Cranberries for preventing urinary tract infections (2024)

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Cochrane Database Syst Rev. 2012 Oct; 2012(10): CD001321.

Published online 2012 Oct 17. doi:10.1002/14651858.CD001321.pub5

PMCID: PMC7027998

PMID: 23076891

Monitoring Editor: Ruth G Jepson, Gabrielle Williams, Jonathan C Craig, and Cochrane Kidney and Transplant Group

Scottish Collaboration for Public Health Research and Policy (SCPHRP), 20 West Richmond Street, EdinburghScotlandUK, EH8 9DX

The Children's Hospital at Westmead, Centre for Kidney Research, Locked Bag 4001, WestmeadNSWAustralia, 2145

The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, WestmeadNSWAustralia, 2145

Ruth G Jepson, Email: ku.ca.de@nospej.htur, Email: ku.ca.prhpcs@nospej.htur.

Author information Copyright and License information PMC Disclaimer

This article has been updated. "Cranberries for preventing urinary tract infections" in volume 2023, CD001321.

This article is an update of "Cranberries for preventing urinary tract infections." onpageCD001321.

Abstract

Background

Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first published in 1998 and updated in 2004 and 2008.

Objectives

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

Search methods

We searched the Cochrane Renal Group's Specialised Register (4 June 2013) through contact with the Trials' Search Co‐ordinator using search terms relevant to this review.We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies.

Date of search: July 2012

Selection criteria

All randomised controlled trials (RCTs) or quasi‐RCTs of cranberry products for the prevention of UTIs.

Data collection and analysis

Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool.

Main results

This updated review includes a total of 24 studies (six cross‐over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated cranberry juice/concentrate; nine studies (1032 participants) evaluated cranberry tablets or capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta‐analyses because either the design was a cross‐over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta‐analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective.

Authors' conclusions

Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.

Plain language summary

Cranberries for preventing urinary tract infections

Cranberries (usually as cranberry juice) have been used to prevent urinary tract infections (UTIs). Cranberries contain a substance that can prevent bacteria from sticking on the walls of the bladder. This may help prevent bladder and other UTIs. This review identified 24 studies (4473 participants) comparing cranberry products with control or alternative treatments. There was a small trend towards fewer UTIs in people taking cranberry product compared to placebo or no treatment but this was not a significant finding. Many people in the studies stopped drinking the juice, suggesting it may not be an acceptable intervention. Cranberry juice does not appear to have a significant benefit in preventing UTIs and may be unacceptable to consume in the long term. Cranberry products (such as tablets or capsules) were also ineffective (although had the same effect as taking antibiotics), possibly due to lack of potency of the 'active ingredient'.

Background

The term urinary tract infection (UTI) refers to the presence of a certain threshold number of bacteria in the urine (usually > 100,000/mL). It consists of cystitis (bacteria in the bladder), urethral syndrome and pyelonephritis (infection of the kidneys). Lower UTIs involve the bladder, whereas upper UTIs also involve the kidneys (pyelonephritis). Bacterial cystitis (also called acute cystitis) can occur in men and women and the signs and symptoms include dysuria (pain on passing urine), frequency, cloudy urine, occasionally haematuria (blood in the urine), and is often associated with pyuria (urine white cell count greater than 10,000/mL). Urethral syndrome (frequency and dysuria syndrome) is used to describe approximately 50% of women with these complaints who have either no bacterial growth or counts less than 100,000 colony‐forming units (cfu)/mL on repeated urine cultures. Pyelonephritis is thought to occur as a result of cystitis, particularly in the presence of transient (occasional) or persistent backflow of urine from the bladder into the ureters or kidney pelvis (vesicoureteric reflux). Signs and symptoms include flank pain or back pain, fever, chills with shaking, general ill feeling plus those symptoms of a lower UTI. Acute pyelonephritis can be severe in the elderly, in infants, and in people who are immunosuppressed (for example, those with cancer or AIDS). Although most people who present to the doctor or hospital have symptomatic UTIs, some can be asymptomatic and only those who are at high risk of developing further infections (pregnant women and the elderly) are considered to need treatment. Some people also have recurrent UTIs with an average of two to three episodes/year (Roberts 1979; Wong 1984). Children often present with a fever and non‐specific symptoms such as lethargy (tiredness), vomiting or poor feeding.

UTIs are one of the most common medical conditions requiring outpatient treatment, and complications resulting from persistent and repeated infections necessitate well over one million hospital admissions annually in the USA (Patton 1991). Specific subpopulations are at increased risk of developing a UTI. These groups include infants, pregnant women, the elderly, patients with spinal cord injuries and/or catheters, patients with diabetes or multiple sclerosis, patients with acquired immunodeficiency disease syndrome/human immunodeficiency virus, and patients with underlying urologic abnormalities (Foxman 2002). Although UTIs can occur in both men and women, they are about 50 times more common in adult women than adult men. This may be because women have a shorter urethra that may allow bacteria to ascend more easily into the bladder. Symptomatic infection of the bladder (lower UTI) has been estimated to occur in up to 30% of women at some stage during their lives (Kelly 1977). The annual incidence of acute uncomplicated UTI is 7% for all ages of women peaking at 15‐24 years and women older than 65 (Giesen 2010). Up to 25% of women who have a UTI are likely to have a reoccurrence within six months (Epp 2010). UTIs often occur in clusters with long periods (several months) where patients are symptom free (Stapleton 1997).

Most UTIs are thought to arise from the 'ascending' route of infection. The first step is colonisation of periurethral tissues with uropathogenic organisms, followed by the passage of bacteria through the urethra. Infection arises from bacterial proliferation (growth) within the otherwise sterile urinary tract. In children, UTI occurs more commonly in boys up to the age of 12 months, but overall occurs about three times more often in girls (1% to 3% in boys, 3% to 7% in girls) (Hellstrom 1991; Winberg 1974).

Cranberries (particularly in the form of cranberry juice) have been used widely for several decades to prevent and treat UTIs. Cranberries comprise nearly 90% water, but also contain various organic substances such as quinic acid, malic acid and citric acid as well as glucose and fructose. Until recently, it was suggested that the quinic acid caused large amounts of hippuric acid to be excreted in the urine which then acted as an antibacterial agent (Kinney 1979). Several studies, however, have shown no difference in the levels, or only a transient effect thus casting some doubt on this theory (Kahn 1967; McLeod 1978). No definitive mechanism of action has been established for cranberry in the prevention or treatment of UTIs. However, research suggests that cranberries prevent bacteria (particularly Escherichia coli) from adhering to uroepithelial cells that line the wall of the bladder (Schmidt 1988; Zafriri 1989). Without adhesion, E. coli cannot infect the mucosal surface of the urinary tract. In vitro, this adhesion is mediated by two components of cranberry; fructose, which inhibits adherence of type 1 (mannose specific) fimbriated E. coli (Foo 2000; Howell 2007), and substances called proanthocyanidins (PAC), which inhibit the adherence of p‐fimbriated (a‐galactose‐(1‐4) specific) E. coli (Zafriri 1989). PAC have A‐ and B‐ type linkages but It is only the PAC which contain the A‐type linkages (found in cranberry juice) which have been associated with preventing adhesion of the E.coli to (Howell 2002; Howell 2005). PAC with B‐type linkages are found in a number of sources including commercial apple and grape juice, dark chocolate but these do not appear to have any anti‐adhesion effects (Howell 2005).

