Lisa Olivo, Associate Editor11.08.16
The use of cranberry to treat urinary tract infections (UTI) is a longstanding and widely-known natural remedy. But new research published in the Journal of the American Medical Association (JAMA) found cranberry juice extract capsules weren’t as effective as many believe them to be.
Dr. Manisha Juthani-Mehta, an infectious disease specialist with the Yale School of Medicine, and her team examined 185 female nursing patients age 65 and up in a double-blind, randomized, placebo-controlled efficacy trial. The participants either did or did not have bacteriuria plus pyuria prior to intervention—bacteria that are prevalent among women residing in nursing homes. According to a 2014 study in JAMA, it was determined that bacteriuria is widespread in 25-50% of women living in nursing homes, and pyuria is present in 90% of those with bacteriuria
Participants were given either two oral cranberry capsules with each capsule containing 36 mg of the active ingredient proanthocyanidin (PAC) (i.e., 72 mg total, equivalent to 20 ounces of cranberry juice) or placebo once daily over the course of year.
After adjusting for missing data and other variables, the researchers concluded that there was no statistically significant difference in presence of bacteriuria plus pyuria between the treatment group (29.1%) and control (29.0%) group over the course of the study. Furthermore, the study found no significant difference in the number of symptomatic UTIs (10 episodes in the treatment group vs. 12 in the control group), rates of death (17 vs. 16 deaths), hospitalization (33 vs. 50 episodes), or antibiotics administered for suspected UTIs.
In an editorial published in JAMA along with the study, Dr. Lindsay E. Nicolle concluded that “cranberry products should not be recommended as a medical intervention for the prevention of UTI,” given what she sees as a lack of sound clinical evidence supporting its benefits, adding “It is time to move on from cranberries.”
In Defense of the Cranberry
In light of these findings leaders in the nutraceuticals field and experts in botanicals have stepped up to support the benefits of the cranberry.
Pharmacist and author of 18 books on complementary medicine and health topics, Sherry Torkos, said she takes exception to the interpretation of the recent JAMA article. “Various forms of cranberry have been used for centuries to combat urinary tract infections, and dozens of studies have been published to show its effectiveness for the condition,” she explained. “There appear to be some major limitations to this study and confounding factors that may explain the poor response rate. There is also a wide variance in cranberry supplements and beverages.”
She said some products, such as Cran-max from Proprietary Nutritionals, Inc., Kearny, NJ, have a “proven record with strong science demonstrating efficacy even compared to antibiotics, but without the troubling issues of antibiotic resistance.”
While the cranberry supplement in the JAMA study may not have been effective in lessening amounts of bacteruria and pyuria in a population of elderly women, other forms of cranberry have been found to be effective in the prevention of UTIs, Ms. Torkos said. She pointed to a published clinical trial in which Cran-Max was found to be just as effective as trimethoprim, the premier antibiotic prescribed for urinary tract infections. Cran-Max also lessened UTI symptoms as well as decreased UTI incidence.
Whole Fruit Extract vs. Juice Extract
Stephen Lukawski, director of business development and global sales for Quebec-based Fruit d'Or Nutraceuticals stressed that not all cranberry extracts are the same. “The study utilizes a juice extract, while Fruit d’Or is a proponent of using the whole fruit extract,” he explained.
Fruit d'Or, he said, focuses not just on the benefits provided by PACs within cranberries, but also the protein, fiber, amino acids and other vital nutrients derived from the whole fruit. Furthermore, the company believes in the vast benefits of cranberry for applications beyond urinary tract health, including areas such as gut health, oral health, cardiovascular health and even skin care, though he said more science is needed.
However, processing of cranberry also plays a big part in the efficacy of end products. Mr. Lukawski emphasized the importance of using a standardized extract, as well to ensuring the end product has effective doses of the natural ingredient. “If you don’t know what’s in your starting raw material to begin with, the end product may not meet up to consumers’ expectations. As a vertically integrated company, Fruit d'Or prides itself on identifying biomarkers and testing raw materials using DNA fingerprinting to avoid adulteration.” He added that if over-heated during processing, cranberries can be stripped of their “natural goodness,” so the company utilizes exact and consistent processing procedures from “farm to finish.”
“PACs are only part of the story,” he concluded. “The whole food, the entire fruit, is the future of cranberry. Both soluble and insoluble PACs play an important role in the benefits of cranberry and that’s what’s really missing from the story of cranberry’s importance for health.”
Botanical Back Up
Stefan Gafner, PhD, and chief science officer for the American Botanical Council, Austin, TX, said that in his opinion the JAMA study did many things right, but also got some things wrong.
