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Urinary Tract Health and Antibacterial Benefits

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Increased salicylate concentrations in urine of human volunteers after consumption of cranberry juice.

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Authors
Duthie GG, Kyle JA, Jenkinson AM, Duthie SJ, Baxter GJ, Paterson JR
Journal
J Agric Food Chem 53(8):2897-2900
Abstract

The aim of this study was to assess whether regular consumption of cranberry juice results in elevations in urinary salicylate concentrations in persons not taking salicylate drugs. Two groups of healthy female subjects (11/group) matched for age, weight, and height consumed 250 mL of either cranberry juice or a placebo solution three times a day (i.e., 750 mL/day) for 2 weeks. At weekly intervals, salicylic acid and salicyluric acid (the major urinary metabolite of salicylic acid) concentrations were determined in urine by HPLC with electrochemical detection. Concentrations of salicylic acid in plasma were also determined. Consumption of cranberry juice was associated with a marked increase (p 0.001) of salicyluric and salicylic acids in urine within 1 week of the intervention. After 2 weeks, there was also a small but significant (p 0.05) increase in salicylic acid in plasma. The regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound that may benefit health.

Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin

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Authors
Chatterjee A, Yasmin T, Bagchi D and Stohs SJ
Journal
Mol Cell Biochem 265(1-2):19-26
Abstract

The objective of this study was to evaluate the effects of various berry extracts, with and without clarithromycin on Helicobacter pylori. Resistance to clarithromycin by H. pylori has been reported, leading to interest in alternatives/adjuncts to therapy with clarithromycin. H. pylori American type culture collection (ATCC) strain 49503 was grown, cell suspensions were made in
PBS and diluted 10-fold. One hundred μl of the suspension was then incubated for 18 h with extracts of raspberry, strawberry, cranberry, elderberry, blueberry, bilberry, and OptiBerry R , a blend of the six berries, at 0.25–1% concentrations. Serially diluted cell suspensions were exposed for 1 h to clarithromycin at 15 μg/ml. Ten μl of bacterial samples from the 10–7 dilution tube
were plated and incubated for 18 h and the number of colonies were counted. Growth of H. pylori was confirmed by the CLO R test. All berry extracts significantly (p 0.05) inhibited H. pylori, compared with controls, and also increased susceptibility of H. pylori to clarithromycin, with OptiBerry R demonstrating maximal effects.

Role of cranberry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment

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Authors
Pinzon-Arango PA, Liu Y and Camesano TA
Journal
J Med Food 12(2):259-270
Abstract

Previous clinical research has suggested that the consumption of cranberry products prevents the adhesion of Escherichia coli to uroepithelial cells by causing changes in bacterial fimbriae. Atomic force microscopy was used to probe the adhesion forces between E. coli (nonfimbriated strain HB101 and the P-fimbriated variant HB101pDC1) and a model surface (silicon nitride), to determine the effect of growth in cranberry products on bacterial adhesion. Bacteria were grown in tryptic soy broth supplemented with either light cranberry juice cocktail (L-CJC) or cranberry proanthocyanidins (PACs). Growth of E. coli HB101pDC1 and HB101 in L-CJC or PACs resulted in a decrease in adhesion forces with increasing number of cultures. In a macroscale bacteria-uroepithelial cell adhesion assay a decrease in bacterial attachment was observed for E. coli HB101pDC1 grown in L-CJC or PACs. This effect was reversible because bacteria that were regrown in cranberry-free medium regained their ability to attach to uroepithelial cells, and their adhesion forces reverted to the values observed in the control condition. Exposure to increasing concentrations of L-CJC resulted in a decrease of bacterial attachment to uroepithelial cells for the P-fimbriated strain after L-CJC treatment (27% by weight) and after PACs treatment (345.8 microg/mL). Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli. The concentration of cranberry products and the number of cultures the bacteria were exposed to cranberry determines how much the adhesion forces and attachment are altered.

Consumption of sweetened dried cranberries versus unsweetened raisins for inhibition of uropathogenic Escherichia coli adhesion in human urine: a pilot study

Posted
Authors
Greenberg JA, Newmann SJ and Howell AB
Journal
J Altern Complement Med 11(5):875-8
Abstract

OBJECTIVES: The aim of this study was to determine whether consumption of sweetened dried cranberries elicits urinary anti-adherence properties against Escherichia coli as previously demonstrated with cranberry juice and/or sweetened cranberry juice cocktail, compared to unsweetened raisins.

