Cranberry

Cranberry supplements for UTIs

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Cranberry supplements are a very popular remedy for UTIs, but are they really effective?

What are UTIs?

Urinary tract infections (UTIs) are considered to be the most common bacterial infection with nearly 7 million office visits and 1 million emergency department visits, resulting in 100,000 hospitalizations.

Women are significantly more likely to experience UTIs than men due to the length of the urethra that facilitates the climbing of bacteria from the perineal area up to the bladder. Other subpopulations at increased risk of UTIs include infants, pregnant women, the elderly, patients with spinal cord injuries and/or catheters, patients with diabetes or multiple sclerosis, patients with acquired immunodeficiency disease syndrome/human immunodeficiency virus, and patients with underlying urologic abnormalities. Catheter-associated UTIs is the most common nosocomial infection, accounting for more than 1 million cases in hospitals and nursing homes.

Luckily, in the nonobstructed, nonpregnant female adult, acute uncomplicated UTI is a benign illness relegated to the lower urinary tract and that most of the times doesn’t require a specific treatment. [1]

Cranberry and cranberry supplements

Cranberries are small fruits coming from a shrub that is native to north America, its scientific name is Vaccinum Macrocarpon. It has been used for decades if not centuries as a natural remedy against UTIs and it is common belief that it can help ameliorate this condition by making the urine more acidic and/or preventing the adhesion of bacteria to the bladder wall. It is used in many different forms: juice (pure or sweetened), powdered juice, extracts, whole fruit powder, whole fresh fruit, whole dessicated fruit, jellies etc. The supplements usually contain sugar or other sweetener because the fruit is very acidic. [2]

The phytochemicals present in cranberry follow under the categories of: proanthocyanidins (abbraviated in PACs), anthocyanins, phenolic acids, terpenes, avonols [3]. In order to establish if they have a real action, it is important to look at both in vitro and in vivo studies.

Mechanism of action

All the studies with the aim of figuring out the mechanism of action involve an incubation period of E.Coli with either cranberry juice or urine of volunteers who took cranberry supplements previously and then some kind of test to determine the ability of E.Coli to adhere to a medium.

One study [4] was able to demonstrate a reduction in adherence capacity of not only E.Coli but also of other G- bacteria. The fact that they tested different species is important since all enterobacteria are able to cause UTIs. They studied a cranberry juice cocktail, urine and urinary epithelial cells obtained after drinking the cocktail; they concluded that all of them demonstrate antiadherence activity against Gram-negative rods isolated from urine and other clinical sources. It is unfortunate that the cocktail was not otherwise described in the abstract.

Two studies tested a cocktail, not urine, directly on the bacteria so they might not be as relevant for patients since it should not be taken for granted that the properties of a juice are the same as the one of urine resulting from the ingestion of the juice. The first [5] demonstrated the ability of cranberry juice to inhibit the adherence of E.Coli expressing type 1 and type p fimbriae. Later it was determined that the inhibition of type 1 fimbriae had to be ascribed to the presence of fructose since this property was dialyzable and other fruit juices had it. The second [6] determined the same decrease in adherence but using a thermodynamic approach.

A different type of study design was used to recognize the capability of cranberry juice to modify cell components production. In this study [8] coltures of E.Coli were grown in a medium with either PACs or cranberry juice and it was found that the bacteria become less adhesive to uroepithelial cells, in a manner that is dose dependant to the amount of PACs/juice they are exposed to. The effect was visible starting from a concentration of PACs of 345.8 microg/mL.

