Abstract
Background
Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections.
Objectives
To assess the effectiveness of cranberries for the treatment of UTIs.
Search methods
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 August 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 Portal (ICTRP) Search Portal and ClinicalTrials.gov.
Selection criteria
All randomised controlled trials (RCTs) or quasi‐RCTs of cranberry juice or cranberry products for the treatment of UTIs. Studies of men, women or children were to be included.
Data collection and analysis
Titles and abstracts of studies that were potentially relevant to the review were screened and studies that were clearly ineligible were discarded. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility.
Main results
No studies were found that fulfilled all of our inclusion criteria. Seven studies were excluded because they were the wrong study design, mixed interventions or did not report any relevant outcomes. One study is ongoing; however, its current status is unknown.
Authors' conclusions
After a thorough search, no RCTs which assessed the effectiveness of cranberry juice for the treatment of UTIs were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of UTIs. Well‐designed parallel‐group, double‐blind studies comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating UTIs are needed. Outcomes should include a reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. The dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these studies.
Keywords: Child, Female, Humans, Male, Beverages, Kidney, Phytotherapy, Randomized Controlled Trials as Topic, Urinary Tract Infections, Urinary Tract Infections/drug therapy, Urinary Tract Infections/prevention & control, Vaccinium macrocarpon
Plain language summary
Still waiting for evidence about whether cranberries are useful for treating urinary tract infections
Cranberries contain a substance that can prevent bacteria from sticking to the walls of the bladder. This may help reduce bladder and other urinary tract infections (UTIs). Cranberries (usually as cranberry juice) have been used to try and treat UTIs, particularly in high‐risk groups such as older people. Cranberries have few adverse effects. This review found no studies reporting the effects of cranberry juice or other cranberry products on the treatment of UTIs.
Background
Description of the condition
The term urinary tract infection (UTI) refers to the presence of a certain threshold number of bacteria in the urine (usually greater than 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, and occasionally haematuria (blood in the urine), and is often associated with pyuria (urine white cell count > 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 most commonly occurs 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, and 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 (e.g. those with cancer or AIDS). Some people have recurrent UTIs with an average of two to three episodes/year (Roberts 1979; Wong 1984). Children typically present with a high fever and systemic symptoms such as lethargy (tiredness), vomiting and poor feeding.
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 tract UTI) has been estimated to occur in up to 30% of women at some stage during their lives (Kelly 1977). Most UTIs arise from the 'ascending' route of infection. The first step is the 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 6 to 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).
Description of the intervention
Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of UTIs. Cranberries contain quinic acid, malic acid and citric acid as well as glucose and fructose.
How the intervention might work
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 (short‐lived) effect, thus casting some doubt on this theory (Kahn 1967; McLeod 1978). More recently, it has been demonstrated that cranberries prevent bacteria (particularly Escherichia coli) from adhering (sticking) to uroepithelial cells that line the wall of the bladder (Schmidt 1988; Sobota 1984). Cranberries contain two compounds which inhibit adherence ‐ fructose and a polymeric compound of unknown nature (Zafriri 1989). Although many juices contain fructose, only cranberries and blueberries contain the polymeric compound (Ofek 1991).
Why it is important to do this review
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). Traditionally UTIs have been treated by antibiotic therapy, but these are expensive, can have side effects and may lead to resistance. The aim of this review is to assess the effectiveness of cranberries in treating symptomatic and asymptomatic UTIs. Although cranberry juice is the form of cranberries most widely used, other cranberry products include cranberry powder in hard or soft gelatin capsules. The amount and concentration of cranberry juice needed to be effective for the treatment of UTIs have not yet been ascertained. One uncontrolled trial, however, found that over 50% of patients had a positive clinical response after consuming 450 mL of cranberry juice for three weeks (Papas 1966).
Cranberries for the prevention of UTIs in susceptible populations have been examined in another review by the same authors (Williams 2023).
Objectives
We wished to test the following hypotheses:
Cranberry juice and other cranberry products are more effective than placebo or no treatment for the treatment of UTIs.
Cranberry juice and other cranberry products are more effective than any other therapy for the treatment of UTIs.
Quantify the side effects of cranberry juice, and the findings will be taken into account in the discussion to determine the benefit‐risk of the treatment.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials (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) will be included, but the quality of the studies will be taken into account during the analysis. Cross‐over studies will be excluded because they are not appropriate for short‐term treatment of acute conditions.
