Title: Cranberry Extract for Symptoms of Acute, Uncomplicated Urinary Tract Infection: A Systematic Review 

Citation: Gbinigie OA, Spencer EA, Heneghan CJ, Lee JJ, Butler CC. Cranberry Extract for Symptoms of Acute, Uncomplicated Urinary Tract Infection: A Systematic Review. Antibiotics (Basel). 2020;10(1):12. Published 2020 Dec 25. doi:10.3390/antibiotics10010012

Aim: The goal of this systematic review is to review any available evidence of the effects cranberry extracts in treating uncomplicated UTIs.

Method: They searched for literature on Medline, Embase, Amed, Cinahl, The Cochrane library, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform and Google scholar with the intention of gathering literature dating from inception to as far as Feb 2020.

Data: There were 3 studies that were ultimately included after inclusion criteria were met. The studies evaluated were 3 RCT (total of 688 participants 18 years of age and above). The RCTs were conducted in outpatient settings, and each conducted in either the US, the UK and India. 2 of the 3 studies used cranberry juice as the intervention and one use encapsulated cranberry powder. The PAC (Proanthocyanin) content of the cranberry extracts varied significantly between studies and participants ranging from as much as 7.5mg -224mg. 

The outcomes explored include the effect of cranberry extract in:

1.  The management of acute, uncomplicated UTI symptoms
2. Antibiotic use
3. Microbiological assessment
4. Biochemical assessment and
5. Adverse events associated with cranberry use 

Results:

1. One of the RCTs (n= 309) found that cranberry use had no significant effect on UTI frequency sxs mean difference (MD) 0.01 (95% CI: 0.37 to 0.34), p = 0.94) , no significant effect on feeling unwell (MD 0.02 (95% CI: 0.36 to 0.39), p = 0.93)) or on antibiotic use (i.e. did not reduce the use of antibiotic. Odds ratio 1.27 (95% CI: 0.47 to 3.43, p = 0.64), in comparison to drinking more water. The advice to drink cranberry juice compared with water did not affect the duration of symptoms rated moderately bad or worse.

• For the second RCT (n=319) they found no symptomatic benefit from combining cranberry juice with immediate antibiotics for an acute UTI, compared to placebo (placebo juice combined w/ antibiotics. (Note: there was no empirical data presented in the RCT to support this finding. There was also no data on between group comparisons)

• The last RCT (n= 60) found that consumption of cranberry extract capsules was associated with a within-group improvement in urinary symptoms and Escherichia coli load at day 10 compared with baseline (p < 0.01). These findings were not seen in the untreated controls (p = 0.72). 

• Lastly, no serious adverse effects associated with cranberry extract consumption. 

Overall conclusion: Based on the findings of this review there are not enough powered and properly conducted studies available from which a conclusion can be drawn. Findings form many studies have been inconclusive and more rigorous and thorough trials are needed

Clinical significance of the study: With the rise in antibiotic resistance, finding other non-antibiotic treatments for UTIs may be beneficial. It is believed that Proanthocyanin (PAC) with A-type linkages, or their metabolites, are the active ingredient in cranberries that prevent Escherichia coli (E. coli) from binding to the bladder uroepithelium and in doing so hinders the development of UTIs. 

Short falls of this study: 

1. The studies included in the review had insufficient data and were unable to perform data analysis (so their data was presented in narrative form rather than statistically)
2. The studies included did not have a primary goal of assessing the effect of the cranberry extract on treating symptoms of acute uncomplicated UTIs but were focused on other goals such as assessing cranberry use for preventing recurrent UTI symptoms. However, the authors of this review believe the studies still provided information relevant to the outcomes for their specific review.
3. Overall the RCTs included in the review were believed to have a moderate level of bias including things such selection and reporting bias, absence of intent to treat analysis, etc.