April 2021 Issue

Cranberry Products & UTI
By Constance Brown-Riggs, MSEd, RDN, CDCES, CDN
Today’s Dietitian
Vol. 23, No. 4, P. 42

Learn what the FDA’s qualified health claims state plus new insights on how to counsel clients.

After decades of research from clinical trials showing associations between consumption of cranberry products and lowered risk of urinary tract infections (UTIs), the FDA has announced its approval of qualified health claims.

The announcement comes in response to a health claim petition submitted on behalf of Ocean Spray Cranberries, Inc. The petition requested that the FDA authorize a health claim regarding the relationship between cranberry product consumption and the reduced risk of recurrent UTIs in healthy women.

This article will discuss UTIs and the pathogens involved in the infection, provide an update on the science regarding the efficacy of cranberry products in UTI prevention and recurrence, review the types of health claims, and offer counseling recommendations and insights for dietitians.

UTIs Explained
UTIs are prevalent and costly. “According to the World Health Organization, an estimated 50% of women report having had a UTI at some point in their lives and account for 8.3 million office visits and more than 1 million hospitalizations, resulting in an annual cost greater than $1 billion,” says Christina Khoo, PhD, director of emerging science, nutrition, and regulatory affairs for the department of research and development at Ocean Spray Cranberries, headquartered in Lakeville-Middleboro, Massachusetts.

The infections occur when bacteria from the gut work their way into the bladder through the urethra and infiltrate the urinary tract. These bacteria can affect several parts of the urinary tract, but the most common type of infection occurs in the bladder and is known as cystitis.1 Eighty percent of outpatient UTIs can be attributed to E coli. However, other types of bacteria, such as Staphylococcus saprophyticus, which accounts for 5% to 15% of outpatient UTIs, Enterococcus, and Klebsiella pneumoniae, also are associated with UTIs.2

Symptoms of a UTI can include pain or burning sensation while urinating, difficulty urinating, bloody or foul-smelling urine, and pressure or cramping in the groin or lower abdomen.2 Bacterial UTIs are treated with antibiotics. But even when treated, UTIs tend to come back. For 25% to 30% of women who’ve had a UTI, the infection returns within six months.3 Historically, low-dose antibiotic therapy has been used for the prevention of recurrent UTIs.2 However, with frequent use of antibiotics, bacteria may develop resistance and antibiotics may not effectively treat subsequent infections.3 To control antibiotic resistance, scientists continue to look for antibiotic-free strategies to prevent and treat recurring UTIs.

In 2019, after reviewing the available literature, the American Urological Association included a recommendation to use cranberry products as an antibiotic-free way to prevent recurrent UTIs.4 Cranberry’s subsequent qualified health claim approved by the FDA strengthens this guidance. “It allows health care facilities and professionals who are already using cranberry to feel even more confident in their recommendations to help alleviate some of the challenges faced by UTI sufferers,” Khoo says.

Cranberries are scientifically recognized as a potent source of unique antioxidants known for their antiadhesion activity. Robin Foroutan, MS, RDN, HHC, owner of Nutrition by Robin in New York City and a spokesperson for the Academy of Nutrition and Dietetics, who specializes in integrative and functional medicine and holistic healing modalities, says, “Cranberries have long been used as a natural treatment for urinary tract infections. They contain proanthocyanidins that may help prevent bacteria from sticking to the lining of the urethra, helping to prevent them from infecting the tissue and so helping to prevent a UTI.” Proanthocyanidins found in cranberries have a different structure than those found in other fruits and vegetables, which is associated with their antiadhesion properties.5 Research continues as scientists seek a better understanding of the mechanisms behind the protective effects of cranberry.

For example, in 2019, Khoo and colleagues conducted a randomized, double-blinded, placebo-controlled pilot study to assess bacterial antiadhesive activity following consumption of a cranberry supplement. In this study, published in Food & Function, subjects without a history of current or recurrent UTI were given two cranberry or placebo chews, one in the morning and one in the evening. The cranberry chew contained cranberry extract, apple juice concentrate, apple purée, and pectin. Urine samples collected at baseline and postintervention were tested every three hours for antiadhesion effects. After consumption of the cranberry chew, urinary antiadhesion activity was significantly greater (p<0.05) than that of the placebo chew. This study suggests that consumption of Cranberry +health Cranberry Supplement (cranberry chew), manufactured by Ocean Spray, may have the potential to help promote urinary tract health. Additional human trials are needed to correlate the level of ex vivo antiadhesion activity with the prevention of clinical UTIs.

