A Trial of D-mannose for the Prophylaxis of Recurrent Urinary Tract Infections

Inclusion Criteria: * Female, post-menopausal, age ≥ 55 years old * Diagnosis of recurrent UTI, defined as ≥ 3 symptomatic culture-proven UTI episodes in 12 months or ≥ 2 in 6 months. * Currently free from a UTI determined based on absence of symptoms as determined by the UTI symptom assessment questionnaire79 and negative urine culture (\<103 colony forming units per ml of urine). * Able to attend all follow-up appointments for the study. * A negative upper and lower urinary tract evaluation, including pelvic examination for pelvic organ prolapse (less than stage 2), measurement of post-void residual (less than 50 ml), and imaging (renal ultrasound and standing voiding cystourethrogram) to exclude kidney stone, hydronephrosis, reflux, or urethral diverticulum. Exclusion Criteria: * Current use of D-mannose. Patients willing to stop taking D-mannose will be offered to join the trial after a 4-week wash-out period. * Complicated UTIs, including need for catheter drainage or intermittent catheterization, neurogenic bladder, bladder augmentation, or urinary diversion. * Ongoing supplement use (Box 1). Patients willing to stop taking the listed supplements will be offered to join the trial after a 4-week wash-out period. * Evidence of upper tract infection (pyelonephritis), including temperature higher than 38°C, flank/lumbar pain or tenderness * Diagnosis of interstitial cystitis or overactive bladder syndrome * Prophylactic antibiotics started in the last 3 months and unwilling to discontinue, or intention to start in the next 12 months * Use of Uromune or other vaccine approaches to reduce rUTI * Participation in a research study involving an investigational product in the past 12 weeks * Receipt of phage treatment * History of chronic diarrhea requiring regular therapy * Inability to swallow or known history of gastrointestinal malabsorption * History of recurrent vaginal yeast infections * Systemic disease precluding enrollment in this study (uncontrolled diabetes with HgA1C above 7, ongoing chemotherapy or immunotherapy, renal insufficiency \[creatinine \> 1.5 g/dl\]), mental or cognitive impairment, weight loss diet requiring excessively large amounts of fluid intake, or other health-related specific diet). * Nursing home resident * BMI \>40 Box 1 Supplements to avoid * Multi-Vitamins and Multi-Mineral capsules * Specific Vitamins or Minerals (e.g., Calcium, Citrical, Calcium Gummies, Vitamin A, D, Niacin, Pyridoxine, Selenium, Vitamin E, B6, Iron, Omega 3, D3, Magnesium, B-Complex, Women's Ultra MultiVitamin, GNC B-Complex, B-12, PreserVision Areds2, Vitamins D, B Pollen) * Probiotics * Cranberry Mannose or Cranberry Extract Weight loss products to avoid * Medifast * Vitafusion * OptiVin Products * Appetite Suppressants * Keto-Fuel