Cranberry Therapy of Urinary Tract Infections

 

Wise Young PhD MD, Professor II & Director

W M Keck Center for Collaborative Neuroscience

Rutgers, State University of New Jersey

604 Allison Rd, Piscataway, NJ 08854-8082

tel: 732/445-2061, fax: 732/445-2063

email: wisey@pipeline.com, young@biology.rutgers.edu

web: http://carecure.rutgers.edu, http://sciwire.com

 

Despite a dramatic decline in mortality due to urinary tract infections (UTI) in the last 20 years, UTI’s remain very common in people with spinal cord injury (SCI) and particularly those with indwelling catheters (Biering-Sorenson, et al., 2001) and older individuals (High, 2001).  Use of prophylactic antibiotics, particularly for asymptomatic cases of bacteriuria is controversial and discouraged.  Thus, many people have been searching for alternative approaches.  Cranberry juice has long been reported to prevent urinary tract infection (Papas, et al., 1966; Kahn, et al. 1967).  Much folklore and science support the use of cranberries to prevent urinary tract infections.  As many as 40% of people with SCI take cranberry concentrates daily to prevent UTI’s.  Are there any bases for this practice?

Early Studies

Avorn, et al. (1994) did a double-blind randomized clinical trial of 153 elderly woman who consumed 300 ml per day of a commercially available cranberry beverage or a synthetic placebo drink that was similar tasting and had vitamin C but lacked cranberry content.  When they sampled the urine of these women, they found that those that drank the cranberry juice had only 27% incidence of bacteria in the urine, compared to 42% in those drinking the placebo (p=0.004).  This led to some clinicians to recommend drinking 300-500 ml of cranberry juice cocktail each day (Fleet, 1994). 

Foxman, et al. (1995) studied first-time UTI’s in young unmarried women using a university health service and who had engaged in sexual intercourse at least once.  Compared against the general population of students, the study found that intercourse significantly increased the risk of UTI’s by 43% but that cranberry juice drinking reduced the risk by 52% and carbonated soft drinks increased the risk by 237%. 

In 1999, Schlager, et al. did a double-blind placebo-controlled crossover trial that compared cranberry or placebo for three months and vice versa for three months in children with neurogenic bladders treated with intermittent catheterization.  They found that 75% of 151 cultures indicated bacteriuria at both time intervals.  It did not differ when the children were drinking cranberry or placebo concentrate. 

Jepson, et al. (2000) recently did Cochrane Reviews of clinical trials on the use of cranberries for preventing or treating UTI’s.  They found five trials that met the inclusion criterion of randomized and controlled trials to assess cranberry prevention of UTI.  Two of the five trials indicated that cranberry therapy was effective in preventing symptomatic or asymptomatic UTI’s.  They found no randomized trials that tested the efficacy of cranberry once the UTI has occurred. They pointed to the high dropout rates in all the trials, the small samples sizes, and called for more clinical trials. 

Recent Trials

Several clinical trials were reported in 2001 and were not covered by the Jepson (2000) review.  The recent clinical trials again suggest opposing results.  Two studies indicate beneficial preventative effects of cranberry and two studies suggest that cranberries do not differ from other juices and do not reduce bacteriuria.  Nevertheless, the best designed trials with the most patients suggest that the cranberry intake reduces the incidence of UTI’s.

In Russia, Kirchhoff, et al. (2001) compared urine tract infection rates in two geriatric units.  One unit drank cranberry juice while the other drank the usual mixed berry juice over a 4-week period.  In all cases of suspected UTI, urine samples were cultured.  In 140/338 cases, urine cultures revealed bacteriuria in 54% of the cases and antibiotic therapy of 44%.  There was no difference in the rates of infections in the two units, suggesting no effect of cranberry juice intake on UTI rate. 

In Finland, Kontiokari, et al. (2001) randomized 150 women with UTI’s due to E. coli to 50 ml of cranberry-ligonberry juice concentrate daily for 6 months, 100 ml of lactobacillus drink 5 days a week for a year, or no intervention.  At 6 months, 16% of the women in the cranberry group, 39% in the lactobacillus group, and 36% in the control group had UTI’s.

Morris & Stickler (2001) studied volunteers who were inoculated with Proteus mirabilis (a common urinary tract bacteria) for 24-48 hours and then examined for the extent of catheter encrustation.  Volunteers who drank 500 ml of cranberry juice did not differ significantly from those who drank 500 ml of water.  Note that volunteers who drank either cranberry juice or water had less encrustation than volunteers who did not supplement their normal fluid intake.

Reid, et al. (2001) examined 15 spinal injured patients, to see if cranberry juice altered bacterial biofilm load in the bladder.  They found that cranberry juice significantly reduced biofilm load, with reduction in adhesion of both gram-positive and gram-negative bacteria to cells.  Water intake did not change bacterial adhesions.  [Note that Ocean Spray Cranberries funded this study.

Possible Mechanisms of Cranberry Effects on Infections

Direct antibacterial and anti-fungal effects of cranberry juice have long been reported (Swartz & Medrek, 1968; Borukh, et al. 1972; Ibragimov & Kazanskaia, 1981) although the mechanisms were not well understood.  Early studies focused on the ability of cranberry juice to reduce urinary pH, i.e. Kinney & Blount (1979; Jackson & Hicks, 1997).  Hippuric acid in cranberry juice reduces pH and may suppress infections (Nahata, et al. 1982; Simpson & Khajawall, 1983; Walsh, 1992) and enhance antibiotic activity (Chernomordik & Vasilenko, 1981).

Over 16 years ago, Sobota, et al. (1984) reported that cranberry juice inhibited bacterial adherence to the bladder surface in mice.  They tested over 77 clinical isolates of the bacteria Escherichia coli (E. coli) and cranberry juice inhibited adhesion to the bladder by more that 75% for over 60% of the strains of bacteria.  Schmidt & Sobota (1988) showed that this was true of many other bacteria besides E. coli, including Proteus, Klebsiella, Enterobacter, and Pseudomonas. 

In 1989, in Israel, Zafriri, et al. confirmed that cranberry juice reduced expression of various surface lectins on E. coli isolated from bladder infections.  Some of this effect apparently was due to the fructose (sugar) present in the juices but there was something else in cranberry juice that orange and pineapple juice did not.  In 1991, Ofek, et al. reported a similar antiadhesion activity of cranberry and blueberry juice on E. coli adhesin activity.  Ahuja, et al. (1998) reported that cranberry juice inhibited formation of fimbria that E. coli uses to attach to cellular surfaces and proposed that cranberry juice prevents expression of molecules in the bacteria that prevents fimbria formation and attachment.  Cranberry extracts also reduce E. coli adhesion to glass (Allison, et al., 2000).

In 1999, Habash, et al. (1999) studied the effects of supplemental water, ascorbic acid, or cranberry concentrations on urine and bacterial adhesions to silicone rubber.  Urine from people taking ascorbic acid and cranberry juice inhibited E. coli and enterococcus faecalis adhesion to silicone rubber but not pseudomonas, staphylococcus epidermidis, or Candida albicans.  Interesting, people with increased water intake had “vastly increased” initial deposition rates and numbers of adherent E. coli and E. faecalis, suggesting that dilution of urine increased bacterial adhesion and that something in urine may inhibit such adhesion. 

