verified UTIs without
versus placebo, no treatment or any other treatment were eligible
symptoms.
for inclusion.
Secondary outcomes
Types of participants
• Death
Inclusion criteria
• Gastrointestinal (GI) adverse effects
Studies of susceptible men, women or children, as defined below, • Adherence to therapy.
were included. These population groups were analysed separately
and in combination. Search methods for identification of studies
• Women with a history of recurrent lower UTIs (usually more than Electronic searches
two episodes in the previous 12 months)
We searched the Cochrane Kidney and Transplant Register
• Elderly institutionalised men and women of Studies up to 13 March 2023 through contact with the
• Pregnant women Information Specialist using search terms relevant to this review.
• Children The Specialised Register contains studies identified from the
• Adults with neuromuscular dysfunction of the bladder with following sources.
incomplete bladder emptying
1. Monthly searches of the Cochrane Central Register of Controlled
• Adults having undergone an intervention leading to an Trials (CENTRAL)
increased susceptibility to UTIs (e.g. urogenital surgery,
2. Weekly searches of MEDLINE OVID SP
radiotherapy to the bladder, or kidney transplant recipients).
3. Searches of kidney and transplant journals and the proceedings
and abstracts from major kidney and transplant conferences

Cranberries for preventing urinary tract infections (Review) 6

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

4. Searching the current year of EMBASE OVID SP • Was there adequate sequence generation (selection bias)?
5. Weekly current awareness alerts for selected kidney and • Was allocation adequately concealed (selection bias)?
transplant journals • Was knowledge of the allocated interventions adequately
6. Searches of the International Clinical Trials Register Search prevented during the study?
Portal (ICTRP) and ClinicalTrials.gov. ◦ Participants and personnel (performance bias)
◦ Outcome assessors (detection bias)
Studies contained in the Register are identified through searches of
CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane • Were incomplete outcome data adequately addressed (attrition
bias)? We chose a cut-off of > 10% missing or excluded data in
Kidney and Transplant. Details of search strategies, as well as a
outcome analysis as a threshold for a high risk of bias in this field.
list of handsearched journals, conference proceedings and current
awareness alerts, are available on the Cochrane Kidney and • Are reports of the study free of suggestion of selective outcome
Transplant website. reporting (reporting bias)?
• Was the study apparently free of other problems that could put
See Appendix 1 for search terms used in strategies for this review. it at risk of bias?
Searching other resources Measures of treatment effect
We searched reference lists of review articles, relevant studies Risk ratio (RR) with 95% confidence intervals (CI) was used
and clinical practice guidelines. We requested information as the measure of effect for dichotomous outcomes. Studies
about unpublished or incomplete studies from investigators with either parallel or cross-over designs were included in the
known to be involved in previous studies. Companies involved review. For cross-over studies, only the period before the cross-
with the promotion and distribution of cranberry preparations over was used for the meta-analyses. Where available, data
were approached and asked to provide information on both were entered into RevMan for meta-analyses; otherwise, it was
published and unpublished studies. Conference abstracts from reported narratively. Infrequent adverse effects and adherence
the Proceedings of the Urological Association (1990 to 1998) and were summarised descriptively in the results.
the Journal of the American Geriatrics Society (1990 to 1998)
were searched for relevant studies for the initial review. We Unit of analysis issues
contacted companies involved with the promotion and distribution
Studies used different units of analysis for the outcome of
of cranberry preparations and checked reference lists of review
symptomatic UTI. Some used the number of UTIs in the entire
articles and relevant studies.
study arm as the unit of analysis, whilst others used the number of
Data collection and analysis participants having one or more UTIs during the study period. As
UTIs can cluster (so that one participant may have several UTIs over
Selection of studies the course of the study period), we believed that the number of UTIs
per study population did not provide enough information on those
The search strategy described was employed to obtain titles and,
people who had no UTIs. Therefore, we decided that the number of
where possible, abstracts of studies that were potentially relevant
participants who had one or more UTIs was more informative, and
to the review. The titles and abstracts were screened independently
we used this unit of analysis for the meta-analyses.
by at least two authors, who discarded studies that were not
applicable; however, studies and reviews that may have included In studies using different doses of cranberry product, for our
relevant data or information on studies were retained initially. Two primary analyses, we combined all cranberry treatment groups
authors independently assessed retrieved abstracts and, where together. For example, we grouped those given one tablet a day
necessary, the full text of these studies to determine which studies with those given two tablets and compared these data to data
satisfied the inclusion criteria. from participants taking a placebo, other control medication or no
treatment. Several studies reported follow-up results beyond the
Data extraction and management
treatment period. For example, treatment in some studies was six
At least two authors independently extracted information using months, but outcomes were reported at six, 12 and 15 months. Our
specially designed data extraction forms. For each included study, analyses used 'on-treatment' outcome events and did not analyse
information was collected regarding the location of the study, 'off-treatment' follow-up as there is no biologically plausible reason
methods of the study, the participants (sex, age, eligibility criteria), that the effects of cranberry products would be maintained over a
the nature of the interventions, and data relating to the outcomes significant period.
specified previously. Where possible, missing data (including
side effects) were sought from the authors. All first authors Dealing with missing data
were contacted for more data if necessary. Five authors replied Further information was sought from the authors of those papers
(Kontiokari 2001; NAPRUTI 2011; Salo 2010; Stothers 2002; Walker that contained insufficient information to make a decision about
1997), but no additional information was obtained from three of eligibility.
these communications (NAPRUTI 2011; Salo 2010; Walker 1997).
Discrepancies in the data extraction were resolved via discussion. Assessment of heterogeneity

Assessment of risk of bias in included studies We first assessed the heterogeneity by visual inspection of the
forest plot. Heterogeneity was then analysed using a Chi2 test on
The following items were assessed independently by two authors N-1 degrees of freedom, with an alpha of 0.05 used for statistical
using the risk of bias assessment tool (Higgins 2022) (Appendix 2). significance and with the I2 test (Higgins 2003). A guide to the
interpretation of I2 values is as follows:
Cranberries for preventing urinary tract infections (Review) 7
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

• 0% to 40%: might not be important • Cranberry product versus placebo or control according to the
• 30% to 60%: may represent moderate heterogeneity amount of the active ingredient (PAC)
• 50% to 90%: may represent substantial heterogeneity • Sponsor type (any commercial involvement versus no
• 75% to 100%: considerable heterogeneity. commercial involvement).

The importance of the observed value of I2 depends on the Summary of findings and assessment of the certainty of the
magnitude and direction of treatment effects and the strength of evidence
evidence for heterogeneity (e.g. P value from the Chi2 test or a CI for We presented the main results of the review in a summary
I2) (Higgins 2022). of findings (SOF) table. This table presents key information
concerning the quality of the evidence, the magnitude of the effects
Assessment of reporting biases of the interventions examined, and the sum of the available data
We had planned to look at funnel plots to assess for the potential for the main outcomes (Schunemann 2022a). The SOF table also
existence of small study bias, but most studies were small and includes an overall grading of the evidence related to each of the
funnel plots did not demonstrate variation in relative risk with main outcomes using the GRADE (Grades of Recommendation,
sample size (Higgins 2022). Assessment, Development and Evaluation) approach (GRADE 2008;
GRADE 2011). The GRADE approach defines the quality of a body
Data synthesis of evidence as the extent to which one can be confident that
an estimate of effect or association is close to the true quantity
The outcome used for the meta-analyses was the number of people
of specific interest. The quality of a body of evidence involves
experiencing at least one UTI by the end of the treatment period.
consideration of the within-trial risk of bias (methodological
Data were pooled using the random-effects model.
quality), directness of evidence, heterogeneity, the precision of
Studies were not included in the meta-analyses for the following effect estimates and risk of publication bias (Schunemann 2022b).
reasons: We presented the following outcome in the SOF tables.

• The design was a cross-over study, and data were not reported • Symptomatic, culture-verified UTIs in all participant groups
separately for the first phase taking any cranberry product compared with a placebo or no
specific treatment
• They did not report data using the same unit of analysis; see
above • GI adverse effects
• There were no UTI outcomes reported (and no information could • Death
be obtained from the authors).
RESULTS
The data for these studies have been described narratively in the
text. Description of studies
Results of the search
Subgroup analysis and investigation of heterogeneity
We undertook the updated search on 13 March 2023. For articles
Studies were sub-grouped by the population types described in the
identified up to 2016, two reviewers checked the abstracts or full-
inclusion criteria (e.g. older people; women with recurrent UTIs).
text publications of articles for further information, a single author
Sensitivity analysis (GW) reviewed articles identified between 2016 and 2020, and four
authors reviewed articles identified between 2020 and 2023. After
• Diagnostic criteria for UTIs (< 108 CFU/L versus ≥ 108 CFU/L) applying the inclusion criteria, we included 26 new studies for a
• High-dose versus low-dose cranberry product total of 50 studies (See Figure 1).

Cranberries for preventing urinary tract infections (Review) 8

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Figure 1. Flow diagram of study identification and selection

Cranberries for preventing urinary tract infections (Review) 9

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Figure 1. (Continued)

Included studies Of these studies, six used cranberry juice, 10 used tablets or
powder, and one study used both (Stothers 2002). Ten studies used
See Characteristics of included studies
a placebo as a comparison (Barbosa-Cesnik 2011; Bruyere 2019;
This updated review includes 50 studies: six cross-over studies Koradia 2019; Maki 2016; Stapleton 2012; Stothers 2002; Stothers
(Foda 1995; Haverkorn 1994; Hess 2008; Linsenmeyer 2004; 2016; Takahashi 2013; Vostalova 2015; Walker 1997), one study
Schlager 1999; Walker 1997); 34 parallel group studies with two used very low dose cranberry in the control arm (Babar 2021),
arms; eight studies with three arms (Ferrara 2009; Juthani-Mehta three studies used no treatment as their comparator (De Leo 2017;
2010; Sengupta 2011; Stapleton 2012; Stothers 2002; Stothers 2016; Kontiokari 2001; Sengupta 2011), and two compared cranberry
Temiz 2018; Wing 2008) and two studies with four arms and a products with antibiotics (McMurdo 2009; NAPRUTI 2011).
factorial design (Bianco 2012; SINBA 2007) with a total of 8857 Elderly institutionalised men and women
randomised participants.
Seven studies evaluated cranberry juice for the prevention of
The number of included studies has increased steadily over the UTIs in elderly populations (Avorn 1994; Bianco 2012; Caljouw
years. Four studies (Avorn 1994; Foda 1995; Haverkorn 1994; Walker 2014; Haverkorn 1994; Juthani-Mehta 2010; Juthani-Mehta 2016;
1997) were included in the first version of this review (Jepson McMurdo 2005). All participants were residents in nursing homes,
1998a); three studies (Kontiokari 2001; Schlager 1999; Stothers care homes or hospital in-patients.
2002) were added in 2003/2004; three studies (Linsenmeyer 2004;
McMurdo 2005; Waites 2004) were added in the 2008 update; and Participants in some of these studies did not require a history of
14 studies were included in the 2012 update (Barbosa-Cesnik 2011; UTIs to be involved, as increased age is a risk factor for UTIs.
Cowan 2012; Essadi 2010; Ferrara 2009; Hess 2008; Juthani-Mehta
2010; McGuiness 2002; McMurdo 2009; NAPRUTI 2011; Salo 2010; Four studies used cranberry tablets as the intervention (Bianco
Sengupta 2011; SINBA 2007; Uberos 2012; Wing 2008). In this latest 2012; Caljouw 2014; Juthani-Mehta 2010; Juthani-Mehta 2016), and
update, 26 additional studies were included (Afshar 2012; Babar three used juice (Avorn 1994; Haverkorn 1994; McMurdo 2005). Four
2021; Bianco 2012; Bonetta 2017; Bruyere 2019; Caljouw 2014; studies used a placebo for the comparison (Avorn 1994; Caljouw
De Leo 2017; Dotis 2014; Fernandes 2016; Foxman 2015; Gallien 2014; Juthani-Mehta 2016; McMurdo 2005), two studies compared
2014; Juthani-Mehta 2016; Koradia 2019; Lopes de Carvalho 2012; cranberry with no treatment (Bianco 2012; Juthani-Mehta 2010),
Maki 2016; Mohammed 2016; Mooren 2020; Scovell 2015; Singh and one study used water as the comparative treatment (Haverkorn
2016; Stapleton 2012; Stothers 2016; Takahashi 2013; Temiz 2018; 1994).
Vostalova 2015; Wan 2016; Wing 2015). Pregnant women
Types of participants Three studies included a total of 708 pregnant women (Essadi 2010;
Wing 2008; Wing 2015). Two studies recruited participants in their
The studies were grouped by the types of participants included in
late first or early second trimesters (Wing 2008; Wing 2015), while
the studies and analysed separately due to clinical heterogeneity.
Essadi 2010 did not report this information. Wing 2008 was a three-
Women with a history of recurrent urinary tract infections arm study comparing a single daily dose (240 mL) or two to three
daily doses of cranberry juice (640 mL to 720 mL) with a placebo
Sixteen studies included non-pregnant, adult women with previous beverage. Essadi 2010 compared four daily doses (totalling 1000
UTIs (Babar 2021; Barbosa-Cesnik 2011; Bruyere 2019; De Leo 2017; mL) of cranberry juice with the same volume of water, and Wing
Kontiokari 2001; Koradia 2019; Maki 2016; McMurdo 2009; NAPRUTI 2015 compared four cranberry tablets per day with placebo tablets.
2011; Sengupta 2011; Stapleton 2012; Stothers 2002; Stothers 2016;
Takahashi 2013; Vostalova 2015; Walker 1997). The age of the Children
women varied considerably, with some studies including a broad
Eight studies enrolled children either at risk of repeat UTIs (Afshar
range (e.g. > 18 years) and others very narrow (e.g. 40 to 50 years).
2012; Dotis 2014; Ferrara 2009; Salo 2010; Uberos 2012; Wan 2016)
Generally, to be included in the studies, women had to have had at
or who had a neurogenic bladder (Foda 1995; Schlager 1999).
least two UTIs in the past 12 months.
Cranberries for preventing urinary tract infections (Review) 10
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

In the six studies of children at risk of UTIs but without a neurogenic cranberry capsule to a placebo. Temiz 2018, a three-armed study,
bladder, five studies included children who had experienced more enrolled patients with a ureterostomy who underwent ileal conduit
than one UTI (Afshar 2012; Dotis 2014; Ferrara 2009; Uberos 2012; diversion and compared cranberry tablets with no treatment or
Wan 2016) and one enrolled children at their first UTI (Salo 2010). bladder training.
Three studies compared cranberry juice with placebo (Afshar 2012;
Salo 2010; Wan 2016), Uberos 2012 compared cranberry syrup with Interventions and comparisons
antibiotics (trimethoprim syrup), Ferrara 2009 compared cranberry Although most of the early studies evaluated cranberry juice,
plus lingonberry concentrate with lactobacillus, and Dotis 2014 later studies tested a range of other products, including tablets,
compared cranberry capsules with no treatment. capsules, concentrate, or powder. Of the 50 included studies, 19
studies (3936 randomised participants) evaluated cranberry juice
In the two studies of children susceptible to UTIs because of a
or juice concentrate (Afshar 2012; Avorn 1994; Barbosa-Cesnik 2011;
neurogenic bladder (Foda 1995; Schlager 1999), the children were
Cowan 2012; Essadi 2010; Ferrara 2009; Foda 1995; Haverkorn
managed by clean intermittent catheterisation. Both were cross-
1994; Kontiokari 2001; Maki 2016; McMurdo 2005; Salo 2010;
over studies which compared cranberry juice to placebo or water
Schlager 1999; Stapleton 2012; Stothers 2016; Takahashi 2013;
and included 40 and 15 children, respectively.
Uberos 2012; Wan 2016; Wing 2008). Twenty-nine studies (4682
Adults with neuromuscular dysfunction of the bladder and incomplete randomised participants) evaluated cranberry tablets, capsules or
bladder emptying powder (Babar 2021; Bianco 2012; Bonetta 2017; Bruyere 2019;
Caljouw 2014; De Leo 2017; Dotis 2014; Fernandes 2016; Foxman
Nine studies evaluated the effectiveness of cranberry products
2015; Gallien 2014; Hess 2008; Juthani-Mehta 2010; Juthani-Mehta
in people with bladder emptying issues caused by a number of
2016; Linsenmeyer 2004; Lopes de Carvalho 2012; McGuiness 2002;
conditions, including multiple sclerosis and spinal cord injuries
McMurdo 2009; Mohammed 2016; Mooren 2020; NAPRUTI 2011;
(Gallien 2014; Hess 2008; Linsenmeyer 2004; Lopes de Carvalho
Scovell 2015; Sengupta 2011; SINBA 2007; Singh 2016; Temiz
2012; McGuiness 2002; Scovell 2015; SINBA 2007; Singh 2016; Waites
2018; Vostalova 2015; Waites 2004; Walker 1997; Wing 2015); one
2004).
study (150 randomised participants) compared cranberry juice and
Three studies enrolled people diagnosed with multiple sclerosis. tablets with placebo (Stothers 2002), and one study (89 randomised
McGuiness 2002 compared cranberry capsules with placebo in participants) compared cranberry tablets plus a probiotic with
patients who voided naturally or who used intermittent self- placebo (Koradia 2019).
catheterisation. Lopes de Carvalho 2012 compared two daily
The control or comparison groups also varied considerably. The
capsules of a cranberry compound with a placebo, and Gallien 2014
control arms used placebo in 34 studies, no treatment in eight
compared cranberry powder with a placebo powder.
studies (Bonetta 2017; De Leo 2017; Dotis 2014; Ferrara 2009;
Five studies evaluated the effect of cranberry products in people Juthani-Mehta 2010; Kontiokari 2001; Sengupta 2011; Temiz 2018)
needing either indwelling catheters or intermittent catheterisation and water in three studies (Essadi 2010; Foda 1995; Haverkorn
(Hess 2008; Linsenmeyer 2004; Scovell 2015; SINBA 2007; Waites 1994). Three studies used antibiotics as the comparison groups
2004). These studies evaluated the effectiveness of cranberry (McMurdo 2009; NAPRUTI 2011; Uberos 2012), and one study used
tablets versus placebo in adults with spinal cord injuries, of which Lactobacillus acidophilus probiotic (Singh 2016).
two were cross-over studies (Hess 2008; Linsenmeyer 2004), one
Four studies had additional comparisons: methenamine hippurate
was a parallel study (Waites 2004), and one used a four-arm factorial
(SINBA 2007), Lactobacillus (Ferrara 2009; Kontiokari 2001), and
design comparing cranberry product with methenamine hippurate
bladder training (Temiz 2018). Seven studies compared different
and placebo (SINBA 2007).
doses of cranberry or different cranberry products (Babar 2021;
One study enrolled people with asymptomatic bacteriuria with Bianco 2012; Juthani-Mehta 2010; Sengupta 2011; Stothers 2002;
or without recurrent UTIs (Singh 2016); 14 participants required Stothers 2016; Wing 2008).
intermittent catheterisation or bladder drainage via a suprapubic
Dosage, concentration and formulation of cranberry products
catheter.
One of the difficulties of undertaking a review of cranberry products
Adults with susceptibility to urinary tract infection associated with an is the lack of standardisation of PAC dose in the products evaluated
intervention in the studies. This is important because the dose and the
Seven studies included participants prone to UTIs with or without type of cranberry product could impact effectiveness. There was
an intervention (Bonetta 2017; Cowan 2012; Fernandes 2016; considerable variation between the studies in terms of:
Foxman 2015; Mohammed 2016; Mooren 2020; Temiz 2018).
• Type of cranberry product
Medical and surgical interventions can cause an increased • Amount of the component believed to be the active ingredient
susceptibility to UTIs. Seven studies included participants (PAC) in the products
undergoing such interventions. Three studies included patients • Dosage of the products.
undergoing radiation treatment for bladder, prostate, pelvic or
cervical cancer and compared cranberry juice or capsules with a Type of cranberry product
placebo (Cowan 2012; Mohammed 2016) or no treatment (Bonetta
There were two main types of products, those that used a liquid
2017). Two studies included women undergoing gynaecological
form (juice or concentrate) and those that used a dried form
surgery and compared cranberry tablets with placebo tablets
(tablets, capsules or powder). Early studies almost exclusively
(Foxman 2015; Mooren 2020). Fernandes 2016 enrolled adult
used the liquid form, and low adherence was common for people
female kidney transplant recipients and compared a daily
Cranberries for preventing urinary tract infections (Review) 11
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

drinking it over long periods, reducing the likelihood that it could Dosage of cranberry products
be effective. In more recent years, tablet and dried forms have been The dosage of cranberry products was difficult to determine across
used most commonly in studies. the studies, especially in those in children, where it was calculated
Cranberry juice, cranberry concentrate or syrup per kg of body weight. The volume of cranberry products does not
equate to the amount of PAC, and concentrations probably vary
Nineteen studies used cranberry juice only, with daily volumes with individual products, and some may contain no PAC at all.
ranging from 30 mL to 1 litre and 0.2 mL/kg to 5 mL/kg. One study
used cranberry juice and tablets (Stothers 2002). Two studies stated Four studies compared different doses of cranberry products
only that 'low dose' juice was given (Stothers 2002) or juice given (Bianco 2012; Juthani-Mehta 2010; Sengupta 2011; Wing 2008) and,
twice daily (Cowan 2012) with no further details. while not comparable across different studies because each used
different products, can be used individually to determine whether
Cranberry tablets, capsules or powder there appears to be a dose effect within the single study. Three of
Thirty studies (including the Stothers 2002 juice and tablets these studies reported the PAC amounts; 16.25 mg versus 32.5 mg
study) evaluated the effectiveness of cranberry tablets, capsules or in Juthani-Mehta 2010, 7.5 mg versus 15 mg in Sengupta 2011 and
powder. Doses ranged from 1 tablet/day up to 4 tablets/day, and 36 mg versus 72 mg versus 108 mg in Bianco 2012.
250 mg powder up to an 8 g tablet.
Definitions of urinary tract infection
Amount of proanthocyanidin administered
Our primary outcome a priori was symptomatic UTIs, verified with
PACs are believed to be the active ingredient of cranberry products, a positive urine culture of ≥ 106 CFU/L. In 34 studies, the outcome
so it is probable that the amount of PAC in a product determines was reported to be symptomatic, culture-verified UTIs; of these, 25
the efficacy of that product. The importance of PAC was less well studies reported the threshold used for diagnosis. Sixteen studies
or not recognised in the early studies, and therefore the amount used a threshold of ≥ 108 CFU/L (Afshar 2012; Barbosa-Cesnik
prescribed was infrequently formally measured or described by 2011; Bonetta 2017; Caljouw 2014; Cowan 2012; Ferrara 2009; Foda
study authors. 1995; Gallien 2014; Juthani-Mehta 2016; Koradia 2019; Salo 2010;
Stapleton 2012; Stothers 2002; Temiz 2018; Uberos 2012; Vostalova
Of the 19 studies evaluating juice or concentrate, six reported 2015), four used ≥ 107 CFU/L (Hess 2008; McMurdo 2009; Schlager
estimates of PAC concentrations. In Afshar 2012, the PAC dose was
1999; Sengupta 2011) and five used ≥ 106 CFU/L (Babar 2021;
reported as 37% of liquid volume with doses of 2 mL/kg/day, but
Koradia 2019; Maki 2016; NAPRUTI 2011; Singh 2016). Seven studies
data on actual volumes taken were not provided. McMurdo 2005
reported asymptomatic UTIs, including Foda 1995, which also
reported the PAC dose as 11.17 μg/g of dry solids, but the amount
reported symptomatic UTIs. Of these, six studies used a threshold
taken was reported as 300 mL. The remaining four studies reported
of ≥ 108 CFU/L (Avorn 1994; Bianco 2012; Foda 1995; Juthani-Mehta
PAC amounts of 112 mg/day (Barbosa-Cesnik 2011), 40 mg/day
(Takahashi 2013), 80 to 240 mg/day (Wing 2008), and 18 mg/kg/day 2010; Waites 2004; Wing 2008), and one used a threshold of ≥ 109
(Uberos 2012). CFU/L (McGuiness 2002). Nine studies did not report symptoms of
UTIs, but four of these reported the threshold used to diagnose
Of the 30 studies evaluating cranberry in a tablet, capsule or UTIs: two studies used a threshold of ≥ 108 CFU/L (Haverkorn
powder form, 18 reported an estimated dose of PAC administered, 1994; Kontiokari 2001 and two used ≥ 107CFU/L (Linsenmeyer 2004;
ranging from 1.4 mg to 120 mg/day (Babar 2021; Bianco 2012; McMurdo 2005).
Bonetta 2017; Caljouw 2014; De Leo 2017; Gallien 2014; Juthani-
Mehta 2010; Juthani-Mehta 2016; Koradia 2019; Mohammed 2016; Excluded studies
Mooren 2020; NAPRUTI 2011; Scovell 2015; Sengupta 2011; Singh Twenty-one studies were excluded.
2016; Temiz 2018; Vostalova 2015; Wing 2015).
• Duration of treatment was less than four weeks: 12 studies (Amin
Of the 24 studies estimating the PAC dose administered, only seven 2018; Barnoiu 2015; Gunnarsson 2017; Howell 2010; Kaspar
studies provided a rationale behind the dosage and amount of 2015; Letouzey 2017; Liu 2019b; Occhipinti 2016; Radulescu
PAC administered (Babar 2021; Bianco 2012; Caljouw 2014; Gallien 2020; Russo 2019; Sappal 2018; Schultz 1984)
2014; Juthani-Mehta 2016; Mooren 2020; Uberos 2012). Babar 2021
• No clinically relevant outcomes: eight studies (Hamilton 2015;
referenced Howell 2010 and Lavigne 2008 as the rationale for the
Howell 2010; Jackson 1997; Jass 2009; Lavigne 2008; Tempera
dosage of PAC used. Bianco 2012, a dosing study itself, investigated
2010; Valentova 2007; Vidlar 2010)
the effect of 36 mg, 72 mg or 108 mg PAC daily and referenced
Avorn 1994 and Lavigne 2008 as the rationale for the dosage • Terminated with no results reported: one study (NCT01079169).
range for the study. Caljouw 2014, Mooren 2020 and Uberos 2012
See Characteristics of excluded studies.
referenced Howell 2010. Gallien 2014 referenced an earlier version
of this review (Jepson 2008), and Juthani-Mehta 2016 referenced Ongoing studies and studies awaiting classification
both Bianco 2012 and Haverkorn 1994 for the rationale behind
the dosages studied. The lack of a standardised PAC dosage was Three potentially relevant studies were identified prior to
identified as a limitation in several studies, with some calling for publication (Cotellese 2023; Hakkola 2023; Madhavan 2021). There
a well-designed, dose-finding study in their discussions (Caljouw are also seven ongoing studies (ACTRN12605000626662; Amador-
2014; Singh 2016). Mulero 2014; ISRCTN55813586; NCT00100061; NCT00247104;
NCT03597152; NCT05730998). These 10 studies will be assessed in
a future update of this review.

Cranberries for preventing urinary tract infections (Review) 12

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

See Characteristics of studies awaiting classification; Risk of bias in included studies

Characteristics of ongoing studies.
See Figure 2 and Figure 3.

Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages
across all included studies.

Random sequence generation (selection bias)

Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias): All outcomes
Blinding of outcome assessment (detection bias): All outcomes
Incomplete outcome data (attrition bias): All outcomes
Selective reporting (reporting bias)
Other bias

0% 25% 50% 75% 100%

Low risk of bias Unclear risk of bias High risk of bias

Cranberries for preventing urinary tract infections (Review) 13

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Figure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Blinding of participants and personnel (performance bias): All outcomes

Blinding of outcome assessment (detection bias): All outcomes
Incomplete outcome data (attrition bias): All outcomes
Random sequence generation (selection bias)
Allocation concealment (selection bias)

Selective reporting (reporting bias)

Other bias

Afshar 2012 + + + + + + ?
Avorn 1994 − − + ? − + −
Babar 2021 + + + + + + −
Barbosa-Cesnik 2011 + + + ? − + −
Bianco 2012 ? ? + ? + − +
Bonetta 2017 + − − ? + + ?
Bruyere 2019 + + + + + + −
Caljouw 2014 + + + + + + +
Cowan 2012 + + + ? + + +
De Leo 2017 ? ? ? ? − − ?
Dotis 2014 ? ? ? ? ? + ?
Essadi 2010 ? ? − ? − + ?
Fernandes 2016 ? ? + ? ? + ?
Ferrara 2009 + ? − ? + + ?
Foda 1995 ? ? − ? − ? ?
Foxman 2015 + + + + + + ?
Gallien 2014 + + + + + + +

Cranberries for preventing urinary tract infections (Review) 14

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Figure 3. (Continued)

Gallien 2014 + + + + + + +
Haverkorn 1994 − − ? ? − ? ?
Hess 2008 ? + + + − + +
Juthani-Mehta 2010 ? ? − − + ? ?
Juthani-Mehta 2016 + + + ? + + +
Kontiokari 2001 + + − + + + ?
Koradia 2019 + + + + + + ?
Linsenmeyer 2004 ? ? + + − + ?
Lopes de Carvalho 2012 ? ? + ? ? ? ?
Maki 2016 + + + ? + + +
McGuiness 2002 ? ? + ? + + ?
McMurdo 2005 + + + + + + +
McMurdo 2009 + + + + + + +
Mohammed 2016 ? ? − − + ? +
Mooren 2020 + + + + + + +
NAPRUTI 2011 + + + + ? + +
Salo 2010 + + + ? + + +
Schlager 1999 ? + + + + + +
Scovell 2015 ? ? + ? ? ? ?
Sengupta 2011 + + − ? + + ?
SINBA 2007 + + + + + + +
Singh 2016 + + ? ? ? + ?
Stapleton 2012 + + ? + ? + ?
Stothers 2002 + + + + + + +
Stothers 2016 ? ? + + − − ?
Takahashi 2013 ? ? + ? − + ?
Temiz 2018 + ? ? ? ? + ?
Uberos 2012 ? + + ? ? + ?
Vostalova 2015 + ? + ? ? + ?
Waites 2004 ? ? + ? − + ?
Walker 1997 ? + + + − + ?
Wan 2016 + ? + + + + ?
Wing 2008 + + + + + + +
Wing 2015 + + + + − + ?

Cranberries for preventing urinary tract infections (Review) 15

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Allocation 2012; Bonetta 2017; Bruyere 2019; Caljouw 2014; Cowan 2012;
Ferrara 2009; Foxman 2015; Gallien 2014; Juthani-Mehta 2010;
Random sequence generation
Juthani-Mehta 2016; Kontiokari 2001; Koradia 2019; Maki 2016;
Twenty-nine studies reported a method of random sequence McGuiness 2002; McMurdo 2005; McMurdo 2009; Mohammed 2016;
generation that was judged to be at low risk bias (Afshar 2012; Mooren 2020; Salo 2010; Schlager 1999; Sengupta 2011; SINBA
Babar 2021; Barbosa-Cesnik 2011; Bonetta 2017; Bruyere 2019; 2007; Stothers 2002; Wan 2016; Wing 2008). Thirteen studies were
Caljouw 2014; Cowan 2012; Ferrara 2009; Foxman 2015; Gallien judged as being at high risk of attrition bias due to incomplete data
2014; Juthani-Mehta 2016; Kontiokari 2001; Koradia 2019; Maki because they had > 10% of patient data excluded or missing data
2016; McMurdo 2005; McMurdo 2009; Mooren 2020; NAPRUTI 2011; from UTIs outcome analysis (Avorn 1994; Barbosa-Cesnik 2011;
Salo 2010; Sengupta 2011; SINBA 2007; Singh 2016; Stapleton 2012; De Leo 2017; Essadi 2010; Foda 1995; Haverkorn 1994; Hess 2008;
Stothers 2002; Temiz 2018; Vostalova 2015; Wan 2016; Wing 2008; Linsenmeyer 2004; Stothers 2016; Takahashi 2013; Waites 2004;
Wing 2015), two studies were judged to be at high risk of bias (Avorn Walker 1997; Wing 2015). The remaining 10 studies were assessed as
1994; Haverkorn 1994), and the remaining 19 studies were judged unclear for attrition bias because quantifying lost or excluded data
to have unclear risk of bias. was not possible as numbers were not reported.

Allocation concealment Selective reporting

Twenty-eight studies reported a method of allocation concealment Forty-one studies were assessed as at low risk for selective
that was judged to be at low risk of bias (Afshar 2012; Babar reporting since they reported a UTIs outcome (Afshar 2012;
2021; Barbosa-Cesnik 2011; Bruyere 2019; Caljouw 2014; Cowan Avorn 1994; Babar 2021; Barbosa-Cesnik 2011; Bonetta 2017;
2012; Foxman 2015; Gallien 2014; Hess 2008; Juthani-Mehta 2016; Bruyere 2019; Caljouw 2014; Cowan 2012; Dotis 2014; Essadi
Kontiokari 2001; Koradia 2019; Maki 2016; McMurdo 2005; McMurdo 2010; Fernandes 2016; Ferrara 2009; Foxman 2015; Gallien 2014;
2009; Mooren 2020; NAPRUTI 2011; Salo 2010; Schlager 1999; Hess 2008; Juthani-Mehta 2016; Kontiokari 2001; Koradia 2019;
Sengupta 2011; SINBA 2007; Singh 2016; Stapleton 2012; Stothers Linsenmeyer 2004; Maki 2016; McGuiness 2002; McMurdo 2005;
2002; Uberos 2012; Walker 1997; Wing 2008; Wing 2015), three McMurdo 2009; Mooren 2020; NAPRUTI 2011; Salo 2010; Schlager
studies were judge to be at high risk of bias (Avorn 1994; Bonetta 1999; Sengupta 2011; SINBA 2007; Singh 2016; Stapleton 2012;
2017; Haverkorn 1994), and the remaining 19 studies were judged Stothers 2002; Takahashi 2013; Temiz 2018; Uberos 2012; Vostalova
to have unclear risk of bias. 2015; Waites 2004; Walker 1997; Wan 2016; Wing 2008; Wing 2015).
Although this varied in definition, 27 studies reported the most
Blinding rigorous definition of UTIs (clinical symptoms combined with a
Performance bias verified positive culture result). Three studies were considered
at high risk of bias for selective reporting: one for using UTI
Thirty-six studies stated that participants and study personnel events as their units instead of patients (De Leo 2017), one
were blind to treatment allocation (Afshar 2012; Avorn 1994; Babar only reported the number of positive cultures rather than the
2021; Barbosa-Cesnik 2011; Bianco 2012; Bruyere 2019; Caljouw number of patients with symptomatic UTIs (Bianco 2012), and one
2014; Cowan 2012; Fernandes 2016; Foxman 2015; Gallien 2014; stated their primary outcome was symptomatic UTIs, but no data
Hess 2008; Juthani-Mehta 2016; Koradia 2019; Linsenmeyer 2004; were reported (Stothers 2016; abstract-only publication). In the
Lopes de Carvalho 2012; Maki 2016; McGuiness 2002; McMurdo remaining six studies, the risk of bias from selective reporting was
2005; McMurdo 2009; Mooren 2020; NAPRUTI 2011; Salo 2010; unclear because UTI definitions or units were unclear.
Schlager 1999; Scovell 2015; SINBA 2007; Stothers 2002; Stothers
2016; Takahashi 2013; Uberos 2012; Vostalova 2015; Waites 2004; Withdrawals, losses to follow-up and intention-to-treat
Walker 1997; Wan 2016; Wing 2008; Wing 2015), eight studies had
The proportion of participants who were randomised but not
no blinding (Bonetta 2017; Essadi 2010; Ferrara 2009; Foda 1995;
included in the outcome analysis varied from 0% to 55%. Twenty-
Juthani-Mehta 2010; Kontiokari 2001; Mohammed 2016; Sengupta
eight studies included all randomised participants in their analysis,
2011), and for the remaining six studies this issue was unclear.
and five studies excluded less than 10% of the randomised group
Detection bias in the outcome analysis. Thirteen studies excluded more than 10%
of their randomised participants from outcome analysis, and four
In 23 studies the outcome assessor was stated as blinded studies did not report data in sufficient detail to determine if any or
(Afshar 2012; Babar 2021; Bruyere 2019; Caljouw 2014; Foxman how many participants were excluded from their analyses.
2015; Gallien 2014; Hess 2008; Kontiokari 2001; Koradia 2019;
Linsenmeyer 2004; McMurdo 2005; McMurdo 2009; Mooren 2020; Several studies stated that the palatability of the cranberry product
NAPRUTI 2011; Schlager 1999; SINBA 2007; Stapleton 2012; Stothers (primarily cranberry juice) was assumed to be the reason for
2002; Stothers 2016; Walker 1997; Wan 2016; Wing 2008; Wing participants discontinuing or withdrawing from the study, but none
2015). Two studies had a high risk of bias due to unblinded provided actual data about this from participants.
outcome assessment (Juthani-Mehta 2010; Bonetta 2017), and in
the remaining 25 studies it was unclear whether the outcome At least one of the studies had serious flaws. In Avorn 1994, some
assessor was blinded to the treatment allocation. of the baseline characteristics of the participants were markedly
different in the cranberry and the placebo groups. In particular,
Incomplete outcome data the rate of UTIs in the previous six months in the placebo group
was over three times that of the cranberry juice group and doubled
Twenty-seven studies were judged as at low risk of bias from for over 12 months. Two letters published in JAMA commented
incomplete data because they had ≤ 10% lost or excluded data from on these differences and inferred that the randomisation and/or
their outcome analysis of UTIs (Afshar 2012; Babar 2021; Bianco blinding scheme had failed (Hopkins 1994; Katz 1994).
Cranberries for preventing urinary tract infections (Review) 16
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Sample sizes across studies differed. Twelve studies randomised 7. Cranberry product versus antibiotics (Analysis 7.1 to Analysis
fewer than 50 participants, 11 studies randomised between 50 7.2)
and 100 people, 15 studies randomised between 100 and 200 8. Cranberry product + probiotic tablet versus placebo or control
participants, and nine studies randomised between 200 and 500 (Analysis 8.1)
people. Three studies randomised more than 500 but fewer than 9. Cranberry product versus placebo or control: PAC dose ( Analysis
1000 participants. One study randomised 21 patients but did not 9.1 to Analysis 9.3)
report any numerical data for the outcomes, so the size of the
10.Cranberry product versus placebo or control: sponsor type
analysed sample was unknown (Lopes de Carvalho 2012). Twenty-
(Analysis 10.1 to Analysis 10.2)
five studies reported a sample size calculation and 24 studies did
not. Nine studies with sample size calculations used a 10% to 15% 11.Cranberry product versus placebo or control: culture threshold
absolute risk difference for UTI risk between cranberry and placebo (Analysis 11.1 to Analysis 11.2)
or no treatment groups, while 14 studies chose a sample size based
1. Cranberry products versus placebo, control or no treatment
on a much higher expected absolute risk difference of 20% to 50%
and two did not quantify the expected difference. The assessment of the certainty of the evidence is shown in
Summary of findings 1.
Other potential sources of bias
Symptomatic, culture-verified urinary tract infection
Seventeen studies were judged to be at low risk of other sources of
bias (Bianco 2012; Caljouw 2014; Cowan 2012; Gallien 2014; Hess Overall, cranberry products reduced the risk of symptomatic,
2008; Juthani-Mehta 2016; Maki 2016; McMurdo 2005; McMurdo culture-verified UTIs in all patient groups (Analysis 1.1 (26 studies,
2009; Mohammed 2016; Mooren 2020; NAPRUTI 2011; Salo 2010; 6211 participants): RR 0.70, 95% CI 0.58 to 0.84; I2 = 69%; moderate
Schlager 1999; SINBA 2007; Stothers 2002; Wing 2008), four were certainty evidence).
judged to be at high risk of bias (Avorn 1994; Babar 2021; Barbosa-
Cesnik 2011; Bruyere 2019), and the remaining 29 studies were Women with recurrent urinary tract infections
judged to have unclear risk of bias. Eleven studies evaluated cranberry products in women with
recurrent UTIs (Barbosa-Cesnik 2011; Bruyere 2019; Kontiokari
Commercial involvement
2001; Maki 2016; Sengupta 2011; Stapleton 2012; Stothers 2002;
Twenty-three studies reported some involvement of a for-profit Stothers 2016; Takahashi 2013; Vostalova 2015; Walker 1997).
organisation; for five of these it was Ocean Spray, a company that
sells cranberry products. Twelve studies reported that the for-profit Cranberry products probably reduce the risk of symptomatic
organisation donated the cranberry products, and most claimed culture-verified UTIs in women with recurrent UTIs (Analysis 1.1.1
the company had no influence over the reporting of the results. In (8 studies, 1555 participants): RR 0.74, 95% CI 0.55 to 0.99; I2 = 54%;
eight studies, it was not clear what involvement the organisation moderate certainty evidence). There was moderate heterogeneity
had in running or reporting the study results. in the results, primarily resulting from a single study (Barbosa-
Cesnik 2011), in which the point estimate was in the opposite
In 17 studies, funding was reported as provided by not-for-profit direction to all other studies. Omitting this study in a sensitivity
grants such as health departments and research foundations, while analysis resulted in a RR of 0.68 (95% CI 0.52 to 0.89) and reduced
four studies reported funding from commercial organisations. In 29 the heterogeneity (I2 = 32%). There may be several reasons why
studies, it was unclear if any funding or sponsorship was involved Barbosa-Cesnik 2011 showed different results from the other
as insufficient details were reported. studies (i.e. no effect of cranberries), including bias introduced
when 100 randomised patients were excluded, the use of a lower
Effects of interventions CFU count leading to over-diagnosis of UTIs, or a chance effect.
See: Summary of findings 1 Any cranberry product versus placebo Three studies (Bruyere 2019; Stothers 2016; Walker 1997) were not
or control for preventing urinary tract infection included in the meta-analyses as they did not report the number
of participants treated (Stothers 2016; Walker 1997) or reported the
Included studies compared cranberry products with a range of
mean numbers of UTIs (Bruyere 2019).
alternatives, including placebo, no specific treatment, different
cranberry products or doses, antibiotics, and probiotics. Some Elderly institutionalised men and women
compared cranberry products to more than one alternative. All the
comparisons are considered separately and are as follows: Five studies evaluated the effectiveness of cranberry products
for elderly institutionalised men and women in residential care
1. Cranberry product versus placebo, control or no treatment (Bianco 2012; Caljouw 2014; Haverkorn 1994; Juthani-Mehta 2016;
(Analysis 1.1 to Analysis 1.5) McMurdo 2005).
2. Cranberry juice or syrup versus placebo or control (Analysis 2.1
Cranberry products may provide little or no benefit in preventing
to Analysis 2.2)
symptomatic, culture-verified UTIs in this group of older people
3. Cranberry tablets or powder versus placebo or control (Analysis (Analysis 1.1.2 (3 studies, 1489 participants): RR 0.93, 95% CI 0.67 to
3.1 to Analysis 3.2) 1.30; I2 = 9%; moderate certainty evidence).
4. Cranberry juice versus cranberry tablets or powder (Analysis 4.1)
5. Cranberry dose: high versus low dose (Analysis 5.1 to Analysis Two studies could not be included in meta-analyses. Haverkorn
5.2) 1994 was a cross-over study and did not provide data separately for
the first part of the study, and Bianco 2012 reported the number of
6. Cranberry product versus probiotics (Analysis 6.1)
UTIs in each group but not the number of participants with UTIs.
Cranberries for preventing urinary tract infections (Review) 17
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Pregnant women Clinical urinary tract infection (symptoms without urine culture)
Three studies evaluated cranberry products for the prevention Overall, cranberry products may reduce clinical UTIs (Analysis 1.2
of symptomatic, culture-verified UTIs in pregnant women (Essadi (5 studies, 1646 participants): RR 0.69, 95% CI 0.49 to 0.98; I2 = 64%).
2010; Wing 2008; Wing 2015). The number of withdrawals from Wing
2008 was very high because of intolerance to the volume of juice Included was one study of women with recurrent UTIs (373
required. participants: RR 0.59, 95% CI 0.42 to 0.83) (Maki 2016), two studies
of elderly institutionalised men and women (1113 participants: RR
Cranberry products may have little or no effect on preventing UTIs 0.91, 95% CI 0.77 to 1.08; I2 = 0%) (Caljouw 2014; Juthani-Mehta
in pregnant women (Analysis 1.1.3 (3 studies, 765 participants): RR 2016), and one study of people with a susceptibility to UTIs after
1.06, 95% CI 0.75 to 1.50; I2 = 3%). an intervention (160 participants: RR 0.50, 95% CI 0.29 to 0.86)
(Foxman 2015). Thus, there may be a benefit of cranberry products
Children
in preventing clinical symptoms of UTIs in these different patient
Seven studies evaluated cranberry products compared with groups.
placebo or control in children with previous UTIs (Afshar 2012; Dotis
2014; Ferrara 2009; Foda 1995; Salo 2010; Schlager 1999; Wan 2016). Microbiological urinary tract infection (positive culture without
known symptoms)
Cranberry products probably reduce the risk of subsequent
Three studies reported the outcome of microbiological UTIs. Two
symptomatic UTIs (Analysis 1.1.4 (5 studies, 504 participants): RR
studies (209 participants) were in the elderly (Avorn 1994; Juthani-
0.46, 95% CI 0.32 to 0.68; I2 = 21%; moderate certainty evidence).
Mehta 2010), and one study (135 participants) studied adults with
Two studies in children with neurogenic bladders were cross-over bladder emptying issues related to multiple sclerosis (McGuiness
studies, and the data could not be included in meta-analyses (Foda 2002).
1995; Schlager 1999). Neither study identified a benefit of cranberry
Overall, there may be no benefit of cranberry products in
preparations.
preventing positive urine cultures (Analysis 1.3 (3 studies, 344
Adults with neuromuscular dysfunction of the bladder and insufficient participants): RR 0.92, 95% CI 0.71 to 1.21; I2 = 0%).
bladder emptying
Death
Eight studies compared cranberry products with placebo or no
treatment in people with bladder emptying issues (Gallien 2014; Four studies reported the number of deaths occurring in each arm
Hess 2008; Linsenmeyer 2004; Lopes de Carvalho 2012; Scovell of the study (Bruyere 2019; Caljouw 2014; Juthani-Mehta 2016;
2015; SINBA 2007; Singh 2016; Waites 2004). McMurdo 2005).

