Can Cranberry’s Bioactive Ingredient Prevent UTIs?

By Brian J. Flynn, MD | Published 6/23/2019 1

cranberries UTIs

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Recurrent urinary tract infections (UTIs) have a large impact on patients’ quality of life.[mfn]Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015; 13(5): 269-284.[/mfn] They account for some 10 million office visits a year and up to 60% of all antibiotic prescriptions.[mfn]Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among us ambulatory care visits, 2010-2011. JAMA. 2016;315(17): 1864-1873. doi: 10.1001/jama.2016.4151.[/mfn] A frustrating “revolving door” of appointments often includes a treat-and-repeat cycle of antibiotics. Perimenopausal women suffer the most from recurrent UTIs, and these troublesome infections can lead to more serious medical problems.1

Antibiotic Overuse

At least 30% of outpatient antibiotic prescriptions in the United States are not needed, according to the Centers for Disease Control and Prevention.2

Global health agencies have asked healthcare providers to curb antibiotic use in light of the widespread concerns over side effects and antibiotic resistance. Resistance occurs when the bacteria is stronger than the antibiotics. Drug-resistant rates for the most common UTI-associated bacteria E coli, for example, are rising at an alarming rate.

Managing Patients with UTIs

Healthcare providers look to current evidence and expert guidelines to manage recurrent UTIs. We aim to limit unnecessary antibiotics, prescribing them only for patients with culture-proven infections. But, this may be confusing for patients who expect to receive an antibiotic when they have UTI-like symptoms.

The growing interest from healthcare providers in cranberry supplements as a non-antibiotic modality for the prevention of recurrent UTIs has taken center stage. This is an attempt to curb antibiotic prescribing and offers patients a proven alternative that poses little risk.

  • Guidelines

In its recent UTI guidelines[mfn]. Anger J, Lee U, Ackerman L, et al. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. https://www.auanet.org/guidelines/recurrent-uti. [/mfn], the American Urological Association states that “clinicians may offer cranberry prophylaxis for women with [recurrent] UTIs.” It is the only non-pharmaceutical recommendation included in the report.

They go on to highlight that an increasing number of randomized clinical trials have studied cranberry in a variety of formulations. This includes juice and tablets. The benefit is thought to be related to the bioactive proanthocyanidins (PAC) compounds and their role in preventing bacterial adhesion to the urinary tract wall.

  • Risks

More specifically, cranberry was associated with decreased risk of experiencing at least one UTI recurrence than placebo or no cranberry in five trials[mfn]Kontiokari T, Sundqvist K, Nuutinen M et al: Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001; 322:1571. doi: https://doi.org/10.1136/bmj.322.7302.1571[/mfn] [mfn]Maki KC, Kaspar KL, Khoo C, et al. Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection. Am J Clin Nutr. 2016;103:1434. https://doi.org/10.3945/ajcn.116.130542.[/mfn][mfn]Stothers L. A randomized trial to evaluate the effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol. 2002;9:1558. https://www.ncbi.nlm.nih.gov/pubmed/12121581.[/mfn][mfn]. Takahashi S, Hamasuna R, Yasuda M et al: A randomized clinical trial to evaluate the preventive effect of cranberry juice (UR65) for patients with recurrent urinary tract infection. J Infect Chemother. 2013;19:112. doi: 10.1007/s10156-012-0467-7.[/mfn]

Additionally, eight randomized trials of cranberry versus placebo/no cranberry (6 randomized controlled trials [RCTs], one with a lactobacillus arm) 4,5,6,7 and cranberry versus antibiotics (2 RCTs) were referenced to support its use for UTI prophylaxis.[mfn]Vostalova J, Vidlar A, Simanek V et al: Are high proanthocyanidins key to cranberry efficacy in the prevention of recurrent urinary tract infection? Phytother Res 2015;29:1559. doi: 10.1002/ptr.5427[/mfn][mfn]Walker EB, Barney DP, Mickelsen JN et al: Cranberry concentrate: UTI prophylaxis. J Fam Pract 1997;45:167[/mfn] Furthermore, researchers noted that in one trial cranberry was associated with a lower risk of resistance in E. coli than antibiotics, trimethoprim, and sulfamethoxazole.[mfn]Beerepoot MA, ter Riet G, Nys S et al: Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med 2011; 171:1270. doi: 10.1001/archinternmed.2011.306[/mfn]

The guidelines continue, stating that “there is little risk to cranberry supplements, further increasing their appeal to patients. However, it must be noted that fruit juices can be high in sugar content, which is a consideration that may limit use in diabetic patients.”

  • Concentrations Vary

Important to note is that the guidelines state that the natural PAC compounds associated with bioactivity are found in varying concentrations depending on the formulation used. And that many products are explicitly developed for research purposes only. It is, therefore, necessary for healthcare providers to discuss the availability of the proper product with patients.