Cranberry have antioxidants that can scavenge free radicals.  Of berries, blackberries, blueberries, cranberries, and raspberries have the higest antioxidant capacity (Wang & Jiao, 2000).  Wilson, et al. (1998) showed that cranberry extracts reduce oxidation of low density of lipoprotein.  Perderson, et al. (2000) studied the effects of blueberry and cranberry consumption of the plasma antioxidant capacity of healthy female volunteers.  Daily ingestion of 500 ml of cranberry juice increased plasma phenolic content and antioxidant capacity.  Consumption of a similar amount of blueberry did not have this effect, perhaps due to the higher vitamin C contents of cranberry.

Foo, et al. (2000) isolated the some chemicals from cranberry juice that might be responsible for its anti-infective traits.  Three proanthocyanidin trimers, in particular, inhibited adhesion of E coli to cellular surfaces.  Weiss, et al. (1998) likewise found a high-molecular weight molecule in cranberries that prevent aggregation of bacteria in the mouth.  Burger, et al. (2000) isolated a high molecular weight constituent of cranberry juice which inhibited sialic acid specific adhesions of Helibacter pylori to mucus. 

Side-Effects of Cranberries

None of the clinical trials reported significant side-effects of 300-500 ml of cranberry juice consumption. There have been no formal published clinical trials of the popular cranberry concentrates packaged in capsules.  One recent study, however, suggest that people should be careful to limit their cranberry intake because it may lead to increased kidney stone formation. 

Terris, et al. (2001) reported that dietary supplementation with cranberry concentrates increase blood and urine oxalate levels, and may contribute to more kidney stones.  They gave manufacturer-recommended doses to 5 volunteers for 7 days and found a significantly increased level of urinary oxalate levels (p=0.01) by 43% in the cranberry group.  Cranberries contain oxalates (2-26 mg per serving) but has much less than spinach (1236 mg), chocolate (126 mg), or tea (66 mg); only spinach has high enough levels to produce significant hyperoxaluria (Brinkley, et al. 1981).  Oxalate is a component of the most common type of kidney stone.  Cranberry juice may reduce the incidence of calcium stones (Light, et al., 1973).

In addition to ascorbic acid, cranberry juice contains a variety of substances that may be biologically active. For example, cranberries contain flavonoids called procyanidins and other phenolic compounds (Chen, et al., 2001).  The levels of procyanidins in cranberry juice (31.9 mg per serving) is higher than red wine (22.0 mg) but lower than chocolates (165 mg) and apples (147 mg).  Red delicious apples have the highest level (208 mg) compared with Granny Smiths (183 mg) and McIntosh (105 mg) varieties.  Approximately 56% of cranberry juice are flavonoids and 44% are other phenolic compounds.  Benzoic acid is the major phenolic compound while the major flavonoids are quercetin and myricetin.  Of course, cranberries contain organic acids, including quinic, malic, and citric acid (Coppola, et al. 1978).

In comparison with the risks of antibiotic and other therapies being used to prevent and treat urinary tract infections, however, cranberries seem innocuous  (Patel & Daniels, 2000).  Cranberries rank in the top four most popular herbal remedies taken by Americans, i.e. garlic, aloe gel, cranberry and echinacea.  A recent survey of patients at a large HMO indicate that over 40% of patients take one or more of these herbal remedies (Bennett & Brown, 2000). 

Bottom Line

Much anecdotal evidence supports the efficacy of cranberry juice in preventing urinary tract infection.  Although there is a dearth of formal clinical randomized trials examining the risk of UTI, enough positive studies have been published suggesting that cranberry is better than other kinds of juices for preventing UTI’s.  Some evidence suggest that there are special substances in cranberry juice that directly affect bacteria and their attachment to cellular surfaces.  In addition, cranberry juice may have other salutory effects, including lowering pH and antioxidant activities. 

At least three randomized clinical trials report that this amount of cranberry juice is necessary and sufficient to reduce the risk of UTI.  Probably the most influential trial was in 1994, when Avorn, et al. at Brigham and Women’s Hospital in Boston showed that regular intake of 300 ml of cranberry juice more than halved the likelihood of bacteria and urinary infection, compared against a placebo drink with ascorbic acid.  A recent trial in Finland (Kontiokari, et al. 2001) likewise showed that cranberry-ligonberry juice more than halved the incidence of urinary tract infections during a 6 month period, compared to a lactobacillus drink 5 days a week. 

None of the trials reported significant deleterious side-effects from drinking 300-500 ml of cranberry juice per day.  Jepson, et al. (2000) pointed out the high dropout rate of women from all the trials and the need for a rigorously randomized and placebo-controlled clinical trial involving larger populations to answer the efficacy question rigorously.  These trials also did not test the most popularly used form of cranberry, i.e. 300-500 mg of cranberry concentrate per day in capsules.

Given the low risk and the potential benefits of a reduction of urinary tract infections, many physicians are encouraging their patients to drink 300-500 ml of cranberry juice per day.  Insufficient data is available regarding the cranberry concentrates.  A well-organized clinical trial that compares cranberry capsules and ascorbic acid in a large number of patients seems to be in order.

References

 

•  Ahuja S, Kaack B and Roberts J (1998). Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth medium of P-fimbriated Escherichia coli. J Urol. 159 (2): 559-62. Summary: PURPOSE: Vaccinium macrocarpon--the American cranberry--irreversibly inhibits the expression of P-fimbriae of E. coli. Further effects on the function and expression of P-fimbriae were studied by growing P-fimbriated E. coli in solid media laced with cranberry juice. METHODS: Cranberry concentrate at pH 7.0 was added to CFA medium to a final concentration of 25%. E. coli strains JR1 and DS17 were plated on this medium with a plain CFA control and incubated at 37C. Cultures were tested for ability to agglutinate P-receptor specific beads. Bacteria were washed in PBS and agglutination retested. Cultures were also replated on plain CFA agar and rechecked for their ability to agglutinate. Transmission electron micrographs were performed on positive control and test bacteria. RESULTS: For E. coli strain JR1, P-fimbrial agglutination was inhibited after the third plating. DS17 was fully inhibited after the second plating. Washing in PBS did not affect agglutination, but replating on CFA agar allowed agglutination to recur. Electron micrographic study of control populations confirmed fimbriae. Fully inhibited bacteria had a 100% reduction in expression of fimbriae. Additionally, inhibited bacteria showed cellular elongation. CONCLUSIONS: Cranberry juice irreversibly inhibits P-fimbriae. Electron micrographic evidence suggests that cranberry juice acts on the cell wall preventing proper attachment of the fimbrial subunits or as a genetic control preventing the expression of normal fimbrial subunits or both. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9649291> Department of Urology and Tulane University Primate Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.

 

•  Allison DG, Cronin MA, Hawker J and Freeman S (2000). Influence of cranberry juice on attachment of Escherichia coli to glass. J Basic Microbiol. 40 (1): 3-6. Summary: An extract from fresh cranberries was shown to decrease the strength of attachment of Escherichia coli to glass coverslips when incubated together for 2 h. Pre-conditioning of the surface prior to biofilm formation also significantly weakened the strength of attached cells. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10746194> School of Pharmacy and Pharmaceutical Sciences, University of Manchester, U.K. DALLISON@MAN.AC.UK

 

•  Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I and Lipsitz LA (1994). Reduction of bacteriuria and pyuria after ingestion of cranberry juice. Jama. 271 (10): 751-4. Summary: OBJECTIVE--To determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women. DESIGN--Randomized, double-blind, placebo-controlled trial. SUBJECTS--Volunteer sample of 153 elderly women (mean age, 78.5 years). INTERVENTION--Subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content. OUTCOME MEASURES--A baseline urine sample and six clean-voided study urine samples were collected at approximately 1-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells. RESULTS--Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering > or = 10(5)/mL) with pyuria that were only 42% of the odds in the control group (P = .004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P = .006). CONCLUSIONS--These findings suggest that use of a cranberry beverage reduces the frequency of bacteriuria with pyuria in older women. Prevalent beliefs about the effects of cranberry juice on the urinary tract may have microbiologic justification. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8093138> Program for the Analysis of Clinical Strategies, Brigham and Women's Hospital, Boston, MA 02115.