Types of participants
Inclusion criteria
Studies of men, women or children with one of the following.
Symptomatic lower UTI
Symptomatic upper UTI
Asymptomatic UTI.
Symptomatic is defined as having one or more of the following symptoms: dysuria, frequency, urgency.
Studies of participants with either a history of recurrent UTIs or an in‐dwelling catheter must have specified that participants have a confirmed UTI (asymptomatic or symptomatic) prior to randomisation.
If studies become available for inclusion in this review, these three groups will be analysed separately. Furthermore, the causative organism (e.g. E. coli) and the methods used to diagnose upper and lower UTIs will be subjected to sensitivity analysis.
The participants in the studies can be from any setting (hospital, clinic, community).
Exclusion criteria
Studies of the prevention of UTIs in susceptible groups of the population (these will be analysed in a separate review by the same authors)
Studies of any urinary tract condition not caused by a bacterial infection (e.g. interstitial cystitis, which is a chronic inflammation of the bladder wall).
Types of interventions
Cranberry juice or a cranberry product (e.g. cranberry capsules) given for at least five days. If studies become available for inclusion in this review, dosage (amount and concentration), duration of treatment and length of treatment will be taken into account in subgroup analyses (see methods section for more details).
Types of outcome measures
Primary outcomes
Number of symptomatic and asymptomatic UTIs in each group at the end of the treatment period.
The 'gold standard' bacteriological criterion for diagnosis of UTI includes microbiological confirmation from a mid‐stream specimen of urine (MSU) (or similar method) with greater than 100 000 bacterial CFU/mL, often associated with pyuria (white cells in the urine). In some situations, a bacterial count < 100 000/mL is acceptable (e.g. when a supra‐pubic bladder tap or a catheter urine specimen is obtained). If studies become available for inclusion in this review, sensitivity analyses will be carried out on the causative organism (e.g. E. coli), the method of collecting a specimen of urine (i.e. catheter, MSU or 'clean catch' specimen) and the presence of mixed organisms in the urine (which signifies contamination).
Secondary outcomes
Reduction in severity of symptoms
Adherence to therapy
Side effects.
Search methods for identification of studies
Electronic searches
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 August 2023 through contact with the Information Specialist using search terms relevant to this review. The Register contains studies identified from the following sources:
Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)
Weekly searches of MEDLINE OVID SP
Searches of kidney and transplant journals, and the proceedings and abstracts from major kidney and transplant conferences
Searching of the current year of EMBASE OVID SP
Weekly current awareness alerts for selected kidney and transplant journals
Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
Studies contained in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of search strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available on the Cochrane Kidney and Transplant website under CKT Register of Studies.
See Appendix 1 for search terms used in strategies for this review.
Searching other resources
Searching other resources: Reference lists of review articles, relevant studies and clinical practice guidelines.
Contacting relevant individuals/organisations seeking information about unpublished or incomplete studies.
Data collection and analysis
Selection of studies
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, who discarded studies that were clearly ineligible but aimed to be overly inclusive rather than risk losing relevant studies. Authors RJ and LM independently assessed, using full copies of the papers, whether the studies met the inclusion criteria, with disagreements resolved by discussion and consultation with the third author JC. Further information was sought from the authors of papers which contained insufficient information to make a decision about eligibility.
Data extraction and management
If studies meeting our inclusion criteria are identified in the future, we will independently extract information using specially designed data extraction forms. For each included trial, information will be collected regarding the location of the study, methods of the study, the participants (sex, age, eligibility criteria), the nature of the interventions, and data relating to the outcomes specified previously. Where possible, missing data (including side effects) will be sought from the authors. Discrepancies in the data extraction will be resolved by discussion.
Assessment of risk of bias in included studies
The following items were to be assessed independently by two authors using the risk of bias assessment tool (Higgins 2022) (seeAppendix 2).
Was there adequate sequence generation (selection bias)?
Was allocation adequately concealed (selection bias)?
-
Was knowledge of the allocated interventions adequately prevented during the study?
Participants and personnel (performance bias)
Outcome assessors (detection bias)
Were incomplete outcome data adequately addressed (attrition bias)?
Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?
Was the study apparently free of other problems that could put it at risk of bias?
