What cranberry supplement is the best to use to prevent UTI's?

What cranberry supplement is best to prevent urinary tract infections (UTIs)?

Comment by InpharmD Researcher

There does not appear to be a consensus upon the most effective cranberry supplement to prevent UTIs, and the efficacy of cranberry supplements, in general, for the prevention of UTIs remains conflicting. One meta-analysis determined cranberry juice to significantly reduce recurrent UTIs compared to cranberry capsules, but the use of cranberry juice may be limited by its sugar content, which may lead to gastrointestinal adverse events. Despite this finding, some systematic reviews suggest cranberry capsules demonstrate favorable efficacy. Additionally, literature has consistently proposed the active ingredient of at least 36 mg proanthocyanidins to adequately prevent recurrent UTIs. Due to a large body of evidence that is limited by confounding variables and heterogeneity, there is a lack of robust data regarding the optimum dosage and formulation of cranberry-derived active compounds (i.e., juice, tablet, capsule, or powder) in this setting.

Background

A 2022 narrative review investigated the use of cranberry products to reduce the recurrence (secondary prevention) of urinary tract infections (UTIs) in older patients. Six systematic review articles of patients with or without recurrent UTIs were included for analysis. All patients were older than 65 years, and most were female from age-care or hospital settings. Interventions greatly varied, including juice, capsules, extracts, and powder formulations. While all studies found some level of support for regular cranberry administration to reduce UTI recurrence versus placebo, one systematic review reported non-significant trends. Their analysis of 15 studies noted that each study was non-significant in reducing symptomatic UTI, and the authors could not support their use as prevention in older patients with urinary catheters. Some systematic reviews note that cranberry capsules demonstrate favorable efficacy, specifically twice daily consumption of cranberry capsules (containing at least 36 mg proanthocyanidins [PCAs]). Adverse event rates were generally mild. The narrative review offers some understanding of cranberry product trends but lacks statistical analysis to validate potential benefits. [1]

A 2021 meta-analysis reviewed the effects of cranberry as adjuvant therapy on the recurrence rate of urinary tract infections in susceptible groups. Among 23 included randomized controlled trials (RCTs; N= 3,979), 15 trials administered cranberry juice, one used both cranberry juice and cranberry tablets, and twelve used cranberry capsules, with daily cranberry amounts ranging from 0.4 to 194.4 g. A subgroup analysis based on the formulation of cranberry-containing products found a relative risk reduction of 35% in patients who used cranberry juice versus cranberry capsules or tablets (risk ratio [RR] 0.65; confidence interval [CI] 0.54 to 0.77). Researchers found 13 studies that evaluated the use of cranberry juice to prevent UTIs (RR 0.65; CI 0.54 to 0.77; I2= 33%) and 10 studies that assessed the same outcome with cranberry capsules or tablets (RR 0.8; CI 0.7 to 0.91; I2= 52.7%). Large volumes of cranberry juice are required, and the sugar content may lead to severe gastrointestinal issues; however, the authors still suggest cranberry in juice form may be more favorable than cranberry in capsules or tablets for the desired result. Throughout the evaluated studies, there was no consistency among the levels of PACs, the active ingredient of cranberry products, believed to provide UTI prevention. The proposed daily recommended dose of PACs is 36 mg. These findings may have led to inconsistencies in the results. Of note, the compiled results did not show a significant decrease in recurrent UTIs in patients with neuropathic bladder, pregnant patients, or elderly patients. [2]

According to a 2017 meta-analysis, cranberry may be effective in preventing UTI recurrence in generally healthy women. This analysis included data from seven randomized controlled trials conducted in healthy women at risk of UTI (N= 1,498). Results showed that cranberry reduced the risk of UTI by 26% (pooled RR 0.74; 95% CI 0.55 to 0.98). Overall, the studies were relatively small, with only two having more than 300 participants. Although the authors state that cranberry may be useful in recurrent UTI prevention, they also mention that larger high-quality studies are needed to confirm these findings. Similarly, there is a lack of robust data regarding the optimum dosage and formulation of cranberry-derived active compounds (i.e., juice, tablet, capsule, or powder) in this setting. [3]

