title: Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study.
abstract: BACKGROUND
  Ingestion of cranberry (Vaccinium macrocarpon Ait.) has traditionally been utilized for prevention of urinary tract infections. The proanthocyanidins (PACs) in cranberry, in particular the A-type linkages have been implicated as important inhibitors of primarily P-fimbriated E. coli adhesion to uroepithelial cells. Additional experiments were required to investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day and to determine if the urinary anti-adhesion effect following cranberry is detected within volunteers of different origins.
  
  
  METHODS
  Two separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urines samples collected from 32 volunteers from Japan, Hungary, Spain and France in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain.
  
  
  RESULTS
  The results indicated a significant bacterial anti-adhesion activity in urine samples collected from volunteers that consumed cranberry powder compared to placebo (p < 0.001). This inhibition was clearly dose-dependent, prolonged (until 24 h with 72 mg of PAC) and increasing with the amount of PAC equivalents consumed in each cranberry powder regimen. An in vivo Caenorhabditis elegans model showed that cranberry acted against bacterial virulence: E. coli strain presented a reduced ability to kill worms after a growth in urines samples of patients who took cranberry capsules. This effect is particularly important with the regimen of 72 mg of PAC.
  
  
  CONCLUSIONS
  Administration of PAC-standardized cranberry powder at dosages containing 72 mg of PAC per day may offer some protection against bacterial adhesion and virulence in the urinary tract. This effect may offer a nyctohemeral protection.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Espri26, Université Montpellier 1, Nîmes, France.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Howell
authors.forename: Henry
authors.initials: H
authors.lastname: Botto
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Anne-Béatrice
authors.initials: AB
authors.lastname: Blanc-Potard
authors.forename: Lluis
authors.initials: L
authors.lastname: Gausa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Peter
authors.initials: P
authors.lastname: Tenke
authors.forename: Albert
authors.initials: A
authors.lastname: Sotto
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lavigne
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001422:Bacterial Adhesion / Q000187:drug effects*; D002460:Cell Line; D004311:Double-Blind Method; D005602:France; D006801:Humans; D006814:Hungary; D007564:Japan; D011208:Powders / Q000737:chemistry*; D044945:Proanthocyanidins / Q000008:administration & dosage*; D013030:Spain; D014556:Urine / Q000737:chemistry*; D056689:Uropathogenic Escherichia coli / Q000187:drug effects*; D029799:Vaccinium macrocarpon / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D011208:Powders; D044945:Proanthocyanidins; C013221:proanthocyanidin
references.citation: J Altern Complement Med. 2005 Oct;11(5):875-8
references.pmid: 16296921
references.citation: J Agric Food Chem. 2001 Mar;49(3):1270-6
references.pmid: 11312849
references.citation: J Urol. 2007 Jun;177(6):2357-60
references.pmid: 17509358
references.citation: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001321
references.pmid: 18253990
references.citation: J Agric Food Chem. 2007 Apr 18;55(8):3217-24
references.pmid: 17381122
references.citation: N Engl J Med. 1998 Oct 8;339(15):1085-6
references.pmid: 9767006
references.citation: J Agric Food Chem. 2005 Nov 16;53(23):8940-7
references.pmid: 16277386
references.citation: JAMA. 1994 Mar 9;271(10):751-4
references.pmid: 8093138
references.citation: Mol Nutr Food Res. 2007 Jun;51(6):732-7
references.pmid: 17487930
references.citation: JAMA. 2002 Jun 19;287(23):3082-3
references.pmid: 12069670
references.citation: Trends Microbiol. 2005 Mar;13(3):119-27
references.pmid: 15737730
references.citation: World J Urol. 2006 Feb;24(1):21-7
references.pmid: 16397814
references.citation: N Engl J Med. 1991 May 30;324(22):1599
references.pmid: 1674106
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10892-7
references.pmid: 11535834
references.citation: Microbes Infect. 2007 Feb;9(2):214-23
references.pmid: 17208486
references.citation: Clin Microbiol Infect. 2006 Dec;12(12):1199-206
references.pmid: 17121626
references.citation: Clin Microbiol Infect. 2008 Apr;14(4):350-5
references.pmid: 18190583
references.citation: Antimicrob Agents Chemother. 1989 Jan;33(1):92-8
references.pmid: 2653218
references.citation: J Urol. 1984 May;131(5):1013-6
references.pmid: 6368872
references.citation: Biotechnol Bioeng. 2006 Feb 5;93(2):297-305
references.pmid: 16142789
references.citation: J Fam Pract. 1997 Aug;45(2):167-8
references.pmid: 9267377
references.citation: Can J Urol. 2002 Jun;9(3):1558-62
references.pmid: 12121581
references.citation: Phytochemistry. 2005 Sep;66(18):2281-91
references.pmid: 16055161
references.citation: Biosci Biotechnol Biochem. 2006 Jul;70(7):1681-7
references.pmid: 16861803
references.citation: J Nat Prod. 2000 Sep;63(9):1225-8
references.pmid: 11000024
references.citation: J Infect Dis. 1981 Mar;143(3):325-45
references.pmid: 7014727