 

•  Bennett J and Brown CM (2000). Use of herbal remedies by patients in a health maintenance organization. J Am Pharm Assoc (Wash). 40 (3): 353-8. Summary: OBJECTIVE: To examine the use of and experiences with herbal remedies among a group of patients enrolled in a health maintenance organization (HMO). DESIGN: Self-administered questionnaire. SETTING: Central Texas city. PARTICIPANTS: 135 HMO patients. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE: Patients' self-reported use of herbal remedies. RESULTS: Almost 40% of patients indicated they had used herbal remedies. The majority had used herbal remedies to treat or prevent a health condition (e.g., common cold). The remedies most frequently used were garlic, aloe gel, cranberry, and echinacea. Most respondents gathered their information on herbal remedies from the popular media, and most based their use decisions primarily on the recommendations of friends and/or relatives. Although most were unsure of the quality of the products, they felt they were safe and somewhat effective, and few had experienced any direct side effects they attributed to the herbal remedies. Most patients used the products without the knowledge of their physician or pharmacist. Herbal remedies were most often used in place of prescription or over-the-counter (OTC) medications and most frequently purchased in health food stores and mass merchandizer/grocery stores. Herbal remedies were sometimes used along with prescription or OTC medications. CONCLUSION: Given that patients are using herbal remedies for a variety of health conditions without medical supervision, pharmacists need to actively and consistently obtain information about herbal remedy use to effectively advise patients and monitor outcomes. More research is needed on herbal remedy use among patient populations and on outcomes in patients who use herbal remedies to treat primary health conditions. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10853535> Methodist Hospital, Omaha, Nebr., USA.

 

•  Biering-Sorensen F, Bagi P and Hoiby N (2001). Urinary tract infections in patients with spinal cord lesions: treatment and prevention. Drugs. 61 (9): 1275-87. Summary: Even though the mortality due to urinary tract complications has decreased dramatically during the last decades in individuals with spinal cord lesions (SCL), urinary tract infections (UTI) still cause significant morbidity in this population. Complicated UTI are caused by a much wider variety of organisms in individuals with SCL than in the general population and are often polymicrobial. Escherichia coli, Pseudomonas spp., Klebsiella spp., Proteus spp., Serratia spp., Providencia spp., enterococci, and staphylococci are the most frequently isolated bacteria in urine specimens taken from individuals with SCL. There is no doubt that the greatest risk for complicated UTI in these individuals is the use of an indwelling catheter. Intermittent catheterisation during the rehabilitation phase has been shown to lower the rate of UTI, and virtually eliminate many of the complications associated with indwelling catheters. Persons with SCL should only be treated for bacteriuria if they have symptoms. Generally, it is advisable to use antibacterial agents with little or no impact on the normal flora. Single agent therapy - in accordance with antimicrobial susceptibility test - is preferred. We advise extending treatment to at least 5 days, and in those with reinfection or relapsing UTI, at least 7 to 14 days, depending on the severity of the infection. The diagnosis of structural and/or functional risk factors is essential in order to plan an optimal treatment for UTI in individuals with SCL, which should include treatment of simultaneously occurring predisposing factors. The treatment of structural risk factors follows general urological principles, aiming for sufficient outlet from the bladder with minimal residual urine and low pressure voiding. For prevention of UTI, general cleanliness and local hygiene should be encouraged. If the patient has a reinfection or relapsing symptomatic UTI, it is important to check for inadequately treated infection and complications, which need special attention, in particular residual urine and urinary stones. No reliable evidence exists of the effectiveness of cranberry juice and other cranberry products. Prophylactic antibacterials should only be used in patients with recurrent UTI where no underlying cause can be found and managed, and in particular if the upper urinary tract is dilated. Antibacterials should not be used for the prevention of UTI in individuals with SCL and indwelling catheters. However, the use of prophylactic antibacterials for individuals with SCL using intermittent catheterisation or other methods of bladder emptying is controversial. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11511022> Clinic for Para- and Tetraplegia, Copenhagen University Hospital, Rigshospitalet, Denmark. finbs@rh.dk

 

•  Borukh IF, Kirbaba VI and Senchuk GV (1972). [Antimicrobial properties of cranberry]. Vopr Pitan. 31 (5): 82. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4198007>

 

•  Brinkley L, McGuire J, Gregory J and Pak CY (1981). Bioavailability of oxalate in foods. Urology. 17 (6): 534-8. Summary: The ability of 7 "oxalate-rich" foods to enhance urinary oxalate excretion was measured in 8 normal volunteers. The analyzed value for oxalate was high for spinach (1,236 mg.), moderate for chocolate (126 mg.) and tea (66 mg.), and for low vegetable juice, cranberry juice, pecans, and orange juice (2 to 26 mg.). The urinary oxalate increased by 29.3 mg. during eight hours after ingestion of spinach. However, it rose by less than 4.2 mg. from consumption of other food items. The bioavailable oxalate (per cent of total appearing in urine) was much less from food items of high or moderate oxalate content (spinach and chocolate) than from standard solutions of sodium oxalate (2.4 to 2.6 versus 6.5 to 7.3 per cent). Thus, only spinach among food items tested was capable of causing hyperoxaluria in normal subjects. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7245443>

 

•  Burger O, Ofek I, Tabak M, Weiss EI, Sharon N and Neeman I (2000). A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus. FEMS Immunol Med Microbiol. 29 (4): 295-301. Summary: Because previous studies have shown that a high molecular mass constituent of cranberry juice inhibited adhesion of Escherichia coli to epithelial cells and coaggregation of oral bacteria, we have examined its effect on the adhesion of Helicobacter pylori to immobilized human mucus and to erythrocytes. We employed three strains of H. pylori all of which bound to the mucus and agglutinated human erythrocytes via a sialic acid-specific adhesin. The results showed that a high molecular mass constituent derived from cranberry juice inhibits the sialic acid-specific adhesion of H. pylori to human gastric mucus and to human erythrocytes. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11118911> Faculty of Food Engineering and Biotechnology, Institute of Technology, Technion, Haifa, Israel.

 

•  Chen H, Zuo Y and Deng Y (2001). Separation and determination of flavonoids and other phenolic compounds in cranberry juice by high-performance liquid chromatography. J Chromatogr A. 913 (1-2): 387-95. Summary: A HPLC method was developed for the separation and determination of flavonoid and phenolic antioxidants in cranberry juices. Free flavonoid and phenolic compounds were fractionated into neutral and acidic groups by means of a solid-phase extraction method, followed by subsequent HPLC separations. Combined flavonoids and phenolics were hydrolyzed by acid before HPLC analysis. This developed method provides a fast and high resolution of individual flavonoid and phenolic compounds. In cranberry fruit, flavonoids and phenolic acids exist predominantly in combined forms, such as glycosides and esters. A total of 400 mg of total flavonoids and phenolic compounds/l of sample was found in a freshly squeezed cranberry juice, which was distributed as about 44% of phenolic acids and 56% of flavonoids. Benzoic acid was the major phenolic compound. Major flavonoids in the freshly squeezed cranberry juice were quercetin and myricetin. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11355837> Department of Chemistry and Biochemistry, University of Massachusetts, Dartmouth, North Dartmouth 02747, USA.