Cranberry products had little or no effect on preventing UTIs in Cranberry products may make no difference to the risk of death
people with bladder emptying issues (Analysis 1.1.5 (3 studies, 464 (Analysis 1.4 (4 studies, 1574 participants): RR 1.07, 95% CI 0.89 to
participants): RR 0.97, 95% CI 0.78 to 1.19; I2 = 0%; low certainty 1.28; I2 = 0%).
evidence).
Gastrointestinal adverse events
Four studies could not be included in the meta-analyses. Two Ten studies reported GI adverse events (Babar 2021; Bonetta 2017;
studies (Hess 2008; Linsenmeyer 2004) were cross-over studies, and Gallien 2014; Koradia 2019; McMurdo 2005; Mooren 2020; Sengupta
data from the first part of the study were not available separately. 2011; Singh 2016; Stothers 2002; Wing 2015).
In two studies, the numbers with UTIs were not reported (Lopes de
Carvalho 2012; Scovell 2015). A fifth study was not included in the Cranberry products probably make no difference to the risk of GI
meta-analyses as only 14 of 72 participants had bladder emptying adverse events (Analysis 1.5 (10 studies, 2166 participants): RR 1.33,
issues, and the definition of further UTIs in participants was unclear 95% CI 1.00 to 1.77; I2 = 0%; moderate certainty evidence).
(Singh 2016).
2. Cranberry juice or syrup versus placebo or control
Adults with susceptibility to urinary tract infection associated with an
intervention Symptomatic culture-verified urinary tract infection

Seven studies compared cranberry products with a placebo or Overall, cranberry juice may reduce the risk of symptomatic,
no specific treatment in participants undergoing an intervention culture-verified UTIs (Analysis 2.1 (13 studies, 2831 participants): RR
(Bonetta 2017; Cowan 2012; Fernandes 2016; Foxman 2015; 0.78, 95% CI 0.62 to 0.97; I2 = 57%).
Mohammed 2016; Mooren 2020; Temiz 2018).
Women with recurrent urinary tract infections
Cranberry products reduced the risk of UTIs in participants Six studies compared cranberry juice or concentrate with a placebo
undergoing an intervention (Analysis 1.1.6 (6 studies, 1434 or no treatment in women with recurrent UTIs (Barbosa-Cesnik
participants): RR 0.47, 95% CI 0.37 to 0.61; I2 = 0%; low certainty 2011; Kontiokari 2001; Maki 2016; Stapleton 2012; Stothers 2002;
evidence) Takahashi 2013).
Cowan 2012 could not be included in the meta-analyses as it Cranberry juice or syrup may make little or no difference to the risk
reported the results according to the number of cultures rather than of symptomatic culture-verified UTIs in women with recurrent UTIs
the number of participants. (Analysis 2.1.1 (6 studies, 1322 participants): RR 0.84, 95% CI 0.63 to
1.10; I2 = 45%).

Cranberries for preventing urinary tract infections (Review) 18

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Children Children

Four studies compared cranberry juice to placebo or no treatment Dotis 2014 reported cranberry tablets may reduce the risk for UTIs
in children (Afshar 2012; Ferrara 2009; Salo 2010; Wan 2016). in children (Analysis 3.1.4 (76 participants): RR 0.29, 95% CI 0.14 to
0.59).
Cranberry juice may reduce the risk of symptomatic culture-verified
UTIs in children (Analysis 2.1.2 (4 studies, 401 participants): RR 0.57, Adults with neuromuscular dysfunction of the bladder with
95% CI 0.37 to 0.87; I2 = 21%). insufficient bladder emptying capacity and residual urine

Elderly institutionalised men and women

Three studies compared cranberry tablets or powder with a placebo
or no treatment in adults with neuromuscular dysfunction of the
McMurdo 2005 reported little or no difference between cranberry bladder with insufficient bladder emptying capacity and residual
juice or syrup and placebo in the risk of symptomatic culture- urine (Gallien 2014; SINBA 2007; Waites 2004).
verified UTIs in elderly men and women in institutions (Analysis
2.1.3 (1 study, 376 participants): RR 0.51, 95% CI 0.21 to 1.22). Cranberry tablets or powder may make no difference to the risk for
UTIs in adults with neuromuscular dysfunction of the bladder with
Pregnant women insufficient bladder emptying capacity and residual urine (Analysis
Two studies compared cranberry juice with a placebo or no 3.1.5 (3 studies, 464 participants): RR 0.97, 95% CI 0.78 to 1.19; I =
treatment in pregnant women (Essadi 2010; Wing 2008). 0%)

People with susceptibility to UTIs due to an intervention

Cranberry juice or syrup may make little or no difference to the risk
of symptomatic culture-verified UTIs in pregnant women (Analysis Six studies compared cranberry tablets or powder with a placebo
2.1.4 (2 studies, 732 participants): RR 1.06, 95% CI 0.75 to 1.50; I2 = or no treatment in people with susceptibility to UTIs due
3%). to an intervention (Bonetta 2017; Ferrara 2009; Foxman 2015;
Mohammed 2016; Mooren 2020; Temiz 2018).
Clinical urinary tract infection (symptoms without urine culture)
Cranberry tablets or powder probably reduce the risk of UTIs in
Maki 2016 reported cranberry juice may reduce the risk of UTIs
people with susceptibility to UTIs due to an intervention (Analysis
in women with symptoms of UTIs with or without culture results
3.1.6 (6 studies, 1454 participants): RR 0.48, 95% CI 0.37 to 0.61; I2
(Analysis 2.2 (373 participants): RR 0.59, 95% CI 0.42 to 0.83).
= 0%).
3. Cranberry tablets or powder versus placebo or no treatment
Clinical urinary tract infection (symptoms without urine culture)
Symptomatic, culture-verified urinary tract infection
Three studies compared cranberry tablets or powder with a placebo
Overall, cranberry tablets or powder compared to placebo or no or no treatment (Caljouw 2014; Foxman 2015; Juthani-Mehta 2010).
treatment may reduce the risk of symptomatic, culture-verified
UTIs (Analysis 3.1 (16 studies, 3473 participants): RR 0.65, 95% CI Cranberry tablets may make no difference to the risk of clinical UTIs
0.49 to 0.84; I2 = 64%). not confirmed on culture (Analysis 3.2 (3 studies, 1273 participants):
RR 0.74, 95% CI 0.47 to 1.16; I2 = 55%). However, the efficacy may
Women with recurrent urinary tract infections vary according to the population.
Three studies compared cranberry tablets or powder with a placebo
• In the elderly (Analysis 3.2.2 (2 studies, 1113 participants): RR
or no treatment in women with recurrent UTIs (Sengupta 2011;
0.91, 95% CI 0.77 to 1.08; I2 = 0%) (Caljouw 2014; Juthani-Mehta
Stothers 2002; Vostalova 2015).
2010), cranberry tablets may have little or no effect on UTIs.
Cranberry tablets or powder may reduce the risk of UTI in women • In contrast, Foxman 2015 reported in people with a susceptibility
with recurrent UTIs (Analysis 3.1.1 (3 studies, 333 participants): RR to UTIs due to an intervention (Analysis 3.2.3 (1 study, 160
0.45, 95% CI 0.28 to 0.72; I2 = 0%). participants): RR 0.50, 95% CI 0.29 to 0.86) cranberry tablets may
be more effective than placebo.
Elderly institutionalised men and women
These findings reflect the results seen in participant groups for the
Two studies compared the effectiveness of cranberry tablets or outcome of symptomatic culture-verified UTIs.
powder in elderly institutionalised men and women (Caljouw 2014;
Juthani-Mehta 2016). Microbiological urinary tract infection (positive culture without
known symptoms)
Cranberry tablets or powder may make little or no difference to the
risk of UTIs in elderly institutionalised men and women (Analysis In two studies, one in the elderly (Juthani-Mehta 2010) and one in
3.1.2 (2 studies, 1113 participants): RR 1.02, 95% CI 0.75 to 1.39; I2 adults with bladder emptying issues (McGuiness 2002), cranberry
= 0%). tablets may make little or no difference in the risk for positive urine
culture without symptoms overall, and in these patient groups
Pregnant women (Analysis 3.3 (2 studies, 191 participants): RR 1.00, 95% CI 0.75 to
Wing 2015 (33 pregnant women) reported no events in either the 1.34; I2 = 0%).
cranberry tablet or placebo group.
4. Cranberry juice versus cranberry tablets
Stothers 2002 reported little or no difference in the risk for
symptomatic UTIs between cranberry juice and cranberry tablets in

Cranberries for preventing urinary tract infections (Review) 19

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

women with recurrent UTIs (Analysis 4.1 (100 participants): RR 0.90, recurrent UTIs compared to placebo (Analysis 8.1 (89 participants):
95% CI 0.40 to 2.02). RR 0.27, 95% CI 0.10 to 0.76).

5. Cranberry dose: high versus low 9. Cranberry product versus placebo or no treatment:
proanthocyanidin dose
Symptomatic, culture-verified urinary tract infection
Symptomatic, culture-verified UTIs
Two studies, one in women with recurrent UTIs (Sengupta 2011)
and one in pregnant women (Wing 2008), compared different Low-dose proanthocyanidin (< 40 mg/day)
amounts of cranberry either as juice or tablets. It is uncertain Six studies compared a cranberry product with a PAC dose < 40 mg/
whether the risk for clinical UTIs differs between groups as the day with a placebo or no treatment (Caljouw 2014; Gallien 2014;
certainty of the evidence is very low (Analysis 5.1 (2 studies 169 Sengupta 2011; Takahashi 2013; Temiz 2018; Vostalova 2015).
participants): RR 1.02, 95% CI 0.27 to 3.91; I2 = 0%).
Overall, low PAC dose may make little or no difference to the risk
Microbiological urinary tract infection (positive culture without for symptomatic UTIs (Analysis 9.1 (6 studies, 1504 participants): RR
known symptoms) 0.75, 95% CI 0.52 to 1.08; I2 = 56%).
One study in elderly people (Juthani-Mehta 2010) compared
different doses of cranberry tablets. It is uncertain whether the risk There may be little or no difference in the risk for UTIs between low
for microbiological UTIs differs between groups as the certainty of PAC dose and placebo or no treatment in women with recurrent
the evidence is very low (Analysis 5.2 (39 participants): RR 1.13, 95% UTIs (Analysis 9.1.1 (3 studies, 423 participants): RR 0.57, 95% CI
CI 0.75 to 1.72). 0.32 to 1.06; I2 = 49%); in elderly men and women (Analysis 9.1.2
(1 study, 928 participants): RR 1.03, 95% CI 0.74 to 1.42), in adults
Clinical urinary tract infection (symptoms without urine culture) with neuropathy or neuropathic bladders (Analysis 9.1.3 (1 study,
111 participants): RR 1.03, 95% CI 0.66 to 1.62), or in those with a
Babar 2021 compared different amounts of cranberry in women susceptibility to UTIs due to an intervention (Analysis 9.1.4 (1 study,
with recurrent UTIs. It is uncertain whether the risk for clinical UTI 40 participants): RR 0.13, 95% CI 0.02 to 0.91).
differs between groups as the certainty of the evidence is very low
(Analysis 5.3 (1 study, 145 participants): RR 0.81, 95% CI 0.57 to Moderate-dose proanthocyanidin (40 to 80 mg/day)
1.13).
Four studies compared a cranberry product with a moderate dose
6. Cranberry products versus probiotics PAC of 40 to 80 mg/day with a placebo or no treatment (Juthani-
Mehta 2016, Mohammed 2016; Mooren 2020; Wing 2015).
Symptomatic, culture-verified urinary tract infection
Overall, there may be little or no difference in the risk for
Three studies compared cranberry products with probiotics; one
symptomatic UTIs when using 40 to 80 mg PAC/day (Analysis 9.2 (4
in children (Ferrara 2009), one in women with recurrent UTIs
studies, 473 participants): RR 0.74, 95% CI 0.41 to 1.31; I2 = 0%).
(Kontiokari 2001), and one in men and women (Singh 2016).
Overall, cranberry products may reduce the risk of symptomatic In elderly men and women (Analysis 9.2.1 (1 study, 185
UTIs in all patient groups (Analysis 6.1 (3 studies, 215 participants): participants): RR 1.01, 95% CI 0.42 to 2.43), or in those with a
RR 0.39, 95% CI 0.27 to 0.56; I = 0%). susceptibility to UTIs due to an intervention (Analysis 9.2.3 (2
studies, 255 participants): RR 0.58, 95% CI 0.27 to 1.25; I2 = 0%) there
7. Cranberry products versus antibiotic prophylaxis
may be little or no difference in the risk for UTIs between moderate
Symptomatic, culture-verified urinary tract infection PAC dose and placebo or no treatment. There were no reported
events in 33 pregnant women (Wing 2015).
Two studies, one in women with recurrent UTIs (NAPRUTI
2011) and one in children (Uberos 2012), compared cranberry High-dose proanthocyanidin (> 80 mg/day)
products (tablets in women, syrup in children) with antibiotics.
Cranberry products may make little or no difference to the risk Two studies, one in women with recurrent UTIs (Barbosa-Cesnik
for symptomatic culture-verified UTIs (Analysis 7.1 (2 studies, 385 2011) and one in pregnant women (Wing 2008), compared a PAC
participants): RR 1.03, 95% CI 0.80 to 1.33; I2 = 0%). dose > 80 mg/day with a placebo or no treatment.

Clinical urinary tract infection (symptoms without urine culture) Overall, there may be little or no difference in the risk for
symptomatic UTIs (Analysis 9.3 (2 studies, 507 participants): RR
Two studies in women with recurrent UTIs compared cranberry 1.47, 95% CI 0.91 to 2.39; I2 = 0%).
tablets with antibiotic tablets (NAPRUTI 2011; McMurdo 2009). It is
uncertain whether the risk for clinical UTIs differs between groups In women with recurrent UTIs (Analysis 9.3.1 (1 study, 319
as the certainty of the evidence is very low (Analysis 7.2 (2 studies, participants): RR 1.43, 95% CI 0.87 to 2.33) and pregnant women
336 participants): RR 1.30, 95% CI 0.79 to 2.14; I2 = 68%). There was (Analysis 9.3.2 (1 study, 188 participants): RR 4.57, 95% CI 0.25
considerable heterogeneity between these studies. to 83.60) there may be little or no difference in the risk for UTIs
between high PAC dose and placebo or no treatment.
8. Cranberry plus probiotic tablet versus placebo or no
treatment 10. Cranberry product versus placebo or no treatment:
sponsor type
Koradia 2019 reported cranberry plus a probiotic reduced the
number of symptomatic, culture-verified UTIs in women with An analysis was conducted to explore whether the involvement
of a commercial entity in the studies had an effect on reported

Cranberries for preventing urinary tract infections (Review) 20

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

results. A study which declared either financial support or provision participants): RR 1.33, 95% CI 1.00 to 1.77; I2 = 0%) suggesting
of the cranberry product by a for-profit organisation was classified that these may be increased in participants receiving a cranberry
as having commercial involvement. Only the most robust outcome, product.
symptomatic, culture-verified UTIs, was used for this analysis.
Other adverse events were not analysed, as these were considered
Symptomatic, culture-verified urinary tract infection too diverse or there was too few data for the different comparator
groups. Three studies reported hospitalisations (Caljouw 2014;
Commercial involvement
Fernandes 2016; Juthani-Mehta 2016), but only two reported these
Thirteen studies reported commercial involvement. Overall, there within treatment groups. Seven studies reported the numbers
may be a reduction in the risk for symptomatic UTIs in studies of serious adverse events without specifying what these events
with commercial involvement (Analysis 10.1 (13 studies, 3202 were (Barbosa-Cesnik 2011; Foxman 2015; Gallien 2014; Juthani-
participants): RR 0.86, 95% CI 0.76 to 0.99; I2 = 0%). However, within Mehta 2016; Maki 2016; NAPRUTI 2011; Sengupta 2011; Stapleton
the individual populations, the risk of UTIs with a cranberry product 2012) and five studies reported occurrences of rash, reported
may be reduced only in participants with a susceptibility to UTIs within treatment arms in four studies (three with antibiotics as the
due to an intervention (Analysis 10.1.6 (2 studies, 370 participants): comparator and one with placebo) and only as a total for one study
RR 0.57, 95% CI 0.35 to 0.92; I2 = 0%) (placebo comparator).
No commercial involvement Adherence to therapy
Twelve studies compared a cranberry product with a placebo or Twenty-nine of the 50 studies reported compliance rates in
no treatment and did not involve commercial involvement. Overall, participants. Appendix 5 provides the individual study estimates for
there may be a reduction in the risk for symptomatic culture- compliance, the methods of measuring compliance in the studies
verified UTIs in studies without commercial involvement (Analysis and each study's risk ratio for repeat UTIs. There was no clear
10.2 (12 studies, 2543 participants): RR 0.61, 95% CI 0.43 to 0.87; relationship between compliance with therapy and the RR for
I2 = 64%).Within the individual populations, the risk of UTIs with repeat UTIs.
a cranberry product may be reduced only in participants with a
susceptibility to UTIs due to an intervention (Analysis 10.2.6 (3 DISCUSSION
studies, 1009 participants): RR 0.61, 95% CI 0.43 to 0.87; I2 = 0%).
Summary of main results
11. Cranberry products versus placebo or no treatment:
culture threshold This is the fifth update of a review first published in 1998 (updated:
2003, 2004, 2008, 2012). We evaluated the efficacy and safety of
Twenty-six studies used a threshold of ≥ 108 CFU/L to define cranberry products to prevent UTIs in 50 RCTs (8857 participants)
a positive urine culture result. Of these, 18 studies reported including different populations at risk of UTIs.
data on symptomatic, culture-verified UTIs (Analysis 11.1) with
a reduction in symptomatic, culture-verified UTIs overall. In • Studies evaluated cranberry products overall and separately in
individual analyses, the number of symptomatic UTIs was reduced six different populations; women with recurrent UTIs, elderly
in children and in people at risk of UTIs following an intervention. men and women in institutions, pregnant women, children
with recurrent UTIs with or without urinary tract abnormalities,
Eleven studies used a threshold of < 188 CFU/L to define a positive adults with neuromuscular dysfunction of the bladder and
urine culture. Of these, three studies (Analysis 11.2) reported data incomplete bladder emptying, and people with a susceptibility
on symptomatic, culture-verified UTIs; two studies of women with to UTIs following an intervention.
recurrent UTIs and one of elderly men and women in institutions. • Overall, cranberry products reduce the risk of symptomatic,
There was insufficient data to make any conclusions. culture-verified UTIs (Analysis 1.1).
• Cranberry products probably reduce the risk of symptomatic,
Thirteen studies stated that they had obtained urine cultures but
culture-verified UTIs in the subgroups of women with recurrent
did not report the results according to the culture threshold.
UTIs (moderate certainty evidence), in children with UTIs but
Adverse events without neurogenic bladders (moderate certainty evidence),
and in people with a susceptibility to UTIs following an
Adverse events were reported in 32 studies (Appendix 3; Appendix intervention (low certainty evidence)
4). In three studies, numbers were not reported within study arms • Cranberry products may reduce the risk of UTI symptoms
(Barbosa-Cesnik 2011; SINBA 2007; Schlager 1999), seven studies when urine culture was not obtained in women with recurrent
only reported there were no adverse events (Cowan 2012; De Leo UTIs and in people with a susceptibility to UTIs following an
2017; Dotis 2014; Ferrara 2009; Kontiokari 2001; Vostalova 2015; intervention (Analysis 1.1.2)
Wan 2016), and 22 studies reported numbers of specific adverse
• Cranberry products may not influence the likelihood of
events within the study arms.
symptomatic, culture-verified UTIs, UTI symptoms without a
The number of deaths and the number of participants with positive culture or positive cultures without symptoms in elderly
GI events were included in meta-analyses as these outcomes men and women in institutions, and adults with neuromuscular
were considered potentially relevant to treatment. Four studies dysfunction of the bladder and incomplete bladder emptying
comparing cranberry products with placebo or no treatment (Analysis 1.1.3).
provided data on the number of deaths (Analysis 1.4 (4 studies, 1574 • Cranberry products may not influence the likelihood of death,
participants): RR 1.07, 95% CI 0.89 to 1.28; I2 = 0%). Ten studies but this outcome was only evaluated in four studies (1574
included data on GI adverse events (Analysis 1.4 (10 studies, 2166 participants) (Analysis 1.4).
Cranberries for preventing urinary tract infections (Review) 21
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

• Cranberry products may be associated with GI adverse events Only one small study compared cranberry tablets with cranberry
(Analysis 1.5). Other adverse events did not appear to differ juice and found that there may be little or no difference in efficacy
between groups (Appendix 3; Appendix 4). between tablets and juice (Stothers 2002). However, comparisons
• Cranberry tablets (Analysis 3.1) or cranberry juice (Analysis 2.1) of cranberry juice or tablets or powder with placebo or control
compared with a placebo or control may reduce the risk of raised the possibility that tablets may be more effective than juice
symptomatic, culture-verified UTIs. because almost all point estimates suggested a greater benefit with
• It remains uncertain whether cranberry tablets differ from tablets in the various populations taking tablets compared with
cranberry juice in efficacy as only one small study compared placebo or control (Analysis 2.1; Analysis 3.1). It is possible that
these two different interventions so the level of evidence is very these data are confounded by adherence issues as people taking
low. juice may be less adherent than those taking tablets because of the
bitter taste of the juice. However, available data were insufficient
• It remains uncertain whether cranberry products are more or
to analyse the effect of medication adherence on outcomes.
less effective than antibiotics or probiotics alone because few
Alternatively, the dose of PAC may be more consistent in the tablet
studies investigated these comparisons so the level of evidence
format compared with juice.
is very low.
• In other comparisons: There was insufficient data to draw conclusions about the efficacy
◦ There may be no differences in efficacy between high- and of cranberry compared with other active interventions. Two studies
low-dose PAC (385 participants) compared a cranberry product with antibiotics
◦ There were insufficient data to determine any differences in and found no difference in symptomatic, culture-verified UTIs.
efficacy according to the threshold cut-off for diagnosing UTIs Since the certainty of the evidence is very low, It is uncertain
(< 108 CFU/L or ≥ 108 CFU/L) whether cranberry reduces the risk of UTIs compared with
antibiotics. Three studies (215 participants) compared a cranberry
◦ There may be no differences in efficacy related to the
presence or absence of industry involvement. product with probiotics in the prevention of symptomatic, culture-
positive UTIs. Thus cranberry may be more effective than probiotics
• There appeared to be no clear relationship between compliance in reducing the risk of UTIs, but the certainty of the evidence is low.
with therapy and the RR for repeat UTIs in individual studies
(Appendix 5). It remains unclear what the optimum dose of cranberry should be.
Ex-vivo studies suggest that the PAC dose should be at least 36
Overall completeness and applicability of evidence mg/day (Babar 2021). Only 13 studies could be included in meta-
In this 2023 update, 26 additional studies of cranberry products analyses, which evaluated the efficacy of different doses of PAC on
to prevent UTIs were added for a total of 50 studies (8857 symptomatic, culture-verified UTIs, with most evaluating low-dose
participants). Compared with the previous update of this review PAC. No conclusions could be drawn from these analyses as to the
(Jepson 2012), analyses now show that cranberry products relative efficacy of different doses of PAC. Proper standardisation
probably reduce the risk of repeat symptomatic, culture-verified of cranberry products for PAC content and correlation of the PAC
UTIs in women with recurrent UTIs, in children, and in people content with anti-adhesion bioactivity may be important to ensure
at risk of UTIs following an intervention (Analysis 1.1). The most that particular cranberry products contain sufficient PAC to be
abundant data are in women with recurrent UTIs and, in this effective (Howell 2010).
group, the data suggest a 26% reduction in the risk of further
Studies that had some involvement from a for-profit organisation
UTIs with a cranberry product. Previous versions of this review
did not report different results for the risk of UTIs with cranberry
did not find this result because the individual studies were fewer
products from those studies with no commercial involvement.
and small. In this update, combining data from more studies
However, our definition of commercial involvement was broad and
reduced the influence of chance and increased the precision of
included studies that reported receiving the cranberry product at
the overall estimate. Six of the eight analysed studies of women
no cost and with no further involvement of the supplier in the
with recurrent UTIs included in the meta-analysis reported a point
reporting of the study.
estimate in favour of cranberry products but 95% CIs often crossed
the point of no effect. Additionally, for this update, we combined The majority of studies used a urine culture for diagnosing UTIs
studies reporting more specific outcomes, the most robust of
of ≥ 108 CFU/L with results for symptomatic, culture-positive UTIs
these being symptomatic, culture-verified UTIs. Prior versions did
reflecting the overall results. There were insufficient studies to
not clearly differentiate between the outcomes of symptomatic,
determine the relative efficacy of studies using a lower threshold
culture-verified UTIs, clinical UTI symptoms without culture, and
for diagnosis.
microbiological UTIs-positive culture without symptoms. Improved
reporting of the specific details of UTI definition enabled more Comparisons between cranberry products and antibiotics or
certainty in this grouping. Clinical UTIs without culture verification probiotics were limited so no definite conclusions can be drawn.
showed a similar pattern of efficacy as the more robust outcome The three studies with antibiotics showed no difference between
symptoms plus culture, although there were fewer data. For the the interventions, but precision was poor. Three studies comparing
outcome of microbiological UTIs, there may be little or no benefit cranberry products with probiotics suggested that there could be a
of cranberry with all estimates including the point of no difference, greater benefit with cranberry, but further studies are required to
but data were limited in these analyses. GI side effects were the confirm or refute this finding.
most frequent side effects reported, but there may be little or no
difference in the risk for these between cranberry and placebo or Our review lists six studies as ongoing. However, only one study
no treatment groups. There may be no difference in risk of death, (NCT03597152) may be underway though there are no updates to
but this outcome was reported in only four studies. confirm whether or not the study has commenced. The remaining

Cranberries for preventing urinary tract infections (Review) 22

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

five studies were identified from study registries between 2004 Agreements and disagreements with other studies or
and 2015, and to date, no publications of these studies have been reviews
identified despite extensive searching of the literature and emails
sent to listed principal investigators. Failure to complete a study Two recent systematic reviews have evaluated cranberry products
and/or report a completed study could indicate that studies, which relative to placebo or no treatment (Fu 2017; Luis 2017). Fu
showed no difference between cranberry and placebo, were not 2017 focused on women with recurrent UTIs, identified seven
published. studies, and reported a RR of 0.74 (95%CI 0.55 to 0.98) which is
almost identical to that obtained in this review, which included
Quality of the evidence eight studies in the participant group (Analysis 1.1: RR 0.74, 95%
CI 0.55 to 0.99; 1555 participants). This is unsurprising given
Study design in approximately half of the studies was relatively the only difference was that we included one additional study
robust and free from significant bias. Only 58% and 56% of (Sengupta 2011) and data from one study (Maki 2016) differed
studies were at low risk of selection bias (sequence generation in that we analysed symptomatic, culture-positive UTIs, while Fu
and allocation concealment). Selection bias was a concern in 2017 used the outcome clinical UTIs-no urine culture, for their
many studies as it was unclear how and why people were analysis. The risk of bias assessments between the two reviews was
identified for admission to the study. Similarly, performance and quite different and somewhat perplexing. This systematic review
detection bias were at low risk in only 72% and 46% of studies, considered an open-label study to be at high risk of bias for blinding
respectively. Attrition bias and reporting bias were at low risk in issues, while Fu 2017 deemed these studies to be at low risk while
54% and 82% of studies, respectively. Other biases were low in classifying a study reported as double-blinded, as high risk of bias
34% of studies. Many studies failed to report adherence numbers, for blinding. Additionally, this review considered a loss to follow-
including some of the studies that reported a method for measuring up or dropout rate of less than 10% as a low risk of incomplete
adherence. Quantitation of the apparent active ingredient, PAC, outcome bias, while Fu 2017 did not appear to use a consistent
was uncommon, possibly due to the technicalities in doing so, but classification for this, for example, an 8.7% dropout rate in one
surprising given the importance of the issue. study was deemed high risk but a 23.6% loss in another was
classified as low risk. The second systematic review by Luis 2017
Forty-five of the 50 included studies compared a cranberry product
included a wider at-risk population, similar to ours, but identified
to a placebo, no specific treatment, or water. However, data from
only 25 studies, three of which were not randomised. The point
only 32 of these 45 studies could be included in our meta-analyses
estimate from these 25 studies was 0.675 (95% CI 0.5516 to 0.7965).
most commonly because the number of participants suffering a
While not very different to our findings, some of the difference was
UTI was not reported adequately in the treatment and control
probably due to the inclusion of the three non-randomised studies
arms. The certainty of the evidence was considered to be moderate
and grouping all types of UTI outcomes together (symptomatic-
for the analyses of women with recurrent UTIs, for children, and
culture verified, clinical UTIs-no culture, microbiological UTIs-no
for people with a susceptibility to UTIs due to an intervention,
symptoms). There were also many differences in the risk of bias
but was considered to be low for elderly men and women and
assessments in the 22 studies, which were included in our review
for adults with bladder emptying issues because of imprecision
and that of Luis 2017. For example, Luis 2017 classified one study
and heterogeneity between studies (Summary of findings 1). There
at high risk of bias for random sequence generation although
were too few studies to assess the certainty of the evidence
the study authors reported that the randomisation sequence was
in studies satisfactorily in studies comparing cranberry to other
obtained using a "computer generated random number table".
interventions such as probiotics or antibiotics.
In this review, that study was classified as at low risk of bias
It should be pointed out that some studies, particularly older for random sequence generation. Similarly, Luis 2017 classified a
studies, were not prospectively registered with ClinicalTrials.gov study, in which "the identities of the treatment assignments were
or equivalent bodies. In future updates of this review, subgroup not known to the subjects, research coordinators or investigators
analyses could include analyses comparing the results from studies and unblinding did not occur until termination of the investigation",
that were prospectively registered with those not registered. as at high risk of bias while the current review considered this study
to be at low risk of bias for those parameters.
Potential biases in the review process
AUTHORS' CONCLUSIONS
For this update, a comprehensive search of Cochrane Kidney and
Transplant’s Specialised Register was performed, which reduced Implications for practice
the likelihood that eligible published studies were omitted from
the review. Eligible studies published after the last search date or • The current body of evidence suggests that cranberry products
published in conference proceedings not routinely searched could (either in juice or as tablets or powder) compared to placebo or
have been missed. Important information particularly on study risk no treatment probably reduce the risk of symptomatic UTIs in
of bias may not have been available from the published results, women with recurrent UTIs, in children, and in people at risk of
particularly in studies only available as abstracts. Data extraction UTIs following an intervention.
was completed independently by two authors or by a single author • The data did not support the use of cranberry products to reduce
with extensive experience in data extraction. This limited the risk of the risk of symptomatic UTIs in elderly men and women, in
errors in determining study eligibility, data extraction, risk of bias pregnant women or in adults with neuromuscular dysfunction of
assessment and data synthesis. No author had a financial interest the bladder and incomplete bladder emptying. However, data in
in the outcome of the studies. The authors believe that the review these latter groups are limited to small studies with considerable
update resulted from an unbiased process limited primarily by the uncertainty around the results.
adequacy of reporting in the included studies.

