Dr. Amy B. Howell is an associate research scientist at the Marucci Center for Blueberry and Cranberry Research at Rutgers University, where she works on isolating natural products from cranberries that benefit health.
Since 1993, Dr. Howell has been engaged in research aimed at identifying the active compounds in cranberries that prevent urinary tract infections and determining their role in maintenance of urinary tract health. Dr. Howell and her team isolated specific compounds from cranberry fruit, called proanthocyanidins (PACs), which they found to be capable of preventing E. coli bacteria from attaching to cells from the urinary tract. This work was published in The New England Journal of Medicine in 1998.
In a subsequent publication in The Journal of the American Medical Association, she reported on cranberry’s potential role in preventing antibiotic resistant bacteria from colonizing the urinary tract. Her work on identification of the unique molecular structures of the A-type cranberry PACs has been published in both Phytochemistry and the Journal of Natural Products.
Currently, she is engaged in projects to identify biomarkers in urine that have bacterial anti-adhesion activity, and determine additional mechanisms of action in the gut for cranberry and maintenance of urinary tract health. She is closely involved in method development for accurate quantification of cranberry PACs in powdered supplements to enable the cranberry industry to develop, manufacture and market high quality, efficacious products for human and animal nutrition. She is currently involved in writing the AHP and USP monographs on cranberry.
She has presented her research findings at numerous professional meetings in the U.S. and internationally, and her work has been featured in magazines and newspapers (NY Times, etc.) and has been a guest on radio and television shows (NPR, Dr. Oz, Today Show, Good Morning America, etc.)
Bacterial Anti-adhesion Activity of Cranberry Proanthocyanidins
The American Cranberry (Vaccinium macrocarpon Ait) has been utilized medicinally for hundreds of years, and more recently has demonstrated a broad array of health benefits in a number of research studies. Consumption of cranberry juice has been associated with prevention of urinary tract infections, and several well-designed clinical studies have confirmed this association (Avorn et al., 1994; Kontiokari et al., 2001) For years, the preventative effects of cranberry were assumed to be due to the acidity of the fruit; however the majority of clinical studies have demonstrated that a bacteriostatic pH is rarely achieved in urine following normal serving sizes of cranberry (Avorn et al., 1994, Walker et al., 1997).
Urinary tract infection is initiated by bacterial adherence to the uroepithelium, followed by bacterial multiplication and colonization of the urinary tract (Beachy, 1981). Cranberries contain a group of polyphenolic compounds called proanthocyanidins (PACs) with double A-type linkages that inhibit P-fimbriated E. coli from adhering to the uroepithelial cells (Howell et al., 1998, Foo et al., 2000a,b), thus preventing growth and subsequent infection. These PACs are different from those found in other foods, such as chocolate and grape that contain single B-type linkages between flavan-3-ol units (Gu et al., 2003). Recent studies suggest that cranberry PACs may induce conformational changes in bacteria that influence their adhesion activity (Liu et al., 2006).
Cranberry PACs are associated with preventing bacterial adhesion not only in the urinary tract, but also in the stomach and oral cavity. They prevented Helicobacter pylori, the bacteria associated with the onset of stomach ulcers, from attaching to isolated stomach cells (Burger et al., 2000). In a randomized placebo-controlled clinical study in China, consumption of two 250-ml servings of cranberry juice cocktail (27% cranberry) per day accounted for a 15% suppression of H. pylori (Zhang et al., 2005). Cranberry PAC extracts have also demonstrated activity in the oral cavity preventing biofilms associated with coaggregation and adhesion of bacteria to teeth and gums (Weiss et al., 2002), and prevented adhesion of Streptoccocus sobrinus to hydroxyapatite (Steinberg et al., 2004).
Inhibiting bacterial adhesion to prevent infections rather than prescribing low-dose antibiotics is of interest to many researchers, as the mechanism of anti-adherence does not kill bacteria and lead to significant selection pressure favoring survival of antibiotic resistant bacterial strains (Ofek et al., 2003). Therefore, utilizing cranberry and/or cranberry PACs to prevent certain bacterial infections could potentially help to slow the pace of antibiotic resistance development. Preventative strategies such as this could become increasingly important as rates of antibiotic resistance continue to increase due to over-use of antibiotics (Gupta et al., 2001).
Keywords: Cranberry, Vaccinium macrocarpon, bacteria, Escherichia coli, adhesion, urinary, ulcer, oral cavity, proanthocyanidin