Measures of treatment effect
If studies that meet our inclusion criteria are identified in the future, statistical analyses will be performed where possible. Briefly, the risk ratio (RR) will be used as the measure of effect for each dichotomous outcome. Where continuous scales of measurement are used to assess the effects of treatment, these data will be analysed using the mean difference (MD). If different scales have been used in different studies, where possible, the results will be standardised and then combined (i.e. standardised mean difference ( SMD)).
Unit of analysis issues
Cross‐over studies are not a suitable study design and were excluded.
Dealing with missing data
We planned to contact the authors of included studies for data missing from the publication.
Assessment of heterogeneity
Heterogeneity in the data will be noted and cautiously explored using previously identified characteristics of the studies, particularly assessments of quality.
Assessment of reporting biases
We planned to use funnel plots to assess the potential existence of small study bias (Higgins 2022). There were insufficient studies to do this.
Data synthesis
Data were to be pooled using the random‐effects model, but the fixed‐effect model was also to be used to ensure the robustness of the model chosen and susceptibility to outliers.
Subgroup analysis and investigation of heterogeneity
Subgroalyses were to be used to explore possible sources of heterogeneity. If studies which meet the inclusion criteria are identified in the future, the groups described previously (see under types of participants) will be analysed separately with the following subgroups:
Dosage (amount and concentration)
Frequency and duration of treatment.
Where possible, we will seek data from within studies where these comparisons have been made rather than across studies.
Sensitivity analysis
Sensitivity analyses were to be undertaken to examine the stability of the results in relation to a number of factors, including study quality, the source of the data (published or unpublished), the causative organism (e.g. E. coli), the method used for confirming the presence of bacteria in the urine (e.g. catheter specimen of urine or midstream specimen of urine) and the method of diagnosing upper or lower UTI.
Summary of findings and assessment of the certainty of the evidence
We planned to present the main results of the review in a 'Summary of findings' table. This table was to present key information concerning the quality of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schünemann 2022a). The 'Summary of findings' table will also include an overall grading of the evidence related to each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach (Guyatt 2008; Guyatt 2011). The GRADE approach defines the certainty of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The certainty of a body of evidence involves consideration of within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schünemann 2022b). We plan to present the following outcomes.
Number of symptomatic and asymptomatic UTIs
Reduction in severity of symptoms
Adherence to therapy
Side effects
Results
Description of studies
The following section contains broad descriptions of the studies considered in this review. For further details on each individual study, please see Excluded studies.
Results of the search
No studies assessing the treatment of UTIs with cranberry juice (or other cranberry products) which met all of the inclusion criteria were found.
Included studies
No studies were found which met the inclusion criteria for this review.
Excluded studies
Seven studies were excluded from the review.
DuGan 1966 compared cranberry juice with no treatment for the reduction of urinary odours (which could have been caused by a UTI). From the description of the trial, it is unlikely it was randomised, and the report contained no relevant outcomes.
Gbinigie 2019 was a description of feasibility protocol which planned to compare antibiotics versus antibiotics plus cranberry product versus cranberry product given for three to five days, followed by antibiotics.
Mainini 2020 was a cohort study for the prevention and treatment of cystitis during menopause: oral nutraceutical compound (inulin (2 g), D‐mannose (500 mg), cranberry (200 mg), bearberry (200 mg), Olea europaea (100 mg), Orthosiphon (10 mg) and tyndallized Lactobacillus acidophilus SGL 11 (10 billion CFU)) taken for 10 days every month, for 12 months
Nahata 1982 was a cross‐over RCT, comparing methenamine mandelate alone, methenamine mandelate plus ascorbic acid, or methenamine mandelate plus ascorbic acid and cranberry juice for people with UTIs. No relevant outcomes were presented, however, and the main purpose of the studies was to see the effect of the methenamine on formaldehyde concentration. The author was contacted but could not provide any further information about the study.
NCT01861353 investigated starting cranberry juice early to prevent recurrent UTI.
Radulescu 2020 compared TMP‑SMX alone or in combination with a mixed product containing cranberry extract plus D‑mannose for seven days.
Shaheen 2015: insufficient information on the intervention and control used; improvement in UTI reported, but unclear of the definition.
See Excluded studies
Ongoing studies
One ongoing study was identified from 2006; however, its current status is listed as unknown (NCT00305071).
