Considerations on D-mannose Mechanism of Action and Consequent Classification of Marketed Healthcare Products

Abstract

Urinary tract infections (UTIs) are very common disorders that affect adult women. Indeed, 50% of all women suffer from UTIs at least one time in their lifetime; 20–40% of them experience recurrent episodes. The majority of UTIs seems to be due to uropathogenic Escherichia coli that invades urothelial cells and forms quiescent bacterial reservoirs. Recurrences of UTIs are often treated with non-prescribed antibiotics by the patients, with increased issues connected to antibiotics resistance. D-mannose, a monosaccharide that is absorbed but not metabolized by the human body, has been proposed as an alternative approach for managing UTIs since it can inhibit the bacterial adhesion to the urothelium. This manuscript discusses the mechanisms through which D-mannose acts to highlight the regulatory aspects relevant for determining the administrative category of healthcare products placed on the market. The existing literature permits to conclude that the anti-adhesive effect of D-mannose cannot be considered as a pharmacological effect and, therefore, D-mannose-based products should be classified as medical devices composed of substances.

Cadaverine Is a Switch in the Lysine Degradation Pathway in Pseudomonas aeruginosa Biofilm Identified by Untargeted Metabolomics

“…The only identified carbohydrate with the opposite trend was mannose, with about a six-fold decrease in biofilm. This is consistent with previous studies, which suggested that mannose acts as a competitive inhibitor of bacterial adherence by binding adhesion proteins or lectins in both E. coli and P. aeruginosa ( Hauck et al., 2013 ; Scaglione et al., 2021 ). Weak organic acids (WOA) such as lactic and acetic acid were significantly decreased in biofilm about 10-fold and three-fold, respectively ( Figure 3 ).…”

D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K/Akt/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver Disease

“…Thus developing effective therapeutic interventions for treating hepatic steatosis is critical to prevent further deterioration of ALD, whereas available effective target drugs are lacking ( 45 ). D-mannose, a monosaccharide widely distributed in nature, can be extracted from many plants and fruits, becoming a supplement for effective therapeutic strategies in various diseases ( 46 ). Recently, mannose supplements have been reported to treat liver-related diseases ( 26 , 27 , 47 ).…”

D-Mannose Slows Glioma Growth by Modulating Myeloperoxidase Activity

“…However, in this study, we opted to administered D-mannose intraperitoneally instead of via oral gavage because a gavage may be too stressful for these glioma-bearing animals. As such, the bioavailability may be different, though a recent pharmacokinetic study showed that 90% of ingested D-mannose is rapidly absorbed into the blood, suggesting that oral and parenteral administration may have similar bioavailability [ 39 ]. Given the inverted parabolic response of D-mannose to MPO activity, a careful dose-finding study as well as studies identifying the distribution of dietary D-mannose in the CNS will be needed for translation.…”