Cranberry Qualified Health Claims
The qualified health claims recently approved by the FDA validate a large body of scientific research conducted throughout the past 25 years that has examined how the cranberry can help reduce recurrent UTIs in women. “Cranberries are now the only food with an approved qualified health claim from the FDA for reducing an infectious disease, positioning cranberries as a healthy food like omega-3 oils and nuts,” Khoo says.

As mentioned, the original request from Ocean Spray asked the FDA to authorize a health claim regarding the relationship between the cranberry product consumption and the decreased risk in recurrent UTIs in healthy women.6

A health claim characterizes the relationship between a substance and a disease or health-related condition. However, after reviewing the petition and other evidence related to the proposed health claim, the FDA determined that the scientific evidence supporting the claim didn’t meet the “significant scientific agreement” standard required for an authorized health claim. As a result, Ocean Spray agreed to have the petition evaluated as a qualified health claim petition.

Based on the subsequent review, the FDA concluded that there’s limited and inconsistent credible scientific evidence in support of qualified health claims for the consumption of cranberry juice beverages containing at least 27% cranberry juice and limited credible scientific evidence to support a qualified health claim for the consumption of cranberry dietary supplements containing at least 500 mg of 100% cranberry fruit powder and a reduced risk of recurrent UTI in healthy women. To ensure this claim isn’t false or misleading to consumers, qualified health claims must accompany a disclaimer or other qualifying language to accurately communicate the level of scientific evidence supporting the claim.6

The following is a list of acceptable qualified health claims provided by the FDA6:

Cranberry Juice Beverages
1. “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection (UTI) may reduce their risk of recurrent UTI.”

2. “Consuming one serving (8 oz) each day of a cranberry juice beverage may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. FDA has concluded that the scientific evidence supporting this claim is limited and inconsistent.”

3. “Consuming one serving (8 oz) each day of [this identified cranberry juice beverage] may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. FDA has concluded that the scientific evidence supporting this claim is limited and inconsistent.”

Cranberry Dietary Supplements
1. “Limited scientific evidence shows that by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection (UTI) may reduce their risk of recurrent UTI.”

2. “Consuming 500 mg each day of cranberry dietary supplement may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. FDA has concluded that there is limited scientific evidence supporting this claim.”

3. “Consuming 500 mg [X capsules/tablets/soft gels] each day of [this identified cranberry dietary supplement] may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. FDA has concluded that there is limited scientific evidence supporting this claim.”

The qualified health claim doesn’t include other conventional foods or products made from or containing cranberries, such as dried cranberries, cranberry sauce, cranberry-containing cereals, or baked products, because the FDA didn’t identify any studies in which these or other cranberry-containing conventional food products were investigated among healthy women with recurrent UTI.6

Khoo believes the qualified health claim will give consumers more confidence in using cranberry to reduce the risk of recurring UTIs. “With this qualified health claim in hand, Ocean Spray can communicate more clearly with consumers, letting them know the scientific evidence demonstrates that the cranberry products that fall within the FDA-approved claim may help reduce the risk of recurrent UTIs in healthy women,” Khoo says.

In response to the conflicting results in the FDA’s review regarding the efficacy of cranberry and UTI prevention, Tambunan and colleagues wondered whether new studies might provide a different result. In 2019, they conducted a meta-analysis to assess the efficacy, safety, and adherence of cranberry as a prophylactic drug for treating recurrent UTI. The analysis included nine randomized controlled trials involving 1,542 participants. The analysis showed that consumption of cranberry, especially cranberry capsule, significantly reduced the incidence of recurrent UTI compared with placebo, with good adherence rates and minor adverse events. In contrast, although antibiotic use had a greater efficacy, it was associated with a higher risk of severe adverse events.7

Nutrient-Drug Interaction
Conflicting evidence on whether cranberry interacts with the anticoagulant warfarin exists.8 Controlled clinical trials show no drug interaction for normal cranberry juice ingestion. However, large quantities of cranberry juice (about 1 to 2 L per day) or cranberry juice concentrates in supplements for an extended period (longer than three to four weeks) may temporally alter the effects of warfarin.9 Several case reports have been published suggesting that warfarin has the potential to interact with several fruit products. Still, it’s difficult to determine their relevance, as scientific evidence is scarce.10 Khoo says that “while Ocean Spray is not aware of any such potential effects from cranberry juice, consumers should consult directly with their health care provider if they have any concerns.”

