A new, groundbreaking study clarifies why some cranberry supplements are effective at managing recurrent Urinary Tract Infections (2 in 6 months or 3 in 12 months), while others are not, arming healthcare providers with much needed clarity on how to advise their patients. For the first time, scientists confirmed cranberry products made with soluble proanthocyanidins (PACs), demonstrating higher Anti-Adhesion Activity (AAA) of uropathogenic bacteria in urine compared to products with insoluble PAC after intake of the products over a one-week period.

In the study funded by Rutgers University and published in the Journal of Dietary Supplements, Rutgers Research Scientist, Amy B. Howell, PhD, Jean-François Dreyfus, MD, PhD, and practicing urologist Bilal Chughtai, MD of Weill Cornell Medicine reported that “water soluble PAC, sourced directly from cranberry juice extract has a direct impact on in vitro and ex vivo AAA of P-fimbriated E. coli bacteria.” The authors explained, “the bacterial AAA of urine following cranberry juice extract consumption interrupts the initial step in the infection process, a potentially important mechanism for UTI prevention. Preventing infection in this way, rather than killing bacteria, may help reduce resistant uropathogenic bacterial strains.”

“Cranberry, Vaccinium macrocarpon, is already widely utilized by consumers for maintenance of urinary tract health.” However, since cranberry supplements are not regulated by the FDA, there is no oversight on what must be included for efficacy. As a result, supplements on the market are often formulated using different components of the cranberry that may or may not be effective. This new study explains that this is a key reason for why there is high variability in AAA across these products.

Previously, Dr. Bilal Chughtai & Researcher Amy Howell compared AAA of 9 commercially available cranberry supplements in a study published in American Journal of Obstetrics and Gynecology in 2016 and discovered significant variability among products. That study elucidated why some supplements don’t work—not enough Anti Adhesion Activity, noting that “products containing 36 mg of PAC have the best AAA,” though there was insufficient evidence to explain the discrepancy in AAA variability even among those containing 36 mg of PAC.

We now know 36 mg of PAC is only part of the story.

The source of the PACs is equally important—which part of the cranberry it comes from. In this new study, the scientists concluded that water-soluble PACs found in concentrated cranberry juice extract elicit the highest AAA in urine after intake.

Anti-Adhesion testing of PACRAN, which is comprised of PACs from every part of the cranberry, versus GIKACRAN with PACs taken only from the juice concentrate extract, and fractions of each supplement containing the distinct molecular classes of compounds in each supplement confirmed that only the soluble PACs from the juice concentrate are responsible for AAA. As explained in the study, “The 36 mg PAC level often reported in cranberry products is specifically indicative of the soluble PAC measured only with the DMAC/A2 reference standard and is the recommended daily intake amount according to large meta-analyses on cranberry clinical trials for UTI prevention (Jepson et al., 2012; Jepson, 2013). The majority of AAA is linked to polyphenolic compounds in cranberry, especially A-type (PAC) found in the water-soluble juice portion of cranberry fruit (Howell et al. 1998, Foo 2000, Gupta 2007, Gupta 2012) and their metabolites (de Llano et al. 2015; Mena et al. 2017).”

The AAA testing for both soluble and insoluble PACs reveals a significant difference between them, with AAA of soluble PAC being almost three times higher than insoluble PAC. “High concentrations of soluble PAC per serving in CJD [concentrated cranberry juice extract] correlated with 94 percent ex vivo urinary AAA, while the lower 23 percent AAA value for WCFD [whole fruit components] was likely due to the low soluble PAC content per serving. When PACs are insoluble, they do not have AAA. The PACs that come from the pomace products (the pulp, seeds, stems, skin of the berry) are insoluble, because the pomace is fibrous. The PACs get stuck in the cellulose matrix, and can’t be easily extracted out, especially by the human body…The insoluble, non-extractable PACs complexed with cellulose fibers in the cranberry skins that remain after the juicing process (Gullickson et al., 2019; Roopchand et al., 2013) have not shown an effect on bacterial adhesion.”

The study provides long-desired direction for healthcare providers to advise their patients: To get the most anti-adhesion benefit, look for a supplement made from cranberry juice extract.

“This study demonstrates the important differences in formulating cranberry supplements for urinary tract health.” said Brian Flynn, MD, UC Health, Denver. “The results show that the type of cranberry fruit component in the supplement directly influences its effectiveness and should guide consumers and healthcare providers when choosing cranberry supplements for urinary tract health.”

“Since day one, the ellura team has sought to deliver reliable solutions for UTI health, made with the best ingredients, and backed by scientific research,” said Kevin Wade, EVP of Clinical and Physician Development and co-founder of Trōphikōs, makers of ellura. “We remain committed to delivering the best of nature, powered by science.”