According to a 2012 Cochrane meta-analysis compared with placebo, water, or no treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04). This study included 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 4,473 participants. Thirteen studies (2,380 participants) evaluated only cranberry juice/concentrate; nine studies (1,032 participants) evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. However, a subgroup analysis based on cranberry formulations was not conducted to further differentiate various products. Of note, many studies reported low compliance and high withdrawal/dropout problems, which they attributed to the palatability/acceptability of the products, primarily the cranberry juice. Again, without a clear definition of the 'active' ingredient that each product contained (i.e., tablet and capsules), inadequate potency could contribute to the overall lack of efficacy. [4]

A 2016 study discussed the need for an alternative prophylactic approach to antibiotics in the case of UTIs. This article further detailed the anti-adhesion properties of cranberry due to the PAC component and tested the PAC levels in seven commercially available cranberry supplements (formulation not specified). Four of the seven products showed no anti-adhesion. The other three products' PAC levels ranged from 4 mg/g to 175 mg/g, with the highest PAC level showing the most anti-adhesion. This article also noted that clinical trials in the past have determined that at least 36 mg of PAC is required to result in significant reductions in recurrent UTIs. Similarly, the variability in quality of supplements available to consumers should be recognized. [5]

Literature Review

A search of the published medical literature revealed 8 studies investigating the researchable question:

What cranberry supplement is best to prevent urinary tract infections (UTIs)?

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Tables 1-8 for your response.

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women
Design	Open-label, randomized controlled trial N = 150
Objective	To determine whether recurrences of urinary tract infection (UTI) can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink
Study Groups	Cranberry-lingonberry (n = 50) Lactobacillus (n = 50) Control (n = 50)
Inclusion Criteria	Women who had a UTI caused by E. coli and were not taking antimicrobial prophylaxis
Exclusion Criteria	Taking postcoital antimicrobials
Methods	Patients were randomized to receive 50 mL of cranberry-lingonberry juice (7.5 g cranberry concentration/1.7 g lingonberry concentrate) daily for 6 months, 100 mL of Lactobacillus GG drink (4x10¹⁰ colony-forming units of Lactobacillus GG/100mL) five days a week for one year, or control.
Duration	Trial: 1993 to 1997 Intervention: 6 months to one year Follow-up: 12 months
Outcome Measures	First recurrence of symptomatic UTI
Baseline Characteristics		Cranberry-lingonberry (n = 50)	Lactobacillus (n = 49)	Control (n = 50)
	Age, years	32 ± 9.8	30 ± 11.8	29 ± 10.5
	Intercourse frequency Less than once/week 1-2 times/week > 3 times/week	16 (33%) 17 (35%) 16 (33%)	25 (51%) 11 (22%) 13 (27%)	13 (27%) 18 (38%) 17 (35%)
	Intercourse during follow-up Less than once/week 1-2 times/week > 3 times/week	10 (23%) 19 (43%) 15 (34%)	9 (19%) 23 (49%) 15 (32%)	7 (15%) 20 (43%) 20 (43%)
	Birth control during follow up	39 (81%)	39 (81%)	38 (83%)
	Pregnancy during follow up	1 (2%)	2 (4%)	2 (4%)
	Antimicrobials for UTI in past year	44 (90%)	41 (85%)	41 (85%)
	UTI antimicrobial prophylaxis Before intervention During follow-up	10 (21%) 1 (2%)	8 (17%) 5 (10%)	5 (11%) 3 (6%)
Results		Cranberry-lingonberry (n = 50)	Lactobacillus (n= 50)	Control (n= 50)
	Incidence density, per person-year at risk E. coli Other bacteria	0.45* 15 (71%) 6 (29%)	0.91 31 (79%) 8 (21%)	0.81 32 (84%) 6 (16%)
	Occurrence of UTI during follow up	21 (21%)	39 (40%)	38 (39%)
	*The difference between the cranberry and control groups was significant (95% confidence interval 0.03 to 0.68, p= 0.03).
Adverse Events	Common Adverse Events: occasional complaints about the cranberry juice's bitter taste
	Serious Adverse Events: N/A
	Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions	Daily consumption of 50 mL of cranberry-lingonberry concentrate seems to reduce symptomatic Ureoccurrencesces in women compared to the control group.
InpharmD Researcher Critique	The trial was an open-label trial, which may limit the results due to bias. Additionally, the trial was stopped prematurely due to a stop in cranberry juice production. Further limitations include a small sample size and a generally younger patient population, potentially limiting the generalizability of the results. Women also self-recorded results, and only half of the subjects returned the compliance sheet.