Cranberries for preventing urinary tract infections (Review) 23

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Implications for research ACKNOWLEDGEMENTS

• There remains considerable uncertainty about the appropriate • The authors of this 2023 update are grateful to Dr Ruth Jepson
dose of PAC intake via cranberry product required to reduce the and Dr Lara Mihaljevic who contributed to the original iterations
risk of UTIs so further studies using different doses of PAC intake of this review and to the earlier updates (Jepson 1998a; Jepson
are required to determine the dose with the highest efficacy and 2003; Jepson 2004; Jepson 2008; Jepson 2012), contributing to
tolerability and the lowest risk of adverse effects in the patient the study selection, quality assessment and data extraction.
groups at risk of symptomatic UTIs.
• The authors would also like to thank the following people for
• The amount of PAC within cranberry products needs to be replying to correspondence:
standardised between products, with products clearly labelled
to include PAC content. • Dr Lyn Stothers (Stothers 2002)
• More studies are required to assess the relative efficacy and • Prof Tero Kontikari (Kontiokari 2001)
safety of cranberry products compared with antibiotics or • Dr Ed Walker (Walker 1997)
probiotics to prevent symptomatic UTIs.
• Dr RJ Woodward (Larkhill Green Farm - cranberry tablets)
• Professor Marion McMurdo (McMurdo 2005)
• Dr Marielle Beerepoot (NAPRUTI 2011)

Cranberries for preventing urinary tract infections (Review) 24

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

REFERENCES

References to studies included in this review for reduction of bacteriuria plus pyuria in female nursing
home residents. Journal of the American Geriatrics Society
Afshar 2012 {published data only}
2012;60(6):1180-1. [MEDLINE: 22690994]
Afshar K, Stothers L, Scott H, MacNeily AE. Cranberry juice for
the prevention of pediatric urinary tract infection: a randomized Madden GR, Argraves SM, Van Ness PH, Juthani-Mehta M.
controlled trial. Journal of Urology 2012;188(4 Suppl):1584-7. Antibiotic susceptibility of urinary isolates in nursing home
[MEDLINE: 22910239] residents consuming cranberry capsules versus placebo.
Infection Control & Hospital Epidemiology 2015;36(3):356-7.
Avorn 1994 {published data only} [MEDLINE: 25695180]
Avorn J, Monane M, Gurwitz J, Glynn R. Reduction of bacteriuria
and pyuria with cranberry beverage: a randomized trial Bonetta 2017 {published data only}
[abstract]. Journal of the American Geriatrics Society 1993;41(10 Bonetta A, Roviello G, Generali D, Zanotti L, Cappelletti MR,
Suppl):SA13. Pacifico C, et al. Enteric-coated and highly standardized
cranberry extract reduces antibiotic and nonsteroidal anti-
* Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, inflammatory drug use for urinary tract infections during
Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of radiotherapy for prostate carcinoma. Research & Reports in
cranberry juice. JAMA 1994;271(10):751-4. [MEDLINE: 8093138] Urology 2017;9:65-9. [MEDLINE: 28491861]
Goodfriend R. Reduction of bacteriuria and pyuria using Bruyere 2019 {published data only}
cranberry juice. JAMA 1994;272(8):588. [MEDLINE: 8057503]
Botto H, Dreyfus JF. The results given in the paper by Bruyere
Hamilton-Miller JM. Reduction of bacteriuria and pyuria using et al. "Multicenter, randomized, placebo-controlled study
cranberry juice. JAMA 1994;272(8):588. [MEDLINE: 8093188] [of] the efficacy of a combination of propolis and cranberry...
(DUAB R) in preventing low urinary tract infection recurrence
Hopkins WJ, Heisey DM, Jonler M, Uehling DT. Reduction in women... [with] recurrent cystitis" should Be used with great
of bacteriuria and pyuria using cranberry juice. JAMA caution. Urologia Internationalis 2020;104(5-6):497-8. [MEDLINE:
1994;272(8):588-9. [MEDLINE: 8057504] 32392560]

Katz LM. Reduction of bacteriuria and pyuria using cranberry Bruyere F, Azzouzi AR, Lavigne JP, Droupy S, Coloby P, Game X,
juice. JAMA 1994;272(8):589. [MEDLINE: 8057505] et al. A multicenter, randomized, placebo-controlled study
evaluating the efficacy of a combination of propolis and
Babar 2021 {published data only} cranberry (Vaccinium macrocarpon) (DUAB®) in preventing low
Babar A, Leblanc V, Dudonne S, Desjardins Y, Howell A, urinary tract infection recurrence in women complaining of
Dodin S. Standardised high dose versus low dose cranberry recurrent cystitis. Urologia Internationalis 2019;103(1):41-8.
Proanthocyanidin extracts for the prevention of recurrent [MEDLINE: 31117097]
urinary tract infection in healthy women [PACCANN]: a double
Bruyere F, Rigaudier F, Sotto A. The results given in the
blind randomised controlled trial protocol. BMC Urology
paper by Bruyere et al. "Multicenter, randomized, placebo-
2018;18(1):29. [MEDLINE: 29716563]
controlled study [of] the efficacy of a combination of propolis
Babar A, Moore L, Leblanc V, Dudonne S, Desjardins Y, and cranberry... (DUAB R) in preventing low urinary tract
Lemieux S, et al. High dose versus low dose standardized infection recurrence in women... [with] recurrent Cystitis"
cranberry proanthocyanidin extract for the prevention of should be used with great caution. Urologia Internationalis
recurrent urinary tract infection in healthy women: a double- 2020;104(5-6):499-500. [MEDLINE: 32101864]
blind randomized controlled trial. BMC Urology 2021;21(1):44.
Caljouw 2014 {published data only}
[MEDLINE: 33757474]
Caljouw MA, van den Hout WB, Putter H, Achterberg WP,
Barbosa-Cesnik 2011 {published data only} Cools HJ, Gussekloo J. Effectiveness of cranberry capsules to
* Barbosa-Cesnik C, Brown MB, Buxton M, Zhang L, prevent urinary tract infections in vulnerable older persons. A
DeBusscher J, Foxman B. Cranberry juice fails to prevent double-blind randomized placebo-controlled trial in long-term
recurrent urinary tract infection: results from a randomized care facilities [abstract no: P325]. European Geriatric Medicine
placebo-controlled trial. Clinical Infectious Diseases 2013;4(Suppl 1):S118-9. [EMBASE: 71182264]
2011;52(1):23-30. [MEDLINE: 21148516]
* Caljouw MA, van den Hout WB, Putter H, Achterberg WP,
Eells SJ, McKinnell JA, Miller LG. Daily cranberry prophylaxis Cools HJ, Gussekloo J. Effectiveness of cranberry capsules to
to prevent recurrent urinary tract infections may be beneficial prevent urinary tract infections in vulnerable older persons:
in some populations of women. Clinical Infectious Diseases a double-blind randomized placebo-controlled trial in long-
2011;52(11):1393-4. [MEDLINE: 21596685] term care facilities. Journal of the American Geriatrics Society
2014;62(1):103-10. [MEDLINE: 25180378]
Bianco 2012 {published data only}
van den Hout WB, Caljouw MA, Putter H, Cools HJ, Gussekloo J.
* Bianco L, Perrelli E, Towle V, Van Ness PH, Juthani-Mehta M.
Cost-effectiveness of cranberry capsules to prevent urinary tract
Pilot randomized controlled dosing study of cranberry capsules

Cranberries for preventing urinary tract infections (Review) 25

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

infection in long-term care facilities: economic evaluation with of Obstetrics & Gynecology 2015;213(2):194-8. [MEDLINE:
a randomized controlled trial. Journal of the American Geriatrics 25882919]
Society 2014;62(1):111-6. [MEDLINE: 25180379]
Gallien 2014 {published data only}
Cowan 2012 {published data only}44646348 * Gallien P, Amarenco G, Benoit N, Bonniaud V, Donze C,
Cowan CC, Hutchison C, Cole T, Barry SJ, Paul J, Reed NS, et al. A Kerdraon J, et al. Cranberry versus placebo in the prevention
randomised double-blind placebo controlled trial to determine of urinary infections in multiple sclerosis: a multicenter,
the effect of cranberry juice on decreasing the incidence of randomized, placebo-controlled, double-blind trial. Multiple
urinary symptoms and urinary tract infections in patients Sclerosis 2014;20(9):1252-9. [MEDLINE: 24402038]
undergoing radiotherapy for cancer of the bladder or cervix.
Clinical Oncology 2012;24(2):e31-8. [MEDLINE: 21703829] Haverkorn 1994 {published data only}
Haverkorn MJ, Mandigers J. Reduction of bacteriuria and
De Leo 2017 {published data only} pyuria using cranberry juice. JAMA 1994;272(8):590. [MEDLINE:
DE Leo V, Cappelli V, Massaro MG, Tosti C, Morgante G. 8057506]
Evaluation of the effects of a natural dietary supplement with
cranberry, Noxamicina® and D-mannose in recurrent urinary Hess 2008 {published data only}
infections in perimenopausal women. Minerva Ginecologica Hess MJ, Hess, PR, Sullivan MR, Nee M, Yalla SV. Evaluation of
2017;69(4):336-41. [MEDLINE: 28608666] cranberry tablets for the prevention of urinary tract infections
in spinal cord injured patients with neurogenic bladder. Spinal
Dotis 2014 {published data only} Cord 2008;46(9):622-6. [MEDLINE: 18392039]
Dotis J, Printza N, Stabouli S, Pavlaki A, Samara S,
Papachristou F. Efficasy of cranberry capsules to prevent Juthani-Mehta 2010 {published and unpublished data}
recurences of urinary tract infections [abstract no: P351]. Juthani-Mehta M, Perley L, Chen S, Dziura J, Gupta K. Feasibility
Pediatric Nephrology 2014;29(9):1793-4. [EMBASE: 71662748] of cranberry capsule administration and clean-catch urine
collection in long-term care residents. Journal of the American
Essadi 2010 {published data only} Geriatrics Society 2010;58(10):2028-30. [MEDLINE: 20929476]
Essadi F, Elmehashi MO. Efficacy of cranberry juice for the
prevention of urinary tract infections in pregnancy [abstract Juthani-Mehta 2016 {published data only}
no: PS 310]. Journal of Maternal-Fetal & Neonatal Medicine Chughtai B, Howell AB, Thomas D, Blumberg JB. Efficacy of
2010;23(Suppl 1):378. [EMBASE: 70200859] cranberry in preventing recurrent urinary tract infections:
have we learned anything new?: Commentary on: Effect of
Fernandes 2016 {published data only} cranberry capsules on bacteriuria plus pyuria among older
Fernandes A, Pereira T, Mendes A, Birne R, Matias P, Jorge C, women in nursing homes: a randomized clinical trial. Urology
et al. Are cranberry capsules effective in preventing urinary 2017;103:2-3. [MEDLINE: 28024965]
tract infections in kidney transplant women?-Randomized
trial [abstract no: MP716]. Nephrology Dialysis Transplantation Datta R, Advani S, Rink A, Bianco L, Van Ness PH, Quagliarello V,
2016;31(Suppl 1):i577. [EMBASE: 72327567] et al. Frequency of infection during fever episodes among long-
term care residents. Journal of Gerontology & Geriatric Research
Ferrara 2009 {published data only} 2018;7(2):467. [MEDLINE: 30197840]
Ferrara P, Romaniello L, Vitelli O, Gatto A, Serva M,
* Juthani-Mehta M, Van Ness PH, Bianco L, Rink A, Rubeck S,
Cataldi L. Cranberry juice for the prevention of recurrent
Ginter S, et al. Effect of cranberry capsules on bacteriuria plus
urinary tract infections: a randomized controlled trial in
pyuria among older women in nursing homes: a randomized
children. Scandinavian Journal of Urology & Nephrology
clinical trial. JAMA 2016;316(18):1879-87. [MEDLINE: 27787564]
2009;43(5):369-72. [MEDLINE: 19921981]
Kontiokari 2001 {published data only}
Foda 1995 {published data only}
Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M,
Foda MM, Middlebrook PF, Gatfield CT, Potvin G, Wells G,
Uhari M. Randomised trial of cranberry-lingonberry juice and
Schillinger JF. Efficacy of cranberry in prevention of urinary
Lactobacillus GG drink for the prevention of urinary tract
tract infection in a susceptible pediatric population. Canadian
infections in women. BMJ 2001;322(7302):1571-3. [MEDLINE:
Journal of Urology 1995;2(1):98-102. [MEDLINE: 12803726]
11431298]
Foxman 2015 {published data only}
Koradia 2019 {published data only}
English EM, Espiritu K, Seiler K, Morgan D, Berger MB,
Koradia P, Kapadia S, Trivedi Y, Chanchu G, Harper A. Probiotic
Cronenwett A, et al. Changes in lower urinary tract symptoms
and cranberry supplementation for preventing recurrent
and urinary incontinence following benign gynecologic surgery
uncomplicated urinary tract infections in premenopausal
[abstract no: 57]. American Journal of Obstetrics & Gynecology
women: a controlled pilot study. Expert Review of Antiinfective
2018;218(2 Suppl 2):S929-30. [EMBASE: 621382530]
Therapy 2019;17(9):733-40. [MEDLINE: 31516055]
Foxman B, Cronenwett AE, Spino C, Berger MB, Morgan DM.
Linsenmeyer 2004 {published data only}
Cranberry juice capsules and urinary tract infection after
surgery: results of a randomized trial. American Journal * Linsenmeyer TA, Harrison B, Oakley A, Kirshblum S, Stock JA,
Millis SR. Evaluation of cranberry supplement for reduction of
Cranberries for preventing urinary tract infections (Review) 26
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

urinary tract infections in individuals with neurogenic bladders with radiotherapy in Iraqi patients with bladder carcinoma.
secondary to spinal cord injury. A prospective, double-blinded, International Journal of Pharmaceutical Sciences Review &
placebo-controlled, crossover study. Journal of Spinal Cord Research 2016;39(2):179-88. [EMBASE: 611820126]
Medicine 2004;27(1):29-34. [MEDLINE: 15156934]
Mooren 2020 {published data only}
Lopes de Carvalho 2012 {published data only} Mooren ES, Liefers WJ, de Leeuw JW. Cranberries after
Lopes De Carvalho L, Francavilla G, Motta R, Brichetto G. D- pelvic floor surgery for urinary tract infection prophylaxis:
mannose, cranberry and vitamin C are effective in preventing A randomized controlled trial. Neurourology & Urodynamics
urinary tract infections in multiple sclerosis subjects [abstract 2020;39(5):1543-9. [MEDLINE: 32449530]
no: 108]. Multiple Sclerosis 2012;18(5):S12-3. [EMBASE:
70762266] NAPRUTI 2011 {published data only}ISRCTN50717094
Beerepoot MA, Stobberingh EE, Geerlings SE. A study of non-
Maki 2016 {published data only} antibiotic versus antibiotic prophylaxis for recurrent urinary-
Maki KC, Kaspar KL, Khoo C, Derrig LH, Schild AL, Gupta K. tract infections in women (the NAPRUTI study) [Onderzoek naar
Consumption of a cranberry juice beverage lowered the number niet-antibiotische versus antibiotische profylaxe bij vrouwen
of clinical urinary tract infection episodes in women with a met recidiverende urineweginfecties (de NAPRUTI-studie)].
recent history of urinary tract infection [Erratum in: Am J Clin Nederlands Tijdschrift voor Geneeskunde 2006;150(10):574-5.
Nutr. 2017 Aug;106(2):708]. American Journal of Clinical Nutrition [MEDLINE: 16566424]
2016;103(6):1434-42. [MEDLINE: 27251185]
Beerepoot MA, ter Riet G, Nys S, van der Wal WM, de Borgie CA,
Maki KC, Nieman KM, Schild AL, Kaspar KL, Khoo C. The effect de Reijke TM, et al. Cranberries vs antibiotics to prevent urinary
of cranberry juice consumption on the recurrence of urinary tract infections: a randomized double-blind noninferiority
tract infection: relationship to baseline risk factors. Journal of trial in premenopausal women. Archives of Internal Medicine
the American College of Nutrition 2018;37(2):121-6. [MEDLINE: 2011;171(14):1270-8. [MEDLINE: 21788542]
29111902]
Bosmans JE, Beerepoot MA, Prins JM, ter Riet G, Geerlings SE.
Nieman KM, Dicklin MR, Schild AL, Kaspar KL, Khoo C, Derrig LH, Cost-effectiveness of cranberries vs antibiotics to prevent
et al. Cranberry beverage consumption reduces antibiotic use urinary tract infections in premenopausal women: a
for clinical urinary tract infection in women with a recent history randomized clinical trial. PLoS ONE [Electronic Resource]
of urinary tract infection [abstract]. FASEB Journal 2017;31(1 2014;9(4):e91939. [MEDLINE: 24705418]
Suppl 1). [EMBASE: 616959251]
Gurley BJ. Cranberries as antibiotics?: Comment on
Straub TJ, Chou WC, Manson AL, Schreiber HL 4th, Walker BJ, "Cranberries vs antibiotics to prevent urinary tract infections: a
Desjardins CA, et al. Limited effects of long-term daily cranberry randomized double-blind noninferiority trial in premenopausal
consumption on the gut microbiome in a placebo-controlled women". Archives of Internal Medicine 2011;171(14):1279-80.
study of women with recurrent urinary tract infections. BMC [MEDLINE: 21788543]
Microbiology 2021;21(1):53. [MEDLINE: 33596852]
Salo 2010 {published and unpublished data}
McGuiness 2002 {published data only (unpublished sought but not * Salo J, Kontiokari T, Helminen M, Korppi M, Nieminen T,
used)} Pokka T, et al. Randomized trial of cranberry juice for the
McGuiness SD, Krone R, Metz LM. A double-blind, randomized, prevention of recurrences of urinary tract infections in
placebo-controlled trial of cranberry supplements in multiple children [abstract no: P1356]. Clinical Microbiology & Infection
sclerosis. Journal of Neuroscience Nursing 2002;34(1):4-7. 2010;16(Suppl 2):S385-6. [EMBASE: 70195963]
[CENTRAL: CN-00724988]
Salo J, Uhari M, Helminen M, Korppi M, Nieminen T, Pokka T, et
McMurdo 2005 {published data only} al. Cranberry juice for the prevention of recurrences of urinary
* McMurdo ME, Bissett LY, Price RJ, Phillips G, Crombie IK. Does tract infections in children: a randomized placebo-controlled
ingestion of cranberry juice reduce symptomatic urinary tract trial. Clinical Infectious Diseases 2011;54(3):340-6. [MEDLINE:
infections in older people in hospital? A double-blind, placebo- 22100577]
controlled trial. Age & Ageing 2005;34(3):256-61. [MEDLINE:
Schlager 1999 {published data only}
15863410]
Schlager TA, Anderson S, Trudell J, Hendley JO. Effect of
McMurdo 2009 {published data only}80031108 cranberry juice on bacteriuria in children with neurogenic
McMurdo ME, Argo I, Phillips G, Daly F, Davey P. Cranberry or bladder receiving intermittent catheterization. Journal of
trimethoprim for the prevention of recurrent urinary tract Pediatrics 1999;135(6):698-702. [MEDLINE: 10586171]
infections? A randomized controlled trial in older women.
Scovell 2015 {published data only}
Journal of Antimicrobial Chemotherapy 2009;63(2):389-95.
[MEDLINE: 19042940] Scovell J, Fletcher S, Stewart J, Khavari R. A prospective
randomized double-blinded placebo control trial on the effects
Mohammed 2016 {published data only} of cranberry supplementation on bacterial colonization and
Mohammed MB, Razzaq BA, Al-Naqqash MA, Jasim SY. Effects symptomatic urinary tract infections in females with neurogenic
of cranberry-PACs against urinary problems associated bladder dysfunction dependent on self catheterization [abstract

Cranberries for preventing urinary tract infections (Review) 27

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

no: PD8-07]. Journal of Urology 2015;193(4 Suppl 1):e192-3. trial [abstract no: 019]. International Urogynecology Journal
[EMBASE: 71858240] 2017;28(1 Suppl 1):S16-7. [EMBASE: 620165630]

Sengupta 2011 {published data only} Stothers L, Levine M, Berkowitz J, Brown P. Patterns and costs
Sengupta K, Alluri KV, Golakoti T, Gottumukkala GV, Raavi J, of health care utilization prior, during and following exposure
Kotchrlakota L, et al. A randomized, double blind, controlled, to cranberry in the prevention of female urinary tract infection:
dose dependent clinical trial to evaluate the efficacy of a Results from a randomized controlled clinical trial (RCT)
proanthocyanidin standardized whole cranberry (Vaccinium involving women with recurrent UTI [abstract no: MP76-20].
macrocarpon) powder on infections of the urinary tract. Current Journal of Urology 2018;199(4 Suppl 1):e1026. [EMBASE:
Bioactive Compounds 2011;7(1):39-46. [EMBASE: 361592064] 621736951]

SINBA 2007 {published data only} Takahashi 2013 {published data only}
Lee BB, Haran MJ, Hunt LM, Simpson JM, Marial O, Takahashi S, Hamasuna R, Yasuda M, Arakawa S, Tanaka K,
Rutkowski SB, et al. Spinal-injured neuropathic bladder Ishikawa K, et al. A randomised clinical trial to evaluate the
antisepsis (SINBA) trial. Spinal Cord 2007;45(8):542-50. preventive effect of cranberry juice (UR65) for patients with
[MEDLINE: 17043681] recurrent urinary tract infection [abstract no: P1402]. Clinical
Microbiology & Infection 2011;17(Suppl 4):S394. [EMBASE:
Singh 2016 {published data only} 70600071]
Gautam L, Singh I, Gautam LK, Kaur IR, Rai S, Joshi MK. Effect
* Takahashi S, Hamasuna R, Yasuda M, Arakawa S, Tanaka K,
of oral cranberry extract (standardised proanthocyanidin-
Ishikawa K, et al. A randomized clinical trial to evaluate
a) on the uropathogenic bacteria in urine of patients with
the preventive effect of cranberry juice (UR65) for patients
subclinical/recurrent uti: A randomised placebo controlled
with recurrent urinary tract infection. Journal of Infection &
clinical study [abstract no: UMP 01-07]. Indian Journal of
Chemotherapy 2013;19(1):112-7. [MEDLINE: 22961092]
Urology 2014;30(Suppl 1):S152. [EMBASE: 71491376]
Takahashi S. Prevention of acute uncomplicated cystitis by
* Singh I, Gautam LK, Kaur IR. Effect of oral cranberry extract
cranberry juice [abstract no: AAUS24-03]. International Journal
(standardized proanthocyanidin-A) in patients with recurrent
of Urology 2012;19(Suppl 1):410. [EMBASE: 70933820]
UTI by pathogenic E. coli: a randomized placebo-controlled
clinical research study. International Urology & Nephrology Temiz 2018 {published data only}
2016;48(9):1379-86. [MEDLINE: 27314247]
Temiz Z, Cavdar I. The effects of training and the use of
Stapleton 2012 {published data only (unpublished sought but not cranberry capsule in preventing urinary tract infections
used)} after urostomy. Complementary Therapies in Clinical Practice
2018;31:111-7. [MEDLINE: 29705442]
Stapleton AE, Dziura J, Hooton TM, Cox ME, Yarova-Yarovaya Y,
Chen S, et al. Recurrent urinary tract infection and urinary Uberos 2012 {published data only}
Escherichia coli in women ingesting cranberry juice daily:
Fernandez-Puentes V, Uberos J, Rodriguez-Belmonte R,
a randomized controlled trial. Mayo Clinic Proceedings
Nogueras-Ocana M, Blanca-Jover E, Narbona-Lopez E. Efficacy
2012;87(2):143-50. [MEDLINE: 22305026]
and safety profile of cranberry in infants and children with
Stothers 2002 {published data only} recurrent urinary tract infection [Eficacia y perfil de seguridad
del arandano americano en lactantes y ninos con infeccion
* Stothers L. A randomized trial to evaluate effectiveness
urinaria recurrente]. Anales de Pediatria 2015;82(6):397-403.
and cost effectiveness of naturopathic cranberry products as
[MEDLINE: 25300782]
prophylaxis against urinary tract infection in women. Canadian
Journal of Urology 2002;9(3):1558-62. [MEDLINE: 12121581] Uberos J, Nogueras-Ocana M, Fernandez-Puentes V, Rodriguez-
Belmonte R, Narbona-López E, Molina-Carballo A, et al.
Stothers 2016 {published data only}
Cranberry syrup vs trimethoprim in the prophylaxis of recurrent
Stothers L, Brown P, Fenster H, Levine M, Berkowitz J. Dose urinary tract infections among children: a controlled trial.
response of cranberry in the treatment of lower urinary tract Open Access Journal of Clinical Trials 2012;4:31–8. [EMBASE:
infections in women [abstract no: MP26-05]. Journal of Urology 2012351759]
2016;195(4 Suppl 1):e355. [EMBASE: 72239569]
Uberos J, Rodrguez-Belmonte R, Fernndez-Puentes V, Narbona-
Stothers L, Brown P, Levine M, Fenster H, Berkowitz J. A Lopez E, Molina-Carballo A, Munoz-Hoyos A. Cranberry syrup vs.
randomized controlled trial examining dose response of trimethoprim in the prophylaxis of recurrent urinary infection: A
cranberry in the treatment of lower urinary tract infections in double-blind randomized clinical trial [abstract no: PP004]. Acta
women and human urine cranberry metabolites [abstract]. Paediatrica 2010;99(Suppl 462):48. [EMBASE: 70313001]
Canadian Urological Association Journal 2016;10(5-6 Suppl
1):S11. [EMBASE: 617745754] * Uberos J, Rodríguez-Belmonte R, Rodríguez-Pérez C, Molina-
Oya M, Blanca-Jover E, Narbona-López E, et al. Phenolic acid
Stothers L, Levine M, Berkowitz J, Brown P. Patterns and costs content and antiadherence activity in the urine of patients
of health care utilization before during and after exposure treated with cranberry syrup (Vaccinium macrocarpon) vs.
to cranberry for the prevention of urinary tract infection trimethoprim for recurrent urinary tract infection. Journal
in women; Results from a randomized controlled clinical

Cranberries for preventing urinary tract infections (Review) 28

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

of Functional Foods 2015;18(Part A):608-16. [DOI: 10.1016/ [abstract no: T-119]. Reproductive Sciences 2015;22(Suppl
j.jff.2015.08.009] 1):146A. [EMBASE: 71847498]

Vostalova 2015 {published data only}

Fromentin E, Vostalova J, Vidlar A, Galandakova A, Vrbkova J, References to studies excluded from this review
Ulrichova J, et al. A randomized, double-blind, placebo- Amin 2018 {published data only}
controlled clinical trial to investigate the efficacy of cranberry
Amin K, Stothers L, Liu Y, Brown PN, Moskowitz D, Lucioni A, et
fruit powder (Pacran) in the prevention of recurrent
al. Effect of whole fruit cranberry on urinary proanthocyanidin
urinary tract infection in women [abstract]. FASEB Journal
metabolites in healthy adult woman [abstract]. Female Pelvic
2014;28(Suppl 1):639.4. [EMBASE: 71421087]
Medicine & Reconstructive Surgery 2018;24(5 Suppl 1):S130-1.
Vidlar A, Vostalova J, Vacek J, Kosina P, Vrbkova J, Ulrichova J, [EMBASE: 627772568]
et al. The effect of cranberry (Vaccinium macrocarpon) on
Amin K, Stothers L, Liu Y, Brown PN, Moskowitz D, Lucioni A, et
the recurrence urinary tract infection in women [abstract no:
al. Effect of whole fruit cranberry on urinary proanthocyanidin
C39]. European Urology Supplements 2011;10(9):622. [EMBASE:
metabolites in women [abstract no: 36]. Neurourology &
70572962]
Urodynamics 2019;38(Suppl 1):S33-4. [EMBASE: 628916652]
* Vostalova J, Vidlar A, Simanek V, Galandakova A, Kosina P,
Barnoiu 2015 {published data only}
Vacek J, et al. Are high proanthocyanidins key to cranberry
efficacy in the prevention of recurrent urinary tract infection? Barnoiu OS, Sequeira-Garcia Del Moral J, Sanchez-Martinez N,
Phytotherapy Research 2015;29(10):1559-67. [MEDLINE: Diaz-Molina P, Flores-Sirvent L, Baena-Gonzalez V. American
26268913] cranberry (proanthocyanidin 120 mg): its value for the
prevention of urinary tracts infections after ureteral catheter
Waites 2004 {published data only} placement. Actas Urologicas Espanolas 2015;39(2):112-7.
* Waites KB, Canupp KC, Armstrong S, DeVivo MJ. Effect of [MEDLINE: 25204992]
cranberry extract on bacteriuria and pyuria in persons with
Gunnarsson 2017 {published data only}
neurogenic bladder secondary to spinal cord injury. Journal of
Spinal Cord Medicine 2004;27(1):35-40. [MEDLINE: 15156935] Gunnarsson AK, Gunningberg L, Larsson S, Jonsson KB.
Cranberry juice concentrate does not significantly decrease
Walker 1997 {published data only} the incidence of acquired bacteriuria in female hip fracture
Walker EB, Barney DP, Mickelsen JN, Walton RJ, Mickelsen RA patients receiving urine catheter: a double-blind randomized
Jr. Cranberry concentrate: UTI prophylaxis. Journal of Family trial. Clinical Interventions In Aging 2017;12:137-43. [MEDLINE:
Practice 1997;45(2):167-8. [MEDLINE: 9267377] 28144131]

Wan 2016 {published data only} Hamilton 2015 {published data only}
Wan KS, Liu CK, Lee WK, Ko MC, Huang CS. Cranberries for Hamilton K, Bennett NC, Purdie G, Herst PM. Standardized
preventing recurrent urinary tract infections in uncircumcised cranberry capsules for radiation cystitis in prostate cancer
boys. Alternative Therapies in Health & Medicine 2016;22(6):20-3. patients in New Zealand: a randomized double blinded,
[MEDLINE: 27866177] placebo controlled pilot study. Supportive Care in Cancer
2015;23(1):95-102. [MEDLINE: 24993395]
Wing 2008 {published data only}
Howell 2010 {published data only}
Wing DA, Rumney PJ, Leu SY, Zaldivar F. Comparison of urinary
cytokines after ingestion of cranberry juice cocktail in pregnant Howell AB, Botto H, Combescure C, Blanc-Potard AB, Gausa L,
subjects: a pilot study. American Journal of Perinatology Matsumoto T, et al. Dosage effect on uropathogenic Escherichia
2010;27(2):137-42. [MEDLINE: 19562652] coli anti-adhesion activity in urine following consumption of
cranberry powder standardized for proanthocyanidin content:
* Wing DA, Rumney PJ, Preslicka CW, Chung JH. Daily cranberry a multicentric randomized double blind study. BMC Infectious
juice for the prevention of asymptomatic bacteriuria in Diseases 2010;10:94. [MEDLINE: 20398248]
pregnancy: a randomized, controlled pilot study. Journal of
Urology 2008;180(4):1367-72. [MEDLINE: 18707726] Howell 2015 {published data only}
Howell A, Souza D, Roller M, Fromentin E. Comparison of the
Wing 2015 {published data only} anti-adhesion activity of three different cranberry extracts on
* Wing DA, Rumney PJ, Hindra S, Guzman L, Le J, Nageotte M. uropathogenic P-fimbriated Escherichia coli: a randomized,
Pilot study to evaluate compliance and tolerability of cranberry double-blind, placebo controlled, ex vivo, acute study. Natural
capsules in pregnancy for the prevention of asymptomatic Product Communications 2015;10(7):1215-8. [MEDLINE:
bacteriuria. Journal of Alternative & Complementary Medicine 26411014]
2015;21(11):700-6. [MEDLINE: 26535612]
Jackson 1997 {published data only}
Wing DA, Rumney PPJ, Hindra S, Le J, Nageotte M. Evaluation of Jackson B, Hicks LE. Effect of cranberry juice on urinary pH
compliance and tolerability of cranberry capsules in pregnancy in older adults. Home Healthcare Nurse 1997;15(3):199-202.
for the prevention of asymptomatic bacteriuria in pregnancy [MEDLINE: 9110682]

Cranberries for preventing urinary tract infections (Review) 29

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Jass 2009 {published data only} Occhipinti 2016 {published data only}
Jass J, Reid G. Effect of cranberry drink on bacterial adhesion Occhipinti A, Germano A, Maffei ME. Prevention of urinary
in vitro and vaginal microbiota in healthy females. Canadian tract infection with Oximacro, a cranberry extract with a high
Journal of Urology 2009;16(6):4901-7. [MEDLINE: 20003665] content of a-type proanthocyanidins: a pre-clinical double-
blind controlled study. Urology Journal 2016;13(2):2640-9.
Kaspar 2015 {published data only} [MEDLINE: 27085566]
Kaspar KL, Howell AB, Khoo C. A randomized, double-blind,
placebo-controlled trial to assess the bacterial anti-adhesion Radulescu 2020 {published data only}
effects of cranberry extract beverages. Food & Function Radulescu D, David C, Turcu FL, Spataru DM, Popescu P,
2015;6(4):1212-17. [MEDLINE: 25723356] Vacaroiu IA. Combination of cranberry extract and D-mannose
- possible enhancer of uropathogen sensitivity to antibiotics in
Lavigne 2008 {published data only} acute therapy of urinary tract infections: results of a pilot study.
Lavigne JP, Bourg G, Combescure C, Botto H, Sotto A. In- Experimental & Therapeutic Medicine 2020;20(4):3399-406.
vitro and in-vivo evidence of dose-dependent decrease of [MEDLINE: 32905041]
uropathogenic Escherichia coli virulence after consumption
of commercial Vaccinium macrocarpon (cranberry) capsules. Russo 2019 {published data only}
Clinical Microbiology & Infection 2008;14(4):350-5. [MEDLINE: Russo E, Montt GM, Giannini A, Mannella P, Palla G, Caretto M,
18190583] et al. Cranberry, D-mannose and anti-inflammatory agents
prevent lower urinary tract symptoms in women undergoing
Letouzey 2017 {published data only} prolapse surgery. Climacteric 2019;23(2):201-5. [MEDLINE:
Botto H, Howell AB. Re: Cranberry capsules to prevent 31674202]
nosocomial urinary tract bacteriuria after pelvic surgery:
a randomised controlled trial: Cranberry for prevention of Sappal 2018 {published data only}
bacteriuria? BJOG: An International Journal of Obstetrics & Sappal S, Goetz LL, Vince R, Klausner AP. Randomized trial of
Gynaecology 2017;124(12):1907. [MEDLINE: 29052361] concentrated proanthocyanidins (PAC) for acute reduction of
bacteriuria in male veterans with spinal cord injury utilizing
Letouzey V, Ulrich D, Demattei C, Alonso S, Huberlant S, clean intermittent catheterization. Spinal Cord Series & Cases
Lavigne JP, et al. Authors' reply re: Cranberry capsules to 2018;4:58. [MEDLINE: 29977609]
prevent nosocomial urinary tract bacteriuria after pelvic
surgery: a randomised controlled trial. BJOG: An International Schultz 1984 {published data only}
Journal of Obstetrics & Gynaecology 2017;124(12):1908. Schultz A. Efficacy of cranberry juice and ascorbic acid in
[MEDLINE: 29052359] acidifying the urine in multiple sclerosis subjects. Journal
of Community Health Nursing 1984;1(3):159-69. [MEDLINE:
Letouzey V, Ulrich D, Demattei C, Alonso S, Huberlant S,
6569071]
Lavigne JP, et al. Cranberry capsules to prevent nosocomial
urinary tract bacteriuria after pelvic surgery: a randomised Tempera 2010 {published data only}
controlled trial. BJOG: An International Journal of Obstetrics &
Tempera G, Corsello S, Genovese C, Caruso FE, Nicolosi D.
Gynaecology 2017;124(6):912-7. [MEDLINE: 28186383]
Inhibitory activity of cranberry extract on the bacterial
Liu 2019b {published data only} adhesiveness in the urine of women: an ex-vivo study.
International Journal of Immunopathology & Pharmacology
Liu H, Howell AB, Zhang DJ, Khoo C. A randomized, double-
2010;23(2):611-8. [MEDLINE: 20646356]
blind, placebo-controlled pilot study to assess bacterial anti-
adhesive activity in human urine following consumption of a Valentova 2007 {published data only}
cranberry supplement. Food & Function 2019;10(12):7645-52.
Valentova K, Stejskal D, Bednar P, Vostalova J, Cihalik C,
[MEDLINE: 31702761]
Vecerova R, et al. Biosafety, antioxidant status, and metabolites
Liu H, Khoo C. A randomized, double-blind, placebo-controlled in urine after consumption of dried cranberry juice in healthy
pilot study to assess the urinary anti-adhesion activity following women: a pilot double-blind placebo-controlled trial. Journal
consumption of cranberry + healthTM cranberry supplement of Agricultural & Food Chemistry 2007;55(8):3217-24. [MEDLINE:
(P06-114-19) [abstract]. Current Developments in Nutrition 17381122]
2019;3(Suppl 1):nzz031. [DOI: 10.1093/cdn/nzz031.P06-114-19]
Vidlar 2010 {published data only}
NCT01079169 {published data only} Vidlar A, Vostalova J, Ulrichova J, Student V, Stejskal D,
NCT01079169. Effect of cranberry capsules on urinary Reichenbach R, et al. The effectiveness of dried cranberries
infection rates in spinal cord injured patients during post ( Vaccinium macrocarpon) in men with lower urinary tract
acute rehabilitation [Evaluation of the effect of cranberry symptoms. British Journal of Nutrition 2010;104(8):1181-9.
capsules on the occurrence of urinary tract infections during [MEDLINE: 20804630]
post-acute rehabilitation of spinal cord injured patients].
www.clinicaltrials.gov/ct2/show/NCT01079169 (accessed 22
July 2016).

Cranberries for preventing urinary tract infections (Review) 30

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

References to studies awaiting assessment NCT03597152 {published data only}

Cotellese 2023 {published data only} D'Anna R. Nutritional supplementation for recurrent urinary
tract infections in women [Nutritional supplementation for
Cotellese R, Ledda A, Belcaro G, Cesarone MR, Scipione C,
extending time between recurrent urinary tract infections
Scipione V, et al. Anthocran® Phytosome®: prevention
in women: a randomized double blind cross-over trial].
of recurring urinary infections and symptoms after
www.clinicaltrials.gov/show/NCT03597152 (first received 24
catheterization. Journal of Dietary Supplements
July 2018).
2023;20(1):55-67. [DOI: 10.1080/19390211.2021.1972074]
[EMBASE: 636356756] NCT05730998 {published data only}
Hakkola 2023 {published data only} NCT05730998. Cranberry for the prevention of urinary tract
infections [The beneficial effects of a cranberry-based oral
Hakkola M, Vehvilinen P, Muotka J, Tejesvi MV, Pokka T,
nutritional supplement on the prevention of urinary tract
Vhasarja P, et al. Cranberry-lingonberry juice affects the gut and
infections in diabetic subjects]. www.clinicaltrials.gov/show/
urinary microbiome in children - a randomized controlled trial.
NCT05730998 (first received 16 February 2023). [CENTRAL:
APMIS 2023;131(3):112-24. [MEDLINE: 36602283]
CN-02524730]
Madhavan 2021 {published data only}
Madhavan K, Rustagi S, Jena R, Singh UP, Ansari MS, Additional references
Srivastava A, et al. A prospective randomized study to define
the role of low dose continuous prophylactic antibiotics and Blatherwick 1923
anti-adherence agents in altering the microbial colonization Blatherwisk NR, Long ML. Studies of urinary acidity. II: the
related to indwelling double-J stents. Asian Journal of Urology increased acidity produced by eating prunes and cranberries.
2021;8(3):269-74. [MEDLINE: 34401333] Journal of Biological Chemistry 1923;57:815-8.

