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.
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.
Howell
Amy B
AB
Institut National de la Santé et de la Recherche Médicale, Espri26, Université Montpellier 1, Nîmes, France.
Botto
Henry
H
Combescure
Christophe
C
Blanc-Potard
Anne-Béatrice
AB
Gausa
Lluis
L
Matsumoto
Tetsuro
T
Tenke
Peter
P
Sotto
Albert
A
Lavigne
Jean-Philippe
JP
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*
D000900:Anti-Bacterial Agents; D011208:Powders; D044945:Proanthocyanidins; C013221:proanthocyanidin
J Altern Complement Med. 2005 Oct;11(5):875-8
16296921
J Agric Food Chem. 2001 Mar;49(3):1270-6
11312849
J Urol. 2007 Jun;177(6):2357-60
17509358
Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001321
18253990
J Agric Food Chem. 2007 Apr 18;55(8):3217-24
17381122
N Engl J Med. 1998 Oct 8;339(15):1085-6
9767006
J Agric Food Chem. 2005 Nov 16;53(23):8940-7
16277386
JAMA. 1994 Mar 9;271(10):751-4
8093138
Mol Nutr Food Res. 2007 Jun;51(6):732-7
17487930
JAMA. 2002 Jun 19;287(23):3082-3
12069670
Trends Microbiol. 2005 Mar;13(3):119-27
15737730
World J Urol. 2006 Feb;24(1):21-7
16397814
N Engl J Med. 1991 May 30;324(22):1599
1674106
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10892-7
11535834
Microbes Infect. 2007 Feb;9(2):214-23
17208486
Clin Microbiol Infect. 2006 Dec;12(12):1199-206
17121626
Clin Microbiol Infect. 2008 Apr;14(4):350-5
18190583
Antimicrob Agents Chemother. 1989 Jan;33(1):92-8
2653218
J Urol. 1984 May;131(5):1013-6
6368872
Biotechnol Bioeng. 2006 Feb 5;93(2):297-305
16142789
J Fam Pract. 1997 Aug;45(2):167-8
9267377
Can J Urol. 2002 Jun;9(3):1558-62
12121581
Phytochemistry. 2005 Sep;66(18):2281-91
16055161
Biosci Biotechnol Biochem. 2006 Jul;70(7):1681-7
16861803
J Nat Prod. 2000 Sep;63(9):1225-8
11000024
J Infect Dis. 1981 Mar;143(3):325-45
7014727