References:

Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ. 2001;322(7302):1571. doi:10.1136/bmj.322.7302.1571

High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial.
Design	Randomized, controlled, double-blind clinical trial N=145
Objective	To assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection
Study Groups	Low-dose group (n = 73) High-dose group (n = 72)
Inclusion Criteria	Sexually active healthy women, aged 18 years and older, recent history of recurrent urinary tract infections (UTIs) defined as (≥ 2 UTIs in the past 6 months and/or ≥ 3 UTIs in the past 12 months and no consumption of cranberry product, polyphenol or antioxidant supplements in the last 2 weeks
Exclusion Criteria	Pregnancy, anticoagulant medication in the last month, known allergy or intolerance to cranberry and history of anatomical urogenital anomalies, urogenital tract surgery, acute or chronic renal failure, nephrolithiasis or intestinal diseases causing malabsorption
Methods	Patients were randomized to receive ether high-dose cranberry proanthocyanidins (PAC) in the form of two 18.5 mg cranberry capsules per day or low-dose PAC in the form of two 1 mg cranberry capsules per day for 24 weeks.
Duration	24 weeks
Outcome Measures	Primary: the number of symptomatic UTIs during the 24-week follow-up period Secondary: symptomatic UTI with pyuria and symptomatic UTI with bacteriuria
Baseline Characteristics		Low-dose group PAC (n = 73)	High-dose group PAC (n = 72)
	Age, years	32.5 ± 14.2	27.2 ± 8.8
	Ethnicity Caucasian Non-Caucasian Biracial	65 (89.0%) 6 (8.2%) 2 (2.7%)	65 (90.3%) 5 (6.9%) 2 (2.8%)
	Number of episodes of UTI in the past 6 months: 1 2 3 4 ≥ 5	13 (17.8%) 34 (46.6%) 17 (23.3%) 6 (8.22%) 3 (4.11%)	8 (11.1%) 37 (51.4%) 16 (22.2%) 7 (9.7%) 4 (5.6%)
	Number of episodes of UTI in the past 12 months: 2 3 4 ≥ 5	13 (17.8%) 22 (30.1%) 11 (15.1%) 27 (37.0%)	7 (9.72%) 29 (40.3%) 15 (20.8%) 21 (26.17%)
	Type of Contraception: Hormonal contraception Spermicide Non-hormonal intrauterine device (IUD) Condom None	43 (58.9%) 1 (1.4%) 7 (9.6%) 17 (23.3%) 5 (6.8%)	53 (73.6%) 0 4 (5.6%) 11 (15.3%) 4 (5.6%)
	Personal history of recurrent UTI: < 1 year 1–2 years 3–5 years 6–10 years > 10 years Missing data	4 (8.2%) 9 (18.4%) 15 (30.6%) 14 (28.6%) 7 (14.3%) 24	2 (4.3%) 12 (25.5%) 15 (31.9%) 10 (21.3%) 8 (17.0%) 25
	Hydration (average liters of water per day): Mean ± SD < 1 ≥ 1–2 > 2–3 ≥ 3 Missing data	1.62 ± 0.75 9 (15.8%) 30 (52.6%) 13 (22.8%) 5 (8.8%) 16	1.81 ± 0.63 4 (7.0%) 27 (47.4%) 23 (40.4%) 3 (7.0%) 15
	Alcohol consumption (per week): < 1 1–3 > 4 Missing data	7 (12.7%) 28 (50.9%) 20 (36.4%) 18	15 (25.9%) 21 (36.2%) 22 (37.9%) 14
	Non-smoker	52 (91.2%)	55 (94.8%)
Results	Endpoint	Low dose group (n = 73)	High dose group (n = 72)
	Subjects reporting symptomatic UTI: 0 1 2 3 4 5 ≥ 1 Total symptomatic UTIs	34 (46.6%) 26 (35.6%) 8 (11.0%) 4 (5.5%) 0 1 (1.4%) 39 (53.4%) 59	41 (57.0%) 21 (29.2%) 7 (9.7%) 2 (2.8%) 1 (1.4%) 0 31 (43.1%) 45
	Symptomatic UTI with pyuria at 24 weeks^a 0 1 2 3 4 ≥ 1 Total symptomatic UTIs with pyuria	50 (68.5%) 17 (23.3%) 5 (6.8%) 0 1 (1.4%) 23 (31.5%) 31	53 (73.6%) 14 (19.4%) 4 (5.6%) 0 1 (1.4%) 19 (26.4%) 26
	Symptomatic UTI with pyuria at 24 weeks^b 0 1 2 3 4 5 ≥ 1 Total symptomatic UTIs with pyuria	39 (53.4%) 23 (31.5%) 6 (8.2%) 4 (5.5%) 0 1 (1.4%) 34 (46.6%) 52	45 (62.5%) 18 (25.0%) 7 (9.7%) 1 (1.4%) 1 (1.4%) 0 27 (37.5%) 39
	Symptomatic UTI with bacteriuria at 24 weeks^a 0 1 2 ≥ 1 Total symptomatic UTIs with bacteriuria	55 (75.3%) 17 (23.3%) 1 (1.4%) 18 (24.7%) 19	63 (87.5%) 7 (9.7%) 2 (2.8%) 9 (12.5%) 11
	Subjects reporting symptomatic UTI with bacteriuria at 24 weeks^b 0 1 2 3 4 ≥ 1	42 (57.5%) 22 (30.1%) 6 (8.2%) 3 (4.1%) 0 31 (42.5%)	51 (70.8%) 15 (20.8%) 4 (5.6%) 1 (1.4%) 1 (1.4%) 21 (29.2%)
	^aSymptomatic UTI episodes without urine sample were considered as no symptomatic UTI ^bSymptomatic UTI episodes without urine sample were considered as symptomatic UTI
Adverse Events	Common Adverse Events: dyspepsia
Adverse Events	Percentage that Discontinued due to Adverse Events: One participant from each group, 2/145 (1.4%).
Study Author Conclusions	High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year.
InpharmD Researcher Critique	The use of a control low-dose PAC instead of a placebo might explain why there was no significant reduction in UTI recurrence between the two groups. Incomplete urine cultures and the exclusion of urine samples due to contamination caused by the improper clean-catch urine technique might have negatively influenced the outcomes of the study.