DESIGN: Uropathogenic E. coli isolates were obtained from five women with culture-confirmed urinary tract infections (UTIs). Four urine samples were collected from each subject. The first urine sample was collected before any study intervention. The second urine sample was collected 2-5 hours after consumption of one box (42.5 g) of raisins. The third urine sample was collected 5-7 days later. The final urine sample was collected 2-5 hours after consumption of approximately 42.5 g of dried cranberries.

MATERIALS AND METHODS: E. coli isolates were incubated separately in each of the four urine samples collected from the five subjects. Bacteria were harvested from the urine and tested for the ability to prevent adhesion of P-fimbriated E. coli bacteria using a mannose-resistant hemagglutination assay with human red blood cells (A1, Rh+).

RESULTS: Of the urine samples collected after dried cranberry consumption, one demonstrated 50% antiadherence activity, two demonstrated 25% activity, and two did not show any increased activity. None of the control urine samples and none of the postraisin consumption samples demonstrated any inhibitory activity.

CONCLUSIONS: Data from this pilot study on only five subjects suggest that consumption of a single serving of sweetened dried cranberries may elicit bacterial antiadhesion activity in human urine, whereas consumption of a single serving of raisins does not. Further studies are needed to verify the antiadhesion effect of sweetened dried cranberries. In addition, dose-response and pharmacokinetics of the active compounds in the dried cranberries need to be determined. If clinical research is positive, dried cranberries could potentially be a viable alternative to cranberry juice consumption for prevention of UTIs.

Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? a randomized controlled trial in older women

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Authors
McMurdo ME, Argo I, Phillips G, Daly F, Davey P
Journal
J Antimicrob Chemother 63(2):389-95
Abstract

OBJECTIVES: To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women.

PATIENTS AND METHODS: One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months.

RESULTS: Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the cranberry group and 14 in the trimethoprim group); difference in proportions relative risk 1.616 (95% CI: 0.93, 2.79) P = 0.084. The time to first recurrence of UTI was not significantly different between the groups (P = 0.100). The median time to recurrence of UTI was 84.5 days for the cranberry group and 91 days for the trimethoprim group (U = 166, P = 0.479). There were 17/137 (12%) withdrawals from the study, 6/69 (9%) from the cranberry group and 11/68 (16%) from the trimethoprim group (P = 0.205), with a relative risk of withdrawal from the cranberry group of 0.54 (95% CI: 0.19, 1.37).

CONCLUSIONS: Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi.

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

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Authors
Howell AB, Botto H, Combescure C, Blanc-Potard A-B, Gausa L, Matsumoto T, Tenke P, Sotto A, Lavigne JP
Journal
BMC Infect Dis 10:94
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.

Predictors of urinary tract infection after menopause: a prospective study

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Authors
Jackson SL, Boyko EJ, Scholes D, Abraham L, Gupta K, Fihn SD
Journal
Am J Med 117(12):903-911
Abstract

Purpose: To describe the incidence of and risk factors for acute cystitis among nondiabetic and diabetic postmenopausal women.
Methods:We conducted a population-based, prospective cohort study of 1017 postmenopausal women, aged 55 to 75 years, who were enrolled in a health maintenance organization and followed for 2 years. A wide range of behavioral and physiologic exposures were assessed at baseline interview and follow-up clinic visits; the main outcome measure was microbiologically confirmed acute symptomatic cystitis. Follow-up was 87% at 12 months and 81% at 24 months.
Results:During 1773 person-years of follow-up, 138 symptomatic urinary tract infections occurred (incidence, 0.07 per person-year). Independent predictors of infection included insulin-treated diabetes (hazard ratio [HR] = 3.4; 95% confidence interval [CI]: 1.7 to 7.0) and a lifetime history of urinary tract infection (HR for six or more infections = 6.9; 95% CI: 3.5 to 13.6). Borderline associations included a history of vaginal estrogen cream use in the last month (HR = 1.8; 95% CI: 1.0 to 3.4), a history of kidney stones (HR = 1.9; 95% CI: 1.0 to 3.7), and asymptomatic bacteriuria at baseline (HR = 1.8; 95% CI: 0.9 to 3.5). Sexual activity, urinary incontinence, parity, postcoital urination, vaginal dryness, use of cranberry juice, vaginal bacterial flora, and postvoid residual bladder volume were not associated with incident acute cystitis after multivariable adjustment.
Conclusion:Insulin-treated diabetes is a potentially modifiable risk factor for incident acute cystitis among postmenopausal women, whereas a lifetime history of urinary tract infection was the strongest predictor. Use of oral or vaginal estrogen was not protective, and a wide range of behavioral and physiologic factors was not associated with acute cystitis episodes in this generally healthy sample.

The effect of cranberry juice and cranberry proanthocyanidins on the infectivity of human enteric viral surrogates.

