D mannose for prevention and treatment of urinary tract infection (UTI)

D-mannose for prevention and treatment of UTIs

• D-mannose is a simple sugar, a monosaccharide extracted from larch rod, closely related to glucose
  • several fruits and vegetables contain D-mannose, including:
    • cranberries (and cranberry juice)
    • apples
    • oranges
    • peaches
    • broccoli
    • green beans
  • D-mannose is rapidly absorbed and in about 30 minutes reaches the peripheral organs, then is excreted by the urinary tract
  • D-mannose cannot be transformed into glycogen and, therefore, is not stored in the body
  • long-term use of D-mannose, in concentrations up to 20%, has not shown any side effect on human metabolism (1)
    
    
• the process of bacterial adhesion on the cell surface is a crucial factor for the onset of most infections
  • occurs because specific lectins on bacterial wall are able to bind molecules such as D-mannose and L-fucose distributed on the human cell surface
    • the bladder wall is coated with various mannosilate proteins, such as Tamm-Horsfall protein (THP) that interfere directly with the adhesion of bacteria on the mucosa
      • THP may fasten to E. coli with a specific bond, which may be inhibited by exogenous D-mannose
      • by inhibiting the adhesion of bacteria to the urothelium, D-mannose mimics urothelial barrier function
      • by binding free D-mannose in the urine rather than proteins on the vesical cell's surface, bacteria are trapped in the urinary flow and consequently eliminated by the urinary tract
        
        
• NICE was aware of the mechanism of action of D-mannose, which is also in cranberry products
  • noted evidence suggesting that D-mannose was effective in reducing the risk of recurrent UTI in non-pregnant women, and noted the low NNT of 3 (range 2 to 3) over 6 months, compared with no treatment (2)
  • however, this was based on 1 small RCT (3)
    • D-mannose (200 ml of 1% solution once daily in the evening) used for up to 6 months significantly reduced the risk of recurrent infection in non-pregnant women compared with no treatment (14.6% versus 60.8%, NNT 3 [range 2 to 3]; high-quality evidence)
      • based on 1 RCT in non-pregnant women presenting with a current UTI and a history of recurrent UTI
  • a study by Domennici et al suggest that D-mannose can be an effective aid in acute cystitis management and also a successful prophylactic agent in a selected population (4)
    
    
• NICE made a recommendation that some women who are not pregnant may wish to try D-mannose, as a self-care treatment, noting the sugar content of this product which should be considered

A randomised controlled trial (RCT) (n=598, ≥2 UTIs in previous 6 months, or ≥3 in 12 months) found daily d-mannose for 6 months did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI vs placebo (51.0% vs 55.7%, respectively; P=0.26) (5)

• study also found that d-mannose supplementation did not improve other important secondary outcomes, including the number of days of at least moderate symptoms of UTI, time to next consultation for a clinically suspected UTI, number of microbiologically proven UTIs, number of prescribed antibiotic courses for suspected UTI, or hospitalisations or serious adverse events

Reference:

1. Rosen DA et al. Molecular variations in Klebsiella pneumonia and Escherichia coli FimH affect function and pathogenesis in the urinary tract. Infect Immun 2008; 76: 3346-3356
2. NICE (October 2018). Urinary tract infection (recurrent): antimicrobial prescribing
3. Kranjcec B, Papes D, Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial.World J Urol. 2014 Feb;32(1):79-84. doi: 10.1007/s00345-013-1091-6. Epub 2013 Apr 30.
4. Domenici L et al. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. Eur Rev Med Pharmacol Sci. 2016 Jul;20(13):2920-5.
5. Hayward G, Mort S, Hay AD, et al. d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial. JAMA Intern Med. Published online April 08, 2024. doi:10.1001/jamainternmed.2024.0264