References:

Babar A, Moore L, Leblanc V, et al. High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial. BMC Urol. 2021;21(1):44. Published 2021 Mar 23. doi:10.1186/s12894-021-00811-w

Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial
Design	Randomized, double-blind, placebo-controlled trial N= 160
Objective	To evaluate the therapeutic efficacy of cranberry juice capsules in preventing urinary tract infections (UTIs) after elective gynecological surgery in which a urinary catheter is placed
Study Groups	Placebo (n= 80) Cranberry (n= 80)
Inclusion Criteria	Nonpregnant women, age ≥ 18 years
Exclusion Criteria	Allergy to cranberry products, requirement for therapeutic anticoagulant medicine during the 6 weeks after surgery or whose surgery involved a fistula repair or a vaginal mesh removal, a history of nephrolithiasis, congenital urogenital anomaly, or neurogenic bladder
Methods	Patients were randomized in a 1:1 ratio to receive two cranberry juice capsules 2 times a day (once in morning and once in evening), equivalent to two 8-ounce servings of cranberry juice, for 6 weeks after surgery or a matching placebo. Patients were instructed to start at the time of discharge for 4-6 weeks, or until their return for their postoperative doctor’s visit, and were instructed to drink an 8 ounce glass of water while taking the capsule with or without food.
Duration	Trial: August 2011 to January 2013 Intervention: 6 weeks
Outcome Measures	Primary: proportion of participants who experienced clinically diagnosed and treated UTI Secondary: incidence of UTI caused by E. coli, time from randomization to UTI
Baseline Characteristics		Placebo (n= 80)	Cranberry (n= 80)
	Age, years < 60 years	56 60%	56 59%
	Race Non-Hispanic white Non-Hispanic black Other or mixed race	88% 5% 7%	84% 5% 11%
	Ever experienced UTI in life	63%	64%
	Experienced UTI in the past 12 months	24%	23%
	Socio-demographic characteristics and most medical history features were not statistically significantly different between groups.
Results	Endpoint	Placebo (n= 80)	Cranberry (n= 80)	Odds ratio (95% confidence interval);p-value
	Occurrence of UTI Culture-confirmed	30 (38%) 23 (29%)	15 (19%) 12 (15%)	0.38 (0.19 to 0.79); p= 0.008 0.44 (0.20 to 0.96); p= 0.04
	E. coli causing UTI	12 of 23 (46%)	5 of 12 (38%)	0.38* (0.13 to 1.13); p= 0.07
	Median time to UTI, days	8.5	18	p= 0.0005
	*Reflecting a reduction of 62%
Adverse Events	No significant difference in incidence of adverse events was reported between groups. Adverse events were reported in 75 patients in the cranberry group vs. 78 patients in the placebo group. Severe adverse events were reported in 4 cranberry patients and 4 placebo patients. The most common adverse event overall was gastrointestinal upset (56% of patients in cranberry group vs. 61% of patients in placebo group).
Study Author Conclusions	Among women undergoing elective benign gynecologic surgery involving urinary catheterization, use of cranberry extract tablets during the postoperative period reduced the rate of UTI by half
InpharmD Researcher Critique	Compared to previous trials, this study utilized cranberry capsules as opposed to juice. Use of capsules is thought to be associated with improved compliance, resulting in more reliable outcomes. Additionally, the use of placebo capsules in this study as opposed to placebo juice (which contained vitamin C) prevents confounding of results due to the presence of vitamin C in the placebo juice, which may impact UTI risk.

