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: Florian WagenlehnerHorst LorenzOda Ewald, and Peter Gerke

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 interferenceprobioticsantimicrobial peptidesbacteriocins, 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.

October 2020 article in PubMed entitledCombination of Cranberry Extract and D-Mannose – Possible Enhancer of Uropathogen Sensitivity to Antibiotics”

Authors: Daniela Rădulescu, Cristiana David, Flavia Liliana Turcu , Daniela Margareta Spătaru, Paula Popescu, Ileana Adela Văcăroiu 

Summary Conclusions: the association of D‑mannose with cranberry extract showed a promising adjuvant effect on empirically‑treated uncomplicated UTI episodes. The cure rate in patients with resistance to the antibiotic of choice was significant when the study medication was associated.

September 2020 Article Posted on National Institutes of Health (NIH) Site Entitled “Role of D-Mannose in the Prevention of Recurrent Urinary Tract Infections: Evidence from a Systematic Review of the Literature”

Authors: Rina Kyriakides, Patrick Jones, Baskar K. Somani

Summary Conclusions: We performed a systematic review to assess the effect of D-mannose in the prevention of recurrent UTIs. Of the eight studies reporting on D-mannose in this context, six were clinical and included 695 individuals. Three studies reported that time to UTI recurrence was longer with D-mannose. D-Mannose improved quality of life and significantly reduced recurrent UTIs in both catheter and non-catheter users. D-Mannose was effective in reducing the incidence of recurrent UTIs and prolonging UTI-free periods, which consequently increased quality of life.

August 2020 Article in VeryWell Health Entitled “The Health Benefits of D-Mannose”

Reviewed By: Lana Butner,ND

Summary Conclusions: As a dietary supplement, D-Mannose is often touted as a natural way to treat and prevent a urinary tract infection (UTI) or bladder infection (cystitis). Since treatment for frequent UTIs is long-term low-dose antibiotic use (six months or longer), having a non-antibiotic treatment for this type of infection—which accounts for more than six million doctor visits a year—would help prevent antibiotic resistance.


August 2020 review of published studies on D-Mannose entitled “D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis”

Authors: Stacy M Lenger , Megan S Bradley,   Debbie A Thomas , Marnie H Bertolet, Jerry L Lowder, Siobhan Sutcliffe 

Summary Conclusions: D-Mannose appears protective for recurrent urinary tract infection (vs placebo) with possibly similar effectiveness as antibiotics. Overall, D-mannose appears well tolerated with minimal side effects-only a small percentage experiencing diarrhea.

July 2020 Article on Women’s Wellness entitled “UTI Treatment Without Antibiotics”

Reviewed by: Daniel Murrell M.D.

Summary Conclusions: D-mannose is a sugar that sticks to E. coli. Recently, researchers have studied the possibility of using D-mannose and other mannose-containing substances to block the binding of FimH to the lining of the urinary tract. One small, limited study from 2014 showed positive results when attempting to prevent recurrent UTIs. More research is needed, but potentially, a medication that utilizes a mannose-containing substance that opposes FimH from attaching to the lining of the urinary tract in one way or another could show promise for the treatment of UTIs caused by E. coli.

June 2020 Article Posted on National Institutes of Health (NIH) Site Entitled Use of D-Mannose in The Prevention of Recurrent Lower Urinary Tract Infection in Women”

Authors: Kuzmenko, Gyaurgiev

Summary Conclusions: D-mannose use for the prevention of relapses of INMP is indicated in the clinical recommendations of the American (AUA) and European (EUA) urological associations. The data presented in the literature allow us to recommend patients with recurrent LUTI long term D-mannose intake helps to reduce the severity of symptoms in acute episodes and prolong relapse-free period.

January 2020 Article Posted on National Institutes of Health (NIH) Site Entitled “D-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications”

Authors: Daniela Scribano, Meysam Sarshar, Carla Prezioso, Marco Lucarelli, Antonio Angeloni, Carlo Zagaglia, Anna Teresa Palamara, and Cecilia Ambrosi

Summary Conclusions: Overall, the low metabolic/energetic advantages for bacterial growth, the lack of selection of altered FimH adhesins after long-term d-mannose exposure, and the bladder cell tolerance emphasize the safe use of d-mannose in the treatment and prevention of UTIs caused by UPEC (Uropathogenic Escherichia coli)

November 2019 Article in Healthline Medical News Entitled “Can D-Mannose Treat or Prevent UTIs?”

Author: Alan Carter PharmD

Summary Conclusions: More research needs to be done, but D-mannose appears to be a promising nutritional supplement that may be an option for treating and preventing urinary tract infections, especially in people who have frequent UTIs.

October 2019 Clinics in Surgery Article Entitled “Oral D-Mannose in the Prevention and Treatment of Recurrent Urinary Tract Infections”

Authors: Porru D, Regina C, Fiorello N , Gardella B , Spinillo A and Jallous H

Summary Conclusions: professional medical review of 13 clinical trials on D-Mannose showed that Several alternatives to antibiotics exist which are currently being explored. Our review allowed us to record that D-mannose helps to prolong the recurrence-free interval, and therefore reduce the prolonged or cyclical use of antibiotics.