“The use of a well-established and well-researched standardized cranberry product, the administration of an appropriate dose, the verification of compliance with the dosage regimen, and the competent sampling by trained nurses are some of its strengths. However, the majority of the older women included in the study did not have urinary tract infection (UTI) issues (75% of those who received the cranberry treatment did not have a UTI in the year prior to enrollment), so the clinical trial was carried out with the wrong target population,” he explained.
He speculated that the lack of benefits found by the study should not have been a surprise as “only 5.4% of the participants in the cranberry treatment group had two or more episodes of an UTI prior to enrollment, and since previous clinical trials have shown cranberry to be mainly effective in the prevention of recurrent UTIs.”
Dr. Gafner added that the presence of bacteriuria in urine is not necessarily an indicator of a UTI, “so the fact that statistically the same number of women that were using cranberry capsules or placebo had bacteria in their urine does not mean that cranberry has no benefits.” Cranberry, he stressed, is not known for its ability to kill bacteria, but for an ability to inhibit adherence to the mucous membranes of the urinary tract. This inhibits bacteria from establishing themselves and causing infection. Overall, he believes no concrete conclusions about the benefits of cranberry extracts to prevent recurrent UTIs should be made based on the results of this clinical trial.
CRN’s Comments
Andrea Wong, PhD, vice president, scientific and regulatory affairs for the Council for Responsible Nutrition (CRN), Washington, D.C., said that while the study adds to the growing knowledge base that exists around cranberry and urinary tract health, she was concerned about the accompanying editorial, which gave conclusions about cranberry and urinary tract infections.
“We did notice several limitations in the study, such as using a very specific population—the study was conducted on elderly women in a nursing home. Their average age was 86, so they tend to have other issues going on that you really need to consider,” she explained. “More importantly though, the researchers did not actually study patients who actually suffered from recurrent UTIs. So it’s difficult to draw conclusions, as the editorial did, about the effectiveness of cranberry when you’re not really studying people who have it in the first place.”
The editorial was most concerning to Dr. Wong because the author made “sweeping conclusions about cranberries and UTIs that really don't consider the breadth of evidence that’s available.” She suggested that dismissing cranberry entirely when it’s been successfully used on a traditional basis with extensive evidence of its benefits from randomized, controlled trials, really isn’t helpful to healthcare providers and their patients. “We know that cranberry has a safe history of use in this area, and we know it’s been very well researched in a clinical setting,” she said. “So women who are recovering from recurrent UTIs are looking for options, and healthcare providers need to know all of this information when they’re giving recommendations to them.”
Dr. Manisha Juthani-Mehta, an infectious disease specialist with the Yale School of Medicine, and her team examined 185 female nursing patients age 65 and up in a double-blind, randomized, placebo-controlled efficacy trial. The participants either did or did not have bacteriuria plus pyuria prior to intervention—bacteria that are prevalent among women residing in nursing homes. According to a 2014 study in JAMA, it was determined that bacteriuria is widespread in 25-50% of women living in nursing homes, and pyuria is present in 90% of those with bacteriuria
Participants were given either two oral cranberry capsules with each capsule containing 36 mg of the active ingredient proanthocyanidin (PAC) (i.e., 72 mg total, equivalent to 20 ounces of cranberry juice) or placebo once daily over the course of year.
After adjusting for missing data and other variables, the researchers concluded that there was no statistically significant difference in presence of bacteriuria plus pyuria between the treatment group (29.1%) and control (29.0%) group over the course of the study. Furthermore, the study found no significant difference in the number of symptomatic UTIs (10 episodes in the treatment group vs. 12 in the control group), rates of death (17 vs. 16 deaths), hospitalization (33 vs. 50 episodes), or antibiotics administered for suspected UTIs.
In an editorial published in JAMA along with the study, Dr. Lindsay E. Nicolle concluded that “cranberry products should not be recommended as a medical intervention for the prevention of UTI,” given what she sees as a lack of sound clinical evidence supporting its benefits, adding “It is time to move on from cranberries.”
In Defense of the Cranberry
In light of these findings leaders in the nutraceuticals field and experts in botanicals have stepped up to support the benefits of the cranberry.
Pharmacist and author of 18 books on complementary medicine and health topics, Sherry Torkos, said she takes exception to the interpretation of the recent JAMA article. “Various forms of cranberry have been used for centuries to combat urinary tract infections, and dozens of studies have been published to show its effectiveness for the condition,” she explained. “There appear to be some major limitations to this study and confounding factors that may explain the poor response rate. There is also a wide variance in cranberry supplements and beverages.”
She said some products, such as Cran-max from Proprietary Nutritionals, Inc., Kearny, NJ, have a “proven record with strong science demonstrating efficacy even compared to antibiotics, but without the troubling issues of antibiotic resistance.”