Recommendations and Insights
Dietitians working with clients experiencing recurrent UTIs should emphasize hydration, according to Foroutan. Drinking water helps dilute urine and ensures frequent urination, enabling bacteria to be flushed from the urinary tract before an infection can begin.11

Cranberry products generally are thought to be safe. However, if consumed in vast amounts, they can cause stomach upset and diarrhea. Little is known about whether it’s safe to use cranberry for health purposes during pregnancy or breast-feeding. And cranberry isn’t effective as a treatment for an existing UTI. People who think they have a UTI should be encouraged to see a health care provider for diagnosis and treatment.8

When using cranberry products to reduce the risk of UTI, dietitians should recommend clients look for cranberry juice beverages containing at least 27% cranberry juice or cranberry dietary supplements containing at least 500 mg of 100% cranberry fruit powder. If there’s a health claim on the product label, clients should look for the keywords “limited and inconsistent scientific evidence” as part of the qualified health claim.

“For women with recurrent UTIs, it’s important to help them find the root cause of this imbalance. In my practice, I’ve found that many women with very persistent and recurrent UTIs also have a significant overgrowth of pathogenic microbes in their digestive tracts, even when they don’t have digestive symptoms. Treating their gut dysbiosis has been critical to their success,” Foroutan says.

Research supported by the National Center for Complementary and Integrative Health is looking at the effects of polyphenols from cranberry on the gut microbiome. “These polyphenols are very bioactive and can help manage oxidative stress and balance the gut microbiome,” Khoo says. “So, there is a lot more research that we are doing to expand the scientific evidence for cranberry bioactive benefits beyond UTI, such as prebiotic benefits.”

Cranberries are the most widely used nonantibiotic preventive treatment for recurrent UTIs in women. “Recognizing cranberry products as a way to prevent recurrence or reduce the risk of UTIs could mean fewer rounds of antibiotics for UTI-prone women,” Foroutan says. Khoo believes the qualified health claims for cranberry products will give health professionals more confidence and justification to provide this important information.

— Constance Brown-Riggs, MSEd, RDN, CDCES, CDN, is a national speaker and author of the award-winning Diabetes Guide to Enjoying Foods of the World, and The African American Guide to Living Well With Diabetes. Learn more about her at ConstanceBrownRiggs.com.


References

1. Antibiotic prescribing and use in doctor’s offices: urinary tract infection. Centers for Disease Control and Prevention website. https://www.cdc.gov/antibiotic-use/community/for-patients/common-illnesses/uti.html. Updated August 27, 2019. Accessed January 21, 2021.

2. Medical student curriculum: adult UTI. American Urological Association website. https://www.auanet.org//education/auauniversity/for-medical-students/medical-students-curriculum/medical-student-curriculum/adult-uti. Updated April 2020. Accessed January 21, 2021.

3. When urinary tract infections keep coming back. Harvard Health Publishing website. https://www.health.harvard.edu/bladder-and-bowel/when-urinary-tract-infections-keep-coming-back. Updated September 17, 2019. Accessed January 27, 2021.

4. Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline (2019). American Urological Association website. https://www.auanet.org/guidelines/recurrent-uti. Published 2019. Accessed January 27, 2021.

5. Fu Z, Liska D, Talan D, Chung M. Cranberry reduces the risk of urinary tract infection recurrence in otherwise healthy women: a systematic review and meta-analysis. J Nutr. 2017;147(12):2282-2288.

6. U.S. Food and Drug Administration. Health claim petition – consumption of cranberry products and reduced risk of recurrent urinary tract infection in healthy women. https://www.fda.gov/media/140304/download. Published July 21, 2020. Accessed January 21, 2021.

7. Tambunan MP, Rahardjo HE. Cranberries for women with recurrent urinary tract infection: a meta-analysis. Med J Indones. 2019;28(3):268-275.

8. Cranberry. National Center for Complementary and Integrative Health website. https://www.nccih.nih.gov/health/cranberry. Updated May 2020. Accessed January 27, 2021.

9. Srinivas NR. Cranberry juice ingestion and clinical drug-drug interaction potentials; review of case studies and perspectives. J Pharm Pharm Sci. 2013;16(2):289-303.

10. Norwood DA, Parke CK, Rappa LR. A comprehensive review of potential warfarin-fruit interactions. J Pharm Pract. 2015;28(6):561-571.

11. Urinary tract infection (UTI). Mayo Clinic website. https://www.mayoclinic.org/diseases-conditions/urinary-tract-infection/care-at-mayo-clinic/mac-20353457. Published October 14, 2020. Accessed January 27, 2021.