 

•  Chernomordik AB and Vasilenko EG (1981). [Increase in novobiocin activity and an expansion of its antimicrobial action spectrum]. Antibiotiki. 26 (6): 456-60. Summary: It was found that with an increase in the medium acidity (pH 6.0 - 6.2) the antistaphylococcal effect of novobiocin significantly rose and the drug began to inhibit gram-negative bacteria, in particular, P. aeruginosa and Proteus. The method efficacy was demonstrated on a limited number of patients with urological infections caused by P. aeruginosa and increased acidity of the urine (because of cranberry juice use). Wider observations in patients with urological and some other diseases caused by gram-negative bacteria are advisable. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7271259>

 

•  Coppola ED, Conrad EC and Cotter R (1978). High pressure liquid chromatographic determination of major organic acids in cranberry juice. J Assoc Off Anal Chem. 61 (6): 1490-2. Summary: A reverse phase high pressure liquid chromatographic method is presented for the simultaneous separation and determination of quinic, malic, and citric acids in single strength, undiluted cranberry juice. After a 1 : 10 dilution and cleanup through a disposable column, major organic acids in cranberry juice are separated on a Bondapak/C18 column and quantitated by using a differential refractometer. Twenty-seven samples of different single strength cranberry juice were analyzed using this method; the mean content of quinic, malic, and citric acids were 1.32 (std dev. 0.150), 0.92 (std dev. 0.079), and 1.08% (std dev. 0.111), respectively. Mean percent recoveries of each acid were quinic 95.4 (std dev. 6.8), malic 96.6 (std dev. 5.8), and citric 94.0% (std dev. 4.8). <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=730655>

 

•  Fleet JC (1994). New support for a folk remedy: cranberry juice reduces bacteriuria and pyuria in elderly women. Nutr Rev. 52 (5): 168-70. Summary: Cranberry juice has developed a following as a simple, nonpharmacologic means to reduce or treat urinary tract infections, yet the scientific basis for such a claim has been lacking. A new study suggests that bacterial infections (bacteriuria) and associated influx of white blood cells into the urine (pyuria) can be reduced by nearly 50% in elderly women who drink 300 mL of cranberry juice cocktail each day over the course of a 6-month study. The results of this study suggest that consumption of cranberry juice is more effective in treating than preventing bacteriuria and pyuria. Along with earlier reports on the ability of cranberry juice to inhibit bacterial adherence to urinary epithelial cells in cell culture, this new work suggests that drinking cranberry juice each day may be clinically useful. Additional work must be conducted, however, to more completely define the efficacy of cranberry juice. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8052456> Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.

 

•  Foo LY, Lu Y, Howell AB and Vorsa N (2000). The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry. 54 (2): 173-81. Summary: Ethyl acetate extracts of Sephadex LH20-purified proanthocyanidins of American cranberry (Vaccinium macrocarpon Ait.) exhibited potent biological activity by inhibiting adherence of uropathogenic isolates of P-fimbriated Escherichia coli bacteria to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on epithelial cells in the urinary tract. The chemical structures of the proanthocyanidins were determined by 13C NMR, electrospray mass spectrometry, matrix-assisted laser absorption time-of-flight mass spectrometry and by acid catalyzed degradation with phloroglucinol. The proanthocyanidin molecules consisted predominantly of epicatechin units with mainly DP of 4 and 5 containing at least one A-type linkage. The procyanidin A2 was the most common terminating unit occurring about four times as frequently as the epicatechin monomer. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10872208> Blueberry Cranberry Research Center, Rutgers University, Chatswortli, NJ 08019, USA. y.foo@irl.cri.nz

 

•  Foo LY, Lu Y, Howell AB and Vorsa N (2000). A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli. J Nat Prod. 63 (9): 1225-8. Summary: Three proanthocyanidin trimers possessing A-type interflavanoid linkages, epicatechin-(4beta-->6)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (4), epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin-(4beta-->8)-epicatechin (5), and epicatechin-(4beta-->8)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (6), were isolated from the ripe fruits of Vaccinium macrocarpon (cranberry) and prevented adherence of P-fimbriated Escherichia coli isolates from the urinary tract to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on uroepithelial cells. The structure of 4 was elucidated by a combination of spectroscopic methods and acid-catalyzed degradation with phloroglucinol. Also isolated were the weakly active epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (procyanidin A2) (3) and the inactive monomer epicatechin (1) and the inactive dimer epicatechin-(4beta-->8)-epicatechin (procyanidin B2) (2). <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11000024> Industrial Research, Gracefield Research Center, PO Box 31-310, Lower Hutt, New Zealand. y.foo@irl.cri.nz

 

•  Foxman B, Geiger AM, Palin K, Gillespie B and Koopman JS (1995). First-time urinary tract infection and sexual behavior. Epidemiology. 6 (2): 162-8. Summary: We studied the relation between sexual and health behaviors of women and first-time urinary tract infection (UTI). The study population was women using a university health service who were unmarried, had no UTI history, and who had engaged in sexual activity at least once. We found 86 cases of UTI, defined as one or more urinary symptoms and > or = 1,000 colony-forming units per ml urine of a known pathogen. We randomly sampled 288 controls from the student body. Vaginal intercourse increased the risk of UTI; this risk was further increased with condom use. After adjusting for vaginal intercourse with other birth control methods and recentness of current sexual partnership, a single sex act with a condom in the past 2 weeks increased UTI risk by 43%. Having a sex partner for less than 1 year vs 1 year or more, after adjustment for frequency of vaginal intercourse and birth control method, was associated with about twice the risk of UTI [odds ratio (OR) = 1.97; 95% confidence interval (CI) = 1.04-3.74]. After adjusting for frequency of vaginal intercourse, regular drinking of cranberry juice was protective against UTI (OR = 0.48; 95% CI = 0.19-1.02), whereas drinking carbonated soft drinks appeared to be associated with increased risk (OR = 2.37; 95% CI = 0.75-7.81). Using deodorant sanitary napkins or tampons was associated with a slight increase in risk of UTI (OR = 1.51; 95% CI = 0.74-3.06). Blacks had five times greater risk of UTI than whites after adjusting for frequency of vaginal intercourse (OR = 5.2; 95% CI = 1.89-24.63). We observed only modest differences in health behavior between racial groups. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7742403> Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, USA.

 

•  Habash MB, Van der Mei HC, Busscher HJ and Reid G (1999). The effect of water, ascorbic acid, and cranberry derived supplementation on human urine and uropathogen adhesion to silicone rubber. Can J Microbiol. 45 (8): 691-4. Summary: In this study, urine was collected from groups of volunteers following the consumption of water, ascorbic acid, or cranberry supplements. Only ascorbic acid intake consistently produced acidic urine. Photospectroscopy data indicated that increased water consumption produced urine with lower protein content. Surface tension measurements of the collected urine showed that both water and cranberry supplementation consistently produced urine with surface tensions higher than the control or urine collected following ascorbic acid intake. These urine samples were also employed to study uropathogen adhesion to silicone rubber in a parallel plate flow chamber. Urine obtained after ascorbic acid or cranberry supplementation reduced the initial deposition rates and numbers of adherent Escherichia coli and Enterococcus faecalis, but not Pseudomonas aeruginosa, Staphylococcus epidermidis, or Candida albicans. Conversely, urine obtained from subjects with increased water intake vastly increased the initial deposition rates and numbers of adherent E. coli and E. faecalis (P < 0.05). <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10528401> Department of Microbiology and Immunology, University of Western Ontario Health Sciences Centre, London, Canada.

