The medical research shown here provides clinical support for two nutritional supplements which are being used today as therapies for urinary tract infections (UTIs): Cranberry Extract and D-Mannose.
The primary reference source for this information is the National Institutes of Health (NH) Library of Science archive known as “PubMed” . PubMed® comprises more than 35 million citations for biomedical literature from MEDLINE, life science journals, and online books.
Research on Efficacy of Cranberry For Recurring UTIs
September 2021 article in PLOS One entitled “Consumption of Cranberry As Adjuvant Therapy For Urinary Tract Infections In Susceptible Populations”
Authors: Jia-yue Xia, Chao Yang, Deng-feng Xu, Hui Xia, Li-gang Yang, Gui-ju Sun
Summary Conclusions: Evidence from our updated meta-analysis indicated that cranberry supplementation significantly reduced the incidence of occurring UTIs in susceptible populations. Furthermore, cranberry may be considered as a promising adjuvant therapy for preventing UTIs in susceptible individuals.
November 2019 article in Today’s Geriatric Medicine entitled “Urinary Tract Infections – Non-Antibiotic Prophylaxis With High Dose Cranberry Proanthocyanidins”
Author: Sophie A. Fletcher, M.D.
Summary Conclusions: More recent evidence has clarified the role of soluble A-type PAC as an important inhibitor of P-fimbriated E. coli adhesion to uroepithelial cells, establishing bacterial antiadhesion activity (AAA) as the evidence-based mechanism of action. Furthermore, a dose-dependent, randomized, double-blind study determined that a minimum of 36 mg of the PAC ingredient is required to promote bacterial AAA and contribute to UTI prevention. Additional research has looked at the 36 mg bioactive PAC formula as a nonantibiotic alternative for UTI prophylaxis, finding it effective compared with the low-dose antibiotic trimethoprim. In a university study, the one 36 mg PAC supplement helped to prevent and reduce catheter-associated UTIs, without the side effects and resistance associated with antibiotics.
June 2019 article in Nutritional Outlook entitled “More Urologists Are Recommending PAC’s For Reducing UTI’s. Here’s Why.”
Author: Sophie A. Fletcher, M.D.
Summary: The American Urological Association’s new guidelines emphasize the need for non-antibiotic alternatives for reducing recurrent urinary tract infections-and highlight cranberry as an effective means of prevention.
October 2018 article in Nature Reviews Urology entitled ” Nonantibiotic Prevention and Management of Recurrent Urinary Tract Infection”
Authors: Néha Sihra, Anna Goodman, Rhana Zakri, Arun Sahai & Sachin Malde
Summary: Evidence is mixed on the use of cranberry and cranberry-containing products as prophylaxis for recurrent UTI . The majority of studies have small numbers of participants and different formulations and doses of cranberry. However, several well-conducted randomized controlled trials suggest that cranberry products might be efficacious in specific populations (women with recurrent UTI, women in general and children). Cranberry products are easily accessible, have a low adverse-effect profile and do not carry the same risk of bacterial resistance as antibiotics.
Research On Safety and Efficacy of D-Mannose For UTIs
August 2022 Article in Biomedical Reports entitled “Systematic Review of the Effect of D-Mannose With or Without Other Drugs in the Treatment of Symptoms of Urinary Tract Infections/Cystitis”
Authors: Fabio Parazzini, Elena Ricci, Francesco Fedele, Francesca Chiaffarino, Giovanna Esposito, and Sonia Cipriani
Summary: Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment of UTI/cystitis-related symptoms is unclear. In this paper, we systematically reviewed the published data on the effect of D-mannose, alone or in association with other compounds, on the typical symptoms of UTI/cystitis. PubMed/Medline and EMBASE databases were searched, from 1990 to January 2022.
Key Findings On Treatment of Cystitis Symptoms: All studies reported that symptoms decreased after treatment with D-mannose. Despite the limitations of the studies, the consistent results observed among all studies give support to the general findings that D-mannose may be useful in the treatment of UTI/cystitis symptoms.
Additional Findings On Long-Term Effects of D-Mannose: At least 90% of ingested D-mannose is absorbed in the upper part of the intestine. Its peculiarity is that despite it being a simple molecule, this sugar is not metabolized by the organism. Consequently, it is not stored in the liver or other organs, but it is excreted unconverted into the urine via the kidneys. About 60 min after ingestion, it arrives unchanged in the urinary tract. D-mannose also has no effect on human metabolism after long-term use.
Furthermore, it has been suggested that the dosages of D-mannose used in clinical practice does not affect E. coli metabolism and growth and does not modify bacterial adhesiveness causing FimH variants. All these characteristics underline the fact that the long term use of D-mannose is safe.
July 2022 Article in Microorganisms entitled “Urinary Tract Infections Caused by Uropathogenic Escherichia coli Strains—New Strategies for an Old Pathogen”
Authors: Carlo Zagaglia, Maria Grazia Ammendolia, Linda Maurizi, Mauro Nicoletti, and Catia Longhi
Summary: Uropathogenic Escherichia coli (UPECs) are the main causative agent of UTIs. UPECs initially colonize the human host adhering to the bladder epithelium. Adhesion is followed by the bacterial invasion of urothelial epithelial cells where they can replicate to form compact aggregates of intracellular bacteria with biofilm-like properties… An increasing resistance rate relative to the antibiotics recommended by current guidelines for the treatment of UTIs and an increasing number of multidrug resistant UPEC isolates were observed. In order to ameliorate the cure rate and improve the outcomes of patients, appropriate therapy founded on new strategies, as alternative to antibiotics, needs to be explored. Here, we take a snapshot of the current knowledge of coordinated efforts to develop innovative anti-infective strategies to control the diffusion of UPECs.