References:

Foxman B, Cronenwett AE, Spino C, Berger MB, Morgan DM. Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial. Am J Obstet Gynecol. 2015;213(2):194.e1-194.e1948. doi:10.1016/j.ajog.2015.04.003

Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial
Design	Randomized, placebo-controlled, double-blind trial N = 376
Objective	To assess whether cranberry juice ingestion is effective in reducing UTIs in older people in hospital
Study Groups	Cranberry juice (n = 187) Placebo (n = 189)
Inclusion Criteria	60 years or older, admitted in rehabilitation or acute settings, provided informed consent
Exclusion Criteria	Mental State Questionaire (MSQ) <5/10, dysphagia, UTI symptoms, received antibiotic treatment, length of stay <1 week, regular cranberry juice drinker, has an in-dwelling catheter, terminal illness, on warfarin during the final 8 weeks of recruitment
Methods	Patients were randomized to receive either 300 mL of cranberry juice (150 mL twice daily) or a placebo beverage. The juice was administered by nursing staff to optimize adherence. The juice contained water, cranberry juice from concentrate (25%), sugar, vitamin C, and non-nutritive sweetener (aspartame). The proanthocyanidin concentration was 11.175 mcg/g. The placebo beverage contained no cranberry solids but additionally contained elderberry extract.
Duration	Intervention duration: placebo = 21 days, cranberry juice = 24 days
Outcome Measures	Primary: first occurrence of symptomatic UTI (positive culture >10⁴ cfu/mL) Secondary: adherence to cranberry juice, antibiotics prescribed, organisms responsible for UTIs
Baseline Characteristics		Placebo group (n= 189)	Cranberry juice (n= 187)
	Mean age, year	81.4	81.3
	Female	133	122
	Median number of medications per stay, range	8	7
	History of culture-positive urine in the past 12 months	48	53
Results		Placebo group (n = 189)	Cranberry juice (n = 187)	Relative risk (RR) (95% confidence interval [CI])	p-Value
	First occurrence of symptomatic UTI	14 (7.4%)	7 (3.7%)	0.51 (0.21 to 1.222)	0.122
	Adherence to cranberry juice, mL (interquartile range [IQR])	300 (44)	300 (28)	--	0.208
	Antibiotic use	35 (19%)	32 (17%)	--	0.721
	Infection caused by E. coli	13	4	0.31 (0.10 to 0.94)	0.027
Adverse Events	Thirteen events occurred (6 in placebo and 7 in the cranberry group) which all led to withdrawal from study. The events included gastrointestinal upset, rash, elevated blood glucose in a known diabetic, and death
Study Author Conclusions	This study has confirmed the acceptability of cranberry juice to older people. Larger trials are now required to determine whether it is effective in reducing UTIs in older hospital patients.
InpharmD Researcher Critique	Because the rate of infection observed was lower than anticipated, the study results were underpowered. The cranberry group received a slightly longer intervention period compared to placebo. Warfarin was added as an exclusion criteria during the final 8 weeks of the study due to a safety alert in the United Kingdom.

