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).

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1. Sharma, V., Ichikawa, M., and Freeze, H.H. Mannose metabolism: More than meets the eye. Biochim. 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 immunopathology. Nat. 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 mice. Nat. 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 1. Biochem. Mol. Med. 61(2), 161-167 (1997).