Epp 2010
References to ongoing studies Epp A, Larochelle A. Recurrent urinary tract infection [Erratum
ACTRN12605000626662 {published data only} in: J Obstet Gynaecol Can. 2011 Jan;33(1):12]. Journal of
Obstetrics & Gynaecology Canada: JOGC 2010;32(11):1082–90.
Hassell S. Cranberry capsules for the prevention of urinary
[MEDLINE: 21176321]
tract infection in an elderly population [A randomised, double-
blind, placebo-controlled crossover trial of cranberry capsules Flores-Mireles 2015
to prevent urinary tract infection in an elderly population].
Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ.
www.anzctr.org.au/Trial/Registration/TrialReview.aspx?
Urinary tract infections: epidemiology, mechanisms of
ACTRN=12605000626662 (first received 11 Oct 2005).
infection and treatment options. Nature Reviews. Microbiology
Amador-Mulero 2014 {published data only} 2015;13(5):269-84. [MEDLINE: 25853778]
Amador-Mulero L, De Santiago CB, Ferreiro-Garcia C, Fontan- Foo 2000
Azpeitia M, Garcia-Diaz MJ, Garcia-Trabajo E, et al. Effectiveness
Foo LY, Lu Y, Howell AB, Vorsa N. The structure of cranberry
of red cranberries ingestion on urinary tract infections in
proanthocyanidins which inhibit adherence of uropathogenic
pregnant women [Efectividad de la ingestion de arandano
P-fimbriated Escherichia coli in vitro. Phytochemistry
rojo sobre las infecciones del tracto urinario en embarazadas].
2000;54(2):173-81. [MEDLINE: 10872208]
Matronas Profesion 2014;15(2):50-5. [EMBASE: 373741052]
Foxman 2002
ISRCTN55813586 {published data only}55813586
Foxman B. Epidemiology of urinary tract infections: incidence,
Chang A. Clinical dosage and effectiveness Study of ShanStar®
morbidity, and economic costs. American Journal of Medicine
cranberry supplement for prevention and treatment
2002;113 Suppl 1A:5-13S. [MEDLINE: 12113866]
against women's urinary tract infections. www.isrctn.com/
ISRCTN55813586 (accessed 15 March 2015). [DOI: 10.1186/ Fu 2017
ISRCTN55813586]
Fu Z, Liska D, Talan D, Chung M. Cranberry reduces the risk of
NCT00100061 {unpublished data only} urinary tract infection recurrence in otherwise healthy women:
a systematic review and meta-analysis. Journal of Nutrition
NCT00100061. Effects of cranberry-containing products
2017;147(12):2282-8. [MEDLINE: 29046404]
in women with recurrent urinary tract infections (UTIs)
[Dose response to cranberry of women with recurrent UTIs]. Giesen 2010
www.clinicaltrials.gov/ct2/show/NCT00100061 (first received 22
Giesen LG, Cousins G, Dimitrov BD, van de Laar FA, Fahey T.
December 2004).
Predicting acute uncomplicated urinary tract infection in
NCT00247104 {published data only} women: a systematic review of the diagnostic accuracy
of symptoms and signs. BMC Family Practice 2010;11:78.
Hochner-Celnikier D, Elchalal U. The use of cranberries in
[MEDLINE: 20969801]
women with preterm premature rupture of membranes.
www.clinicaltrials.gov/ct2/show/NCT00247104 (first received 31
Oct 2005).
Cranberries for preventing urinary tract infections (Review) 31
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

GRADE 2008 Katz 1994

Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso- Katz LM. Reduction of bacteriuria and pyuria using cranberry
Coello P, et al. GRADE: an emerging consensus on rating juice. JAMA 1994;272(8):589. [MEDLINE: 8057505]
quality of evidence and strength of recommendations. BMJ
2008;336(7650):924-6. [MEDLINE: 18436948] Kinney 1979
Kinney AB, Blount M. Effect of cranberry juice on urinary pH.
GRADE 2011 Nursing Research 1979;28(5):287-90. [MEDLINE: 38439]
Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al.
GRADE guidelines: 1. Introduction-GRADE evidence profiles and Kwok 2022
summary of findings tables. Journal of Clinical Epidemiology Kwok M, McGeorge S, Mayer-Coverdale J, Graves B, Paterson DL,
2011;64(4):383-94. [MEDLINE: 21195583] Harris PN, et al. Guideline of guidelines: management of
recurrent urinary tract infections in women. BJU International
Hellstrom 1991 2022;130 Suppl 3:11-22. [MEDLINE: 35579121]
Hellstrom A, Hanson E, Hansson S, Hjalmas K, Jodal U.
Association between urinary symptoms at 7 years old and Luis 2017
previous urinary tract infection. Archives of Disease in Childhood Luis A, Domingues F, Pereira L. Can cranberries contribute to
1991;66(2):232-4. [MEDLINE: 2001110] reduce the incidence of urinary tract infections? A systematic
review with meta-analysis and trial sequential analysis of
Higgins 2003 clinical trials. Journal of Urology 2017;198(3):614-21. [MEDLINE:
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring 28288837]
inconsistency in meta-analyses. BMJ 2003;327(7414):557-60.
[MEDLINE: 12958120] McLeod 1978
McLeod DC, Nahata MC. Methenamine therapy and urine
Higgins 2022 acidification with ascorbic acid and cranberry juice. American
Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et Journal of Hospital Pharmacy 1978;35(6):654. [MEDLINE: 27096]
al. Cochrane Handbook for Systematic Reviews of Interventions
version 6.3 (updated February 2022). Cochrane, 2022. Available Patton 1991
from www.training.cochrane.org/handbook. Patton JP, Nash DB, Abrutyn E. Urinary tract infection:
economic considerations. Medical Clinics of North America
Hopkins 1994 1991;75(2):495-513. [MEDLINE: 1996046]
Hopkins WJ, Heisley DM, Jonler M, Uehling DT. Reduction
of bacteriuria and pyuria using cranberry juice. JAMA Prior 2010
1994;272(8):588-9. [MEDLINE: 8057504] Prior RL, Fan E, Hongping J, Howell A, Nio C, Payne M, et
al. Multi-laboratory validation of a standard method for
Howell 2002 quantifying proanthocyanidins in cranberry powders. Journal of
Howell AB, Foxman B. Cranberry juice and adhesion of the Science of Food & Agriculture 2010;90(9):1473-8. [MEDLINE:
antibiotic-resistant uropathogens. JAMA 2002;287(23):3082-3. 20549799]
[MEDLINE: 12069670]
Roberts 1979
Howell 2005 Roberts AP, Phillips R. Bacteria causing symptomatic urinary
Howell AB, Reed JD, Kreuger CG, Winterbottom R, tract infection or asymptomatic bacteriuria. Journal of Clinical
Cunningham DG, Leahy M. A-type cranberry proanthocyanidins Pathology 1979;32(5):492-6. [MEDLINE: 381327]
and uropathogenic bacterial anti-adhesion activity.
Phytochemistry 2005;66(18):2281-91. [MEDLINE: 16055161] Schmidt 1988
Schmidt DR, Sobota AE. An examination of the anti-adherence
Howell 2007 activity of cranberry juice on urinary and nonurinary bacterial
Howell AB. Bioactive compounds in cranberries and their role isolates. Microbios 1988;55(224-255):173-81. [MEDLINE:
in prevention of urinary tract infections. Molecular Nutrition & 3063927]
Food Research 2007;51(6):732-7. [MEDLINE: 17487930]
Schunemann 2022a
Jepson 1998b Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA,
Jepson RG, Mihaljevic L, Craig JC. Cranberries for Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’
treating urinary tract infections. Cochrane Database of tables and grading the certainty of the evidence. In: Higgins
Systematic Reviews 1998, Issue 4. Art. No: CD001322. [DOI: JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch
10.1002/14651858.CD001322] VA (editors). Cochrane Handbook for Systematic Reviews of
Interventions version 6.3 (updated February 2022). Cochrane,
Kahn 1967 2022. www.training.cochrane.org/handbook.
Kahn HD, Panariello VA, Saeli J, Sampson JR, Schwartz E. Effect
of cranberry juice on urine. Journal of the American Dietetic Schunemann 2022b
Association 1967;51(3):251-4. [MEDLINE: 6035629] Schünemann HJ, Vist GE, Higgins JP, Santesso N, Deeks JJ,
Glasziou P, et al. Chapter 15: Interpreting results and
Cranberries for preventing urinary tract infections (Review) 32
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

drawing conclusions. In: Higgins JP, Thomas J, Chandler J, References to other published versions of this review
Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane
Jepson 1998a
Handbook for Systematic Reviews of Interventions version
6.3 (updated February 2022). Cochrane, 2022. Available from Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing
www.training.cochrane.org/handbook. urinary tract infections. Cochrane Database of Systematic
Reviews 1998, Issue 2.
Stapleton 1997
Jepson 2003
Stapleton A, Stamm WE. Prevention of urinary tract infection.
Infectious Disease Clinics of North America 1997;11(3):719-33. Jepson RG, Mihaljevic L, Craig J. Cranberries for
[MEDLINE: 9378932] preventing urinary tract infections. Cochrane Database of
Systematic Reviews 2003, Issue 1. Art. No: CD001321. [DOI:
Winberg 1974 10.1002/14651858.CD001321.pub2]
Winberg J, Andersen HJ, Bergstrom T, Jacobsson B, Larson H,
Jepson 2004
Lincoln K. Epidemiology of symptomatic urinary tract infection
in childhood. Acta Paediatrica Scandinavica - Supplement 1974; Jepson RG, Mihaljevic L, Craig J. Cranberries for
(252):1-20. [MEDLINE: 4618418] preventing urinary tract infections. Cochrane Database of
Systematic Reviews 2004, Issue 2. Art. No: CD001321. [DOI:
Wong 1984 10.1002/14651858.CD001321.pub3]
Wong ES, Fennell Cl, Stamm WE. Urinary tract infection among
Jepson 2008
women attending a clinic for sexually transmitted diseases.
Sexually Transmitted Diseases 1984;11(1):18-23. [MEDLINE: Jepson RG, Craig JC. Cranberries for preventing urinary tract
6546811] infections. Cochrane Database of Systematic Reviews 2008, Issue
1. Art. No: CD001321. [DOI: 10.1002/14651858.CD001321.pub4]
Zafriri 1989
Jepson 2012
Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity
of cranberry juice on adherence of type 1 and type P fimbriated Jepson RG, Williams G, Craig JC. Cranberries for
Escherichia coli to eucaryotic cells. Antimicrobial Agents & preventing urinary tract infections. Cochrane Database of
Chemotherapy 1989;33(1):92-8. [MEDLINE: 2653218] Systematic Reviews 2012, Issue 10. Art. No: CD001321. [DOI:
10.1002/14651858.CD001321.pub5]

* Indicates the major publication for the study

CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]

Afshar 2012
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on UTIs rate over 12 months
• ITT analysis: yes, stated

Time frame

• Duration of study: not reported

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: Canada
• Setting: single centre
• Inclusion criteria: aged 5 to 8 years; toilet trained; 2 symptomatic, culture-proven UTIs in the calendar
year before recruitment; living in metropolitan Vancouver
• Exclusion criteria: posterior urethral valves; neurogenic bladder; obstruction

Baseline characteristics

Cranberries for preventing urinary tract infections (Review) 33

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Afshar 2012 (Continued)

• Number: intervention group (20); control group (20)
• Median age, range (years): intervention group (7, 5 to 18); control group (7, 5 to 17)
• Sex (M/F): intervention group (1/19); control group (0/20)

Interventions Intervention group

• Cranberry juice: 2 cc/kg cranberry juice containing 37% PAC

Control roup

• Placebo: identical in terms of colour, taste and packaging, same volume of juice with no PAC or other
cranberry products

Intervention duration: 12 months

Outcomes Outcomes of interest/reported

• Symptomatic UTI rate/participant/year

• UTI rate ratio

Notes Additional information

• Six patients in each group did not complete the study, average follow-up for these children was 3
months; all included in analysis
• Culture threshold: 108 CFU/L, or 107 CFU/L plus positive WCC and or nitrites in dipstick
• Symptomatic: any one of: fever, dysuria, frequency or hematuria
• Funding source: Lions Gate HealthCare Research Foundation grant

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer generated random number table
tion (selection bias)

Allocation concealment Low risk States that randomisation was concealed

(selection bias)

Blinding of participants Low risk States participants and clinicians blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk States blinded

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk 12 of 40 patients did not complete the study but all included in the analysis
(attrition bias)
All outcomes

Selective reporting (re- Low risk States number for repeat UTIs
porting bias)

Other bias Unclear risk Patient selection is poorly detailed and uncertain how representative these
children are of the wider group of children with UTIs

Cranberries for preventing urinary tract infections (Review) 34

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Avorn 1994
Study characteristics

Methods Study design

• Quasi-RCT
• Power calculation: yes
• ITT analysis: no

Time frame

• Duration of study: not reported

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: USA
• Setting: multicentre (10 sites)
• Inclusion criteria: women were recruited from a single long-term care facility for the elderly and 9
housing complexes for the elderly; participants had to be willing to ingest at least 300 mL of cranberry
juice daily for a 6-month period
• Exclusion criteria: terminal disease or severe dementia; men

Baseline characteristics

• Number: intervention group (72); control group (81)

• Mean age ± SD (years): intervention group (78.1 ± 8.3); control group (79.0 ± 9.4)
• Sex (M/F): all female

Interventions Intervention group

• Cranberry juice cocktail: 300 mL/day (30% cranberry concentrate)

• PAC content: not reported

Control group

• Placebo beverage: looked and tasted similar but contained no cranberry juice

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Presence of bacteriuria (≥ 108 CFU/L) with the presence of pyuria

• Presence of bacteriuria
• Presence of bacteriuria with the presence of pyuria plus symptoms of a UTI

Notes Additional information

• Data were presented for 153 subjects who provided a baseline urine sample and at least one additional
sample after randomisation
• Method of obtaining urine sample: MSU, clean-voided
• Definition of bacteriuria: organisms ≥ 108 CFU/L regardless of organism
• Definition of pyuria: not reported
• Exclusions post randomisation: none
• Adherence; bottle caps collected and counted
• Funding source: research grant from Ocean Spray Cranberries Inc

Risk of bias

Cranberries for preventing urinary tract infections (Review) 35

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Avorn 1994 (Continued)

Bias Authors' judgement Support for judgement

Random sequence genera- High risk Odd versus even numbers in institutional identification number or telephone
tion (selection bias) number (quasi-RCT)

Allocation concealment High risk Inadequate, could subvert system by excluding people with certain number, or
(selection bias) include more of those with a certain number

Blinding of participants Low risk Quote: "Neither participants nor investigators were aware of whether a given
and personnel (perfor- subject was receiving cranberry beverage or placebo beverage"
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Not reported

sessment (detection bias)
All outcomes

Incomplete outcome data High risk Absolute numbers not always provided; 39 patients lost to follow-up/with-
(attrition bias) drawn
All outcomes

Selective reporting (re- Low risk Study includes an outcome of symptomatic culture-verified UTI
porting bias)

Other bias High risk Source of funding: Research grant from Ocean Spray Cranberries, Inc

Babar 2021
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on 25% difference between groups
• ITT analysis: yes, stated

Time frame

• Duration of study: August 2015 to April 2017

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: Canada
• Setting: Laval University community in Quebec City, Canada
• Inclusion criteria: sexually active healthy women; ≥ 18 years; recent history of recurrent UTI; ≥ 2 UTIs in
the past 6 months and/or ≥ 3 UTIs in the past 12 months; no consumption of cranberry juice, polyphe-
nol or antioxidant supplements in the last 2 weeks; UTIs did not have to be verified by culture
• Exclusion criteria: pregnancy; history of anatomical urogenital anomalies, urogenital tract surgery;
history of AKI or CKD; nephrolithiasis; history of intestinal diseases causing malabsorption; anticoag-
ulant medication in the last month; known allergy or intolerance to cranberry

Baseline characteristics

• Number: intervention group 1 (72); intervention group 2 (73)

• Mean age ± SD (years): intervention group 1 (27.2 ± 8.8); intervention group 2 (32.5 ± 14.2)

Cranberries for preventing urinary tract infections (Review) 36

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Babar 2021 (Continued)

• Sex (M/F): all female

Interventions Intervention group 1

• Cranberry extract: formulated in high PAC content capsules (2 capsules of 18.5 mg PAC/day)

Intervention group 2

• Cranberry extract: formulated in low PAC content capsules (2 capsules of 1 mg PAC/day)

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Symptomatic UTI: defined as acute urinary symptoms (frequency, urgency, dysuria, pelvic pain,
haematuria) in the absence of alternate diagnoses as assessed by study staff
• Symptomatic UTI with pyuria on leucocyte esterase test
• Symptomatic UTI with bacteriuria in the presence of ≥ 107 CFU/mL of uropathogenic bacteria

Notes Additional information

• Funding source: "Ministry of Agriculture, Fisheries and Food of Quebec and Nutra Canada (now part of
Diana Food Canada)." "Diana Food scientists did have a role in the approval of the manuscript and the
decision to submit the manuscript for publication. Diana Food Canada manufactured and donated
the cranberry capsules used in this study."

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Quote: "Concealed randomization was generated using computer assisted
tion (selection bias) randomization by blocks of 10"

Allocation concealment Low risk Quote: "Concealed randomization was generated using computer assisted
(selection bias) randomization by blocks of 10"

Blinding of participants Low risk Quote: “All clinical investigation, laboratory analysis, data collection and as-
and personnel (perfor- sessment were blinded to the randomization allocation”
mance bias)
All outcomes Quote: “Capsules were distributed in opaque packaging in order to conceal
slight colour variations from the research team”

Blinding of outcome as- Low risk Quote: “All clinical investigation, laboratory analysis, data collection and as-
sessment (detection bias) sessment were blinded to the randomization allocation”
All outcomes
Quote: “Capsules were distributed in opaque packaging in order to conceal
slight colour variations from the research team”

Incomplete outcome data Low risk All patients accounted for: 86% completed study, 18 (12%) lost to follow-up
(attrition bias)
All outcomes

Selective reporting (re- Low risk All expected outcomes reported

porting bias)

Other bias High risk Quote: “This research project was funded by the Ministry of Agriculture, Fish-
eries and Food of Quebec and Nutra Canada (now part of Diana Food Canada).
The funders had no role in the design and conduct of this clinical trial nor the
collection, management, analysis, and interpretation of data. Diana Food sci-
entists did have a role in the approval of the manuscript and the decision to

Cranberries for preventing urinary tract infections (Review) 37

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Babar 2021 (Continued)

submit the manuscript for publication. Diana Food Canada manufactured and
donated the cranberry capsules used in this study”

Barbosa-Cesnik 2011
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes
• ITT analysis: no

Time frame

• Duration of study: August 2005 and October 2007

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: USA
• Setting: single centre
• Inclusion criteria: women presenting to a health service with symptoms of UT aged 18 to 40 years;
residing in Ann Arbor next 6 months 3 to 4 previous UTIs, 1 in previous year
• Exclusion criteria: antibiotics in past 48 hours; hospitalisation or catheterisation within past 2 weeks;
kidney stones; DM; pregnancy; cranberry allergy; negative urine culture

Baseline characteristics

• Number (randomised/analysed): intervention group (205/155); control group (214/184)

• Mean age ± SD (years): intervention group (21.2 ± 3.4); control group (21.2 ± 3.5)
• Sex (M/F): all female

Interventions Intervention group

• Low-calorie cranberry cocktail: 240 mL twice/day

• Mean PAC: 112 mg/240 mL

Control group

• Placebo drink: same volume matched for flavour and colour

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• UTI: ≥ 103 CFU/L of known pathogen

• Urinary symptoms and vaginal symptoms at day 3, 1 to 2 weeks, and ≥ 1 month

Notes Additional information

• Compliance measured by direct questioning

• Source of funding: National centre for alternative medicine at NIH

Risk of bias

Bias Authors' judgement Support for judgement

Cranberries for preventing urinary tract infections (Review) 38

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Barbosa-Cesnik 2011 (Continued)

Random sequence genera- Low risk Computer generated

tion (selection bias)

Allocation concealment Low risk External, web based allocation

(selection bias)

Blinding of participants Low risk Placebo drink matched, participants and clinicians blinded
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data High risk 100 participants randomised but no outcomes reported for them, they were
(attrition bias) actually not eligible to be randomised since they were culture negative
All outcomes

Selective reporting (re- Low risk UTI is most appropriate outcome

porting bias)

Other bias High risk Selection bias, representative nature of those who consented is questionable

Bianco 2012
Study characteristics

Methods Study design

• Parallel, 4-arm RCT

◦ Stratification on the presence or absence of baseline bacteriuria
• Power calculation: no
• ITT analysis: not reported

Time frame

• Duration of study: not reported

• Duration of follow-up: 4 weeks

Participants Study characteristics

• Country: USA
• Setting: multicentre (11 sites)
• Inclusion criteria: female long-term nursing home residents with past history of UTIs aged ≥ 65 years;
English speaking
• Exclusion criteria: total incontinence; warfarin therapy; < 4 weeks residence; chronic indwelling
catheter; terminal prognosis; antibiotic therapy; kidney stones; dialysis; currently on cranberry ther-
apy; cranberry allergy

Baseline characteristics

• Number: intervention group 1 (20); intervention group 2 (20); intervention group 3 (20); control group
(20)
• Mean age ± SD: 89.2 ± 7 years
• Sex (M/F): all female

Cranberries for preventing urinary tract infections (Review) 39

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Bianco 2012 (Continued)

Interventions Intervention group 1

• Cranberry tablet/s: 1 (36 mg)

• Placebo tablet/s: 2

Intervention group 2

• Cranberry tablet/s: 2 (72 mg)

• Placebo tablet/s: 1

Intervention group 3

• Cranberry tablet/s: 3 (108 mg)

Control group

• Placebo tablets: 3

Each cranberry tablet contained 36 mg of PAC

Intervention duration: 30 days

Outcomes Outcomes of interest/reported

• Episodes of bacteriuria and pyuria at 7, 14, 21 and 28 days of tablet taking

Notes Additional information

• Data not included in meta-analysis, unit of analysis was urine samples, not people
• Culture threshold; > 108 CFU/L
• Funding source: Cranberry and placebo donated by Pharmatoka Inc, and National Institute on Aging,
National Institutes of Health, Claude D. Pepper Older Americans Independence Center and the Na-
tional Center for Research Resources at the National Institutes of Health

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk No details of randomisation process but stratification stated
tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk States double blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Low rate of exclusions and lost data for outcome analysis: 22/320 urine sam-
(attrition bias) ples
All outcomes

Selective reporting (re- High risk Does not specify patients with UTIs, unit of analysis is urine specimen and par-
porting bias) ticipants had multiple of these

Cranberries for preventing urinary tract infections (Review) 40

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Bianco 2012 (Continued)

Other bias Low risk Good detail on screened patients and exclusion groups

Bonetta 2017
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: no
• ITT analysis: not reported

Time frame

• Duration of study: 2006 to 2016

• Duration of follow-up: 6 weeks

Participants Study characteristics

• Country: Italy
• Setting: single centre
• Inclusion criteria: men diagnosed with prostatic adenocarcinoma were treated with radiotherapy to
the prostatic area and also to the pelvic area
• Exclusion criteria: history of pelvic external beam radiotherapy; previous pelvic malignancies; a
Karnofsky score < 8; kidney failure; refusal of preventive daily intervention with cranberry extract

Baseline characteristics

• Number: intervention group (489); control group (435)

• Mean age ± SD (years): intervention group (69.63 ± 7.16); control group (70.15 ± 6.45)
• Sex (M/F): all males

Interventions Intervention group

• One tablet/day of enteric-coated, highly standardized extract, titred as 30% PAC according to the Eu-
ropean Pharmacopoeia method (version 6.0)
◦ Sold as MonoselectMacrocarpon® by PharmExtracta (Italy) and in the rest of the world as Ressuro®
by Helsinn Integrative Care (Helsinn Healthcare SA, Switzerland)

Control group

• No intervention

Intervention duration: 6 to 7 weeks

Outcomes Outcomes of interest/reported

• UTI: culture verified (> 108 CFU/L) with symptoms

• Recurrent UTI infection
• E coli in culture
• E faecalis in culture
• Days on antibiotics
• Days on NSAIDs
• Dysuria
• Nocturia
• Urgency

Cranberries for preventing urinary tract infections (Review) 41

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Bonetta 2017 (Continued)

• Change in average daily urination frequency

Notes Additional information

• Funding source: not reported

• Conflict of interest: FRP involved with company selling cranberry products

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Coin toss

tion (selection bias)

Allocation concealment High risk Easy to manipulate by repeating toss if unhappy with result
(selection bias)

Blinding of participants High risk Open-label study, all aware of intervention arm
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Does not state details on whether analysis done blind to intervention arm
sessment (detection bias)
All outcomes

Incomplete outcome data Low risk All who were reported to be randomised are included in the analyses
(attrition bias)
All outcomes

Selective reporting (re- Low risk Wide range of outcomes, patient centred and UTI required culture and symp-
porting bias) toms

Other bias Unclear risk No description of who was screened for the study and who or how many re-
fused

Bruyere 2019
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes
• ITT analysis: yes, for those who had taken the product at least once

Time frame

• Duration of study: October 2013 to June 2015

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: France
• Setting: multicentre (9 sites)
• Inclusion criteria: women aged > 18 years; at least 4 episodes of cystitis in the previous 12 months

Cranberries for preventing urinary tract infections (Review) 42

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Bruyere 2019 (Continued)

• Exclusion criteria: cystitis due to microorganisms other than E coli; anatomical abnormalities or his-
tory of surgery of the urinary tract; urinary stones; kidney failure; DM; immune deficiency acquired or
linked to long-term corticosteroid medication; pregnant or whose were not receiving effective con-
traception; undergoing continuous or discontinuous antibiotic prophylaxis or treatment with antivi-
tamin K; an intolerance to beehive products or red fruits

Baseline characteristics

• Number (randomised/analysed): intervention group (43/38); control group (43/36)

• Mean age ± SD (years): intervention group (53.0 ± 17.4); control group (53.0 ± 19.2)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry and Propolis extract: 4 capsules on day 1, then 2 capsules/day

◦ (Propolis is a chemically complex sticky "glue" collected from beehives. It contains resins collected
from the buds and leaves of plants, volatile oils, and wax)

Control group

• Placebo: 4 capsules on day 1, then 2 capsules/day

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Mean number of infections

• Total number of cystitis episodes
• Time to onset of first UTI: positive urine culture was defined as > 105 CFU/mL urinary enterobacteria
• Tolerance to intervention

Notes Additional information

• Funding source: "This study was funded by Nutrivercell"

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Quote: "The randomization sequence was generated by the statistician at Eu-
tion (selection bias) raxi Pharma (Tours, France) using SAS software version 8.2 and was centralized
in block size 4 with no stratification"

Allocation concealment Low risk Quote: "The centralized randomization list was kept and securely managed by
(selection bias) Euraxi Pharma."

Blinding of participants Low risk Quote: "The investigator at each site completed a Randomization Request
and personnel (perfor- Form for each subject after protocol eligibility criteria were met and the com-
mance bias) pleted form was faxed to Euraxi Pharma. The subject was randomized accord-
All outcomes ing to the randomization schedule and the Randomization Request Form faxed
back to the site with details of the treatment allocation for the subject"

Blinding of outcome as- Low risk Quote: "an independent CRO of Nutrivercell, performed the statistical analyses
sessment (detection bias) of this trial in accordance with the protocol and the statistical analysis plan at
All outcomes the end of the study"

Incomplete outcome data Low risk One patient asked to stop the study in the intervention group and was exclud-
(attrition bias) ed from the ITT analysis; all patients accounted for
All outcomes

Cranberries for preventing urinary tract infections (Review) 43

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Bruyere 2019 (Continued)

Selective reporting (re- Low risk Outcomes of interest were reported

porting bias)

Other bias High risk Funded by Nutricercell, and all analyses carries out by Nutricercell

Caljouw 2014
Study characteristics

Methods Study design

• Parallel RCT
• Stratified into high and low risk
◦ High risk: long-term catheterisation (> 1 month), DM, or at least 1 UTI in the preceding year
◦ Low risk: does not fulfil high risk criteria (assumed)
• Power calculation: yes, based on 40% reduction in incidence of UTIs with cranberry intervention
• ITT analysis: not reported, but analysed all who were randomised, within their randomised group

Time frame

• Duration of study: November 2008 to August 2009

• Duration of follow-up: study stopped in June 2011

Participants Study characteristics

• Country: Netherlands
• Setting: multicentre (number of sites not reported)
• Inclusion criteria: long-term aged care home residents. aged ≥ 65 years
• Exclusion criteria: use of coumarin; life expectancy ≤ 1 month

Baseline characteristics

• Number
◦ Low-risk group: intervention group (205); control group (207)
◦ High-risk group: intervention group (253); control group (263)
• Mean age, IQR (years)
◦ Low-risk group: intervention group (84.0, 78.5 to 88.5); control group (83.0, 79.0 to 88.0)
◦ High-risk group: intervention group (85.0, 79.0 to 89.0); control group (84.0, 79.0 to 88.0)
• Sex (M/F)
◦ Low-risk group: intervention group (62/143); control group (48/153)
◦ High-risk group: intervention group (65/188); control group (50/213)

Interventions Intervention group

• Cranberry tablet: 1 tablet, twice/day, containing 500 mg cranberry product, 1.8% (9 mg) PAC

Control group

• Placebo: 1 tablet twice/day

Intervention duration: 12 months

Outcomes Outcomes of interest/reported

• Clinical UTI: clinical symptoms alone

• Strict UTI: symptoms plus positive culture (> 108 CFU/L)

Cranberries for preventing urinary tract infections (Review) 44

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Caljouw 2014 (Continued)

• Hospitalisation
• Death

Notes Additional information

• Clinical UTI: a minimum of one of the following

◦ Specific and nonspecific micturition-related symptoms and signs
◦ Positive test (nitrite, leukocyte esterase test, dip slide, or culture)
◦ Antibiotic intervention for UTI
◦ UTI reported in the medical record
• Funding; Dutch Organization for Health Research, Springfield Nutraceuticals B.V. supplied the cran-
berry and placebo capsules and Dutch Organization of Scientific Research (NWO) for Open Access pub-
lication of this paper

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Block randomisation (blocks of 6) was used, stratified for risk profile and abili-
tion (selection bias) ty to give informed consent, generated using a computer random number gen-
erator

External randomisation

Allocation concealment Low risk Random number in sealed envelopes

(selection bias)

Blinding of participants Low risk Quote: "Participants,family, nursing staff, physicians, pharmacists, and re-
and personnel (perfor- search nurses were blinded to intervention"
mance bias)
All outcomes

Blinding of outcome as- Low risk Quote: "Participants, family, nursing staff, physicians, pharmacists, and re-
sessment (detection bias) search nurses were blinded to intervention"
All outcomes

Incomplete outcome data Low risk Low rate of excluded data for outcome analysis: 0/928
(attrition bias)
All outcomes

Selective reporting (re- Low risk Clinically relevant outcomes reported

porting bias)

Other bias Low risk Good detail on study design and recruitment/selection of patients

Cowan 2012
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, assumed 20% reduction in bladder problems
• ITT analysis: yes

Time frame

Cranberries for preventing urinary tract infections (Review) 45

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Cowan 2012 (Continued)

• Duration of study: recruitment between March 2003 and June 2006
• Duration of follow-up: 6 weeks

Participants Study characteristics

• Country: UK
• Setting: single centre
• Inclusion criteria: > 18 years with cervical or bladder cancer requiring radiation therapy
• Exclusion criteria: pregnant or lactating women; irritable bowel syndrome; DM; rheumatoid arthritis;
> Common Toxicity Criteria grade 1 urinary symptoms or UTI at baseline; receiving antispasmodics or
antibiotics for urinary symptoms; indwelling urinary catheter; receiving warfarin therapy

Baseline characteristics

• Number (randomised/analysed): intervention group (64/57); control group (64/56)

• Median age, range (years): intervention group (67.5, 27 to 89); control group (69.0, 28 to 85)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry juice twice/day; volume and PAC not reported

Control group

• Matched placebo juice twice/day; volume not reported

Intervention duration: 6 weeks

Outcomes Outcomes of interest/reported

• Urinary symptoms
• UTI: single organism, ≥ 108 CFU/L in a non-catheterised patient and/or other abnormal findings such
as pus cells in the urine with or without subjective symptoms

Notes Additional information

• Funding source: "West Research Endowment Fund, NHS Greater Glasgow and Clyde; the juice and
placebo were supplied by Ocean Spray Cranberries, Inc., Lakeville-Middleboro, MA, USA

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer based deterministic minimisation algorithm
tion (selection bias)

Allocation concealment Low risk Externally allocated; c omputer algorithm generated a blinded juice pack
(selection bias)

Blinding of participants Low risk Double blinding stated, patients blinded to intervention arm, clinicians blind-
and personnel (perfor- ed
mance bias)
All outcomes

Blinding of outcome as- Unclear risk For UTI outcome probably low risk, microbiology results independent
sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Very little missing/excluded data for outcome analysis: 9/128
(attrition bias)
Cranberries for preventing urinary tract infections (Review) 46
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Cowan 2012 (Continued)

All outcomes

Selective reporting (re- Low risk Urinary symptoms and UTI

porting bias)

Other bias Low risk Source of funding: West Research Endowment fund, NHS greater Glasgow and
Clyde, Juice and placebo supplied by Ocean Spray

De Leo 2017
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: not reported

Time frame

• Duration of study: not reported

• Duration of follow-up: 3 months

Participants Study characteristics

• Country: Italy
• Setting: multicentre (number of sites not reported)
• Inclusion criteria: women aged 40 to 50 years with ≥ 8 episodes of cystitis/year
• Exclusion criteria: cancer; endocrine diseases; urinary calculus; drug intervention that could create
interactions with therapy

Baseline characteristics

• Number: intervention group (100); control group (50)

• Mean age ± SD (years): intervention group (47.3 ± 4.1); control group (47.9 ± 4)
• Sex (M/F): all women

Interventions Intervention group

• 1 sachet once/day for the first 10 days of the month

◦ Cranberry: 90 mg (PAC 72 mg)
◦ Noxamicin (Kistinox Forte): 100 mg (from propolis extract)
◦ D-mannose: 500 mg

Control group

• No intervention

Intervention duration: 3 months

Outcomes Outcomes of interest/reported

• Episodes of cystitis
• Frequency of symptoms (dysuria, frequency, intensity of urination pain)

Notes Additional information

• UTI definition: not reported

Cranberries for preventing urinary tract infections (Review) 47
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

De Leo 2017 (Continued)

• Cystitis: self-reported episodes
• Funding source: not reported, states there were no conflicts of interest

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Unclear risk Insufficient information to permit judgement

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data High risk 3 dropouts (of 45) but 4 missing
(attrition bias)
All outcomes

Selective reporting (re- High risk UTI definition poor

porting bias)

Other bias Unclear risk Selection bias, unable to determine how and where patients were recruited
from

Dotis 2014
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: not reported

Time frame

• Duration of study: not reported

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: Greece
• Setting: not reported
• Inclusion criteria: children aged 2 to 18 years with a history of recurrent UTI
• Exclusion criteria: children with VUR ≥ grade III

Baseline characteristics

• Number: intervention group (38); control group (38)

Cranberries for preventing urinary tract infections (Review) 48
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Dotis 2014 (Continued)

• Mean age ± SD (years): not reported
• Sex (M/F): 23/53

Interventions Intervention group

• Cranberry capsules (Mirtygil, Istituto Ganassini, SpA, Epsilon Health): 2/day, for at least 3 months

Control group

• No intervention

Outcomes Outcomes of interest/reported

• UTI: definition not specified, no culture threshold reported

• Initiation of antimicrobial intervention
• Days on antimicrobial intervention
• Side effects

Notes Additional information

• Abstract-only publication
• Contacted author for further details (18 May 2017), no response
• Funding source: not reported

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Unclear risk Insufficient information to permit judgement

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk Unsure, no denominators given so uncertain if all children included in the
(attrition bias) analysis
All outcomes

Selective reporting (re- Low risk Repeat UTIs reported

porting bias)

Other bias Unclear risk Abstract-only publication; unable to determine representativeness of sample,
and study design issues incomplete

Essadi 2010
Study characteristics

Cranberries for preventing urinary tract infections (Review) 49

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Essadi 2010 (Continued)

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: not reported

Time frame

• Duration of study: October 2008 to December 2009

• Duration of follow-up: not reported

Participants Study characteristics

• Country: Libya
• Setting: single centre
• Inclusion criteria: pregnant women attending an antenatal clinic
• Exclusion criteria: not reported

Baseline characteristics

• Number (randomised/analysed): intervention group (380/258); control group (380/286)

• Mean age ± SD (years): not reported
• Sex (M/F): all women

Interventions Intervention group

• Cranberry juice: 250 mL 4 times/day

Control group

• Water: 250 mL 4 times/day

Intervention duration: not reported

Outcomes Outcomes of interest/reported

• UTI: definition not reported, no culture threshold reported

• Premature delivery

Notes Additional information

• Abstract-only publication, few details

• Funding source: not reported

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants High risk No, participants could tell difference between intervention and drinking water
and personnel (perfor-
mance bias)
All outcomes

Cranberries for preventing urinary tract infections (Review) 50

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Essadi 2010 (Continued)

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data High risk Loss to follow-up excluded and no best-worst case scenario analysis
(attrition bias) High rate of losses to follow-up/withdrawals/exclusions for UTI outcome
All outcomes analysis: 196/760

Selective reporting (re- Low risk Appropriate outcomes

porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Fernandes 2016
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: not reported; unclear from outcomes data

Time frame

• Duration of study: not reported

• Duration of follow-up: not reported

Participants Study characteristics

• Country: Portugal
• Setting: not reported
• Inclusion criteria: women ≥ 18 years; received kidney transplant > 1 year earlier; eGFR ≥ 30 mL/
min/1.72 m2
• Exclusion criteria: pregnancy; urological anomaly; cranberry intolerance; ongoing antibiotics or cot-
rimoxazole prophylaxis

Baseline characteristics

• Number: intervention group (25); control group (30)

• Mean age ± SD (years): not reported
• Sex (M/F): all women

Interventions Intervention group

• Daily cranberry capsule

Control group

• Daily placebo capsule

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• UTI: culture threshold not stated

• UTI caused by E coli

Cranberries for preventing urinary tract infections (Review) 51

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Fernandes 2016 (Continued)

• UTI caused by Klebsiella pneumoniae
• UTI caused by Proteus mirabilis
• Antibiotic resistance to amoxicillin-clavulanate
• Quinolones resistance
• SMP-TMP resistance
• ESBL bacterial infections
• Number of hospitalised patients

Notes Additional information

• Abstract-only publication
• Funding source: not reported
• Authors contacted for further details 18 May 2017: no response

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk States double-blind

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk Unable to determine, no denominators and no lost to follow-up reported
(attrition bias)
All outcomes

Selective reporting (re- Low risk Clinically relevant outcomes reported

porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Ferrara 2009
Study characteristics

Methods Study design

• Parallel, 3-arm RCT

• Power calculation: not reported
• ITT analysis: no

Time frame

• Duration of study: June 2005 to July 2007

Cranberries for preventing urinary tract infections (Review) 52

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Ferrara 2009 (Continued)

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: Italy
• Setting: single centre
• Inclusion criteria: girls aged 3 to 14 years attending an ambulatory paediatric nephrology clinic; > 1
UTI in previous 12 months
• Exclusion criteria: structural abnormalities; deformities of the urinary tract; impaired kidney function

Baseline characteristics

• Number (randomised/analysed): intervention group 1 (28/27); intervention group 2 (27/26); control

group (29/27)
• Mean age ± SD (years): not reported
• Sex (M/F): all girls

Interventions Intervention group 1

• Cranberry-lingonberry concentrate
◦ Cranberry concentrate: 50 mL/day for 6 months (97.5 g cranberry concentrate)
◦ Lingonberry concentrate: 1.7 g in 50 mL water
◦ No sugar additive

Intervention group 2

• Lactobacillus GG drink: 100 mL on 5 days each month for 6 months (contains 4 x 107 CFU/100 mL)

Control group

• No intervention

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Symptomatic UTI (symptoms being frequency, dysuria, urgency, haematuria, nocturia, fever, back or
hip pain) and ≥ 108 CFU/L

Notes Additional information

• Funding source: not reported

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Random numbers table

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants High risk No, participants knew what intervention they were taking
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)

Cranberries for preventing urinary tract infections (Review) 53

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Ferrara 2009 (Continued)

All outcomes

Incomplete outcome data Low risk Low rate of those excluded from outcome analysis: 4/84
(attrition bias)
All outcomes

Selective reporting (re- Low risk Appropriate outcome

porting bias)

Other bias Unclear risk Details on patients are limited, selection bias may be present

Source of funding not reported

Foda 1995
Study characteristics

Methods Study design

• Cross-over RCT
• Power calculation: not reported
• ITT analysis: no

Time frame

• Duration of study: not reported

• Duration of follow-up: 12 months total

Participants Study characteristics

• Country: Canada
• Setting: single centre
• Inclusion criteria: children with neuropathic bladder managed by clean intermittent catheterisation;
outpatients’ residence at a distance not exceeding 150 km from the Children’s Hospital of Eastern
Ontario
• Exclusion criteria: not reported

Baseline characteristics

• Number (randomised/analysed): 40/21

• Mean age (range): 9.35 years (1.4 to 18)
• Sex (M/F): 19/21

Interventions Intervention group

• Cranberry cocktail: 15 mL/kg/day (30% cranberry concentrate)

Control group

• Water

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Number of months of positive cultures plus a symptomatic UTI

• Number of months of positive cultures plus an asymptomatic UTI

Cranberries for preventing urinary tract infections (Review) 54

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Foda 1995 (Continued)

• Side effects and compliance

Notes Additional information

• Method of urine collection

◦ Sterile catheter urine samples
• Definition of bacteriuria
◦ ≥ 108 CFU/L of a pathogenic organism after 24 hours incubation
◦ Any growth in a symptomatic patient was considered significant
• Funding source: not reported

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants High risk Unable to blind participants; blinding of physician only
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data High risk High rate of losses to follow-up/withdrawals excluded for outcome analysis:
(attrition bias) 19/40 excluded
All outcomes

Selective reporting (re- Unclear risk Insufficient information to permit judgement

porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Foxman 2015
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on 65% to 75% relative risk reduction in cranberry group, compared to
placebo, based on recurrence risk of 15% to 18% recurrence risk in placebo
• ITT analysis: not reported but group tallies with numbers randomised to each group

Time frame

• Duration of study: recruited between August 2011 and January 2013

• Duration of follow-up: 6 weeks

Participants Study characteristics

Cranberries for preventing urinary tract infections (Review) 55

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Foxman 2015 (Continued)

• Country: USA
• Setting: single centre
• Inclusion criteria: non-pregnant women; > 18 years; undergoing gynaecological surgery
• Exclusion criteria: history of nephrolithiasis; congenital urogenital anomaly; neurogenic bladder;
known allergy to cranberry; on anticoagulant medicine; fistula repair or vaginal mesh removal

Baseline characteristics

• Number: intervention group (80); control group (80)

• Mean age ± SD (years): intervention group (56 ± 12.5); control group (56 ± 14.3)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry capsules (Theracran): 2 capsules twice/day (4/day) equivalent to 2 x 8-ounce servings of

cranberry juice

Control group

• Placebo: no details, made by Theralogix, LLC

Intervention duration: 6 weeks

Outcomes Outcomes of interest/reported

• Symptomatic UTI: confirmed with culture, no threshold reported

• Clinical UTI: not confirmed with culture
• Median time to UTI
• Adverse events
• Severe adverse events

Notes Additional information

• Funding source: NIH (R21-DK-085290) and University of Michigan (for 1 CIs salary)
• Pills supplied free from Theralogix

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer-generated permuted blocks

tion (selection bias)

Allocation concealment Low risk Data coordinating centre managed allocation

(selection bias)

Blinding of participants Low risk Quote: "masked to intervention assignment"

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Cultures performed by laboratory

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk All women accounted for in analysis
(attrition bias) Low rate of missing data for outcome analysis: 0/160
All outcomes

Cranberries for preventing urinary tract infections (Review) 56

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Foxman 2015 (Continued)

Selective reporting (re- Low risk Relevant outcomes reported, includes culture-verified UTI
porting bias)

Other bias Unclear risk Few details on why so many eligible women (n = 359) were not randomised

Gallien 2014
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on estimation of 35% recurrence rate in placebo, and 15% reduction in
cranberry group
• ITT analysis: yes, stated; reports results within randomised groups with correct totals

Time frame

• Duration of study: recruitment from 26 January 2006 to 5 November 2007

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: France
• Setting: multicentre (8 sites)
• Inclusion criteria: MS with an EDSS score ≥ 3; clinically stable for at least 3 months; able to undergo
evaluation; aged 18 to 70 years; urinary disorders (at least one of these 4 symptoms: pollakiuria, ur-
gency, dysuria and urinary incontinence); agree to a 1-year follow-up
• Exclusion criteria: pregnant or breast-feeding; kidney failure; risk of uric acid lithiasis; peptic ulcer;
intolerance to cranberry and/or excipients; receiving UTI antibiotic prophylaxis; receiving oral antico-
agulants; consumed cranberry in some form within the previous 3 months; indwelling catheter; UTI
at the time of randomisation

Baseline characteristics

• Number: intervention group (82); control group (89)

• Mean age ± SD (years): intervention group (49 ± 9); control group (48 ± 11)
• Sex (M/F): intervention group (19/63); control group (27/62)

Interventions Intervention group

• Cranberry powder: twice/day (36 mg PAC/day)

Control group

• Placebo: matching powder

Intervention duration: 12 months

Outcomes Outcomes of interest/reported

• Rate of UTIs
• UTIs in 12 months
• Number of UTIs per person in 12 months
• MS relapses in 12 months
• Number of patients who took at least one script for antibiotics

Cranberries for preventing urinary tract infections (Review) 57

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Gallien 2014 (Continued)

• Mean number of days on antibiotics

Notes Additional information

• Culture threshold: ≥ 108 CFU/L

• Funding source: French Ministry of Health (PHRC 2005)

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Blocks of four according to a computer generated random number table with
tion (selection bias) a 1:1 allocation reported

Allocation concealment Low risk Centrally performed across 8 centres

(selection bias)

