Cranberry for the Prevention of Urinary Tract Infection
October 1999; Volume 2: 116-118
By Victoria Rand, MD
Cranberry juice and extract from the ripe fruit (Vaccinium macrocarpon) have been used for many years for the prevention and treatment of urinary tract infections (UTIs) in women. American folk tradition supports cranberry use for the treatment of UTIs, but supportive clinical data are lacking. More data exist on the use of cranberry for the prevention of UTIs, though the information published is mostly in vitro and animal data. Prevention of UTIs could have dramatic effects on health care costs and quality of life for many women.
Etiology and Prevalence of Disease
Escherichia coli (E. coli) is by far the most common urinary pathogen, accounting for 85% of community-acquired UTIs. Far less common are other enteric gram-negative organisms such as Klebsiella and Proteus. It is estimated that 25% of women have at least one UTI in their lifetime and many will have several.1 The presentation of a UTI to a physician’s office accounts for more than seven million office visits each year in the United States alone.
History/Tradition
Historically, cranberries have been used for the prevention of kidney stones and were believed to remove toxins from the blood. The pilgrims learned about cranberries from Native Americans. Since the early part of the 20th century, most of the focus has been on the prevention of urinary tract infections.
The most common urinary pathogen is:
a. Klebsiella enterobacter.
b. Escherichia coli.
c. Proteus mirabilis.
d. Proteus vulgaris.
e. Proteus morganii.
Pharmacology
The pharmacologically active ingredients of cranberry are unknown but probably include high molecular weight compounds called proanthocyanidins.2 This group of compounds is believed to decrease bacterial adherence to the bladder epithelium, thus decreasing the risk of bacterial colonization and infection. This same group of compounds is found in blueberries. Other constituents of cranberry include various carbohydrates, fiber, and flavonoids (quercetin and myrecetin), as well as a number of plant acids, including ascorbic, benzoic, citric, malic, and quinic.
Other fruits have been studied to see if they contain those compounds that prevent bacterial bladder adhesion. In one study of seven juices (cranberry, blueberry, grapefruit, guava, mango, orange, and pineapple), only cranberry and blueberry contained the bladder inhibitor. Though not studied as well, blueberry juice is probably a reasonable alternative to cranberry juice for the prevention of urinary tract infections.3
Mechanism of Action
American scientists in the 1920s believed that cranberry acidified the urine. Cranberry extracts and juice contain hippuric acid, which at that time was thought to exert a potent antibacterial effect in the urinary tract since bacteria prefer an alkaline pH for growth.4 In 1984, Sobota et al at Youngstown State University disproved the acidifying theory of cranberry.5 They demonstrated that the acidification of urine does not produce an antibacterial effect. They also showed that cranberry prevents the adhesion of E. coli to the bladder epithelium, making it easier to wash bacteria out with the urine.
Two different constituents of cranberry juice inhibit E. coli adhesion activity. Fructose in the juice inhibits the type 1 fimbrial adhesion that does not have a role in the prevention of UTIs. Proanthocyanidins seem to inhibit the type P fimbrial adhesion of uropathogenic strains by inhibiting the alpha-D-Galactopyranosyl recognition site on uroepithelial cells.6 There are no data about whether dried or cooked cranberry has an effect on the urogenital system. It has been reported that the quinic acids in cranberry may prevent kidney stones, but there are no controlled data to confirm this.
Clinical Studies
Avorn and colleagues conducted a randomized placebo-controlled trial to assess the reputed ability of cranberry juice to influence the bacterial flora of the urinary tract.7 The investigators studied 153 women (mean 78.6 years) randomized to drink 300 ml (10 oz) daily of cranberry juice or a placebo drink that looked and tasted like cranberry. Urine samples were collected monthly for six months and tested for the presence of pyuria and bacteriuria.
The pH measurements in both groups were identical, supporting the fact that urinary acidification did not explain the improved urine findings in the experimental group. Women in the experimental group had significantly less pyuria and bacteriuria than the control group, but only after 4-8 weeks of the study. The results of this study were compromised from the outset; six months prior to the study, the experimental group had significantly fewer UTIs than did the control group. The study was funded by Ocean Spray.