References:

McMurdo ME, Bissett LY, Price RJ, Phillips G, Crombie IK. Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial. Age Ageing. 2005;34(3):256-261. doi:10.1093/ageing/afi101

Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women
Design	Randomized, active-controlled, double-blind trial N= 137
Objective	To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women
Study Groups	Cranberry (n= 69) Trimethoprim (n= 68)
Inclusion Criteria	Women aged ≥ 45 years with at least two antibiotic-treated UTIs or confirmed episodes of cystitis in the previous 12 months confirmed by general practitioner (not necessarily confirmed by microbiological culture)
Exclusion Criteria	Previous urological surgery, stones or anatomical abnormalities of the urinary tract, urinary catheter, diabetes mellitus, immunocompromised, pyelonephritis, severe renal impairment, blood dyscrasias, symptomatic UTI at baseline, cognitive impairment, resident in institutional care, on long-term antibiotic therapy, on warfarin therapy, regular cranberry consumers, childbearing potential
Methods	Participants were randomized to receive either one capsule of 500 mg of cranberry extract (Cran-Max™) taken at bedtime for 6 months or one capsule of 100 mg of trimethoprim. Both sets of capsules were identical in appearance. Urine specimens were obtained from all participants at baseline and during follow-up visits for culture and susceptibility testing in participants presenting with symptoms of UTI.
Duration	Duration: 6 months Follow-up: Home visits occurred at 3 and 6 months while participants were telephoned at 1, 2, 4, and 5 months to encourage adherence and record adverse events.
Outcome Measures	Primary: proportion of participants in each group experiencing a recurrence of an antibiotic-treated UTI and the time to first recurrence Secondary: adherence to treatment
Baseline Characteristics		Cranberry (n= 69)	Trimethoprim (n= 68)
	Age, years	62.6 ± 10.8	63.3 ± 10.1
	Median number of medications (range)	3 (0-13)	4 (0-11)
	Median length of history of UTIs, years (range)	11 (1-50)	18 (1-53)
	Median number of self-reported UTIs in past 12 months (range)	3 (2-15)	3 (2-8)
	Median number of antibiotic-treated UTIs in past 12 months (range)	3 (2-15)	2 (2-8)
	Bacteriuria at baseline E. coli K. pneumoniae Streptococcus B E. faecalis	5 (7.2%) 2 1 1 1	7 (10.3%) 6 0 1 0
Results	Endpoint	Cranberry (n= 69)	Trimethoprim (n= 68)	RR (95% CI)	p-value
	Symptomatic antibiotic-treated UTI, n	25	14	1.616 (0.93-2.79)	0.084
	Median time to first recurrence of UTI, days	84.5	91	N/A	0.479
	Median adherence, % (range)	99 (25-149)	100 (66-112)	N/A	N/A
	CI: confidence interval, RR: Relative Risk
Adverse Events	Common Adverse Events: non-UTI urinary symptoms (17% vs. 13%), gastrointestinal upset (13% vs. 19%), thrush (4% vs. 4%), colds/flu (6% vs. 6%)
	Serious Adverse Events: abdominal abscess (1% vs. 0), breast carcinoma (1% vs. 0), shingles (0 vs. 1%), type II diabetes (0 vs. 1%)
	Percentage that Discontinued due to Adverse Events: cranberry 6 (9%) vs. trimethoprim 11 (16%); p= 0.205
Study Author Conclusions	Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi.
InpharmD Researcher Critique	The difference in occurrence of recurrent UTI in both groups was not statistically significant potentially due to a limited sample size. Additionally, this trial was specific to older women with a history of UTI, thus, potentially limiting generalizability. Further evidence may be needed to assess the benefits of cranberry in younger adults. Also, this study utilized an extract from cranberry rather than juice.