Key Findings/Conclusions: An increasing resistance rate relative to the antibiotics was evidenced by current guidelines for the treatment of UTIs. Multidrug and pandrug resistance in UPEC isolates was observed. The need for a rationally designed and developed alternative treatment is, therefore, increasing.
Among these, plant-based options could represent appealing choices because they are cost-effective, readily available, and reduce antimicrobial resistance hazards. However, further studies must be conducted to reveal the chemical composition linked to pharmaceutical activities and their mechanisms.
The vaccine, with whole or lysed fractions of inactivated bacteria, was suggested as effective to generate protective immunity against UTIs.
Probiotics are also considered because of their ability to reduce UTI risks and vaginal infections.
Phage therapy appears to be one of the most promising alternatives to fight various pathogens, including uropathogens that are resistant to commonly available antibiotics.
Finally, the emerging role of nanotechnology may open up new avenues for therapeutic interventions because of the intrinsic properties of nanomaterials and their ability to target intracellular reservoirs.
March 2022 article in the Nutrition Journal entitled “Role of D-Mannose in Urinary Tract Infections – A Narrative Review”
Authors: Reeta Ala-Jaakkola, Arja Laitila, Arthur C. Ouwehand, Liisa Lehtoranta
Summary Conclusions: In addition to female gender, sexual activity at young age and higher age in general, specific conditions such as diabetes, neurologic conditions, chronic institutional residence, and chronic urinary catheterization might predispose to recurring UTIs (rUTIs).
Therefore, individuals in need of repetitive antibiotic treatments, going through urogenital procedures or women with changed bacterial environment in the urogenital area would benefit the most from a non-antibiotic alternative.
Due to increasing antibiotic resistance among UTI pathogens, the burden caused by UTIs is expected to increase creating a high demand for alternative options.
For the treatment of acute UTI, antibiotics are likely to remain the first choice. Supplementing antibiotics with D-mannose may increase treatment success. However, for prophylaxis in reducing rUTI, D-mannose appears to have great potential with minimal side effects.
March 2022 article in Antibiotics magazine entitled “Why D-Mannose May be As Efficient as Antibiotics in the Treatment of Acute Uncomplicated Lower Urinary Tract Infections-Preliminary Considerations and Conclusions from A Non-Interventional Study”
Authors: , , , and
Summary Conclusions: Our post hoc analysis shows that patients using D-mannose as monotherapy in AUC (acute uncomplicated cystitis) achieved very good clinical cure rates, similar to those achieved by patients receiving antibiotic treatments. Furthermore, symptom relief after 3 days of treatment was also comparable between D-mannose monotherapy and antibiotics. These findings are in line with previous studies showing similar effectiveness of D-mannose to that of antibiotics in UTI prevention. Therefore, D-mannose may be a safe and effective alternative to antibiotics in the treatment of AUC. However, further randomized, controlled trials including a relevant number of patients are necessary, in order to confirm the beneficial effect of d-mannose in AUC.
March 2022 Article in Science Direct entitled “The Urinary Microbiome and Biological Therapeutics: Novel Therapies for Urinary Tract Infections”
Authors: Ciara Kenneally, Craig P. Murphy, Roy D. Sleator, Eamonn P. Culligan
Summary: The discovery of microbial communities in the urinary tract (the urobiome) has fundamentally altered the previous doctrine regarding urine sterility and associated urinary disorders. Recent advances in culturing and culture-independent DNA sequencing technologies have characterized the resident microbial community in the urobiome, and has, in turn, demonstrated how community imbalances potentially contribute to infection and disease.
As we enter a post-antibiotic era, the effectiveness of standard antimicrobial treatments against multi-drug resistant (MDR) uropathogens is vastly diminished. Preliminary research is accumulating surrounding microbiome-based therapies, and their potential as non-antibiotic therapeutics. In this context, the urobiome is significantly underexplored, and knowledge regarding the fundamental role of its constituents is lacking.
Herein, we review the current state of the art concerning the urobiome; specifically, how it impacts health and disease states, in the context of urinary tract infections (UTIs).
Key Findings/Conclusions: The development of novel biological therapeutics that may have the potential to provide significant advancements in UTI therapy, with a particular focus on bacterial interference, probiotics, antimicrobial peptides, bacteriocins, and bacteriophage.
April 2021 article in the Antibiotics Journal entitled “The Role of D-Mannose in Prevention of Recurrent Uncomplicated Cystitis: State of The Art and Future Perspectives”
Authors: Cosimo De Nunzio, Riccardo Bartoletti, Andrea Tubaro, Alchiede Simonato, and Vincenzo Ficarra
Summary Conclusions: Particularly, our findings support and confirm that D-mannose reduces the incidence of rUTIs (recurrent UTIs) and determines a longer interval between UTI episodes, with a significant improvement in patients’ quality of life, and therefore, its administration could be considered as one of the possible strategies to be used or to be investigated for the prevention of recurrent UTI in women.