The last study [9] evaluated the capacity of urine of women who consumed cranberry capsules to make E.Coli strains less virulent in vivo and in vitro. The study has a good design being a double blind, randomized crossover trial. The study was carried out using a French supplement called Urell which is produced by Pharmatoka, specifically they used the capsule which contains: cranberry juice extract, manniol, magnesium stearate, silicium dioxide and hypromellose [10]. Each volunteer received three successive regimens with her evening meal. These comprised: three capsules of cranberry (108 mg), or three capsules of placebo, or one capsule of cranberry (36 mg) and two capsules of placebo. The urine was collected as the first urine of the morning twelve hours after consumption of cranberry or placebo hard capsules. The study was conducted both in vitro (using human UC) and in vivo testing the capacity of E.Coli to kill a nematode. Three capsules of cranberry preparation caused a highly significant reduction in bacterial adherence to UC cells as compared with placebo and it was statistically significant. There was also a dose-dependent decrease in bacterial adherence following cranberry intake. Also, all the namatodes infected with susceptible E. coli grown in urine containing cranberry metabolites were killed in around 9 days, while nematodes infected with E. coli grown in urine containing placebo died in about 7 days.

Is cranberry really able to prevent or treat UTIs?

First it is important to determine whether or not the active components of cranberry pass through in the urine, and it appears that they do, as at least two studies suggest. [11], [12] In particular one study found that "the urinary levels of anthocyanins reached a maximum between 3 and 6 hours after ingestion, and the recovery of total anthocyanins in the urine over 24 hours was estimated to be 5.0% of the amount consumed" [12] while the second found that "plasma concentrations of the individual anthocyanins ranged between 0.56 and 4.64 nmol/L. Total recovery of urinary anthocyanin was 0.79 +/- 0.90 % of the dose delivered."

There have also been studies clinical studies to determine if the presence of PACs in urine leads to a real reductions of UTIs. One study involved randomizing 150 women (sexually active, aged 21 through 72 years) for one year to one of three groups of prophylaxis: placebo juice + placebo tablets versus placebo juice + cranberry tablets, versus cranberry juice + placebo tablets. Tablets were taken twice daily, juice 250 ml three times daily. This study noted a 50% decrease in symptomatic UTIs per year and a 50% decrease in annual antibiotic consumption [13].

Another study on the other end [14] found that among otherwise healthy college women with an acute UTI, those drinking 8 oz of a 27% cranberry juice twice a day, did not experience a decrease in the 6-month incidence of a second UTI, compared with those drinking a placebo. This difference in the outcome could be explained, among other things, by a different dosage and potency of the supplement. The second study used a juice that was very low in cranberry so this might explain the lack of positive outcome. It is unfortunate that a more detailed explanation of dosage is lacking.

While these previous studies looked at an otherwise healthy population, one other study [15] looked at a more fragile population: 376 elderly people in the hospital. The participants were randomised to daily ingestion of 300 ml of cranberry juice or matching placebo beverage. A total of 21/376 participants developed a symptomatic UTI: 14/189 in the placebo group and 7/187 in the cranberry juice group. The number was lower in the cranberry group but it wasn’t statistically significant.

Finally a study [16] was made on 153 elderly women volunteers (mean age, 78.5 years). Again the subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink. Subjects randomized to the cranberry beverage had odds of bacteriuria with pyuria that were only 42% of the odds in the control group and 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.

Conclusions

So, in conclusion, there seems to be a scientifc base to recommend cranberry supplementation in the prevention of UTIs but the lack of accurate description of quantity and type of supplement make it almost impossible to recommend a specific daily dosage; but since there is a dose dependent effect on bacteria adhesion and there are no side effects with its consumption it might be advisable to drink/eat larger quantities.