References:

McMurdo ME, Argo I, Phillips G, Daly F, Davey P. Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women. J Antimicrob Chemother. 2009;63(2):389-395. doi:10.1093/jac/dkn489

A Randomized Trial to Evaluate Effectiveness and Cost Effectiveness of Naturopathic Cranberry Products as Prophylaxis Against Urinary Tract Infection in Women
Design	Randomized, double-blind, controlled trial N= 150
Objective	To determine from a societal perspective, the effectiveness and cost-effectiveness of concentrated cranberry tablets, versus cranberry juice, versus placebo used as prophylaxis against lower urinary tract infection (UTI) in adult women
Study Groups	Placebo (n= 50) Tablet (n= 50) Juice (n= 50)
Inclusion Criteria	At least 2 symptomatic, single organism, culture-positive UTIs in the prior calendar year; currently free of UTI on urinalysis and culture
Exclusion Criteria	Neurogenic bladder dysfunction, pregnancy, insulin-dependent diabetes, intermittent or indwelling catheterization, allergy to cranberry products, immunosuppressive disease, steroid use
Methods	Eligible patients were randomized in blocks of 10 into one of three groups: 1. Placebo: one placebo tablet twice daily and 250 mL of placebo juice three times per day 2. Tablet: one tablet of concentrated cranberry juice (at least 1:30 parts concentrated juice) twice daily and 250 mL of placebo juice three times per day 3. Juice: 250 mL of pure unsweetened cranberry juice three times per day and one tablet of placebo twice daily If symptoms of UTI occurred, culture-directed antibiotics were given for 3 days; then, prophylaxis was restarted.
Duration	Duration of intervention: 12 months
Outcome Measures	Symptomatic UTIs per year, patient-reported complications
Baseline Characteristics		Placebo (n= 50)	Tablet (n= 50)	Juice (n= 50)
	Mean age, years (range)	43 (21-72)	40 (23-68)	44 (21-70)
	Premenopausal:postmenopausal	34:16	30:20	37:13
	Mean UTIs in the preceding year (range)	3.5 (2-5)	3.1 (2-4)	3.3 (2-5)
Results	Endpoint	Placebo (n= 50)	Tablet (n= 50)	Juice (n= 50)	p-value
	At least 1 UTI during treatment	16 (32%)	9 (18%)	10 (20%)	< 0.05
	Mean number of UTIs in a calendar year following treatment	0.72	0.39	0.3	< 0.05
Adverse Events	Common Adverse Events: placebo (headache n= 2 and mild nausea n= 2), tablet (mild nausea n= 4 and increased frequency of bowel movements n= 1), juice (symptoms of reflux n= 3)
	Serious Adverse Events: N/A
	Percentage that Discontinued due to Adverse Events: 2 patients in the juice group due to reflux
Study Author Conclusions	Cranberry juice and cranberry tablets with increased fluid intake are more effective than fluid intake alone in preventing urinary tract infections in sexually active women with recurrent UTIs. 10-15% of women will experience fewer clinical lower urinary tract infections if cranberry products are added to the conservative measure of simply increasing fluid intake.
InpharmD Researcher Critique	This study has some limitations regarding the cranberry products that were used, as they were not regulated. Therefore the concentration of the active ingredients was not known. Additionally, researchers did not enroll pregnant women, and compliance was measured by self-reporting. The results did show that cranberry tablets are better tolerated than cranberry juice.

References:

Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol. 2002;9(3):1558-1562.