 

•  Hammerstone JF, Lazarus SA and Schmitz HH (2000). Procyanidin content and variation in some commonly consumed foods. J Nutr. 130 (8S Suppl): 2086S-92S. Summary: Procyanidins are a subclass of flavonoids found in commonly consumed foods that have attracted increasing attention due to their potential health benefits. However, little is known regarding their dietary intake levels because detailed quantitative information on the procyanidin profiles present in many food products is lacking. Therefore, the procyanidin content of red wine, chocolate, cranberry juice and four varieties of apples has been determined. On average, chocolate and apples contained the largest procyanidin content per serving (164.7 and 147.1 mg, respectively) compared with red wine and cranberry juice (22.0 and 31.9 mg, respectively). However, the procyanidin content varied greatly between apple samples (12.3-252.4 mg/serving) with the highest amounts on average observed for the Red Delicious (207.7 mg/serving) and Granny Smith (183.3 mg/serving) varieties and the lowest amounts in the Golden Delicious (92.5 mg/serving) and McIntosh (105.0 mg/serving) varieties. The compositional data reported herein are important for the initial understanding of which foods contribute most to the dietary intake of procyanidins and may be used to compile a database necessary to infer epidemiological relationships to health and disease. <http://www.nutrition.org/cgi/content/full/130/8/2086S

http://www.nutrition.org/cgi/content/abstract/130/8/2086S

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10917927> Analytical and Applied Sciences Group, Mars, Incorporated, Hackettstown, NJ 07840, USA.

 

•  High KP (2001). Nutritional Strategies to Boost Immunity and Prevent Infection in Elderly Individuals. Clin Infect Dis. 33 (11): 1892-1900. Summary: Older adults are at risk for malnutrition, which may contribute to their increased risk of infection. Nutritional supplementation strategies can reduce this risk and reverse some of the immune dysfunction associated with advanced age. This review discusses nutritional interventions that have been examined in clinical trials of older adults. The data support use of a daily multivitamin or trace-mineral supplement that includes zinc (elemental zinc, >20 mg/day) and selenium (100 &mgr;g/day), with additional vitamin E, to achieve a daily dosage of 200 mg/day. Specific syndromes may also be addressed by nutritional interventions (for example, cranberry juice consumption to reduce urinary tract infections) and may reduce antibiotic use in older adults, particularly those living in long-term care facilities. Drug-nutrient interactions are common in elderly individuals, and care providers should be aware of these interactions. Future research should evaluate important clinical end points rather than merely surrogate markers of immunity. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11692301> Sections of Infectious Diseases and Hematology/Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA. khigh@wfubmc.edu

 

•  Ibragimov DI and Kazanskaia GB (1981). [Antimicrobial action of cranberry bush, common yarrow and Achillea biebersteinii]. Antibiotiki. 26 (2): 108-9. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7212689>

 

•  Jackson B and Hicks LE (1997). Effect of cranberry juice on urinary pH in older adults. Home Healthc Nurse. 15 (3): 198-202. Summary: Most research suggests that ingestion of cranberry juice may be useful in preventing urinary tract infections. This pilot study examines the effect of drinking moderate amounts of commercially available cranberry juice cocktail on urinary pH in older, institutionalized adults. The results of the study have implications for home care nurses who have similar patients in their case loads. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9110682> Department of Veteran Affairs, Medical Center, Bay Pines, Florida, USA.

 

•  Jepson RG, Mihaljevic L and Craig J (2000). Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. (2): CD001321. Summary: BACKGROUND: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections. The aim of this review is to assess the effectiveness of cranberries in preventing such infections. OBJECTIVES: To assess the effectiveness of cranberry juice and other cranberry products in preventing urinary tract infections in susceptible populations. SEARCH STRATEGY: Electronic databases and the Internet were searched using English and non English language terms; companies involved with the promotion and distribution of cranberry preparations were contacted; reference lists of review articles and relevant trials were searched. SELECTION CRITERIA: All randomised or quasi randomised controlled trials of cranberry juice/products for the prevention of urinary tract infections in susceptible populations. Trials of men, women or children were included. DATA COLLECTION AND ANALYSIS: Reviewers RJ and LM independently assessed and extracted information using specially designed data extraction forms. For each included trial, information was collected on methods of the trial, participants, interventions and outcomes. We were unable to perform statistical analysis due to the nature of the data available for review. MAIN RESULTS: Four trials met the inclusion criteria (three cross-over, one parallel group). Three compared the effectiveness of cranberry juice versus placebo juice or water and one compared the effectiveness of cranberry capsules versus placebo. Two further trials were excluded. The outcomes of interest were number of urinary tract infections in each group (symptomatic and asymptomatic), side effects and adherence to therapy. Data from three out of the four trials indicated that cranberries were effective for at least one of the outcomes of interest. The quality of the four included trials was poor, however, and thus the reliability of the results must be questionable. REVIEWER'S CONCLUSIONS: The small number of poor quality trials gives no reliable evidence of the effectiveness of cranberry juice and other cranberry products. The large number of dropouts/withdrawals from the trials indicates that cranberry juice may not be acceptable over long periods of time. Other cranberry products such as cranberry capsules may be more acceptable. On the basis of the available evidence, cranberry juice cannot be recommended for the prevention of urinary tract infections in susceptible populations. Further properly designed trials with relevant outcomes are needed. <http://www.update-software.com/abstracts/ab001321.htm

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10796774> 15 Blackwood Crescent, Edinburgh, UK, EH9 1QZ. ruthj@ibm.net

 

•  Jepson RG, Mihaljevic L and Craig J (2000). Cranberries for treating urinary tract infections. Cochrane Database Syst Rev. (2): CD001322. Summary: BACKGROUND: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections. The aim of this review is to assess the effectiveness of cranberries in treating such infections. OBJECTIVES: To assess the effectiveness of cranberries for the treatment of urinary tract infections. SEARCH STRATEGY: The search strategy developed by the Cochrane Renal Group was used. Also, companies involved with the promotion and distribution of cranberry preparations were contacted; electronic databases and the Internet were searched using English and non English language terms; reference lists of review articles and relevant trials were also searched. SELECTION CRITERIA: All randomised or quasi randomised controlled trials of cranberry juice or cranberry products for the treatment of urinary tract infections. Trials of men, women or children were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts of studies that were potentially relevant to the review were screened by one reviewer, RJ, who discarded studies that were clearly ineligible but aimed to be overly inclusive rather than risk losing relevant studies. Reviewers RJ and LM independently assessed whether the studies met the inclusion criteria. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility. MAIN RESULTS: No trials were found which fulfilled all of the inclusion criteria. Two trials were excluded because they did not have any relevant outcomes. REVIEWER'S CONCLUSIONS: After a thorough search, no randomised trials which assessed the effectiveness of cranberry juice for the treatment of urinary tract infections were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of urinary tract infections. Well-designed parallel group, double blind trials comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating urinary tract infections are needed. Outcomes should include reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. Dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these trials. <http://www.update-software.com/abstracts/ab001322.htm

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10796775> 15 Blackwood Crescent, Edinburgh, UK, EH9 1QZ. ruthj@ibm.net