While the cranberry supplement in the JAMA study may not have been effective in lessening amounts of bacteruria and pyuria in a population of elderly women, other forms of cranberry have been found to be effective in the prevention of UTIs, Ms. Torkos said. She pointed to a published clinical trial in which Cran-Max was found to be just as effective as trimethoprim, the premier antibiotic prescribed for urinary tract infections. Cran-Max also lessened UTI symptoms as well as decreased UTI incidence.
Whole Fruit Extract vs. Juice Extract
Stephen Lukawski, director of business development and global sales for Quebec-based Fruit d'Or Nutraceuticals stressed that not all cranberry extracts are the same. “The study utilizes a juice extract, while Fruit d’Or is a proponent of using the whole fruit extract,” he explained.
Fruit d'Or, he said, focuses not just on the benefits provided by PACs within cranberries, but also the protein, fiber, amino acids and other vital nutrients derived from the whole fruit. Furthermore, the company believes in the vast benefits of cranberry for applications beyond urinary tract health, including areas such as gut health, oral health, cardiovascular health and even skin care, though he said more science is needed.
However, processing of cranberry also plays a big part in the efficacy of end products. Mr. Lukawski emphasized the importance of using a standardized extract, as well to ensuring the end product has effective doses of the natural ingredient. “If you don’t know what’s in your starting raw material to begin with, the end product may not meet up to consumers’ expectations. As a vertically integrated company, Fruit d'Or prides itself on identifying biomarkers and testing raw materials using DNA fingerprinting to avoid adulteration.” He added that if over-heated during processing, cranberries can be stripped of their “natural goodness,” so the company utilizes exact and consistent processing procedures from “farm to finish.”
“PACs are only part of the story,” he concluded. “The whole food, the entire fruit, is the future of cranberry. Both soluble and insoluble PACs play an important role in the benefits of cranberry and that’s what’s really missing from the story of cranberry’s importance for health.”
Botanical Back Up
Stefan Gafner, PhD, and chief science officer for the American Botanical Council, Austin, TX, said that in his opinion the JAMA study did many things right, but also got some things wrong.
“The use of a well-established and well-researched standardized cranberry product, the administration of an appropriate dose, the verification of compliance with the dosage regimen, and the competent sampling by trained nurses are some of its strengths. However, the majority of the older women included in the study did not have urinary tract infection (UTI) issues (75% of those who received the cranberry treatment did not have a UTI in the year prior to enrollment), so the clinical trial was carried out with the wrong target population,” he explained.
He speculated that the lack of benefits found by the study should not have been a surprise as “only 5.4% of the participants in the cranberry treatment group had two or more episodes of an UTI prior to enrollment, and since previous clinical trials have shown cranberry to be mainly effective in the prevention of recurrent UTIs.”
Dr. Gafner added that the presence of bacteriuria in urine is not necessarily an indicator of a UTI, “so the fact that statistically the same number of women that were using cranberry capsules or placebo had bacteria in their urine does not mean that cranberry has no benefits.” Cranberry, he stressed, is not known for its ability to kill bacteria, but for an ability to inhibit adherence to the mucous membranes of the urinary tract. This inhibits bacteria from establishing themselves and causing infection. Overall, he believes no concrete conclusions about the benefits of cranberry extracts to prevent recurrent UTIs should be made based on the results of this clinical trial.
CRN’s Comments
Andrea Wong, PhD, vice president, scientific and regulatory affairs for the Council for Responsible Nutrition (CRN), Washington, D.C., said that while the study adds to the growing knowledge base that exists around cranberry and urinary tract health, she was concerned about the accompanying editorial, which gave conclusions about cranberry and urinary tract infections.
“We did notice several limitations in the study, such as using a very specific population—the study was conducted on elderly women in a nursing home. Their average age was 86, so they tend to have other issues going on that you really need to consider,” she explained. “More importantly though, the researchers did not actually study patients who actually suffered from recurrent UTIs. So it’s difficult to draw conclusions, as the editorial did, about the effectiveness of cranberry when you’re not really studying people who have it in the first place.”
The editorial was most concerning to Dr. Wong because the author made “sweeping conclusions about cranberries and UTIs that really don't consider the breadth of evidence that’s available.” She suggested that dismissing cranberry entirely when it’s been successfully used on a traditional basis with extensive evidence of its benefits from randomized, controlled trials, really isn’t helpful to healthcare providers and their patients. “We know that cranberry has a safe history of use in this area, and we know it’s been very well researched in a clinical setting,” she said. “So women who are recovering from recurrent UTIs are looking for options, and healthcare providers need to know all of this information when they’re giving recommendations to them.”