Cranberry products include juice, syrup, capsules and tablets. A commonly recommended amount for UTI prevention is daily consumption of 300 mL of cranberry juice co*cktail containing 36 mg PAC (Howell 2010). However, processing of cranberries into various products such as tablets or capsules can impact on the PAC composition (Howell 2010) which may result in products which contain little or no PAC ‐ the 'active' anti‐adhesion ingredient. In addition, the complexities of the PAC structures and A‐type linkages means that measurement of PAC content can often be erroneous and may not be reproducible (Prior 2010). To ensure potency in cranberry powders, levels of PAC must be quantified properly; and the 4‐dimethylaminocinnamaldehyde method is currently the most validated standard method for quantifying PAC in cranberry powders (Prior 2010). A randomised controlled trial (RCT) evaluating the dosage effect of cranberry powder found that to achieve a bacterial anti‐adhesion effect in urine, 36 mg of cranberry PAC equivalents/d is effective, but 72 mg may offer better protection in some cases. As the anti‐adhesion activity decreases over time, it is recommended that cranberries products should be consumed in the morning and in the evening (Howell 2010).

The aim of this review is to assess the effectiveness of cranberries in the prevention of UTIs in susceptible populations including children, women with recurrent UTIs, people with a neuropathic bladder, and older people.

The treatment of UTIs with cranberries is evaluated in another review by the same authors (New Reference).

Objectives

We wished to test the following hypotheses:

Cranberry juice/cranberry products are more effective than placebo/no treatment in the prevention of UTIs in susceptible populations.
Cranberry juice/ cranberry products are more effective than any other treatment in the prevention of UTIs in susceptible populations.
Different cranberry products (juice, capsules, tablets, concentrate) may differ in the effectiveness for preventing UTIs in susceptible populations

An attempt was also made to quantify the side effects of cranberry juice and the findings were taken into account in the discussion to determine the risk‐benefit of the treatment.

Methods

Criteria for considering studies for this review

Types of studies

All RCTs of cranberry juice (or derivatives) versus placebo, no treatment or any other treatment. Quasi‐RCTs (e.g. those studies which randomised participants by date of birth, or case record number) were included, but the quality of the studies was taken into account during the analysis and discussion. Both parallel group and cross‐over design were included.

Types of participants

Inclusion criteria

Studies of susceptible men, women or children as defined below. These categories were analysed separately.

Participants with a history of recurrent lower UTIs (more than two episodes in the previous 12 months)
Elderly men and women
Participants needing intermittent catheterization
Pregnant women
Participants with an in‐dwelling catheter
Participants with an abnormality of the urinary tract
Children with a first or subsequent UTI.

Exclusion criteria

Studies of the treatment of asymptomatic or symptomatic UTI (these are analysed in a separate review by the same authors New Reference).
Studies of any urinary tract condition not caused by bacterial infection (e.g. interstitial cystitis ‐ a chronic inflammation of the bladder wall).

Types of interventions

Cranberry juice or a cranberry product (e.g. cranberry capsules, tablets or extract) taken by participants for at least one month. The amount taken/d, concentration of the juice/cranberry product and length of treatment was also taken into account in subgroup analyses.

Types of outcome measures

Primary outcomes

Number (incidence) of UTIs in each group (confirmed by a catheter specimen of urine (CSU), midstream specimen of urine (MSU) if possible, or a 'clean catch' specimen).

The 'gold standard' bacteriological criteria for diagnosis of UTI includes microbiological confirmation from a MSU (or similar method) with greater than 100,000 bacterial cfu/mL, with some clinicians also requiring concurrent pyuria (white cells in the urine). In some situations a bacterial count < 100,000/mL is acceptable. For example, when a supra‐pubic bladder tap or a catheter urine specimen is obtained. If further studies become available for review, the method of collecting a specimen of urine, the causative organism (e.g. E. coli) and the presence of mixed organisms in the urine (which signifies contamination) will be subject to sensitivity analyses.

If further studies become available for review, this outcome will also be subgrouped into rate of symptomatic lower UTIs, rate of symptomatic upper UTIs (UTI plus fever) and rate of asymptomatic UTIs. Symptomatic is defined as having one or more or the following symptoms: dysuria, frequency, urgency or fever.

Methods used to diagnose upper and lower UTIs will also be subjected to sensitivity analysis if enough data is available.

Secondary outcomes

Adherence to therapy.
Side effects.

Search methods for identification of studies

Review update

We searched the Cochrane Renal Group's Specialised Register (4 June 2013) through contact with the Trials' Search Co‐ordinator using search terms relevant to this review.

The Cochrane Renal Group’s Specialised Register contains studies identified from:

Quarterly searches of the Cochrane Central Register of Controlled Trials CENTRAL;
Weekly searches of MEDLINE OVID SP;
Handsearching of renal‐related journals & the proceedings of major renal conferences;
Searching of the current year of EMBASE OVID SP;
Weekly current awareness alerts for selected renal‐journals;
Searches of the International Clinical Trials Register (ICTRP) Search Portal & ClinicalTrials.gov.

Studies contained in the Specialised register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of the Cochrane Renal Group. Details of these strategies as well as a list of handsearched journals, conference proceedings and current awareness alerts are available in the 'Specialised Register' section of information about the Cochrane Renal Group.

See Appendix 1 for search terms used in strategies for this review.

Initial search

Relevant studies were obtained from the following sources.

Registry of randomised studies for the Cochrane Collaboration Field in Complementary Medicine.
Companies involved with the promotion and distribution of cranberry preparations were approached and asked to provide information on both published and unpublished studies.
Electronic databases including Psycl*t, LILACS, CINAHL, Biological Abstracts, Current Contents. These databases were searched using the following terms*:

(beverages.sh. or cranberr$.ti,ab or fruit adj5 beverage$.ti,ab. or fruit adj5 drink$.ti,ab. or fruit adj5 juice$ or vaccinium macrocarpon.ti,ab. or vaccinium oxycoccus.ti,ab. or vaccinium vitis‐idaea.ti,ab.)
(UTIs.sh. or cystitis.sh. or bacteriuria.sh. or pyelonephritis.sh. or UTI$.ti,ab. or urinary adj5 infection$.ti,ab. or bacter$.ti,ab. or pyelonephrit$.ti,ab. or cystitis.ti,ab.)
1 and 2

The following terms were searched to identify non‐English language studies:

- Danish ‐ (Tranebaersaft.ti,ab. or tranebaer.ti,ab. or orkaempetranebaer.ti,ab. or store tranebaer.ti,ab. or cranberry.ti,ab.) and (urinvejsinfektion.ti,ab. or cystitis.ti,ab. or blaerebetaendelse.ti,ab. or pyelonephritis.ti,ab. or pyelonefrit.ti,ab.)
- Dutch ‐ (veenbes.ti,ab. or lepeltjeheide.ti,ab. or lepeltjesheide.ti,ab. or Amerikaanse veenbes.ti,ab. or cranberry.ti,ab.) and (cystitis.ti,ab. or catarrhus.ti,ab. or vesicalis.ti,ab. or blaasontsteking.ti,ab. or urineweginfectie.ti,ab. or pyelonephritis.ti,ab. or nephropyelitis.ti,ab.)
- French ‐ (canneberges ronce d'Amerique.ti,ab. or cranberry.ti,ab. or cranberrie.ti,ab.) and (cystite.ti,ab. or infection urinaire.ti,ab. or pyélonéphrite.ti,ab.)
- German ‐ (moosbeere.ti,ab or kranbeere.ti,ab.) and (zystitis.ti,ab. or cystitis.ti,ab. or harnwegsinfektion.ti,ab. or harninfekt.ti,ab. or pyelonephritis.ti,ab.)
- Italian ‐ (vaccinium oxycoccus.ti,ab. or ossicocco palustro.ti,ab.) and (cistite.ti,ab. or infezione del tratto urinario.ti,ab or infezione urinaria.ti,ab. or infezione delle vie urinarie.ti,ab. or pielonefrite.ti,ab. or nefropielite.ti,ab.)
- Portuguese ‐ (cranberry.ti,ab. or oxicoco$.ti,ab. or vaccinium oxycoccos.ti,ab. or oxycoccus palustris) and (cistite.ti,ab. or pielonefrite.ti,ab.)
- Spanish ‐ (arandano agrio.ti,ab or arandano americano.ti,ab.) and (cistitis.ti,ab. or infección urinaria.ti,ab or pielonefritis.ti,ab.)

The Internet was searched using the terms listed.
Reference lists of review articles and relevant studies were searched.
Conference abstracts from The Proceedings of the Urological Association (1990‐1998), and The Journal of the American Geriatrics Society (1990 ‐1998) were searched for relevant studies for the initial review. Handsearching was then undertaken by the Cochrane Renal Group.
The National Research Register was searched for studies currently underway.

Data collection and analysis

The search strategy described previously was employed to obtain titles and, where possible, abstracts of studies that were potentially relevant to the review. The titles and abstracts were screened by RJ and for the 2012 update, GW, who discarded studies that were clearly ineligible but aimed to be overly inclusive rather than risk losing relevant studies. Two authors independently assessed, using full copies of the papers, whether the studies met the inclusion criteria, with disagreements resolved by discussion. Further information was sought from the authors of those papers which contained insufficient information to make a decision about eligibility.

The quality of all studies which were deemed eligible for the review were then assessed independently by two authors, with discrepancies resolved by discussion. The 2012 update included Cochrane risk of bias assessments, these details were recorded by two authors (RJ and GW) and compared for discrepancies. Differences were resolved through discussion and a third author (JC) when necessary. Summary descriptors are provided in the additional tables (Table 1 ‐ Characteristics of studies;Table 2 ‐ Study design and quality of reporting).

1

Characteristics of studies

Stduy name	Year	N	Country	Setting	Participants	Intervention
Avorn 1994	1994	192	USA	Nursing homes	Elderly women, mean age 78.5 years	Cranberry juice co*cktail: 300 mL/d (30% cranberry concentrate) Placebo beverage PAC content: NS
Haverkorn 1994	1994	38	Netherlands	Hospital	Elderly men (9) and women (29), mean age 81 years	Cranberry juice: 15 mL, twice a day (30 mL cranberry juice/d, concentration not specified) PAC content: NS
Foda 1995	1995	40	Canada	Hospital clinic	Children with neuropathic bladder requiring clean intermittent catheterisation, mean age 9.35 years	Cranberry juice co*cktail: 15 mL/kg/d (30% cranberry concentrate) 3‐4 times a day PAC content: NS
Walker 1997	1997	19	USA	Family practice	Young women with recurrent UTI, median age 37 years	Cranberry capsules: 400 mg of cranberry solids (total amount/d: NS) PAC content: NS
Schlager 1999	1999	15	USA	Hospital clinic	Children with neuropathic bladder requiring clean intermittent catheterisation, aged 2‐18 years	Cranberry juice co*cktail: 300 mL/d (30% cranberry concentrate) PAC content: NS
Kontiokari 2001	2001	150	Finland	Student health service	Young women (mean age 29‐32 years) with previous UTI	Cranberry‐lingonberry juice: 50 mL once/d, 5 days/week (7.5 g cranberry concentrate) PAC content: NS
McGuiness 2002	2002	135	Canada	Outpatient clinic for MS patients	Patinets with multiple sclerosis	Cranberry tablet: 8000 mg, once/d (am) for 6 months PAC content: NS
Stothers 2002	2002	150	Canada	Unclear	Women with recurrent UTI (aged 21‐72 years)	Cranberry juice: 250 mL three times/d or one concentrated cranberry juice tablet twice daily (dose NS apart from 'at least 1:30 parts concentrated juice) PAC content: NS (study authors did not know if the product contained active PAC or not)
Linsenmeyer 2004	2004	21	USA	Urology rehabilitation clinic	Spinal cord injury patients with neuropathic bladders	Cranberry tablets: 1200 mg/d (3 x 400 mg tablets) PAC content: NS
Waites 2004	2004	48	USA	Hospital clinic	Spinal cord injury patients with neuropathic bladders	Cranberry juice capsule: 2000 mg/d PAC content: NS
McMurdo 2005	2005	376	Scotland	Hospital	Elderly inpatients	Cranberry juice: 300 mL once/d PAC concentration: 11.175 µg/g (dry solids basis)
Lee 2007	2007	305	Australia	Community	Spinal cord injury patients	Cranberry tablets: 1600 mg/d Methenamine hippurate tablet: 2 mg PAC content: NS
Wing 2008	2008	115	USA	Pre‐natal clinic	Pregnant women	Cranberry juice ‐ Group 2: 240 mL cranberry drink at breakfast, placebo juice at other meals ‐ Group 3: 240 mL cranberry juice 3 times/d (dosage changed throughout) Mean PAC content: 80 mg/240 mL
Hess 2008	2008	47	USA	SpInal cord injury patients in Veterans Admin Hospital	Spinal cord injury patients with neurogenic bladders	Cranberry tablet: 1000 mg/d (500 mg tablet) PAC concentration: NS
Ferrara 2009	2009	80	Italy	Paediatric nephrology ambulatory clinic	Girls with > 1 UTI in past year	Cranberry concentrate, 50 mL in 50 mL water Lactobacillus GG drink: 100 mL PAC content: NS
McMurdo 2009	2009	137	UK	Scottish primary care research network	Women ≥ 45 years with ≥ 2 UTIs in the previous 12 months	Cranberry tablet: 500 mg Antibiotic: 100 mg TMP PAC content: NS
Essadi 2010	2010	544	Unsure	Antenatal clinic	Pregnant women	Cranberry juice: 250 mL, 4 times/d PAC content: NS
PACS Study 2008	2010	56	USA	Nursing home	Elderly men and women (> 60 years) with dementia	Cranberry tablet: 1 x 650 mg or 2 x 1300 mg PAC content: NS
Salo 2010	2010	252	Finland	Hospital	Children with UTI	Cranberry juice: 5 mL/kg up to 300 mL PAC concentration: NS
Uberos 2010	2010	51	Spain	Unclear, possibly hospital	Children with UTI	Cranberry syrup: 0.2 mL/kg Antibiotic: 8 mg/kg TMP 'The concentration guarantees that 5 mL of the syrup contains 36 mg of highly bioactive PAC extracted from the cranberry syrup, measured by the BL‐DMAC method.'
Barbosa‐Cesnik 2011	2011	319	USA	University Health Service	Adult women with urinary symptoms	Cranberry juice: 2 x 240 mL (480 mL/d) PAC concentration: 112 mg (range 83–136 mg; SD 614.1 mg)
NAPRUTI Study 2011 I	2011	199	Netherlands	Primary care physicians	Adult women (premenopausal) with at least 3 UTIs in previous 12 months	Cranberry tablet: 2 x 500 mg/d Antibiotic: 480 mg TMP‐SMX Type A PAC in cranberry extract: 9.1 mg/g
Sengupta 2011	2011	57	India	Medical clinic	Adult women	Cranberry tablets: 500 mg/d or 1000 mg/d PAC content: 1.5%
Cowan 2012	2012	128	UK	Oncology unit	Adults with bladder or cervical cancer	Cranberry juice: twice daily, volume (NS), PAC concentration (NS)