 

•  Kahn HD, Panariello VA, Saeli J, Sampson JR and Schwartz E (1967). Effect of cranberry juice on urine. J Am Diet Assoc. 51 (3): 251-4. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6035629>

 

•  Kinney AB and Blount M (1979). Effect of cranberry juice on urinary pH. Nurs Res. 28 (5): 287-90. Summary: Twenty-one female and 19 male subjects who had normal physical and laboratory examinations were randomly assigned into four groups of 10 subjects each. Each group was then randomly assigned a number (150, 180, 210, 240) which determined the amount of cranberry juice, in milliliters, members of that group would ingest with each meal during the experimental phase of the study. The study took place over a 12-day period. A one-group before-and-after design was used, with each subject serving as his or her own control. Diet was controlled; menus on days 1 through 6 were repeated on days 7 through 12 with the addition of cranberry juice at each meal. Subjects used nitrazine pH tape to measure the pH of midstream urine at each voiding. There were significant (.01 level) differences in mean urinary pH between each control group and its corresponding experimental group. Anticipated problems with increased number of bowel movements, weight gain, increased voiding frequency, and subject pH measurement inaccuracy did not occur. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=38439>

 

•  Kirchhoff M, Renneberg J, Damkjaer K, Pietersen I and Schroll M (2001). [Can ingestion of cranberry juice reduce the incidence of urinary tract infections in a department of geriatric medicine?]. Ugeskr Laeger. 163 (20): 2782-6. Summary: INTRODUCTION: The incidence of urinary tract infections was compared in two geriatric units, where patients were offered cranberry juice and the usual mixed berry juice, respectively. METHODS: In all cases where urinary tract infection was suspected, the doctors noted symptoms and signs used as indication for urinary culture. The urine collected from men was the usual mid-flow specimen, whereas the specimens from women were taken from a bedpan and by catheter. End points were the prevalence of symptoms leading to urine culture, specimens with significant growth of bacteria, and the use of antibiotics. RESULTS: Urine specimens were cultured in 140/338 cases. The reason for culture in 23% was general symptoms and in 62% urinary tract symptoms. A significant growth of bacteria was found in 54% and this information led to antibiotic treatment in 44%. In all cases (n = 55) where bedpan and catheter specimens were taken, the results were identical. CONCLUSION: Cranberry juice in a geriatric department, where the mean stay was 4 weeks, did not influence the incidence of urinary tract infections. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11374214> H:S Kommunehospitalet, geriatrisk afdeling, og.

 

•  Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M and Uhari M (2001). Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. Bmj. 322 (7302): 1571. Summary: OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial. SETTING: Health centres for university students and staff of university hospital. PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen. RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection. <http://bmj.com/cgi/content/full/322/7302/1571

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11431298> Department of Pediatrics, University of Oulu, Oulu, Fin-90220, Finland. terokontiokari@oulu.fi

 

•  Light I, Gursel E and Zinnser HH (1973). Urinary ionized calcium in urolithiasis. Effect of cranberry juice. Urology. 1 (1): 67-70. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4792290>

 

•  Morris NS and Stickler DJ (2001). Does drinking cranberry juice produce urine inhibitory to the development of crystalline, catheter-blocking Proteus mirabilis biofilms? BJU Int. 88 (3): 192-7. Summary: OBJECTIVE: To test the recommendation that to avoid the complications of long-term indwelling bladder catheterization (e.g. encrustation and blockage by crystalline Proteus mirabilis biofilms) patients should drink cranberry juice. MATERIALS AND METHODS: Urine was collected from groups of volunteers who had drunk up to 2 x 500 mL of cranberry juice or water within an 8-h period. Laboratory models of the catheterized bladder were supplied with urine from these groups and inoculated with P. mirabilis. After incubation for 24 or 48 h, the extent of catheter encrustation was determined by chemical analysis for calcium and magnesium. Encrustation was also visualized by scanning electron microscopy. RESULTS: The amounts of calcium and magnesium recovered from catheters incubated in urine pooled from individuals who had drunk 500 mL of cranberry juice was not significantly different from that on catheters incubated in pooled urine from control subjects who had drunk 500 mL of water. However, there was significantly less encrustation (P = 0.007) on catheters from models receiving urine from volunteers who had drunk 2 x 500 mL of water than on catheters incubated in models supplied with urine from volunteers who had drunk 2 x 500 mL of cranberry juice. The amounts of encrustation on these two groups of catheters were also significantly less than that on catheters incubated in models supplied with urine from volunteers who had not supplemented their normal fluid intake. (P < 0.001). Experiments in the models using artificial urine showed that increasing the low fluid intake (720 mL/24 h) characteristic of many patients undergoing long-term catheterization by factors of three and six, significantly (P < 0.01) reduced the amounts of calcium and magnesium that formed on catheters. At a simulated fluid intake of 720 mL/24 h, catheters blocked with encrustation after a mean of 42.5 h, while those supplied with urine produced from an intake of 4320 mL/24 h, drained freely for > 10 days. CONCLUSION: In this in vitro study, drinking cranberry juice did not produce urine that was inhibitory to the development of crystalline catheter-blocking P. mirabilis biofilms. The important factor in preventing catheter encrustation is a high fluid intake. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11488728> Cardiff School of Biosciences, Cardiff University, Cardiff CF1 3TL, Wales, UK.

 

•  Nahata MC, Cummins BA, McLeod DC, Schondelmeyer SW and Butler R (1982). Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy. Eur J Clin Pharmacol. 22 (3): 281-4. Summary: Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one 1/day. Proteus vulgaris, Pseudomonas aeruginosa, and E. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7106162>

 

•  Ofek I, Goldhar J, Zafriri D, Lis H, Adar R and Sharon N (1991). Anti-Escherichia coli adhesin activity of cranberry and blueberry juices. N Engl J Med. 324 (22): 1599. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1674106>

 

•  Papas PN, Brusch CA and Ceresia GC (1966). Cranberry juice in the treatment of urinary tract infections. Southwest Med. 47 (1): 17-20. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5900988>

 

•  Patel N and Daniels IR (2000). Botanical perspectives on health: of cystitis and cranberries. J R Soc Health. 120 (1): 52-3. Summary: With generalised increased use of antibiotics there has been the accompanying development of antibiotic resistance. It has been suggested that the therapy of uncomplicated cystitis is one area in which it is possible to reduce the usage of such compounds. Many women have long drunk cranberry juice--and it has become an 'old-wives' tale in the treatment of this infection. Perhaps it is now time for science to investigate further the benefits of the humble cranberry. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10918785> Department of Medicine, Mayday Hospital, Croydon, Surrey.

 

•  Pedersen CB, Kyle J, Jenkinson AM, Gardner PT, McPhail DB and Duthie GG (2000). Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers. Eur J Clin Nutr. 54 (5): 405-8. Summary: OBJECTIVE: To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity. DESIGN: Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml of blueberry juice, cranberry juice or a sucrose solution (control); each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained by venipuncture at intervals up to four hours after consumption of the juices. Urine samples were also obtained four hours after consuming the juice. RESULTS: Consumption of cranberry juice resulted in a significant increase in the ability of plasma to reduce potassium nitrosodisulphonate and Fe(III)-2,4, 6-Tri(2-pyridyl)-s-triazine, these measures of antioxidant capacity attaining a maximum after 60-120 min. This corresponded to a 30% increase in vitamin C and a small but significant increase in total phenols in plasma. Consumption of blueberry juice had no such effects. CONCLUSION: The increase in plasma antioxidant capacity following consumption of cranberry juice could mainly be accounted for by an increase in vitamin C rather than phenolics. This also accounted for the lack of an effect of the phenolic-rich but vitamin C-low blueberry juice. Sponsorship: Funded by the Scottish Executive Rural Affairs Department and the Danish Government. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10822287> Technical University of Denmark, 2800-Lyngby, Copenhagen, Denmark.

