D-Mannose

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 Pmm2^R137H/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)