Cranberry Pomegranate Synbiotic

Urinary tract infection (UTI) is one of the most common bacterial infections (Foxman, 2014), often caused by Gram-negative bacteria, enterobacteriaceae (Bader, Loeb & Brooks, 2017), and more specifically within this large bacterial family, the familiar Escherichia coli (Jensen et al., 2017). In recent years, more women suffer from chronic UTIs due to the climbing rise of antibiotic resistant bacteria. As a natural alternative or a supportive adjunct treatment with antibiotics, the Cranberry Pomegranate Synbiotic Formula offers well-researched phyto nutrients, probiotics, prebiotics, and D- mannose. Studies and clinical trials find cranberries (Bader et al., 2017; Jensen et al., 2017; de Llano et al., 2015), Pomegranates (Pagliarulo et al., 2016; Heber, 2011; Duman et al., 2009), along with probiotics, prebiotics, and D- mannose (Spaulding et al., 2017; 2017a; Domenici et al., 2016), to offer effective management and support for UTI.*

Historically, cranberries and cranberry juice have long been used to alleviate urinary tract infections, with research linking the ability of cranberries’ proanthocyanidins (Krueger et al., 2013) to inhibit adhesion of E. coli bacteria (Neto, 2007). As early as 1933, research by Fellers et al. has shown cranberries to positively effect urinary health. Cowan’s (1999) seminal work on plant products as antimicrobial agents, which includes cranberries, has been cited in approximately 7,500 research articles. Studies on cranberries show not only an alternative to antibiotic but also as a daily supplement for a steady prevention of UTIs.*

Recent studies continue to observe and explain cranberries’ excellent antimicrobial properties, especially the phenol elements and mechanism that are beneficial for the management and prevention of UTI (Jensen et al., 2017; Rodríguez-Pérez et al., 2017; Baranowska & Bartoszek, 2016; Sagdic et al, 2006; Lee, 2000). As stated above, proanthocyanidins in cranberries are found to prevent the adherence of Escherichia coli to uroepithelial cells in the urinary tract (Sun et al., 2015; Rowley, 2012; Burger et al., 2000), and disrupt hard to treat biofilm-mediated infections caused by Pseudomonas aeruginosa (Ulrey et al., 2014).*

Cranberries also pack other antimicrobial, antioxidant and anti-inflammatory benefits. With their powerful anti-adhesion properties, cranberries are found to inhibit growth of Helicobacter Pylori (Shmuely et al., 2007; Zhang et al., 2005; Burger et al., 2002), suppress tumor cell proliferation and offer support during cancer treatment (Bshayee et al., 2016; Kresty et al., 2015), as well as lower markers of cardio-metabolic risk (Novotny et al., 2015), and enhance the GI’s microbiota (Blumberg et al., 2016). Cranberries are shown to be effective agents for health.*

Pomegranate has enjoyed an exalted status since ancient times, and no wonder (Parseh et al., 2012). Studies show pomegranates contain 124 different phyto-nutrients with curative and preventative qualities. The pomegranate fruit is actually considered a berry, or more accurately, each pomegranate contains 600 seeds, each surrounded by fleshy white to dark red pulp (Rahimi et al., 2012).*

With their potent polyphenolic flavonoids, pomegranates show higher concentrations of antioxidants than green tea (Noda et al., 2002; Nori-Okamoto et al., 2004), cranberries, apples, grapes, or pears (Hmid et al., 2017; Heber, 2011; Heber et al., 2006). The pomegranate’s high concentration of polyphenols wields an inhibitory effect on pathogenic Staphylococcus aureus and Escherichia coli, serving as natural antimicrobial agents (Pagliarulo et al., 2016; Naz et al., 2007; Voravuthikunchai et al., 2005). Other microbial organisms are shown to be sensitive to the pomegranate phenolic flavonoids. Nascimento et al. (2000) tested extracts from a variety of plants in search of a natural support against antibiotic resistant microorganisms and found the pomegranate to be especially effective against Pseudomonas aeruginosa. Machado et al. (2002) identified antimicrobial ellagitannin of the pomegranate to be valuable to treat methicillin-resistant Staphylococcus aureus (MRSA) strains.*

Similarly, the pomegranate’s antioxidants work as scavengers and metal chelators (Kulkarni et al., 2007). The antioxidant, antimalarial, and antimicrobial activities of the tannin-rich fractions, ellagitannins and phenolic acids from pomegranates offer excellent daily dietary food supplement to enhance the immune system (Reddy et al., 2007).*

Probiotics and Supernatant are important to the health of our urogenital system. The genus Lactobacillus has been studied for their promising preventative and/or treatment potential against UTIs (de Llano et al., 2017). Three strains of lactobacillus were tested for their capabilities to inhibit pathogenic adherence of E. coli, E. faecalis, and Staphylococcus epidermidis to T24 epithelial bladder cells. L. salivarious, L. acidophilus showed a significantly inhibited the adherence of pathogens (de Llano et al., 2017; see also Shim et al., 2016). Lactobacillus species were also studies with infants experiencing acute pyelonephritis [kidney infection], and found effective in the prevention of urinary tract infections (Lee et al., 2016).*

The “anti-infective activities” of lactobacillus strains are exhibiting a great promise as innovative anti-infectious agents (Liévin-Le Moal et al., 2014), and especially for recurrent UTIs (Manzoor et al., 2016).*

Depletion of vaginal Lactobacilli has also found in research to be linked with UTI risk, which suggests that repletion (re-colonization of Lactobacilli) might be beneficial (Syngai et al., 2016; Fontana et al., 2013; Maurya et al., 2014).*

Supernatant is the fermented medium crated during the culturing process of probiotics. Supernatant is the fermented “soup” that contains important probiotic metabolites which is comprised of enzymes, peptides, proteins, vitamins, and other nutrients and factors, including antimicrobials such as bacitracins. Supernatant is shown in research to have powerful antimicrobial properties with the potential to block adhesion, invasion and translocation of E. coli, yet it is gentle enough to be used to ‘enhance neonatal resistance to systemic Escherichia coli K1 infection by accelerating development of intestinal defense’ (He et al., 2017). In fact, Lazar et al. (2009) in vitro study concluded that the soluble probiotic metabolites, or supernatant, might actually interfere with the beginning stages of adherence and colonization of selected E. coli. This means that the supernatant itself exudes protective effects (Lazar et al., 2009), as well as work synergistically with probiotics organism to stimulate the immune system against pathogenic invasion (Ditu et al., 2014).*

D-mannose has long shown an ability to support acute UTIs, inhibiting bacterial adhesion to the urothelium (Domenici et al., 2016; Kranjčec et al., 2014). Testing more sensitive populations, such as people with multiple sclerosis (MS) who suffer from recurrent UTIs, showed that D-mannose effected a reduction in the number of UTIs as well as reduction for the need of antibiotics (Panicker et al., 2016).*

Since 150 million people suffer from UTIs annually, using natural foods and nutriceutical agents to combat recurrence of UTI infections is advisable (Spaulding et al., 2017). The use of cranberries, pomegranates, probiotics, supernatant, and D-mannose form a potent synergistic effect that is shown in research to be very effective (Vicarotto, 2014).*

There are many more health functions that cranberries and pomegranates perform. For many years cranberries and pomegranates were studied to understand their anti-tumorigenic elements (e.g., Castonguay et al., 1997). More recent studies continue to reveal and explain the bioactivity of pomegranate (Panth et al., 2017; Bishayee et al., 2016; Faria & Calhau, 2011) and cranberries (Kresty et al., 2015; Hochman et al., 2008; Ferguson et al., 2006) as promising suppressants and inhibitors of different kinds of cancer cells (Weh et al., 2016; Liberty et al., 2009; Adams et al., 2006).*

And there is more: Research studies find pomegranate and cranberries phenolics to contribute to heart health (Taheri et al., 2017; Novotny et al., 2015; Aviram et al., 2008, 2002), to balance the gut microbiota (Blumberg et al., 2016), and to offer liver support (Bishayee et al., 2013, 2011). Check the Research Tab for more in depth studies.*

The Cranberry Pomegranate Synbiotic Formula is an excellent choice for UTIs. Cranberries, Pomegranates, Probiotics, supernatant, and D-mannose have all shown in research to provide a potent effect against UTIs. The combination of these ingredients offers a promising natural supplement to prevent and maintain a healthy balance of the urogenital system. We suggest 2-4 capsules twice daily for UTI management, and 1-2 capsules daily for preventative support.*