I recommend cranberry prophylaxis to my patients in the form of a once-daily medical-grade supplement containing 36 milligrams (mg) of bioactive PAC from cranberry.

  • Alternative Option

The most important take away from these guidelines is that healthcare providers have an alternative preventive option to effectively manage recurrent UTIs. But they must do their homework to identify the appropriate PAC product that meets established criteria for efficacy.

With an understanding of the mechanism of action and a clear window into a PAC product’s bioactive formulation, its manufacturing process, and its content, this approach could be a welcome alternative to ongoing antibiotic use perpetuating a cycle of “treat and repeat”.

Ingredients Matter to Realize the Benefits of Cranberry.

For centuries, cranberry has been thought to benefit urinary tract health. However, evidence on how and why has been limited.

Research now confirms that a minimum of 36 mg of bioactive PAC extracted from the pure juice concentrate prevents UTI-causing bacteria from attaching to the bladder wall. This feature is called bacterial anti-adhesion activity or AAA.[mfn] Howell A, Botto H, Combescure C, et al. Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double-blind study. BMC Infectious Diseases 2010,10:94. https://doi.org/10.1186/1471-2334-10-94.[/mfn][mfn] Howell AB, Reed JD, Krueger CG, et al. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry. 2005;66(18):2281-2291. DOI: 10.1016/j.phytochem.2005.05.022[/mfn][mfn]Prior RL, Fan E, Ji H, et al. Multi-laboratory validation of a standard method for quantifying proanthocyanidins in cranberry powders. J Sci Food Agric. 2010;90(9):1473-1478. doi: 10.1002/jsfa.3966[/mfn][mfn]Sintara M, Li L, Cunningham DG, Prior RL, Wu X, Chang T. Single-laboratory validation for determination of total soluble proanthocyanidins in cranberry using 4-dimethylaminocinnamaldehyde. J AOAC Int. 2018 May 1;101(3):805-809. doi: 10.5740/jaoacint.17-0288.[/mfn]

Is It Soluble?

Science supports this powerful high-dose of bioactive PAC.3 It is important to note, however, only the soluble type of PAC has maximum AAA and is powerful enough to reduce recurrent UTIs. This type of PAC is found mostly in pure cranberry concentrate and not the whole berry. Local grocery stores or pharmacies offer products that vary widely in their ingredients making them unreliable and ineffective.

In fact, many contain less than 5 mg of PAC and minimal AAA. This is insufficient for UTI prevention.[mfn]Chughtai B, Thomas D, Howell A. Variability of commercial cranberry dietary supplements for the prevention of uropathogenic bacterial adhesion. Am J Obstet Gynecol 2016;215(1):122-3. doi: 10.1016/j.ajog.2016.03.046[/mfn]

These supplements are often inexpensively made from the juicing leftovers like dried skins, stems, and seeds. Some supplements may include sugar or added ingredients that fuel the UTI fire. These may be inappropriate in diabetes patients or those with other medical conditions.

Product Considerations in Unregulated Market

The Food and Drug Administration FDA does not require manufacturers to prove claims and labeling for supplements. This means it is crucial for providers and patients to carefully review product ingredients.

To be effective, a formula must contain 36 mg bioactive PAC extracted from pure juice. In a clinical study, one supplement with 36 mg of soluble PAC was as effective a low-dose antibiotic for preventing UTIs.[mfn]Uberos J, Nogueras Ocana M, Fernandez-Puentes V, et al. Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial Open Access Journal of Clinical Trials. 2012:4:31-38. https://www.dovepress.com/cranberry-syrup-vs-trimethoprim-in-the-prophylaxis-of-recurrent-urinar-peer-reviewed-article-OAJCT.[/mfn] The same supplement prevented UTIs in catheter users, without the side effects and resistance associated with antibiotics.[mfn]17. Thomas D, Rutman M, Cooper K, et al. Does cranberry have a role in CA-UTIs?. Can Urol Assoc J. 2017;11(11): E42 1-4. DOI: 10.5489/cuaj.4472[/mfn]

Proactive UTI Prevention

The urgent battle against recurrent UTIs and antibiotic resistance requires a fresh look at cranberry for UTI prevention. The benefits of 36 mg PAC provide an opportunity to broaden the conversation with UTI sufferers. Healthcare providers can inform patients that antibiotics must only be used when absolutely necessary and discouraged as a preventive option.

Proper self-care—drinking more water, urinating after intercourse, and wiping front to back—should not be overlooked. When those behavioral options are not enough, we now have a proven alternative solution.