References

  1. Betsy Foxman Epidemiology of urinary tract infections: incidence, morbid-ity, and economic costs. Am J Med. 2002 Jul 8;113 Suppl 1A:5S-13S. doi: 10.1016/s0002-9343(02)01054-9.
  2. https://en.wikipedia.org/wiki/Cranberry
  3. Je rey B. Blumberg, Terri A. Camesano, Aedin Cassidy, Penny Kris-Etherton, Amy Howell, Claudine Manach, Luisa M. Ostertag, Helmut Sies, Ann Skulas-Ray, Joseph A. Vita Author Notes Cranberries and Their Bioac-tive Constituents in Human Health Advances in Nutrition, Volume 4, Issue 6, November 2013, Pages 618{632, https://doi.org/10.3945/an.113.004473
  4. D R Schmidt 1, A E Sobota An examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates Microbios. 1988;55(224-225):173-81.
  5. D Zafriri, I Ofek, R Adar, M Pocino, and N Sharon Inhibitory activity of cranberry juice on adherence of type 1 and type P mbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Chemother. 1989 Jan; 33(1): 92{98. doi: 10.1128/aac.33.1.92
  6. Yatao Liu 1, Amparo M Gallardo-Moreno, Paola A Pinzon-Arango, Yorke Reynolds, Guadalupe Rodriguez, Terri A Camesano Cranberry changes the physicochemical surface properties of E. coli and adhesion with uroep-ithelial cells Colloids Surf B Biointerfaces. 2008 Aug 1;65(1):35-42. doi: 10.1016/j.colsurfb.2008.02.012. Epub 2008 Feb 26.
  7. D Zafriri, I Ofek, R Adar, M Pocino, and N Sharon Inhibitory activity of cranberry juice on adherence of type 1 and type P mbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Chemother. 1989 Jan; 33(1): 92{98. doi: 10.1128/aac.33.1.92
  8. Paola A Pinzon-Arango 1, Yatao Liu, Terri A Camesano Role of cran-berry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment J Med Food. 2009 Apr;12(2):259-70. doi: 10.1089/jmf.2008.0196.
  9. Jean-Philippe Lavigne,1,* Gisele Bourg,1 Christophe Combescure,2 Henri Botto,3 and Albert Sotto1 In-vitro and in-vivo evidence of dose-dependent decrease of uropathogenic Escherichia coli virulence after consumption of commercial Vaccinium macrocarpon (cranberry) capsules Clin Microbiol Infect. 2008 Apr; 14(4): 350{355. Published online 2008 Jan 7. doi: 10.1111/j.1469-0691.2007.01917.x
  10. http://www.urell.fr/maison-urell/
  11. Paul E Milbury 1, Joseph A Vita, Je rey B Blumberg Anthocyanins are bioavailable in humans following an acute dose of cranberry juice J Nutr. 2010 Jun;140(6):1099-104. doi: 10.3945/jn.109.117168. Epub 2010 Apr 7.
  12. Ryoko Ohnishi 1, Hideyuki Ito, Naoki Kasajima, Miyuki Kaneda, Reiko Kariyama, Hiromi Kumon, Tsutomu Hatano, Takashi Yoshida Urinary ex-cretion of anthocyanins in humans after cranberry juice ingestion Biosci Biotechnol Biochem. 2006 Jul;70(7):1681-7. doi: 10.1271/bbb.60023.
  13. Lynn Stothers A randomized trial to evaluate e ectiveness and cost e ec-tiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women Can J Urol. 2002 Jun;9(3):1558-62.
  14. Cibele Barbosa-Cesnik 1, Morton B Brown, Miatta Buxton, Lixin Zhang, Joan DeBusscher, Betsy Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomized placebo-controlled trial Clin Infect Dis. 2011 Jan 1;52(1):23-30. doi: 10.1093/cid/ciq073.
  15. Marion E T McMurdo 1, Linda Y Bissett, Rosemary J G Price, Gabby Phillips, Iain K Crombie Does ingestion of cranberry juice reduce symp-tomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial Age Ageing. 2005 May;34(3):256-61. doi: 10.1093/ageing/a 101.
  16. J Avorn 1, M Monane, J H Gurwitz, R J Glynn, I Choodnovskiy, L A Lipsitz Reduction of bacteriuria and pyuria after ingestion of cranberry juice JAMA 1994 Mar 9;271(10):751-4. doi: 10.1001/jama.1994.03510340041031.