REFERENCES

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Baranowska, M., & Bartoszek, A. (2016). Antioxidant and antimicrobial properties of bioactive phytochemicals from cranberry. Postepy higieny i medycyny doswiadczalnej (Online), 70, 1460-1468. DOI: 10.5604/17322693.1227896

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Cowan, M. M. (1999). Plant products as antimicrobial agents. Clinical microbiology reviews, 12(4), 564-582. Abstract

de Llano, D. G., Arroyo, A., Cárdenas, N., Rodríguez, J. M., Moreno-Arribas, M., & Bartolomé, B. (2017). Strain-specific inhibition of the adherence of uropathogenic bacteria to bladder cells by probiotic Lactobacillus spp. Pathogens and Disease, 75(4). DOI:10.1093/femspd/ftx043

de Llano, D.G., Esteban-Fernández, A., Sánchez-Patán, F., Martínlvarez, P.J., Moreno-Arribas, M.V., Bartolomé, B. (2015). Anti-Adhesive Activity of Cranberry Phenolic Compounds and Their Microbial-Derived Metabolites against Uropathogenic Escherichia coli in Bladder Epithelial Cell Cultures. Int J Mol Sci, 16(6), 12119-30. DOI:10.3390/ijms160612119

Ditu, L.M., Chifiriuc, M.C., Bezirtzoglou, E., Marutescu, L., Bleotu, C., Pelinescu, D., Mihaescu, G., Lazar, V. (2014). Immunomodulatory effect of non-viable components of probiotic culture stimulated with heat-inactivated Escherichia coli and Bacillus cereus on holoxenic mice. Microb Ecol Health Dis, 25. DOI:10.3402/mehd.v25.23239

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Ermel, G., Georgeault, S., Inisan, C., Besnard, M. (2012). Inhibition of adhesion of uropathogenic Escherichia coli bacteria to uroepithelial cells by extracts from cranberry. J Med Food, 15(2):126-34. DOI: 10.1089/jmf.2010.0312

Fellers, C. R., Redmon, B. C., & Parrott, E. M. (1933). Effect of cranberries on urinary acidity and blood alkali reserve. Journal of Nutrition, 6, 455-463. Abstract

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Hochman, N., Houri-Haddad, Y., Koblinski, J., Wahl, L., Roniger, M., Bar-Sinai, A. …Hochman, J. (2008). Cranberry juice constituents impair lymphoma growth and augment the generation of antilymphoma antibodies in syngeneic mice. Nutr Cancer, 60, 511–7. DOI:10.1080/01635580801956493

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Kresty, L.A., Weh, K.M., Zeyzus-Johns, B., Perez, L.N., Howell, A.B. (2015). Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation. Oncotarget, 6, 33438–33455. DOI:10.18632/oncotarget.5586

Krueger, C. G., Reed, J. D., Feliciano, R. P., & Howell, A. B. (2013). Quantifying and characterizing proanthocyanidins in cranberries in relation to urinary tract health. Analytical and bioanalytical chemistry, 405(13), 4385-4395. DOI: 10.1007/s00216-013-6750-3

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Lee, Y. L., Owens, J., Thrupp, L., & Cesario, T. C. (2000). Does cranberry juice have antibacterial activity?. Jama, 283(13), 1691-1691.

Liberty, A.M., Amoroso, J.W., Hart, P.E., Neto, C.C. (2009). Cranberry PACs and triterpenoids: anti-cancer activities in colon tumor cell lines. Proceedings of the Second International Symposium on Human Health Effects of Fruits and Vegetables. Acta Horticulturae, 841, 61–66. DOI: 10.17660/ActaHortic.2009.841.4

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Machado, T. D. B., Leal, I. C., Amaral, A. C. F., Santos, K., Silva, M. G. D., & Kuster, R. M. (2002). Antimicrobial ellagitannin of Punica granatum fruits. Journal of the Brazilian Chemical Society, 13(5), 606-610. Article

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Maurya, P., Mogra, R., & Bajpai, P. (2014). Probiotics: an approach towards health and disease. Trends in Biosciences, 7(20), 3107-3113. Abstract

Noda, Y., Kaneyuki, T., Mori, A., Packer, L. (2002). Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin. J Agric Food Chem, 50(1), 166-71. DOI: 10.1021/jf0108765

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Novotny, J. A., Baer, D. J., Khoo, C., Gebauer, S. K., & Charron, C. S. (2015). Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults. The Journal of nutrition, 145(6), 1185-1193. DOI:10.3945/jn.114.203190

Pagliarulo, C., De Vito, V., Picariello, G., Colicchio, R., Pastore, G., Salvatore, P., & Volpe, M. G. (2016). Inhibitory effect of pomegranate (Punica granatum L.) polyphenol extracts on the bacterial growth and survival of clinical isolates of pathogenic Staphylococcus aureus and Escherichia coli. Food chemistry, 190, 824-831. DOI: 10.1016/j.foodchem.2015.06.028

Panth, N., Manandhar, B., Paudel, K.R. (2017). Anticancer Activity of Punica granatum (Pomegranate): A Review. Phytother Res, 31(4), 568-578. DOI:10.1002/ptr.5784

Parseh, H., Hassanpour, S., Emam-Djome, Z., Lavasani, A. S., Mahmoodabady, H. Z., CHabok, M., ... & Ghahsareh, A. M. (2012, April). Antimicrobial properties of Pomegranate (Punica granatum L.) as a Tannin rich Fruit: a review. In The 1st International and The 4th National Congress on Recycling of Organic Waste in Agriculture. Iran.

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Reddy, M. K., Gupta, S. K., Jacob, M. R., Khan, S. I., & Ferreira, D. (2007). Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L. Planta medica, 53(05), 461-467. DOI: 10.1055/s-2007-967167

Rodríguez-Pérez, C., Quirantes-Piné, R., Uberos, J., Jiménez-Sánchez, C., Peña, A., & Segura-Carretero, A. (2016). Antibacterial activity of isolated phenolic compounds from cranberry (Vaccinium macrocarpon) against Escherichia coli. Food & function, 7(3), 1564-1573. DOI:10.1039/c5fo01441g

Sagdic, O., Aksoy, A., & Ozkan, G. (2006). Evaluation of the antibacterial and antioxidant potentials of cranberry (gilaburu, Viburnum opulus L.) fruit extract. Acta Alimentaria, 35(4), 487-492. https://doi.org/10.1556/AAlim.35.2006.4.12

Shmuely, H., Burger, O., Neeman, I., Yahav, J., Samra, Z., Niv, Y…. Ofek, I. (2004). Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a high-molecular-weight constituent of cranberry. Diagn Microbiol Infect Dis, 50(4), 231-5. DOI:10.1016/j.diagmicrobio.2004.08.011

Spaulding, C. N., Klein, R. D., Ruer, S., Kau, A. L., Schreiber, H. L., Cusumano, Z. T., ... & Remaut, H. (2017). Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist. Nature, 546(7659), 528-532. DOI:10.1038/nature22972

Spaulding, C. N., Kau, A. L., Klein, R. D., Janetka, J. W., Gordon, J. I., & Hultgren, S. J. (2017a). Small-molecule inhibitors against type 1 pili selectively target uropathogenic E. coli in the gut and bladder. The FASEB Journal, 31(1 Supplement), 939-9. Abstract

Sun, J., Marais, J. P., Khoo, C., LaPlante, K., Vejborg, R. M., Givskov, M., ... & Rowley, D. C. (2015). Cranberry (Vaccinium macrocarpon) oligosaccharides decrease biofilm formation by uropathogenic Escherichia coli. Journal of functional foods, 17, 235-242. DOI:10.1016/j.jff.2015.05.016

Syngai, G. G., Gopi, R., Bharali, R., Dey, S., Lakshmanan, G. A., & Ahmed, G. (2016). Probiotics-the versatile functional food ingredients. Journal of food science and technology, 53(2), 921-933. DOI: 10.1007/s13197-015-2011-0

Vicariotto, F. (2014). Effectiveness of an association of a cranberry dry extract, D-mannose, and the two microorganisms Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09 in women affected by cystitis: a pilot study. Journal of clinical gastroenterology, 48, S96-S101. DOI:10.1097/MCG.0000000000000224

Voravuthikunchai, S. P., Sririrak, T., Limsuwan, S., Supawita, T., Iida, T., & Honda, T. (2005). Inhibitory effects of active compounds from Punica granatum pericarp on verocytotoxin production by enterohemorrhagic Escherichia coli O157: H7. Journal of health science, 51(5), 590-596. DOI:10.1016/j.foodchem.2015.06.028

FOOD SCIENCE: THE APPLICATION AND USE OF CRANBERRY, POMEGRANATE, PROBIOTICS (BULGARIAN ORIGIN), SUPERNATANT, D-MANNOSE, AND CHICORY SOLUBLE FIBER.*

Historical and Clinical Reviews of Cranberries and Pomegranate

Heber, D. (2011). Pomegranate Ellagitannins. In I.F.F., Benzie, & S. Wachtel-Galor (Eds.), Herbal medicine: Biomolecular and clinical aspects. 2^nd edition. Boca Raton, FL: CRC Press/Taylor & Francis. https://www.ncbi.nlm.nih.gov/books/NBK92772/

Neto, C.C., & Vinson, J.A. (2011). Cranberry. In I.F.F., Benzie, & S. Wachtel-Galor (Eds.), Herbal medicine: Biomolecular and clinical aspects. 2^nd edition. Boca Raton, FL: CRC Press/Taylor & Francis. https://www.ncbi.nlm.nih.gov/books/NBK92771/

Usta, C., Ozdemir, S., Schiariti, M., & Puddu, P. E. (2013). The pharmacological use of ellagic acid-rich pomegranate fruit. International journal of food sciences and nutrition, 64 (7), 907-913. DOI: 10.3109/09637486.2013.798268

Cranberries : UTI Support and Management

Avorn, J., Monane, M., Gurwitz. J.H., Glynn. R.J., Choodnovskiy, I., Lipsitz, L.A. (1994). Reduction ofbacteriuria and pyuria after ingestion of cranberry juice. J Am Med Assoc, 271, 751–4. doi:10.1001/jama.1995.03510340041031

Bailey, D.T., Dalton, C., Daugherty, F.J., & Tempesta, M.S. (2007). Can a concentrated cranberry extract prevent recurrent urinary tract infections in women? A pilot study. Phytomed, 14, 237–41. DOI: 10.1016/j.phymed.2007.01.004

Bader, M. S., Loeb, M., & Brooks, A. A. (2017). An update on the management of urinary tract infections in the era of antimicrobial resistance. Postgraduate medicine, 129(2), 242-258. http://dx.doi.org/10.1080/00325481.2017.1246055

Cowan, M. M. (1999). Plant products as antimicrobial agents.Clinical microbiology reviews, 12(4), 564-582. Abstract

Davidson, E., Zimmermann, B.F., Jungfer, E., & Chrubasik-Hausmann, S. (2014). Prevention of Urinary Tract Infections with Vaccinium Products. Phytotherapy Research, 28, (3), 465-470. DOI: 10.1002/ptr.5047

de Llano, D.G., Esteban-Fernández, A., Sánchez-Patán, F., Martínlvarez, P.J., Moreno-Arribas, M.V., Bartolomé, B. (2015). Anti-Adhesive Activity of Cranberry Phenolic Compounds and Their Microbial-Derived Metabolites against Uropathogenic Escherichia coli in Bladder Epithelial Cell Cultures.Int J Mol Sci, 16(6), 12119-30. DOI: 10.3390/ijms160612119

Di Martino, P., Agniel, R., David, K., Templer, C., Gaillard, J.L., Denys, P., & Botto, H. (2006). Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: A double-blind,randomized placebo-controlled cross-over trial. WorldJ Urol, 24, 21–7. DOI: 10.1007/s00345-005-0045-z

Ermel, G., Georgeault, S., Inisan, C., Besnard, M. (2012). Inhibition of adhesion of uropathogenic Escherichia coli bacteria to uroepithelial cells by extracts from cranberry. J Med Food, 15(2):126-34. DOI: 10.1089/jmf.2010.0312

Feliciano, R.P., Krueger, C.G., Reed, J.D. (2015). Methods to determine effects of cranberry proanthocyanidins on extraintestinal infections: Relevance for urinary tract health. Mol Nutr Food Res, 59 (7), 1292-306. DOI: 10.1002/mnfr.201500108

Fleet, J.C. (1994). New support for a folk remedy: cranberry juice reduces bacteriuria and pyuria in elderly women. Nutr Rev, 52(5),168-70. DOI:10.1111/j.1753-4887.1994.tb01413.x

Foo, L.Y., Lu, Y., Howell, A.B., & Vorsa, N. (2000). The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry, 54(2), 173-81. https://doi.org/10.1016/S0031-9422(99)00573-7

Foxman, B., Cronewett, A.E.W., Spino, C., Berger, M.B., Morgan, D.M. (2015). Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial. American Journal of Obstetrics and Gynecology, 213(2), 123-124. DOI: 10.1016/j.ajog.2015.04.003

Foxman B. (2014). Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect. Dis. Clin. North. Am. 28, 1–13. DOI: 10.1016/j.idc.2013.09.003

Gupta, A., Dwivedi, M., Mahdi, A.A., Nagana Gowda, G.A., Khetrapal, C.L., Bhandari, M. (2012). Inhibition of adherence of multi-drug resistant E. coli by proanthocyanidin. Urol Res, 40(2), 143-50. DOI: 10.1007/s00240-011-0398-2

Gupta, K., Chou, M.Y., Howell, A., Wobbe, C., Grady, R., Stapleton, A.E. (2007). Cranberry products inhibit adherence of p-fimbriated Escherichia coli to primary cultured bladder and vaginal epithelial cells. J Urol, 177(6), 2357-60. DOI: 10.1016/j.juro.2007.01.114

Hisano, M., Bruschini, H., Nicodemo, A.C., & Srougi, M. (2012). Cranberries and lower urinary tract infection prevention. CLINICS, 67(6), 661-667. doi: 10.6061/clinics/2012(06)18

Howell, A., Souza, D., Roller, M., Fromentin, E. (2015). Comparison of the Anti-Adhesion Activity of Three Different Cranberry Extracts on Uropathogenic P-fimbriated Escherichia coli: a Randomized, Double-blind, Placebo Controlled, Ex Vivo, Acute Study. Nat Prod Commun. 2015 Jul; 10(7):1215-8. Abstract

Howell, A.B., Botto, H., Combescure, C., Blanc-Potard, A.B., Gausa, L., Matsumoto, T., … Lavigne, J.P. (2010). 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 Infect Dis, 10, 95. doi: 10.1186/1471-2334-10-94 .

Howell A. (2002). Cranberry proanthocyanidins and the maintenance of urinary tract health. Crit Rev Food Sci Nutr; 42S, 273–8. DOI: 10.1080/10408390209351915

Howell A.B, Vorsa N, Der Marderosian A, Foo L.Y. (1998). Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial-cell surfaces by proanthocyanidin extracts from cranberries. N Eng J Med, 339,1085–6. DOI: 10.1056/NEJM199810083391516

Jensen, H.D., Carsten, S., Christensen, S.B., & Krogfelt, K.A. (2017). Cranberry juice and combinations of its organic acids are effective against experimental urinary tract infection. Front Microbiol, 8, 542. doi: 10.3389/fmicb.2017.00542

Kaspar, K.L., Howell, A.B., & Khoo, C. (2015). A randomized, double-blind, placebo-controlled trial to assess the bacterial anti-adhesion effects of cranberry extract beverages.Food Funct, 6(4), 1212-7. DOI: 10.1039/c4fo01018c

Krueger, C. G., Reed, J. D., Feliciano, R. P., & Howell, A. B. (2013). Quantifying and characterizing proanthocyanidins in cranberries in relation to urinary tract health. Analytical and bioanalytical chemistry, 405(13), 4385-4395. DOI: 10.1007/s00216-013-6750-3

Liu, Y., Pinzón-Arango, P.A., Gallardo-Moreno, A.M., Camesano, T.A. (2010). Direct adhesion force measurements between E. coli and human uroepithelial cells in cranberry juice cocktail. Mol Nutr Food Res, 54(12), 1744-52. DOI: 10.1002/mnfr.200900535

Liu, Y., Gallardo-Moreno, A.M., Pinzon-Arango, P.A., Reynolds, Y., Rodriguez, G., Camesano TA. (2008). Cranberry changes the physicochemical surface properties of E. coli and adhesion with uroepithelial cells. Colloids Surf B Biointerfaces, 65(1), 35-42. DOI: 10.1016/j.colsurfb.2008.02.012

Liu, Y., Black, M.A., Caron, L., Camesano, T.A. (2006). Role of cranberry juice on molecular-scale surface characteristics and adhesion behavior of Escherichia coli. Biotechnol Bioeng, 93(2), 297-305. DOI: 10.1002/bit.20675

Margetis, D., Roux, D., Gaudry, S., Messika, J., Bouvet, O., Branger, C….Ricard, J.D. (2015). Effects of Proanthocyanidins on Adhesion, Growth, and Virulence of Highly Virulent Extraintestinal Pathogenic Escherichia coli Argue for Its Use to Treat Oropharyngeal Colonization and Prevent Ventilator-Associated Pneumonia. Crit Care Med, 43(6), e170-8. DOI: 10.1097/CCM.0000000000000972

Mathers, M.J., von Rundstedt, F., Brandt, A.S., Koig, M., Lazica, D.A., & Roth, S. (2009). [Myth or truth. Cranberry juice for prophylaxis and treatment of recurrent urinary tract infection]. Urologe A, 48 (10), 1203-9. [Article in German]. DOI: 10.1007/s00120-009-2051-z

Mathison, B.D., Kimble, L.L., Kaspar, K.L., Khoo, C., Chew, B.P. (2014). Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial. Nutr Res, 34(5), 420-7. DOI: http://dx.doi.org/10.1016/j.nutres.2014.03.006

McMurdo, M.E., Argo, I., Phillips, G., Daly, F., & Davey, P. (2009). Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women.J Antimicrob Chemother, 63, 389–95. DOI: 10.1093/jac/dkn489

McMurdo, M.E., Bissett, L.Y., Price, R.J., Phillips, G., & Crombie, I.K. (2005). Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial. Age Ageing, 34(3), 256-61. DOI: 10.1093/ageing/afi101

Nicolosi, D., Tempera, G., Genovese, C., Furneri, P.M. (2014). Anti-Adhesion Activity of A2-type Proanthocyanidins (a Cranberry Major Component) on Uropathogenic E. coli and P. mirabilis Strains. Antibiotics (Basel), 3(2), 143-54. doi: 10.3390/antibiotics3020143

Pérez-López, F.R., Haya, J., Chedraui, P. (2009). Vaccinium macrocarpon: an interesting option for women with recurrent urinary tract infections and other health benefits. J Obstet Gynaecol Res, 35(4), 630-9. DOI: 10.1111/j.1447-0756.2009.01026.x

Pinzón-Arango, P.A., Liu, Y., Camesano, T.A. (2009). Role of cranberry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment. J Med Food, 12(2), 259-70. DOI: 10.1089/jmf.2008.0196

Rafsanjany, N., Senker, J., Brandt, S., Dobrindt, U., & Hensel, A. (2015). In Vivo Consumption of Cranberry Exerts ex Vivo Antiadhesive Activity against FimH-Dominated Uropathogenic Escherichia coli: A Combined in Vivo, ex Vivo, and in Vitro Study of an Extract from Vaccinium macrocarpon. J Agric Food Chem, 63(40), 8804-18. DOI: 10.1021/acs.jafc.5b03030

Rane, H.S., Bernardo, S.M., Howell, A.B., Lee, S.A. (2014). Cranberry-derived proanthocyanidins prevent formation of Candida albicans biofilms in artificial urine through biofilm- and adherence-specific mechanisms. J Antimicrob Chemother, 69(2), 428-36. DOI: 10.1093/jac/dkt398

Rodríguez-Pérez, C., Quirantes-Piné, R., Uberos, J., Jiménez-Sánchez, C., Peña, A., & Segura-Carretero, A. (2016). Antibacterial activity of isolated phenolic compounds from cranberry (Vaccinium macrocarpon) against Escherichia coli. Food & function, 7(3), 1564-1573. DOI:10.1039/c5fo01441g

Rossi, R., Porta, S., & Canovi, B. (2010). Overview on cranberry and urinary tract infections in females. J Clin Gastroenterol, 44 (1), S61-2. DOI: 10.1097/MCG.0b013e3181d2dc8e

Shin, C.N. (2014). The effects of cranberries on preventing urinary tract infections. Clin Nurs Res, 23(1), 54-79. DOI: 10.1177/1054773813475448

Sobota, A.E. (1984). Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections.J Urol, 131(5), 1013-6. Abstract

Skrovankova, S., Sumczynski, D., Mlcek, J., Jurikova, T., & Sochor, J. (2015). Bioactive compounds and antioxidant activity in different types of berries. International journal of molecular sciences, 16 (10), 24673-24706. doi: 10.3390/ijms161024673

Stothers L. (2002). A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol, 9, 1558–62. Abstract

Sun, J., Marais, J.P.J., Khoo, C., LaPlante, K., Vejborg, R.M., Givskov, M., Tolker-Nielsen, T.,Seeram, N.P., Rowley, D.C. (2015). Cranberry (Vaccinium macrocarpon) oligosaccharides decrease biofilm formation by uropathogenic Escherichia coli. J. Funct. Foods, 17, 235–242. https://doi.org/10.1016/j.jff.2015.05.016

Tao, Y., Pinzon-Arango, P.A., Howel, A.B., & Camesano, T.A. (2011). Oral consumption of cranberry juice cocktail inhibits molecular-scale adhesion of clinical uropathogenic Escherichia coli.J Med Food, 14(7-8), 739-45. DOI: 10.1089/jmf.2010.0154

Tempera, G., Corsello, S., Genovese, C., Caruso, F.E., & Nicolosi, D. (2010). Inhibitory activity of cranberry extract on the bacterial adhesiveness in the urine of women: an ex-vivo study. Int J Immunopathol Pharmacol, 23(2), 611-8. DOI: 10.1177/039463201002300223

Ulrey, R.K., Barksdale, S.M., Zhou, W., van Hoek, M.L. (2014). Cranberry proanthocyanidins have anti-biofilm properties against Pseudomonas aeruginosa. BMC Complement Altern Med, 14, 499. DOI: 10.1186/1472-6882-14-499

Vasileiou, I., Katsargyris, A., Theocharis, S., & Giaginis, C. (2013). Current clinical status on the preventive effects of cranberry consumption against urinary tract infections. Nutr Res, 33(8), 595-607. DOI: 10.1016/j.nutres.2013.05.018

Wang, C. H., Fang, C. C., Chen, N. C., Liu, S. S., Yu, P. H … Chen, S.C. (2012). Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials. Arch. Intern. Med, 172, 988–996. DOI: 10.1001/archinternmed.2012.3004

Wing, D.A., Rumney, P.J., Preslicka, C.W., & Chung, J.H. (2008). Daily cranberry juice for the prevention of asymptomatic bacteriuria in pregnancy: A randomized, controlled pilot study. J Urol, 180,1367–72. DOI: 10.1016/j.juro.2008.06.016

Zafriri, D., Ofek, I., Pocino, A.R., & Sharon, N. (1989). Inhibitory activity of cranberry juice on adherence of type 1 and type P-fimbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Chemother, 33, 92–8. Abstract

Pomegranate: Antimicrobial Effect

Al-Zoreky, N. S. (2009). Antimicrobial activity of pomegranate (Punica granatum L.) fruit peels. International journal of food microbiology, 134(3), 244-248. https://doi.org/10.1016/j.ijfoodmicro.2009.07.002

Bialonska D, Kasimsetty SG, Schrader KK, Ferreira D. (2009). The effect of pomegranate (Punica granatum L.) byproducts and ellagitannins on the growth of human gut bacteria. J Agric Food Chem, 57(18):8344-9. DOI:10.1021/jf901931b

Braga, L. C., Shupp, J. W., Cummings, C., Jett, M., Takahashi, J. A., Carmo, L. S., ... & Nascimento, A. M. A. (2005). Pomegranate extract inhibits Staphylococcus aureus growth and subsequent enterotoxin production. Journal of Ethnopharmacology, 96(1), 335-339. https://doi.org/10.1016/j.jep.2004.08.034

Cowan, M. M. (1999). Plant products as antimicrobial agents.Clinical microbiology reviews, 12(4), 564-582. Article

Dahham, S. S., Ali, M. N., Tabassum, H., & Khan, M. (2010). Studies on antibacterial and antifungal activity of pomegranate (Punica granatum L.). Am. Eurasian J. Agric. Environ. Sci, 9(3), 273-281. Abstract

Duman, A. D., Ozgen, M., Dayisoylu, K. S., Erbil, N., & Durgac, C. (2009). Antimicrobial activity of six pomegranate (Punica granatum L.) varieties and their relation to some of their pomological and phytonutrient characteristics. Molecules, 14(5), 1808-1817. DOI: 10.3390/molecules14051808

Hmid, I., Elothmani, D., Hanine, H., Oukabli, A., & Mehinagic, E. (2017). Comparative study of phenolic compounds and their antioxidant attributes of eighteen pomegranate (Punica granatum L.) cultivars grown in Morocco. Arabian Journal of Chemistry, 10, S2675-S2684. https://doi.org/10.1016/j.arabjc.2013.10.011

Jurenka, J. (2008). Therapeutic applications of pomegranate (Punica granatum L.): a review. Alternative medicine review, 13 (2), 128. Article

Machado, T. D. B., Leal, I. C., Amaral, A. C. F., Santos, K., Silva, M. G. D., & Kuster, R. M. (2002). Antimicrobial ellagitannin of Punica granatum fruits. Journal of the Brazilian Chemical Society, 13(5), 606-610. Article

Nascimento, G. G., Locatelli, J., Freitas, P. C., & Silva, G. L. (2000). Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria. Brazilian journal of microbiology, 31(4), 247-256. Abstract

Naz, S., Siddiqi, R., Ahmad, S., Rasool, S. A., & Sayeed, S. A. (2007). Antibacterial activity directed isolation of compounds from Punica granatum. Journal of food science, 72(9). http://onlinelibrary.wiley.com/doi/10.1111/j.1750-3841.2007.00533.x/abstract

Negi, P. S., & Jayaprakasha, G. K. (2003). Antioxidant and antibacterial activities of Punica granatum peel extracts. Journal of food science, 68(4), 1473-1477. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2621.2003.tb09669.x/full

Pagliarulo, C., De Vito, V., Picariello, G., Colicchio, R., Pastore, G., Salvatore, P., & Volpe, M. G. (2016). Inhibitory effect of pomegranate (Punica granatum L.) polyphenol extracts on the bacterial growth and survival of clinical isolates of pathogenic Staphylococcus aureus and Escherichia coli. Food chemistry, 190, 824-831. DOI: 10.1016/j.foodchem.2015.06.028

Parseh, H., Hassanpour, S., Emam-Djome, Z., Lavasani, A. S., Mahmoodabady, H. Z., CHabok, M., ... & Ghahsareh, A. M. (2012, April). Antimicrobial properties of Pomegranate (Punica granatum L.) as a Tannin rich Fruit: a review. In The 1st International and The 4th National Congress on Recycling of Organic Waste in Agriculture. Iran .

Rahimi, H. R., Arastoo, M., & Ostad, S. N. (2012). A comprehensive review of Punica granatum (pomegranate) properties in toxicological, pharmacological, cellular and molecular biology researches. Iranian journal of pharmaceutical research: IJPR, 11(2), 385. Article

Reddy, M. K., Gupta, S. K., Jacob, M. R., Khan, S. I., & Ferreira, D. (2007). Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L. Planta medica, 53(05), 461-467. DOI: 10.1055/s-2007-967167

Shaygannia, E., Bahmani, M., Zamanzad, B., & Rafieian-Kopaei, M. (2016). A review study on Punica granatum L. Journal of evidence-based complementary & alternative medicine , 21(3), 221-227. DOI: 10.1177/2156587215598039

Voravuthikunchai, S. P., Sririrak, T., Limsuwan, S., Supawita, T., Iida, T., & Honda, T. (2005). Inhibitory effects of active compounds from Punica granatum pericarp on verocytotoxin production by enterohemorrhagic Escherichia coli O157: H7. Journal of health science, 51 (5), 590-596. DOI: 10.1016/j.foodchem.2015.06.028

Wafa, B. A., Makni, M., Ammar, S., Khannous, L., Hassana, A. B., Bouaziz, M., ... & Gdoura, R. (2017). Antimicrobial effect of the Tunisian Nana variety Punica granatum L. extracts against Salmonella enterica (serovars Kentucky and Enteritidis) isolated from chicken meat and phenolic composition of its peel extract. International journal of food microbiology, 241, 123-131. DOI: 10.1016/j.ijfoodmicro.2016.10.007

Probiotics and Supernatant: UTI Support and Management

de Llano, D. G., Arroyo, A., Cárdenas, N., Rodríguez, J. M., Moreno-Arribas, M., & Bartolomé, B. (2017). Strain-specific inhibition of the adherence of uropathogenic bacteria to bladder cells by probiotic Lactobacillus spp. Pathogens and Disease, 75(4). DOI: 10.1093/femspd/ftx043

Ditu, L.M., Chifiriuc, M.C., Bezirtzoglou, E., Marutescu, L., Bleotu, C., Pelinescu, D., Mihaescu, G., Lazar, V. (2014). Immunomodulatory effect of non-viable components of probiotic culture stimulated with heat-inactivated Escherichia coli and Bacillus cereus on holoxenic mice.Microb Ecol Health Dis, 25. DOI: 10.3402/mehd.v25.23239

Fontana, L., Bermudez-Brito, M., Plaza-Diaz, J., Munoz-Quezada, S., & Gil, A. (2013). Sources, isolation, characterisation and evaluation of probiotics. British journal of nutrition, 109(S2), S35-S50. DOI: 10.1017/S0007114512004011

He, X., Zeng, Q., Puthiyakunnon, S., Zeng, Z., Yang, W., Qiu, J… Cao H.. .(2017). Lactobacillus rhamnosus GG [ATCC 53103] supernatant enhance neonatal resistance to systemic Escherichia coli K1 infection by accelerating development of intestinal defense. Sci Rep, 7, 43305. DOI: 10.1038/srep43305

Hütt, P., Shchepetova, J., Loivukene, K., Kullisaar, T., & Mikelsaar, M. (2006). Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero‐and uropathogens. Journal of Applied Microbiology, 100(6), 1324-1332. DOI: 10.1111/j.1365-2672.2006.02857.x

Lazar, V., Miyazaki, Y., Hanawa, T., Chifiriuc, M. C., Ditu, L. M., Marutescu, L., ... & Kamiya, S. (2009). The influence of some probiotic supernatants on the growth and virulence features expression of several selected enteroaggregative E. coli clinical strains.Roum Arch Microbiol Immunol, 68(4), 207-214. Abstract

Lee, S. J., Cha, J., & Lee, J. W. (2016). Probiotics prophylaxis in pyelonephritis infants with normal urinary tracts. World Journal of Pediatrics, 12(4), 425-429. DOI: 10.1007/s12519-016-0013-2

Liévin-Le Moal, V., & Servin, A. L. (2014). Anti-infective activities of lactobacillus strains in the human intestinal microbiota: from probiotics to gastrointestinal anti-infectious biotherapeutic agents. Clinical microbiology reviews, 27(2), 167-199. DOI: 10.1128/CMR.00080-13

Manzoor, A., Ul-Haq, I., Baig, S., Qazi, J. I., & Seratlic, S. (2016). Efficacy of locally isolated lactic acid bacteria against antibiotic-resistant uropathogens.Jundishapur journal of microbiology, 9(1). DOI: 10.5812/jjm.18952

Maurya, P., Mogra, R., & Bajpai, P. (2014). Probiotics: an approach towards health and disease. Trends in Biosciences, 7(20), 3107-3113. Abstract

Shim, Y. H., Lee, S. J., & Lee, J. W. (2016). Antimicrobial activity of lactobacillus strains against uropathogens.Pediatrics International, 58(10), 1009-1013. DOI: 10.1111/ped.12949

Syngai, G. G., Gopi, R., Bharali, R., Dey, S., Lakshmanan, G. A., & Ahmed, G. (2016). Probiotics-the versatile functional food ingredients. Journal of food science and technology, 53(2), 921-933. DOI: 10.1007/s13197-015-2011-0

D-mannose: UTI Support and Management

Domenici, L., Monti, M., Bracchi, C., Giorgini, M., Colagiovanni, V., Muzii, L., & Panici, P. B. (2016). D-mannose: a promising support for acute urinary tract infections in women. A pilot study.Eur Rev Med Pharmacol Sci, 20(13), 2920-5. Article

Kranjčec, B., Papeš, D., Altarac, S.(2014). D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol, 32(1), 79-84.DOI: 10.1007/s00345-013-1091-6

Palleschi, G., Carbone, A., Zanello, P. P., Mele, R., Leto, A., Fuschi, A., ... & Maurizi, A. (2017). Prospective study to compare antibiosis versus the association of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract in preventing urinary tract infections in patients submitted to urodynamic investigation. Archivio Italiano di Urologia e Andrologia, 89(1), 45-50. DOI: 10.4081/aiua.2017.1.45

Panicker, J., Phé, V., Pakzad, M., Haslam, C., Gonzales, G., Curtis, C., ... & Chataway, J. (2016). D-MANNOSE TO PREVENT URINARY TRACT INFECTIONS IN MULTIPLE SCLEROSIS. http://dx.doi.org/10.1136/jnnp-2016-315106.151

Spaulding, C. N., Klein, R. D., Ruer, S., Kau, A. L., Schreiber, H. L., Cusumano, Z. T., ... & Remaut, H. (2017). Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist. Nature, 546(7659), 528-532. DOI: 10.1038/nature22972

Spaulding, C. N., Kau, A. L., Klein, R. D., Janetka, J. W., Gordon, J. I., & Hultgren, S. J. (2017a). Small-molecule inhibitors against type 1 pili selectively target uropathogenic E. coli in the gut and bladder. The FASEB Journal, 31(1 Supplement), 939-9. Abstract

Vicariotto, F. (2014). Effectiveness of an association of a cranberry dry extract, D-mannose, and the two microorganisms Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09 in women affected by cystitis: a pilot study. Journal of clinical gastroenterology, 48, S96-S101. DOI: 10.1097/MCG.0000000000000224

Cranberries and Helicobacter Pylori

Burger, O., Weiss, E., Sharon, N., Tabak, M., Neeman, I., Ofek, I. (2002). Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr, 42(3), 279-84. DOI: 10.1080/10408390209351916

Burger, O., Ofek, I., Tabak, M., Weiss. E.I,, Sharon, N., & Neeman, I. (2000). A high molecular mass constituent of cranberry juice inhibitsHelicobacter pylori adhesion to human gastric mucus.FEMS Immunol Med Microbiol, 29, 295–301. Abstract

Matsushima, M., Suzuki, T., Masui, A., (Edss). (2008). Growth inhibitory action of cranberry on Helicobacter pylori. J Gastroenterol Hepatol, 2, S175–80. DOI: 10.1111/j.1440-1746.2008.05409.x

Shmuely, H., Yahav, J., Samra, Z., Chodick, G., Koren, R., Niv, Y., Ofek, I. (2007). Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor.Mol Nutr Food Res, 51(6), 746-51. DOI: 10.1002/mnfr.200600281

Shmuely, H., Burger, O., Neeman, I., Yahav, J., Samra, Z., Niv, Y…. Ofek, I. (2004). Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a high-molecular-weight constituent of cranberry. Diagn Microbiol Infect Dis, 50(4), 231-5. DOI: 10.1016/j.diagmicrobio.2004.08.011

Zhang, L., Ma, J., Pan, K., Go, V.L., Chen, J., You, W.C. (2005). Efficacy of cranberry juice on Helicobacter pylori infection: A double-blind randomized placebo-controlled trial. Helicobacter, 10, 139–45. DOI: 10.1111/j.1523-5378.2005.00301.x

Cranberries and Pomegranate for Cancer Support

Adams, L.S., Seeram, N.P., Aggarwal, B.B., Takada, Y., Sand, D., Heber, D. (2006). Pomegranate juice, total pomegranate tannins and punicalagin suppress inflammatory cell signaling in colon cancer cells.J Agric Food Chem, 54, 980–5. DOI: 10.1021/jf052005r

Afaq, F., Saleem, M., Krueger, C.G., Reed, J.D., Mukhtar, H. (2005). Anthocyanin- and hydrolysable tannin-rich pomegranate fruit extract modulates MAPK and NF-κBpathways and inhibits skin tumorigenesis in CD-1 mice. Int J Cancer, 113, 423–33. DOI: 10.1002/ijc.20587

Bishayee, A., Mandal, A., Bhattacharyya, P., Bhatia, D. (2016). Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis. Nutr Cancer, 68(1), 120-30. DOI: 10.1080/01635581.2016.1115094

Castonguay, A., Gali, H., Perchellet, E., Gao, X, Boukharta, M., Jalbert, G…. Perchellet, J. (1997). Antitumorigenic and antipromoting activities of ellagic acid, ellagitannins and oligomeric anthocyanin and procyanidin. Int J Oncol, 10, 367–73. Abstract

Faria, A., & Calhau, C. (2011). The bioactivity of pomegranate: impact on health and disease. Criti Rev Food Sci Nutri, 51(7), 626-34. DOI: 10.1080/10408391003748100

Ferguson, P.J., Kurowska, E.M., Freeman, D.J., Chambers, A.F., Koropatnick, D.J. (2006). In vivo inhibition of growth of human tumor lines by flavonoid fractions from cranberry extract. Nutr Cancer, 56, 86–94. DOI: 10.1207/s15327914nc5601_12

Ferguson, P., Kurowska, E., Freeman, D.J., Chambers, A.F., Koropatnick, D.J. (2004). A flavonoid fraction from cranberry extract inhibits proliferation of human tumor cell lines. J Nutr, 134, 1529–35. Abstract

Griffin, L., Rego, S., Correiro, E., Neto, C., Hart, P. (2005). Induction of Apoptosis in Tumor Cell Lines by Polyphenolic Compounds Isolatedfrom Vaccinium Macrocarpon. Molecular Biology of the Cell, 11, 184a. Citation

Heber, D. (2011). Pomegranate Ellagitannins. In I.F.F., Benzie, & S. Wachtel-Galor (Eds.), Herbal medicine: Biomolecular and clinical aspects. 2^nd edition. Boca Raton, FL: CRC Press/Taylor & Francis. Chapter 10

Hochman, N., Houri-Haddad, Y., Koblinski, J., Wahl, L., Roniger, M., Bar-Sinai, A. …Hochman, J. (2008). Cranberry juice constituents impair lymphoma growth andaugment the generation of antilymphoma antibodies in syngeneic mice. Nutr Cancer, 60, 511–7. DOI: 10.1080/01635580801956493

Kandil, F.E., Smith, M. A. L., Rogers, R.B., Pepin, MF., Song, L.L., Pezzuto, J.M., Seigler, D.S. (2002). Composition of a chemopreventive proantho-cyanidin-rich fraction from cranberry fruits responsible for the inhibition of TPA-induced ODC activity. J Agric Food Chem, 50, 1063–9. DOI:10.1021/jf011136z

Kresty, L.A., Weh, K.M., Zeyzus-Johns, B., Perez, L.N., Howell, A.B. (2015). Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation. Oncotarget, 6, 33438–33455. DOI: 10.18632/oncotarget.5586

Kresty, L.A., Clarke, J., Ezell, K., Exum, A., Howell, A.B., Guettouche, T. (2011). MicroRNA alterations in Barrett's esophagus, esophageal adenocarcinoma, and esophageal adenocarcinoma cell lines following cranberry extract treatment: Insights for chemoprevention. J. Carcinog, 10, 34. DOI: 10.4103/1477-3163.91110

Kresty, L.A., Howell, A.B., & Baird, M. (2008). Cranberry proanthocyanidins induce apoptosis and inhibit acid-induced proliferation of human esophageal adenocarcinoma cells. J Agric Food Chem, 56 (3), 676-80. DOI: 10.1021/jf071997t

Lansky, E.P., Newman, R.A. (2007). Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol, 109(2), 177-206. DOI: 10.1016/j.jep.2006.09.006

Liberty, A.M., Amoroso, J.W., Hart, P.E., Neto, C.C. (2009). Cranberry PACs and triterpenoids: anti-cancer activities in colon tumor cell lines. Proceedings of the Second International Symposium on Human Health Effects of Fruits and Vegetables. Acta Horticulturae, 841, 61–66. DOI: 10.17660/ActaHortic.2009.841.4

Liu, M.L., Lin, L.Q., Song, B.B., Wang, L.F., Zhang, C.P., & Liu J.R. (2009). Cranberry phytochemical extract inhibits SGC-7901 cell growth and human tumor xenografts in Balb/c nu/nu mice. J Agric Food Chem, 57, 762–8. DOI: 10.1021/jf802780k

Longtin R. (2003). The pomegranate: Nature's power fruit? J Natl Cancer Inst, 95, 346–8. DOI: https://doi.org/10.1093/jnci/95.5.346

Neto, C.C. (2007). Cranberry and its phytochemicals: a review of in vitro anticancer studies. J Nutr, 137(1), 186S-193S. Article

Neto, C.C., Krueger, C.G., Lamoureaux, T.L., Kondo, M, Vaisberg, A.J., Hurta, R.A.R. … Reed, J.D. (2006). MALDI-TOF MS characterization of proanthocyanidins from cranberry fruit (Vaccinium macrocarpon) that inhibit tumor cell growth and matrix metalloproteinase expression in vitro. J Sci Food Agric, 86, 18–25. DOI:10.1002/jsfa.2347

Panth, N., Manandhar, B., Paudel, K.R. (2017). Anticancer Activity of Punica granatum (Pomegranate): A Review. Phytother Res, 31(4), 568-578. DOI:10.1002/ptr.5784

Pinzon-Arango, P.A., Liu, Y., Camesano, T.A. (2009). Role of cranberry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment. J Med Food, 12, 259–70. DOI: 10.1089/jmf.2008.0196

Prasain, J.K., Rajbhandari, R., Keeton, A.B., Piazza, G.A., Barnes, S. (2016). Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells. Food Funct, 7(9), 4012-4019. DOI:10.1039/c6fo00499g

Seeram, N.P. (2008). Berry fruits for cancer prevention: current status and future prospects. J Agric Food Chem; 56(3): 630-5. DOI: 10.1021/jf072504n

Seeram, N.P., Adams, L.S., Hardy, M.L., Heber, D. (2004). Total cranberry extract versus its phytochemical constituents: Antiproliferative and synergistic effects against human tumor cell lines.J Agric Food Chem, 52, 2512–7. DOI: 10.1021/jf0352778

Seeram, N.P., Adams, L.S., Henning, S.M., Niu, Y., Zhang, Y., Nair, M.G., Heber, D. (2005). In vitro anti-proliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem, 16, 360–7. DOI: 10.1016/j.jnutbio.2005.01.006

Sharma, P., McClees, S.F., Afaq, F. (2017). Pomegranate for Prevention and Treatment of Cancer: An Update. Molecules, 22(1). DOI: 10.3390/molecules22010177

Sun, J., & Liu, R.H. (2006). Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells. Cancer Lett, 241, 124–34. DOI: 10.1016/j.canlet.2005.10.027

Taheri Rouhi, S.Z., Sarker, M.M., Rahmat, A., Alkahtani, S.A., Othman, F. (2017). The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats. BMC Complement Altern Med, 17(1):156. DOI: 10.1186/s12906-017-1667-6

Tibullo, D., Caporarello, N., Giallongo, C., Anfuso, C.D., Genovese, C., Arlotta, C… Raccuia, S.A. (2016). Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM).Nutrients, 8(10). DOI: 10.3390/nu8100611

Vattem, D. A., JANG, H. D., Levin, R., & Shetty, K. (2006). Synergism of cranberry phenolics with ellagic acid and rosmarinic acid for antimutagenic and DNA protection functions. Journal of food biochemistry, 30(1), 98-116. Abstract

Vu, K.D., Carlettini, H., Bouvet, J., Cote, J., Doyon, G., Sylvain, J.-F., Lacroix, M. (2012). Effect of different cranberry extracts and juices during cranberry juice processing on the antiproliferative activity against two colon cancer cell lines. Food Chem., 132, 959–967. https://doi.org/10.1016/j.foodchem.2011.11.078

Weh, K.M., Clarke, J., & Kresty, L.A. (2016). Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents.Antioxidants (Basel), 5(3). DOI: 10.3390/antiox5030027

Weh, K.M., Aiyer, H.S., Howell, A.B., Kresty, L.A. (2016). Cranberry proanthocyanidins modulate reactive oxygen species in Barrett's and esophageal adenocarcinoma cell lines. J Berry Res, 6(2), 125-136. DOI:10.3233/JBR-160122

Yan, X., Murphy, B.T., Hammond, G.B., Vinson, J.A., Neto, C.C. (2002). Antioxidant activities and antitumor screening of extracts from cranberry fruit (Vaccinium macrocarpon). J. Agric. Food Chem, 50, 5844–5849. DOI:10.1021/jf0202234

Pomegranate and Cranberries: Prostate Cancer Support

Bonetta, A., & Di Pierro, F. (2012). Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma. Cancer Manag Res, 4 , 281-6. DOI: 10.2147/CMAR.S35342

Deziel, B., MacPhee, J., Patel, K. Catalli, A., Kulka, M., Neto, C., … Hurta, R. (2012). American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators. Food Funct, 3(5), 556-64. DOI:10.1039/c2fo10145a

Hong, M.Y., Seeram, N.P., & Heber, D. (2008). Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor. J Nutr Biochem, 19(12), 848-55. DOI: 10.1016/j.jnutbio.2007.11.006

Koyama, S., Cobb, L.J., Mehta, H.H., Seeram, N.P., Heber, D., Pantuck, A.J., & Cohen, P. (2010). Pomegranate extract induces apoptosis in human prostate cancer cells by modulation of the IGF-IGFBP axis. Growth Horm IGF Res, 20(1), 55-62. DOI: 10.1016/j.ghir.2009.09.003

Malik, A., Afaq, F., Sarfaraz, S., Adhami, V.M., Syed, D.N., Mukhtar, H. (2005). Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci USA, 102, 14813–8. DOI: 10.1073/pnas.0505870102

Pantuck, A.J., Leppert, J.T., Zomorodian, N., Aronson, W., Hong, J., Barnard, R.J., … Belldegrun, A. (2006). Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res, 12(13), 4018-26. DOI: 10.1158/1078-0432.CCR-05-2290

Retting, M.B., Heber, D., An, J. Seeram, N.P., Rao, J.Y., Rao, J.Y., Liu, H., … Pantuck, A. (2008). Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer ther, 7(9), 2662-71. DOI: 10.1158/1535-7163.MCT-08-0136

Seeram, N.P., Aronson, W.J., Zhang, Y., Henning, S.M., Moro, A., Lee, R.P., … Heber, D. (2007). Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland.J Agric Food Chem, 55(19), 7732-7. DOI: 10.1021/jf071303g

Seeram, N.P., Henning, S.M., Zhang, Y., Suchard, M., Li, Z., & Heber, D. (2006). Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours.J Agric Food Chem, 136(10), 2481-5. Article

Seeram, N.P., Adams, L.S., Hardy, M.L., & Heber, D. (2004). Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines.J Agric Food Chem, 52(9), 2512-7. DOI: 10.1021/jf0352778

Cranberries & Pomegranate: Heart Health, Gut Microbiota, Liver Support

Aviram, M., Volkova, N., Coleman, R., Dreher, M., Reddy, M.K., Ferreira D., Rosenblat, M. (2008). Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies in vivo in atherosclerotic apolipoprotein e-deficient (E 0) mice and in vitro in cultured macrophages and lipoproteins. J Agric Food Chem, 56(3),1148-57. DOI: 10.1021/jf071811q

Aviram, M., Dornfeld, L., Kaplan, M., Coleman, R., Gaitini, D., Nitecki, S…. Fuhrman, B. (2002). Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Drugs Exp Clin Res, 28(2-3), 49-62. Abstract

Aviram, M., Dornfeld, L., Rosenblat, M., Volkova, N., Kaplan, M., Coleman, R., Hayek, T., Presser, D., & Fuhrman, B. (2000). Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: Studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr,71, 1062–1076. Article

Blumberg, J.B., Basu, A., Krueger, C.G., Lila, M.A., Neto, C.C., Novotny, JA… Toner, C.D. (2016). Impact of Cranberries on Gut Microbiota and Cardiometabolic Health: Proceedings of the Cranberry Health Research Conference 2015. Adv Nutr, 7(4), 759S-70S. DOI: 10.3945/an.116.012583