 

•  Reid G (1999). Potential preventive strategies and therapies in urinary tract infection. World J Urol. 17 (6): 359-63. Summary: There are perhaps five strategies either presently advocated or under investigation for prevention of recurrent urinary tract infection (UTI): antibiotics, including natural peptides; functional foods; vaccines; probiotics; and miscellaneous, including avoidance of spermicides and maintenance of good hygiene. It is not possible to state the proportion of patients using antibiotics versus foods such as cranberry or using alternative approaches such as avoidance of spermicides. The majority of women who are referred to specialists will be prescribed long-term, low-dose antibiotics. However, given the magnitude of the problem, it is safe to state that large numbers of women are at least experimenting with alternative remedies such as drinking of cranberry juice or ingestion of herbal remedies with a view to enhancing their immune response. Vaccine development remains a long way from human use and has yet to be developed for organisms other than Escherichia coli. The use of probiotics of restore the normal vaginal flora and provide a competitive bacterial barrier to pathogens is close to becoming available as an alternative preventive approach. The next decade should see the introduction of new methods for reduction of the high incidence of UTI and better management of recurring urogenital infections. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10654366> Lawson Research Institute, London, Ontario, Canada. gregor@julian.uwo.ca

 

•  Reid G, Hsiehl J, Potter P, Mighton J, Lam D, Warren D and Stephenson J (2001). Cranberry juice consumption may reduce biofilms on uroepithelial cells: pilot study in spinal cord injured patients. Spinal Cord. 39 (1): 26-30. Summary: STUDY DESIGN: A pilot study of 15 spinal cord injured patients. Objective: To determine whether alteration of fluid intake and use of cranberry juice altered the bacterial biofilm load in the bladder. SETTING: London, Ontario, Canada. METHODS: Urine samples were collected on day 0 (start of study), on day 7 following each patient taking one glass of water three times daily in addition to normal diet, and on day 15 following each patient taking one glass of cranberry juice thrice daily. One urine sample was sent for culture and a second processed to harvest, examine by light microscopy and Gram stain non-squamous uroepithelial cells to generate bacterial adhesion per 50 cells data. RESULTS: The results showed that cranberry juice intake significantly reduced the biofilm load compared to baseline (P=0.013). This was due to a reduction in adhesion of Gram negative (P=0.054) and Gram positive (P=0.022) bacteria to cells. Water intake did not significantly reduce the bacterial adhesion or biofilm presence. CONCLUSION: The findings provide evidence in support of further, larger clinical trials into the use of functional foods, particularly cranberry juice, to reduce the risk of UTI in a patient population highly susceptible to morbidity and mortality associated with drug resistant uropathogens. SPONSORSHIP: This study was funded by Ocean Spray Cranberries, Lakeville, MA, USA. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11224011> Lawson Health Research Institute, London, Ontario, Canada.

 

•  Schlager TA, Anderson S, Trudell J and Hendley JO (1999). Effect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization. J Pediatr. 135 (6): 698-702. Summary: OBJECTIVE: To determine the effect of cranberry prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with neurogenic bladder receiving clean intermittent catheterization. DESIGN: Double-blind, placebo-controlled, crossover study of 15 children receiving cranberry concentrate or placebo concentrate for 6 months (3 months receiving one concentrate, followed by 3 months of the other). Weekly home visits were made. During each visit, a sample of bladder urine was obtained by intermittent catheterization. Signs and symptoms of urinary tract infection and all medications were recorded, and juice containers were counted. RESULTS: During consumption of cranberry concentrate, the frequency of bacteriuria remained high. Cultures of 75% (114 of 151) of the 151 samples obtained during consumption of placebo were positive for a pathogen (>/=10(4) colony-forming units/mL) compared with 75% (120 of 160) of the 160 samples obtained during consumption of cranberry concentrate. Escherichia coli remained the most common pathogen during placebo and cranberry periods. Three symptomatic infections each occurred during the placebo and cranberry periods. No significant difference was observed in the acidification of urine in the placebo group versus the cranberry group (median, 5.5 and 6.0, respectively). CONCLUSION: The frequency of bacteriuria in patients with neurogenic bladder receiving intermittent catheterization is 70%; cranberry concentrate had no effect on bacteriuria in this population. <http://www1.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a102375&target=

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10586171> University of Virginia, Department of Pediatrics and Emergency Medicine, Charlottesville 22906-0014, USA.

 

•  Schmidt DR and Sobota AE (1988). An examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates. Microbios. 55 (224-225): 173-81. Summary: In a previous investigation it was demonstrated that cranberry juice cocktail was able to inhibit adherence in 77 clinical isolates of Escherichia coli obtained from patients with diagnosed urinary tract infections. This work has been extended to include clinical isolates of E. coli, Proteus, Klebsiella, Enterobacter and Pseudomonas isolated from urine, sputum, wound and stool. Bacterial strains isolated from urine adhere in greater numbers to urinary tract epithelial cells than organisms isolated from sputum, stool and wound sources. E. coli, isolated from urine, adheres to urinary epithelial cells, in numbers three times greater than E. coli isolated from other clinical sources, and thus appears to represent a unique population of cells in terms of adherence. Cranberry juice cocktail and urine and urinary epithelial cells obtained after drinking the cocktail all demonstrate antiadherence activity against Gram-negative rods isolated from urine and other clinical sources. Drinking the cocktail may be useful in managing urinary tract infections in certain patients. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3063927> Alliance City Hospital, Ohio.

 

•  Swartz JH and Medrek TF (1968). Antifungal properties of cranberry juice. Appl Microbiol. 16 (10): 1524-7. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5684203>

•  Simpson GM and Khajawall AM (1983).

 

Urinary acidifiers in phencyclidine detoxification. Hillside J Clin Psychiatry. 5 (2): 161-8. Summary: Urinary acidification is widely used to increase the excretion rate of PCP in abusers. Various acidifying techniques were used and compared with regard to efficacy in lowering pH, side effects, and patient acceptability. On the basis of our findings and data from routine monitoring with test tapes, we would recommend the following acidifications procedures as efficacious and reasonably well tolerated: Ammonium chloride, 4 gm. per day, 1 gm. q.i.d., with sufficient water or cranberry juice. Lysine dihydrochloride, 6 gm. per day, 2 gm. t.i.d., with sufficient water or cranberry juice. Lysine hydrochloride, 8 gm. per day, 2 gm. q.i.d., with water or cranberry juice. Cranberry juice, 18 or more oz. per day alone, or plus lysine, ammonium chloride, or ascorbic acid. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6423507>

 