Study name	Design	Study duration	Urine collection	Threshold	Other definitions	Allocation	Loss to follow‐up	Blinding	Intention‐to‐treat
Avorn 1994	Parallel	6 months	Voided	≥ 10⁸/L	Pyuria (not defined)	No (quasi‐RCT by ID or phone number)	39/192 (20%)	Participants: yes Investigators: yes	No
Haverkorn 1994	Cross‐over	4 weeks	NS	= 10⁸/L	NS	No (quasi‐RCT by date of birth)	21/38 (55%)	Unclear	Unclear
Foda 1995	Cross‐over	12 months (6 months of each treatment)	CSU	≥ 10⁸/L (1 or 2 organisms)	Symptoms (not defined)	Unclear	19/40 (47.5%)	Investigators: yes	Unclear
Walker 1997	Cross‐over	3 months	NS	NS	Symptoms present (not defined)	Unclear	9/19 (47.4%)	Participants: yes Investigators: yes	Unclear
Schlager 1999	Cross‐over	3 months	CSU	= 10⁷/L	Symptoms present (defined)	Yes, pharmacy	0/15 (0%)	Participants: yes Investigators: yes	Yes
Kontiokari 2001	Parallel, 3 groups	6 months	Voided	= 10⁸/L	Symptoms present (defined)	Yes, sealed opaque envelopes	13/150 (8.7%)	Unclear	Yes
McGuiness 2002	Parallel	6 months	Intermittent catheterisation or voided	≥ 10⁹/L	Leucocytes, blood or nitrite plus culture positive (symptoms may be unrecognised in these patients)	Unclear	3 lost to follow‐up, 9 withdrew	States double blinded, unsure who	Yes
Stothers 2002	Parallel, 3 group factorial design	12 months	Voided	= 10⁸/L	Symptoms present (undefined)	Yes, sealed envelopes	2/150 (1.3%)	Participants: yes Investigators: yes	Yes
Linsenmeyer 2004	Cross‐over	9 weeks	CSU or voided	= 10⁸/L	WBC count	Unclear	16/37	Participants: yes Investigators: yes
Waites 2004	Parallel	6 months	CSU or voided	= 10⁷/L	Symptoms (defined)	Unclear	26/74	Participants: yes Investigators: yes	No
McMurdo 2005	Parallel	6 months	Voided	= 10⁴/L	Symptoms present (not defined)	Yes, sealed envelopes	0/376	Participants: yes Investigators: yes	Yes
Lee 2007	Parallel, 4 group factorial design	6 months	CSU or reflex voided	≥ 10⁸/L	Symptoms present (defined)	External and robust	0/305	Participants: yes Investigators: yes Outcome assessors: yes	Yes
Wing 2008	Parallel, 3 groups	5‐7 months (to delivery)	Voided	≥ 10⁸/L	Symptoms (defined)	Unclear	0/115	Participants: yes Investigators: yes Outcome assessors: yes	Yes
Hess 2008	Cross‐over	6 months	Assume voided	≥ 10⁷ cfu/L	Symptoms (defined)	Yes, stated	10/57	Participants: yes Clinicians: yes	No
Ferrara 2009	Parallel, 3 groups	6 months	Voided	≥ 10⁸/L	Symptoms (defined)	Unclear	4/84 (5%)	Participants: no Investigators: unclear Outcome assessors: unclear	Unclear
McMurdo 2009	Parallel	6 months	Voided	≥ 10⁷/L	Symptoms (defined)	Externally managed, trial number given	0/137	Participants: yes Investigators: yes Outcome assessors: yes	Yes
Essadi 2010	Parallel	NS	Assume voided	NS	NS	NS	216/760	Participants: no Investigators: NS	Unclear
PACS Study 2008	Parallel, 3 groups	6 months	Assume voided	≥ 10⁸/L	NS	NS	2/56	Stated no blinding	No
Salo 2010	Parallel	6 months	NS	NS	NS	NS	11/263	Participants: yes Investigators: yes	Unclear
Uberos 2010	Parallel	when a UTI was recorded	Voided, MSU	= 10⁴/L	Symptoms	Yes, hospital pharmacy	6/198	Participants: yes Clinicians: yes	Yes
Barbosa‐Cesnik 2011	Parallel	6 months	Voided, MSU	≥ 10⁶ cfu/L	Symptoms (defined)	Yes, external	100/419	Participants: yes Investigators: yes Outcome assessors: yes	Yes
NAPRUTI Study 2011 I	Parallel	12 months	Voided	≥ 10⁶ cfu/L	Symptoms (not defined)	Yes	22/221	Participants: yes Investigators: yes Outcome assessors: yes	Unclear
Sengupta 2011	Parallel, 3 groups	90 days	Voided, MSU	≥ 10⁷ cfu/L	Symptoms (not defined)	Yes, sealed pre prepared envelopes	3/60	High and low dose participants: yes 'no treatment' participants: no Investigators: no	Unclear
Cowan 2012	Parallel	6 weeks	Voided	≥ 10⁸/L	Symptoms (not defined)	Unclear	15/128	Participants: yes Clinicians: yes Outcome assessors: unclear	Yes