Blinding of participants Low risk Stated, patients, pharmacists, medical staff and nurses all blinded
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Stated, patients, pharmacists, medical staff and nurses all blinded
sessment (detection bias)
All outcomes

Incomplete outcome data Low risk All randomised patients included in analysis, denominators reported
(attrition bias)
All outcomes

Selective reporting (re- Low risk Clinically relevant outcomes reported

porting bias)

Other bias Low risk Well reported and all patients accounted for, selection bias probably limited

Haverkorn 1994
Study characteristics

Methods Study design

• Cross-over RCT
• Power calculation: not reported
• ITT analysis: no

Time frame

• Duration of study: end of 1992 to early 1994

• Duration of follow-up: not reported

Participants Study characteristics

• Country: the Netherlands

• Setting: single centre
• Inclusion criteria: those who had hospital treatment and were waiting transfer to a nursing home
• Exclusion criteria: not reported

Cranberries for preventing urinary tract infections (Review) 58

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Haverkorn 1994 (Continued)

Baseline characteristics

• Number (randomised/analysed): 38/7

• Mean age: 81 years
• Sex (M/F): 9/29

Interventions Intervention group

• Cranberry juice: 30 mL/day mixed with water (PAC not reported)

Control group

• Water: same volume as intervention

Intervention duration: 4 weeks active intervention (8 weeks total)

Outcomes Outcomes of interest/reported

• Bacteriuria

Notes Additional information

• Method of obtaining urine sample: not reported

• Definition of bacteriuria
◦ ≥ 108 CFU/L of one of the Enterobacteriaceae
• Report is a letter only, so very few methodological details
• Funding source: not reported

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- High risk Date of birth (odd versus even numbers)
tion (selection bias)

Allocation concealment High risk Inadequate, able to subvert system by not enrolling some if they were to start
(selection bias) on water only

Blinding of participants Unclear risk Insufficient information to permit judgement

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data High risk High rate of missing or excluded data from outcome analysis: 21/38 (55%)
(attrition bias)
All outcomes

Selective reporting (re- Unclear risk Few details, can't be certain all outcomes collected were reported
porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Cranberries for preventing urinary tract infections (Review) 59

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Hess 2008
Study characteristics

Methods Study design

• Cross-over RCT
• Power calculation: yes
• ITT analysis: no

Time frame

• Duration of study: enrolled between August 2002 to August 2004

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: USA
• Setting: single centre
• Inclusion criteria: clinically documented spinal cord injury with neurogenic bladder
• Exclusion criteria: spinal cord injury duration < 12 months; GFR < 30 mL/min; immunosuppression;
current malignancy

Baseline characteristics

• Number (randomised/analysed): 57/47

• Median age (range): 53 years (28 to 79)
• Sex (M/F): all men

Interventions Intervention group

• Cranberry tablet: 500 mg twice/day

Control group

• Placebo tablet: rice flour, matched to cranberry tablet

Intervention duration: 6 months then crossed over

Outcomes Outcomes of interest/reported

• Symptomatic UTI: ≥ 107 CFU/L

• Significant bacteriuria: at least 1 UTI over 6 months; rate of UTI/person-years

Notes Additional information

• Cross-over design without data on 1st phase being separate, not analysed
• Funding source: Spinal Cord Research Foundation, sponsored by the Paralyzed Veterans of America

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Low risk Concealed, managed by the pharmacy

(selection bias)

Cranberries for preventing urinary tract infections (Review) 60

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Hess 2008 (Continued)

Blinding of participants Low risk Blinding stated

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Unsure if outcome assessors blind, but all others were and outcome is objec-
sessment (detection bias) tively measured
All outcomes

Incomplete outcome data High risk High rate of missing or excluded data for outcome analysis: 10/57
(attrition bias)
All outcomes

Selective reporting (re- Low risk Appropriate outcome

porting bias)

Other bias Low risk No apparent additional bias

Source of funding: Spinal Cord Research Foundation, sponsored by the Para-
lyzed Veterans of America

Juthani-Mehta 2010
Study characteristics

Methods Study design

• Parallel, 3-arm RCT

• Power calculation: not reported
• ITT analysis: appears all were included

Time frame

• Duration of study: September 2007 to June 2008

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: USA
• Setting: multicentre (4 sites)
• Inclusion criteria: > 60 years with dementia and a resident of a nursing home or assisted living facility
for > 30 days
• Exclusion criteria: chronic indwelling catheter; residence < 4 weeks; prednisone therapy; active UTI
symptoms; terminal; ESKD; < 60 years; chronic suppressive antibiotic therapy; history of kidney
stones; unable to provide baseline urine; warfarin therapy

Baseline characteristics

• Number: intervention group 1 (20); intervention group 2 (19); control group (17)
• Mean age: 87 years
• Sex (M/F): 82.1% female

Interventions Intervention group 1

• Cranberry: 650 mg capsule once/day (16.25 mg PAC)

Intervention group 2

Cranberries for preventing urinary tract infections (Review) 61

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Juthani-Mehta 2010 (Continued)

• Cranberry: 650 mg capsule twice/day (32.50 mg PAC)

Control group

• No intervention

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Number of urine cultures collected

• Number of participants with E. coli isolated from urine culture
• Number of participants with ≥ 108 CFU/L of any organism

Notes Additional information

• Details from clinical trials register, not from a published paper

• Designed as a feasibility pilot for a larger study, wanted to determine if collecting urine was feasible
• Funding source: Patrick and Catherine Weldon Donaghue Medical Research Foundation
GrantDF06-005 (KG, MJM)
• The cranberry capsules used in the study were donated by Theralogix Inc

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Open-label study, could be possible to subvert randomisation
(selection bias)

Blinding of participants High risk Open-label study

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- High risk Open-label study

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Low rate of exclusions from outcome analysis; 0/56
(attrition bias)
All outcomes

Selective reporting (re- Unclear risk Outcomes are about feasibility not efficacy
porting bias)

Other bias Unclear risk Many details missing or poorly detailed

Juthani-Mehta 2016
Study characteristics

Methods Study design

• Parallel RCT

Cranberries for preventing urinary tract infections (Review) 62

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Juthani-Mehta 2016 (Continued)

• Power calculation: yes, based on a rate of bacteriuria and pyuria of 0.45 in placebo and a 33% reduc-
tion in cranberry
• ITT analysis: yes, stated and groups analysed as randomised

Time frame

• Duration of study: 24 August 2012 to 7 October 2014

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: USA
• Setting: multicentre (21 sites)
• Inclusion criteria: women in long-term care facilities > 60 years; English speaking; with or without bac-
teriuria plus pyuria
• Exclusion criteria: not expected to be a resident for at least 1 month; taking chronic suppressive antibi-
otics or anti-infective agents; on dialysis; unable to produce urine sample; on warfarin; nephrolithi-
asis; indwelling bladder catheter; allergy to cranberry; intervention with cranberry product; nursing
home resident < 4 weeks

Baseline characteristics

• Number: intervention group (92); control group (93)

• Mean age ± SD (years): intervention group (86.4 ± 8.2); control group (87.1 ± 8.4)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry capsules (made by Pharmatoka): 2 capsules once/day (72 mg PAC)

Control group

• Placebo: 2 capsules once/day

Intervention duration: 360 days

Outcomes Outcomes of interest/reported

• Bacteriuria plus pyuria (culture threshold ≥ 108 CFU/L)

• Symptomatic UTI
• Death (any cause)
• Hospitalisation (any cause)
• Multi-drug resistance organisms
• Antibiotics for suspected UTI
• Antimicrobial prescriptions

Notes Additional information

• Funding source: Pepper Older Americans Independence Centre, National Institute of Health
• Cranberry and placebo capsules donated by Pharmatoka

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Permuted block design with variable block size, 4-6, stratified by nursing
tion (selection bias) home. States designed by statistician, implemented by statistical programmer

Cranberries for preventing urinary tract infections (Review) 63

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Juthani-Mehta 2016 (Continued)

Allocation concealment Low risk Investigational drug services pharmacist made intervention assignments. Only
(selection bias) programmer and pharmacist had access to randomisation codes during enrol-
ment

Blinding of participants Low risk States double blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk 19 lost to follow-up in cranberry group, and 19 lost to follow-up in placebo, in-
(attrition bias) cluded in analysis
All outcomes Low rate of missing or excluded data for outcome analysis: 0/185

Selective reporting (re- Low risk Comprehensive list of outcomes and clinically relevant ones reported
porting bias)

Other bias Low risk Well reported study with clear selection process

Kontiokari 2001
Study characteristics

Methods Study design

• Parallel, 3-arm RCT

• Power calculation: yes, but recruitment stopped before appropriate number recruited
• ITT analysis: yes

Time frame

• Duration of study: 1993 to 1997

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: Finland
• Setting: single centre
• Inclusion criteria: women who had a UTI caused by E coli (105 CFU/mL in clean voided MSU) and were
not taking antimicrobial prophylaxis
• Exclusion criteria: not reported

Baseline characteristics

• Number: intervention group 1 (50); intervention group 2 (50); control group (50)
• Mean age ± SD (years): intervention group 1 (30 ± 9.8); intervention group 2 (30 ± 11.8); control group
(29 ± 10.5)
• Sex (M/F): all women

Interventions Intervention group 1

• Cranberry-lingonberry juice concentrate (Maija, Marli, Finland): 50 mL/day

◦ Cranberry concentrate: 7.5 g

Cranberries for preventing urinary tract infections (Review) 64

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Kontiokari 2001 (Continued)

◦ Lingonberry concentrate: 1.7 g
◦ Water: 50 mL with no added sugars

Intervention group 2

• Lactobacillus GG drink (Gefilus, Valio, Finland): 100 mL for 5 days/week

Control group

• No intervention

Intervention duration

• Cranberry-lingonberry concentrate: 6 months

• Lactobacillus GG drink: 12 months

Outcomes Outcomes of interest/reported

• First recurrence of symptomatic UTI

Notes Additional information

• Method of obtaining urine sample: clean voided MSU specimen

• Definition of bacteriuria
◦ Bacterial growth ≥ 108 CFU/L
• Recruitment had to be stopped prematurely because the cranberry juice supplier stopped producing
the juice. A total of 150 women gave their informed consent and were randomly allocated into three
groups, 50 in each. One subject in the lactobacillus group who was taking post-coital antimicrobials
was excluded from the analysis
• Funding source: Emil Aaltonen, Juho Vainio, and Alma and K A Snellman Foundations
• Marli and Valio provided the study products

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Tables of random numbers and block technique with block size of 6
tion (selection bias)

Allocation concealment Low risk Sealed opaque envelopes (additional information provided by authors)
(selection bias)

Blinding of participants High risk Participants and physicians not blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Lab staff blinded

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Low rate of excluded or missing data from outcome analysis: 13/150
(attrition bias)
All outcomes

Selective reporting (re- Low risk Appropriate outcomes

porting bias)

Other bias Unclear risk Uncertain about selection bias, few details

Cranberries for preventing urinary tract infections (Review) 65

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Koradia 2019
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on a reduction from 0% to 10%
• ITT analysis: yes, also gives per protocol

Time frame

• Duration of study: August 2016 to June 2018

• Duration of follow-up: 180 days

Participants Study characteristics

• Country: India
• Setting: multicentre (4 sites)
• Inclusion criteria: females aged 18 to 55 years; ≥ 2 episodes of uncomplicated acute UTI in the last 6
months, or ≥ 3 episodes of uncomplicated acute UTI in the last 12 months; agree to avoid pregnancy
• Exclusion criteria: active UTI; any use of antibiotics within 2 weeks of screening; use of any natural
product one month prior to starting the study; a positive pregnancy test; postmenopausal; concurrent
use of corticosteroids, anticoagulants, antidepressants, other mood-stabilizing medications, or any
medication that could interact with the supplement; significant concurrent illness or conditions in-
cluding, psychiatric, cardiac, poorly-controlled hypertension, renal (including anatomical irregulari-
ties, catheterisation, kidney stones or kidney transplant), hepatic, neurological, endocrine, metabol-
ic, or lymphatic disease that, in the opinion of the investigator, could adversely affect the subjects
participation in the study; immunosuppressive disease; active participation in any clinical trial within
1 month of study entry; known allergy to any ingredient

Baseline characteristics

• Number (randomised/analysed): intervention group (44/40); control group (45/44)

• Mean age ± SD (years): intervention group (34.6 ± 9.6); control group (34.8 ± 10.1)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry and probiotic capsule (BKPro-Cyan (ADM Protexin, Somerset, UK): 1 capsule, twice/day
◦ Cranberry: minimum of 18 mg PAC/capsule
◦ Probiotic: > 500 x 106 live probiotic micro-organisms/capsule

Control group

• Placebo

Intervention duration: 26 weeks

Outcomes Outcomes of interest/reported

• Repeat UTI by 26 weeks

• Days to first UTI after randomisation
• Days of active UTI
• Number of patients requiring antibiotics for active UTI
• Days of antibiotics for active UTI
• Number of antibiotic courses

Notes Additional information

Cranberries for preventing urinary tract infections (Review) 66

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Koradia 2019 (Continued)

• UTI definition: ≥ 106 CFU/L of uropathogens in an MSU in participants presenting with symptoms of
uncomplicated cystitis (dysuria, urinary frequency, urgency, suprapubic pain, and haematuria)
• Funding source: ADM Protexin Ltd

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Quote: "Performed by an independent statistician using unique three-digit
tion (selection bias) subject identification numbers [based upon a single-digit study center number
followed by a two-digit individual number"

Allocation concealment Low risk Independent data monitor maintained codes and records locked
(selection bias)

Blinding of participants Low risk States patients blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk States blinding

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk States blinding

(attrition bias)
All outcomes

Selective reporting (re- Low risk Includes most appropriate outcome of microbiologically verified symptomatic
porting bias) UTI

Other bias Unclear risk No details on how and where patients were recruited; 1 author and a reviewer
stated involvement with commercial entities selling cranberry and probiotics

Linsenmeyer 2004
Study characteristics

Methods Study design

• Cross-over RCT
• Power calculation: not reported
• ITT analysis: no

Time frame

• Duration of study: not reported

• Duration of follow-up: 9 weeks

Participants Study characteristics

• Country: USA
• Setting: single centre
• Inclusion criteria: neurogenic bladders secondary to spinal cord injury
• Exclusion criteria: not reported

Cranberries for preventing urinary tract infections (Review) 67

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Linsenmeyer 2004 (Continued)

Baseline characteristics

• Number (randomised/analysed): 37/21

• Mean age ± SD (years): not reported
• Sex (M/F): 16/5

Interventions Intervention group

• Cranberry tablets: 400 mg standardised tablets

Control group

• Placebo

Intervention duration: 9 weeks (4 weeks on each, plus one week wash out)

Outcomes Outcomes of interested/reported

• Urinary bacterial counts and WBC counts and the combination of bacterial and WBC counts

Notes Additional information

• Method of obtaining urine sample

◦ CSU or MSU
• Definition of bacteriuria
◦ MSU: ≥ 107 CFU/L
◦ CSU: ≥ 105 CFU/L
• Funding source: Eastern Paralyzed Veterans Association

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk States participants and researchers blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk States researchers are blinded, assume outcomes assessors included
sessment (detection bias)
All outcomes

Incomplete outcome data High risk High proportion excluded from outcome analysis: 16/37
(attrition bias)
All outcomes

Selective reporting (re- Low risk Primary outcome is appropriate

porting bias)

Other bias Unclear risk Some methods are vague, not a well reported study

Cranberries for preventing urinary tract infections (Review) 68

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Lopes de Carvalho 2012

Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: not reported

Time frame

• Duration of study: not reported

• Duration of follow-up: 90 days

Participants Study characteristics

• Country: Italy
• Setting: not reported
• Inclusion criteria: fulfil McDonald criteria for MS diagnosis
• Exclusion criteria: not reported

Baseline characteristics

• Number: intervention group (11); control group (10)

• Mean age ± SD (years): not reported
• Sex (M/F): not reported

Interventions Intervention group

• Cranberry-D-mannose-vitamin C: 2 capsules/day
◦ Cranberry extract: 40 mg/capsule
◦ D-mannose: 100 mg/capsule
◦ Vitamin C: 60 mg/capsule

Control group

• Placebo: 2 capsules/day

Intervention duration: 90 days

Outcomes Outcomes of interest/reported

• Number of UTIs
• Number of urine cultures (threshold not reported)
• Bladder symptoms
• Post void residual

Notes Additional information

• Abstract-only publication
• Funding source: not reported
• Author emailed for further details, no response

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Cranberries for preventing urinary tract infections (Review) 69

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Lopes de Carvalho 2012 (Continued)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk States examiner physicians and subjects blinded
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk Insufficient information to permit judgement

(attrition bias)
All outcomes

Selective reporting (re- Unclear risk No data reported for any outcomes
porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Maki 2016
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on 32% of women having a UTI and 17.8% reduction in this rate for
cranberry group
• ITT analysis: yes, stated and numbers in groups reflect randomised numbers

Time frame

• Duration of study: February 2013 to March 2015

• Duration of follow-up: 24 weeks

Participants Study characteristics

• Countries: USA, France

• Setting: multicentre (18 sites)
• Inclusion criteria: women aged 20 to 70 years; BMI < 40; ≥ 2 UTIs treated by a health professional in the
past year, of which ≥ 1 UTI treated ≤ 6 months before screening visit
• Exclusion criteria: currently using prophylactic antibiotics; active UTI infection with symptoms; blad-
der catheter; polycystic disease; interstitial cystitis; previous urologic surgery; stones; anatomical
abnormality of urinary tract; spinal cord injury; immunocompromised; kidney impairment; DM with
HbA1c ≥ 8%; DM treated with insulin; cancer in past 2 years; major trauma or surgery; oral anticoagu-
lants ≤ 4 weeks before screening; pregnancy; lactating

Baseline characteristics

• Number: intervention group (185); control group (188)

• Mean age ± SEM (years): intervention group (40.9 ± 1.1); control group (41.0 1.0)
• Sex (M/F): all women

Interventions Intervention group

Cranberries for preventing urinary tract infections (Review) 70

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Maki 2016 (Continued)

• Cranberry juice (Ocean Spray Cranberries Inc): 240 mL bottle/day

Control group

• Placebo beverage (Ocean Spray Cranberries Inc): 240 mL bottle/day, matched for smell and taste

intervention duration: 24 weeks

Outcomes Outcomes of interest/reported

• Clinical UTI
• Annual UTI incidence density
• UTI by 24 weeks
• Microbiologically-proven UTI (≥ 106 CFU/L)
• Adverse effects

Notes Additional information

• Funding source: Ocean Spray Cranberries Inc

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer generated, SAS for Windows software
tion (selection bias)

Allocation concealment Low risk Coded data trak system

(selection bias)

Blinding of participants Low risk States double blind

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Low rate of missing or excluded data from outcome analysis: 0/373
(attrition bias)
All outcomes

Selective reporting (re- Low risk Amongst the outcomes was the most relevant, symptomatic UTI verified by
porting bias) culture

Other bias Low risk Detailed reporting

McGuiness 2002
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not mentioned in methods but mentioned in discussion
• ITT analysis: reported to be "yes" (although percentages in results do not make sense)
Cranberries for preventing urinary tract infections (Review) 71
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

McGuiness 2002 (Continued)

Time frame

• Duration of study: not reported

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: Canada
• Setting: single centre
• Inclusion criteria: MS diagnosis (Poser criteria), EDSS 0–8; consented; refrain from cranberries during
study; no indwelling or condom catheter, if intermittent catheterisation, no more than 6 times/day;
symptoms of neurogenic bladder; no current UTI
• Exclusion criteria: not reported

Baseline characteristics

• Number (randomised/analysed): 135/106 (number per group not reported)

• Mean age ± SD (years): intervention group (44.8 ± 9.9); control group (45.4 ± 9.8)
• Sex (M/F): intervention group (21%/79%); control group (21.9%/78.1%)

Interventions intervention group

• Cranberry-containing tablet (NOW Natural Foods): 8000 mg tablet, one tablet/day

Control group

• Beetroot powder placebo tablet: identical appearance to cranberry, one tablet/day

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Microbiological UTI (≥ 109 CFU/L) "with leucocytes, blood or nitrites on microscopy"

• Symptoms were not required because these are usually masked in people with MS

Notes Additional information

• Results reported separately for patients with intermittent catheterisation and normal voiding, but
study did not mention if it was stratified for this and numbers of each in the 2 intervention groups are
not provided
• Very poorly reported study and percentages reported for incidence of UTIs do not make sense
• Funding source: Alberta Association of Registered Nurses, American Association of Neuroscience
Nurses

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk Title states the study was double-blinded, assume this refers to participants
and personnel (perfor- and healthcare providers
mance bias)
All outcomes

Cranberries for preventing urinary tract infections (Review) 72

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

McGuiness 2002 (Continued)

Blinding of outcome as- Unclear risk Blinding of microbiologists is assumed so culture result is likely to be unbi-
sessment (detection bias) ased. Less certain about how objectively measured the other criteria were
All outcomes

Incomplete outcome data Low risk Low rate of exclusions from outcome analysis: 12/135 participants withdrew or
(attrition bias) were lost to follow-up but the numbers in each intervention arm were not pro-
All outcomes vided

Selective reporting (re- Low risk UTI was appropriate outcomes and definition was provided
porting bias)

Other bias Unclear risk No details provided on how participants were selected and from how large the
group, possible selection bias

McMurdo 2005
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes
• ITT analysis: yes
• Stratified by gender and hospital

Time frame

• Duration of study: not reported

• Duration of follow-up: 35 days following randomisation or until hospital discharge

Participants Study characteristics

• Country: UK
• Setting: multicentre (5 sites)
• Inclusion criteria: ≥ 60 years admitted to either acute medicine for the elderly assessment or rehabil-
itation units for elderly people
• Exclusion criteria: MSQ score < 5/10; dysphagia; symptoms of a UTI; antibiotic intervention; anticipat-
ed length of stay < 1 week; regular drinkers of cranberry juice; presence of an indwelling catheter; ter-
minal illness
◦ In light of a UK Committee on Safety of Medicines alert about a potential interaction between
cranberry juice and warfarin which emerged during the final 8 weeks of recruitment, warfarin was
added as an exclusion for that period only

Baseline characteristics

• Number: intervention group (187); control group (189)

• Mean age ± SD (years): intervention group (81.3 ± 7.3); control group (81.4 ± 7.6)
• Sex (M/F): intervention group (56/133); control group (65/122)

Interventions Intervention group

• Cranberry juice: 300 mL

Control group

• Matching placebo beverage: 300 mL

Cranberries for preventing urinary tract infections (Review) 73

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

McMurdo 2005 (Continued)

Intervention duration: unclear

Outcomes Outcomes of interest/reported

• Time to onset of first symptomatic UTI: defined as a culture-positive urine growing a single organism
of > 107 CFU/L urine specimen
• Adherence to beverage drinking, courses of antibiotics prescribed, and organisms responsible for UTI

Notes Additional information

• Method of obtaining urine sample: clean catch

• Definition of bacteriuria
◦ Only pure growths of ≥ 107 CFU/L were reported with an antibiotic sensitivity
• Funding source: "funded by project grant K/OPR/2/2/D398 from the Chief Scientist Office at the Scot-
tish Executive Department of Health. The cranberry juice and matching placebo were supplied by
Ocean Spray Cranberries, Inc., Lakeville-Middleboro, MA, USA."

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Stratified by gender and computer generated
tion (selection bias)

Allocation concealment Low risk Held by pharmacy, sealed numbered enveloped

(selection bias)

Blinding of participants Low risk Blinding stated

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Blinding stated

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Low rate of excluded or missing data from outcome analysis: 0/376
(attrition bias)
All outcomes

Selective reporting (re- Low risk Appropriate clinical outcomes

porting bias)

Other bias Low risk No other bias apparent, well reported study

McMurdo 2009
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes
• ITT analysis: yes
• Recruited predominantly through primary care services but also from newspaper ads

Cranberries for preventing urinary tract infections (Review) 74

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

McMurdo 2009 (Continued)

Time frame

• Duration of study: not reported

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: UK
• Setting: single centre
• Inclusion criteria: community-dwelling women ≥ 45 years with at least 2 antibiotic-treated UTIs in pre-
vious 12 months confirmed by GP, but not necessarily culture proven
• Exclusion criteria: previous urological surgery, stones or anatomical abnormalities of the urinary
tract; urinary catheter; DM; immunocompromised; pyelonephritis; severe kidney impairment; blood
dyscrasias; symptomatic UTI at baseline; cognitive impairment precluding informed consent; resi-
dent in institutional care; on long-term antibiotic therapy; on warfarin therapy; regular cranberry con-
sumers; childbearing potential; unwilling to participate

Baseline characteristics

• Number: intervention group (69); control group (68)

• Mean age ± SD (years): intervention group (62.6 ± 10.8); control group (63.3 ± 10.1)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry: 500 mg capsule, once/day

Control group

• TMP: 100 mg capsule, once/day

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Clinical UTI treated with antibiotics (with or without culture), time to recurrence of clinical UTI
• Symptomatic and culture-verified UTI (culture threshold ≥ 107 CFU/L)
• Adherence
• Adverse events

Notes Additional information

• Matched tablets with over-coating

• Funding source: Moulton Charitable Foundation; Buckton Scott Health ProductsLtd, UK supplied the
Cran-MaxTM free of charge

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Off-site by DHP Pharma in Powys, UK, blocks of 4 using Prisym PFW clin soft-
tion (selection bias) ware to generate random numbers

Allocation concealment Low risk Externally managed, not able to be influenced

(selection bias)

Blinding of participants Low risk Blinding stated

and personnel (perfor-
mance bias)

Cranberries for preventing urinary tract infections (Review) 75

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

McMurdo 2009 (Continued)

All outcomes

Blinding of outcome as- Low risk Stated as blinded

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk All patients accounted for

(attrition bias) No lost or missing data from outcome analysis: 0/137
All outcomes

Selective reporting (re- Low risk Symptomatic UTI is most appropriate

porting bias)

Other bias Low risk Well reported, no other bias apparent

Mohammed 2016
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: not reported

Time frame

• Duration of study: recruitment period November 2014 to April 2016

• Duration of follow-up: 6 weeks

Participants Study characteristics

• Country: Iraq
• Setting: single centre
• Inclusion criteria: patients with bladder cancer (stage 2 or above = MIBC) undergoing radiation
• Exclusion criteria: cranberry allergy; UTI and/or severe lower urinary tract symptoms at baseline; ure-
thral catheterisation during or around the course of radiation therapy, previous pelvic radiation ther-
apy, prostate and other pelvic malignancy; MIBC stages T4a and T4b; on chemotherapy or receiv-
ing chemotherapy in 3 months before the study; DM; neurogenic bladder; history of kidney dysfunc-
tion; severe macrohaematuria; irritable bowel syndrome; using medications such as NSAIDs, corticos-
teroids, antibiotics, antispasmodics and other analgesics; on warfarin therapy

Baseline characteristics

• Number: intervention group (22); control group (23)

• Mean age ± SD (years): not reported
• Sex (M/F): intervention group (16/6); control group (17/6)

Interventions Intervention group

• Cranberry: 2 tablets/day of pure PAC (36 mg) extracted from American cranberry according to the
American extraction method (Urinal Akut®, by Walmark)

Control group

• Placebo: 2 capsules/day of pure lactose (500 mg)

Cranberries for preventing urinary tract infections (Review) 76

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Mohammed 2016 (Continued)

Intervention duration: 6 weeks during radiation therapy

Outcomes Outcomes of interest/reported

• Number with UTI

• Number with urinary tract symptoms (frequency, nocturia, urgency) in participants without UTI

Notes Additional information

• Primarily a study of urinary tract symptoms in those without UTI

• Funding source: 'nil'

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Said to be randomly allocated

tion (selection bias)

Allocation concealment Unclear risk Said to be randomly allocated

(selection bias)

Blinding of participants High risk No blinding reported

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- High risk All outcomes were clinically based and not blinded
sessment (detection bias)
All outcomes

Incomplete outcome data Low risk UTIs reported for all participants; 13% (6/45) excluded from other reported
(attrition bias) outcomes
All outcomes

Selective reporting (re- Unclear risk No report on adverse effects

porting bias)

Other bias Low risk Study appears free of other biases

Mooren 2020
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: yes

Time frame

• Duration of study: recruitment period October 2016 to September 2018

• Duration of follow-up: 6 weeks

Participants Study characteristics

Cranberries for preventing urinary tract infections (Review) 77

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Mooren 2020 (Continued)

• Country: the Netherlands
• Setting: single centre
• Inclusion criteria: women > 18 years undergoing elective surgery for pelvic organ prolapse or inconti-
nence surgery (with use of an indwelling catheter); able to understand the Dutch language
• Exclusion criteria: pregnant

Baseline characteristics

• Number: intervention group (105); control group (105)

• Mean age (years): intervention group (61); control group (64)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry capsules: 36 mg PAC + small portion of grape seed extract; 1 capsule twice/day started on
the evening before surgery. Total dose 70 mg daily.

Control group

• Placebo capsules: 1 capsule twice/day started on the evening before surgery

Co-interventions in both groups

• Clean intermittent catheterisation or indwelling catheter if required for urinary retention

Intervention duration: 6 weeks

Outcomes Outcomes of interest/reported

• UTI symptoms postoperatively

• Culture-positive UTI: definition not reported
• Compliance rates
• Adverse effects: GI, allergic reactions, others

Notes Additional information

• The study protocol was registered with trial number NL57693.101.16

• Funding source: "OrthoBasics for providing the study medication for our trial" "The costs of the study
medication were equally shared by OrthoBasics and the research department of our clinic. OrthoBa-
sics was not involved in the design, analysis nor publication of the results."

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Quote: “After signing informed consent, women were randomly allocated (1:1)
tion (selection bias) to cranberry capsules or placebo capsules using block randomization with a
block size of 10 that was created with a computerized random number genera-
tor”

Allocation concealment Low risk Quote: “After signing informed consent, women were randomly allocated (1:1)
(selection bias) to cranberry capsules or placebo capsules using block randomization with a
block size of 10 that was created with a computerized random number genera-
tor”

Blinding of participants Low risk Quote: “All investigators, participants, and medical staff were blinded for the
and personnel (perfor- randomization during the trial. Study medication was produced and packed by
mance bias) the manufacturer in identical packages for both groups and numbered accord-
All outcomes ing to the randomization list. Placebo capsules were identical to the cranberry

Cranberries for preventing urinary tract infections (Review) 78

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Mooren 2020 (Continued)

capsules with regard to color and flavor and differed only in the absence of the
extract from cranberry and grapefruit”

Blinding of outcome as- Low risk The outcome (urine culture) was laboratory based and unlikely to be influ-
sessment (detection bias) enced by lack of blinding
All outcomes

Incomplete outcome data Low risk All participants accounted for

(attrition bias)
All outcomes

Selective reporting (re- Low risk Expected outcomes reported

porting bias)

Other bias Low risk Quote: “All study medication was produced and packed by OrthoBasics, Mid-
woud, the Netherlands.”

Quote: “The costs of the study medication were equally shared by OrthoBasics
and the research department of our clinic. OrthoBasics was not involved in the
design, analysis nor publication of the results”

NAPRUTI 2011
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes
• ITT analysis: no

Time frame

• Duration of study: recruitment period 1 January 2005 to 21 August 2007

• Duration of follow-up: 15 months

Participants Study characteristics

• Country: the Netherlands

• Setting: multicentre (10 sites)
• Inclusion criteria: premenopausal women > 18 years with at least 3 symptomatic UTIs in the year prior
to enrolment, self-reported
• Exclusion criteria: symptoms of UTI at inclusion; use of antibiotics or cranberry in previous 2 weeks;
relevant interaction with other medications or contraindications for TMP-SMX or cranberries; preg-
nancy; breastfeeding; kidney transplantation

Baseline characteristics

• Number (randomised/analysed): intervention group (111/104); control group (110/95)

• Medina age, IQR (years): intervention group (34.8, 22.8 to 44.4); control group (36.1, 26.9 to 46.3)
• Sex (M/F): all women

Interventions intervention group

• Cranberry extract: 500 mg capsule twice/day (9.1 mg/g type A PAC)

• Placebo tablet: 1 tablet at night

Control group
Cranberries for preventing urinary tract infections (Review) 79
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NAPRUTI 2011 (Continued)

• TMP-SMX: 480 mg tablet at night
• Placebo capsule: 1 capsule twice/day

Intervention duration: 12 months

Outcomes Outcomes of interest/reported

• Mean number of clinically defined UTIs over 12 months

• Microbiological confirmed symptomatic UTI
• Median time to microbiologically confirmed symptomatic UTI
• Bacterial resistance to active intervention
• Asymptomatic culture-positive UTI
• Serious adverse events

Notes Additional information

• Recruited through direct advertising and primary care facilities as well as secondary and tertiary level
hospital referrals
• Placebo and active tablets were identical
• Culture threshold: ≥106 CFU/L
• Email correspondence from Marielle Beerepoot on 5 June 2012 provided the actual numbers of par-
ticipants in each arm who experienced a UTI
• Cranberry and placebo capsules supplied by Springfield Nutraceuticals BV
• Funding source: Netherlands Organisation for Health Research and Development

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Generation of the allocation list was computer-aided block randomisation
tion (selection bias) with stratification by centre and presence of complicating host factors. Pre-
pared in advance by coordinating centre, unlikely to be influenced by clini-
cians/researchers on site

Allocation concealment Low risk External to clinical site

(selection bias)

Blinding of participants Low risk Matched drug and dose regimen

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Stated

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk High rate of exclusions from outcome analysis: 22/221
(attrition bias)
All outcomes

Selective reporting (re- Low risk Many outcomes reported, clinically appropriate
porting bias)

Other bias Low risk Appears to be a representative sample

Cranberries for preventing urinary tract infections (Review) 80

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Salo 2010
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes
• ITT analysis: no

Time frame

• Duration of study: 2001 to 2008

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: Finland
• Setting: multicentre (7 sites)
• Inclusion criteria: children referred to paediatric departments for verified UTI in previous 2 months;
aged 1 to 16 years
• Exclusion criteria: grade III-V VUR or severe genitourethral malformations

Baseline characteristics

• Number (randomised/analysed): intervention group (129/126); control group (134/129)

• Mean age ± SD (years): intervention group (3.8 ± 2.5); control group (4.5 ± 2.9)
• Sex (M/F): intervention group (11/115); control group (12/117)

Interventions Intervention group

• Cranberry juice: 5mL/kg up to 300mL; 1 to 2 doses/day

Control group

• Placebo juice: same volume and dose/day as cranberry

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Symptomatic, culture-verified repeat UTI (≥ 108 CFU/L of 1 species in a midstream catch, bag or
catheter sample or any amount of bacteria in a suprapubic bladder aspirate sample in 2 consecutive
samples
• UTI incidence density
• Antimicrobial use

Notes Additional information

• 27 dropped out by 12 months (16 in cranberry group, 11 in placebo group)

• Funding source: Paivikki and Sakari Sohlberg Foundation, Foundation for Paediatric Research, Paulo
Foundation, Ocean Spray

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Block size 4, externally managed

tion (selection bias)

Cranberries for preventing urinary tract infections (Review) 81

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Salo 2010 (Continued)

Allocation concealment Low risk Sealed envelopes

(selection bias)

Blinding of participants Low risk Double blind, states clinician and parents blind
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Few missing data

(attrition bias) Losses to follow-up/withdrawals: 27 drop outs (16 in cranberry arm, 11 in
All outcomes placebo group)
Exclusions post randomisation: 8, low rate of missing or excluded data from
outcome analysis; 11/263

Selective reporting (re- Low risk Most appropriate outcome used

porting bias)

Other bias Low risk Well reported study

Schlager 1999
Study characteristics

Methods Study design

• Cross-over RCT
• Power calculation: no
• ITT analysis: yes

Time frame

• Duration of study: November 1996 to November 1997

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: USA
• Setting: single centre
• Inclusion criteria: children aged 2 to 18 years with neuropathic bladder and managed by clean inter-
mittent catheterisation; lived at home; normal findings on kidney ultrasonography and voided cys-
tourethrogram; lived within a 1 hour drive of the hospital
• Exclusion criteria: not reported

Baseline characteristics

• Number: 15
• Mean age ± SD (years): not reported
• Sex (M/F): not reported

Interventions Intervention group

• Cranberry juice cocktail: 300 mL/day (30% cranberry concentrate)

Cranberries for preventing urinary tract infections (Review) 82

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Schlager 1999 (Continued)

Control group

• Placebo beverage: looked and tasted similar but contained no cranberry juice

Intervention duration: 3 months

Outcomes Outcomes of interest/reported

• Presence of bacteriuria
• Symptomatic UTI

Notes Additional information

• Method of obtaining urine sample

◦ CSU
• Definition of symptomatic bacteriuria
◦ Defined as bacteriuria with fever, abdominal pain, change in continence pattern, or change in
colour or odour of urine
• Definition of bacteriuria
◦ ≥ 107 CFU/L
• Funding source: Grants from Spinal Cord Research Foundation and the Pendleton Pediatric Infectious
Disease Research Laboratory

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk No details provided, states only "randomly assigned"
tion (selection bias)

Allocation concealment Low risk Adequate, randomly assigned by research pharmacist

(selection bias)

Blinding of participants Low risk Stated as double blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Culture results not available to investigators during the study
sessment (detection bias)
All outcomes

Incomplete outcome data Low risk All children and results accounted for, no data excluded or missing from out-
(attrition bias) come analysis: 0/15
All outcomes

Selective reporting (re- Low risk Symptomatic UTI reported as appropriate

porting bias)

Other bias Low risk Study appears free of other biases

Scovell 2015
Study characteristics

Methods Study design

Cranberries for preventing urinary tract infections (Review) 83

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Scovell 2015 (Continued)

• Parallel RCT
• Power calculation: yes, "based on prior in vivo studies"
• ITT analysis: not reported

Time frame

• Duration of study: March 2012 to July 2014

• Duration of follow-up: 16 weeks

Participants Study characteristics

• Country: USA
• Setting: not reported
• Inclusion criteria: women > 18 years who self-catheterise for neurogenic bladder > 3 times/day
• Exclusion criteria: augmentation cystoplasty; pregnancy

Baseline characteristics

• Number: intervention group (14); control group (10)

• Mean age: 46.5 years
• Sex (M/F): all women

Interventions Intervention group

• Cranberry supplement: 36 mg PACBL-DMAC daily

Control group

• Placebo: no further details reported

Intervention duration: 16 weeks

Outcomes Outcomes of interest/reported

• Bacterial colony count (culture threshold not reported)

• Symptomatic UTI
• Time to symptomatic UTI

Notes Additional information

• Abstract-only publication
• Funding source: TROPHIKOS "funded the study drug, placebo, and some administrative expenses"

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk States double blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
Cranberries for preventing urinary tract infections (Review) 84
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Scovell 2015 (Continued)

All outcomes

Incomplete outcome data Unclear risk Low rate of exclusions from outcome analysis: 2/24
(attrition bias) 24 randomised, 22 completed the study, uncertain if all randomised included,
All outcomes no data provided

Selective reporting (re- Unclear risk Outcomes included symptomatic UTI, but no data are given
porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Sengupta 2011
Study characteristics

Methods Study design

• Parallel, 3-arm RCT

• Power calculation: no
• ITT analysis: no

Time frame

• Duration of study: not reported

• Duration of follow-up: 90 days

Participants Study characteristics

• Country: India
• Setting: unclear
• Inclusion criteria: females with a history of recurrent UTIs, with dysuria, frequency, blood in urine or
pain in suprapubic region and negative pregnancy test
• Exclusion criteria: antibiotics in past 48 hours; catheterised within last 2 weeks; DM; cardiovascular
disease; pyelonephritis; kidney stones

Baseline characteristics

• Number: intervention group 1 (21); intervention group 2 (23); control group (16)
• Age range: 18 to 40 years
• Sex (M/F): all women

Interventions Intervention group 1

• Cranberry: 500 mg/day (PAC standardized whole cranberry powder, PS-WCP; 1.5% PAC, Decas Botan-
ical Synergies)

Intervention group 2

• Cranberry: 1000 mg/day (PAC standardized whole cranberry powder, PS-WCP; 1.5% PAC, Decas Botan-
ical Synergies)

Control group

• No intervention

Intervention: duration 90 days

Outcomes Outcomes of interest/reported

Cranberries for preventing urinary tract infections (Review) 85

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Sengupta 2011 (Continued)

• Symptomatic UTI with > 107 CFU/L E. coli pure growth

Notes Additional information

• Funding source: not reported

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer generated

tion (selection bias)

Allocation concealment Low risk Externally managed, sealed envelopes opened in order; completed by inde-
(selection bias) pendent person

Blinding of participants High risk Participants were not blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Uncertain if researchers or assessors were blind to allocated intervention
sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Low rate of exclusions from outcome analysis: 3/60
(attrition bias)
All outcomes

Selective reporting (re- Low risk Symptomatic culture-proven UTI is most appropriate outcome
porting bias)

