Wednesday, 17 May 2017

Re: Standardized Cranberry Extract, Cranpac™, Reduces Bacterial Adhesion in Patients with Recurrent Urinary Tract Infection

Date: 05-15-2017HC# 101672-568

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. September 2016;48(9):1379-1386.

Recurrent urinary tract infections (r-UTI) due to Escherichia coli or Clostridium difficile are common and may complicate health problems during convalescence. A-type proanthocyanidins (PAC-As) from cranberry (Vaccinium macrocarpon, Ericaceae) fruit have been studied to reduce adherence of mannose-resistant E. coli to uroepithelial cells. Due to conflicting study results on the efficacy of prophylactic cranberry therapy for r-UTI, the goal of this randomized, controlled, human study was to clarify the effect of cranberry therapy as an alternative to antimicrobials.
A 12-week study was conducted by researchers at the Departments of Surgery (Urology), University College of Medical Sciences (University of Delhi) & GTB Hospital in Shahdara, Dilshad Garden, Delhi, India. The study objective was to compare the effects of a standardized cranberry extract capsule (Cranpac™, containing 60 mg of PAC-A/capsule; IPCA Laboratories Ltd.; Mumbai, India) versus a control (Lactobacillus acidophilus, 400 million cfu/capsule; manufacturer not provided). However, the method for quantifying the PAC level in Cranpac was not disclosed, making it difficult to compare the PAC levels with those found in other standardized cranberry extract powders.
Seventy-two patients (36 in each group) were recruited and randomly assigned to either the cranberry or the control group. Patients with subclinical asymptomatic bacteriuria and/or r-UTI or prone to r-UTI were included; no exclusion criteria were provided. Both groups were instructed to orally consume 1 capsule twice daily. Follow-up study visits were done at 3, 6, and 12 weeks to measure efficacy, adverse events, and compliance. The following endpoints were measured at all time points: incidence of UTI (primary endpoint); urinary pH; urinary culture including pyuria score, biofilm formation, and bacterial adhesion scores; and mannose-resistant hemagglutination assay (MRHA).
Both the treatment and control groups had similar baseline demographics, as well as urine chemistry and biology. There were no dropouts or adverse events associated with the treatments. Thirty-three percent of patients in the treatment group had r-UTI during the study versus 89% of patients in the control group (P<0.001). Patients in the treatment group experienced significant improvements in urinary pH, urinary bacterial growth (87% reduction), bacterial adhesion (70% reduction), and MRHA (97% negative), as well as biofilm formation (61% reduction), over 12 weeks, which were all significant versus control (P<0.001 for all). Cranberry did not demonstrate any in vitro antibacterial activity (reductions in bacterial growth) in any patient.
Multiple endpoints appeared to be time-dependent, but no statistics were given to permit a time-dependent analysis. For example, microscopic pyuria score decreased by 41%, 70%, and 84% in the cranberry group, while increasing by 8%, 20%, and 25% in the Lactobacillus group, after 3, 6, and 12 weeks, respectively. A comparison to previous clinical studies on cranberry extract in r-UTI also was shown to be favorable to support the efficacy of cranberry extracts standardized for PAC-As.
Admitted limitations include the relatively small study size and short duration, the use of a probiotic as a control, and lack of a true placebo group. Despite these limitations, the authors conclude that efficacy and tolerability of the cranberry extract was superior to the control group in terms of reduced bacterial adhesion, urine pH reduction, and prevention of r-UTI. While larger studies are needed, the authors state this suggests the standardized PAC-A cranberry extract is beneficial when used prophylactically in patients with r-UTI.
—Blake Ebersole
Peer Review Comments:
The original manuscript does not describe precisely what the 60 mg of PAC-A in each capsule used in the study really is. After an internet search, it can be assumed that the Cranpac used in the study is a 300-mg tablet of cranberry extract, which may contain 60 mg of PAC-A as stated. Therefore, the drug used in the study would be a 20% PAC-A standardized extract. However, this is only conjecture, as Cranpac and Cranpac-D, made by the same manufacturer, both contain 300 mg of cranberry extract, with the latter also containing 600 mg of d-mannose. This is important information, as the most significant aspect of an effective cranberry extract is how concentrated the spectrum of total phenolic compounds is, especially the PAC-As.