Study name	Pre cross‐over	P value	End of study data	P value	Notes
Schlager 1999	Cranberries: 85/97 Placebo: 33/55	NS	Cranberries: 120/160 (75%) Placebo 114/151 (75%)	NS
Haverkorn 1994	NS	NS	NS	P = 0.004	Actual number of people in each group: NS
Avorn 1994	N/A	N/A	Cranberries: 20/473 (4%) of the urine samples Placebo: 7% (37/498)	(P = not significant)
Foda 1995	NS	NS	Cranberry: 27/112 months (24.1%) Placebo: 34/117 months (29%)	NS	Outcome was months with positive/significant culture but no UTI symptoms
Linsenmeyer 2004	NS	NS	NS	NS	The authors report that, 'We failed to find a statistically significant treatment effect for the cranberry tablets beyond the placebo effect when evaluating urinary bacterial count (t20 = ‐0.05, P = 0.96), urinary WBC (t20 = 1.14, P = 0.27), or urinary bacterial and WBC in combination (t20 = 1.14, P = 0.27)"
Wing 2008	N/A	N/A	Cranberry, 1 dose: 5/67 Cranberry 2‐3 doses: 2/58 Placebo; 7/63	NS	This data are for asymptomatic UTI specifically
Hess 2008	NS	NS	Cranberry: 31 positive culture episodes Placebo: 37 positive culture episodes	P = 0.52	This study reported symptomatic and positive culture results
PACS Study 2008	N/A	N/A	Cranberry, 1 dose: 13/20 Cranberry, 2 doses: 14/19 No treatment: 12/17	NS
Uberos 2010	N/A	N/A	Cranberry: 8/23 Antibiotic: 15/28	NS	In this report (abstract only) it isn't clear if the repeat UTI was symptomatic or a positive culture result

Date	Event	Description
2 April 2013	Amended	Minor spelling corrections made throughout
14 September 2012	New citation required and conclusions have changed	Updated the review in 2012 with 14 new studies. Conclusions have changed to say that the evidence suggests that cranberry products are not effective in preventing UTIs.
13 August 2009	Amended	Contact details updated.
13 May 2009	Amended	Contact details updated.
23 September 2008	Amended	Converted to new review format.
10 September 2007	New citation required and conclusions have changed	Substantive amendment

Database	Search terms used
CENTRAL	MeSH descriptor Beverages, this term only in MeSH products MeSH descriptor Fruit, this term only in MeSH products cranberr* in All Fields in all products fruit near beverage* in All Fields in all products fruit near drink* in All Fields in all products fruit near juice* in All Fields in all products MeSH descriptor Phytotherapy, this term only in MeSH products MeSH descriptor Vaccinium macrocarpon, this term only in MeSH products MeSH descriptor Vaccinium vitis‐idaea, this term only in MeSH products vaccinium oxycoccus in All Fields in all products vaccinium vitis‐idaea in All Fields in all products (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11) MeSH descriptor Urinary Tract Infections explode all trees in MeSH products MeSH descriptor Pyelonephritis explode all trees in MeSH products MeSH descriptor Cystitis explode all trees in MeSH products uti in All Fields in all products bacter* in All Fields in all products cystitis in All Fields in all products pyelonephritis in All Fields in all products MeSH descriptor Urine, this term only in MeSH products (urin* near infect*) in All Fields in all products (#13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21) (#12 AND #22)
MEDLINE	Beverages/ FRUIT/ cranberr$.tw. (fruit adj5 beverage$).tw. (fruit adj5 drink$).tw. (fruit adj5 juice$).tw. PHYTOTHERAPY/ Vaccinium macrocarpon/ vaccinium oxycoccus.tw. vaccinium vitisidaea.tw. or/1‐10 urinary tract infections/ or bacteriuria/ or pyuria/ PYELONEPHRITIS/ cystitis/ or cystitis, interstitial/ urine/ uti.tw. cystitis.tw. pyelonephritis.tw. bacter$.tw. (urinary adj5 infection$).tw. or/12‐20 11 and 21
EMBASE	fruit juice/ cranberr$.tw. (fruit adj5 beverage$).tw. (fruit adj5 drink$).tw. (fruit adj5 juice$).tw. vaccinium macrocarpon.tw. vaccinium vitisidaea.tw. vaccinium oxycoccus.tw. or/1‐8 Urinary Tract Infection/ pyelonephritis/ or acute pyelonephritis/ or chronic pyelonephritis/ exp Cystitis/ Bacteriuria/ ASYMPTOMATIC BACTERIURIA/ uti.tw. cystitis.tw. pyelonephritis.tw. bacteriuria.tw. (urinary adj5 infection$).tw. or/10‐19 9 and 20

Potential source of bias	Assessment criteria
Random sequence generation Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence	Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random).
	High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
	Unclear: Insufficient information about the sequence generation process to permit judgement.
Allocation concealment Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment	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 allocation, including telephone, web‐based, and pharmacy‐controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).
	High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment 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 number; any other explicitly unconcealed procedure.
	Unclear: Randomisation stated but no information on method used is available.
Blinding of participants and personnel Performance bias due to knowledge of the allocated interventions by participants and personnel during the study	Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome 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.
	High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
	Unclear: Insufficient information to permit judgement
Blinding of outcome assessment Detection bias due to knowledge of the allocated interventions by outcome assessors.	Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
	High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be 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 Attrition bias due to amount, nature or handling of incomplete outcome data.	Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed 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 induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible 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 Reporting bias due to selective outcome 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; the study protocol is not available but it is clear that the published reports include all expected outcomes, 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 cannot 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 Bias due to problems not covered elsewhere in the table	Low risk of bias: The study appears to be free of other sources of bias.
	High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data‐dependent process (including a formal‐stopping rule); had extreme baseline 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 rationale or evidence that an identified problem will introduce bias.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Participants with one or more UTIs at follow‐up	13	2462	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.71, 1.04]
1.1 Women with recurrent UTIs	4	594	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.42, 1.31]
1.2 Elderly men and women	2	413	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.39, 1.44]
1.3 People with neuropathic bladder/spinal injuries	2	353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.75, 1.20]
1.4 Pregnant women	2	674	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.93, 1.17]
1.5 Children	2	309	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.19, 1.22]
1.6 Radiotherapy patients	1	119	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.75, 1.77]
2 Adverse effects	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.1 Stomach burn and general weakness	1	34	Risk Ratio (M‐H, Random, 95% CI)	0.13 [0.01, 2.46]
2.2 Vomitting	1	37	Risk Ratio (M‐H, Random, 95% CI)	6.0 [0.33, 108.56]
2.3 Nausea	2	187	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.23, 3.94]
2.4 Diarrhoea	1	37	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.06, 12.59]
2.5 Gastroenteritis	2	413	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.10, 1.96]
2.6 Any gastrointestinal effect	4	597	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.31, 2.27]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Repeat symptomatic UTI	3	536	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.79, 1.73]
1.1 Adult women	2	344	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.85, 2.02]
1.2 Children	1	192	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.32, 1.51]
2 Adverse effects	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.1 Gastrointestinal	2	344	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.42, 1.42]
2.2 Rash or urticaria	1	207	Risk Ratio (M‐H, Random, 95% CI)	0.54 [0.25, 1.18]
2.3 vagin*l	1	207	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.40, 1.40]
2.4 Allergic reaction	1	207	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.01, 7.28]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic UTI	3	208	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.75, 1.68]
1.1 Pregnant women	1	125	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.17, 7.94]
1.2 Adult women	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.14, 5.92]
1.3 Elderly men and women	1	39	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.75, 1.72]
2 Adverse effects	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
2.1 Weakness and abdominal pain	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 Mild fever	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.3 Heart burn	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.4 Stomach burn and general weakness	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic UTI	2	152	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.24, 0.74]
1.1 Children with previous UTI	1	53	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.18, 1.09]
1.2 Adult women	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.20, 0.85]

