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. 2022 Aug 30;8(8):CD013608.
doi: 10.1002/14651858.CD013608.pub2.

D-mannose for preventing and treating urinary tract infections

Tess E Cooper  1   2 , Claris Teng  2   3 , Martin Howell  2   3 , Armando Teixeira-Pinto  2   3 , Allison Jaure  2   3 , Germaine Wong  2   3   4
Affiliations

D-mannose for preventing and treating urinary tract infections

Tess E Cooper et al. Cochrane Database Syst Rev. .

Abstract

Background: Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their lifetime and are generally responsive to standard antibiotics, a significant proportion of adults and children (approximately 15% to 25%) are chronic symptomatic UTI sufferers. Certain population groups are at greater risk than others, such as immunosuppressed and people with chronic kidney disease. D-mannose is a sugar part of normal human metabolism found within most diets. The mechanism of action is to prevent bacterial adherence to the uroepithelial cells. The D-mannose-based inhibitors can block uropathogenic Escherichia coli adhesion and invasion of the uroepithelial cells. The bacteria are then understood to essentially be eliminated by urination. Early pilot studies on animals and humans have trialled concentrated forms of D-mannose (tablets or sachets) in doses ranging from 200 mg up to 2 to 3 g and found possible efficacy in reducing UTI symptoms or recurrence. Although the anti-adhesive effects of D-mannose have been well-established, only recently have we seen a small number of pilot studies and small clinical trials conducted.

Objectives: To assess the benefits and harms of D-mannose for preventing and treating UTIs in adults and children.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 22 February 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: We included RCTs measuring and reporting the effect of D-mannose, in any combination and any formulation, to prevent or treat UTIs in adults and children, females and males, in any setting (including perioperative). Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.

Data collection and analysis: Data extraction was independently carried out by two authors using a standard data extraction form. Methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another author. The certainty of the evidence was assessed using the GRADE approach.

Main results: We included seven RCTs (719 participants) in adult females and males who had either acute cystitis or a history of recurrent (at least two episodes in six months or three episodes in 12 months) UTIs (symptomatic or asymptomatic). Two were prevention studies, four were prevention and treatment studies (two perioperative and one in people with multiple sclerosis), and one was a treatment study. Time periods ranged from 15 days to six months. No two studies were comparable (by dose or treatments), and we could not undertake meta-analyses. Individual studies reported no clear evidence to determine whether D-mannose is more or less effective in preventing or treating UTIs. D-mannose (2 g) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to no treatment (1 study, 205 participants; very low certainty evidence) and antibiotics (nitrofurantoin 50 mg) (1 study, 206 participants; very low certainty evidence). D-mannose, in combination with herbal supplements, had uncertain effects on symptomatic and bacteria-confirmed UTI and pain when compared to no treatment (1 study, 40 participants; very low certainty evidence). D-mannose 500 mg plus supplements (N-acetylcysteine and Morinda citrifolia fruit extract) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to an antibiotic (prulifloxacin 400 mg) (1 study, 75 participants; very low certainty evidence). Adverse events were very few and poorly reported; none were serious (mostly diarrhoea and vaginal burning). Overall, the quality of the evidence is poor. Most studies were judged to have unclear or high risk of bias across most domains. Data was sparse and addressed very few outcomes. The GRADE evaluation was rated as very low certainty evidence due to very serious limitations in the study design or execution (high risk of bias across all studies) and sparse data (single study data and small sample sizes).

Authors' conclusions: There is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs in all populations. This review highlights the severe lack of high-quality RCTs testing the efficacy of D-mannose for UTIs in any population. Despite UTIs being one of the most common adult infections (affecting 50% of women at least once in their lifetime) and the growing global antimicrobial resistance, we found very few studies that adequately test this alternative treatment. Future research in this field requires, in the first instance, a single adequately powered RCT comparing D-mannose with placebo.

Trial registration: ClinicalTrials.gov NCT01808755 NCT03497598 NCT03996057 NCT03597152.

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Conflict of interest statement

  1. TC: no relevant interests were disclosed

  2. CT: no relevant interests were disclosed

  3. MH: no relevant interests were disclosed

  4. ATP: no relevant interests were disclosed

  5. AJ: no relevant interests were disclosed

  6. GW: no relevant interests were disclosed

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: D‐mannose (2 g) versus no treatment, Outcome 1: Symptomatic and bacteriuria‐confirmed UTI (positive culture) at 24 weeks
1.2
1.2. Analysis
Comparison 1: D‐mannose (2 g) versus no treatment, Outcome 2: Adverse events
2.1
2.1. Analysis
Comparison 2: D‐mannose (2 g) versus nitrofurantoin (50 mg), Outcome 1: Symptomatic and bacteriuria‐confirmed UTI (positive culture) at 24 weeks
2.2
2.2. Analysis
Comparison 2: D‐mannose (2 g) versus nitrofurantoin (50 mg), Outcome 2: Adverse events
3.1
3.1. Analysis
Comparison 3: D‐mannose (no dose provided) plus herbal combination versus no treatment, Outcome 1: Symptomatic and bacteriuria‐confirmed UTI (positive culture) at 2 weeks
3.2
3.2. Analysis
Comparison 3: D‐mannose (no dose provided) plus herbal combination versus no treatment, Outcome 2: Symptomatic only UTI at 3 months
3.3
3.3. Analysis
Comparison 3: D‐mannose (no dose provided) plus herbal combination versus no treatment, Outcome 3: Pain (mean score (VAS 1‐10)): average/patient (day 1 postop)
4.1
4.1. Analysis
Comparison 4: D‐mannose (500 mg) plus N‐acetylcysteine (100 mg) plus Morinda citrifolia fruit extract (300 mg) versus prulifloxacin (400 mg), Outcome 1: Symptomatic and bacteriuria‐confirmed UTI (positive culture) at 15 days
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

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Domenici 2016 {published data only}
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References to ongoing studies

ACTRN12616001619437 {published data only}
    1. Subramanian S. D-mannose for prophylaxis against urinary tract Infection in spinal cord injury [D-mannose for prophylaxis against urinary tract Infection in SCI: pilot randomised control study]. www.anzctr.org.au/ACTRN12616001619437.aspx (first received 23 November 2016).
ACTRN12619000183189 {published data only}
    1. Patton V. The effectiveness of D-Mannose in patients with high risk of recurrent urinary tract infections. www.anzctr.org.au/ACTRN12619000183189.aspx (first received 8 February 2019).
DRKS00013240 {published data only}
    1. Hellemann M. Effects of a food for special medical purposes containing d-mannose, birch extract, vitamin D and vitamin A for the dietary management of acute symptomatic uncomplicated urinary tract infections in females - a randomized, double-blind, placebo-controlled, parallel-design study. www.trialsearch.who.int/Trial2.aspx?TrialID=DRKS00013240 (first received 11 June 2017). [CENTRAL: CN-01890405]
MERIT 2021 {published data only}13283516
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NCT03597152 {published data only}
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References to other published versions of this review

Cooper 2020
    1. Cooper TE, Teng C, Howell M, Teixeira-Pinto A, Tong A, Wong G. D‐mannose for preventing and treating urinary tract infections. Cochrane Database of Systematic Reviews 2020, Issue 5. Art. No: CD013608. [DOI: 10.1002/14651858.CD013608] - DOI - PMC - PubMed

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