Other bias Unclear risk Unclear how the 225 patients were recruited, may be some selection bias

SINBA 2007
Study characteristics

Methods Study design

• Parallel, 4-group factorial design RCT

• Power calculation: yes
• ITT analysis: yes

Time frame

• Duration of study: November 2000 to August 2002

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: Australia
• Setting: multicentre (2 sites; spinal cord injuries database, predominantly community-dwelling pa-
tients)
• Inclusion criteria: spinal cord injured people with neurogenic bladder; bladder management with ei-
ther indwelling urethral or suprapubic catheter, intermittent catheterisation, or reflex voiding with or
without a condom drainage divide; absence of complex urological or serious kidney or hepatic pathol-
Cranberries for preventing urinary tract infections (Review) 86
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

SINBA 2007 (Continued)

ogy; not being prescribed antibiotics at the time of enrolment and absence of symptoms of a UTI at
enrolment; willing to stop any intercurrent urinary antiseptics before entering the study
• Exclusion criteria: previous allergy to any of the test interventions

Baseline characteristics

• Number: intervention group 1 (75); intervention group 2 (75); intervention group 3 (78); control group
(77)
• Mean age ± SD: 53.5 ± 13.5 years
• Sex (M/F): 83%/17%

Interventions Intervention group 1

• Methenamine hippurate: 2 g
• Cranberry: 1600 mg

Intervention group 2

• Methenamine hippurate: 2 g
• Cranberry placebo

Intervention group 3

• Cranberry: 1600 mg
• Methenamine hippurate placebo

Control group

• Methenamine hippurate placebo

• Cranberry placebo

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Symptomatic UTI: current criteria for treating patients in the spinal injured population (culture thresh-
old ≥ 108 CFU/L)

Notes Additional information

• Funding source: Motor Accidents Authority and Brucia Pharmaceuticals

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Dynamically balanced, centralised randomisation performed externally
tion (selection bias)

Allocation concealment Low risk External trial centre controlled, sent to pharmacy
(selection bias)

Blinding of participants Low risk States all staff and participants were blinded
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk States all staff were blinded
sessment (detection bias)
All outcomes

Cranberries for preventing urinary tract infections (Review) 87

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

SINBA 2007 (Continued)

Incomplete outcome data Low risk All accounted for in results. Rate of excluded or missing data from outcome
(attrition bias) analysis: 34/305
All outcomes

Selective reporting (re- Low risk Well described

porting bias)

Other bias Low risk No other bias apparent, well reported study

Singh 2016
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on 30% change in mean
• ITT analysis: not stated but totals in analysed group match number randomised to each group

Time frame

• Duration of study: November 2011 to March 2013

• Duration of follow-up: 12 weeks

Participants Study characteristics

• Country: India
• Setting: single centre
• Inclusion criteria: patients aged 15 to 76 years with subclinical asymptomatic bacteriuria and/or re-
current UTI, not responding to antimicrobials; patients prone to repeat UTIs
• Exclusion criteria: not reported

Baseline characteristics

• Number: intervention group (25/11); control group (24/12)

• Mean age, range (years): intervention group (41.6, 15 to 76); control group (35.8, 18 to 70)
• Sex (M/F): not reported

Interventions Intervention group

• Cranberry: Cranpac PAC-A 60 mg/capsule, 1 capsule twice/day

Control group

• Lactobacillus acidophilus: 400 mg/capsule, 1 capsule twice/day

Intervention duration: 12 weeks

Outcomes Outcomes of interest/reported

• Number with UTI by 12 weeks: does not state UTO definition but references European guideline; symp-
tomatic and culture > 106 CFU/L
• Mean urinary pH
• Burning micturition score
• Micro pyuria score
• Bacterial growth number
• Bacterial adhesion
Cranberries for preventing urinary tract infections (Review) 88
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Singh 2016 (Continued)

• Biofilm formation
• Mannose-resistant haemagglutination assay

Notes Additional information

• Included 8 patients with indwelling catheters or on intermittent catheterisation in each group

• Funding source: within regular running expenditure available to the government institution and no
extra-institutional financial grant or funding was required
• Additional data on gender of patients received from authors

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Used www.randomization.com

tion (selection bias)

Allocation concealment Low risk Managed externally

(selection bias)

Blinding of participants Unclear risk Insufficient information to permit judgement

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk Denominators given in one outcome, not for many others
(attrition bias)
All outcomes

Selective reporting (re- Low risk Symptomatic UTI is reported but many outcomes are primarily surrogates and
porting bias) may not reflect clinical effects

Other bias Unclear risk Uncertainty about blinding (participants and clinicians)

Stapleton 2012
Study characteristics

Methods Study design

• Parallel, 3-arm RCT

◦ Study flowchart shows 4 groups; control groups are different volumes of placebo juice
• Power calculation: yes, based on 35% risk UTi in placebo, and 15% absolute risk reduction in cranberry
• ITT analysis: yes, though modified due to drop-out before first follow-up

Time frame

• Duration of study: 16 November 2005 to 21 December 2008

• Median duration of follow-up: 186 days

Participants Study characteristics

• Country: USA
Cranberries for preventing urinary tract infections (Review) 89
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Stapleton 2012 (Continued)

• Setting: multicentre (2 sites)
• Inclusion criteria: premenopausal women, 18 to 45 years; history of ≥ 1 clinician diagnosed UTI in past
12 months
• Exclusion criteria: prediagnosed anatomical abnormality of the urinary tract; history of kidney stones;
DM; malignant neoplasm; allergy or intolerance to cranberry; symptoms of vaginitis or cystitis or
asymptomatic bacteriuria; pregnant or lactating; not using contraceptives; on prophylactic antibi-
otics; taking warfarin; antibiotics used in past 7 days; investigational drug in past 30 days

Baseline characteristics

• Number (randomised/completed): intervention group 1 (63/41); intervention group 2 (62/44); control

group 1 (31/17); control group 2 (30/18)
• Mean age ± SD (years): intervention group (25.3 ± 6.6); control group (26.4 ± 6.5)
• Sex (M/F): all women

Interventions Intervention group 1

• Cranberry juice: 4 oz (118 mL)/day

Intervention group 2

• Cranberry juice: 8 oz (236 mL)/day

Control group 1

• Placebo juice: 4 oz (118 mL)/day

Control group 2

• Placebo juice: 8 oz (236 mL)/day

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Clinical: UTI (dysuria+one or more of; frequency, urgency, suprapubic pain, haematuria, and pyuria >
10 cells/µL in un-spun urine or positive leucocyte esterase on dipstick)
• Symptomatic, culture-verified UTI: clinical UTI + positive culture (threshold > 106 CFU/L)
• Time to symptomatic UTI
• Asymptomatic bacteriuria (> 108 CFU/L) with no symptoms
• Adverse effects
• Adherence

Notes Additional information

• Dose groups combined for analysis

• Reports results for people with at least 1 follow-up, not all who were randomised
• Funding source: Grant ROI AT002105 from the National Centre for Complementary and Alternative
Medicine and Clinical and Translational Science Award grant ULI RR024139 from National Centre for
Research Resources

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer generated list, performed by biostatistician; stratified by site
tion (selection bias)

Allocation concealment Low risk Web-based system to allocate and store randomisation codes
(selection bias)

Cranberries for preventing urinary tract infections (Review) 90

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Stapleton 2012 (Continued)

Blinding of participants Unclear risk Not stated as blinded but placebo was used
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk States laboratory procedures performed blind to intervention allocation
sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk 10 randomised women were excluded from analysis, failed to attend first as-
(attrition bias) sessment
All outcomes

Selective reporting (re- Low risk Clinically important outcomes reported

porting bias)

Other bias Unclear risk Some uncertainties over 10 excluded post-randomisation

Stothers 2002
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: no
• ITT analysis: yes

Time frame

• Duration of study: not reported

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: Canada
• Setting: single centre
• Inclusion criteria: women, 21 to 72 years; at least two symptomatic, single-organism, culture-positive
UTIs in the previous calendar year, but were currently free of UTI on urinalysis and culture; sexually
active women
• Exclusion criteria: neurogenic bladder dysfunction; insulin-dependent diabetes; immunosuppressive
disease; steroid use; intermittent or indwelling catheterisation

Baseline characteristics

• Number: intervention group 1 (50); intervention group 2 (50); control group (50)
• Mean age, range (years): intervention group 1 (40, 23 to 68); intervention group 2 (44, 21 to 70); control
group (43, 21 to 72)
• Sex (M/F): all women

Interventions Intervention group 1

• Cranberry tablets: 1 tablet of 1:30 parts concentrated juice, twice/day

• Placebo juice: filtered water with food colouring + 20 mL pineapple juice, 3 times/day

Intervention group 2

Cranberries for preventing urinary tract infections (Review) 91

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Stothers 2002 (Continued)

• Cranberry juice: 250 mL, 3 times/day
• Placebo tablets: 1 placebo tablet, twice/day

Control group

• Placebo juice: filtered water with food colouring + 20 mL pineapple juice

• Placebo tablets: 1 placebo tablet, twice/day

Intervention duration: 1 year

Outcomes Outcomes of interest/reported

• Cost-effectiveness of cranberry juice and tablets

• Compliance rates
• Side effects and complications
• Symptomatic culture-positive UTI: threshold > 108 CFU/L of a single organism
• Mean number of UTIs in a calendar year

Notes Additional information

• Method of obtaining urine sample: CSU

• Definition of bacteriuria
◦ Bacteria in the urine ≥ 100,000/mL
• Funding source: not reported

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Patients randomised in blocks of 10 to one arm of the study, computer-gener-
tion (selection bias) ated (additional information provided by authors)

Allocation concealment Low risk Adequate, pharmacist dispensed allocated intervention packages
(selection bias)

Blinding of participants Low risk States double blind

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Researchers blind and microbiology laboratory probably blind when interpret-
sessment (detection bias) ing plated results
All outcomes

Incomplete outcome data Low risk All patients accounted for in results
(attrition bias) Losses to follow-up/withdrawals: 2 patients in the cranberry juice arm
All outcomes dropped out

Selective reporting (re- Low risk UTI appropriate outcome

porting bias)

Other bias Low risk None apparent

Stothers 2016
Study characteristics

Cranberries for preventing urinary tract infections (Review) 92

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Stothers 2016 (Continued)

Methods Study design

• Parallel, 3-arm RCT

• Power calculation: not reported
• ITT analysis: yes, stated

Time frame

• Duration of study: not reported

• Duration of follow-up: 1 year

Participants Study characteristics

• Country: Canada
• Setting: not reported
• Inclusion criteria: women only, no other information provided
• Exclusion criteria: not reported

Baseline characteristics

• Number: 263; numbers per group not reported

• Age range: 19 to 85 years
• Sex (M/F): all women

Interventions Intervention group 1

• Cranberry juice: low dose, twice/day (dose not reported)

Intervention group 2

• Cranberry juice: medium dose, twice/day (dose not reported)

Control group

• Placebo, twice/day

Intervention duration: 1 year

Outcomes Outcomes of interest/reported

• Number of symptomatic, culture-positive UTI (culture threshold not stated, single organism only)
• Urine chemistry P3Ga levels

Notes Additional information

• Abstract-only publication
• Funding source: NIH NCCAM

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Cranberries for preventing urinary tract infections (Review) 93

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Stothers 2016 (Continued)

Blinding of participants Low risk Physicians blinded, unsure about participants

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Outcome assessors stated as blinded

sessment (detection bias)
All outcomes

Incomplete outcome data High risk No data given, cannot determine completeness
(attrition bias)
All outcomes

Selective reporting (re- High risk Primary outcome appropriate, symptomatic UTI, but no data
porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Takahashi 2013
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not done to justify sample size, power calculated for the sample size obtained
• ITT analysis: excluded the 5 males and 9 self-catheterised women from the analysis

Time frame

• Duration of study: October 2007 to September 2009

• Duration of follow-up: 200 days

Participants Study characteristics

• Country: Japan
• Setting: multicentre (40 sites)
• Inclusion criteria: aged 20 to 79 years; acute exacerbation of uncomplicated cystitis or chronic com-
plicated cystitis (including self-catheterising); past history of multiple relapses of UTI and in whom
healing by antimicrobial agents had been confirmed by expert urologists
• Exclusion criteria: current or past history of uric acid stone disease in the urinary tract or hyperuri-
caemia that required urological manipulation for urinary tract stone disease; urinary tract obstruction;
urinary tract malignant disease; indwelling urinary catheter; urogenital infection such as urethritis,
acute or chronic bacterial prostatitis, or acute epididymitis; systemic diseases or severe complications
such as uncontrolled DM, collagen disease, leukaemia, advanced cancer, congenital heart failure, or
severe hepatic or kidney dysfunction; history of allergic reaction to cranberry products; non-eligibility
for this study as judged by the doctor in the clinic

Baseline characteristics

• Number: intervention group (107); control group (106)

• Mean age, range (years): intervention group (55, 20 to 79); control group (59, 20 to 79)
• Sex (M/F): 5/232 randomised; 213 women analysed

Interventions Intervention group

• Cranberry juice: 125 mL/day before sleep (40 mg PAC)

Cranberries for preventing urinary tract infections (Review) 94
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Takahashi 2013 (Continued)

Control group

• Placebo juice: 125 mL/day before sleep, colour and taste matched to cranberry juice

intervention duration: 24 weeks

Outcomes Outcomes of interest/reported

• Repeat UTI (defined as when antibiotics were administered), no culture mentioned

• Adverse event

Notes Additional information

• Funding source; Partly supported, in regard to data collection, by Kikkoman Food Products Company
and The Nisshin Oillio Group, Ltd., Tokyo, Japan
• No definition of UTI, no culture threshold or verification stated

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk States double blinded and used a matching placebo
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data High risk States 5 men, and 9 women who self-catheterised were excluded from the
(attrition bias) analysis
All outcomes

Selective reporting (re- Low risk Repeat UTI, probably symptomatic, was the only outcome but is clinically the
porting bias) most important one

Other bias Unclear risk Many details missing so unable to determine other biases

Temiz 2018
Study characteristics

Methods Study design

• Parallel, 3-arm RCT

• Power calculation: yes, 2 "unit" difference
• ITT analysis: not reported

Time frame

Cranberries for preventing urinary tract infections (Review) 95

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Temiz 2018 (Continued)

• Duration of study: June 2013 to November 2014
• Duration of follow-up: 3 months

Participants Study characteristics

• Country: Turkey
• Setting: single centre
• Inclusion criteria: ≥ 18 years; underwent ileal conduit diversion; conscious, cooperative, and fully ori-
ented
• Exclusion criteria: UTI; pregnant; irritable bowel syndrome; DM; rheumatoid arthritis; taking antibi-
otics; on warfarin

Baseline characteristics

• Number: intervention group 1 (20); intervention group 2 (20); control group (20)
• Mean age ± SD: 68.83 ± 4.72 years
• Sex (M/F): 68% men

Interventions Intervention group 1

• Cranberry capsule: 400 mg cranberry (1.8% PAC (9 mg)), 2 capsules/day, before breakfast and dinner
for 3 months

Intervention group 2

• Training about preventing UTI: verbal information from the researcher at the appropriate time and
place about UTI, and they were also given informational brochures that could be taken home and
used later

Control group

• No intervention

Outcomes Outcomes of interest/reported

• Mean body temperature

• Mean flank pain scores
• Mean urine pH
• Mean WCC and C-reactive protein
• Period of time passed without a UTI
• E coli positive cultures (culture positive threshold > 108 CFU/L)
• Pseudomonas positive cultures
• Klebsiella positive cultures

Notes Additional information

• Funding source: not reported, states no conflicts of interest and no disclosures

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk A randomisation list was generated using a software program (https://
tion (selection bias) www.random.org/lists/)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Cranberries for preventing urinary tract infections (Review) 96

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Temiz 2018 (Continued)

Blinding of participants Unclear risk Insufficient information to permit judgement

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk Reports that 87 were "reached" 13 left the cranberry group, may have exclud-
(attrition bias) ed these and kept recruiting specifically to the cranberry group, numbers (20
All outcomes in each) are very convenient

Selective reporting (re- Low risk Patient centred outcome of symptomatic UTI was reported, others were lab
porting bias) measures

Other bias Unclear risk No details on patient recruitment, screening, selection

Uberos 2012
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on equivalence of ± 10% from 20% baseline risk of recurrent UTI in an-
tibiotic group
• ITT analysis: yes, stated as performed

Time frame

• Duration of study: 1 January 2009 to 31 October 2010

• Duration of follow-up: 1 year

Participants Study characteristics

• Country: Spain
• Setting: single
• Inclusion criteria: children with a history of recurrent UTI (more than 2 episodes of infection in the past
6 months) with or without VUR of any grade
• Exclusion criteria: concurrent presence during episodes of UTI of other infectious diseases; metabol-
ic disorders; CKD; kidney stones; liver failure; allergy or intolerance to any components of cranberry
or TMP; the presence of blood dyscrasias; the express desire of the legal guardian that the child not
participate in the study

Baseline characteristics

• Number (randomised/analysed): intervention group (75/72); control group (117/114)

◦ VUR: intervention group (17/75); control group (23/117)
• Mean age ± SD (months): intervention group (28.3 ± 30.7); control group (30.7 ± 33.9)
• Sex (M/F): intervention group (32/43); control group (48/69)

Interventions Intervention group

• Cranberry: glucose syrup with 2.8% cranberry extract, 0.2 mL/kg/night

Control group

Cranberries for preventing urinary tract infections (Review) 97

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Uberos 2012 (Continued)

• TMP: glucose syrup with 8 mg/mL TMP, 0.2 mL/kg/night

Intervention duration: maximum of 12 months

Outcomes Outcomes of interest/reported

• Symptomatic UTI (culture threshold 108 CFU/L for clean catch or bag, 107 CFU/L for catheter)
• GI intolerance
• Rash
• Multi-drug resistance in repeat UTI organism

Notes Additional information

• Funding source: Fundo de Investigacianos Sanitarias (Health Research Fund) of the Instituo de Salud
Carlos III Madrid
• Study design detail in Uberos publications are no more detailed

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Low risk Register numbers held by the Hospital Pharmacy Service (2012 reference)
(selection bias)

Blinding of participants Low risk States double blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk Lost to follow-up: cranberry group (3); antibiotic group (3); denominators in-
(attrition bias) clude losses
All outcomes

Selective reporting (re- Low risk UTI reported, microbial resistance reported
porting bias)

Other bias Unclear risk Screening and selection of participants is not clear, unable to determine repre-
sentativeness of sample

Vostalova 2015
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: yes, based on 30% baseline risk of repeat UTI reduced to 15% in cranberry group
• ITT analysis: yes stated, analysis reflects randomised group numbers, loss to follow-up included but
6 excluded from cranberry group for ineligibility

Cranberries for preventing urinary tract infections (Review) 98

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Vostalova 2015 (Continued)

Time frame

• Duration of study: January 2010 and April 2011

• Duration of follow-up: 180 days

Participants Study characteristics

• Country: Czech Republic

• Setting: single centre
• Inclusion criteria: women, 18 to 75 years; at least 2 episodes of symptomatic UTI in the previous 12
months treated with antibiotics; clinical laboratory tests within normal range
• Exclusion criteria: symptomatic UTI at baseline; antibiotic intervention for reasons other than UTI;
pregnancy or breastfeeding; anatomical anomalies; insulin-dependent DM; cardiovascular disease;
immunocompromised; indwelling catheter; use of narcotics; heavy alcohol use; participating in an-
other trial

Baseline characteristics

• Number: intervention group (89); control group (93)

• Mean age ± SD (years): intervention group (35.61 ± 12.97); control group (38.03 ± 13.40)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry: 2 capsules once/day after breakfast. Each capsule contained 250 mg cranberry fruit pow-
der, with total PAC 0.56%

Control group

• Placebo: identical to cranberry capsules

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Symptomatic UTI: bacteriuria ≥ 108 CFU/L on culture plus symptoms of UTI

• UTI caused by E coli
• Average count of UTIs
• Haematology measurements

Notes Additional information

• Funding source: Palacky University Olomouc

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Online software QuickCalcs

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk States double blinded

and personnel (perfor-
mance bias)
All outcomes

Cranberries for preventing urinary tract infections (Review) 99

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Vostalova 2015 (Continued)

Blinding of outcome as- Unclear risk Insufficient information to permit judgement

sessment (detection bias)
All outcomes

Incomplete outcome data Unclear risk 6 post-randomisation exclusions all in the cranberry group
(attrition bias)
All outcomes

Selective reporting (re- Low risk Appropriate outcome of symptomatic UTI reported
porting bias)

Other bias Unclear risk Unclear because of uncertainty of some design details

Waites 2004
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: no
• ITT analysis: no

Time frame

• Duration of study: not reported

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: USA
• Setting: single centre
• Inclusion criteria: community residing men and women at least 1-year post spinal cord injury; ≥ 16
years; neurogenic bladder managed by clean intermittent catheterisation or external collection de-
vice; no systemic antimicrobials or urinary acidifying agents taken within 7 days, no current fever and
chills suggestive of acute symptomatic UTI; agreement not to ingest and cranberry-containing prod-
ucts whilst participation in the clinical study; baseline urine culture demonstrating at least 105 CFU/
mL
• Exclusion criteria: not reported

Baseline characteristics

• Number (randomised/analysed): intervention group (36/26); control group (38/22)

• Age range (years): intervention group (20 to 73); control group (27 to 71)
• Sex (M/F): intervention group (20/6); control group (22/0)

Interventions Intervention group

• Concentrated cranberry extract: 2 g in capsule form

Control group

• Placebo capsule

Intervention duration: 6 months

Outcomes Outcomes or interest/reported

Cranberries for preventing urinary tract infections (Review) 100

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Waites 2004 (Continued)

• Baseline urinalysis and cultures were performed at the time of the initial clinic visit and monthly for
6 months

Notes Additional information

• Microbiologic data were evaluated using analysis of variance with repeated measures
• Method of obtaining urine sample: CSU or clean catch
• Definition of bacteriuria: ≥ 108 CFU/L
• Funding source: not reported, but Cranberry capsules were provided by Aim This Way, Cambridge,
Massachusetts

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Unclear risk Insufficient information to permit judgement

(selection bias)

Blinding of participants Low risk Patients and clinicians were blind to intervention allocation
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Unclear risk Probably likely that microbiology staff assessing culture results were blind to
sessment (detection bias) intervention, but this wasn't stated
All outcomes

Incomplete outcome data High risk High rate of missing or excluded data from outcome analysis: 26/74
(attrition bias)
All outcomes

Selective reporting (re- Low risk The primary outcome was symptomatic UTI which is appropriate
porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Walker 1997
Study characteristics

Methods Study design

• Cross-over RCT
• Power calculation: no
• ITT analysis: no

Time frame

• Duration of study: not reported

• Duration of follow-up: 6 months

Participants Study characteristics

• Country: USA
Cranberries for preventing urinary tract infections (Review) 101
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Walker 1997 (Continued)

• Setting: single centre
• Inclusion criteria: non-pregnant, sexually active women; 18 and 45 years; recurrent UTI (4 UTIs during
the past year or at least one during the previous 3 months)
• Exclusion criteria: not reported

Baseline characteristics

• Number (randomised/analysed): 19/10

• Median age (range): 37 years (28 to 44)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry capsules: 400 mg of cranberry solids

Control group

• Placebo capsule

Intervention duration: each patient had 3 months of active intervention and 3 months of placebo

Outcomes Outcomes of interest/reported

• Symptomatic, culture-verified UTI (no culture threshold reported, but culture performed as bacterial
species known)

Notes Additional information

• Letter to the Editor

• Method of obtaining urine sample: not reported
• Definition of symptomatic UTI
• Women notified the physician and then submitted a urine sample (method: not reported)
• To ensure a consistent entry point into the study, each participant was held in a queue until suffering
a symptomatic UTI
• Each subsequent UTI episode was treated with antibiotics
• Capsules provided by Solaray a health supplements, for-profit organisation

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk Insufficient information to permit judgement

tion (selection bias)

Allocation concealment Low risk States clinicians unaware of allocation

(selection bias)

Blinding of participants Low risk States double blinding and opaque matching bottles
and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk States double blind, likely that culture results read without knowledge of inter-
sessment (detection bias) vention arm
All outcomes

Incomplete outcome data High risk Unclear reporting of results, culture appears the units rather than patients
(attrition bias) High rate of lost or excluded data from outcome analysis: 9/19
All outcomes

Cranberries for preventing urinary tract infections (Review) 102

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Walker 1997 (Continued)

Selective reporting (re- Low risk Symptomatic UTI most appropriate outcome
porting bias)

Other bias Unclear risk Insufficient information to permit judgement

Wan 2016
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: not reported
• ITT analysis: not specified but numbers are correct for analysis within randomised groups

Time frame

• Duration of study: not reported

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: Taiwan
• Setting: single centre
• Inclusion criteria: uncircumcised boys aged 6 to 18 years with uncomplicated UTI who were patients
at the hospital
• Exclusion criteria: not reported

Baseline characteristics

• Number: intervention group (28); control group (27)

• Mean age (years): intervention group (9.6); control group (9.7)
• Sex (M/F): all boys

Interventions Intervention group

• Cranberry juice: 120 mL/day of commercial brand

Control group

• Placebo juice: 120 mL/day, diluted tomato juice with sugar

Intervention duration: 6 months

Outcomes Outcomes of interest/reported

• Symptomatic, culture-verified UTI (> 108 CFU/L)

• Adverse events

Notes Additional information

• A 3rd group reported, but not randomised to intervention, all were circumcised and received placebo
juice
• Funding source: Chih Kuang Liu (President of U Best Innovative Technology Company, which produces
chemicals and other products)

Risk of bias

Cranberries for preventing urinary tract infections (Review) 103

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Wan 2016 (Continued)

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer generated random numbers

tion (selection bias)

Allocation concealment Unclear risk Not specifically reported, questionable placebo used (diluted tomato juice)
(selection bias)

Blinding of participants Low risk Stated

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Specified outcome assessors blinded

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk All children completed the study and were included in the analysis
(attrition bias) Missing data: 0/55
All outcomes

Selective reporting (re- Low risk Most clinically relevant outcome, symptomatic UTI was reported as were ad-
porting bias) verse events

Other bias Unclear risk Uncertainty over how representative these patients are

Wing 2008
Study characteristics

Methods Study design

• Parallel, 3-arm RCT

• Power calculation: no, feasibility pilot
• ITT analysis: yes

Time frame

• Duration of study: June 2005 to July 2007

• Duration of follow-up: until delivery

Participants Study characteristics

• Country: USA
• Setting: multicentre (2 sites)
• Inclusion criteria: women < 16 weeks gestation presenting for prenatal care
• Exclusion criteria: underlying medical conditions (e.g. DM, kidney failure, sickle cell disease, chronic
hypertension, CKD); previous or current antimicrobial therapy; known urological abnormalities

Baseline characteristics

• Number: intervention group 1 (67); intervention group 2 (58); control group (63)
• Mean age ± SD (years): intervention group 1 (27.7 ± 5.4); intervention group 2 (25.8 ± 5.6); control group
(25.6 ± 5.0)
• Sex (M/F): all women

Cranberries for preventing urinary tract infections (Review) 104

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Wing 2008 (Continued)

Interventions Intervention group 1

• Cranberry juice: 240 mL (106 mg PAC) at breakfast, placebo juice at other meals

Intervention group 2

• Cranberry drink: 240 mL, 3 times/day (720 mL/day, 318 mg PAC) reduced to twice/day (480 mL, 212
mg PAC) after 52 enrolments because not well tolerated

Control group

• Placebo: 3 doses/day of matched juice product

Intervention duration: until delivery

Outcomes Outcomes of interest/reported

• Asymptomatic bacteriuria: > 108 CFU/L of a single organism and no symptoms

• Acute cystitis/symptomatic bacteriuria: > 108 CFU/L of single organism and dysuria or frequency or
urgency
• Pyelonephritis: "urinalysis and/or urine culture" as above, + flank pain, fever > 100.4°F, chills nausea,
vomiting
• At least 1 UTI: UTI due to enteric bacteria
• Pregnancy outcomes: preterm delivery, spontaneous vaginal delivery, instrumental vaginal delivery,
caesarean/caesarean hysterectomy, mean birth weight, low birth weight, 1 min Apgar < 7, 5 min Apgar
< 9, admission to NICU, tolerability and compliance

Notes Additional information

• Funding source: National Institute of Diabetes, and Digestive and Kidney Diseases (NIDDK) and the
National Center for Complementary and Alternative Medicine

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer generated randomisation table, stratified by site
tion (selection bias)

Allocation concealment Low risk Intervention options were not known to researchers
(selection bias)

Blinding of participants Low risk States all were blinded

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Clearly stated

sessment (detection bias)
All outcomes

Incomplete outcome data Low risk Data are well reported for completeness
(attrition bias) Low rate of missing or excluded data from outcome analysis: 0/188
All outcomes

Selective reporting (re- Low risk Appropriate outcomes

porting bias)

Other bias Low risk Details suggest free of bias, although selection methods a little unclear

Cranberries for preventing urinary tract infections (Review) 105

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Wing 2015
Study characteristics

Methods Study design

• Parallel RCT
• Power calculation: no, feasibility study
• ITT analysis: yes, analysed within randomised groups

Time frame

• Duration of study: 2009 to 2012

• Duration of follow-up: until birth

Participants Study characteristics

• Country: USA
• Setting: multicentre (2 sites)
• Inclusion criteria: pregnant with non-anomalous foetuses between 12 and 16 weeks of gestation
• Exclusion criteria: DM; kidney failure; sickle cell disease; chronic hypertension; CKD; previous or cur-
rent antibiotics within 2 weeks

Baseline characteristics

• Number: intervention group (24); control group (25)

• Mean age ± SD (years): intervention group (30.9 ± 6.2); control group (31.0 ± 7.1)
• Sex (M/F): all women

Interventions Intervention group

• Cranberry tablets (TheraCran): 4/day (2 at night, 2 in the morning), equivalent to 250 mL juice (4 tablets
= 64 to 68 mg PAC)

Control group

• Placebo tablet: matched for colour and taste

intervention duration: 34 to 38 weeks (until delivery of baby)

Outcomes Outcomes of interest/reported

• Asymptomatic bacteriuria
• Cystitis
• Pyelonephritis
• GI intolerance
• Nausea
• Constipation
• Vomiting
• Heartburn
• Loss of appetite
• Diarrhoea
• Stomach ache
• Taste intolerance
• Pathogen in culture
• Fetal malformation, Intrauterine growth retardation, oligo- and polyhydramnios
• Preterm delivery
• Low birth weight (< 2500 g)
Cranberries for preventing urinary tract infections (Review) 106
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Wing 2015 (Continued)

• Neonatal intensive care admission
• Apgar score
• Birthweight
• Delivery route
• Compliance

Notes Additional information

• Culture threshold: ≥ 108 CFU/L of single pathogen

• Funding source: Ocean Spray Cranberries donated cranberry capsules and placebo. National Centre
for research resources, National Centre for Advancing translational sciences, NIH
• TheraCran, contains dried cranberry powder from Vaccinium macrocarpon Aiton berries. Provided by
Ocean Spray Cranberries Inc
• Placebo provided by Ocean Spray

Risk of bias

Bias Authors' judgement Support for judgement

Random sequence genera- Low risk Computer generated randomisation table, stratified by site
tion (selection bias)

Allocation concealment Low risk Stated as concealed and bottles managed by individual not associated with
(selection bias) study

Blinding of participants Low risk Stated as blinded and placebo used

and personnel (perfor-
mance bias)
All outcomes

Blinding of outcome as- Low risk Stated as blinded

sessment (detection bias)
All outcomes

Incomplete outcome data High risk High rate of missing or excluded data from outcome analysis;:16/49
(attrition bias)
All outcomes

Selective reporting (re- Low risk Many outcomes reported, clinically relevant cystitis and pyelonephritis includ-
porting bias) ed

Other bias Unclear risk Uncertain about representativeness of sample with many drop outs

AKI: acute kidney injury; BMI: body mass index; CFU: colony forming units; CKD: chronic kidney disease; CSU: catheter specimen of urine;
DM: diabetes mellitus; EDSS: Expanded Disability Status Scale; ESBL: extended spectrum beta-lactamase; ESKD: end-stage kidney disease;
GFR: glomerular filtration rate; GI: gastrointestinal; HbA1c: glycated haemoglobin; IQR: interquartile range; ITT: intention-to-treat; M/F:
male/female; MIBC: muscle-invasive bladder cancer; MS: multiple sclerosis; MSQ: Mental State Questionnaire; MSU: mid-stream urine;
NSAID/s: nonsteroidal anti-inflammatory drug/s; PAC: proanthocyanidin; SD: standard deviation; SEM: standard error of the mean; SMP:
sulphamethoxazole; TMP: trimethoprim; UTI: urinary tract infection; VUR: vesicoureteral reflux; WBC: white blood cell; WCC: white cell
count

Characteristics of excluded studies [ordered by study ID]

Cranberries for preventing urinary tract infections (Review) 107

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Study Reason for exclusion

Amin 2018 Intervention duration < 4 weeks

Barnoiu 2015 Acute intervention study: 5 days

Gunnarsson 2017 Acute intervention study: 5 days

Hamilton 2015 No clinically relevant outcomes: focused on radiation cystitis

Howell 2010 No clinically relevant outcomes: only laboratory measures

Howell 2015 Acute intervention study: < 7 days; single dose given

Jackson 1997 RCT of elderly people looking at the effect of cranberry juice on urinary acidity; no relevant out-
comes reported

Jass 2009 No clinically relevant outcomes: laboratory measures of urine chemistry

Kaspar 2015 Acute intervention study: 24 hours

Lavigne 2008 No clinically relevant outcomes: only laboratory measures of urine kinetics

Letouzey 2017 Acute intervention study: 10 days

Liu 2019b Intervention duration < 4 weeks

NCT01079169 Study terminated, no results available

Occhipinti 2016 Acute intervention study: 7 days

Radulescu 2020 Intervention duration < 4 weeks

Russo 2019 Intervention duration < 4 weeks

Sappal 2018 Intervention duration < 4 weeks

Schultz 1984 Intervention < 4 weeks (20 days)

Tempera 2010 No clinically relevant outcomes: only laboratory measures of adhesion

Valentova 2007 No clinically relevant outcomes: only laboratory measures of urine biochemistry

Vidlar 2010 No clinically relevant outcomes: only laboratory measures of urine biochemistry

RCT: randomised controlled trial

Characteristics of studies awaiting classification [ordered by study ID]

Cotellese 2023
Methods Study design

• Pilot RCT
• Power calculation: not reported
• ITT analysis: unclear

Cranberries for preventing urinary tract infections (Review) 108

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Cotellese 2023 (Continued)

Time frame

• Duration of study: not reported

• Duration of follow-up: variable

Participants Study characteristics

• Country: Italy
• Setting: unclear
• Inclusion criteria: healthy subjects (BMI < 26) who underwent a non-complicated surgical proce-
dure (i.e. intestinal resection for localized tumours with no metastasis, no occlusion and no com-
plication) and required urinary catheterisation during the perioperative period because of a his-
tory of recurrent UTI or risk for UTI. Subjects were defined as at risk if they had reported at least
two symptomatic UTIs in the previous year or an episode of UTI in the previous month. During
the peri-surgical period, patients also received appropriate antibiotic coverage (cephalosporin as
individually appropriate for each subject)
• Exclusion criteria: diabetes, any other chronic clinical condition or risk conditions, immune-com-
promising diseases, co-morbidities, corticosteroids treatment for any reason, mycosis or
chemotherapy treatment within 6 months before inclusion, chronic inflammatory bowel disease,
and any possible or suspected intolerance or allergy to PS supplements and specifically cranberry

Baseline characteristics

• Number: intervention group (24); control group (18)

• Mean age ± SD (years): unclear
• Sex (M/F): unclear

Interventions Intervention group

• standardized cranberry extract at the dose of either

◦ 120 mg/day (n = 12)
◦ 240 mg/day (n = 12)

Control group

• standard management: (n = 18) or nitrofurantoin administration (n = 22)

Duration of intervention: 4 weeks

Outcomes Outcomes of interest/reported

• UTI symptoms
• Haematuria
• Urine bacterial contamination
• Recurrence of signs and symptoms
• Adverse events
• Dropouts

Notes Additional information

• Funding source: unclear

Hakkola 2023
Methods Study design

• Parallel RCT
• Power calculation: yes
Cranberries for preventing urinary tract infections (Review) 109
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Hakkola 2023 (Continued)

• ITT analysis: no

Time frame

• Duration of study: 12 July 2013 to 27 February 2018

• Duration of follow-up: 12 months

Participants Study characteristics

• Country: Finland
• Setting:
• Inclusion criteria: children aged 1 year and 16 years and a confirmed UTI within 7 days of entry.
UTI at entry was defined as fever and/or a local urinary tract symptom, the presence of pyuria or
nitrite and a positive urine culture, defined as the growth of > 105 CFU/mL of the same pathogen in
clean-voided urine or a urine collection pad sample. If the child had two urine samples available,
growth of > 105 CFU of the same pathogen in one sample and at least 104–5 CFU in the other was
required
• Exclusion criteria: continuous antimicrobial prophylaxis or a severe congenital kidney or urinary
tract anomaly as seen in ultrasound

Baseline characteristics

• Number: intervention group (56); control group (57)

• Mean age ± SD (years): intervention group (7.2 ± 4.0); control group (5.2 ± 2.9)
• Sex (M/F): intervention group (1/55); control group (1/56)

Interventions Intervention group

• Cranberry-lingonberry juice

Control group

• Placebo juice

Duration of intervention: 6 months

Outcomes Outcomes of interest/reported

• Gut and urinary microbiome

• UTI and time to recurrence

Notes Additional information

• Funding source: "This was an investigator-driven academic clinical study. The cranberry-lin-
gonberry juice was donated by Eckes-Granini, Turku, Finland. Eckes-Granini did not participate in
the study design, analysis, or writing of the manuscript"

Madhavan 2021
Methods Study design

• Parallel RCT
• Power calculation: unclear
• ITT analysis: unclear

Time frame

• Duration of study: 1 February 2017 to 20 July 2017

Cranberries for preventing urinary tract infections (Review) 110

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Madhavan 2021 (Continued)

• Duration of follow-up: 7 days post stent removal

Participants Study characteristics

• Country: India
• Setting: single centre
• Inclusion criteria: aged 18 to 65 years, who underwent unilateral elective DJ stenting
(polyurethane 6 Fr and 26 cm in length) following various urological procedures
• Exclusion criteria: unclear

Baseline characteristics

• Number: intervention group 1 (48); intervention group 2 (46); control group (40)
• Medina age, range SD (years): intervention group 1 (39, 21 to 59); intervention group 2 (36, 19 to
64); control group (33, 18 to 55)
• Sex (M/F): intervention group 1 (40/8); intervention group 2 (35/11); control group (31/9)

Interventions Intervention group 1

• Cranberry extract 300 mg and D-mannose 600 mg twice daily throughout the period of the in-
dwelling stent

Intervention group 2

• Low dose continuous antibiotic prophylaxis: nitrofurantoin 100 mg once daily throughout the pe-
riod of the indwelling stent

Control group

• No prophylaxis

Duration of intervention: 15 to 45 days (till stent removal)

Outcomes Outcomes of interest/reported

• Stent-related symptoms such as urgency, frequency, dysuria or flank pain and febrile UTI prior to
DJ stent removal
• Febrile UTI
• Adverse events

Notes Additional information

• Funding source: not reported

BMI: body mass index; CFU: colony-forming units; M/F: male/female; PS: Pharma Standard; RCT: randomised controlled trial; SD: standard
deviation; UTI: urinary tract infection

Characteristics of ongoing studies [ordered by study ID]

ACTRN12605000626662
Study name Cranberry capsules for the prevention of urinary tract infection in an elderly population

Methods Cross-over RCT

Participants Elderly people

Interventions Cranberry tablets compared with placebo

Outcomes The incidence of UTI in elderly clients

Cranberries for preventing urinary tract infections (Review) 111
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

ACTRN12605000626662 (Continued)
To determine the effectiveness of urine clarity tests for diagnostic use in an elderly population

To examine the extent to which agitation in clients is associated with UTI

Starting date 1/11/2005 (anticipated)

Contact information Ms Stacey Hassall

Blue Care Research Unit

PO Box 1539
Milton BC QLD 4064

Australia

Phone +61 7 33773346

Fax +61 7 33773377

Email s.hassall@bluecare.org.au

Notes Commercial funder: Mayne Consumer Pty Ltd

Charity funded: Blue Care Research Unit

No publication found, email contact failed

Amador-Mulero 2014
Study name Effectiveness of red cranberries ingestion on urinary tract infections in pregnant women

Methods RCT; triple-blind study

Participants Healthy first-time mothers belonging to these healthcare centers, who are subject to accidental
non-probability sampling and randomly assigned to test or control group

Interventions 1 capsule daily cranberry extract (118 mg PAC)

Outcomes Incidence of UTI

Starting date

Contact information L. Amador Mulero - lorenaam82@hotmail.com

Notes Matronas Profession 2017; 15(2):50-55 (protocol paper)

ISRCTN55813586
Study name Clinical dosage and effectiveness study of ShanStar® cranberry supplement for prevention and in-
tervention against women's urinary tract infections

Methods Double-blind, placebo-controlled RCT

Participants Women

Interventions ShanStar® cranberry extract 150 mg and 300 mg/day

Cranberries for preventing urinary tract infections (Review) 112

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

ISRCTN55813586 (Continued)
Participants in each group are given 3-months supply of pills. Participants are instructed to take
one tablet twice a day by mouth for 3 months. At 1, 2 and final 3 months follow-up, they will score
the UTI symptoms and provide urine for complete urine analysis and urine culture

Total duration of the intervention will be 3 months

Outcomes Effectiveness of ShanStar® cranberry extract against recurrent UTIs on the basis of symptoms, bac-
teriuria and pyuria in the urine and urine culture

At 1, 2 and 3 months, the participants will return to answer urinary tract symptoms questions and
provide urine for complete urinalysis and culture

Starting date 31/01/2011 to 30/04/2011

Contact information Dr Albert Chang - shadycanyon@yahoo.com

Notes Completed, awaiting publication of results (last edited 18/03/2011)

Have not located a publication, searched Google scholar, PubMed and Google

Email contact failed

NCT00100061
Study name Dose response to cranberry of women with recurrent UTIs

Methods RCT

Participants Women with recurrent UTI

Interventions Cranberry juice

Outcomes UTI

Starting date May 2007

Contact information Principal investigator: Lynn Stothers, Bladder Care Centre, University of British Columbia

Notes Although due to finish in 2011, the website states 'This study is ongoing, but not recruiting partici-
pants'.