Methods	Study design: quasi‐RCT Power calculation: Yes Intention‐to‐treat analysis: No
Participants	Inclusion criteria Setting: Recruited from a single long‐term care facility for the elderly, and 9 housing complexes for the elderly Country: USA Not clearly stated, but participants had to be willing to ingest at least 300 mL of cranberry juice daily for a 6 month period. Number: 192 randomised, 153 analysed Mean age: 78.5 years Exclusion criteria Terminal disease or severe dementia; men
Interventions	Treatment group Cranberry juice co*cktail: 300 mL/d (30% cranberry concentrate) PAC content: NS Control group Placebo beverage that looked and tasted similar but contained no cranberry juice Treatment duration: 6 months
Outcomes	Presence of bacteriuria (bacteria in the urine ≥ 100,000/mL) with the presence of pyuria (white cells in the urine) Presence of bacteriuria Presence of bacteriuria with the presence of pyuria plus symptoms of a UTI
Notes	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: mid‐stream clean‐voided Definition of bacteriuria: organisms ≥ 100,000/mL regardless of organism Definition of pyuria: NS Exclusions post randomisation: None
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Odd versus even numbers in institutional identification number or telephone number (quasi‐RCT)
Allocation concealment (selection bias)	High risk	Inadequate, could subvert system by excluding people with certain number, or include more of those with a certain number
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding stated
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	NS
Incomplete outcome data (attrition bias) All outcomes	High risk	Absolute numbers not always provided; 39 patients lost to follow‐up/withdrawn
Selective reporting (reporting bias)	Low risk	Primary outcome is reasonable though symptomatic would be better
Other bias	High risk	Source of funding: Research grant from Ocean Spray Cranberries, Inc.

Methods	Study design: parallel RCT Power calculation: yes Intention‐to‐treat analysis: no
Participants	Inclusion criteria Setting: Women presenting to a health service with symptoms of UTI Country: USA Women 18‐40 years, with UTI symptoms, residing in Ann Arbor next 6 months Number: 419 randomised; 319 analysed Average age: 21 years Previous UTIs: 3‐4 previously; 1 in previous year Exclusion criteria Antibiotics in past 48 hours; hospitalisation or catheterisation within past 2 weeks; kidney stones; diabetes; pregnancy; cranberry allergy; negative urine culture
Interventions	Treatment group Low calorie cranberry co*cktail: 240 mL (8 oz) twice a day Mean PAC: 112 mg/240 mL Control group Placebo drink: same volume matched for flavour and colour Treatment duration: 6 months
Outcomes	Primary outcome: UTI (≥ 10³ cfu/L of known pathogen) Secondary outcome: urinary symptoms and vagin*l symptoms at day 3, 1‐2 weeks, and ≥ 1 month
Notes	Compliance measured by direct questioning
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated
Allocation concealment (selection bias)	Low risk	External, web based allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo drink matched, participants and clinicians blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	NS
Incomplete outcome data (attrition bias) All outcomes	High risk	100 participants randomised but no outcomes reported for them, they were actually not eligible to be randomised since they were culture negative
Selective reporting (reporting bias)	Low risk	UTI is most appropriate outcome
Other bias	High risk	Selection bias, representative nature of consenters is questionable Source of funding: National centre for alternative medicine at NIH

Methods	Study design: parallel design Power calculation: provided, assumed 20% reduction in bladder problems Intention‐to‐treat analysis: yes
Participants	Inclusion criteria Setting: radiotherapy booking system used to identify patients, patients had cervical cancer or bladder cancer at 1 centre Country: UK Adults > 18 years with cervical or bladder cancer requiring radiation therapy Number: 128 randomised; 113 analysed (7 in placebo arm, 8 in cranberry arm) Exclusion criteria: NS
Interventions	Treatment group Cranberry juice twice/d; volume (NS); PAC (NS) Control group Matched placebo juice twice/d; volume (NS)
Outcomes	Urinary symptoms
Notes	Exclusions post randomisation: 0
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer based deterministic minimisation algorithm, externally allocated
Allocation concealment (selection bias)	Low risk	Computer algorithm generated a blinded juice pack
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blinding stated, patients blinded to treatment arm, clinicians blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	For UTI outcome probably low risk, microbiology results independent
Incomplete outcome data (attrition bias) All outcomes	Low risk	Very little missing data
Selective reporting (reporting bias)	Low risk	Urinary symptoms and UTI
Other bias	Low risk	Source of funding: west Research Endowment fund, NHS greater Glasgow and Clyde, Juice and placebo supplied by Ocean Spray

Methods	Study design: parallel 3 arm RCT Power calculation: no Intention‐to‐treat analysis: no
Participants	Inclusion criteria Setting: ambulatory paediatric nephrology clinic; single centre Country: Italy Girls 3‐14 years attending an ambulatory paediatric nephrology clinic; more than 1 UTI in previous 12 months Number: 84 randomised; 80 analysed Mean age: 7.5 years Exclusion criteria Structural abnormalities; deformities of the urinary tract; impaired kidney function
Interventions	Treatment group Cranberry‐lignoberry concentrate Cranberry concentrate: 50 mL/d for 6 months (97.5 g cranberry concentrate) Ligonberry concentrate: 1.7 g in 50 mL water No sugar additives Lactobacillus GG drink: 100 mL on 5 days each month for 6 months (contains 4 x 10⁷ cfu/100 mL) Control group No treatment
Outcomes	Symptomatic UTI (symptoms being frequency, dysuria, urgency, haematuria, nocturia, fever, back or hip pain and ≥ 10⁸ cfu/L
Notes	Exclusions post randomisation: 0
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random numbers table
Allocation concealment (selection bias)	Unclear risk	No details on how well allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	No, girls knew what treatment they were taking
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details stated
Incomplete outcome data (attrition bias) All outcomes	High risk	Those lost to follow‐up were excluded, no analysis of best and worst case scenarios Losses to follow‐up/withdrawals: 4
Selective reporting (reporting bias)	Low risk	Appropriate outcome
Other bias	Unclear risk	Details on patients are limited, selection bias may be present Source of funding: NS

Methods	Design: Cross‐over RCT Power calculation: No Intention‐to‐treat analysis: No
Participants	Inclusion criteria Setting: Outpatients’ residence at a distance not exceeding 150 km from the Children’s Hospital of Eastern Ontario Country: Canada Children with neuropathic bladder and managed by clean intermittent catheterisation Number: 40 randomised; 21 analysed Age range (mean): 1.4 to 18 years (9.35 years) Exclusion criteria: NS
Interventions	Treatment group Cranberry co*cktail: 15 mL/kg/d (30% cranberry concentrate) Control group Water Duration of treatment: 6 months
Outcomes	Number of months of positive cultures plus a symptomatic UTI Number of months of positive cultures plus an asymptomatic UTI Side effects and compliance
Notes	Exclusions post randomisation: none Method of collection urine Sterile catheter urine samples Definition of bacteriuria ≥ 100,000 cfu/L of a pathogenic organism after 24 hours incubation Any growth in a symptomatic patient was considered significant
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	NS
Allocation concealment (selection bias)	Unclear risk	NS
Blinding of participants and personnel (performance bias) All outcomes	High risk	Unable to blind participants; blinding of physician only
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	NS
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses to follow‐up/withdrawals: 19
Selective reporting (reporting bias)	Unclear risk	Not enough detail
Other bias	Unclear risk	Not enough detail Source of funding: NS

Methods	Study design: cross‐over RCT Power calculation: yes Intention‐to‐treat analysis: no
Participants	Inclusion criteria Setting: spinal cord injury service in Veterans Admin Hospital; single centre Country: USA Number: 57 randomised; 47 analysed Median age: 53 years Sex (M/F): all men Exclusion criteria Spinal cord injury duration < 12 mo; GFR < 30 mL/min; immunosuppression; current malignancy
Interventions	Treatment group Cranberry tablet: 500 mg twice daily Control group Placebo tablet: rice flour, matched to cranberry tablet
Outcomes	Primary outcome: symptomatic UTI Secondary outcome: significant bacteriuria; at least 1 UTI over 6 months; rate of UTI/person‐years
Notes	Cross‐over design without data on 1st phase being separate, not analysed
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No method reported
Allocation concealment (selection bias)	Low risk	Concealed, managed by the pharmacy
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding stated
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Unsure if outcome assessors blind, but all others were and outcome is objectively measured
Incomplete outcome data (attrition bias) All outcomes	High risk	10 patients lost to follow‐up and no details provided
Selective reporting (reporting bias)	Low risk	Appropriate outcome
Other bias	Low risk	No apparent additional bias Source of funding: NS

Methods	Study design: parallel 3‐arm RCT Power calculation: yes, but recruitment stopped before appropriate number recruited Intention‐to‐treat analysis: yes
Participants	Inclusion criteria Setting: Finnish student health service; single centre Country: Finland Women who had a UTI caused by E. coli (10⁵ cfu/mL in clean voided MSU) and were not taking antimicrobial prophylaxis. Number: 150 randomised/analysed Mean age: 29‐32 years Exclusion criteria: NS
Interventions	Treatment group 1 Cranberry‐lingonberry juice concentrate (Maija, Marli, Finland): 50 mL/d Cranberry concentrate: 7.5 g Lingonberry concentrate: 1.7 g Water: 50 mL with no added sugars Treatment group 2 Lactobacillus GG drink (Gefilus, Valio, Finland): 100 mL for five days a week Control group No intervention Duration of treatment: 6 months cranberry‐lingonberry concentrate; 12 months lactobacillus
Outcomes	First recurrence of symptomatic UTI
Notes	Method of obtaining urine sample: clean voided MSU specimen Definition of bacteriuria Bacterial growth 10⁵ cfu/mL 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. Exclusions post randomisation: none
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Tables of random numbers and block technique with block size of 6
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes (additional information provided by authors)
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and physicians not blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Lab staff blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses to follow‐up/withdrawals: 13. Analysed drop outs and withdrawals
Selective reporting (reporting bias)	Low risk	Appropriate outcomes
Other bias	Unclear risk	Uncertain about selection bias, few details Source of funding: Emil Aaltonen, Juho Vainio, and Alma and K A Snellman Foundations

Methods	Study design: 4 group factorial design, parallel RCT Power calculation: yes Intention‐to‐treat analysis: yes
Participants	Inclusion criteria Setting: spinal cord injuries database, predominantly community dwelling patients Country: Australia Spnal cord injured people with neurogenic bladder, bladder management with either indwelling urethral or suprapubic catheter, intermittent catheterization, or reflex voiding with or without a condom drainage divide, absence of complex urological or serious renal or hepatic pathology, not being prescribed antibiotics at the time of enrolment and absence of symptoms of a UTI at enrolment. Had to be willing to stop any intercurrent urinary antiseptics before entering the study, Number: 305 randomised/analysed Mean age: 43.5 years Sex: 253 males Exclusion criteria Previous allergy to any of the test interventions
Interventions	Treatment group 1 Methenamine hippurate: 2 g Cranberry: 1600 mg Treatment group 2 Methenamine hippurate: 2 g Cranberry placebo Treatment group 3 Cranberry: 1600 mg Methenamine hippurate placebo Control group Methenamine hippurate placebo Cranberry placebo
Outcomes	Symptomatic UTI: current criteria for treating patients in the spinal injured population
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Dynamically balanced, centralized randomisation performed externally
Allocation concealment (selection bias)	Low risk	External trial centre controlled, sent to pharmacy
Blinding of participants and personnel (performance bias) All outcomes	Low risk	States all staff and participants were blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	States all staff were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	All accounted for in results
Selective reporting (reporting bias)	Low risk	Well described
Other bias	Low risk	No other bias apparent, well reported study Source of funding: Motor accidents authority and Brucia Pharmaceuticals

Methods	Study design: parallel group Power calculation: yes Intention‐to‐treat analysis: yes
Participants	Inclusion criteria Setting: single centre Country: UK (Scotland) 60 years or over admitted to either acute medicine for the elderly assessment or rehabilitation units for elderly people Number: 376 randomised and analysed Exclusion criteria Mental State Questionnaire (MSQ) score < 5/10; dysphagia; symptoms of a UTI; antibiotic treatment; anticipated length of stay < 1 week; regular drinkers of cranberry juice; presence of an in‐dwelling catheter; terminal 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.
Interventions	Treatment group Cranberry juice: 300 mL Control group Matching placebo beverage Duration of treatment: 6 months
Outcomes	Time to onset of first symptomatic UTI: defined as a culture positive urine growing a single organism of > 10⁴ cfu/mL urine specimen Adherence to beverage drinking, courses of antibiotics prescribed, and organisms responsible for UTIs
Notes	Exclusions post randomisation: none Method of obtaining urine sample: clean catch Definition of bacteriuria Only pure growths of ≥ 10⁴ cfu/mL were reported with an antibiotic sensitivity
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Stratified by gender and computer generated
Allocation concealment (selection bias)	Low risk	Held by pharmacy, sealed numbered enveloped
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding stated
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding stated
Incomplete outcome data (attrition bias) All outcomes	Low risk	All patients analysed and reported; Losses to follow‐up/withdrawals: 115
Selective reporting (reporting bias)	Low risk	Appropriate clinical outcomes
Other bias	Low risk	No other bias apparent, well reported study Source of funding: Chief Scientist Office at the Scottish Executive Department of Health. The cranberry juice and matching placebo were supplied by Ocean Spray Cranberries, Inc.