Related Content:  Holistic Preventive Medicine Can Change Your Life for the Better

Conclusion

I focus on a proactive approach to recurrent UTI prevention, recommending a medical-grade supplement with the clinically proven dose of 36 mg bioactive PAC. This approach empowers patients to prevent recurrent UTIs naturally and with confidence.

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References

  1. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015; 13(5): 269-284. DOI:10.1038/nrmicro3432
  2. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among us ambulatory care visits, 2010-2011. JAMA. 2016;315(17): 1864-1873. doi: 10.1001/jama.2016.4151
  3. Anger J, Lee U, Ackerman L, et al. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. https://www.auanet.org/guidelines/recurrent-uti.
  4. Kontiokari T, Sundqvist K, Nuutinen M et al: Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001; 322:1571. doi:https://doi.org/10.1136/bmj.322.7302.1571
  5. Maki KC, Kaspar KL, Khoo C, et al. Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection. Am J Clin Nutr. 2016;103:1434. https://doi.org/10.3945/ajcn.116.130542
  6. Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol. 2002;9:1558. https://www.ncbi.nlm.nih.gov/pubmed/12121581
  7. Takahashi S, Hamasuna R, Yasuda M et al: A randomized clinical trial to evaluate the preventive effect of cranberry juice (UR65) for patients with recurrent urinary tract infection. J Infect Chemother. 2013;19:112. doi: 10.1007/s10156-012-0467-7.
  8. Vostalova J, Vidlar A, Simanek V et al: Are high proanthocyanidins key to cranberry efficacy in the prevention of recurrent urinary tract infection? Phytother Res 2015;29:1559. doi: 10.1002/ptr.5427
  9. Walker EB, Barney DP, Mickelsen JN et al: Cranberry concentrate: UTI prophylaxis. J Fam Pract 1997;45:167. [no doi]
  10. Beerepoot MA, ter Riet G, Nys S et al: Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med 2011; 171:1270. doi: 10.1001/archinternmed.2011.306
  11. Howell A, Botto H, Combescure C, et al. Dosage effect on uropathogenic Escherichia colianti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double-blind study. BMC Infectious Diseases 2010,10:94. https://doi.org/10.1186/1471-2334-10-94.
  12. Howell AB, Reed JD, Krueger CG, et al. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry. 2005;66(18):2281-2291. DOI: 10.1016/j.phytochem.2005.05.022
  13. Prior RL, Fan E, Ji H, et al. Multi-laboratory validation of a standard method for quantifying proanthocyanidins in cranberry powders. J Sci Food Agric. 2010;90(9):1473-1478. doi: 10.1002/jsfa.3966
  14. Sintara M, Li L, Cunningham DG, Prior RL, Wu X, Chang T. Single-laboratory validation for determination of total soluble proanthocyanidins in cranberry using 4-dimethylaminocinnamaldehyde .J AOAC Int. 2018 May 1;101(3):805-809. doi: 10.5740/jaoacint.17-0288
  15. Chughtai B, Thomas D,Howell A. Variability of commercial cranberry dietary supplements for the prevention of uropathogenic bacterial adhesion. Am J Obstet Gynecol 2016;215(1):122-3. doi: 10.1016/j.ajog.2016.03.046
  16. Uberos J, Nogueras Ocana M, Fernandez-Puentes V, et al. Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial  Open Access Journal of Clinical Trials. 2012:4:31-38 https://www.dovepress.com/cranberry-syrup-vs-trimethoprim-in-the-prophylaxis-of-recurrent-urinar-peer-reviewed-article-OAJCT
  17. Thomas D, Rutman M, Cooper K, et al. Does cranberry have a role in CA-UTIs?. Can Urol Assoc J. 2017;11(11):E42 1-4. DOI: 10.5489/cuaj.4472

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Brian J. Flynn, MD

Brian J. Flynn, MD is the Co-Director of Female Pelvic Medicine and Reconstructive Surgery at the University of Colorado School Hospital and is a Professor of Surgery/Urology. He received his Bachelor of Science Degree in Electrical Engineering from the University of Rochester, Rochester, New York, Doctorate of Medicine from Temple University School of Medicine, Philadelphia, Pennsylvania, residency in Urology at Geisinger Medical Center, Danville, Pennsylvania and fellow from Duke University. Dr. Flynn is a consultant to Trophikos.

Comments:

  • This is a great article! Cranberries really do help prevent UTI’s! I know that cause I’ve had so many recurrent UTI’s throughout my life, it was getting to a point that my life was unbearable! I was so done with antibiotics, it was so bad for my body! Until I went to CVS one day and went through other alternatives! Thank god I found a dietary supplement for preventing UTI’s!! Cystex Urinary Health Maintenance is legit my savior!! never had to take antibiotics ever since then!

    Reply

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