Possibly same as Stothers 2016, which has only been published as an abstract as of 2017. Email
contact failed

NCT00247104
Study name The use of cranberries in women with preterm premature rupture of membranes

Methods RCT

Participants Pregnant with premature rupture of membranes

Interventions Cranberry, comparison not reported

Outcomes Length (in days) of the latent period

Cranberries for preventing urinary tract infections (Review) 113
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT00247104 (Continued)
Neonatal infection

Respiratory distress

Admission to NICU (in days)

Neonatal complications rate (e.g. NEC, IVH)

Maternal infections (uterus, UTI)

• Urinary and vaginal flora before and after intervention

• Vaginal pH before and after intervention
• Amniotic fluid pH before and after intervention

Starting date May 2007

Contact information Contact: Arik Tzukert, DMD 00 972 2 6776095 arik@hadassah.org.il

Contact: Hadas Lemberg, PhD 00 972 2 6777572 lhadas@hadassah.org.il

Notes Searched on author names in PubMed, Google and Google scholar. No publication found. No re-
sponse to emails

NCT03597152
Study name Nutritional supplementation for recurrent urinary tract infections in women

Methods Double-blind placebo-controlled cross-over RCT

Participants 250 women, aged 18 to 75 years, who have suffered from 3 to 4 uncomplicated UTI in the past 12
months

Interventions Dietary supplement: WelTract (contains extracts from hibiscus flowers and cranberry fruit, lactofer-
rin, D-mannose, and vitamins C and D) compared with placebo

Outcomes The primary outcome will be time to recurrence of next UTI

Starting date Estimated starting date 1-8-2020; estimated completion date 31-12-2020

Contact information Katie O'Brien, Arkansas Urology (katie@arkansasurology.com); Richard Dennis, AmPurity Nu-
traceuticals, LLC (protocols@att.net)

Notes Unclear whether recruitment has commenced

NCT05730998
Study name Cranberry for the prevention of urinary tract infections

Methods Parallel RCT

Participants Diabetic women ≥ 70 years

Interventions Anthocran phytosome or placebo will be taken in the quantity of 1 capsule of 120 mg, once/day, for
6 months

Cranberries for preventing urinary tract infections (Review) 114

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT05730998 (Continued)

Outcomes Urinalysis, urine culture

Starting date 1 September 2022

Contact information Azienda di Servizi alla Persona di Pavia

Notes

IVH: intraventricular haemorrhage; NEC: necrotizing enterocolitis; NICU: neonatal intensive care unit; PAC: proanthocyanidin; RCT:
randomised controlled trial; UTI: urinary tract infection

DATA AND ANALYSES

Comparison 1. Any cranberry product versus placebo, control or no treatment

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

1.1 Symptomatic UTI: culture-verified 28 6211 Risk Ratio (M-H, Random, 0.70 [0.58, 0.84]
UTI 95% CI)

1.1.1 Women with recurrent UTIs 8 1555 Risk Ratio (M-H, Random, 0.74 [0.55, 0.99]
95% CI)

1.1.2 Elderly men and women in insti- 3 1489 Risk Ratio (M-H, Random, 0.93 [0.67, 1.30]
tutions 95% CI)

1.1.3 Pregnant women 3 765 Risk Ratio (M-H, Random, 1.06 [0.75, 1.50]
95% CI)

1.1.4 Children 5 504 Risk Ratio (M-H, Random, 0.46 [0.32, 0.68]
95% CI)

1.1.5 Adults with neuromuscular dys- 3 464 Risk Ratio (M-H, Random, 0.97 [0.78, 1.19]
function of the bladder with incom- 95% CI)
plete bladder emptying

1.1.6 People with a susceptibility to 6 1434 Risk Ratio (M-H, Random, 0.47 [0.37, 0.61]
UTIs due to an intervention 95% CI)

1.2 Clinical UTI: symptoms, no culture 4 1646 Risk Ratio (M-H, Random, 0.69 [0.49, 0.98]
95% CI)

1.2.1 Women with recurrent UTI 1 373 Risk Ratio (M-H, Random, 0.59 [0.42, 0.83]
95% CI)

1.2.2 Elderly men and women in insti- 2 1113 Risk Ratio (M-H, Random, 0.91 [0.77, 1.08]
tutions 95% CI)

1.2.3 People with a susceptibility to 1 160 Risk Ratio (M-H, Random, 0.50 [0.29, 0.86]
UTI due to interventions 95% CI)

1.3 Microbiological UTI: positive cul- 3 344 Risk Ratio (M-H, Random, 0.92 [0.71, 1.21]
ture without known symptoms 95% CI)

Cranberries for preventing urinary tract infections (Review) 115

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

1.3.1 Elderly men and women in insti- 2 209 Risk Ratio (M-H, Random, 0.85 [0.54, 1.32]
tutions 95% CI)

1.3.2 Adults with neuromuscular dys- 1 135 Risk Ratio (M-H, Random, 1.03 [0.64, 1.66]
function of the bladder with incom- 95% CI)
plete bladder emptying

1.4 Death 4 1574 Risk Ratio (M-H, Random, 1.07 [0.89, 1.28]
95% CI)

1.5 Gastrointestinal adverse events 10 2166 Risk Ratio (M-H, Random, 1.33 [1.00, 1.77]
95% CI)

Cranberries for preventing urinary tract infections (Review) 116

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 1.1. Comparison 1: Any cranberry product versus placebo, control or no treatment, Outcome 1:
Symptomatic UTI: culture-verified UTI

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

1.1.1 Women with recurrent UTIs

Sengupta 2011 4 44 4 13 1.7% 0.30 [0.09 , 1.02]
Kontiokari 2001 8 46 18 45 3.5% 0.43 [0.21 , 0.90]
Vostalova 2015 9 83 24 93 3.5% 0.42 [0.21 , 0.85]
Stothers 2002 19 100 16 50 4.3% 0.59 [0.34 , 1.05]
Barbosa-Cesnik 2011 31 155 23 164 4.8% 1.43 [0.87 , 2.33]
Stapleton 2012 33 120 17 56 4.8% 0.91 [0.55 , 1.48]
Maki 2016 30 185 34 188 5.2% 0.90 [0.57 , 1.40]
Takahashi 2013 32 107 38 106 5.6% 0.83 [0.57 , 1.23]
Subtotal (95% CI) 840 715 33.4% 0.74 [0.55 , 0.99]
Total events: 166 174
Heterogeneity: Tau² = 0.09; Chi² = 15.26, df = 7 (P = 0.03); I² = 54%
Test for overall effect: Z = 2.03 (P = 0.04)

1.1.2 Elderly men and women in institutions

McMurdo 2005 7 187 14 189 2.7% 0.51 [0.21 , 1.22]
Juthani-Mehta 2016 9 92 9 93 2.8% 1.01 [0.42 , 2.43]
Caljouw 2014 62 458 62 470 6.0% 1.03 [0.74 , 1.42]
Subtotal (95% CI) 737 752 11.5% 0.93 [0.67 , 1.30]
Total events: 78 85
Heterogeneity: Tau² = 0.01; Chi² = 2.20, df = 2 (P = 0.33); I² = 9%
Test for overall effect: Z = 0.42 (P = 0.67)

1.1.3 Pregnant women

Wing 2015 0 14 0 19 Not estimable
Wing 2008 4 125 0 63 0.4% 4.57 [0.25 , 83.60]
Essadi 2010 182 258 194 286 7.2% 1.04 [0.93 , 1.16]
Subtotal (95% CI) 397 368 7.6% 1.06 [0.75 , 1.50]
Total events: 186 194
Heterogeneity: Tau² = 0.03; Chi² = 1.03, df = 1 (P = 0.31); I² = 3%
Test for overall effect: Z = 0.34 (P = 0.73)

1.1.4 Children
Afshar 2012 5 20 8 20 2.6% 0.63 [0.25 , 1.58]
Ferrara 2009 5 27 18 27 2.9% 0.28 [0.12 , 0.64]
Wan 2016 7 28 10 27 3.1% 0.68 [0.30 , 1.51]
Dotis 2014 7 38 24 38 3.5% 0.29 [0.14 , 0.59]
Salo 2010 16 152 22 127 4.1% 0.61 [0.33 , 1.11]
Subtotal (95% CI) 265 239 16.2% 0.46 [0.32 , 0.68]
Total events: 40 82
Heterogeneity: Tau² = 0.04; Chi² = 5.09, df = 4 (P = 0.28); I² = 21%
Test for overall effect: Z = 3.95 (P < 0.0001)

1.1.5 Adults with neuromuscular dysfunction of the bladder with incomplete bladder emptying
Waites 2004 10 26 8 22 3.4% 1.06 [0.51 , 2.21]
Gallien 2014 21 51 24 60 5.1% 1.03 [0.66 , 1.62]
SINBA 2007 67 153 71 152 6.5% 0.94 [0.73 , 1.20]
Subtotal (95% CI) 230 234 15.0% 0.97 [0.78 , 1.19]
Total events: 98 103
Heterogeneity: Tau² = 0.00; Chi² = 0.19, df = 2 (P = 0.91); I² = 0%
Test for overall effect: Z = 0.33 (P = 0.74)

1.1.6 People with a susceptibility to UTIs due to an intervention

Mohammed 2016 0 22 3 23 0.4% 0.15 [0.01 , 2.73]
Temiz 2018 1 20 8 20 0.8% 0.13 [0.02 , 0.91]
Fernandes 2016 4 25 5 30 1.8% 0.96 [0.29 , 3.20]
Mooren 2020 9 105 14 105 3.1% 0.64 [0.29 , 1.42]
Foxman 2015 12 80 23 80 4.0% 0.52 [0.28 , 0.98]
Bonetta 2017 53 489 107 435 6.2% 0.44 [0.33 , 0.60]

Cranberries for preventing urinary tract infections (Review) 117

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 1.1. (Continued)

Mooren 2020 9 105 14 105 3.1% 0.64 [0.29 , 1.42]
Foxman 2015 12 80 23 80 4.0% 0.52 [0.28 , 0.98]
Bonetta 2017 53 489 107 435 6.2% 0.44 [0.33 , 0.60]
Subtotal (95% CI) 741 693 16.2% 0.47 [0.37 , 0.61]
Total events: 79 160
Heterogeneity: Tau² = 0.00; Chi² = 4.58, df = 5 (P = 0.47); I² = 0%
Test for overall effect: Z = 5.90 (P < 0.00001)

Total (95% CI) 3210 3001 100.0% 0.70 [0.58 , 0.84]

Total events: 647 798
Heterogeneity: Tau² = 0.12; Chi² = 83.48, df = 26 (P < 0.00001); I² = 69% 0.005 0.1 1 10 200
Test for overall effect: Z = 3.78 (P = 0.0002) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 30.53, df = 5 (P < 0.0001), I² = 83.6%

Analysis 1.2. Comparison 1: Any cranberry product versus placebo,

control or no treatment, Outcome 2: Clinical UTI: symptoms, no culture

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

1.2.1 Women with recurrent UTI

Maki 2016 39 185 67 188 31.5% 0.59 [0.42 , 0.83]
Subtotal (95% CI) 185 188 31.5% 0.59 [0.42 , 0.83]
Total events: 39 67
Heterogeneity: Not applicable
Test for overall effect: Z = 3.04 (P = 0.002)

1.2.2 Elderly men and women in institutions

Juthani-Mehta 2016 4 92 5 93 6.3% 0.81 [0.22 , 2.92]
Caljouw 2014 157 458 176 470 40.5% 0.92 [0.77 , 1.09]
Subtotal (95% CI) 550 563 46.8% 0.91 [0.77 , 1.08]
Total events: 161 181
Heterogeneity: Tau² = 0.00; Chi² = 0.04, df = 1 (P = 0.85); I² = 0%
Test for overall effect: Z = 1.04 (P = 0.30)

1.2.3 People with a susceptibility to UTI due to interventions

Foxman 2015 15 80 30 80 21.7% 0.50 [0.29 , 0.86]
Subtotal (95% CI) 80 80 21.7% 0.50 [0.29 , 0.86]
Total events: 15 30
Heterogeneity: Not applicable
Test for overall effect: Z = 2.53 (P = 0.01)

Total (95% CI) 815 831 100.0% 0.69 [0.49 , 0.98]

Total events: 215 278
Heterogeneity: Tau² = 0.07; Chi² = 8.40, df = 3 (P = 0.04); I² = 64% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 2.06 (P = 0.04) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 8.30, df = 2 (P = 0.02), I² = 75.9%

Cranberries for preventing urinary tract infections (Review) 118

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 1.3. Comparison 1: Any cranberry product versus placebo, control or no

treatment, Outcome 3: Microbiological UTI: positive culture without known symptoms

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

1.3.1 Elderly men and women in institutions

Avorn 1994 12 72 21 81 17.6% 0.64 [0.34 , 1.21]
Juthani-Mehta 2010 27 39 12 17 51.4% 0.98 [0.68 , 1.42]
Subtotal (95% CI) 111 98 69.0% 0.85 [0.54 , 1.32]
Total events: 39 33
Heterogeneity: Tau² = 0.04; Chi² = 1.63, df = 1 (P = 0.20); I² = 39%
Test for overall effect: Z = 0.73 (P = 0.46)

1.3.2 Adults with neuromuscular dysfunction of the bladder with incomplete bladder emptying
McGuiness 2002 21 62 24 73 31.0% 1.03 [0.64 , 1.66]
Subtotal (95% CI) 62 73 31.0% 1.03 [0.64 , 1.66]
Total events: 21 24
Heterogeneity: Not applicable
Test for overall effect: Z = 0.12 (P = 0.90)

Total (95% CI) 173 171 100.0% 0.92 [0.71 , 1.21]

Total events: 60 57
Heterogeneity: Tau² = 0.00; Chi² = 1.66, df = 2 (P = 0.44); I² = 0% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 0.58 (P = 0.56) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 0.35, df = 1 (P = 0.56), I² = 0%

Analysis 1.4. Comparison 1: Any cranberry product versus placebo, control or no treatment, Outcome 4: Death

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

Bruyere 2019 0 42 0 43 Not estimable

McMurdo 2005 3 187 2 189 1.0% 1.52 [0.26 , 8.97]
Juthani-Mehta 2016 17 92 16 93 8.4% 1.07 [0.58 , 1.99]
Caljouw 2014 150 458 145 470 90.6% 1.06 [0.88 , 1.28]

Total (95% CI) 779 795 100.0% 1.07 [0.89 , 1.28]

Total events: 170 163
Heterogeneity: Tau² = 0.00; Chi² = 0.15, df = 2 (P = 0.93); I² = 0% 0.01 0.1 1 10 100
Test for overall effect: Z = 0.70 (P = 0.48) Less with cranberry product Less with placebo/control
Test for subgroup differences: Not applicable

Cranberries for preventing urinary tract infections (Review) 119

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 1.5. Comparison 1: Any cranberry product versus placebo,

control or no treatment, Outcome 5: Gastrointestinal adverse events

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

Koradia 2019 3 44 0 45 1.0% 7.16 [0.38 , 134.62]

Bonetta 2017 4 489 0 435 1.0% 8.01 [0.43 , 148.32]
Sengupta 2011 4 43 0 13 1.0% 2.86 [0.16 , 49.96]
Babar 2021 1 72 1 73 1.1% 1.01 [0.06 , 15.90]
Singh 2016 1 36 1 36 1.1% 1.00 [0.07 , 15.38]
McMurdo 2005 2 187 4 189 2.9% 0.51 [0.09 , 2.73]
Stothers 2002 8 100 2 50 3.6% 2.00 [0.44 , 9.07]
Mooren 2020 6 105 4 105 5.4% 1.50 [0.44 , 5.16]
Gallien 2014 14 51 18 60 23.7% 0.92 [0.51 , 1.65]
Wing 2015 13 14 12 19 59.3% 1.47 [1.01 , 2.13]

Total (95% CI) 1141 1025 100.0% 1.33 [1.00 , 1.77]

Total events: 56 42
Heterogeneity: Tau² = 0.00; Chi² = 6.48, df = 9 (P = 0.69); I² = 0% 0.005 0.1 1 10 200
Test for overall effect: Z = 1.94 (P = 0.05) Less with cranberry product Less with placebo/control
Test for subgroup differences: Not applicable

Comparison 2. Cranberry juice or syrup versus placebo or control

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

2.1 Symptomatic UTI: cul- 13 2831 Risk Ratio (M-H, Random, 95% 0.78 [0.62, 0.97]
ture-verified UTI CI)

2.1.1 Women with recurrent UTIs 6 1322 Risk Ratio (M-H, Random, 95% 0.84 [0.63, 1.10]
CI)

2.1.2 Children 4 401 Risk Ratio (M-H, Random, 95% 0.57 [0.37, 0.87]
CI)

2.1.3 Elderly men and women in 1 376 Risk Ratio (M-H, Random, 95% 0.51 [0.21, 1.22]
institutions CI)

2.1.4 Pregnant women 2 732 Risk Ratio (M-H, Random, 95% 1.06 [0.75, 1.50]
CI)

2.2 Clinical UTI: symptoms, no 1 Risk Ratio (M-H, Random, 95% Subtotals only
culture CI)

2.2.1 Women with recurrent UTI 1 373 Risk Ratio (M-H, Random, 95% 0.59 [0.42, 0.83]
CI)

Cranberries for preventing urinary tract infections (Review) 120

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 2.1. Comparison 2: Cranberry juice or syrup versus placebo

or control, Outcome 1: Symptomatic UTI: culture-verified UTI

Cranberry juice Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

2.1.1 Women with recurrent UTIs

Kontiokari 2001 8 46 18 45 6.2% 0.43 [0.21 , 0.90]
Stothers 2002 19 100 16 50 8.2% 0.59 [0.34 , 1.05]
Barbosa-Cesnik 2011 31 155 23 164 9.5% 1.43 [0.87 , 2.33]
Stapleton 2012 33 120 17 56 9.5% 0.91 [0.55 , 1.48]
Maki 2016 30 185 34 188 10.3% 0.90 [0.57 , 1.40]
Takahashi 2013 32 107 38 106 11.5% 0.83 [0.57 , 1.23]
Subtotal (95% CI) 713 609 55.3% 0.84 [0.63 , 1.10]
Total events: 153 146
Heterogeneity: Tau² = 0.05; Chi² = 9.17, df = 5 (P = 0.10); I² = 45%
Test for overall effect: Z = 1.27 (P = 0.21)

2.1.2 Children
Afshar 2012 5 20 8 20 4.4% 0.63 [0.25 , 1.58]
Ferrara 2009 5 27 18 27 5.1% 0.28 [0.12 , 0.64]
Wan 2016 7 28 10 27 5.4% 0.68 [0.30 , 1.51]
Salo 2010 16 125 22 127 7.9% 0.74 [0.41 , 1.34]
Subtotal (95% CI) 200 201 22.7% 0.57 [0.37 , 0.87]
Total events: 33 58
Heterogeneity: Tau² = 0.04; Chi² = 3.79, df = 3 (P = 0.29); I² = 21%
Test for overall effect: Z = 2.57 (P = 0.01)

2.1.3 Elderly men and women in institutions

McMurdo 2005 7 187 14 189 4.7% 0.51 [0.21 , 1.22]
Subtotal (95% CI) 187 189 4.7% 0.51 [0.21 , 1.22]
Total events: 7 14
Heterogeneity: Not applicable
Test for overall effect: Z = 1.51 (P = 0.13)

2.1.4 Pregnant women

Wing 2008 4 125 0 63 0.6% 4.57 [0.25 , 83.60]
Essadi 2010 182 258 194 286 16.7% 1.04 [0.93 , 1.16]
Subtotal (95% CI) 383 349 17.3% 1.06 [0.75 , 1.50]
Total events: 186 194
Heterogeneity: Tau² = 0.03; Chi² = 1.03, df = 1 (P = 0.31); I² = 3%
Test for overall effect: Z = 0.34 (P = 0.73)

Total (95% CI) 1483 1348 100.0% 0.78 [0.62 , 0.97]

Total events: 379 412
Heterogeneity: Tau² = 0.08; Chi² = 28.06, df = 12 (P = 0.005); I² = 57% 0.01 0.1 1 10 100
Test for overall effect: Z = 2.18 (P = 0.03) Less with cranberry juice Less with placebo/control
Test for subgroup differences: Chi² = 6.12, df = 3 (P = 0.11), I² = 51.0%

Cranberries for preventing urinary tract infections (Review) 121

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 2.2. Comparison 2: Cranberry juice or syrup versus

placebo or control, Outcome 2: Clinical UTI: symptoms, no culture

Cranberry juice Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

2.2.1 Women with recurrent UTI

Maki 2016 39 185 67 188 100.0% 0.59 [0.42 , 0.83]
Subtotal (95% CI) 185 188 100.0% 0.59 [0.42 , 0.83]
Total events: 39 67
Heterogeneity: Not applicable
Test for overall effect: Z = 3.04 (P = 0.002)

Test for subgroup differences: Not applicable 0.1 0.2 0.5 1 2 5 10

Less with cranberry juice Less with placebo/control

Comparison 3. Cranberry tablets or powder versus placebo or control

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

3.1 Symptomatic UTI: culture-verified 16 3473 Risk Ratio (M-H, Random, 0.65 [0.49, 0.84]
UTI 95% CI)

3.1.1 Women with recurrent UTIs 3 333 Risk Ratio (M-H, Random, 0.45 [0.28, 0.72]
95% CI)

3.1.2 Elderly men and women 2 1113 Risk Ratio (M-H, Random, 1.02 [0.75, 1.39]
95% CI)

3.1.3 Pregnant women 1 33 Risk Ratio (M-H, Random, Not estimable

95% CI)

3.1.4 Children 1 76 Risk Ratio (M-H, Random, 0.29 [0.14, 0.59]

95% CI)

3.1.5 Adults with bladder emptying is- 3 464 Risk Ratio (M-H, Random, 0.97 [0.78, 1.19]
sues or multiple sclerosis 95% CI)

3.1.6 People with a susceptibility to 6 1454 Risk Ratio (M-H, Random, 0.48 [0.37, 0.61]
UTIs due to an intervention 95% CI)

3.2 Clinical UTI: symptoms, no culture 3 1273 Risk Ratio (M-H, Random, 0.74 [0.47, 1.16]
95% CI)

3.2.1 Elderly 2 1113 Risk Ratio (M-H, Random, 0.91 [0.77, 1.08]
95% CI)

3.2.2 People with a susceptibility to 1 160 Risk Ratio (M-H, Random, 0.50 [0.29, 0.86]
UTIs due to an intervention 95% CI)

3.3 Microbiological UTI: positive cul- 2 191 Risk Ratio (M-H, Random, 1.00 [0.75, 1.34]
ture without known symptoms 95% CI)

3.3.1 Elderly men and women in insti- 1 56 Risk Ratio (M-H, Random, 0.98 [0.68, 1.42]
tutions 95% CI)

Cranberries for preventing urinary tract infections (Review) 122

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

3.3.2 Adults with neuromuscular dys- 1 135 Risk Ratio (M-H, Random, 1.03 [0.64, 1.66]
function of the bladder with incom- 95% CI)
plete bladder emptying

Cranberries for preventing urinary tract infections (Review) 123

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 3.1. Comparison 3: Cranberry tablets or powder versus

placebo or control, Outcome 1: Symptomatic UTI: culture-verified UTI

Cranberry tablet/powder Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

3.1.1 Women with recurrent UTIs

Sengupta 2011 4 44 4 13 3.4% 0.30 [0.09 , 1.02]
Stothers 2002 9 50 16 50 6.8% 0.56 [0.27 , 1.15]
Vostalova 2015 9 83 24 93 6.9% 0.42 [0.21 , 0.85]
Subtotal (95% CI) 177 156 17.1% 0.45 [0.28 , 0.72]
Total events: 22 44
Heterogeneity: Tau² = 0.00; Chi² = 0.85, df = 2 (P = 0.65); I² = 0%
Test for overall effect: Z = 3.34 (P = 0.0009)

3.1.2 Elderly men and women

Juthani-Mehta 2016 9 92 9 93 5.5% 1.01 [0.42 , 2.43]
Caljouw 2014 62 458 62 470 11.1% 1.03 [0.74 , 1.42]
Subtotal (95% CI) 550 563 16.6% 1.02 [0.75 , 1.39]
Total events: 71 71
Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 0.97); I² = 0%
Test for overall effect: Z = 0.15 (P = 0.88)

3.1.3 Pregnant women

Wing 2015 0 14 0 19 Not estimable
Subtotal (95% CI) 14 19 Not estimable
Total events: 0 0
Heterogeneity: Not applicable
Test for overall effect: Not applicable

3.1.4 Children
Dotis 2014 7 38 24 38 6.8% 0.29 [0.14 , 0.59]
Subtotal (95% CI) 38 38 6.8% 0.29 [0.14 , 0.59]
Total events: 7 24
Heterogeneity: Not applicable
Test for overall effect: Z = 3.39 (P = 0.0007)

3.1.5 Adults with bladder emptying issues or multiple sclerosis

Waites 2004 10 26 8 22 6.6% 1.06 [0.51 , 2.21]
Gallien 2014 21 51 24 60 9.7% 1.03 [0.66 , 1.62]
SINBA 2007 67 153 71 152 12.0% 0.94 [0.73 , 1.20]
Subtotal (95% CI) 230 234 28.3% 0.97 [0.78 , 1.19]
Total events: 98 103
Heterogeneity: Tau² = 0.00; Chi² = 0.19, df = 2 (P = 0.91); I² = 0%
Test for overall effect: Z = 0.33 (P = 0.74)

3.1.6 People with a susceptibility to UTIs due to an intervention

Mohammed 2016 0 22 3 23 0.8% 0.15 [0.01 , 2.73]
Temiz 2018 1 20 11 40 1.6% 0.18 [0.03 , 1.31]
Fernandes 2016 4 25 5 30 3.6% 0.96 [0.29 , 3.20]
Mooren 2020 9 105 14 105 6.1% 0.64 [0.29 , 1.42]
Foxman 2015 12 80 23 80 7.7% 0.52 [0.28 , 0.98]
Bonetta 2017 53 489 107 435 11.4% 0.44 [0.33 , 0.60]
Subtotal (95% CI) 741 713 31.2% 0.48 [0.37 , 0.61]
Total events: 79 163
Heterogeneity: Tau² = 0.00; Chi² = 3.74, df = 5 (P = 0.59); I² = 0%
Test for overall effect: Z = 5.86 (P < 0.00001)

Total (95% CI) 1750 1723 100.0% 0.65 [0.49 , 0.84]

Total events: 277 405
Heterogeneity: Tau² = 0.14; Chi² = 38.98, df = 14 (P = 0.0004); I² = 64% 0.005 0.1 1 10 200
Test for overall effect: Z = 3.22 (P = 0.001) Less with cranberry tablet/powder Less with placebo/control
Test for subgroup differences: Chi² = 33.42, df = 4 (P < 0.00001), I² = 88.0%

Cranberries for preventing urinary tract infections (Review) 124

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 3.2. Comparison 3: Cranberry tablets or powder versus

placebo or control, Outcome 2: Clinical UTI: symptoms, no culture

Cranberry tablet/powder Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

3.2.1 Elderly
Juthani-Mehta 2016 4 92 5 93 10.4% 0.81 [0.22 , 2.92]
Caljouw 2014 157 458 176 470 56.6% 0.92 [0.77 , 1.09]
Subtotal (95% CI) 550 563 67.0% 0.91 [0.77 , 1.08]
Total events: 161 181
Heterogeneity: Tau² = 0.00; Chi² = 0.04, df = 1 (P = 0.85); I² = 0%
Test for overall effect: Z = 1.04 (P = 0.30)

3.2.2 People with a susceptibility to UTIs due to an intervention

Foxman 2015 15 80 30 80 33.0% 0.50 [0.29 , 0.86]
Subtotal (95% CI) 80 80 33.0% 0.50 [0.29 , 0.86]
Total events: 15 30
Heterogeneity: Not applicable
Test for overall effect: Z = 2.53 (P = 0.01)

Total (95% CI) 630 643 100.0% 0.74 [0.47 , 1.16]

Total events: 176 211
Heterogeneity: Tau² = 0.09; Chi² = 4.45, df = 2 (P = 0.11); I² = 55% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 1.30 (P = 0.19) Less with cranberry tablet/powder Less with placebo/control
Test for subgroup differences: Chi² = 4.40, df = 1 (P = 0.04), I² = 77.3%

Analysis 3.3. Comparison 3: Cranberry tablets or powder versus placebo or

control, Outcome 3: Microbiological UTI: positive culture without known symptoms

Cranberry tablet/powder Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

3.3.1 Elderly men and women in institutions

Juthani-Mehta 2010 27 39 12 17 62.3% 0.98 [0.68 , 1.42]
Subtotal (95% CI) 39 17 62.3% 0.98 [0.68 , 1.42]
Total events: 27 12
Heterogeneity: Not applicable
Test for overall effect: Z = 0.10 (P = 0.92)

3.3.2 Adults with neuromuscular dysfunction of the bladder with incomplete bladder emptying
McGuiness 2002 21 62 24 73 37.7% 1.03 [0.64 , 1.66]
Subtotal (95% CI) 62 73 37.7% 1.03 [0.64 , 1.66]
Total events: 21 24
Heterogeneity: Not applicable
Test for overall effect: Z = 0.12 (P = 0.90)

Total (95% CI) 101 90 100.0% 1.00 [0.75 , 1.34]

Total events: 48 36
Heterogeneity: Tau² = 0.00; Chi² = 0.03, df = 1 (P = 0.86); I² = 0% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 0.01 (P = 1.00) Less with cranberry tablet/powder Less with placebo/control
Test for subgroup differences: Chi² = 0.03, df = 1 (P = 0.87), I² = 0%

Comparison 4. Cranberry juice versus cranberry tablets or powder

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

4.1 Symptomatic UTI: culture-verified 1 Risk Ratio (M-H, Random, 95% Subtotals only
UTI CI)

Cranberries for preventing urinary tract infections (Review) 125

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

4.1.1 Women with recurrent UTIs 1 100 Risk Ratio (M-H, Random, 95% 0.90 [0.40, 2.02]
CI)

Analysis 4.1. Comparison 4: Cranberry juice versus cranberry

tablets or powder, Outcome 1: Symptomatic UTI: culture-verified UTI

Cranberry tablet Cranberry juice Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

4.1.1 Women with recurrent UTIs

Stothers 2002 9 50 10 50 100.0% 0.90 [0.40 , 2.02]
Subtotal (95% CI) 50 50 100.0% 0.90 [0.40 , 2.02]
Total events: 9 10
Heterogeneity: Not applicable
Test for overall effect: Z = 0.25 (P = 0.80)

Test for subgroup differences: Not applicable 0.1 0.2 0.5 1 2 5 10

Less with cranberry tablet Less with cranberry juice

Comparison 5. Cranberry dose: high versus low

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

5.1 Symptomatic UTI: culture-verified 2 169 Risk Ratio (M-H, Random, 1.02 [0.27, 3.91]
UTI 95% CI)

5.1.1 Women with recurrent UTI 1 44 Risk Ratio (M-H, Random, 0.91 [0.14, 5.92]
95% CI)

5.1.2 Pregnant women 1 125 Risk Ratio (M-H, Random, 1.16 [0.17, 7.94]
95% CI)

5.2 Microbiological UTI: positive cul- 1 Risk Ratio (M-H, Random, Subtotals only
ture without known symptoms 95% CI)

5.2.1 Elderly 1 39 Risk Ratio (M-H, Random, 1.13 [0.75, 1.72]

95% CI)

5.3 Clinical UTI without culture verifi- 1 145 Risk Ratio (M-H, Random, 0.81 [0.57, 1.13]
cation 95% CI)

Cranberries for preventing urinary tract infections (Review) 126

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 5.1. Comparison 5: Cranberry dose: high versus low, Outcome 1: Symptomatic UTI: culture-verified UTI

High dose Low low Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

5.1.1 Women with recurrent UTI

Sengupta 2011 2 23 2 21 51.6% 0.91 [0.14 , 5.92]
Subtotal (95% CI) 23 21 51.6% 0.91 [0.14 , 5.92]
Total events: 2 2
Heterogeneity: Not applicable
Test for overall effect: Z = 0.10 (P = 0.92)

5.1.2 Pregnant women

Wing 2008 2 58 2 67 48.4% 1.16 [0.17 , 7.94]
Subtotal (95% CI) 58 67 48.4% 1.16 [0.17 , 7.94]
Total events: 2 2
Heterogeneity: Not applicable
Test for overall effect: Z = 0.15 (P = 0.88)

Total (95% CI) 81 88 100.0% 1.02 [0.27 , 3.91]

Total events: 4 4
Heterogeneity: Tau² = 0.00; Chi² = 0.03, df = 1 (P = 0.86); I² = 0% 0.01 0.1 1 10 100
Test for overall effect: Z = 0.03 (P = 0.97) Less with high dose Less with low dose
Test for subgroup differences: Chi² = 0.03, df = 1 (P = 0.86), I² = 0%

Analysis 5.2. Comparison 5: Cranberry dose: high versus low, Outcome

2: Microbiological UTI: positive culture without known symptoms

High dose Low low Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

5.2.1 Elderly
Juthani-Mehta 2010 14 19 13 20 100.0% 1.13 [0.75 , 1.72]
Subtotal (95% CI) 19 20 100.0% 1.13 [0.75 , 1.72]
Total events: 14 13
Heterogeneity: Not applicable
Test for overall effect: Z = 0.59 (P = 0.56)

Test for subgroup differences: Not applicable 0.1 0.2 0.5 1 2 5 10

Less with high dose Less with low dose

Analysis 5.3. Comparison 5: Cranberry dose: high versus low, Outcome 3: Clinical UTI without culture verification

High dose cranberry Low dose cranberry Risk Ratio Risk Ratio
Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

Babar 2021 31 72 39 73 100.0% 0.81 [0.57 , 1.13]

Total (95% CI) 72 73 100.0% 0.81 [0.57 , 1.13]

Total events: 31 39
Heterogeneity: Not applicable 0.01 0.1 1 10 100
Test for overall effect: Z = 1.24 (P = 0.22) Higher dose of cranberry Lower dose of cranberry
Test for subgroup differences: Not applicable

Cranberries for preventing urinary tract infections (Review) 127

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Comparison 6. Cranberry product versus probiotics

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

6.1 Symptomatic UTI: cul- 3 215 Risk Ratio (M-H, Random, 95% 0.39 [0.27, 0.56]
ture-verified UTI CI)

6.1.1 Women with recurrent UTIs 1 90 Risk Ratio (M-H, Random, 95% 0.40 [0.20, 0.82]
CI)

6.1.2 Children 1 53 Risk Ratio (M-H, Random, 95% 0.44 [0.18, 1.09]
CI)

6.1.3 Adults (men and women) 1 72 Risk Ratio (M-H, Random, 95% 0.38 [0.23, 0.60]
prone to UTI CI)

Analysis 6.1. Comparison 6: Cranberry product versus

probiotics, Outcome 1: Symptomatic UTI: culture-verified UTI

Cranberry product Probiotics Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

6.1.1 Women with recurrent UTIs

Kontiokari 2001 8 46 19 44 25.8% 0.40 [0.20 , 0.82]
Subtotal (95% CI) 46 44 25.8% 0.40 [0.20 , 0.82]
Total events: 8 19
Heterogeneity: Not applicable
Test for overall effect: Z = 2.49 (P = 0.01)

6.1.2 Children
Ferrara 2009 5 27 11 26 16.0% 0.44 [0.18 , 1.09]
Subtotal (95% CI) 27 26 16.0% 0.44 [0.18 , 1.09]
Total events: 5 11
Heterogeneity: Not applicable
Test for overall effect: Z = 1.78 (P = 0.08)

6.1.3 Adults (men and women) prone to UTI

Singh 2016 12 36 32 36 58.2% 0.38 [0.23 , 0.60]
Subtotal (95% CI) 36 36 58.2% 0.38 [0.23 , 0.60]
Total events: 12 32
Heterogeneity: Not applicable
Test for overall effect: Z = 4.04 (P < 0.0001)

Total (95% CI) 109 106 100.0% 0.39 [0.27 , 0.56]

Total events: 25 62
Heterogeneity: Tau² = 0.00; Chi² = 0.10, df = 2 (P = 0.95); I² = 0% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 5.06 (P < 0.00001) Less with cranberry product Less with probiotics
Test for subgroup differences: Chi² = 0.10, df = 2 (P = 0.95), I² = 0%

Cranberries for preventing urinary tract infections (Review) 128

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Comparison 7. Cranberry product versus antibiotics

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

7.1 Symptomatic UTI: cul- 2 385 Risk Ratio (M-H, Random, 95% 1.03 [0.80, 1.33]
ture-verified UTI CI)

7.1.1 Women with recurrent UTI 1 199 Risk Ratio (M-H, Random, 95% 1.02 [0.76, 1.37]
CI)

7.1.2 Children 1 186 Risk Ratio (M-H, Random, 95% 1.07 [0.65, 1.78]
CI)

7.2 Clinical UTI: symptoms, no 2 336 Risk Ratio (M-H, Random, 95% 1.30 [0.79, 2.14]
culture CI)

7.2.1 Women with recurrent UTIs 2 336 Risk Ratio (M-H, Random, 95% 1.30 [0.79, 2.14]
CI)

Analysis 7.1. Comparison 7: Cranberry product versus

antibiotics, Outcome 1: Symptomatic UTI: culture-verified UTI

Cranberry products Antibiotics Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

7.1.1 Women with recurrent UTI

NAPRUTI 2011 49 104 44 95 74.1% 1.02 [0.76 , 1.37]
Subtotal (95% CI) 104 95 74.1% 1.02 [0.76 , 1.37]
Total events: 49 44
Heterogeneity: Not applicable
Test for overall effect: Z = 0.11 (P = 0.91)

7.1.2 Children
Uberos 2012 19 72 28 114 25.9% 1.07 [0.65 , 1.78]
Subtotal (95% CI) 72 114 25.9% 1.07 [0.65 , 1.78]
Total events: 19 28
Heterogeneity: Not applicable
Test for overall effect: Z = 0.28 (P = 0.78)

Total (95% CI) 176 209 100.0% 1.03 [0.80 , 1.33]

Total events: 68 72
Heterogeneity: Tau² = 0.00; Chi² = 0.03, df = 1 (P = 0.85); I² = 0% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 0.24 (P = 0.81) Less with cranberry product Less with antibiotics
Test for subgroup differences: Chi² = 0.03, df = 1 (P = 0.85), I² = 0%

Cranberries for preventing urinary tract infections (Review) 129

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 7.2. Comparison 7: Cranberry product versus antibiotics, Outcome 2: Clinical UTI: symptoms, no culture

Cranberry products Antibiotics Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

7.2.1 Women with recurrent UTIs

McMurdo 2009 25 69 14 68 36.6% 1.76 [1.00 , 3.09]
NAPRUTI 2011 81 104 68 95 63.4% 1.09 [0.92 , 1.28]
Subtotal (95% CI) 173 163 100.0% 1.30 [0.79 , 2.14]
Total events: 106 82
Heterogeneity: Tau² = 0.10; Chi² = 3.16, df = 1 (P = 0.08); I² = 68%
Test for overall effect: Z = 1.02 (P = 0.31)