October 2018 Article Published in Nature Reviews Urology entitled “Nonantibiotic Prevention and Management of Recurrent Urinary Tract Infection”

Authors: Neha Sirha, Anna Goodman, Rhana Zakri, Arun Sahai, Sachin Malde

Summary Conclusions: Results suggest that D-mannose could be an alternative to antibiotics in treating uncomplicated UTI in women and reduces the risk of recurrence. The evidence shows that D-mannose is well tolerated, but larger randomized studies are required to further validate its use.

June 2018 Pilot Study Entitled “Recurrent Bacterial Symptomatic Cystitis: A Pilot Study on a New Natural Option for Treatment”

Authors: Populo and Nelli

Summary Conclusions: A study of 85 subjects with UTIs showed that this therapeutic approach combining D-Mannose with Salicin (acute treatment) and Lactobacillus acidophilus La-14 (maintaining treatment) seems to be effective in symptomatic bacterial UTIs.

May 2018 UK National Institute for Health and Care Excellence (NICE) Recommends D-Mannose

Summary Conclusions: Trimethoprim and nitrofurantoin remain the first-line antibiotics of choice in all groups, except pregnant women. Pivmecillinam and fosfomycin are recommended as second-line choices for non-pregnant women who do not improve after 48 h.

For women with recurrent UTIs, the NICE guidance now suggests that clinicians consider recommending D-mannose (a sugar, found naturally in many fruits, available in powder form), and vaginal estrogen (for postmenopausal women) before considering single-dose antibiotic prophylaxis.

D-Mannose Supported By NICE

March 2018 Cleveland Clinic Article Entitled “The Truth About UTIs In Older Adults”

Author: Dr. Howard Goldman, MD

Summary Conclusions: D-Mannose is a relatively new supplement that is being studied for its potential ability to prevent UTIs while causing few side effects. According to Dr. Goldman, D-Mannose sticks to the receptors in the bladder that would normally attract E. coli, the most common bacteria that causes UTIs. By sticking to these receptors, D-Mannose helps prevent E. coli from staying in the bladder, which may help reduce the risk of UTIs. D-Mannose works similarly in the bowels and is thought to prevent pathologic bacteria from colonizing the gastrointestinal tract, which is where the bacteria that cause UTIs in women may originate.

September 2017 Cell and BioScience article published by the National Institutes of Health (NIH) entitled “A Good Sugar, D-mannose, Suppresses Autoimmune Diabetes”

Authors: Yun-Bo Shi and Deling Yin

Summary Conclusions: In sum, the studies by Dr. Chen and his colleagues have discovered that d-mannose is a “healthy/good” monosaccharide and suggest that this unique sugar could be a safe dietary supplement to promote immune tolerance and to treat/prevent human diseases associated with autoimmunity and allergy.

April 2016 Paper in Comprehensive Reviews of Food Science and Food Safety Describing D-Mannose: “Properties, Production, and Applications: An Overview”

Authors: Xing Hu, Yaning Shi, Peng Zhang, Ming Miao, Tao Zhang, and Bo Jiang

Summary Conclusions: This review of literature has revealed that d-mannose, as a highly potential functional and valuable ingredient, exhibits relatively impressive biological functions of great interest in the cosmetic, pharmaceutical, and food industries. The use of chemical methods in the production of d-mannose has the advantages of applying rapid and convenient processes, but some consumers do not agree with the production by chemical methods. Thus, with ongoing efforts in research and development, the biotransformation approach to d-mannose production with enzymes has gradually gained increasing interest and has become the most promising method.

Properties and Benefits of D-Mannose Based on Research in China

February 2014 PubMed/NIH Report Entitled “D-Mannose: A Promising Support For Acute Urinary Tract Infections In Women. A Pilot Study”

Author: Department of Gynecological Obstetrics and Urologic Sciences, University Sapienza of Rome, Rome, Italy.

Summary Conclusions: D-mannose: a promising support for acute urinary tract infections in women. 45 women evaluated over a 15-month period. D-mannose had a significant positive effect on resolving UTI’s and improving patients’ quality of life. As a preventative administered for 6 months, it also showed promising results.

February 2014 Article – Published By The NIH Entitled “D-Mannose Powder for Prophylaxis of Recurrent Urinary Tract Infections in Women: A Randomized Clinical Trial”

Authors: Bojana Kranjcec, Dino Papes, Silvio Altarac

Summary Conclusions: In a clinical trial assessing 308 women with recurrent urinary tract infections, results for those taking D-mannose powder were equal to the results in the Nitrofurantoin group in significantly reducing the risk of recurrent UTI. More studies will be needed to validate the results of this study, but initial findings show that D-mannose may be useful for UTI prevention.