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Variability of commercial cranberry dietary supplements for the prevention of uropathogenic bacterial adhesion

Published:April 05, 2016DOI:https://doi.org/10.1016/j.ajog.2016.03.046

      Objective

      In the United States, urinary tract infections are one of the most common bacterial infections, affecting 8 million people per year.
      • Barber A.E.
      • Norton J.P.
      • Spivak A.M.
      • Mulvey M.A.
      Urinary tract infections: current and emerging management strategies.
      Approximately 50% of women will develop a urinary tract infection during their lifetime.
      • Barber A.E.
      • Norton J.P.
      • Spivak A.M.
      • Mulvey M.A.
      Urinary tract infections: current and emerging management strategies.
      In 2000, the United States spent $2.14 billion toward UTI treatment.
      • Barber A.E.
      • Norton J.P.
      • Spivak A.M.
      • Mulvey M.A.
      Urinary tract infections: current and emerging management strategies.
      Urinary tract infections are generally considered easily treatable, with the majority of patients prescribed a regimen of antibiotics. Overuse of antibiotic therapy has burdened the clinical management of urinary tract infections, which has led to the increasing prevalence of antibiotic resistance.
      • Barber A.E.
      • Norton J.P.
      • Spivak A.M.
      • Mulvey M.A.
      Urinary tract infections: current and emerging management strategies.
      An alternative prophylactic is needed to combat the emergence of ineffective treatments. Cranberry may be beneficial in preventing recurrent urinary tract infections in certain at-risk populations.
      • Dieter A.A.
      Cranberry capsules (2 taken twice daily for an average 38 days) reduce the risk of postoperative urinary tract infection in women undergoing benign gynaecological surgery involving intraoperative catheterisation.
      The mechanism of action of cranberry was initially thought to be due to the fruit’s acidity, producing a bacteriostatic effect in the urine.
      • Dieter A.A.
      Cranberry capsules (2 taken twice daily for an average 38 days) reduce the risk of postoperative urinary tract infection in women undergoing benign gynaecological surgery involving intraoperative catheterisation.
      More recently it was found that components in cranberry called proanthocyanidins, condensed tannin molecules with A-type linkages, exhibit potent bacterial antiadhesion activity.
      • Sanchez-Patan F.
      • Bartolome B.
      • Martin-Alvarez P.J.
      • Anderson M.
      • Howell A.
      • Monagas M.
      Comprehensive assessment of the quality of commercial cranberry products. Phenolic characterization and in vitro bioactivity.
      Herbals, such as cranberry, are not required to undergo the same rigorous testing to establish efficacy, dosage and safety as pharmaceutical agents regulated by the Food and Drug Administration.
      • Feifer A.H.
      • Fleshner N.E.
      • Klotz L.
      Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease.
      We sought to measure the bacterial anti-adhesion activity and proanthocyanidin levels in 7 commercially available cranberry supplements.

      Study Design

      The bioactivity of the 7 cranberry supplements in preventing adhesion of uropathogenic P-fimbriated Escherichia coli was tested by measuring the ability of the supplements to suppress agglutination of human red blood cells (A1, Rh+) following incubation with the bacteria.
      • Foo L.Y.
      • Lu Y.
      • Howell A.B.
      • Vorsa N.
      A-type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli.
      Endpoint concentrations were compared among the cranberry products, with the lowest concentration representing the highest bacterial antiadhesion activity. Wells containing bacteria plus phosphate-buffered saline, human red blood cells plus phosphate-buffered saline, bacteria plus test fraction, and human red blood cells plus test fraction served as negative controls for agglutination, and wells containing bacteria plus human red blood cells served as a positive control for agglutination.

      Results

      Antiadhesion activity of the supplements ranged from 0.47 to 60 mg/mL, with 4 products yielding negative results (Table). Typically, cranberry products that result in production of antiadhesion activity in urine when consumed have whole-product activities of 0.47–7.5 mg/mL. Proanthocyanidin levels ranged from 0.56 to 175 mg/g. In clinical trials, consumption of cranberry products containing about 36 mg of proanthocyanidin have resulted in significant reductions in recurrent urinary tract infections.
      TableComparison of cranberry products with PAC level, antiadhesion activity of the whole product, and antiadhesion of the isolated PACs
      ProductPAC level, mg/gAntiadhesion (MIC) whole product, mg/mLAntiadhesion (MIC) of PACs, μg/mL
      125.43.5-7.5156
      24Negative5000
      340.60312
      41750.4778
      51.2Negative2496
      61.4Negative2496
      70.56Negative312–624
      MIC, minimal inhibitory concentrations; PAC, proanthocyanidin.
      Chughtai. Commercial cranberry dietary supplements. Am J Obstet Gynecol 2016.

      Conclusion

      Despite clinical trials showing the efficacy of cranberry in preventing urinary tract infections, the actual antiadhesion activity and concentration of active proanthocyanidins in commercially available supplements is highly variable. In this study, several products contained virtually no active cranberry compounds. The clinical significance of this suggests that, although some are very potent, not all cranberry supplements have sufficient active compound to potentially achieve biologically relevant outcomes for urinary tract infection prevention. Although the benefits of utilizing cranberry for the maintenance of urinary tract health are definitely warranted because of resistance issues associated with antibiotic use, both physicians and patients alike need to be aware of the variability in quality of supplements available to consumers. Additionally, there needs to be stricter guidelines on the labeling and claims of these herbal medications.

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        Urinary tract infections: current and emerging management strategies.
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