NCT00305071 will enrol women aged 20 to 65 with non‐complicated acute bacterial cystitis. The intervention group will receive three‐day oral trimethoprim/sulfamethoxazole (80/400 mg), two tablets twice/day on days one to three, plus oral compound cranberry extract tablets (UmayC, 900 mg), two tablets three times/day on days one to seven. The control group will receive the same oral antibiotics plus an identical placebo prescribed as the same protocol of the intervention arm. Outcomes to be assessed are the time to symptoms relief and pyuria eradication rate. This study states it has not started recruiting.
Risk of bias in included studies
No studies were found which met the inclusion criteria for this review.
Allocation
No studies were found which met the inclusion criteria for this review.
Blinding
No studies were found which met the inclusion criteria for this review.
Incomplete outcome data
No studies were found which met the inclusion criteria for this review.
Selective reporting
No studies were found which met the inclusion criteria for this review.
Other potential sources of bias
No studies were found which met the inclusion criteria for this review.
Effects of interventions
No studies were found which met the inclusion criteria for this review.
Discussion
No studies assessing cranberries for the treatment of UTIs which met our inclusion criteria were found. Only a few uncontrolled studies examining the effectiveness of cranberry juice in treating the symptoms of UTI have been reported. Two of these did show a beneficial effect (Papas 1966; Rogers 1991) but no firm conclusions can be drawn from such studies.
Summary of main results
No studies were included.
Overall completeness and applicability of evidence
No studies were included.
Quality of the evidence
No studies were included.
Potential biases in the review process
We searched Cochrane Kidney and Transplant's Sprecialised Register to 1 August 2023. Studies contained in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant, as well as handsearching journals and conference proceedings.
Agreements and disagreements with other studies or reviews
There are no reviews on the treatment of UTIs with cranberry products.
Authors' conclusions
Implications for practice.
No RCTs have been performed to assess the effectiveness of cranberry juice or cranberry products for the treatment of UTIs. Therefore, at the present time, there is no evidence to suggest that cranberry juice or other cranberry products are effective in treating UTIs.
Implications for research.
More research is need to assess the effectiveness of cranberry juice in treating UTIs. Well‐designed parallel group, double blind studies of cranberry juice and other cranberry products for the treatment of UTIs are needed. The outcomes should include reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. Dosage (amount and concentration) and duration of therapy should also be evaluated. Consumers and clinicians will welcome the evidence from these studies.
What's new
| Date | Event | Description |
|---|---|---|
| 14 December 2023 | New citation required but conclusions have not changed | No included studies |
| 14 December 2023 | New search has been performed | New search 1 August 2023, no new studies included. |
History
Protocol first published: Issue 4, 1998 Review first published: Issue 4, 1998
| Date | Event | Description |
|---|---|---|
| 19 August 2020 | Review declared as stable | Search of register undertaken 18 August 2020; no new or ongoing studies were identified |
| 18 March 2015 | Amended | Updated search strategies for MEDLINE, EMBASE, CENTRAL |
| 13 July 2010 | Amended | 13 July 2010: Searched for new studies, none identified |
Notes
As of Issue 11, 2023, this Cochrane Review is no longer being updated. There have been no studies published on this topic there are currently no new registered ongoing studies.
Acknowledgements
Ruth Jepson would like to thank the Nuffield Trust for giving her a short‐term fellowship for this review.
