7.1 Introduction and Mechanism of Action

d-Mannose is a monosaccharide simple sugar found within human metabolism. It was originally used in cats, dogs and horses to prevent UTIs in the past. However there are now increasing evidence for its use in humans [1].

d-Mannose is rapidly absorbed into the body within 30 minutes and excreted in the urinary tract where it exerts its effect. d-Mannose cannot be stored in the body as it cannot be converted into glycogen.

d-Mannose is thought to work by inhibiting the adherence of the bacteria to the urothelial cells found on the inner lining of the bladder. E. coli causes the vast majority of UTIs. This bacterium contains a virulence factor called FimH that aids in the binding of the bacteria to the bladder mucosa lining.

d-Mannose inhibits this binding by mimicking the bladder lining to attract the bacterial instead. This causes the bacteria to bind onto the d-Mannose in the urine instead of the bladder wall, trapping them within the urine itself and subsequently, when the patient voids, both are flushed out and removed.

This has been supported by laboratory based in vitro and in vivo experiments. In particularly, when rats were injected with d-Mannose, their urine grew significantly less bacteria compared to the control group [2].

7.2 Clinical Evidence

In 308 women, d-Mannose (2 g dissolved in 200 ml of water daily for 6 months) was compared against Nitrofurantoin (50 mg once a day) low dose prophylaxis and placebo. The study found a significant reduction in UTI recurrences with d-Mannose when compared with Nitrofurantoin and placebo with a risk reduction of 0.24 [1].

Smaller studies have also supported the beneficial use of d-Mannose in recurrent UTIs either as a stand-alone prophylaxis [3] or even combined with other non-antibiotic prophylaxis therapies such as cranberry [4] and plant based extracts [5].

A pilot study also found using d-Mannose may be effective in treating acute uncomplicated UTIs. Mannocist^® (Laboratori Farmaceutici Krymi, Rome, Italy) is composed of d-Mannose (1.5 g), sodium bicarbonate, sorbitol and silicon dioxide. A 2016 study reported in 43 women with acute uncomplicated cystitis that the use of Mannocist^® twice a day for 3 days and then once a day for 10 days significantly improved cystitis symptoms and achieved UTI resolution, as well as significantly decreasing the risk of recurrence over the following 12 months. This study however was only a small pilot with no control group and the inability to control for the placebo effect, however the provisional results are promising [3].

The EAU guidelines currently state that d-Mannose therapy is indicative but is not sufficient for a recommendation. This is due to a lack of any high quality data. The EAU guidelines currently suggest the use of d-Mannose only within the frame of high quality clinical investigations.