D-Mannose is an aldohexose monosaccharide and an epimer of glucose. D-Mannose is found in animals, microbes, and plants, can be used as an energy source by conversion to glucose, and can also be produced from glucose.1 It is converted via hexokinase to mannose-6-phosphate and then to intermediates that are incorporated into proteins via N-linked glycosylation. It decreases T cell proliferation and increases FoxP3+ T regulatory cells in vitro and prevents diabetes in non-obese diabetic (NOD) mice, a model of autoimmune diabetes, when administered at a dose of 1.1 M in the drinking water.2 D-Mannose administration during gestation at a dose of 9 mg/ml in the drinking water rescues the embryonic lethal phenotype and prevents deficits in glycosylation in Pmm2R137H/F118L mice, a transgenic model of the congenital glycosylation disorder (CDG) PMM2-CDG, which is characterized by phosphomannomutase 2 (PMM2) gene mutations.3 Levels of D-mannose are reduced in the serum of patients with PMM2-CDG.4 Formulations containing D-mannose have been used in the treatment of mannose phosphate isomerase CDG (MPI-CDG).
1.Sharma, V., Ichikawa, M., and Freeze, H.H.Mannose metabolism: More than meets the eyeBiochim. Biophys. Res. Commun.453(2)220-228(2014) 2.Zhang, D., Chia, C., Jiao, X., et al.D-mannose induces regulatory T cells and suppresses immunopathologyNat. Med.23(9)1036-1045(2017) 3.Schneider, A., Theil, C.R., J., DeRossi, C., et al.Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in miceNat. Med.18(1)71-73(2011) 4.Panneerselvam, K., Etchison, J.R., Skovby, F., et al.Abnormal metabolism of mannose in families with carbohydrate-deficient glycoprotein syndrome type 1Biochem. Mol. Med.61(2)161-167(1997)