*Effect of Oral Cranberry Extract (Standardized Proanthocyanidin-A) in Patients with Recurrent UTI by Pathogenic E.Coli:* A Randomized Placebo-Controlled Clinical Research Study**
Design	Randomized, placebo-controlled N=72
Objective	To evaluate the effect of cranberry extract (PAC-A~ proanthocyanidin-A) on the in vitro bacterial properties of uropathogenic (E. coli) and its efficacy/tolerability in patients with subclinical or uncomplicated recurrent UTI (r-UTI)
Study Groups	Group 1 (n= 36) Group 2 (n= 36)
Inclusion Criteria	Subclinical asymptomatic bacteriuria, or r-UTI, or not responding to antimicrobials
Exclusion Criteria	Pregnant or lactating, age <18 years
Methods	Patients were randomized into Group 1 or Group 2. Group 1 (PAC-A) received Cranpac, which contains 60mg PAC-A per capsule, 1 capsule twice a day for 12 weeks while Group 2 (placebo) received lactobacillus, which contains 400 million lactobacillus acidophilus per capsule, 1 capsule twice a day for 12 weeks. Adherence was assessed weekly
Duration	Enrollment: November 2011 to March 2013 Intervention: 12 weeks Follow up: at 3 weeks, 6 weeks, and 12 weeks
Outcome Measures	Primary: change in the incidence of recurrent uncomplicated urinary tract infection (r-UTI): Bacterial adhesion score (1 to 20 with 20 representing the highest adhesion rate between bacterial/urothelia cell) Detection of bacterial growth and biofilm from urinary catheter samples grown on blood agar plates, incubated 24 hours at 35°C
Baseline Characteristics		Group 1 (n= 36)	Group 2 (n= 36)
	Age, years	41.6	35.8
	Detection of bacterial growth	33	36
	Bacterial adhesion score	2.11	1.81
	Detection of biofilm formation	8	6
Results	Endpoint	Group 1 (n= 36)	Group 2 (n= 36)	p-Value
	Detection of bacterial growth at 12 weeks	8	35	<0.001
	Bacterial adhesion score at 12 weeks	0.28	2.14	<0.001
	Detection of biofilm formation at 12 weeks	3	6	0.018
Adverse Events	Self-limiting conspiration occurred in one patient in each group
Study Author Conclusions	The overall efficacy and tolerability of standardized cranberry extract containing (PAC-A) were superior to placebo in terms of reduced bacterial adhesion... and in preventing recurrent UTI (dysuria, bacteria, and pyuria). Larger randomized controlled trials are needed to elucidate the precise role, exact dose, and duration of PAC-A therapy in patients with recurrent UTI. Despite these limitations, the results of the present study appear to suggest a beneficial effect of cranberry when used prophylactically as a food supplement in selected patients with recurrent uncomplicated UTI.
InpharmD Researcher Critique	While this study was open to male and female patients, the baseline sex was not disclosed. Follow-up was limited to 12 weeks which may not provide a comprehensive overview of efficacy and safety.

References:

Singh I, Gautam LK, Kaur IR. Effect of oral cranberry extract (standardized proanthocyanidin-A) in patients with recurrent UTI by pathogenic E. coli: a randomized placebo-controlled clinical research study. Int Urol Nephrol. 2016;48(9):1379-1386. doi:10.1007/s11255-016-1342-8

Effectiveness of Cranberry Capsules to Prevent Urinary Tract Infections in Vulnerable Older Persons: A Double-Blind Randomized Placebo-Controlled Trial in Long-Term Care Facilities
Design	Randomized, double-blind, placebo-controlled trial N= 928
Objective	To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents
Study Groups	High-Risk UTI Patients Treatment Group: received cranberry capsule (n= 187) Placebo Group: received matching controlled capsule (n= 189) Low-Risk UTI Patients Treatment Group: received cranberry capsule (n= 205) Placebo Group: received matching controlled capsule (n= 207)
Inclusion Criteria	LTCF residents aged 65 and older
Exclusion Criteria	Life expectancy of 1 month or less
Methods	Cranberry 500 mg capsules and placebo capsules were taken twice daily. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥1 UTI in preceding year).
Duration	12 months
Outcome Measures	Incidence of UTI according to a clinical definition
Baseline Characteristics		Cranberry (n= 253)	Placebo (n = 263)
	Age, years	85	84
	Female	74.3%	81%
	Length of stay, months, n, median	17	19

Results	Endpoint	Cranberry (n= 253)	Placebo (n = 263)	p-value
	Clinically Defined UTI	62.8%	84.8%	0.04
	No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412).
Adverse Events	None reported
Study Author Conclusions	In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTIs, although it does not reduce the incidence of strictly defined UTIs. No difference in the incidence of UTI was found in residents with low UTI risk.
InpharmD Researcher Critique	This study had a limited patient population once subjects were stratified into low-risk vs. high-risk UTI groups. Future studies should include a larger patient population with stricter inclusion/exclusion criteria.

References:

Griebling TL. Re: Effectiveness of cranberry capsules to prevent urinary tract infections in vulnerable older persons: a double-blind randomized placebo-controlled trial in long-term care facilities. J Urol. 2015;193(1):152.