-
The authors would also like to thank the following people for replying to correspondence, even though they could provide no further information:
Prof Nahata (Nahata 1982)
Dr RJ Woodward (Larkhill Green Farm ‐ cranberry tablets)
Appendices
Appendix 1. Electronic search strategies
| Database | Search terms |
| CENTRAL |
|
| MEDLINE |
|
| EMBASE |
|
Appendix 2. Risk of bias selection tool
| 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 risk of bias: 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 risk of bias: Randomisation was 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 risk of bias: 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 risk of bias: 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 risk of bias: 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 risk of bias: 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 risk of bias: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias. |
Characteristics of studies
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| DuGan 1966 | Cross‐over RCT of cranberry juice versus no treatment. The 220 participants were elderly and from two hospital wards ‐ one male and one female. The female ward received the cranberry juice first followed by the male ward. This trial was excluded because from the description of the study design, it looked unlikely that this trial had be randomised. Also, the outcome was urinary odours, and no information was given about urinary tract infections. Furthermore, cross‐over trials may not be a relevant trial design for acute conditions such as urinary tract infections. |
| Gbinigie 2019 | Feasibility protocol: antibiotics vs antibiotics + cranberry product vs cranberry product for 3 to 5 days, followed by antibiotics. Cranberry product not given for a minimum of 5 days to all patients in group 3 |
| Mainini 2020 | Cohort study for the prevention and treatment of cystitis during menopause: oral nutraceutical compound (inulin (2 g), D‐mannose (500 mg), cranberry (200 mg), bearberry (200 mg), Olea europaea (100 mg), Orthosiphon (10 mg) and tyndallized Lactobacillus acidophilus SGL 11 (10 billion CFU)) taken for 10 days every month, for 12 months |
| Nahata 1982 | Cross‐over RCT of 27 people with bacteriuria comparing methenamine mandelate alone, with ascorbic acid or with ascorbic acid and cranberry juice. The primary purpose of this review was to assess the effect of methenamine on formaldehyde concentrations. Each patient was randomised to 5 days of each therapy. The trial was excluded because it contained no relevant outcomes. Furthermore, cross‐over trials may not be a relevant trial design for acute conditions such as urinary tract infections. |
| NCT01861353 | Looking at the effects of starting cranberry juice early after an acute to prevent recurrent urinary tract infection |
| Radulescu 2020 | Intervention: compared TMP‑SMX alone or in combination with mixed product containing cranberry extract plus D‑mannose for 7 days |
| Shaheen 2015 | Interventions and outcomes: insufficient information on the intervention and control used; improvement in UTI reported, but unclear of the definition |
RCT: randomised controlled trial; UTI: urinary tract infection
Characteristics of ongoing studies [ordered by study ID]
NCT00305071.
| Study name | Effect of adjuvant treatment with compound cranberry extract tablets in acute bacterial cystitis |
| Methods | Double‐blind, placebo‐controlled RCT |
| Participants | Planned characteristics
|
| Interventions | Intervention group
Control group
|
| Outcomes | Primary outcome measures
Secondary outcome measures
|
| Starting date | April 2006 |
| Contact information | Contact: Po‐Chien Huang, MD 886‐3‐3179599 ext 8223 m001435@e‐ms.com.tw Contact: Hung‐Ju Yang, MD 886‐3‐3179599 ext 8225 m001436@e‐ms.com.tw |
| Notes | Recruitment status at 21 March 2006: not yet recruiting No results have been published as of 21 August 2023 |
RCT: randomised controlled trial; TMP/SMX: trimethoprim/sulfamethoxazole
Differences between protocol and review
New Cochrane methodology shall be used (Higgins 2022).
Contributions of authors
The titles and abstracts were screened by RJ.
RJ and LM independently assessed studies.
Disagreements resolved by discussion and consultation with JC.
The quality of all studies which were deemed eligible for the review were then assessed independently by two of the reviewers RJ and LM.
Discrepancies resolved by discussion with the third, JC.
Sources of support
Internal sources
No sources of support provided
External sources
No sources of support provided
Declarations of interest
Ruth Jepson: no relevant interests were disclosed
Lara Mihaljevic: no relevant interests were disclosed
Jonathan Craig: no relevant interests were disclosed
New search for studies and content updated (no change to conclusions)
References
References to studies excluded from this review
DuGan 1966 {published data only}
- DuGan CR, Cardaciootto PS. Reduction of ammonial urinary odors by the sustained feeding of cranberry juice. Journal of Psychiatric Nursing 1966;4(5):467-9. [Google Scholar]
Gbinigie 2019 {published data only}
- Gbinigie O, Allen J, Boylan AM, Hay A, Heneghan C, Moore M, et al. Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? Protocol for a feasibility study. Trials [Electronic Resource] 2019;20(1):767. [PMID: ] [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gbinigie O, Allen J, Williams N, Moore M, Hay AD, Heneghan C, et al. Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? A feasibility randomised trial. BMJ Open 2021;11(2):e046791. [PMID: ] [DOI] [PMC free article] [PubMed] [Google Scholar]
Mainini 2020 {published data only}
- Mainini G, Passaro M, Schiattarella A, Franciscis P, Di Donna MC, Trezza G. Prevention and treatment of cystitis during menopause: efficacy of a nutraceutical containing D-mannose, inulin, cranberry, bearberry, olea europaea, orthosiphon and Lactobacillus acidophilus. Przeglad Menopauzalny 2020;19(3):130-4. [EMBASE: 2008338294] [DOI] [PMC free article] [PubMed] [Google Scholar]
Nahata 1982 {published data only}
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