•  Sobota AE (1984). Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol. 131 (5): 1013-6. Summary: Cranberry juice has been widely used for the treatment and prevention of urinary tract infections and is reputed to give symptomatic relief from these infections. Attempts to account for the potential benefit derived from the juice have focused on urine acidification and bacteriostasis. In this investigation it is demonstrated that cranberry juice is a potent inhibitor of bacterial adherence. A total of 77 clinical isolates of Escherichia coli were tested. Cranberry juice inhibited adherence by 75 per cent or more in over 60 per cent of the clinical isolates. Cranberry cocktail was also given to mice in the place of their normal water supply for a period of 14 days. Urine collected from these mice inhibited adherence of E. coli to uroepithelial cells by approximately 80 per cent. Antiadherence activity could also be detected in human urine. Fifteen of 22 subjects showed significant antiadherence activity in the urine 1 to 3 hours after drinking 15 ounces of cranberry cocktail. It is concluded that the reported benefits derived from the use of cranberry juice may be related to its ability to inhibit bacterial adherence. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6368872>

 

•  Terris MK, Issa MM and Tacker JR (2001). Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis. Urology. 57 (1): 26-9. Summary: OBJECTIVES: Cranberry juice has been recommended for patients with recurrent urinary tract infections. However, cranberry juice has a moderately high concentration of oxalate, a common component of kidney stones, and should be limited in patients with a history of nephrolithiasis. Cranberry concentrate tablets are currently available at nutrition stores and are sold as promoters of urinary tract health. After one of our patients with a distant history of calcium oxalate nephrolithiasis developed recurrent stones following self-administration of cranberry concentrate tablets, we sought to investigate the potential lithogenic properties of cranberry supplements. METHODS: Five healthy volunteers on a normal diet provided 24-hour urine collection for pH, volume, creatinine, oxalate, calcium, phosphate, uric acid, sodium, citrate, magnesium, and potassium. Cranberry tablets were administered to these volunteers at the manufacturer's recommended dosage for 7 days. On the seventh day, a second 24-hour urine collection was obtained. RESULTS: The urinary oxalate levels in the volunteers significantly increased (P = 0.01) by an average of 43.4% while receiving cranberry tablets. The excretion of potential lithogenic ions calcium, phosphate, and sodium also increased. However, inhibitors of stone formation, magnesium and potassium, rose as well. CONCLUSIONS: Cranberry concentrate tablets are marketed for urinary tract ailments. Physicians and manufacturers of cranberry products should make an effort to educate patients at risk for nephrolithiasis against ingestion of these dietary supplements. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11164137> Department of Urology, Stanford University Medical Center, Stanford, California, USA.

 

•  Walsh BA (1992). Urostomy and urinary pH. J ET Nurs. 19 (4): 110-3. Summary: Significant variations of urinary pH can cause problems for all human beings, but these problems are magnified when an individual has a urostomy. Most significant stomal and peristomal complications are related to an alkaline urine including hyperkeratosis; stoma bleeding, incrustation, and ulceration; stoma stenosis; urinary tract infection; odor; and urinary calculi. Treatment of these conditions includes both external and internal measures. External methods of treatment involve keeping urine away from the stoma and the peristomal skin by use of a correctly fitting clean appliance and a night drainage system. Vinegar solution compresses can help to restore the acid mantle of the skin. Internal methods of treatment that are advocated in the literature include ingestion of cranberry juice and ascorbic acid to promote urine acidity. Increasing oral intake of fluids is the least risky method to promote the production of acidic, dilute urine, and results are equally effective. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1637908>

 

•  Wang SY and Jiao H (2000). Scavenging capacity of berry crops on superoxide radicals, hydrogen peroxide, hydroxyl radicals, and singlet oxygen. J Agric Food Chem. 48 (11): 5677-84. Summary: The antioxidant activities against superoxide radicals (O(2)(*)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radicals (OH(*)), and singlet oxygen ('O(2)) was evaluated in fruit juice from different cultivars of thornless blackberries (Rubus sp.), blueberries (Vaccinium spp.), cranberries (Vaccinium macrocarpon Aiton), raspberries (Rubus idaeus L. and Rubus occidentalis L.), and strawberries (Fragaria x ananassa Duch.). Among the different cultivars, juice of 'Hull Thornless' blackberry, 'Earliglow' strawberry, 'Early Black' cranberry, 'Jewel' raspberry, and 'Elliot' blueberry had the highest antioxidant capacity against superoxide radicals (O(2)(*)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radicals (OH(*)), and singlet oxygen ('O(2)). In general, blackberries had the highest antioxidant capacity inhibition of O(2)(*)(-), H(2)O(2), and OH(*). Strawberry was second best in the antioxidant capacity assay for these same free radicals. With regard to 'O(2) scavenging activity, strawberry had the highest value, while blackberry was second. Cranberries had the lowest inhibition of H(2)O(2) activity. Meanwhile, blueberries had the lowest antioxidant capacity against OH(*) and 'O(2). There were interesting and marked differences among the different antioxidants in their abilities to scavenge different reactive oxygen species. beta-Carotene had by far the highest scavenging activity against 'O(2) but had absolutely no effect on H(2)O(2). Ascorbic acid was the best at inhibiting H(2)O(2) free radical activity. For OH(*), there was a wide range of scavenging capacities from a high of 15.3% with alpha-tocopherol to a low of 0.88% with ascorbic acid. Glutathione had higher O(2)(*)(-) scavenging capacity compared to the other antioxidants. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11087538> Fruit Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland 20705, USA. wangs@ba.ars.usda.gov

 

•  Weiss EI, Lev-Dor R, Kashamn Y, Goldhar J, Sharon N and Ofek I (1998). Inhibiting interspecies coaggregation of plaque bacteria with a cranberry juice constituent [published erratam appear in J Am Dent Assoc 1999 Jan;130(1):36 and 1999 Mar;130(3):332]. J Am Dent Assoc. 129 (12): 1719-23. Summary: Dental plaque stability depends on bacterial adhesion to acquired pellicle, and on interspecies adhesion (or coaggregation). A high-molecular-weight cranberry constituent at 0.6 to 2.5 milligrams per milliliter reversed the coaggregation of 49 (58 percent) of 84 coaggregating bacterial pairs tested. It acted preferentially on pairs in which one or both members are gram-negative anaerobes frequently involved in periodontal diseases. Thus, the anticoaggregating cranberry constituent has the potential for altering the subgingival microbiota, resulting in conservative control of gingival and periodontal diseases. However, the high dextrose and fructose content of the commercially available cranberry juice makes it unsuitable for oral hygiene use, and the beneficial effect of the high-molecular-weight constituent requires animal and clinical studies. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9854922> Department of Oral Biology, Maurice and Gabriela Goldschlager School of Dental Medicine, Tel Aviv University, Israel.

 

•  Wilson T, Porcari JP and Harbin D (1998). Cranberry extract inhibits low density lipoprotein oxidation. Life Sci. 62 (24): PL381-6. Summary: Cranberry juice consumption is often used for the treatment of urinary tract infections, but the effect of cranberry juice on heart disease has not been investigated. We evaluated how a cranberry extract containing 1,548 mg gallic acid equivalents/liter (initial pH=2.50) affected low density lipoprotein (LDL) oxidation induced by 10 micromolar cupric sulfate. When LDL oxidation took place in the presence of diluted cranberry extracts, the formation of thiobarbituric acid reactive substances (TBARS) and LDL electrophoretic mobility were reduced. LDL electrophoretic migration was also reduced when the cranberry extract had a pH of 7.00 prior to dilution. This study suggests that cranberry extracts have the ability to inhibit the oxidative modification of LDL particles. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9627085> La Crosse Exercise and Health Program, University of Wisconsin-La Crosse, 54601, USA. wilso_ef@mail.uwlax.edu

 

•  Zafriri D, Ofek I, Adar R, Pocino M and Sharon N (1989). Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Chemother. 33 (1): 92-8. Summary: Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2653218> Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel.