Uqora Scientific Background

Urinary Tract Infection Background and Treatment Options

Urinary Tract Infections (UTI) are painful and uncomfortable, yet avoidable. Over 50% of women have had at least one UTI and over 20% have had multiple. UTI’s are responsible for over 8 million doctor’s visits per year (9). Sexual activity is a high risk factor for developing UTI’s in women (5).

UTI’s are most typically caused by E. coli that has been transferred to the urinary tract from the bowel. This transfer can be initiated through sexual activity (9). When E. coli enters the urinary tract, the bacterium adheres to wall of the urinary mucosa using a type of fimbrial adhesin called P fimbriae. These P fimbriae are used by E. coli strands that colonize the urethra to specifically bind to glycoprotein receptors on urothelial cells (3,7). These glycoproteins have a mannose residue that is the binding site for the P fimbriae proteins. The bacterium uses this adhesion process to colonize the urinary tract (15). E. coli strands that do not possess P fimbriae are significantly less likely to cause infection, and much higher bacterial numbers are needed (15).

Current treatment for a UTI caused by the gram-negative E. coli is an antibiotic regiment. There are several common antibiotics used to treat UTI’s, which are typically diagnosed on symptoms alone. Antibiotic resistance in gram-negative bacteria is of increasing concern, particularly for broad-spectrum antibiotics, which are used more and more frequently for urinary infections (14). For patients with recurrent UTI’s, prophylactic antibiotic regiments and post-sexual activity antibiotic prophylaxis are common (12). Recurrent and long-term antibiotic use risks increased bacterial resistance. In addition, antibiotic use can increase a woman’s risk of developing a yeast infection. As bacterial populations in the vagina are killed due to antibiotics taken to treat a UTI, vaginal yeast populations have the opportunity to proliferate. This leads to further infection, discomfort, and anti-fungal medication. This is a growing problem for treating UTI’s specifically, which can lead to more serious infections. It is extremely important that antibiotics are used sparingly, and that alternative prevention options are made available (12).

Cranberry juice is commonly referenced as a tool to reduce UTI risk. Evidence has not been established that UTI risk is reduced with cranberry juice or cranberry extract consumption. A 1,400-person study of college-aged women indicated that cranberry juice was not effective in reducing UTI risk, and less effective than vitamin C alone (4). The theorized mechanism of action for the efficacy of cranberry juice is a reduction in urine pH and the presence of D-mannose sugar. Cranberry juice is not acidic enough to significantly alter urine pH, and D-mannose is present is very small concentrations in cranberries (1, 6). In addition, cranberry juice is very high in sugar, and large quantities would be needed to have a positive effect, if any.

The Uqora Product

The Uqora drink-mix is a dietary supplement product designed to reduce the likelihood of urinary tract infections caused by sexual activity in women. Uqora is a preventative drink-mix intended for consumption after intercourse. Uqora’s ingredients include: D-mannose, Vitamin C, Vitamin B6, Potassium Citrate, Magnesium Citrate.

D-mannose is a 6-carbon sugar that has been the subject of research in relation to UTI’s due to the mannose-specific adherence of E. coli to urothelial cells. Quickly excreted in the urine, D-mannose acts as a competitive inhibitor for the P fimbriae protein in the urinary tract. D-mannose binds the fimbrial adhesin, preventing it from binding the mannose-containing glycoproteins on the exterior urothelial membrane (1,8). Unable to bind to the urinary tract wall, E. coli is flushed out during urination (11). The mechanism as well as clinical efficacy of D-mannose is strongly supported in the literature.

The ability of E. coli strands to colonize the urinary tract is dependent on the presence of the P fimbriae, confirming its role in adhering to the urinary tract wall (15). In a 308 subject, randomized clinical trial, D-mannose supplementation was compared to control over a 6-month period. Those without D-mannose supplementation were 4 times as likely to develop a UTI over a 6-month period, with 15 individuals developing UTI’s in the D-mannose group, compared to 59 in the control (1). The dose during this study was 2g, which is the dose in one packet of the Uqora product. Bacteriuria was measured over a period of 9 days in rats that were administered a 10% D-mannose containing solution. Researchers measured E. coli possessing mannose-specific adhesins. The research strongly demonstrated that “D-mannose can significantly reduce bacteriuria within 1 day” (8). A similar mechanism has been demonstrated for the mannose-containing Tamm-Horsfall protein, which is commonly excreted in the urine and binds to E. coli’s P fimbriae in the urinary tract (13), and this mechanism has been confirmed in an animal model (2).

The Uqora product also contains 600mg of vitamin C. An antioxidant, vitamin C has been demonstrated to support immune system function and be bacteriostatic. Vitamin C has also been demonstrated to reduce UTI risk. A study with over 1,400 college-aged women concluded that vitamin C consumption significantly decreased the risk of developing UTI (4). Additionally, a 110-subject study in pregnant women compared vitamin C consumption to control in decreasing UTI risk. Researchers found that UTI frequency was significantly lower in women receiving prophylactic vitamin C (10).

Vitamin B6 is a safe mild diuretic present in the Uqora product. Vitamin B6 increases urination and urinary flow. Urinating after sexual activity is a common recommendation made by physicians to their patients, as urination physically flushes free bacteria out of the urinary tract (5). Potassium and magnesium citrate salts are also included in the Uqora product to replace the loss of these ions through urination.

Conclusion:

The Uqora product is an efficacious combination of ingredients that should be taken soon after sexual activity to reduce the risk of developing a UTI. A major problem with nutraceutical products is consumer dosage compliance. The Uqora product links reducing UTI risk by drinking the product with the specific behavior that puts individuals at the highest risk. Taking the Uqora product after intercourse creates a strong behavioral association and provides these ingredients when a woman is most vulnerable to infection. Bacteria introduced to the urethral opening during sexual intercourse can then be flushed out through urination in combination with the Uqora product. UTI’s are an enormous problem with no safe and effective long-term solution. Uqora’s drink-mix is an innovative combination of the biochemical mechanisms that cause a UTI, strong clinical research, and an easy-to-use, great tasting consumer product.

References:

1. Altarac, S and1,Papeš, D. “Use of d-mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women.” BJU International, Vol. 113, Issue 1. 2014.

2. Bates, JM, et al. “Tamm-Horsfall protein knockout mice are more prone to urinary   tract infection: rapid communication.” Kidney International, Vol. 65, Issue 3. 2004.

3. Bergsten, G, et al. “Escherichia coli, fimbriae, bacterial persistence and host response induction in the human urinary tract.” Journal of Medical Microbiology, Vol. 295, Issue 6. 2005.

4. Foxman, B and Chi, JW. “Health behavior and urinary tract infection in college-aged women.” Journal of Clinical Epidemiology, Vol. 43, pages 329-337. 1990.

5. Head, K. “Natural Approaches to Prevention and Treatment of Infections of the Lower Urinary Tract.” Alternative Medicine Review, Vol. 13, Issue 3. 2008.

6. Kaye, D. “Antibacterial activity of human urine.” Journal of Clinical Investigation, Vol. 47, Issue 10. 1968.

7. Krogfelt, K, et al. “Direct evidence that the FimH protein is the mannose-specific adhesin of Escherichia coli type 1 fimbriae.” Infection and Immunology, Vol. 58, Issue 6. 1990.

8. Michaels, EK, et al. Effect of D-mannose and D-glucose on Escherichia coli bacteriuria in rats. Urological Research, Vol. 11, Issue 2. 1983.

9. National Kidney and Urological Diseases Information Clearinghouse. “Urinary Tract Infections in Adults.” NIH. http://kidney.niddk.nih.gov/kudiseases/pubs/utiadult/. (2012).

10. Ochoa-Brust GJ, et al. “Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy.” Gynecologica Scandenavia, Vol. 86, pages 783-787. 2007.

11. Ofek, I, et al. “Mannose-specific adherence of E. coli freshly excreted in the urine of patients with urinary tract infections, and of isolates subcultured from the infected urine.” Infection and Immunity, Vol. 34, Issue 3. 1981.

12. Pallet, A and Hand, K. “Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria." Antimicrobial Chemotherapy, Vol. 65, Issue 3. 2010.

13. Serafini-Cessi, F, et al. “N-Glycans carried by Tamm-Horsfall glycoprotein have a crucial role in the defense against urinary tract diseases.” Glycoconjugate Journal, Vol. 22, Issue 7. 2005.

14. Shepherd, AK and Pottinger, PS. “"Management of urinary tract infections in the era of increasing antimicrobial resistance.". The Medical Clinics of North America, Vol. 97, Issue 4. 2013.

15. Wullt, B. “The role of P fimbriae for Escherichia coli establishment and mucosal inflammation in the human urinary tract.” International Journal of Antimicrobial Agents, Vol. 21, Issue 6. 2003.