Use of d‐mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women

Abstract

Recurrent UTIs, defined as at least two UTIs in 6 months or three UTIs in 1 year, are a significant burden for the patient and result in high costs to the health system. There are several options for preventing recurrent UTIs, including antibiotic prophylaxis, methenamin prophylaxis and topical oestrogen. The two most commonly used strategies are long-term low-dose antibiotic prophylaxis and post-coital antibiotic prophylaxis for women who have UTI associated with sexual intercourse. Large reviews have shown that antibiotic prophylaxis lasting from 6 to 12 months (or even longer) significantly reduces the number of clinical recurrences in women with recurrent UTIs, but there is no consensus on when to start the prophylaxis, on how long it should last or at which dose and schedule the antibiotic should be taken. Several prophylactic antibiotic regimens can be used with the same efficiency. The most commonly prescribed regimens are trimethoprim-sulfamethoxazole (or trimethoprim alone), nitrofurantoin, cephalexin and the fluoroquinolones at a quarter of the usual daily dose for 6 months. The downsides of long-term antibiotic prophylaxis are possible adverse reactions (although rare), costs and increasing bacterial resistance to antibiotics; therefore, alternative prophylactic agents, such as cranberry juice and probiotics have been extensively studied. One such agent is D-mannose, which is normally present in human metabolism and has an important role, especially in the glycosylation of certain proteins. The supposed mechanism of action is inhibition of bacterial adherence to urothelial cells. In vitro experiments have shown that D-mannose binds and blocks FimH adhesin, which is positioned at the tip of the type 1 fimbria of enteric bacteria. During bacterial colonization, FimH binds to carbohydrate-containing glycoprotein receptors on the epithelium of the urinary tract. As it is similar in structure to the binding site of urothelial glycoprotein receptors, D-mannose acts as a competitive inhibitor of bacterial adherence; in sufficient concentration in urine D-mannose causes saturation of FimH adhesins and prevents the bacteria from binding to urothelial receptors. As well as in vitro, reduction of bacteriuria levels has also been confirmed in in vivo animal UTI models [1]. A similar anti-adhesive effect mechanism has been suggested for Tamm D-mannose powder has been available for some time for the treatment of UTIs in horses, cats and dogs. Its efficiency has not been validated in larger studies but it has been shown that in vitro D-mannose applied locally reduces the adherence of Escherichia coli, Pseudomonas aeruginosa and Streptococcus zooepidemicus (important causes of sterility in mares) to endometrial epithelial cells in mares [4]. D-mannose is also widely available and used for UTI prevention in humans as a food supplement, but clinical studies on the topic are lacking; therefore, in 2012, after obtaining institutional ethics board approval, we conducted a clinical trial that included 308 women >18 years o...

Prospective study to compare antibiosis versus the association of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract in preventing urinary tract infections in patients submitted to urodynamic investigation

“…In vitro studies and preliminary clinical experiences demonstrated that D-mannose and N-acetylcysteine can provide a favourable effect in preventing UTIs (12,(15)(16)(17)(18)(19)(20). The present study shows that D-mannose, N-acetylcysteine in association with Morinda citrifolia fruit extract in the formulation of Ausilium NAC ® , like plurifloxacine, may provide a favourable effect in preventing UTI in case of mini-invasive diagnostic procedures which require bladder catheterism.…”

“…The results obtained suggest to better explore, on larger case series, the advantage of this particular association of nutraceuticals, whose action mechanisms are of particularly suitable interest in UTIs prevention. The synergy between D-mannose, N-acetylcysteine, and Morinda citrifolia fruit extract, has suggested a great role in recurrent UTIs prevention (15)(16)(17)(18)(19)(20)(21). A larger experience is needed, also in different type of populations, to amplify the outcomes shown in the present study.…”

“…D-mannose plays an important role also in other functions such as the ability to regenerate glycosaminoglycans (GAGs) of bladder and mucosal surface, after injury, and to detach bacteria already linked at the urothelium (12)(13)(14). Its beneficial effects in reducing UTI and complementary and integrative therapy for lower urinary tract inflammatory diseases have been shown by various studies (15)(16)(17). However, D-mannose is ineffective against the pathogens inside biofilm thus to induce the need of further action to better prevent the persistence and recurrence of UTI, and the bacterial resistance.…”

The role of nutraceuticals and phytotherapy in the management of urinary tract infections: What we need to know?

“…The hypothesis is that D-mannose inhibits bacterial adherence to uroepithelial cells (30). In fact, in vitro and in vivo animal studies demonstrated that D-mannose can inhibit the adhesion of Type 1 fimbriae of the uropathogenic bacteria to uroepithelial cells (31). Only one RCT evaluated its effect as preventive agent in recurrent UTI.…”

Recovery, Purification, and Reusability of Building Blocks for Solid Phase Synthesis

“…[27][28][29][30][31][32] As exemplary carbohydrate building blocks, azide-derivatives of acetylated mannose (Man) (7), N-acetylglucosamine (GlcNAc) (8), and lactose (Lac) (9) were selected for this work. [33][34][35] For our recovery strategy to be relevant to other groups working with solid phase synthesis, we also expanded our methodology to a first series of BBs differing in size, polarity and solubility. [33][34][35] For our recovery strategy to be relevant to other groups working with solid phase synthesis, we also expanded our methodology to a first series of BBs differing in size, polarity and solubility.…”