Bishayee, A., Thoppil, R.J., Darvesh, A.S., Ohanyan, V., Meszaros, J.G., Bhatia, D. (2013). Pomegranate phytoconstituents blunt the inflammatory cascade in a chemically induced rodent model of hepatocellular carcinogenesis. J. Nutr. Biochem, 24, 178–187. DOI: 10.1016/j.jnutbio.2012.04.009

Bishayee, A., Bhatia, D., Thoppil, R.J., Darvesh, A.S., Nevo, E. & Lansky, E.P. (2011). Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms.Carcinogenesis, 32(6), 688-96. DOI: 10.1093/carcin/bgr045

Chu, Y.F., & Liu, R.H. (2005). Cranberries inhibit LDL oxidation and induce LDL receptor expression in hepatocytes. Life Sci, 77, 1892–1901. DOI: 10.1016/j.lfs.2005.04.002

Gil, M.I., Tomàs-Barberàn, F.A., Hess-Pierce, B., Holcroft, D.M., Kader, A.A. (2000). Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem, 48, 4581–9. Abstract

Kaplan, M., Hayek, T., Raz, A., Coleman, R., Dornfeld, L., Vaya, J., & Aviram, M. (2001). Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis.The Journal of nutrition, 131(8), 2082-2089. Abstract

Novotny, J. A., Baer, D. J., Khoo, C., Gebauer, S. K., & Charron, C. S. (2015). Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults. The Journal of nutrition,145(6), 1185-1193. DOI: 10.3945/jn.114.203190

McKay, D. L., & Blumberg, J. B. (2007). Cranberries (Vaccinium macrocarpon) and cardiovascular disease risk factors. Nutrition reviews, 65(11), 490-502. https://doi.org/10.1111/j.1753-4887.2007.tb00273.x

Taheri Rouhi, S.Z., Sarker, M.M., Rahmat, A., Alkahtani, S.A., Othman, F. (2017). The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats. BMC Complement Altern Med, 17(1):156. DOI: 10.1186/s12906-017-1667-6

Vinson, J.A., Bose, P., Proch, J. AI Kharrant, H., & Samman, N. (2008). Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants. J Agric Food Chem, 56(14), 5884-91. DOI: 10.1021/jf073309b

Duthie, S. J., Jenkinson, A. M., Crozier, A., Mullen, W., Pirie, L., Kyle, J., ... & Duthie, G. G. (2006). The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers. European journal of nutrition, 45(2), 113-122. DOI: 10.1007/s00394-005-0572-9

Pomegranate: Neuro-regeneration and Cognitive Support

Braidy, N., Essa, M. M., Poljak, A., Selvaraju, S., Al-Adawi, S., Manivasagm, T., ... & Guillemin, G. J. (2016). Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease. Oncotarget, 7(40), 64589. DOI: 10.18632/oncotarget.10905

Braidy, N., Selvaraju, S., Essa, M.M., Vishnav, R., Al-Adawi, S., Al-Senawi, H., … Guillemin, G.J. (2013). Neuroprotective effects of a variety of pomegranate juice extracts against MPTP-induced cytotoxicity and oxidative stress in human primary neurons. Oxid Med Cell Longev. DOI:10.1155/2013/685909

Essa, M.M., Subash, S., Akbar, M., Al-Adawi, S., & Guillemin, G.J. (2015). Long-term dietary supplementation of pomegranates, figs and dates alleviate neuroinflammation in a transgenic mouse model of Alzheimer's disease. PLoS One, 10(3). DOI: 10.1371/journal.pone.0120964

Subash, S., Braidy, N., Essa, M.M., Al-Buraiki, Z., Vaishnav, R., Al-Adawi, S., Al-Asmi, A., Guillemin, G.J. (2014). Long Term (15 Months) Dietary Supplementation with Pomegranates from Oman Attenuates Cognitive and Behavioural Deficts in a Transgenic Mice Model of Alzheimer's Disease. Nutrition, 31223-9.DOI: 10.1016/j.nut.2014.06.004

Yan, T., Ma, H., Liu, W., Niesen, D.B., Shah, N., Crews, R., … Seeram, N.P. (2016). Pomegranate's Neuroprotective Effects against Alzheimer's Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites. ACS Chem Neurosci, 7(1), 26-33. DOI: 10.1021/acschemneuro.5b00260

The Bioavailability of Cranberry and Pomegranate

Carlsen, M.H., Halvorsen, B.L., Holte, K., Bohn, S.K., Dragland, S., Sampson, L., … Blomhoff, R. (2010). The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr J, 9,3. doi: 10.1186/1475-2891-9-3

Duthie, G.G., Kyle, J.A., Jenkinson, A.M., Duthie, S.J., Baxter, G.J., Paterson, J.R. (2005). Increased salicylate concentrations in urine of human volunteers after consumption of cranberry juice.J Agric Food Chem, 53, 2897–9000. DOI: 10.1021/jf040393b

Grace, M.H., Massey, A.R., Mbeunkui. F., Yousef, G.G., & Lila, M.A. (2012). Comparison of health-relevant flavonoids in commonly consumed cranberry products. J Food Sci, 77(8), H176-83. DOI: 10.1111/j.1750-3841.2012.02788.x

Lila, M.A., Burton-Freeman, B., Grace, M., & Kalt, W. (2016). Unraveling Anthocyanin Bioavailability for Human Health. Annu Rev Food Sci Technol,7, 375-93. DOI: 10.1146/annurev-food-041715-033346

Ohnishi R, Ito H, Kasajima N, editors. (2006). Urinary excretion of anthocyanins in humans after cranberry juice ingestion.Biosci Biotechnol Biochem, 70, 1681–7. DOI: 10.1271/bbb.60023

Sandhu, A.K., Huang, Y., Xiao, D., Par, E., Edirisinghe, I., & Burton-Freeman, B. (2016). Pharmacokinetic Characterization and Bioavailability of Strawberry Anthocyanins Relative to Meal Intake. J Agric Food Chem, 64(24), 4891-9. DOI: 10.1021/acs.jafc.6b00805

Seeram, N. P., Zhang, Y., McKeever, R., Henning, S. M., Lee, R. P., Suchard, M. A., ... & Nguyen, M. (2008). Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects. Journal of medicinal food, 11(2), 390-394. DOI: 10.1089/jmf.2007.650

Zhang, K., Zuo, Y. (2004). GC-MS Determination of flavonoids and phenolic and benzoic acids in human plasma after consumption of cranberry juice. J Agric Food Chem, 52:222–7. DOI: 10.1021/jf035073r

Cranberry Pomegranate Synbiotic: UTI Support

A Proprietary blend of:                                        500mg

Phytonutrients- Organic Cranberry 6%, Pomegranate Extract with 40% Punicalagins, D-Mannose.

BioImmersion Probiotic Master Blend – Probiotics- Bifidobacterium longum, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus bulgaricus and streptococcus thermophilus; Prebiotic- Inulin from chicory Root; Supernatant- probiotic metabolites, and ORNs. 30 billion CFU.

Capsule- Cellulose & Water

CRANBERRY POMEGRANATE — The Cranberry Pomegranate is designed to care for the bladder, kidneys, and prostate. *

UTI (urinary tract infection) support: Take 2-4 capsules every 3 hours till the bladder relaxes and urine flow improves, then reduce to 2 caps X 3 daily for several days. For maintenance, take 1-2 a day. Add Garlic as an antimicrobial agent, 1-2 capsules, and Original for added probiotics and fiber.*

Prostate support: Take 1-2 a day.  If it is difficult to urinate, take 2-4 every 3 hours till inflammation subsides and urine flows. Add 1 capsule of Phyto Power, Fructo Borate, and 1 teaspoon of No 7 to reduce swelling, and along with 1 capsule of Glucosamine & Sulforaphanes (broccoli cruciferous sprouts) to support DNA cellular integrity.*

Bloating and swelling: Excellent to help the kidneys and bladder flush. Take 2 capsules with extra water till swelling or bloating subsides (every 3 hours).*

Our favorite: The Cran/Pom is Dr. Dohrea Bardell’s third favorite product (yes, she has a list: Blueberry Extract and No 7, respectively). During travel or stressful times, the microbiome (GI Tract), along with the bladder and prostate, can easily become unbalanced (bloating, swelling, aching). The Cranberry Pomegranate is an exceptionally potent anti-inflammatory for the whole GI Tract, bladder, prostate, and even helps that achy low back pain. Take up to 4-6 when very uncomfortable, and drink plenty of water. *