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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 created 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:

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

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

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

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

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

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

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

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

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

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

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

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

Heber, D., Schulman, R. N., & Seeram, N. P. (Eds.). (2006). Pomegranates: ancient roots to modern medicine. CRC press. Summary

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

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

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

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

Kulkarni, A. P., Mahal, H. S., Kapoor, S., & Aradhya, S. M. (2007). In vitro studies on the binding, antioxidant, and cytotoxic actions of punicalagin. Journal of agricultural and food chemistry, 55(4), 1491-1500. DOI:10.1021/jf0626720

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

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

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

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

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

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

Mori-Okamoto J, Otawara-Hamamoto Y, Yamato H, Yoshimura H. (2004). Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice. J Ethnopharmacol, 92(1), 93-101. https://doi.org/10.1016/j.jep.2004.02.006

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.

Quinlan, J. D., & Jorgensen, S. K. (2017). Recurrent UTIs in women: how you can refine your care. Journal of Family Practice, 66(2), 94-100. 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

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

Article by Dohrea Bardell, PhD

Sincerely yours,

Seann

We have developed our products based on scientific research and/or the practical experience of many healthcare practitioners. There is a growing body of literature on food based nutrition and supplements and their application in support of our health. Please use our products under the advisement of your doctor.

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