Another group published a 1997 study that compared cranberry capsule extracts to placebo in a group of sexually active women ages 18-45 with recurrent UTIs.8 This small study used a crossover control and only included 10 women. Each participant was held in queue until suffering a symptomatic UTI. They were then treated with 10 days of standard antibiotic therapy. Before completing therapy, each subject was randomly assigned to either cranberry or placebo for three months and then switched to the other group for the remaining three months of the study. A total of 21 UTIs were recorded during the six-month period. In these women, 15 UTIs occurred during the three months the subjects were taking placebo (P < 0.005).
A 1995 study by Foxman et al examined first-time urinary tract infection and sexual behavior.9 The women in this study were using a university health service, were unmarried, had no UTI history, and had engaged in sexual activity at least once. Cranberry use was ascertained by questionnaires that the women filled out. The investigators found 86 cases of UTI. Vaginal intercourse, use of condoms, and having a sexual partner for less than one year increased the UTI risk. The regular consumption of cranberry juice was protective against UTI with an odds ratio = 0.48; 95% confidence interval = 0.19-1.02.
Formulation and Dosage
The usual dosage for prevention of UTIs is one capsule (300-400 mg of concentrated cranberry juice extract) in the morning and in the evening.10 Up to 300 ml/d of commercial cranberry juice cocktail drink can be consumed. There have been no studies looking specifically at the amount of proanthocyanidin that is necessary for beneficial urinary tract infection prevention. Though manufacturers offer concentrated cranberry extracts in pill form, there are no data on standardized extracts of any cranberry components.
Adverse Effects
No adverse effects have been reported in the doses studied. There are no safety data published in pregnant or lactating women.
Conclusion
Cranberry has biologic activity against bacterial adhesion in the bladder. The randomized data suggest a decrease in potential risk factors for UTIs such as asymptomatic bacteria and pyuria in elderly women. The available studies do point to a preventive role for UTIs in both young and elderly women.
Investigators have not compared cranberry vs. antibiotics for the treatment of acute UTIs. No large-scale, randomized, controlled trials, systematic reviews, or meta-analyses have examined the use of cranberry juice for the prevention or treatment of acute UTIs. Better studies that include harder end points, such as infection as opposed to asymptomatic urine sediment abnormalities, are needed.
Recommendation
Cranberry is a time-tested folk remedy that is safe and well-tolerated. For women who are watching their sugar and caloric intake, unsweetened cranberry juice or extracts might prove helpful for the prevention of UTIs. However, if UTI symptoms develop, it would be prudent to treat with antibiotics. There is no harm in trying regular cranberry juice or concentrated extracts for prevention in those women with a history of recurrent UTIs whose only other choice might be chronic suppressive antibiotic therapy. There is probably no harm in using cranberry in elderly women, institutionalized patients, and those who have chronic indwelling foleys or who routinely self-catheterize.
Dr. Rand is Assistant Clinical Professor of Medicine and the Medical Director of the Screening and Acute Care Clinic at the University of California, San Francisco.
Proanthocyanidins, the pharmacologically active components of cranberry, have been found:
a. to inhibit the type P fimbrial adhesion of uropathogenic strains.
b. to inhibit the alpha-D-Galactopyranosyl recognition site on uroepithelial cells.
c. to decrease the risk of bacterial colonization and infection of the urinary tract.
d. in blueberries.
e. All of the above.
References
1. Kuzminski LN. Cranberry juice and urinary tract infections: Is there a beneficial relationship? Nutr Rev 1996;54(11Pt2):S87-S90.
2. Robbers JE, Tyler VE. Tyler’s Herbs of Choice: The Therapeutic Use of Phytomedicinals. Binghamton, NY: The Haworth Herbal Press, Inc.; 1999.
3. Ofek I, et al. Anti-Escherichia coli adhesin activity of cranberry and blueberry juices. New Engl J Med 1991;324:1599.
4. Murray MT, Pizzorno JE. Encyclopedia of Natural Medicine. Rocklin, CA: Prima Health Publishing; 1998.
5. Sobota AE. Inhibition of bacterial adherence by cranberry juice: Potential use for the treatment of urinary tract infections. J Urol 1984;131:1013-1016.
6. Zafriri D, et al. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Chemother 1989;33:92-98.
7. Avorn J, et al. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA 1994;271: 751-754.
8. Walker EB, et al. Cranberry concentrate: UTI prophylaxis. J Fam Pract 1997;45:167-168.
9. Foxman B, et al. First-time urinary tract infection and sexual behavior. Epidemiology 1995;6:162-168.
10. Brown D. Herbal Prescriptions for Better Health. Rocklin, CA: Prima Publishing; 1996.
October 1999; Volume 2: 116-118
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