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Authors
Su X, Howell AB, D'Souza DH
Journal
Food Microbiol 27(4):535-40
Abstract

The effect of cranberry juice (CJ) and cranberry proanthocyanidins (PAC) on the infectivity of human enteric virus surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), MS2(ssRNA) bacteriophage, and phiX-174(ssDNA) bacteriophage was studied. Viruses at high (approximately 7 log(10) PFU/ml) or low (approximately 5 log(10) PFU/ml) titers were mixed with equal volumes of CJ, 0.30, 0.60, and 1.20 mg/ml final PAC concentration, or water and incubated for 1 h at room temperature. Viral infectivity after treatments was evaluated using standardized plaque assays. At low viral titers, FCV-F9 was undetectable after exposure to CJ or the three tested PAC solutions. MNV-1 was reduced by 2.06 log(10) PFU/ml with CJ, and 2.63, 2.75, and 2.95 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. MS2 titers were reduced by 1.14 log(10) PFU/ml with CJ, and 0.55, 0.80, and 0.96 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. phi-X174 titers were reduced by 1.79 log(10) PFU/ml with CJ, and 1.95, 3.67, and 4.98 log(10) PFU/ml with PAC at 0.15, 0.30, and 0.60 mg/ml, respectively. Experiments using high titers showed similar trends but with decreased effects. CJ and PAC show promise as natural antivirals that could potentially be exploited for foodborne viral illness treatment and prevention.

Cranberry juice and adhesion of antibiotic-resistant uropathogens

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Authors
Howell AB and Foxman B
Journal
JAMA 287(23):3082-3
Abstract

No abstract - Introduction: Urinary tract infections (UTIs) account for more than 11 million physician visits annually in the United States and have become increasingly resistant to first-line antibiotic therapy. Recent evidence suggests that consumption of cranberry juice beverages is effective at preventing UTIs, although further studies are needed to validate potential treatment effects. While early research focused on a mechanism of urinary acidification, the largest clinical trial to date found no evidence to support this. Recent studies suggest that cranberry proanthocyanidins (condensed tannins) may inhibit P-fimbriated Escherichia coli from adhering to uroepithelial cells, the initial step in development of UTI. The effectiveness of cranberry proanthocyanidins and cranberry beverages against antibiotic-resistant E coli, however, has not been previously tested. We assessed whether consumption of cranberry juice cocktail prevents adhesion of antibiotic-resistant uropathogenic P-fimbriated E coli to the uroepithelium.

Cranberry juice and bacterial colonization in children--a placebo-controlled randomized trial

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Authors
Kontiokari T, Salo J, Eerola E and Uhari M
Journal
Clin Nutr 24(6):1065-72
Abstract

BACKGROUND: The cranberry produces antimicrobial compounds such as proanthocyanidines in response to microbial invasion. In vitro it is able to prevent growth, adhesion or biofilm formation of a large number of bacteria, while clinically, cranberry juice has been shown to prevent urinary tract infections (UTI) in women. However, the effect of cranberry on bacterial colonization more widely has not been evaluated. We were interested in studying cranberry juice in children since many children with recurrent UTI need long-term antimicrobial prophylaxis and would benefit from an alternative.

OBJECTIVE: To evaluate the effect of cranberry juice on nasopharyngeal and colonic bacterial flora, to evaluate how well cranberry juice is accepted by children and to evaluate its effect on infectious diseases and related symptoms.

DESIGN: Children (mean age 4.3 years) in day care centers were randomized to receive either cranberry juice (n=171) or a placebo (n=170) for 3 months. Bacterial samples were collected before and after the intervention and analyzed for both respiratory bacterial pathogens and enteric fatty acid composition, reflecting changes in the colonic bacterial flora. Infectious diseases and their symptoms were monitored using symptom diaries. Compliance was evaluated as the number of drop-outs during the trial and by counting the numbers of doses taken.

RESULTS: The carriage of respiratory bacteria did not change significantly during the intervention, while fecal fatty acid composition changed significantly with time (P0.001) but did not differ between the groups (P>0.05). Cranberry juice had no effect on common infectious diseases or their symptoms. The cranberry juice was well accepted: the number of drop-outs in 3 months was 18 (11%) in the cranberry group and 11 (7%) in the placebo group, and most of the doses were taken as instructed, 145 (88%) and 129 (77%) children, respectively, taking at least 90% of the doses.

CONCLUSIONS: Cranberry juice was well accepted by the children, but led to no change in either the bacterial flora in the nasopharynx or the bacterial fatty acid composition of stools. Thus cranberries seem to have beneficial effect on urinary health only and this is not compromised by other unexpected antimicrobial effects.