Folate dietary insufficiency and folic acid supplementation similarly impair metabolism and compromise hematopoiesis.

Folate dietary insufficiency and folic acid supplementation similarly impair metabolism and compromise hematopoiesis. Haematologica. 2017 Sep 07;: Authors: Henry CJ, Nemkov T, Casas-Selves M, Bilousova G, Zaberezhnyy V, Higa KC, Serkova NJ, Hansen KC, D' Alessandro A, DeGregori J Abstract While dietary folate deficiency is associated with increased risk for birth defects and other diseases, evidence suggests that supplementation with folic acid can contribute to predisposition to some diseases, including immune dysfunction and cancer. Here we show that diets supplemented with folic acid both below and above the recommended levels led to significantly altered metabolism in multiple tissues in mice. Surprisingly, both low and excessive dietary folate induced similar metabolic changes, which were particularly evident for nucleotide biosynthetic pathways in B-progenitor cells. Diet-induced metabolic changes in these cells partially phenocopied those observed in mice treated with anti-folate drug, suggesting that both deficiency and excessive levels of dietary folic acid compromise folate-dependent biosynthetic pathways. Both folate deficiency and excessive dietary folate levels compromise hematopoiesis resulting in defective cell cycle progression, persistent DNA damage, and impaired production of lymphocytes. These defects reduce reconstitution potential in transplantation settings and increase radiation-induced mortality. We conclude t...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research