Methods	Study design: 3‐arm parallel RCT Power calculation: no Intention‐to‐treat analysis: appears all were included
Participants	Setting: 4 dementia units Country: USA Elderly mean and women > 60 years of age with dementia and a resident of a nursing home or assisted living facility for > 30 days Number: 56 randomised and analysed
Interventions	Treatment group 1 Cranberry capsule: 1 x 650 mg once daily Treatment group 2 Cranberry capsule: 1 x 650 mg twice daily Control group No treatment
Outcomes	Number of urine cultures collected Number of participants with E.coli isolated from urine culture Number of participants with > 100,000 cfu/mL if any organism
Notes	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
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details on this aspect
Allocation concealment (selection bias)	Unclear risk	Open label study, could be possible to subvert randomisation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open label
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Expected number of urine samples was less than expected. Losses to follow‐up/withdrawals: 2 lost and 28 did not complete treatment
Selective reporting (reporting bias)	Unclear risk	Outcomes are about feasibility not efficacy
Other bias	Unclear risk	Many details missing or poorly detailed Source of funding: NS

Methods	Study design: 3‐arm RCT Power calculation: no, feasibility pilot Intention‐to‐treat analysis: yes
Participants	Inclusion criteria Setting: 2 centres Country: USA Women < 16 weeks gestation presenting for prenatal care at 1 of 2 centres Number: 188 randomised and analysed Exclusion criteria Underlying medical conditions (e.g. diabetes mellitus, kidney failure, sickle cell disease, chronic hypertension, chronic kidney disease) previous or current antimicrobial therapy; known urological abnormalities
Interventions	Treatment group 1 Cranberry juice: 240 mL at breakfast, placebo juice at other meals Treatment group 2 Cranberry drink: 240 mL, 3 times/d, reducing to twice/d after 52 enrolments because not well tolerated Control group Placebo: 3 daily doses of matched juice product
Outcomes	Primary outcome: asymptomatic bacteriuria, > 10⁸ cfu of a single organism and no symptoms Secondary outcomes Symptomatic bacteriuria, > 10⁸ cfu of single organism and dysuria or frequency or urgency Pyelonephritis, culture as above, + flak pain, fever > 100.4°F, chills nausea, vomiting At least 1 UTI, UTI due to enteric bacteria, Pregnancy outcomes: preterm delivery, spontaneous vaginl delivery, instrumental vaginl 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
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated randomisation table, stratified by site
Allocation concealment (selection bias)	Low risk	Treatment options were not known to researchers
Blinding of participants and personnel (performance bias) All outcomes	Low risk	States all were blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Clearly stated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data are well reported for completeness Losses to follow‐up/withdrawals: 73 withdrawals
Selective reporting (reporting bias)	Low risk	Appropriate outcomes
Other bias	Low risk	Details suggest free of bias, although selection methods a little unclear Source of funding: NS

Cranberries for preventing urinary tract infections (2024)

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Background

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Inclusion criteria

Exclusion criteria

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Review update

Initial search

Data collection and analysis

1

2

3

4

Results

Description of studies

Included studies

Types of participants

Participants with a history of recurrent lower UTIs or young women with an uncomplicated UTI

Elderly men and women

Participants (adults and children) needing catheterisation (intermittent or indwelling)

Pregnant women

Children at risk of repeat UTI

Other populations

Dosage, concentration and formulation of cranberries

Cranberry juice or cranberry concentrate

Cranberry capsules or tablets

Outcome measures

Excluded studies

Risk of bias in included studies

Allocation

Random sequence generation

Allocation concealment

Blinding

Incomplete outcome data

Selective reporting

Withdrawals, losses to follow‐up and intention‐to‐treat

Effects of interventions

Cranberry product compared with placebo or no treatment

Overall

Women with a recurrent UTI

Older men and women

Participants (adults and children) needing catheterisation (intermittent or indwelling)

Pregnant women

Children with a susceptibility to UTIs

Other populations

Cranberry product compared with antibiotic prophylaxis

Low (1 dose) versus high (≥ 2 doses) dose cranberry product

High dose cranberry versus placebo

Cranberry versus complementary therapies

Adverse effects

Adherence to therapy

Withdrawals and losses to follow‐up

Cost effectiveness

Discussion

Summary of main results

Overall completeness and applicability of evidence

Quality of the evidence

Potential biases in the review process

Agreements and disagreements with other studies or reviews

Authors' conclusions

Implications for practice

Implications for research

What's new

Study	Reason for exclusion
Howell 2010	No clinically relevant outcomes, only laboratory measures
Jackson 1997	RCT of elderly people looking at the effect of cranberry juice on urinary acidity. No relevant outcomes reported.
Jass 2009	No clinically relevant outcomes, laboratory measures of urine chemistry
Lavigne 2008	No clinically relevant outcomes, only laboratory measures of urine kinetics
Schultz 1984	RCT, (placebo controlled) of eight subjects with multiple sclerosis. Only randomised to 20 days of treatment. The inclusion criteria for this review was a minimum length of treatment of one month. Furthermore, number of UTIs was not a primary outcome and only descriptively reported.
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

Methods	Not clear
Participants	Men with prostate cancer undergoing radiotherapy
Interventions	Cranberry extract
Outcomes	UTIs
Notes	Abstract only

Methods	RCT
Participants	Women who have had a UTI within the past year
Interventions	Cranberry juice co*cktail
Outcomes	Rate of UTIs
Notes	Study completed in 2009: no publications

Trial name or title	Dose response to cranberry of women with recurrent UTIs
Methods	RCT
Participants	Women with recurrent UTIs
Interventions	Cranberry juice
Outcomes	UTIs
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 participants'.

Trial name or title	Prospective, randomized, double‐blind, placebo‐controlled study on parallel groups evaluating the efficacy and safety of cranberry (Vaccinium macrocarpon) in prevention of urinary tract infections in multiple sclerosis patients
Methods	RCT
Participants	Patients with multiple sclerosis
Interventions	Dry essence of cranberry presented as 18 mg of PAC sachets of powdered cranberry. Cranberry juice is administered twice a day (in the morning and in the evening).
Outcomes	Time to onset of a first UTI within one year of treatment
Starting date	2006
Contact information	Philippe Gallien, http://clinicaltrials.gov/ct2/show/NCT00280592
Notes	Study completed February 2008: no publications

Trial name or title	Pilot study: Dosing study of cranberry capsules for the prevention of bacteriuria in nursing home residents
Methods	RCT
Participants	Females at least 65 years of age or older who live in a nursing home and who have a history of UTIs
Interventions	Different doses of cranberry capsules
Outcomes	Time to onset of first UTI
Starting date	2009
Contact information	http://clinicaltrials.gov/ct2/show/NCT01033383
Notes	Should completed December 2010: no publications