Efficacy of D-Mannose in the Management of Urinary Tract Infections: From Acute Treatment to Long-term Prophylaxis — A Systematic Review and Meta-analysis

Purpose: To evaluate the efficacy of D-mannose for preventing recurrent urinary tract infections (UTIs), including in kidney transplant recipients, and to clarify discrepancies between early openlabel and placebo-controlled trials.Materials and Methods: PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science were searched from inception to February 2026. Randomized controlled trials (RCTs) comparing D-mannose with placebo, no treatment, antibiotics, or active controls were included. Risk of bias (RoB) was assessed using RoB 2, and certainty of evidence using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).Results: Eleven RCT reports involving 1,724 participants were included; 10 independent study populations involving 1,631 participants contributed to quantitative analyses. In placebo-controlled trials, D-mannose did not significantly reduce UTI recurrence or persistence versus placebo (risk ratio [RR], 0.38; 95% confidence interval [CI], 0.06–2.36). No-treatment comparisons showed reduced recurrence (RR, 0.23; 95% CI, 0.08–0.66), but were more vulnerable to expectation, performance, and detection biases. The exploratory combined estimate favored D-mannose (RR, 0.28; 95% CI, 0.12–0.66), but certainty was very low. Antibiotic comparisons were inconclusive (RR, 0.43; 95% CI, 0.18–1.05), whereas proanthocyanidins active-control comparisons favored D-mannose-containing regimens (RR, 0.57; 95% CI, 0.40–0.82), including data from kidney transplant recipients.Conclusions: Current placebo-controlled evidence does not establish superiority of D-mannose over placebo. Apparent benefits were mainly driven by no-treatment comparisons with very low certainty. D-mannose remains biologically plausible but clinically uncertain; adequately powered, double-blind, placebo-controlled trials are needed before firm recommendations can be made.