Total (95% CI) 173 163 100.0% 1.30 [0.79 , 2.14]

Total events: 106 82
Heterogeneity: Tau² = 0.10; Chi² = 3.16, df = 1 (P = 0.08); I² = 68% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 1.02 (P = 0.31) Less with cranberry product Less with antibiotics
Test for subgroup differences: Not applicable

Comparison 8. Cranberry + probiotic tablet versus placebo or control

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

8.1 Symptomatic UTI: culture-verified 1 Risk Ratio (M-H, Fixed, 95% Subtotals only
UTI CI)

8.1.1 Women with recurrent UTI 1 89 Risk Ratio (M-H, Fixed, 95% 0.27 [0.10, 0.76]
CI)

Analysis 8.1. Comparison 8: Cranberry + probiotic tablet versus

placebo or control, Outcome 1: Symptomatic UTI: culture-verified UTI

Cranberry+probiotic Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI

8.1.1 Women with recurrent UTI

Koradia 2019 4 44 15 45 100.0% 0.27 [0.10 , 0.76]
Subtotal (95% CI) 44 45 100.0% 0.27 [0.10 , 0.76]
Total events: 4 15
Heterogeneity: Not applicable
Test for overall effect: Z = 2.49 (P = 0.01)

Test for subgroup differences: Not applicable 0.01 0.1 1 10 100

Less with cranberry+probiotic Less with placebo/control

Comparison 9. Cranberry product versus placebo or control: PAC dose

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

9.1 Symptomatic UTI: culture-verified 6 1504 Risk Ratio (M-H, Random, 0.75 [0.52, 1.08]
UTI (low dose PAC < 40 mg/day) 95% CI)

Cranberries for preventing urinary tract infections (Review) 130

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

9.1.1 Women with recurrent UTIs 3 425 Risk Ratio (M-H, Random, 0.57 [0.31, 1.06]
95% CI)

9.1.2 Elderly men and women 1 928 Risk Ratio (M-H, Random, 1.03 [0.74, 1.42]
95% CI)

9.1.3 Adults with neuropathy or neuro- 1 111 Risk Ratio (M-H, Random, 1.03 [0.66, 1.62]
pathic bladders 95% CI)

9.1.4 People with a susceptibility to 1 40 Risk Ratio (M-H, Random, 0.13 [0.02, 0.91]
UTIs due to an intervention 95% CI)

9.2 Symptomatic UTI: culture-verified 4 473 Risk Ratio (M-H, Random, 0.74 [0.41, 1.31]
UTI (moderate dose PAC 40 to 80 mg/ 95% CI)
day)

9.2.1 Elderly men and women 1 185 Risk Ratio (M-H, Random, 1.01 [0.42, 2.43]
95% CI)

9.2.2 Pregnant women 1 33 Risk Ratio (M-H, Random, Not estimable

95% CI)

9.2.3 People with a susceptibility to 2 255 Risk Ratio (M-H, Random, 0.58 [0.27, 1.25]
UTIs due to an intervention 95% CI)

9.3 Symptomatic UTI: culture-verified 2 507 Risk Ratio (M-H, Random, 1.47 [0.91, 2.39]
UTI (high dose PAC > 80 mg/day) 95% CI)

9.3.1 Women with recurrent UTIs 1 319 Risk Ratio (M-H, Random, 1.43 [0.87, 2.33]
95% CI)

9.3.2 Pregnant women 1 188 Risk Ratio (M-H, Random, 4.57 [0.25, 83.60]
95% CI)

Cranberries for preventing urinary tract infections (Review) 131

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 9.1. Comparison 9: Cranberry product versus placebo or control: PAC

dose, Outcome 1: Symptomatic UTI: culture-verified UTI (low dose PAC < 40 mg/day)

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

9.1.1 Women with recurrent UTIs

Sengupta 2011 2 23 4 13 4.9% 0.28 [0.06 , 1.34]
Vostalova 2015 9 83 24 93 15.4% 0.42 [0.21 , 0.85]
Takahashi 2013 32 107 38 106 25.6% 0.83 [0.57 , 1.23]
Subtotal (95% CI) 213 212 45.9% 0.57 [0.31 , 1.06]
Total events: 43 66
Heterogeneity: Tau² = 0.15; Chi² = 4.18, df = 2 (P = 0.12); I² = 52%
Test for overall effect: Z = 1.78 (P = 0.08)

9.1.2 Elderly men and women

Caljouw 2014 62 458 62 470 27.8% 1.03 [0.74 , 1.42]
Subtotal (95% CI) 458 470 27.8% 1.03 [0.74 , 1.42]
Total events: 62 62
Heterogeneity: Not applicable
Test for overall effect: Z = 0.15 (P = 0.88)

9.1.3 Adults with neuropathy or neuropathic bladders

Gallien 2014 21 51 24 60 23.2% 1.03 [0.66 , 1.62]
Subtotal (95% CI) 51 60 23.2% 1.03 [0.66 , 1.62]
Total events: 21 24
Heterogeneity: Not applicable
Test for overall effect: Z = 0.13 (P = 0.90)

9.1.4 People with a susceptibility to UTIs due to an intervention

Temiz 2018 1 20 8 20 3.2% 0.13 [0.02 , 0.91]
Subtotal (95% CI) 20 20 3.2% 0.13 [0.02 , 0.91]
Total events: 1 8
Heterogeneity: Not applicable
Test for overall effect: Z = 2.05 (P = 0.04)

Total (95% CI) 742 762 100.0% 0.75 [0.52 , 1.08]

Total events: 127 160
Heterogeneity: Tau² = 0.10; Chi² = 11.45, df = 5 (P = 0.04); I² = 56% 0.01 0.1 1 10 100
Test for overall effect: Z = 1.56 (P = 0.12) Cranberry product Placebo/control
Test for subgroup differences: Chi² = 6.84, df = 3 (P = 0.08), I² = 56.1%

Cranberries for preventing urinary tract infections (Review) 132

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 9.2. Comparison 9: Cranberry product versus placebo or control: PAC dose,
Outcome 2: Symptomatic UTI: culture-verified UTI (moderate dose PAC 40 to 80 mg/day)

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

9.2.1 Elderly men and women

Juthani-Mehta 2016 9 92 9 93 43.1% 1.01 [0.42 , 2.43]
Subtotal (95% CI) 92 93 43.1% 1.01 [0.42 , 2.43]
Total events: 9 9
Heterogeneity: Not applicable
Test for overall effect: Z = 0.02 (P = 0.98)

9.2.2 Pregnant women

Wing 2015 0 14 0 19 Not estimable
Subtotal (95% CI) 14 19 Not estimable
Total events: 0 0
Heterogeneity: Not applicable
Test for overall effect: Not applicable

9.2.3 People with a susceptibility to UTIs due to an intervention

Mohammed 2016 0 22 3 23 3.9% 0.15 [0.01 , 2.73]
Mooren 2020 9 105 14 105 52.9% 0.64 [0.29 , 1.42]
Subtotal (95% CI) 127 128 56.9% 0.58 [0.27 , 1.25]
Total events: 9 17
Heterogeneity: Tau² = 0.00; Chi² = 0.93, df = 1 (P = 0.34); I² = 0%
Test for overall effect: Z = 1.39 (P = 0.16)

Total (95% CI) 233 240 100.0% 0.74 [0.41 , 1.31]

Total events: 18 26
Heterogeneity: Tau² = 0.00; Chi² = 1.80, df = 2 (P = 0.41); I² = 0% 0.005 0.1 1 10 200
Test for overall effect: Z = 1.03 (P = 0.30) Cranberry product Placebo/control
Test for subgroup differences: Chi² = 0.87, df = 1 (P = 0.35), I² = 0%

Analysis 9.3. Comparison 9: Cranberry product versus placebo or control: PAC dose,
Outcome 3: Symptomatic UTI: culture-verified UTI (high dose PAC > 80 mg/day)

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

9.3.1 Women with recurrent UTIs

Barbosa-Cesnik 2011 31 155 23 164 97.2% 1.43 [0.87 , 2.33]
Subtotal (95% CI) 155 164 97.2% 1.43 [0.87 , 2.33]
Total events: 31 23
Heterogeneity: Not applicable
Test for overall effect: Z = 1.41 (P = 0.16)

9.3.2 Pregnant women

Wing 2008 4 125 0 63 2.8% 4.57 [0.25 , 83.60]
Subtotal (95% CI) 125 63 2.8% 4.57 [0.25 , 83.60]
Total events: 4 0
Heterogeneity: Not applicable
Test for overall effect: Z = 1.02 (P = 0.31)

Total (95% CI) 280 227 100.0% 1.47 [0.91 , 2.39]

Total events: 35 23
Heterogeneity: Tau² = 0.00; Chi² = 0.61, df = 1 (P = 0.43); I² = 0% 0.01 0.1 1 10 100
Test for overall effect: Z = 1.56 (P = 0.12) Cranberry product Placebo/control
Test for subgroup differences: Chi² = 0.60, df = 1 (P = 0.44), I² = 0%

Cranberries for preventing urinary tract infections (Review) 133

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Comparison 10. Cranberry product versus placebo or control: sponsor type

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

10.1 Symptomatic UTI: culture-veri- 13 3202 Risk Ratio (M-H, Random, 0.86 [0.76, 0.99]
fied UTI (commercial involvement) 95% CI)

10.1.1 Women with recurrent UTIs 2 586 Risk Ratio (M-H, Random, 0.86 [0.64, 1.15]
95% CI)

10.1.2 Elderly men and women 4 1526 Risk Ratio (M-H, Random, 0.94 [0.74, 1.20]
95% CI)

10.1.3 Pregnant women 1 33 Risk Ratio (M-H, Random, Not estimable

95% CI)

10.1.4 Children 2 334 Risk Ratio (M-H, Random, 0.63 [0.39, 1.02]
95% CI)

10.1.5 Adults with neuropathy or neu- 2 353 Risk Ratio (M-H, Random, 0.95 [0.75, 1.20]
ropathic bladders 95% CI)

10.1.6 People with a susceptibility to 2 370 Risk Ratio (M-H, Random, 0.57 [0.35, 0.92]
UTIs due to an intervention 95% CI)

10.2 Symptomatic UTI: culture-veri- 12 2543 Risk Ratio (M-H, Random, 0.61 [0.43, 0.87]
fied UTI (no commercial involvement) 95% CI)

10.2.1 Women with recurrent UTIs 5 819 Risk Ratio (M-H, Random, 0.66 [0.38, 1.14]
95% CI)

10.2.2 Elderly men and women 1 376 Risk Ratio (M-H, Random, 0.51 [0.21, 1.22]
95% CI)

10.2.3 Pregnant women 1 188 Risk Ratio (M-H, Random, 1.52 [0.06, 36.88]
95% CI)

10.2.4 Children 1 40 Risk Ratio (M-H, Random, 0.62 [0.25, 1.58]

95% CI)

10.2.5 Adults with neuropathy 1 111 Risk Ratio (M-H, Random, 1.03 [0.66, 1.62]
95% CI)

10.2.6 People with a susceptibility to 3 1009 Risk Ratio (M-H, Random, 0.41 [0.28, 0.60]
UTI due to an intervention 95% CI)

Cranberries for preventing urinary tract infections (Review) 134

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 10.1. Comparison 10: Cranberry product versus placebo or control: sponsor
type, Outcome 1: Symptomatic UTI: culture-verified UTI (commercial involvement)

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

10.1.1 Women with recurrent UTIs

Maki 2016 30 185 34 188 9.0% 0.90 [0.57 , 1.40]
Takahashi 2013 32 107 38 106 12.1% 0.83 [0.57 , 1.23]
Subtotal (95% CI) 292 294 21.2% 0.86 [0.64 , 1.15]
Total events: 62 72
Heterogeneity: Tau² = 0.00; Chi² = 0.06, df = 1 (P = 0.81); I² = 0%
Test for overall effect: Z = 1.01 (P = 0.31)

10.1.2 Elderly men and women

McMurdo 2005 7 187 14 189 2.3% 0.51 [0.21 , 1.22]
Juthani-Mehta 2016 9 92 9 93 2.3% 1.01 [0.42 , 2.43]
Juthani-Mehta 2010 13 20 12 17 9.1% 0.92 [0.59 , 1.44]
Caljouw 2014 62 458 62 470 16.8% 1.03 [0.74 , 1.42]
Subtotal (95% CI) 757 769 30.6% 0.94 [0.74 , 1.20]
Total events: 91 97
Heterogeneity: Tau² = 0.00; Chi² = 2.20, df = 3 (P = 0.53); I² = 0%
Test for overall effect: Z = 0.49 (P = 0.62)

10.1.3 Pregnant women

Wing 2015 0 14 0 19 Not estimable
Subtotal (95% CI) 14 19 Not estimable
Total events: 0 0
Heterogeneity: Not applicable
Test for overall effect: Not applicable

10.1.4 Children
Wan 2016 7 28 10 27 2.8% 0.68 [0.30 , 1.51]
Salo 2010 16 152 22 127 5.0% 0.61 [0.33 , 1.11]
Subtotal (95% CI) 180 154 7.8% 0.63 [0.39 , 1.02]
Total events: 23 32
Heterogeneity: Tau² = 0.00; Chi² = 0.04, df = 1 (P = 0.84); I² = 0%
Test for overall effect: Z = 1.88 (P = 0.06)

10.1.5 Adults with neuropathy or neuropathic bladders

Waites 2004 10 26 8 22 3.3% 1.06 [0.51 , 2.21]
SINBA 2007 67 153 71 152 29.6% 0.94 [0.73 , 1.20]
Subtotal (95% CI) 179 174 32.9% 0.95 [0.75 , 1.20]
Total events: 77 79
Heterogeneity: Tau² = 0.00; Chi² = 0.09, df = 1 (P = 0.76); I² = 0%
Test for overall effect: Z = 0.44 (P = 0.66)

10.1.6 People with a susceptibility to UTIs due to an intervention

Mooren 2020 9 105 14 105 2.9% 0.64 [0.29 , 1.42]
Foxman 2015 12 80 23 80 4.6% 0.52 [0.28 , 0.98]
Subtotal (95% CI) 185 185 7.5% 0.57 [0.35 , 0.92]
Total events: 21 37
Heterogeneity: Tau² = 0.00; Chi² = 0.16, df = 1 (P = 0.69); I² = 0%
Test for overall effect: Z = 2.28 (P = 0.02)

Total (95% CI) 1607 1595 100.0% 0.86 [0.76 , 0.99]

Total events: 274 317
Heterogeneity: Tau² = 0.00; Chi² = 8.23, df = 11 (P = 0.69); I² = 0% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 2.14 (P = 0.03) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 5.60, df = 4 (P = 0.23), I² = 28.6%

Cranberries for preventing urinary tract infections (Review) 135

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 10.2. Comparison 10: Cranberry product versus placebo or control: sponsor
type, Outcome 2: Symptomatic UTI: culture-verified UTI (no commercial involvement)

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

10.2.1 Women with recurrent UTIs

Sengupta 2011 4 44 4 13 5.5% 0.30 [0.09 , 1.02]
Kontiokari 2001 8 46 18 45 9.9% 0.43 [0.21 , 0.90]
Vostalova 2015 9 83 24 93 10.1% 0.42 [0.21 , 0.85]
Barbosa-Cesnik 2011 31 155 23 164 12.6% 1.43 [0.87 , 2.33]
Stapleton 2012 33 120 17 56 12.6% 0.91 [0.55 , 1.48]
Subtotal (95% CI) 448 371 50.7% 0.66 [0.38 , 1.14]
Total events: 85 86
Heterogeneity: Tau² = 0.27; Chi² = 13.92, df = 4 (P = 0.008); I² = 71%
Test for overall effect: Z = 1.49 (P = 0.14)

10.2.2 Elderly men and women

McMurdo 2005 7 187 14 189 8.2% 0.51 [0.21 , 1.22]
Subtotal (95% CI) 187 189 8.2% 0.51 [0.21 , 1.22]
Total events: 7 14
Heterogeneity: Not applicable
Test for overall effect: Z = 1.51 (P = 0.13)

10.2.3 Pregnant women

Wing 2008 1 125 0 63 1.2% 1.52 [0.06 , 36.88]
Subtotal (95% CI) 125 63 1.2% 1.52 [0.06 , 36.88]
Total events: 1 0
Heterogeneity: Not applicable
Test for overall effect: Z = 0.26 (P = 0.80)

10.2.4 Children
Afshar 2012 5 20 8 20 7.8% 0.63 [0.25 , 1.58]
Subtotal (95% CI) 20 20 7.8% 0.63 [0.25 , 1.58]
Total events: 5 8
Heterogeneity: Not applicable
Test for overall effect: Z = 0.99 (P = 0.32)

10.2.5 Adults with neuropathy

Gallien 2014 21 51 24 60 13.1% 1.03 [0.66 , 1.62]
Subtotal (95% CI) 51 60 13.1% 1.03 [0.66 , 1.62]
Total events: 21 24
Heterogeneity: Not applicable
Test for overall effect: Z = 0.13 (P = 0.90)

10.2.6 People with a susceptibility to UTI due to an intervention

Mohammed 2016 0 22 3 23 1.4% 0.15 [0.01 , 2.73]
Temiz 2018 1 20 8 20 2.7% 0.13 [0.02 , 0.91]
Bonetta 2017 53 489 107 435 14.8% 0.44 [0.33 , 0.60]
Subtotal (95% CI) 531 478 18.9% 0.41 [0.28 , 0.60]
Total events: 54 118
Heterogeneity: Tau² = 0.02; Chi² = 2.04, df = 2 (P = 0.36); I² = 2%
Test for overall effect: Z = 4.55 (P < 0.00001)

Total (95% CI) 1362 1181 100.0% 0.61 [0.43 , 0.87]

Total events: 173 250
Heterogeneity: Tau² = 0.20; Chi² = 30.60, df = 11 (P = 0.001); I² = 64% 0.005 0.1 1 10 200
Test for overall effect: Z = 2.71 (P = 0.007) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 9.74, df = 5 (P = 0.08), I² = 48.7%

Cranberries for preventing urinary tract infections (Review) 136

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Comparison 11. Cranberry product versus placebo or control: culture threshold

Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants

11.1 Symptomatic UTI: culture-veri- 18 4102 Risk Ratio (M-H, Random, 0.72 [0.57, 0.91]
fied UTI (# 108 CFU/L) 95% CI)

11.1.1 Women with recurrent UTIs 5 912 Risk Ratio (M-H, Random, 0.71 [0.45, 1.12]
95% CI)

11.1.2 Elderly men and women 2 1113 Risk Ratio (M-H, Random, 1.02 [0.75, 1.39]
95% CI)

11.1.3 Pregnant women 2 221 Risk Ratio (M-H, Random, 4.57 [0.25, 83.60]
95% CI)

11.1.4 Children 4 428 Risk Ratio (M-H, Random, 0.53 [0.36, 0.78]
95% CI)

11.1.5 Adults with bladder emptying 3 464 Risk Ratio (M-H, Random, 0.97 [0.78, 1.19]
issues or multiple sclerosis 95% CI)

11.1.6 People with a susceptibility to 2 964 Risk Ratio (M-H, Random, 0.35 [0.13, 0.92]
UTIs due to an intervention 95% CI)

11.2 Symptomatic UTI: culture-veri- 3 806 Risk Ratio (M-H, Random, 0.62 [0.34, 1.14]
fied UTI (< 108 CFU/L) 95% CI)

11.2.1 Women with recurrent UTIs 2 430 Risk Ratio (M-H, Random, 0.60 [0.21, 1.71]
95% CI)

11.2.2 Elderly men and women 1 376 Risk Ratio (M-H, Random, 0.51 [0.21, 1.22]
95% CI)

Cranberries for preventing urinary tract infections (Review) 137

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 11.1. Comparison 11: Cranberry product versus placebo or control: culture threshold, Outcome 1:
Symptomatic UTI: culture-verified UTI (# 108 CFU/L)

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

11.1.1 Women with recurrent UTIs

Kontiokari 2001 8 46 18 45 5.4% 0.43 [0.21 , 0.90]
Vostalova 2015 9 83 24 93 5.5% 0.42 [0.21 , 0.85]
Stothers 2002 19 100 16 50 6.7% 0.59 [0.34 , 1.05]
Barbosa-Cesnik 2011 31 155 23 164 7.4% 1.43 [0.87 , 2.33]
Stapleton 2012 33 120 17 56 7.4% 0.91 [0.55 , 1.48]
Subtotal (95% CI) 504 408 32.5% 0.71 [0.45 , 1.12]
Total events: 100 98
Heterogeneity: Tau² = 0.19; Chi² = 12.44, df = 4 (P = 0.01); I² = 68%
Test for overall effect: Z = 1.47 (P = 0.14)

11.1.2 Elderly men and women

Juthani-Mehta 2016 9 92 9 93 4.3% 1.01 [0.42 , 2.43]
Caljouw 2014 62 458 62 470 9.1% 1.03 [0.74 , 1.42]
Subtotal (95% CI) 550 563 13.4% 1.02 [0.75 , 1.39]
Total events: 71 71
Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 0.97); I² = 0%
Test for overall effect: Z = 0.15 (P = 0.88)

11.1.3 Pregnant women

Wing 2015 0 14 0 19 Not estimable
Wing 2008 4 125 0 63 0.6% 4.57 [0.25 , 83.60]
Subtotal (95% CI) 139 82 0.6% 4.57 [0.25 , 83.60]
Total events: 4 0
Heterogeneity: Not applicable
Test for overall effect: Z = 1.02 (P = 0.31)

11.1.4 Children
Afshar 2012 5 20 8 20 4.0% 0.63 [0.25 , 1.58]
Ferrara 2009 5 27 18 27 4.6% 0.28 [0.12 , 0.64]
Wan 2016 7 28 10 27 4.8% 0.68 [0.30 , 1.51]
Salo 2010 16 152 22 127 6.4% 0.61 [0.33 , 1.11]
Subtotal (95% CI) 227 201 19.9% 0.53 [0.36 , 0.78]
Total events: 33 58
Heterogeneity: Tau² = 0.00; Chi² = 2.97, df = 3 (P = 0.40); I² = 0%
Test for overall effect: Z = 3.26 (P = 0.001)

11.1.5 Adults with bladder emptying issues or multiple sclerosis

Waites 2004 10 26 8 22 5.3% 1.06 [0.51 , 2.21]
Gallien 2014 21 51 24 60 7.9% 1.03 [0.66 , 1.62]
SINBA 2007 67 153 71 152 9.9% 0.94 [0.73 , 1.20]
Subtotal (95% CI) 230 234 23.0% 0.97 [0.78 , 1.19]
Total events: 98 103
Heterogeneity: Tau² = 0.00; Chi² = 0.19, df = 2 (P = 0.91); I² = 0%
Test for overall effect: Z = 0.33 (P = 0.74)

11.1.6 People with a susceptibility to UTIs due to an intervention

Temiz 2018 1 20 8 20 1.2% 0.13 [0.02 , 0.91]
Bonetta 2017 53 489 107 435 9.3% 0.44 [0.33 , 0.60]
Subtotal (95% CI) 509 455 10.6% 0.35 [0.13 , 0.92]
Total events: 54 115
Heterogeneity: Tau² = 0.28; Chi² = 1.53, df = 1 (P = 0.22); I² = 35%
Test for overall effect: Z = 2.13 (P = 0.03)

Total (95% CI) 2159 1943 100.0% 0.72 [0.57 , 0.91]

Total events: 360 445
Heterogeneity: Tau² = 0.13; Chi² = 45.25, df = 16 (P = 0.0001); I² = 65% 0.01 0.1 1 10 100
Test for overall effect: Z = 2.74 (P = 0.006) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 13.88, df = 5 (P = 0.02), I² = 64.0%

Cranberries for preventing urinary tract infections (Review) 138

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Analysis 11.1. (Continued)

Heterogeneity: Tau² = 0.13; Chi² = 45.25, df = 16 (P = 0.0001); I² = 65% 0.01 0.1 1 10 100
Test for overall effect: Z = 2.74 (P = 0.006) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 13.88, df = 5 (P = 0.02), I² = 64.0%

Analysis 11.2. Comparison 11: Cranberry product versus placebo or control:

culture threshold, Outcome 2: Symptomatic UTI: culture-verified UTI (< 108 CFU/L)

Cranberry product Placebo/control Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI

11.2.1 Women with recurrent UTIs

Sengupta 2011 4 44 4 13 18.2% 0.30 [0.09 , 1.02]
Maki 2016 30 185 34 188 52.9% 0.90 [0.57 , 1.40]
Subtotal (95% CI) 229 201 71.1% 0.60 [0.21 , 1.71]
Total events: 34 38
Heterogeneity: Tau² = 0.39; Chi² = 2.73, df = 1 (P = 0.10); I² = 63%
Test for overall effect: Z = 0.95 (P = 0.34)

11.2.2 Elderly men and women

McMurdo 2005 7 187 14 189 28.9% 0.51 [0.21 , 1.22]
Subtotal (95% CI) 187 189 28.9% 0.51 [0.21 , 1.22]
Total events: 7 14
Heterogeneity: Not applicable
Test for overall effect: Z = 1.51 (P = 0.13)

Total (95% CI) 416 390 100.0% 0.62 [0.34 , 1.14]

Total events: 41 52
Heterogeneity: Tau² = 0.13; Chi² = 3.52, df = 2 (P = 0.17); I² = 43% 0.01 0.1 1 10 100
Test for overall effect: Z = 1.53 (P = 0.13) Less with cranberry product Less with placebo/control
Test for subgroup differences: Chi² = 0.06, df = 1 (P = 0.80), I² = 0%

APPENDICES

Appendix 1. Electronic search strategies

Database Search terms used

CENTRAL 1. MeSH descriptor: [Beverages] this term only

2. MeSH descriptor: [Fruit] this term only
3. MeSH descriptor: [Phytotherapy] this term only
4. MeSH descriptor: [Vaccinium macrocarpon] this term only
5. Vaccinium macrocarpon:ti,ab,kw (Word variations have been searched)
6. vaccinium oxycoccus:ti,ab,kw (Word variations have been searched)
7. vaccinium vitisidaea:ti,ab,kw (Word variations have been searched)
8. cranberry or cranberries:ti,ab,kw (Word variations have been searched)
9. {or #1-#8}
10.MeSH descriptor: [Urinary Tract Infections] this term only
11.MeSH descriptor: [Bacteriuria] this term only
12.MeSH descriptor: [Pyuria] this term only
13.MeSH descriptor: [Cystitis] this term only
14.uti or utis:ti,ab,kw (Word variations have been searched)
15.cystitis:ti,ab,kw (Word variations have been searched)
Cranberries for preventing urinary tract infections (Review) 139
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

(Continued)
16.pyelonephritis:ti,ab,kw (Word variations have been searched)
17.bacteriuria:ti,ab,kw (Word variations have been searched)
18.urinary tract infection*:ti,ab,kw (Word variations have been searched)
19.{or #10-#18}
20.{and #9, #19}

MEDLINE 1. Beverages/
2. FRUIT/
3. cranberr$.tw.
4. (fruit$ and (juice$ or beverage$ or drink$)).tw.
5. PHYTOTHERAPY/
6. Vaccinium macrocarpon/
7. vaccinium oxycoccus.tw.
8. vaccinium vitisidaea.tw.
9. or/1-8
10.Urinary tract infections/
11.Bacteriuria/
12.Pyuria/
13.Cystitis/
14.(uti or utis).tw.
15.cystitis.tw.
16.pyelonephritis.tw.
17.bacter$.tw.
18.urinary tract infection$.tw.
19.or/10-18
20.and/9,19

EMBASE 1. cranberry/
2. cranberry juice/
3. cranberry extract/
4. vaccinium macrocarpon.tw.
5. vaccinium vitisidaea.tw.
6. vaccinium oxycoccus.tw.
7. cranberr$.tw.
8. or/1-7
9. urinary tract infection/
10.pyuria/
11.bacteriuria/
12.asymptomatic bacteriuria/
13.cystitis/
14.(uti or utis).tw.
15.urinary tract infection$.tw.
16.bacteriuria.tw.
17.cystitis.tw.
18.or/9-17
19.and/8,18

Appendix 2. Risk of bias assessment tool

Cranberries for preventing urinary tract infections (Review) 140

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Potential source of bias Assessment criteria

Random sequence genera- Low risk of bias: Random number table; computer random number generator; coin tossing; shuf-
tion fling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be imple-
mented without a random element, and this is considered to be equivalent to being random).
Selection bias (biased alloca-
tion to interventions) due to High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; se-
inadequate generation of a quence generated by hospital or clinic record number; allocation by judgement of the clinician; by
randomised sequence preference of the participant; based on the results of a laboratory test or a series of tests; by avail-
ability of the intervention.

Unclear: Insufficient information about the sequence generation process to permit judgement.

Allocation concealment Low risk of bias: Randomisation method described that would not allow investigator/participant to
know or influence intervention group before eligible participant entered in the study (e.g. central
Selection bias (biased alloca- allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequential-
tion to interventions) due to ly numbered drug containers of identical appearance; sequentially numbered, opaque, sealed en-
inadequate concealment of al- velopes).
locations prior to assignment
High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); as-
signment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or
non-opaque or not sequentially numbered); alternation or rotation; date of birth; case record num-
ber; any other explicitly unconcealed procedure.

Unclear: Randomisation stated but no information on method used is available.

Blinding of participants and Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome
personnel is not likely to be influenced by lack of blinding; blinding of participants and key study personnel
ensured, and unlikely that the blinding could have been broken.
Performance bias due to
knowledge of the allocated High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by
interventions by participants lack of blinding; blinding of key study participants and personnel attempted, but likely that the
and personnel during the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
study
Unclear: Insufficient information to permit judgement

Blinding of outcome assess- Low risk of bias: No blinding of outcome assessment, but the review authors judge that the out-
ment come measurement is not likely to be influenced by lack of blinding; blinding of outcome assess-
ment ensured, and unlikely that the blinding could have been broken.
Detection bias due to knowl-
edge of the allocated interven- High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be
tions by outcome assessors. influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could
have been broken, and the outcome measurement is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement.

Incomplete outcome data Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be relat-
ed to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome
Attrition bias due to amount, data balanced in numbers across intervention groups, with similar reasons for missing data across
nature or handling of incom- groups; for dichotomous outcome data, the proportion of missing outcomes compared with ob-
plete outcome data. served event risk not enough to have a clinically relevant impact on the intervention effect esti-
mate; for continuous outcome data, plausible effect size (difference in means or standardized dif-
ference in means) among missing outcomes not enough to have a clinically relevant impact on ob-
served effect size; missing data have been imputed using appropriate methods.

High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either
imbalance in numbers or reasons for missing data across intervention groups; for dichotomous
outcome data, the proportion of missing outcomes compared with observed event risk enough to

Cranberries for preventing urinary tract infections (Review) 141

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

(Continued)
induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausi-
ble effect size (difference in means or standardized difference in means) among missing outcomes
enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with
substantial departure of the intervention received from that assigned at randomisation; potentially
inappropriate application of simple imputation.

Unclear: Insufficient information to permit judgement

Selective reporting Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and
secondary) outcomes that are of interest in the review have been reported in the pre-specified way;
Reporting bias due to selective the study protocol is not available but it is clear that the published reports include all expected out-
outcome reporting comes, including those that were pre-specified (convincing text of this nature may be uncommon).

High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or
more primary outcomes is reported using measurements, analysis methods or subsets of the data
(e.g. subscales) that were not pre-specified; one or more reported primary outcomes were not pre-
specified (unless clear justification for their reporting is provided, such as an unexpected adverse
effect); one or more outcomes of interest in the review are reported incompletely so that they can-
not be entered in a meta-analysis; the study report fails to include results for a key outcome that
would be expected to have been reported for such a study.

Unclear: Insufficient information to permit judgement

Other bias Low risk of bias: The study appears to be free of other sources of bias.

Bias due to problems not cov- High risk of bias: Had a potential source of bias related to the specific study design used; stopped
ered elsewhere in the table early due to some data-dependent process (including a formal-stopping rule); had extreme base-
line imbalance; has been claimed to have been fraudulent; had some other problem.

Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient ra-
tionale or evidence that an identified problem will introduce bias.

Appendix 3. Adverse events: cranberry product versus control

Adverse event Cranberry product Control

Patients with Total Patients with Total

event event

Death

McMurdo 2005 3 187 2 189

Caljouw 2014 150 458 145 470

Juthani-Mehta 2016 17 92 16 93

Bruyere 2019 0 42 0 43

Hospitalisations

Fernandes 2016 1 25 2 30

Juthani-Mehta 2016 33 92 50 93

Cranberries for preventing urinary tract infections (Review) 142

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

(Continued)

Serious adverse events (not specified)

Sengupta 2011 0 44 0 13

Stapleton 2012 0 120 0 56

Gallien 2014 0 51 0 60

Foxman 2015 4 80 4 80

Juthani-Mehta 2016 50 (events) - 66 (events) -

Maki 2016 1 185 4 188

Gastrointestinal events

Stothers 2002 8 100 2 50

McMurdo 2005 2 187 4 189

Sengupta 2011 4 44 0 13

Gallien 2014 14 51 18 60

Wing 2015 13 14 12 19

Singh 2016 1 36 1 36

Bonetta 2017 4 489 0 435

Koradia 2019 3 44 0 45

Babar 2021 1 72 1 73

Mohammed 2016 0 22 0 23

Rash

McMurdo 2005 1 187 0 189

Appendix 4. Adverse events: cranberry product versus antibiotics

Adverse event Cranberry product Antibiotics

Patients with Total Patients with Total

event event

Gastrointestinal events

McMurdo 2009 4 69 4 68

NAPRUTI 2011 13 104 16 95

Cranberries for preventing urinary tract infections (Review) 143

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

(Continued)

Uberos 2012 2 72 5 114

Rash or urticaria

McMurdo 2009 0 69 3 68

NAPRUTI 2011 9 104 15 95

Uberos 2012 1 72 1 114

Vaginal problems

NAPRUTI 2011 15 104 18 95

Allergic reaction

NAPRUTI 2011 0 109 1 98

Antibiotic resistance (positive cultures)

Uberos 2012 4 19 9 28

Severe adverse events (unspecified)

NAPRUTI 2011 8 104 12 95

Appendix 5. Adherence to cranberry product

Study ID Cranberry type Adherence (%) How measured Reported result for symptomatic UTI
(verified on culture unless otherwise
specified)

Afshar 2012 Juice Not reported Bottle count RR 0.63 (95% CI 0.25 to 1.58)

Avorn 1994 Juice 80% Bottle caps counted Not estimable (units = cultures)

Babar 2021 Pill 92.9% versus Self-reported in a daily RR 0.69 (95% CI 0.57 to 1.13)
92.7% journal
(symptomatic UTI not verified by culture)
Pill count

Barbosa-Cesnik Juice 70% to 75% Self-report RR 1.43 (95% CI 0.87 to 2.33)

2011

Caljouw 2014 Pill 97% Pill count RR 1.03 (95% CI 0.74 to 1.42)

Cowan 2012 Juice 79% Self-report Not estimable (units = cultures)

Ferrara 2009 Juice 96.4% Self-report RR 0.28 (95% CI 0.12 to 0.64)

Foda 1995 Juice 52% Self-report Not estimable (cross-over RCT)

Cranberries for preventing urinary tract infections (Review) 144

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

(Continued)

Foxman 2015 Pill 85% took pills Pill count and ques- RR 0.52 (95% CI 0.28 to 0.98)
most or all of the tioned by staff
time

Gallien 2014 Powder 80% were > 70% Sachets counted RR 1.03 (95% CI 0.66 to 1.62)

Hess 2008 Pill Not reported Pill count and ques- Not estimable (cross-over RCT)
tioned

Juthani-Mehta Pill 77.5% Pill count RR 1.01 (95% CI 0.42 to 2.43)

2016

Kontiokari 2001 Juice 91% Self-report sheet RR 0.43 (95% CI 0.21 to 0.90)

Koradia 2019 Pill 80% Self-report-Diary cards RR 0.27 (95% CI 0.1 to 0.76)

(cranberry + probiotic versus placebo)

Maki 2016 Juice 98% Bottles returned and RR 0.90 (95% CI 0.57 to 1.4)
self-report diary

McGuiness 2002 Pill Not reported Questioned by re- RR 1.03 (95% CI 0.64 to 1.66)
searcher
(microbiological UTI)

McMurdo 2005 Juice Close to 100% Self-report RR 0.51 (95% CI 0.21 to 1.22)

McMurdo 2009 Pill 99% Pill count RR 1.76 (95% CI 1.0 to 3.09)

(cranberry versus antibiotic; clinical UTI)

Mooren 2020 Pill 85.7% versus Self-reported on ques- RR 0.64 (95% CI 0.29 to 1.42)
80% tionnaire

Pill count

Salo 2010 Juice 46% were > 90%, Self-report and bottle RR 0.61 (95% CI 0.33 to 1.11)
17% were 50% to count
90%, 37% were <
50%

Schlager 1999 Juice Not reported Bottle count Not estimable (cross-over RCT)

Singh 2016 Pill Not reported Returned empty pill RR 0.38 (95% CI 0.23 to 0.60)
packets

Stapleton 2012 Juice 91.8% Questionnaire RR 0.91 (95% CI 0.55 to 1.48)

Stothers 2002 Pill or Juice Pills > 85% Pill count RR 0.59 (95% CI 0.34 to 1.05)

Juice < 80%

Takahashi 2013 Juice Not reported Questioned by doctor RR 0.83 (95% CI 0.57 to 1.23)

Waites 2004 Pill Not reported Monthly telephone calls RR 1.06 (95% CI 0.51 to 2.21)
for pill count

Cranberries for preventing urinary tract infections (Review) 145

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

(Continued)

Walker 1997 Pill Not reported Returned capsule bot- Not estimable (cross-over study)
tles and interviewed

Wing 2008 Juice 50.7% (2 to 3 Self-report RR 4.57 (95% CI 0.25 to 83.6)

dose group)

39.7% (1 dose
group)

Wing 2015 Pill 82% Self-report Not estimable (no UTI events)

Footnotes

CI: confidence interval; RR: relative risk; UTI: urinary tract infection

WHAT'S NEW

Date Event Description

10 November 2023 New search has been performed One study reclassified from cranberry product vs control to high
vs low dose cranberry product - no change to conclusions.

One study moved from low PAC to medium PAC - no change to

conclusions.

10 November 2023 New citation required but conclusions Authorship corrected.

have not changed

HISTORY
Protocol first published: Issue 2, 1998
Review first published: Issue 2, 1998

Date Event Description

17 April 2023 New citation required and conclusions New studies identified
have changed

17 April 2023 New search has been performed 24 new studies added and conclusions changed

18 March 2015 Amended Updated search strategies for MEDLINE, EMBASE & CENTRAL

16 June 2014 Amended Minor grammatical correction made

2 April 2013 Amended Minor spelling corrections made throughout

14 September 2012 New citation required and conclusions Updated the review in 2012 with 14 new studies. Conclusions
have changed have changed to say that the evidence suggests that cranberry
products are not effective in preventing UTIs

13 August 2009 Amended Contact details updated

Cranberries for preventing urinary tract infections (Review) 146

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Date Event Description

13 May 2009 Amended Contact details updated

23 September 2008 Amended Converted to new review format

10 September 2007 New citation required and conclusions Substantive amendment

have changed

CONTRIBUTIONS OF AUTHORS
• JCC: study design, writing review,(pre 2012), review text (2012-2023)
• GW: update search, study selection, quality assessment, data extraction(50 studies), writing(2012-2022), review text (2023)
• EMH: data extraction (3 RCTs) updating text (2023)
• DH: risk of bias tables (3 RCTs), review text (2023)
• JHS: data extraction (3 RCTs), review text (2023)
• CS: data extraction (14 RCTS), review text (2015)

DECLARATIONS OF INTEREST
• Gabrielle Williams: no relevant interests were disclosed
• Christopher Stothart: no relevant interests were disclosed
• Deirdre Hahn: no relevant interests were disclosed
• Jacqueline H Stephens: no relevant interests were disclosed
• Jonathan C Craig: no relevant interests were disclosed
• Elisabeth M Hodson: no relevant interests were disclosed

SOURCES OF SUPPORT

Internal sources
• No sources of support provided

External sources
• New Source of support, Australia

Salary support for GW through a National Health and Medical Research Council (NHMRC) program grant (ID numbers; 211205 and
402764)
• New Source of support, UK

Cochrane Collaboration, funding for update 2015

DIFFERENCES BETWEEN PROTOCOL AND REVIEW

2023: Risk of bias assessment tool has replaced quality assessment checklist. GRADE has been used to describe the certainty of the
evidence.

INDEX TERMS

Medical Subject Headings (MeSH)

Anti-Bacterial Agents; Kidney; Phytotherapy [methods]; Plant Extracts [therapeutic use]; *Urinary Tract Infections [prevention &
control]; *Vaccinium macrocarpon

MeSH check words

Adult; Aged; Child; Female; Humans; Male

Cranberries for preventing urinary tract infections (Review) 147

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.